Pathophysiology and clinical relevance of pulmonary remodelling in pulmonary hypertension due to left heart diseases

Abstract

Pulmonary hypertension (PH) in left heart disease, classified as group II, is the most common form of PH that occurs in approximately 60% of cases of reduced and preserved left ventricular ejection fraction. Although relatively much is known about hemodynamic stages (passive or reactive) and their consequences on the right ventricle (RV) there is no consensus on the best hemodynamic definition of group II PH. In addition, the main pathways that lead to lung capillary injury and impaired biology of small artery remodelling processes are largely unknown. Typical lung manifestations of an increased pulmonary pressure and progressive RV-pulmonary circulation uncoupling are an abnormal alveolar capillary gas diffusion, impaired lung mechanics (restriction), and exercise ventilation inefficiency. Of several classes of pulmonary vasodilators currently clinically available, oral phosphodiesterase 5 inhibition, because of its strong selectivity for targeting the cyclic guanosine monophosphate pathway in the pulmonary circulation, is increasingly emerging as an attractive opportunity to reach hemodynamic benefits, reverse capillary injury, and RV remodelling, and improve functional capacity. Guanylate cyclase stimulators offer an additional intriguing opportunity but the lack of selectivity and systemic effects might preclude some of the anticipated benefits on the pulmonary circulation. Future trials will determine whether new routes of pharmacologic strategy aimed at targeting lung structural and vascular remodelling might affect morbidity and mortality in left heart disease populations. We believe that this therapeutic goal rather than a pure hemodynamic effect might ultimately emerge as an important challenge for the clinician.