Pulmonary Hypertension Viva

Long Case Viva Defence

Candidate's opening statement (model answer)

"Ms Emma Lawson is a 34-year-old childcare worker referred to the respiratory physician with an 18-month history of progressive exertional dyspnoea. She now notices breathlessness climbing a single flight of stairs, and six weeks ago she had an episode of near-syncope while running for a bus. She has no chest pain, palpitations, or orthopnoea. She has no significant past medical history, takes only an oral contraceptive pill, and has never been pregnant. She does not smoke and drinks alcohol occasionally. [1]

On examination she is comfortable at rest. Her blood pressure is 106 over 70, heart rate 94 and regular, and her oxygen saturation is 95 percent at rest falling to 89 percent on walking. Her JVP is elevated three centimetres with a prominent a wave. There is a right ventricular heave at the lower left sternal edge. On auscultation the second heart sound has a loud pulmonary component, there is a soft pansystolic murmur at the lower left sternal edge, and a right ventricular fourth sound. There is trace ankle oedema. The chest is clear. [1]

Her ECG shows right axis deviation with p-pulmonale and a right bundle branch block. Her echocardiogram estimates a right ventricular systolic pressure of 58 mmHg with a moderately dilated and dysfunctional right ventricle, flattened interventricular septum, and a small pericardial effusion. Her pulmonary function tests show preserved lung volumes with a DLCO of 55 percent predicted. Her NT-proBNP is 980. An autoimmune screen, HIV serology, and liver function tests are all normal, and her V/Q scan shows no perfusion defects. [1]

Her problems are:

1. Pre-capillary pulmonary hypertension, probable idiopathic PAH — the primary problem
2. Right ventricular dysfunction with early right heart failure — the determinant of prognosis
3. Exertional syncope — an ominous marker of advanced disease
4. A need for diagnostic confirmation, risk stratification, and lifelong specialist therapy [1]

My working diagnosis is idiopathic pulmonary arterial hypertension. My immediate priorities are to confirm the diagnosis with right heart catheterisation, exclude the associated causes, risk-stratify her, and initiate combination therapy at a specialist pulmonary hypertension centre." [1]

Examiner probing questions and model answers

Q1: "She has an estimated RVSP of 58 on the echo. Why do you need a right heart catheter?" [1]

"Because echocardiography estimates but cannot diagnose pulmonary hypertension. The echo derives an estimated right ventricular systolic pressure from the tricuspid regurgitation jet velocity, which is dependent on image quality, the presence of an adequate envelope, and an estimated right atrial pressure — it is an approximation, not a measurement. [1]

Right heart catheterisation is the definitive test and is mandatory before any PAH-specific therapy. It does four things the echo cannot. First, it directly measures the mean pulmonary artery pressure, confirming the diagnosis using the 2022 ESC/ERS threshold of above 20 mmHg. Second, it measures the pulmonary artery wedge pressure, which distinguishes pre-capillary from post-capillary disease — a wedge of 15 or below with a PVR above 2 Wood units defines pre-capillary PAH, whereas a wedge above 15 indicates left heart disease, which requires a fundamentally different approach. Third, it quantifies the pulmonary vascular resistance, the cardiac index, and the right atrial pressure, all of which drive risk stratification and prognosis. Fourth, it allows acute vasoreactivity testing — which, while rarely positive in associated PAH, is worth performing in idiopathic PAH because a positive response, defined as a fall in mPAP of at least 10 mmHg to a value of 40 or below with normal or increased cardiac output, identifies the 6 to 15 percent of idiopathic PAH patients who respond to high-dose calcium channel blockers and have a markedly better prognosis. [1]

Starting PAH-specific therapy on the basis of echo alone is unsafe — I could misclassify a post-capillary patient and give vasoactive drugs that worsen left heart disease. So the catheter is non-negotiable." [1]

Q2: "How do you risk-stratify her using the 2022 ESC/ERS model?" [1]

"The 2022 ESC/ERS guidelines use a simplified three-strata model — low, intermediate, and high estimated one-year mortality — built from a multi-parameter assessment that I apply at baseline and at every follow-up. The therapeutic goal is to achieve and maintain a low-risk profile. [1]

The parameters I assess are: WHO functional class; 6-minute walk distance; NT-proBNP; right atrial pressure and cardiac index on catheterisation; mixed venous oxygen saturation; and imaging findings of right ventricular size and function and the presence of a pericardial effusion. Each parameter carries a low, intermediate, or high-risk value, and the overall risk is the integrated picture. [1]

Applying this to Ms Lawson: her WHO functional class is III — she is breathless climbing one flight of stairs, which is intermediate. Her 6-minute walk distance is yet to be formally measured but her functional limitation suggests an intermediate range. Her NT-proBNP of 980 is in the intermediate band. Her right ventricle is moderately dysfunctional with a pericardial effusion, which is a high-risk imaging finding. And her exertional syncope is an ominous clinical marker of low cardiac output that places her toward the high-risk end. So overall she sits at intermediate-to-high risk at presentation. [1]

