Identifying Important Risk Factors for Survival in Patient With Systolic Heart Failure Using Random Survival Forests

Background— Heart failure survival models typically are constructed using Cox proportional hazards regression. Regression modeling suffers from a number of limitations, including bias introduced by commonly used variable selection methods. We illustrate the value of an intuitive, robust approach to variable selection, random survival forests (RSF), in a large clinical cohort. RSF are a potentially powerful extensions of classification and regression trees, with lower variance and bias. Methods and Results— We studied 2231 adult patients with systolic heart failure who underwent cardiopulmonary stress testing. During a mean follow-up of 5 years, 742 patients died. Thirty-nine demographic, cardiac and noncardiac comorbidity, and stress testing variables were analyzed as potential predictors of all-cause mortality. An RSF of 2000 trees was constructed, with each tree constructed on a bootstrap sample from the original cohort. The most predictive variables were defined as those near the tree trunks (averaged over the forest). The RSF identified peak oxygen consumption, serum urea nitrogen, and treadmill exercise time as the 3 most important predictors of survival. The RSF predicted survival similarly to a conventional Cox proportional hazards model (out-of-bag C-index of 0.705 for RSF versus 0.698 for Cox proportional hazards model). Conclusions— An RSF model in a cohort of patients with heart failure performed as well as a traditional Cox proportional hazard model and may serve as a more intuitive approach for clinicians to identify important risk factors for all-cause mortality.