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Aims: Guidelines for suspected cardiac chest pain have used historical risk stratification tools, advocating invasive coronary angiography (ICA) first-line in those at highest risk. We aimed to determine whether different strategies to manage suspected stable angina affected medium-term cardiovascular event rates and patient-reported quality of life (QoL) measures., Methods: CE-MARC 2, a three-arm parallel group trial, randomised patients with suspected stable cardiac chest pain and a Duke Clinical pretest likelihood of coronary artery disease between 10% and 90%. Patients were randomised to either first-line cardiovascular magnetic resonance (CMR), single-photon emission computed tomography (SPECT) or the UK National Institute for Health and Care Excellence (NICE) CG95 (2010) guidelines-directed care. For the three arms, 1-year and 3-year first major adverse cardiovascular event (MACE) rates and QoL assessed by the Seattle Angina Questionnaire, Short Form 12 (V.12) Questionnaire and EuroQol-5 Dimension Questionnaire were recorded., Results: 1202 patients were randomised to CMR (n=481), SPECT (n=481) and NICE (n=240). Forty-two patients (18 CMR, 18 SPECT, 6 NICE) experienced one or more MACEs. The percentage rates (95% CIs) of MACE in the CMR, SPECT and NICE groups at 3 years were 3.7% (2.4%, 5.8%), 3.7% (2.4%, 5.8%) and 2.1% (0.9%, 4.8%), respectively. QoL scores did not significantly differ across domains., Conclusion: Despite a fourfold increase in referrals for ICA, the NICE CG95 (2010) guidelines risk-stratified care strategy did not significantly reduce 3-year MACE or improve QoL, as compared with functional imaging with CMR or SPECT., Trial Registration Number: ClinicalTrials.gov Registry (NCT01664858)., Competing Interests: Competing interests: CB is employed by the University of Glasgow which holds research and/or consultancy agreements with AstraZeneca, Abbott Vascular, Boehringer Ingelheim, GSK, HeartFlow, Neovasc and Novartis., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Myocardial injury in patients with COVID-19 and suspected cardiac involvement is not well understood., Objectives: The purpose of this study was to characterize myocardial injury in a multicenter cohort of patients with COVID-19 and suspected cardiac involvement referred for cardiac magnetic resonance (CMR)., Methods: This retrospective study consisted of 1,047 patients from 18 international sites with polymerase chain reaction-confirmed COVID-19 infection who underwent CMR. Myocardial injury was characterized as acute myocarditis, nonacute/nonischemic, acute ischemic, and nonacute/ischemic patterns on CMR., Results: In this cohort, 20.9% of patients had nonischemic injury patterns (acute myocarditis: 7.9%; nonacute/nonischemic: 13.0%), and 6.7% of patients had ischemic injury patterns (acute ischemic: 1.9%; nonacute/ischemic: 4.8%). In a univariate analysis, variables associated with acute myocarditis patterns included chest discomfort (OR: 2.00; 95% CI: 1.17-3.40, P = 0.01), abnormal electrocardiogram (ECG) (OR: 1.90; 95% CI: 1.12-3.23; P = 0.02), natriuretic peptide elevation (OR: 2.99; 95% CI: 1.60-5.58; P = 0.0006), and troponin elevation (OR: 4.21; 95% CI: 2.41-7.36; P < 0.0001). Variables associated with acute ischemic patterns included chest discomfort (OR: 3.14; 95% CI: 1.04-9.49; P = 0.04), abnormal ECG (OR: 4.06; 95% CI: 1.10-14.92; P = 0.04), known coronary disease (OR: 33.30; 95% CI: 4.04-274.53; P = 0.001), hospitalization (OR: 4.98; 95% CI: 1.55-16.05; P = 0.007), natriuretic peptide elevation (OR: 4.19; 95% CI: 1.30-13.51; P = 0.02), and troponin elevation (OR: 25.27; 95% CI: 5.55-115.03; P < 0.0001). In a multivariate analysis, troponin elevation was strongly associated with acute myocarditis patterns (OR: 4.98; 95% CI: 1.76-14.05; P = 0.003)., Conclusions: In this multicenter study of patients with COVID-19 with clinical suspicion for cardiac involvement referred for CMR, nonischemic and ischemic patterns were frequent when cardiac symptoms, ECG abnormalities, and cardiac biomarker elevations were present., Competing Interests: Funding Support and Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Aims: Recently developed in-line automated cardiovascular magnetic resonance (CMR) myocardial perfusion mapping has been shown to be reproducible and comparable with positron emission tomography (PET), and can be easily integrated into clinical workflows. Bringing quantitative myocardial perfusion CMR into routine clinical care requires knowledge of sex- and age-specific normal values in order to define thresholds for disease detection. This study aimed to establish sex- and age-specific normal values for stress and rest CMR myocardial blood flow (MBF) in healthy volunteers., Methods and Results: A total of 151 healthy volunteers recruited from two centres underwent adenosine stress and rest myocardial perfusion CMR. In-line automatic reconstruction and post processing of perfusion data were implemented within the Gadgetron software framework, creating pixel-wise perfusion maps. Rest and stress MBF were measured, deriving myocardial perfusion reserve (MPR) and were subdivided by sex and age. Mean MBF in all subjects was 0.62 ± 0.13 mL/g/min at rest and 2.24 ± 0.53 mL/g/min during stress. Mean MPR was 3.74 ± 1.00. Compared with males, females had higher rest (0.69 ± 0.13 vs. 0.58 ± 0.12 mL/g/min, P < 0.01) and stress MBF (2.41 ± 0.47 vs. 2.13 ± 0.54 mL/g/min, P = 0.001). Stress MBF and MPR showed significant negative correlations with increasing age (r = -0.43, P < 0.001 and r = -0.34, P < 0.001, respectively)., Conclusion: Fully automated in-line CMR myocardial perfusion mapping produces similar normal values to the published CMR and PET literature. There is a significant increase in rest and stress MBF, but not MPR, in females and a reduction of stress MBF and MPR with advancing age, advocating the use of sex- and age-specific reference ranges for diagnostic use., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Objectives: In patients of advanced age, the feasibility of myocardial ischemia testing might be limited by age-related comorbidities and falling compliance abilities. Therefore, we aimed to test the accuracy of 3D cardiac magnetic resonance (CMR) stress perfusion in the elderly population as compared to reference standard fractional flow reserve (FFR)., Methods: Fifty-six patients at age 75 years or older (mean age 79 ± 4 years, 35 male) underwent 3D CMR perfusion imaging and invasive coronary angiography with FFR in 5 centers using the same study protocol. The diagnostic accuracy of CMR was compared to a control group of 360 patients aged below 75 years (mean age 61 ± 9 years, 262 male). The percentage of myocardial ischemic burden (MIB) relative to myocardial scar burden was further analyzed using semi-automated software., Results: Sensitivity, specificity, and positive and negative predictive values of 3D perfusion CMR deemed similar for both age groups in the detection of hemodynamically relevant (FFR < 0.8) stenosis (≥ 75 years: 86%, 83%, 92%, and 75%; < 75 years: 87%, 80%, 82%, and 85%; p > 0.05 all). While MIB was larger in the elderly patients (15% ± 17% vs. 9% ± 13%), the diagnostic accuracy of 3D CMR perfusion was high in both elderly and non-elderly populations to predict pathological FFR (AUC: 0.906 and 0.866)., Conclusions: 3D CMR perfusion has excellent diagnostic accuracy for the detection of hemodynamically relevant coronary stenosis, independent of patient age., Key Points: • The increasing prevalence of coronary artery disease in elderly populations is accompanied with a larger ischemic burden of the myocardium as compared to younger individuals. • 3D cardiac magnetic resonance perfusion imaging predicts pathological fractional flow reserve in elderly patients aged ≥ 75 years with high diagnostic accuracy. • Ischemia testing with 3D CMR perfusion imaging has similarly high accuracy in the elderly as in younger patients and it might be particularly useful when other non-invasive techniques are limited by aging-related comorbidities and falling compliance abilities., (© 2022. The Author(s).)

