Predictors of Response to Cardiac Resynchronization Therapy in the Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy (MADIT-CRT)

Abstract

Background— We hypothesized that combined assessment of factors that are associated with favorable reverse remodeling after cardiac resynchronization-defibrillator therapy (CRT-D) can be used to predict clinical response to the device. Methods and Results— The study population comprised 1761 patients enrolled in the Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy (MADIT-CRT). Best-subset regression analysis was performed to identify factors associated with echocardiographic response (defined as percent reduction in left ventricular end-diastolic volume 1 year after CRT-D implantation) and to create a response score. Cox proportional hazards regression analysis was used to evaluate the CRT-D versus defibrillator-only reduction in the risk of heart failure or death by the response score. Seven factors were identified as associated with echocardiographic response to CRT-D and made up the response score (female sex, nonischemic origin, left bundle-branch block, QRS ≥150 milliseconds, prior hospitalization for heart failure, left ventricular end-diastolic volume ≥125 mL/m 2 , and left atrial volume <40 mL/m 2 ). Multivariate analysis showed a 13% ( P <0.001) increase in the clinical benefit of CRT-D per 1-point increment in the response score (range, 0–14) and a significant direct correlation between risk reduction associated with CRT-D and response score quartiles: Patients in the first quartile did not derive a significant reduction in the risk of heart failure or death with CRT-D (hazard ratio=0.87; P =0.52); patients in the second and third quartiles derived 33% ( P =0.04) and 36% ( P =0.03) risk reductions, respectively; and patients in the upper quartile experienced a 69% ( P <0.001) risk reduction ( P for trend=0.005). Conclusion— Combined assessment of factors associated with reverse remodeling can be used for improved selection of patients for cardiac resynchronization therapy. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00180271.