Pulmonary Hypertension

Primary Pulmonary Hypertension

⚠️ Pulmonary hypertension (PH) is a progressive condition of raised pulmonary artery pressures leading to right heart strain and failure. Early recognition is crucial as treatment can slow progression but rarely reverses disease.

📖 About

• Defined as mean pulmonary artery pressure (mPAP) > 25 mmHg at rest, > 30 mmHg with exercise.
• 🟣 Primary Pulmonary Hypertension (PPH) = no identifiable cause.
• Rare disease: ~2 cases per million per year.

⚙️ Aetiology & Pathophysiology

• ⬆️ Pulmonary vascular resistance → sustained pressure overload on right ventricle.
• Flow equal in systemic & pulmonary circuits (no shunts), but pulmonary bed is normally much larger.
• Imbalance: vasoconstriction, endothelial dysfunction, fibrosis & thrombosis → progressive narrowing.

🔗 Associations

• 💊 Appetite suppressants (e.g. fenfluramine).
• 🔥 Vasculitis affecting pulmonary vessels.
• 🤲 Connective tissue diseases (esp. systemic sclerosis).

🧬 Genetics

• Familial PH: autosomal dominant, often BMPR2 or ALK1 mutations.

📂 Classification

• 🟣 Pulmonary arterial hypertension (PAH).
• 🔵 Pulmonary venous hypertension (often left heart disease).
• 🟤 PH with respiratory disease or hypoxia (e.g. COPD, OSA, ILD).
• 🟠 PH due to chronic thromboembolic disease (CTEPH).
• 🟢 PH due to miscellaneous pulmonary vascular disorders.

🩺 Clinical

• Most common in 👩 women aged 20–30 years.
• Symptoms: progressive exertional breathlessness, fatigue.
• Signs: loud P2 🔊, RV heave, right-sided S3.
• JVP: prominent "a" & "v" waves; TR murmur (pansystolic).
• Pulmonary flow murmur may be heard.

🔍 Investigations

• 🧪 Bloods: FBC → polycythaemia; U&E for renal function.
• 📈 ECG: RVH, RBBB, P pulmonale.
• 📸 CXR: Enlarged pulmonary arteries, peripheral pruning.
• 🫀 Echo: RV dilatation, TR, pressure estimates.
• CT-PA: Rule out chronic thromboembolic disease.
• Pathology: Plexiform lesions, in situ thrombosis.

💊 Management

• Oxygen for hypoxia, diuretics for oedema, anticoagulation, digoxin (supportive).
• 🟢 Calcium channel blockers (high-dose nifedipine/amlodipine) if vasoreactive subset.
• 🟣 Prostacyclin analogues (Iloprost infusion/nebulised) for advanced disease (NYHA III/IV).
• 🔴 Endothelin receptor antagonists (e.g. Bosentan).
• 🟡 PDE-5 inhibitors (Sildenafil) → nitric oxide–like vasodilation.
• ⚪ Atrial septostomy (palliative, under evaluation).
• 🫁 Lung / heart-lung transplantation for end-stage cases.
• 👩‍🍼 Contraception strongly advised – pregnancy is contraindicated.
• Advice: avoid high altitude ✈️, restrict strenuous exercise.
• 🩸 Venesection if severe polycythaemia (symptomatic hyperviscosity).

📚 References

• ESC/ERS Guidelines on Pulmonary Hypertension
• NICE CKS: Pulmonary Hypertension

Cases - Primary Pulmonary Hypertension (Pulmonary Arterial Hypertension, PAH)

• Case 1 - Young woman with exertional symptoms 👩‍🦰: A 27-year-old previously healthy woman presents with 6 months of progressive exertional dyspnoea and fatigue. She has near-syncope on climbing stairs. Exam: loud P2, right ventricular heave, peripheral oedema. Echocardiogram: dilated RV, estimated pulmonary artery systolic pressure 70 mmHg. Right heart catheterisation confirms raised mean PAP. Diagnosis: idiopathic PAH. Managed with endothelin receptor antagonists and pulmonary vasodilators.
• Case 2 - Family history 🧬: A 33-year-old man with two relatives who died young of unexplained right heart failure presents with progressive breathlessness. Exam: raised JVP, hepatomegaly, ankle oedema. BNP elevated. CT pulmonary angiography normal (no thromboembolism). Genetic testing: BMPR2 mutation. Diagnosis: heritable PAH. Managed with specialist pulmonary hypertension unit input, prostacyclin analogues, and anticoagulation.
• Case 3 - Advanced disease with syncope ⚠️: A 42-year-old woman presents with recurrent syncope, chest pain, and worsening dyspnoea. Exam: cyanosis, loud P2, pansystolic murmur of tricuspid regurgitation. Echo: severe PAH with right atrial/ventricular enlargement. She is in right heart failure. Diagnosis: advanced primary PAH. Managed with oxygen, intravenous prostacyclin, and consideration of lung transplantation.

Teaching Point 🩺: Primary (idiopathic or heritable) pulmonary arterial hypertension is a rare, progressive disease of the pulmonary arterioles causing elevated pulmonary artery pressures and right heart failure. Presents with dyspnoea, syncope, chest pain, and signs of right-sided overload. Diagnosis confirmed with right heart catheterisation. Treatment includes endothelin receptor antagonists, phosphodiesterase-5 inhibitors, prostacyclin analogues, and transplant in advanced cases.

