Pulmonary Hypertension — Clinical Case

DCE Long Case

Patient brief (provided to trainee)

Patient: Mrs Margaret Chen, 49 years old, accountant. [1]

Presenting complaint: Referred by her general practitioner with a 9-month history of progressive exertional dyspnoea. She is now breathless walking 100 metres on flat ground and has had two episodes of near-syncope on exertion in the past month. She denies chest pain, palpitations, orthopnoea, or paroxysmal nocturnal dyspnoea. She reports increasing fatigue and noticed her ankles swelling over the last two months. [1]

Past history: Limited cutaneous systemic sclerosis (CREST syndrome) diagnosed 6 years ago — calcinosis, Raynaud phenomenon, oesophageal dysmotility for which she takes pantoprazole, and sclerodactyly. She also has hypertension, mild, for which she takes amlodipine. No prior pulmonary embolism or deep vein thrombosis. She has never been pregnant. [1]

Medications: Pantoprazole, amlodipine 5 mg daily for Raynaud phenomenon and hypertension. [1]

Social history: Non-smoker, drinks alcohol rarely. Works part-time as an accountant. Lives with her husband. [1]

Examination findings (trainee elicits):

• Comfortable at rest, no respiratory distress, no central cyanosis. Hands show sclerodactyly and digital pitting scars consistent with systemic sclerosis.
• Blood pressure 104 over 68, heart rate 92 and regular.
• Oxygen saturation 94 percent on room air at rest, falling to 86 percent on ambulation.
• JVP elevated 5 cm with a prominent v wave.
• Right ventricular heave at the lower left sternal edge.
• Loud pulmonary component of the second heart sound; pansystolic murmur at the lower left sternal edge; right ventricular fourth sound.
• Chest clear to auscultation.
• Pitting oedema to the mid-shin. Resting exam otherwise unremarkable. [1]

Investigations:

• ECG: right axis deviation, p-pulmonale, right bundle branch block
• Echocardiography: estimated RVSP 62 mmHg; dilated right ventricle with moderate systolic dysfunction; flattened interventricular septum; small pericardial effusion; left ventricular ejection fraction 58 percent; no significant valvular disease
• Pulmonary function tests: FVC 90 percent predicted, FEV1 88 percent predicted, DLCO 48 percent predicted
• NT-proBNP 1450 ng/L
• Autoimmune screen: ANA positive, anti-centromere positive; anti-Scl70 negative
• V/Q scan: no segmental perfusion defects
• High-resolution CT chest: mild basal interstitial changes consistent with early scleroderma-related fibrosis, no honeycombing [1]

Candidate's structured presentation (model)

Opening statement: [1]

"Mrs Chen is a 49-year-old woman with limited cutaneous systemic sclerosis who presents with 9 months of progressive exertional dyspnoea, now limited to 100 metres, and two episodes of exertional near-syncope. Her examination and echocardiogram are consistent with pulmonary hypertension with right ventricular dysfunction: a loud pulmonary component to the second heart sound, a right ventricular heave, signs of tricuspid regurgitation, an estimated RVSP of 62 mmHg with right ventricular dilation and a pericardial effusion, and exertional desaturation. Her DLCO is disproportionately reduced at 48 percent with preserved lung volumes, the classic pattern of pulmonary vascular disease in scleroderma. Her V/Q scan excludes chronic thromboembolic disease. [1]

Her problems are:

1. Pre-capillary pulmonary hypertension, probable scleroderma-associated 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 and low cardiac output
4. Systemic sclerosis with multisystem involvement — Raynaud, oesophageal, early lung fibrosis [1]

My immediate priority is to confirm the diagnosis and phenotype with right heart catheterisation, distinguish PAH from post-capillary involvement of scleroderma myocardial fibrosis, and initiate combination therapy at a specialist pulmonary hypertension centre." [1]

Key management discussion — the right heart catheter and phenotype: [1]

"The right heart catheterisation is mandatory and non-negotiable. The echo estimates RVSP but cannot diagnose pulmonary hypertension. The catheter will confirm the mPAP is above 20 mmHg and, critically, measure the pulmonary artery wedge pressure. If the wedge is 15 or below with a PVR above 2 Wood units, she has pre-capillary PAH — scleroderma-associated, Group 1. If the wedge is above 15, she has post-capillary pulmonary hypertension from scleroderma myocardial fibrosis, Group 2, which requires a fundamentally different approach — treating the left heart disease, not using PAH-specific therapy, which could be harmful. [1]

This distinction is the single most important diagnostic step in a scleroderma patient, because scleroderma causes both PAH through pulmonary vascular remodelling and left heart disease through myocardial fibrosis, and the two conditions can coexist. I will also perform acute vasoreactivity testing, though it is rarely positive in scleroderma-associated PAH and is mainly used to identify idiopathic PAH patients who respond to calcium channel blockers." [1]

Risk stratification and therapy — treat to target: [1]

"Applying the 2022 ESC/ERS three-strata model, she sits at high risk at presentation: WHO functional class III to IV, a 6-minute walk distance around 100 metres, an NT-proBNP of 1450, right ventricular dysfunction, a pericardial effusion, and exertional syncope. Her amlodipine should be stopped — she is not vasoreactive and calcium channel blockers are inappropriate and may worsen her haemodynamics. [1]

