Impact of coronary disease patterns, anatomical factors, micro-vascular disease and non-coronary cardiac factors on invasive coronary physiology

Invasive coronary physiology has been applied by interventional cardiologists to guide the management of coronary artery disease (CAD), with well-defined thresholds applied to determine whether CAD should be managed with optimal medical therapy (OMT) alone or OMT and percutaneous coronary intervention (PCI). There are multiple modalities in clinical use, including hyperaemic and non-hyperaemic indices. Despite endorsement in the major guidelines, there are various factors which impact and confound the readings of invasive coronary physiology, both within the coronary tree and beyond. This review article aims to summarise the mechanisms by which these factors impact invasive coronary physiology, and distinguish factors that contribute to ischaemia from confounding factors. The potential for mis-classification of ischaemic status is highlighted. Lastly, the authors identify targets for future research to improve the precision of physiology-guided management of CAD. Abbreviations CAD, coronary artery disease; OMT, optimal medical therapy; FFR, fractional flow reserve; iFR, instantaneous wave-free ratio; RFR, resting full-cycle ratio; dPR, diastolic pressure ratio; CFR, coronary flow reserve; IMR, index of micro-circulatory resistance; RRR, resistance reserve ratio; CT, computed tomography; CTCA, computed tomography coronary angiography; IVUS, intra-vascular ultrasound; OCT, optical coherence tomography; LAP, low attenuation plaque; LD-NCP, low-density non-calcified plaque; RVD, reference vessel diameter; TCFA, thin-cap fibroatheroma; TAVI, transcatheter aortic valve implantation; PIV, particle image velocimetry; CFD, computational fluid dynamics; MI, myocardial infarction; PCI, percutaneous coronary intervention; PET, positron emission tomography; CMR, cardiac magnetic resonance; MACE, major adverse cardiovascular events; MBF, myocardial blood flow; CVR, coronary vasodilatory reserve; LVEDP, left ventricular end diastolic pressure; LVM, left ventricular mass; HMR, hyperaemic microvascular resistance; LAD, left anterior descending artery; RCA, right coronary artery Author Affiliation: (a) Royal North Shore Hospital, Department of Cardiology, Sydney, NSW, Australia (b) University of Sydney Northern Clinical School, Sydney, NSW, Australia (c) Kolling Institute of Medical Research, Sydney, NSW, Australia * Reprint requests: Avedis Ekmejian, MBBS, MSc, FRACP, Royal North Shore Hospital, University of Sydney, Mail: Level 5, Department of Cardiology, Royal North Shore Hospital, Reserve Rd, St Leonards, 2065, Australia. Article History: Received 26 September 2022; Accepted 7 December 2022 Byline: Avedis Ekmejian, MBBS, MSc [aekmejian@hotmail.com] (a,b,c,*), Usaid Allahwala, BSc (Med) (Hons), MBBS (Hons I), PhD (a,b,c), Michael Ward, MBBS, PhD (a,b,c), Ravinay Bhindi, MBBS, MSc, PhD (a,b,c)