Coronary pathophysiology in idiopathic pulmonary arterial hypertension

BACKGROUNDIdiopathic pulmonary arterial hypertension (IPAH) alters right ventricular size and function, curtailing life expectancy. Patients may experience angina and myocardial ischemia. However, the underlying mechanisms are poorly understood.METHODSThis study had a cross-sectional, case-control design. Patients with IPAH undergoing right heart catheterization were prospectively enrolled and underwent functional testing during coronary angiography using a dual pressure/temperature-sensitive guidewire. Cardiovascular MRI measured left and right ventricular mass and function. Right ventricular tissue from individuals with end-stage PAH and control individuals were analyzed for pathophysiology.RESULTSEleven IPAH and 15 control participants completed the protocol: 73% of IPAH patients had an elevated index of microcirculatory resistance (IMR > 25) and 55% had reduced coronary flow reserve (CFR < 2.0). Mean IMR was significantly higher in IPAH participants (39.2 ± 27.0 vs. 15.3 ± 5.0, P = 0.002), whereas mean CFR was lower (2.8 ± 2.1 vs. 4.0 ± 1.4; P = 0.077). Paired right coronary artery/ventricular measurements (n = 6) revealed IMR positively correlated with right ventricular mass (r = 0.91, P = 0.12) and negatively with CFR (r = -0.82, P = 0.046). Compared with controls (n = 5), PAH participants (n = 4) had reduced right ventricular capillary density, increased cardiomyocyte area, and increased mural area in pre-capillary arterioles.CONCLUSIONInvasive coronary function testing was feasible and safe in IPAH. Coronary microvascular dysfunction was prevalent in IPAH and correlated with increased right ventricular mass. Histopathology revealed vascular rarefaction and remodeling of pre-capillary arterioles.FUNDINGThe British Heart Foundation (BHF) (PG/18/6134217) and the Golden Jubilee Research Foundation.