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Review
. 2024 Mar-Apr;18(3-4):189-205.
doi: 10.1080/17476348.2024.2361037. Epub 2024 May 30.

Extrapulmonary manifestations of pulmonary arterial hypertension

Navneet Singh  1 , Nadine Al-Naamani  2 , Mary Beth Brown  3 , Gary Marshall Long  4 , Thenappan Thenappan  5 , Soban Umar  6 , Corey E Ventetuolo  1   7 , Tim Lahm  8   9   10
Affiliations
Review

Extrapulmonary manifestations of pulmonary arterial hypertension

Navneet Singh et al. Expert Rev Respir Med. 2024 Mar-Apr.

Abstract

Introduction: Extrapulmonary manifestations of pulmonary arterial hypertension (PAH) may play a critical pathobiological role and a deeper understanding will advance insight into mechanisms and novel therapeutic targets. This manuscript reviews our understanding of extrapulmonary manifestations of PAH.

Areas covered: A group of experts was assembled and a complimentary PubMed search performed (October 2023 - March 2024). Inflammation is observed throughout the central nervous system and attempts at manipulation are an encouraging step toward novel therapeutics. Retinal vascular imaging holds promise as a noninvasive method of detecting early disease and monitoring treatment responses. PAH patients have gut flora alterations and dysbiosis likely plays a role in systemic inflammation. Despite inconsistent observations, the roles of obesity, insulin resistance and dysregulated metabolism may be illuminated by deep phenotyping of body composition. Skeletal muscle dysfunction is perpetuated by metabolic dysfunction, inflammation, and hypoperfusion, but exercise training shows benefit. Renal, hepatic, and bone marrow abnormalities are observed in PAH and may represent both end-organ damage and disease modifiers.

Expert opinion: Insights into systemic manifestations of PAH will illuminate disease mechanisms and novel therapeutic targets. Additional study is needed to understand whether extrapulmonary manifestations are a cause or effect of PAH and how manipulation may affect outcomes.

Keywords: Pulmonary hypertension; central nervous system; gut dysbiosis; inflammation; metabolism; myopathy; obesity; retina.

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Conflict of interest statement

Declarations of Interest:

T Lahm has received consulting fees from Allinaire Therapeutics, Arrowhead Pharmaceuticals, Guidepoint, and GLG.

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Figures

Figure 1.
Figure 1.
Extrapulmonary Manifestations of Pulmonary Arterial Hypertension. RV=right ventricle. PH=pulmonary hypertension. MCT=monocrotaline. PAH=pulmonary arterial hypertension. HSC=hematopoietic stem cell. EPC=endothelial stem/progenitor cell. MSC=mesenchymal stem cell. PAH=pulmonary arterial hypertension. BMI=body mass index.
Figure 2.
Figure 2.
Extrinsic and intrinsic factors that contribute to muscle dysfunction in pulmonary arterial hypertension. Adapted from Manders, et al. [148]
See this image and copyright information in PMC

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References

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