7.
Hospital Management
7.1. Location
7.1.1. Coronary Care Unit
Class I
1. STEMI patients should be admitted to a quiet and comfortable
environment that provides for continuous monitoring of the ECG and
pulse oximetry and has ready access to facilities for hemodynamic
monitoring and defibrillation. (Level of Evidence: C)
2. The patient’s medication regimen should be reviewed to
confirm the administration of aspirin and betablockers in an adequate
dose to control heart rate and to assess the need for intravenous
nitroglycerin for control
of angina, hypertension, or heart failure. (Level of Evidence:
A)
3. The ongoing need for supplemental oxygen should be assessed by
monitoring arterial oxygen saturation. When stable for 6 hours,
the patient should be reassessed for oxygen need (i.e., O2 saturation
of less than 90%), and discontinuation of supplemental oxygen should
be considered. (Level of Evidence: C)
4. Nursing care should be provided by individuals certified in critical
care, with staffing based on the specific needs of patients and
provider competencies, as well as organizational priorities.
(Level of Evidence: C)
5. Care of STEMI patients in the coronary care unit (CCU) should
be structured around protocols derived from practice guidelines.
(Level of Evidence: C)
6. Electrocardiographic monitoring leads should be based on the
location and rhythm to optimize detection of ST deviation, axis
shift, conduction defects, and dysrhythmias. (Level of Evidence:
B)
Class III
It is not an effective use of the CCU environment to admit terminally
ill, “do not resuscitate” patients with STEMI, because
clinical and comfort needs can be provided outside of a critical
care environment. (Level of Evidence: C)
Treatment of the patient with STEMI begins in the EMS system/ED/catheterization
laboratory and is consolidated in the CCU. On arrival at the CCU,
initial patient evaluation includes assessment of vital signs, pulse
oximetry, cardiac rhythm and ST segments, and symptoms of acute
cardiac ischemia. Research has also shown the importance of assessing
anxiety and depression, because outcomes are worse in patients with
even moderate elevations in dysphoria. Outstanding (and abnormal)
laboratory results should be followed up, and standard orders to
CCU should be implemented. All CCUs should have the equipment and
personnel necessary to monitor intra-arterial pressure and pulmonary
artery catheter pressures (Swan-Ganz catheter). Such monitoring
is useful for severely hypotensive patients. An IABP should be available
in tertiary care CCUs for treatment of cardiogenic shock. The patient’s
medication orders should be reviewed to confirm the administration
of aspirin and betablockers in an adequate dose to control heart
rate and to assess the need for intravenous nitroglycerin for control
of angina, hypertension, or acute heart failure.
Ideally, all CCU nursing staff should have certification in critical
care nursing (CCRN, Critical Care Registered Nurse) as endorsed
by the American Association of Critical-Care Nurses (647).
Advanced cardiac life support certification (ACLS) is highly recommended.
The need for ACLS certification is usually determined by institutional
policy.
There has been documentation of the positive correlation between
nurse staffing levels and patient outcome in intensive care units
(648-650).
The nurse-to-patient ratio has varied depending on nurse availability
and the needs of the patient,
e.g., 1 nurse per patient for an intubated patient, to 1:2 (651).
In 1999, the state of California mandated a ratio of 1:2 in the
intensive care unit/CCU, 1:4 in the stepdown unit, and 1:5 in the
telemetry unit (652). A study of
the effect of the California state law showed a continued wide variation
of staffing ratios among hospitals (653).
The American Association of Critical Care Nurses has issued a policy
statement that staffing decisions in the critical care setting should
optimally be based on the specific needs of patients and provider
competencies, as well as organizational priorities. Within this
framework, staffing should reflect the number and type of staff
that meet a group of patients’ needs instead of a mandated
single staffing ratio or mix (654).
Patients with STEMI may experience heart failure, serious arrhythmias,
or recurrent ischemia (655). Accordingly,
nursing- related care is commonly prescribed as part of a standing
order (i.e., measurement of height and weight on admission and thereafter
daily weight, especially if heart failure is present; routine post-STEMI
vital signs, including oxygen saturation; ECG monitoring; and activity
level such as bathroom privileges and progressive cardiac rehabilitation).
Medications such as stool softeners or antianxiety agents should
be given based on nursing judgment.
The current medical-legal-economic climate demands that CCUs be
operated at peak efficiency, optimizing quality of care and minimizing
complications. Practical and ethical dilemmas present the CCU director
with issues of futile care, triage, and the administration of appropriate
care (656). It is generally accepted
that terminal patients (no-code) or patients whose comorbidities
make survival unlikely should not be admitted to a CCU. Similarly,
patients with improving CHF or stable dysrhythmia should be transferred
to a non-CCU, monitored bed.
7.1.1.1. Monitoring and Treatment forAdverse
Events
Early general measures focus on monitoring for adverse events,
preventing such events through protective measures, and treating
these adverse events when they do occur. Electrocardiographic monitoring
is an essential role of CCU staff, who must be adept at rhythm interpretation,
lead selection based on infarct location and rhythm, and lead placement
for detection of RV involvement (657-660).
Computer algorithms have proved superior to medical personnel for
detection of arrhythmias (661).
Accurate and consistent lead placement and careful electrode and
skin preparation are important to improve the clinical usefulness
of ST monitoring (662).
Nurses should monitor the ST segment for ischemia, particularly
during routine morning care, because patients have been reported
to have a greater likelihood of ischemic events between 6 AM and
noon than at other times (663).
Currently, ECG monitors operate with computerized arrhythmia analysis
alone or with both arrhythmia and ischemia analysis. STsegment monitoring
is generally underutilized in American hospitals.
Because
changes in the ST segment can shift among various ECG leads in the
same person over time owing to different ischemic mechanisms, a
consensus statement on ST monitoring has recommended that 12-lead
monitoring be done (662). Patients
with acute coronary syndromes, including STEMI, are the highest
priority for ST-segment monitoring. It is recommended they be monitored
for a minimum of 24 hours and until they remain event-free for 12
to 24 hours. Potential benefits in patients with STEMI include the
ability to assess patency of the culprit artery after fibrinolytic
therapy (664-668);
detect abrupt reocclusion after PCI (669);
detect ongoing ischemia (i.e., failed reperfusion therapy), recurrent
ischemia, and infarct extension; and detect transient myocardial
ischemia.
Blood pressure should be measured repeatedly; actual frequency will
depend on the severity of the illness. Although invasive arterial
monitoring is preferred in the hypotensive patient, noninvasive
monitoring is adequate for most patients. Monitoring with an automatic
device that inflates and deflates at programmed intervals is useful,
but it must be recognized that measurements may be inaccurate because
of inappropriate cuff size or muscle contractions; marked peripheral
vasoconstriction can result in falsely low readings. Furthermore,
many patients report that the device is irritating and disrupts
rest.
7.1.2. Stepdown Unit
Class I
1.
It is a useful triage strategy to admit low-risk STEMI patients
who have undergone successful PCI directly to the stepdown unit
for post-PCI care rather than to the CCU. (Level of Evidence:
C)
2. STEMI patients originally admitted to the CCU who demonstrate
12 to 24 hours of clinical stability (absence of recurrent ischemia,
heart failure, or hemodynamically compromising dysrhythmias) should
be transferred to the stepdown unit. (Level of Evidence: C)
Class IIa
1. It is reasonable for patients recovering from STEMI who have
clinically symptomatic heart failure to be managed on the stepdown
unit, provided that facilities for continuous monitoring of pulse
oximetry and appropriately skilled nurses are available. (Level
of Evidence: C)
2.
It is reasonable for patients recovering from STEMI who have arrhythmias
that are hemodynamically well tolerated (e.g., AF with a controlled
ventricular response; paroxysms of nonsustained VT lasting less
than 30 seconds) to be managed on the stepdown unit, provided that
facilities for continuous monitoring of the ECG, defibrillators,
and appropriately skilled
nurses are available. (Level of Evidence: C)
Class
IIb
Patients recovering from STEMI who have clinically significant pulmonary
disease requiring high-flow supplemental
oxygen or noninvasive mask ventilation/bilevel positive airway pressure/continuous
positive airway pressure may be considered for care on a stepdown
unit provided that facilities for continuous monitoring of pulse
oximetry and appropriately skilled nurses with a sufficient nurse:patient
ratio are available. (Level of Evidence: C)
Although the CCU was traditionally the hospital location to which
patients with STEMI were first admitted, increasing use of catheter-based
reperfusion and increasing sophistication of monitoring equipment
and staff experience has resulted in a shift toward admitting patients
with low-risk STEMI who have undergone successful reperfusion with
PCI directly to a stepdown unit. In addition, patients originally
admitted to the CCU who demonstrate 12 to 24 hours of clinical stability
are typically transferred to the stepdown unit. The same nurse staffing
and certification considerations apply to the stepdown unit (coronary
observation unit, telemetry unit) as described for the CCU to ensure
optimal evaluation and response to any deterioration of the patient
with STEMI. Pulse oximetry and ECG monitoring and defibrillation
equipment should be available. Optimally, the nursing staff should
have a skill set similar to CCU nurses so that they may evaluate
and respond to any deterioration of a patient with STEMI. The initial
evaluation of patients with STEMI who are admitted directly to the
stepdown unit is similar to that described in Section
7.1.1 for the CCU.
7.2.
Early, General Measures
7.2.1. Level of Activity
Class IIa
After 12 to 24 hours, it is reasonable to allow patients with hemodynamic
instability or continued ischemia to have bedside commode privileges.
(Level of Evidence: C)
Class III
Patients with STEMI who are free of recurrent ischemic discomfort,
symptoms of heart failure, or serious disturbances of heart rhythm
should not be on bed rest for more than 12 to 24 hours. (Level
of Evidence: C)
Limiting early physical exertion and minimizing sympathetic stimulation
(e.g., acute ischemic-type chest discomfort and anxiety) are methods
of minimizing myocardial oxygen demand (670).
In an earlier era, the duration of bed rest was extended to several
weeks, until it was ascertained that prolonged immobility is harmful
because of the physiological deconditioning that occurs after even
6 hours in the supine position (671).
Preload decreases because of plasma volume losses that occur early
in the bedrest period. Shifts in ventricular filling activate the
body’s compensatory mechanisms to buffer pressure and volume
alterations.
The
current literature suggests that the deconditioning effects of bedrest
are independent of the patient’s clinical condition but rather
are associated with the absence of regular exposure to “orthostatic
stress” (produced by assumption of an upright posture). The
absence of habitual exposure to the upright posture occurs naturally
with prolonged periods of bedrest and deprives the cardiovascular
system of stimulation needed to maintain adequate blood pressure
regulation. As a result, these patients commonly develop orthostatic
hypotension or frank syncope during their initial ambulation attempt
in the in-patient setting. Studies have found that intermittent
but regular exposure to sitting or standing during convalescence
can counteract these deconditioning effects (672).
The 1996 ACC/AHA Guidelines for the Management of Patients with
Acute MI cited evidence of the continued practice of “coronary
precautions” that were advocated in the 1960s (2),
and specific directions were given about what were or were no longer
considered to be coronary precautions. It is assumed that current
practice has advanced sufficiently such that patients with STEMI
are no longer kept on bedrest or fed by nurses. Avoidance of the
Valsalva maneuver remains an important consideration (673,674),
especially in younger patients (e.g., under the age of 45 years)
(673-676).
Otherwise, current practice routinely entails a short period of
bedrest (except for patients who have recurrent ischemic discomfort,
symptoms of heart failure, or serious rhythm disturbances). Low
level activities such as toileting, assisted bathing, and light
ambulation can prevent physiological deconditioning (673-676).
Sample admitting orders reflecting the standard of care are presented
in Table 23 (3).
7.2.2.
Diet
Class I
1. Patients with STEMI should be prescribed the NCEP Adult
Treatment Panel III (ATP III) Therapeutic Lifestyle Changes (TLC)
diet, which focuses on reduced intake of fats and cholesterol, less
than 7% of total calories as saturated fats, less than 200 mg of
cholesterol per day, increased consumption of omega-3 fatty acids,
and appropriate caloric intake for energy needs. (Level of Evidence:
C)
2. Diabetic patients with STEMI should have an appropriate food
group balance and caloric intake. (Level of Evidence: B)
3. Sodium intake should be restricted in STEMI patients with hypertension
or heart failure. (Level of Evidence: B)
The NCEP ATP III has recommended that a complete blood lipid profile
be taken in all patients with established CHD (50).
In the STEMI patient, this should be done at the time of admission
or within 24 hours of the onset of symptoms, because low-density
lipoprotein cholesterol (LDL-C) levels begin to decrease soon after
an event and are significantly reduced by 48 hours and remain so
for many weeks. Thus, LDL-C measurements several days after STEMI
may not be representative of the patient’s average LDL-C.
In the context of possible early cardiac catheterization, it would
be helpful for patients to have been on a clear liquid diet that
extended to a period of “nothing by mouth” (NPO) before
the procedure. Patients with STEMI should receive a reduced saturated
fat and cholesterol diet per the ATP III TLC approach (677).
(See Section 7.12.2.) Diabetes experts no
longer recommend a single meal plan for all people with diabetes.
Instead, they recommend meal plans that are flexible and take into
account a person’s lifestyle and particular health needs,
ideally with consultation from a registered dietitian to design
a meal plan. Sodium intake should be restricted in patients with
STEMI with hypertension or heart failure to a maximum of 2000 mg/d
(Table 23) (3).
Blood pressure increases after caffeine intake (678),
but the increase is not clinically significant until 400 mg of caffeine
(i.e., 2 to 4 cups of coffee, depending on strength and brewing
method) is ingested (679,680).
Moderately high doses (450 mg) of caffeine did not increase ventricular
arrhythmias in a small group of patients with ischemic heart disease
(681). People who drink caffeinated
beverages regularly develop a tolerance after 1 to 4 days (682,683),
regardless of dose. Withdrawal of caffeine is associated with headache
(684,685)
and increases in heart rate (686).
The available evidence suggests that patients with STEMI who are
routine caffeine drinkers be allowed to consume up to 4 to 5 cups
of caffeinated coffee a day while in the CCU or progressive care
unit, under the surveillance of nursing staff (680,687).
As a practical matter in the acute care setting, 1 to 2 cups of
coffee, enough to avert caffeine withdrawal, seems appropriate.
7.2.3. Patient Education in the Hospital
Setting
Class I
1. Patient counseling to maximize adherence to evidence-based post-STEMI
treatments (e.g., compliance with taking medication, exercise prescription,
and smoking
cessation) should begin during the early phase of hospitalization,
occur intensively at discharge, and continue at follow-up visits
with providers and through cardiac rehabilitation programs and community
support groups, as appropriate. (Level of Evidence: C)
2. Critical pathways and protocols and other quality improvement
tools (e.g., the ACC’s “Guidelines Applied in Practice”
and the AHA’s “Get with the Guidelines”) should
be used to improve the application of evidence-based treatments
by patients with STEMI, caregivers, and institutions. (Level
of Evidence: C)
Patient education should be viewed as a continuous process that
should be part of every patient encounter (i.e., on hospital arrival,
at inpatient admission, at discharge, and at followup visits). On
admission to the coronary care unit, patients should receive an
orientation to their surroundings (e.g., location of the call light),
an explanation of the equipment used for their care (e.g., electrodes
and cardiac monitor, IV line/ heparin lock, central line, nasal
cannula, and pulse oximetry), nursing care routines and their “round-the-clock”
nature, level of activity permitted, an explanation of the pain
assessment scale that will be used, and the importance of reporting
any symptoms.
In general, effective education involves the use of a combination
of good communication skills, patient assessment of prior knowledge
and readiness to learn, and effective teaching strategies. One-to-one
teaching is the most common patient education method in the inpatient
setting and is preferred by patients as well (688).
Ideally, family members should be present to hear what patients
are being told so they can reinforce the information later (689).
For more complex topics, the most effective educational intervention
involves being responsive to the patient’s attempts to communicate
(e.g., not changing the topic abruptly or engaging in tasks unrelated
to the conversation); using good eye contact; not denying the patient’s
feelings (e.g., “You should not worry about that!”);
and being aware of one’s own nonverbal cues that encourage
or discourage communication (e.g., failure to sit down), as well
as those of the patient’s.
Inpatient education has been reported to stimulate some lifestyle
change after discharge, most frequently in the areas of activity
and smoking cessation (690). However,
post-MI knowledge alone does not ensure behavioral change (691,692).
Providers should be aware that many patients who have had a STEMI
may be in the early stages of behavioral change, such as “precontemplation,”
where they do not yet see a need to change behavior. Others may
be in the “contemplation” stage, where, for example,
the experience of STEMI may cause them to acknowledge that they
need and want to make a change, but that thought is not yet translated
into action (691-694).
With 1-to-1 teaching in the hospital, the provider should strike
a balance between not using any teaching aids when educating the
patient and simply handing out written information or other media
without discussion. One-to-one teaching is effectively enhanced
and reinforced with the use of appropriate media (688,695).
Challenges to patient education in the inpatient setting are shorter
lengths of hospital stay (696);
older, sicker patients with more psychosocial issues; cultural and
literacy barriers (697); and patient
anxiety (698). Inpatient education
has been shown to reduce anxiety (699,700),
improve knowledge (688), and decrease
length of hospital stay (700,701).
In standardizing care for these patients, the use of guidelinebased
tools has been reported to facilitate improvement in the quality
of care for patients with STEMI among a variety of institutions,
patients, and caregivers (5). Programs
such as the AHA’s “Get With the Guidelines” (see
the “Get With the Guidelines’ Hospital Tool Kit”
at: http://www.americanheart.org/downloadable/heart/1107_HospTool.pdf)
and the ACC’s “Guidelines Applied in Practice”
(see sample forms at: http://www.acc.org/gap/mi/ami_permissionprocess.htm)
offer tools such as educational plans for patients explaining what
they can expect over the course of their hospitalization (e.g.,
procedures and the treatment plan), care paths, standing orders
for providers, discharge protocols that incorporate evidence-based
recommendations (for providers and patients), and a data-based patient
management tool (702).
Support groups provided by some hospitals and cardiac rehabilitation
programs may help patients adjust to their diagnosis and newly prescribed
lifestyle and medication regimens. For example, Mended Hearts is
a national nonprofit organization affiliated with the AHA that offers
visiting programs, support group eetings, and educational forums
through partnerships with hospitals and rehabilitation clinics.
The organization is particularly interested in helping patients
deal with the emotional recovery from heart disease through facilitating
a positive patient-care experience for heart disease patients, their
families, caregivers, and others impacted by heart disease (703).
Table 24 shows suggested topics
for educating the patient with STEMI.
7.2.4. Analgesia/Anxiolytics
Class IIa
1. It is reasonable to use anxiolytic medications in STEMI patients
to alleviate short-term anxiety or altered behavior related to hospitalization
for STEMI. (Level of Evidence: C)
2. It is reasonable to routinely assess the patient's anxiety level
and manage it with behavioral interventions and referral for counseling.
(Level of Evidence: C)
It is useful to monitor patients for increased anxiety or altered
behavior of the patient in the CCU. Anxiolytics can play an important
role in patient management in this setting. Treatment with benzodiazepines
should be limited to the minimal dose for a limited period of time
(261).
Hospitalized smokers may experience symptoms of nicotine withdrawal,
including anxiety, insomnia, depression, difficulty concentrating,
irritability, anger, restlessness, and slowed heart rate (704).
Patients experiencing nicotine withdrawal can benefit from anxiolytics.
Use of bupropion and nicotine replacement therapy in the acute setting
should also be considered as options, depending on the severity
of the patient's withdrawal syndrome. Agitation and delirium are
not uncommon in the CCU, particularly in patients with complicated
STEMI and protracted stays in the intensive care setting. In addition,
a number of medications used in the CCU, such as lidocaine, mexiletine,
procainamide, atropine, cimetidine, and meperidine, can induce delirium.
Intravenous haloperidol is a rapidly acting neuroleptic that can
be given safely and effectively to cardiac patients with agitation.
It rarely produces hypotension or need for assisted ventilation.
If patients exhibit altered sensorium and have received fibrinolytics,
consideration should be given to ordering a computed axial tomography/magnetic
resonance imaging scan to rule out ICH before sedating the patient.
Anxiety and depression are prevalent in patients hospitalized for
STEMI because patients are confronted with a diagnosis that is major,
both psychologically and physically (705,706).
In addition, the experience of a cardiac event is a significant
source of stress for family members trying to adjust to the initial
diagnosis and confront the uncertainties associated with hospitalization
and the initial recovery phase. Anxiety has been demonstrated to
predict inhospital recurrent ischemia and arrhythmias (707)
and cardiac events during the first year after an MI (708).
Physicians’ and nurses’ subjective judgments of patient
anxiety are not accurate when compared with measurements of anxiety
on validated scales (709,710).
The provision of information, discussed later in this guideline,
and liberal visiting policies can also help patients with STEMI
feel more in control (711,712).
In addition, psychological support and counseling during hospitalization
can decrease anxiety and depression immediately and for up to 6
months after STEMI (713,714).
At least 1 randomized controlled trial demonstrated that in-hospital
anxiety and depression could be reduced by a structured nursing
support intervention (714).
Liberalized visiting rules for patients in critical care can be
helpful; several studies have demonstrated no harmful physiological
effects attributable to unrestricted visiting policies (711,
712). Patients whose anxiety is
very severe or persistent in spite of medications should be referred
for consultation for formal anxiety assessment and treatment. Consultation
could be obtained from a nurse specialist, psychiatric social worker,
or a psychiatrist.
7.3. Risk Stratification During Early
Hospital Course
Several groups have proposed risk stratification scores for patients
with suspected STEMI based on their admission characteristics (241,242,394).
Risk stratification is a continuous process and requires the updating
of initial assessments with data obtained during the hospital stay.
Indicators of failed reperfusion (e.g., recurrence of chest pain,
persistence of ECG findings indicating infarction) identify a patient
who should undergo coronary angiography. Similarly, findings consistent
with mechanical complications (e.g., sudden onset of heart failure,
presence of a new murmur) herald increased risk and suggest the
need for rapid intervention. For patients who did not undergo primary
reperfusion, changes in clinical status (e.g., development of shock)
may herald a worsening clinical status and are an indication for
coronary angiography.
Patients
with a low risk of complications may be candidates for early discharge.
The lowest-risk patients are those who did not have STEMI, despite
the initial suspicions. Clinicians should strive to identify such
patients within 8 to 12 hours of onset of symptoms. Serial sampling
of serum cardiac biomarkers and use of 12-lead ECGs and their interpretation
in the context of the number of hours that have elapsed since onset
of the patient's symptoms can determine the presence of STEMI better
than adherence to a rigid protocol that requires that a specified
number of samples be drawn in the hospital. Among those with STEMI
treated with reperfusion, it
has been suggested that an uncomplicated course after 72 hours of
hospitalization identifies a group with a low enough risk for discharge
(715). Newby and colleagues calculated
that extending the hospital stay of these patients by another day
would cost $105 629 per year of life saved (715).
Concerns have been raised that shortening the length of stay to
72 hours may adversely affect patient education regarding STEMI
and the identification of the optimum dose of critical medications
such as beta-blockers and ACE inhibitors (696).
Work on transitional care has shown the effectiveness of an advanced
practice nurse intervention in helping patients, many with ischemic
heart disease, during the transition from hospital to home and in
reducing costs in the process (716).
7.4. Medication Assessment
7.4.1. Beta-Blockers
Class I
1. Patients receiving beta-blockers within the first 24 hours of
STEMI without adverse effects should continue to receive them during
the early convalescent phase of STEMI. (Level of Evidence: A)
2. Patients without contraindications to beta-blockers who did not
receive them within the first 24 hours after STEMI should have them
started in the early convalescent phase. (Level of Evidence:
A)
3. Patients with early contraindications within the first 24 hours
of STEMI should be re-evaluated for candidacy for beta-blocker therapy.
(Level of Evidence: C)
There
is overwhelming evidence for the benefits of early beta-blockade
in patients with STEMI and without contraindications to their use
(see Section 6.3.1.5).
Benefits have been demonstrated for patients with and without concomitant
fibrinolytic therapy, both early and late after STEMI. Metaanalysis
of trials from the prefibrinolytic era involving more than 24 000
patients receiving beta-blockers in the convalescent phase showed
a 14% RRR in mortality through 7 days and a 23% RRR in long-term
mortality (717). These data are
summarized in Figure 27 (718).
Beta-blockers should be initiated early in the course of STEMI and
continued unless adverse effects have been observed. In appropriately
selected patients, these benefits occur at a risk of approximately
a 3% incidence of provocation of CHF or complete heart block and
a 2% incidence of the development of cardiogenic shock. Beta-blockers
are especially beneficial in patients in whom STEMI is complicated
by persistent or recurrent ischemia, evidence for infarct extension,
or tachyarrhythmias.
Some clinicians do not start beta-blockers in the emergency phase
of STEMI management because of error, late presentation, concern
about relative or absolute contraindications, or concern about the
benefits of beta-blockade in the face of other contemporary treatments.
Benefits of beta blockers initiated in the convalescent phase for
secondary prevention of ischemic events are established (717).
The Beta-blocker Heart Attack Trial (BHAT) (719)
and the more contemporary CAPRICORN trial (273)
confirm the substantial benefit of beta-blockers in addition to
ACE inhibitor therapy in patients with transient or sustained postinfarction
LV dysfunction. A reasonable general rule is to initiate beta-blockade
after 24 to 48 hours of freedom from a relative contraindication,
such as bradycardia, mild-to-moderate heart failure, or first-degree
heart block.
7.4.2. Nitroglycerin
Class I
1. Intravenous nitroglycerin is indicated in the first 48 hours
after STEMI for treatment of persistent ischemia, CHF, or hypertension.
The decision to administer intravenous nitroglycerin and the dose
used should take into account that it should not preclude therapy
with other proven mortality-reducing interventions such as beta-blockers
or ACE inhibitors.
(Level of Evidence: B)
2. Intravenous, oral, or topical nitrates are useful beyond the
first 48 hours after STEMI for treatment of recurrent angina or
persistent CHF if their use does not preclude therapy with beta-blockers
or ACE inhibitors. (Level of Evidence: B)
Class IIb
The continued use of nitrate therapy beyond the first 24 to 48 hours
in the absence of continued or recurrent angina or CHF may be helpful,
although the benefit is likely to be small and is not well established
in contemporary practice. (Level of Evidence: B)
Class III
Nitrates should not be administered to patients with systolic blood
pressure less than 90 mm Hg or greater than or equal to 30 mm Hg
below baseline, severe bradycardia (less than 50 bpm), tachycardia
(more than 100 bpm), or RV infarction. (Level of Evidence: C)
The
use of nitrates in the patient with STEMI on presentation and in
the early phase of infarction is reviewed in Section
6.3.1.2. Clinical trials have suggested only a modest benefit
of nitroglycerin used acutely in STEMI and continued subsequently
(152,586).
Nitrates are most clearly indicated for persistent or recurrent
ischemia and in patients with CHF. Because protocols in large clinical
trials included acute followed by sustained therapy, there is little
evidence to establish the duration of nitrate therapy after STEMI.
Common clinical practice is to continue nitrate therapy for 24 to
48 hours. In view of their marginal treatment benefits, nitrates
should not be used if hypotension limits the administration of beta-blockers
or ACE inhibitors, which have more powerful benefits for both early
use and secondary prevention after STEMI.
Nitrate
tolerance develops with prolonged continuous exposure to nitrates,
presumably through the mechanism of depletion of sulfhydryl groups
in the vessel wall. If sustained therapy with nitrates is planned,
intravenous nitrate therapy is usually changed to oral or topical
preparations with a nitrate-free interval.
7.4.3. Inhibition of the Renin-Angiotensin-Aldosterone
System
Class I
1. An ACE inhibitor should be administered orally during
convalescence from STEMI in patients who tolerate this class of
medication, and it should be continued over the long term. (Level
of Evidence: A)
2. An ARB should be administered to STEMI patients who are intolerant
of ACE inhibitors and have either clinical or radiological signs
of heart failure or LVEF less than 0.40. Valsartan and candesartan
have demonstrated efficacy for this recommendation. (Level of
Evidence: B)
3. Long-term aldosterone blockade should be prescribed for post-STEMI
patients without significant renal dysfunction (creatinine should
be less than or equal to 2.5 mg/dL in men and less than or equal
to 2.0 mg/dL in women) or hyperkalemia (potassium should be less
than or equal to 5.0 mEq/L) who are already receiving therapeutic
doses of an ACE inhibitor, have an LVEF of less than or equal to
0.40, and have either symptomatic heart failure or diabetes. (Level
of Evidence: A)
Class IIa
In STEMI patients who tolerate ACE inhibitors, an ARB can be useful
as an alternative provided there are either clinical or radiological
signs of heart failure or LVEF is less than 0.40. Valsartan and
candesartan have established efficacy for this recommendation. (Level
of Evidence: B)
The use of ACE inhibitors in the initial management of the patient
with STEMI is reviewed in Section
6.3.1.6.9.1. The proportional benefit of ACE inhibitor therapy
is largest in higher-risk subgroups, including those with previous
sevinfarction,
heart failure, depressed LVEF, and tachycardia (585,589,720).
Survival benefit for patients more than 75 years old and for a low-risk
subgroup without the features noted above is equivocal (589,720).
The duration of ACE inhibitor therapy after STEMI requires detailed
analysis of trial results. In general, the trials that administered
ACE inhibitors to an unselected population of patients early after
MI had a short follow-up of 5 to 7 weeks. In contrast, trials that
selected patients with post-MI LV dysfunction or clinical heart
failure followed patients up to 5 years. Thus, when there is no
evidence of symptomatic or asymptomatic LV dysfunction by 4 to 6
weeks, the indications for long term ACE inhibitor use should be
re-evaluated. The Heart Outcomes Prevention Evaluation (HOPE) trial
enrolled patients whose entry characteristics were age 55 years
or older, evidence of vascular disease, or diabetes plus 1 other
cardiovascular risk factor (721).
In the HOPE population, the use of ramipril at doses up to 10 mg
daily demonstrated a significant reduction in the primary outcome,
a composite of MI, stroke, or death of cardiovascular causes (3.8%
absolute risk reduction; RRR 0.78, 95% CI, 0.70 to 0.86; p less
than 0.001).
Aldosterone blockade is another means of inhibiting the renin-angiotensin-aldosterone
system that has been applied to patients in the post-STEMI setting.
Again, additional information can be inferred from heart failure
studies that enrolled a large proportion of patients with a history
of MI. The RALES study (Randomized Aldactone Evaluation Study) randomized
patients with New York Heart Association class III to IV heart failure
to either spironolactone (initial dose 25 mg daily with the option
to increase to 50 mg daily) or placebo (722).
Ischemic heart disease was the cause of heart failure in 55% of
patients, and 95% were treated concurrently with an ACE inhibitor.
Over 24 months of follow-up, spironolactone treatment was associated
with an 11% ARD (24% RRR) in all cause mortality. The EPHESUS study
(Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy
and Survival Study) randomized 6632 post-MI patients with an ejection
fraction of 0.40 or less and heart failure or diabetes to receive
the aldosterone blocker eplerenone (target dose 50 mg daily) or
placebo in conjunction with routine indicated cardiac medications.
There was a significant reduction in overall mortality, cardiovascular
mortality, and cardiac hospitalizations (723).
The benefit was seen in patients managed with optimal therapy, including
reperfusion, aspirin, ACE inhibitors, beta-blockers, and statins.
Thus, the RALES and EPHESUS studies support the long-term use of
an aldosterone blocker in patients with STEMI with heart failure
and/or an ejection fraction of 0.40 or less, provided the serum
creatinine is less than or equal to 2.5 mg/dL in men and less than
or equal to 2.0 mg/dL in women and serum potassium concentration
is less than or equal to 5.0 mEq/L. The risk of hyperkalemia was
greatest in patients with creatinine clearance estimated to be less
than 50 mL/min. Close monitoring of potassium levels is indicated
for those patients, and the risk-to-benefit ratio should be weighed
for those with moderate to severe reductions despite a serum creatinine
of less than 2.5 mg/dL.
The
use of ARBs after STEMI has not been explored as thoroughly as ACE
inhibitors in patients with STEMI. The OPTIMAAL trial (Optimal Trial
in Myocardial Infarction with Angiotensin II Antagonist Losartan)
found no significant differences between losartan (target dose 50
mg once daily) and\ captopril (target dose 50 mg 3 times daily)
in allcause mortality (724), but
there was a trend toward better outcome with captopril. The VALIANT
trial (Valsartan in Acute Myocardial Infarction Trial) compared
the effects of captopril (target dose 50 mg 3 times daily), valsartan
(target dose 160 mg twice daily), and their combination (captopril
target dose 50 mg 3 times daily; valsartan target dose 80 mg twice
daily) on mortality in post-MI patients with LV dysfunction (725).
During a median follow-up of 24.7 months, death occurred in 19.9%
of the valsartan group, 19.5% of the captopril group, and 19.3%
of the combined-treatment group. The hazard ratio for death in the
valsartan group compared with the captopril group was 1.00 (97.5%
CI, 0.90 to 1.11; p equals 0.98), and the hazard ratio for death
in the valsartan and captopril combined versus the captopril group
was 0.98 (97.5% CI, 0.8 to 1.09; p equals 0.73) (725).
The combination captopril and valsartan group had the most drugrelated
adverse events. In the monotherapy groups, hypotension and renal
dysfunction were more common in the valsartan group, and cough,
rash, and taste disturbance were more common in the captopril group.
Given
the extensive randomized trial and routine clinical experience with
ACE inhibitors, they remain the logical first agent for inhibition
of the renin-angiotensin-aldosterone system in patients convalescing
from STEMI (726). Valsartan monotherapy
(target dose 160 mg twice daily) should be administered to patients
with STEMI who are intolerant of ACE inhibitors and who have evidence
of LV dysfunction. Valsartan monotherapy can be a useful alternative
to ACE inhibitors; the decision in individual patients may be influenced
by physician and patient preference, cost, and anticipated side-effect
profile.
7.4.4. Antiplatelets
Class I
1. Aspirin 162 to 325 mg should be given on day 1 of STEMI and in
the absence of contraindications should be continued indefinitely
on a daily basis thereafter at a dose of 75 to 162 mg. (Level
of Evidence: A)
2. A thienopyridine (preferably clopidogrel) should be administered
to patients who are unable to take aspirin because of hypersensitivity
or major gastrointestinal intolerance. (Level of Evidence: C)
3. For patients taking clopidogrel for whom CABG is planned, the
drug should be withheld for at least 5 days if possible, and preferably
for 7, unless the urgency for revascularization outweighs the risks
of bleeding. (Level of Evidence: B)
4. For patients who have undergone diagnostic cardiac catheterization
and for whom PCI is planned, clopidogrel should be started and continued
for at least 1 month after bare metal stent implantation and for
several
months after drug-eluting stent implantation (3 months for sirolimus,
6 months for paclitaxel) and for up to 12 months in patients who
are not at high risk
for bleeding. (Level of Evidence: B)
Aspirin. The use of aspirin in patients with STEMI on initial
presentation and in early management is discussed above (Sections
6.3.1.4 and 6.3.1.6.8.2.1).
Aspirin should be given to the patient with suspected STEMI as early
as possible and continued indefinitely, regardless of the strategy
for reperfusion and regardless of whether additional antiplatelet
agents are administered. True aspirin allergy is the only exception
to this recommendation. Maintenance aspirin doses for secondary
prevention of cardiovascular events in large trials have varied
from 75 to 325 mg per day, but no trial has directly compared the
efficacy of different doses after STEMI. An overview of trials with
different doses of aspirin in the longterm treatment of patients
with coronary disease suggests similar efficacy for daily doses
ranging from 75 to 325 mg (727).
An analysis from the CURE trial (Clopidogrel in Unstable angina
to prevent Recurrent Events) suggests a dose-dependent increase
in bleeding in patients receiving aspirin plus placebo: The major
bleeding event rate was 2.0% in patients taking less than 100 mg
of aspirin, 2.3% with 100 to 200 mg, and 4.0% with greater than
200 mg per day (728,729).
Therefore, lower aspirin doses of 75 to 162 mg per day are preferred
for long-term treatment.
The side effects of aspirin are mainly gastrointestinal and dose
related (730). Gastric side effects
may also be reduced by administration of diluted solutions of aspirin
(731), treatment with H2 antagonists
(732), antacids (731,733),
or use of enteric-coated or buffered aspirin (734,735).
