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Review Assessment of the Coronary Microcirculation in the Cardiac Catheterisation Laboratory Cuneyt Ada 1, Andy Yong 1Department

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Review Assessment of the Coronary Microcirculation in the Cardiac Catheterisation Laboratory Cuneyt Ada 1, Andy Yong 1Department 1 Review 2 3 Assessment of the coronary microcirculation in the cardiac catheterisation laboratory 4 5 Cuneyt Ada1, Andy Yong2 6 7 1Department of Cardiology, Concord Repatriation General Hospital, Sydney, Australia. 8 2The University of Sydney, Sydney, Australia. 9 10 Correspondence to: A/Prof. Andy Yong, Department of Cardiology, Concord Repatriation 11 General Hospital, Concord 2139, Sydney, Australia. E-mail: [email protected] 12 13 How to cite this article: Ada C, Yong A. Assessment of the coronary microcirculation in the 14 cardiac catheterisation laboratory. Vessel Plus 2021;5:[Accept]. 15 http://dx.doi.org/10.20517/2574-1209.2021.51 16 17 Received: 29 Mar 2021 Revised: 17 May 2021 Accepted: 27 May 2021 First online: 27 18 May 2021 19 20 21 Abstract 22 The coronary microcirculation is a key determinant of blood supply to the myocardium and 23 outweighs the epicardial arteries in its abundance and distribution. Recent studies have shown 24 the clinical benefit of assessing the microcirculation, and this practice has now been given a 25 recommendation within latest international guidelines and consensus statements. However, 26 the uptake of assessing the microcirculation remains low. We continue to focus our efforts in 27 diagnosing and managing epicardial coronary disease in the cardiac catheterisation laboratory, 28 and mostly ignore the microvasculature. This is in large part due to the lack of familiarity 29 with available tools to perform these assessments. This review aims to summarise the various 30 techniques available to invasively assessing the coronary microcirculation in the 31 catheterisation laboratory. The advantages, disadvantages, pitfalls and clinical implications of 32 each method will be discussed. 33 2 34 Keywords: Coronary microvascular disease, microvascular angina, index of microcirculatory 35 resistance, coronary physiology 36 37 38 INTRODUCTION 39 Assessment of coronary microcirculatory function in the cardiac catheterisation laboratory is 40 valuable for both treatment of angina2 and prognostication3-5 and has recently been 41 incorporated into European Society of Cardiology guidelines6 as well as a consensus 42 document by the European Association of Percutaneous Coronary Intervention7. The aim of 43 this review is to provide a comprehensive review of the techniques of invasive assessment of 44 coronary microvascular function in the cardiac catheterisation laboratory. 45 46 Indications for assessment of coronary microvascular function include, but are not limited to, 47 ischemia and no obstructive coronary artery disease (INOCA)2, myocardial infarction with 48 non-obstructive coronary arteries (MINOCA)8, ST-elevation myocardial infarction (STEMI)4 49 and those with stable coronary artery disease6. 50 51 ANATOMY, FUNCTION AND DYSFUNCTION OF THE MICROCIRCULATION 52 The coronary microcirculation is broadly defined as vessels smaller than 300 microns, or 53 more generally through pre-arterioles, arterioles, capillaries and venules9. In addition to 54 serving as capacitance vessels holding 90% of the myocardial blood volume, the 55 microcirculation is the major source of regulation of myocardial blood flow, a role which 56 becomes vital in the presence of a stenosis where coronary autoregulation is required to 57 maintain flow 10. In the absence of a stenosis, the microvasculature acts in the same way to 58 regulate flow in response to varying physiological demands such as exercise11. 59 60 Microvascular dysfunction is an umbrella term which encompasses multiple possible 61 pathologies including vascular wall infiltration, extraluminal compression, sympathetic 62 dysfunction and altered remodelling. However, the exact pathophysiological chain remains 63 poorly understood12. There are now an increasing number of in vivo experimental models of 64 coronary microvascular dysfunction which are useful in elucidating the pathophysiology of 65 coronary microvascular dysfunction and may identify future therapeutic targets13. 66 3 67 68 Figure 1: Coronary physiology measurements in the cardiac catheterisation laboratory. 69 FFR: Fractional flow reserve; iFR: instantaneous wave-free ratio; RFR: Resting full-cycle 70 ratio; dPR: Diastolic pressure ratio; DFR: Diastolic hyperaemia-free ratio; QFR: Quantitative 71 flow ratio; IMR: Index of microcirculatory resistance; Rmicro: Microvascular resistance 72 (derived by continuous thermodilution); mMR: Minimal microvascular resistance; hMR: 73 Hyperaemic microvascular resistance; Pzf: Zero-flow pressure; RRR: Resistive reserve ratio; 74 IMRangio: Angiography-derived index of microcirculatory resistance. 