Editor’s Note: Part 1 of this article covering 1968–1989 appeared in the May 2018 issue of ACEP Now.

At an estimated 8 to 10 million visits a year, chest pain remains an everyday complaint in the emergency department and one associated with some significant angst on the part of clinicians. It is difficult to provide an exact chronology of the evolution of the assessment and treatment of chest pain, but some general timeframes can be given.

2000 Troponins as Markers of Cardiac Injury

Although discovered in 1958, it was not until 2000 that the European Society of Cardiology (ESC) and the American College of Cardiology (ACC) recognized the pivotal role of biomarkers and made elevations in their levels the cornerstone of the diagnosis of acute myocardial infarction (AMI). They also acknowledged that cardiac troponins I and T had supplanted creatinine phosphokinase–MB as the biomarkers of choice for diagnosis. Although troponin T (which is more specific for cardiac tissue) and I isoforms are found in cardiac and skeletal muscle, there are now assays using high-affinity antibodies that test for troponins specific to cardiac muscle. Although measurement of troponins is an essential part of the evaluation of suspected acute coronary syndrome (ACS), there are a large variety of other disorders that can cause leakage of these proteins from cardiac muscle (eg, pulmonary embolism, sepsis, critical illness, renal failure, severe gastrointestinal bleeding, stroke, diabetes, heart failure and other causes). For many of these conditions, it is unclear how they elevate troponins.

Primary Percutaneous Intervention at Hospitals Without Surgical Back-up

With it becoming clear that primary transcutaneous interventions were superior to thrombolytic treatment for the treatment of an ST-elevation myocardial infarction (STEMI), the ability to perform this lifesaving procedure without cardiac surgical back-up became a major issue. Being that surgical back-up was only available in a small minority of hospitals, it required that patients be transferred from outlying hospitals to surgical centers, a process that was time consuming and often very impractical. With the advent of stenting, percutaneous coronary intervention (PCI) without surgical back-up became much safer in that stents were able to treat coronary artery dissections occurring at the angioplasty site, the most common reason for emergent surgery. In 2005, Wharton published an article in Circulation, which was a review of 15 trials of PCI without surgical back-up.¹ He noted that since the widespread introduction of stenting in 2000, a total of 7,319 patients participated in eight studies representing 180 hospitals, and the incidence of patients needing emergency surgery due to PCI failure was 0.53 percent. Performance of PCI at community hospitals without surgical backup is, without doubt, one of the major breakthroughs in the care of STEMI patients over the last 50 years.

2006 American Heart Association (AHA) and ACC Promote the Designation of “STEMI Receiving Centers”

Underpinned by the concept that “time is muscle,” the regionalization of care for suspected MIs was undertaken. The core concept that patients with suspected MIs would be taken to hospitals that had the ability, 24-7, to provide rapid interventional care resulted in standards for “STEMI centers.” These hospitals would have immediate access to catheterization laboratory personnel and a cardiologist, with rapid transport through the emergency department. Ultimately, paramedics could obtain electrocardiograms (ECGs) in the field and the call to a cardiologist/catheterization laboratory could be made before the patient arrived at the hospital. If a patient with suspected MI arrived at a non-STEMI hospital, rapid transfer to a STEMI center was routinely initiated.

2008 Introduction of Coronary CT Angiography (CCTA)

Although the initial studies of CCTA were published in the early 2000s, the ACCURACY trial compared coronary CT angiograph with invasive coronary angiography in 230 chest pain patients and found that there was high diagnostic accuracy for detecting 50 percent and 70 percent stenosis and a 99 percent negative predictive value.² This study accelerated the widespread use of this procedure. However, given that most low-risk chest pain patients don’t have coronary artery disease (CAD), it is viewed as grossly overutilized by many. The utilization of CCTA represents an anatomic approach to the assessment of chest pain (determining visually the amount of stenosis in a given coronary artery) as opposed to a functional test (treadmill test or exercise myocardial perfusion imaging).

