Exercise Right Atrial Stiffness From Pressure-Volume Loops and Prognosis in Pulmonary Hypertension
BACKGROUND: In pulmonary hypertension (PH), risk assessment focuses on right ventricular function and may overlook exercise-related right atrial (RA) functional limitation. We investigated whether RA stiffness during exercise reflects impaired right-heart filling reserve and is associated with prognosis beyond conventional measures. METHODS: We prospectively enrolled 68 participants in this observational study, including 42 with precapillary PH. Participants who had PH ruled out and patients with postcapillary PH formed reference groups. Participants underwent 3-dimensional echocardiography, right heart catheterization, and invasive RA pressure-volume loop analysis at rest and during standardized semisupine exercise. RA filling stiffness was derived from the reservoir phase. Patients with precapillary PH were stratified by median exercise RA filling stiffness. RESULTS: At rest, high- and low-stiffness groups had comparable right ventricular function, afterload, and cardiac index, but the high-stiffness group exhibited impaired phasic RA strain and venous congestion (median [interquartile range] liver stiffness, 7.1 [6.0–8.8] versus 5.2 [4.8–5.8] kPa; P =0.021). During exercise, mean RA pressure increased similarly, but the high-stiffness group had impaired peak cardiac index (3.3±1.0 versus 4.1±0.9 L/min per m 2 ; P =0.015) and RA strain. Unlike resting RA stiffness, high exercise RA stiffness was independently associated with mortality (adjusted hazard ratio, 4.37 [95% CI, 1.20–15.96]). A model including RA conduit strain and right ventricular functional reserve discriminated high RA stiffness (area under the receiver operating characteristic curve, 0.90). CONCLUSIONS: RA stiffness during exercise integrates resting congestion with limited cardiac reserve and unmasks mortality risk missed by resting metrics. RA conduit strain and right ventricular functional reserve noninvasively identify the high-stiffness subgroup.
Authors
- Rahi S. Alipour Symakani (ORCID: https://orcid.org/0000-0002-6830-9560)
- Philipp Douschan (ORCID: https://orcid.org/0000-0003-2505-7831)
- Werner Seeger (ORCID: https://orcid.org/0000-0003-1946-0894)
- Barry A. Borlaug (ORCID: https://orcid.org/0000-0001-9375-0596)
- Daphne Merkus (ORCID: https://orcid.org/0000-0002-4852-831X)
- Zvonimir Andelko Rako (ORCID: https://orcid.org/0000-0003-0539-0362)
- Horst Olschewski (ORCID: https://orcid.org/0000-0002-2834-7466)
- Nils Kremer (ORCID: https://orcid.org/0000-0002-5615-0214)
- Khodr Tello (ORCID: https://orcid.org/0000-0002-5557-623X)
- Athiththan Yogeswaran (ORCID: https://orcid.org/0000-0001-9505-8608)
- Hossein Ardeschir Ghofrani (ORCID: https://orcid.org/0000-0002-2029-4419)
- Patrick Janetzko (ORCID: https://orcid.org/0009-0002-1241-1627)
- Bruno R. Thal (ORCID: https://orcid.org/0009-0001-3625-2416)
- Linus Bußmann (ORCID: https://orcid.org/0009-0006-1068-6386)
Institutions
- Sigmund Freud Privatuniversität Wien (AT)
- Mayo Clinic (US)
- Justus-Liebig-Universität Gießen (DE)
- Medical University of Graz (AT)
- Catharina Ziekenhuis (NL)
- Erasmus MC (NL)
- Ludwig Boltzmann Institute for Lung Vascular Research (AT)
- German Center for Lung Research (DE)
- Universities of Giessen and Marburg Lung Center (DE)
- Kerckhoff Klinik (DE)
- Institut für Chirurgische Forschung (DE)
- Imperial College London (GB)
- Charité - Universitätsmedizin Berlin (DE)
- Ludwig-Maximilians-Universität München (DE)
Publication Details
- Journal
- Circulation Heart Failure
- Published
- 2026-11-02
- DOI
- https://doi.org/10.1161/circheartfailure.126.014761
- Primary Topic
- Pulmonary Hypertension Research and Treatments
- Type
- article
- Field-Weighted Citation Impact
- 0.00