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 1

Flow diagram and schematic of invasive and noninvasive phenotyping.

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Flow diagram and schematic of invasive and noninvasive phenotyping. (A) ...
(A) Participant enrollment and exclusions. Patients with IPAH undergoing right heart catheterization were assessed for eligibility. Numbers completing invasive coronary function testing, multi-vessel assessment, and cardiovascular MRI are shown. Representative examples of invasive and noninvasive investigations. Left panels show findings from a patient with IPAH demonstrating abnormal coronary physiology despite no obstructive CAD on invasive coronary angiography. Coronary function testing shows increased microvascular resistance in the LAD and RCA, consistent with coronary microvascular dysfunction (e.g., elevated IMR, reduced CFR). Corresponding CMR imaging of a dilated right ventricle with reduced ejection fraction. In contrast, right panels show control data with normal coronary angiography, preserved coronary physiological indices, and normal right ventricular size and systolic function on CMR. mPAP, mean pulmonary artery pressure; PCWP, pulmonary capillary wedge pressure; CMR, cardiac magnetic resonance; LAD, left anterior descending artery; RCA, right coronary artery; IMR, index of microcirculatory resistance corrected for central venous pressure; CFR, coronary flow reserve; FFR, fractional flow reserve; RVEDVi, right ventricular end-diastolic volume indexed to body surface area; RVEF, right ventricular ejection fraction.