Overnight Trials With Heat Stress in Autonomic Failure Patients With 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.

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.