Local Heat Stress in Autonomic Failure Patients With Supine Hypertension

Patients with autonomic failure are characterized by disabling orthostatic hypotension (low blood pressure on standing), and at least half of them also have high blood pressure while lying down (supine hypertension). Exposure to heat, such as in hot environments, often worsens their orthostatic hypotension. The causes of this are not fully understood. The purpose of this study is to evaluate whether applying local heat over the abdomen of patients with autonomic failure and supine hypertension would decrease their high blood pressure while lying down. This will help us better understand the mechanisms underlying this phenomenon, and may be of use in the treatment of supine hypertension.

Primary autonomic failure is a neurodegenerative condition characterized by severe impairment of the autonomic nervous system. The clinical hallmark of autonomic failure is disabling orthostatic hypotension, but at least half of patients are also hypertensive while lying down. This supine hypertension can be severe and associated with end-organ damage and worsening of orthostatic hypotension due to increased pressure natriuresis. It also complicates the management of these patients by limiting the use of daytime pressor agents for the treatment of orthostatic hypotension. It is well known that heat exposure (e.g. hot weather or a hot bath or shower) produces an acute and temporary worsening of orthostatic hypotension in autonomic failure patients. However, the mechanisms underlying this phenomenon are completely unexplored. Factors that may predispose autonomic failure patients to the acute lowering blood pressure effects of heat stress include 1) impaired heat dissipation due to inability to sweat, 2) preserved heat-mediated skin vasodilation, and 3) blunted sympathetic hemodynamic responses to maintain blood pressure. In this study, we test the hypothesis that moderate levels of local (abdominal) passive heat stress will lower blood pressure in autonomic failure patients with supine hypertension. To test this hypothesis, we propose this pilot study with the following specific aims: To evaluate the acute blood pressure effects of local passive heat stress in autonomic failure patients with supine hypertension, we will compare changes in BP between controlled local heat stress (~44ºC) using a commercial heating pad that covers the abdomen and part of the torso, and a control (non-heating) study day using the same heating pad but turned off. To evaluate the mechanisms underlying BP changes during local heat stress, we will compare changes in hemodynamic parameters (cardiac output, stroke volume and peripheral vascular resistance), segmental fluid shifts (measured by segmental bioimpedance), skin blood flow and skin temperature between the heat and non-heating study days.

Passive heat stress will be applied with a commercial heating pad that covers all the abdomen and part of the torso to provide local heating at ~44ºC continuously for 2 hr.

Percent Change in Hemodynamic Parameters (Cardiac Output, Stroke Volume and Systemic Vascular Resistance)

Percent change from baseline ([post-intervention - baseline]/baseline X 100) in cardiac output, stroke volume and systemic vascular resistance at 2 hours post-intervention

Inclusion Criteria: Male and female patients, between 18-80 yrs., with primary autonomic failure (Parkinson Disease, Multiple System Atrophy, and Pure Autonomic Failure) and supine hypertension. Supine hypertension will be defined as SBP≥150 mmHg. Patients able and willing to provide informed consent. Exclusion Criteria: Pregnancy Significant cardiac, renal or hepatic illness, or with contraindications to administration of pressor agents or with other factors, which in the investigator's opinion would prevent the subject from completing the protocol including clinically significant abnormalities in clinical, mental or laboratory testing.

Okamoto LE, Celedonio JE, Smith EC, Gamboa A, Shibao CA, Diedrich A, Paranjape SY, Black BK, Muldowney JAS 3rd, Peltier AC, Habermann R, Crandall CG, Biaggioni I. Local Passive Heat for the Treatment of Hypertension in Autonomic Failure. J Am Heart Assoc. 2021 Apr 6;10(7):e018979. doi: 10.1161/JAHA.120.018979. Epub 2021 Mar 19.