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Item Acute effects of leg heat therapy on walking performance and cardiovascular and inflammatory responses to exercise in patients with peripheral artery disease(Wiley, 2021) Monroe, Jacob C.; Song, Qifan; Emery, Michael S.; Hirai, Daniel M.; Motaganahalli, Raghu L.; Roseguini, Bruno T.; Surgery, School of MedicineLower-extremity peripheral artery disease (PAD) is associated with increased risk of cardiovascular events and impaired exercise tolerance. We have previously reported that leg heat therapy (HT) applied using liquid-circulating trousers perfused with warm water increases leg blood flow and reduces blood pressure (BP) and the circulating levels of endothelin-1 (ET-1) in patients with symptomatic PAD. In this sham-controlled, randomized, crossover study, sixteen patients with symptomatic PAD (age 65 ± 5.7 years and ankle-brachial index: 0.69 ± 0.1) underwent a single 90-min session of HT or a sham treatment prior to a symptom-limited, graded cardiopulmonary exercise test on the treadmill. The primary outcome was the peak walking time (PWT) during the exercise test. Secondary outcomes included the claudication onset time (COT), resting and exercise BP, calf muscle oxygenation, pulmonary oxygen uptake (V̇O2 ), and plasma levels of ET-1, interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α). Systolic, but not diastolic BP, was significantly lower (~7 mmHg, p < .05) during HT when compared to the sham treatment. There was also a trend for lower SBP throughout the exercise and the recovery period following HT (p = .057). While COT did not differ between treatments (p = .77), PWT tended to increase following HT (CON: 911 ± 69 s, HT: 954 ± 77 s, p = .059). Post-exercise plasma levels of ET-1 were also lower in the HT session (CON: 2.0 ± 0.1, HT: 1.7 ± 0.1, p = .02). Calf muscle oxygenation, V̇O2 , COT, IL-6, and TNF-α did not differ between treatments. A single session of leg HT lowers BP and post-exercise circulating levels of ET-1 and may enhance treadmill walking performance in symptomatic PAD patients.Item Effects of home-based leg heat therapy on walking performance in patients with symptomatic peripheral artery disease: a pilot randomized trial(American Physiological Society, 2022) Monroe, Jacob C.; Pae, Byung Joon; Kargl, Christopher; Gavin, Timothy P.; Parker, Jason; Perkins, Susan M.; Han, Yan; Klein, Janet; Motaganahalli, Raghu L.; Roseguini, Bruno T.; Radiology and Imaging Sciences, School of MedicineFew noninvasive therapies currently exist to improve functional capacity in people with lower extremity peripheral artery disease (PAD). The goal of the present study was to test the hypothesis that unsupervised, home-based leg heat therapy (HT) using water-circulating trousers perfused with warm water would improve walking performance in patients with PAD. Patients with symptomatic PAD were randomized into either leg HT (n = 18) or a sham treatment (n = 16). Patients were provided with water-circulating trousers and a portable pump and were asked to apply the therapy daily (7 days/wk, 90 min/session) for 8 wk. The primary study outcome was the change from baseline in 6-min walk distance at 8-wk follow-up. Secondary outcomes included the claudication onset-time, peak walking time, peak pulmonary oxygen consumption and peak blood pressure during a graded treadmill test, resting blood pressure, the ankle-brachial index, postocclusive reactive hyperemia in the calf, cutaneous microvascular reactivity, and perceived quality of life. Of the 34 participants randomized, 29 completed the 8-wk follow-up. The change in 6-min walk distance at the 8-wk follow-up was significantly higher (P = 0.029) in the group exposed to HT than in the sham-treated group (Sham: median: -0.9; 25%, 75% percentiles: -5.8, 14.3; HT: median: 21.3; 25%, 75% percentiles: 10.1, 42.4, P = 0.029). There were no significant differences in secondary outcomes between the HT and sham group at 8-wk follow-up. The results of this pilot study indicate that unsupervised, home-based leg HT is safe, well-tolerated, and elicits a clinically meaningful improvement in walking tolerance in patients with symptomatic PAD. NEW & NOTEWORTHY: This is the first sham-controlled trial to examine the effects of home-based leg heat therapy (HT) on walking performance in patients with peripheral artery disease (PAD). We demonstrate that unsupervised HT using water-circulating trousers is safe, well-tolerated, and elicits meaningful changes in walking ability in patients with symptomatic PAD. This home-based treatment option is practical, painless, and may be a feasible adjunctive therapy to counteract the decline in lower extremity physical function in patients with PAD.Item Leg heat therapy improves perceived physical function but does not enhance walking capacity or vascular function in patients with peripheral artery disease(American Physiological Society, 2020-12) Monroe, Jacob C.; Lin, Chen; Perkins, Susan M.; Han, Yan; Wong, Brett J.; Motaganahalli, Raghu L.; Roseguini, Bruno T.; Biostatistics and Health Data Science, School of MedicineA single session of leg heat therapy (HT) has been shown to elicit increases in leg blood flow and reduce blood pressure (BP) and the circulating levels of endothelin-1 (ET-1) in patients with symptomatic peripheral artery disease (PAD). We assessed whether 6 wk of supervised leg HT (3 times/wk) with water-circulating trousers perfused with water at 48°C improved 6-min walk distance in individuals with PAD compared with a sham treatment. Secondary outcomes included the assessment of leg vascular function, BP, quality of life, and serum ET-1 and nitrite plus nitrate (NOx) levels. Of 32 PAD patients randomized, 30 [age: 68 ± 8 yr; ankle-brachial index (ABI): 0.6 ± 0.1] completed the 3- and 6-wk follow-ups. Participants completed 98.7% of the treatment sessions. Compared with the sham treatment, exposure to HT did not improve 6-min walk distance, BP, popliteal artery reactive hyperemia, cutaneous microvascular reactivity, resting ABI, or serum NOx levels. The change from baseline to 6 wk in scores of the physical functioning subscale of the 36-item Short Form Health Survey was significantly higher in the HT group (control -6.9 ± 10 vs. HT 6.8 ± 15; 95% confidence interval: 2.5-24.3, P = 0.017). Similarly, the change in ET-1 levels after 6 wk was different between groups, with the HT group experiencing a 0.4 pg/mL decrease (95% confidence interval: -0.8-0.0, P = 0.03). These preliminary results indicate that leg HT may improve perceived physical function in symptomatic PAD patients. Additional, larger studies are needed to confirm these findings and determine the optimal treatment regimen for symptomatic PAD patients. NEW & NOTEWORTHY: This is the first sham-controlled study to investigate the effects of leg heat therapy (HT) on walking performance, vascular function, and quality of life in patients with peripheral artery disease (PAD). Adherence to HT was high, and the treatment was well tolerated. Our findings revealed that HT applied with water-circulating trousers evokes a clinically meaningful increase in perceived physical function and reduces the serum concentration of the potent vasoconstrictor endothelin-1 in patients with PAD.