Aspirin should be avoided in those with a known hypersensitivity
and used cautiously in those with blood dyscrasias or severe hepatic
disease (see additional discussion in Sections
7.12.5 and 7.12.11). If the patient has
a history of bleeding peptic ulcers, the use of rectal aspirin suppositories
may be safer because it eliminates the local effect of aspirin on
the gastric mucosa. However, antiplatelet effects may still pose
a risk. Another potentially deleterious effect of aspirin is risk
of bleeding from surgical sites. Patients who received aspirin in
the Veterans Administration Cooperative Study (736)
were noted to have significantly increased postoperative chest drainage
and reoperation for bleeding (6.5% for aspirin groups compared with
1.7% for nonaspirin groups; p less than 0.01). Others have noted
that preoperative aspirin use has been associated with increased
postoperative chest drainage but not an increased rate of reoperation
for bleeding (737,738).
In another Veterans Administration Cooperative Study (739),
starting aspirin 6 hours after surgery conferred the benefits of
improved saphenous vein bypass graft patency without the increased
postoperative bleeding seen with preoperative administration of
aspirin. Aspirin (81 to 365 mg) should be administered as soon as
possible (within 24 hours) after CABG unless contraindicated (see
Section 7.10.7).
Use
of the thienopyridines ticlopidine and clopidogrel in the early
management of STEMI is discussed above (Section
6.3.1.6.8.2.2). Clopidogrel 75 mg daily is generally preferred
to ticlopidine 250 mg twice daily because of fewer side effects
and once-daily dosing (740,741).
In
the Clopidogrel vs. Aspirin in Patients at Risk of Ischemic Events
(CAPRIE) trial of patients with UA/NSTEMI, there was a statistically
significant risk reduction in vascular death, MI, or stroke in favor
of clopidogrel (0.51% ARD; RRR 8.7%) (742).
Clopidogrel has also demonstrated efficacy in addition to aspirin
versus aspirin alone in patients with acute coronary syndrome (728).
Therefore, a thienopyridine (preferably clopidogrel) should be substituted
for aspirin in patients with STEMI for whom aspirin is contraindicated
because of hypersensitivity or major gastrointestinal intolerance.
On the basis of several randomized trials of combination antiplatelet
therapy (577,741,743),
clopidogrel,in combination with low-dose aspirin (75 to 162 mg,
to minimize the risk of bleeding), is recommended for all patients
after stent implantation (432).
7.4.5.
Antithrombotics
Class I
Intravenous UFH (bolus of 60 U/kg, maximum 4000-U IV bolus; initial
infusion of 12 U/kg/h, maximum 1000 U/h) or LMWH should be used
in patients after STEMI who are at high risk for systemic emboli
(large or anterior MI, AF, previous embolus, known LV thrombus,
or cardiogenic shock). (Level of Evidence: C)
Class IIa
It is reasonable that STEMI patients not undergoing reperfusion
therapy who do not have a contraindication to anticoagulation be
treated with intravenous or subcutaneous UFH or with subcutaneous
LMWH for at least 48 hours. In patients whose clinical condition
necessitates prolonged bedrest and/or minimized activities, it is
reasonable that treatment be continued until the patient is ambulatory.
(Level of Evidence: C)
Class IIb
Prophylaxis for DVT with subcutaneous LMWH (dosed appropriately
for specific agent) or with subcutaneous UFH, 7500 to 12 500 U twice
per day until completely ambulatory, may be useful, but the effectiveness
of such a strategy is not well established in the contemporary era
of routine aspirin use and early mobilization. (Level of Evidence:
C)
In patients treated with fibrinolytic therapy, there is
little evidence of the benefit of UFH in the modern era, during
which aspirin, beta-blockers, nitrates, and ACE inhibitors are routinely
available. Nevertheless, the best available data emanate from a
series of randomized clinical trials performed before the reperfusion
era. A systematic overview of these studies demonstrated a reduction
in mortality (3.5% ARD; 23% RRR) and a reduction in risk of reinfarction
(1.5% ARD; 18% RRR) with UFH (537).
The control groups in these trials were not treated with other therapies,
particularly aspirin, that are now considered routine. Notwithstanding
this, it is primarily these randomized data from an earlier era
that support the recommendation to use UFH in patients not treated
with fibrinolytic therapy.
The occurrence of a large anterior infarction, documentation of
thrombus in the LV by echocardiography, history of a previous embolic
event, and AF have been associated with a high risk of embolic stroke.
Although no randomized trial evidence exists to demonstrate a definite
benefit specific to this group, some empirical evidence exists that
the risk of systemic emboli in the general population of MI patients
can be reduced by early initiation of UFH (744).
In the SCATI trial (Studio sulla Calciparina nell’Angina e
nella Trombosi Ventricolare nell’Infarto), patients were randomly
assigned to a 2000-IU bolus of UFH followed by 12 500 U subcutaneously
twice per day or to placebo. In the subgroup also treated with streptokinase,
aspirin was withheld. In-hospital mortality was 4.6% in the UFH
group and 8.8% in the control group, and a reduction in stroke was
observed. Therefore, UFH is recommended for these patients at high
risk for systemic arterial emboli, regardless of the fibrinolytic
agent given. A LMWH may be used in place of UFH. Initial anticoagulation
with UFH or a LMWH should be followed by warfarin in patients at
high risk for systemic emboli (see Section 7.12.11
for additional discussion).
The previous ACC/AHA guidelines on acute MI (744)
and the American College of Chest Physicians’ guidelines (746)
recommended 7500 U of subcutaneous UFH twice per day. The empirical
basis for this recommendation was the demonstration that DVT was
reduced from 12% to 4% in an overview of 3 randomized controlled
trials (747). Continued adherence
to this practice may be useful, although routine earlier mobilization
and use of aspirin may make this treatment unnecessary.
7.4.6. Oxygen
Class I
Supplemental oxygen therapy should be continued beyond the first
6 hours in STEMI patients with arterial oxygen desaturation (SaO2
less than 90%) or overt pulmonary congestion. (Level of Evidence:
C)
The use of oxygen in patients presenting with STEMI is discussed
in Section 6.3.1.1. In
view of its expense (approximately $70 per day), there is little
justification for continuing its routine use beyond 6 hours in uncomplicated
cases.
Pulse oximetry is now routine for continuous monitoring of oxygen
saturation and is helpful for providing early warning of hypoxemia.
In patients with oxygen saturation less than 90%, supplemental oxygen
by nasal prongs is usually administered, especially if the patient
is experiencing ongoing or intermittent ischemia. This therapy is
based on experimental data that suggest that normal levels of oxygen
reduce infarct size. In patients with severe heart failure, pulmonary
edema, or mechanical complications of STEMI, significant hypoxemia
may require continuous positive pressure breathing or endotracheal
intubation and mechanical ventilation.
7.5. Estimation of Infarct Size
Measurement of infarct size is an important element in the overall
care of patients with STEMI. The extent of infarction bears a direct
relationship to prognosis, assists in establishing the efficacy
of reperfusion therapy, guides both shortand long-term therapeutic
decision making, and provides a useful surrogate for the investigation
of novel experimental therapies.
There
are 5 major modalities that can be applied to sizing MI. A discussion
of each follows.
7.5.1.
ECG Techniques
Class I
All patients with STEMI should have follow-up ECGs at 24 hours and
at hospital discharge to assess the success of reperfusion and/or
the extent of infarction, defined in part by the presence or absence
of new Q waves. (Level of Evidence: B)
The extent of ST-segment deviation on the baseline ECG provides
a semiquantitative measure of the amount of jeopardized myocardium
and an estimate of the subsequent infarct size likely to ensue in
a nonreperfused population. With a QRS scoring system based on the
duration and amplitude of individual waveforms within the QRS complex,
the size of the infarction can be estimated from a point score derived
and weighted from the 12-lead ECG (748).
Each point so derived represents approximately 3% of the LV, and
the utility of this approach has been validated in postmortem studies
of patients with confirmed MI (749).
This method, however, is time consuming and is limited in patients
with concomitant LV hypertrophy or fascicular or bundle-branch block
and when major ST-segment shift distorts the appearance of the QRS
complex.
In the fibrinolytic era, simple characterization of the presence
or absence of the Q wave has also been used. In the early convalescent
period after fibrinolytic therapy, the 20% of patients in the GUSTO
angiographic study who did not develop Q waves had better global
and regional LV function and improved 2-year survival (6.3% versus
10.1% for patients with developed Q waves; p equals 0.02) (750).
7.5.2. Cardiac
Biomarker Methods
The most widely accepted method for quantifying infarction has been
the use of serial CK and the CK-MB isoenzyme. With a mathematical
formulation based on rates of degradation in specific compartments,
the rate of myocardial biomarker release, its volume of distribution,
and its clearance rate, it is possible to estimate the quantity
of myocardium infarcted (751).
Reasonable correlations have been established with anatomic estimates
derived from postmortem human studies (752).
Whereas other biomarkers of myocardial
necrosis exist, such as myoglobin and lactate dehydrogenase, the
highly sensitive cardiac troponins (I or T) have greater myocardial
tissue specificity and higher sensitivity than conventional biomarkers.
Measurement of cardiac troponin T at 72 hours provides an estimate
of infarct size in patients with STEMI who do and do not receive
reperfusion therapy (753,754).
In a consensus document of the Joint European Society of Cardiology
and the ACC, the use of cardiac troponins was supported for the
assessment of MI. The Joint Committee has emphasized that high-sensitivity
cardiac biomarkers, such as troponins, can identify patients with
small areas of myocardial necrosis weighing less than 1.0 g (755).
7.5.3. Radionuclide
Imaging
The most comprehensive assessment of STEMI with radionuclide imaging
was developed with the Technetium sestamibi SPECT approach (756).
This technique has been validated extensively and offers the opportunity
for both early and late imaging to initially assess the area of
ischemic risk as opposed to the ultimate infarct size. This approach
is well delineated in the ACC/AHA/ASNC Guidelines on Cardiac Radionuclide
Imaging (239). Radionuclide angiography
with a variety of radiolabeled isotopes can also provide an estimate
of regional and global LV function.
7.5.4. Echocardiography
Global and regional LV function provides an assessment of the functional
consequences of STEMI and ischemia. Such measures may be enhanced
by an assessment of the extent of regional systolic wall thickening.
Readers are referred Section 7.11.1.2 and
to the ACC/AHA/ASE 2003 Guideline Update for the Clinical Application
of Echocardiography (226).
7.5.5.
Magnetic Resonance Imaging
Measurement of infarct size with magnetic resonance imaging is a
promising new technique that affords enhanced spatial resolution,
thereby permitting more accurate assessment of both the transmural
and circumferential extent of infarction (757).
However, additional experience and comparison with other methods
of assessing infarct size are required before any clinical recommendations
can be provided.
7.6.
Hemodynamic Disturbances
7.6.1. Hemodynamic Assessment
Class I
1. Pulmonary artery catheter monitoring should be performed for
the following:
a. Progressive hypotension, when unresponsive to fluid administration
or when fluid administration may be contraindicated. (Level
of Evidence: C)
b. Suspected mechanical complications of STEMI, (i.e., VSR, papillary
muscle rupture, or free wall rupture with pericardial tamponade)
if an echocardiogram
has not been performed. (Level of Evidence: C)
2. Intra-arterial pressure monitoring should be performed for the
following:
a. Patients with severe hypotension (systolic arterial pressure
less than 80 mm Hg). (Level of Evidence: C)
b. Patients receiving vasopressor/inotropic agents. (Level of
Evidence: C)
c. Cardiogenic shock. (Level of Evidence: C)
Class IIa
1. Pulmonary artery catheter monitoring can be useful for the following:
a. Hypotension in a patient without pulmonary congestion who has
not responded to an initial trial of fluid administration. (Level
of Evidence: C)
b. Cardiogenic shock. (Level of Evidence: C)
c. Severe or progressive CHF or pulmonary edema that does not respond
rapidly to therapy. (Level of Evidence: C)
d. Persistent signs of hypoperfusion without hypotension or pulmonary
congestion. (Level of Evidence: C)
e. Patients receiving vasopressor/inotropic agents. (Level of
Evidence: C)
2. Intra-arterial pressure monitoring can be useful for patients
receiving intravenous sodium nitroprusside or other potent vasodilators.
(Level of Evidence: C)
Class IIb
Intra-arterial pressure monitoring might be considered in patients
receiving intravenous inotropic agents. (Level of Evidence:
C)
Class III
1. Pulmonary artery catheter monitoring is not recommended in patients
with STEMI without evidence of hemodynamic instability or respiratory
compromise. (Level of Evidence: C)
2. Intra-arterial pressure monitoring is not recommended for patients
with STEMI who have no pulmonary congestion and have adequate tissue
perfusion without use of circulatory support measures. (Level
of Evidence: C)
Measurements made via pulmonary artery catheter readings may be
helpful in the management of STEMI and concomitant hemodynamic instability,
including low cardiac output, hypotension, persistent tachycardia,
pulmonary edema, and apparent cardiogenic shock. In the patient
with hypotension and tachycardia, the pulmonary artery catheter
can assist in the differentiation of 1) inadequate intravascular
volume, with a resultant low left-sided filling pressure; 2) adequate
intravascular volume and a high left-sided filling pressure due
to extensive LV dysfunction; and 3) low leftsided filling pressure
with elevated right atrial pressure consistent with RV infarction
(758). Treatment of the former
is prompt expansion of intravascular volume (with normal saline),
whereas management of the latter often includes diuresis, inotropic
support, afterload reduction, or other supportive
measures. In those with extensive LV dysfunction, a pulmonary artery
catheter can be used to monitor therapeutic efforts to adjust the
left-sided filling pressure so as to maximize cardiac output at
the lowest possible filling pressure (758).
In some patients, these sophisticated manipulations of intracardiac
pressures and cardiac output are facilitated by information provided
by a pulmonary artery catheter.
Although
the pulmonary artery catheter is quite safe when used by experienced
operators, its use has a recognized association with adverse events,
including ventricular tachyarrhythmias (during its manipulation)
and pulmonary hemorrhage or infarction. Transient right bundle-branch
block may develop, which can lead to heart block in those with preexisting
LBBB. In addition, it causes some patient discomfort and requires
that the patient be relatively immobile. Because the pressure waveform
recorded from the catheter tip may be distorted, the clinician should
routinely examine the actual waveform rather than rely on the digital
display of pressure. Because of the risk of infection, pulmonary
artery catheters generally should not remain in the same site for
more than 4 to 5 days. The catheter should not be inserted if the
patient quickly responds to other interventions or if treatment
is expected to be futile. The catheter should be removed expeditiously
when it is no longer needed to monitor therapy.
The
diagnosis of acute mechanical complications (MR, ventricular septal
defect, myocardial rupture) usually can be diagnosed quickly and
safely in the ED by transthoracic echocardiography. However, the
ordering and performing of an echocardiogram should not delay transfer
of a hemodynamically unstable patient to the interventional cardiology
laboratory, where hemodynamic stabilization, diagnosis, and treatment
can usually best be initiated. Similarly, insertion of a pulmonary
artery catheter in the CCU should not delay transfer of the patient
to the interventional cardiology laboratory if indicated.
Insertion
of a pulmonary artery catheter to measure hemodynamics in patients
developing progressive CHF or hypotension may permit the early diagnosis
of a preshock state in which appropriate support can prevent the
onset of cardiogenic shock (759).
Before PCI is performed for cardiogenic shock, the interventional
cardiologist should insert a pulmonary artery catheter to maximize
the hemodynamic status of the patient and to diagnose unrecognized
mechanical complications. After reperfusion therapy, if shock does
not rapidly reverse, the pulmonary artery catheter may be used to
guide diuretic, inotropic, and vasopressor agents in hemodynamically
unstable patients while stunned myocardium is recovering. Unfortunately,
there are no data from randomized controlled trials testing whether
or not hemodynamic monitoring alters clinical outcome in STEMI.
It
is possible that therapeutic interventions in response to erroneous
data or inappropriate maneuvers in response to accurate data contribute
to the excess mortality rates previously associated with pulmonary
artery catheter use (760-762).
Clinicians should understand the multiple determinants of pulmonary
capillary wedge pressure (PCWP) to avoid equating filling pressure
with intravascular volume (compliance, veno-vasodilation, intrathoracic
pressure, position, volume). Dynamic changes in ventricular compliance
and the use of vasodilating medications result in rapid changes
in PCWP that do not reflect intravascular volume. For example, pulmonary
artery catheter placement after intravenous nitroglycerin administration
for pulmonary edema may reflect PCWP less than 15 mm Hg despite
marked elevation 1 hour earlier. An acute ischemic episode may raise
PCWP substantially without a concomitant change in volume.
All
CCUs should have sufficient equipment and skilled personnel to monitor
intra-arterial pressure. Such monitoring is useful in all hypotensive
patients, particularly those with cardiogenic shock. Long-term monitoring
is best accomplished through the radial artery, although the brachial
or femoral arteries may be used as alternatives. Perfusion of the
limb or hand distal to the catheter site must be examined carefully
and periodically for evidence of ischemia. Intraarterial and central
catheters can be left in place with a sterile occlusive dressing.
Before insertion, the site should be adequately prepared under sterile
conditions. Antibacterial ointments are no longer recommended. Because
of the risk of arterial thrombosis and infection, intra-arterial
catheters generally should not remain in the same arterial site
for longer than 4 to 5 days (763).
7.6.2. Hypotension
Class I
1. Rapid volume loading with an intravenous infusion should be administered
to patients without clinical evidence for volume overload. (Level
of Evidence: C)
2. Rhythm disturbances or conduction abnormalities causing hypotension
should be corrected. (Level of Evidence: C)
3. Intra-aortic balloon counterpulsation should be performed in
patients who do not respond to other interventions, unless further
support is futile because of the patient’s wishes or contraindications/unsuitability
for further invasive care. (Level of Evidence: B)
4. Vasopressor support should be administered for hypotension that
does not resolve after volume loading. (Level of Evidence: C)
5. Echocardiography should be used to evaluate mechanical complications
unless these are assessed by invasive measures. (Level of Evidence:
C)
Hypotension (systolic pressure less than 90 mm Hg or 30 points below
previous systolic arterial pressure) can result from hypovolemia,
arrhythmias, RV or LV failure, mechanical complications of MI, or
superimposed complications, such as sepsis or pulmonary embolism.
Hypovolemia is a common occurrence and may be due to inadequate
intake, diaphoresis and vomiting, overdiuresis, excessive use of
vasodilators, or inappropriate reflex peripheral vasodilation. Hemorrhage
is an increasingly common problem associated with the use of invasive
procedures, fibrinolytics, antiplatelet agents, and anticoagulant
agents. Therefore, rapid volume loading is recommended as an initial
therapeutic strategy in all patients without clinical evidence for
volume overload. Persistent hypotension should be evaluated with
an echocardiogram to define the cardiac anatomy and with a hemoglobin
measurement. Correction or control of rhythm disturbances or conduction
abnormalities often reverses hypotension. In patients with inotropic
failure, vasopressors and inotropic agents are required. Vasopressor
agents, including high-dose dopamine and norepinephrine, have alpha-vasoconstricting
properties, whereas inotropic agents such as dobutamine have beta-receptor–stimulating
properties. Norepinephrine and dopamine have both vasopressor and
inotropic properties. When blood pressure is low, dopamine is the
agent of first choice. If the patient is markedly hypotensive, intravenous
norepinephrine, which is a more potent vasoconstrictor with less
potential for tachycardia, should be administered until systolic
arterial pressure rises to at least 80 mm Hg, at which time a change
to dopamine may be attempted, initiated at 2.5 to 5 mcg/kg/min and
titrated as needed to 5 to 15 mcg/kg/min. Once arterial pressure
is brought to at least 90 mm Hg, intravenous dobutamine may be given
simultaneously in an attempt to reduce the rate of the dopamine
infusion. In addition, consideration should be given to initiating
intra-aortic balloon counterpulsation. (See Section
7.6.1.)
7.6.3. Low-Output State
Class I
1. Left ventricular function and potential presence of a mechanical
complication should be assessed by echocardiography if these have
not been evaluated by invasive measures. (Level of Evidence:
C)
2. Recommended treatments for low output states include:
a. Inotropic support. (Level of Evidence: B)
b. Intra-aortic counterpulsation. (Level of Evidence: B)
c. Mechanical reperfusion with PCI or CABG. (Level of Evidence:
B)
d. Surgical correction of mechanical complications. (Level of
Evidence: B)
Class III
Beta-blockers or calcium channel antagonists should not be administered
to patients in a low-output state due to pump failure. (Level
of Evidence: B)
A preshock state of hypoperfusion with normal blood pressure may
develop before circulatory collapse and is manifested by cold extremities,
cyanosis, oliguria, or decreased mentation (759).
Hospital mortality is high, so these patients should be aggressively
diagnosed and treated as though they had cardiogenic shock. The
initial pharmacological intervention for low cardiac output is often
a dobutamine infusion. Intra-aortic counterpulsation therapy may
be required to improve coronary artery perfusion pressure if hypotension
is present. If the blood pressure permits, afterload-reducing agents
should be added to decrease cardiac work and pulmonary
congestion. Coronary artery revascularization of ischemic myocardium
with either PCI or CABG has been shown to decrease mortality in
patients with cardiogenic shock and is strongly recommended in suitable
candidates (184,301).
Likewise, patients with VSR, papillary muscle rupture, or free wall
rupture with pericardial tamponade may benefit from emergency surgical
repair.
7.6.4. Pulmonary Congestion
Class I
1. Oxygen supplementation to arterial saturation greater than 90%
is recommended for patients with pulmonary congestion. (Level
of Evidence: C)
2. Morphine sulfate should be given to patients with pulmonary congestion.
(Level of Evidence: C)
3. ACE inhibitors, beginning with titration of a shortacting ACE
inhibitor with a low initial dose (e.g., 1 to 6.25 mg of captopril)
should be given to patients with pulmonary edema unless the systolic
blood pressure is less than 100 mm Hg or more than 30 mm Hg below
baseline. Patients with pulmonary congestion and marginal or low
blood pressure often need circulatory support with inotropic and
vasopressor agents and/or intra-aortic balloon counterpulsation
to relieve pulmonary congestion and maintain adequate perfusion.
(Level of Evidence: A)
4. Nitrates should be administered for patients with pulmonary congestion
unless the systolic blood pressure is less than 100 mm Hg or more
than 30 mm Hg below baseline. Patients with pulmonary congestion
and marginal or low blood pressure often need circulatory support
with inotropic and vasopressor agents and/or intra-aortic balloon
counterpulsation to relieve pulmonary congestion and maintain adequate
perfusion. (Level of Evidence: C)
5. A diuretic (low- to intermediate-dose furosemide, or torsemide
or bumetanide) should be administered to patients with pulmonary
congestion if there is associated volume overload. Caution is advised
for patients who have not received volume expansion. (Level
of Evidence: C)
6. Beta-blockade should be initiated before discharge for secondary
prevention. For those who remain in heart failure throughout the
hospitalization, low doses should be initiated, with gradual titration
on an outpatient basis. (Level of Evidence: B)
7. Long-term aldosterone blockade should be prescribed for post-STEMI
patients without significant renal dysfunction (creatinine should
be less than or equal to 2.5 mg/dL in men and less than or equal
to 2.0 mg/dL in women) or hyperkalemia (potassium should be less
than or equal to 5.0 mEq/L) who are already receiving therapeutic
doses of an ACE inhibitor, have an LVEF of less than or equal to
0.40, and have either symptomatic heart failure or diabetes. (Level
of Evidence: A)
8.
Echocardiography should be performed urgently to estimate LV and
RV function and to exclude a mechanical complication. (Level
of Evidence: C)
Class IIb
It may be reasonable to insert an IABP for the management of patients
with refractory pulmonary congestion. (Level of Evidence: C)
Class III
Beta-blockers or calcium channel blockers should not be administered
acutely to STEMI patients with frank cardiac failure evidenced by
pulmonary congestion or signs of a low-output state. (Level
of Evidence: B)
Left ventricular filling pressures, and hence PCWP, may rise rapidly
after acute coronary occlusion. This rise is due to acute systolic
or diastolic dysfunction that may be associated with superimposed
MR. The rise in PCWP leads to rapid redistribution of fluid from
the intravascular space into the extravascular space (lung interstitium
and alveoli). The presence of any pulmonary congestion on examination
or X-ray increases the risk of dying, and pulmonary edema is associated
with a 20% to 40% 30-day mortality rate even in the fibrinolytic
era (28,240,242,764).
Immediate management goals include adequate oxygenation and preload
reduction to relieve pulmonary congestion. Because of sympathetic
stimulation, the blood pressure should be elevated in the presence
of pulmonary edema. Patients with this appropriate response can
typically tolerate the required medications, all of which lower
blood pressure. However, iatrogenic cardiogenic shock may result
from aggressive simultaneous use of agents that cause hypotension,
initiating a cycle of hypoperfusion-ischemia. If acute pulmonary
edema is not associated with elevation of the systemic blood pressure,
impending cardiogenic shock must be suspected. If pulmonary edema
is associated with hypotension, cardiogenic shock is diagnosed.
Those patients often need circulatory support with inotropic and
vasopressor agents and/or intra-aortic balloon counterpulsation
to relieve pulmonary congestion and maintain adequate perfusion
(see Section 7.6.5 and Figure
26).
Pulmonary
edema may occur as an acute event with the onset of STEMI or reinfarction
or as the culmination of slowly progressive CHF over the first several
days after infarction. Acute pulmonary edema on presentation with
STEMI may occur in a patient with prior myocardial damage and systolic
dysfunction, with or without a prior diagnosis of CHF. Alternatively,
it may develop in patients with a first STEMI, especially those
with preceding diastolic dysfunction due to hypertension or diabetes.
Pulmonary edema days after STEMI or on presentation in patients
who have prior CHF or LV dysfunction is often associated with hypervolemia.
In contrast, patients who present with pulmonary edema without prior
LV dysfunction (and who have not received fluid administration)
usually have a normal total body sodium and fluid status. The acute
redistribution of fluid into the lungs results in relative intravascular
volume depletion in the early phase. Acute diuresis and agents that
induce hypotension can precipitate cardiogenic shock.
The cause of pulmonary edema (i.e., systolic, diastolic, or a mechanical
complication [MR or VSR]) should be assessed rapidly with a 2-dimensional
echocardiograph with color flow Doppler. Indications for right heart
catheterization are reviewed in Section 7.6.1.
On the basis of data that high-risk patients derive greater benefit
from PCI than from fibrinolytic therapy, primary PCI is preferred
when available for those who present with pulmonary edema complicating
STEMI. There are no randomized trials that assess this comparison.
However, analysis of the GUSTO-IIB trial shows similar relative
and greater absolute benefit from PCI for Killip class 2 to 3 patients
(765). The NRMI registry showed
a marked benefit of PCI compared with fibrinolysis for patients
with CHF (447). Coronary angiography
and revascularization, based on the anatomy, should be performed
when late CHF complicates the hospital course. Mechanical ventilation
may be required during angiography and PCI, especially for primary
PCI during STEMI.
Management includes the use of agents that acutely reduce preload
(i.e., nitrates, morphine sulfate, and diuretics) (Figure
28) (766), and avoidance of
acute administration of negative inotropic agents (i.e., beta-blockers
and calcium channel antagonists). Nitrates are initially administered
by sublingual tablets or spray nitroglycerin followed by intravenous
nitroglycerin. Intravenous nitroglycerin is a venodilator that acutely
reduces ventricular filling pressures. At high doses, it dilates
arterioles. It is effective at relieving pulmonary congestion and
ischemia and may be used in patients who have normal or elevated
systemic arterial pressure. A 10- to 20-mcg bolus should be administered,
followed by 10 mcg per minute, increased by 5 to 10 mcg per minute
every 5 to 10 minutes until dyspnea is relieved, the mean arterial
pressure is lowered by 10% in normotensive patients or 30% in hypertensive
patients, or until the heart rate increases by more than 10 bpm.
Loop diuretics (furosemide, torsemide, or bumetanide) should be
initiated in low to intermediate doses only in patients with associated
hypervolemia (see above). Low doses should be used unless there
is renal insufficiency, chronic diuretic use, or the presence of
chronic CHF and hypervolemia as described above. Typical furosemide
doses range from 20 to 80 mg IV (0.5 to 1.0 mg/kg).
Angiotensin
converting enzyme inhibitors are indicated for patients with pulmonary
congestion. Oral ACE inhibitors, preferably a short-acting agent
such as captopril, beginning with 1 to 6.25 mg, should be instituted
early in normotensive or hypertensive patients. The dosage may be
doubled with each subsequent dose as tolerated up to 25 to 50 mg
every 8 hours, then changed to a long acting agent. Although the
risk of hypotension and shock after vasodilator or diuretic administration
during the acute phase of MI is substantial for those without a
hypertensive response to pulmonary edema, the risk is lower in the
late phase after MI. Hence, most patients can tolerate ACE inhibitors
before discharge. For patients who presented with CHF complicating
MI, ramipril administration between days 3 and 10 significantly
reduced 30-day mortality (relative hazard 0.73; 95% CI 0.602 to
0.89; p greater than 0.002) in 2006 patients in the Acute Infarction
Ramipril Efficacy Study (767).
Given the good tolerability of ACE inhibition within 24 hours of
MI in the ISIS-4 and GISSI-3 (lisinopril) studies and the beneficial
effects on early infarct expansion, it is recommended that ACE inhibitors
be initiated early for those who have pulmonary congestion. However,
hypotension should be avoided, particularly during and immediately
after reperfusion therapy (767,768).
Routine intravenous enalapril is not recommended (769)
unless severe hypertension is present. ACE inhibitors are the only
adjunctive medication (beyond aspirin and reperfusion therapy) demonstrated
to reduce 30-day mortality when CHF complicates STEMI. Therefore,
if blood pressure limits use of vasodilators, ACE inhibitors are
preferred. Intravenous sodium nitroprusside substantially reduces
afterload and preload; however, its use has been associated with
coronary steal. Digitalis has no role in the management of pulmonary
edema complicating STEMI unless rapid AF is present. Nesiritide
(synthetic natriuretic brain peptide) is a new vasodilator agent
that promotes diuresis in patients with volume overload and decompensated
chronic CHF (class 3 to 4) (770).
It has not been investigated in STEMI and is not indicated for treatment
of pulmonary edema in these patients. Nesiritide is a potent vasodilator
and may result in hypotension, particularly in patients with STEMI,
in whom CHF usually is not due to volume overload.
An
aldosterone antagonist, eplerenone, was found to be effective for
secondary prevention of death and recurrent hospitalization in patients
3 to 14 days after MI with CHF and LVEF less than 0.40. Spironolactone
has been demonstrated to improve survival in a population of patients
with chronic CHF, which includes those with remote MI (722)
(see Section 7.12.6). In contrast to the recommendation
to avoid initiation of beta-blockade during pulmonary edema, beta-blockers
are strongly recommended before hospital discharge for secondary
prevention of cardiac events (273).
The initial dose and titration should be based on clinical heart
failure status and LVEF. For patients who remain in heart failure
during the hospitalization, a low dose should be initiated and gradually
titrated as an outpatient, per CHF guidelines (771).
This is supported by the beneficial effects of beta-blockade in
patients with LV dysfunction after STEMI (771).
See also Sections 7.4.3 (hospital phase) and
7.12.6 (secondary prevention) for recommendations
on ARBs.
7.6.5.
Cardiogenic Shock
Class I
1. Intra-aortic balloon counterpulsation is recommended for STEMI
patients when cardiogenic shock is not quickly reversed with pharmacological
therapy. The IABP is a stabilizing measure for angiography and prompt
revascularization. (Level of Evidence: B)
2. Intra-arterial monitoring is recommended for the management of
STEMI patients with cardiogenic shock. (Level of Evidence: C)
3. Early revascularization, either PCI or CABG, is recommended for
patients less than 75 years old with ST elevation or LBBB who develop
shock within 36 hours of MI and who are suitable for revascularization
that can be performed within 18 hours of shock unless further support
is futile because of the patient’s wishes or contraindications/unsuitability
for further invasive care. (Level of Evidence: A)
4. Fibrinolytic therapy should be administered to STEMI patients
with cardiogenic shock who are unsuitable for further invasive care
and do not have contraindications to fibrinolysis. (Level of
Evidence: B)
5. Echocardiography should be used to evaluate mechanical complications
unless these are assessed by invasive measures. (Level of Evidence:
C)
Class IIa
1. Pulmonary artery catheter monitoring can be useful for the management
of STEMI patients with cardiogenic shock. (Level of Evidence:
C)
2. Early revascularization, either PCI or CABG, is reasonable for
selected patients 75 years or older with ST elevation or LBBB who
develop shock within 36 hours of MI and who are suitable for revascularization
that can be performed within 18 hours of shock. Patients with good
prior functional status who agree to invasive care may be selected
for such an invasive strategy. (Level of Evidence: B)
Cardiogenic shock in patients with STEMI is most commonly (75% of
cases) caused by extensive LV dysfunction, but important other causes
include mechanical complications (acute severe MR, VSR, and subacute
free-wall rupture with tamponade). Important conditions that may
mimic cardiogenic
shock include aortic dissection and hemorrhagic shock. Echocardiography
with color flow Doppler is extremely useful to assess the cause
of shock. (See Section 7.6.1 for discussion
on hemodynamic assessment.)
Nonrandomized
studies have suggested that mechanical reperfusion of occluded coronary
arteries by PCI or CABG may improve survival in patients with MI
and cardiogenic shock. In large clinical trials, such patients have
an in-hospital survival rate that ranges from 20% to 50% when treated
with intravenous fibrinolytic therapy (482,483,772,773).
In other case series, mechanical reperfusion with PCI has been reported
to result in hospital survival rates as high as 70%, but selection
bias influenced these findings. However, a multicenter, prospective,
randomized study confirmed this general approach (184).
The SHOCK trial tested the hypothesis that emergency revascularization
for cardiogenic shock due to an ST-elevation/Q-wave or new LBBB
MI would result in reduction in all cause 30-day mortality compared
with initial medical stabilization and delayed revascularization
as clinically determined. In the SHOCK trial, cardiogenic shock
was defined as clinical evidence of systemic hypoperfusion with
systolic blood pressure less than 90 mm Hg for at least 30 minutes
(or the need for supportive measures to maintain systolic blood
pressure greater than 90 mm Hg), cardiac index of no more than 2.2
L/min/m2 and PCWP of at least 15 mmHg.
In the SHOCK trial, 152 patients were randomly assigned to the emergency
revascularization strategy, and 150 patients were assigned to a
strategy of initial medical stabilization. The 30-day mortality
rate for emergency revascularization patients was 46.7% versus 56.0%
for initial medical stabilization patients (95% CI minus 20.5 to
plus 1.9%, p equals 0.11). However, the mortality rate at 6 and
12 months (secondary end points) was significantly lower in the
emergency revascularization group (53.3% versus 66.4%, p less than
0.03, 12 months) (184,494).
The prespecified subgroup analysis of patients less than 75 years
old showed a 15.4% absolute reduction in the primary end point at
30 days (initial medical stabilization group 56.8% versus emergency
revascularization group 41.4%, p less than 0.01), whereas no treatment
benefit was apparent for the 56 patients greater than 75 years old.
Intra-aortic balloon pump support was used in 86% of both groups;
63% of the initial medical stabilization group received thrombolytic
agents, and 25% underwent delayed revascularization (Figure
29) (184). The (S)MASH study
[(Swiss) Multicenter Trial of Angioplasty for Shock] randomly assigned
55 refractory shock patients to either PCI or conventional care.
The mortality rate in the PCI group was 9 absolute percentage points
lower at 30 days (69% versus 78%) than in the conventional therapy
group but did not reach statistical significance (495).
The group difference was similar to that observed at 30 days in
the SHOCK trial (494).
Given
the large overall treatment benefit of 13 lives saved per 100 patients
treated, emergency revascularization is recommended for those less
than 75 years who are suitable for revascularization. Patients with
life-shortening illnesses, no vascular access, previously defined
coronary anatomy that was unsuitable for revascularization, anoxic
brain damage, and prior cardiomyopathy were excluded from the trial.
For those enrolled, the treatment benefit was similar for all other
subgroups examined: diabetics, women, prior MI or hypertension,
and early or late developing shock. The elderly pose a special problem.
