Pathophysiologic Principles in the Management of Severe PAH

In the face of tremendous advances in our understanding of the pathophysiology and new treatment options, for many patients, pulmonary arterial hypertension (PAH) remains a progressive condition. The often-relentless reduction in the cross-sectional area of the pulmonary vasculature leads to progressive increase in right ventricular (RV) afterload. Although the right ventricle can adapt to an increase in afterload, progression of the pulmonary vasculopathy in PAH causes many patients to develop progressive RV failure.1 Alternately, for those with other forms of pulmonary hypertension, worsening lung disease or cardiac disease may destabilize the RV function. Acute RV decompensation may be triggered by disorders that lead to either an acute increase in cardiac demand (such as sepsis, surgery, or pregnancy), or an increase in ventricular afterload (such as an interruption in medical therapy or pulmonary embolism), or destabilization of a compensated RV (such as arrhythmia or volume overload). The poor reserve of the RV, RV ischemia, and adverse RV influence on left ventricular filling may lead to a global reduction in oxygen delivery and multi-organ failure.2 The goals of this article are to provide an approach to right heart failure in the context of an increase in its afterload. This article will focus on pathophysiologic principles on which to build an approach to medical therapies. Mechanical and surgical strategies will be the focus in the accompanying article by Dr de Perrot.