Precision Medicine for Cardiac Resynchronization: Predicting Quality of Life Benefits for Individual Patients-An Analysis From 5 Clinical Trials.

Abstract

Clinical trials have established the average benefit of cardiac resynchronization therapy (CRT), but estimating benefit for individual patients remains difficult because of the heterogeneity in treatment response. Accordingly, we created a multivariable model to predict changes in quality of life (QoL) with and without CRT. Patient-level data from 5 randomized trials comparing CRT with no CRT were used to create a prediction model of change in QoL at 3 months using a partial proportional odds model for no change, small, moderate, and large improvement, or deterioration of any magnitude. The C statistics for not worsening or obtaining at least a small, moderate, and large improvement were calculated. Among the 3614 patients, regardless of assigned treatment, 33.3% had a deterioration in QoL, 9.2% had no change, 9.2% had a small improvement, 13.5% had a moderate improvement, and the remaining 34.9% had a large improvement. Patients undergoing CRT were less likely to have a decrement in their QoL (28.2% versus 38.9%; P<0.001) and more likely to have a large QoL improvement (38.7% versus 30.6%; P<0.001). A partial proportional odds model identified baseline QoL, age, and an interaction of CRT with QRS duration as predictors of QoL benefits 3 months after randomization. C statistics of 0.65 for not worsening, 0.68 for at least a small improvement, 0.69 for at least a moderate improvement, and 0.73 for predicting a large improvement were observed. There is marked heterogeneity of treatment benefit of CRT that can be predicted based on baseline QoL, age, and QRS duration.