Objectives

The first aim was to identify the molecular basis of pulmonary vascular disease (PVD) regardless of WHO clinical classification, by comparison of current subsets of pulmonary hypertension (PH) patients.

The second aim was to discover biological measures of disease and therapeutic responses that may be useful not only in diagnosis but also as outcome measures in treatment and possibly prevention trials.

Background

Patients with various forms of heart and lung disease exhibit varying degrees of pulmonary hypertension, pulmonary vascular remodeling, and right ventricular dysfunction. The genetic, molecular, and cellular processes driving these phenomena are not well understood. Rapid advances in high throughput omic methodology, combined with powerful bioinformatics and network biology capability, have created the opportunity to conduct studies that broadly search for homologies and differences across the spectrum of disease states associated with pulmonary hypertension, and determinants of the spectrum of right ventricular compensation that accompanies these conditions.

Participants

The PVDOMICS Study was conducted across seven clinical centers throughout the United States, with ongoing annual follow-up for heart and lung transplant status as well as vital status for up to 10 years among the parent study participants. The study included patients over 18 years of age who were referred for right heart catheterization to further evaluate known pulmonary vascular disease (PVD) or to assess risk for PVD due to existing cardiac or pulmonary conditions. Participants needed to be capable of completing the comprehensive diagnostic testing outlined, including catheterization, echocardiography, exercise testing, pulmonary function tests, chest CT, quality of life assessments, ventilation/perfusion scans, and ideally cardiac MRI. Exclusion criteria comprised patients who were dialysis-dependent, too ill to perform the protocol-required tests, or, if female, pregnant or nursing. A total of 1,195 individuals were enrolled in the parent study between November 30, 2016, and October 18, 2019. The cohort consisted of 750 patients with pulmonary hypertension (PH), 347 at-risk individuals serving as comparators, 96 healthy controls, and 2 participants excluded from analyses.

Design

Participants were enrolled at seven clinical centers across the United States. The study recruited patients, at-risk comparators, and healthy controls. Patients presenting for evaluation of pulmonary hypertension (PH), heart failure, lung disease, dyspnea, or exercise intolerance at various PH, heart failure, or advanced lung disease clinics were targeted for inclusion. Following catheterization, patients were categorized into groups to ensure balanced enrollment across the standard WHO PH Groups 1-5 or comparator groups for at-risk populations with similar underlying conditions. Partners, spouses, or accompanying friends of participating patients were invited to serve as healthy controls. Efforts were made to ensure healthy controls representation across race, ethnicity, and age that closely matched the patient populations within each participating clinical center.

Conclusions

PVDOMICS represented a major advance beyond any other previous study in the amount and types of data that were collected from individuals with and without pulmonary hypertension. This study opened new frontiers for discovery and innovation for people with heart, lung, blood and sleep disorders. The data and resources have and will continue to deepen our understanding of pulmonary vascular diseases. The knowledge from this network will drive transformative discoveries that will benefit healthcare and patient outcomes globally for many years to come.

Publications

Hemnes AR, Leopold JA, Beck GJ, et al. and the PVDOMICS Study Group. PVDOMICS: a multi-center study to improve understanding of pulmonary vascular disease though phenomics. Circulation Research. 2017; 121:1136-1139. PMID: 29074534 PMCID: PMC5685561

Hemnes AR, Leopold JA, Radeva MK, et al. and the PVDOMICS Study Group. Clinical characteristics and transplant-free survival across the spectrum of pulmonary vascular disease. Journal of the American College of Cardiology. 2022;80(7), 697-718. PMID: 35953136; PubMed Central PMCID: PMC9897285.

Tang W, Wilcox JD, Jacob MS, Rosenzweig EB, Borlaug BA, Frantz RP, Hassoun PM, Hemnes AR, Hill NS, Horn EM, Singh HS, Systrom DM, Tedford RJ, Vanderpool RR, Waxman AB, Xiao L, Leopold JA, Rischard FP, and the PVDOMICS Study Group. Comprehensive diagnostic evaluation of cardiovascular physiology in patients with pulmonary vascular disease: Insights from the PVDOMICS Program. Circulation Heart Failure. 2020;13(3), March 2020; e006363. PMID: 32088984 PMCID: PMC7046052

Jellis CL, Park MM, Abidov A, Rosenzweig EB, Borlaug BA, Brittain E, Frantz R, Hassoun PM, Horn EM, Jaber W, Jiwon K, Karas M, Kwon D, Leopold J, Maron B, Mathai S, Mehra R, Rischard F, Tang WHW, Vanderpool R, Thomas JD and the PVDOMICS Study Group. Comprehensive echocardiographic evaluation of the right heart in patients with pulmonary vascular diseases: The PVDOMICS experience. European Heart Journal Cardiovascular Imaging. 2022 Jun 21;23(7):958-969. PMID: 34097027 PMCID: PMC9212349

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