Heart Rate Variability as a Marker of Disease Severity in Pulmonary Arterial Hypertension: A Prospective Cohort Study

Pulmonary arterial hypertension (PAH) is a disease that can eventually progress to right ventricular failure. Heart rate variability (HRV), including standard deviation of R-to-R intervals (SDNN), has been associated with increased mortality across different populations. The purpose of this study was to examine the association between HRV and disease severity in PAH. This was a prospective cohort study of adult incident PAH patients who underwent cardiac magnetic resonance imaging (CMR) at baseline and following 6 months. Study subjects recorded HRV using wearable chest actigraphy devices for at least 1 h every 2 weeks. The primary end point was correlation between HRV and right ventricular ejection fraction (RVEF) on CMR. Multivariable mixed effects regression models were used. A total of 20 subjects completed the study, predominantly female and White race, with severe PAH at the time of enrollment that improved significantly following 6 months of treatment. Linear relationships were observed between HRV (SDNN) and measures of PAH severity on CMR, including RVEF (SDNN coefficient 0.18, p = 0.006) and right ventricular-pulmonary arterial coupling ratio (SDNN coefficient 0.008, p = 0.003). Comparable relationships were observed between heart rate captured using HRV device and these CMR measures (RVEF coefficient -0.37, p = 0.007; coupling ratio coefficient -0.013, p = 0.016). We conclude that noninvasively captured HRV (SDNN) and heart rate strongly correlate with PAH disease severity (right ventricular structure and function) on CMR, and may complement existing methods of risk assessment in PAH, particularly in high-risk incident PAH.