Reduced Risk of Life-Threatening Ventricular Tachyarrhythmias with Cardiac Resynchronization Therapy: Relationship to Left Ventricular Ejection Fraction

AIMS: We hypothesized that the relationship between LVEF and the risk of life-threatening ventricular tachyarrhythmias (VTAs) may modify the effect of a CRT device with a defibrillator (CRT-D) on VTA risk. METHODS AND RESULTS: The risk of fast (≥200 b.p.m.) ventricular tachycardia/ventricular fibrillation (VT/VF) and the benefit of CRT-D in reducing VT/VF were assessed by baseline LVEF (categorized as ≤30% or 30% and assessed as a continuous measurement) in 1783 patients with mild heart failure (HF) implanted with an implantable cardioverter defibrillator (ICD) or CRT-D, enrolled in MADIT-CRT. Higher LVEF (>30%) at baseline was associated with a significantly lower risk of fast VT/VF [hazard ratio (HR) 0.54, P = 0.006], VT/VF (HR 0.62, P = 0.005), and VT/VF/death (HR 0.64, P = 0.003). Treatment with CRT-D was shown to reduce the risk of fast VT/VF in patients with LVEF ≤ 30% (n = 1100) [HR 0.64, 95% confidence interval (CI) 0.48-0.85, P = 0.002], but not among those with LVEF > 30% (n = 683) (HR 1.19, 95% CI 0.73-1.91, P = 0.502, interaction P-value = 0.03). When LVEF was assessed as a continuous measure, each 5% increment was shown to be associated with a significant 30% (P < 0.001) reduction in the risk for fast VT/VF, and with a corresponding linear reduction in the benefit of CRT-D in reducing fast VTA risk (P -value for treatment by LVEF interaction = 0.003). CONCLUSIONS: Our data suggest that in mild HF patients with cardiomyopathy there is an inverse correlation between LVEF and the risk of life-threatening VTAs, possibly contributing to the attenuation in the antiarrhythmic properties of CRT with increasing left ventricular function. TRIAL REGISTRATION: NCT00180271.