Affiliation:
1. University Health Network and Sinai Health Division of Cardiology, Toronto General Hospital Research Institute and Department of Medicine, University of Toronto, Toronto, Ontario, Canada
Abstract
Defined as a structural or functional cardiac abnormality accompanied by symptoms, signs, or biomarkers of altered ventricular pressures or volumes, heart failure also is a state of autonomic disequilibrium. A large body of evidence affirms that autonomic disturbances are intrinsic to heart failure; basal or stimulated sympathetic nerve firing or neural norepinephrine (NE) release more often than not exceed homeostatic need, such that an initially adaptive adrenergic or vagal reflex response becomes maladaptive. The magnitude of such maladaptation predicts prognosis. This Ludwig lecture develops two theses: the elucidation and judiciously targeted amelioration of maladaptive autonomic disturbances offers opportunities to complement contemporary guideline-based heart failure therapy, and serendipitous single-participant insights, acquired in the course of experimental protocols with entirely different intent, can generate novel insight, inform mechanisms, and launch entirely new research directions. I précis six elements of our current synthesis of the causes and consequences of maladaptive sympathetic disequilibrium in heart failure, shaped by patient-inspired epiphanies: arterial baroreceptor reflex modulation, excitation stimulated by increased cardiac filling pressure, paradoxical muscle sympathetic activation as a peripheral neurogenic constraint on exercise capacity, renal sympathetic restraint of natriuresis, coexisting sleep apnea, and augmented chemoreceptor reflex sensitivity and then conclude by envisaging translational therapeutic opportunities.
Funder
Medical Research Council of Canada
Canada Research Chairs
Gouvernement du Canada | CIHR | Institute of Circulatory and Respiratory Health
Heart and Stroke Foundation of Canada
Publisher
American Physiological Society
Subject
Physiology (medical),Physiology
Cited by
8 articles.
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