There were only 56 patients 75 years of age or older in the SHOCK
trial, and firm conclusions cannot be drawn. The mortality rate
for the elderly patients assigned to initial medical stabilization
was similar to younger patients assigned to initial medical stabilization
and was therefore unexpectedly low (53.1%). Imbalances in baseline
characteristics of the 56 elderly patients assigned to the emergency
revascularization versus initial medical stabilization groups may
also have played a role in the apparent lack of treatment effect
(301). Those elderly patients (n
equals 277) who were clinically selected for early revascularization
(17% of the cohort) in the larger, nonrandomized SHOCK registry
had a marked survival benefit compared with those with late or no
revascularization, even after covariate adjustment and exclusion
of early deaths (496). Two other
large registries reported a substantial survival benefit for the
elderly who were clinically selected on the basis of physician judgment.
In these 2 registries, 16% to 33% of the elderly were selected for
an invasive strategy (497,498).
Although not reported, selection is typically based on prior functional
status, comorbidity, suitability for revascularization, and patient
and family preferences. An analysis of Medicare patients admitted
to hospitals with or without revascularization capability reported
no significant reduction in mortality by institution type for patients
who presented in shock (0.6%) (774).
They did not examine the much larger cohort (approximately 7%) who
develop shock. The elderly require individualized judgments, and
it is reasonable to consider those with a good functional status
and who agree to an aggressive strategy for early revascularization.
Interventions
should be performed as soon as possible. However, the time window
for early revascularization, as defined in the SHOCK trial, extends
to shock that develops up to 36 hours after MI and revascularization
within 18 hours of shock. Triple-vessel disease (60%) and left main
disease (20%) are often present when shock complicates STEMI. Coronary
artery bypass graft surgery is the preferred mode of revascularization
for many of these patients on the basis of unsuitability for PCI
and to achieve complete revascularization, unload the heart, and
administer cardioprotective agents (775,776).
The SHOCK trial recommended emergency CABG within 6 hours of randomization
for those with severe 3-vessel or left main coronary artery disease.
Among the
group of patients who underwent emergency early revascularization,
60% received PCI, and 40% had CABG; the 30-day mortality rate was
45% and 42%, respectively. Thirtyday outcome was similar despite
more severe coronary artery disease and twice the frequency of diabetes
in those who underwent CABG. This is in contrast to the 69% in-hospital
mortality rate reported for those with 3-vessel disease who underwent
PCI for shock (777). Perhaps distal
embolization in the non–infarct-related artery is not tolerated
by patients in shock. For moderate 3-vessel disease, the SHOCK trial
recommended proceeding with PCI of the infarct-related artery, followed
by delayed CABG for those who stabilized (Figure
26) (494,502).
It is recommended that patients who arrive at the hospital in cardiogenic
shock (15% of cases) or who develop cardiogenic shock after arrival
at the hospital (85%) be transferred to a regional tertiary care
center with revascularization facilities and experience with these
patients. (The SHOCK trial included both transferred [55%] and directly
admitted patients and demonstrated the same relative treatment benefit).
If skilled personnel are available, IABP placement before transport
will help stabilize the patient. If the patient presents in shock
within 3 to 6 hours of MI onset and delays in transport and intervention
are anticipated, fibrinolytic therapy and IABP may be initiated.
Nonrandomized studies suggest that this combination is beneficial
(778), and a small randomized trial
observed a trend toward benefit for those in classic shock, with
acceptable complication rates. Fibrinolytic therapy should be administered
to those patients who are not candidates for early revascularization
and who do not have a contraindication to fibrinolysis.
When shock has resolved, ACE inhibitors and beta-blockers, initiated
in low doses with progressive increases as recommended in the ACC/AHA
Guidelines for the Evaluation and Management of Heart Failure, should
be administered before discharge (771).
(See Section 7.6.7.6 for discussion of mechanical
support for the failing heart.)
7.6.6.
Right Ventricular Infarction
Class I
1. Patients with inferior STEMI and hemodynamic compromise should
be assessed with a right precordial V4R lead to detect ST-segment
elevation and an echocardiogram to screen for RV infarction. (See
the ACC/AHA/ASE 2003 Guideline Update for the Clinical Application
of Echocardiography (226)).
(Level of Evidence: B)
2. The following principles apply to therapy for patients with STEMI
and RV infarction and ischemic dysfunction:
a. Early reperfusion should be achieved if possible. (Level
of Evidence: C)
b. Atrioventricular synchrony should be achieved, and bradycardia
should be corrected. (Level of Evidence: C)
c. Right ventricular preload should be optimized, which usually
requires initial volume challenge in patients with hemodynamic instability
provided the jugular venous pressure is normal or low. (Level
of Evidence: C)
d. Right ventricular afterload should be optimized, which usually
requires therapy for concomitant LV dysfunction. (Level of Evidence:
C)
e. Inotropic support should be used for hemodynamic instability
not responsive to volume challenge. (Level of Evidence: C)
Class IIa
After infarction that leads to clinically significant RV dysfunction,
it is reasonable to delay CABG surgery for 4 weeks to allow recovery
of contractile performance. (Level of Evidence: C)
Right Ventricular Infarction and Dysfunction. Right ventricular
infarction encompasses a spectrum of disease states ranging from
asymptomatic mild RV dysfunction through cardiogenic shock. Most
patients demonstrate a return of normal RV function over a period
of weeks to months, which suggests that RV stunning, rather than
irreversible necrosis, has occurred. In this sense, RV ischemia
can be demonstrated in up to half of all inferior STEMIs, although
only 10% to 15% of patients show classic hemodynamic abnormalities
of clinically significant RV infarction (780,781).
Right ventricular infarction with hemodynamic abnormalities accompanying
inferior STEMI is associated with a significantly higher mortality
(25% to 30%) and thus identifies a high-risk subgroup of patients
with inferior STEMIs (6%) who should be considered high-priority
candidates for reperfusion (780).
One group of investigators reported a 31% inhospital mortality rate
in patients with inferior STEMIs complicated by RV infarction compared
with 6% in patients who had an inferior STEMI without RV involvement
(780). An analysis of patients
with predominant RV infarction and cardiogenic shock from the SHOCK
trial registry demonstrated an unexpectedly high mortality rate
similar to that for patients with LV shock (53.1% versus 60.8%)
(782). The treatment of patients
with RV ischemic dysfunction is different and, in several ways,
diametrically opposed to management of LV dysfunction.
Anatomic and Pathophysiological Considerations. The right
coronary artery usually supplies most of the RV myocardium; thus,
occlusion of this artery proximal to the RV branches will lead to
RV ischemia (783). Hemodynamically
significant RV infarctions occur almost exclusively in the setting
of inferior STEMIs (784). Because
the RV has a much smaller muscle mass than the LV, owing to the
lower vascular resistance of the pulmonary circuit, myocardial oxygen
demand is significantly less than that of the LV (785).
Coronary perfusion of the RV occurs in both systole and diastole
(785). The RV also has a more favorable
oxygen supply-demand ratio than the LV because of the more extensive
collateral flow from left to right (786,787).
These factors likely explain the absence of hemodynamically significant
RV ischemia in most patients with proximal right coronary artery
occlusions, as well as improvement in RV function observed in the
majority of patients after RV ischemia (788).
The
severity of the hemodynamic derangements associated with RV ischemia
is related to 1) the extent of ischemia and subsequent RV dysfunction,
2) the restraining effect of the surrounding pericardium, and 3)
interventricular dependence related to the shared interventricular
septum. When the RV becomes ischemic, it dilates acutely, which
results in increased intrapericardial pressure caused by the restraining
forces of the pericardium. As a consequence, there is a reduction
in RV systolic pressure and output, decreased LV preload, a reduction
in LV end-diastolic dimension and stroke volume, and a shifting
of the interventricular septum toward the LV (789).
Because of this RV systolic and diastolic dysfunction, the pressure
gradient between the right and left atria becomes an important driving
force for pulmonary perfusion. Factors that reduce preload (volume
depletion, diuretics, nitrates) or diminish augmented right atrial
contraction (concomitant atrial infarction, loss of AV synchrony)
and factors that increase RV afterload (concomitant LV dysfunction)
are likely to have profoundly adverse hemodynamic effects (790-794).
Goldstein and coworkers (791,794)
demonstrated the importance of a paradoxical interventricular septal
motion that bulges in piston-like fashion into the RV, generating
systolic force, which allows pulmonary perfusion. The loss of this
compensatory mechanism, with concomitant septal infarction, may
result in further deterioration in patients with RV ischemia.
Clinical
Diagnosis. Evidence of RV ischemia/infarction should be sought
in all patients with inferior STEMI. The clinical triad of hypotension,
clear lung fields, and elevated jugular venous pressure in the setting
of a STEMI is characteristic of RV ischemia/infarction. Although
specific, this triad has a sensitivity of less than 25% (795).
Distended neck veins alone or the presence of Kussmaul’s sign
(distention of the jugular vein on inspiration) are both sensitive
and specific for RV ischemia/ infarction in patients with a STEMI
(796). These findings may be masked
in the setting of volume depletion and may only become evident after
adequate volume loading. Right heart catheterization may be helpful
in diagnosing RV ischemia/infarction. A right atrial pressure of
10 mm Hg or greater and greater than 80% of pulmonary wedge pressure
is a relatively sensitive and specific finding in patients with
RV ischemia/infarction (797).
Patients
with RV hypertrophy, commonly due to the pulmonary hypertension
associated with chronic obstructive pulmonary disease, have increased
myocardial demand and may be more likely to suffer RV MI. Demonstration
of 1-mm ST-segment elevation in lead V1 and in the right precordial
lead V4R is the single most predictive ECG finding in patients with
RV ischemia (798). The finding
may be transient; half of patients show resolution of ST elevation
within 10 hours of onset of symptoms (799).
It is important for physicians to ensure that hospital personnel
(house officer, nurse, technician) recording the ECG in this setting
know how to properly record lead V4R, especially in view of the
variety of multilead recording systems available. All patients with
inferior STEMI should be screened initially for this finding at
the time of admission. Echocardiography can be helpful in patients
with suspicious but nondiagnostic findings (226).
It can show RV dilation and asynergy, abnormal interventricular
and interatrial septal motion, and even right to left shunting through
a patent foramen ovale (800-802).
Right to left shunting should be suspected when persistent hypoxia
is not responsive to supplemental oxygen (802).
Management
of RV Ischemia/Infarction. Treatment of RV ischemia/infarction
includes early maintenance of RV preload, reduction of RV afterload,
inotropic support of the dysfunctional RV, and early reperfusion
(Figure 30) (257,803).
Because of their influence on preload, drugs routinely used in management
of LV infarctions, such as nitrates and diuretics, may reduce cardiac
output and produce severe hypotension when the RV is ischemic. Indeed,
a common clinical presentation is profound hypotension after administration
of sublingual nitroglycerin, with the degree of hypotension often
out of proportion to the ECG severity of the infarct. Volume loading
with normal saline alone often resolves accompanying hypotension
and improves cardiac output (804).
The Trendelenburg position may effectively raise preload in patients
who develop hypotension after vasodilator administration. Although
volume loading is a critical first step in the management of hypotension
associated with RV ischemia/infarction, inotropic support (in particular,
dobutamine hydrochloride) should be initiated promptly if cardiac
output fails to improve after 0.5 to 1 L of fluid have been given.
Excessive volume loading may further alleviate the right-sided filling
pressure and RV dilatation, resulting in decreased LV output (805-807)
through shift of the interventricular septum for RV toward the LV.
Another
important factor for sustaining adequate RV preload is maintenance
of AV synchrony. High-degree heart block is common, occurring in
as many as half of these patients (808).
Atrioventricular sequential pacing leads to significant increase
in cardiac output and reversal of shock, even when ventricular pacing
alone has not been of benefit (806).
Atrial fibrillation may occur in up to one third of patients with
RV ischemia/infarction (807) and
has profound hemodynamic effects. Prompt cardioversion from AF should
be considered at the earliest sign of hemodynamic compromise. When
LV dysfunction accompanies RV ischemia/infarction, the RV is further
compromised because of increased RV afterload and reduction in stroke
volume (809).In such circumstances,
the use of afterload-reducing agents or an intra-aortic counterpulsation
device is often necessary to unload the LV and subsequently the
RV. Fibrinolytic therapy and primary PCI with subsequent reperfusion
have been shown to improve RV ejection fraction (793,810)
and reduce the incidence of complete heart block (810-812).
Right ventricular failure secondary to an ischemic RV (either infarction
or stunning) presents a particularly hazardous situation (813).
The prototypical patient has an occluded right coronary artery proximal
to the major RV branches and presents with an inferior MI with or
without recognized RV failure (784,795,814-821).
Angiography may demonstrate that the coronary anatomy is best treated
surgically, but the opportunity for maximal benefit of an emergency
operation (initial 4 to 6 hours) has often passed. There is substantial
risk in operating after this small window of opportunity but before
the recovery of RV function, which usually occurs at 4 weeks after
injury (793). During this postinfarct
month, the RV is at great risk for severe postoperative dysfunction,
which often requires extraordinary levels of perioperative pharmacological
and mechanical support and is associated with a very high mortality
rate. The nonsurgical postinfarction patient can most often be supported
with pacing, volume loading, and judicious inotropic administration
(792). In the surgical setting,
the RV takes on different characteristics. There is loss of the
pericardial constraint immediately on exposing the heart, which
results in acute dilation of the dysfunctional RV. The RV often
fails to recover in this setting, even when state-of-the-art myocardial
protection schemes and revascularization are used (822).
The parallel effects of RV dilatation and dysfunction on LV diastolic
and systolic function are magnified and may be associated with the
need for high levels of support, inability to close the chest owing
to cardiac dilation, need for ventricular assist devices, prolonged
convalescence, transplantation, or death (792).
The
best defense is an index of suspicion and recognition of the RV
dysfunction by physical examination (795,810)
ECG (right precordial leads), echocardiography, or radionuclide-
gated blood pool study (793,810,823,824).
If early PCI of the right coronary artery is indicated on the basis
of angiography, this should be performed promptly. It is reasonable
to delay coronary bypass surgery for 4 weeks to allow recovery of
RV function.
Prognosis.
The mere presence of RV ischemia/infarction that is evident by noninvasive
criteria is associated with significantly increased short-term morbidity
and mortality and may also influence long-term outcome (780,812,825).
However, clinical and hemodynamic recovery often occur even in patients
with RV dysfunction that persists for weeks or months (796,826-828).
This return to normal may be due to improvement of concomitant LV
dysfunction, which results in a reduction in RV afterload, or to
a gradual stretching of the pericardium with amelioration of its
restraining effect (826).
7.6.7. Mechanical Causes of Heart Failure/Low-Output
Syndrome
7.6.7.1.
Diagnosis
Mechanical
defects, when they occur, usually present within the first week
after STEMI. On physical examination, the presence of a new cardiac
murmur indicates the possibility of either a VSR or MR. Detailed
characteristics of these mechanical defects are listed in Table
25 (829) (Figure
31). A precise diagnosis can usually be established with transthoracic
or transesophageal echocardiography. A pulmonary artery monitoring
catheter may also be useful in establishing the diagnosis of a mechanical
defect and in its subsequent management. In VSR, oxygen saturation
will be higher (“step-up”) in the pulmonary artery than
in the right atrium. With acute MR, a large C-V wave may be evident
on the pulmonary artery wedge pressure tracing. However, a prominent
V wave does not necessarily indicate the presence of MR and may
also be present in patients with severe LV dysfunction associated
with decreased left atrial compliance (830).
A V wave may also be seen with VSR. In patients with free-wall ventricular
rupture and subsequent pericardial tamponade, equalization of diastolic
pressures may be seen.
Surgical consultation should be obtained when a mechanical defect
is suspected so that an early decision regarding surgical management
can be made. In general, prompt surgical repair is indicated in
most cases, because medical treatment alone is associated with an
extremely high mortality. Insertion of an IABP, particularly in
patients with papillary muscle rupture or VSR, can help stabilize
the patient. Although there is a need to minimize invasive procedures
before early surgical correction of mechanical complications, initial
coronary angiography to assess coronary anatomy appears warranted
in most cases of VSR and papillary muscle rupture. However, the
evidence for the benefit of concomitant CABG associated with surgical
repair of acute VSR is inconclusive (831).
In the majority of patients, right and left heart catheterization
are unnecessary unless other studies (e.g., echocardiography) are
not clear in demonstrating a mechanical defect.
7.6.7.2. Mitral Valve Regurgitation
Class
I
1. Patients with acute papillary muscle rupture should be considered
for urgent cardiac surgical repair, unless further support is considered
futile because of the patient’s wishes or contraindications/unsuitability
for further invasive care. (Level of Evidence: B)
2.
Coronary artery bypass graft surgery should be undertaken at the
same time as mitral valve surgery. (Level of Evidence: B)
Severe
MR after STEMI, accompanied by cardiogenic shock, has a poor prognosis.
In the SHOCK trial registry, approximately 10% of patients with
shock presented with severe MR and had an overall hospital mortality
of 55% (832). Mortality with medical
treatment only was 71% compared with 40% with surgery (832).
In the Survival and Ventricular Enlargement (SAVE) trial, in which
patients were treated with an ACE inhibitor after MI, even patients
with mild MR experienced a worse prognosis than those without MR
(833).
Severe MR may be due to infarction of the posterior papillary muscle,
and in such instances, the area of infarction tends to be less extensive
than in those patients in whom the MR is due to severe LV dysfunction.
Consequently, LV function may also be better preserved in these
patients. The presence of pulmonary edema or cardiogenic shock in
a patient with inferior STEMI should alert the physician to the
possibility of acute MR and papillary muscle rupture (Figure
31). Diagnosis is made by transthoracic or transesophageal
echocardiography.
All patients with papillary muscle rupture should be considered
for urgent surgery. The patient should be stabilized with an IABP,
inotropic support, and afterload reduction (to reduce regurgitant
volume and pulmonary congestion) while emergency surgery is arranged.
Coronary angiography should also be undertaken before surgery. Although
emergency mitral valve replacement is associated with a relatively
high mortality rate (20%), overall mortality and ventricular function
are improved compared with medical therapy alone. Delay in operation
appears to increase the risk of further myocardial injury, other
organ injury, and subsequent death (834).
Most patients will require mitral valve replacement, although mitral
valve repair has also been reported in selected circumstances. Five-year
survival after surgery has been reported to be 60% to 70% (835-839).
Severe MR, in the absence of papillary muscle rupture, often indicates
extensive infarction and severe LV dysfunction. These patients may
present a much more difficult management problem, particularly if
surgery is required. Initial management should include afterload
reduction and possible IABP. In many cases, the MR will improve
over the next several days with aggressive medical management. If
surgery required because of critical coronary anatomy or ongoing
ischemia, an intraoperative transesophageal echo should undertaken
to assess the mitral valve. Mitral valve surgery, usually annuloplasty,
should be undertaken at the same time as CABG for patients with
ischemic MR greater than 2+ (840,841).
Clearly, operative mortality is increased in such patients, particularly
in the elderly, with a marked decrease LV function.
7.6.7.3. Ventricular Septal Rupture
After STEMI
Class
I
1. Patients with STEMI complicated by the development of
a VSR should be considered for urgent cardiac surgical repair, unless
further support is considered futile because of the patient’s
wishes or contraindications/ unsuitability for further invasive
care. (Level of Evidence: B)
2.
Coronary artery bypass grafting should be undertaken at the same
time as repair of the VSR. (Level of Evidence: B)
The
frequency of acute rupture of the intraventricular septum (VSR)
(Figure 31) appears to have declined
in the reperfusion era. It is estimated to occur in fewer than 1%
of patients with STEMI (GUSTO-I) (829,842).
Whereas previous pathological and clinical studies indicated the
mean time from MI to rupture as 3 to 5 days, data from the GUSTO-I
trial and SHOCK registry indicate that the highest risk for development
of a postinfarct VSR occurred within the first 24 hours after infarction
in patients receiving fibrinolytic therapy (842,843).
Although emergency surgical repair was formerly thought to be necessary
only in patients with pulmonary edema or cardiogenic shock, it is
now recognized as equally important in hemodynamically stable patients
(844-846).
Because all septal perforations are exposed to shear forces and
necrotic tissue removal processes by macrophages, the rupture site
can abruptly expand, resulting in sudden hemodynamic collapse even
in patients who appear to be clinically stable with normal LV function
(846). Insertion of an IABP and
prompt surgical referral are recommended for almost every patient
with an acute VSR. Invasive monitoring is recommended in all patients,
together with judicious use of inotropes and a vasodilator to maintain
optimal hemodynamics. Nitroprusside is often used because it provides
afterload reduction and can be titrated intravenously. Surgical
repair usually involves excision of all necrotic tissue and patch
repair of the VSR, together with coronary artery grafting. Surgical
mortality remains high and has been reported to be between 20% and
50% (842-845,847,848).
Mortality is particularly high in patients with cardiogenic shock
(844,849)
and was reported to be 87% in the SHOCK registry. However, surgical
mortality is significantly less than for medically treated patients.
In GUSTO-I (842), the mortality
rates for surgical or medically treated patients were 47% and 94%,
respectively.
A limited number of patients with postinfarction VSR have been treated
by transcatheter closure with a septal occluding device. Most of
these cases have been managed several weeks after infarction or
have had prior surgical intervention with a residual defect. At
this time, surgical closure remains the procedure of choice, although
percutaneous closure does offer some hope for the future (850).
7.6.7.4. Left Ventricular Free-Wall Rupture
Class I
1. Patients with free-wall rupture should be considered
for urgent cardiac surgical repair, unless further support is considered
futile because of the patient’s wishes or contraindications/
unsuitability for further invasive care. (Level of Evidence:
B)
2.
CABG should be undertaken at the same time as repair of free wall
rupture. (Level of Evidence: C)
Cardiac rupture may account for recurrent pain and occurs in 1%
to 6% of all patients admitted with STEMI (829,851-854)
(Figure 31). Left ventricular
free-wall rupture is typically heralded by chest pain and ECG ST-T-wave
changes, with rapid progression to hemodynamic collapse and electromechanical
dissociation. The frequency of cardiac rupture has 2 peaks: an early
peak within 24 hours and a late one from 3 to 5 days after STEMI.
Early rupture is related to the initial evolution of infarction
before significant collagen deposition, and late rupture is related
to expansion of the infarctrelated ventricular wall (852,855).
Cardiac rupture is observed most frequently in patients with their
first MI, those with anterior infarction, the elderly, and women.
Other risk factors include hypertension during the acute phase of
STEMI, lack of previous angina and MI, lack of collateral blood
flow, Q waves on the ECG, use of corticosteroids or nonsteroidal
anti-inflammatory drugs (NSAIDs), and use of fibrinolytic therapy
more than 14 hours after onset (854,855).
Fibrinolytic therapy decreases risk of cardiac rupture (853,856).
Although there is an increase in the risk of early rupture after
late administration of fibrinolytic therapy (i.e., more than 14
hours), the overall incidence of rupture is reduced. The most important
determinants in preventing rupture are successful early reperfusion
and the presence of collateral circulation (852,853).
Pseudoaneurysm is a serious complication after rupture of the free
wall. Clot forms in the pericardial space, and an aneurysmal wall
containing clot and pericardium prevents exsanguination. Prompt
surgical correction is always indicated for pseudoaneurysm to prevent
rupture.
Pericardiocentesis for relief of tamponade and emergency surgical
repair may be lifesaving (857,858).
Ideally, the pericardium in this case should be opened surgically
or tapped in the operating room. Echocardiography is valuable in
the diagnosis of free-wall rupture and pseudoaneurysm, but for relief
of tamponade in this setting, rapid fluid replacement is essential.
Ideally, the patient should be in the operating room as soon as
possible and fully prepared for cardiopulmonary bypass to prevent
hemodynamic collapse. In these circumstances, delay to perform coronary
angiography is inadvisable (859).
Surgery includes repair of the ventricle with a direct suture technique
or patch to cover the ventricular perforation (857),
in addition to CABG as needed. Alternatively, the use of cyanoacrylate
glue has been described to hold the patch in place over necrotic
myocardium (860). Most series of
patients reaching the operating room for management of this complication
are small, with the surgical mortality rate in these patients being
up to 60% (859,861).
7.6.7.5. Left Ventricular Aneurysm
Class IIa
It is reasonable that patients with STEMI who develop a ventricular
aneurysm associated with intractable ventricular tachyarrhythmias
and/or pump failure unresponsive to medical and catheter-based therapy
be considered for LV aneurysmectomy and CABG surgery. (Level
of Evidence: B)
Ventricular aneurysm after STEMI usually occurs on the anterior
aspect of the LV in association with total LAD occlusion and a wide
area of infarction. Clinical consequences include angina pectoris,
CHF, thromboembolism, and ventricular arrhythmias. Patients with
STEMI who receive fibrinolytic therapy and exhibit a patent infarct-related
artery have a significantly reduced incidence of LV aneurysm formation
compared with those who do not (7.2% versus 18.8%) (862).
The need for surgery for ventricular aneurysm early after STEMI
is rare, but it may be necessary for control of heart failure or
intractable ventricular arrhythmias unresponsive to conventional
therapy (863). Surgical techniques
include plication, excision with linear repair, and ventricular
reconstruction with endoventricular patches to maintain better physiological
function (863-865).
The adequacy of the residual LV in terms of size and function is
critical determinant on prognosis. Current mortality rates are reported
to be 3.3% to 7.2% (863,864).
Patients with severe LV dysfunction have an increase in mortality
that has been reported to be as high as 19% for an ejection fraction
less than 0.20 (866). Operative
survivors have clear improvement in New York Heart Association class
and a 60% 5-year survival rate (867).
7.6.7.6. Mechanical Support of the Failing
Heart
7.6.7.6.1. Intra-Aotic Balloon
Counterpulsation.
Class I
1. Intra-aortic balloon counterpulsation should be used in STEMI patients
with hypotension (systolic blood pressure less than 90 mmHg or 30
mmHg below baseline mean arterial pressure) who do not respond to
other interventions, unless further support is futile because of the
patient’s wishes or contraindications/ unsuitability for further
invasive care. See Section 7.6.2. (Level
of Evidence: B)
2. Intra-aortic balloon counterpulsation is recommended for STEMI
patients with low-output state. See Section 7.6.3.
(Level of Evidence: B)
3. Intra-aortic balloon counterpulsation is recommended for STEMI
patients when cardiogenic shock is not quickly reversed with pharmacological
therapy. IABP is a stabilizing measure for angiography and prompt
revascularization. See Section 7.6.5. (Level
of Evidence: B)
4. Intra-aortic balloon counterpulsation should be used in addition
to medical therapy for STEMI patients with recurrent ischemic-type
chest discomfort and signs of hemodynamic instability, poor LV function,
or a large area of myocardium at risk. Such patients should be referred
urgently for cardiac catheterization and should undergo revascularization
as needed. See Section 7.8.2. (Level of Evidence:
C)
Class
IIa
It is reasonable to manage STEMI patients with refractory polymorphic
VT with intra-aortic balloon counterpulsation to reduce myocardial
ischemia. See Section 7.7.1.2. (Level
of Evidence: B)
Class IIb
It may be reasonable to use intra-aortic balloon counterpulsation
in the management of STEMI patients with refractory pulmonary congestion.
See Section 7.6.4. (Level of Evidence: C)
The IABP improves diastolic coronary blood flow and reduces myocardial
work. These physiological effects of the IABP are especially helpful
in patients with STEMI with ongoing or recurrent ischemic discomfort,
hypotension from ischemia-mediated LV dysfunction, and cardiogenic
shock (see Section 7.6.5). The IABP is a useful
stabilizing measure for patients in whom cardiac catheterization
and revascularization are being considered.
Selected patients with cardiogenic shock after STEMI, especially
if not candidates for revascularization, may be considered for either
a short- or long-term mechanical support device to serve as a bridge
to recovery or to subsequent cardiac transplantation. Of the many
devices available to support these patients (868),
short-term devices include centrifugal pumps and LV assist devices
(LVADs) (869). Extracorporeal membrane
oxygenation (ECMO), a cardiopulmonary bypass system placed through
either the femoral or intrathoracic vessels, serves patients with
heart failure and concomitant respiratory failure. These systems
are limited by their short-term usefulness of less than 1 week and
by problems with bleeding and thrombosis. Some consider ECMO a poor
method of support because it does not decompress the LV (869).
Patients who are subsequently determined to be transplant candidates
may also be converted to a bridge-to-transplant device, thus creating
a bridge to a bridge. About 10% of all patients treated with LVADs
have them inserted for hemodynamic support after STEMI. This application
has not been widely used because of the many comorbidities encountered
in such patients, many of whom die before surgery. Experience with
LVADs implanted in selected patients within 14 days after infarction
has shown survival rate of 74% to transplantation or explantation
(870). This experience suggests
that ventricular assist device implantation for cardiogenic shock
after STEMI may reduce the mortality currently associated with medical
management. The use of assist devices has been extensively reviewed
in separate ACC consensus conference report (868).
7.6.7.7. Cardiac Transplantation After
STEMI
Cardiac transplantation has been reported for patients who have
sustained irreversible acute myocardial injury associated with cardiogenic
shock (871-873).
Most patients so transplanted have been initially treated with an
LVAD as a bridge to recovery or transplantation. Many such patients,
however, do not meet criteria for transplantation because of advancedage
and extensive comorbidity. With appropriate case selection, satisfactory
results can be obtained. Of 25 patients with post-STEMI cardiogenic
shock and a mean age of 48 years, 3 died while on devices and 18
(72%) survived transplantation (873).
7.7. Arrhythmias After STEMI
Cardiac arrhythmias are common in patients with STEMI and occur
most frequently early after development of symptoms. The mechanisms
for ventricular tachyarrhythmias include loss of transmembrane resting
potential, reentrant mechanisms due to dispersion of refractoriness
in the border zones between infarcted and nonischemic tissues (874),
and the development of foci of enhanced automaticity. Reperfusion
arrhythmias, more commonly seen in the postfibrinolytic era, appear
to involve washout of toxic metabolites and of various ions such
as lactate and potassium (875).
Atrial arrhythmias have as additional causes excessive sympathetic
stimulation, increased atrial stretch due to ventricular failure
or AV valvular insufficiency, proarrhythmic effects of pericarditis,
and atrial infarction. Bradyarrhythmias may be due to overstimulation
of vagal afferent receptors and resulting cholinergic stimulation,
as well as to ischemic injury of conducting tissues. The treatment
of cardiac arrhythmias is based on the presumptive mechanism, the
ongoing hemodynamic consequences, and, whenever possible, the results
of clinical studies.
7.7.1. Ventricular Arrhythmias
7.7.1.1. Ventricular Fibrillation
Class I
Ventricular fibrillation or pulseless VT should be treated
with an unsynchronized electric shock with an initial monophasic
shock energy of 200 J; if unsuccessful, a second shock of 200 to
300 J should be given, and then, if necessary, a third shock of
360 J. (Level of Evidence: B)
Class IIa
1. It is reasonable that VF or pulseless VT that is refractory to
electric shock be treated with amiodarone (300 mg or 5 mg/kg, IV
bolus) followed by a repeat unsynchronized electric shock. (Level
of Evidence: B)
2. It is reasonable to correct electrolyte and acid-base disturbances
(potassium greater than 4.0 mEq/L and magnesium greater than 2.0
mg/dL) to prevent recurrent episodes of VF once an initial episode
of VF has been treated. (Level of Evidence: C)
Class IIb
It may be reasonable to treat VT or shock-refractory VF with boluses
of intravenous procainamide. However, this has limited value owing
to the length of time required for administration. (Level of
Evidence: C)
Class
III
Prophylactic administration of antiarrhythmic therapy is not recommended
when using fibrinolytic agents. (Level of Evidence: B)
Disturbances of cardiac rhythm are common during STEMI. Early-phase
arrhythmias are probably largely a result of microreentry. Although
other electrophysiological mechanisms such as enhanced automaticity
and triggered activity have been proposed in experimental models
of STEMI, convincing evidence for their role in human STEMI is not
yet established (876). Important
contributory factors include heightened adrenergic nervous system
tone, hypokalemia, hypomagnesemia, intracellular hypercalcemia,
acidosis, free fatty acid production from lipolysis, and free radical
production from reperfusion of ischemic myocardium (876-878).
The relative importance of each of these factors in the pathogenesis
of arrhythmias during STEMI has not been established, nor has it
been clearly shown that aggressive measures specifically targeted
at 1 or more of these mechanisms can be relied on clinically to
reduce arrhythmia frequency in STEMI.
Primary VF should be distinguished from secondary VF, the latter
occurring in the presence of severe CHF or cardiogenic shock (879).
Late VF develops more than 48 hours after onset of STEMI. Ventricular
fibrillation is more common in the elderly (greater than 75 years
of age) (880). The incidence of
primary VF is highest (around 3% to 5%) in the first 4 hours after
STEMI and declines markedly thereafter (881).
Some epidemiological data suggest that the incidence of primary
VF in STEMI may be decreasing in the current era, possibly owing
to aggressive attempts at infarct-size reduction, correction of
electrolyte deficits, and a greater use of beta-adrenoceptor–blocking
agents (882). Additional epidemiological
data from the Worcester Heart Attack Study more convincingly demonstrate
that the case-fatality rate of primary VF has declined over time
(883). Contrary to prior belief,
primary VF appears to be associated with significantly higher in-hospital
mortality, but those persons who survive to hospital discharge,
particularly if primary VF occurred within the first 4 hours after
STEMI, have the same longterm prognosis as patients who do not experience
primary VF (884).
Primary VF remains an important contributor to risk of mortality
during the first 24 hours after STEMI. Therefore, a reliable method
for its prediction and prevention remains desirable but has not
been established despite extensive clinical investigation. Classification
of ventricular arrhythmias in ascending order of risk of primary
VF (warning arrhythmias) was proposed, but this approach lacks appropriate
specificity and sensitivity (885-887).
Accelerated idioventricular rhythm occurs frequently during the
first 12 hours of infarction. Data from the prereperfusion era do
not support development of accelerated idioventricular rhythm as
a risk factor for development of VF (886,888).
In patients receiving fibrinolysis or undergoing primary PCI, accelerated
idioventricular rhythm may be a reperfusion arrhythmia and does
not indicate an increased risk of VF (889).
Thus, it is best managed by observation and should not trigger initiation
of antiarrhythmic prophylaxis against VF.
A meta-analysis of randomized trials of prophylaxis with lidocaine
has shown a relative reduction in the incidence of primary VF by
about 33%, but this was offset by a trend toward increased mortality,
probably from fatal episodes of bradycardia and asystole (890).
The use of prophylactic lidocaine was assessed in patients with
STEMI in the GUSTO-I and GUSTO-IIb trials (891).
After adjustment for baseline imbalances, the odds of death were
not significantly different with or without lidocaine. Thus, even
though it is less clear that lidocaine causes harm, there is no
convincing evidence that its prophylactic use reduces mortality,
and the prior practice of routine (prophylactic) administration
of lidocaine to all patients with known or suspected STEMI has been
largely abandoned.
Routine administration of intravenous beta-adrenoceptor blockers
to patients without hemodynamic or electrical (AV block) contraindications
is associated with a reduction in incidence of early VF (892).
In the absence of contraindications (see Section
6.3.1.5), it is reasonable to initiate betablockade intravenously,
followed by an oral regimen. Suitable regimens include intravenous
metoprolol at 5 mg every 2 minutes for 3 doses, if tolerated, followed
by 50 mg orally twice per day for at least 24 hours and then increased
to 100 mg twice per day. An alternative regimen is atenolol 5 to
10 mg IV followed by 100 mg orally on a daily basis.
Clinical
experience and observational data from CCU populations have identified
hypokalemia as an arrhythmogenic risk factor for VF (877,878).
Low serum levels of magnesium have not been clearly shown to be
associated with an increased risk of VF (878),
although tissue depletion of magnesium remains a potential risk
factor. Although randomized clinical trial data do not exist to
confirm the benefits of repletion of potassium and magnesium deficits
in preventing VF, it is sound clinical practice to maintain serum
potassium levels at greater than 4.0 mEq/L and magnesium levels
at greater than 2.0 mEq/L in patients with acute MI.
Ventricular
fibrillation should be treated with an unsynchronized electric shock
using an initial monophasic shock energy of 200 J. If this is unsuccessful,
a second shock using 200 to 300 J and, if necessary, a third shock
using 360 J is indicated (893).
