Risk Stratification for Ventricular Tachyarrhythmia in Patients with Non-Ischemic Cardiomyopathy

Background The implantable cardioverter defibrillator reduces mortality among patients with heart failure (HF) due to ischemic heart disease. Clinical trial data have called into question the benefit of an ICD in patients with HF due to non-ischemic cardiomyopathy (NICM). Objective We developed a risk stratification score for ventricular tachyarrhythmia (VTA) among patients with NICM receiving a primary prevention ICD. Methods The study population comprised of 1,515 patients with NICM who were enrolled in the landmark MADIT trials. Fine and Gray analysis was used to develop a model to predict the occurrence of VTAs and ICD therapies while accounting for the competing risk of non-arrhythmic mortality. External validation was carried out in the RAID Trial population. Results Four risk factors associated with increased risk for VTA were identified: male sex, left ventricular ejection fraction ≤25%, no indication for cardiac resynchronization therapy with a defibrillator (CRT-D), and Black race. A score was generated based on this model and patients were stratified into low (N=390), intermediate (N=728), and high-risk (N=387) groups. The five-year cumulative incidences of VTA were 15%, 24%, 42% respectively. Application of score groups for the secondary endpoints of Fast VT or VF and Appropriate ICD Shock revealed similar findings. Recurrent event analysis yielded consistent results. The AUC in the validation cohort for the endpoint of Appropriate ICD Shock was 69.3. Conclusions Our study shows that patients with NICM can be risk stratified using demographic and clinical variables and may be used when evaluating such patients for a primary prevention ICD. CONDENSED ABSTRACT Data regarding the effectiveness of the ICD is lacking in patients with HF and NICM. The purpose of this study was to develop a risk score for ventricular tachyarrhythmia (VTA) among patients with NICM. We included patients from the MADIT trials to generate a risk score. Four risk factors associated with increased risk for VTA were identified and incorporated into the score. Patients were stratified into low, intermediate, and high-risk groups. The five-year cumulative incidences of VTA were 15%, 24%, 42% respectively. Our risk prediction model can support patient-physician shared decision making regarding primary ICD implantation in patients with NICM. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement Each of the MADIT trials were funded by an unrestricted research grant from Boston Scientific to the University of Rochester Medical Center, Rochester, NY. The RAID Trial was supported by NHLBI grants: UO1 HL096607 and UO1 HL096610 and by a grant from the Gilead Sciences Inc. (Foster City, CA): IN-US-259-0125. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: All of the trials involved in the manuscript have been approved by the institutional review boards (IRB) at the participating centers. We have obtained ethical approval from the University of Rochester IRB for conducting this study. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The original contributions presented in this study are included in the article/Supplementary material, further inquiries can be directed to the corresponding author. * ### Abbreviations HF : Heart Failure ICD : implantable cardioverter defibrillator NICM : non-ischemic cardiomyopathy VTA : ventricular tachyarrhythmia MADIT : multicenter automated defibrillator trial RAID : ranolazine in high-risk patients with implantable cardioverter defibrillators CRT : D-cardiac resynchronization therapy with a defibrillator