Hypertension, Pure Autonomic Failure, Multiple System Atrophy, Autonomic Failure
Conditions
Keywords
Supine hypertension, Autonomic failure, Heat intolerance, Orthostatic hypotension, Heat stress
Brief 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 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.
Detailed description
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: 1. 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. 2. 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.
Interventions
OTHERPassive heat stress
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.
OTHERControl (non-heating)
Heating pad will be applied over the abdomen and part of the torso but it will be turned off.
Sponsors
Vanderbilt University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
SINGLE (Subject)
Masking description
Patients were blinded to the intervention
Intervention model description
randomized, 2-arm crossover study (heat vs. sham)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Systolic Blood Pressure | 2 hours of heat stress or sham | Change from baseline in systolic blood pressure at 2 hr post-intervention |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in Hemodynamic Parameters (Cardiac Output, Stroke Volume and Systemic Vascular Resistance) | 2 hours of heat stress or sham | Percent change from baseline (\[post-intervention - baseline\]/baseline X 100) in cardiac output, stroke volume and systemic vascular resistance at 2 hours post-intervention |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Study Participants Participants who were randomized to receive local passive heat stress and sham control in any order. | 22 |
| Total | 22 |
Baseline characteristics
| Characteristic | All Study Participants |
|---|---|
| Age, Continuous | 73 years STANDARD_DEVIATION 6 |
| BMI | 27 kg/m^2 STANDARD_DEVIATION 4 |
| Diagnosis Multiple System Atrophy | 1 Participants |
| Diagnosis Parkinson Disease + Autonomic Failure | 7 Participants |
| Diagnosis Pure Autonomic Failure | 14 Participants |
| Disease Duration | 7 years STANDARD_DEVIATION 4 |
| Heart rate, supine | 67 bpm STANDARD_DEVIATION 12 |
| Heart rate, upright | 77 bpm STANDARD_DEVIATION 11 |
| Heat intolerance | 15 Participants |
| Medical history of essential hypertension | 10 Participants |
| Plasma norepinephrine, supine | 132 pg/mL STANDARD_DEVIATION 70 |
| Plasma norepinephrine, upright | 199 pg/mL STANDARD_DEVIATION 136 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 21 Participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 16 Participants |
| Systolic BP, supine | 170 mm Hg STANDARD_DEVIATION 23 |
| Systolic BP, upright | 100 mm Hg STANDARD_DEVIATION 33 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 22 | 0 / 22 |
| other Total, other adverse events | 0 / 22 | 0 / 22 |
| serious Total, serious adverse events | 0 / 22 | 0 / 22 |
Outcome results
Primary
Change in Systolic Blood Pressure
Change from baseline in systolic blood pressure at 2 hr post-intervention
Time frame: 2 hours of heat stress or sham
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Local Heat Stress | Change in Systolic Blood Pressure | 19 mm Hg | Standard Error 4 |
| Control (Non-heating) | Change in Systolic Blood Pressure | 3 mm Hg | Standard Error 4 |
Secondary
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
Time frame: 2 hours of heat stress or sham
Population: Systemic hemodynamics were measured in 13 of the 22 participants
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Local Heat Stress | Percent Change in Hemodynamic Parameters (Cardiac Output, Stroke Volume and Systemic Vascular Resistance) | Cardiac Output | -15 percentage change | Standard Error 5 |
| Local Heat Stress | Percent Change in Hemodynamic Parameters (Cardiac Output, Stroke Volume and Systemic Vascular Resistance) | Stroke Volume | -18 percentage change | Standard Error 5 |
| Local Heat Stress | Percent Change in Hemodynamic Parameters (Cardiac Output, Stroke Volume and Systemic Vascular Resistance) | Systemic Vascular Resistance | 9 percentage change | Standard Error 6 |
| Control (Non-heating) | Percent Change in Hemodynamic Parameters (Cardiac Output, Stroke Volume and Systemic Vascular Resistance) | Cardiac Output | -2 percentage change | Standard Error 4 |
| Control (Non-heating) | Percent Change in Hemodynamic Parameters (Cardiac Output, Stroke Volume and Systemic Vascular Resistance) | Stroke Volume | -4 percentage change | Standard Error 4 |
| Control (Non-heating) | Percent Change in Hemodynamic Parameters (Cardiac Output, Stroke Volume and Systemic Vascular Resistance) | Systemic Vascular Resistance | 4 percentage change | Standard Error 5 |