Background:
Pulmonary hypertension (PH) is a heterogeneous pathophysiological disorder with multiple entities, such as pulmonary vascular disease (precapillary PH) or left heart disease (postcapillary PH), both leading to ventricular and atrial dysfunction. Endothelial cell dyfunction is the main common pathology in PH and coronary microvascular dysfunction (CMD), with CMD emerging as a potential contributor to myocardial impairment. However, its impact in pulmonary hypertension remains unclear. We aimed to evaluate CMD in precapillary and postcapillary PH and its association with left and right heart impairment.
Methods:
Forty-two patients with PH (29 precapillary, 13 postcapillary) underwent detailed echocardiographic and invasive hemodynamic assessment. Coronary physiological measurements were performed with bolus-based thermodilution and included the assessment of coronary flow reserve (CFR) and microcirculatory resistance during adenosine-infusion (Ad-IMR). Cardiac function was evaluated using biventricular echocardiographic parameters, including right ventricular fractional area change (FAC RV), tricuspid annular plane systolic excursion/systolic pulmonary artery pressure ratio (TAPSE/sPAP), and left atrial reservoir strain (LARS). CMD was defined by CFR < 2.5 and/or an Ad-IMR > 25.
Results:
CMD was highly prevalent in both PH phenotypes (precapillary PH 62% (18/29), vs. postcapillary PH 69% (9/13); P = 0.74).
Among precapillary PH patients with CMD more right heart remodelling was present, with larger right atrial area (24 [19-35] vs. 18 [14-22]; P = 0.046), reduced RV systolic function (FAC RV, %) (25 [20-29] vs. 32 [28-36] ; P = 0.049), and impaired RV-arterial coupling (TAPSE/sPAP) (0.4 [0.3-0.5] vs. 0.6 [0.5-0.9]; P = 0.034), but also left atrial dysfunction (LARS) (10 [8-22] vs. 20 [16-47]; P= 0.04) opposed to precapillary PH patients without CMD.
Among postcapillary-PH patients with CMD, elevated NT-proBNP (525 [79-2838] vs. 158 [120-3439]; P = 0.01), presence of atrial fibrillation (28% (7) vs. 0% (9); P = 0.02) and reduced external myocardial work (RPP) (5330 [4680-7740] vs. 9155 [7540-10080]; P = 0.02) was observed compared to postcapillary PH patients without CMD.
In a subgroup analysis a comparison between precapillary PH with CMD compared to postcapillary PH with CMD demonstrated more frequently left ventricular dysfunction with lower stroke volume (54 [33-87] vs. 73 [66-110]; P=0.006) and consequently reduced cardiac index (2.2 [1.7-2.9] vs. 2.9 [2.2-3.4]; P= 0.03) and right ventricular dysfunction with reduced RV systolic function (28 [21-32] vs. 35 [29-40]; P=0.03) and impaired RV-arterial coupling (TAPSE/sPAP)(0.35 [0.24-0.45] vs. 0.46 [0.41-0.55]; P=0.04) in precapillary PH with CMD.
Conclusions:
CMD is common in both phenotypes of pulmonary hypertension and is associated with worse myocardial function, manifesting as right ventricular-arterial uncoupling in precapillary PH and left atrial dysfunction in postcapillary PH.
