ACCEL: American College of Cardiology Extended Learning

CardioSource WorldNews | Rapid Rule Out: How PROACTive Should EMS Be?

Noncardiac chest pain (NCCP) is defined as recurring angina-like substernal chest pain of noncardiac origin. That’s straightforward; what to do about it, most certainly, is not. It is very common, affecting roughly 25% of the adult population in the United States.1,2 To put that in perspective, NCCP is as common as having medium brown to blonde hair (24% of the world population).

With that kind of prevalence, you can imagine that chest pain and symptoms consistent with myocardial ischemia are among the most common reasons for emergency department (ED) evaluation, accounting for approximately 5.2% (or 7.1 million) of the 136 million ED visits each year. That’s according to the National Hospital Ambulatory Medical Care Survey: 2011 Emergency Department Summary (made available in 2015). This puts chest pain as the second most common reason for an ED visit, behind stomach/abdominal pain (11.1 million) but ahead of fever (5.1 million visits).

The majority of these chest pain patients are ultimately discovered to have NCCP, leading to speculation that these patients should be able to be more effectively and rapidly managed.

Troponin testing in the ED is the standard of care for patients with chest pain to “rule out” an acute cardiac event. Recent advances in the sensitivity of troponin has led to earlier, more precise detection of events; can such testing be moved up and out of the ED?


Investigators wondered whether prehospital point-of-care (POC) troponin—done in the ambulance—might accelerate time to diagnosis in patients with chest pain. The randomized trial, known as PROACT-3 (Providing Rapid Out of Hospital Acute Cardiovascular Treatment 3), was disappointing.3 Justin A. Ezekowitz, MD, FACC, and colleagues at the University of Alberta and other provincial centers, found that prehospital testing of B-type natriuretic peptide or POC-troponin did not shorten time from first medical contact to final disposition in patients with a broad range of cardiovascular symptoms.

In retrospect, the investigators gained insight into specific subsets of patients with chest pain. First, they enrolled a broad cohort of patients and tested two biomarkers; this may have diminished their ability to see a difference, if one existed, because of heterogeneity of symptoms, patients, and final diagnosis. Second, in their urban Canadian environment, patients spend between 8 and 9 hours—first in an ambulance and then in the ED—when presenting with chest pain. Finally, they realized that greater integration of information from the ambulance (including blood test results) to the multidisciplinary ED clinical team would be necessary to ensure this information is dealt with appropriately.

Consequently, Ezekowitz, et al. conducted PROACT-4, again evaluating prehospital POC-troponin testing (without BNP assessment) in the ambulance. They chose to use the same endpoint as PROACT-3 since it reflects the total amount of time “exposed” to the health care system.

In PROACT-4, patients with chest pain presenting by ambulance were randomized to usual care (UC; n = 296) or POC-troponin (n = 305), with a conventional sensitivity troponin assay approved for POC use by Health Canada.4 ST-elevation myocardial infarction (MI) patients or those with noncardiovascular symptoms were excluded. Pre-hospital high-sensitivity troponin was analyzed on a POC device and made available to the paramedic and ED staff. The final diagnosis was centrally adjudicated. The primary endpoint was time from first medical contact to discharge from ED or admission to hospital.

After ambulance arrival, the first troponin was available in 38 minutes in POC-troponin and 139 minutes in UC patients. In the study group, troponin was > 0.01 ng/ml in 17.4% and > 0.03 ng/ml in 9.8%. Patients spent a median of 9.0 hours from first medical contact to final disposition, and 165 (27.4%) were admitted to the hospital. Despite the gain of 101 minutes in time to first troponin, the primary endpoint was just a little shorter in patients randomized to POC-troponin (median 8.8 hours [6.2 to 10.8]) compared with UC (median 9.1 hours [6.7 to 11.2]; p = 0.05). That suggests there is still some optimization to be gained with this approach. Plus, it was encouraging to find no difference in the secondary endpoint of repeat ED visits, hospitalizations, or death in the next 30 days.