Aims: The 2016 European Society of Cardiology Heart Failure Guidelines defined a new category: heart failure with mid-range ejection fraction (HFmrEF) of 40-49%. This new category was highlighted as having limited evidence and research was advocated into underlying characteristics, pathophysiology, and diagnosis. We used multi-parametric cardiovascular magnetic resonance (CMR) to define the cardiac phenotype of presumed non-ischaemic HFmrEF., Methods and Results: Patients (N = 300, 62.7 ± 13 years, 63% males) with a clinical diagnosis of heart failure with no angina symptoms, history of myocardial infarction, or coronary intervention were prospectively recruited. Patients underwent clinical assessment and CMR including T1 mapping, extracellular volume (ECV) mapping, late gadolinium enhancement, and measurement of myocardial blood flow at rest and maximal hyperaemia. Of 273 patients in the final analysis, 93 (34%) patients were categorized as HFmrEF, 46 (17%) as heart failure with preserved ejection fraction (HFpEF), and 134 (49%) as heart failure with reduced ejection fraction (HFrEF). Nineteen (20%) patients with HFmrEF had evidence of occult ischaemic heart disease. Diffuse fibrosis and hyperaemic myocardial blood flow were similar in HFmrEF and HFpEF, but HFmrEF showed significantly lower native T1 (1311 ± 32 vs. 1340 ± 45 ms, P < 0.001), ECV (24.6 ± 3.2 vs. 26.3 ± 3.1%, P < 0.001), and higher myocardial perfusion reserve (2.75 ± 0.84 vs. 2.28 ± 0.84, P < 0.001) compared with HFrEF., Conclusion: Patients with HFmrEF share most phenotypic characteristics with HFpEF, including the degree of microvascular impairment and fibrosis, but have a high prevalence of occult ischaemic heart disease similar to HFrEF. Further work is needed to confirm how the phenotype of HFmrEF responds to medical therapy., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Coronary artery disease (CAD) is the single most common cause of death worldwide. Recent technological developments with coronary cardiovascular magnetic resonance angiography (CCMRA) allow high-resolution free-breathing imaging of the coronary arteries at submillimeter resolution without contrast in a predictable scan time of ~ 10 min. The objective of this study was to determine the diagnostic accuracy of high-resolution CCMRA for CAD detection against the gold standard of invasive coronary angiography (ICA)., Methods: Forty-five patients (15 female, 62 ± 10 years) with suspected CAD underwent sub-millimeter-resolution (0.6 mm 3 ) non-contrast CCMRA at 1.5T in this prospective clinical study from 2019-2020. Prior to CCMR, patients were given an intravenous beta blockers to optimize heart rate control and sublingual glyceryl trinitrate to promote coronary vasodilation. Obstructive CAD was defined by lesions with ≥ 50% stenosis by quantitative coronary angiography on ICA., Results: The mean duration of image acquisition was 10.4 ± 2.1 min. On a per patient analysis, the sensitivity, specificity, positive predictive value and negative predictive value (95% confidence intervals) were 95% (75-100), 54% (36-71), 60% (42-75) and 93% (70-100), respectively. On a per vessel analysis the sensitivity, specificity, positive predictive value and negative predictive value (95% confidence intervals) were 80% (63-91), 83% (77-88), 49% (36-63) and 95% (90-98), respectively., Conclusion: As an important step towards clinical translation, we demonstrated a good diagnostic accuracy for CAD detection using high-resolution CCMRA, with high sensitivity and negative predictive value. The positive predictive value is moderate, and combination with CMR stress perfusion may improve the diagnostic accuracy. Future multicenter evaluation is now required., (© 2022. The Author(s).)

Objective: Given recent data on published diagnostic accuracies, this study sought to determine the most cost-effective diagnostic strategy for detection of significant coronary artery disease (CAD) in stable angina patients using invasive coronary angiography (ICA) and fractional flow reserve (FFR) as the reference standard., Methods: A probabilistic decision-analytical model was developed which modelled a cohort of patients with stable angina. We investigated 17 diagnostic strategies between standalone and combination of different imaging tests to establish a correct diagnosis of CAD, using no testing as the baseline reference. These tests included CT coronary angiography (CTCA), stress echocardiography, CT-based FFR, single-photon emission computed tomography (SPECT), cardiovascular magnetic resonance (CMR), positron emission tomography, ICA, and ICA with FFR. Incremental cost-effectiveness ratios were calculated as the additional cost per correct diagnosis., Results: SPECT followed by CTCA and ICA-FFR is the most cost-effective strategy between a cost-effectiveness threshold (CET) value of £1000-£3000 per correct diagnosis. CMR followed by CTCA and ICA-FFR is cost-effective within a CET range of £3000-£17 000 per correct diagnosis. CMR and ICA-FFR is cost-effective within a CET range of £17 000-£24 000. ICA-FFR as first line is the most-cost effective if the CET value exceeds the £24 000 per correct diagnosis. Sensitivity analysis showed that direct ICA-FFR may be cost-effective in patients with a high pre-test probability of CAD., Conclusion: First-line testing with functional imaging is cost-effective at low to intermediate value of correct diagnosis in patients with low to intermediate risk of CAD. ICA is not cost effective although ICA-FFR may be at higher CET., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Aims: To provide an overview of the role of cardiovascular (CV) imaging in facilitating and advancing the field of precision medicine in CV disease., Methods and Results: Non-invasive CV imaging is essential to accurately and efficiently phenotype patients with heart disease, including coronary artery disease (CAD) and heart failure (HF). Various modalities, such as echocardiography, nuclear cardiology, cardiac computed tomography (CT), cardiovascular magnetic resonance (CMR), and invasive coronary angiography, and in some cases a combination, can be required to provide sufficient information for diagnosis and management. Taking CAD as an example, imaging is essential for the detection and functional assessment of coronary stenoses, as well as for the quantification of cardiac function and ischaemic myocardial damage. Furthermore, imaging may detect and quantify coronary atherosclerosis, potentially identify plaques at increased risk of rupture, and guide coronary interventions. In patients with HF, imaging helps identify specific aetiologies, quantify damage, and assess its impact on cardiac function. Imaging plays a central role in individualizing diagnosis and management and to determine the optimal treatment for each patient to increase the likelihood of response and improve patient outcomes., Conclusions: Advances in all imaging techniques continue to improve accuracy, sensitivity, and standardization of functional and prognostic assessments, and identify established and novel therapeutic targets. Combining imaging with artificial intelligence, machine learning and computer algorithms, as well as with genomic, transcriptomic, proteomic, and metabolomic approaches, will become state of the art in the future to understand pathologies of CAD and HF, and in the development of new, targeted therapies., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2022. For permissions, please email: journals.permissions@oup.com.)

Background: Quantification of myocardial blood flow (MBF) and myocardial perfusion reserve (MPR) by cardiovascular magnetic resonance (CMR) perfusion requires sampling of the arterial input function (AIF). While variation in the AIF sampling location is known to impact quantification by CMR and positron emission tomography (PET) perfusion, there is no evidence to support the use of a specific location based on their diagnostic accuracy in the detection of coronary artery disease (CAD). This study aimed to evaluate the accuracy of stress MBF and MPR for different AIF sampling locations for the detection of abnormal myocardial perfusion with expert visual assessment as the reference., Methods: Twenty-five patients with suspected or known CAD underwent vasodilator stress-rest perfusion with a dual-sequence technique at 3T. A low-resolution slice was acquired in 3-chamber view to allow AIF sampling at five different locations: left atrium (LA), basal left ventricle (bLV), mid left ventricle (mLV), apical left ventricle (aLV) and aortic root (AoR). MBF and MPR were estimated at the segmental level using Fermi function-constrained deconvolution. Segments were scored as having normal or abnormal perfusion by visual assessment and the diagnostic accuracy of stress MBF and MPR for each location was evaluated using receiver operating characteristic curve analysis., Results: In both normal (300 out of 400, 75 %) and abnormal segments, rest MBF, stress MBF and MPR were significantly different across AIF sampling locations (p < 0.001). Stress MBF for the AoR (normal: 2.42 (2.15-2.84) mL/g/min; abnormal: 1.71 (1.28-1.98) mL/g/min) had the highest diagnostic accuracy (sensitivity 80 %, specificity 85 %, area under the curve 0.90; p < 0.001 versus stress MBF for all other locations including bLV: normal: 2.78 (2.39-3.14) mL/g/min; abnormal: 2.22 (1.83-2.48) mL/g/min; sensitivity 91 %, specificity 63 %, area under the curve 0.81) and performed better than MPR for the LV locations (p < 0.01). MPR for the AoR (normal: 2.43 (1.95-3.14); abnormal: 1.58 (1.34-1.90)) was not superior to MPR for the bLV (normal: 2.59 (2.04-3.20); abnormal: 1.69 (1.36-2.14); p = 0.717)., Conclusions: The AIF sampling location has a significant impact on MBF and MPR estimates by CMR perfusion, with AoR-based stress MBF comparing favorably to that for the current clinical reference bLV.

