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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

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 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 P P =1.00) but was significantly worse in women with SPECT ( P 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: There are no prospective, prognostic data comparing cardiovascular magnetic resonance (CMR) and singlephoton emission computed tomography (SPECT) in the same population of patients with suspected coronary heart disease (CHD). Objective: To establish the ability of CMR and SPECT to predict major adverse cardiovascular events (MACEs). Design: Annual follow-up of the CE-MARC (Clinical Evaluation of MAgnetic Resonance imaging in Coronary heart disease) study for a minimum of 5 years for MACEs (cardiovascular death, acute coronary syndrome, unscheduled revascularization or hospital admission for cardiovascular cause). (Current Controlled Trials registration: ISRCTN77246133) Setting: Secondary and tertiary care cardiology services. Participants: 752 patients from the CE-MARC study who were being investigated for suspected CHD. Measurements: Prediction of time to MACE was assessed by using univariable (log-rank test) and multivariable (Cox proportional hazards regression) analysis. Results: 744 (99%) of the 752 recruited patients had complete follow-up. Of 628 who underwent CMR, SPECT, and the reference standard test of X-ray angiography, 104 (16.6%) had at least 1 MACE. Abnormal findings on CMR (hazard ratio, 2.77 [95% CI, 1.85 to 4.16]; P < 0.001) and SPECT (hazard ratio, 1.62 [CI, 1.11 to 2.38; P = 0.014) were both strong and independent predictors of MACE. Only CMR remained a significant predictor after adjustment for other cardiovascular risk factors, angiography result, or stratification for initial patient treatment. Limitation: Data are from a single-center observational study (albeit conducted in a high-volume institution for both CMR and SPECT). Conclusion: Five-year follow-up of the CE-MARC study indicates that compared with SPECT, CMR is a stronger predictor of risk for MACEs, independent of cardiovascular risk factors, angiography result, or initial patient treatment. This further supports the role of CMR as an alternative to SPECT for the diagnosis and management of patients with suspected CHD. Primary Funding Source: British Heart Foundation.

Many of the issues raised by Dr Einstein have been addressed in the article1 and in previous correspondence relating to the Clinical Evaluation of Magnetic Resonance Imaging in Coronary Heart Disease (CE-MARC) study.2,3 Einstein argues that the inclusion of magnetic resonance angiography offered cardiovascular magnetic resonance (CMR) an unfair advantage. However, as discussed in the article, secondary analyses from CE-MARC showed that excluding the magnetic resonance angiography component not only had a neutral effect on overall diagnostic accuracy, but actually led to a superior positive-predictive value for CMR in comparison with single-photon emission computed tomography (SPECT; owing to a reduction in false positives).2 We also included a detailed perfusion-only component analysis that Einstein makes no reference to in his critique. For perfusion-only components, CMR still significantly outperformed SPECT in females (area under the curve, 0.90 versus …

Background Left main stem (LMS) disease occurs in approximately 5% of patients with stable angina. It confers adverse prognosis, with potential for prognostic gain with revascularization. Single-photon emission computed tomography (SPECT) and CMR fail to detect ischemia in 41% and 18% of patients with significant LMS stenosis respectively [1], likely in part because of balanced reduction in coronary perfusion. It is not known whether quantitative assessment of myocardial blood flow (MBF) can improve diagnostic rates. The CE-MARC study prospectively enrolled 752 patients with suspected coronary artery disease, scheduled to undergo CMR, SPECT and X-ray coronary angiography [2]. We assessed the diagnostic performance of visual and quantitative perfusion CMR in CE-MARC patients with LMS disease. Methods All patients from the CE-MARC population with LMS disease ≥50%, or LMS equivalent disease (proximal LAD and proximal LCx ≥70%) on quantitative angiography were studied. A control group (matched for age and gender, excluding LMS or 3-vessel disease) was randomly selected from the CE-MARC population. Visual SPECT and CMR analyses were from the original, blinded read of CE-MARC. Only perfusion components of the CE-MARC CMR and SPECT protocols were analyzed. MBF was calculated offline (PMI v0.4) using the Fermi model from CMR stress perfusion images, with arterial input defined in LV blood pool, and LAD and LCx segments in the mid-LV short axis myocardial slice as tissue response. Results

