The sympathetic nervous system in heart failure with preserved ejection fraction

The sympathetic nervous system (SNS) is a major mediator of cardiovascular physiology during exercise in healthy people. However, its role in heart failure with preserved ejection fraction (HFpEF), where exercise intolerance is a cardinal symptom, has remained relatively unexplored. The present review summarizes and critically explores the currently limited data on SNS changes in HFpEF patients with a particular emphasis on caveats of the data and the implications for its subsequent interpretation. While direct measurements of SNS activity in HFpEF patients is scarce, modest increases in resting levels of muscle sympathetic nerve activity are apparent, although this may be due to the co-morbidities associated with the syndrome rather than HFpEF per se. In addition, despite some evidence for dysfunctional sympathetic signaling in the heart, there is no clear evidence for elevated cardiac sympathetic nerve activity. The lack of a compelling prognostic benefit with use of β-blockers in HFpEF patients also suggests a lack of sympathetic hyperactivity to the heart. Similarly, while renal and splanchnic denervation studies have been performed in HFpEF patients, there is no concrete evidence that the sympathetic nerves innervating these organs exhibit heightened activity. Taken together, the totality of data suggests limited evidence for elevated sympathetic nerve activity in HFpEF and that any SNS perturbations that do occur are not universal to all HFpEF patients. Finally, how the SNS responds during exertion in HFpEF patients remains unknown and requires urgent investigation.