This review presents a substudy analysis of the Defibrillators in Non-Ischemic Cardiomyopathy Treatment Evaluation (DEFINITE) trial, which examined the role of prophylactic implantable cardioverter defibrillator (ICD) implantation in patients with nonischemic cardiomyopathy.
This review presents a substudy analysis of the Defibrillators in Non-Ischemic Cardiomyopathy Treatment Evaluation (DEFINITE) trial, which examined the role of prophylactic implantable cardioverter defibrillator (ICD) implantation in patients with nonischemic cardiomyopathy. This trial, which assigned 458 patients with nonischemic cardiomyopathy (left ventricular ejection fraction [LVEF] < 36%) to randomly receive standard medical therapy versus medical therapy plus single chamber ICD, showed no significant difference in mortality. There are several possible reasons for this, as proposed by the authors of the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT). Probably most significant is that 22% of patients enrolled had New York Heart Association (NYHA) I symptoms of heart failure whereas patients randomized in SCD-HeFT were required to have at least NYHA II symptoms.1 In this post-hoc analysis of the DEFINITE data, the authors found that patients with diagnosed cardiomyopathy who received an ICD had significantly improved survival compared with those with standard therapy. By contrast there was no significant difference between treatment groups among patients with a remote diagnosis of cardiomyopathy.
Indications for ICDs have recently been expanded based on the results of several landmark trials including the Multicenter Automatic Defibrillator Implantation Trial II (MADIT II) and SCD-HeFT trials. The MADIT II trial enrolled patients with a prior myocardial infarction (MI) and LVEF < 30%. This trial demonstrated a significant reduction in mortality among those patients who received an ICD. The SCD-HeFT trial by contrast, did not require the presence a previous MI. Rather, this trial enrolled 2521 patients with NYHA II and III congestive heart failure (CHF). There was a fairly even mix between ischemic and nonischemic cardiomyopathy. The Comparison of Medical Therapy, Pacing and Defibrillation in Chronic Heart Failure (COMPANION) trial supports these trials and also found a significant benefit in patients with CHF who underwent ICD implantation.3 Based on this data regarding primary prevention of sudden death in CHF, the American College of Cardiology/ American Heart Asssociation clinical guidelines for the treatment of patients with CHF (published in 2005) list implantation of a prophylactic ICD as a class I indication in those patients who have LVEF < 30% and who have class II or III CHF (patients with LVEF 31%-35% are listed as class II a). Centers for Medicare and Medicaid Services guidelines were updated in 2005 to reflect these expanded indications. However, patients with nonischemic cardiomyopathy must have CHF diagnosed > 9 months before implantation. The current study suggests that this is not the correct approach, however, and that patients with recent diagnoses should be considered for ICD implantation.
One major issue to contend with is the appropriate medical treatment of CHF. In these trials, all patients were on optimal medical therapy. It may be argued that the 3- to 9-month waiting period is appropriate to: (1) ensure that medical therapy has been initiated and is working: (2) ensure that the cardiomyopathy and CHF is not reversible; and (3) ensure that acute CHF is appropriately treated and the patient is stable enough to undergo ICD implantation. In fact, the Defibrillator in Acute MI Trial (DINAMIT) study showed that ICD implantation early after an acute MI may be deleterious.4 There may be similar danger in patients in the early stages of their CHF treatment.
This is an important study because it points out that a waiting period before prophylactic ICD implantation may not be appropriate in patients with nonischemic cardiomyopathy. However, there are some important reasons why it may not be appropriate to treat patients in the early phase of their diagnosis. Further study is needed to fully answer this question. After all, timing is everything.