The appearance of biphasic waveform defibrillators has led to some
confusion regarding the comparability of biphasic to monophasic
defibrillating energies. Overall, the energy requirement for equivalent
biphasic therapeutic effect is about one half of the energy requirement
for a monophasic discharge. Given the rapid evolution of resuscitation
methodology, clinicians should follow the most current ACLS protocol
(629). For example, for patients
with VF not easily converted by defibrillation, vasopressin 40 U
IV push may be substituted for epinephrine 1 mg. Randomized trials
have addressed the use of intravenous amiodarone versus placebo
and versus lidocaine for patients with out-of-hospital cardiac arrest.
Although this population is somewhat different from the CCU population
with primary VF, many patients with out-of-hospital VF have STEMI
as the precipitating cause (894).
These randomized trials have shown that the use of intravenous amiodarone
is superior to placebo (895) and
to lidocaine (896) in survival to
hospital admission for patients with shock-resistant VF or VT. Neither
trial, however, demonstrated improved survival to hospital discharge.
In contrast, small studies comparing lidocaine to bretylium failed
to show significant differences in the proportion of patients surviving
to hospital admission (897,898);
the use of procainamide in cardiac arrest is based on a small, 20-patient
study (899). The use of lidocaine
to treat VF refractory to electric shock or pulseless VT followed
by unsynchronized electric shock has not been demonstrated to be
beneficial in this setting and has been labeled “class indeterminate”
by the Guidelines 2000 for Cardiopulmonary Resuscitation and Emergency
Cardiovascular Care (900).
There
are no firm data to help define an optimal management strategy for
prevention of recurrent VF in patients who have sustained an initial
episode of VF in the setting of STEMI. It seems prudent to correct
any electrolyte and acidbase disturbances and to administer beta-adrenoceptor–
blocking agents to inhibit increased sympathetic nervous system
tone and prevent ischemia (876).
The clinical trials of amiodarone cited above studied bolus administration
of amiodarone only during the arrest setting. Thus, in the absence
of arrhythmia recurrence, antiarrhythmic drugs should not be maintained
beyond a 6- to 24-hour period. They should then be discontinued
so that the patient’s ongoing need for antiarrhythmic treatment
can be reassessed.
7.7.1.2. Ventricular Tachycardia
Class I
1. Sustained (more than 30 seconds or causing hemodynamic collapse)
polymorphic VT should be treated with an unsynchronized electric
shock with an initial monophasic shock energy of 200 J; if unsuccessful,
a second shock of 200 to 300 J should be given, and, if necessary,
a third shock of 360 J. (Level of Evidence: B)
2. Episodes of sustained monomorphic VT associated with angina,
pulmonary edema, or hypotension (blood pressure less than 90 mm
Hg) should be treated with a synchronized electric shock of 100
J of initial monophasic shock energy. Increasing energies may be
used if not initially successful. Brief anesthesia is desirable
if hemodynamically tolerable. (Level of Evidence: B)
3. Sustained monomorphic VT not associated with angina, pulmonary
edema, or hypotension (blood pressure less than 90 mm Hg) should
be treated with:
a. Amiodarone: 150 mg infused over 10 minutes (alternative
dose 5 mg/kg); repeat 150 mg every 10 to 15 minutes as needed. Alternative
infusion: 360 mg over 6 hours (1 mg/min), then 540 mg over the next
18 hours (0.5 mg/min). The total cumulative dose, including additional
doses given during cardiac arrest, must not exceed 2.2 g over 24
hours. (Level of Evidence: B)
b. Synchronized electrical cardioversion starting at monophasic
energies of 50 J (brief anesthesia is necessary). (Level of
Evidence: B)
Class IIa
It is reasonable to manage refractory polymorphic VT by:
a. Aggressive attempts to reduce myocardial ischemia, and adrenergic
stimulation, including therapies such as beta-adrenoceptor blockade,
IABP use, and consideration of emergency PCI/CABG surgery. (Level
of Evidence: B)
b.
Aggressive normalization of serum potassium to greater than 4.0
mEq/L and of magnesium to greater than 2.0 mg/dL. (Level of
Evidence: C)
c.
If the patient has bradycardia to a rate less than 60 bpm or long
QTc, temporary pacing at a higher rate may be instituted. (Level
of Evidence: C)
Class IIb
It may be useful to treat sustained monomorphic VT not associated
with angina, pulmonary edema, or hypotension (blood pressure less
than 90 mm Hg) with a procainamide bolus and infusion (Level
of Evidence: C)
Class III
1. The routine use of prophylactic antiarrhythmic drugs (i.e., lidocaine)
is not indicated for suppression of isolated ventricular premature
beats, couplets, runs of accelerated idioventricular rhythm, and
nonsustained VT. (Level of Evidence: B)
2. The routine use of prophylactic antiarrhythmic therapy is not
indicated when fibrinolytic agents are administered. (Level
of Evidence: B)
Several definitions have been used for VT in the setting of STEMI.
Nonsustained VT lasts less than 30 seconds, whereas sustained VT
lasts more than 30 seconds and/or causes earlier hemodynamic compromise
that requires immediate intervention. On the basis of ECG appearance,
VT has also been categorized as monomorphic or polymorphic. Although
short bursts (fewer than 5 beats) of nonsustained VT of either monomorphic
or polymorphic configuration may be seen frequently, contemporary
epidemiological data do not suggest that they are associated with
a sufficiently increased risk of sustained VT or VF to warrant prophylactic
therapy.
The
vast majority of episodes of VT and VF after STEMI occur within
the first 48 hours (881). Traditionally,
sustained VT or VF that occurs outside of this time frame is thought
to deserve especially careful evaluation, including consideration
of electrophysiology (EP) studies. In addition, monomorphic VT at
rates less than 170 bpm is unusual as an arrhythmia early after
STEMI and suggests a more chronic (mature) arrhythmogenic substrate
(515,901-903).
VT that occurs more than 48 hours after STEMI may denote an arrhythmic
substrate deserving of further evaluation by EP study.
MANAGEMENT STRATEGIES FOR VT. Cardioversion is always indicated
for episodes of sustained, hemodynamically compromising VT (876).
In the absence of clinical evidence effective perfusion, urgent
electrical conversion of VT indicated. Rapid, polymorphic-appearing
VT should be considered similar to VF and managed with an unsynchronized
discharge of 200 J, whereas monomorphic VT with greater than 150
bpm can usually be treated with a 100-J synchronized discharge (893).
Immediate cardioversion is generally not needed for rates below
150 bpm unless hemodynamic compromise is present.
Episodes
of sustained VT that are somewhat better tolerated hemodynamically
may initially be treated with drug regimens including amiodarone
or procainamide. Unfortunately, the data supporting the use of any
specific antiarrhythmic therapy in this setting are scant. Although
the Guidelines 2000 for Cardiopulmonary Resuscitation and Emergency
Cardiac Care differentiate between patients with normal impaired
LV function, impairment of LV function is likely the STEMI setting.
Thus, recommendations for patients STEMI parallel the Guidelines
2000 for Cardiopulmonary Resuscitation and Emergency Cardiac Care
for patients impaired LV function and place the use of amiodarone
above that of other antiarrhythmics (900).
Indeed, amiodarone produced favorable data in cardiac arrest, and
in long- randomized trials, it is associated with a reduction in
arrhythmic death and a small reduction in overall mortality (Knowledge
of the pharmacokinetics of antiarrhythmic agents in patients with
STEMI is important because dosing varies considerably, depending
on age, weight, and hepatic renal function.
Rare episodes of drug-refractory sustained polymorphic VT (electrical
storm) have been reported in cases of STEMI. Anecdotal evidence
suggests that these episodes may related to uncontrolled ischemia
and increased sympathetic tone and are best treated by intravenous
beta-adrenoceptor blockade (905),
intravenous amiodarone (906), left
stellate ganglion blockade (907),
IABP, or emergency revascularization. Intravenous amiodarone and/or
intravenous magnesium may also be used.
Nonsustained VT is not a common cause of hemodynamic compromise
and consequently does not require acute therapy (Figure
10) (223). Nonetheless, it
is an important arrhythmia that may denote a high-risk arrhythmic
substrate. Indeed, when it occurs more than 4 days after STEMI in
patients with a depressed ejection fraction, it may be a harbinger
of future risk of sudden death (908).
In unusual cases, although the VT is nonsustained, the rate may
be so rapid as to reduce cerebral perfusion sufficiently to cause
symptoms (i.e., nonsustained VT at a rate of 200 bpm for 10 seconds).
In those cases, pharmacotherapy similar to that recommended for
sustained VT may be instituted.
7.7.1.3.
Ventricular Premature Beats
Class III
Treatment of isolated ventricular premature beats, couplets, and
nonsustained VT is not recommended unless they lead to hemodynamic
compromise. (Level of Evidence: A)
Before
the present era of care of the STEMI patient with antiplatelet therapy,
beta-blockade, ACE inhibitors, and, above all, reperfusion strategies,
it was thought that ventricular warning arrhythmias preceded VF.
Careful monitoring has refuted this concept, and treatment of these
rhythm disturbances is not recommended unless they lead to hemodynamic
compromise. All post-STEMI patients with ventricular arrhythmias
should undergo assessment of electrolyte levels (especially potassium
and magnesium) and have other metabolic parameters (i.e., arterial
pH) assessed. The effect on survival of the pharmacological suppression
of ventricular premature beats after MI was assessed in the Cardiac
Arrhythmia Suppression Trial (909).
Patients receiving class I antiarrhythmic drugs for suppression
of ventricular premature beats did more poorly than the placebo-treated
patients. Therefore, suppression of ventricular premature beats
with class I antiarrhythmic drugs is not a goal of post-STEMI therapy.
7.7.1.4. Accelerated Idioventricular
Rhythms and Accelerated Junctional Rhythms
Class III
1. Antiarrhythmic therapy is not indicated for accelerated idioventricular
rhythm. (Level of Evidence: C)
2. Antiarrhythmic therapy is not indicated for accelerated junctional
rhythm. (Level of Evidence: C)
Accelerated idioventricular rhythms are characterized by a wide
QRS complex, with a regular rate higher than the atrial rate and
lower than 100 bpm. The appearance of an idioventricular rhythm
is an inexact indicator of reperfusion. Treatment of idioventricular
rhythm is not indicated, and suppression of the rhythm may lead
to hemodynamic compromise.
Accelerated junctional rhythms are characterized by a regular narrow
QRS not preceded by atrial activity, with rates above 60 bpm. This
rhythm may indicate digitalis intoxication and is more often seen
in inferior STEMI than in anterior STEMI. In general, treatment
of accelerated junctional rhythm is not indicated.
7.7.1.5. Implantable Cardioverter
Defibrillator Implantation in Patients After STEMI
Class I
1. An implantable cardioverter defibrillator (ICD) is indicated
for patients with VF or hemodynamically significant sustained VT
more than 2 days after STEMI, provided the arrhythmia is not judged
to be due to transient or reversible ischemia or reinfarction. (Level
of Evidence: A)
2. An ICD is indicated for patients without spontaneous VF or sustained
VT more than 48 hours after STEMI whose STEMI occurred at least
1 month previously, who have an LVEF between 0.31 and 0.40, demonstrate
additional evidence of electrical instability (e.g., nonsustained
VT), and have inducible VF or sustained VT on EP testing. (Level
of Evidence: B)
Class
IIa
If there is reduced LVEF (0.30 or less) at least 1 month post-STEMI
and 3 months after coronary artery revascularization, it is reasonable
to implant an ICD in post-STEMI patients without spontaneous VF
or sustained VT more than 48 hours after STEMI. (Level of Evidence:
B)
Class
IIb
1. The usefulness of an ICD is not well established in STEMI patients
without spontaneous VF or sustained VT more than 48 hours after
STEMI who have a reduced LVEF (0.31 to 0.40) at least 1 month after
STEMI but who have no additional evidence of electrical instability
(e.g., nonsustained VT). (Level of Evidence: B)
2. The usefulness of an ICD is not well established in STEMI patients
without spontaneous VF or sustained VT more than 48 hours after
STEMI who have a reduced LVEF (0.31 to 0.40) at least 1 month after
STEMI and additional evidence of electrical instability (e.g., nonsustained
VT) but who do not have inducible VF or sustained VT on EP testing.
(Level of Evidence: B)
Class III
An ICD is not indicated in STEMI patients who do not experience
spontaneous VF or sustained VT more than 48 hours after STEMI and
in whom the LVEF is greater than 0.40 at least 1 month after STEMI.
(Level of Evidence: C)
In general, VF or hemodynamically significant sustained VT taking
place more than 2 days after STEMI in the absence of recurrent MI
or potentially reversible ischemia indicates electrical instability
and portends a poor prognosis (910,911).
There are only 3 randomized trials (AVID [Antiarrhythmics Versus
Implantable Defibrillators], CASH (Cardiac Arrest Study Hamburg),
and CIDS [Canadian Implantable Defibrillator Study]) that compare
the ICD with antiarrhythmic therapy in this patient population (912-914).
Although the focus of these studies was not specifically the patient
with prior or recent STEMI, the populations, as expected, all had
a high prevalence of coronary disease and prior MI (Table
26) (912-914).
Only
the AVID study showed a benefit of ICD therapy on mortality. However,
the meta-analysis by Connolly et al. (914)
clearly demonstrated the similarity of the trials and the consistency
of overall results for patients with prior MI. The summary hazard
ratio was 0.72 (95% CI 0.60 to 0.87; p equals 0.0006) for total
mortality and 0.50 (95% CI 0.37 to 0.67; p less than 0.0001) for
arrhythmic death. Thus, patients with VF or hemodynamically significant
sustained VT that takes place more than 2 to 3 days after STEMI
in the absence of recurrent MI or other readily reversible cause
should receive an ICD (Table 27)
(915-918).
The
management of nonsustained VT in patients with prior MI has proven
more challenging. In the presence of LV dysfunction, this arrhythmia
is associated with a 2-year mortality estimated at 30% (919,920),
of which approximately 50% is believed to be arrhythmic in origin.
Subsequent studies suggest that this degree of risk occurs principally
in patients with inducible sustained VT not treated with an ICD
(921). Three large randomized trials
have been performed to study primary prevention of sudden death
in these patients. However, because these trials were purposely
not designed as post-STEMI trials, a conservative interpretation
requires knowledge of when patients were randomized in relationship
to their last previous known MI.
In the first prospective randomized trial completed in such a patient
population, improved survival was documented after implantation
of ICDs in patients with nonsustained VT and EP study–inducible
and nonsuppressible ventricular tachyarrhythmias compared with conventional
drug therapy, including amiodarone (915).
Patients could not be randomized until at least 3 weeks after MI.
Results of another prospective randomized trial, the Multicenter
Unsustained Tachycardia Trial (MUSTT), showed reduced mortality
with aggressive therapy for patients with low ejection fraction
(0.40 or less), nonsustained VT on Holter monitoring, and inducible
sustained ventricular tachyarrhythmias at EP study (916).
Most of this benefit appeared to be due to ICD placement (918).
In MUSTT, patients could be randomized as early as 4 days after
MI; however, only 16% of patients were enrolled within 1 month of
MI, which limits conclusions regarding benefit in patients early
after STEMI. The MADIT 2 (Multicenter Automatic Defibrillator Implantation
Trial 2) study enrolled 1232 post-MI patients with an LVEF of 0.30
or less. Patients were randomized to ICD therapy or not without
the requirement for EP screening for inducible ventricular tachyarrhythmia
(917). At a mean follow-up of 20
months, mortality was 14.2% in individuals who had ICDs and 19.8%
in the conventionally treated group, a 5.6% absolute and 31% relative
risk reduction for death. Of potential importance for management
of patients recovering from STEMI, ICD therapy was not implemented
until at least 1 month after MI and 3 months after coronary artery
revascularization (Figure 32).
Thus, evidence from the randomized trials conclusively supports
the concept that for patients with coronary disease, LV dysfunction,
and high risk of life-threatening ventricular arrhythmias, ICD therapy
is more effective than antiarrhythmic therapy. Indeed, an important
contribution of the randomized clinical trials has been to refine
the estimated contribution of risk factors for arrhythmic death
or cardiac arrest in patients with coronary disease and LV dysfunction.
For example, in the MUSTT database, each 5% decrease in LVEF from
0.40 to 0.20 conferred a 19% incremental relative risk of arrhythmic
death or cardiac arrest. Inducibility at EP study increased risk
by 63%. These simple risk factors, therefore, allow the clinician
to select those patients most likely to benefit from ICD therapy
in the late post-STEMI phase (922).
The published studies, however, do not systematically address management
considerations within the first month after STEMI. MADIT enrolled
patients at least 3 weeks after MI, MUSTT at least 4 days, and MADIT
2 at least 1 month. Nonetheless, there is conceptual uniformity
of the results of all 3 trials to support ICD therapy for patients
at high risk of sudden cardiac death after STEMI.
Although the ejection fraction criteria used to define a degree
of LV dysfunction severe enough to confer high risk are not uniform
from study to study, a reduced ejection fraction remains the critical
measurement to determine whether a post-STEMI patient is at high
risk for late ventricular arrhythmia. Furthermore, ejection fraction
is not always stable after STEMI. In a cohort of 252 patients who
had sustained an anterior wall STEMI, 53% had at least a 5-point
increase in ejection fraction at 90 days, whereas only 16% had a
drop of at least 5 points (923).
Thus, ejection fraction should be measured at least 1 month after
STEMI before a decision regarding ICD placement is made. Finally,
the variability of ejection fraction measured by different techniques
(924) should also be taken into
account by the clinician caring for the patient.
If
there is reduced EF (0.30 or less) at least 1 month after STEMI
and 3 months after coronary artery revascularization, it is reasonable
to implant an ICD without a preceding diagnostic EP study. If the
patient has an EF between 0.31 and 0.40, additional evidence of
electrical instability should be sought to help with management
decisions. If markers of electrical instability are detected on
noninvasive testing (nonsustained on monitoring), an EP study is
the next diagnostic step. If inducible VF or sustained VT is found
at EP study, an ICD is indicated. The Writing Committee endorses
additional research on noninvasive markers of electrical instability
and the results of EP testing to help clarify management of decisions
in such patients (see Section 7.11). The usefulness
of an ICD is less well established for patients in whom no inducible
VF or sustained VT is detected at EP study. As shown in Figure
32, such patients do not receive an ICD but should receive medical
therapy (post-STEMI) as discussed in this guideline. An ICD is not
indicated in patients with STEMI who do not experience spontaneous
VF or sustained VT more than 48 hours after STEMI and in whom the
ejection fraction is greater than 0.40 at least 1 month after STEMI.
Unfortunately, published clinical trials have not addressed the
patient with a low ejection fraction within the first month after
STEMI, which is thought to be a particularly high-risk period. Preliminary
findings from DINAMIT (Defibrillator in Acute Myocardial Infarction
Trial), a clinical trial of ICD versus conventional therapy in patients
6 to 40 days after MI with ejection fraction less than 0.35 and
evidence of impaired autonomic tone, showed a reduction in arrhythmic
mortality at the cost of an increase in nonarrhythmic mortality,
yielding no net benefit of an ICD implanted in the first month after
STEMI (Connelly S; oral presentation, American College of Cardiology
53rd Annual Scientific Session, March 2004, New Orleans, LA). Given
this gap in knowledge, the ongoing Home Automatic External Defibrillator
Trial is testing the hypothesis that provision of an AED to patients
with anterior STEMI for home use will improve survival beyond that
achieved from the typical lay response to sudden cardiac arrest
(135). Additionally, wearable external
defibrillators have been developed that may be applicable for high-risk
patients after STEMI (926).
7.7.2. Supraventricular Arrhythmia/AF
Class I
1. Sustained AF and atrial flutter in patients with hemodynamic
compromise should be treated with one or more of the following:
a. Synchronized cardioversion with an initial monophasic shock of
200 J for AF and 50 J for flutter, preceded by brief general anesthesia
or conscious sedation whenever possible. (Level of Evidence:
C)
b. For episodes of AF that do not respond to electrical cardioversion
or recur after a brief period of sinus rhythm, the use of antiarrhythmic
therapy aimed at slowing the ventricular response is indicated.
One or more of these pharmacological agents may be used:
i. Intravenous amiodarone (927).
(Level of Evidence: C)
ii. Intravenous digoxin for rate control, principally for patients
with severe LV dysfunction and heart failure. (Level of Evidence:
C)
2.
Sustained AF and atrial flutter in patients with ongoing ischemia
but without hemodynamic compromise should be treated with one or
more of the following:
a. Beta-adrenergic blockade is preferred, unless contraindicated.
(Level of Evidence: C)
b. Intravenous diltiazem or verapamil. (Level of Evidence: C)
c. Synchronized cardioversion with an initial monophasic shock of
200 J for AF and 50 J for flutter, preceded by brief general anesthesia
or conscious sedation whenever possible. (Level of Evidence:
C)
3. For episodes of sustained AF or flutter without hemodynamic compromise
or ischemia, rate control is indicated. In addition, patients with
sustained AF or flutter should be given therapy with anticoagulants.
Consideration should be given to conversion of sinus rhythm in patients
without a history of atrial fibrillation or flutter prior to STEMI.
(Level of Evidence: C)
4. Re-entrant paroxysmal supraventricular tachycardia, because of
its rapid rate, should be treated with the following in the sequence
shown:
a. Carotid sinus massage. (Level of Evidence: C)
b. Intravenous adenosine (6 mg × 1 over 1 to 2 seconds; if
no response, 12 mg IV after 1 to 2 minutes may be given; repeat
12 mg dose if needed. (Level of Evidence: C)
c. Intravenous beta-adrenergic blockade with metoprolol (2.5 to
5.0 mg every 2 to 5 minutes to a total of 15 mg over 10 to 15 minutes)
or atenolol (2.5 to 5.0 mg over 2 minutes to a total of 10 mg in
10 to 15 minutes. (Level of Evidence: C)
d. Intravenous diltiazem (20 mg [0.25 mg/kg]) over 2 minutes followed
by an infusion of 10 mg/h. (Level of Evidence: C)
e. Intravenous digoxin, recognizing that there may be a delay of
at least 1 hour before pharmacological effects appear (8 to 15 mcg/kg
[0.6 to 1.0 mg in a person weighing 70 kg]). (Level
of Evidence: C)
Class III
Treatment of atrial premature beats is not indicated. (Level
of Evidence: C)
Atrial fibrillation occurs more frequently than atrial flutter or
paroxysmal supraventricular tachycardia in patients with STEMI.
The consequences and acute treatment of all 3 arrhythmias may be
considered together, recognizing that in atrial flutter and supraventricular
tachycardia, atrial pacing may be effective in terminating the tachycardia
(928-933).
Estimates of the incidence of AF in patients with STEMI vary depending
on the population sampled. In the CCP, 22% of Medicare patients
aged 65 years or older who were hospitalized for STEMI had AF (934).
In the Trandolapril Cardiac Evaluation (TRACE) study of patients
with LV dysfunction associated with STEMI, 21% had AF (935).
Among the causes of AF in the immediate post-STEMI setting are excessive
sympathetic stimulation, atrial stretch due to LV or RV dysfunction,
atrial infarction due to circumflex or right coronary lesions, pericarditis,
hypokalemia, underlying chronic lung disease, and hypoxia (807,929,936-940).
Thus, AF occurs more often in patients with larger infarcts or anterior
location of reinfarction and in those whose hospital course is complicated
by CHF, complex ventricular arrhythmias, advanced AV block, atrial
infarction, or pericarditis. Atrial fibrillation may also occur
in patients with inferior STEMI secondary to proximal right coronary
artery occlusion with compromise of flow in the sinoatrial nodal
artery, the major blood supply to the atria. In some studies, the
incidence of AF after STEMI is decreased in patients receiving fibrinolytic
therapy (929,941),
whereas in other studies, the incidence is similar (942).
In the GUSTO trial, patients treated with accelerated alteplase
and intravenous UFH had a significantly lower incidence of AF and
atrial flutter than patients treated with other fibrinolytic therapies
(25). Systemic embolization is more
frequent in patients with paroxysmal AF (1.7%) than in those without
(0.6%), with half of the embolic events occurring on the first day
of hospitalization and more than 90% occurring by the fourth day
(943). Because AF can be associated
with pericarditis, the development of PR-segment displacement on
serial ECGs may predict risk of developing AF during hospitalization
(941).
The
development of AF is associated with a worse in-hospital and long-term
prognosis. In a study of 106 780 elderly (Medicare) patients with
AF during MI, about half presented with AF and half developed AF
during hospitalization (934). The
presence of AF during hospitalization increased shortand long-term
relative mortality by 20% and 34%, respectively (Table
28) (935,944-946).
Patients who developed AF during hospitalization had a worse prognosis
than those with AF on admission (934).
Stroke rates are also increased in patients with MI and AF compared
with those without AF (944). Outcomes
appear to have improved in the fibrinolytic era for patients with
AF and STEMI compared with experience between 1981 and 1983 (942),
but a stroke rate of 3.1% in the setting of AF and STEMI (944)
emphasizes the importance of this association even in the era of
fibrinolysis.
When
AF occurs, the clinician must consider and correct, if possible,
the underlying causes. The initial clinical decision is whether
to proceed immediately to electrical cardioversion if the patient
is unstable with a rapid heart rate and hypotension, intractable
heart failure, or ischemic pain. Cardioversion should be performed
when the patient is under adequate general anesthesia or has received
medication to produce conscious sedation to avoid pain related to
delivery of the electric shock. Short-acting anesthetic drugs or
agents that produce conscious sedation are preferred because cardioversion
patients should recover rapidly after the procedure (947).
Proper synchronization of the electric shock with the QRS complex
calls for triggering by monitoring the R wave with an appropriately
selected lead. In addition to R-wave amplitude, it is important
that the monitored lead give a good view of P waves, thus facilitating
assessment of the outcome of the procedure. The initial energy delivered
with a monophasic waveform may be low (50 J) for cardioversion of
atrial flutter. Higher monophasic shock energy is required for AF
cardioversion, starting with at least 200 J. The monophasic shock
energy output is increased successively in increments of 100 J until
a maximum of 400 J is reached. Some physicians begin with higher
energies to reduce the number of shocks (and thus the total energy)
delivered (948). Energy settings
should be reduced by about 50% of those noted above for monophasic
shocks if a device that delivers a biphasic waveform is used. To
avoid myocardial damage, the interval between 2 consecutive shocks
should not be less than 1 minute (949).
The optimal paddle position remains controversial; however, the
electrodes should be in direct contact with the chest wall and not,
for example, positioned over breast tissue. There is little experience
with novel methods such as transvenous electrical cardioversion
in patients with STEMI.
When medical therapy is selected, and in the absence of CHF or severe
pulmonary disease, one of the most effective means of slowing the
ventricular rate in AF is the use of intravenous beta-adrenoceptor–blocking
agents such as metoprolol (2.5 to 5.0 mg every 2 to 5 minutes to
a total of 15 mg over 10 to 15 minutes) or atenolol (2.5 to 5.0
mg over 2 minutes to a total of 10 mg in 10 to 15 minutes). Heart
rate, blood pressure, and the ECG should be monitored, and treatment
should be halted when therapeutic efficacy is achieved or if systolic
blood pressure falls below 100 mm Hg or there is excessive bradycardia
(e.g., a heart rate below 50 bpm during treatment).
When
there are absolute contraindications to beta-adrenergic blockade
(bronchospastic lung disease or allergy), rate slowing may also
be achieved by intravenous diltiazem (20 mg [0.25 mg/kg]) over 2
minutes followed by an infusion of 10 mg/h) or verapamil (2.5 to
10 mg IV over 2 minutes; may repeat a 5- to 10-mg dose after 15
to 30 minutes). There are concerns regarding the negative inotropic
effects of these drugs and reports of increased post-STEMI mortality
in patients with LV dysfunction taking long-term, short-acting oral
diltiazem (950). Calcium antagonists,
therefore, are not recommended for long-term rate control in post-STEMI
patients; however, they may be useful for short-term rate control
in hospitalized patients when beta-blockers are absolutely contraindicated.
Amiodarone has both sympatholytic and calcium antagonistic properties,
depresses AV conduction, and is effective in controlling the ventricular
rate in patients with AF. Intravenous amiodarone is effective and
well tolerated in critically ill patients who develop rapid atrial
tachyarrhythmias refractory to conventional treatment, but its effectiveness
has not been evaluated sufficiently in patients with STEMI. In a
small observational study of critically ill patients, there was
a reduction in ventricular rate of 37 bpm after a 1-hour infusion
of 242 mg of amiodarone (951). Amiodarone
is considered a first-line agent for heart rate control in critically
ill patients (951) and a second-line
agent for those patients who are less hemodynamically unstable and
can tolerate intravenous diltiazem. Amiodarone is the preferred
agent to control repeat AF in patients with CHF or a low-output
state.
Although intravenous digoxin may effectively slow the ventricular
rate at rest, there is a delay of at least 60 minutes before onset
of a therapeutic effect in most patients, and a peak effect does
not develop for up to 6 hours. Digoxin is no more effective than
placebo in converting AF to sinus rhythm (790,792,795)
and may prolong the duration of AF (790,952).
The efficacy of digoxin is reduced in states of high sympathetic
tone, a common precipitant of paroxysmal AF. In a review of 139
episodes of paroxysmal AF recorded on Holter monitoring, there was
no difference in the ventricular rates of patients taking digoxin
and those not taking this medication (952).
Other investigators, however, have found that digoxin reduces the
frequency and severity of AF recurrence (953).
Furthermore, the combination of digoxin and atenolol has been shown
to be effective for ventricular rate control (954).
Given the availability of more effective agents, digoxin is no longer
first-line therapy for management of acute AF, but it plays a continuing
role in patients with heart failure or LV dysfunction (955).
Rapid administration of digoxin to achieve rate slowing may be accomplished
by giving intravenous digoxin (8 to 15 mcg/kg [0.6 to 1.0 mg in
a person weighing 70 kg]), with half the dose administered initially
and the additional increment in 4 hours (956).
This method provides a slower response than intravenous betaadrenoceptor
blockade or amiodarone; however, some effect on rate slowing may
be detectable in 30 minutes to 2 hours.
Given
that the databases reporting a marked increase in the risk of stroke
in post-STEMI patients with AF do not report the time duration of
AF at which stroke risk increases, it is unclear whether all post-STEMI
patients with AF, even if transient, should receive anticoagulation
or whether this aggressive posture should be reserved only for those
with sustained AF of at least a few hours’ duration. Indeed,
the clinical circumstances, in particular whether there are other
risk factors for post-STEMI stroke, should modulate the threshold
for anticoagulation in the patient with transient AF.
When
it has been determined that anticoagulation is required, either
UFH or LMWH may be used. When UFH is selected, an intravenous bolus
of 60 U/kg followed by a continuous intravenous infusion at 12 U/kg/h
to maintain an aPTT of 50 to 70 seconds (approximately 1.5 to 2
times control) should be given. Alternatively, one of the LMWHs
may be used at doses recommended by the manufacturer for full anticoagulation.
Once
rate control has been accomplished, clinicians may opt to convert
the patient to sinus rhythm to attain optimal hemodynamics and ultimately
permit discontinuation of anticoagulants. Guidelines for electrical
and chemical cardioversion for the stable patient with AF have been
formulated (955). In patients with
STEMI, special attention must be given to considerations of proarrhythmia
with many commonly used antiarrhythmic agents. The preferred agent
for intermediate or long-term use in the STEMI patient, based on
the best safety record in post-MI trials, is amiodarone. Indeed,
in a meta-analysis of 6553 randomized patients, 78% of whom were
in post-MI trials, amiodarone resulted in a relative reduction in
risk of death of 13%, which was wholly due to a greater reduction
in arrhythmic death (914). The excess
risk of pulmonary toxicity was only 1% per year. A post hoc analysis
of GUSTO-III patients with AF also addressed the relative safety
of other antiarrhythmic agents, including sotalol, in the post-STEMI
setting. In a total of 317 patients with AF who received antiarrhythmic
agents, no agent or class of agents was associated with increased
mortality (957). However, the totality
of evidence is much less compelling than for amiodarone after STEMI.
Transient AF does not obligate the patient to receive long-term
anticoagulation or antiarrhythmic agents, but if such treatment
is elected, it is appropriate to limit their use to 6 weeks if sinus
rhythm has been restored. In outpatients with paroxysmal AF, a controversy
regarding the relative merits of rate control versus maintenance
of sinus rhythm has been addressed by a large randomized clinical
trial (958). AFFIRM (Atrial Fibrillation
Follow-up Investigation of Rhythm Management) demonstrated no clear
survival benefit for either strategy. However, patients with STEMI
were not enrolled, and only 38.2% of the population had a prior
diagnosis of coronary artery disease. Thus, the conclusions of AFFIRM
should not be applied to the STEMI population, and the decision
to continue chronic adjustable-dose oral anticoagulation indefinitely
should be based on an overall assessment of the risk of thromboembolism
in the individual patient.
7.7.3.
Bradyarrhythmias
See
Table 29 for recommendations.
Sinus bradycardia occurs frequently, constituting 30% to 40% of
AMI-associated cardiac arrhythmias. It is especially frequent within
the first hour of inferior STEMI and with reperfusion of the right
coronary artery (Bezold-Jarisch reflex) as a result of increased
parasympathetic activity (vagal tone) (959).
There are several other potential mechanisms, operating in isolation
or in parallel, that account for the high incidence of sinus bradycardia.
These include local increases in adenosine, local hyperkalemia,
systemic metabolic derangements, and concomitant use of bradycardia-promoting
medications (960).
Heart block may develop in approximately 6% to 14% of patients with
STEMI. Intraventricular conduction delay has been reported in about
10% to 20% of patients with STEMI in past reviews (961).
The development of AV and intraventricular blocks during STEMI is
generally related to the extent of the ischemic/infarcted segment.
As such, AV block predicts an increased risk of in-hospital mortality
but is less predictive of long-term mortality in those who survive
to hospital discharge (962-964).
Nonetheless, in fibrinolysis trials, bundle-branch block was present
on admission in only 4% but was predictive of a substantially increased
in-hospital mortality rate (156). Indeed, the
development of sudden AV block in the setting of anterior STEMI,
once a feared complication, is quite unusual in the present CCU
population in the postreperfusion era. Thus, the use of transvenous
pacing has diminished, and the reliance on transcutaneous pacing
has increased (Table 30) (965).
7.7.3.1. Acute Treatment of Conduction
Disturbances and Bradyarrhythmias
Treatment
of the conduction disturbances and resulting bradyarrhythmias can
have either a prophylactic or therapeutic focus. The purpose of
prophylactic pacing is to prevent symptomatic or catastrophic bradycardia
by selecting and placing a transcutaneous or transvenous temporary
pacemaker. Prophylactic pacing requires the clinician to predict
which patients will develop sudden complete heart block with an
inadequate ventricular escape mechanism. Fortunately, conduction
disturbances generally occur in a stepwise fashion, so that knowledge
of the specific ECG pattern can be used to estimate the risk of
developing complete heart block and thus to guide the need for prophylactic
temporary pacing. These estimates of risk, however, must be interpreted
in the context of the risk of performing a procedure, particularly
transvenous temporary pacing, on an unstable patient in the acute
phase after STEMI, with all the attendant modern antithrombotic
therapies increasing the risk of bleeding complications. Additionally,
most of the clinically based algorithms to estimate risk of developing
complete heart block were developed in the prefibrinolytic era,
so they must be interpreted cautiously when applied to a modern
post-STEMI population. In some cases, after the development of advanced
AV block after STEMI, temporary transcutaneous or transvenous pacing
must be used to maintain a stable cardiac rhythm and adequate hemodynamics.
When the patient becomes pacemaker- dependent owing to a persistent
conduction defect, however, temporary transvenous pacing is preferred
compared with long-term transcutaneous pacing.
The
pharmacological treatment of bradycardia and AV conduction disturbances
during STEMI is a therapeutic, not prophylactic, measure. Pharmacotherapy
centers on the use of atropine at doses of 0.6 to 1.0 mg IV repeated
every 5 minutes until there is the desired effect or a total dose
of 0.04 mg/kg (2 mg for a 50-kg person) has been reached. When there
is infranodal block, however, atropine may increase the sinus rate
without affecting infranodal conduction, and so the effective ratio
of conduction may decrease, and the ventricular rate may decrease.
