Pulmonary Hypertension

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Meet the patient

A 34-year-old woman presents with eighteen months of progressive breathlessness going upstairs and two episodes of near-syncope while carrying groceries. Her chest examination is entirely normal, her ECG shows right-axis deviation, and her echo reports a TR Vmax of 3.7 m/s with a dilated right ventricle. She has never smoked and has no history of cardiac or respiratory disease.[1]

The two questions that decide her next three months are the two that decide every PH case: is the pressure in her pulmonary circulation raised, and is the cause pre-capillary or post-capillary? Echo can only suggest; right heart catheterisation confirms. Hold those two questions and the whole topic organises itself around them.[1]

mPAP above 20 on RHC — the number that defines the disease

Pulmonary hypertension is a haemodynamic diagnosis, and the number is mPAP above 20 mmHg at rest on right heart catheterisation. The 2022 ESC/ERS Guidelines lowered the threshold from the historical 25 mmHg to catch disease earlier — a change every final-prof candidate is expected to reproduce.[1]

The definition then forks on two further numbers that separate pre-capillary from post-capillary disease and drive every treatment decision:[1]

• Pre-capillary PH (Groups 1, 3, 4 and most of 5) — mPAP above 20 mmHg, PAWP at or below 15 mmHg (a left-heart cause excluded), and PVR above 2 Wood units (the threshold for pulmonary vascular disease worth treating).
• Isolated post-capillary PH (Group 2, left-heart-driven) — mPAP above 20 mmHg, PAWP above 15 mmHg, PVR at or below 2 WU; treat the left-heart cause.
• Combined pre- and post-capillary PH — PAWP above 15 mmHg and PVR above 2 WU; a hybrid that may need PAH therapy layered onto left-heart treatment in selected cases.[1][2]

The stricter definition of pulmonary arterial hypertension (PAH, WHO Group 1) layers on top: mPAP above 20 mmHg, PAWP at or below 15 mmHg, and PVR above 2 WU — this is the population in whom PAH-specific therapy has trial evidence.[2]

Echo screens, RHC confirms — never treat PAH on echo alone

The classic trap: treating PAH on the basis of an echocardiographic estimate without a right heart catheter. Echo reports a TR Vmax that feeds the Bernoulli equation (RVSP roughly equals 4 times TR Vmax squared plus right atrial pressure) — a surrogate, not a measurement. RHC is the only test that delivers mPAP, PAWP, PVR and vasoreactivity, and every patient considered for PAH-specific therapy must have one.[1]

The WHO Groups 1 to 5 face-off — one discriminator each

Classification is the single most important decision in PH, because the group dictates the therapy. The 2022 ESC/ERS clinical classification sorts PH into five groups by pathophysiology, not severity:[2]

[2]

The classic trap: reaching for PAH-specific therapy in Group 2 left-heart PH. The trials are negative in HFrEF and HFpEF, and vasodilators can worsen gas exchange and fluid retention. PAH drugs are for Group 1 (and selected Group 4) — confirm the group before the prescription.[1]

WHO functional class I to IV — bedside severity

WHO functional class is the simple bedside severity scale carried over from the NYHA system, and it is the single strongest predictor of outcome in PAH.[2]

• Class I — asymptomatic with ordinary activity; no breathlessness, fatigue, chest pain or pre-syncope.
• Class II — slight limitation; symptoms on ordinary activity (two flights of stairs, walking uphill), comfortable at rest.
• Class III — marked limitation; symptoms on less-than-ordinary activity (dressing, walking a few metres on the flat).
• Class IV — symptoms at rest; unable to do any physical activity without symptoms; signs of right-heart failure.[2]

Class IV at presentation is the strongest single marker of poor outcome — and class IV with syncope is the patient who needs parenteral prostacyclin today, not next month.[1]