Aims: Assessment of hyperaemia during adenosine stress cardiovascular magnetic resonance (CMR) remains a clinical challenge with lack of a gold-standard non-invasive clinical marker to confirm hyperaemic response. This study aimed to validate maximum stress myocardial blood flow (SMBF) measured using quantitative perfusion mapping for assessment of hyperaemic response and compare this to current clinical markers of adenosine stress., Methods and Results: Two hundred and eighteen subjects underwent adenosine stress CMR. A derivation cohort (22 volunteers) was used to identify a SMBF threshold value for hyperaemia. This was tested in a validation cohort (37 patients with suspected coronary artery disease) who underwent invasive coronary physiology assessment on the same day as CMR. A clinical cohort (159 patients) was used to compare SMBF to other physiological markers of hyperaemia [splenic switch-off (SSO), heart rate response (HRR), and blood pressure (BP) fall]. A minimum SMBF threshold of 1.43 mL/g/min was derived from volunteer scans. All patients in the coronary physiology cohort demonstrated regional maximum SMBF (SMBFmax) >1.43 mL/g/min and invasive evidence of hyperaemia. Of the clinical cohort, 93% had hyperaemia defined by perfusion mapping compared to 71% using SSO and 81% using HRR. There was no difference in SMBFmax in those with or without SSO (2.58 ± 0.89 vs. 2.54 ± 1.04 mL/g/min, P = 0.84) but those with HRR had significantly higher SMBFmax (2.66 1.86 mL/g/min, P < 0.001). HRR >15 bpm was superior to SSO in predicting adequate increase in SMBF (AUC 0.87 vs. 0.62, P < 0.001)., Conclusion: Adenosine-induced increase in myocardial blood flow is accurate for confirmation of hyperaemia during stress CMR studies and is superior to traditional, clinically used markers of adequate stress such as SSO and BP response., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Objectives: The authors sought to compare the diagnostic accuracy of quantitative perfusion maps to visual assessment (VA) of first-pass perfusion images for the detection of multivessel coronary artery disease (MVCAD)., Background: VA of first-pass stress perfusion cardiac magnetic resonance (CMR) may underestimate ischemia in MVCAD. Pixelwise perfusion mapping allows quantitative measurement of regional myocardial blood flow, which may improve ischemia detection in MVCAD., Methods: One hundred fifty-one subjects recruited at 2 centers underwent stress perfusion CMR with myocardial perfusion mapping, and invasive coronary angiography with coronary physiology assessment. Ischemic burden was assessed by VA of first-pass images and by quantitative measurement of stress myocardial blood flow using perfusion maps., Results: In patients with MVCAD (2-vessel [2VD] or 3-vessel disease [3VD]; n = 95), perfusion mapping identified significantly more segments with perfusion defects (median segments per patient 12 [interquartile range (IQR): 9 to 16] by mapping vs. 8 [IQR: 5 to 9.5] by VA; p < 0.001). Ischemic burden (IB) measured using mapping was higher in MVCAD compared with IB measured using VA (3VD mapping 100 % (75% to 100%) vs. first-pass 56% (38% to 81%) ; 2VD mapping 63% (50% to 75%) vs. first-pass 41% (31% to 50%); both p < 0.001), but there was no difference in single-vessel disease (mapping 25% (13% to 44%) vs. 25% (13% to 31%). Perfusion mapping was superior to VA for the correct identification of extent of coronary disease (78% vs. 58%; p < 0.001) due to better identification of 3VD (87% vs. 40%) and 2VD (71% vs. 48%)., Conclusions: VA of first-pass stress perfusion underestimates ischemic burden in MVCAD. Pixelwise quantitative perfusion mapping increases the accuracy of CMR in correctly identifying extent of coronary disease. This has important implications for assessment of ischemia and therapeutic decision-making., Competing Interests: Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2020 American College of Cardiology Foundation. All rights reserved.)

Background: Myocardial perfusion reflects the macro- and microvascular coronary circulation. Recent quantitation developments using cardiovascular magnetic resonance perfusion permit automated measurement clinically. We explored the prognostic significance of stress myocardial blood flow (MBF) and myocardial perfusion reserve (MPR, the ratio of stress to rest MBF)., Methods: A 2-center study of patients with both suspected and known coronary artery disease referred clinically for perfusion assessment. Image analysis was performed automatically using a novel artificial intelligence approach deriving global and regional stress and rest MBF and MPR. Cox proportional hazard models adjusting for comorbidities and cardiovascular magnetic resonance parameters sought associations of stress MBF and MPR with death and major adverse cardiovascular events (MACE), including myocardial infarction, stroke, heart failure hospitalization, late (>90 day) revascularization, and death., Results: A total of 1049 patients were included with a median follow-up of 605 (interquartile range, 464-814) days. There were 42 (4.0%) deaths and 188 MACE in 174 (16.6%) patients. Stress MBF and MPR were independently associated with both death and MACE. For each 1 mL·g -1 ·min -1 decrease in stress MBF, the adjusted hazard ratios for death and MACE were 1.93 (95% CI, 1.08-3.48, P =0.028) and 2.14 (95% CI, 1.58-2.90, P <0.0001), respectively, even after adjusting for age and comorbidity. For each 1 U decrease in MPR, the adjusted hazard ratios for death and MACE were 2.45 (95% CI, 1.42-4.24, P =0.001) and 1.74 (95% CI, 1.36-2.22, P <0.0001), respectively. In patients without regional perfusion defects on clinical read and no known macrovascular coronary artery disease (n=783), MPR remained independently associated with death and MACE, with stress MBF remaining associated with MACE only., Conclusions: In patients with known or suspected coronary artery disease, reduced MBF and MPR measured automatically inline using artificial intelligence quantification of cardiovascular magnetic resonance perfusion mapping provides a strong, independent predictor of adverse cardiovascular outcomes.

Background: The UK National Institute for Health and Care Excellence (NICE) updated its guidelines on stable chest pain in 2016 and recommended computed tomography coronary angiography (CTCA) as first line investigation for all patients with new onset symptoms. We implemented the guideline and audited downstream testing., Methods: We undertook a retrospective search of the local radiology database from January 2017 to May 2018., Results: Six-hundred and fifty-two patients underwent CTCA (mean age of 55 years, 330 were male). Thirty-four patients were found to have severe coronary artery disease (CAD), with 30 undergoing invasive coronary angiography (ICA) which confirmed severe CAD in 22, a yield of 73%.Fifty-eight patients were found to have moderate CAD on CTCA with 36 referred for ICA, of which, 33 attended and 18 were found to have severe CAD. Eighteen were referred for imaging stress tests and one was positive. The total yield of severe CAD at ICA was 55%. The majority of patients had normal coronary arteries., Conclusions: CTCA was an effective rule-out test for most patients. In patients that went on to have ICA, the overall yield of severe CAD was relatively high. This compares well with our previous audit applying the NICE 2010 guidelines which recommended ICA for all high probability patients wherein the yield of severe CAD was 30%., (© Royal College of Physicians 2020. All rights reserved.)

Objectives: This study sought to assess the performance of cardiovascular magnetic resonance (CMR) myocardial perfusion mapping against invasive coronary physiology reference standards for detecting coronary artery disease (CAD, defined by fractional flow reserve [FFR] ≤0.80), microvascular dysfunction (MVD) (defined by index of microcirculatory resistance [IMR] ≥25) and the ability to differentiate between the two., Background: Differentiation of epicardial (CAD) and MVD in patients with stable angina remains challenging. Automated in-line CMR perfusion mapping enables quantification of myocardial blood flow (MBF) to be performed rapidly within a clinical workflow., Methods: Fifty patients with stable angina and 15 healthy volunteers underwent adenosine stress CMR at 1.5T with quantification of MBF and myocardial perfusion reserve (MPR). FFR and IMR were measured in 101 coronary arteries during subsequent angiography., Results: Twenty-seven patients had obstructive CAD and 23 had nonobstructed arteries (7 normal IMR, 16 abnormal IMR). FFR positive (epicardial stenosis) areas had significantly lower stress MBF (1.47 ± 0.48 ml/g/min) and MPR (1.75 ± 0.60) than FFR-negative IMR-positive (MVD) areas (stress MBF: 2.10 ± 0.35 ml/g/min; MPR: 2.41 ± 0.79) and normal areas (stress MBF: 2.47 ± 0.50 ml/g/min; MPR: 2.94 ± 0.81). Stress MBF ≤1.94 ml/g/min accurately detected obstructive CAD on a regional basis (area under the curve: 0.90; p < 0.001). In patients without regional perfusion defects, global stress MBF <1.82 ml/g/min accurately discriminated between obstructive 3-vessel disease and MVD (area under the curve: 0.94; p < 0.001)., Conclusions: This novel automated pixel-wise perfusion mapping technique can be used to detect physiologically significant CAD defined by FFR, MVD defined by IMR, and to differentiate MVD from multivessel coronary disease. A CMR-based diagnostic algorithm using perfusion mapping for detection of epicardial disease and MVD warrants further clinical validation., (Copyright © 2019. Published by Elsevier Inc.)

