Local Passive Heat for the Treatment of Hypertension in Autonomic Failure

Author:

Okamoto Luis E.123ORCID,Celedonio Jorge E.123,Smith Emily C.123ORCID,Gamboa Alfredo123ORCID,Shibao Cyndya A.123ORCID,Diedrich André1234,Paranjape Sachin Y.123,Black Bonnie K.123,Muldowney James A. S.1253,Peltier Amanda C.126,Habermann Ralf1273,Crandall Craig G.8ORCID,Biaggioni Italo1239

Affiliation:

1. Vanderbilt Autonomic Dysfunction Center Vanderbilt University Medical Center Nashville TN

2. Division of Clinical Pharmacology Vanderbilt University Medical Center Nashville TN

3. Department of Medicine Vanderbilt University Medical Center Nashville TN

4. Department of Biomedical Engineering Vanderbilt University Medical Center Nashville TN

5. Division of Cardiology Vanderbilt University Medical Center Nashville TN

6. Department of Neurology Vanderbilt University Medical Center Nashville TN

7. Division of Geriatrics Vanderbilt University Medical Center Nashville TN

8. Institute for Exercise and Environmental Medicine Texas Health Presbyterian Hospital and UT Southwestern Medical Center Dallas TX

9. Department of Pharmacology Vanderbilt University Medical Center Nashville TN

Abstract

BackgroundSupine 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 ResultsIn 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 pmto 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).ConclusionsLocal 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.RegistrationURL:https://www.clinicaltrials.gov; Unique identifiers: NCT02417415 and NCT03042988.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Cardiology and Cardiovascular Medicine

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