How common, who, and which group dominates

Group 2 left-heart PH is the commonest cause overall; Group 1 PAH is rare but lethal. Untreated idiopathic PAH had a median survival of about 2.8 years in historical series; modern combination therapy has lifted five-year survival above 60 percent. CTEPH develops in about 4 percent of pulmonary-embolism survivors — a number that makes the V/Q scan non-negotiable in any post-PE patient with new dyspnoea.[1]

The numbers that earn marks:[2]

• Group 1 PAH — prevalence 15 to 50 per million adults (a true orphan disease); incidence 2 to 5 per million per year; female-to-male ratio roughly 3 to 4 to 1; heritable BMPR2 mutations in 15 to 25 percent of seemingly idiopathic cases.
• Group 2 left-heart PH — present in 40 to 75 percent of HFrEF, 50 to 80 percent of HFpEF, and almost all severe mitral stenosis.
• Group 3 lung PH — roughly 30 to 70 percent of advanced COPD and 30 to 50 percent of interstitial lung disease.
• Group 4 CTEPH — cumulative incidence about 4 percent after a symptomatic pulmonary embolism.[2]

The Group 1 risk factors an examiner expects you to name: systemic sclerosis (PAH in 8 to 12 percent, screened with annual echo and DLCO), anorexigens (fenfluramine, dexfenfluramine, benfluorex), dasatinib, HIV (about 0.5 percent), portal hypertension (portopulmonary, 2 to 6 percent of cirrhosis), uncorrected congenital shunts (Eisenmenger), and heritable BMPR2 mutations.[2]

Three vasomotor pathways — the pharmacological substrate

Every approved PAH drug is built on three vasomotor pathways gone wrong: reduced nitric oxide, reduced prostacyclin, and raised endothelin-1. Memorise the triad and the pharmacology writes itself.[1]

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The cluster rule, mapped to drug class:[1]

• Nitric oxide / cGMP axis (reduced). Endothelial nitric oxide synthase falls, so less NO activates soluble guanylate cyclase, so less cGMP, so smooth muscle fails to relax; PDE5 degrades what cGMP remains. Two ways to restore it: PDE5 inhibitors (sildenafil, tadalafil) stop the breakdown; riociguat stimulates soluble guanylate cyclase directly.
• Prostacyclin / cAMP axis (reduced). Prostacyclin synthase falls and thromboxane rises, so less cAMP-mediated vasodilation and anti-proliferation. Replaced by prostacyclin analogues (epoprostenol, iloprost, treprostinil, beraprost) and the selective IP-receptor agonist selexipag.
• Endothelin-1 axis (raised). Endothelin-1 is the most potent endogenous vasoconstrictor and drives smooth-muscle proliferation and fibrosis; levels are markedly raised in PAH. Blocked by endothelin-receptor antagonists — bosentan, ambrisentan, macitentan.[1]

The histological result of all three is intimal proliferation, medial hypertrophy, adventitial fibrosis, in-situ thrombosis, and plexiform lesions — the lumen narrows and the wall stiffens, raising PVR. The haemodynamic result is raised mPAP; the clinical result is RV pressure overload.[1]

The right ventricle decides who lives

Patients do not die of a high pulmonary pressure; they die of right ventricular failure. Sustained pressure overload first produces adaptive RV hypertrophy — preserved contractility, increased stroke work. With time the RV transitions to maladaptive dilation, eccentric remodelling, tricuspid annular dilatation with functional tricuspid regurgitation, septal shift towards the left ventricle, and falling forward cardiac output. Right coronary perfusion falls as aortic pressure drops and RV wall tension rises, producing RV ischaemia that compounds failure.[1]

Acute RV failure is the commonest mode of death in PH, and it is the emergency that every junior reaches for the wrong way — by intubating. More on that below.[1]

Exertional dyspnoea with a normal chest exam — the signature

The clinical signature of PAH is exertional dyspnoea disproportionate to a normal lung examination. The history dominates because the chest is quiet:[1]

