Respiratory : Pulmonary Vascular Disease

• Pulmonary embolism: PE: Anticoagulation and Follow-up | Chronic Thromboembolic Pulmonary Hypertension
• Pulmonary hypertension: Pulmonary Hypertension: Overview | Investigating Pulmonary Hypertension | Pulmonary Arterial Hypertension | PH from Heart and Lung Disease | Pulmonary AVMs and Liver-related Lung Disease
• Revision: Drug Reference Table | Spot the Diagnosis | Exam-style Scenarios | Key Points | Guidelines and Further Reading

🌙 Pulmonary vascular and sleep disorders cover the "plumbing" and the "control" of breathing: blood clots and high pressure in the lung circulation, and conditions in which breathing fails during sleep. They are often missed because the lungs look normal on a chest X-ray. This chapter also covers home oxygen, flying and altitude. Acute PE is covered in the Respiratory and Cardiac Emergencies chapters.
Your four questions for every patient: Is there unexplained breathlessness with a normal chest X-ray and spirometry (think pulmonary vascular disease)? Is the right heart under strain? Is breathing failing at night (snoring, sleepiness, morning headaches)? Is the patient safe to drive and to fly?

PE: Anticoagulation and Follow-up

Choice of anticoagulant (NICE NG158):

• Most patients: A DOAC - apixaban or rivaroxaban (no heparin lead-in needed), or LMWH then dabigatran or edoxaban.
• Cancer-associated VTE: A DOAC is usually offered. LMWH is used if a DOAC is unsuitable - for example GI or genitourinary cancers with bleeding risk, or drug interactions.
• Antiphospholipid syndrome (especially triple-positive): Warfarin (INR 2–3) - DOACs are less effective.
• Pregnancy: LMWH (warfarin and DOACs are contraindicated).
• Severe renal impairment or extremes of weight: LMWH, unfractionated heparin or warfarin, depending on the situation.

Duration:

• Provoked PE (major surgery, trauma, immobility, pregnancy - with the risk factor now gone): 3 months.
• Unprovoked PE: At least 3 months, then consider long-term anticoagulation. Weigh recurrence risk against bleeding risk (e.g. using an ORBIT-type assessment), and the patient's preference.
• Active cancer: Usually 3–6 months or longer, while the cancer is active.
• Recurrent VTE: Usually lifelong.

Investigations after unprovoked PE:

• History, examination, basic bloods and chest X-ray to look for cancer. Do not routinely do extensive cancer screening (e.g. CT abdomen).
• Thrombophilia testing is not routinely needed. Consider antiphospholipid antibody testing if stopping anticoagulation is being considered, or there is a suggestive history. Consider hereditary thrombophilia testing in people with a strong family history.

Follow-up at 3 months:

• Review symptoms, bleeding and the duration plan.
• Persistent breathlessness or exercise limitation after PE should prompt an echo and a V/Q scan, to look for chronic thromboembolic disease.

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Chronic Thromboembolic Pulmonary Hypertension

• What it is: Clots from a PE fail to dissolve and turn into fibrous scar tissue that blocks the pulmonary arteries. Pressure rises and the right heart fails. It follows about 2–4% of acute PEs, and some patients have no known PE.
• Suspect it: Breathlessness that persists or worsens 3–6 months or more after a PE despite anticoagulation, or unexplained pulmonary hypertension.
• Diagnosis:
  • V/Q scan - the best screening test. A normal V/Q scan effectively rules it out.
  • Echo - pulmonary hypertension.
  • CT pulmonary angiography - webs, bands, narrowing.
  • Right heart catheter - confirms PH.
  • After at least 3 months of anticoagulation.
• Treatment (UK national CTEPH service):
  • Pulmonary endarterectomy - surgery that removes the scar tissue. It can be curative.
  • Balloon pulmonary angioplasty for inoperable distal disease.
  • Riociguat (a soluble guanylate cyclase stimulator) for inoperable or residual disease.
  • Lifelong anticoagulation.

💡 Clinical Pearl: CTEPH is the one form of pulmonary hypertension that can be cured by surgery - so always screen for it with a V/Q scan when PH is found, and in anyone who stays breathless after a PE.

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Pulmonary Hypertension: Overview

Definition (ESC/ERS 2022): A mean pulmonary artery pressure above 20 mmHg at rest, measured by right heart catheterisation.