Background Whilst exercise tolerance testing (ETT) has been a corner stone investigation for the diagnosis of patients with suspected angina, increasingly imaging techniques have gained prominence. We aimed to determine the diagnostic accuracy of ETT in the CE-MARC study population compared to single photon emission computed tomography (SPECT) and cardiovascular magnetic resonance (CMR) and to examine the clinical utility of performing CMR or SPECT after an inconclusive ETT result. Methods CE-MARC was the largest prospective real-world evaluation of CMR, SPECT and ETT, in 752 patients with suspected angina. Results for CMR and SPECT have been reported. For this analysis, results of the ETT were analysed and compared with CMR and SPECT as well as combinations of tests. Results 580 patients had ETT and angiography (disease prevalence 39%). The sensitivity, specificity, positive and negative predictive values (95%CI) of ETT were 68.3 (61.9, 74.0), 72.5

Previous work has shown that truncating the carboxyl terminus (C-terminus) of the rat angiotensin AT1A receptor to 309 amino acids abolished G-protein coupling and receptor internalization. This suggests that domains responsible for these functions lie beyond amino acid 309 of the C-terminus. The objective of this study was to determine the effect on angiotensin AT1A receptor function and regulation of deleting 41 amino acids from the C-terminus, which include the putative protein kinase C phosphorylation sites. Using site directed mutagenesis, the codon for Tyr319 was converted to a stop codon and the resulting truncated receptor permanently expressed in cultured human kidney cells. The properties of the truncated receptor were compared to those of the full length receptor. Expression of the truncated receptor was confirmed by sodium dodecyl sulphate polyacrylamide gel electrophoresis analysis of photolabelled membrane preparations. Angiotensin II activation of both full length and truncated receptors resulted in mobilization of inositol phosphates. However, whereas this was associated with rapid internalization of the full length receptor, the truncated receptor failed to internalize. Furthermore, pretreatment of cells with phorbol 12-myristate 13-acetate, a direct activator of protein kinase C, markedly attenuated the full length, but no the truncated receptor's ability to mobilise inositol phosphates. Thus, we conclude that the domain between amino acids 309 & 318 is important for G-protein coupling; that amino acids beyond 318 regulate internalization and one or more of the putative protein kinase C phosphorylation sites, present in the C-terminus of the angiotensin At1A receptor, actively regulate the receptor.

Summary We compared detection rate sf or cardiovascular magnetic resonance (CMR) perfusion and single photon emission tomography (SPECT) in the subset of patients from the CE-MARC study with significant left main stem (LMS) disease. Detection rates for LMS disease by CMR perfusion were higher than for SPECT, and CMR identified a classical LMS pattern with higher frequency. Visual perfusion defects occurred with similar frequency in patients with ≥50% and ≥70% LMS stenosis. Background Left main stem (LMS) disease is found in approximately 5% of patients with stable angina. Three-year survival in patients with >50% left main stenosis may be as low as 50%. Single photon emission tomography (SPECT) fails to detect ischemia in up to 15% of LMS stenoses, and identification of the ‘classical’ pattern of both left anterior descending (LAD) and circumflex (LCx) coronary territory ischaemia is lower still. To date, the utility of cardiovascular magnetic resonance (CMR) perfusion in LMS disease is poorly established. The CE-MARC study was a prospective study of 752 patients with suspected coronary artery disease, enrolled to undergo CMR, SPECT and X-ray coronary angiography. We assessed the diagnostic performance of SPECT and CMR to detect LMS disease in the group of CE-MARC patients with ≥50% LMS disease on quantitative X-ray angiography. We also compared subsets of patients with ≥50% and ≥70% LMS stenosis. Methods All patients with LMS disease ≥50% on quantitative angiography were identified from the CE-MARC study. All patients had undergone adenosine stress perfusion by CMR and SPECT and also invasive X-ray angiography [1]. By visual analysis we compared detection rates for LMS disease from the CMR and SPECT perfusion studies. Results Of 23 patients in the CE-MARC cohort with LMS stenosis ≥50%, one patient could not be analysed. CMR identified evidence of inducible perfusion defects in 18/ 22 (82%) of the LMS group; SPECT identified 13/22 (59%). For CMR and SPECT respectively, inducible perfusion defects were found in both LAD and LCx territories for 6/18 (33%) and 2/13 (15%). Only one patient had normal perfusion analyses (false negative) for both CMR and SPECT. Of 11 patients with ≥70% LMS stenosis, 10 (91%) had inducible perfusion defects with CMR vs. 5 (45%) with SPECT. Six (55%) vs. 2 (18%) had a LAD and LCx disease pattern. Perfusion abnormalities were detected with similar frequency in ≥50% and ≥70% groups by both CMR (p=0.64) and SPECT (p=0.49). Figure 1 summarises the detection rate of CMR and SPECT in LMS disease.