• Exertional dyspnoea — gradually progressive, out of proportion to examination; the commonest presenting symptom across all groups.
• Fatigue — loss of cardiac output reserve on exertion.
• Pre-syncope or syncope on exertion — a fixed, high PVR means cardiac output cannot rise with demand; a sinister sign in PAH and an independent marker of death.
• Chest pain — RV ischaemia from raised wall tension and falling right coronary flow.
• Palpitations — atrial flutter and atrial fibrillation from a dilated right atrium; loss of atrial kick critically drops RV preload.
• Right-heart failure symptoms — abdominal distension, right upper-quadrant pain from hepatic congestion, early satiety, ankle swelling.[1]

The signature negative finding is the one juniors under-value: the lungs are clear in PAH despite crippling dyspnoea. Wheeze or crackles redirect you to Group 2 or Group 3.[1]

Loud P2, RV heave, TR murmur, Graham Steell — the bedside cluster

Four signs cluster at the bedside in advanced PH, and naming them in the right order earns the viva marks.[1]

• Loud pulmonary component of the second heart sound (P2) — raised pulmonary artery diastolic pressure; a palpable P2 at the upper left sternal edge is classic.
• Left parasternal (RV) heave — RV hypertrophy or dilation transmitted to the chest wall.
• Tricuspid regurgitation murmur — pansystolic at the lower left sternal edge, louder on inspiration (Carvallo); functional, from annular dilation.
• Graham Steell murmur — early diastolic decrescendo at the upper left sternal edge from pulmonary regurgitation; the RV-failure sign of advanced disease.[1]

Add the right-heart failure stigmata: raised JVP with prominent a and v waves, hepatojugular reflux, tender pulsatile hepatomegaly, ascites, and peripheral oedema. A single loud P2 in a young woman with exertional dyspnoea is PAH until proven otherwise.[1]

Echo TR Vmax — the 2.8 and 3.4 number rule

Two numbers govern echocardiographic probability of PH: under 2.8 m/s is low, 2.9 to 3.4 is intermediate, above 3.4 is high. The TR Vmax feeds Bernoulli (RVSP roughly equals 4 times TR Vmax squared plus right atrial pressure) and stratifies who needs catheterisation:[1]

• Low probability — TR Vmax at or below 2.8 m/s with no other echo features: PH unlikely.
• Intermediate — TR Vmax 2.9 to 3.4 m/s: needs second-line screening and clinical context.
• High probability — TR Vmax above 3.4 m/s plus RV hypertrophy, dilation, septal flattening, pulmonary artery dilation, or pericardial effusion: expedite RHC.[1]

Other echo markers of severity: RV basal diameter above 4.2 cm, RA area above 18 cm², TAPSE under 1.8 cm (RV systolic dysfunction), pericardial effusion (a poor prognostic sign), and IVC plethora (raised RAP).[1]

Right heart catheterisation — the definitive test

RHC is the only test that confirms PH, separates pre- from post-capillary, measures PVR, and tests vasoreactivity. Every patient considered for PAH-specific therapy has one.[1]

RHC delivers the four numbers that drive management:[1]

• mPAP — mean of several cardiac cycles of the pulmonary artery tracing; must exceed 20 mmHg for PH.
• PAWP — at or below 15 mmHg for pre-capillary (Groups 1, 3, 4, 5); above 15 mmHg for post-capillary (Group 2).
• PVR — (mPAP minus PAWP) divided by cardiac output; above 2 WU for pulmonary vascular disease (1 WU equals 1 mmHg per litre per minute).
• Cardiac output and cardiac index — by thermodilution or Fick.[1]

Vasoreactivity testing — the 10-and-40 rule. A positive test is a fall in mPAP of at least 10 mmHg to a value of 40 mmHg or below, with maintained or increased cardiac output, on inhaled nitric oxide (or IV epoprostenol or adenosine). It identifies the roughly 5 percent of idiopathic, heritable, or drug-induced PAH patients who benefit from high-dose calcium-channel blockers — amlodipine 5 to 20 mg daily, nifedipine 30 to 120 mg daily, or diltiazem 120 to 360 mg daily. The other 95 percent get combination PAH therapy.[1]