Other
pharmacotherapies to treat bradyarrhythmias, such as isoproterenol
and aminophylline, are not recommended because they are arrhythmogenic
and increase myocardial dia caused by beta-blockers and calcium
antagonists, although principally only when these agents have been
used in toxic doses, particularly in combination (966).
The recommendations for prophylactic treatment of AV and intraventricular
conduction blocks and the possible combinations are contained in
Table 29.
7.7.3.1.1. Ventricular Asystole.
Class I
Prompt resuscitative measures, including chest compressions, atropine,
vasopressin, epinephrine, and temporary pacing, should be administered
to treat ventricular asystole. (Level of Evidence: B)
Ventricular
asystole may be caused either by failure of the sinus node to generate
a cardiac impulse or by the development of complete heart block.
In either case, there is concurrent failure of the usual underlying
escape mechanisms, whether atrial, junctional, or ventricular. Treatment
of the acute event requires prompt institution of transcutaneous
pacing, vasopressin, epinephrine, and atropine. It is important
to address the underlying cause and discontinue medications that
either suppress sinus node function, decrease AV nodal conduction,
or suppress a potential escape mechanism. Cardiopulmonary resuscitation
according to guidelines must be instituted (900).
Transvenous pacing should be instituted unless the asystole is brief
and a precipitating cause is found (893,967,968).
Vasopressin is an effective vasopressor and is as useful as epinephrine
for the treatment of adult shockrefractory VF and pulseless electrical
activity (969). In a study of patients
with asystole out of the hospital, vasopressin use was associated
with significantly higher rates of hospital admission (29.0% versus
20.3% in the epinephrine group; p equals 0.02) and hospital discharge
(4.7% versus 1.5%, p equals 0.04). Among patients in whom spontaneous
circulation was not restored with 2 injections of either vasopressin
or epinephrine, additional treatment with epinephrine resulted in
significant improvement in the rates of survival to hospital admission
and hospital discharge in the vasopressin group but not in the epinephrine
group (hospital admission rate 25.7% versus 16.4%; p equals 0.002;
hospital discharge rate 6.2% versus 1.7%; p equals 0.002). Cerebral
performance was similar in the 2 groups (969).
Thus, in patients with STEMI with ventricular asystole, vasopressin
(40 IU) would appear to be the preferable vasoconstrictor to administer
first.
7.7.3.2.
Use of Permanent Pacemakers
7.7.3.2.1. Permanent Racing For BRADYCARDIA
Or CONDUCTION BLOCKS ASSOCIATED WITH STEMI.
Class I
1. Permanent ventricular pacing is indicated for persistent second-degree
AV block in the His-Purkinje system with bilateral bundle-branch
block or thirddegree AV block within or below the His-Purkinje system
after STEMI. (Level of Evidence: B)
2. Permanent ventricular pacing is indicated for transient advanced
second- or third-degree infranodal AV block and associated bundle-branch
block. If the site of block is uncertain, an EP study may be necessary.
(Level of Evidence: B)
3. Permanent ventricular pacing is indicated for persistent and
symptomatic second- or third-degree AV block. (Level of Evidence:
C)
Class IIb
Permanent ventricular pacing may be considered for persistent second-
or third-degree AV block at the AV node level. (Level of Evidence:
B)
Class III
1. Permanent ventricular pacing is not recommended for transient
AV block in the absence of intraventricular conduction defects.
(Level of Evidence: B)
2. Permanent ventricular pacing is not recommended for transient
AV block in the presence of isolated left anterior fascicular block.
(Level of Evidence: B)
3. Permanent ventricular pacing is not recommended for acquired
left anterior fascicular block in the absence of AV block. (Level
of Evidence: B)
4. Permanent ventricular pacing is not recommended for persistent
first-degree AV block in the presence of bundle-branch block that
is old or of indeterminate age. (Level of Evidence: B)
Indications
for permanent pacing after STEMI in patients experiencing AV block
are related in large measure to the presence of intraventricular
conduction defects (Table 29).
Unlike some other indications for permanent pacing, the criteria
for patients with STEMI and AV block do not necessarily depend on
the presence of symptoms. Furthermore, the requirement for temporary
pacing in STEMI does not by itself constitute an indication for
permanent pacing (3).
The
long-term prognosis for survivors of STEMI who have had AV block
is related primarily to the extent of myocardial injury and the
character of intraventricular conduction disturbances rather than
the AV block itself (970-974).
Patients with STEMI who have intraventricular conduction defects,
with the exception of isolated left anterior fascicular block, have
an unfavorable short- and long-term prognosis and an increased risk
of sudden death (970,971,973,975).
This unfavorable prognosis is not necessarily due to development
of high-grade AV block, although the incidence of such block is
higher in postinfarction patients with abnormal intraventricular
conduction (971,976,977).
When
AV or intraventricular conduction block complicates STEMI, the type
of conduction disturbance, location of infarction, and relation
of electrical disturbance to infarction must be considered if permanent
pacing is contemplated. Even with data available, the decision is
not always straightforward because the reported incidence and significance
of various conduction disturbances vary widely (978).
Despite the use of fibrinolytic therapy and primary PCI, which have
decreased the incidence of AV block in STEMI, mortality remains
high if AV block occurs (962,979-981).
Although
more severe disturbances in conduction are generally associated
with greater arrhythmic and nonarrhythmic mortality (971-974,976,978),
the impact of pre-existing bundle- branch block on mortality after
STEMI is controversial (978,982).
A particularly ominous prognosis is associated with LBBB combined
with advanced second- or third-degree AV block and with right bundle-branch
block combined with left anterior or left posterior fascicular block
(964,972,974,982)
(Figure 33). Irrespective of whether
the infarction is anterior or inferior, the development of an intraventricular
conduction delay reflects extensive myocardial damage rather than
an electrical problem in isolation (974).
Although AV block that occurs during inferior STEMI can be associated
with a favorable long-term clinical outcome, inhospital survival
is impaired, regardless of the use of temporary or permanent pacing
in this situation (964,979,980,983).
Furthermore, pacemakers should not be implanted if the periinfarctional
AV block is expected to resolve or to not have a negative effect
on long-term prognosis, as in the case of inferior STEMI (981)
with Mobitz I second-degree AV block.
With
regard to sinus node dysfunction precipitated or unmasked by STEMI
or associated necessary medical therapy, the indications for permanent
pacing do not differ from the indications.
7.7.3.2.2.
Sinus Node Dysfunction After STEMI
Class I
Symptomatic sinus bradycardia, sinus pauses greater than 3 seconds,
or sinus bradycardia with a heart rate less than 40 bpm and associated
hypotension or signs of systemic hemodynamic compromise should be
treated with an intravenous bolus of atropine 0.6 to 1.0 mg. If
bradycardia is persistent and maximal (2 mg) doses of atropine have
been used, transcutaneous or transvenous (preferably atrial) temporary
pacing should be instituted. (Level of Evidence: C)
Sinus node dysfunction may be unmasked or caused by MI owing to
disruption in the blood supply to the sinoatrial node, or owing
to the use of medications such as beta-adrenergic blocking agents
or calcium antagonists. The overall recommendations, indications,
and levels of evidence are not different in non-MI and patients
with STEMI, except that transient sinus bradycardia often occurs
in the setting of inferior wall infarction, and treatment should
avoid permanent pacing whenever possible. Thus, the published ACC/
AHA/NASPE 2002 Guideline Update for Implantation of Cardiac Pacemakers
and Antiarrhythmia Devices (984)
should be used to guide therapy in patients with STEMI with persistent
sinus node dysfunction. These guidelines should be applied with
the proviso that new sinus node dysfunction that has first appeared
during STEMI may be reversible, and when clinically possible, the
decision to implant a permanent pacemaker should be delayed several
days.
7.7.3.2.3.
Pacing Mode Selection In STEMI Patients
Class I
All patients who have an indication for permanent pacing after STEMI
should be evaluated for ICD indications. (Level of Evidence:
C)
Class IIa
1. It is reasonable to implant a permanent dual-chamber pacing system
in STEMI patients who need permanent pacing and are in sinus rhythm.
It is reasonable that patients in permanent AF or atrial flutter
receive a single-chamber ventricular device. (Level of Evidence:
C)
2. It is reasonable to evaluate all patients who have an indication
for permanent pacing after STEMI for biventricular pacing (cardiac
resynchronization therapy). (Level of Evidence: C)
With regard to permanent pacing mode, there are no randomized trials
that specifically address pacing mode selection (dual-chamber versus
single-chamber ventricular pacing, with or without rate modulation)
in patients with STEMI. In general, patients who need permanent
pacing systems and are in sinus rhythm should receive a permanent
dual-chamber pacemaker. In contrast, patients who have permanent
AF or atrial flutter should receive a ventricular-pacing system.
In post-STEMI patients with frequent episodes of paroxysmal AF or
a persistent episode for which eventual cardioversion is planned,
the clinician must judge the likelihood of the patient being in
sinus rhythm chronically before selecting a permanent dual-chamber
or ventricular device. The data from randomized trials of pacing
mode selection, although admittedly not obtained in a post-STEMI
population, suggest specific programming features and goals to improve,
or at least not further impair, LV function due to forced ventricular
desynchronization by RV pacing. The DAVID (Dual Chamber and VVI
Implantable Defibrillator ) trial in ICD patients without bradycardia
but with LV dysfunction demonstrated that patients programmed to
DDD at 70 bpm developed more heart failure than did patients programmed
to VVI backup at a low rate (985).
A post hoc analysis of the Mode Selection Trial (MOST) reported
that in dual-chamber–paced patients with sinus node dysfunction
and a median ejection fraction of 0.55, cumulative percent ventricular
pacing above 40% was associated with an increase in heart failure
hospitalizations. These emerging data suggest that when bradycardia
pacing is instituted, the clinician might consider minimizing ventricular
dyssynchrony through selection of devices and programming strategies
to maintain low cumulative percent ventricular pacing (986).
Whether the clinical application of these concepts will improve
post-STEMI outcomes is unknown because these studies did not address
the specific population on which these guidelines focus. Thus, the
Committee has chosen not to incorporate these programming recommendations
into the guidelines, pending the design and execution of more applicable
prospective trials.
Nonetheless,
when a permanent pacemaker is being considered for a post-STEMI
patient, the clinician should address 2 additional questions regarding
the patient: is there an indication for biventricular pacing, and
is there an indication for ICD use? (986)
Biventricular pacing has found a place in the treatment of advanced
heart failure for patients with a low ejection fraction and a QRS
duration greater than 130 ms (984).
Patients with severe LV dysfunction may be eligible for implantation
of an ICD for primary prevention of life-threatening ventricular
arrhythmia, as well as bradycardia support. The algorithm to define
whether an ICD is indicated is contained in Figure
32. See Section 7.7.1.5 for further discussion.
7.8.
Recurrent Chest Pain After STEMI
The 2 most common cardiac causes of recurrent chest pain after STEMI
are pericarditis and ischemia, the latter being the more common
and potentially more serious. An ECG taken during the recurrent
pain should be compared with ECGs from the index STEMI event (987).
Usually, recurrent pain within the first 12 hours after onset of
STEMI is considered to be related to the original infarction itself.
Pericarditis is probably not responsible for significant chest discomfort
in the first 24 hours.
7.8.1.
Pericarditis
Class I
1. Aspirin is recommended for treatment of pericarditis after STEMI.
Doses as high as 650 mg orally (entericcoated) every 4 to 6 hours
may be needed. (Level of Evidence: B)
2. Anticoagulation should be immediately discontinued if pericardial
effusion develops or increases. (Level of Evidence: C)
Class IIa
For episodes of pericarditis after STEMI that are not adequately
controlled with aspirin, it is reasonable to administer 1 or more
of the following:
a. Colchicine 0.6 mg orally every 12 hours (Level of Evidence:
B)
b. Acetaminophen 500 mg orally every 6 hours. (Level of Evidence:
C)
Class IIb
1. Corticosteroids might be considered only as a last resort in
patients with pericarditis refractory to aspirin or NSAIDs. Although
corticosteroids are effective for pain relief, their use is associated
with an increased risk of scar thinning and myocardial rupture.
(Level of Evidence: C)
2. Nonsteroidal anti-inflammatory drugs may be considered for pain
relief; however, they should not be used for extended periods because
of their effect on platelet function, an increased risk of myocardial
scar thinning, and infarct expansion. (Level of Evidence: B)
Class III
Ibuprofen should not be used for pain relief because it blocks the
antiplatelet effect of aspirin and it can cause myocardial scar
thinning and infarct expansion. (Level of Evidence: B)
Pericarditis in STEMI occurs with extension of necrosis across the
full thickness of the myocardial wall to the epicardium. Patients
with pericarditis have larger infarcts, a lower ejection fraction,
and a higher incidence of CHF (988,989).
Pericarditis may appear up to several weeks after STEMI. Anterior
chest discomfort mimicking ischemia can occur with pericarditis.
However, pericardial pain usually has distinguishing characteristics,
such as pleuritic and/or positional discomfort; radiation to the
left shoulder, scapula, or trapezius muscle; and a pericardial rub,
ECG J-point elevation with concave upward ST-segment elevation and
PR depression. Detection of a 3-component rub is diagnostic of pericarditis.
Pericardial effusion is evident echocardiographically in more than
40% of cases (990) but is rarely
of hemodynamic consequence. A small effusion is not diagnostic of
pericarditis because it can be demonstrated in the majority of patients
with STEMI (991). On occasion, pericarditis
may be a clinical clue to the presence of subacute myocardial rupture
(see Section 7.6.7.4).
Focal
pericarditis can be diagnosed electrocardiographically by either
persistently positive T waves or reversal of initially inverted
T waves during the first week after STEMI. However, similar T-wave
alterations have also been observed when postinfarction pericardial
effusion exists in the absence of clinically recognized pericarditis
(992). Pericarditis is not associated
with re-elevation of CK-MB. There are data suggest its incidence
has decreased in the reperfusion era (993-995).
Interestingly, the Dressler syndrome (post-MI syndrome), an autoimmune-type
carditis, has essentially disappeared (996)
in the reperfusion era.
Neither
the configuration of the ECG nor the absence presence of the cardiac
markers can absolutely establish diagnosis of, or rule out, pericarditis.
Jain described anterior ST-segment elevation secondary to acute
pericarditis (997). Bonnefoy et
al. studied 69 consecutive patients with idiopathic acute pericarditis
(998). Cardiac troponin I was detected
in 34 patients (49%), and the level of troponin was beyond the 1.5
ng/ml threshold in 15 (22%). Seven of these patients underwent coronary
angiography. All 7 patients had normal coronary angiograms. ST-segment
elevation was found in 93% of the patients with troponin I greater
than 1.5 ng/ml compared with 57% without troponin elevation (p less
than 0.01). Patients with cardiac troponin I higher than 1.5 ng/ml
were more likely to have had a recent infarction (66% versus 31%;
p equals 0.01) and were younger (age 37 plus minus 14 years versus
52 plus or minus 16 years; p equals 0.002).
Aspirin
(162 to 325 mg/d) is the treatment of choice, but higher doses (650
mg every 4 to 6 hours) may be required (956,999).
Nonsteroidal anti-inflammatory drugs may considered for pain relief;
however, they should not be used for extended periods because of
their effect on platelet function, an increased risk of myocardial
scar thinning, and infarct expansion. Corticosteroids, which are
also efficacious for pain relief, are associated with scar thinning
in the infarct zone and myocardial rupture (1000,1001).
Therefore, corticosteroids should not be used except as a last resort.
The riskbenefit ratio of continuing antithrombotic therapy in the
presence of acute pericarditis always presents a clinical challenge.
Usually such therapy can be continued safely but requires added
vigilance for the detection of enlarging pericardial effusion or
signs of hemodynamic instability. Any evidence of impending cardiac
tamponade is an indication for prompt termination of antithrombotic
therapy.
If
NSAIDs are used, misoprostol, 200 mcg every 6 hours, should be used
for gastric and renal protection (1002-1004).
On the basis of the proven efficacy of colchicine therapy for familial
Mediterranean fever, several small studies showed that colchicine
could successfully treat or prevent the recurrence of acute pericarditis
after conventional therapy, including corticosteroid therapy, had
failed (1005). Colchicine may be
administered at 0.6 mg every 12 hours, with or without loading dose
(1006-1008).
7.8.2.
Recurrent Ischemia/Infarction
Class
I
1.
Patients with recurrent ischemic-type chest discomfort after initial
reperfusion therapy for STEMI should undergo escalation of medical
therapy with nitrates and beta-blockers to decrease myocardial oxygen
demand and reduce ischemia. Intravenous anticoagulation should be
initiated if not already accomplished. (Level of Evidence: B)
2. In addition to escalation of medical therapy, patients with recurrent
ischemic-type chest discomfort and signs of hemodynamic instability,
poor LV function, or a large area of myocardium at risk should be
referred urgently for cardiac catheterization and undergo revascularization
as needed. Insertion of an IABP should also be considered. (Level
of Evidence: C)
3.
Patients with recurrent ischemic-type chest discomfort who are considered
candidates for revascularization should undergo coronary arteriography
and PCI or CABG as dictated by coronary anatomy. (Level of Evidence:
B)
Class
IIa
It is reasonable to (re)administer fibrinolytic therapy to patients
with recurrent ST elevation and ischemictype chest discomfort who
are not considered candidates for revascularization or for whom
coronary angiography and PCI cannot be rapidly (ideally less than
60 minutes from the onset of recurrent discomfort) implemented.
(Level of Evidence: C)
Class
III
Streptokinase should not be readministered to treat recurrent ischemia/infarction
in patients who received a non–fibrin-specific fibrinolytic
agent more than 5 days previously to treat the acute STEMI event.
(Level of Evidence: C)
It is important to differentiate pain due to pericarditis from pain
due to ischemia. The latter is more likely when the chest pain is
similar to the initial ischemic-type chest discomfort, occurring
at rest or with limited activity during hospitalization. This may
or may not be associated with re-elevation of the CK-MB, ST-segment
depression or elevation, or pseudonormalization of inverted T waves
(T-wave inversion on baseline ECG becoming upright during ischemia)
(990).
Reinfarction
occurs in 4% to 5% of patients who have received fibrinolytic therapy
and aspirin (25,43,851,1009,1010).
Reinfarction is associated with reelevation of biomarkers after
the initial peak of the index infarction. Diagnosis of reinfarction
within 18 hours after initiation of fibrinolytic therapy should
be based on recurrence of severe ischemic-type chest discomfort
that lasts at least 30 minutes, usually but not always accompanied
by recurrent ST-segment elevation of at least 0.1 mV in at least
2 contiguous ECG leads and re-elevation of CK-MB to more than the
upper limit of normal or increased by at least 50% over the previous
value (37). Pathological findings
of rein-farction show areas of healing myocardium along with the
more recent necrosis, usually in the same vascular risk region of
myocardial tissue perfused by the original infarct-related artery.
Death, severe CHF, and arrhythmias are early complications of reinfarction,
and there is an increased incidence of cardiogenic shock or cardiac
arrest (25,43,1011).
An algorithm for diagnosing reinfarction both early and late after
fibrinolytic therapy is shown in Figure
12. In patients with recurrent MI after fibrinolysis, the mortality
rate is increased up to 2 years; however, most of the deaths occur
early (in the hospital), with little additional risk of death between
the index hospitalization and 2 years later (512).
Patients with recurrent ischemic-type chest discomfort should undergo
escalation of medical therapy, including beta-blockers (intravenously
and then orally) and nitrates (sublingually and then intravenously);
consideration should be given to initiation of intravenous anticoagulation
if the patient is not already therapeutically anticoagulated. Secondary
causes of recurrent ischemia, such as poorly controlled heart failure,
anemia, and arrhythmias, should be corrected (Figure
34) (1012).
With
recurrent suspected ischemic-type chest discomfort, coronary arteriography
often clarifies the cause of chest discomfort with demonstration
of a high-grade coronary obstruction. For patients who are considered
candidates for revascularization, prompt reperfusion with PCI or
CABG is indicated as dictated by the coronary anatomy (Figure
34) (509,515,1012).
For patients who are not considered candidates for revascularization
or for whom coronary angiography and PCI cannot be implemented rapidly
(ideally in less than 60 minutes), readministration of fibrinolytic
therapy is reasonable.
Another cause of chest discomfort to consider in patients recovering
from STEMI is infarct expansion. This is characterized by nonspecific
repolarization of abnormalities on the ECG, worsening hemodynamics,
but no re-elevation of cardiac biomarkers (43).
Management of infarct expansion should focus on diuresis and inhibition
of the reninangiotensin- aldosterone system (see Section
7.4.3).
7.9. Other Complications
7.9.1. Ischemic Stroke
Class I
1. Neurological consultation should be obtained in STEMI patients
who have an acute ischemic stroke. (Level of Evidence: C)
2.
STEMI patients who have an acute ischemic stroke should be evaluated
with echocardiography, neuroimaging, and vascular imaging studies
to determine the cause of the stroke. (Level of Evidence: C)
3. STEMI patients with acute ischemic stroke and persistent AF should
receive lifelong moderate-intensity (INR 2 to 3) warfarin therapy.
(Level of Evidence: A)
4. STEMI patients with or without acute ischemic stroke who have
a cardiac source of embolism (AF, mural thrombus, or akinetic segment)
should receive moderate- intensity (INR 2 to 3) warfarin therapy
in addition to aspirin (see Figure
35). The duration of warfarin therapy should be dictated by
clinical circumstances (e.g., at least 3 months for patients with
an LV mural thrombus or akinetic segment and indefinitely in patients
with persistent AF). The patient should receive LMWH or UFH until
adequately anticoagulated with warfarin. (Level of Evidence:
B)
Class IIa
1. It is reasonable to assess the risk of ischemic stroke in patients
with STEMI. (Level of Evidence: A)
2.
It is reasonable that STEMI patients with nonfatal acute ischemic
stroke receive supportive care to minimize complications and maximize
functional outcome. (Level of Evidence: C)
Class IIb
Carotid angioplasty/stenting, 4 to 6 weeks after ischemic stroke,
might be considered in STEMI patients who have an acute ischemic
stroke attributable to an internal carotid artery–origin stenosis
of at least 50% and who have a high surgical risk of morbidity/mortality
early after STEMI. (Level of Evidence: C)
Acute stroke complicates 0.75% to 1.2% of MIs and is one of the
most dreaded outcomes of STEMI (326,1013,1014).
Although survival from STEMI has been increasing, mortality from
post-STEMI stroke remains over 40% (1013).
Prior stroke, hypertension, old age, decreased ejection fraction
or multiple ulcerated plaques, and AF are the major risk factors
for embolic stroke after STEMI (326,944,1015-1017).
Anterior STEMI is often cited as a risk factor, but other infarct
locations appear to have similar risk (1015,1018).
AF is by far the most important of these risk factors (1019).
In the SAVE trial (1017), decreased
ejection fraction (18% increased risk per every 5% decrease in ejection
fraction) was independently associated with long-term stroke risk
in patients with STEMI. Thrombus formation is promoted by extensive
wall-motion abnormality, such as anteroapical akinesia or dyskinesia,
and Killip class III or IV (1020).
Embolic stroke after STEMI originates from LV thrombus or from the
left atrium in the setting of AF and occurs even in patients treated
with fibrinolysis (1015). It does
not appear to be useful to test patients with STEMI, even with mural
thrombus formation, for prothrombotic syndromes such as factor V
Leiden mutation (1021). Several
studies in patients with STEMI suggest that aggressive short- and
long-term anticoagulation may reduce but not totally prevent mural
thrombus formation (744,1022,1023)
and occurrence of stroke (1024-1028).
Most ischemic cerebral infarctions after fibrinolytic therapy for
STEMI occur more than 48 hours after treatment (218,320,322,586).
The highest-risk period is the first 28 days after STEMI (1014),
but risk is elevated at least to 1 year. In GUSTO-I (1015),
Mahaffey et al. found that the risk of ischemic stroke after coronary
fibrinolysis may be predicted (1015).
Prospective studies are needed to verify this observation. Compared
with ICH, patients with ischemic cerebral infarction present more
commonly with focal neurological deficits and less commonly with
depressed level of consciousness; headache, vomiting, and coma are
uncommon (360).
An
algorithm for evaluation and antithrombotic therapy for ischemic
stroke is shown in Figure 35.
If the STEMI patient has sudden onset of a focal neurological deficit
and the initial CT scan is negative for blood or mass effect, then
ischemic cerebral dysfunction may be presumed in the absence of
a severe metabolic disorder, seizures, autoimmune disease, or cancer.
Neurological consultation is recommended to assist with planning
the neurovascular evaluation and management issues. The location
and nature of the ischemic brain lesion should be defined with repeat
CT scan or magnetic resonance imaging scan. Vascular lesions should
be evaluated with noninvasive techniques, such as carotid duplex
sonography, transcranial Doppler, magnetic resonance angiography,
CT angiography, or transesophageal echocardiography. For carotid
territory symptoms and signs, evidence for a surgically important
stenosis (greater than 50% linear diameter reduction on a catheter-based
cerebral angiogram using the North American Symptomatic Carotid
Endarterectomy Trial [NASCET] method) (1029)
should clearly be sought.
The
subacute to chronic pathophysiology of STEMI provides a rationale
for clinicians to consider when choosing antithrombotic therapies
for stroke prevention and treatment in this setting. A hypercoagulable
state may exist for up to 6 months after STEMI (1030).
This state may be accentuated by withdrawal of heparin and warfarin
therapy (555).
In
ISIS-2 (1031), use of aspirin
was shown to reduce the occurrence of ischemic stroke. Thus, aspirin
administration after STEMI, with or without ischemic cerebral infarction,
is appropriate. However, for patients with ischemic cerebral infarction
who undergo PCI and have no cardioembolic risk factors, the use
of clopidogrel 75 mg/d (for at least 12 months) plus aspirin 75
to 162 mg/d (indefinitely) after STEMI is reasonable (578,728,1032).
Patients with STEMI who have ischemic stroke but do not undergo
PCI and do not have a cardiac source of embolism or surgically important
carotid stenosis may be treated with aspirin/ extended-release dipyridamole
25/200 mg plus aspirin 81 mg/d (1033).
A subgroup analysis from the CAPRIE trial (1032)
in patients with a prior history of ischemic events suggested a
benefit of clopidogrel (mean duration of treatment 1.6 years) over
aspirin for the composite end point of ischemic stroke, MI, or vascular
death (3.4% ARD, 95% CI 0.2 to 7.0; 14.9% RRR; p equals 0.045).
Thus, for the STEMI patient who has an ischemic stroke without a
documented cardiac source of embolism while on aspirin therapy,
clopidogrel may be added for a period of 18 months.
Patients with cardiogenic sources of embolism, such as AF, LV mural
thrombi, or akinetic segment of the LV myocardium, should receive
moderate-intensity (INR 2 to 3) warfarin anticoagulation in combination
with aspirin. The duration of moderate-intensity warfarin anticoagulation
will vary according to the underlying strong source of cardiogenic
embolism. Ischemic stroke patients with pre-existing or persistent
AF require lifelong warfarin therapy (958),
irrespective of 2-dimensional echocardiography findings. In general,
patients with STEMI with LV mural thrombus should receive 3 months
of warfarin therapy, a time believed to be sufficiently long for
clot adherence and re-endothelialization to occur, leading to reduced
embolic risk. However, if followup 2-dimensional echocardiography
at 3 months in the STEMI patient with acute ischemic stroke shows
findings that suggest an ongoing risk of cardiogenic embolism (e.g.,
new or enlarging mural thrombi or thrombi that are pedunculated
or mobile), then long-term moderate-intensity warfarin anticoagulation
is recommended.
If
a surgically important internal carotid artery stenosis that explains
the clinical findings is found, either carotid endarterectomy (1029,1034,1035)
or carotid angioplasty with stenting and a distal protection device
(1036,1037)
(Yadav J; oral presentation, 2002 American Heart Association Annual
Scientific Session, November 2002, Chicago, IL) could be performed.
If surgical morbidity and mortality are acceptable, carotid endarterectomy
may be performed 4 to 6 weeks after cerebral infarction. Preliminary
data from 307 randomized patients in the Stenting and Angioplasty
with Protection in Patients at High Risk for Endarterectomy (SAPPHIRE)
trial (Yadav J; oral presentation, 2002 American Heart Association
Annual Scientific Session, November 2002, Chicago, IL) showed a
significant reduction in the composite end point of 30-day death,
STEMI/NSTEMI, or stroke in the stent arm compared with the endarterectomy
arm (5.8% versus 12.6%, p equals 0.047). There was no difference
in the occurrence of TIAs or major bleeding between the 2 groups,
although the occurrence of cranial nerve injury was significantly
higher in the endarterectomy arm (0% versus 5.3%, p less than 0.01).
Oneyear follow-up data are pending.
7.9.2. Deep Venous Thrombosis and Pulmonary
Embolism
Class I
1. Deep venous thrombosis or pulmonary embolism after STEMI should
be treated with full-dose LMWH for a minimum of 5 days and until
the patient is adequately anticoagulated with warfarin. Start warfarin
concurrently with LMWH and titrate to INR of 2-3. (Level of
Evidence: A)
2. Patients with CHF after STEMI who are hospitalized for prolonged
periods, unable to ambulate, or considered at high risk for DVT
and are not otherwise anticoagulated should receive low-dose heparin
prophylaxis, preferably with LMWH. (Level of Evidence: A)
Prevention. Deep venous thrombosis and pulmonary embolism
historically were relatively frequent complications of STEMI, but
in the current era in which patients with STEMI almost universally
receive anticoagulants, specific prophylaxis is seldom needed (1039).
For patients with CHF after STEMI who are hospitalized for prolonged
periods or unable to ambulate and who are not otherwise anticoagulated,
the best evidence of safety and efficacy supports the use of low-dose
LMWH (1040). Dosing depends on
the specific LMWH chosen, and product-specific information should
be consulted at the time of treatment.
Treatment. A high index of suspicion for DVT and pulmonary
embolism is necessary, and patients suspected of having either condition
should be evaluated immediately with an appropriate evidence-based
diagnostic strategy (1041). Most
patients with DVT or pulmonary embolism should be anticoagulated
with LMWH. It is at least as effective as UFH in clinical trials,
and a meta-analysis suggests offers a lower total mortality (1042).
Outside of carefully supervised clinical trials, LMWH is generally
superior, because overshooting and undershooting the therapeutic
range is commonplace with UFH in routine clinical practice. Low-molecular-weight
heparin is less costly overall because it avoids intravenous administration
and frequent laboratory testing. Dosing of LMWH depends on the specific
product, and product-specific information should be consulted at
the time of treatment. Warfarin should be initiated concurrently
with LMWH, and LMWH should be continued until the INR reaches the
therapeutic range of 2 to 3 (1041,1043).
Warfarin should be continued for a duration specific to the individual
patient’s risk profile (1044).
Patients with contraindications to anticoagulation with heparins
will require alternative therapies, and some will require placement
of an inferior vena cava filter. Detailed discussion of warfarin
therapy duration, alternative anticoagulants, and vena cava filter
placement criteria are beyond the scope of this guideline, and the
reader should consult an evidence-based guideline on venous thromboembolic
disease (1041,1043).
7.10. Coronary Artery Bypass Graft Surgery
After STEMI
7.10.1. Timing of Surgery
Class IIa
In patients who have had a STEMI, CABG mortality is elevated
for the first 3 to 7 days after infarction, and the benefit of revascularization
must be balanced against this increased risk. Patients who have
been stabilized (no ongoing ischemia, hemodynamic compromise, or
life-threatening arrhythmia) after STEMI and who have incurred a
significant fall in LV function should have their surgery delayed
to allow myocardial recovery to occur. If critical anatomy exists,
revascularization should be undertaken during the index hospitalization.
(Level of Evidence: B)
There are no clear data regarding optimal timing of bypass surgery
after STEMI (518,1045-1047).
Most published studies are retrospective and observational in nature,
with heterogenous patient cohorts and differences in inclusion criteria.
Moreover, many patients undergoing emergency surgery tend to have
comorbidities and risk factors, including decreased LV function,
which are normally associated with an increase in operative mortality.
Coronary
artery bypass grafting early after STEMI may carry substantial risk,
particularly in unstable patients with Q-wave infarction and decreased
LV function. Prior CABG, female gender, and advanced age compound
this risk considerably (1045).
Lee et al. (1048) reviewed 44
365 patients from New York State undergoing CABG. Mortality for
those with or without a history of MI was 3.1% and 1.6%, respectively.
Mortality was higher for patients with transmural infarction who
underwent surgery within the first 24 hours (12.1% at less than
6 hours, 13.6% at 6 to 23 hours). At 2 weeks, mortality was 2.6%.
Mortality for patients with nontransmural MIs was also elevated
(11.5% at less than 6 hours, 6.2% at 6 to 23 hours) (Table
31) (1048). In another large
series of 2296 patients undergoing CABG after MI, Creswell et al.
reported mortality from surgery to be 9.1% at less than 6 hours
after MI, 8.3% at 6 to 48 hours, 5.2% at 2 to 14 days, 6.5% at 2
to 6 weeks, and 2.9% at greater than 6 weeks. Urgency of surgery
was the most important predictor of operative mortality (1049).
When adjustments were made for the independent risk factors of urgency
of operation, increased patient age, renal insufficiency, number
of previous MIs, and hypertension, the timing between MI and CABG
was not a significant predictor for death.
In reviewing 11 retrospective and prospective observational studies
regarding CABG and MI, Crossman et al. (1046)
concluded that timing of surgery after infarction was not necessarily
an independent predictor of outcome. However, these studies did
“appear to support an approach of medical stabilization for
unstable patients post MI wherever possible to convert high risk
emergency operations to lower risk more elective procedures”
(1046). The Writing Committee believes
that if stable patients with STEMI with preserved LV function require
surgical revascularization, then CABG can be undertaken within several
days of the infarction without an increased risk. In addition, surgery
for patients who have mechanical complications of MI, such as VSR
or papillary muscle rupture, or who have ongoing ischemia that has
been unresponsive to other medical therapy and have vessels suitable
for bypass, cannot usually be delayed. However, patients who have
had a significant decrease in LV function as a result of STEMI and
who are hemodynamically stable may benefit from a longer period
of medical treatment to allow myocardial recovery to occur before
surgical revascularization is undertaken. If a patient has critical
coronary anatomy, such as greater than 75% left main coronary artery
stenosis, then CABG should be undertaken during the same hospitalization.
(See Section 3.2.2 of the ACC/AHA
Guidelines for Coronary Artery Bypass Graft Surgery (518).)
7.10.2. Arterial Grafting
Class I
An internal mammary artery graft to a significantly stenosed LAD
should be used whenever possible in patients undergoing CABG after
STEMI. (Level of Evidence: B)
The routine use of the left internal mammary artery (IMA) for LAD
grafting, with supplemental saphenous vein grafts to other coronary
lesions, is generally accepted as the standard grafting method.
A large, long-term follow-up study comparing patients receiving
the left IMA-to-LAD and supplemental vein grafts to patients receiving
saphenous vein grafts only demonstrated a significantly lower rate
of recurrent angina and MI, a lower incidence of reoperation or
PCI, and a higher actuarial 10-year survival among patients with
IMA grafts (1050). Despite the
clear advantage of the IMA graft, not all patients receive arterial
grafts. In the PAMI-2 trial (522)
of 120 patients undergoing surgery, only 31% received an IMA graft;
no patients had cardiogenic shock at the time of surgery. On the
other hand, Hirose et al. (1051)
used arterial conduits in 96% of 47 patients undergoing emergency
CABG within a mean of 27 hours from infarction, and operative mortality
was 6.4%. In a further study, Hirotani et al. (1052)
performed CABG on 68 patients within 30 days of infarction, with
a mortality rate of 7.4%. CABG without arterial grafts was the sole
predictor of an adverse survival. Although surgeons may be reluctant
to use the IMA in patients after STEMI because of limited flow through
the arterial graft and the time necessary to harvest it, the data
suggest that IMA grafts can be used safely soon after STEMI with
no increase in mortality; their use is associated with better long-term
survival.
7.10.3.
Coronary Artery Bypass Graft Surgery After Fibrinolytic Therapy
In the 3339 patients enrolled in the TIMI-II trial, CABG was performed
as an emergency procedure (1.6%) or electively (10% during initial
hospitalization), primarily for left main coronary stenosis or coronary
anatomy not amenable to PCI and continuing, recurrent, or exercise-induced
ischemia (1053). Of the 41 021
patients enrolled in the GUSTO-I trial, CABG was used in 8.6% at
a mean of 8.5 days after fibrinolytic therapy (1054).