For a high-risk patient I will be aggressive. I will refer her urgently to the specialist pulmonary hypertension centre. The initial strategy is guided by her risk: the AMBITION trial established initial oral combination of an endothelin receptor antagonist plus a phosphodiesterase-5 inhibitor as the standard for most patients, reducing clinical failure by 50 percent versus monotherapy. Given her high-risk presentation with syncope and right heart failure, I would favour initial or early parenteral prostacyclin — intravenous epoprostenol is the most potent agent and the only therapy proven to improve survival in severe PAH — alongside oral combination therapy. I will start a loop diuretic for her volume overload and supplemental oxygen to maintain saturation at 90 percent or above. [1]

At follow-up, I will treat to target — escalating therapy until she achieves a low-risk profile. Escalation options include adding the oral IP-receptor agonist selexipag, or the activin-signalling inhibitor sotatercept, which the STELLAR trial showed improves 6-minute walk distance by 40.8 metres and reduces pulmonary vascular resistance as add-on therapy. If she does not respond to maximal combination therapy, I will refer her for transplant assessment early, because evaluation takes months and her window can narrow quickly." [1]

Examiner discussion questions

Q: "Her DLCO is 48 percent. How do you know this is pulmonary vascular disease and not interstitial lung disease?" [1]

"Because the pattern is one of disproportionate reduction in DLCO relative to lung volumes. Her FVC is 90 percent predicted, which is preserved, whereas her DLCO is 48 percent predicted — a marked dissociation. In interstitial lung disease, the FVC and DLCO fall together, reflecting a loss of ventilated lung. In pulmonary vascular disease, the lung parenchyma is relatively preserved so the volumes are maintained, but the diffusion capacity falls because the pulmonary capillary bed is destroyed or obstructed. A DLCO under 60 percent predicted with preserved lung volumes is the classic screening red flag for pulmonary vascular disease in systemic sclerosis, and it is why annual screening of scleroderma patients combines spirometry and DLCO with echocardiography. Her high-resolution CT shows only mild basal interstitial change, insufficient to account for either her dyspnoea or her DLCO, which supports the pulmonary vascular diagnosis. The right heart catheterisation will confirm it definitively." [1]

Q: "She had near-syncope. Why is that concerning?" [1]

"Exertional syncope or near-syncope is one of the most ominous symptoms in pulmonary hypertension because it signals a failing right ventricle unable to augment cardiac output with exertion. The pathophysiology is that during exercise the systemic vasodilation and increased oxygen demand require an increase in cardiac output, which the obstructed pulmonary circulation and failing right ventricle cannot deliver. The result is cerebral hypoperfusion and syncope. Exertional syncope places a patient firmly in the high-risk stratum and is associated with a markedly worse prognosis. It is the symptom that most strongly argues for aggressive initial therapy with parenteral prostacyclin and early transplant referral. I take it very seriously — it is the pulmonary hypertension equivalent of syncope in aortic stenosis, a marker of decompensation." [1]

Q: "What do you tell her about pregnancy?" [1]

"I tell her that pregnancy is absolutely contraindicated. Pregnancy in pulmonary arterial hypertension carries a maternal mortality of 30 to 56 percent, from the haemodynamic stress of pregnancy — a 50 percent increase in blood volume and cardiac output, decreased systemic vascular resistance, and the haemodynamic demands of labour and delivery — superimposed on a circulation that cannot tolerate them. The 2022 ESC/ERS guidelines state that pregnancy is contraindicated in PAH, and effective contraception is mandatory. I would discuss reliable long-acting contraception — a progestogen-only implant or intrauterine device are preferred; oestrogen-containing contraceptives carry a thrombotic risk and are generally avoided. If she desires children in the future, the discussion is about disease control first, and the only safe path is surrogacy or adoption. I would document this discussion and involve her partner in the counselling." [1]

Q: "She is on amlodipine for her Raynaud. Should she continue it?" [1]

"I would stop or reduce it. She is almost certainly not vasoreactive — scleroderma-associated PAH is rarely vasoreactive — and high-dose calcium channel blockers are inappropriate and potentially harmful, causing systemic hypotension and negative inotropy that worsens her right ventricular function. However, her Raynaud does need management. I would switch her Raynaud therapy to a more pulmonary-vasculature-neutral option, or carefully use a low dose, and I would coordinate this with the rheumatology team. The key point is that calcium channel blockers are reserved for confirmed vasoreactive idiopathic PAH patients at high dose, and they are not appropriate as a general vasodilator in non-vasoreactive pulmonary hypertension." [1]

DCE Short Case — Chronic Thromboembolic Pulmonary Hypertension

Instruction

"This 62-year-old man was referred with two years of progressive exertional dyspnoea following two pulmonary emboli, the last three years ago. Examine his cardiovascular system and discuss your findings. You have 7 minutes for examination and 8 minutes for discussion." [1]

