Classification and pathophysiology of pulmonary hypertension

Pulmonary hypertension is a fatal disease of multiple etiologies that is estimated to affect over 100 million people worldwide. The disease is defined hemodynamically as a mean pulmonary artery pressure ≥ 25 mmHg at rest. Despite important advances in our understanding of the pathobiology of this disease and improvements in patient management, outcomes are still poor and no curative treatments are currently available. The complex nature of this disease requires detailed clinical evaluation for accurate diagnosis and treatment. Recent advances in clinical recognition, classification, and understanding of the underlying pathological processes in pulmonary hypertension have led to improved diagnostic testing and therapeutic options for patients. A hallmark of pulmonary hypertension is an increased pulmonary vascular resistance which leads to progressive elevations in pulmonary artery pressure, resulting in compensatory right ventricular hypertrophy and, ultimately, heart failure. Clinically, these pulmonary vascular changes initially present as nonspecific symptoms, including unexplained dyspnea on exertion, fatigue, chest pain, and syncope. Signs of right ventricular dysfunction are also frequently present. Common pathogenic features of pulmonary hypertension include sustained pulmonary vasoconstriction, vascular remodeling of the small pulmonary arteries, in situ thrombosis, and increased vascular wall stiffness, resulting in increased pulmonary arterial pressure due to increased pulmonary vascular resistance. Despite improvements in clinical classification and understanding of the underlying pathogenic mechanisms of pulmonary hypertension, current therapies are limited to supportive care and targeting pulmonary vasoconstriction. There remains a need to identify novel therapeutic targets in this disease. This review provides a succinct overview of the clinical classification and pathophysiology of PH that can be used as a reference by physicians and physician-scientists.