Rationale and design of the Coronary Microvascular Angina Cardiac Magnetic Resonance Imaging (CorCMR) diagnostic study: the CorMicA CMR sub-study

David Corcoran, Thomas J Ford, Li-Yueh Hsu, Amedeo Chiribiri, Vanessa Orchard, Kenneth Mangion, Margaret McEntegart, Paul Rocchiccioli, Stuart Watkins, Richard Good, Katriona Brooksbank, Sandosh Padmanabhan, Naveed Sattar, Alex McConnachie, Keith G Oldroyd, Rhian M Touyz, Andrew Arai, Colin Berry, David Corcoran, Thomas J Ford, Li-Yueh Hsu, Amedeo Chiribiri, Vanessa Orchard, Kenneth Mangion, Margaret McEntegart, Paul Rocchiccioli, Stuart Watkins, Richard Good, Katriona Brooksbank, Sandosh Padmanabhan, Naveed Sattar, Alex McConnachie, Keith G Oldroyd, Rhian M Touyz, Andrew Arai, Colin Berry

Abstract

Introduction: Angina with no obstructive coronary artery disease (ANOCA) is a common syndrome with unmet clinical needs. Microvascular and vasospastic angina are relevant but may not be diagnosed without measuring coronary vascular function. The relationship between cardiovascular magnetic resonance (CMR)-derived myocardial blood flow (MBF) and reference invasive coronary function tests is uncertain. We hypothesise that multiparametric CMR assessment will be clinically useful in the ANOCA diagnostic pathway.

Methods/analysis: The Stratified Medical Therapy Using Invasive Coronary Function Testing In Angina (CorMicA) trial is a prospective, blinded, randomised, sham-controlled study comparing two management approaches in patients with ANOCA. We aim to recruit consecutive patients with stable angina undergoing elective invasive coronary angiography. Eligible patients with ANOCA (n=150) will be randomised to invasive coronary artery function-guided diagnosis and treatment (intervention group) or not (control group). Based on these test results, patients will be stratified into disease endotypes: microvascular angina, vasospastic angina, mixed microvascular/vasospastic angina, obstructive epicardial coronary artery disease and non-cardiac chest pain. After randomisation in CorMicA, subjects will be invited to participate in the Coronary Microvascular Angina Cardiac Magnetic Resonance Imaging (CorCMR) substudy. Patients will undergo multiparametric CMR and have assessments of MBF (using a novel pixel-wise fully quantitative method), left ventricular function and mass, and tissue characterisation (T1 mapping and late gadolinium enhancement imaging). Abnormalities of myocardial perfusion and associations between MBF and invasive coronary artery function tests will be assessed. The CorCMR substudy represents the largest cohort of ANOCA patients with paired multiparametric CMR and comprehensive invasive coronary vascular function tests.

Ethics/dissemination: The CorMicA trial and CorCMR substudy have UK REC approval (ref.16/WS/0192).

Trial registration number: NCT03193294.

Keywords: angina; cardiovascular magnetic resonance; coronary microvascular dysfunction; endoEndothelial dysfunction; myocardial perfusion.

Conflict of interest statement

Competing interests: CB is employed by the University of Glasgow, which holds consultancy and research agreements with companies that have commercial interests in the diagnosis and treatment of angina. The companies include Abbott Vascular, AstraZeneca, Boehringer Ingelheim, Menarini Pharmaceuticals and Siemens Healthcare. KGO has received consultant and speaker fees from Abbott Vascular and Volcano Corporation which manufacture pressure wires. SW has worked as a consultant for Abbott Vascular. None of these companies have had any involvement with this study. None of the other authors have any potential conflicts of interest.

Figures

Figure 1
Figure 1
CorCMR substudy flow diagram. ANOCA, angina with no obstructive coronary artery disease; CMR, cardiovascular magnetic resonance; CorCMR, Coronary Microvascular Angina Cardiac MRI; CorMicA, coronary microvascular angina.
Figure 2
Figure 2
CorCMR multiparametric imaging protocol. CorCMR, Coronary Microvascular Angina Cardiac MRI.

