Extrapulmonary manifestations of pulmonary arterial hypertension

Navneet Singh, Nadine Al-Naamani, Mary Beth Brown, Gary Marshall Long, Thenappan Thenappan, Soban Umar, Corey E. Ventetuolo, Tim Lahm

Research output: Contribution to journalReview articlepeer-review


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.

Original languageEnglish (US)
Pages (from-to)189-205
Number of pages17
JournalExpert Review of Respiratory Medicine
Issue number3-4
StatePublished - 2024

Bibliographical note

Publisher Copyright:
© 2024 Informa UK Limited, trading as Taylor & Francis Group.


  • Pulmonary hypertension
  • central nervous system
  • gut dysbiosis
  • inflammation
  • metabolism
  • myopathy
  • obesity
  • retina


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