The Importance of Early Evaluation after Cardiac Resynchronization Therapy to Redefine Response: Pooled Individual Patient Analysis from Five Prospective Studies.

Abstract Background Cardiac resynchronization therapy (CRT) reduces mortality and improves outcomes in appropriately selected patients with heart failure (HF); however, response may vary. Objective We sought to correlate 6-month CRT response assessed by clinical composite score (CCS) and left ventricular systolic volume index (LVESVi) with longer-term mortality and heart failure hospitalizations. Methods Individual patient data from five prospective CRT -studies (MIRACLE, MIRACLE-ICD, InSync III Marquis, PROSPECT, and Adaptive CRT) were pooled. Classification of CRT response status using CCS and LVESVi were made at 6 months. Kaplan-Meier analyses were used to assess time-to-mortality. Cox proportional hazards regression models were used to compute hazard ratios for the three levels of CRT response (Improved, Stabilized, Worsened). Adjusted models controlled for baseline factors known to influence both CRT response and mortality. HF-related hospitalization was compared between CRT response categories using incidence rate ratios (IRRs). Results Among a total of 1603 patients, 1426 and 1165 were evaluated in the CCS and LVESVi outcomes assessments, respectively. Mortality was significantly lower for patients in the Improved (CCS: Hazard Ratio (HR) = 0.22; 95% CI 0.15-0.31; LVESVi: HR=0.40; 95% CI 0.27-0.60) and Stabilized groups (CCS: HR=0.38; 95% CI 0.24-0.61; LVESVi: HR=0.41; 95% CI 0.25-0.68) relative to the Worsened group for both measures after adjusting for potential confounders. Conclusions Patients with a Worsened CRT response status have a high mortality rate and heart failure hospitalizations. Stabilized patients have a more favorable prognosis than Worsened patients, and thus should not be considered CRT non-responders.