Pulmonary Hypertension: Types and Causes

• Pulmonary hypertension (PH) is diagnosed when mean pulmonary artery pressure exceeds 25mmHg at rest, as determined by right heart catheterisation.
• PH is an umbrella term encompassing various diseases that elevate pressure in the pulmonary arteries.
• Pulmonary arterial hypertension (PAH) is a PH subtype characterized by pre-capillary pulmonary hypertension without identifiable causes like lung or systemic diseases.
• The UK prevalence of PH is 97 cases per million, with left heart disease being the most common cause.

Aetiology

• PH arises when pulmonary arteries narrow due to vasoconstriction or thrombosis, thicken, or become damaged, elevating pressure.
• Left heart disease can impede right heart flow, increasing pulmonary artery pressure.

PH Subtypes

• Pulmonary arterial hypertension (PAH): Can be idiopathic (IPAH), inherited, linked to systemic diseases like HIV or connective tissue disorders, or drug-induced (e.g., SSRIs).
• Pulmonary hypertension due to left heart disease: Includes left ventricular dysfunction (systolic and diastolic), valve disease, inflow/outflow obstruction, and congenital cardiomyopathies.
• Pulmonary hypertension due to lung disease: Caused by chronic obstructive pulmonary disease, interstitial lung disease, obstructive sleep apnoea, and prolonged high-altitude exposure.
• Chronic thromboembolic pulmonary hypertension (CTEPH): Results from vascular bed obstruction, typically from chronic pulmonary embolism. Rarer causes include arteritis and intravascular tumours.
• Pulmonary hypertension with unclear/multifactorial mechanisms: Associated with myeloproliferative disorders, sarcoidosis, glycogen storage disease, and chronic renal failure.

Risk Factors

• Risk factors correlate with PH subtype such as pre-existing lung disease, left or congenital heart disease, connective tissue disorders, obesity, sleep apnoea, and high altitude exposure.
• PAH risk factors include family history and female gender.

Symptoms

• PH symptoms stem from declining right ventricular function, initially during exertion, progressing to rest in severe cases.
• Common symptoms include shortness of breath, weakness, fatigue, chest pain, syncope, and haemoptysis (rare, but possible in chronic thromboembolic disease or due to abnormal blood flow).
• Family history of PAH and medication history including SSRIs and weight loss medications are important to note.

Examination Findings

• Cardiovascular examination is crucial in PH cases.
• Clinical signs include a loud S2, third heart sound, pansystolic murmur (tricuspid regurgitation), and diastolic murmur (pulmonary regurgitation).
• Later stages may involve ascites, peripheral oedema, parasternal heave, elevated jugular venous pressure, and hepatomegaly.
• Specific clinical features may indicate underlying diseases like connective tissue disease or interstitial lung disease.

Investigations

• Echocardiogram estimates pulmonary pressure.
• Right heart catheterisation is typically performed in suspected pulmonary arterial hypertension.

Bedside Investigations

• ECG can reveal right ventricular strain (hypertrophy, right axis deviation, right bundle branch block) and arrhythmias.
• A normal ECG does not rule out PH.

Laboratory Investigations

• Liver function tests assess for liver disease.
• Serology screens for HIV and hepatitis.
• Autoimmune screen checks for connective tissue disease markers like anti-centromere antibodies and U3-RNP in scleroderma.
• Arterial blood gas assesses respiratory function.

Imaging

• Chest X-ray detects underlying lung disease or left ventricular dysfunction signs such as pulmonary venous congestion.
• PAH may show central pulmonary arterial dilatation, peripheral vessel pruning, and right atrial/ventricular enlargement. A normal chest X-ray does not exclude PH.
• Echocardiography assesses right ventricular function and estimates pulmonary arterial pressure.
• Ventilation/perfusion (V/Q) scan and/or CT chest detect chronic thromboembolic disease or other lung diseases; CT can help with prognostication.
• Cardiac MRI evaluates cardiac structure and function and aids in prognostication.

Other Investigations

• Pulmonary function tests and overnight oximetry can identify underlying lung disease.
• PAH can cause mild to moderate lung volume reduction.
• Right heart catheterisation diagnoses PAH, assesses severity, and guides treatment.
• Genetic testing is used in select PAH patients.

Management

• Management focuses on treating the underlying cause of PH.
• Specialist referral is needed for PAH or severe PH.

Conservative Management

• Exercise (within symptom limits) and rehabilitation should be considered.
• Influenza and pneumococcal vaccination should be administered.
• Sex and contraception advice is important (pregnancy carries a 30-50% mortality risk for PAH patients).
• Psychosocial support should be provided.

Medical Management

• Medical management for PAH has uncertain long-term outcomes; options include:
  • Diuretics: For symptomatic relief in decompensated right heart failure.
  • Long term oxygen therapy: Including ambulatory oxygen.
  • Digoxin: Improves cardiac output acutely but has unknown long-term efficacy.
  • Oral anticoagulation: Due to increased thrombosis risk from the disease and comorbid factors. -Specific drug therapy: calcium channel blockers, endothelin receptor antagonists (i.e. bosentan), phosphodiesterase inhibitors (e.g. sildenafil), prostanoids and prostacyclin analogues.

Cardiopulmonary Transplantation

• Cardiopulmonary transplant may be needed in selected cases.
• There is a good prognosis with long term immunosuppressive therapy.

Complications

• Worsening right heart failure can cause peripheral oedema, and severe exertional dyspnoea.
• Pneumonia and sudden cardiac death (including during childbirth) are possiblities.
• Prognosis varies with the underlying disorder.
• The prognosis for untreated idiopathic PAH is at least 5 years.
• PAH with systemic sclerosis has a worse prognosis.