2009 Use of CCTA to Rapidly Evaluate Chest Pain Patients

The ROMICAT trial demonstrated that, of 368 ED chest pain patients, CCTA was 100% sensitive for CAD and that 50% of patients with chest pain and low to intermediate likelihood of ACS were free of CAD.³ These results suggest that a large percentage of chest pain patients could be confidently discharged from the emergency department, a major change in the disposition of chest pain patients. Criticisms of the use of CCTA included the question of whether such a test is necessary at all. Although the number of ED discharges may be increased, the patient-related outcomes (ie, missed MI) may not be any different. Further, patients with a positive CCTA are more likely to be subjected to additional testing and procedures, and some of those tests are due to a false positive CCTA.

2010 High Sensitivity Troponins

The first papers on the development of high sensitivity troponin tests were published around 2010. These tests are based on the fourth-generation troponin T test but use a more refined antibody to detect subtle levels of troponin elevations. The trade off with a more sensitive test is that there are more likely to be elevations not due to cardiac ischemia or myocyte death. Multiple strategies have been proposed using high sensitivity troponin levels to expedite the determination of chest pain-related cardiac necrosis, including an initial and two-hour comparison. Although the negative predictive value is very good, the high sensitivity results in false positives.

2012 Downstream Consequences of CCTA Determined

As CCTA became more and more popular in the ED setting, major studies started to elucidate the downstream consequences of widespread use of CCTAs. In a randomized study by Hoffman, et al, CCTA was compared with standard evaluation in 1,000 acute chest pain patients, all of whom had normal troponins and non-ischemic ECGs and no prior history of CAD.⁴ Bottom line: hospital length of stay was reduced by 7.6 hours with CCTA and 47 percent of CCTA patients were discharged from the emergency department versus 12 percent with standard care. Major adverse cardiac events at 28 days were similar, but more downstream testing occurred in the CCTA patients, and as a result, more procedures. This finding of more subsequent testing has been demonstrated by others, although advocates of CCTA suggest that a negative study should reassure the physician and the patient, essentially exclude the diagnosis of new or unstable angina, and result in fewer subsequent tests. As a result, more and more CCTAs are being ordered.

2013 Validation of the HEART Score for ACS Risk Stratification

First described in the Neth⁵ Using historical factors, ECG findings, age, risk factors, and troponin levels, the prediction of major adverse cardiac events (MACE)—including AMI, coronary artery bypass grafting, PCI, and death—at six weeks has been reliably determined. The validation of the HEART score was also performed in the Netherlands and involved 2,440 unselected chest pain patients seen at 10 emergency departments.⁶ Patients with low-risk scores (0–3) had a MACE incidence at six weeks of 1.7 percent (36 percent of patients were low-risk). Intermediate-risk score patients (4–6) had a MACE incidence of 17 percent, while high-risk patients (7–10) had a 50 percent incidence.

In a U.S. study of 1,070 low-risk chest pain patients, MACE occurred in 0.6 percent (95% CI, 0.2–1.1%) of patients with a HEART score of 0–3 within 30 days.⁷ Use of the HEART score to guide patient disposition would have resulted in 5 cases of missed ACS (0.5 percent) and a potential cardiac function testing/imaging decrease of 82 percent. Functional testing was routinely performed in the observation unit where these patients were treated, and 94 percent had an exercise stress ECG, dobutamine stress ECG, coronary CT angiogram, or stress cardiac MRI. ECG stress testing without imaging was not performed, nor was technetium or sestamibi myocardial perfusion imaging.