Background: Cardiac MR stress perfusion remains a qualitative technique in clinical practice due to technical and postprocessing challenges. However, automated inline perfusion mapping now permits myocardial blood flow (MBF, ml/g/min) quantification on-the-fly without user input., Purpose: To investigate the diagnostic performance of this novel technique in detecting occlusive coronary artery disease (CAD) in patients scheduled to undergo coronary angiography., Study Type: Prospective, observational., Subjects: Fifty patients with suspected CAD and 24 healthy volunteers., Field Strength: 1.5T. SEQUENCE: "Dual" sequence multislice 2D saturation recovery., Assessment: All patients underwent cardiac MR with perfusion mapping and invasive coronary angiography; the healthy volunteers had MR with perfusion mapping alone., Statistical Tests: Comparison between numerical variables was performed using an independent t-test. Receiver operator characteristic (ROC) curves were generated for transmyocardial, endocardial stress MBF, and myocardial perfusion reserve (MPR, the stress:rest MBF ratio) to diagnose severe (>70%) stenoses as measured by 3D quantitative coronary angiography (QCA). ROC curves were compared by the method of DeLong et al. RESULTS: Compared with volunteers, patients had lower stress MBF and MPR even in vessels with <50% stenosis (2.00 vs. 3.08 ml/g/min, respectively). As stenosis severity increased (<50%, 50-70%, >70%), MBF and MPR decreased. To diagnose occlusive (>70%) CAD, endocardial and transmyocardial stress MBF were superior to MPR (area under the curve 0.92 [95% CI 0.86-0.97] vs. 0.90 [95% CI 0.84-0.95] and 0.80 [95% CI 0.72-0.87], respectively). An endocardial threshold of 1.31 ml/g/min provided a per-coronary artery sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 90%, 82%, 50%, and 98%, with a per-patient diagnostic performance of 100%, 66%, 57%, and 100%, respectively., Data Conclusion: Perfusion mapping can diagnose occlusive CAD with high accuracy and, in particular, high sensitivity and NPV make it a potential "rule-out" test., Level of Evidence: 1 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2019;50:756-762., (© 2019 The Authors. Journal of Magnetic Resonance Imaging published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.)

Cardiovascular magnetic resonance (CMR) assesses cardiac function, ischaemia, viability and tissue characterisation, all within a single scan. Many studies regarding the role of CMR in stable coronary artery disease (CAD) have been published over the last decade providing important technical advances, large-scale clinical validation and prognostic data. As a result, CMR has emerged as a highly accurate technique for diagnosis and risk stratification in stable CAD and has been incorporated into national and international guidelines. Furthermore, clinical pathways utilising CMR have been shown to be the most cost-effective in several healthcare systems. In this review, we summarise the key roles and guideline recommendations for CMR in stable CAD supported by contemporary clinical evidence., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: Assessment of left main stem (LMS) stenosis has prognostic and therapeutic implications. Data on assessment of LMS disease by cardiovascular magnetic resonance (CMR) and single photon emission computed tomography (SPECT) are limited. CE-MARC is the largest prospective comparison of CMR and SPECT against quantitative invasive coronary angiography (QCA) for detection of coronary artery disease (CAD), and provided the framework for this evaluation. The aims of this study were to compare diagnostic accuracy of visual and quantitative perfusion CMR to SPECT in patients with LMS stable CAD., Methods: Fifty-four patients from the CE-MARC study were included: 27 (4%) with significant LMS or LMS-equivalent disease on QCA, and 27 age/sex-matched patients with no flow-limiting CAD. All patients underwent multi-parametric CMR, SPECT and QCA. Performance of visual and quantitative perfusion CMR by Fermi-constrained deconvolution to detect LMS disease was compared with SPECT., Results: Of 27 patients in the LMS group, 22 (81%) had abnormal CMR and 16 (59%) had abnormal SPECT. All patients with abnormal CMR had abnormal perfusion by visual analysis. CMR demonstrated significantly higher area under the curve (AUC) for detection of disease (0.95; 0.85-0.99) over SPECT (0.63; 0.49-0.76) (p = 0.0001). Global mean stress myocardial blood flow (MBF) by CMR in LMS patients was significantly lower than controls (1.77 ± 0.72 ml/g/min vs. 3.28 ± 1.20 ml/g/min, p < 0.001). MBF of <2.08 ml/g/min had sensitivity of 78% and specificity of 85% for diagnosis of LMS disease, with an AUC (0.87; 0.75-0.94) not significantly different to visual CMR analysis (p = 0.18), and more accurate than SPECT (p = 0.003)., Conclusion: Visual stress perfusion CMR had higher diagnostic accuracy than SPECT to detect LMS disease. Quantitative perfusion CMR had similar performance to visual CMR perfusion analysis.

Aims: Coronary artery disease (CAD) is a leading cause of morbidity and mortality in women and non-invasive testing for CAD in women can be more challenging than in men. This study compared the diagnostic performance of whole-heart dynamic 3D cardiovascular magnetic resonance (CMR) stress perfusion imaging in female and male patients with quantitative coronary angiography (QCA) and fractional flow reserve (FFR) as reference tests., Methods and Results: Four hundred sixteen patients with suspected or known CAD were enrolled in five European centres. CMR imaging was performed prior to clinically indicated coronary angiography. QCA was performed in all patients and FFR in 357 of 416 patients. Whole-heart dynamic 3D CMR first-pass perfusion imaging was conducted at rest and during adenosine stress. All CMR analyses were operated by experienced investigators blinded to all clinical data. One hundred nineteen female and 297 male patients were included and successfully examined (mean age 65 ± 11 and 63 ± 11 years, respectively). FFR was performed in 106 female and 251 male patients. Sensitivity and specificity of whole-heart dynamic 3D CMR stress perfusion imaging were 89% (95% CI: 77-96) and 82% (95% CI: 70-90) in the female population and 83% (95% CI: 77-86) and 79% (95% CI: 71-86) in the male population relative to QCA (P = 0.474 and P = 0.83, P-values for comparison between genders). Sensitivity and specificity were 95% (95% CI: 82-99) and 84% (95% CI: 73-92) in the female population and 83% (95% CI: 76-89) and 82% (95% CI: 74-88) in the male population when using FFR as the reference (P = 0.134 and P = 0.936, P-values for comparison between genders). Diagnostic accuracy in females was 92% (95% CI: 85-96) and 86% (95% CI: 81-90) in males when using FFR as the reference. The prevalence of CAD as defined by FFR (<0.8) was 36% in females and 53% in males., Conclusion: Whole-heart dynamic 3D CMR stress perfusion imaging has a high diagnostic accuracy for the detection of significant CAD irrespective of gender and is therefore a suitable non-invasive testing tool to detect myocardial ischaemia in both genders., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.)

The coronary arterial system consists of large epicardial coronary arteries, pre-arterioles, and arterioles, which together closely regulate CBF. Structural, functional, and extravascular abnormalities of the microcirculation lead to CMD. CMD can present with symptoms suggestive of CAD, often in the absence of significant obstructive epicardial CAD. Conventional invasive angiography does not allow direct visualization of the microcirculation. Invasive indices, such as CBF and CFR, and non-invasive imaging modalities, such as CMR and PET, can be used to quantify absolute MBF and enable a direct and accurate assessment of coronary microvascular function. CMD appears to be more prevalent in women, typically presenting with symptoms of ischemia with unobstructed coronary arteries, and has a relatively unfavorable prognosis. CMD is classified clinically depending on the presence or absence of epicardial CAD, myocardial disease, or iatrogenic causes. Although invasive intracoronary techniques can be used to detect CMD, these cannot provide insight into the mechanisms involved in its pathogenesis. Imaging modalities such as CMR and cardiac PET are becoming indispensable tools in the evaluation of suspected CMD., (© 2016 John Wiley & Sons Ltd.)

