In conjunction with the 50th anniversary of the founding of ACEP, it seems appropriate to look at the 50-year evolution of the assessment and care of chest pain in the emergency department. I have not been around for all 50 years, but I have been an ACEP member since 1975 and have personally experienced the majority of the evolution of chest pain care over that time.

At an estimated 8 to 10 million visits a year, chest pain remains an everyday complaint in the emergency department and one that is associated with some significant angst on the part of clinicians. Until the recent past, missed myocardial infarction had been the leading cause of malpractice suits and even though the top position is now related to stroke care, the fear of making a mistake in the assessment of chest pain patients remains high. A recent study of closed malpractice claims by The Doctors Company (the largest physician-owned malpractice insurer) found it ranked number two on the list.

It seems the core problem with the assessment of chest pain patients, who largely turn out not to have serious disease, relates to the concept of the “acceptable miss rate.” What percentage of patients with chest pain (or an equivalent) who are discharged after a seemingly benign evaluation will actually have a major adverse cardiac outcome that may have been averted if the patient was admitted? Historically, about 2 percent of patients with an acute myocardial infarction (AMI) or sudden death were mistakenly sent home after an ED visit. Is this percentage still the case? It is hard to conceive of how we could still miss this many, given the current extraordinarily high rate of admissions for chest pain. However, the core issue is, What percentage of misses is U.S. society willing to accept, given it is impossible to get to 0 percent?

Although it is difficult to provide an exact chronology regarding the evolution of the assessment and treatment of chest pain over the last 50 years, there are some general timeframes that can be given. Henceforth, the assumption will be made that the goal of the endeavor is to exclude or make the diagnosis of ischemic chest pain and that all other diagnoses will not be considered.

1968

History and Physical Exam

By far, the emphasis at this early stage in the assessment of chest pain was the importance of the history and, to a lesser extent, the physical exam. Despite all of the advances in ED diagnostic capabilities, obtaining a careful history remains the single most important element in making the diagnosis of acute coronary syndrome (ACS).

Electrocardiograms (ECGs)

Obtaining a 12-lead ECG has been a routine part of the evaluation of potential cardiogenic chest pain. However, in the early days there were no guidelines advising that an ECG be obtained within 10 minutes of arrival, as is currently recommended by the American Heart Association. In addition, there was no computer software, which is routinely available now, to interpret an ECG.

Chest X-Rays

Even 50 years ago, a portable chest X-ray was routinely performed in the assessment of potential cardiogenic chest pain. The machines were big and unwieldy, and the films were just that—sheets of radiographic film that were developed in a dark room using a variety of liquid chemicals. When the films needed to be read immediately, they were often still wet, and the term “wet reading” was commonly used for a stat interpretation.

Cardiac Enzymes

In the late 1960s, the creatinine phosphokinase (CK) enzyme was routinely measured in chest pain patients. This enzyme was found to have a variety of isoforms. Skeletal muscle expresses CK-MM (98 percent) and low levels of CK-MB (1 percent). The heart expresses CK-MM at 70 percent and CK-MB at 25 to 30 percent. A third variety is CK-BB, which is predominantly expressed in the brain and smooth muscle. The overlap between CK-MM and CK-MB allowed for multiple causes of CK elevation to be found (eg, rhabdomyolysis, muscle trauma, myocardial infarction, myositis, and myocarditis). Other causes of CK elevations included hypothyroidism, malignant hyperthermia, and neuroleptic malignant syndrome. In addition, CK elevations could occur in the myopathy associated with use of statins, which were discovered in 1976 and introduced for patient care with lovastatin in 1987. The bottom line: CK-MB elevations were not at all specific for myocardial cell damage, but they remained the standard for assessment until the development of the troponins. Even today, some older clinicians refer to the troponins as “enzymes” when, in fact, they are not, but the term “enzymes” was routinely used to refer to chemicals in the blood that may be elevated in the setting of cardiac cellular injury.

1975

Automated ECG Interpretation

Hewlett-Packard was among the first companies to develop the technology to measure ECG waveforms and interpret ECG readings. The machines were very large and expensive, about $5,000. In fact, they were so costly at the time that you could lease a machine just like a car ($5,000 is just what the average car cost in 1975) and make monthly payments. Now, all ECG machines have software that interprets the ECG with substantial accuracy at a much lower cost. A study by Hughes et al found that of 222 ECGs interpreted as normal by the Marquette 12SL software, only one, on over-read, was interpreted by one of two emergency physicians as requiring immediate bedding, and the patient had a normal stress test.¹ This is not to say that there are not multiple subtle ECG patterns that are worrisome that can be missed by computerized readings. Thus, review by an experienced clinician is mandatory.

