Pulmonary hypertension and right heart dysfunction in chronic lung disease

Abstract

Group 3 pulmonary hypertension (PH) is a common complication of chronic lung disease (CLD), including chronic obstructive pulmonary disease (COPD), interstitial lung disease, and sleep-disordered breathing. Development of PH is associated with poor prognosis and may progress to right heart failure, however, in the majority of the patients with CLD, PH is mild to moderate and only a small number of patients develop severe PH. The pathophysiology of PH in CLD is multifactorial and includes hypoxic pulmonary vasoconstriction, pulmonary vascular remodeling, small vessel destruction, and fibrosis. The effects of PH on the right ventricle (RV) range between early RV remodeling, hypertrophy, dilatation, and eventual failure with associated increased mortality. The golden standard for diagnosis of PH is right heart catheterization, however, evidence of PH can be appreciated on clinical examination, serology, radiological imaging, and Doppler echocardiography. Treatment of PH in CLD focuses on management of the underlying lung disorder and hypoxia. There is, however, limited evidence to suggest that PH-specific vasodilators such as phosphodiesterase-type 5 inhibitors, endothelin receptor antagonists, and prostanoids may have a role in the treatment of patients with CLD and moderate-to-severe PH.

Figure 1

Schematic illustration of the site of action for each of the pathogenic mechanisms for pulmonary hypertension in COPD. LA: left atrium; LV: left ventricle; MPA: muscular pulmonary artery; PA: pulmonary artery; PV: pulmonary vein; RV: right ventricle [19]. Reproduced with permission of the European Respiratory Society [60].

Figure 2

Mechanisms contributing to PH in COPD. BMSC: bronchial smooth muscle cells, VSMC: vascular smooth muscle cells, VEGF: vascular endothelial growth factor, ET-1: endothelin-1, NO: nitric oxide, PGI₂: prostacyclin, TGF-β: tumor growth factor-β, PCWP: pulmonary capillary wedge pressure. Yellow: endothelium, pink: vascular smooth muscle cells blue/sand: respiratory wall [20]. Reproduced with permission.

Figure 3

Cumulative survival from date of diagnosis in pulmonary hypertension associated with COPD by mean PAP [21]. Reproduced with permission.

Figure 4

PH as a predictor of survival in patients with IPF [22]. Reproduced with permission.