Importance: Among patients with suspected coronary heart disease (CHD), rates of invasive angiography are considered too high., Objective: To test the hypothesis that among patients with suspected CHD, cardiovascular magnetic resonance (CMR)-guided care is superior to National Institute for Health and Care Excellence (NICE) guidelines-directed care and myocardial perfusion scintigraphy (MPS)-guided care in reducing unnecessary angiography., Design, Setting, and Participants: Multicenter, 3-parallel group, randomized clinical trial using a pragmatic comparative effectiveness design. From 6 UK hospitals, 1202 symptomatic patients with suspected CHD and a CHD pretest likelihood of 10% to 90% were recruited. First randomization was November 23, 2012; last 12-month follow-up was March 12, 2016., Interventions: Patients were randomly assigned (240:481:481) to management according to UK NICE guidelines or to guided care based on the results of CMR or MPS testing., Main Outcomes and Measures: The primary end point was protocol-defined unnecessary coronary angiography (normal fractional flow reserve >0.8 or quantitative coronary angiography [QCA] showing no percentage diameter stenosis ≥70% in 1 view or ≥50% in 2 orthogonal views in all coronary vessels ≥2.5 mm diameter) within 12 months. Secondary end points included positive angiography, major adverse cardiovascular events (MACEs), and procedural complications., Results: Among 1202 symptomatic patients (mean age, 56.3 years [SD, 9.0]; women, 564 [46.9%] ; mean CHD pretest likelihood, 49.5% [SD, 23.8%]), number of patients with invasive coronary angiography after 12 months was 102 in the NICE guidelines group (42.5% [95% CI, 36.2%-49.0%])], 85 in the CMR group (17.7% [95% CI, 14.4%-21.4%]); and 78 in the MPS group (16.2% [95% CI, 13.0%-19.8%]). Study-defined unnecessary angiography occurred in 69 (28.8%) in the NICE guidelines group, 36 (7.5%) in the CMR group, and 34 (7.1%) in the MPS group; adjusted odds ratio of unnecessary angiography: CMR group vs NICE guidelines group, 0.21 (95% CI, 0.12-0.34, P < .001); CMR group vs the MPS group, 1.27 (95% CI, 0.79-2.03, P = .32). Positive angiography proportions were 12.1% (95% CI, 8.2%-16.9%; 29/240 patients) for the NICE guidelines group, 9.8% (95% CI, 7.3%-12.8%; 47/481 patients) for the CMR group, and 8.7% (95% CI, 6.4%-11.6%; 42/481 patients) for the MPS group. A MACE was reported at a minimum of 12 months in 1.7% of patients in the NICE guidelines group, 2.5% in the CMR group, and 2.5% in the MPS group (adjusted hazard ratios: CMR group vs NICE guidelines group, 1.37 [95% CI, 0.52-3.57]; CMR group vs MPS group, 0.95 [95% CI, 0.46-1.95])., Conclusions and Relevance: In patients with suspected angina, investigation by CMR resulted in a lower probability of unnecessary angiography within 12 months than NICE guideline-directed care, with no statistically significant difference between CMR and MPS strategies. There were no statistically significant differences in MACE rates., Trial Registration: Clinicaltrials.gov Identifier: NCT01664858.

Aims: Typically, myocardial perfusion imaging with two-dimensional (2D) cardiovascular magnetic resonance (CMR) acquires data in three to four myocardial slices at a spatial resolution of 2-3 mm. However, accelerated data acquisition can facilitate higher spatial resolution (<2 mm) or three-dimensional (3D) whole-heart coverage (up to 16 slices). This study aims to compare image quality, diagnostic confidence, and quantitation of myocardial ischaemic burden (MIB) between 2D high-resolution and 3D whole-heart perfusion-CMR., Methods and Results: Twenty-seven patients with stable angina underwent both high-resolution 2D and whole-heart 3D perfusion-CMR. Total perfusion defect (TPD) and total scar burden (TSB) areas were contoured and expressed as percentage myocardium. MIB was calculated by subtracting TSB from TPD. Image quality, artefact, and diagnostic confidence scores were similar for both techniques (P>0.05). The mean MIB from high-resolution and 3D acquisition was similar (4.3±5.2% vs. 4.1±4.9%; P=0.81), with a strong correlation between techniques (r=0.72; P<0.001). There was no systematic bias for estimates of MIB between techniques [mean bias=-0.17%, 95% confidence interval (CI): -1.7 to -1.3%] and the 95% limits of agreement were -7.5 to 7.2%. When used to categorize MIB as >10% or <10%, there was only fair agreement between the two techniques (κ=0.29, 95% CI: -0.12 to 0.70)., Conclusion: There is strong correlation and broad agreement between estimates of MIB from both techniques. However, the 95% limits of agreement are relatively wide and therefore a larger comparative study is needed before they can be considered interchangeable-particularly around the clinically relevant 10% threshold., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.)

Noninvasive cardiac imaging has an important role in the assessment of patients with acute-onset chest pain. In patients with suspected acute coronary syndrome (ACS), cardiac imaging offers incremental value over routine clinical assessment, the electrocardiogram, and blood biomarkers of myocardial injury, to confirm or refute the diagnosis of coronary artery disease and to assess future cardiovascular risk. This Review covers the current guidelines and clinical use of the common noninvasive imaging techniques, including echocardiography and stress echocardiography, computed tomography coronary angiography, myocardial perfusion scintigraphy, positron emission tomography, and cardiovascular magnetic resonance imaging, in patients with suspected ACS, and provides an update on the developments in noninvasive imaging techniques in the past 5 years.

Purpose: To examine factors associated with false-negative cardiovascular magnetic resonance (MR) perfusion studies within the large prospective Clinical Evaluation of MR imaging in Coronary artery disease (CE-MARC) study population. Myocardial perfusion MR has excellent diagnostic accuracy to detect coronary heart disease (CHD). However, causes of false-negative MR perfusion studies are not well understood., Materials and Methods: CE-MARC prospectively recruited patients with suspected CHD and mandated MR, myocardial perfusion scintigraphy, and invasive angiography. This subanalysis identified all patients with significant coronary stenosis by quantitative coronary angiography (QCA) and MR perfusion (1.5T, T1 -weighted gradient echo), using the original blinded image read. We explored patient and imaging characteristics related to false-negative or true-positive MR perfusion results, with reference to QCA. Multivariate regression analysis assessed the likelihood of false-negative MR perfusion according to four characteristics: poor image quality, triple-vessel disease, inadequate hemodynamic response to adenosine, and Duke jeopardy score (angiographic myocardium-at-risk score)., Results: In all, 265 (39%) patients had significant angiographic disease (mean age 62, 79% male). Thirty-five (5%) had false-negative and 230 (34%) true-positive MR perfusion. Poor MR perfusion image quality, triple-vessel disease, and inadequate hemodynamic response were similar between false-negative and true-positive groups (odds ratio, OR [95% confidence interval, CI]: 4.1 (0.82-21.0), P = 0.09; 1.2 (0.20-7.1), P = 0.85, and 1.6 (0.65-3.8), P = 0.31, respectively). Mean Duke jeopardy score was significantly lower in the false-negative group (2.6 ± 1.7 vs. 5.4 ± 3.0, OR 0.34 (0.21-0.53), P < 0.0001)., Conclusion: False-negative cardiovascular MR perfusion studies are uncommon, and more common in patients with lower angiographic myocardium-at-risk. In CE-MARC, poor image quality, triple-vessel disease, and inadequate hemodynamic response were not significantly associated with false-negative MR perfusion., (© 2015 The Authors Journal of Magnetic Resonance Imaging published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.)

Purpose: To demonstrate the feasibility of an automatic adaptive acquisition sequence. Magnetic resonance perfusion pulse sequences often leave potential acquisition time unused in patients with lower heart-rates (HR) and smaller body size., Materials and Methods: A perfusion technique was developed that automatically adapts to HR and field-of-view by maximizing in-plane spatial resolution while maintaining temporal resolution every cardiac cycle. Patients (n = 10) and volunteers (n = 10) were scanned with both a standard resolution and adaptive method. Image quality was scored, signal-to-noise ratio (SNR) calculated, and width of dark-rim artifact (DRA) measured., Results: The acquired spatial resolution of the adaptive sequence (1.92 × 1.92 mm(2)  ± 0.34) was higher than the standard resolution (2.42 × 2.42 mm(2) ) (P < 0.0001). Mean DRA width was reduced using the adaptive pulse sequence (1.94 ± 0.60 mm vs. 2.82 ± 0.65 mm, P < 0.0001). The signal-to-noise ratio (SNR) was higher with the standard pulse sequence (6.7 ± 2.2 vs. 3.8 ± 1.8, P < 0.0001). There was no difference in image quality score between sequences in either volunteers (1.1 ± 0.31 vs. 1.0 ± 0.0, P = 0.34) or patients (1.3 ± 0.48 vs. 1.3 ± 0.48, P = 1.0)., Conclusion: Optimizing the use of available imaging time during first-pass perfusion with a magnetic resonance imaging pulse sequence that adapts image acquisition duration to HR and patient size is feasible. Acquired in-plane spatial resolution is improved, the DRA is reduced, and while SNR is reduced with the adaptive sequence consistent with the lower voxel size used, image quality is maintained., (© 2015 Wiley Periodicals, Inc.)