The classic trap: a positive vasoreactivity test in connective-tissue-disease or congenital PAH does not predict a calcium-channel-blocker response — restrict the test and the therapy to idiopathic, heritable, or drug-induced disease. And in pulmonary veno-occlusive disease (PVOD), vasodilators can precipitate life-threatening pulmonary oedema — suspect PVOD when PAH presents with hypoxaemia, crackles, and ground-glass opacities on CT, and refer for transplant.[1]

V/Q scan is mandatory — never miss CTEPH

Every newly diagnosed PH patient gets a V/Q scan. It is the screening test for CTEPH, and missing CTEPH means missing the only potentially curable form of PH. The V/Q is more sensitive than CTPA for chronic organised thrombus; one or more mismatched segmental perfusion defects is CTEPH until proven otherwise.[1]

The full aetiology work-up, in the order an examiner expects:[1]

• V/Q scan — mandatory; mismatched segmental perfusion defects mean CTEPH until proven otherwise.
• CTPA and high-resolution CT — thrombus anatomy for surgical planning, plus ILD, emphysema, and the ground-glass and septal-line pattern of PVOD.
• PFTs with DLCO — DLCO is reduced in PAH (often under 60 percent predicted); DLCO under 40 percent is a poor prognostic marker.
• Autoimmune screen — ANA, anti-centromere, anti-Scl-70, anti-RNA polymerase III, anti-RNP, anti-dsDNA — driven by clinical features.
• HIV serology, hepatitis and liver function, thyroid panel, haemoglobin electrophoresis — for the Group 1 associated conditions.
• Thrombophilia screen for CTEPH — antiphospholipid antibodies, factor V Leiden, prothrombin G20210A, protein C and S, antithrombin, JAK2.
• Abdominal ultrasound with portal venous Doppler — cirrhosis and portopulmonary hypertension.
• Cardiac MRI — the gold standard for RV volumes, ejection fraction, mass, and late gadolinium enhancement at the RV-to-LV insertion points (characteristic of PAH).[1]

Risk stratification — low, intermediate, high

Every PAH patient is risk-stratified at diagnosis and at every follow-up, because risk category drives drug choice and escalation. The 2022 ESC/ERS three-strata model:[1]

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Acute RV failure — the commonest mode of death

Acute right-heart failure is the commonest mode of death in advanced PH, the most feared perioperative complication, and the emergency where juniors kill patients by intubating them. It is precipitated by intercurrent infection, anaesthesia and positive-pressure ventilation, pulmonary embolism, withdrawal of PAH therapy, atrial fibrillation or flutter, pregnancy, or volume overload.[1]

The single rule: avoid intubation and positive pressure wherever possible. Positive-pressure ventilation raises RV afterload, lowers RV preload, and worsens RV ischaemia — the patient with pulmonary hypertension who deteriorates after intubation has a mortality above 50 percent in most series. Pre-oxygenate, sit the patient up (the right ventricle wants a low afterload and a high preload), use non-invasive ventilation (CPAP 5 to 10 cm water) if needed, and intubate only as a last resort with a vasopressor already running.[1]

The resuscitation bundle, in order:[1]

• Treat the trigger — source control for sepsis, cardiovert the new atrial fibrillation, restart the discontinued prostacyclin, consider pulmonary-embolism response.
• Volume — RV filling is critical but excess volume worsens RV dilation and tricuspid regurgitation. If the JVP is not raised, a cautious 250 mL crystalloid challenge; if the JVP is raised, furosemide 40 mg IV (escalate to 80 mg IV then a continuous infusion 5 to 20 mg per hour), aiming for right atrial pressure at or below 8 mmHg.
• Vasopressor — noradrenaline 0.05 to 1.0 mcg/kg/min titrated to MAP above 65 mmHg to defend right coronary perfusion; vasopressin 0.5 to 4 mU/kg/min if noradrenaline fails.
• Inotrope — dobutamine 2 to 10 mcg/kg/min or milrinone 0.125 to 0.75 mcg/kg/min for RV contractility; milrinone lowers PVR and SVR, so combine with a vasopressor if hypotensive.
• Pulmonary vasodilator — inhaled nitric oxide 10 to 40 ppm, inhaled iloprost 5 mcg 6 to 9 times daily, or IV epoprostenol 1 to 2 ng/kg/min titrated to 10 to 20 ng/kg/min — the rescue agent of choice for an acute PAH crisis.
• Mechanical support — VA-ECMO as a bridge to recovery or transplant for refractory acute RV failure; an RVAD for persistent isolated RV failure.[1]

