Evolution of Hypoxic Burden and Sympathetic/Parasympathetic Balance in Patients With Pulmonary Hypertension
- Sponsor
- University Hospital, Rouen
- Study ID
- NCT07464184
- Status
- Not Yet Recruiting
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Conditions
- Autonomic Nervous System Dysfunction
- Cardiovascular Risk
- Heart Rate Variability (HRV)
- Nocturnal Hypoxemia
- Precapillary Pulmonary Hypertension
- Pulmonary Arterial Hypertension
- Sleep-disordered Breathing
Eligibility Criteria
- Sex
- ALL
- Age
- 18 Years - N/A
- Healthy Volunteers
- Not accepted
Interventions
- Standard Clinical and Functional Assessment — OTHERRoutine 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.
- Overnight Polysomnography — OTHERStandard 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).
Study Details
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: 1. To describe the evolution of nocturnal hypoxic burden over time in patients with precapillary pulmonary hypertension (at baseline, 12 months, and 24 months). 2. To describe the longitudinal evolution of HRV parameters (RMSSD, LF/HF ratio, HF) at baseline, 12 months, and 24 months. 3. To evaluate cross-sectional correlations (at baseline, M12, and M24) between HRV parameters, hypoxic burden, oxygen desaturation, apnea-hypopnea index (AHI), and clinical status. 4. To evaluate longitudinal correlations between changes in HRV parameters, hypoxic burden, desaturation, AHI, and clinical status between baseline and M12, and between baseline and M24. 5. To assess the 2-year prognostic value of HRV parameters and hypoxic burden for adverse clinical outcomes. Study Design and Population: This is a prospective, single-center observational cohort study conducted at the Pulmonary Hypertension Referral Center of Rouen University Hospital. The cohort design allows longitudinal assessment of HRV, hypoxic burden, and clinical status, enabling both cross-sectional and longitudinal correlation analyses, as well as prognostic evaluation. A total of 60 adult patients (≥18 years) with precapillary pulmonary hypertension confirmed by right heart catheterization and requiring pulmonary arterial vasodilator therapy will be included. Participants will undergo full overnight polysomnography (PSG) at: * 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.
Key Dates
- First listed
- Mar 11, 2026
- Start date
- Jun 1, 2026
- Status verified
- Apr 2026
- Primary completion
- Jan 1, 2030
- Completion
- Jan 1, 2030
Study Design
- Enrollment
- 60 participants (estimated)
- Allocation
- NA
- Intervention model
- SINGLE_GROUP
- Primary purpose
- BASIC_SCIENCE
Arms
- Experimental: Precapillary Pulmonary Hypertension CohortParticipants 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
Primary Outcome Measure
Hypoxic Load [ Time Frame: Baseline, after 12 months and after 24 months ]
Central Contacts
- DRCI02 32 88 56 07
- Marie-Anne Melone, Dr
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