Chronic heart failure (HF) has developed into a major public health concern. Recent data suggests ~6 million Americans currently live with HF. Approximately 700,000 new diagnoses of HF are made each year which accounts for over 30% of cardiac admissions per year. Importantly, approximately half of all HF diagnoses are in patients with normal (preserved) ejection fraction. Through the emergence of new diagnostic technologies, improved survival after myocardial infarction, and the increasing age of the population, an upward trend is expected to continue. As a whole, patients with HF are limited in their activities of daily living and as such exercise intolerance is hallmark of HF and closely linked to reduced quality of life, increased morbidity and worse prognosis. Interestingly, initial studies failed to link measures of central hemodynamics or ventricular function to exercise capacity. Regardless of the etiology, HF quickly becomes a systemic disease involving multiple physiologic systems. Of the physiologic systems involved, the pulmonary and musculoskeletal have gained considerable attention for their role in symptom development. In fact, the two most pervasive symptoms limiting HF patients are dyspnea and fatigue. Potential mediators linking functional limitation and multisystem involvement in HF include neurologic receptors in skeletal muscle. This link has spawned the 'muscle hypothesis', relating afferent neural traffic from locomotor muscles to ventilatory and hemodynamic responses to exercise. Appropriately, the 'muscle hypothesis' has identified an area that is poorly understood but has the potential to address a major clinical problem. The objective of this application is to use novel methodologies to quantify the contribution of locomotor muscle afferent feedback on changes in ventilation and cardiovascular hemodynamics during exercise in HF patients. Our central hypothesis is that enhanced afferent feedback from locomotor muscles leads to increased sympathetic outflow during exercise, resulting in excessive ventilation and increased systemic vascular resistance which promotes exercise intolerance. The rationale for this proposal is that mechanisms of exercise intolerance and symptom development in HF are poorly understood but known to be related to morbidity and mortality. As such, identifying the specific mechanisms leading to changes in ventilatory and cardiovascular control may provide new avenues for patient treatment, rehabilitation, and disease management.
Heart failure is a progressive chronic disease associated with significant morbidity and mortality. Understanding the underlying mechanisms responsible for the etiology, pathology, and symptomology associated with this disease is imperative. In particular, we aim to understand the neural link between receptors in skeletal muscle and ventilation and cardiovascular hemodynamics during exercise. Generating a thorough understanding of these fundamental mechanisms will lead to novel therapeutic approaches and contribute to individualized treatment strategies in the HF population.
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