overnight trials with heat stress in autonomic failure patients with supine hypertension

Conditions: Hypertension; Pure Autonomic Failure; Multiple System Atrophy; Autonomic Failure

Summary: 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 during the night would decrease their nocturnal 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 loss of efferent sympathetic function and severe baroreflex impairment. 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. currently, no antihypertensive drug effectively lowers bp and prevents pressure natriuresis without worsening standing bp. 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. factors that may predispose these patients to the lowering bp 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 bp (increases in cardiac output, heart rate, and vaso- and venoconstriction). our preliminary results showed that 2 hours of passive heat stress lowers bp in these patients through a decrease in central volume. in this study, we will assess the efficacy and safety of passive heat stress in the treatment of nocturnal supine hypertension in autonomic failure patients. our hypothesis is that controlled local (abdominal) passive heat stress applied during the night will lower nocturnal bp in autonomic failure patients with supine hypertension. to test this hypothesis, we propose to compare the bp effects of passive heat applied during the night vs. a sham control in a randomized crossover study in autonomic failure patients with supine hypertension.

Eligibility criteria:
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.

Keywords: supine hypertension autonomic failure heat stress orthostatic hypotension