Predictors of super-response to cardiac resynchronization therapy and associated improvement in clinical outcome: The MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy) study

Objectives: The authors investigated predictors of left ventricular ejection fraction (LVEF) super-response to cardiac resynchronization therapy with defibrillator (CRT-D) and whether super-response translated into improved event-free survival in patients with mildly symptomatic heart failure (HF). Background: Few data exist on predictors of super-response to CRT-D and associated morbidity and mortality in mildly symptomatic HF populations. Methods: Patients were assigned to CRT-D with paired echocardiograms at baseline and at 12 months (n = 752). Super-response was defined by the top quartile of LVEF change. Best-subset regression analysis identified predictors of LVEF super-response. Kaplan-Meier survival analysis and Cox proportional hazards regression were performed to investigate associations of response category with development of nonfatal HF event or all-cause death. Results: All 191 super-responders experienced an LVEF increase of <14.5% (mean LVEF increase 17.5 ± 2.7%). Six predictors were associated with LVEF super-response to CRT-D therapy: female sex (odds ratio [OR]: 1.96; p = 0.001), no prior myocardial infarction (OR: 1.80; p = 0.005), QRS duration <150 ms (OR: 1.79; p = 0.007), left bundle branch block (OR: 2.05; p = 0.006), body mass index <30 kg/m ² (OR: 1.51; p = 0.035), and smaller baseline left atrial volume index (OR: 1.47; p < 0.001). Cumulative probability of HF or all-cause death at 2 years was 4% in super-responders, 11% in responders, and 26% in hypo-responders (log-rank p < 0.001 overall). In multivariate analysis, hyporesponse was associated with increased risk of HF or all-cause death, compared with super-response (hazard ratio: 5.25; 95% confidence interval: 2.01 to 13.74; p = 0.001). Conclusions: Six baseline factors predicted LVEF super-response in CRT-D-treated patients with mild HF. Super-response was associated with reduced risk of subsequent cardiac events.