PVDOMICS

WHO WE ARE

The Redefining Pulmonary Hypertension through Pulmonary Vascular Disease Phenomics (PVDOMICS) program is a network of seven clinical sites and a data coordinating center—funded by the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health (NIH) with additional support from the Pulmonary Hypertension Association (PHA) — that will perform comprehensive, deep phenotyping across the current World Health Organization (WHO)-classified pulmonary hypertension (PH) Groups 1 through 5. By collecting information from 1,000 participants with various types of PH, and 500 participants without or at risk for PH, PVDOMICS hopes to deconstruct the traditional classification and define new groups, or “sub-classifications,” of patients with PH.

The long-term goal is to use in-depth clinical information as well as genomic, proteomic, metabolomics, coagulomic and cellular information for earlier diagnosis, more targeted at-risk screening and personalized approaches for interventions and/or prevention of pulmonary vascular disease.

GOALS OF PVDOMICS

The overall goal of PVDOMICS is to use deep phenotyping to identify the molecular basis of pulmonary vascular disease to inform the current WHO Groups, by comparing subsets of PH patients with healthy subjects and patients with heart and lung diseases who are at risk for PH. The second goal is to discover biological markers of disease risk or progression and response to therapy that may be useful not only in the diagnosis, but also as outcome measures in treatment and possibly prevention trials.

Specifically, PVDOMICS seeks to:

1. Create an advanced description of structural and functional abnormalities of the heart and pulmonary circulation in patients with pulmonary vascular disease (PVD) to define novel phenotypic clusters of PVD.
   1. Compare and contrast imaging assessment using echocardiography, computed tomography (CT) and magnetic resonance imaging (MRI) with clinical, hemodynamic and gas exchange data;
   2. Compare and contrast exercise assessment with baseline hemodynamics, hemodynamics after provocative testing, cardiac and pulmonary imaging, and PH etiology
2. Create a detailed molecular endotype of all PVD patients—including genomic, transcriptomic, proteomic, metabolomics, cell biomic and coagulomic metrics.
   1. Test for known PH mutations, new genetic variants and genomic correlations with all PVD and PH Group designations, including acute vasodilator responders and appropriate controls;
   2. Compare and contrast transcriptomic, proteomic, metabolomic, cell biomic and coagulomic data in all categories of demographic features, known etiology (such as genetic) exercise physiology, pharmaceutical management and outcomes (where feasible);
   3. Compare all omics data without regard to WHO Group to generate a new, more robust classification of PVD leading to PH.
3. Cross-validate variants of PH between PVDOMICS genetic data with that of the PAH Biobank (https://www.pahbiobank.org/), funded through the NHLBI (5R24HL105333-03).

Some participants in PVDOMICS will be invited to participate in a longitudinal component of the study. The overall goal of the longitudinal study will be to:

1. Associate and compare OMICS data with clinical sets and OMICS clusters between baseline and follow-up visits, with attention to reproducibility, predictive capacity as biomarkers for diagnosis, disease progression, phenotypic changes, functional capacity, therapeutic response and survival.