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Multicenter Study
. 2025 Apr;11(4):685-693.
doi: 10.1016/j.jacep.2024.11.015. Epub 2025 Jan 29.

Sudden Unexpected Death in Patients With Implanted Cardiac Defibrillators: Results of Postmortem Interrogation in MADIT-CRT

Robert E Goldstein  1 , Margaret L McCarthy  2 , Ronald J Krone  3 , Mark C Haigney  4 , Wojciech Zareba  5 ; MADIT-CRT Trial Investigators
Affiliations
Multicenter Study

Sudden Unexpected Death in Patients With Implanted Cardiac Defibrillators: Results of Postmortem Interrogation in MADIT-CRT

Robert E Goldstein et al. JACC Clin Electrophysiol. 2025 Apr.

Abstract

Background: Ventricular tachyarrhythmia presumably causes sudden unexpected death (SUD) in patients lacking an implantable cardioverter-defibrillator (ICD). The mechanism of SUD is less clear in patients with an ICD to remedy ventricular tachycardia (VT) or ventricular fibrillation (VF).

Objectives: This study sought to assess mechanisms of SUD in patients with an ICD.

Methods: MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy) compared ICD alone with ICD with added cardiac resynchronization therapy in 1,820 patients with ischemic or nonischemic cardiomyopathy. In the current analysis, all 35 postmortem device interrogations were reviewed among the trial's 191 decedents. SUD (<3 hours after symptom onset or found dead <3 days after last seen) occurred in 39 (20%) of 191 decedents, including 24 with and 15 without ICD interrogation.

Results: Interrogation showed 11 of 24 with SUD had fatal VT/VF: 6 had inadequate ICD performance (inappropriate shock initiating VT/VF in 2 and failure to detect low-amplitude and/or slow VF in 4), 4 had refractory or recurrent VT/VF, and 1 had refractory bradycardia following defibrillating shock. The remaining 13 interrogated SUDs had no tachyarrhythmia initiating device activation. Autopsy in 3 disclosed only scattered myocardial fibrosis. No clinical features discriminated 11 interrogated SUD patients with VT/VF from 13 without VT/VF.

Conclusions: First, spontaneous VT/VF, undetected by ICD or refractory to ICD shock, caused a minority (33%) of SUD in 24 MADIT-CRT patients. Second, no tachyarrhythmia was identified in many (54%), suggesting SUD unrelated to tachyarrhythmia - or due to VT/VF undersensing. Last, ICD-related proarrhythmia instigated SUD in 2 (17%). Postmortem device interrogation revealed important outcomes and should be encouraged for decedents with ICD, particularly when investigating cardiovascular therapies.

Keywords: implanted defibrillator; sudden unexplained death; ventricular fibrillation.

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Conflict of interest statement

Funding Support and Author Disclosures MADIT-CRT was supported by a research grant from Boston Scientific. Partial support was received from Award # HU00012120008 from the Defense Health Agency to the Military Cardiovascular Outcomes Research program, Uniformed Services University, Bethesda, Maryland. The views expressed in this paper are those of the authors and do not reflect the official policy of the Department of Army/Navy/Air Force, the Uniformed Services University of the Health Sciences, the Department of Defense, or U.S. government or the policy of the Henry M. Jackson Foundation. The authors have reported that they have no relationships relevant to the contents of this paper to disclose.

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