American College of Cardiology Extended Learning
ACCEL interviews and topical summaries of cardiology’s most interesting research areas
Considerations in the Peripartum Patient
MI in pregnancy is different
An estimated 3 million women aged 18-44 years in the U.S. have heart disease, and many of these women would like to have children. In 2007, the European Registry on Pregnancy and Heart Disease was initiated by the European Society of Cardiology. Over a 4-year period, the registry enrolled 1,321 consecutive pregnant patients with valvular heart disease (25%), congenital heart disease (CHD) (66%), ischemic heart disease (IHD; 2%), or cardiomyopathy (7%).1 Of the patients with CHD, 579 (66%) had at least one intervention before pregnancy.
Data were compared to a matched population of pregnant women without heart disease.1 Maternal death occurred in 1% of the registry patients compared with 0.007% in the normal population. However, clear differences were found in pregnancy outcomes with respect to the underlying diagnosis, with the highest maternal mortality in patients with cardiomyopathy (2.4%). Fetal mortality occurred in 1.7% and neonatal mortality in 0.6%, both higher than in the normal population.
The authors concluded that the vast majority of patients can safely go through pregnancy and delivery as long as adequate pre-pregnancy evaluation and specialized high-quality care during pregnancy and delivery are available.
Besides those problems already mentioned, other conditions that may be associated with HF during pregnancy include hypertensive diseases (preeclampsia), pulmonary arterial hypertension (PAH), and acute myocardial infarction (MI).
According to Uri Elkayam, MD, FACC, Professor of Medicine at the University of Southern California, Los Angeles, CA, patients with simple congenital heart disease without pulmonary vascular disease tolerate pregnancy well. Among patients with complex congenital heart disease, there is an increased rate of fetal loss, prematurity, and more maternal complications (heart failure (HF), arrhythmias, and thromboembolic events) than in women with simple congenital heart disease.
Dr. Elkayam and colleagues also conducted an analysis using the same 1,321 registry patients, this time looking at the pharmacological management of these women with CVD in order to assess the relationship between medication use and fetal outcome.2 Medication was used by 424 patients (32%) at some time during pregnancy: 22% used beta-blockers, 8% antiplatelet agents, 7% diuretics, 2.8% ACE inhibitors, and 0.5% statins.
The odds ratio of fetal adverse events in users versus non-users of medication was 2.6 (95% CI: 2.0-3.4) and, after adjusting for cardiac and obstetric parameters, was 2.0 (95% CI: 1.4-2.7). Babies of patients treated with beta-blockers had a significantly lower adjusted birth weight (3,140 vs. 3240 g; p = 0.002). The highest rate of fetal malformation was found in women taking ACE inhibitors (8%).
The authors noted that a randomized trial is needed to distinguish the effects of the medication from the effects of the underlying maternal cardiac condition.
Recently in JACC, Dr. Elkayam published a review of peripartum cardiomyopathy (PPCM), a pregnancy-associated myocardial disease with marked LVSD.3 Although this condition can lead to major complications, including severe HF, arrhythmias, thromboembolic events, and death, the majority of women with this condition demonstrate a complete or partial recovery.
Many of these women desire to become pregnant again and are concerned regarding the safety of additional pregnancies. So Dr. Elkayam reviewed the available literature in an attempt to reach conclusions regarding the risk of such pregnancies in this group of patients. Although information was somewhat limited, the available data strongly suggest that subsequent pregnancies in women with a history of peripartum cardiomyopathy (PPCM) is associated with a risk of relapse.
This risk is high in women with persistent left ventricular systolic dysfunction (LVSD) before their subsequent pregnancy, who are also at risk of deterioration due to the increased hemodynamic burden of pregnancy. Almost 50% of such women were reported to have deterioration of LV function during or following pregnancy, potentially leading to major morbidity and even mortality.
There also appeared to be an increased risk of premature delivery and abortions in women with persistent LV dysfunction. Complete recovery of LV function before any subsequent pregnancy is associated with better prognosis, and most women are likely to have a normal pregnancy. However, uneventful pregnancy is not guaranteed, and approximately 20% will have a relapse of PPCM associated with a substantial decrease in LV systolic function.
Although the rate of recovery is relatively high and the incidence of mortality is low, relapse of PPCM, even in this group, may be associated with deterioration of LV function, congestive HF, arrhythmias, and the need for aggressive therapy, including the use of temporary and permanent devices. Additionally, in some cases, the persistence of LVSD may have detrimental long-term consequences.
Is it preeclampsia or PPCM? Dr. Elkayam said the data suggest that for patients with preeclampsia presenting with heart failure, think PPCM. Likewise, preeclampsia plus LVSD equals PPCM.
MI in Pregnancy is Different
Finally, Elkayam et al. recently evaluated 150 cases of pregnancy-associated MI (PAMI).4 Pregnancy has been shown to increase the risk of acute MI ≈3-fold compared with the risk in non-pregnant women of similar age. Dr. Elkayam and his colleagues demonstrated that PAMI is different from acute MI in non-pregnant patients in several important aspects. Atherosclerotic coronary artery disease (CAD), the most common cause of acute MI in the non-pregnant population, is responsible for only one third of PAMI cases; the majority of patients develop their acute MI by other mechanisms.
