Hemodynamics Response to Upper Airway Obstruction in Marfan Syndrome

Johns Hopkins University31 enrolled

Overview

Upper airway obstruction (UAO) is an unrecognized source of hemodynamic stress that may contribute to aortic adverse events in persons with Marfan Syndrome (MFS). UAO occurs during snoring and sleep apnea and is characterized by repetitive partial or complete obstruction of the upper airway during sleep. These obstructive breathing events lead to intermittent surges in blood pressure (BP) REF and large decreases in pleural pressure (Pes), thereby increasing the trans-mural aortic pressure (TMP) and imposing mechanical stress on the aorta during sleep. Although UAO is known to increase mechanical stress on the aorta, the magnitude of the increase is not known for persons with MFS. In this project, therefore, the investigators will also examine the changes in Pes and BP responses in periods of obstructed breathing and compare the diurnal markers or vascular stress between Baseline and CPAP studies in MFS persons.

Research Objective/Significance: Specific Aim 1a: To quantify the Pes and BP during periods with and without UAO during sleep in persons with MFS. Specific Aim 1b: To examine the effect of CPAP treatment of UAO on Pes and BP in MFS persons. Specific Aim 2: To examine the effect of CPAP treatment of UAO on daytime markers of hemodynamic stress (augmentation index, reactive hyperemia index) in MFS persons. Primary Outcomes: * Overnight measure of hemodynamic stress (blood pressure, pleural pressure swings) Secondary Outcomes: * Changes in diurnal markers of hemodynamic stress (augmentation index, reactive hyperemia index)

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Eligibility

Sex: ALLMin age: 18 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: People with Marfan syndrome. * Age ≥ 18yrs * Able and willing to provide informed consent * Willing to sleep connected to research apparatus Exclusion Criteria: * Unstable cardiovascular disease (CHF, myocardial infarction or revascularization procedures, and unstable arrhythmias) * Uncontrolled hypertension (BP \> 190/110) * Underlying obstructive or other intrinsic lung disease * Renal failure on dialysis * Cirrhosis * Pregnancy

Outcomes

Primary Outcomes

Pleural Pressure (Pes)

Pleural pressure (Pes) in mmHg monitored using an esophageal catheter.

Time frame: Overnight on both CPAP and No CPAP nights

Mean Arterial Blood Pressure (MAP)

Continuous blood pressure monitored using a non-invasive finger cuff. Data captured in mmHg.

Time frame: Overnight on both Baseline and CPAP studies

Secondary Outcomes

Augmentation Index (AI)

The AI (measured as "percentage of pulse pressure") was assessed in the morning after both Baseline and CPAP studies. It is a measure of arterial stiffness that represents the degree of and can range from -10% to +10% in healthy individuals, with values generally higher in females and increases with age.

Time frame: 15 minutes in the morning post Baseline and CPAP studies

Reactive Hyperemia Index (RHI)

The RHI is a measure of endothelial function that was measured in the morning after both Baseline and CPAP studies. It is unitless and scored on a range of 1 to 3 in healthy individuals with lower values indicating poor endothelial function.

Time frame: 15 minutes