Data-driven, patient-specific simulations of long-term heart rate variability and cardiac alternans formation.

Abstract

Individuals suffering from chronic heart failure (CHF) have a greater risk for death mediated by ventricular arrhythmias, which may be related to changes in heart rate. Heart rate constantly fluctuates from beat-to-beat on a timescale ranging from seconds to hours under physiological conditions, termed heart rate variability (HRV). Individuals with CHF have reduced HRV and faster heart rates, both of which influence the formation of pro-arrhythmic alternans, a beat-to-beat alternation in the action potential duration (APD) and intracellular calcium (Ca) levels. It is unclear how long-term changes in heart rate influence alternans and arrhythmia formation. We obtained sequences of RR intervals (time between successive R waves in an electrocardiogram) from individuals with normal sinus rhythm (NSR) and CHF from a Physionet database. These RR-sequences are used to define the pacing period for a discrete-time coupled map model of APD and intracellular Ca cycling for a single cardiac myocyte, modified to account for human heart rates and pathological Ca-remodeling in CHF. These modifications include fitting human ventricular myocyte APD restitution parameters, including a new term for Ca leak from the sarcoplasmic reticulum (SR), and scaling SR Ca-related parameters. Importantly, this minimal model enables simulation of long-term trends, on the order of 24 hours, in large populations. We find that the alternations in APD and Ca vary over time, such that there are periods with both small and large beat-to-beat differences in both populations. However, the CHF population tends to have a larger alternations magnitude, demonstrating that CHF-associated heart rates promotes more pro-arrhythmic phenomena. Future work will extend this methodology to determine what statistical properties govern the CHF RR-sequences, and further to test to what extent pro-arrhythmic alternans depends on CHF-related changes in heart rate or remodeling.