There is frequent involvement of the left anterior descending and left main coronary arteries, and the location of PAMI is commonly the anterior wall, resulting in a high incidence of LV dysfunction, congestive HF, cardiogenic shock, and mortality. Because many women with PAMI have coronary dissection (43%) or normal coronary anatomy, the risk of thrombolytic therapy may outweigh a potential benefit, and they emphasized that “blinded use of such therapy does not seem advisable.”
The high incidence of iatrogenic coronary dissection secondary to intracoronary contrast injection and mechanical interventions suggests that an invasive approach to PAMI should be limited to high-risk patients, and that mechanical coronary manipulations should be limited to cases in which potential benefits clearly outweigh the risk.
The use of guideline-recommended antiplatelet therapy may be desirable for maternal protection. At the same time, however, women should be informed about the paucity of information available on the safety of these drugs for their fetuses.
- Roos-Hesselink JW, Ruys TP, Stein JI, et al. Eur Heart J. 2013;34:657-65. Ruys TP, Maggioni A, Johnson MR, et al. Int J Cardiol. 2014;177:124-8.
- Elkayam U. J Am Coll Cardiol. 2014;64:1629-36.
- Elkayam U, Jalnapurkar S, Barakkat MN, et al. Circulation. 2014;129:1695-702.
Exercise to Assess Pulmonary Hypertension
Defining its role for early diagnosis and risk stratification
Guidelines define the diagnosis of pulmonary hypertension (PH) as a mean pulmonary arterial pressure (mPAP) > 25 mm Hg at rest. Not long ago, it was also defined as an mPAP of > 30 mm Hg during exercise. That seemed clear cut, but there were some questions as to whether an mPAP > 30 mm Hg during exercise is always pathological. In a word: no.
Kovacs et al. performed a comprehensive literature review, analyzing all accessible data obtained by right heart catheter studies from healthy individuals to determine normal mPAP at rest and during exercise.1 Data on 1,187 individuals from 47 studies in 13 countries were included. They determined that, while mPAP at rest is virtually independent of age and rarely exceeds 20 mm Hg, with slight exercise, mPAP is age-related and frequently exceeds 30 mm Hg, especially in elderly individuals; this makes it difficult to define normal mPAP values during exercise.
According to Ryan James Tedford, MD, who is Director of Cardiovascular Hemodynamics, Heart Failure, Mechanical Circulatory Support, and Cardiac Transplantation at Johns Hopkins School of Medicine, based on the Kovacs study—coupled with uncertainty regarding the proper type, posture, or intensity of exercise necessary for diagnosis—exercise-related definitions were removed from the PH guidelines in 2009.
This was not because of the lack of any potential value of exercise pulmonary pressure measures (as we’re about to see), but rather because of the lack of a suitable definition, meaning an exercise criterion for PH was just not feasible at that time.
A Stepchild No More?
The issue relates to the stepchild of the ever-popular left ventricle: the right ventricle (RV). Together with Dr. Tedford, Brian A. Houston, MD, also of Johns Hopkins in Baltimore, MD, recently noted that when Eugene Braunwald, MD, addressed the Right Heart Failure Summit in 2012, he echoed the sentiments of cardiologists throughout history by saying that he had “not paid [his] dues to the right ventricle.”2
For years, the RV was viewed as merely a conduit for transmitting blood to the lungs, but we now know (without argument!) that right ventricular function predicts clinical outcomes in a myriad of conditions including HF with preserved or reduced ejection fraction, after implantation of LV assist devices, and—pertinent to our discussion, here—pulmonary arterial hypertension (PAH).
When distilling the field’s rising recognition of the importance of the RV, Dr. Braunwald declared it a “stepchild no more.”
If the RV has finally been afforded its due respect in many disease states, there remains an important issue: the definition and assessment of the seemingly simple concept of “RV function” has proven vexingly elusive. Given that we have known for decades that evaluation of LV function under stress is prognostic in coronary artery disease (CAD), heart failure (HF), and valvular disease, Dr. Tedford wrote very recently that “it is perhaps surprising that we have been unable to see across the interventricular septum to consider the benefits of stress evaluation of the right ventricle.”2
As imaging techniques have improved, he said, we certainly have a greater ability today to look across the septum to consider the RV during stress. High‐quality exercise evaluation of the RV is possible and can provide important clinical information about our patients. However, should at‐rest evaluations of the RV be put to rest? Probably.3 Here’s some advice Dr. Tedford provided at AHA.14.
Going with the Flow
You will recall that mPAP is a function of the product of pulmonary vascular resistance (PVR) and cardiac output (CO), as well as downstream left heart pressure (estimated by pulmonary artery wedge pressure—also known as pulmonary capillary wedge pressure or PCWP).
