Timing of arrhythmic death after myocardial infarction: does it affect timing of ICD implantation?

This editorial refers to ‘Temporal trends on the risk of arrhythmic vs. non-arrhythmic deaths in high-risk patients after myocardial infarction: a combined analysis from multicentre trials’ { by Y.G. Yap et al., on page 1385 In spite of significant reduction in total mortality observed in patients discharged after an acute myocardial infarction (MI), ventricular arrhythmias still account for 30–40% of deaths. This figure, which was initially provided by studies carried out in the pre-thrombolytic era, has been subsequently confirmed when most of the patients had been revascularized by thrombolysis or percutaneous coronary intervention (PCI). 1 Early revascularization and a more generalized use of beta blockers, angiotensin-converting enzyme-inhibitors, statins, and antiplatelet agents have largely contributed to the improvement in the prognosis of patients presenting with an ST-elevated acute MI. Nevertheless, identification of patients at risk remains an issue far from being adequately addressed. There is a general consensus that depressed ventricular function, as reflected by a left ventricular ejection fraction (LVEF) ,40%, represents the strongest negative prognostic factor in these patients. 1 Different cut-off values have proved effective in recent clinical trials and an LVEF ,30% has been used as a single inclusion criteria in studies aimed to evaluate, for example, the beneficial effect of implantable cardioverter defibrillator (ICD) after MI. After the publication of MADIT II results 2 that have clearly indicated a significant reduction of total and arrhythmic mortality in post-MI patients with ICD when compared with controls, ICD implantation has been recommended for almost all post-MI patients with an LVEF ,30%. This position has been only partially accepted by the most recent ACC/ AHA/NASPE and ESC guidelines. 3,4 The issue has become even more controversial after the publication of the results of the DINAMIT study. 5 More than 600 patients with a recent acute MI and reduced left ventricular function (LVEF , 35%) were randomized to ICD and control. Revascularization rate (either thrombolysis or PCI) was 62%. The so-called ‘best’ medical treatment was provided to most of the patients. The main result of the study was that prophylactic ICD therapy did not reduce overall mortality in this high-risk population. Moreover, by considering the type of death, it was evident that the reduction in the rate of death due to arrhythmia was offset by an increase in the rate of death from non-arrhythmic causes. A careful comparison of MADIT II with DINAMIT study characteristics provides a partial explanation for such a difference. In addition to the inevitable differences in study population and patient management, it is evident that in MADIT II, the mean time for enrolment was 81 months, whereas in DINAMIT it was 6–40 days. Thus, timing of implantation in relation to the index event was a critical factor not fully considered in the original report and only recently appreciated in the discussion of ICD indication in post-MI patients. Indeed, on reviewing a recent report by MADIT II study group, it is evident that no benefit from ICD could be observed in patients with a less remote MI (,18 months), whereas a tendency for a favourable effect or a significant benefit from ICD was detectable, respectively, at 18–59 months or longer (from 60 to .120 months) after the acute event. One could therefore extrapolate that, according to DINAMIT and MADIT II, ICD benefit cannot be detected in the first 2 years after an acute MI, thus casting additional doubts to the recommendation of an early ICD implantation in all patients with a depressed LVEF. The lack of benefit from ICD implantation in the first 2 years after an acute MI could be interpreted as an indirect evidence in which, in the reperfusion era, the risk of arrhythmic death becomes predominant only several months after the acute event. Is this opinion founded?