Title
Risk Stratification for Ventricular Tachyarrhythmia in Patients with Non-Ischemic Cardiomyopathy
Authors
Ido Goldenberg, MD, Arwa Younis, MD, David T. Huang, MD, Spencer Rosero, MD, Valentina Kutyifa, MD PhD, Scott McNitt, MS, Bronislava Polonsky, MS, Jonathan S. Steinberg, MD, Wojciech Zareba, MD, PhD, Ilan Goldenberg MD, Mehmet K. Aktas, MD, MBA
Introduction
The implantable cardioverter defibrillator is effective in reducing mortality among patients with heart failure due to ischemic heart disease(1). Recent clinical trial data have called into question the benefit of an ICD in patients with heart failure due to non-ischemic cardiomyopathy (NICM)(2). The purpose of this study was to develop and externally validate a risk stratification score for ventricular tachyarrhythmia (VTA) among patients with NICM receiving an ICD for primary prevention of sudden cardiac death.
Methods
The study population comprised 1,515 patients with NICM who were enrolled in the landmark Multicenter Automated Defibrillator Trials. Fine and Gray analysis was used to develop a model to predict the occurrence of Ventricular Tachycardia>=170 b.p.m or Ventricular Fibrillation (VT/VF), while accounting for the competing risk of death. A risk score was subsequently created using the selected parameters. The patients were then divided into three categories based on the cumulative incidence of VT/VF: low-risk, intermediate-risk, and high-risk. Cumulative incidence curves were generated for each of the groups and compared using Gray's test. Regression modeling was also carried out to assess the relative risk among the groups for both the first occurrence of VT/VF and the burden of VT/VF using Fine and Gray regression analysis and Anderson-Gill recurrent events model, respectively. Internal validation was carried out by using 100 bootstrap samples of the total study population. External validation was carried out in 322 NICM patients who were implanted with a primary prevention ICD in the contemporary Ranolazine in High-Risk Patients With Implanted Cardioverter-Defibrillators (RAID) trial.
Results
Four risk factors associated with increased risk for VTA were identified: ICD vs cardiac resynchronization therapy with a defibrillator (CRT-D), male sex, left ventricular ejection fraction<=25%, and Black race. A score was generated based on this model and the 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 (>=200 bpm) or VF and Appropriate ICD Shocks revealed similar statistically significant findings. Consistently, the burden of recurrent VTA in the high-risk and intermediate-risk groups was significantly higher when compared to the low-risk group. Harrel’s c-index of the model in the development cohort (internal validation) and in the external validation cohort were 0.712 and 0.691, respectively.
Conclusion
We developed and externally validated a risk score based on four simple clinical factors. We believe that our novel risk score can be used to supplement shared patient-physician decision making with regard to prophylactic ICD placements in patients with heart failure due to NICM.
References
1. Moss AJ, Zareba W, Hall WJ, Klein H, Wilber DJ, Cannom DS, Daubert JP, Higgins SL, Brown MW and Andrews ML. Prophylactic Implantation of a Defibrillator in Patients with Myocardial Infarction and Reduced Ejection Fraction. New England Journal of Medicine. 2002;346:877-883. 2. Kober L, Thune JJ, Nielsen JC, Haarbo J, Videbaek L, Korup E, Jensen G, Hildebrandt P, Steffensen FH, Bruun NE, Eiskjaer H, Brandes A, Thogersen AM, Gustafsson F, Egstrup K, Videbaek R, Hassager C, Svendsen JH, Hofsten DE, Torp-Pedersen C, Pehrson S and Investigators D. Defibrillator Implantation in Patients with Nonischemic Systolic Heart Failure. N Engl J Med. 2016;375:1221-30.