The preventable-harm list — every item is a real death that did not need to happen:[1]

• The PH patient intubated electively who arrests on induction — positive pressure collapsed the RV.
• PAH-specific drugs given to Group 2 left-heart PH, worsening gas exchange for no benefit.
• The missed CTEPH — no V/Q scan, no endarterectomy, a curable disease left to progress.
• The vasodilator given to PVOD, precipitating pulmonary oedema.
• The woman with known PAH who becomes pregnant against advice, with maternal mortality up to 30 to 50 percent.[1]

Group 1 PAH — risk-stratified combination therapy

The default in treatment-naive low- or intermediate-risk Group 1 PAH is upfront oral combination therapy with an endothelin-receptor antagonist plus a phosphodiesterase-5 inhibitor — established by AMBITION, where initial ambrisentan plus tadalafil halved clinical-failure events versus either monotherapy.[3]

The drug-dose cluster for initial combination therapy:[3]

• Endothelin-receptor antagonists — ambrisentan 5 to 10 mg daily (minimal LFT monitoring), bosentan 62.5 mg twice daily for 4 weeks then 125 mg twice daily (monthly LFTs; avoid if transaminases above 3 times the upper limit), or macitentan 10 mg daily (no LFT monitoring).
• Phosphodiesterase-5 inhibitors — sildenafil 20 mg three times daily or tadalafil 40 mg daily; avoid co-administration with nitrates.
• Soluble guanylate-cyclase stimulator — riociguat 1 mg three times daily, titrated by 0.5 mg every 2 weeks to a maximum of 2.5 mg three times daily (avoid in pregnancy; do not combine with a PDE5i).[3]

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Escalation at follow-up: add oral selexipag (the selective IP-receptor agonist, 200 mcg twice daily titrated in 200 mcg increments to a maximum of 1600 mcg twice daily) per GRIPHON, which reduced the morbidity-mortality composite when added to background ERA with or without PDE5i. For high-risk disease or rapid progression, escalate straight to parenteral prostacyclin — IV epoprostenol continuous infusion starting at 1 to 2 ng/kg/min titrated to 10 to 20 ng/kg/min — the only PAH therapy proven to improve survival in a randomised trial (Barst et al, 1996).[4]

The calcium-channel blockers go only to the vasoreactive 5 percent — high-dose amlodipine, nifedipine, or diltiazem (doses above), restricted to idiopathic, heritable, or drug-induced PAH with a positive vasoreactivity test. Giving them to non-responders does nothing; giving them to Group 2 or CTD-PAH does harm.[1]

Supportive measures for all groups — oxygen to keep SpO2 above 92 percent in PAH (above 90 percent in CTEPH and lung-disease PH), diuretics (furosemide 40 mg once or twice daily with spironolactone 25 to 50 mg daily), supervised rehabilitation, iron replacement if deficient, vaccination, anticoagulation (warfarin INR 2.0 to 3.0) controversial and reserved for idiopathic, heritable, or drug-induced PAH — and pregnancy avoidance.[1]

Groups 2 to 5 — treat the cause, not the pressure

For Groups 2, 3, and 5 the cause is the treatment. PAH-specific therapy has no role until the group is confirmed and the cause addressed first.[1]

