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Vascular

Pulmonary Arterial Hypertension (PAH)

Added by Dr. Andrew · Last updated 2024-01-15

Overview

PAH (Group 1 PH) is characterized by progressive pulmonary vascular remodeling leading to elevated PVR, right heart failure, and death. The 2022 ESC/ERS guidelines recommend risk stratification and upfront combination therapy for most patients.

Key Points

  • 1Hemodynamic definition: mPAP >20 mmHg + PCWP ≤15 mmHg + PVR >2 WU (2022 ESC/ERS)
  • 2WHO Groups: 1 (PAH), 2 (left heart), 3 (lung disease), 4 (CTEPH), 5 (unclear/multifactorial)
  • 3RHC required for diagnosis — echo is screening only
  • 4Vasoreactivity testing: positive if mPAP decreases ≥10 to ≤40 mmHg with preserved/increased CO
  • 5Upfront combination therapy: ambrisentan + tadalafil (AMBITION trial) for most PAH patients
  • 6Sotatercept (Winrevair): new mechanism (ActRIIA inhibitor) — FDA approved 2024 (STELLAR trial)

Clinical Pearls

  • BMPR2 mutation: most common genetic cause of heritable PAH (~70% of familial cases)
  • Connective tissue disease (SSc-PAH): worst prognosis among PAH subtypes
  • Prostacyclin analogs (epoprostenol, treprostinil): for high-risk PAH; epoprostenol is the only drug proven to improve survival in PAH
  • Anticoagulation: no longer routinely recommended for all PAH (COMPERA registry data)

Board High-Yield

Exam Focus
  • AMBITION: upfront ambrisentan + tadalafil superior to monotherapy — now standard of care
  • STELLAR: sotatercept improved 6MWD and PVR — first new mechanism in 20 years
  • Vasoreactive PAH: high-dose CCB (amlodipine, diltiazem) — only ~10% of IPAH
  • New mPAP threshold: >20 mmHg (was >25) per 2022 ESC/ERS guidelines
  • Epoprostenol: only PAH drug with RCT-proven mortality benefit

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