Background Left main stem (LMS) disease occurs in approximately 5% of patients with stable angina. It confers adverse prognosis, with potential for prognostic gain with revascularization. Single-photon emission CT (SPECT) and cardiovascular magnetic resonance (CMR) fail to detect ischaemia in 41% and 18% of patients with significant LMS stenosis respectively, likely in part because of balanced reduction in coronary perfusion. It is not known whether quantitative assessment of myocardial blood flow (MBF) can improve diagnostic rates. The CE-MARC study prospectively enrolled 752 patients with suspected coronary artery disease, scheduled to undergo CMR, SPECT and X-ray coronary angiography. We assessed the diagnostic performance of visual and quantitative perfusion CMR in CE-MARC patients with LMS disease. Methods All patients from the CE-MARC population with LMS disease ≥50%, or LMS equivalent disease (proximal LAD and proximal LCx ≥70%) on quantitative angiography were studied. A control group (matched for age and gender, excluding LMS or 3-vessel disease) was randomly selected from the CE-MARC population. Visual SPECT and CMR analyses were from the original, blinded read of CE-MARC. Only perfusion components of the CE-MARC CMR and SPECT protocols were analysed. MBF was calculated offline (PMI v0.4) using the Fermi model from CMR stress perfusion images, with arterial input defined in LV blood pool, and LAD and LCx segments in the mid-LV short axis myocardial slice as tissue response. Results 47 patients were included in the analysis (22 LMS, 1 LMS equivalent, 24 controls); 1 LMS patient did not have CMR. Visual detection rates for ischsemia in LMS disease were non-significantly higher for CMR than SPECT (83% vs 61%, p=0.19). On quantitative CMR perfusion analysis, stress MBF was significantly lower in LMS patients than controls (2.67±0.94 ml/g/min vs 3.97±1.25 ml/g/min, p Conclusions Quantitative CMR identifies LMS disease with higher sensitivity than visual SPECT analysis. Quantitative CMR analysis of MBF compared to visual CMR analysis did increase diagnostic sensitivity numerically; however this did not reach statistical significance in this small population from CE-MARC.

Introduction Approximately 5% of patients with stable angina have disease of the left main stem (LMS). Three-year survival in patients with >50% LMS stenosis may be as low as 50%. Single photon emission tomography (SPECT) fails to detect ischaemia in up to 15% of LMS stenoses, and identification of the “classical” pattern of both left anterior descending (LAD) and circumflex (LCx) coronary territory ischaemia is lower still. To date, the utility of cardiovascular magnetic resonance (CMR) perfusion in LMS disease is poorly established. The CE-MARC study was a prospective study of 752 patients with suspected coronary artery disease, enrolled to undergo CMR, SPECT and x-ray coronary angiography; we assessed the diagnostic performance of SPECT and CMR to detect LMS disease. Methods All patients with LMS disease ≥50% on quantitative angiography were identified from the CE-MARC study. All patients had undergone adenosine stress perfusion by CMR and SPECT and also invasive x-ray angiography.1 We compared detection rates for visual perfusion analysis from both the CMR and SPECT perfusion studies in patients with ≥50% and ≥70% LMS stenosis on angiography. Results Of 23 patients in the CE-MARC cohort with LMS stenosis ≥50%, one patient could not be analysed. CMR identified evidence of inducible perfusion defects in 18/22 (82%) of the LMS group; SPECT identified 13/22 (59%). For CMR and SPECT respectively, inducible perfusion defects were found in both LAD and LCx territories for 6/18 (33%) and 2/13 (15%). Only one patient had normal perfusion analyses (false negative) for both CMR and SPECT. Of 11 patients with ≥70% LMS stenosis, 10 (91%) had inducible perfusion defects with CMR vs 5 (45%) with SPECT. Six (55%) vs 2 (18%) had a LAD and LCx disease pattern. Perfusion abnormalities were detected with similar frequency in ≥50% and ≥70% groups by both CMR (p=0.64) and SPECT (p=0.49). Abstract 088 figures 1 and 2 summarise the detection rate of CMR and SPECT in LMS disease in the ≥50% and ≥70% LMS groups respectively. Conclusions CMR stress perfusion imaging identifies ischaemia in a higher proportion of patients with significant LMS disease than SPECT, and identifies a “classical” LMS pattern with higher frequency. Perfusion abnormalities are detected with similar frequency in patients with ≥50% and ≥70% LMS stenosis.

