New Insights Regarding Acute Myocardial Infarction

Abstract & Commentary

By Jonathan Abrams, MD, Professor of Medicine, Division of Cardiology, University of New Mexico, Albuquerque. Dr. Abrams serves on the speaker’s bureau for Merck, Pfizer, and Parke-Davis.

Synopsis: Recurrent MI a major cause of death in post MI LV dysfunction patients.

Source: Orn S, et al. Recurrent Infarction Causes the Most Deaths Following Myocardial Infarction with Left Ventricular Dysfunction. Am J Med. 2005;118:752-758.

This report is a retrospective analysis of the large OPTIMAAL trial that randomized 5500 patients with acute myocardial infarction (MI) to losartan or captopril (Lancet. 2002;360:752). All patients had left ventricular (LV) systolic dysfunction or clinical congestive heart failure (CHF). Follow up was an average of 2.7 years. The focus of the present study was LV pathology in the 20% of patients who died during the trial and underwent an autopsy. The study was carried out in 7 European countries. Primary analysis was to compare the pathological diagnosis with the clinical diagnosis as to the cause of death occurring > 7 days after MI. Clinical causes of death analyzed included progressive CHF, sudden cardiac death, SCD, and recurrent MI. There were 946 deaths during the OPTIMAAL trial and, of these, 20% or 180 patients underwent an autopsy; 165 deaths occurred more than 7 days after the index MI. Those who had an autopsy were younger, less likely to die of unwitnessed (SCD), and more likely to die in hospital. Baseline demographics of those who underwent an autopsy vs those that did not were quite similar, including use of appropriate post MI medications.

Results: One hundred two of the 180 patients who underwent autopsy had a new acute MI as the presumed cause of death; in 80 patients, the recurrent MI was in the same territory as the index infarct. Twenty-five of this group had a fresh thrombus in the infarct related artery (IRA), whereas in 16 patients without new myocardial damage who died suddenly, a fresh thrombus was noted. The clinical cause of death compared to autopsy findings was changed in half of the patients, mostly due to an “undiagnosed acute MI.”

The clinical adjudicated diagnosis was SCD in 37% and progressive CHF in 21%. Events suggesting a re-MI in the 30 days prior to death were noted in only 20% of the cohort. SCD was diagnosed in 88 patients, the majority of which were not felt to have a clinical re-MI. However, an acute second MI was found in 60% of autopsy patients who died suddenly; 80% of these infarcts were not clinically recognized. Fresh coronary thrombus was noted in half of the patients who had sudden death associated with recurrent MI. In those who were not felt to have re-MI, a new acute MI was identified in only 20% clinically but 53% by autopsy; 80% of such individuals had symptoms of progressive heart failure. There was a decreasing trend for re-MI at autopsy related to time after the index event; 78% in the first 30 days, falling to 30% in the last years of the study.

Orn and colleagues conclude that their data “….demonstrates that recurrent MI is a common finding at autopsy in patients who die after an index MI irrespective of the mode of death.” However, the recurrent MI is often not recognized either because of atypical symptoms or because it presents as sudden death.”

Much clinical trial data has demonstrated that beta blockers and ACE inhibitors reduce these complications, including total mortality. Furthermore, the advent of defibrillator therapy in recent years has resulted in an increase in nonfatal acute MI, but a decrease in mortality, suggesting that the “device prevented death among patients who suffered what would otherwise have been fatal acute MI.” The findings of a high likelihood of acute MI at autopsy are concordant with other reports in the literature of SCD following MI. For instance, in those individuals with progressive heart failure who died, an acute MI was found in 80% of the cases. Orn et al state that “recurrent MI remains very much under-diagnosed among both patients who die suddenly and those who die with progressive heart failure.” This is particularly likely in deaths outside of the hospital. They recommend that “prevention of recurrent MI may be the primary objective in prolonging survival in this population.” These autopsy results are in line with other data, even though only a small number of patients receive a pathologic examination. Ruptured plaque was rarely seen at autopsy, presumably because of extensive coronary calcium in the large majority of individuals and the difficulty of finding residual thrombus, which has not been lysed.

Commentary

This analysis demonstrated that a silent or unrecognized new acute MI (or perhaps the term should be re-infarction) is very common after a large infarct, and is not surprising and deserves emphasis. The data raises the issue of how to classify sudden cardiac death. The clinical diagnosis of SCD was common, and yet the majority of individuals diagnosed actually had a new infarction superimposed upon significant old myocardial damage. The same is true for death following CHF, which was often precipitated by an unrecognized re-MI. What to do about these findings is another matter. Clearly, in a clinical trial such as OPTIMAAL, the use of appropriate post-MI medications should be excellent; of concern, the use of beta-blockers was only 70% and one could argue it should have been higher. The only other drugs that have been shown to reduce hard end points following acute MI are the statins; here utilization was low. Aspirin use was 90%. It should be recognized that OPTIMAAL was designed in the late 1990s, when the statin mania of today was just beginning.

What should the clinician do with these data? Certainly, the routine use of echocardiography needs to be emphasized in any patient who has had an MI and subsequently demonstrates signs of CHF. Sudden cardiac death following a silent or unrecognized re-MI remains very difficult to predict. The increasing use of defibrillators in appropriate patients with CAD and reduced LV function, certainly should reduce some of these deaths. These data do raise a concern that we may not be doing as good a job as we think in the months following an acute MI. Careful clinical assessment, closer follow-up, and appropriate use of mandated vascular protective drugs, as well as an echocardiography with any change in symptoms, appear to be mandated by the results of these observations. Furthermore, cardiac biomarkers should be obtained in patients who have even vague or atypical symptoms post-MI. Many individuals with a re-MI are unrecognized until it is too late.