References

    1. GBD 2015 Mortality and Causes of Death Collaborators Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980-2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet 2016;388:1459–544. 10.1016/S0140-6736(16)31012-1
    1. Excellence NIfHaC , 2010. Chest pain of recent onset: assessment and diagnosis. Available from: [Accessed 20 Jun 2017].
    1. Task Force M, Montalescot G, Sechtem U. ESC guidelines on the management of stable coronary artery disease: the task force on the management of stable coronary artery disease of the european society of cardiology. Eur Heart J 2013;34:2949–3003.
    1. Patel MR, Peterson ED, Dai D, et al. . Low diagnostic yield of elective coronary angiography. N Engl J Med 2010;362:886–95. 10.1056/NEJMoa0907272
    1. Ford TJ, Corcoran D, Berry C. Stable coronary syndromes: pathophysiology, diagnostic advances and therapeutic need. Heart 2018;104:284–92. 10.1136/heartjnl-2017-311446
    1. Pries AR, Badimon L, Bugiardini R, et al. . Coronary vascular regulation, remodelling, and collateralization: mechanisms and clinical implications on behalf of the working group on coronary pathophysiology and microcirculation. Eur Heart J 2015;36:3134–46. 10.1093/eurheartj/ehv100
    1. Camici PG, Crea F. Coronary microvascular dysfunction. N Engl J Med 2007;356:830–40. 10.1056/NEJMra061889
    1. Lee JM, Jung JH, Hwang D, et al. . Coronary flow reserve and microcirculatory resistance in patients with intermediate coronary stenosis. J Am Coll Cardiol 2016;67:1158–69. 10.1016/j.jacc.2015.12.053
    1. Gulati M, Cooper-DeHoff RM, McClure C, et al. . Adverse cardiovascular outcomes in women with nonobstructive coronary artery disease: a report from the women's ischemia syndrome evaluation study and the st james women take heart project. Arch Intern Med 2009;169:843–50. 10.1001/archinternmed.2009.50
    1. Suwaidi JA, Hamasaki S, Higano ST, et al. . Long-term follow-up of patients with mild coronary artery disease and endothelial dysfunction. Circulation 2000;101:948–54. 10.1161/01.CIR.101.9.948
    1. Murthy VL, Naya M, Taqueti VR, et al. . Effects of sex on coronary microvascular dysfunction and cardiac outcomes. Circulation 2014;129:2518–27. 10.1161/CIRCULATIONAHA.113.008507
    1. van de Hoef TP, van Lavieren MA, Damman P, et al. . Physiological basis and long-term clinical outcome of discordance between fractional flow reserve and coronary flow velocity reserve in coronary stenoses of intermediate severity. Circ Cardiovasc Interv 2014;7:301–11. 10.1161/CIRCINTERVENTIONS.113.001049
    1. Berry C. Stable coronary syndromes: the case for consolidating the nomenclature of stable ischemic heart disease. Circulation 2017;136:437–9. 10.1161/CIRCULATIONAHA.117.028991
    1. Kirchhof P, Sipido KR, Cowie MR, et al. . The continuum of personalized cardiovascular medicine: a position paper of the European Society of Cardiology. Eur Heart J 2014;35:3250–7. 10.1093/eurheartj/ehu312
    1. Crea F, Lanza GA. Treatment of microvascular angina: the need for precision medicine. Eur Heart J 2016;37:1514–6. 10.1093/eurheartj/ehw021
    1. Bairey Merz CN, Pepine CJ, Walsh MN, et al. . Ischemia and No Obstructive Coronary Artery Disease (INOCA): developing evidence-based therapies and research agenda for the next decade. Circulation 2017;135:1075–92. 10.1161/CIRCULATIONAHA.116.024534
    1. Ong P, Camici PG, Beltrame JF, et al. . International standardization of diagnostic criteria for microvascular angina. Int J Cardiol 2018;250:16–20. 10.1016/j.ijcard.2017.08.068
    1. Galassi AR, Crea F, Araujo LI, et al. . Comparison of regional myocardial blood flow in syndrome X and one-vessel coronary artery disease. Am J Cardiol 1993;72:134–9. 10.1016/0002-9149(93)90148-6
    1. Meeder JG, Blanksma PK, Crijns HJ, et al. . Mechanisms of angina pectoris in syndrome X assessed by myocardial perfusion dynamics and heart rate variability. Eur Heart J 1995;16:1571–7. 10.1093/oxfordjournals.eurheartj.a060780
    1. Camici PG, Crea F. Microvascular angina: a women's affair? Circ Cardiovasc Imaging 2015;8 10.1161/CIRCIMAGING.115.003252
    1. Hsu LY, Jacobs M, Benovoy M, et al. . Diagnostic performance of fully automated pixel-wise quantitative myocardial perfusion imaging by cardiovascular magnetic resonance. JACC Cardiovasc Imaging 2018;11:697–707. 10.1016/j.jcmg.2018.01.005
