Pulmonary Hypertension — Written Clinical Reasoning

SAQ 1 — Scleroderma-Associated PAH: Investigation and Management (20 marks, 30 minutes)

Prompt: Outline your integrated investigation and management plan for this patient, including the role of right heart catheterisation, the haemodynamic classification, the ESC/ERS 2022 risk stratification, and the evidence-based pharmacological strategy. Justify each decision with reference to guidelines and key trials. ^[1]

Model Answer

Problem list and provisional diagnosis (2 marks): ^[1]

1. Progressive exertional dyspnoea with exertional presyncope in a patient with systemic sclerosis — the cardinal concern is scleroderma-associated pulmonary arterial hypertension (Group 1 PAH), which is the leading cause of death in systemic sclerosis.
2. Echocardiographic evidence of pulmonary hypertension — estimated RVSP of 62 mmHg with right ventricular dilation, dysfunction, and a pericardial effusion, all of which are high-risk features.
3. Disproportionately reduced DLCO — a DLCO of 48 percent predicted with preserved lung volumes (FVC 90 percent) is the classic pattern of pulmonary vascular disease rather than interstitial lung disease.
4. Clinical signs of right heart failure — raised JVP, tricuspid regurgitation murmur, peripheral oedema, and exertional desaturation indicating advanced disease. ^[1]

The provisional diagnosis is scleroderma-associated PAH. However, I must distinguish this from two competing diagnoses in systemic sclerosis: interstitial lung disease with secondary PH (Group 3), and left heart disease from scleroderma myocardial fibrosis (Group 2). The right heart catheterisation is essential to make this distinction. ^[1]

Investigation — right heart catheterisation is mandatory (5 marks): ^[1]

Right heart catheterisation is the definitive diagnostic test and is mandatory before any PAH-specific therapy. Echocardiography estimates right ventricular systolic pressure but cannot diagnose pulmonary hypertension. The catheterisation will: ^[1]

Acute vasoreactivity testing should be performed, though it is rarely positive in scleroderma-associated PAH and is mainly used in idiopathic PAH to identify the minority who respond to calcium channel blockers. ^[1]

Additional workup to confirm the cause and exclude the other groups:

• V/Q lung scan to exclude chronic thromboembolic pulmonary hypertension (Group 4) — a normal V/Q effectively excludes CTEPH.
• High-resolution CT chest to quantify the extent of interstitial lung disease.
• Autoimmune serology review (anti-centromere pattern fits limited scleroderma).
• HIV serology, liver function, and hepatitis serology to exclude HIV-associated and portopulmonary PAH.
• Six-minute walk test for objective functional capacity. ^[1]

Haemodynamic classification (2 marks): ^[1]

If the catheterisation shows mPAP above 20 mmHg, PAWP 15 or below, and PVR above 2 Wood units, the diagnosis is pre-capillary pulmonary hypertension. In the context of systemic sclerosis with a disproportionately low DLCO and no significant interstitial lung disease, this confirms Group 1 PAH (scleroderma-associated). If the PAWP is above 15, the diagnosis is post-capillary PH (Group 2) from myocardial fibrosis, which requires a fundamentally different management approach — treating the left heart disease, not using PAH-specific therapy. ^[1]

Risk stratification — ESC/ERS 2022 three-strata model (3 marks): ^[1]

Applying the 2022 ESC/ERS risk model to this patient places her at high risk of one-year mortality: ^[1]

A high-risk profile mandates aggressive initial therapy and early consideration of escalation. ^[1]

Pharmacological management — the evidence-based strategy (6 marks): ^[1]

Given her high-risk profile with signs of right heart failure, the management strategy must be aggressive and directed by a specialist pulmonary hypertension centre: ^[1]

1. Initial therapy: For a high-risk patient with right ventricular failure, the 2022 ESC/ERS guidelines support initial triple therapy or initial parenteral prostacyclin. Intravenous epoprostenol is the most potent agent and the only therapy proven to improve survival in severe idiopathic PAH; it is the first choice for WHO functional class IV. A loop diuretic is started for her volume overload. ^[1]

2. Combination therapy: The AMBITION trial (PMID 26308684) established that initial oral combination of an endothelin receptor antagonist (ambrisentan) plus a phosphodiesterase-5 inhibitor (tadalafil) reduced clinical failure by 50 percent versus monotherapy. ^[4] For a lower-risk patient this dual combination is the standard initial strategy. Given her high-risk status, this should be combined with parenteral prostacyclin from the outset, or introduced once she stabilises. ^[1]

3. Escalation: At follow-up, therapy is escalated until she achieves a low-risk profile. This may include adding the oral IP-receptor agonist selexipag (GRIPHON), switching to a sGC stimulator if appropriate (noting riociguat must never be combined with a PDE5 inhibitor), or adding the activin-signalling inhibitor sotatercept (STELLAR, PMID 36877098), which improved 6-minute walk distance by 40.8 metres and reduced pulmonary vascular resistance as add-on therapy. ^[1]

4. Supportive measures: Oxygen to maintain saturation at 90 percent or above, anticoagulation is not routine in associated PAH, vaccination, supervised rehabilitation, and strict pregnancy avoidance (PAH carries 30 to 56 percent maternal mortality). ^[1]

5. Transplant referral: She should be referred early for transplant assessment given her high-risk presentation, because evaluation takes months and the window for listing can narrow quickly. ^[1]

Communication and follow-up (2 marks): ^[1]

I would explain the diagnosis honestly — a serious but treatable condition of the lung blood vessels related to her scleroderma. I would explain that modern combination therapy has transformed outcomes, that she will be managed jointly with the specialist pulmonary hypertension service, and that her progress will be monitored with serial 6-minute walk tests, NT-proBNP, and echocardiography to treat to a low-risk target. I would address her Raynaud management, advise against pregnancy, and arrange psychosocial support for a chronic, life-limiting disease. ^[1]