• Pre-capillary PH (the problem is in the lung arteries): Also has a pulmonary vascular resistance above 2 Wood units and a normal left-sided (wedge) pressure.
• Post-capillary PH (backlog from the left heart): A raised wedge pressure (above 15 mmHg).

The five groups:

• Group 1 - Pulmonary arterial hypertension (PAH): Disease of the small pulmonary arteries - idiopathic, heritable, drugs, connective tissue disease, HIV, portal hypertension, congenital heart disease.
• Group 2 - Left heart disease - the commonest. Heart failure (including with preserved EF) and mitral or aortic valve disease.
• Group 3 - Lung disease and hypoxia: COPD, ILD, sleep-disordered breathing, altitude.
• Group 4 - Pulmonary artery obstruction: Mainly CTEPH.
• Group 5 - Unclear or multifactorial: Sarcoidosis, haemolytic anaemias (sickle cell), myeloproliferative disease, CKD on dialysis.

Clinical pattern:

• Exertional breathlessness and fatigue - often attributed to other causes for years.
• Exertional chest pain or syncope (a warning sign of severe disease).
• Signs of right heart strain:
  • Loud P2.
  • Right ventricular heave.
  • Raised JVP (large V waves from tricuspid regurgitation).
  • Ankle oedema, ascites, hepatomegaly.
• Signs of the cause - clubbing (ILD, congenital heart disease), sclerodactyly, signs of liver disease.

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Investigating Pulmonary Hypertension

• Echocardiogram - the key screening test:
  • Estimates the probability of PH (tricuspid regurgitation velocity, RV size and function).
  • Shows left heart disease, valve disease and shunts.
• ECG: Right axis deviation, RV hypertrophy and strain, P pulmonale, RBBB.
• Chest X-ray: Enlarged pulmonary arteries, "pruning" of peripheral vessels, lung disease.
• NT-proBNP - for severity and prognosis.
• Lung function: A disproportionately low TLCO in PAH; restriction or obstruction in group 3.
• V/Q scan - to look for CTEPH (in everyone with unexplained PH).
• CT chest - lung disease, PE, pulmonary artery size.
• Bloods: Autoimmune screen (systemic sclerosis), HIV, LFTs (portal hypertension), TFTs, haemoglobinopathy screen.
• Overnight oximetry or sleep study if sleep apnoea or hypoventilation is suspected.
• Right heart catheterisation at a specialist PH centre to confirm the diagnosis, measure severity and test vasoreactivity.

💡 Clinical Pearl: Unexplained breathlessness with a normal chest X-ray and normal spirometry, but a low TLCO, should make you think of pulmonary vascular disease - order an echo and a V/Q scan.

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Pulmonary Arterial Hypertension

Mechanism: The small pulmonary arteries thicken, constrict and become blocked (vascular remodelling). Resistance rises until the right ventricle fails. Untreated, median survival is only a few years.

Causes:

• Idiopathic - often young to middle-aged women.
• Heritable - BMPR2 mutations; screen relatives.
• Drugs and toxins - appetite suppressants (fenfluramine), methamphetamine, dasatinib, interferon.
• Connective tissue disease - especially systemic sclerosis (limited, anticentromere) - screen yearly with echo, lung function and NT-proBNP.
• HIV.
• Portal hypertension (portopulmonary hypertension).
• Congenital heart disease - left-to-right shunts. Untreated, they can reverse, causing cyanosis - Eisenmenger syndrome.
• Schistosomiasis (worldwide).

Treatment (only at UK specialist PH centres):

• General:
  • Diuretics for fluid overload.
  • Oxygen for hypoxaemia.
  • Supervised exercise.
  • Vaccinations.
  • Iron replacement.
  • Avoid pregnancy - very high maternal mortality - so effective contraception is essential.
• Vasoreactivity testing during right heart catheterisation: A small number of patients (mostly idiopathic PAH) respond to high-dose calcium channel blockers.
• PAH-specific drugs (often combined from the start):
  • Endothelin receptor antagonists - ambrisentan, bosentan, macitentan. They are teratogenic, and bosentan needs LFT monitoring.
  • PDE5 inhibitors - sildenafil, tadalafil. Do not combine with nitrates (severe hypotension).
  • Soluble guanylate cyclase stimulator - riociguat (not with PDE5 inhibitors).
  • Prostacyclin pathway - oral selexipag; inhaled iloprost; continuous IV or subcutaneous epoprostenol or treprostinil for severe disease.
  • Sotatercept (an activin signalling inhibitor) - a newer add-on that targets vascular remodelling.
• Lung (or heart–lung) transplantation for those failing medical treatment.