Not Huge, but Still…

OK, it was not a huge difference, and it fell short of the proposed 60 minutes the investigators were anticipating. Still, as Dr. Ezekowitz put it, “It was a small gain from a simple intervention—and there is a lot more to learn.” As he and his colleagues emphasized, it translates into a 23-minute reduction in time by use of POC-troponin overall and 27 minutes (primary analysis) or 26 minutes (per-protocol analysis) in those patients discharged from the ED. (It makes sense that the magnitude of the effect was greatest in patients discharged from the ED.)

Moreover, if you consider the 19-month duration of the PROACT-4 trial, this translates into roughly 1,500 hours saved using POC-troponin. If all patients with chest pain in the region were to be considered, the authors argue, POC-troponin use would have significant health care and cost implications. “In a cost-constrained system,” Dr. Ezekowitz said, “moving people through the ER is important.”

So, in this pragmatic trial conducted in a broad population of patients with chest pain, prehospital POC-troponin testing shortened the time from first medical contact to final disposition in the ED with no difference in clinical outcomes.

The authors added that future randomized controlled trials evaluating the utility of POC testing in the ambulance should consider the use of ultrasensitive troponin, randomization, which might have an impact although likely not a dramatic one. Also, benefits might be gained by integrating troponin testing into an algorithm that crosses health care boundaries. In PROACT-4, for example, patient data were measured across five different hospitals varying in size, volume, and expertise, as well as across emergency personnel and ED staff.

Overall, based on the data, the news is encouraging: it appears that enhanced and more cost effective early ED discharge of the majority of patients with chest pain delivered by ambulance is viable.


  1. Wong WM, Lam KF, Cheng C, et al. World J Gastroenterol. 2004;10:707-12.
  2. Eslick GD, Jones MP, Talley NJ. Aliment Pharmacol Ther. 2003;17:1115-24.
  3. Ezekowitz JA, Welsh RC, Gubbels C, et al. Can J Cardiol. 2014;30:1208-15.
  4. Ezekowitz JA, Welsh RC, Weiss D, et al. J Am Heart Assoc. 2015;4(12). pii: e002859.

Cardiac Risk of Noncardiac Surgery: Clinical Risk Assessment

Major perioperative cardiac events are estimated to complicate between 1.4% and 3.9% of the more than 50 million surgical procedures performed annually in the United States. Given that the great majority of surgeries are elective, that means there is an opportunity to implement strategies to reduce this risk.

Recently in JACC, Akshar Patel, MD, and Kim Eagle, MD both from the University of Michigan Medical School, Ann Arbor, MI, and Prashant Vaishnava, MD, Mount Sinai Heart in New York City, NY wrote a review covering “Cardiac Risk of Noncardiac Surgery.”1 They discussed important features of the initial preoperative clinical risk assessment, indications for diagnostic testing to quantify cardiac risk, and methods and indications for pre-emptive therapies.

According to Valentin Fuster, MD, PhD, MACC, the editor-in-chief of JACC, “The subject is important for two reasons: the cardiac risk from noncardiac surgery is in front of us every day; and the second one, which is critical, is the patient has to be informed of the pros and cons of how we manage his or her situation and their risk of perioperative cardiac events including all noncardiac events, including mortality.”

The perioperative incidence of major adverse cardiac events is, first and foremost, related to baseline risk. For many patients, their surgery may not be cardiac-related but they already have cardiovascular conditions that put them at higher risk. Here is the number to remember: An estimated 85.6 million American adults (more than one in three) have one or more types of cardiovascular disease (CVD).2

Because of overlap across conditions, it is impossible to add these conditions to arrive at a total, but here are the current individual estimates3:

  • Congenital heart disease: 750,000 survivors with simple lesions, 400,000 with moderate lesions, and 180,000 with complex lesions (most optimistic estimation); in addition, 3.0 million people in the U.S. have bicuspid aortic valves
  • Coronary artery disease: 15.5 million
  • Heart failure: 5.7 million (≥ 20 years of age)
  • Hypertension: 80.0 million
  • Peripheral artery disease: 8.5 million (≥ 40 years of age)
  • Stroke: 6.6 million
  • Valve disease: 7.97 million

