Local Passive Heat for the Treatment of Hypertension in Autonomic Failure

Abstract

Background Supine hypertension affects a majority of patients with autonomic failure; it is associated with end‐organ damage and can worsen daytime orthostatic hypotension by inducing pressure diuresis and volume loss during the night. Because sympathetic activation prevents blood pressure (BP) from falling in healthy subjects exposed to heat, we hypothesized that passive heat had a BP‐lowering effect in patients with autonomic failure and could be used to treat their supine hypertension. Methods and Results In Protocol 1 (n=22), the acute effects of local heat (40–42°C applied with a heating pad placed over the abdomen for 2 hours) versus sham control were assessed in a randomized crossover fashion. Heat acutely decreased systolic BP by −19±4 mm Hg (versus 3±4 with sham, P <0.001) owing to decreases in stroke volume (−18±5% versus −4±4%, P =0.013 ) and cardiac output (−15±5% versus −2±4%, P =0.013). In Protocol 2 (proof‐of‐concept overnight study; n=12), we compared the effects of local heat (38°C applied with a water‐perfused heating pad placed under the torso from 10 pm to 6 am ) versus placebo pill. Heat decreased nighttime systolic BP (maximal change −28±6 versus −2±6 mm Hg, P <0.001). BP returned to baseline by 8 am . The nocturnal systolic BP decrease correlated with a decrease in urinary volume ( r =0.57, P =0.072) and an improvement in the morning upright systolic BP ( r =−0.76, P =0.007). Conclusions Local heat therapy effectively lowered overnight BP in patients with autonomic failure and supine hypertension and offers a novel approach to treat this condition. Future studies are needed to assess the long‐term safety and efficacy in improving nighttime fluid loss and daytime orthostatic hypotension. Registration URL: https://www.clinicaltrials.gov ; Unique identifiers: NCT02417415 and NCT03042988.

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“…The benefit suggests that excess mineralocorticoid secretion may be a contributing mechanism of nocturnal hypertension [ 92 ]. Nebivolol has been used successfully [ 93 ] as has a low-dose nitroglycerine patch (0.1 mg/h) administered at night and removed in the morning [ 94 ]. Midodrine, a peripherally selective α-1-adrenogic agonist increases vasomotor tone and peripheral vascular resistance and may limit the symptoms of orthostatic hypotension.…”

“…Supine hypertension occurs in many patients with autonomic dysfunction and failure (Okamoto) and can cause symptoms, end-organ injury and worsen day-time orthostatic hypotension from diuresis and volume depletion. Okamoto et al [ 93 ] showed that passive heat (heating pad applied to the abdomen) reduced systemic blood pressure by ~ 20 mmHg (n = 12). In a proof-of-concept study performed in patients with autonomic failure, overnight passive heat (38 °C applied with a water perfused heating pad placed under the back) reduced systolic blood pressure by 28 ± 6 mmHg.…”

Management of Patients With Hypertension and Orthostatic Hypotension. Parallel Progress

“…13 Recent proof-of-concept trials found that use of constant positive airway pressure (by increasing splanchnic venous capacitance) and local application of heat (by increasing skin capacitance) effectively controlled nighttime hypertension with an effect comparable to antihypertensive medications, and this was associated with reduced nocturia and improved daytime OH. 14 If validated, these approaches may represent alternative strategies to treat supine nocturnal hypertension while simultaneously improving daytime OH.…”

2021 Distinguished Scientists of the American Heart Association

“…8 Conversely, he found that increasing splanchnic venous compliance by increasing intrathoracic pressure with CPAP, 9 and skin capacitance by local heat, are effective in the treatment of nocturnal supine hypertension in these patients. 10…”

“…8 Conversely, he found that increasing splanchnic venous compliance by increasing intrathoracic pressure with CPAP, 9 and skin capacitance by local heat, are effective in the treatment of nocturnal supine hypertension in these patients. 10 He has defined interactions between neural (autonomic), metabolic (insulin), and hormonal (nitric oxide) factors contributing to the pathophysiology of hypertension and autonomic disorders. By eliminating the homeostatic counter effects of autonomic baroreflexes he found that endogenous nitric oxide normally restrains blood pressure by 30 mm Hg.…”