10th March 2024

Group 1: Pulmonary Arterial Hypertension

Pulmonary Arterial hypertension (PAH) is a rare disease which is idiopathic in about 50% of cases. It is typically a disorder of younger individuals, and females are affected more than males. Pathophysiologically, PAH is a proliferative vasculopathy characterised by extensive vasoconstriction, fibrosis, and micro-thrombosis. Some medications have been identified as definite risk factors for developing PAH (methamphetamines, rapeseed oil, benfluorex), while others represent possible risk factors (chronic use of cocaine, amphetamines, interferon therapy, and dasatinib). Other common conditions that can be associated with PAH include connective tissue diseases and HIV, and for this reason, all patients presenting with idiopathic PAH should be screened for these. A subset of patients also present with hereditary forms of PAH.

Diagnosis is confirmed by right heart catheterisation. Alternative tests need to be carried out at the same time to rule out other causes of pulmonary hypertension or concomitant pathology.

Treatment for this subgroup of pulmonary hypertension is different from the other ones in that there are evidence-based PH-targeted treatments available. Choosing what treatment regimen should be used is based on the patient’s WHO performance scale and whether their vasculature is vasoreactive on acute vasoreactivity testing. Some of the medications that are commonly used include:

• Calcium-channel blockers (long-acting nifedipine, diltiazem): these should be offered only to patients that have been positive on acute vasoreactivity testing. These are usually patients that have idiopathic PAH, hereditary PAH, or drug-related PAH. About half of the vasoreactive patients respond to CCB therapy, though the response is usually short-lived, and they may require the addition of another agent of a different class.
• Phosphodiesterase-5 inhibitors (sildenafil, tadalafil): agents in this class enhance the production or function of nitric oxide, a potent vasodilator.
• Endothelin receptor antagonist (ambrisentan, bosentan): endothelin-1 is a potent vasoconstrictor and smooth muscle mitogen. These medications target both endothelin receptors A and B, thus causing vasodilation. The main side effects are hepatotoxicity, peripheral oedema, and they are potent teratogens. 
• Parenteral prostanoids (epoprostenol): synthetic analogue prostacyclin
• Inhaled prostanoid (iloprost): prostacyclin analogue, it has the advantage that it specifically targets the lung vasculature and does not require intravenous administration. The main disadvantage is the need for frequent administration as it needs to be administered up to nine times per day.

PAH is a progressive disease, and in some cases, patients may progress to a point where they are refractory to PAH-specific therapy. One temporising measure is the creation of a right-to-left shunt. Lung transplantation is a definitive form of therapy and should be offered if the patient meets the following criteria:

• WHO functional class III or IV during escalating therapy
• Rapidly progressive disease
• Use of parenteral prostanoid therapy (independent of WHO classification)

Bilateral lung or heart-lung transplantation is the procedure of choice.