• Group 2 — left-heart disease: optimise GDMT, repair valves, diurese cautiously. PAH-specific therapy is not indicated (negative trials in HFrEF and HFpEF).
• Group 3 — lung disease or hypoxia: treat the lung — oxygen for at least 15 hours per day for chronic hypoxaemia in COPD, bronchodilators, CPAP for OSA. PAH-specific therapy is unproven; a case-by-case trial of inhaled treprostinil in ILD-PH in selected centres.
• Group 5 — multifactorial: treat the underlying cause (sickle cell, sarcoidosis, myeloproliferative disease, thyroid, dialysis).[1]

Group 4 — CTEPH is different, because it is the only potentially curable PH. Defined as pre-capillary PH (mPAP above 20 mmHg, PAWP at or below 15 mmHg) with mismatched perfusion defects on V/Q and signs of organised thrombus on CTPA more than 3 months after adequate anticoagulation. Pulmonary endarterectomy (PEA) is first-line and potentially curable — every CTEPH patient is referred to a PEA-capable centre. For inoperable or residual disease after PEA, riociguat 1 mg three times daily titrated to 2.5 mg three times daily (the only licensed medical therapy, per CHEST-1); balloon pulmonary angioplasty (BPA) for distal disease in expert centres.[5]

The trials you must name

Five trials carry the evidence base for PAH and CTEPH therapy; an examiner expects you to name each and what it changed.[3]

• AMBITION (Galie, NEJM 2015) — initial ambrisentan plus tadalafil halved clinical-failure events versus either monotherapy in treatment-naive PAH. The basis of upfront oral combination therapy.
• GRIPHON (Sitbon, NEJM 2015) — selexipag reduced the morbidity-mortality composite in PAH when added to background ERA with or without PDE5i. The basis of oral triple therapy.
• CHEST-1 (Ghofrani, NEJM 2013) — riociguat improved 6MWD in inoperable or residual CTEPH. The only licensed medical therapy for CTEPH.
• SERAPHIN (Pulido, NEJM 2013) — macitentan reduced morbidity and mortality in PAH.
• Barst et al (NEJM 1996) — epoprostenol improved survival in class III to IV idiopathic PAH; the only PAH drug with a proven survival benefit in a randomised trial.[3][4][5]

Special populations — scleroderma, pregnancy, portopulmonary, Eisenmenger

Systemic sclerosis is the single most important associated condition in Group 1 PAH. PAH develops in 8 to 12 percent, mortality is higher than in idiopathic PAH, and annual echocardiographic screening with TR Vmax plus annual DLCO is the surveillance standard — a falling DLCO can precede the rise in TR Vmax.[2]

Pregnancy is contraindicated in Group 1 PAH. Maternal mortality in published series is 30 to 50 percent, even with modern therapy. Pre-conception counselling and long-acting contraception (levonorgestrel intrauterine system, sterilisation) are mandatory. If pregnancy occurs, multidisciplinary counselling about termination; if continued, planned admission to a PH centre in the second trimester, parenteral epoprostenol titrated upward, planned caesarean under epidural with ECMO on standby, and avoidance of ergometrine.[1]

Portopulmonary hypertension (Group 1.4.2) — PAH in 2 to 6 percent of patients with portal hypertension. Severe PH (PVR above 3 WU or mPAP above 35 mmHg) excludes liver-transplant candidacy because perioperative mortality is prohibitive. Sildenafil and tadalafil are first-choice (avoid ERAs in cirrhosis for hepatotoxicity); parenteral epoprostenol as a bridge to transplant.[1]

Eisenmenger syndrome (Group 1.4.3) — uncorrected large left-to-right shunts (VSD, PDA, ASD) that reverse to right-to-left after PVR exceeds systemic vascular resistance. Central cyanosis, finger clubbing, polycythaemia, paradoxical embolism (stroke, brain abscess), and hyperviscosity. PAH-specific therapy (bosentan or tadalafil) improves symptoms and 6MWD; avoid systemic vasodilators that worsen the right-to-left shunt; venesection only for severe hyperviscosity; pregnancy is contraindicated; transplant is heart-lung or bilateral lung with defect repair.[1]

