Assessment and Therapeutic Modulation of Heart Rate Variability: Potential Implications in Patients with COVID-19

Abstract

Cardiac damage has been attributed to SARS-CoV-2-related pathology contributing to increased risk of vascular events. Heart rate variability (HRV) is a parameter of functional neurocardiac integrity with low HRV constituting an independent predictor of cardiovascular mortality. Whether structural cardiac damage translates into neurocardiac dysfunction in patients infected with SARS-CoV-2 remains poorly understood. Hypothesized mechanisms of possible neurocardiac dysfunction in COVID-19 comprise direct systemic neuroinvasion of autonomic control centers, ascending virus propagation along cranial nerves and cardiac autonomic neuropathy. While the relationship between the autonomic nervous system and the cytokine cascade in general has been studied extensively, the interplay between the inflammatory response caused by SARS-CoV-2 and autonomic cardiovascular regulation remains largely unclear. We reviewed the current literature on the potential diagnostic and prognostic value of autonomic neurocardiac function assessment via analysis of HRV including time domain and spectral analysis techniques in patients with COVID-19. Furthermore, we discuss potential therapeutic targets of modulating neurocardiac function in this high-risk population including HRV biofeedback and the impact of long COVID on HRV as well as the approaches of clinical management. These topics might be of particular interest with respect to multimodal pandemic preparedness concepts.

Keywords: COVID-19; SARS-CoV-2; autonomic; cardiac; cardiovascular; heart rate variability; parasympathetic; sympathetic.

Figure 1

Decomposing a wave function into simple sinusoidal functions. (A) is a wave function s3 that consists of the sum of two simple sinusoidal functions, s1 (blue) and s2 (yellow) in (B). The complex signal composed of a myriad of frequencies is transformed by a filter into simple waves. Analysis of HRV using frequency domain methods functions in a similar fashion; the oscillation of the HRV is converted into a complex signal (analog to (A)), which then can be decomposed into various frequencies (analog to (B)) so that their individual contribution can be measured.

Figure 2

Possible pathways whereby SARS-CoV-2 might reach neural targets within the autonomic nervous system to cause neurocardiac dysfunction.

Figure 3

HRV Biofeedback training. The drawing shows a subject undergoing HRV biofeedback with continuous measurement of HRV via an ear clip and visualization on the computer screen via a hovering butterfly that rises in response to an increase and descents during a decrease in HRV while the subjects perform a metronomic breathing exercise to increase parasympathetic outflow and thereby HRV.