Whether a 30-day to six-week time frame for MACE to develop (what about six months?) is reasonable or whether one in 60 to 167 patients meets the “acceptable miss rate” are reasonable concerns. It should be noted that, given the extraordinary low yield of positive stress tests/imaging studies, some have concluded that they not be performed in low-risk HEART score patients, despite the 2010 recommendation of the AHA/ACC (which were not changed in the 2015 update) that further testing occur within 72 hours in discharged patients.^8,9

In 2015, a head-to-head randomized comparison of the HEART pathway and usual care (as based on ACC/AHA recommendations) was conducted.¹⁰ A total of 282 patients with chest pain suspicious of ACS but with ECGs negative for ST elevation took part. With the HEART pathway, patients stratified to low risk (0–3) and who had negative standard-sensitivity troponins at zero and three hours of arrival were discharged without further testing, but were advised to follow up with their primary provider. When compared with usual care, the low-risk patients treated via the HEART pathway had decreased testing at 30 days by 12 percent, a shorter length of stay by nine hours in the hospital, and increased early discharge of 21 percent. No patient identified for early discharge had a MACE within 30 days.

Too good to be true? There are a few caveats. The clinicians were all at one academic facility and were not bound to follow the HEART pathway. Nonadherence to the HEART pathway occurred in 26 percent of the cases, although adherence in these cases would still have been associated with a 0 percent 30-day MACE rate in that no patient who was discharge via the HEART pathway or usual care had a MACE within 30 days. Also, the 30-day MACE rate for all the patients in the study was only 6 percent, and all occurred during the initial admission. Finally, there was a moderate bit of “kick the can down the road” in that further testing occurred during follow up in 57 percent of the low-risk HEART score patients versus 69 percent of usual care patients, so the absolute decrease in testing was small.

2015 Summary of Most Recent Medication Recommendations of the AHA and ACC for ACS

There was an extensive update of the AHA recommendations in 2015.⁹ Below are some changes from the 2010 guidelines. Updates regarding aspirin (ASA), nitroglycerine, and morphine were not included.

• Adenosine diphosphate receptor (ADP) inhibitors: In STEMI patients undergoing PCI, dual antiplatelet agents in advance improves clinical outcomes. An option to provide these medications in the prehospital setting is noted, but there seems to be no advantage over giving them in the emergency department. No recommendation regarding which ADP inhibitor to use is made. The assumption is made that all patients have receive 180 mg of non-enteric coated ASA.
• Unfractionated heparin
  • In the setting of a STEMI patient anticipated to have a PCI, prehospital administration is a reasonable option, as is enoxaparin.
• Routine Supplemental Oxygen
  • In normoxic ACS patients, the benefit of supplemental oxygen has not been established. Withholding oxygen may be associated with minimally reduced infarction size.
• Fibrinolytic Therapy
  • Prehospital administration is reasonable if transport times exceed 30 minutes in patients with a STEMI and they are going to a hospital where thrombolytic treatment is the standard.
  • If a STEMI patient is being taken to a PCI center, prehospital fibrinolytic therapy is without evidence of benefit and associated with a small risk of intracranial bleeding.

2017 Summary of the European Guidelines for Managing AMI with ST-Segment Elevation

The ESC released a total update of the guidelines for ST-segment and non-STEMI infarctions.11 It now advises:

• Left and right bundle branch block are considered equal for recommending urgent angiography if ischemic symptoms are of “STEMI diagnosis.”
  • PCI is preferred over thrombolysis if the time to get a wire across the clot is 120 minutes or less from time zero.
  • The maximum delay time from “STEMI diagnosis” to bolus of fibrinolysis is 10 minutes.
  • The “door-to-balloon” phase is eliminated.

Over the last 50 years there have been remarkable gains in the management of ACS. Mortality of STEMI patients is now in the range of 4 to 5 percent when just 50 years ago it was in the teens. Now there is active curative therapy, while in the past, palliative therapy (rest) was really the only treatment.

Editor’s Note: Visit ACEPNow.com to view the references for this article.

Dr. Bukata is the founding editor of Emergency Medical Abstracts, medical director of the Center for Medical Education, and adjunct clinical professor of emergency Medicine at the Keck School of Medicine of USC in Los Angeles.