Background: The CE-MARC study assessed the diagnostic performance investigated the use of cardiovascular magnetic resonance (CMR) in patients with suspected coronary artery disease (CAD). The study used a multi-parametric CMR protocol assessing 4 components: i) left ventricular function; ii) myocardial perfusion; iii) viability (late gadolinium enhancement (LGE)) and iv) coronary magnetic resonance angiography (MRA). In this pre-specified CE-MARC sub-study we assessed the diagnostic accuracy of the individual CMR components and their combinations., Methods: All patients from the CE-MARC population (n = 752) were included using data from the original blinded-read. The four individual core components of the CMR protocol was determined separately and then in paired and triplet combinations. Results were then compared to the full multi-parametric protocol., Results: CMR and X-ray angiography results were available in 676 patients. The maximum sensitivity for the detection of significant CAD by CMR was achieved when all four components were used (86.5%). Specificity of perfusion (91.8%), function (93.7%) and LGE (95.8%) on its own was significantly better than specificity of the multi-parametric protocol (83.4%) (all P < 0.0001) but with the penalty of decreased sensitivity (86.5% vs. 76.9%, 47.4% and 40.8% respectively). The full multi-parametric protocol was the optimum to rule-out significant CAD (Likelihood Ratio negative (LR-) 0.16) and the LGE component alone was the best to rue-in CAD (LR+ 9.81). Overall diagnostic accuracy was similar with the full multi-parametric protocol (85.9%) compared to paired and triplet combinations. The use of coronary MRA within the full multi-parametric protocol had no additional diagnostic benefit compared to the perfusion/function/LGE combination (overall accuracy 84.6% vs. 84.2% (P = 0.5316); LR- 0.16 vs. 0.21; LR+ 5.21 vs. 5.77)., Conclusions: From this pre-specified sub-analysis of the CE-MARC study, the full multi-parametric protocol had the highest sensitivity and was the optimal approach to rule-out significant CAD. The LGE component alone was the optimal rule-in strategy. Finally the inclusion of coronary MRA provided no additional benefit when compared to the combination of perfusion/function/LGE., Trial Registration: Current Controlled Trials ISRCTN77246133.

We evaluated the clinical efficacy and cost of a cardiac imaging strategy versus a traditional exercise tolerance test (ETT) strategy for the investigation of suspected stable coronary artery disease (CAD). We retrospectively collected data of consecutive patients seen in rapid access chest pain clinics at 2 UK hospitals for a period of 12 months. Hospital A investigated patients by performing ETT. Hospital B investigated patients using cardiac imaging test; 483 patients from hospital A and 295 from hospital B were included. In hospital A, 209 patients (43.3%) had contraindication to ETT. Of those who had ETT, 151 (55.1%) had negative ETT, 68 (24.8%) had equivocal ETT, and 55 (20.1%) had positive ETT, of which 53 (96.4%) had invasive coronary angiography (ICA), and of these 23 (43.4%) had obstructive CAD. In hospital B, 26 patients (8.8%) with low pretest probability had calcium score and 3 (11.5%) were positive leading to computed tomography coronary angiography; 98 patients (33.2%) with intermediate pretest probability had computed tomography coronary angiography and 5 (5.1%) were positive; 77 patients (26.1%) had stress echocardiogram and 6 (7.8%) were positive; and 57 patients (19.3%) had myocardial perfusion scintigraphy and 11 (19.3%) were positive. Hospital A performed 127 ICA (26.3% of population) and 52 (40.9%) had obstructive CAD. Hospital B performed 63 ICA (21.4% of population) and 32 (50.8%) had obstructive CAD. The average cost per patient in hospital A was £566.6 ± 490.0 ($875 ± 758) and in hospital B was £487.9 ± 469.6 ($750 ± 725) (p <0.001). In conclusion, our results suggest that a cardiac imaging pathway leads to fewer ICA and a higher yield of obstructive CAD at lower cost per patient., (Copyright © 2015 Elsevier Inc. All rights reserved.)

The European Society of Cardiology (ESC) and UK National Institute for Health and Care Excellence (NICE) have recently published guidelines for investigating patients with suspected coronary artery disease (CAD). Both provide a risk score (RS) to assess the pre-test probability for CAD to guide clinicians to undertake the most effective investigation. The aim of the study was to establish whether there is a difference between the two RS models. We retrospectively reviewed records of 479 patients who presented to a UK district general hospital with chest pain between August 2011 and April 2013. The RS was calculated using ESC and NICE guidelines and compared. From the 479 patients, 277 (58%) were male and the mean age was 60 years. The mean RS was greater using NICE guidelines compared with ESC (66.3 vs 47.9%, 18.4% difference; p<0.0001). The difference in mean RS was smaller in patients with typical chest pain (13.0%). When we divided the cohort based on NICE criteria into 'high'- and 'low'-risk groups, the difference in the mean RS was 24.3% in the 'high'-risk group (p<0.001) compared with 2.8% in the 'low'-risk group. The UK NICE risk score model overestimates risk compared with the ESC model., (© Royal College of Physicians 2015. All rights reserved.)

Background: First-pass myocardial perfusion cardiovascular magnetic resonance (CMR) imaging yields high diagnostic accuracy for the detection of coronary artery disease (CAD). However, standard 2D multislice CMR perfusion techniques provide only limited cardiac coverage, and hence considerable assumptions are required to assess myocardial ischemic burden. The aim of this prospective study was to assess the diagnostic performance of 3D myocardial perfusion CMR to detect functionally relevant CAD with fractional flow reserve (FFR) as a reference standard in a multicenter setting., Methods and Results: A total of 155 patients with suspected CAD listed for coronary angiography with FFR were prospectively enrolled from 5 European centers. 3D perfusion CMR was acquired on 3T MR systems from a single vendor under adenosine stress and at rest. All CMR perfusion analyses were performed in a central laboratory and blinded to all clinical data. One hundred fifty patients were successfully examined (mean age 62.9±10 years, 45 female). The prevalence of CAD defined by FFR (<0.8) was 56.7% (85 of 150 patients). The sensitivity and specificity of 3D perfusion CMR were 84.7% and 90.8% relative to the FFR reference. Comparison to quantitative coronary angiography (≥50%) yielded a prevalence of 65.3%, sensitivity and specificity of 76.5% and 94.2%, respectively., Conclusions: In this multicenter study, 3D myocardial perfusion CMR proved highly diagnostic for the detection of significant CAD as defined by FFR., (© 2015 American Heart Association, Inc.)

Background: The purpose of this study was to establish the feasibility of three-dimensional (3D) balanced steady-state-free-precession (bSSFP) myocardial perfusion cardiovascular magnetic resonance (CMR) at 3T using local RF shimming with dual-source RF transmission, and to compare it with spoiled gradient echo (TGRE) acquisition., Methods: Dynamic contrast-enhanced 3D bSSFP perfusion imaging was performed on a 3T MRI scanner equipped with dual-source RF transmission technology. Images were reconstructed using k-space and time broad-use linear acquisition speed-up technique (k-t BLAST) and compartment based principle component analysis (k-t PCA)., Results: In phantoms and volunteers, local RF shimming with dual source RF transmission significantly improved B1 field homogeneity compared with single source transmission (P=0.01). 3D bSSFP showed improved signal-to-noise, contrast-to-noise and signal homogeneity compared with 3D TGRE (29.8 vs 26.9, P=0.045; 23.2 vs 21.6, P=0.049; 14.9% vs 12.4%, p=0.002, respectively). Image quality was similar between bSSFP and TGRE but there were more dark rim artefacts with bSSFP. k-t PCA reconstruction reduced artefacts for both sequences compared with k-t BLAST. In a subset of five patients, both methods correctly identified those with coronary artery disease., Conclusion: Three-dimensional bSSFP myocardial perfusion CMR using local RF shimming with dual source parallel RF transmission at 3T is feasible and improves signal characteristics compared with TGRE. Image artefact remains an important limitation of bSSFP imaging at 3T but can be reduced with k-t PCA.

Background: The incidence of cardiovascular disease (CVD) in rheumatoid arthritis (RA) is increased compared to the general population. Immune dysregulation and systemic inflammation are thought to be associated with this increased risk. Early diagnosis with immediate treatment and tight control of RA forms a central treatment paradigm. It remains unclear, however, whether using tumor necrosis factor inhibitors (TNFi) to achieve remission confer additional beneficial effects over standard therapy, especially on the development of CVD., Methods/design: Coronary Artery Disease Evaluation in Rheumatoid Arthritis (CADERA) is a prospective cardiovascular imaging study that bolts onto an existing single-centre, randomized controlled trial, VEDERA (Very Early versus Delayed Etanercept in Rheumatoid Arthritis). VEDERA will recruit 120 patients with early, treatment-naïve RA, randomized to TNFi therapy etanercept (ETN) combined with methotrexate (MTX), or therapy with MTX with or without additional synthetic disease modifying anti-rheumatic drugs with escalation to ETN following a 'treat-to-target' regimen. VEDERA patients will be recruited into CADERA and undergo cardiac magnetic resonance (CMR) assessment with; cine imaging, rest/stress adenosine perfusion, tissue-tagging, aortic distensibility, T1 mapping and late gadolinium imaging. Primary objectives are to detect the prevalence and change of cardiovascular abnormalities by CMR between TNFi and standard therapy over a 12-month period. All patients will enter an inflammatory arthritis registry for long-term follow-up., Discussion: CADERA is a multi-parametric study describing cardiovascular abnormalities in early, treatment-naïve RA patients, with assessment of changes at one year between early biological therapy and conventional therapy., Trials Registration: This trial was registered with Current Controlled Trials (registration number: ISRCTN50167738) on 8 November 2013.

