Dallas, TX - Among patients with ischemic cardiomyopathy and an implantable cardioverter-defibrillator (ICD), the risk of new or recurrent heart failure climbs steeply after the first delivery of an appropriate shock, according to a retrospective analysis [1] of a major 2002 randomized trial [2]. On the other hand, the study found, inappropriate shocks apparently don't increase later HF risk.

"Our interpretation of this is that the ICD shocks by themselves don't damage the heart and don't increase the risk of heart failure—it's the life-saving ICD therapy transforming the risk of sudden death into a subsequent heart-failure risk," according to Dr Ilan Goldenberg (University of Rochester, NY), lead author of the post hoc study from the second Multicenter Automatic Defibrillator Implantation Trial (MADIT-2). Their report is published online before print in Circulation on June 12, 2006.

Another major finding from the analysis, he told heartwire, is that HF risk started rising after appropriate-shock delivery by either single- or dual-chamber ICDs compared with nondevice conventional therapy. That appears to contrast with some earlier studies suggesting that dual-chamber ICDs, as compared with backup single-chamber devices, can promote HF. But Goldenberg said a subanalysis including only patients with ICDs showed dual-chamber devices accounted for "a little more" of the risk increase.

ICD shocks by themselves don't damage the heart and don't increase the risk of heart failure—it's the life-saving ICD therapy transforming the risk of sudden death into a subsequent heart-failure risk.

The MADIT-2 trial had randomized 1232 post-MI patients with an LVEF <30% to receive either single- or dual-chamber ICDs or to be treated medically according to the convention of the era; the current analysis excludes 24 ICD recipients with insufficient follow-up data, which covered an average of 20 months. As extensively covered by heartwire, the MADIT-2 primary findings played a major role in the eventual extension of ICDs from secondary to primary prevention of sudden cardiac death (SCD).

Importantly, single-chamber ICDs (n=402) were usually set to engage ventricular backup pacing when the native rate dropped to between 40 and 50 bpm. Dual-chamber devices (n=313) were generally set to pace at 60 to 70 bpm. The investigators estimated that 92% of patients with single-chamber devices "received little or no" pacing throughout the study, whereas RV pacing was engaged >50% of the time ("mostly in the range of 90% to 100%") in two thirds of those with dual-chamber units.

Also according to their analysis:

• Significantly fewer (p=0.03) of the conventional-therapy patients (n=482) than those in either of the single- or dual-chamber ICD groups were hospitalized for HF during the study: 17%, 22%, and 25% respectively.
• Compared with non-ICD patients, those with devices showed significant jumps in the risks of first and recurrent HF hospitalizations, respectively. The risks of both end points were significantly and independently higher for both single- and especially dual-chamber devices.
• After appropriate ICD shocks, but not inappropriate ones, the risks of first HF and recurrent HF hospitalizations went up significantly and steeply.
• Beta-blocker therapy cut the hazard ratio for HF hospitalization by 41% (95% CI 0.43-0.80, p<0.001) in the combined ICD groups, but the conventional-therapy group received no such significant benefit.
• Hospitalization for HF during the study almost quadrupled the subsequent all-cause-mortality risk in multivariate analysis (95% CI 3.86 2.71-5.31, p<0.001).

Clinicians, according to Goldenberg, should keep in mind that an elevated HF risk and probably reduced quality of life are trade-offs for the immense prophylactic SCD-prevention benefit of ICDs. The current analysis, he said, suggests that intensified HF medical therapy, especially beta blockade, should be considered for ICD recipients and that those with current ICD indications should be "very strongly" considered for a device with biventricular pacing.

Goldenberg said an ongoing third MADIT study is prospectively testing the latter strategy, comparing the effects of ICD therapy with or without cardiac resynchronization therapy on SCD and HF outcomes.