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 4

Histological analysis of vascular density and arteriole morphology.

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Histological analysis of vascular density and arteriole morphology. (A) ...
(A) Representative images of right ventricular tissue from IPAH and control patient groups stained with WGA (gray) and αSMA (red). (B) Cropped regions of interest from lower magnification images of arterioles classified by vascular smooth muscle cell (VSMC) number visualized via αSMA staining. (C) Quantification of the number of αSMA+ arterioles identified histologically and classified by VSMC number between control and IPAH right ventricular samples. (D) Quantification of the number of 1-VSMC arterioles identified per patient showed no significant difference between IPAH and controls (IPAH 28.2, control 29.75, unpaired 2-tailed t test P = 0.8363). (E) Quantification of the outer arterial area, inner lumen area, and mural area for all arterioles identified with 1, 2, or 3 VSMCs. One VSMC: outer arteriole area (control = 141.6 μm2, IPAH = 181.3 μm2, P = 0.01 unpaired t test; luminal arteriole area, control = 31.39 μm2, IPAH = 37.32 μm2, P = 0.1429 unpaired t test; mural area, control = 107.2 μm2, IPAH = 127.3 μm2, P = 0.0416 unpaired t test). Two VSMCs: outer arteriole area (control = 499.8 μm2, IPAH = 519.4 μm2, P = 0.8282 unpaired t test; luminal arteriole area, control = 109.32, IPAH = 143.7 μm2, P = 0.3433 unpaired t test; mural area, control = 435.5 μm2, IPAH = 372.2 μm2, P = 0.3446 unpaired t test). Three VSMCs: outer arteriole area (control = 3,132 μm2, IPAH = 3,198 μm2, P = 0.9694 unpaired t test; luminal arteriole area, control = 552.8 μm2, IPAH = 369.4 μm2, P = 0.3199 unpaired t test; mural area, control = 2,580 μm2, IPAH = 2,640 μm2, P = 0.1905 unpaired t test). *P < 0.05.