Background: The extent and severity of ischemia on myocardial perfusion scintigraphy (MPS) is commonly used to risk-stratify patients with coronary artery disease. Estimation of ischemic burden by cardiovascular magnetic resonance (CMR) with conventional 2-dimensional myocardial perfusion methods is limited by incomplete cardiac coverage. More recently developed 3-dimensional (3D) myocardial perfusion CMR, however, provides whole-heart coverage. The aim of this study was to compare ischemic burden on 3D myocardial perfusion CMR with (99m)Tc-tetrofosmin MPS., Methods and Results: Forty-five patients who had undergone clinically indicated MPS underwent rest and adenosine stress 3D myocardial perfusion and late gadolinium enhancement CMR. Summed stress and rest scores were calculated for MPS and CMR using a 17-segment model and expressed as a percentage of the maximal possible score. Ischemic burden was defined as the difference between stress and rest scores. 3D myocardial perfusion CMR and MPS agreed in 38 of the 45 patients for the detection of any inducible ischemia. The mean ischemic burden for MPS and CMR was similar (7.5±8.9% versus 6.8±9.5%, respectively, P=0.82) with a strong correlation between techniques (rs=0.70, P<0.001). In a subset of 33 patients who underwent clinically indicated invasive coronary angiography, sensitivities and specificities of the 2 techniques to detect angiographic coronary artery disease were similar (McNemar P=0.45)., Conclusions: 3D myocardial perfusion CMR is an alternative to MPS for detecting the presence and rating the severity of ischemia., (© 2014 American Heart Association, Inc.)

Aims: This study compared the myocardial ischaemic burden (MIB) in patients with angiographic three-vessel coronary artery disease (3VD) using high-resolution and standard-resolution myocardial perfusion cardiovascular magnetic resonance (perfusion CMR) imaging., Methods and Results: One hundred and five patients undergoing coronary angiography had two separate stress/rest perfusion CMR studies, one with standard-resolution (2.5 mm in-plane) and another with high-resolution (1.6 mm in-plane). Quantitative coronary angiography was used to define patients with angiographic 3VD. Perfusion CMR images were anonymized, randomly ordered and visually reported by two observers acting in consensus and blinded to all clinical and angiographic data. Perfusion was graded in each segment on a four-point scale and summed to produce a perfusion score and estimate of MIB for each patient. In patients with angiographic 3VD (n = 35), high-resolution acquisition identified more abnormal segments (7.2 ± 3.8 vs. 5.3 ± 4.0; P = 0.004) and territories (2.4 ± 0.9 vs. 1.6 ± 1.1; P = 0.002) and a higher overall perfusion score (20.1 ± 7.7 vs. 11.9 ± 9.4; P < 0.0001) per patient compared with standard-resolution. The number of segments with subendocardial ischaemia was greater with high-resolution acquisition (195 vs. 101; P < 0.0001). Hypoperfusion in all three territories was identified in 57% of 3VD patients by high-resolution compared with only 29% by standard-resolution (P = 0.04). The area-under-the-curve (AUC) for detecting angiographic 3VD using the estimated MIB was significantly greater with high-resolution than standard-resolution acquisition (AUC = 0.90 vs. 0.69; P < 0.0001)., Conclusion: In patients with angiographic 3VD, the ischaemic burden detected by perfusion CMR is greater with high-resolution acquisition due to better detection of subendocardial ischaemia. High-resolution perfusion CMR may therefore be preferred for risk stratification and management of this high-risk patient group., (© The Author 2014. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Coronary artery disease is the leading cause of death in women, and underdiagnosis contributes to the high mortality. This study compared the sex-specific diagnostic performance of cardiovascular magnetic resonance (CMR) and single-photon emission computed tomography (SPECT)., Methods and Results: A total of 235 women and 393 men with suspected angina underwent CMR, SPECT, and x-ray angiography as part of the Clinical Evaluation of Magnetic Resonance Imaging in Coronary Heart Disease (CE-MARC) study. CMR comprised adenosine stress/rest perfusion, cine imaging, late gadolinium enhancement, and magnetic resonance coronary angiography. Gated adenosine stress/rest SPECT was performed with (99m)Tc-tetrofosmin. For CMR, the sensitivity in women and men was similar (88.7% versus 85.6%; P=0.57), as was the specificity (83.5% versus 82.8%; P=0.86). For SPECT, the sensitivity was significantly worse in women than in men (50.9% versus 70.8%; P=0.007), but the specificities were similar (84.1% versus 81.3%; P=0.48). The sensitivity in both the female and male groups was significantly higher with CMR than SPECT (P<0.0001 for both), but the specificity was similar (P=0.77 and P=1.00, respectively). For perfusion-only components, CMR outperformed SPECT in women (area under the curve, 0.90 versus 0.67; P<0.0001) and in men (area under the curve, 0.89 versus 0.74; P<0.0001). Diagnostic accuracy was similar in both sexes with perfusion CMR (P=1.00) but was significantly worse in women with SPECT (P<0.0001)., Conclusions: In both sexes, CMR has greater sensitivity than SPECT. Unlike SPECT, there are no significant sex differences in the diagnostic performance of CMR. These findings, plus an absence of ionizing radiation exposure, mean that CMR should be more widely adopted in women with suspected coronary artery disease., Clinical Trial Registration Url: http://www.controlled-trials.com. Unique identifier: ISRCTN77246133.

Background: Two-dimensional (2D) perfusion cardiovascular magnetic resonance (CMR) remains limited by a lack of complete myocardial coverage. Three-dimensional (3D) perfusion CMR addresses this limitation and has recently been shown to be clinically feasible. However, the feasibility and potential clinical utility of quantitative 3D perfusion measurements, as already shown with 2D-perfusion CMR and positron emission tomography, has yet to be evaluated. The influence of systolic or diastolic acquisition on myocardial blood flow (MBF) estimates, diagnostic accuracy and image quality is also unknown for 3D-perfusion CMR. The purpose of this study was to establish the feasibility of quantitative 3D-perfusion CMR for the detection of coronary artery disease (CAD) and to compare systolic and diastolic estimates of MBF., Methods: Thirty-five patients underwent 3D-perfusion CMR with data acquired at both end-systole and mid-diastole. MBF and myocardial perfusion reserve (MPR) were estimated on a per patient and per territory basis by Fermi-constrained deconvolution. Significant CAD was defined as stenosis ≥70% on quantitative coronary angiography., Results: Twenty patients had significant CAD (involving 38 out of 105 territories). Stress MBF and MPR had a high diagnostic accuracy for the detection of CAD in both systole (area under curve [AUC]: 0.95 and 0.92, respectively) and diastole (AUC: 0.95 and 0.94). There were no significant differences in the AUCs between systole and diastole (p values >0.05). At stress, diastolic MBF estimates were significantly greater than systolic estimates (no CAD: 3.21 ± 0.50 vs. 2.75 ± 0.42 ml/g/min, p < 0.0001; CAD: 2.13 ± 0.45 vs. 1.98 ± 0.41 ml/g/min, p < 0.0001); but at rest, there were no significant differences (p values >0.05). Image quality was higher in systole than diastole (median score 3 vs. 2, p = 0.002)., Conclusions: Quantitative 3D-perfusion CMR is feasible. Estimates of MBF are significantly different for systole and diastole at stress but diagnostic accuracy to detect CAD is high for both cardiac phases. Better image quality suggests that systolic data acquisition may be preferable.

Background: In patients with stable coronary artery disease (CAD), decisions regarding revascularisation are primarily driven by the severity and extent of coronary luminal stenoses as determined by invasive coronary angiography. More recently, revascularisation decisions based on invasive fractional flow reserve (FFR) have shown improved event free survival. Cardiovascular magnetic resonance (CMR) perfusion imaging has been shown to be non-inferior to nuclear perfusion imaging in a multi-centre setting and superior in a single centre trial. In addition, it is similar to invasively determined FFR and therefore has the potential to become the non-invasive test of choice to determine need for revascularisation., Trial Design: The MR-INFORM study is a prospective, multi-centre, randomised controlled non-inferiority, outcome trial. The objective is to compare the efficacy of two investigative strategies for the management of patients with suspected CAD. Patients presenting with stable angina are randomised into two groups: 1) The FFR-INFORMED group has subsequent management decisions guided by coronary angiography and fractional flow reserve measurements. 2) The MR-INFORMED group has decisions guided by stress perfusion CMR. The primary end-point will be the occurrence of major adverse cardiac events (death, myocardial infarction and repeat revascularisation) at one year. Clinical trials.gov identifier NCT01236807., Conclusion: MR INFORM will assess whether an initial strategy of CMR perfusion is non-inferior to invasive angiography supplemented by FFR measurements to guide the management of patients with stable coronary artery disease. Non-inferiority of CMR perfusion imaging to the current invasive reference standard (FFR) would establish CMR perfusion imaging as an attractive non-invasive alternative to current diagnostic pathways.