    1. Schulz-Menger J, Bluemke DA, Bremerich J, et al. . Standardized image interpretation and post processing in cardiovascular magnetic resonance: Society for Cardiovascular Magnetic Resonance (SCMR) board of trustees task force on standardized post processing. J Cardiovasc Magn Reson 2013;15:35 10.1186/1532-429X-15-35
    1. Panza JA, Laurienzo JM, Curiel RV, et al. . Investigation of the mechanism of chest pain in patients with angiographically normal coronary arteries using transesophageal dobutamine stress echocardiography. J Am Coll Cardiol 1997;29:293–301. 10.1016/S0735-1097(96)00481-0
    1. Bruder O, Wagner A, Lombardi M, et al. . European Cardiovascular Magnetic Resonance (EuroCMR) registry--multi national results from 57 centers in 15 countries. J Cardiovasc Magn Reson 2013;15:9 10.1186/1532-429X-15-9
    1. Marroquin OC, Holubkov R, Edmundowicz D, et al. . Heterogeneity of microvascular dysfunction in women with chest pain not attributable to coronary artery disease: implications for clinical practice. Am Heart J 2003;145:628–35. 10.1067/mhj.2003.95
    1. Panting JR, Gatehouse PD, Yang GZ, et al. . Abnormal subendocardial perfusion in cardiac syndrome X detected by cardiovascular magnetic resonance imaging. N Engl J Med 2002;346:1948–53. 10.1056/NEJMoa012369
    1. Vermeltfoort IA, Bondarenko O, Raijmakers PG, et al. . Is subendocardial ischaemia present in patients with chest pain and normal coronary angiograms? A cardiovascular MR study. Eur Heart J 2007;28:1554–8. 10.1093/eurheartj/ehm088
    1. Karamitsos TD, Arnold JR, Pegg TJ, et al. . Patients with syndrome X have normal transmural myocardial perfusion and oxygenation: a 3-T cardiovascular magnetic resonance imaging study. Circ Cardiovasc Imaging 2012;5:194–200. 10.1161/CIRCIMAGING.111.969667
    1. Thomson LE, Wei J, Agarwal M, et al. . Cardiac magnetic resonance myocardial perfusion reserve index is reduced in women with coronary microvascular dysfunction. a national heart, lung, and blood institute-sponsored study from the women's ischemia syndrome evaluation. Circ Cardiovasc Imaging 2015;8 10.1161/CIRCIMAGING.114.002481
    1. Liu A, Wijesurendra RS, Liu JM, et al. . Diagnosis of microvascular angina using cardiac magnetic resonance. J Am Coll Cardiol 2018;71:969–79. 10.1016/j.jacc.2017.12.046
    1. Williams RP, de Waard GA, De Silva K, et al. . Doppler versus thermodilution-derived coronary microvascular resistance to predict coronary microvascular dysfunction in patients with acute myocardial infarction or stable angina pectoris. Am J Cardiol 2018;121:1–8. 10.1016/j.amjcard.2017.09.012
    1. Ford TJ, Corcoran D, Oldroyd KG, et al. . Rationale and design of the British heart foundation (bhf) coronary microvascular angina (cormica) stratified medicine clinical trial. Am Heart J 2018;201:86–94. 10.1016/j.ahj.2018.03.010
    1. Ford TJ, Rocchiccioli P, Good R, et al. . Systemic microvascular dysfunction in microvascular and vasospastic angina. Eur Heart J 2018. 10.1093/eurheartj/ehy529
    1. Murthy VL, Naya M, Foster CR, et al. . Association between coronary vascular dysfunction and cardiac mortality in patients with and without diabetes mellitus. Circulation 2012;126:1858–68. 10.1161/CIRCULATIONAHA.112.120402
    1. Pepine CJ, Anderson RD, Sharaf BL, et al. . Coronary microvascular reactivity to adenosine predicts adverse outcome in women evaluated for suspected ischemia results from the national heart, lung and blood institute wise (women's ischemia syndrome evaluation) study. J Am Coll Cardiol 2010;55:2825–32. 10.1016/j.jacc.2010.01.054
    1. Taqueti VR, Hachamovitch R, Murthy VL, et al. . Global coronary flow reserve is associated with adverse cardiovascular events independently of luminal angiographic severity and modifies the effect of early revascularization. Circulation 2015;131:19–27. 10.1161/CIRCULATIONAHA.114.011939
    1. Fukushima K, Javadi MS, Higuchi T, et al. . Prediction of short-term cardiovascular events using quantification of global myocardial flow reserve in patients referred for clinical 82Rb PET perfusion imaging. J Nucl Med 2011;52:726–32. 10.2967/jnumed.110.081828
