Coronary pathophysiology in idiopathic pulmonary arterial hypertension: A systems medicine study

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

doi:10.1172/jci.insight.194613

Coronary pathophysiology in idiopathic pulmonary arterial hypertension: A systems medicine study

Erin Boland,¹ Michael G. Freeman,¹ David S. Corcoran,¹ Thomas J. Ford,² Barry Hennigan,¹ Damien Collison,¹ Aida Llucià-Valldeperas,³ Frances S. de Man,³ Kanarath P. Balachandran,⁴ Martin Johnson,⁵ Colin Church,⁵ and Colin Berry¹

Published January 22, 2026 - More info

View PDF

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 mechanisms underlying these changes are poorly understood.

METHODS. A cross-sectional, case-control design of coronary pathophysiology (in vivo and ex vivo) in IPAH. Patients with IPAH (Group-1.1) undergoing clinically indicated right heart catheterization were prospectively enrolled. Participants underwent functional testing during coronary angiography using a dual pressure/temperature-sensitive guidewire. Cardiovascular magnetic resonance measured left and right ventricular mass and function. Autopsy cardiac tissues from end-stage PAH (Group-1) and control individuals were analyzed for right ventricular pathophysiology.

RESULTS. Eleven participants with IPAH and 15 control participants completed the protocol (IPAH: 45±15 years, 73% female; controls: 58.3±9.1 years, 73% female). 73% (n=8) of IPAH patients had an elevated index of microcirculatory resistance (IMR >25) and 55% (n=6) had reduced coronary flow reserve (CRF <2.0). The 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 to controls (n=5), PAH participants (n=4) had reduced right ventricular capillary density (111±18 vs. 167±20, p=0.032), increased cardiomyocyte area (383±118μm² vs. 231±61μm², p=0.0390), and increased mural area in small pre-capillary arterioles (127±10μm² vs. 107±20μm², p=0.041).

CONCLUSIONS. Coronary microvascular dysfunction is prevalent in IPAH and correlates with increased right ventricular mass. Histopathology revealed vascular rarefaction and remodeling of pre-capillary arterioles. The clinical significance merits prospective evaluation. Invasive coronary function testing was feasible and safe in IPAH, providing a platform to assess therapeutic impacts on cardiac microvascular function.

Coronary pathophysiology in idiopathic pulmonary arterial hypertension: A systems medicine study

Erin Boland,¹ Michael G. Freeman,¹ David S. Corcoran,¹ Thomas J. Ford,² Barry Hennigan,¹ Damien Collison,¹ Aida Llucià-Valldeperas,³ Frances S. de Man,³ Kanarath P. Balachandran,⁴ Martin Johnson,⁵ Colin Church,⁵ and Colin Berry¹

Article tools

Metrics

Go to

Coronary pathophysiology in idiopathic pulmonary arterial hypertension: A systems medicine study

Erin Boland,1 Michael G. Freeman,1 David S. Corcoran,1 Thomas J. Ford,2 Barry Hennigan,1 Damien Collison,1 Aida Llucià-Valldeperas,3 Frances S. de Man,3 Kanarath P. Balachandran,4 Martin Johnson,5 Colin Church,5 and Colin Berry1

Article tools

Metrics

Go to

Sign up for email alerts

Erin Boland,¹ Michael G. Freeman,¹ David S. Corcoran,¹ Thomas J. Ford,² Barry Hennigan,¹ Damien Collison,¹ Aida Llucià-Valldeperas,³ Frances S. de Man,³ Kanarath P. Balachandran,⁴ Martin Johnson,⁵ Colin Church,⁵ and Colin Berry¹