Unstable patients undergoing CABG shortly after fibrinolytic therapy,
primarily for continuing myocardial ischemia, have a higher operative
mortality rate (13% to 17%) and increased use of blood products
(1053,1055,1056)
than hemodynamically stable patients operated on within 8 hours
of fibrinolytic therapy, who have a relatively low (2.8%) mortality
rate (1057). The only independent
predictor of perioperative mortality in TIMI-II was performance
of CABG within 24 hours of entry or PCI. The low 1-year mortality
rate (2.2%) noted for operative survivors in this group may support
the use of emergency operation for selected patients, however (1053).
In the SHOCK trial (301), CABG was
as successful as PCI in reducing mortality in patients with cardiogenic
shock, although they had more complex coronary artery anatomy. The
intraoperative use of aprotinin may reduce hemorrhage related to
use thrombolytic agents (1058).
7.10.4.
Coronary Artery Bypass Graft Surgery for Recurrent Ischemia After
STEMI
Class
I
Urgent CABG is indicated if the coronary angiogram reveals anatomy
that is unsuitable for PCI. (Level of Evidence: B)
Coronary artery bypass graft surgery should be considered
when recurrent ischemia occurs in patients with STEMI whose coronary
artery anatomy is not suitable for PCI. Operative mortality in such
patients is correlated closely with ejection fraction, and for patients
with normal ejection fraction, it is nearly the same as that of
elective CABG (1059-1061).
The survival benefit for patients with reduced LV function supports
the use of CABG in this situation.
7.10.5.
Case Selection Concerns in CABG After STEMI
As cardiac surgical programs and individual surgeons come under
scrutiny with regard to operative mortality rates, concern has been
raised about the possibility that salvageable but high-risk patients
may not be offered surgery. Omoigui et al. (1062)
suggested that the reduction in mortality noted in New York State
was caused by an outmigration of high-risk patients due to the increased
scrutiny provoked by public release of mortality data. In a survey
of New York State cardiac surgeons, Burack et al. (1063)
reported that many surgeons refused to operate on at least 1 high-risk
patient over the prior year, primarily because of public reporting.
The Writing Committee believes strongly that patients should be
offered surgical treatment if the treating team believes that the
benefits outweigh the risks and that meaningful survival of the
patient could result. Furthermore, appropriately validated risk-adjusted
outcome measures should be used when evaluating the performance
of an individual surgeon or surgical program. The ACC/AHA Guideline
Update on Coronary Artery Bypass Graft Surgery has addressed the
issue of institutional and individual surgical caseloads (518).
Studies suggest that survival after CABG has improved over the last
decade but is negatively affected when the surgery is performed
in institutions that do fewer than a threshold of 200 cases per
year. However, some institutions and practitioners maintain excellent
outcomes despite relatively low volumes. In reviewing the outcome
of 13 644 CABG procedures at 56 US hospitals, mortality was significantly
lower at high-volume hospitals only for those patients considered
as being at high or moderate risk (1064).
Therefore, targeted transfer of high- to moderate-risk post-STEMI
patients to high-volume institutions may be appropriate.
7.10.6. Elective CABG After STEMI in
Patients With Angina
Class I
1. Coronary artery bypass graft surgery is recommended for patients
with stable angina who have significant left main coronary artery
stenosis. (Level of Evidence: A)
2.
Coronary artery bypass graft surgery is recommended for patients
with stable angina who have left main equivalent disease: significant
(at least 70%) stenosis of the proximal LAD and proximal left circumflex
artery. (Level of Evidence: A)
3. Coronary artery bypass graft surgery is recommended for patients
with stable angina who have 3-vessel disease. (Survival benefit
is greater when LVEF is less than 0.50.). (Level of Evidence:
A)
4. Coronary artery bypass graft surgery is beneficial for patients
with stable angina who have 1- or 2-vessel coronary disease without
significant proximal LAD stenosis but with a large area of viable
myocardium and high-risk criteria on noninvasive testing. (Level
of Evidence: B)
5. Coronary artery bypass graft surgery is recommended in patients
with stable angina who have 2-vessel disease with significant proximal
LAD stenosis and either ejection fraction less than 0.50 or demonstrable
ischemia on noninvasive testing. (Level of Evidence: A)
The
role of surgical revascularization has been reviewed extensively
in the ACC/AHA Guideline Update on Coronary Artery Bypass Graft
Surgery (518). Consideration for
revascularization after STEMI includes PCI and CABG. Providers should
individualize patient management on the basis of clinical circumstances,
available revascularization options, and patient preference. Elective
CABG should improve survival relative to medical therapy in patients
with MI who have 1) left main coronary artery stenosis; 2) left
main equivalent (significant [at least 70%] stenosis of the proximal
LAD and proximal left circumflex artery); 3) 3-vessel disease, particularly
with decreased LV function; 4) 2-vessel disease with significant
proximal LAD stenosis not amenable to PCI and either ejection fraction
less than 0.50 or demonstrable ischemia on noninvasive testing;
and 5) 1- or 2-vessel disease not amenable to PCI without proximal
LAD stenosis but with a large area of viable myocardium at risk
and high-risk criteria on noninvasive testing. The optimal timing
of surgery has not been established. The risk is greatest within
the first 48 hours of infarction and decreases over the next 2 weeks.
Risk of operation is greatest for patients with decreased LV function,
advanced age, female sex, renal failure, peripheral vascular disease,
diabetes, chronic obstructive pulmonary disease, and previous CABG
(1048,1061,1065).
7.10.7. Coronary Artery Bypass Surgery After
STEMI and Antiplatelet Agents
Class I
1. Aspirin should not be withheld before elective or nonelective
CABG after STEMI. (Level of Evidence: C)
2. Aspirin (75 to 325 mg/d) should be prescribed as soon as possible
(within 24 hours) after CABG unless contraindicated. (Level
of Evidence: B)
3. In patients taking clopidogrel in whom elective CABG is planned,
the drug should be withheld for 5 to 7 days. (Level of Evidence:
B)
Aspirin
therapy, particularly within the first 48 hours after CABG, appears
to have significant benefits (1066,1067).
Mangano et al. (1066) studied
5022 patients in a global registry who survived CABG. Aspirin therapy
begun within 48 hours after surgery resulted in a 60% lower death
rate at 30 days, as well as decreased rates of MI, stroke, renal
failure, and bowel infarction. It is likely that these effects are
mediated by both the anti-inflammatory and antithrombotic actions
of aspirin (1067). Bleeding complications
were also lower in the aspirin-treated group.
Patients
with STEMI undergoing revascularization frequently receive 1 or
more antiplatelet agents in addition to heparin, all of which may
increase risk of serious bleeding during and after cardiac surgery.
Because the mechanism and duration of action of the antiplatelet
effects of aspirin, the ADP antagonists (ticlopidine and clopidogrel),
and GP IIb/IIIa receptor antagonists (abciximab and eptifibatide)
differ, the potential exists for an additive effect with a combination
of these agents. In the CURE trial (728),
in which 12562 patients with unstable angina or NSTEMI were randomized
to placebo plus aspirin or clopidogrel plus aspirin, there was an
increased risk of major bleeding in the clopidogrel group (3.7%)
compared with the placebo group (2.7%). Also, risk of bleeding was
increased in patients undergoing CABG within the first 5 days of
stopping clopidogrel. In a prospective study of 224 patients having
CABG, Hongo et al. (1068) found
reoperation for bleeding to be 10-fold higher in patients who had
received clopidogrel within 7 days of surgery than in those who
had received no clopidogrel. In the EPIC trial (Evaluation Prevention
of Ischemic Complications; placebo or abciximab bolus or abciximab
infusion) (1069), transfusion
of red blood cells and platelets was significantly higher after
treatment with abciximab.
Singh
et al. (1070) found transfusion
requirements to be higher for patients who underwent urgent CABG
after having received abciximab during PCIs. In an analysis of 85
surgical patients in the EPILOG (Evaluation of PTCA to Improve Long-Term
Outcome by c7E3 GP IIb/IIIa Receptor Blockade) and EPISTENT (Evaluation
of Platelet IIb/IIIa Inhibition in Stenting) trials, although platelet
transfusions were higher in the abciximab groups, rates of major
blood loss and transfusions of whole blood and packed red cells
were the same in the abciximab and placebo groups (1071).
Management strategies for patients who require surgery and subsequent
treatment with antiplatelet agents will differ according to type
of agent used and the urgency of surgery. In many circumstances,
it may not be feasible to delay surgery until platelet function
has recovered. In patients treated with the small-molecule GP IIb/IIIa
receptor antagonists, tirofiban and eptifibatide, platelet function
returns toward normal within 4 hours of stopping treatment. Platelet
aggregation does not return toward normal for more than 48 hours
in patients treated with abciximab. Management strategies other
than delaying surgery include platelet transfusions for patients
who were recently treated with abciximab, reduced heparin dosing
during cardiopulmonary bypass, and possible use of antifibrinolytic
agents such as aprotinin or tranexamic acid (1072).
Because clopidogrel, when added to aspirin, increases the risk of
bleeding during major surgery, clopidogrel should be withheld for
at least 5 days (728) and preferably
for 7 days before surgery in patients who are scheduled for elective
CABG (1073).
7.11. Convalescence, Discharge, and
Post-MI Care
7.11.1. Risk Stratification at Hospital Discharge
Informal risk estimates are updated continually as the
patient's clinical condition evolves and other information becomes
available. For example, tests such as an echocardiogram may be obtained
early during hospitalization to define an abnormal physical finding
and thus provide data for risk stratification, even though they
were not ordered for that purpose. Because patient preference is
a critical determinant for any management pathway, it is difficult
to produce a rigid algorithm for risk stratification.
There is, nevertheless, value in outlining general strategies for
performing risk stratification testing, with an emphasis on avoiding
redundancy. The most important immediate management decision is
whether to refer a patient for cardiac catheterization. Patients
who have not had catheterization as part of their initial treatment
strategy should be evaluated for their risk of future cardiac events.
Another major decision is referral for EP testing and possible placement
of an ICD.
The risk stratification approach for decision making about catheterization
is described in Figure 36. For
patients who did not have an early catheterization and in whom revascularization
therapy would be considered, the approach includes an early quantitative
assessment of LVEF. Patients with an LVEF less than 0.40 should
be considered for catheterization. For those with a higher LVEF,
further stratification with stress testing is recommended. Various
approaches are considered acceptable, including a submaximal stress
test, a symptom-limited stress imaging test, or a pharmacological
stress imaging test. Ambulatory ECG monitoring for ischemia after
STEMI has significant limitations (e.g., resting ECG abnormal after
infarction) and has not been incorporated into the algorithm in
Figure 36 (71,1074).
A symptom-limited stress test was not formerly recommended but is
supported by data from DANAMI (515).
The decision for referral to cardiac catheterization should then
be based on the stress test results, with an indication related
to the amount of ischemia quantified by test results. Patients with
little or no ischemia may be better treated with medical therapy,
a strategy supported by DANAMI.
The suggested algorithm for EP testing and ICD placement is shown
in Figure 32. Electrophysiology
testing is not indicated for patients with an LVEF less than 0.30
because they are presumed to benefit from an ICD, and an EP test
is not necessary. Patients with VF after 48 hours, sustained VT,
or hemodynamically significant VT are recommended for ICD placement
without an EP test. For patients with an ejection fraction less
than 0.40, an EP test is reserved those whose telemetry or Holter
monitor show nonsustained VT.
Physicians
and their patients must make decisions about risk-reduction lifestyle
and pharmacological approaches. At this point, however, all patients
with STEMI are considered to be at sufficiently high risk to merit
use of these secondary prevention interventions, including the use
of cardiac rehabilitation, aspirin, appropriate lipid-lowering therapy,
and beta-blockers (Table 32) (68).
There is a clear need for tools that can integrate comprehensive
risk-stratification information in explicit estimates of absolute
risks of cardiovascular outcomes with management decisions. Current
risk stratification tests generally provide relative risk information,
indicating average increases in risk, but their utility in guiding
clinical decisions remains to be defined. The Writing Committee
believes that further research in this area is necessary before
making recommendations about the best use of these emerging risk
stratification tools.
7.11.1.1. Role of Exercise Testing
Class I
1. Exercise testing should be performed either in the hospital or
early after discharge in STEMI patients not selected for cardiac
catheterization and without high-risk features to assess the presence
and extent of inducible ischemia. (Level of Evidence: B)
2. In patients with baseline abnormalities that compromise ECG interpretation,
echocardiography or myocardial perfusion imaging should be added
to standard exercise testing. (Level of Evidence: B)
Class IIb
Exercise testing might be considered before discharge of patients
recovering from STEMI to guide the postdischarge exercise prescription
or to evaluate the functional significance of a coronary lesion
previously identified at angiography. (Level of Evidence: C)
Class III
1. Exercise testing should not be performed within 2 to 3 days of
STEMI in patients who have not undergone successful reperfusion.
(Level of Evidence: C)
2. Exercise testing should not be performed to evaluate patients
with STEMI who have unstable postinfarction angina, decompensated
CHF, life-threatening cardiac arrhythmias, noncardiac conditions
that severely limit their ability to exercise, or other absolute
contraindications to exercise testing (1075).
(Level of Evidence: C)
3. Exercise testing should not be used for risk stratification in
patients with STEMI who have already been selected for cardiac catheterization.
(Level of Evidence: C)
Exercise testing after STEMI may be performed to 1) assess functional
capacity and the patient’s ability to perform tasks at home
and at work; 2) establish exercise parameters for cardiac rehabilitation;
3) evaluate the efficacy of the patient’s current medical
regimen; 4) risk-stratify the postpatient with STEMI according to
the likelihood of a subsequent cardiac event (1076-1080);
5) evaluate chest pain symptoms after STEMI; and 6) provide reassurance
to patients regarding their functional capacity after STEMI as a
guide to return to work.
Patients who receive reperfusion therapy have a smaller infarct
size (1081). Coronary angiography
is frequently performed during hospitalization due to recurrent
chest pain, which identifies many patients with severe disease who
subsequently undergo revascularization (1082).
The low cardiac event rate after discharge in patients with STEMI
who are successfully reperfused substantially reduces the predictive
accuracy of early exercise testing. The ability to perform an exercise
test 1 month after STEMI provides a favorable prognosis irrespective
of the test results (1075).
Low-level exercise testing appears to be safe if patients have undergone
in-hospital cardiac rehabilitation, including low-level exercise,
have had no symptoms of angina or heart failure, and have a stable
baseline ECG 48 to 72 hours before the exercise test. Two different
protocols have been used to determine the end points of these very
early exercise tests (1083-1085):
The traditional submaximal exercise test (done at 3 to 5 days in
patients without complications) incorporates a series of end points,
including a peak heart rate of 120 to 130 bpm or 70% of maximal
predicted heart rate for age, a peak work level of 5 metabolic equivalents
(METs), or clinical or ECG end points of mild angina or dyspnea,
ST-segment depression greater than 2 mm, exertional hypotension,
or 3 or more consecutive premature ventricular contractions, whichever
end point is reached first. The second protocol is performance of
a symptom-limited exercise test (done at 5 days or later) without
stopping for target heart rates or MET levels. Although this level
will result in a higher frequency of abnormal exercise tests, the
prognostic value of ST depression that occurs at higher work levels
in deconditioned patients is uncertain. The safety of early symptom-limited
exercise testing is based on relatively limited data; therefore,
clinical judgment must be used (1075).
The results of this symptomlimited test can also be used to establish
intensity and target heart rate during cardiac rehabilitation.
The duration of exercise is also known to be an important predictor
of outcomes, and the ability to perform at least 5 METs without
early exercise ST depression and show a normal rise in systolic
blood pressure is important in constituting a negative predictive
value (1086,1087).
The optimum time for performing the exercise test after STEMI remains
unresolved. It is argued that a predischarge exercise test provides
psychological benefits to the patient and will permit detection
of profound ischemia that could be associated with postdischarge
cardiac events that might occur before a scheduled 3- to 6-week
postdischarge, symptom-limited stress test. It also provides parameters
for cardiac rehabilitation exercise programs. On the other hand,
deferring exercise testing until approximately 3 weeks after STEMI
in clinically low-risk patients appears safe and reasonable and
enables more optimal assessment of functional capacity. It is the
consensus of this Writing Committee that patients without complications
who have not undergone coronary arteriography before discharge from
the hospital and who might be potential candidates for revascularization
procedures should undergo exercise electrocardiography before or
just after discharge.
7.11.1.2. Role of Echocardiography
Noninvasive imaging in patients recovering from STEMI includes echocardiography
and radionuclide imaging. This section discusses the role of echocardiography.
(See Sections 7.11.1.3, 7.11.1.4,
and 7.11.1.5 for additional discussion on
imaging considerations.)
Class I
1. Echocardiography should be used in patients with STEMI
not undergoing LV angiography to assess baseline LV function, especially
if the patient is hemodynamically unstable. (Level of Evidence:
C)
2. Echocardiography should be used to evaluate patients with inferior
STEMI, clinical instability, and clinical suspicion of RV infarction.
(See the ACC/AHA/ASE 2003 Guideline Update for Clinical Application
of Echocardiography (226).) (Level
of Evidence: C)
3. Echocardiography should be used in patients with STEMI to evaluate
suspected complications, including acute MR, cardiogenic shock,
infarct expansion, VSR, intracardiac
thrombus, and pericardial effusion. (Level of Evidence: C)
4. Stress echocardiography (or myocardial perfusion imaging) should
be used in patients with STEMI for in-hospital or early postdischarge
assessment for inducible ischemia when baseline abnormalities are
expected to compromise ECG interpretation. (Level of Evidence:
C)
Class IIa
1. Echocardiography is reasonable in patients with STEMI to re-evaluate
ventricular function during recovery when results are used to guide
therapy. (Level of Evidence: C)
2. Dobutamine echocardiography (or myocardial perfusion imaging)
is reasonable in hemodynamically and electrically stable patients
4 or more days after STEMI to assess myocardial viability when required
to define the potential efficacy of revascularization. (Level
of Evidence: C)
3. In STEMI patients who have not undergone contrast ventriculography,
echocardiography is reasonable to assess ventricular function after
revascularization. (Level of Evidence: C)
Class III
Echocardiography should not be used for early routine re-evaluation
in patients with STEMI in the absence of any change in clinical
status or revascularization procedure. Reassessment of LV function
30 to 90 days later may be reasonable. (Level of Evidence: C)
The widespread availability, portability, and relatively low cost
of echocardiography have resulted in its increased use as a practical
and reliable means of assessing both global ventricular function
and regional wall-motion abnormalities. Transthoracic imaging and
Doppler techniques are generally sufficient for evaluating patients
with suspected or documented ischemic heart disease. However, transesophageal
echocardiography may be needed in some patients, particularly those
with serious hemodynamic compromise but nondiagnostic transthoracic
echocardiography studies. The uses of echocardiography in STEMI
are discussed in detail in the ACC/AHA/ASE 2003 Guideline Update
for the Clinical Application of Echocardiography (226).
Assessment of Prognosis and Complication. Echocardiography
assesses global and regional ventricular function. The sum of segmental
wall-motion abnormalities may overestimate infarct size because
it includes regions of prior infarction and areas with ischemic
stunning or hibernation of myocardium. However, LVEF and echocardiographically
derived infarct size are predictive of early and late complications
and mortality (1088-1091).
Echocardiography can be used to evaluate at the bedside, when needed,
virtually any complication of STEMI. These complications include
acute MR, cardiogenic shock, infarct expansion,
VSR, intracardiac thrombus, and pericardial effusion.
Assessment
of Therapy. Given the frequent use of reperfusion therapy (fibrinolytic
agents or primary angioplasty) in patients with STEMI, assessment
of myocardial salvage is an important clinical issue. After successful
reperfusion, myocardial stunning may occur and may last for days
to months. Wall-motion segments that demonstrate hypokinesia or
akinesia at rest but improved function during low-dose dobutamine
infusion often recover contractility (1092-1101),
which suggests that these segments are stunned. Failure of such
segments to show improvement suggests functional recovery is unlikely
to occur (1092-1101).
These issues are discussed in more detail in the ACC/AHA/ASE 2003
Guideline Update for the Clinical Application of Echocardiography
(226).
Predischarge Evaluation With Stress Echocardiography. The
role of exercise testing in evaluation of patients with STEMI before
discharge is discussed in Section 7.11.1.1.
As previously noted, the ability to perform an exercise test 1 month
after STEMI provides a favorable prognosis regardless of test results
(1075). The incremental value
of exercise echocardiography over regular exercising testing after
STEMI has not been established. Prospective natural history studies
are difficult to accomplish because many clinicians now perform
angiography and recommend revascularization in patients with significant
coronary obstructions. Echocardiography or perfusion imaging (see
Section 7.11.1.3) should be added to exercise
testing whenever baseline abnormalities are expected to compromise
ECG interpretation.
Although serious complications have been reported (1093),
general experience suggests that pharmacological stress echocardiography
with a graded protocol and with low doses of dobutamine initially
appears to be feasible and safe when performed 4 to 10 days after
STEMI (1092,1094-1102).
Pharmacological challenge can substitute for exercise in predischarge
functional testing for ischemia in patients with limited exercise
capacity and can help in assessing myocardial viability early after
STEMI (1092,1094,1103-1112).
Betablockade may limit the sensitivity of dobutamine echocardiography
in assessing ischemia.
7.11.1.3. Exercise Myocardial Perfusion
Imaging
Noninvasive imaging in patients recovering from STEMI includes echocardiography
and radionuclide imaging. This section discusses the role of exercise
myocardial perfusion imaging. (See Sections 7.11.1.2,
7.11.1.4, and 7.11.1.5
for additional discussion on imaging considerations.)
Class I
Dipyridamole or adenosine stress perfusion nuclear scintigraphy
or dobutamine echocardiography before or early after discharge should
be used in patients with STEMI who are not undergoing cardiac catheterization
to look for inducible ischemia in patients judged to be unable to
exercise. (Level of Evidence: B)
Class IIa
Myocardial perfusion imaging or dobutamine echocardiography is reasonable
in hemodynamically and electrically stable patients 4 to 10 days
after STEMI to assess myocardial viability when required to define
the potential efficacy of revascularization. (Level of Evidence:
C)
Before the use of reperfusion therapy, the prognostic value of exercise
myocardial perfusion imaging was found to be superior to that of
exercise ECG testing (1113-1116).
Pharmacological stress perfusion imaging was shown to have predictive
value for postinfarction cardiac events (1117-1119).
The key issues are whether these results apply to current patient
populations in the reperfusion era and whether myocardial perfusion
imaging is worth the additional cost for risk stratification (1120).
The same issues outlined previously with respect to exercise echocardiographic
testing apply to this methodology. In patients with STEMI who have
received fibrinolytic therapy, several studies using myocardial
perfusion imaging have found that it is less valuable than previously
thought for risk stratification (1121-1123),
primarily because of the low rate of late cardiac events.
In
patients in the current era who have not received reperfusion therapy,
particularly those who have not undergone revascularization, the
same considerations regarding subsequent patient outcome that were
outlined above for exercise ECG testing apply. There is evidence
that myocardial perfusion imaging is useful for risk stratification
in such patients, despite their better overall prognosis (1124).
It appears likely that the previously demonstrated superiority of
stress myocardial perfusion imaging probably continues to apply
to this population, although there is limited evidence on this point.
Prospective studies are difficult to conduct because clinicians
frequently intervene in patients with abnormal predischarge stress
perfusion imaging studies.
Myocardial perfusion imaging with either Tl 201 (1125),
Tc 99m sestamibi (1126), or Tc
99m tetrofosmin can assess infarct size. The measurement of infarct
size by any one of these techniques is significantly associated
with subsequent patient mortality after fibrinolytic therapy (1125-1127).
Data are also emerging to suggest that vasodilator stress nuclear
scintigraphy is safe and can be used for early (48 to 72 hours)
risk stratification (1128). The
ACC/AHA/ASNC Guidelines for the Clinical Use of Cardiac Radionuclide
Imaging, a revision of the 1995 guidelines, stress the ability of
pharmacological stress perfusion imaging to risk-stratify patients
after STEMI early and safely, thereby facilitating the development
of clinical strategies (239).
Recommended strategies for exercise test evaluations after STEMI
are presented in Figure 36. These
strategies and the data on which they are based are reviewed in
more detail in the ACC/AHA 2002 Guideline Update for Exercise Testing
(1075).rdiography and radionuclide
imaging. This section discusses the role of exercise myocardial
perfusion imaging. (See Sections 7.11.1.2,
7.11.1.4, and 7.11.1.5
for additional discussion on imaging considerations.)
7.11.1.4. Left Ventricular Function
Noninvasive
imaging in patients recovering from STEMI includes echocardiography
and radionuclide imaging. This section discusses the importance
of measurement of LV function. Either of the above imaging techniques
can provide clinically useful information.
Class I
Left
ventricular ejection fraction should be measured in all STEMI patients.
(Level of Evidence: B)
Assessment
of LV function after STEMI has been shown to be one of the most
accurate predictors of future cardiac events in both the prereperfusion
(1129) and the reperfusion (1130,1131)
eras. Multiple techniques for assessing LV function of patients
after STEMI have important prognostic value. Because of the dynamic
nature of LV function recovery after STEMI, clinicians should consider
the timing of the imaging study relative to the index event when
assessing LV function. (See Table
6 of the ACC/AHA/ASE 2003 Guideline Update for the Clinical
Application of Echocardiography for further discussion of the impact
of timing on assessment of LV function and inducible ischemia) (226).
The assessment can include such basic factors as clinical estimates
based on patients’ symptoms (e.g., exertional dyspnea, functional
status), physical findings (e.g., rales, murmurs, elevated jugular
venous pressure, cardiomegaly, S3 gallop), and measurement of ejection
fraction by contrast ventriculography, radionuclide ventriculography,
and 2-dimensional echocardiography. Zaret and colleagues (1130)
found that an LVEF less than 0.30 as assessed by radionuclide ventriculography
was still predictive of mortality in patients surviving infarction
treated with fibrinolytic therapy, despite the significantly reduced
mortality of these patients compared with those in the prereperfusion
era. White and colleagues (1132)
performed contrast left ventriculography in 605 patients 1 to 2
months after MI. They found that postinfarction LV dilation, demonstrated
by increased end-systolic volume greater than 130 ml, was an even
better predictor of mortality after MI than an LVEF less than 0.40
or increased end-diastolic volume. In patients with normal ejection
fractions, however, end-systolic volume did not provide any further
stratification according to risk.
Assessment of LV function by different techniques may produce different
results. The SOLVD (Studies Of Left Ventricular Dysfunction) investigators
compared LVEF determined by echocardiography or radionuclide angiography
and noted higher mortality for patients with LVEF less than 0.35
by echocardiography than for patients with the same value determined
by the radionuclide technique (1133).
LVEFs derived by radionuclide angiography and by cardiac catheterization
were compared in the SAVE study, with higher values derived by catheterization
(924). Radionuclear and catheterization-derived
LVEF were poorly correlated, but lower values by either technique
predicted a worse prognosis. In some circumstances, assessment of
ventricular function by several techniques may be useful.
7.11.1.5.
Myocardial Viability
Noninvasive imaging in patients recovering from STEMI includes echocardiography
and radionuclide imaging. This section discusses techniques for
assessing myocardial viability. Either of the above imaging techniques
can provide clinically useful information.
As previously noted, LV function is a well established and powerful
predictor of outcome after STEMI. In some patients, LV dysfunction
results from necrosis and scar formation. In others, viable but
dysfunctional myocardium contributes to LV dysfunction and may be
significantly reversible with revascularization. Myocardial hibernation
(chronic low-flow state associated with depressed myocardial function)
(1134) and stunning (depression
of ventricular function after acute ischemia despite adequate restoration
of blood flow) (1135) contribute
to the potential reversibility of ventricular function. Up to one
third of patients with significant ischemic LV dysfunction may improve
with revascularization (1136).
Therefore, the distinction between ventricular dysfunction caused
by fibrosis and that arising from viable but dysfunctional myocardium
may have important prognostic and therapeutic implications.
Several noninvasive imaging modalities have been established as
predictors of myocardial viability. Radionuclide imaging and dobutamine
echocardiography have acceptable accuracy in predicting recovery
of regional wall-motion abnormalities (239).
More recently, relatively small studies have suggested the ability
of viability studies to identify patients most likely to benefit
from revascularization in terms of symptoms and natural history
(1137-1140).
These data are reviewed in more detail in the ACC/AHA/ASNC Guidelines
for Cardiac Radionuclide Imaging (239)
and the ACC/AHA/ASE 2003 Guideline Update for the Clinical Application
of Echocardiography (226). Positron
emission tomography, although not currently as widely available
as other radionuclide techniques, may provide slightly better overall
accuracy in predicting recovery of regional function (1141).
More recently, contrast-enhanced magnetic resonance imaging has
demonstrated promising results in predicting improvement of regional
myocardial function in patients after STEMI (1142-1144).
The data noted above suggest that assessment of myocardial viability
after STEMI, particularly in patients with severe LV dysfunction,
may identify those with the highest risk, in whom revascularization
can be of clinical benefit. However, myocardial viability remains
incompletely understood. Viability testing is not a standard until
more conclusive diagnostic efficacy studies are performed to demonstrate
patient benefit.
7.11.1.6. Invasive
Evaluation
Class I
1. Coronary arteriography should be performed in patients with spontaneous
episodes of myocardial ischemia or episodes of myocardial ischemia
provoked by
minimal exertion during recovery from STEMI. (Level of Evidence:
A)
2. Coronary arteriography should be performed for intermediate-
or high-risk findings on noninvasive testing after STEMI (see Table
23 of the ACC/AHA 2002 Guideline Update for the Management of
Patients With Chronic Stable Angina) (71).
(Level of Evidence: B)
3. Coronary arteriography should be performed if the patient is
sufficiently stable before definitive therapy of a mechanical complication
of STEMI, such as acute MR, VSR, pseudoaneurysm, or LV aneurysm.
(Level of Evidence: B)
4. Coronary arteriography should be performed in patients with persistent
hemodynamic instability. (Level of Evidence: B)
5. Coronary arteriography should be performed in survivors of STEMI
who had clinical heart failure during the acute episode but subsequently
demonstrated well-preserved LV function. (Level of Evidence:
C)
Class IIa
1. It is reasonable to perform coronary arteriography when STEMI
is suspected to have occurred by a mechanism other than thrombotic
occlusion of an atherosclerotic plaque. This would include coronary
embolism, certain metabolic or hematological diseases, or coronary
artery spasm. (Level of Evidence: C)
2. Coronary arteriography is reasonable in STEMI patients with any
of the following: diabetes mellitus, LVEF less than 0.40, CHF, prior
revascularization, or life-threatening ventricular arrhythmias.
(Level of Evidence: C)
Class IIb
Catheterization and revascularization may be considered as part
of a strategy of routine coronary arteriography for risk assessment
after fibrinolytic therapy (see Section
6.3.1.6.4.7). (Level of Evidence: B)
Class III
Coronary arteriography should not be performed in survivors of STEMI
who are thought not to be candidates for coronary revascularization.
(Level of Evidence: A)
In contrast to noninvasive testing, coronary arteriography provides
detailed structural information to allow an assessment of prognosis
and to provide direction for appropriate management. Indications
for coronary arteriography are interwoven with indications for possible
therapeutic plans such as PCI or CABG. All survivors of STEMI who
are candidates for revascularization therapy with spontaneous ischemia,
intermediate- or high-risk findings on noninvasive testing, hemodynamic
or electrical instability, mechanical defects, prior revascularization,
or high-risk clinical features should be considered for coronary
arteriography. Percutaneous coronary intervention or CABG may be
considered in these patients if they are found to have significant
obstructive coronary artery disease (1145-1147).
Given
the adverse clinical consequences of recurrent infarction, it would
be highly desirable to minimize the chance of its occurrence after
initial treatment for STEMI. Routine referral for angiography of
all patients after fibrinolytic therapy is intuitively attractive
and supported indirectly by retrospective analyses from trials of
fibrinolytic therapy that suggest that patients treated with PCI
during the index hospitalization had a lower risk of recurrent MI
and a lower 2-year mortality (512).
However, previous randomized trials testing a strategy of routine
catheterization after fibrinolysis suggested that such an approach
was deleterious (480,503,505,516,1148).
However, the previous trials were conducted in an era during which
aspirin was inconsistently administered, high doses of UFH without
monitoring of activated clotting time were used, and the interventional
catheters, radiographic imaging equipment, and supportive antiplatelet
agents were suboptimal. The Writing Committee encourages contemporary
research into the benefit of routine catheterization versus watchful
waiting after fibrinolytic therapy in the contemporary era (1149,1149a).
See Section 6.3.1.6.4.7.
7.11.1.7. Ambulatory ECG Monitoring
for Ischemia
The value of ambulatory ECG monitoring in assessing reversible myocardial
ischemia and the risk of a subsequent coronary event early after
MI has been evaluated in a number of studies (1150-1157).
Up to 25% of patients will show residual ischemia detected on ambulatory
ECG monitoring. Most episodes of transient myocardial ischemia are
silent and occur at rest or during times of low-level physical activity
or mental stress (1158). During
long-term follow-up studies, a number of investigators have reported
that the presence of ischemia detected by ambulatory ECG monitoring
in the postinfarction period is predictive of a subsequent poor
outcome and increases the risk of cardiac events (1150-1157).
One study found that the odds ratio for patients with ambulatory
ischemia, compared with those without it, was 2.3 for death or nonfatal
MI at 1 year (1157).
Despite the promising initial results with ambulatory ECG monitoring,
the totality of evidence does not support a general statement about
its role in patients with STEMI. Some studies have shown that the
results of ambulatory ECG monitoring could be predicted from exercise
test data (1152,1155),
whereas others have found that additional prognostic information
could be obtained by ambulatory ECG monitoring in postinfarction
patients (1153). At present, a
cost-effective strategy has not been developed to identify patients
who are at increased risk for ambulatory ischemia and in whom ambulatory
ECG monitoring might be more helpful for stratification into high-
and low-risk subgroups for future coronary events.
7.11.1.8.
Assessment of Ventricular Arrhythmias
Class IIb
Noninvasive assessment of the risk of ventricular arrhythmias
may be considered (including signalaveraged ECG, 24-hour ambulatory
monitoring, heart rate variability, micro T-wave alternans, and
Twave variability) in patients recovering from STEMI. (Level
of Evidence: B)
A number of noninvasive strategies have been used to try to identify
patients at high risk for arrhythmic events. Although most of these
measure some aspect of the excessive activation of the autonomic
nervous system commonly observed in high-risk patients with LV dysfunction,
others measure impulse conduction through the infarct zone. Thus,
noninvasive determinants of arrhythmia risk encompass measurement
of changes in ventricular repolarization, alterations of autonomic
tone, and delayed and disordered myocardial conduction.
The
most frequently used techniques are signal-averaged or high-resolution
ECG, heart rate variability, baroreflex sensitivity, and T-wave
alternans. Signal-averaged electrocardiography identifies delayed,
fragmented conduction in the infarct zone in the form of late potentials
at the terminus of the QRS complex and represents an anatomic substrate
that predisposes the patient to re-entrant VT. Kuchar et al. (1159)
reported that late potentials predict an increased incidence of
sudden death in the post-MI patient population. Gomes et al (1160)
found late potentials to be the best single predictor when considering
Holter monitoring and ejection fraction and found that they contributed
independently to a combined index, although the positive predictive
value of each was poor. The filtered QRS duration was the most predictive
feature of signal-averaged electrocardiography in a Cardiac Arrhythmia
Suppression Trial (CAST) substudy (1161).
More recent studies have shown that reperfusion therapy reduces
the incidence of late potentials after STEMI (1162).
In the setting of frequent use of fibrinolysis, the predictive value
of signal-averaged electrocardiography has been variable (1163-1165).
