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Chronic Thromboembolic Pulmonary Hypertension: the Bench

  • Heart Failure (HJ Eisen, Section Editor)
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Abstract

Purpose of Review

Chronic thromboembolic pulmonary hypertension (CTEPH) is an uncommon complication of acute pulmonary embolism (PE), in which the red, platelet-rich thrombus does not resolve but forms into an organized yellow, fibrotic scar-like obstruction in the pulmonary vasculature. Here we review the pathobiology of CTEPH.

Recent Findings

Our current knowledge has predominantly been informed by studies of human samples and animal models that are inherently limited in their ability to recapitulate all aspects of the disease. These studies have identified alterations in platelet biology and inflammation in the formation of a scar-like thrombus that comprised endothelial cells, myofibroblasts, and immune cells, along with a small vessel pulmonary arterial hypertension-like vasculopathy.

Summary

The development of CTEPH-specific therapies is currently hindered by a limited knowledge of its pathobiology. The development of new CTEPH medical therapies will require new insights into its pathobiology that bridge the gap from bench to bedside.

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Abbreviations

CEC:

Circulating endothelial cells

CRP:

C-reactive protein

CTEPH:

Chronic thromboembolic pulmonary hypertension

DVT:

Deep venous thrombosis

endoMT:

Endothelial-to-mesenchymal transition

EPC:

Endothelial progenitor cells

ET-1:

Endothelin-1

IVC:

Inferior Vena Cava

mPAP:

Mean pulmonary arterial pressure

MMP-9:

Matrix metalloproteinase-9

PA:

Pulmonary artery

PAH:

Pulmonary arterial hypertension

PE:

Pulmonary embolism

PEA:

Pulmonary endarterectomy

PECAM-1:

Platelet endothelial cell adhesion molecule-1

PH:

Pulmonary hypertension

PVR:

Pulmonary vascular resistance

RV:

Right ventricle

TGF-β:

Transforming growth factor β

TNF-α:

Tumor necrosis factor α

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Authors and Affiliations

  1. Division of Pulmonary and Critical Care, Massachusetts General Hospital, Boston, MA, USA

    George A. Alba

  2. Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women’s Hospital, Boston, MA, USA

    Deepak Atri & Bradley A. Maron

  3. College of Natural Sciences, The University of Texas, Austin, TX, USA

    Sriranjani Darbha

  4. Division of Pulmonary, Critical Care, and Sleep Medicine, Yale New Haven Hospital and Yale School of Medicine, New Haven, CT, USA

    Inderjit Singh

  5. Division of Pulmonary and Critical Care Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA

    Victor F. Tapson & Michael I. Lewis

  6. Section of Cardiovascular Medicine, Department of Internal Medicine, Yale Cardiovascular Research Center, Yale School of Medicine, New Haven, CT, USA

    Hyung J. Chun

  7. Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, Duke University Medical Center, Durham, NC, USA

    Yen-Rei Yu

  8. Section of Cardiology, Veterans Affairs Boston Healthcare System, Boston, MA, USA

    Bradley A. Maron

  9. Division of Cardiology, Department of Medicine, Duke University Medical Center, Durham, NC, USA

    Sudarshan Rajagopal

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  1. George A. Alba
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Conflict of Interest

Dr. Tapson reports grants from Bayer, and grants and personal fees from Janssen and Actelion, outside the submitted work.

Dr. Maron reports personal fees from Actelion, outside the submitted work. In addition, Dr. Maron has a patent US patent 9,605,047 issued, a patent US pending patent PCT/US2019/059890 pending, and patent applications 62475955 and 029672 pending.

Dr. Rajagopal reports grants and personal fees from Janssen and United Therapeutics, and personal fees from Altavant, Apie Therapeutics, Bayer, Insmed, and Liquidia Technologies, outside the submitted work. In addition, Dr. Rajagopal has a patent US Patent 62/673,175. “Dynamic 129Xe Gas Exchange Spectroscopy” licensed to Polarean Corporation.

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Alba, G.A., Atri, D., Darbha, S. et al. Chronic Thromboembolic Pulmonary Hypertension: the Bench. Curr Cardiol Rep 23, 141 (2021). https://doi.org/10.1007/s11886-021-01572-6

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