75 76 NON-INVASIVE METHODS 77 A number of non-invasive modalities can be used to assess the coronary microcirculation. 78 These include positron emission tomography (PET), magnetic resonance imaging (MRI), 79 single-photon emission computed tomography (SPECT), myocardial contrast 80 echochardiography10 and computed tomography (CT) perfusion14. These modalities can be 81 used to quantify myocardial blood flow both at rest and during hyperaemia using various 82 hyperamic agents. By then comparing resting perfusion to hyperaemic perfusion, a coronary 4 83 flow reserve (CFR) is able to be calculated. Unlike invasive angiography, these methods are 84 not able to directly visualise the coronary artery (except for CT) and hence cannot distinguish 85 between causes of a low CFR incuding focal epicardial stenosis, diffuse epicardial stenosis 86 and microvascular dysfunction, and this limits their capacity to reliably diagnose coronary 87 microvascular dysfunction. As listed in Table 1, there are now a variety of invasive methods 88 available to evaluate the coronary microcirculation that will be discussed in this review. 89 90 Table 1. Techniques to assess for coronary microvascular dysfunction in the cardiac 91 catheterisation laboratory 92 Index Ease Method Normal Advantages Disadvantages range IMR15 +++ Thermodiluti <25 -Specific to the -If FFR < 0.45, requires on microcirculation wedge pressure for -Reproducible correction -Independent of haemodynamic perturbations - Predictive of subsequent death or rehospitalisation in STEMI patients - Predictive of subsequent MACE in patients undergoing elective PCI CFR16 ++ Thermodiluti >2.0 -Predicts all-cause death -Cannot distinguish on between macrovascular and microvascular disease RRR17 ++ Thermodiluti >3.5 -Predicts cardiac death in -Influenced by extrinsic on a wide range of patients factors like CFR -More specific to the 5 microcirculation than CFR CFVR1 ++ Doppler >2.0 -Predicts all-cause death -As with CFR, but 8 additionally there are the technical issues associated with Doppler signal acquisition hMR19, +++ Doppler <3.0 -Does not require -Technical issues 20 correction provided FFR associated with Doppler is above 0.6 signal acquisition -Limited prognostic data 21 Rmicro ++ Continuous <500 -Does not require -Equipment not yet thermodilutio Woods adenosine, as the saline widely available n Units infusion induces -Currently unclear how hyperaemia to correct for the presence of a stenosis - Limited prognostic data mMR22 N/A Doppler Unknow -Does not require -Requires further n hyperaemia validation given only one study available to date, published in 2016 -Limited prognostic data IHDV + Doppler Not -Correlates with -Difficult to interpret in PS23 defined histological the presence of a microvascular stenosis abnormalities -Time consuming -Not generally altered by -Limited prognostic most haemodynamic data parameters 24 Pzf + Doppler < 42 -Can indicate extrinsic -As with IHDVPS with 6 mmHg microvascular the addition that data compression in STEMI for use is limited to STEMI -Limited prognostic data TFC25 +++ Angiography <21 -No guidewire required -Qualitative + -Limited accuracy and reproducibility MBG26 +++ Angiography 2-3 -No guidewire required -Qualitative + -Limited accuracy and reproducibility IMRang - Angiography As per -No guidewire required -Calculated on PC post- 27 io IMR procedure -Steep learning curve, difficult to perform -Needs further validation -Limited prognostic data PB- ++ Arterial >2 -Can be derived from -Poor accuracy CFR 28 Pressure pressure alone -Limited prognostic data 93 IMR: Index of microcirculatory resistance; STEMI: ST-elevation myocardial infarction; 94 MACE: Major adverse cardiovascular events, PCI: Percutaneous coronary intervention; CFR: 95 Coronary flow reserve; RRR: Resistive reserve ratio; CFVR: Coronary flow velocity reserve; 96 hMR: Hyperaemic microvascular resistance; Rmicro: Microvascular resistance (derived using 97 continuous thermodilution); mMR: Minimal microvascular resistance; IHDVPS: 98 Instantaneous hyperaemic diastolic velocity–pressure slope; Pzf: Zero-flow pressure, TFC: 99 TIMI frame count; MBG: Myocardial blush grade, IMRangio: Angiography-derived index of 100 microcirculatory resistance; PB-CFR: Pressure-bounded coronary flow reserve. 101 102 ANGIOGRAPHIC METHODS 103 7 104 Coronary angiography-based techniques have historically been used to assess the status of the 105 microvasculature with methods such as the TIMI myocardial perfusion grading system and 106 myocardial blush grade providing an indirect, qualitative measures of the state of the 107 microvasculature. Whilst being simple, angiographic methods have poor reproducibility and 108 accuracy29 and are of limited utility in the modern era with the advent more advanced 109 techniques as discussed below. 110 111 THERMODILUTION METHODS 112 Index of Microcirculatory Resistance (IMR) 113 The index of microcirculatory
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