Nonlinear Indices of Heart Rate Variability in Chronic Heart Failure Patients: Redundancy and Comparative Clinical Value

Abstract

We aimed to assess the mutual interrelationships and to compare the prognostic value of a comprehensive set of nonlinear indices of heart rate variability (HRV) in a population of chronic heart failure (CHF) patients. Twenty nonlinear HRV indices, representative of symbolic dynamics, entropy, fractality-multifractality, predictability, empirical mode decomposition, and Poincaré plot families, were computed from 24-hour Holter recordings in 200 stable CHF patients in sinus rhythm (median age [interquartile range]: 54 [47-58] years, LVEF: 23 [19-28]%, NYHA class II-III: 88%). End point for survival analysis (Cox model) was cardiac death or urgent transplantation. Homogeneous variables were grouped by cluster analysis, and in each cluster redundant variables were discarded. A prognostic model including only known clinical and functional risk factors was built and the ability of each selected HRV variable to add prognostic information to this model assessed. Bootstrap resampling was used to test the models stability. Four nonlinear variables showed a correlation >0.90 with classical linear ones and were discarded. Correlations >0.80 were found between several nonlinear variables. Twelve clusters were obtained and from each cluster a candidate predictor was selected. Only two variables (from empirical mode decomposition and symbolic dynamics families) added prognostic information to the clinical model. This exploratory study provides evidence that, despite some redundancies in the informative content of nonlinear indices and strong differences in their prognostic power, quantification of nonlinear properties of HRV provides independent information in risk stratification of CHF patients.