Heart rate variability, an analysis of the beat-to-beat variation
in cycle length, largely reflects the sympathovagal interaction
that regulates heart rate. Heart rate variability can be quantified
in a number of ways, with either time- or frequency- domain parameters
(1166). Low heart rate variability,
indicative of decreased vagal tone, is a predictor of increased
mortality, including sudden death, in patients after MI (1166,1167)
and may add significant prognostic information to other parameters
(1167). The Autonomic Tone and
Reflexes After Myocardial Infarction (ATRAMI) study (1168)
was a prospective multicenter study that enrolled 1284 patients
with a recent (fewer than 28 days) MI. Decreased heart rate variability
was a significant and independent predictor of cardiac mortality
(hazard ratio 3.2, p equals 0.005) (1168).
The predictive value of heart rate variability after STEMI, although
significant, is modest when used alone. In combination with other
techniques, its positive predictive accuracy improves. The most
practical, feasible, and cost-efficient combination of noninvasive
predictive tests with heart rate variability remains to be determined.
Baroreceptor
sensitivity also quantifies the influence of parasympathetic tone
on the heart. It is measured as the slope of a regression line relating
beat-to-beat heart rate change in response to a change in blood
pressure, often accomplished by giving a small bolus of phenylephrine
(1169). Reductions in baroreflex
sensitivity have been associated with an increased susceptibility
to arrhythmic events and sudden death in experimental models and
initial clinical reports (1170-1172).
Finally, abnormalities in ventricular repolarization are detectable
by microvolt alterations of T-wave amplitude, or T-wave alternans.
In experimental preparations, the presence of T-wave alternans was
predictive of a lower fibrillation threshold. Clinical studies have
demonstrated that T-wave alternans is associated with ventricular
arrhythmias during EP testing, as well as with clinically evident
arrhythmias. Microvolt T-wave alternans was subsequently shown to
be associated with inducible ventricular arrhythmias during programmed
ventricular stimulation and spontaneous arrhythmic events (1173,1174).
The clinical applicability of these tests to the post-STEMI patient
is in a state of evolution. Although the negative predictive value
of most of these tests taken in isolation is high (generally greater
than 90%), the positive predictive value is unacceptably low (less
than 30%). Whereas the positive predictive value of noninvasive
testing for future arrhythmic events can be modestly increased by
combining several test results, the therapeutic implications of
positive findings are unclear. Insufficient data are available to
indicate whether general therapies, such as beta-adrenoceptor blockade,
ACE inhibition, and revascularization procedures, or specific interventions,
such as treatment with amiodarone or an ICD, targeted toward high-risk
patients identified by a combination of noninvasive tests after
MI can more favorably impact mortality (1175).
The widening indications for ICD implantation in patients with LV
dysfunction may encourage the use of these studies to find the lowest-risk
patients (i.e., those without any high-risk markers whatsoever)
to avoid ICD implantation. Finally, it is difficult to justify the
costs of the routine use of these procedures in the absence of demonstrated
clinical benefits. Until these issues are resolved, these tests
are used only to support routine management and risk assessment.
7.12. Secondary Prevention
Class I
Patients who survive the acute phase of STEMI should have plans
initiated for secondary prevention therapies. (Level of Evidence:
A)
Secondary prevention therapies, unless contraindicated,
are an essential part of the management of all patients with STEMI
(Table 32) (68),
regardless of sex (69,1176).
Inasmuch as atherosclerotic vascular disease is frequently found
in multiple vascular beds, the physician should search for
symptoms or signs of peripheral vascular disease or cerebrovascular
disease in patients presenting with STEMI. Approximately 70% of
CHD deaths and 50% of MIs occur in patients who have previously
established coronary artery disease (677).
It is estimated that the likelihood of fatal and nonfatal MI is
4 to 7 times higher in patients with apparent coronary disease.
The institution of secondary prevention therapies and risk reduction
strategies in patients recovering from STEMI represents major opportunities
to reduce the toll of cardiovascular disease.
Smoking cessation, aggressive lipid lowering, control of hypertension
and diabetes, and prophylactic use of aspirin, beta-blockers, and
ACE inhibitors are key components of secondary prevention that have
a demonstrated benefit. Dietary cholesterol contributes to elevations
in LDL-C and should be included in the list of dietary modifications
(reduction in total calories, saturated fat, cholesterol, and salt
and increase in vegetables, fruits, and grain fiber) given to the
post-STEMI patient. These changes are both directly beneficial and
aid in hypertension control and lipid lowering. The specifics of
these therapies and recommendations for their use are discussed
in the following sections (68).
Secondary
prevention services remain discouragingly underutilized (1177)
despite the compelling evidence for and large magnitude of their
benefits (1178-1180).
The ACC and AHA urge all healthcare providers to implement systems
that ensure the reliable identification of patients who can benefit
from secondary prevention interventions and to ensure that these
interventions occur (1181,69).
Evidence exists that lifestyle modifications (as discussed below),
including regular physical exercise, weight reduction, cessation
of cigarette smoking, and stress reduction strategies, have a favorable
impact on blood coagulation, fibrinolysis, and platelet reactivity,
shifting the patient to a less atherogenic and prothrombotic state
(Table 32) (68,1182).
Referral to outpatient cardiac rehabilitation can aid in attainment
of these goals (1183,1184).
Many institutions have clinical pathways for improving quality of
care of patients with STEMI (205).
Use of clinical pathways or other management protocols in hospital
settings has resulted in improved adherence to therapy by CHD patients
and better cholesterol control. The Cardiac Hospitalization Atherosclerosis
Management Program (CHAMP) focused on the initiation of therapy
with aspirin, beta-blockers, ACE inhibitors, statins, diet, and
exercise in persons with established CHD before hospital discharge
(1185). There was a significant
increase in the use of aspirin, beta-blockers, ACE inhibitors, and
statin therapy. The program used postdischarge follow-up visits
to titrate the statin dose to achieve an LDL-C level less than 100
mg/dL. One year after discharge, 91% of patients were being treated
with cholesterol-lowering therapy, and 58% were at treatment goals.
These results suggest that the initiation of treatment during hospitalization
for CHD adds needed emphasis to the importance of cholesterol-lowering
treatment along with other cardiac medications. There was also a
reduction in recurrent MI and 1-year mortality. Evidence exists
that adherence to practice guidelines for the management of patients
after STEMI is associated with significant reductions in short-
and long-term mortality (1186).
7.12.1.
Patient Education Before Discharge.
Class I
1. Before hospital discharge, all STEMI patients should be educated
about and actively involved in planning for adherence to the lifestyle
changes and drug therapies that are important for the secondary
prevention of cardiovascular disease. (Level of Evidence: B)
2. Post-STEMI patients and their family members should receive discharge
instructions about recognizing acute cardiac symptoms and appropriate
actions to take in response (i.e., calling 9-1-1 if symptoms are
unimproved or worsening 5 minutes after onset, or if symptoms are
unimproved or worsening 5 minutes after 1 nitroglycerin dose sublingually)
to ensure early evaluation and treatment should symptoms recur.
(Level of Evidence: C)
3. Family members of STEMI patients should be advised to learn about
AEDs and CPR and be referred to a CPR training program. Ideally,
such training programs would have a social support component targeting
family members of high-risk patients. (Level of Evidence: C)
Once STEMI has occurred, secondary prevention, including aggressive
risk factor management through medical and lifestyle therapy, is
the mainstay of therapy.
It
is important for providers in the inpatient setting to communicate
with the patient’s primary care provider to facilitate coordination
of care. The discharge summary should include the patient’s
medical, psychological, and functional status; prescribed medication
and lifestyle regimens; and the patient's living/social support
situation (1187).
Effective
education is critical to enlist patients’ full participation
in therapeutic regimens and secondary prevention efforts and to
minimize their natural concerns and anxieties. It ideally leads
to a patient who is better informed and more satisfied with his
or her care and who is also able to achieve a better quality of
life and improved survival (71,688,1188-1190).
In general, the outcomes of educational interventions depend on
the outcome studied (e.g., largest for knowledge change, smallest
for behavioral and psychological outcomes) (692)
and the strategies applied (688).
Principles of Patient Education. A thorough discussion
of the philosophies of and approaches to patient education is beyond
the scope of this guideline. There are useful reviews on this topic
(688,692,1191),
including a few that focus on ischemic heart disease (1192-1194).
Well-designed educational programs can improve patients’ knowledge
and in some instances can improve outcomes (688,1195).
These approaches form the basis for commonly used educational programs,
such as those conducted before CABG (1196)
and after MI (690,1197).
A variety of guidelines should be followed to help ensure that educational
efforts are successful (71):
1. Assess the patient’s baseline understanding. This not only
establishes a starting point for education but also engages the
patient. Healthcare providers are often surprised at the idiosyncratic
notions that patients have about their own medical conditions and
therapeutic approaches (688,1198,1199).
2. Elicit the patient's desire for information. Adults prefer to
set their own agendas, and they learn better when they can control
the flow of information.
3. Use epidemiological and clinical evidence. As clinical decision
making becomes increasingly based on scientific evidence, it is
reasonable to share that evidence with patients. Epidemiological
data can assist in formulating an approach to patient education,
such as conveying information on the major cardiovascular disease
risk factors. Scientific evidence about the reduction in cardiovascular
disease risk to be derived from risk factor modification/ lowering
can help persuade patients about the effectiveness of various interventions.
4. Use allied professional personnel. Even though physicians may
feel constrained with the limited amount of time available for a
patient encounter, interpersonal contact with and encouragement
from physicians is nevertheless a vital component of the patient’s
overall health education. Medical encounters represent powerful
“teaching moments” for initiating discussion and shaping
perceptions and expectations, and they are perceived as highly credible
sources of information (1200,1201).
In many settings, trained health educators, many of whom specialize
in diabetes or cardiac disease, are available. Personnel from disciplines
such as nursing, physical therapy, nutrition, pharmacy, and others
can provide reinforcement, more in-depth information, and ongoing
educational support and thus have much to offer patients with ischemic
heart disease (1202). Reimbursement
for educational activities by these allied providers is poor, although
this can also be accomplished as part of a cardiac rehabilitation
program for which funding is generally available.
5. Use professionally prepared resources when available. Studies
have shown that combined teaching strategies, including written
and audiovisual materials in addition to verbal instruction, group
approaches, and enhanced education methods, are the most effective
in achieving desired outcomes (688,692,1192).
The decreasing length of hospital stays has raised concern about
adequate opportunity for appropriate patient education (369,697),
although short educational sequences can produce outcomes comparable
to lengthy sessions (690). Innovative
presentation styles (e.g., programmed instruction, audiovisual techniques,
and health education television programs) can produce benefits comparable
to individual educational sessions (1203).
Use of a single repository for all educational materials (e.g.,
a binder that
travels with the patient) may provide consistency, document material
taught, identify goals that remain, and promote independent study,
an effective education strategy (688,1191).
6. Although any planned teaching strategy is better than none (688),
computer-assisted instruction is the newest approach to patient
education. Patients without computer access can be directed to a
work station in the physician’s office, clinic, hospital education
department/ library, or local library, where relevant pages can
be printed. A review of the literature on computer-based approaches
to patient education supports the use of computer- based education
as an effective strategy for transfer of knowledge and skill development
for patients (1204). The World
Wide Web is convenient for medical personnel and patients with access
to personal computers. The AHA maintains a Web site (http://www.americanheart.org)
that presents detailed and practical dietary recommendations and
information about heart disease, physical activity, heart attacks,
and CPR. The NHLBI Web site (http://www.nhlbi.nih.gov)
has links to the National High Blood Pressure Education Program,
NCEP, and the NHAAP’s “Act In Time to Heart Attack Signs,”
which have information for patients and professionals. Both the
ACC’s “Guidelines Applied in Practice” program
(http://www.acc.org/gap/images/Discharge.gif)
and the AHA’s “Get With the Guidelines Hospital Tool
Kit” (http://www.americanheart.org/
downloadable/heart/1107_HospTool.pdf) provide discharge information
as part of a separate patient-specific discharge form (Guidelines
Applied in Practice) or incorporated into a patient pathway (Get
With the Guidelines). The discharge information for patients reviews
and documents the important lifestyle changes and drug therapies
for the secondary prevention of cardiovascular disease that are
part of their discharge instructions. An important issue currently
receiving attention is the issue of health literacy. Studies with
patients and the public have found average reading abilities do
not exceed the eighth-grade level (688,695).
The current recommendation is that materials be written at the sixth-grade
level to ensure that the maximum number of people can read and understand
them.
7. Develop an action plan with the patient for their longterm management.
If it is necessary to convey a great deal of information to patients
about their condition, be cognizant of the patient’s level
of sophistication, readiness to change, prior educational attainment,
language barriers, relevant clinical factors, and social support.
A realistic goal might be to motivate an internal change that results
in the patient’s desire to ask for information on an important
topic such as smoking cessation (691).
It may be counterproductive to attempt to coax a patient into simultaneously
changing several behaviors, such as smoking, diet, and exercise,
and taking (and purchasing) multiple new medications. Achieving
optimal adherence often requires talking to patients to identify
barriers to compliance such as complex regimens and cost of medications
(1205) and addressing these barriers
through problem solving with the patient.
8. Involve family members in educational efforts. It is advisable
and often essential to include family members in educational efforts.
Many activities require the participation of family members; an
example is meal preparation. Efforts to encourage smoking cessation,
weight loss, or increased physical activity may be enhanced by enlisting
the support of family members who can reinforce the behavior and
may themselves benefit from participation.
9. Remind, repeat, and reinforce. Almost all learning deteriorates
without reinforcement. At regular intervals, the patients’
understanding should be reassessed, and key information should be
repeated as warranted. Feedback is a powerful motivator, and patients
should be congratulated for progress even when their ultimate goals
are not fully achieved. Even though the patient who has reduced
his or her use of cigarettes from 2 packs to 1 pack per day has
not quit smoking, that 50% reduction in exposure is important and
may simply represent a milestone on the path to complete cessation
(688).
The secondary prevention targets for post-STEMI patients, around
which education and follow-up/management should occur, are discussed
in the following sections. Within 6 years after a recognized heart
attack, 18% of men and 35% of women will have another heart attack
(46); most episodes of cardiac arrest
occur within 18 months after hospital discharge for STEMI (1206).
Thus, it is critical that patients and family members are educated
in advance about recognition of acute ischemic symptoms and the
appropriate action steps to take to ensure early evaluation and
treatment (see Section 3.3). Furthermore,
patients who have had a STEMI have a sudden death rate that is 4
to 6 times that of the general population (46).
Thus, family members of patients with STEMI should be advised to
learn CPR and should be given community resources to obtain this
training. In addition, research has shown that patients whose family
members received a social support intervention in conjunction with
being taught CPR reported better psychosocial adjustment and less
anxiety and hostility than those whose families received CPR training
only or CPR training with risk factor education. Family members
should be referred to a CPR program that combines CPR training with
social support (132,133).
(See Section 4.2.)
7.12.2.
Lipid Management
Class I
1. Dietary therapy that is low in saturated fat and cholesterol
(less than 7% of total calories as saturated fat and less than 200
mg/d cholesterol) should be started on discharge after recovery
from STEMI. Increased consumption of the following should be encouraged:
omega-3 fatty acids, fruits, vegetables, soluble (viscous)
fiber, and whole grains. Calorie intake should be balanced with
energy output to achieve and maintain a healthy weight. (Level
of Evidence: A)
2. A lipid profile should be performed, or obtained from recent
past records, for all STEMI patients, preferably after they have
fasted and within 24 hours of symptom onset. (Level of Evidence:
C)
3. The target LDL-C level after STEMI should be substantially less
than 100 mg/dL. (Level of Evidence: A)
a. Patients with LDL-C 100 mg/dL or above should be prescribed drug
therapy on hospital discharge, with preference given to statins.
(Level of Evidence: A)
b. Patients with LDL-C less than 100 mg/dL or unknown LDL-C levels
should be prescribed statin therapy on hospital discharge. (Level
of Evidence: B)
4. Patients with non–high-density lipoprotein cholesterol
(HDL-C) levels less than 130 mg/dL who have an HDL cholesterol level
less than 40 mg/dL should receive special emphasis on nonpharmacological
therapy (e.g., exercise, weight loss, and smoking cessation) to
increase HDL. (Level of Evidence: B)
Class IIa
1. It is reasonable to prescribe drug therapy at hospital discharge
to patients with non–HDL-C greater than or equal to 130 mg/dL,
with a goal of reducing non–HDL-C to substantially less than
130 mg/dL. (Level of Evidence: B)
2. It is reasonable to prescribe drugs such as niacin or fibrate
therapy to raise HDL-C levels in patients with LDL-C less than 100
mg/dL and non–HDL-C less than 130 mg/dL but HDL-C less than
40 mg/dL despite dietary and other nonpharmacological therapy. Dietary-supplement
niacin must not be used as a substitute for prescription niacin,
and over-the-counter niacin should be used only if approved and
monitored by a physician. (Level of Evidence: B)
3. It is reasonable to add drug therapy with either niacin or a
fibrate to diet regardless of LDL and HDL levels when triglyceride
levels are greater than 500 mg/dL. In this setting, non–HDL-C
(goal substantially less than 130 mg/dL) should be the cholesterol
target rather than LDL-C. Dietary-supplement niacin must not be
used as a substitute for prescription niacin, and over-the-counter
niacin should be used only if approved and monitored by a physician.
(Level of Evidence: B)
Early secondary prevention trials conducted before the use of statin
therapy, using the then-available drugs and diet to lower cholesterol,
demonstrated significant reductions of 25% in nonfatal MIs and 14%
in fatal MIs (59). Subsequently,
a growing body of evidence derived mainly from large randomized
clinical trials of statin therapy has firmly established the desirability
of lowering atherogenic serum lipids in patients who have recovered
from a STEMI.
The
Scandinavian Simvastatin Survival Study (1207)
reported results in 4444 men and women with CHD and moderate hypercholesterolemia
observed over 5.4 years. Coronary heart disease mortality was reduced
by 42% and total mortality by 30% among those receiving simvastatin
compared with placebo. The relative risk reduction seen in this
trial was similar among those with the lowest quartile compared
with the highest quartile of baseline serum LDLC. The CARE trial
was a similar study in a population of patients who had recovered
from an earlier MI and whose total cholesterol (mean 209 mg/dL)
and LDL-C (mean 139 mg/dL) were essentially the same as the average
for the general US population. In this trial, 4159 patients were
randomly assigned to either 40 mg of pravastatin a day or placebo.
After a median follow-up of 5 years, there was a significant reduction
in the primary end point of fatal CHD and nonfatal confirmed MIs
in the pravastatin cohort (3% ARD; 24% RRR; p equals 0.003) (1208).
The results of the large Long-Term Intervention With Pravastatin
in Ischemic Disease (LIPID) Study have been reported for more than
9000 patients randomly assigned to either placebo or 40 mg of pravastatin
daily (1209). The trial was conducted
in patients with a prior history of MI or unstable angina. Patient
age at time of entry ranged from 21 to 75 years. The LIPID trial
was stopped prematurely because of the efficacy of pravastatin in
reducing major cardiovascular events, including significant decreases
in CHD deaths (1.9% ARD; 24% RRR), total mortality rate (3.1% ARD;
22% RRR), and stroke (0.8% ARD; 19% RRR). Benefit has also been
seen in patients with symptomatic coronary disease who were treated
with fluvastatin. In the Lescol in Severe Atherosclerosis (LiSA)
Study, patients with symptomatic CHD and hypercholesterolemia who
were given fluvastatin had 71% fewer cardiac events than those in
the placebo group (1210).
The effect of cholesterol lowering combined with lowintensity oral
anticoagulation on late saphenous vein graft status has also been
investigated (1211). In an angiographic
trial attempting to reduce atherosclerosis in saphenous vein grafts
after CABG surgery, aggressive lowering of LDL to less than 100
mg/dL with lovastatin 40 to 80 mg daily (and 8 g of cholestyramine
daily, if needed), in addition to a Step I AHA diet, achieved a
significant reduction (2.7% ARD; 29% RRR) in obstructive changes
in the vein grafts at 4 to 5 years compared with moderate lipid
lowering to an LDL-C of 132 to 136 mg/dL (1211).
There was no benefit of low-dose warfarin therapy at 5 years. The
results of 7.5-year follow-up revealed significant reductions of
30% in revascularization and 24% for the composite end point (death,
nonfatal MI, stroke, CABG, or PCI) in the group treated with aggressive
lipid-lowering therapy. The investigators concluded that the study
provided support for the NCEP recommendation that LDL-C levels should
be reduced to less than 100 mg/dL in patients who have coronary
artery disease (1212).
The Heart Protection Study (1213)
trial randomized more than 20 000 men and women aged 40 to 80 years
with coronary disease, other vascular disease, diabetes, and/or
hypertension
to simvastatin 40 mg or placebo for a mean followup of 5 years.
The primary end point, total mortality, was significantly reduced
with statin treatment (1.8% ARD; 12% RRR, p equals 0.0003). The
advantages of simvastatin therapy were demonstrated in all important
prespecified subgroups, including women, patients more than 75 years
old, diabetics, and individuals with baseline LDL-C of less than
100 mg/dL. The study supports the benefit of statin therapy for
all groups and argues for the use of statins among patients with
CHD and LDL-C values 100 to 129 mg/dL who had previously been considered
candidates for diet and lifestyle changes to lower LDL-C before
implementation of statin therapy (59).
Approximately 25% of patients who have recovered from STEMI demonstrate
desirable total cholesterol values but a low HDL-C fraction on a
lipid profile. Low HDL-C is an independent risk factor for development
of coronary artery disease (1214),
and therefore a rationale exists for attempting to raise HDL-C when
it is found to be low in the patient with coronary artery disease.
The Veterans Affairs High-Density Lipoprotein Cholesterol Intervention
Trial (VA-HIT) (1215) revealed
that modification of other lipid risk factors can reduce risk for
CHD when LDL-C is in the range of 100 to 129 mg/dL. In this trial,
male patients with a relatively low LDL-C (mean 112 mg/dL) were
treated with gemfibrozil for 5 years. Gemfibrozil therapy, which
raised HDL-C and lowered triglycerides, reduced the primary end
point of fatal and nonfatal MI (4.4% ARD; 22% RRR) without significantly
lowering LDL-C levels. There was no evidence of an increased risk
of non-CHD mortality. This trial supports the concept that when
LDL-C is in the range of 100 to 129 mg/dL, the use of other lipid-modifying
drugs (e.g., fibrates) is a therapeutic option if the patient has
a low HDL-C (less than 40 mg/dL).
The effect of hypertriglyceridemia is somewhat controversial because
in many cases, the triglyceride level varies inversely with HDL-C
levels. However, if hypertriglyceridemia (triglyceride greater than
200 mg/dL) exists after lifestyle changes such as diet and exercise
and statin therapy have been initiated, it is recommended that additional
therapy be initiated to lower triglycerides for patients with established
CHD (59). In this setting, the target
goal of therapy should be non–HDL-C less than 130 mg/dL.
Diet and drug treatments available for the correction of lipid abnormalities
are as effective in the elderly as in the young. Clinical trials
have shown that such treatment can reduce total mortality up to
age 70 years (1207) and the rate
of recurrent coronary events up to age 75 years (1208).
In addition, the PROSPER trial (1208)
studied the value of lipid control for the prevention of initial
coronary events in 5804 older persons (2804 men and 3000 women aged
70 to 82 years). Treatment with pravastatin 40 mg daily resulted
in a reduction in LDL-C by 34% and significantly reduced the primary
end point (CHD death, nonfatal MI, and fatal or nonfatal stroke)
over 3.2 years (2.1% ARD; 15% RRR). Unlike previous trials involving
elderly patients, the risk of stroke in PROSPER was unaffected,
possibly because of the relatively short duration of the trial.
Among elderly patients, other risk factors such as high blood pressure,
cigarette smoking, and diabetes are frequently present. Thus, it
is especially important in this group, as in younger patients, to
develop comprehensive treatment programs, such as cardiac rehabilitation,
to address all risk factors that might contribute to future CHD
events in addition to treating their dyslipidemia.
The early secondary prevention trials of statins specifically excluded
patients with STEMI in the acute phase. Thus, although the data
supporting the efficacy and benefit of statin therapy for patients
after STEMI are robust, statin therapy in the early studies was
started 4 to 6 months after STEMI. Subsequent studies have addressed
the potential benefits of early initiation of statin therapy during
hospitalization for acute coronary syndrome. The results from several
of these studies, wherein statins were initiated during the hospital
phase of acute coronary syndromes, indicate improved cardiovascular
outcomes. The Lipid-Coronary Artery Disease trial (1216)
randomized 126 patients with acute coronary syndrome to early treatment
with pravastatin with or without cholestyramine or niacin therapy
versus usual care. Treatment initiated during hospitalization significantly
reduced clinical events at 2 years. The Myocardial Ischemia Reduction
with Aggressive Cholesterol Lowering (MIRACL) trial randomized 3086
patients admitted for acute coronary syndrome to treatment with
atorvastatin 80 mg per day or placebo within 96 hours after admission
(1217). The primary end point
of death, nonfatal MI, resuscitated cardiac arrest, or recurrent
severe myocardial ischemia was reduced from 17.4% to 14.8% (p equals
0.048) by treatment with atorvastatin. The major clinical benefits
were fewer strokes and a lower risk of severe recurrent ischemia
among those treated with atorvastatin. In the Swedish Registry of
Cardiac Intensive Care of nearly 20 000 patients, a 25% reduction
in mortality at 1 year was observed among patients when statin therapy
was initiated before hospital discharge (1218).
Early initiation of therapy has been recommended by the NCEP (59).
The Pravastatin or Atorvastatin Evaluation and Infection Therapy-
Thrombolysis in Myocardial Infarction 22 study (PROVE-ITTIMI 22)
(1219) compared intensive lipid-lowering
therapy to moderate lipid-lowering therapy initiated within 10 days
after hospital admission in 4162 patients with acute coronary syndrome.
Lipid lowering to a goal of LDL-C less than 100 mg/dL (median 95
mg/dL) with pravastatin 40 mg per day was compared with lipid-lowering
to a goal of LDL-C less than 70 mg/dL (median 62 mg/dL) with atorvastatin
80 mg daily. After 2 years of therapy, the primary end point (death
due to any cause, MI, unstable angina requiring rehospitalization,
coronary revascularization, and stroke) was 26.3% for the group
undergoing moderate lipid-lowering therapy and 22.4% in the intensive
lipid-lowering group, reflecting a 16% reduction in the hazard ratio
favoring intensive lipidlowering therapy (p equals 0.005). Benefits
were observed within 30 days of initiation of therapy and occurred
at all levels of LDL-C, even among those patients with LDL-C less
than 100 mg/dL, although the greatest benefit was seen among patients
with LDL-C of 125 mg/dL or greater. The benefits were observed in
all important subgroups, including men and women, young and old,
and patients with and without diabetes. These data support the early,
intensive treatment of patients with acute coronary syndromes to
LDL-C goals substantially less than 100 mg/dL with statin therapy.
Patients hospitalized with CHD who start lipid-lowering therapy
before discharge have been shown to be nearly 3 times as likely
to be taking medication at 6 months as those starting therapy after
discharge (1220).
7.12.3. Weight Management
Class I
1. Measurement of waist circumference and calculation of body mass
index are recommended. Desirable body mass index range is 18.5 to
24.9 kg/m2. A waist circumference greater than 40 inches in men
and 35 inches in women would result in evaluation for metabolic
syndrome and implementation of weight-reduction strategies. (Level
of Evidence: B)
2. Patients should be advised about appropriate strategies for weight
management and physical activity (usually accomplished in conjunction
with cardiac rehabilitation). (Level of Evidence: B)
3. A plan should be established to monitor the response of body
mass index and waist circumference to therapy (usually accomplished
in conjunction with cardiac rehabilitation). (Level of Evidence:
B)
Obesity is a recognized major risk factor for cardiovascular disease
and an important component of the metabolic syndrome (59).
The clinical criteria for the metabolic syndrome include any 3 of
the following: waist circumference greater than 40 inches in men
and greater than 35 inches in women; triglycerides of at least 150
mg/dL; HDL-C less than 40 mg/dL in men or less than 50 mg/dL in
women; blood pressure greater than 130 mm Hg systolic and greater
than 85 mm Hg diastolic; and fasting blood glucose of at least 110
mg/dL. The metabolic syndrome contributes significantly to CHD risk.
Its treatment has weight control and physical activity as primary
strategies. Because approximately 65% of the US adult population
is overweight or obese (1221),
it is suggested that this risk factor be carefully addressed as
part of the secondary prevention strategy for all patients after
STEMI. The suggested goal should be the achievement or maintenance
of a healthy weight, defined in the “Dietary Guidelines for
Americans” (1222) as a body
mass index from 18.5 to 24.9 kg/m2. It is suggested that overweight
patients be instructed in a weight loss regimen as part of their
cardiac rehabilitation program after STEMI, with emphasis on the
importance of regular exercise and a lifelong prudent diet to maintain
healthy weight. Weight reduction enhances lowering of other risk
factors for cardiovascular disease, including LDL-C, triglycerides,
impaired glucose, and blood pressure. An initial weight loss of
10% of body weight achieved over 6 months is a recommended target.
The rate of weight loss should be 1 to 2 pounds each week.
7.12.4.
Smoking Cessation
Class I
1. Patients recovering from STEMI who have a history of cigarette
smoking should be strongly encouraged to stop smoking and to avoid
secondhand smoke. Counseling should be provided to the patient and
family, along with pharmacological therapy (including nicotine replacement
and bupropion) and formal smoking cessation programs as appropriate.
(Level of Evidence: B)
2. All STEMI patients should be assessed for a history of cigarette
smoking. (Level of Evidence: A)
Smoking cessation is essential for patients with STEMI. Smoking
triggers coronary spasm, reduces the anti-ischemic effects of beta-adrenoceptor
blockers, and doubles mortality after STEMI (1223-1225).
Smoking cessation reduces rates of reinfarction and death within
1 year of quitting, but one third to one half of patients with STEMI
relapse within 6 to 12 months (1226).
Because exposure to secondary cigarette smoke has been identified
as a risk factor, family members who live in the same household
should also be encouraged to quit smoking to help reinforce the
patient’s effort and to decrease the risk of secondhand smoke
(1227).
The most effective strategies for encouraging quitting are those
that identify the patient's level or stage of readiness and provide
information, support, and, if necessary, pharmacotherapy targeted
at the individual’s readiness and specific needs (66,1228).
Houston-Miller and Taylor (1229)
advocate a stepped approach to smoking cessation:
a. Provide a firm, unequivocal message to quit smoking
b. Determine whether the patient is willing to quit
c. Determine the best quitting method
d. Plan for problems associated with withdrawal
e. Set a quit date
f. Help the patient cope with urges to smoke
g. Provide additional help as needed
h. Follow-up by telephone call or visit
The stepwise strategies are summarized in Table
30 of the ACC/AHA 2002 Guideline Update for the Management of
Patients with Chronic Stable Angina (71).
The most effective pharmacological adjuncts for treating nicotine
dependence are nicotine replacement therapy and bupropion in the
sustained-release form. When these are combined with behavioral
counseling, the best treatment outcomes have been reported (1230).
Nicotine replacement therapy (gum and patches) has been shown to
increase smoking cessation rates, particularly when combined with
counseling (1231). Nicotine replacement
therapy can mitigate symptoms of nicotine withdrawal in recovering
patients (1232). A population-
based case-control study did not find an association between
nicotine patches and first-time MI (1233).
Several studies have suggested that nicotine replacement therapy
does not increase the risk for cardiovascular events, even in people
with underlying CHD (1234-1237),
although the studies had few or no patients with MI (1235-1237)
and were not designed (1235) or
sufficiently powered (1234) to
examine cardiovascular effects. Thus, routine use of these agents
is not recommended during hospitalization for STEMI because of the
sympathomimetic effects of the active ingredient, nicotine. However,
the dose of nicotine in gums and patches is significantly lower
than that found in cigarettes and may be preferable to cigarette
smoking if the patient is experiencing acute withdrawal. Therefore,
at the time of discharge, if blood pressure and heart rate are stable,
these agents may be used in selected patients. Clonidine has been
shown to be effective in women but not men (1238);
the reason for this finding is unclear. Lobeline has not been shown
to have an advantage over placebo (1239-1241)
but is again under investigation.
Bupropion has been shown to help smokers quit (1242,1243).
Nicotine intake is reinforced by activating the central nervous
system to release norepinephrine, dopamine, and other neurotransmitters.
Bupropion is a weak inhibitor of the neuronal uptake of neurotransmitters.
A study of 615 subjects randomly assigned to take placebo or bupropion
achieved good initial quit rates with treatment augmented by brief
counseling at baseline, weekly counseling during treatment, and
intermittent counseling for up to 1 year (1244).
Seven weeks of treatment with bupropion was associated with a smoking
cessation rate of 28.8% (100 mg/d), 38.6% (150 mg/d), and 44.2%
(300 mg/d); 19.6% of subjects assigned to placebo quit (p less than
0.001). At 1 year, 12.4% of the placebo group and 19.6% (100 mg/d),
22.9% (150 mg/d), and 23.1% (300 mg/d) of the bupropion group remained
abstinent. The drug was well tolerated (37 [8%] of 462 stopped treatment
prematurely because of headache, insomnia, or dry mouth), although
the study was insufficiently powered to detect an incidence of seizures
known to occur with related medications. It reduced the weight gain
common in smokers who quit. Bupropion appears to be a valuable option
for patients who need to quit smoking after STEMI. In an actual
large group-practice setting, the combination of slow-release bupropion
and minimal or moderate counseling was associated with 1-year quit
rates of 24% and 33%, respectively (1243).
7.12.5. Antiplatelet Therapy
Class I
1. A daily dose of aspirin 75 to 162 mg orally should be given indefinitely
to patients recovering from STEMI. (Level of Evidence: A)
2. If true aspirin allergy is present, preferably clopidogrel (75
mg orally per day) or, alternatively, ticlopidine (250 mg orally
twice daily) should be substituted. (Level of Evidence: C)
3.
If true aspirin allergy is present, warfarin therapy with a target
INR of 2.5 to 3.5 is a useful alternative to clopidogrel in patients
less than 75 years of age who are at low risk for bleeding and who
can be monitored adequately for dose adjustment to maintain a target
INR range. (Level of Evidence: C)
Class III
Ibuprofen should not be used because it blocks the antiplatelet
effects of aspirin. (Level of Evidence: C)
On the basis of 12 randomized trials in 18 788 patients with prior
infarction, the Antiplatelet Trialists’ Collaboration reported
a 25% reduction in the risk of recurrent infarction, stroke, or
vascular death in patients receiving prolonged antiplatelet therapy
(36 fewer events for every 1000 patients treated) (263).
No antiplatelet therapy has proved superior to aspirin in this population,
and daily doses of aspirin between 80 and 325 mg appear to be effective
(1245). The CAPRIE trial, which
compared aspirin with clopidogrel in 19 185 patients at high risk
for vascular events, demonstrated a modest but significant reduction
in serious vascular events with clopidogrel compared with aspirin
(0.51% ARD; 8.6% RRR; p equals 0.043) (742).
These data suggest clopidogrel as the best alternative to aspirin
in patients with true aspirin allergy.
These compelling data suggest that all patients recovering from
STEMI should, in the absence of contraindications, continue taking
aspirin for an indefinite period (1246).
Clopidogrel or ticlopidine may be substituted in patients with true
aspirin allergy.
The use of warfarin therapy for secondary prevention of vascular
events in patients after STEMI is discussed in Section
7.12.11. Large randomized trials have demonstrated that oral
anticoagulants, when given in adequate doses, reduce the rates of
adverse outcomes, at the cost of a small increase in hemorrhagic
events (1247-1249).
In the Warfarin, Aspirin, Reinfarction Study (WARIS II), warfarin
without aspirin in a dose intended to achieve an INR of 2.8 to 4.2
resulted in a significant reduction in a composite end point (death,
nonfatal reinfarction, or thromboembolic stroke) compared with therapy
with aspirin alone (16.7% versus 20.0%) (1247).
Warfarin therapy resulted in a small but significant increase in
major, nonfatal bleeding compared with therapy with aspirin alone
(0.62% per year versus 0.17% per year). Chronic therapy with warfarin
after STEMI presents an
alternative to clopidogrel in patients with aspirin allergy.
A small increase in incidence of stroke in healthy men treated with
aspirin was reported in both the American physician and the British
doctors primary prevention studies (1250,1251).