As Dr. Tedford explains, pressure must be considered in the context of flow. Exercise stresses the pulmonary circulation through increases in CO and left atrial pressure (LAP). Invasive as well as noninvasive studies in healthy volunteers show that the slope of mPAP-flow relationships ranges from 0.5 to 3 mm Hg/l/min. Thus, mPAP/CO >3 mm Hg/l/min is considered abnormal. However, this does not differentiate between increases in mPAP due to pulmonary vasculature disease versus rising LAP, which increases with exercise; indeed, there is an average upstream transmission to PAP in a nearly 1-for-1 mm Hg fashion.
Elevated resting PAP in patients with left ventricular systolic dysfunction (LVSD) is associated with poor prognosis. What about PAP response patterns to exercise in LVSD? Lewis and colleagues have reported that a steep increment in PAP during exercise and failure to augment PAP throughout exercise are associated with decreased exercise capacity and decreased survival in patients with LVSD, and may therefore represent therapeutic targets.4
We noted above the difficulty differentiating between increases in mPAP due to pulmonary vasculature disease versus rising LAP. What about PCWP? At rest, that would be a PCWP of 6 ± 1 mm Hg; with peak exercise it seems to be 17 ± 1 mm Hg. What about with less than peak exercise? Recently, Anderson and colleagues conducted right heart catheterization in 14 patients with HF with preserved EF (HFpEF) and 12 controls.5 PCWP was assessed at rest, during supine exercise, and with acute saline loading in a prospective study. In controls, RA pressure, PAP, and PCWP increased similarly with saline and exercise, whereas in HFpEF subjects, exercise led to ≈2-fold greater increases in PA pressure (10 ± 4 vs. 6 ± 3 mm Hg; p = 0.02), PAP (22 ± 8 vs. 11 ± 4 mm Hg; p = 0.0001), and PCWP (18 ± 5 vs. 10 ± 4 mm Hg; p < 0.0001) compared with saline. The fact that exercise elicits greater PCWP elevation compared with saline in HFpEF but not controls, suggests that hemodynamic stresses beyond passive stiffness and increased venous return explain the development of pulmonary venous hypertension in HFpEF.
What are the possible PCWP cutoffs? According to Dr. Tedford, in his opinion, at peak exercise, a PCWP ≥ 25 mm Hg if supine would be abnormal. If upright, then a PCWP ≥ 20 mm Hg would be abnormal. However, he noted that well-trained athletes may show more elevated PCWP than in sedentary patients, but usually not > 25 mm Hg. He added that clinicians should consider evaluating the transmural LV filling pressure; a rising transmural pressure suggests LV contribution. Also, care must be taken to insure a complete wedge (PCWP saturation should be considered).
Overall, he said, there are several important factors to consider with exercise measurements. Position matters:
PCWP pressures will be higher with supine versus upright while PVR will be lower with supine. Upright may better reproduce symptoms and proper transducer leveling is important. As for the type of exercise, he said, bicycle exercise is preferred versus upper extremity exercise. He suggests avoiding resistive exercise due to increase in systemic vascular resistance.
He said it is important to differentiate PAH (World Health Organization [WHO] group I) from PH due to left heart disease (WHO group II). According to Dr. Tedford:
- Identify occult left heart disease, which may explain symptomatology and be pathologic.
- Identify exercise-induced PAH, which may explain symptoms and be pathologic and better predict progression compared to resting PAH.
- Detect exercise-induced PAH, which might suggest a role for early treatment.
- Define RV contractile reserve, which appears to be prognostic and will identify patients with ‘hidden’ right heart failure.
Of course, he said, significant care must be taken to insure exercise measures are done properly. When done properly, Dr. Tedford said, exercise measurements can be useful in several clinical circumstances.
While mPAP/CO > 3 mm Hg/l/min is abnormal, it does not discriminate between WHO Group I and Group 2 PH. And while a PCWP ≥ 20 (upright) or PCWP ≥ 25 (supine) is generally abnormal, examine the transmural pressure because it suggests left heart disease if it’s increasing.
A test that accurately, reproducibly, and noninvasively identifies intrinsic RV contractile dysfunction in PAH patients, and specifically impaired RV-PA coupling, represents the holy grail of prognostication in PAH. Such a test would allow for improved therapeutic targeting, potentially identifying the patients who would benefit from more aggressive multidrug approaches or consideration of advanced therapies such as transplant. Identifying patients with normal resting echocardiographic measures of right ventricular function and stratifying them by presence of RV contractile reserve to compare clinical outcomes would be of particular interest.
Until then, there is much information to be obtained from assessment of the former “stepchild ventricle.”
- Kovacs G, Berghold A, Scheidl S, et al. Eur Respir J. 2009;34:888-94.
- Houston BA, Tedford RJ. Eur Respir J. 2015;45:604-7.
- Houston BA, Tedford RJ. J Am Heart Assoc. 2015 Mar. 23;4(3):e001895.
- Lewis GD, Murphy RM, Shah RV, et al. Circ Heart Fail. 2011;4:276-85.
- Andersen MJ, Olson TP, Melenovsky V, et al. Circ Heart Fail. 2015;8:41-8.
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