Key signs the patient demonstrates

• Loud pulmonary component of the second heart sound (loud P2) — the cardinal auscultatory finding
• Right ventricular heave at the lower left sternal edge — the pressure-loaded right ventricle
• Raised JVP with a prominent v wave from functional tricuspid regurgitation
• Pansystolic murmur at the lower left sternal edge
• Peripheral oedema from right heart failure
• Exertional desaturation — oxygen saturation falling on ambulation [1]

Presentation template (model)

"I examined Mr Wright's cardiovascular system. He is comfortable at rest at 45 degrees. There is no clubbing, pallor, or central cyanosis. [1]

The pulse is regular at 88 beats per minute, normal volume. The blood pressure is 118 over 72. The JVP is elevated four centimetres with a prominent v wave. There is a right ventricular heave at the lower left sternal edge. [1]

On auscultation the first heart sound is normal and the second heart sound has a loud pulmonary component. There is a pansystolic murmur at the lower left sternal edge consistent with tricuspid regurgitation. There is no diastolic murmur. The chest is clear. There is pitting oedema to the knees. [1]

In summary, these findings — the loud pulmonary component of the second heart sound, the right ventricular heave, and the signs of tricuspid regurgitation and right heart failure — are consistent with pulmonary hypertension with right ventricular dysfunction. Given his history of pulmonary embolism, I am specifically concerned about chronic thromboembolic pulmonary hypertension. I would confirm with echocardiography, perform a V/Q scan to identify perfusion defects, and proceed to right heart catheterisation." [1]

Discussion template

1. Summarise findings and the diagnostic concern [1]

"This man presents with progressive exertional dyspnoea and the physical signs of pulmonary hypertension with right ventricular dysfunction. In the context of two prior pulmonary emboli, the leading diagnosis is chronic thromboembolic pulmonary hypertension. CTEPH develops in approximately 0.1 to 9 percent of patients within two years of an acute pulmonary embolism, from incomplete resolution of the thrombus with organisation and fibrosis of the pulmonary arterial bed. It is the only potentially curable form of pulmonary hypertension, which makes the diagnostic and operability assessment pivotal." [1]

2. The investigation pathway [1]

"My investigation pathway is: echocardiography to estimate the right ventricular systolic pressure and assess right ventricular function; a V/Q scan to identify the segmental perfusion defects characteristic of CTEPH — the V/Q scan, not the CTPA, is the recommended screening test because it is more sensitive for the perfusion abnormalities of chronic disease; right heart catheterisation to confirm pre-capillary pulmonary hypertension with an mPAP above 20, a wedge of 15 or below, and a PVR above 2; and pulmonary angiography to define the anatomy and assess operability." [1]

3. Operability — the core decision [1]

"Every patient with confirmed CTEPH must be referred to a multidisciplinary CTEPH team for operability assessment. If the organised thrombus is in the proximal main, lobar, or proximal segmental arteries and is surgically accessible, pulmonary endarterectomy is the definitive and potentially curative treatment. It is performed under deep hypothermic circulatory arrest and removes the organised material, which can normalise pulmonary pressures. Operability is determined by the surgical team based on the match between the haemodynamic lesions and the angiographic location of the disease." [1]

4. Options for inoperable disease [1]

"For inoperable distal disease, or persistent or recurrent PH after endarterectomy, two options are available. Riociguat, a soluble guanylate cyclase stimulator, is the only drug approved for inoperable CTEPH — the CHEST-1 trial showed a 46-metre improvement in 6-minute walk distance. And balloon pulmonary angioplasty, a staged percutaneous procedure, dilates segmental and subsegmental arteries and improves haemodynamics for distal disease. All patients receive lifelong anticoagulation and should be investigated for thrombophilia." [1]

Examiner: "Why is the V/Q scan preferred over CTPA for excluding CTEPH?" [1]

"Because V/Q scanning is more sensitive for the chronic thromboembolic process. V/Q directly compares regional perfusion with ventilation, so a segmental perfusion defect with preserved ventilation is detected clearly. CTPA visualises the contrast-filled lumen and is excellent for acute embolus and proximal thrombus, but it can miss the webs, bands, and distal obstructions of chronic organised disease, because the contrast may still pass around partial obstructions and the distal vessels are below the resolution of CT. The 2022 ESC/ERS guidelines recommend V/Q as the screening test to exclude CTEPH, and a normal V/Q effectively excludes the diagnosis. I would not rely on a CTPA alone — a patient with CTEPH can have a deceptively normal-looking CTPA. This is a classic and high-yield exam point." [1]

Examiner: "What determines his prognosis?" [1]

"Two things: whether he is operable, and the state of his right ventricle. For operable disease, pulmonary endarterectomy can be curative with good long-term survival. For inoperable disease, the prognosis is that of progressive pulmonary hypertension, though riociguat and balloon pulmonary angioplasty have improved outcomes substantially. The single most important prognostic factor across all groups of pulmonary hypertension is right ventricular function — not the pulmonary pressure itself. His right ventricular dysfunction and right heart failure are therefore concerning and make operability assessment urgent, because the longer the right ventricle remains under pressure load, the less likely it is to recover." [1]