Figure 1. Underlying mechanisms and potential treatment targets for pulmonary hypertension in left heart disease.

A, Gene expression changes or genetic polymorphisms, resulting in altered protein function, have been associated with pulmonary hypertension (PH) in left heart disease (LHD) prompting a new approach in understanding the possible mechanisms of its development by studying the function of the affected proteins. B, Metabolic syndrome has been suggested as a predisposing factor for PH in LHD. It can result in macrophage accumulation and increased interleukin‐6 levels, implicating inflammation as a potential treatment target. Oxidative stress has been proposed to contribute to the development of right ventricular remodeling and PH in LHD with reactive oxygen species potentially serving as disease progression biomarkers and/or therapeutic targets. C, The degree of pulmonary vascular remodeling, attributable to fibrosis and myofibroblast proliferation and leukocyte infiltration, has been correlated with the severity of PH development in LHD quantified by increased pulmonary hemodynamics. D, Right ventricular fibrosis in pulmonary hypertension in heart failure with preserved ejection fraction has been associated with worsening right ventricular diastolic volume and right ventricular free wall strain and has offered a distinct mechanism and treatment target compared with other forms of PH. mPAP indicates mean pulmonary artery pressure; PH‐HFpEF, pulmonary hypertension in heart failure with preserved ejection fraction; PH‐LHD, pulmonary hypertension in left heart disease; and SNP, single nucleotide polymorphism.