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INTRODUCTION

Pulmonary hypertension (PH) is a heterogenous disease involving pathogenic remodeling of the pulmonary vasculature, which increases pulmonary artery pressure and vascular resistance. The most common causes of PH are left heart or primary lung disease; PH is also observed in some patients as a late complication of luminal pulmonary embolism. Pulmonary arterial hypertension (PAH) is an uncommon, but distinct, PH subtype characterized by the interplay between molecular and genetic events that cause an obliterative arteriopathy and symptoms of dyspnea, chest pain, and syncope. If left untreated, PH carries a high mortality rate, largely owing to decompensated right heart failure.

There have been significant advances in the field with regard to understanding disease pathogenesis, diagnosis, and classification. For example, the mean pulmonary artery pressure (mPAP) used to diagnose PH has been lowered from ≥25 mmHg to >20 mmHg. This adjustment emphasizes earlier detection of PH, as a substantial delay in diagnosis of up to 2 years is common and has important implications for both quality of life and life span. Clinicians should be able to recognize the signs and symptoms of PH and complete a systematic evaluation in at-risk patients. In this way, prompt diagnosis, appropriate treatment, and optimized patient outcome are achievable.

PATHOBIOLOGY

Apoptosis resistance, cell proliferation, dysregulated metabolism, and increased oxidant stress involving pulmonary vascular cells and adventitial fibroblasts underlie the pathogenesis of PAH. These events lead to hypertrophic, fibrotic, and plexogenic remodeling of distal (small) pulmonary arterioles, which decreases vascular compliance and promotes in situ thrombosis (Fig. 283-1). A minority of patients appear to have a vasoconstriction-dominant phenotype, which, if present, requires a unique treatment strategy discussed in greater detail below.

FIGURE 283-1

Panels on the left show examples of plexogenic pulmonary arteriopathy. Representative images of a normal lung (A) and examples of pulmonary vascular remodeling in pulmonary arterial hypertension (B–F), including idiopathic pulmonary arterial hypertension (B–E) and pulmonary venoocclusive disease (F), are shown. A. Normal pulmonary artery (arrow) adjacent to a terminal bronchiole (Br). B. Marked media and intima thickening of small vessels (arrow), partly surrounded by lymphoid cells form a cluster reminiscent of a primary follicle (arrowhead). C. Idiopathic pulmonary hypertension lung with a markedly muscularized medium-sized pulmonary artery (arrow), which distally branches into a plexiform lesion (lower arrowhead) and an adjacent plexiform lesion (upper arrowhead). D. Complex vascular lesion (circle) with a combination of telangiectatic-like dilations of the pulmonary artery (arrowheads) and a plexiform lesion (arrow). E. Medium-sized pulmonary artery with complete lumen obliteration with a loose collagen, poorly cellular matrix (arrows). F. Interlobular septal, medium-sized vein (arrowhead) obliterated by loose connective tissue (arrows), likely the result of an organized thrombus, characteristic of venoocclusive disease. (These representative images were provided ...

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