Autonomic cardiovascular reflex control of hemodynamics during exercise in heart failure with reduced ejection fraction and the effects of exercise training

Heart failure with reduced ejection fraction is associated with increased exercise intolerance, morbidity, and mortality. Importantly, exercise intolerance in heart failure with reduced ejection fraction is a key factor limiting patient quality of life and survival. Exercise intolerance in heart failure with reduced ejection fraction stems from a multi-organ failure to maintain homeostasis at rest and during exercise, including the heart, skeletal muscle, and autonomic nervous system, lending itself to a system constantly trying to "catch-up". Hemodynamic control during exercise is regulated primarily by the autonomic nervous system, whose operation, in turn, is partly regulated via reflexive information from exercise-stimulated receptors throughout the body (e.g., arterial baroreflex, central and peripheral chemoreceptors, and the muscle metabo- and mechanoreflexes). Persons with heart failure with reduced ejection fraction exhibit malfunctioning autonomic reflexes, which lead to exaggerated sympathoexcitation and attenuated parasympathetic tone. Chronic elevation of sympathetic activity is associated with increased morbidity and mortality. In this review, we provide an overview of how each main exercise-related autonomic reflex is changed in heart failure with reduced ejection fraction, and the role of exercise training in attenuating or reversing the counterproductive changes.