Evolution of Hypoxic Burden and Sympathetic/Parasympathetic Balance in Patients With Pulmonary Hypertension

NCT07464184 | Not Yet Recruiting

• 2 other identifiers: 2023/0292/HP2025-A00017-42
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Background and Rationale: Sleep-disordered breathing and nocturnal hypoxemia are highly prevalent in patients with precapillary pulmonary hypertension (PH), and current guidelines recommend systematic sleep assessment in this population. In obstructive sleep apnea, nocturnal hypoxic burden-defined as the area under the SpO₂ desaturation curve associated with respiratory events (%.min/h)-has demonstrated strong prognostic value for cardiovascular morbidity and mortality. However, its role in precapillary PH has not yet been investigated. Evaluating hypoxic burden in this population may refine indications and therapeutic targets for nocturnal oxygen therapy. In addition, pulmonary hypertension is characterized by autonomic nervous system (ANS) dysfunction, including increased sympathetic tone, reduced heart rate variability (HRV), and a higher incidence of cardiac arrhythmias, all associated with worse prognosis. The reduction in HRV is particularly deleterious when occurring during restorative slow-wave sleep (N3), a phase marked by predominant parasympathetic activity essential for cardiovascular recovery and homeostasis. A better understanding of the interaction between nocturnal hypoxemia and ANS modulation may provide new prognostic markers and potential therapeutic targets in PH. Objectives:

• Baseline (inclusion)
• 12 months (M12)
• 24 months (M24) For incident cases, baseline PSG will be performed prior to initiation of vasodilator therapy. All patients will continue to receive standard-of-care management according to current European guidelines for pulmonary hypertension. Descriptive analyses and cross-sectional correlations will pool repeated measures (excluding incident baseline values for generalization to prevalent cases). Intra-subject correlation will be accounted for using bootstrap methods. Longitudinal analyses will assess changes over time and prognostic associations. The prognostic value of HRV and hypoxic burden will be evaluated over a 2-year follow-up period. This study explores an original dimension of precapillary pulmonary hypertension pathophysiology by investigating the interaction between nocturnal oxygenation, autonomic dysfunction, and clinical evolution. Identification of hypoxic burden and HRV as prognostic markers may contribute to improved risk astratification and therapeutic optimization in this high-risk population.

Conditions

Precapillary Pulmonary Hypertension; Pulmonary Arterial Hypertension; Sleep-disordered Breathing; Nocturnal Hypoxemia; Autonomic Nervous System Dysfunction; Heart Rate Variability (HRV); Cardiovascular Risk

Keywords

Precapillary pulmonary hypertension; Pulmonary arterial hypertension; Hypoxic burden; Nocturnal hypoxia; Polysomnography; Sleep-disordered breathing; Heart rate variability (HRV); RMSSD; LF/HF ratio; High frequency; Autonomic nervous system; Sympathetic activation; Parasympathetic tone; Risk stratification; Prognostic markers; Right heart failure; Apnea-Hypopnea Index (AHI)

Outcome Measures

Primary Outcomes (1)

• Hypoxic Load

  Assessed by the area under the SpO2 curve during desaturations associated with respiratory events divided by sleep time expressed as % min/h during polysomnographies

  Baseline, after 12 months and after 24 months

Secondary Outcomes (18)

• Root mean square of successive differences (RMSSD)

  Baseline, after 12 months and after 24 months

• Low frequency / high frequency (LF/HF)

  Baseline, after 12 months and after 24 months

• High frequency (HF)

  Baseline, after 12 months and after 24 months

• Cross-sectional correlation - HRV RMSSD

  Baseline, after 12 months and after 24 months

• Cross-sectional correlation - HRV LF/HF

  Baseline, after 12 months and after 24 months

Study Arms (1)

