Treatment
In general, if pulmonary hypertension occurs in association with other conditions, treatment of the primary disorder should be optimised first. Algorithms for the treatment of PAH vary around the world. Typically therapeutic agents specifically targeting pulmonary hypertension are given to those patients who are in Groups 1 and 4 and these who are in renal failure on dialysis. Advanced pulmonary vasodilation therapy is prescribed if the mean pulmonary artery pressure exceeds 25 mmHg and the mean pulmonary capillary wedge pressure is <15 mmHg. Such therapy is usually given to patients who are in World Health Organization (WHO) functional class II, III or IV.
There is concern that treating patients with pulmonary vasodilating agents whose left atrial filling pressure exceeds 15 mmHg will lead to increased venous return to the heart that in turn could lead to, or exacerbate, left heart failure.
There is little evidence to justify treating patients with advanced pulmonary vasodilator therapy who have pulmonary hypertension associated with lung disease. Those with obstructive sleep apnoea should have appropriate treatment e.g with nocturnal nasal continuous positive airway pressure (CPAP) and lifestyle advice and only have consideration given to treating pulmonary hypertension should it persist after standard therapies for sleep disordered breathing having been tried.
There is no effective cure for patients who develop PAH but specific targeted therapeutic agents have been shown to improve exercise capacity, WHO functional class, haemodynamic parameters and time to clinical worsening. Recently there has been a suggestion that a newer endothelin receptor antagonist (ERA) may be associated with improved survival although further studies are needed to confirm this. However, it is accepted that the prognosis for patients with PAH is improving.
Approximately 10 % of patients with PAH will respond to calcium channel blockers, and such patients will usually demonstrate reversibility (a reduction in mean pulmonary artery pressure by >10 mmHg to achieve an absolute value of <40 mmHg with an unchanged or increased cardiac output) at right heart catheterisation.
Sildenafil and tadalalfil are phosphodiesterase 5 inhibitors and act on the nitric oxide pathway to cause vasodilation. Sildenafil may also possess anti proliferative effects on vascular smooth muscle. A newer class of agents, soluble guanylate cyclase stimulators, reduce intracellular calcium in an NO dependant and independent fashion and have been used to treat patients with PAH and chronic thromboembolic pulmonary hypertension (CTEPH).
Endothelin levels are increased in PAH and relate to disease severity and prognosis. Different ERA can block one (A) or both of the endothelin receptors (A and B) to antagonise vasoconstriction and vascular remodelling promoted by excessive endothelin release.
The deficiency of endogenous prostacyclin can be addressed by administration of prostacyclin or its analogues by continuous intravenous (IV) infusion, by regular inhalational therapy or by subcutaneous injection. The precise role of combination therapies and the timing of their introduction into the therapeutic regime of the PAH patient is being evaluated. Other therapies under trial include lipid- lowering drugs, anti-inflammatory agents, monoclonal antibodies and anti-platelet agents.
Atrial septostomy is available for a small number of patients with class IV disease in an attempt to offload the failing right ventricle as a bridge to transplantation.
Thereisencouragingexperiencewithpulmonarythromboendarterectomy for selected patients with CTEPH. However, this is a major operation with a high (almost 50 %) complication rate. Bilateral lung transplantation is available for some patients with PAH but donor organ availability and the late complication of obliterative bronchiolitis remain major problems to be addressed.