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Precision Medicine for Cardiac Resynchronization: Predicting Quality of Life Benefits for Individual Patients-An
Michael E Nassif1, Yuanyuan Tang1, John G Cleland1
1From the Division of Cardiology, Saint Luke's Mid America Heart Institute, Kansas City, MO (M.E.N., Y.T., P.G.J., S.V.A., J.A.S.); Division of Bioinformatics, University of Missouri-Kansas City (M.E.N., P.G.J., S.V.A., J.A.S.); Division of Cardiology, National Heart and Lung Institute, Imperial College London, England, United Kingdom (Royal Brompton and Harefield Hospitals) (J.G.C.); Department of Cardiology, Castle Hill Hospital, University of Hull, Kingston upon Hull, United Kingdom (J.G.C.); Division of Cardiovascular Medicine (W.T.A.) and Davis Heart and Lung Research Institute (W.T.A.), Ohio State University, Columbus (W.T.A.); Department of Cardiology, Karolinska University Hospital, Stockholm, Sweden (C.L.); Division of Cardiology, Medical University of South Carolina, Charleston (M.R.G.); Division of Cardiology, Cleveland Clinic Lerner College of Medicine, OH (J.B.Y.); Departement de Cardiologie, CHU Rennes, France (J.C.D.); Medtronic, Inc, Minneapolis, MN (L.S., D.S.); and Division of Cardiology, Island Medical Program, University of British Columbia, Vancouver, Canada (A.S.L.T.).
Background:
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.
Methods And Results:
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.
Conclusions:
There is marked heterogeneity of treatment benefit of CRT that can be predicted based on baseline QoL, age, and QRS duration.
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