Hemodynamics Response to Upper Airway Obstruction in Marfan Syndrome

Not Applicable

Completed

Brief Summary: 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.

Detailed Description: 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)

Recruitment & Eligibility

Inclusion Criteria

People with Marfan syndrome.

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

Arm && Interventions

Group	Intervention	Description
Baseline Sleep Study	CPAP	Baseline sleep polysomnography will involve the collection of electroencephalogram, electromyogram, electrocardiogram, airflow, heart rate, blood pressure, and pleural pressure during sleep with no CPAP. Participants in this arm would switch to CPAP within one week of the study.
CPAP Sleep Study	CPAP	Participants will be treated with continuous positive airway pressure to relieve sleep-disordered breathing. Participants in this arm would switch to Baseline study within one week of the study.

Primary Outcome Measures

Name	Time	Method
Pleural Pressure (Pes)	Overnight on both CPAP and No CPAP nights	Pleural pressure (Pes) in mmHg monitored using an esophageal catheter.
Mean Arterial Blood Pressure (MAP)	Overnight on both Baseline and CPAP studies	Continuous blood pressure monitored using a non-invasive finger cuff. Data captured in mmHg.

Secondary Outcome Measures

Name	Time	Method
Augmentation Index (AI)	15 minutes in the morning post Baseline and CPAP studies	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.
Reactive Hyperemia Index (RHI)	15 minutes	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.