Aside from the presence of CVD, the type of surgery the patient will undergo contributes substantially to the perioperative cardiac risk. Consequently, proper risk assessment is important. One source of clinical guidance is the 2014 ACC/AHA Guideline on Perioperative Cardiovascular Evaluation and Management of Patients Undergoing Noncardiac Surgery.4

Preoperative Risk Assessment

Several multivariate risk indexes may be helpful forpreoperative assessment. The Revised Cardiac Risk Index (RCRI) is, perhaps, the most well-known as well as the simplest tool. Other risk prediction tools include those of the American College of Surgeons (ACS) and the National Surgical Quality Improvement Program (NSQIP), the Myocardial Infarction and Cardiac Arrest (MICA), and the ACS NSQIP Surgical Risk Calculator.

Patel et al. noted that cardiac risk in noncardiac surgery patients is best tackled by a perioperative team approach, utilizing the collaborative efforts and shared decision making of the patient, primary caregiver, cardiologist, surgeon, and anesthesiologist. That team approach, they noted, is key to ensuring proper implementation of current evidence-based guidelines.

As the authors of the JACC review wrote, “Accurate identification of patients at risk may not only help to better inform patients about the benefit-to-risk ratio of procedures, but also guide the allotment of limited clinical resources, utilization of preventive interventions, and areas of future research.”

(Editor’s note: Follow the references below to access the paper by Patel, Eagle, and Vaishnava. The paper’s central illustration features a decision tree to use when considering noncardiac surgery. The graphic details key considerations in the determination and treatment of perioperative cardiac risk of noncardiac surgery and provides crucial facts regarding common risk factors. It lists, in succinct snippets, the effectiveness of various possible therapeutic interventions and the overall algorithm could help you determine the appropriate level of preoperative cardiac testing in individual patients.)


  1. Patel AY, Eagle KA, Vaishnava P. J Am Coll Cardiol. 2015;66:2140-8.
  2. Mozaffarian D, Benjamin EJ, Go AS, et al. Circulation. 2016;133:e38-e360.
  3. Fleisher LA, Fleischmann KE, Auerbach AD, et al.
  4. J Am Coll Cardiol. 2014;64:e77-e137.

Cardiorespiratory Fitness as a Vital Sign
Yes, but how?

Is weight loss the optimal target for obesity-related cardiovascular disease risk reduction? Probably not. That’s based on the life’s work of several pioneers in this field, including Robert Ross, PhD, a professor of exercise physiology at the School of Kinesiology and Health Studies, Queen’s University, Kingston, Ontario.

Sure, weight loss is associated with substantial reduction in obesity-related CVD risk and certainly is a desired outcome. However, Dr. Ross and others have established that increasing physical activity is associated with marked reduction in waist circumference, visceral fat, and cardiometabolic risk factors, concurrent with an increase in cardiorespiratory fitness (CRF)—despite minimal or no change in body weight.

Consider the 2004 paper Dr. Ross published with Steven N. Blair, PhD, a professor at the Arnold School of Public Health, University of South Carolina, Columbia, SC, and another pioneer in exercise and CRF.1 Cardiorespiratory fitness is associated with lower abdominal fat independent of body mass index (BMI). Specifically, in comparing men with high CRF (n = 169) with men showing low CRF (n = 124), they demonstrated that for a given BMI, men in the high CRF group had significantly lower waist circumference (p < 0.001) as well as lower total abdominal tissue (p < 0.001), visceral adipose tissue (p < 0.001), and abdominal subcutaneous adipose tissue (p < 0.001) compared with men in the low CRF group.

