Review

. 2021 Apr 27;77(16):2040-2052.

doi: 10.1016/j.jacc.2021.02.056.

NHLBI-CMREF Workshop Report on Pulmonary Vascular Disease Classification: JACC State-of-the-Art Review

William M Oldham¹, Anna R Hemnes², Micheala A Aldred³, John Barnard⁴, Evan L Brittain², Stephen Y Chan⁵, Feixiong Cheng⁴, Michael H Cho⁶, Ankit A Desai³, Joe G N Garcia⁷, Mark W Geraci⁸, Susan D Ghiassian⁹, Kathryn T Hall⁶, Evelyn M Horn¹⁰, Mohit Jain¹¹, Rachel S Kelly⁶, Jane A Leopold⁶, Sara Lindstrom¹², Brian D Modena¹³, William C Nichols¹⁴, Christopher J Rhodes¹⁵, Wei Sun⁵, Andrew J Sweatt¹⁶, Rebecca R Vanderpool⁸, Martin R Wilkins¹⁵, Beth Wilmot¹⁷, Roham T Zamanian¹⁶, Joshua P Fessel¹⁸, Neil R Aggarwal¹⁸, Joseph Loscalzo⁶, Lei Xiao¹⁹

Affiliations

¹ Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA. Electronic address: woldham@bwh.harvard.edu.
² Vanderbilt University Medical Center, Nashville, Tennessee, USA.
³ Indiana University School of Medicine, Indianapolis, Indiana, USA.
⁴ Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA.
⁵ Center for Pulmonary Vascular Biology and Medicine, Pittsburgh Heart, Lung, Blood, and Vascular Medicine Institute, Division of Cardiology, Department of Medicine, University of Pittsburgh and University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
⁶ Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
⁷ University of Arizona, Tucson, Arizona, USA.
⁸ Department of Medicine, University of Pittsburgh and University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
⁹ Scipher Medicine, Inc., Waltham, Massachusetts, USA.
¹⁰ Weill Cornell Medical Center, New York, New York, USA.
¹¹ University of California at San Diego, San Diego, California, USA.
¹² University of Washington, Seattle, Washington, USA.
¹³ National Jewish Health, Denver, Colorado, USA.
¹⁴ Cincinnati Children's Hospital Medical Center and the University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
¹⁵ Imperial College London, London, United Kingdom.
¹⁶ Stanford University School of Medicine, Stanford, California, USA.
¹⁷ Division of Geriatrics and Clinical Gerontology, National Institute on Aging and the School of Medicine, Oregon Health and Science University, Portland, Oregon, USA.
¹⁸ Division of Lung Diseases, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA.
¹⁹ Division of Lung Diseases, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA. Electronic address: lei.xiao@nih.gov.

PMID: 33888254
PMCID: PMC8065203
DOI: 10.1016/j.jacc.2021.02.056

Review

NHLBI-CMREF Workshop Report on Pulmonary Vascular Disease Classification: JACC State-of-the-Art Review

William M Oldham et al. J Am Coll Cardiol. 2021.

. 2021 Apr 27;77(16):2040-2052.

doi: 10.1016/j.jacc.2021.02.056.

Authors

Affiliations

¹ Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA. Electronic address: woldham@bwh.harvard.edu.
² Vanderbilt University Medical Center, Nashville, Tennessee, USA.
³ Indiana University School of Medicine, Indianapolis, Indiana, USA.
⁴ Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA.
⁵ Center for Pulmonary Vascular Biology and Medicine, Pittsburgh Heart, Lung, Blood, and Vascular Medicine Institute, Division of Cardiology, Department of Medicine, University of Pittsburgh and University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
⁶ Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
⁷ University of Arizona, Tucson, Arizona, USA.
⁸ Department of Medicine, University of Pittsburgh and University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
⁹ Scipher Medicine, Inc., Waltham, Massachusetts, USA.
¹⁰ Weill Cornell Medical Center, New York, New York, USA.
¹¹ University of California at San Diego, San Diego, California, USA.
¹² University of Washington, Seattle, Washington, USA.
¹³ National Jewish Health, Denver, Colorado, USA.
¹⁴ Cincinnati Children's Hospital Medical Center and the University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
¹⁵ Imperial College London, London, United Kingdom.
¹⁶ Stanford University School of Medicine, Stanford, California, USA.
¹⁷ Division of Geriatrics and Clinical Gerontology, National Institute on Aging and the School of Medicine, Oregon Health and Science University, Portland, Oregon, USA.
¹⁸ Division of Lung Diseases, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA.
¹⁹ Division of Lung Diseases, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA. Electronic address: lei.xiao@nih.gov.

