Monday, December 30, 2024
12/30/2024
PROJECT SUMMARY Heart failure with preserved ejection fraction (HFpEF) is a debilitating disease with high morbidity, mortality and health care expenditures. Impaired physical capacity is the primary symptom and a strong determinant of prognosis and reduced quality of life (QoL). The prevalence of HFpEF is higher in women and increases with age. Women with HFpEF present with worse exercise intolerance, microvascular dysfunction, and QoL relative to men. However, older women remain consistently underrepresented in clinical trials. The specific problem is that very few therapies currently exist to improve functional performance and QoL in patients with HFpEF. For these reasons, HFpEF is recognized as the single greatest unmet need in cardiovascular medicine today. The objective of this proposal is to determine, for the first time, the benefits of home-based leg heat therapy (HT) on exercise tolerance and QoL in older women with HFpEF. This novel approach consists of custom engineered trousers, instrumented with a network of small flexible tubes connected to a portable water pump. Hot water is circulated through the tubes, evenly heating the buttocks, thighs and calves. The system is convenient for application in the home setting without supervision. These customized trousers were demonstrated to be safe, well-tolerated and to enhance exercise tolerance in elderly individuals with restricted mobility. In a preclinical model of HFpEF, we recently found that repeated HT enhanced skeletal muscle mass, microvascular function and treadmill running performance. Building upon our preliminary data, we propose to conduct a randomized, double-blind, sham-controlled clinical trial in 34 older women (≥60 years of age) with HFpEF to establish the effect of daily, home-based leg HT for 8 weeks on functional capacity and QoL. Patients randomized to the leg HT group (n=17) will be asked to apply the treatment daily for 90 min using water-circulating trousers perfused with water heated at 42°C. In the sham group (n=17), water at 33°C will be circulated through the trousers. The primary outcome is the change in exercise capacity during treadmill tests between baseline and the 8-week follow-up. Secondary outcomes include changes in perceived QoL and cardiovascular responses to exercise. In Aim#2, we will determine the tissue-level mechanisms by which HT affects muscle strength and exercise performance. We will assess skeletal muscle morphology (magnetic resonance imaging), leg strength (isokinetic dynamometry), microvascular oxygenation and blood flow (near-infrared spectroscopy, Fick equation), and mitochondrial respiration (31P-magnetic resonance spectroscopy). If the conclusions based on our preliminary data are substantiated, the proposed experiments will provide an evidence-based framework of feasibility and efficacy of a novel, straightforward approach to improve functional performance and QoL in patients with HFpEF. Given its accessibility, tolerability and ease of use, HT has the potential for rapid translation and application in the clinical setting, thereby opening new horizons for the non-invasive management of HFpEF.
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