Sleep-disordered Breathing in Eisenmenger Syndrome

Sleep-disordered breathing (SDB) is a wellknown comorbidity in cardiovascular disease. Knowledge about SDB in adult congenital heart disease is limited.

Study Overview

• Status: Completed
• Conditions: Congenital Heart Disease; Sleep-disordered Breathing; Eisenmenger Syndrome
• Intervention / Treatment: Other: Polysomnography

Detailed Description

Congenital heart defects (CHD) occur in approximately 1% of all live births. Around 5% of adults with CHD develop pulmonary arterial hypertension (PAH), with 25-50% of these patients exhibiting the most serious form, Eisenmenger syndrome. Eisenmenger syndrome is caused by a systemic-to-pulmonary shunt, which eventually leads to high pulmonary vascular resistance with right-to-left or bi-directional shunt. Right-to-left shunting reduces the systemic arterial oxygen capacity and consequently causes cyanosis, which may result in hypoxic tissue damage and multi-organ disease.

The natural history of Eisenmenger syndrome (ES) is generally poor compared to the general population with the latest reported actual survival rates of 94%, 74% and 52% at 40, 50 and 60 years of age, respectively. Until recently conventional symptomatic treatment with diuretics, digitalis, antiarrhythmic, anticoagulants, iron supplement, oxygen therapy, and ultimately heart-lung transplantation were the only options. Most patients die from progressive cardiovascular disease and heart failure, sudden heart death or haemoptysis.

However, the introduction of advanced therapy (AT) has improved symptoms and may also have changed to prognosis of these patients. Thus, newer studies have shown beneficial effect of treatment with advanced therapy including endothelin receptor antagonists, phosphodiesterase-5 inhibitors, and prostanoids. These pulmonary vasodilators are now recognized as targeted therapy in Eisenmenger syndrome.

Sleep-disordered breathing (SDB) with predominantly obstructive or central sleep apnoea (OSA/CSA) with Cheyne-Stokes respiration (CSR) is shown to be a common comorbidity in patients with heart failure (HF), as it is present in at least 50 % of these patients. In the general Danish population the estimated prevalence is 3-18% in men and 5-7% in women.

Studies in HF patients also suggest an increased rate of central sleep apnoea (CSA) versus obstructive sleep apnoea (OSA) compared to the general population. SDB may promote the progression of chronic heart failure (HF) and is independently associated with a decreased survival rate.

The standard treatment for patients with OSA is nocturnal continuous positive airway pressure (CPAP) usually delivered with a tight fitting nasal mask. The benefits of CPAP are well established in this group of patients, as opposed to CSA-patients. The largest randomized study demonstrated no effect of nocturnal CPAP in patients with HF and CSA on heart transplant-free survival, but improvements in apnoea frequency, blood oxygenation and left ventricle function. While CPAP and other assisted breathing devices may be used in SDB related to HF, this have no place in the treatment of patients with ES, as any rise in the intra-thoracic pressure and consequently increased PVR and right-to-left shunting will worsen the cyanosis.

The treatment of CSA in HF remains controversial; however aggressive optimization of the medical treatment in congestive heart failure seems to improve the condition.

In these patients, the effect of CPAP, nocturnal oxygen and drugs stimulating the central respiratory drive are less well documented or related to adverse events such as increased risk of arrhythmias.

Though the relationship between HF and SDB is well established, the prevalence and influence of SDB in Eisenmenger syndrome has not previously been examined.

There are many similarities between ES and HF, but several important differences are also present. In congestive heart failure the ventricular insufficiency is related to an increased left side filling pressure followed by pulmonary stasis or oedema, whereas ES patients often have a normal filling pressure and normal systemic vascular resistance, but high pulmonary vascular resistance (PVR) and cyanosis due to the right-left shunt.

The aims of this study are to examine a group of Eisenmenger Syndrome patients to establish the prevalence of SDB in this patient group, to examine the mechanism (CSA or OSA) behind SDB in Eisenmenger syndrome, and to relate the presence of SDB to a higher level of secondary erythrocytosis.

If a role of SDB in ES is demonstrated, further studies will be necessary to demonstrate whether SDB in Eisenmenger syndrome can be altered by advanced therapy.

Hypotheses

• The prevalence of SDB in Eisenmenger syndrome is higher than in the general population.
• SDB in Eisenmenger syndrome is caused by a central rather than obstructive mechanism.
• SDB in Eisenmenger syndrome is related to a more pronounced secondary erythrocytosis than explained by a daytime measurement of oxygen saturation.

• Study Type: Observational
• Enrollment (Actual): 20

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Patients with Eisenmenger syndrome

Description

Inclusion Criteria:

• Eisenmenger Syndrome (definition: Pulmonary ≥ systemic vascular resistance with pulmonary-to-systemic shunt and cyanosis (periphery oxygen saturation < 92% at rest and/or < 87% during exercise).
• Stable for ≥ 3 months (no hospitalization, no change of medication, no deterioration).

Exclusion Criteria:

• Down's syndrome.
• Iron deficiency (definition: Ferritin < 12 µg/l and/or transferring saturation < 20%).
• Regular phlebotomy.
• Suspicion of risk of non-compliance.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Polysomnography; Patients undergo an one-night in-hospital polysomnography to diagnose sleep-disordered breathing

Other: Polysomnography; One night polysomnography performed using standard techniques and scored in accordance with American Academy of Sleep Medicine standards. Polysomnography monitors sleep by electroencephalography (F4-A1, C4-M1, O2-M1 F3-M2, C3-M2, O1-A2), electro-myography (submental and tibialis anterior muscles), electro-oculography, nasal flow, respiratory effort, pulse oximetry and transcutaneous carbon dioxide partial pressure.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Apnoea-hypopnoea index	Prevalence of sleep-disordered breathing during 1 night polysomnography measured by apnoea-hypopnoea index.	1 night on Day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sleep stages	Characterize the sleep architecture during 1 night polysomnography by evaluating the time spend in various sleep stages (N1, N2, N3, REM, measured by EEG)	1 night on Day 1

Collaborators and Investigators

• Sponsor: Rigshospitalet, Denmark

Study record dates

Study Major Dates

• Study Start: June 1, 2013
• Primary Completion (Actual): August 1, 2015
• Study Completion (Actual): September 1, 2015

Study Registration Dates

• First Submitted: September 28, 2015
• First Submitted That Met QC Criteria: November 23, 2015
• First Posted (Estimate): November 25, 2015

Study Record Updates

• Last Update Posted (Estimate): November 25, 2015
• Last Update Submitted That Met QC Criteria: November 23, 2015
• Last Verified: November 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Nervous System Diseases; Respiratory Tract Diseases; Apnea; Respiration Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Disease; Congenital Abnormalities; Cardiovascular Abnormalities; Heart Diseases; Sleep Apnea Syndromes; Syndrome; Respiratory Aspiration; Heart Defects, Congenital; Eisenmenger Complex
• Other Study ID Numbers: 2012-01 (AP HM)