Meta-analysis of Risk of Ventricular Arrhythmias After Improvement in Left Ventricular Ejection Fraction During Follow-Up in Patients With Primary Prevention Implantable Cardioverter Defibrillators

Implantable cardioverter defibrillators (ICDs) reduce the risk of sudden cardiac death in patients with impaired left ventricular ejection fraction (LVEF). However, there are limited data on the long-term benefit of ICD therapy in patients whose LVEF subsequently improves. We conducted a meta-analysis to evaluate the effect of LVEF improvement on ICD therapy during follow-up. Incidence rate ratios (IRRs) with 95% confidence intervals (CIs) were calculated using random-effects modeling. Sixteen studies with 3,959 patients were included in our analysis. Study arms were defined by LVEF improvement at follow-up (improved LVEF [>35%]: 1,622; low LVEF [≤35%] 2,337). Mean age (64.8 vs 64.9 years, p = 0.97) was similar, whereas men were overrepresented in the persistent low LVEF group (79% vs 72%, p <0.001). Appropriate ICD therapy rate was 9.7% (improved LVEF) versus 21.8% (low LVEF) over a median follow-up period of 2.9 years. In the meta-analysis, improved LVEF group had significantly lower (3.3% vs 7.2% per year IRR 0.52; CI 0.38 to 0.70; p <0.001) appropriate ICD therapies which was uniformly seen across all subgroups (ICD-only studies: IRR 0.59; p = 0.004) (cardiac resynchronization therapy-defibrillator-only studies: IRR 0.31; p = 0.002) (super-responder studies [mean LVEF > 45%]: IRR 0.53; p = 0.002). Inappropriate ICD therapy rates were, however, similar in both groups (3.01% vs 2.56% per year IRR 0.76; CI 0.43 to 1.36; p = 0.35). All-cause mortality rates in our meta-analysis favored (3.63% vs 8.23% per year IRR 0.49; CI 0.35 to 0.69; p <0.001) the improved LVEF group. In conclusion, our meta-analysis demonstrates that an improvement in LVEF is associated with a significantly reduced risk of ventricular arrhythmia and mortality. However, inappropriate ICD therapy rates remain similar.