17th January 2024

Management

Group 1 – Pulmonary Arterial Hypertension

Supportive

• Oral anticoagulation is indicated due to increased risk of VTE in this patient group
• Supplemental oxygen as required to aim of pO2 >8kPa
• Correct iron deficiency anaemia
• Diuretic therapy for clinically fluid-overloaded patients
• Treatment of co-existing atrial arrhythmias; digoxin is often the drug of choice
• Counsel patients regarding substantial mortality associated with pregnancy and offer appropriate birth control
• Offer routine influenza and pneumococcal vaccinations
• Encourage physical activity within symptom limits

Disease-modifying pharmacological therapy, used as both monotherapy and in combination:

• Calcium channel blocker therapy
  • Both dihydropyridine (amlodipine; nifedipine) and non-dihydropyridine (diltiazem) CCBs are used, depending on baseline heart rate.
  • Can be used only in patients shown to be responsive to vasodilator therapy when tested during right heart catheterization
• Endothelin receptor antagonists
  • Work by interfering with the endothelin pathway, blocking pulmonary vascular smooth muscle vasoconstriction
  • Taken as oral agents, they have been shown to improve exercise capacity as well as echocardiographic and haemodynamic measurements.
  • Examples include bosentan, ambrisentan (both of which require monthly liver function test monitoring) and macitentan
• Phosphodiesterase type 5 inhibitors
  • Work by preventing degradation of the enzyme cyclic guanosine monophosphate (cGMP), resulting in pulmonary vasodilation
  • Examples include sildenafil, tadalafil and vardenafil, all of which are oral agents originally approved for use in erectile dysfunction.
  • Shown to improve exercise tolerance as well as echocardiographic and haemodynamic measurements
• Prostacyclin analogues and prostacyclin receptor agonists
  • Endothelial cells produce prostacyclin, which acts as a potent vasodilator of the pulmonary vascular bed. Synthetic prostacyclins have the same effect.
  • Epoprostenol is a synthetic prostacyclin, which is the only treatment shown to have a mortality benefit when used in idiopathic PAH (although other similar agents include iloprost and treprostinil). The half-life of epoprostenol is very short, at only 3-5 minutes, necessitating it to be administered as a continuous IV infusion, which should not be abruptly stopped. This is associated with infection risks of having a long-term central venous catheter in situ, as well as a side effect profile of flushing, diarrhoea, headache and jaw pain.
  • Selexipag is an oral prostacyclin receptor agonist proven to reduce pulmonary arterial hypertension.

Interventional

• Balloon atrial septostomy – the intentional creation of an atrial septal defect to allow for right-to-left shunting and decompression of the high-pressure right heart and increase cardiac output. This procedure is used very rarely, either as a palliative measure or bridge to lung transplant.
• Lung transplantation – bilateral lung transplantation in PAH patients can have up to 75% 5-year survival rates.
• Bronchial artery embolisation – can be used to symptomatically control severe haemoptysis.

Group 2 – pulmonary hypertension due to left heart disease

The primary goal of treatment here is to optimise the underlying condition, for example, valve replacements or heart failure therapies where indicated. The use of specific therapies approved in PAH is not evidenced in group 2 disease.

Group 3 – pulmonary hypertension due to lung disease

Appropriate treatment of the primary lung disease, with additional oxygen supplementation for hypoxaemia, is the goal of treatment. Similarly to group 2 disease, there is no evidence for the effectiveness of any disease-modifying therapy in this subtype.

Group 4 – chronic thromboembolic pulmonary hypertension

Medical

Lifelong anticoagulation is the mainstay of medical management for CTEPH, even if surgical intervention takes place. In patients deemed not fit for surgical intervention, anticoagulation alone is recommended.

Surgical

Pulmonary endarterectomy is the gold-standard treatment of choice for CTEPH. There is proven to be a substantial benefit both symptomatically and haemodynamically post-operatively, with patients debilitated by breathlessness often able to return to normal functioning. However, the procedure is performed with the patient in a hypothermic state under induced circulatory arrest, so not all CTEPH patients would be appropriate candidates. In patients with co-existing coronary artery disease, bypass grafting can be performed simultaneously.

Group 5 – pulmonary hypertension with unclear or multifactorial aetiology

Like with group 2 and group 3 cases, the primary aim should be rigorous diagnostic investigations to try and establish the underlying cause and treat this accordingly. There are no specific disease-modifying therapies in this group.