Reduction in human heart rate variability (HRV) is recognized in both clinical and athletic domains as a marker for stress or disease, but previous mathematical and clinical analyses have not fully explained the physiological mechanisms of the variability. Our analysis of HRV using the tools of control mathematics reveals that the occurrence and magnitude of observed HRV is an inevitable outcome of a controlled system with known physiological constraints. In addition to a deeper understanding of physiology, control analysis may lead to the development of timelier monitors that detect control system dysfunction, and more informative monitors that can associate HRV with specific underlying physiological causes.

Abstract

The correlation of healthy states with heart rate variability (HRV) using time series analyses is well documented. Whereas these studies note the accepted proximal role of autonomic nervous system balance in HRV patterns, the responsible deeper physiological, clinically relevant mechanisms have not been fully explained. Using mathematical tools from control theory, we combine mechanistic models of basic physiology with experimental exercise data from healthy human subjects to explain causal relationships among states of stress vs. health, HR control, and HRV, and more importantly, the physiologic requirements and constraints underlying these relationships. Nonlinear dynamics play an important explanatory role––most fundamentally in the actuator saturations arising from unavoidable tradeoffs in robust homeostasis and metabolic efficiency. These results are grounded in domain-specific mechanisms, tradeoffs, and constraints, but they also illustrate important, universal properties of complex systems. We show that the study of complex biological phenomena like HRV requires a framework which facilitates inclusion of diverse domain specifics (e.g., due to physiology, evolution, and measurement technology) in addition to general theories of efficiency, robustness, feedback, dynamics, and supporting mathematical tools.