Subsequently, a much larger study was performed providing compelling evidence that waste circumference explains both diabetes and CVD risk beyond that explained by BMI alone. The IDEA study (International Day for Evaluation of Abdominal Obesity) involved 6,407 randomly chosen primary care physicians in 63 countries, who evaluated 168,159 patients ages 18 to 80 years.2

There was a graded increase in the frequency of CVD and diabetes mellitus with both BMI and waist circumference but there was a stronger relationship for waist circumference than for BMI across regions for both sexes. Shortly thereafter, Ross and colleagues demonstrated that waist circumference predicts diabetes risk beyond BMI and other commonly measured cardiometabolic risk factors, such as smoking, dyslipidemia and blood pressure.3

The data are summarized in a paper published by Dr. Ross and Peter M Janiszewski, MSc.4 Together, the evidence underscored the importance of waist circumference as a routine measure in clinical practice that should be a primary treatment target for strategies designed to reduce obesity-related CVD risk. Indeed, Dr. Ross and others think that exercise should be viewed as a cost-effective medication for all patients with or at-risk for CVD.

How Do You That?

It’s not easy—as most clinicians probably try this approach regularly (usually feeling as if their efforts just don’t work)—but there are suggestions that Dr. Ross and colleagues promote5 that can be highly beneficial.

Motivating exercise in the physician office or clinical environment: If physicians, physical therapists, dietitians, and other health professionals all consistently assess and promote physical activity as a routine component of every clinical encounter, they note “it is likely that we would start to see changes in patient self-reported physical activity.”

Think realistically: Dr. Ross noted recently, “The clinical reality for most in patient care disciplines is that our patients are mostly sedentary and have been that way for their entire adult lives. The expectation that they will suddenly become someone who performs 30 minutes of exercise on most days of the week is simply unrealistic.

Key to promoting cardiorespiratory fitness in the clinical setting is the use of a physical activity vital sign in which every patient’s exercise habits are assessed and recorded in their medical record. Those not meeting the guideline-recommended 150 minutes per week of moderate intensity physical activity should be encouraged to increase their physical activity levels with a proper exercise prescription. According to Dr. Ross: “If you maintain that 150 minutes of activity most weeks, you will improve your cardiorespiratory fitness and you will reduce morbidity and mortality substantially.

They write, “We can improve compliance by assessing our patient’s barriers to being more active and employing new and evolving technology like accelerometers and smart phones applications, along with various websites and programs that have proven efficacy.”5

Manage realistically: Help patients access and manage their exercise and physical activity; you can only manage what you measure. Encourage patients to keep track of their adherence to exercise and track their daily activity. This can be done on paper, or increasingly, with a myriad of digital devices and smart phone applications.

Practice what you preach: “Each and every health care professional involved with helping patients manage chronic disease conditions that may benefit from increased adherence to exercise and physical activity must be aware that our patients often ask what we do. If we do not adhere to exercise therapies, then they may be less likely to themselves,” he emphasized.

According to Dr. Ross, physical inactivity is the major public health problem of our time. While obesity is most often publicized, its adverse effects on health are largely mitigated by engaging in regular physical activity.

Physicians cannot do it alone: Everyone on the health care team, from the front desk receptionist to the medical assistant, nursing staff, dietitians, physical therapists, etc., needs to be on the same page: actively promoting regular physical activity as a key to improved health outcomes. Likewise, the expanded use of technology to track activity can help support the achievement of step goals.

According to Dr. Ross, ultimately, to succeed, “we need to leverage all the tools in our toolbox and continue to investigate and add new tools in our efforts to help our patients, our families, and our communities move more.”


  1. Wong SL, Katzmarzyk P, Nichaman MZ, et al. Med Sci Sports Exerc. 2004;36:286-91.
  2. Balkau B, Deanfield JE, Despres JP, et al. Circulation. 2007;116:1942-51.
  3. Janiszewski PM, Janssen I, Ross R. Diabetes Care. 2007;30:3105-9.
  4. Ross R, Janiszewski PM. Can J Cardiol. 2008;24(Suppl D):25D-31D.
  5. Sallis R, Franklin B, Joy L, et al. Prog Cardiovasc Dis. 2015;57:375-86.
Read the full June issue of CardioSource WorldNews at

Keywords: CardioSource WorldNews, Angina Pectoris, Chest Pain, Obesity, Risk Reduction Behavior, Weight Loss, Obesity

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