Abstract and Introduction
Abstract
Pulmonary arterial hypertension (PAH) is a vascular remodeling disease that pathologically increases pulmonary vascular resistance. Ultimately, this leads to right ventricular failure and premature death. Current therapeutic strategies are mainly designed to induce relaxation of the pulmonary arteries, but are not directly aimed to improve vascular remodeling that characterize PAH. Although these treatments modestly improve patient symptoms, pulmonary hemodynamics and survival, none of them are curative and approximately 15% of patients die within 1 year of medical follow-up despite treatment. Within the last 5 years, tremendous advances in our understanding of the PAH pathophysiology have arisen. These advances have a high potential for the development of better patient care by providing novel therapeutic targets. The goal of this report is to review the current PAH treatments, as well as novel therapies that will pave the future in this devastating disease.
Introduction
Pulmonary arterial hypertension (PAH) is characterized by an intense pulmonary vascular remodeling leading to the progressive increase in pulmonary vascular resistance (PVR), right heart failure and eventually death. PAH may be idiopathic or associated with various conditions. It predominantly affects young adults, and its prevalence is estimated at 50 persons per million. Over the last two decades, the authors have seen major advances in our understanding of PAH pathology. As a result, the first PAH-specific therapies targeting the endothelial dysfunction were developed and commercialized, leading to improvement in patients' pulmonary hemodynamics, exercise capacity and survival. Nevertheless, long-term prognosis in PAH remains poor and most patients display persistent and significant dyspnea, exercise intolerance and poor health-related quality of life despite current therapies. Thus, treatment algorithms will probably change dramatically in upcoming years. Newer paradigms in the PAH pathophysiology, including pro-proliferative and antiapoptotic phenotype of pulmonary artery smooth muscle cells (PASMCs) and the confirmation of genetic, inflammatory and metabolic abnormalities will pave the future for the development of novel therapeutic targets. The current treatment algorithm for PAH is reviewed, as well as new therapeutic targets that have a high potential to impact on functional status, quality of life and survival of patients with PAH in the near future.