Coronary pathophysiology in idiopathic pulmonary arterial hypertension
Erin Boland, Michael G. Freeman, David S. Corcoran, Thomas J. Ford, Barry Hennigan, Damien Collison, Aida Llucià-Valldeperas, Frances S. de Man, Kanarath P. Balachandran, Martin Johnson, Colin Church, Colin Berry
Erin Boland, Michael G. Freeman, David S. Corcoran, Thomas J. Ford, Barry Hennigan, Damien Collison, Aida Llucià-Valldeperas, Frances S. de Man, Kanarath P. Balachandran, Martin Johnson, Colin Church, Colin Berry
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Clinical Research and Public Health Cardiology Pulmonology Vascular biology

Coronary pathophysiology in idiopathic pulmonary arterial hypertension

Abstract

BACKGROUND Idiopathic 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.METHODS This 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.RESULTS Eleven 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.CONCLUSION Invasive 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.FUNDING The British Heart Foundation (BHF) (PG/18/6134217) and the Golden Jubilee Research Foundation.

Authors

Erin Boland, Michael G. Freeman, David S. Corcoran, Thomas J. Ford, Barry Hennigan, Damien Collison, Aida Llucià-Valldeperas, Frances S. de Man, Kanarath P. Balachandran, Martin Johnson, Colin Church, Colin Berry

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Figure 3

Patients with IPAH display reduced capillary density with a strong correlation to cardiomyocyte hypertrophy.

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Patients with IPAH display reduced capillary density with a strong corre...
(A) Overlay of capillary density analysis quantified via the ImageJ Analyze Particles plug-in identifying capillary structures. (B) Quantification of capillary density revealed significantly decreased right ventricular capillary density in patients with IPAH compared with controls (controls 199/ROI, IPAH 139.3/ROI, unpaired 2-tailed t test, P = 0.0138). (C) Quantification of variance between IPAH and control groups showed no difference in capillary density variability (controls 45.86/ROI, IPAH 46.69/ROI, unpaired 2-tailed t test, P = 0.9414). (D) Correlation between capillary density and cardiomyocyte cross-sectional area (CSA) between all patients identified correlation between capillary density and CSA across both groups (R2 = 0.762, P = 0.0021); 95% CI also displayed (dashed lines).