1979

Advent of Thrombolytic Therapy for ST-Elevation Myocardial Infarction (STEMI)

In 1958, Sol Sherry, MD, of Temple University in Philadelphia, started using streptokinase in AMI patients, and he and his colleagues began the era of “cure” versus palliation of myocardial infarction. Bed rest for weeks was the mainstay of treatment at the time. In 1979, K.P. Rentrop, MD, PhD, and colleagues began the use of intracoronary streptokinase infusions.

1986

Widespread Use of Thrombolytic Therapy for STEMI

In 1986, the GISSI trial of 11,712 AMI patients demonstrated that compared to standard care, an IV infusion of 1.5 million units of streptokinase resulted in a 21-day mortality of 10.7 percent versus 13 percent in controls.² The results of this trial prompted progressive initiation of thrombolytic therapy, but it took at least 10 years until the practice was broadly available. The gap between when thrombolytic therapy was first found to be beneficial and the widespread adoption of its use is a classic example in which knowledge translation moved very slowly. Unfortunately, many patients who could have benefited from thrombolysis did not receive it and, as a result, suffered needless mortality, recurrent myocardial infarctions, and heart failure.

1988

Demonstration of the Benefit of Both Aspirin and Thrombolysis for STEMI

In August 1988, the results of the 17,187-patient ISIS-2 trial demonstrated that aspirin, 180 mg daily given for one month, resulted in a reduced five-week vascular mortality in AMI patients compared to standard care (9.4 percent versus 11.8 percent, a 21.³ percent relative reduction).3 The results produced by streptokinase alone were virtually identical to those produced by aspirin (9.2 percent versus 12 percent). As anticipated, the combination of aspirin and streptokinase was superior to either treatment alone (8 percent versus 13 percent). This study reaffirmed the efficacy of aspirin and solidified its crucial role in the treatment of all patients suspected of having cardiogenic chest pain.

1989

Demonstration That Percutaneous Transvenous Coronary Angioplasty (PTCA) Was Superior to Thrombolysis in STEMI

Early trials comparing PTCA (ballooning and stenting) with IV thrombolysis (streptokinase or recombinant tissue plasminogen activator) demonstrated the superiority of PTCA. In 1997, a 10-trial meta-analysis demonstrated that 30-day mortality was 4.4 percent with PTCA versus 6.5 percent with early thrombolysis.⁴ Most of the studies were very small in size, with GUSTO-IIb, published in 1997, being the largest (565 patients of the 2,606 total patients in the 10 randomized controlled trials).⁵

Dr. Bukata is executive editor of Emergency Medical Abstracts and clinical professor of emergency medicine at the Keck School of Medicine of the University of Southern California in Los Angeles.

References

1. Hughes KE, Lewis SM, Katz L, et al. Safety of computer interpretation of normal triage electrocardiograms. Acad Emerg Med. 2017;24(1):120-124.
2. Effectiveness of intravenous thrombolytic treatment in acute myocardial infarction. Gruppo Italiano per lo Studio della Streptochinasi nell‘Infarto Miocardico (GISSI). Lancet. 1986;1(8478):397-402.
3. Randomised trial of intravenous streptokinase, oral aspirin, both, or neither among 17,187 cases of suspected acute myocardial infarction: ISIS-2. ISIS-2 (Second International Study of Infarct Survival) Collaborative Group. Lancet. 1988;2(8607):349-360.
4. Weaver WD, Simes RJ, Betriu A, et al. Comparison of primary coronary angioplasty and intravenous thrombolytic therapy for acute myocardial infarction: a quantitative review. JAMA. 1997;278(23):2093-2098.
5. The Global Use of Strategies to Open Occluded Coronary Arteries in Acute Coronary Syndromes (GUSTO IIb) Angioplasty Substudy Investigators. A clinical trial comparing primary coronary angioplasty with tissue plasminogen activator for acute myocardial infarction. N Engl J Med. 1997;336:1621-1628.

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