Association between myocardial substrate, implantable cardioverter defibrillator shocks and mortality in MADIT-CRT

Nitesh Sood1†, Anne-Christine H. Ruwald2,3†*, Scott Solomon4, James P. Daubert5, Scott McNitt2, Bronislava Polonsky2, Christian Jons3, Christopher A. Clyne1, Wojciech Zareba2, and Arthur J. Moss

Objective The aim of the present study wasto assess a possible association between myocardial substrate, implantable cardioverter
defibrillator (ICD) shocks, and subsequent mortality.
Methods Within the multicentre automatic defibrillator implantation trial-cardiac resynchronization therapy (MADIT-CRT)
population (n ¼ 1790), we investigated the association between myocardial substrate, ICD shocks and subsequent mortality
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 [HR ¼ 2.3 (1.47–3.54), P , 0.001], which remained increased after adjusting for echocardiographic remodelling
at 1 year (HR ¼ 2.8, P ¼ 0.001). Appropriate anti-tachycardia pacing (ATP) only was not associated with increased
mortality (P ¼ 0.42). We were not able to show an association between inappropriate shocks (P ¼ 0.53), or inappropriate
ATP (P ¼ 0.10) and increased mortality. Advanced myocardial structural disease, i.e. higher baseline echocardiographic
volumes and lack of remodelling at 1 year, was present in patients who received appropriate shocks but not in
patients who received inappropriate shocks or no shocks.
Conclusion 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.
Clinical trials.gov identifier: NCT00180271.

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