Medicine · Rheumatology (SLE, RA, Vasculitis, Crystal Arthropathies, Scleroderma)

A 45-year-old woman with limited systemic sclerosis develops progressive exertional dyspnoea. Echocardiogram shows PASP 52 mmHg. Right heart catheterization confirms mean PAP 32 mmHg, PCWP 10 mmHg, PVR 5 Wood units. According to current ESC/ERS guidelines, what is her WHO functional classification and recommended first-line therapy?

  • A WHO FC III; IV epoprostenol monotherapy
  • B WHO FC II; sildenafil monotherapy followed by add-on ERA at 6 months
  • C WHO FC III; riociguat monotherapy as phosphodiesterase inhibitors are contraindicated with ambrisentan
  • D WHO FC III; combination ambrisentan plus tadalafil (AMBITION trial)
Correct answer: D. WHO FC III; combination ambrisentan plus tadalafil (AMBITION trial)

Explanation

Scleroderma-associated pulmonary arterial hypertension (Group 1 PAH) with exertional dyspnoea and haemodynamic criteria (mPAP >25 mmHg, PCWP ≤15 mmHg, PVR ≥3 WU) classifies as WHO FC III when symptoms occur with less-than-ordinary activity. The AMBITION trial demonstrated superiority of initial combination therapy (ambrisentan + tadalafil) over monotherapy in reducing clinical failure events and is now guideline-recommended first-line combination for FC II–III patients. Epoprostenol is reserved for FC IV or rapidly deteriorating patients. Riociguat must not be combined with PDE5 inhibitors due to hypotension risk.

Reference: Harrison's Principles of Internal Medicine, 21st ed.

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