    1. Serruys PW, di Mario C, Piek J, et al. . Prognostic value of intracoronary flow velocity and diameter stenosis in assessing the short- and long-term outcomes of coronary balloon angioplasty: the debate study (doppler endpoints balloon angioplasty trial Europe). Circulation 1997;96:3369–77.
    1. Chiribiri A, Villa AD, Sammut E, et al. . Perfusion dyssynchrony analysis. Eur Heart J Cardiovasc Imaging 2016;17:1414–23. 10.1093/ehjci/jev326
    1. Miller CA, Hsu LY, Ta A, et al. . Quantitative pixel-wise measurement of myocardial blood flow: the impact of surface coil-related field inhomogeneity and a comparison of methods for its correction. J Cardiovasc Magn Reson 2015;17:11 10.1186/s12968-015-0117-1
    1. Benovoy M, Jacobs M, Cheriet F, et al. . Robust universal nonrigid motion correction framework for first-pass cardiac MR perfusion imaging. J Magn Reson Imaging 2017;46:1060–72. 10.1002/jmri.25659
    1. Zierler KL. Equations for measuring blood flow by external monitoring of radioisotopes. Circ Res 1965;16:309–21. 10.1161/01.RES.16.4.309
    1. Cerqueira MD, Weissman NJ, Dilsizian V, et al. . Standardized myocardial segmentation and nomenclature for tomographic imaging of the heart. A statement for healthcare professionals from the cardiac imaging committee of the council on clinical cardiology of the American heart association. Circulation 2002;105:539–42.
    1. Jerosch-Herold M, Wilke N, Stillman AE. Magnetic resonance quantification of the myocardial perfusion reserve with a Fermi function model for constrained deconvolution. Med Phys 1998;25:73–84. 10.1118/1.598163
    1. Axel L. Tissue mean transit time from dynamic computed tomography by a simple deconvolution technique. Invest Radiol 1983;18:94–9. 10.1097/00004424-198301000-00018
    1. Hsu LY, Groves DW, Aletras AH, et al. . A quantitative pixel-wise measurement of myocardial blood flow by contrast-enhanced first-pass CMR perfusion imaging: microsphere validation in dogs and feasibility study in humans. JACC Cardiovasc Imaging 2012;5:154–66. 10.1016/j.jcmg.2011.07.013
    1. Moon JC, Messroghli DR, Kellman P, et al. . Myocardial t1 mapping and extracellular volume quantification: a Society for Cardiovascular Magnetic Resonance (scmr) and cmr working group of the european society of cardiology consensus statement. J Cardiovasc Magn Reson 2013;15:92 10.1186/1532-429X-15-92
    1. Kellman P, Arai AE, McVeigh ER, et al. . Phase-sensitive inversion recovery for detecting myocardial infarction using gadolinium-delayed hyperenhancement. Magn Reson Med 2002;47:372–83. 10.1002/mrm.10051
    1. NICE , 2016. Chest pain of recent onset: assessment and diagnosis (NICE Guideline 95, updated November 2016). Available from: [ [Accessed 5 Jan 2017].
    1. Task Force Members, Montalescot G, Sechtem U. 2013 ESC guidelines on the management of stable coronary artery disease: the task force on the management of stable coronary artery disease of the european society of cardi ology. Eur Heart J 20132013;34:2949–3003. 10.1093/eurheartj/eht296
    1. Plein S, Schwitter J, Suerder D, et al. . k-Space and time sensitivity encoding-accelerated myocardial perfusion MR imaging at 3.0 T: comparison with 1.5 T. Radiology 2008;249:493–500. 10.1148/radiol.2492080017
    1. Lockie T, Ishida M, Perera D, et al. . High-resolution magnetic resonance myocardial perfusion imaging at 3.0-Tesla to detect hemodynamically significant coronary stenoses as determined by fractional flow reserve. J Am Coll Cardiol 2011;57:70–5. 10.1016/j.jacc.2010.09.019
    1. Mygind ND, Michelsen MM, Pena A, et al. . Coronary microvascular function and myocardial fibrosis in women with angina pectoris and no obstructive coronary artery disease: the iPOWER study. J Cardiovasc Magn Reson 2016;18:76 10.1186/s12968-016-0295-5
    1. Wei J, Bakir M, Darounian N, et al. . Myocardial scar is prevalent and associated with subclinical myocardial dysfunction in women with suspected ischemia but no obstructive coronary artery disease: from the women's ischemia syndrome evaluation-coronary vascular dysfunction study. Circulation 2018;137:874–6. 10.1161/CIRCULATIONAHA.117.031999

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