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Updated: Nov 26, 2025

Lumped-Parameter and Finite Element Modeling of Heart Failure with Preserved Ejection Fraction
Published on: February 13, 2021
Cardiovascular Autonomic Disturbances in Heart Failure With Preserved Ejection Fraction
Mark B Badrov1, Susanna Mak1, John S Floras1
1Division of Cardiology, Department of Medicine, University Health Network and Sinai Health System, University of Toronto, Toronto, Ontario, Canada.
Abstract:
In heart failure with reduced ejection fraction (HFrEF), diminished tonic and reflex vagal heart rate modulation and exaggerated sympathetic outflow and neural norepinephrine release are evident from disease inception. Each of these disturbances of autonomic regulation has been independently associated with shortened survival, and β-adrenoceptor antagonism and therapeutic autonomic modulation by other means have been demonstrated, in clinical trials, to lessen symptoms and prolong survival. In contrast, data concerning the autonomic status of patients with heart failure with preserved ejection fraction (HFpEF) are comparatively sparse. Little is known concerning the prognostic consequences of autonomic dysregulation in such individuals, and therapies applied with success in HFrEF have in most trials failed to improve symptoms or survival of those with HFpEF. A recent HFpEF Expert Scientific Panel report emphasised that without a deeper understanding of the pathophysiology of HFpEF, establishing effective treatment will be challenging. One aspect of such pathology may be cardiovascular autonomic disequilibrium, often worsened by acute exercise or routine daily activity. This review aims to summarise existing knowledge concerning parasympathetic and sympathetic function of patients with HFpEF, consider potential mechanisms and specific consequences of autonomic disturbances that have been identified, and propose hypotheses for future investigation.
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