Precapillary Pulmonary Hypertension Cohort

EXPERIMENTAL

Participants are hospitalized for 5 days (4 nights) at baseline, Month 12 (M12), and Month 24 (M24) in the pulmonology department for routine clinical reassessment. During each hospitalization, patients undergo standard-of-care clinical evaluation including physical examination, NYHA functional class assessment, NT-proBNP measurement, arterial blood gas analysis, 6-minute walk test, transthoracic echocardiography, and pulmonary function testing. At baseline (incident cases only), additional diagnostic procedures may include thoracic CT scan, ventilation/perfusion lung scintigraphy, and right heart catheterization. An overnight polysomnography (PSG) is performed during each hospitalization (baseline, M12, M24). Heart rate variability (HRV) parameters and nocturnal hypoxic burden are derived from PSG recordings. No experimental therapeutic intervention is assigned. All patients receive guideline-based management according to current European recommendations for pulmonary hypertension

Other: Standard Clinical and Functional Assessment; Other: Overnight Polysomnography

Interventions

Standard Clinical and Functional Assessment OTHER

Routine evaluation of pulmonary hypertension during scheduled hospitalizations at baseline, Month 12, and Month 24, including: * Physical examination and NYHA functional class assessment * NT-proBNP measurement * Arterial blood gases * 6-minute walk test * Transthoracic echocardiography * Pulmonary function testing For incident cases at diagnostic evaluation only: thoracic CT scan, ventilation/perfusion lung scintigraphy, and right heart catheterization. All procedures are performed as part of standard clinical care.

Precapillary Pulmonary Hypertension Cohort

Overnight Polysomnography OTHER

Standard overnight in-hospital polysomnography performed at baseline, Month 12, and Month 24. The recording includes electrocardiogram (ECG), oxygen saturation (SpO₂), respiratory parameters, and sleep staging. Heart rate variability (HRV) is assessed using RMSSD, LF/HF ratio, and HF power derived from ECG during a continuous ≥30-minute NREM sleep period. Nocturnal hypoxic burden is calculated as the area under the SpO₂ desaturation curve associated with respiratory events divided by total sleep time (%.min/h).

Precapillary Pulmonary Hypertension Cohort

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients over 18 years of age
• With precapillary pulmonary hypertension confirmed by pulmonary artery catheterization
• With an indication for pulmonary artery vasodilator treatment
• Affiliation with a social security system
• Individuals who have read and understood the information letter and signed the consent form
• Treatment with non-invasive ventilation
• Eisenmenger syndrome
• Systemic scleroderma
• Neurodegenerative disease other than isolated peripheral neuropathies.
• Untreated and/or uncontrolled cardiac rhythm or conduction disorders, including permanent AF
• Untreated coronary artery disease or diagnosis of myocardial infarction within the last six months
• Pacemaker wearer
• Pregnant or breastfeeding women, or women who are not using reliable contraception
• Persons deprived of their liberty by administrative or judicial decision or persons under judicial protection/guardianship or curatorship
• History of psychological or sensory illness or abnormality that may prevent the subject from fully understanding the conditions required for participation in the protocol or prevent them from giving their informed consent

Sponsors & Collaborators

• University Hospital, Rouen: lead

Study Sites (1)

Chu Rouen

Rouen, 76031, France

Location

MeSH Terms

Conditions

Pulmonary Arterial Hypertension; Sleep Apnea Syndromes; Heart Failure

Condition Hierarchy (Ancestors)

Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases; Apnea; Respiration Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases; Heart Diseases; Cardiovascular Diseases

Central Study Contacts

DRCI

CONTACT

02 32 88 56 07; secretariat.DRC@chu-rouen.fr

Marie-Anne Melone, Dr

CONTACT

Marieanne.Melone@chu-rouen.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Prospective, single-center, longitudinal cohort study of adult patients with precapillary pulmonary hypertension confirmed by right heart catheterization. Participants undergo standardized overnight polysomnography (PSG) at baseline, 12 months, and 24 months as part of routine clinical follow-up. The study evaluates longitudinal changes in nocturnal hypoxic burden and heart rate variability parameters and their cross-sectional and longitudinal correlations with clinical status and 2-year prognosis. No experimental intervention is assigned. All patients receive standard-of-care management according to current European guidelines for pulmonary hypertension.

Study Record Dates

• First Submitted: February 27, 2026
• First Posted: March 11, 2026
• Study Start: June 1, 2026
• Primary Completion (Estimated): January 1, 2030
• Study Completion (Estimated): January 1, 2030
• Last Updated: April 15, 2026

Record last verified: 2026-04

Locations

FR (1)