Competing Risk of Ventricular Tachyarrhythmia and Nonarrhythmic Mortality in Advanced Heart Failure: Impact of Left...

Patients with heart failure and reduced left ventricular ejection fraction (LVEF) are at elevated risk of ventricular tachycardia or fibrillation (VT/VF), pump failure, and noncardiac death.

The purpose of this study was to evaluate the relationship between LVEF and VT/VF risk, accounting for nonarrhythmic mortality as a competing event.

We analyzed primary prevention implantable cardioverter-defibrillator (ICD) recipients from 5 major trials (MADIT-II [Multicenter Automatic Defibrillator Implantation Trial II], MADIT-CRT [Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy], MADIT-RIT [Multicenter Automatic Defibrillator Implantation Trial-Reduce Inappropriate Therapy], MADIT-RISK, RAID [Ranolazine in High-Risk Patients With Implanted Cardioverter-Defibrillator]), stratified by LVEF tertiles (≤20%, 21%-29%, 30%-35%). Outcomes included sustained VT/VF (primary), fast VT/VF (≥200 beats/min), appropriate ICD shocks, and all-cause mortality. Fine and Gray models were used to adjust for the competing risk of nonarrhythmic mortality.

The study population comprised 5,168 patients. At 3 years, the cumulative incidence of sustained VT/VF was inversely correlated with increasing LVEF tertiles: 28% for LVEF ≤20%, 23% for LVEF 21%-29%, and 20% for LVEF 30%-35% (P < 0.001). In multivariable models, patients with LVEF ≤20% had a 23% higher cumulative incidence of sustained VT/VF (P = 0.004), 33% higher cumulative incidence of fast VT/VF (P = 0.001), and 31% higher cumulative incidence of ICD shocks (P = 0.003) compared with those with LVEF >20%. These associations were similar across subgroups, cardiac resynchronization therapy-defibrillator use, and cardiomyopathy etiology. Patients with LVEF ≤20% also had a 1.5-fold increased risk of all-cause mortality (P < 0.001).

Patients with very low LVEF have higher cumulative incidence of sustained VT/VF and ICD shocks, along with an increased competing risk of death. These findings suggest that LVEF is an important factor in the shared decision-making process for a primary prevention ICD.