The key principle is treat to target. She will be reassessed at three to six monthly intervals, and therapy escalated — adding a second or third agent, switching to parenteral prostacyclin — until she reaches a low-risk profile. A patient who remains intermediate or high risk despite dual oral therapy needs escalation or transplant assessment." [1]

Q3: "Describe your initial pharmacological strategy." [1]

"She has idiopathic PAH at intermediate-to-high risk, vasoreactivity pending. Assuming a negative vasoreactivity test, which is the most likely outcome, I will initiate combination therapy under the guidance of the specialist pulmonary hypertension centre. [1]

The AMBITION trial, published by Galie and colleagues in the New England Journal of Medicine in 2015, randomised 500 treatment-naive patients to initial ambrisentan plus tadalafil or to either monotherapy. Initial combination therapy reduced the primary composite of clinical failure by 50 percent, hazard ratio 0.50, driven mainly by fewer PAH hospitalisations. On this evidence, the 2022 ESC/ERS guidelines recommend initial oral combination with an endothelin receptor antagonist plus a phosphodiesterase-5 inhibitor as the standard for most low- and intermediate-risk patients. [1]

So I will start ambrisentan 10 mg daily plus tadalafil, titrated to 40 mg daily. I will add a loop diuretic if she is congested. I will monitor her liver function, given that ambrisentan is an ERA, though it is less hepatotoxic than bosentan. I will provide supplemental oxygen to maintain saturation at 90 percent or above. I will advise her that pregnancy is contraindicated — PAH carries a maternal mortality of 30 to 56 percent — and ensure effective contraception. [1]

If she presents in or progresses to WHO functional class IV or high-risk status, I would instead start continuous intravenous epoprostenol, which is the most potent agent and the only therapy proven to improve survival in severe idiopathic PAH, and consider adding oral agents and early transplant referral." [1]

Q4: "She is not vasoreactive. Could you still use a calcium channel blocker?" [1]

"No. High-dose calcium channel blockers are effective only in the minority of idiopathic PAH patients who demonstrate a positive acute vasoreactivity response at catheterisation — about 6 to 15 percent. These patients have a markedly better prognosis and can be managed with agents such as amlodipine, nifedipine, or diltiazem at high dose. A patient who is not vasoreactive does not respond to calcium channel blockers, and using them exposes her to systemic hypotension and negative inotropy without benefit. The 2022 ESC/ERS guidelines restrict calcium channel blocker therapy to confirmed vasoreactive patients with idiopathic, heritable, or drug-associated PAH. So her therapy is the combination of ERA and PDE5 inhibitor I described, escalated as guided by her risk assessment." [1]

Q5: "She remains in functional class III after three months of dual therapy. What next?" [1]

"This is the treat-to-target principle in action. She has not achieved a low-risk profile, so I escalate. The options are to add a third agent from a different pathway. [1]

First, the oral selective IP-receptor agonist selexipag. The GRIPHON trial, Sitbon and colleagues in NEJM 2015, randomised 1156 patients to selexipag or placebo and showed a 40 percent reduction in the composite of death or PAH complication, hazard ratio 0.60, with a tolerable side-effect profile of prostacyclin-type symptoms. Adding selexipag to her ERA and PDE5 gives triple oral therapy targeting three pathways. [1]

Second, the activin-signalling inhibitor sotatercept. The STELLAR trial, Hoeper and colleagues in NEJM 2023, showed that sotatercept, added to stable background therapy, improved 6-minute walk distance by 40.8 metres versus placebo and improved pulmonary vascular resistance, NT-proBNP, functional class, and time to clinical worsening. It is a first-in-class anti-remodelling agent that works by a different mechanism — trapping activin to restore the balance between pro-proliferative and anti-proliferative signalling — and it was approved by the FDA in 2024 as add-on therapy. [1]

If she does not respond to maximal combination therapy, or if she remains high-risk, I refer her for transplant assessment. Bilateral lung transplantation is the final option, and early referral is essential because evaluation takes months and her window can narrow quickly." [1]

Q6: "Could you use riociguat in her regimen?" [1]

"Only if I stop the tadalafil first, and I would not combine them. Riociguat, a soluble guanylate cyclase stimulator, and the PDE5 inhibitors both act on the nitric oxide to cyclic GMP pathway — riociguat stimulates cyclic GMP production while PDE5 inhibitors prevent its degradation. Combined use produces excessive cyclic GMP accumulation with a risk of profound and potentially fatal hypotension. This contraindication was identified in the PATENT-1 trial and is absolute. So if I wanted to use riociguat, I would switch it for the tadalafil rather than add it. In practice, for her initial combination, the ERA plus PDE5 is the established AMBITION strategy, and I would add a prostacyclin-pathway agent or sotatercept for escalation rather than switching to riociguat." [1]