Background The prognostic importance of the ischaemic and scar burden, and their impact on coronary heart disease (CHD) patient management is well established from single photon emission computed tomography (SPECT) studies. Recently, cardiac magnetic resonance (CMR) has been shown to have superior sensitivity for the detection of CHD compared with SPECT [1]. However, the ischaemic and the scar burden measured by CMR and SPECT have not been compared. Methods From the prospective CE-MARC study, all patients who had significant coronary artery stenosis (≥70% of a first order coronary artery or ≥50% of the left main artery) on quantitative invasive coronary angiography and ischaemia on both CMR and SPECT were selected. The summed stress score (SSS), the summed rest score (SRS) as well as the summed difference score (SDS) were assessed based on a 5-point scoring scale (0=normal; 4=severe) for perfusion defects and/or late gadolinium enhancement (LGE)

Methods Thirty-nine patients with 3VD at X-ray coronary angiography and 39 matched patients with no significant coronary disease were identified from the CE-MARC study population [1]. Patients were matched by age, gender, hypertension and diabetes. CMR adenosine stress perfusion imaging was undertaken using a saturation-recovery gradient echo pulse sequence producing three image slices per R-R interval. Visual and Fermi deconvolutionderived CMR myocardial perfusion reserve (MPR) analyses were performed. Gated SPECT imaging was performed and interpreted by an experienced observer blinded to other test results.

SummaryBackgroundIn patients with suspected coronary heart disease, single-photon emission computed tomography (SPECT) is the most widely used test for the assessment of myocardial ischaemia, but its diagnostic accuracy is reported to be variable and it exposes patients to ionising radiation. The aim of this study was to establish the diagnostic accuracy of a multiparametric cardiovascular magnetic resonance (CMR) protocol with x-ray coronary angiography as the reference standard, and to compare CMR with SPECT, in patients with suspected coronary heart disease.MethodsIn this prospective trial patients with suspected angina pectoris and at least one cardiovascular risk factor were scheduled for CMR, SPECT, and invasive x-ray coronary angiography. CMR consisted of rest and adenosine stress perfusion, cine imaging, late gadolinium enhancement, and MR coronary angiography. Gated adenosine stress and rest SPECT used 99mTc tetrofosmin. The primary outcome was diagnostic accuracy of CMR. This trial is registered at controlled-trials.com, number ISRCTN77246133.FindingsIn the 752 recruited patients, 39% had significant CHD as identified by x-ray angiography. For multiparametric CMR the sensitivity was 86·5% (95% CI 81·8–90·1), specificity 83·4% (79·5–86·7), positive predictive value 77·2%, (72·1–81·6) and negative predictive value 90·5% (87·1–93·0). The sensitivity of SPECT was 66·5% (95% CI 60·4–72·1), specificity 82·6% (78·5–86·1), positive predictive value 71·4% (65·3–76·9), and negative predictive value 79·1% (74·8–82·8). The sensitivity and negative predictive value of CMR and SPECT differed significantly (p

Left main stem (LMS) disease is found in approximately 5% of patients with stable angina and in approximately 7% of patients presenting with an acute myocardial infarction. Accurate assessment of the degree of left main stem stenosis has important prognostic and therapeutic implications. Clinically, angiographic LMS stenosis of 50% or more is considered significant. However, it is not known how accurately myocardial perfusion imaging detects LMS disease at this severity threshold.

Background First pass myocardial perfusion imaging by CMR may permit the detection of myocardial ischaemia with greater accuracy than single photon emission computed tomography (SPECT). Technical developments have led to improvements in myocardial perfusion CMR, particularly through accelerated data acquisition methods. These permit the acquisition of data at higher spatial resolution than conventional CMR techniques, though it is unknown whether this improves diagnostic performance.

The CE-MARC study is the largest, prospective evaluation of cardiovascular magnetic resonance (CMR) in patients with suspected coronary artery disease (CAD). This predefined CE-MARC substudy compared the diagnostic performance of CMR and single-photon emission computed tomography (SPECT) in the female cohort.