Non-invasive prediction of pulmonary vascular disease-related exercise intolerance and survival in non-group 1 pulmonary hypertension

Yogesh N V Reddy; Hilary Dubrock; Paul M Hassoun; Anna Hemnes; Evelyn Horn; Jane A Leopold; Franz Rischard; Erika B Rosenzweig; Nicholas S Hill; Serpil C Erzurum; Gerald J Beck; Stephen C Mathai; Monica Mukherjee; W H Wilson Tang; Barry A Borlaug; Robert P Frantz; and the PVDOMICS Study Group

doi:10.1002/ejhf.3396

Non-invasive prediction of pulmonary vascular disease-related exercise intolerance and survival in non-group 1 pulmonary hypertension

Eur J Heart Fail. 2024 Jul 26. doi: 10.1002/ejhf.3396. Online ahead of print.

Authors

Yogesh N V Reddy¹, Hilary Dubrock¹, Paul M Hassoun², Anna Hemnes³, Evelyn Horn⁴, Jane A Leopold⁵, Franz Rischard⁶, Erika B Rosenzweig⁷, Nicholas S Hill⁸, Serpil C Erzurum⁹, Gerald J Beck¹⁰, Stephen C Mathai², Monica Mukherjee¹¹, W H Wilson Tang¹², Barry A Borlaug¹, Robert P Frantz¹; and the PVDOMICS Study Group

Affiliations

¹ Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN, USA.
² Division of Pulmonary and Critical Care Medicine, Johns Hopkins University, Baltimore, MD, USA.
³ Division of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
⁴ Perkin Heart Failure Center, Division of Cardiology, Weill Cornell Medicine, New York, NY, USA.
⁵ Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
⁶ Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, University of Arizona, Tucson, AZ, USA.
⁷ Department of Pediatrics and Medicine, Columbia University, New York, NY, USA.
⁸ Division of Pulmonary, Critical Care, and Sleep Medicine, Tufts Medical Center, Boston, MA, USA.
⁹ Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
¹⁰ Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH, USA.
¹¹ Division of Cardiovascular Medicine, Johns Hopkins University, Baltimore, MD, USA.
¹² Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, OH, USA.

PMID: 39058211
DOI: 10.1002/ejhf.3396

Abstract

Aims: The clinical utility of pulmonary hypertension (PH) risk scores in non-group 1 PH with pulmonary vascular disease (PVD) remains unresolved.

Methods and results: We utilized the prospective multicenter PVDOMICS cohort with group 2, 3, 4 or 5 PH-related PVD and calculated group 1 PH risk scores (REVEAL 2.0, REVEAL Lite 2, French registry score and COMPERA 2). The c-statistic to predict death was compared separately in (i) pre-capillary PH groups 3/4/5, and (ii) combined post- and pre-capillary PH group 2. Exercise right heart catheterization reserve, ventricular interdependence and right ventricular-pulmonary artery (RV-PA) coupling were compared across risk categories. Among 449 individuals with group 3/4/5 PH, the REVEAL 2.0 risk score had the highest c-statistic for predicting death (0.699, 95% confidence interval [CI] 0.660-0.737, p < 0.0001) with comparable performance using the simpler REVEAL Lite 2 score (0.695, 95% CI 0.656-0.734, p < 0.0001). The French and COMPERA 2 risk scores were also predictive of mortality, but performance of both was statistically inferior to REVEAL 2.0 (c-statistic difference -0.072, 95% CI -0.123 to -0.020, p = 0.006, and -0.043, 95% CI -0.067 to -0.018, p = 0.0007, respectively). RV function and RV-PA coupling measures were prognostic in isolation, but did not add incremental value to REVEAL (p > 0.50 for all). Findings were similar in patients with group 2 PH (n = 239). Stratification by the REVEAL Lite 2 score non-invasively identified non-group 1 PH with more advanced PVD with worse exercise capacity, RV-PA uncoupling, ventricular interdependence and impaired cardiac output reserve (p < 0.05 for all).

Conclusions: Non-invasive REVEAL risk predicts mortality in non-group 1 PH without incremental prognostic value from detailed RV function or RV-PA coupling assessment. Baseline REVEAL Lite 2 risk stratification non-invasively identifies greater pulmonary vascular dysfunction and right heart-related exercise limitation, which may help guide patient selection for targeted pulmonary vascular therapies in non-group 1 PH.

Keywords: Exercise haemodynamics; Pulmonary hypertension; REVEAL; Risk scores.

Grants and funding

K23HL164901/NHLBI Division of Intramural Research