PMID: 33888254
PMCID: PMC8065203
DOI: 10.1016/j.jacc.2021.02.056

Abstract

The National Heart, Lung, and Blood Institute and the Cardiovascular Medical Research and Education Fund held a workshop on the application of pulmonary vascular disease omics data to the understanding, prevention, and treatment of pulmonary vascular disease. Experts in pulmonary vascular disease, omics, and data analytics met to identify knowledge gaps and formulate ideas for future research priorities in pulmonary vascular disease in line with National Heart, Lung, and Blood Institute Strategic Vision goals. The group identified opportunities to develop analytic approaches to multiomic datasets, to identify molecular pathways in pulmonary vascular disease pathobiology, and to link novel phenotypes to meaningful clinical outcomes. The committee suggested support for interdisciplinary research teams to develop and validate analytic methods, a national effort to coordinate biosamples and data, a consortium of preclinical investigators to expedite target evaluation and drug development, longitudinal assessment of molecular biomarkers in clinical trials, and a task force to develop a master clinical trials protocol for pulmonary vascular disease.

Keywords: drug repurposing; integrative omics; master clinical trial protocol; precision medicine; pulmonary hypertension; systems biology.

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Conflict of interest statement

Funding Support and Author Disclosures Several authors report funding support from the National Institutes of Health/National Heart, Lung, and Blood Institute (K08HL128802 to Dr. Oldham; R35HL140019 to Dr. Aldred; R01HL146588 to Dr. Brittain; R01HL135142, R01HL137927, R01HL089856, and R01HL147148 to Dr. Cho; R01HL136603 to Dr. Desai; K01HL146980 to Dr. Kelly; U01HL125215 to Dr. Leopold; and K23HL144418 to Dr. Modena). Dr. Oldham has received a research grant from the Cardiovascular Medical Research and Education Fund. Dr. Leopold was supported by grants from the American Heart Association. Dr. Wilkins was supported by the British Heart Foundation (RE/18/4/34215 and SP/18/10/33975). Dr. Hemnes has served as a consultant for Actelion, Bayer, Complexa, and United Therapeutics; and owns shares in PHPrecisionMed, all outside of the submitted work. Dr. Chan has served as a consultant for Zogenix, Aerpio, and United Therapeutics; is a director, officer, and shareholder in Synhale Therapeutics; has held research grants from Actelion and Pfizer; and has filed patent applications regarding the targeting of BMP signaling and metabolic pathways in pulmonary hypertension, all outside of the submitted work. Dr. Cho has received grant support from Bayer and GlaxoSmithKline; and served as a consultant for Genentech, AstraZeneca, and Illumina, all outside of the submitted work. Dr. Desai has served as a consultant for Novartis, outside of the submitted work. Dr. Modena has received honoraria from AstraZeneca, Genentech, GlaxoSmithKline, Regeneron, Sanofi, and Teva for consulting or lectures in the past; and has current research funding from Genentech and GlaxoSmithKline, all outside of the submitted work. Dr. Rhodes has received personal advisory board fees from Janssen and United Therapeutics, outside of the submitted work. Dr. Wilkins has consulted with Actelion, Novartis, GlaxoSmithKline, and MorphogenIX in the development of biomarkers for pulmonary hypertension, all outside of the submitted work. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Figures

**Figure 1.. Deep phenotyping performed as part of the PVDOMICS study.**
PVDOMICS collected data across a broad range of clinical, imaging, and molecular parameters. A standard clinical evaluation was supplemented with quality-of-life questionnaires. Hemodynamic assessment by pulmonary artery catheterization incorporated provocative testing with fluid challenge and pulmonary vasodilators. Molecular profiling was performed on blood samples using leukocyte DNA for genomics, whole-blood RNA for transcriptomics, and plasma for aptamer-based proteomics and untargeted metabolomics.

**Central Illustration.. Key principles identified for using deep phenotyping to improve patient care in patients with pulmonary vascular disease.**
The goal is to develop a new classification system for pulmonary vascular disease based on shared clinical and molecular phenotypes to improve outcomes for patients with pulmonary vascular disease. By applying novel analytical approaches to these disease phenotypes, new molecular targets will be identified, and therapeutics developed. Several key principles were identified in this joint NIH/NHBLI and Cardiovascular Medical Research and Education Fund workshop that should focus future efforts in this area.

See this image and copyright information in PMC

References

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1. Huston JH, Maron BA, French J et al. Association of Mild Echocardiographic Pulmonary Hypertension With Mortality and Right Ventricular Function. JAMA Cardiol 2019. - PMC - PubMed
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NHLBI-CMREF Workshop Report on Pulmonary Vascular Disease Classification: JACC State-of-the-Art Review

Affiliations

NHLBI-CMREF Workshop Report on Pulmonary Vascular Disease Classification: JACC State-of-the-Art Review

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

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Grants and funding

LinkOut - more resources

Full Text Sources

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Medical

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