AbstractMyocardial infarction is a major trigger for living benefits claims and the survivability of infarction is such that a history is increasingly common in applicants. Medical definitions of infarction have changed markedly over the last century, from what was initially a postmortem diagnosis of a condition that was considered inevitably fatal to a condition defined by circulating biological markers and where survival is the expectation.
Population demographics and the evolution of concepts as to how infarction should be defined and classified in various clinical settings have resulted in changes in incidence that have driven a need to continually monitor and revise pricing, underwriting, and claims models.
The basic tenet that a diagnosis of infarction is made when death of myocardial cells occurs as a result of inadequate blood supply has not changed, but assays of biological markers that reflect cell death have become surrogates for histopathological proofs.
Until the end of the 19th century infarction was considered a fatal entity only diagnosable post-mortem. The diagnosis required evidence of thrombotic occlusion of a coronary artery in the context of sudden death, or death within a short period of time following the onset of chest pain.
That prevailing concept was re-examined by Dr. James Herrick in 1912 in the first classification of the clinical features of coronary obstruction. Herrick disputed the long-held view that infarction was inevitably fatal in providing clinical evidence that it was often survived without necessarily being associated with major morbidity.1, 2 Acceptance of that view drove a need to define reliable parameters for diagnosing infarction in those with chest pain who had not succumbed to sudden death and who presented to medical attention.
In Herrick’s time the diagnosis was based purely on clinical grounds with ischemic chest pain being the usual criterion. ECG accompaniments became supporting criteria following their description by Herrick in 1919.15 In that era, mortality rates were of the order of 30% and treatment options were limited to weeks of bed rest. There was no material pharmacological capacity to influence prognosis and the resumption of a normal lifestyle with return to work was discouraged.
By the 1950s and 1960s myocardial infarction had become the most common cause of death in Europe and North America. The health and socioeconomic burden resulted in the establishment of dedicated coronary care units and work on pharmacological and interventional strategies that had the capacity to reduce mortality and limit infarct size. That focus saw the creation of protocols that enabled earlier discharge and resulted in reductions in mortality from 30% to 15% over the next few decades.3
Strategies which improved outcomes mandated reliable parameters for diagnosis. It was recognized that standardized and universally accepted definitions would provide benchmarks by which emerging treatments could be compared and judged with statistical certainty. Recognizing the need for such protocols in the clinical and research setting, the World Health Organization (WHO) published the first guideline for the definition of myocardial infarction in 1959. That definition was based on ischemic pain and ECG changes.
In 1979, WHO published a revision that allowed the detection of elevated cardiac enzymes in the circulation to be included as a third criterion although elevated enzymes were not mandated for a diagnosis. Given the limited sensitivity of the ECG in the more common non-ST elevation ECG syndromes, this revision resulted in an increase in incidence. A diagnosis was now possible in those with ischemic pain who did not satisfy ECG requirements.
Despite the benefits of including enzymes as markers of cell death, definitions remained very imperfect by today’s standards. Enzymes lacked good sensitivity for damage and there was a lack of specificity because these enzymes were not absolutely cardiac-restricted. Coupled with the fact that there was no analytic standardization across various enzyme assays, levels were required to rise to twice upper reference limits (URL) to reduce false positives.
During the 1970s and 1980s there was research interest in the structure of actin and myosin, the two filaments in heart muscle cells responsible for cell contraction. Two proteins associated with the thin actin filament (contractile proteins troponin I and troponin T) were identified and were shown to be cardiac-specific. These proteins were undetectable in the blood of normal populations at the time and there was interest in determining if they were released into the circulation in detectable amounts following cell damage.
A protein associated with the thick myosin filament (myosin binding protein c) was also identified and also shown to be cardiac-specific. Research interest in that protein became directed towards the identification of the mutations in that protein that had become implicated in the development of cardiomyopathy. As such that protein was not pursued as a potential marker for ischemic damage at that time (Fig 1).4