Treating the right ventricle directly in pulmonary hypertension

Right ventricular failure due to pressure overload and increased wall stress is the cause of morbidity and mortality in patients with severe pulmonary arterial hypertension. While a significant drop in the afterload decreases the stress on the right ventricle (RV), drugs targeting pulmonary hypertension do not achieve a significant and lasting afterload reduction in all patients, and few patients mount a successful long-term adaptation to the increased load resulting in a robustly muscularized and well-perfused RV. Patients that lack this homeostatic resilience of the RV enter into a vicious cycle where inflammatory mediators and cells released by the sick lung circulation and a hyper-activated neuroendocrine system worsen RV function leading to a microvascular angiopathy, capillary rarefaction, and myocardial fibrosis. The presently used vasodilator drugs are unlikely to have significant direct effects on the myocardium with the exception of prostacyclin, which may exert anti-inflammatory and anti-fibrotic actions. Carvedilol, without reducing the PVR, has been shown to improve the RVEF in some patients with severe PAH. A number of catheter-guided and surgical procedures generate shunts and directly unload the RV. A therapy focused directly on the RV is likely to fail when the adaptive responses to the persistent stress of a high afterload, inflammation, and inadequate myocardial perfusion are impaired.