Secondary Pulmonary hypertension - Cor pulmonale

🫁 Shunts will always try to shift blood to the low-pressure pulmonary circulation, but this eventually causes pulmonary hypertension. PH is defined by a mean pulmonary artery pressure > 25 mmHg at rest (or > 30 mmHg on exercise).

📖 About

• 💔 Pulmonary hypertension (PH) / cor pulmonale = right heart failure due to lung disease, often linked to chronic hypoxia (e.g., COPD).
• 🫀 Cor pulmonale = secondary PH due to hypoxic vasoconstriction and vascular remodelling, most common in emphysema.
• 📊 Defined as chronic elevation of pulmonary artery pressure (> 25 mmHg at rest, > 30 mmHg on exercise; some use systolic PA pressure > 40 mmHg).

📌 Classification

• Group 1: Pulmonary arterial hypertension
• Group 2: Pulmonary venous hypertension (e.g., LV failure, mitral disease)
• Group 3: PH due to respiratory disease / hypoxia
• Group 4: PH due to thromboembolic disease
• Group 5: PH due to pulmonary vasculature disorders (miscellaneous)

🧬 Pathophysiology

• ⬆️ LV filling pressure with normal PVR (e.g., mitral stenosis)
• 🌐 Pulmonary vascular disease with elevated PVR (e.g., pulmonary embolism, CTEPH)
• 🌫️ Parenchymal lung disease with elevated PVR (e.g., diffuse lung fibrosis, COPD)
• 🌀 Combination of these mechanisms → sustained pulmonary hypertension

⚠️ Causes

• 🚬 COPD, emphysema
• 🌫️ Interstitial lung disease (e.g., IPF)
• 🫀 Idiopathic pulmonary hypertension
• 🩸 Multiple pulmonary emboli (CTEPH)
• 🫁 Congenital heart disease with Eisenmenger’s syndrome
• 💔 Mitral stenosis, LV failure, LA myxoma
• 🧬 Neuromuscular weakness (MND, muscular dystrophy)
• 🦴 Chest wall deformities (kyphoscoliosis)
• 🧪 Drugs (e.g., dexfenfluramine)
• 🧬 Sickle cell disease
• ⛰️ Living at high altitude (chronic hypoxia)

👀 Clinical Features

• 🏃 Progressive exertional dyspnoea (esp. in COPD)
• 🫀 Right heart strain → raised JVP, tricuspid regurgitation, loud P2, parasternal heave
• 💧 Fluid overload → peripheral oedema, ankle swelling, ascites (advanced)

🔎 Investigations

• 🩸 FBC: Polycythaemia from chronic hypoxia
• 🧪 U&E, LFTs, CRP: Baseline + comorbidity assessment
• 📉 ECG: RVH, RBBB, P pulmonale, RV strain
• 💨 ABG: Hypoxia ± hypercapnia (late)
• 🩻 CXR: Prominent pulmonary arteries, pruning of peripheral vessels
• 🫀 Echo: RV dilatation, TR, estimated PA pressures
• 🖥️ CT-PA: Evaluate for CTEPH, pulmonary emboli

💊 Management

• 💨 Long-term oxygen therapy (LTOT): Reduces hypoxaemia and pulmonary vasoconstriction; improves survival in COPD with PaO₂ ≤ 7.3 kPa.
• 💊 Anticoagulation: Indicated in recurrent emboli / atrial fibrillation / CTEPH.
• 💧 Diuretics: For oedema & ascites (caution: avoid over-diuresis → ↓ RV filling).
• 💊 Vasodilators / CCBs: Reserved for select idiopathic PH cases (specialist care).
• 🌬️ Treat underlying lung disease: COPD, ILD, etc.
• 🫁 Transplant: Consider in advanced refractory disease.
• 🌷 Palliative care: Symptom control (breathlessness, oedema, anxiety).

3 Clinical Cases - Secondary Pulmonary Hypertension 💓🫁

• Case 1 - Left heart disease (post-capillary PH) ❤️: A 72-year-old man with long-standing hypertension and heart failure with preserved ejection fraction (HFpEF) presents with worsening exertional dyspnoea and ankle swelling. Echo shows concentric LVH, diastolic dysfunction, dilated left atrium, and estimated pulmonary artery systolic pressure of 55 mmHg. Teaching: Left-sided heart disease is the most common cause of secondary PH. Chronically raised left atrial pressure is transmitted backward to the pulmonary vasculature → pulmonary venous hypertension.
• Case 2 - Chronic lung disease / hypoxia 🌫️: A 66-year-old ex-miner with advanced COPD reports worsening breathlessness, reduced exercise tolerance, and peripheral oedema. Oxygen saturation 86% on air. Echo shows dilated RV with moderate pulmonary hypertension. Teaching: Chronic hypoxaemia causes pulmonary vasoconstriction and vascular remodelling, leading to “cor pulmonale.” Long-term oxygen therapy improves survival in these patients.
• Case 3 - Chronic thromboembolic pulmonary hypertension (CTEPH) 🩸: A 59-year-old woman with a history of recurrent unprovoked DVTs and a pulmonary embolism 18 months ago reports progressive dyspnoea. V/Q scan shows multiple segmental perfusion defects; CT pulmonary angiography confirms organised chronic thrombus. Teaching: CTEPH is an important cause of secondary PH. It is potentially curable with pulmonary endarterectomy or balloon angioplasty, and all patients should be referred to a specialist centre.