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PH from Heart and Lung Disease

• Group 2 (left heart disease):
  • The commonest cause of PH - often older people with hypertension, AF, diabetes and obesity (heart failure with preserved EF).
  • Treat the heart - diuretics, valve repair, AF control.
  • PAH drugs are not recommended and can be harmful.
• Group 3 (lung disease and hypoxia):
  • COPD, ILD, combined fibrosis and emphysema, obesity hypoventilation, OSA.
  • Usually mild to moderate. Treat the lung disease and correct hypoxaemia (long-term oxygen).
  • Severe disproportionate PH needs specialist referral.
• Cor pulmonale: Right heart failure caused by lung disease - peripheral oedema, raised JVP and hypoxaemia. Treat with oxygen if eligible, diuretics, and the underlying cause.

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Pulmonary AVMs and Liver-related Lung Disease

• Pulmonary arteriovenous malformations (AVMs):
  • What they are: Abnormal direct connections between pulmonary arteries and veins, bypassing the lung capillaries - a right-to-left shunt.
  • Cause: Most are due to hereditary haemorrhagic telangiectasia (HHT) - recurrent nosebleeds, telangiectasia on the lips, tongue and fingers, GI bleeding and a family history.
  • Problems:
    • Hypoxaemia, cyanosis, clubbing, polycythaemia.
    • Paradoxical embolism - stroke and brain abscess (clots and bacteria bypass the lung filter).
    • Haemoptysis and haemothorax.
  • Diagnosis: Contrast (bubble) echo, then CT.
  • Treatment: Embolisation.
  • Precautions: Antibiotic prophylaxis before dental and other procedures; IV line air filters; screen family members.
• Hepatopulmonary syndrome:
  • Liver disease with dilated lung capillaries, causing hypoxaemia.
  • Platypnoea (breathlessness when sitting up) and orthodeoxia (falling oxygen when upright).
  • Contrast echo shows a delayed shunt.
  • Resolves after liver transplant.
• Portopulmonary hypertension: PAH in people with portal hypertension. Severe disease can make liver transplant unsafe - screen transplant candidates with echo.

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Drug Reference Table

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Spot the Diagnosis

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Exam-style Scenarios

1. A 48-year-old man had an unprovoked PE 3 months ago and is on apixaban. He has no bleeding risk factors.
Answer: Unprovoked PE.

• Discuss long-term anticoagulation (e.g. continuing apixaban, possibly at the reduced 2.5 mg dose after 6 months).
• Assess bleeding risk and preference.
• If still breathless: echo and V/Q scan to look for CTEPH.

2. A 38-year-old woman has 2 years of worsening exertional breathlessness and a recent faint while climbing stairs. Chest X-ray and spirometry are normal; TLCO is 48%; echo shows a high probability of PH.
Answer: Suspected pulmonary arterial hypertension.

• V/Q scan (exclude CTEPH); autoimmune screen, HIV, LFTs.
• Refer to a specialist PH centre for right heart catheterisation and treatment.
• Contraception advice - pregnancy is dangerous.

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Key Points

• Most PE: DOAC for 3 months if provoked; consider long-term if unprovoked. Warfarin for antiphospholipid syndrome; LMWH in pregnancy.
• Persistent breathlessness after PE: echo and V/Q scan for CTEPH - potentially curable by pulmonary endarterectomy.
• Pulmonary hypertension: mean PAP above 20 mmHg on right heart catheter. The commonest causes are left heart and lung disease.
• Normal chest X-ray and spirometry with a low TLCO: think pulmonary vascular disease.
• PAH is treated only in specialist centres: ERAs, PDE5 inhibitors, riociguat, prostacyclin drugs. Avoid pregnancy; never combine PDE5 inhibitors with nitrates.
• HHT: pulmonary AVMs cause stroke and brain abscess - embolise; antibiotic prophylaxis.

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Guidelines and Further Reading

• NICE NG158: Venous thromboembolic diseases - diagnosis, management and thrombophilia testing
• ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension (2022)
• NHS England: National pulmonary hypertension service specification

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