Reinstating respiratory heart rate variability improves hemodynamic responses during exercise in heart failure with reduced ejection fraction

Individuals with heart failure have significantly reduced exercise capacity, a critical life-limiting symptom for those living with the disease. Heart failure is negatively correlated with decreased heart rate variability, including the loss of heart rate variability in tune with breathing-termed respiratory heart rate variability (RespHRV). We tested the hypothesis that restoration of RespHRV would improve exercise tolerance. Heart failure was induced in adult female sheep using a microembolization technique, and the sheep were divided into two groups: RespHRV paced and monotonically paced. Following a 1-week baseline recording, the sheep underwent 2 weeks of pacing. Direct recordings of hemodynamic parameters, including arterial pressure, cardiac output, coronary artery blood flow, and heart rate, were taken at rest and during treadmill exercise. Reinstating RespHRV significantly increased resting cardiac output, a change not observed in monotonically paced sheep. Neither group showed a change in resting coronary artery blood flow. During exercise, RespHRV-paced sheep showed increased cardiac output, coronary artery blood flow, cardiac power output, and faster heart rate recovery post-exercise. In contrast, monotonically paced sheep showed no changes in exercise-induced cardiac function. A separate group of heart failure animals were studied to determine if these benefits would persist alongside heart failure medications. RespHRV pacing continued to improve resting cardiac output with concurrent heart failure medications. Our results indicate that reinstating RespHRV may be a novel approach for improving outcomes in heart failure, including exercise capacity.