Association Between Myocardial Substrate, Implantable Cardioverter Defibrillator Shocks and Mortality in MADIT-CRT

Study Questions:

Was there an association between myocardial substrate, implantable cardioverter-defibrillator (ICD) shocks, and mortality in the MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy) trial?

Methods:

Within the MADIT-CRT population (n = 1,790), the association between myocardial substrate, ICD shocks, and subsequent mortality was investigated using multivariate Cox regression analyses and landmark analyses at 1-year follow-up.

Results:

The 4-year cumulative probability of ICD shocks was 13% for appropriate shock and 6% for inappropriate shock. Compared with patients who never received ICD therapy, patients who received appropriate shock had an increased risk of mortality (hazard ratio, 2.3; 95% confidence interval, 1.47-3.54; p < 0.001), which remained increased after adjusting for echocardiographic remodeling at 1 year (hazard ratio, 2.8; p < 0.001). Appropriate antitachycardia pacing (ATP) only was not associated with increased mortality (p = 0.42).There was no apparent association between inappropriate shocks (p = 0.53), or inappropriate ATP (p = 0.10) and increased mortality. Advanced myocardial structural disease (i.e., higher baseline echocardiographic volumes and lack of remodeling at 1 year) was observed in patients who received appropriate shocks, but not in patients who received inappropriate shocks or no shocks.

Conclusions:

In the MADIT-CRT study, receiving appropriate ICD shocks was associated with an increased risk of subsequent mortality. This association was not evident for appropriate ATP only. These findings, along with advanced cardiac structural disease in the patients who received appropriate shocks, suggest that the compromised myocardium is a contributing factor to the increased mortality associated with appropriate ICD shock therapy.

Perspective:

Several prior studies have suggested a relationship between both appropriate and inappropriate ICD shocks and mortality. This post hoc analysis does not provide definitive answers, but it raises the possibility of the substrate-ICD shock and mortality association. It is possible that the severity of heart failure determines whether shocks result in higher mortality. The MADIT-CRT enrolled patients with New York Heart Association class I and II, and had patients with less advanced heart failure. A randomized controlled clinical trial evaluating both myocardial substrate and clinical outcomes in patients receiving ICD shocks is very much needed.

Clinical Topics: Arrhythmias and Clinical EP, Heart Failure and Cardiomyopathies, Noninvasive Imaging, Implantable Devices, SCD/Ventricular Arrhythmias, Atrial Fibrillation/Supraventricular Arrhythmias, Acute Heart Failure, Echocardiography/Ultrasound

Keywords: Defibrillators, Follow-Up Studies, Shock, Ventricular Fibrillation, New York, Tachycardia, Cardiac Resynchronization Therapy, Death, Cardiomyopathies, Heart Failure, Confidence Intervals, Regression Analysis, Echocardiography


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