The mantra, and the mnemonic

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The mantra: echo screens, RHC confirms, classify by group, treat by group, never intubate the failing right ventricle, and never miss CTEPH.[1]

Ward-round test — three stems

Three stems, thirty seconds each. Answer before you open the reveal.[1]

Stem 1 — the young woman with syncope on exertion (answer)

A 34-year-old woman has eighteen months of progressive exertional dyspnoea, two episodes of near-syncope carrying groceries, a normal chest examination, and an echo showing TR Vmax 3.7 m/s with RV dilation. What is the next step, and what must you NOT do? Model: This is suspected pulmonary arterial hypertension (Group 1) until proven otherwise — a TR Vmax above 3.4 m/s puts her in high echo probability. The next step is right heart catheterisation to confirm mPAP above 20 mmHg, PAWP at or below 15 mmHg, PVR above 2 WU, and to test vasoreactivity — plus a V/Q scan to exclude CTEPH and an autoimmune screen for scleroderma. Do NOT start PAH-specific therapy on the echo alone, and do NOT allow pregnancy. Syncope on exertion is a high-risk feature — she needs a PH centre, not a clinic appointment next month.[1]

Stem 2 — the deteriorating PH patient on the ward (answer)

A 58-year-old with known idiopathic PAH on ambrisentan plus tadalafil is admitted with sepsis and becomes hypoxic and hypotensive. The registrar wants to intubate. What is the right call? Model: This is acute right-heart failure — the commonest mode of death in PH. Do not intubate if it can be avoided: positive pressure will raise RV afterload, drop RV preload, and worsen RV ischaemia, with a post-intubation mortality above 50 percent. Sit her up, pre-oxygenate, try CPAP 5 to 10 cm water, treat the sepsis (the trigger), give a cautious fluid challenge only if the JVP is not raised, furosemide 40 mg IV if it is, noradrenaline titrated to MAP above 65 mmHg for right coronary perfusion, dobutamine or milrinone for inotropy, and inhaled nitric oxide or IV epoprostenol for selective pulmonary vasodilation. VA-ECMO as a bridge if refractory. If intubation becomes unavoidable, have the vasopressor running first and use a low tidal volume, low PEEP lung-protective vent.[1]

Stem 3 — dyspnoea six months after a pulmonary embolism (answer)

A 62-year-old presents with progressive dyspnoea six months after an unprovoked pulmonary embolism, clear lung fields, a loud P2, and a raised JVP. What is the single most important investigation, and what is the potentially curative treatment? Model: This is chronic thromboembolic pulmonary hypertension (Group 4) until proven otherwise — CTEPH develops in about 4 percent of PE survivors. The single most important investigation is a V/Q scan (more sensitive than CTPA for chronic organised thrombus); mismatched segmental perfusion defects confirm the diagnosis, and right heart catheterisation confirms pre-capillary PH. The potentially curative treatment is pulmonary endarterectomy (PEA) at a specialist centre — the only curative therapy in PH. For inoperable or residual disease, riociguat 1 mg three times daily titrated to 2.5 mg three times daily (CHEST-1) or balloon pulmonary angioplasty for distal lesions.[5]

References

1. [1]Humbert M, Kovacs G, Hoeper MM, et al. 2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Heart J, 2022.PMID 36017548
2. [2]Simonneau G, Montani D, Celermajer DS, et al. Haemodynamic definitions and updated clinical classification of pulmonary hypertension. Eur Respir J, 2019.PMID 30545968
3. [3]Galiè N, Barberà JA, Frost AE, et al. Initial Use of Ambrisentan plus Tadalafil in Pulmonary Arterial Hypertension. N Engl J Med, 2015.PMID 26308684
4. [4]Sitbon O, Channick R, Chin KM, et al. Selexipag for the Treatment of Pulmonary Arterial Hypertension. N Engl J Med, 2015.PMID 26699168
5. [5]Ghofrani HA, D'Armini AM, Grimminger F, et al. Riociguat for the treatment of chronic thromboembolic pulmonary hypertension. N Engl J Med, 2013.PMID 23883377