Objectives: The goal of this study was to determine the diagnostic accuracy of dynamic 3-dimensional (3D) whole heart myocardial perfusion cardiovascular magnetic resonance (CMR) against invasively determined fractional flow reserve (FFR) and to establish the correlation between myocardium at risk defined by using the invasive Duke Jeopardy Score (DJS) and noninvasive 3D whole heart myocardial perfusion CMR., Background: 3D whole heart myocardial perfusion CMR overcomes the limited spatial coverage of conventional two-dimensional perfusion CMR methods and allows estimation of the extent of ischemia. The method has shown good diagnostic accuracy for the detection of coronary artery disease (CAD) as defined by using quantitative coronary angiography. However, quantitative coronary angiography does not provide a functional assessment of CAD as available from pressure wire-derived FFR. In the catheter laboratory, the DJS can complement FFR to estimate the myocardium at risk., Methods: Fifty-three patients referred for angiography underwent rest and adenosine stress 3D whole heart myocardial perfusion CMR at 3-T. Perfusion was scored visually on a patient and coronary territory basis, and ischemic burden was calculated by quantitative segmentation of the volume of hypoenhancement. FFR was measured in vessels with ≥50% severity stenosis and an FFR <0.75 considered as hemodynamically significant. The DJS was calculated from the coronary angiograms to quantify the myocardium at risk., Results: FFR was measured in 64 of 159 coronary vessels, and 39 had an FFR <0.75. Sensitivity, specificity, and diagnostic accuracy of CMR for the detection of significant CAD were 91%, 90%, and 91%, on a patient basis and 79%, 92%, and 88%, respectively, by coronary territory. There was a strong correlation between the DJS and ischemic burden on CMR (p < 0.0001; Pearson's r = 0.82)., Conclusions: 3D whole heart myocardial perfusion CMR accurately detects functionally significant CAD as defined by using FFR and provides an assessment of ischemic burden in agreement with the invasive DJS. The accurate detection of significant CAD combined with an estimation of ischemic burden by using 3D myocardial perfusion CMR holds promise for noninvasive guidance of therapy and risk stratification of patients with CAD., (Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Although accelerated high-spatial-resolution cardiovascular MR (CMR) myocardial perfusion imaging has been shown to be clinically feasible, there has not yet been a direct comparison with standard-resolution methods. We hypothesized that higher spatial resolution detects more subendocardial ischemia and leads to greater diagnostic accuracy for the detection coronary artery disease. This study compared the diagnostic accuracy of high-resolution and standard-resolution CMR myocardial perfusion imaging in patients with suspected coronary artery disease., Methods and Results: A total of 111 patients were recruited to undergo 2 separate perfusion-CMR studies at 1.5 T, 1 with standard-resolution (2.5×2.5 mm in-plane) and 1 with high-resolution (1.6×1.6 mm in-plane) acquisition. High-resolution acquisition was facilitated by 8-fold k-t broad linear speed-up technique acceleration. Two observers visually graded perfusion in each myocardial segment on a 4-point scale. Segmental scores were summed to produce a perfusion score for each patient. All patients underwent invasive coronary angiography and coronary artery disease was defined as stenosis ≥50% luminal diameter (quantitative coronary angiography). CMR data were successfully obtained in 100 patients. In patients with coronary artery disease (n=70), more segments were determined to have subendocardial ischemia with high-resolution than with standard-resolution acquisition (279 versus 108; P<0.001). High-resolution acquisition had a greater diagnostic accuracy than standard resolution for identifying single-vessel disease (area under the curve, 0.88 versus 0.73; P<0.001) or multivessel disease (area under the curve, 0.98 versus 0.91; P=0.002) and overall (area under the curve, 0.93 versus 0.83; P<0.001)., Conclusions: High-resolution perfusion-CMR has greater overall diagnostic accuracy than standard-resolution acquisition for the detection of coronary artery disease in both single- and multivessel disease and detects more subendocardial ischemia.

Background: The dual-bolus protocol enables accurate quantification of myocardial blood flow (MBF) by first-pass perfusion cardiovascular magnetic resonance (CMR). However, despite the advantages and increasing demand for the dual-bolus method for accurate quantification of MBF, thus far, it has not been widely used in the field of quantitative perfusion CMR. The main reasons for this are that the setup for the dual-bolus method is complex and requires a state-of-the-art injector and there is also a lack of post processing software. As a solution to one of these problems, we have devised a universal dual-bolus injection scheme for use in a clinical setting. The purpose of this study is to show the setup and feasibility of the universal dual-bolus injection scheme., Methods: The universal dual-bolus injection scheme was tested using multiple combinations of different contrast agents, contrast agent dose, power injectors, perfusion sequences, and CMR scanners. This included 3 different contrast agents (Gd-DO3A-butrol, Gd-DTPA and Gd-DOTA), 4 different doses (0.025 mmol/kg, 0.05 mmol/kg, 0.075 mmol/kg and 0.1 mmol/kg), 2 different types of injectors (with and without "pause" function), 5 different sequences (turbo field echo (TFE), balanced TFE, k-space and time (k-t) accelerated TFE, k-t accelerated balanced TFE, turbo fast low-angle shot) and 3 different CMR scanners from 2 different manufacturers. The relation between the time width of dilute contrast agent bolus curve and cardiac output was obtained to determine the optimal predefined pause duration between dilute and neat contrast agent injection., Results: 161 dual-bolus perfusion scans were performed. Three non-injector-related technical errors were observed (1.9%). No injector-related errors were observed. The dual-bolus scheme worked well in all the combinations of parameters if the optimal predefined pause was used. Linear regression analysis showed that the optimal duration for the predefined pause is 25s to separate the dilute and neat contrast agent bolus curves if 0.1 mmol/kg dose of Gd-DO3A-butrol is used., Conclusion: The universal dual-bolus injection scheme does not require sophisticated double-head power injector function and is a feasible technique to obtain reasonable arterial input function curves for absolute MBF quantification.

Three-dimensional myocardial perfusion imaging requires significant acceleration of data acquisition to achieve whole-heart coverage with adequate spatial and temporal resolution. The present article introduces a compartment-based k-t principal component analysis reconstruction approach, which permits three-dimensional perfusion imaging at 10-fold nominal acceleration. Using numerical simulations, it is shown that the compartment-based method results in accurate representations of dynamic signal intensity changes with significant improvements of temporal fidelity in comparison to conventional k-t principal component analysis reconstructions. Comparison of the two methods based on rest and stress three-dimensional perfusion data acquired with 2.3 × 2.3 × 10 mm(3) during a 225 msec acquisition window in patients confirms the findings and demonstrates the potential of compartment-based k-t principal component analysis for highly accelerated three-dimensional perfusion imaging., (Copyright © 2010 Wiley-Liss, Inc.)

Aims: To evaluate the feasibility and diagnostic performance of high spatial resolution myocardial perfusion cardiac magnetic resonance (perfusion-CMR)., Methods and Results: Fifty-four patients underwent adenosine stress perfusion-CMR. An in-plane spatial resolution of 1.4 × 1.4 mm(2) was achieved by using 5× k-space and time sensitivity encoding (k-t SENSE). Perfusion was visually graded for 16 left ventricular and two right ventricular (RV) segments on a scale from 0 = normal to 3 = abnormal, yielding a perfusion score of 0-54. Diagnostic accuracy of the perfusion score to detect coronary artery stenosis of >50% on quantitative coronary angiography was determined. Sources and extent of image artefacts were documented. Two studies (4%) were non-diagnostic because of k-t SENSE-related and breathing artefacts. Endocardial dark rim artefacts if present were small (average width 1.6 mm). Analysis by receiver-operating characteristics yielded an area under the curve for detection of coronary stenosis of 0.85 [95% confidence interval (CI) 0.75-0.95] for all patients and 0.82 (95% CI 0.65-0.94) and 0.87 (95% CI 0.75-0.99) for patients with single and multi-vessel disease, respectively. Seventy-four of 102 (72%) RV segments could be analysed., Conclusion: High spatial resolution perfusion-CMR is feasible in a clinical population, yields high accuracy to detect single and multi-vessel coronary artery disease, minimizes artefacts and may permit the assessment of RV perfusion.