However, there has been no evidence of an increased incidence of
stroke in studies in which aspirin was used for secondary prevention
of coronary artery disease. These secondary prevention trials clearly
indicate that in patients with clinical manifestations of atherosclerotic
disease, aspirin reduces risk of stroke. It is likely that as a
consequence of its antihemostatic effect, aspirin produces a small
increase in risk of cerebral hemorrhage, which is masked by the
beneficial effects of aspirin in patients with an increased risk
for thromboembolic stroke but becomes manifest in healthy individuals
at very low risk for this event.
Aspirin and NSAIDs are among the most commonly consumed drugs. An
interaction between aspirin and ibuprofen on platelet function has
been demonstrated in an in vivo model, with concomitant administration
of ibuprofen (but not rofecoxib, diclofenac, or acetaminophen) antagonizing
the irreversible platelet inhibition induced by aspirin (1252).
A subsequent epidemiological study demonstrated increased all-cause
and cardiovascular mortality in patients with cardiovascular disease
taking aspirin plus ibuprofen compared with those taking aspirin
alone, aspirin plus diclofenac, or aspirin plus other NSAIDs (1253).
The use of NSAIDs in patients taking aspirin was also assessed in
an observational subgroup analysis of the Physician's Health Study
(1254). Regular (greater than
60 days per year) use of NSAIDs inhibited the clinical benefits
of aspirin, although intermittent use (fewer than 59 days per year)
had no effect. These findings suggest that ibuprofen may limit the
cardioprotective effects of aspirin. Pending further data, clinicians
should discourage patients with cardiovascular disease who are taking
aspirin from using ibuprofen on a regular basis.
7.12.6. Inhibition of the Renin-Angiotensin-
Aldosterone System
Class I
1. An ACE inhibitor should be prescribed at discharge for all patients
without contraindications after STEMI. (Level of Evidence: A)
2. Long-term aldosterone blockade should be prescribed for post-STEMI
patients without significant renal dysfunction (creatinine should
be less than or equal to 2.5 mg/dL in men and less than or equal
to 2.0 mg/dL in women) or hyperkalemia (potassium should be less
than or equal to 5.0 mEq/L) who are already receiving therapeutic
doses of an ACE inhibitor, have an LVEF less than or equal to 0.40,
and have either symptomatic heart failure or diabetes. (Level
of Evidence: A)
3. An ARB should be prescribed at discharge to those STEMI patients
who are intolerant of an ACE inhibitor and have either clinical
or radiological signs of heart failure and LVEF less than 0.40.
Valsartan and candesartan have established efficacy for this recommendation.
(Level of Evidence: B)
Class IIa
In STEMI patients who tolerate ACE inhibitors, an ARB can be useful
as an alternative to ACE inhibitors in the long-term management
of STEMI patients, provided there are either clinical or radiological
signs of heart failure or LVEF less than 0.40. Valsartan and candesartan
have established efficacy for this recommendation. (Level of
Evidence: B)
Class
IIb
The combination of an ACE inhibitor and an ARB may be considered
in the long-term management of STEMI patients with persistent symptomatic
heart failure and LVEF less than 0.40. (Level of Evidence: B)
The use of ACE inhibitors early in the acute phase of STEMI and
in the hospital management phase has been described earlier in Sections
6.3.1.6.9.1 and 7.4.3. Through their ability
to interfere with ventricular remodeling, thereby attenuating ventricular
dilation over time, ACE inhibitors improve clinical outcomes among
patients with LV dysfunction (LVEF less than 0.40) after STEMI.
The clinical result is a lessened likelihood for development of
CHF, recurrent MI, and death. They are also of value in patients
without clinical evidence of CHF but with a history of previous
MI, in whom they have been shown to reduce cardiovascular mortality,
future MI, and cardiac arrest.
These observations, coupled with experience in both the rat model
of STEMI (1255) and large randomized
clinical trials (585,1256,1257),
have established that use of ACE inhibitors begun after a patient
has recovered from STEMI improves long-term survival, provided the
infarct was large and anterior in location, and results in significant
impairment of LV contractility. Specifically, in the SAVE trial,
patients took captopril at a mean 11 days after onset of infarction,
which resulted in an approximate 20% reduction in mortality (1256).
The Acute Infarction Ramipril Efficacy (AIRE) trial, in which patients
who had been in clinical heart failure during the first day of their
infarct and then were randomly assigned to either ramipril or placebo
an average of 5 days after onset of infarction, resulted in significant
risk reduction in all-cause mortality (6% ARD; 27% RRR) (1257).
Similarly, the TRACE trial, in which patients with LV dysfunction
on echocardiogram were randomly assigned to receive either trandolapril
or placebo a median of 4 days after onset of infarction, demonstrated
a significant reduction in mortality (7.6% ARD; 22% RRR) (1258).
The SOLVD trial evaluated the ACE inhibitor enalapril in 4228 asymptomatic
patients with LVEF less than 0.35, 80% of whom had experienced a
prior MI (1259). However, randomization
was performed considerably later on the average than in the SAVE
and AIRE trials. This prevention arm of the SOLVD trial revealed
a trend toward improved mortality but not a statistically significant
difference (1260). On the other
hand, SOLVD did demonstrate a significant risk reduction of 20%
for the combined end points of death or development of CHF requiring
hospitalization.
In secondary analyses of the initial ACE inhibitor trials, the benefit
of treatment appeared to be primarily in patients with anterior
infarctions or LVEF below 0.40. However, based on post hoc analysis
of the SAVE trial, in which the likelihood of recurrent MI was reduced
by approximately 25% in treated patients, studies were initiated
to determine the benefits of ACE inhibitor therapy among patients
with known CHD but no clinical evidence for CHF (1261).
Compelling evidence now supports the broad chronic use of ACE inhibitors
after STEMI.
The HOPE trial evaluated the effect of long-term (4 to 6 years)
ACE inhibition therapy with ramipril 10 mg per day in 9297 high-risk
patients, 2480 of whom were women. Fifty-two percent of the patients
had a history of MI, and in 10%, the MI was within 1 year. Overall,
there was a highly significant reduction in the combined end point
of MI, stroke, and all-cause cardiovascular mortality (3.8% ARD;
22% RRR; p less than 0.001). Significant reductions were seen for
each individual component of the primary end point: MI 2.4% ARD,
RRR 20%; stroke 1.5% ARD, RRR 32%; and death of any cause 1.8% ARD,
RRR 16%. Importantly, the study was performed in patients who were
not known to have low ejection fraction or heart failure. The European
Trial on Reduction of Cardiac Events With Perindopril in Stable
Coronary Artery Disease (EUROPA) evaluated the use of the ACE inhibitor
perindopril given 8 mg per day among 13 655 patients (age range
26 to 89 years, mean 60 years) with known CHD but no history of
clinical heart failure (1262).
Nearly two thirds (64%) of the patients had a history of previous
MI (more than 3 months before screening). After a mean follow-up
of 4.2 years, treatment with perindopril was associated with a significant
reduction (2% ARD; 20% RRR; p equals 0.0003) in the combined end
point of nonfatal MI, cardiovascular mortality and resuscitated
cardiac arrest. The benefit began to appear at 1 year and gradually
progressed throughout the trial. Patients in EUROPA all had CHD
but a lower risk than those in HOPE, in which the enrollment age
was 55 years or older and 39% had diabetes. In EUROPA, nearly one
third of the patients were younger than 55 years, and fewer had
diabetes and hypertension. Moreover, the benefits of ACE inhibitor
therapy with perindopril were observed in spite of relatively high
use of other secondary prevention therapies such as platelet inhibitors
(91%), lipidlowering medications (69%), and beta-blockers (63%).
Given the results of the HOPE trial and the secondary analysis from
the initial ACE inhibitor trials, ACE inhibitor therapy is recommended
for all patients after STEMI unless otherwise contraindicated.
The results of the VALIANT study evaluating the ARB valsartan are
discussed in Section 7.4.3. The series of CHARM
studies (Candesartan in Heart Failure Assessment in Reduction of
Mortality, although focusing on the evaluation of the ARB candesartan
in patients with chronic heart failure, provides information that
can be extrapolated to the longterm management of the STEMI patient,
because 50% to 60% of the patients studied had ischemic heart disease
as the cause of heart failure. In patients with symptomatic heart
failure and LVEF 0.40 or less who were intolerant of ACE inhibitors
(CHARM-Alternative trial), candesartan (target dose 32 mg once daily)
was more effective than placebo in preventing cardiovascular death
or hospital admission for heart failure (7% ARD; 23% RRR) (1263).
In patients with symptomatic heart failure and LVEF 0.40 or less
who were being treated with an ACE inhibitor (CHARM-Added trial),
candesartan (target dose 32 mg) was more effective than placebo
in preventing cardiovascular death or hospital admission for heart
failure (4% ARD; 15% RRR) (1264).
Inpatients with symptomatic heart failure but with a preserved LVEF
(greater than 0.40; CHARM-Preserved trial), candesartan had no impact
on cardiovascular death compared with placebo but was associated
with a trend toward fewer admissions for heart failure (1265).
Given the extensive randomized trial and routine clinical experience
with ACE inhibitors, they remain the logical first agent for inhibition
of the renin-angiotensin-aldosterone system in the long-term management
of patients with STEMI (726). The
ARBs valsartan and candesartan should be administered over the long
term to patients with STEMI with symptomatic heart failure who are
intolerant of ACE inhibitors. As described in Section
7.4.3, the choice between an ACE inhibitor and an ARB in patients
who are tolerant of ACE inhibitors over the long term will vary
with individual physician and patient preference, as well as cost
and anticipated side-effect profile (726).
The results of the most relevant clinical trials testing combinations
of ACE inhibitors and ARBs have subtly different but clinically
relevant results. Whereas the CHARM-Added (1264)
trial demonstrated a reduction in the combined end point of heart
failure hospitalization and death over ACE inhibition alone, the
VALIANT study (725) reported that
the combination of captopril and valsartan was equivalent to either
alone, but with a greater number of adverse effects. Thus, when
combination ACE inhibition and angiotensin receptor blockade is
considered, the preferred ARB is candesartan. Although there is
evidence that the combination of an ACE inhibitor and an aldosterone
inhibitor is effective at reducing mortality and is well tolerated
in patients with a serum creatinine less than or equal to 2.5 mg/dL
and serum potassium concentration less than or equal to 5.0 mmol/L
(see Section 7.4.3), much less experience exists
with the combination of an ARB and an aldosterone inhibitor (24%
of 2028 patients in the CHARM-Alternative trial) and the triple
combination of an ACE inhibitor, ARB, and an aldosterone antagonist
(17% of 2548 patients in the CHARM-Added trial) (1263,1264).
The combination of an ACE inhibitor and an ARB (valsartan 20 mg
orally per day initially, titrated up to 160 mg orally twice per
day, or candesartan 4 to 8 mg orally per day initially, titrated
up to 32 mg orally per day) or an ACE inhibitor and an aldosterone
inhibitor may be considered for the longterm management of patients
with STEMI with symptomatic heart failure and ejection fraction
less than 0.40, provided the serum creatinine is less than or equal
to 2.5 mg/dL in men and less than or equal to 2.0 mg/dL in women
and serum potassium concentration is less than or equal to 5.0 mEq/L.
(See Sections 7.4.3 and 7.6.4.)
7.12.7.
Beta-Blockers
Class I
1. All patients after STEMI except those at low risk (normal or
near-normal ventricular function, successful reperfusion, absence
of significant ventricular arrhythmias) and those with contraindications
should receive
beta-blocker therapy. Treatment should begin within a few days of
the event, if not initiated acutely, and continue indefinitely.
(Level of Evidence: A)
2. Patients with moderate or severe LV failure should receive beta-blocker
therapy with a gradual titration scheme. (Level of Evidence:
B)
Class IIa
It is reasonable to prescribe beta-blockers to low-risk patients
after STEMI who have no contraindications to that class of medications.
(Level of Evidence: A)
The
use of beta-blockers in the early phase of STEMI and in hospital
management is reviewed in Sections
6.3.1.6 and 7.4.1. The benefits of beta-blocker
therapy in patients without contraindications have been demonstrated
with or without reperfusion, initiated early or later in the clinical
course, and for all age groups. The greatest mortality benefit is
seen in patients with the greatest baseline risk: those with impaired
ventricular function or ventricular arrhythmias and those who do
not undergo reperfusion (1266,1267).
The benefits of beta-blocker therapy for secondary prevention are
well established (717,1012).
In patients with moderate or severe LV failure, beta-blocker therapy
should be administered with a gradual titration scheme (1268).
Long-term betablocker therapy should be administered to survivors
of STEMI who have subsequently undergone revascularization, because
there is evidence of a mortality benefit from their use despite
revascularization either with CABG surgery or with PCI (1269).
Given these well-documented benefits, it is disturbing that this
therapy continues to be underused, especially in highrisk groups
such as the elderly (1270). Beta-blockers
should be prescribed for all high-risk patients provided no contraindications
are present. In patients with an extremely good prognosis (first
STEMI, good ventricular function, no angina, negative stress test,
and no complex ventricular ectopy), the effect of beta-blockers
on survival will be less (1271).
However, beta-blockers are often prescribed for these patients to
minimize the likelihood of recurrent ischemic symptoms and to help
control surges of heart rate and blood pressure with exertion.
Although relative contraindications may once have been thought to
preclude the use of beta-blockers in some patients, evidence now
suggests that the benefits of beta-blockers in reducing reinfarctions
and mortality may actually outweigh the risks, even in patients
with mild asthma not currently active, insulin-dependent diabetes
mellitus, chronic obstructive pulmonary disease, severe peripheral
vascular disease, PR interval greater than 0.24 seconds, and moderate
LV failure. The use of beta-blockers in such patients requires monitoring
to be certain that adverse events do not occur (1270,1272,1273).
Some controversy exists as to how long patients should be treated
(1274). Data from large trials
suggest that therapy should be continued for at least 2 to 3 years
(851,1275).
Thereafter, if the beta-blocker is well tolerated, such therapy
should probably be continued in most patients, although data are
lacking.
7.12.8. Blood Pressure Control
Class I
1. Blood pressure should be treated with drug therapy to less than
140/90 mm Hg and to less than 130/80 mmHg for patients with diabetes
or chronic kidney disease. (Level of Evidence: B)
2. Lifestyle modification (weight control, dietary changes, physical
activity, and sodium restriction) should be initiated in all patients
with blood pressure greater than or equal to 120/80 mm Hg. (Level
of Evidence: B)
Class IIb
A target goal of 120/80 mm Hg for post-STEMI patients may be reasonable.
(Level of Evidence: C)
Class III
Short-acting dihydropyridine calcium channel blocking agents should
not be used for the treatment of hypertension. (Level of Evidence:
B)
The Seventh Report of the Joint National Committee on Prevention,
Detection, Evaluation, and Treatment of High Blood Pressure (JNC-7)
(1276) recommends that patients
be treated after MI with ACE inhibitors, beta-blockers, and, if
necessary, aldosterone antagonists to a target blood pressure of
less than 140/90 mm Hg, or less than 130/80 mm Hg for those with
chronic kidney disease or diabetes (1276).
Most patients will require 2 or more drugs to reach goal, and when
the blood pressure is greater than 20/10 mm Hg above goal, 2 drugs
should usually be used from the outset. The Antihypertensive and
Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT)
(1277) demonstrated that an antihypertensive
regimen based on a thiazide diuretic was equal to an ACE inhibitor–
or long-acting calcium channel blocker–based regimen in coronary
outcomes and superior in other outcomes (CHF, stroke). Most patients
received a betablocker in addition to the thiazide.
Beta-blockers reduce the risk for subsequent MI or sudden cardiac
death and are indicated in all patients after STEMI absent specific
contraindications; they may be especially efficacious in patients
with CHF. In general, beta-blockers without intrinsic sympathomimetic
activity should be used. Beta-blockers are sufficiently important
that they should be withheld only for high-grade heart block, demonstrated
intolerance, or other absolute contraindications. Most patients
with asthma are able to tolerate cardioselective beta-blockers (1278).
Because of the demonstrated effectiveness of thiazide diuretics
for reducing adverse outcomes, they should be strongly considered
when a second or third agent is needed. ACE inhibitors (or ARBs
if ACE inhibitors are not tolerated) should be used long term for
the treatment of hypertension when LV dysfunction is present to
prevent subsequent heart failure and mortality (1279).
ACE inhibitors and ARBs have been shown to favorably affect the
progression of diabetic and nondiabetic kidney disease but should
be given with careful attention to the development of hyperkalemia
(1276). Long-acting calcium channel
blockers may be used if other agents are not tolerated or are not
sufficient to reach blood pressure goal. Short-acting calcium antagonists
should not be used (636).
JNC-7 emphasizes the importance of lifestyle modifications for all
patients with blood pressure of 120/80 mm Hg or greater (1276).
These modifications include: weight reduction if overweight or obese,
consumption of a diet rich in fruits and vegetables and low in total
fat and saturated fat, and reduction of sodium to no more than 2.4
g/d (1276).
7.12.9. Diabetes Management
Class I
Hypoglycemic therapy should be initiated to achieve HbA1C less than
7%. (Level of Evidence: B)
Class III
Thiazolidinediones should not be used in patients recovering from
STEMI who have New York Heart Association class III or IV heart
failure. (Level of Evidence: B)
Tight glucose control in diabetics during and after STEMI has been
shown to lower acute and 1-year mortality rates (602).
Tight glucose control, defined as an HbA1C of less than 7.0%, reduces
microvascular disease and is strongly recommended, although further
data are needed regarding its specific benefits for macrovascular
disease (1280). Control of hyperglycemia
has been shown to reduce diabetes-related events, including MI (2.7%
absolute reduction; 16% relative reduction), for patients aged 25
to 65 years with newly detected type 2 diabetes but without symptomatic
macrovascular disease (1280).
Thiazolidinediones are frequently used as monotherapy or in combination
with other oral hypoglycemic agents, insulin, and diet for control
of diabetes. Although thiazolidinediones may be helpful in combating
insulin resistance and thereby may improve vascular, neurohormonal,
and myocardial function, their use may also be associated with fluid
retention and an increase in LV preload (1281)
that is resistant to diuretics. Therefore, thiazolidinediones should
not be used in patients recovering from STEMI who have New York
Heart Association class III or IV heart failure (1281,1282).
7.12.10. Hormone Therapy
Class III
1. Hormone therapy with estrogen plus progestin should not be given
de novo to postmenopausal women after STEMI for secondary prevention
of coronary events. (Level of Evidence: A)
2. Postmenopausal women who are already taking estrogen plus progestin
at the time of a STEMI should not continue hormone therapy. However,
women who are beyond 1 to 2 years after initiation of hormone therapy
who wish to continue such therapy for another compelling indication
should weigh the risks and benefits, recognizing a greater risk
of cardiovascular events. Hormone therapy should not be continued
while patients are on bedrest in the hospital. (Level of Evidence:
B)
Landmark randomized clinical trials have provided firm evidence
that combination estrogen and progestin replacement therapy should
not be used for either primary or secondary prevention of cardiovascular
disease in women. Observational studies (1283,1284)
have been interpreted as indicating that oral unopposed estrogen
is effective in primary prevention of cardiovascular disease. Confounding
factors such as compliance (1285),
selection bias, and baseline health in these studies make it difficult
to be certain of the effect of estrogen therapy alone.
Clinical trials have shown that estrogen given alone or in combination
with progestin improves the lipid profile and lowers fibrinogen
(1286). Favorable effects of estrogen
on the lipid profile would theoretically be expected to produce
a favorable result in preventing coronary atherosclerosis. However,
combining estrogen with a progestin (hormone therapy) (1287)
reduces the potential beneficial effect of estrogen given alone
on the lipid profile. In addition, hormone therapy has been reported
to increase high-sensitivity C-reactive protein levels (1288).
The first large-scale, randomized, double-blind, placebocontrolled
trial that addressed the question of estrogen plus progestin for
secondary prevention of CHD in postmenopausal women was published
by Hulley et al. (1287) for the
Heart and Estrogen/progestin Replacement Study (HERS) Research Group.
Contrary to conventional wisdom and several observational studies
(1289-1292),
this trial of 3763 postmenopausal women with established coronary
disease and an average age of 66.7 years found no reduction in overall
risk for nonfatal MI or coronary death, nor any other cardiovascular
outcome, during an average of 4.1 years of follow-up when comparing
0.625 mg of conjugated equine estrogen plus 2.5 mg of medroxyprogesterone
acetate in 1 tablet daily (1380 patients) to placebo (1383 patients).
This lack of an overall effect occurred despite a net 11% lower
LDL-C level and a 10% higher HDL-C level in the group given hormone
therapy compared with the placebo group (p less than 0.001). There
was a statistically significant time trend, however, with more primary
coronary events in the hormone therapy group than in the placebo
group in year 1 and fewer in years 4 and 5. However, the latter
was due to nonfatal MI, because CHD deaths were similar in the 2
groups in years 4 and 5. More women in the hormone group than in
the placebo group experienced venous thromboembolic events (34 versus
12; RR 2.89; 95% CI 1.50 to 5.58) and gallbladder disease (84 versus
62; RR 1.38; 95% CI 1.00 to 1.92). HERS II extended the unblinded
follow-up of the HERS cohort (93% of survivors) for an additional
2.7 years (total 6.8 years of observation) (1293).
The lower rates of CHD in the hormone therapy–assigned women
in the latter years of HERS did not persist during additional observation.
Hormone therapy did not reduce CHD events after 6.8 years. The Estrogen
Replacement and Atherosclerosis (ERA) trial showed no effect of
estrogen alone or estrogen plus progesterone on the progression
of coronary artery disease, despite favorable effects on lipids
(1292). A small randomized controlled
trial of transdermal estradiol for women after non–STelevation
acute coronary syndrome showed no benefit, with a trend toward excess
events (1294). The Women's Health
Initiative (WHI) Hormone Trial (HT) includes a group of women who
have had hysterectomies (10 000) and receive unopposed estrogen
and women with intact uteruses who receive the same estrogen plus
progestin used in HERS (1295-1297).
Participants are not required to have CHD and are generally younger
than those in the HERS cohort. The HT trial completed its enrollment
of 27 348 women and planned to report the results of the trial in
2005 after 9 years of treatment. However, the data and safety monitoring
board recommended early termination of the combination of estrogen
and progestin trial after 5.2 years’ average follow-up on
the basis of an excess of invasive breast cancer (HR 1.26, 1.00
to 1.59) and CHD (HR 1.29, 1.02 to 1.63), stroke (HR 1.41, 1.07
to 1.85), and pulmonary embolism (HR 2.13, 1.39 to 3.25) in study
participants receiving active hormone replacement therapy. The estrogen-only
versus placebo trial of the WHI study is continuing. In the Women’s
Angiographic Vitamin and Estrogen (WAVE) Trial, assignment to conjugated
equine estrogen, with or without progestin, resulted in worsening
of angiographic and clinical outcomes (1298,1299).
In a similar trial, WELL-HART (Women's Estrogen-Progestin Lipid-Lowering
Hormone Atherosclerosis Regression Trial), there was no effect of
17- beta-estradiol, with or without progestin, on angiographic progression
of disease (1299). Of note, no
randomized trial enrolled women within 3 to 6 months of an acute
coronary syndrome.
Inherited thrombophilias may increase the risk of thrombosis due
to estrogen (1300). However, none
have been clearly identified that would permit screening and exclusion
of women at excess risk. The role of selective estrogen receptor
modulators is yet to be defined (1291,1293,1301).
On the basis of WHI, HERS, and HERS II, postmenopausal women should
not receive combination estrogen and progestin therapy for primary
or secondary prevention of CHD (1287,1293,1297).
It is recommended that hormone therapy be discontinued for women
who have STEMI (1297). However,
women who are beyond 1 to 2 years after initiation of HT and wish
to continue it for another compelling indication should weigh the
risks and benefits, recognizing a greater risk of cardiovascular
events. Hormone therapy should not be continued while patients are
on bedrest in the hospital.
7.12.11.
Warfarin Therapy
Class I
1. Warfarin should be given to aspirin-allergic post- STEMI patients
with indications for anticoagulation as follows:
a. Without stent implanted (INR 2.5 to 3.5) (Level of Evidence:
B).
b. With stent implanted and clopidogrel 75 mg/d administered concurrently
(INR 2.0 to 3.0) (Level of Evidence: C)
2. Warfarin (INR 2.5 to 3.5) is a useful alternative to clopidogrel
in aspirin-allergic patients after STEMI who do not have a stent
implanted. (Level of Evidence: B)
3. Warfarin (INR 2.0 to 3.0) should be prescribed for post-STEMI
patients with either persistent or paroxysmal AF. (Level of
Evidence: A)
4. In post-STEMI patients with LV thrombus noted on an imaging study,
warfarin should be
prescribed for at least 3 months (Level of Evidence: B) and indefinitely
in patients without an increased risk of bleeding. (Level of
Evidence: C)
5. Warfarin alone (INR 2.5 to 3.5) or warfarin (INR 2.0 to 3.0)
in combination with aspirin (75 to 162 mg) should be prescribed
in post-STEMI patients who have no stent implanted and who have
indications for anticoagulation. (Level of Evidence: B)
Class IIa
1. In post-STEMI patients less than 75 years of age without specific
indications for anticoagulation who can have their level of anticoagulation
monitored reliably, warfarin alone (INR 2.5 to 3.5) or warfarin
(INR 2.0 to 3.0) in combination with aspirin (75 to 162 mg) can
be useful for secondary prevention. (Level of Evidence: B)
2. It is reasonable to prescribe warfarin to post-STEMI patients
with LV dysfunction and extensive regional wall-motion abnormalities.
(Level of Evidence: A)
Class IIb
Warfarin may be considered in patients with severe LV dysfunction,
with or without CHF. (Level of Evidence: C)
The indications for long-term anticoagulation after STEMI remain
controversial and are evolving. Although the use of warfarin has
been demonstrated to be cost-effective compared with standard therapy
without aspirin, the superior safety, efficacy, and cost-effectiveness
of aspirin has made it the antithrombotic agent of choice for secondary
prevention (Figure 37; Table
33) (1248,1249,1302-1305).
Two trials failed to demonstrate a statistically significant reduction
in the combined end points of death, reinfarction, or stroke using
a regimen of low-dose aspirin in combination with low-dose warfarin
(INR less than 2) (1306,1307).
Several
trials (1247-1249,1303-1305)
have examined the use of moderate- and high-intensity warfarin in
secondary prevention. Two of these trials, WARIS II and APRICOT
(Antithrombotics in the Prevention of Reocclusion In Coronary Thrombolysis)
II, were STEMI specific. In the APRICOT II trial (1249),
patients less than 75 years old with STEMI received UFH, aspirin,
and fibrinolytic therapy. Those who achieved TIMI 3 flow were randomized
to aspirin alone (80 mg) or warfarin (INR 2 to 3) plus 80 mg of
aspirin. The combined group had fewer reocclusions (15% versus 28%;
p less than 0.02) and a significant reduction in the combined end
points of death, MI, and revascularization (20% ARD; 23% RRR; p
less than 0.01) (Figure 37; Table
33) (1248,1249,1303-1305).
The WARIS II study of 3630 subjects compared highintensity warfarin
(INR 2.8 to 4.2) alone, medium-intensity warfarin (INR 2 to 2.5)
plus aspirin (75 mg), and aspirin alone (160 mg) (1303).
Patients were less than 75 years of age. At follow-up in 4 years,
the combined group had a lower risk for an event (death, nonfatal
reinfarction, thromboembolic cerebral stroke) (3.3% ARD; 29% RRR;
p equals 0.03) and the high-intensity warfarin group had a lower
risk (5% ARD; 19% RRR; p equals 0.001) than the aspirin group. There
was no survival difference, and the benefit resulted from a reduction
in nonfatal MI and nonfatal thromboembolic stroke. Bleeding was
more common in the warfarin groups, and approximately 35% of patients
discontinued warfarin therapy (Figure
37; Table 33) (1248,1249,1303-1305).
In ASPECT (Anticoagulants in the Secondary Prevention of Events
in Coronary Thrombosis) II, aspirin (81 mg) (1248)
was compared with high-intensity anticoagulation (INR 3 to 4) and
with medium-intensity warfarin (INR 2 to 2.5) plus aspirin (1248)
for secondary prevention in 999 subjects (1308).
Significantly fewer patients in the high-dose warfarin and the combined
regimen had death, MI, or stroke than in the aspirin group (5%,
5%, and 9%, respectively). Major bleeding was low in all groups.
Minor bleeding was higher in the combined group. However, almost
20% of the warfarin and combined group discontinued therapy, and
only about 40% remained in the therapeutic range.
Although in these studies, medium-intensity warfarin plus low-dose
aspirin clearly reduced the rate of nonfatal reinfarctions and nonfatal
strokes, this was achieved at the expense of increased bleeding
and significant dropout rates. Patients over 75 years of age have
not been studied adequately. Therefore, the Writing Committee wishes
to make no definitive recommendation in this age group at this time.
The high rate of discontinuation and the relatively large number
of patients not on target remain problematic. Unless there are indications
for anticoagulation, at this time, the Writing Committee reserves
its current level IIa recommendation for those patients under 75
years of age and not at risk of bleeding who are at high risk for
reinfarction or thromboembolic events and who can be monitored reliably.
For patients in whom anticoagulation is indicated, warfarin (INR
2.5 to 3.5) or medium-intensity warfarin (INR 2.0 to 3.0) plus aspirin
(75 to 162 mg) may be used for secondary prevention. When warfarin
is used in combination with aspirin, an INR of 2.0 to 3.0 is acceptable
with tight control, but the lower end of the range is preferable
(Figure 37).
The use of clopidogrel and direct thrombin inhibitors in STEMI remains
to be studied more thoroughly. Although definitive data are not
available, the consensus of this Writing Committee is that clopidogrel
is preferred over warfarin in aspirin-intolerant patients for secondary
prevention unless reasons for anticoagulation are present (Figure
37). Patients who have undergone stenting may need to take aspirin,
clopidogrel, and warfarin (INR 2.0 to 3.0) if anticoagulation is
indicated (i.e., AF, LV thrombus, cerebral emboli, or extensive
regional wall-motion abnormality) (Figure
37). In this situation, the Writing Committee believes that
clopidogrel may be stopped 1 month after a bare metal stent is implanted
and several months after a drug-eluting stent is implanted (3 months
after sirolimus and 6 months after paclitaxel) because of the potential
risk of bleeding with warfarin and the antiplatelet agents (1309,1310).
(See Section 7.12.5.)
The previous ACC/AHA guidelines strongly recommended the use of
oral anticoagulants with an INR of 2.0 to 3.0 in patients with a
ventricular mural thrombus or a large akinetic region of the LV
for at least 3 months. In a meta-analysis and other observational
studies (1311-1317),
patients with LV thrombus after STEMI had better outcomes and fewer
cerebral emboli when they underwent anticoagulation with heparin
and warfarin. Despite the absence of controlled studies, late thromboembolism
was reduced in postinfarction patients with LV aneurysm treated
with warfarin in a number of studies (1314-1316).
A cohort analysis from the SOLVD trial (1318)
demonstrated that warfarin use was associated with improved survival
and reduced morbidity in post-MI patients with LV dysfunction. Other
studies and a Cochrane review suggest that we be cautious in recommending
warfarin for this indication alone (1017,1319).
Warfarin is indicated in patients with persistent AF after STEMI,
given the results of multiple trials in other patients with AF (955,958).
7.12.12. Physical Activity
Class I
1. On the basis of assessment of risk, ideally with an exercise
test to guide the prescription, all patients recovering from STEMI
should be encouraged to exercise for a minimum of 30 minutes, preferably
daily but at least 3 or 4 times per week (walking, jogging, cycling,
or other aerobic activity), supplemented by an increase in daily
lifestyle activities (e.g., walking breaks at work, gardening, and
household work). (Level of Evidence: B)
2.
Cardiac rehabilitation/secondary prevention programs, when available,
are recommended for patients with STEMI, particularly those with
multiple modifiable risk factors and/or those moderate- to high-risk
patients in whom supervised exercise training is warranted. (Level
of Evidence: C)
Federal guidelines recommend that all Americans strive for at least
30 minutes of moderate physical activity most days of the week,
preferably daily (1320). The 30
minutes can be spread out over 2 or 3 segments during the day. For
postpatients with STEMI, daily walking can be encouraged immediately
after discharge. Physical activity is important in efforts to lose
weight because it increases energy expenditure and plays an integral
role in weight maintenance. Physical activity reduces symptoms in
patients with cardiovascular disease and improves other cardiovascular
disease risk factors. Beyond the instructions for daily exercise,
patients require specific instruction on those strenuous activities
(e.g., heavy lifting, climbing stairs, yard work, household activities)
that are permissible and those they should avoid. As emphasized
by the US Public Health Service, comprehensive cardiac rehabilitation
services include long-term programs involving medical evaluation,
prescribed exercise, cardiac risk factor modification, education,
and counseling (1184). These programs
are designed to limit the physiological and psychological effects
of cardiac illness, reduce the risk for sudden death or reinfarction,
control cardiac symptoms, stabilize or reverse the atherosclerotic
process, and enhance the psychosocial and vocational status of selected
patients. Enrollment in a cardiac rehabilitation program after discharge
may enhance patient education and compliance with the medical regimen
and assist with the implementation of a regular exercise program
(1183,1322-1324).
In addition to aerobic training, mild- to moderate-resistance training
is also recommended. This can be started 2 to 4 weeks after aerobic
training has begun (1325).
7.12.13. Antioxidants
Class III
Antioxidant vitamins such as vitamin E and/or vitamin C supplements
should not be prescribed to patients recovering from STEMI to prevent
cardiovascular disease. (Level of Evidence: A)
Earlier observational data from epidemiological studies suggested
that an increased intake of lipid-soluble antioxidant vitamins (vitamin
E and beta-carotene) is associated with reduced rates of cardiovascular
events, including STEMI (1326-1328).
In support of these data, one randomized placebo-control study of
vitamin E treatment in 2002 patients with documented coronary disease
indicated a reduction in nonfatal MI (27% ARD; 77% RRR) but no effect
on cardiovascular death or overall mortality (1329).
However, a midstudy change in the vitamin E dose and some imbalance
in the use of beta-adrenoceptor blockers in subjects receiving vitamin
E make interpretation of that study problematic. A prospective cohort
study of more than 34 000 postmenopausal women suggested that an
increase in dietary vitamin E but not supplemental vitamin E was
associated with decreased cardiovascular risk (1330).
In a randomized trial involving 11 324 patients surviving recent
(less than 3 months) MI, patients were assigned to treatment with
the following: vitamin E (300 mg daily; n equals 2830); n-3 polyunsaturated
fatty acids (1 g daily; n equals 2836); both (n equals 2830); or
neither (n equals 2828) for 3.5 years. Treatment with n-3 polyunsaturated
fatty acids but not vitamin E significantly lowered the relative
risk of the primary end point (death, nonfatal MI, or stroke) by
10% (p equals 0.048) (1331). Thus,
although dietary supplementation with n-3 polyunsaturated fatty
acids may have clinical benefits for patients after STEMI, this
trial failed to demonstrate a treatment benefit for vitamin E. With
regard to beta-carotene, several prospective studies have convincingly
shown a lack of beneficial effect on cardiovascular disease (1332-1334),
and 2 studies have indicated an increase in lung cancer with betacarotene
treatment (1332,1333).
There is even less evidence to support the use of water-soluble
enzymatic antioxidants for cardiovascular disease. Although one
study suggested reduced cardiovascular risk in subjects taking supplemental
vitamin C (1335), the majority
of other large epidemiological studies have not indicated a benefit
(1326-1328).
Thus, routine use of vitamin C after STEMI cannot be recommended.
Despite promising experimental studies, recombinant superoxide dismutase
failed to reduce infarct size in a wellcontrolled primary PCI trial
(1336). One small study showed
a trend for reduced restenosis with vitamin E treatment after coronary
angioplasty (restenosis rate 35.5% for treatment group versus 47.5%
for placebo group; n equals 100, p equals 0.06) (1337).
A larger study evaluating the combination of vitamin E in association
with omega-3 fatty acids 2 weeks before elective PCI showed no effect
on the restenosis rate (1338).
Thus, there is no convincing evidence to support lipid- or water-soluble
antioxidant supplementation in patients after STEMI or in patients
with or without established coronary disease (1338a).
Because these agents are not harmless, the growing practice of recommending
antioxidant supplements in these patients should be discouraged
until the results of ongoing, well-controlled studies become available
and unequivocally indicate a beneficial effect. An extensive review
of this subject has been published (1338).
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