Response to Letter Regarding Article “Comparison of Cardiovascular Magnetic Resonance and Single-Photon Emission Computed Tomography in Women With Suspected Coronary Artery Disease From the Clinical Evaluation of Magnetic Resonance Imaging in Coronary Heart Disease (CE-MARC) Trial”
Authors: John P. Greenwood, Manish Motwani, Neil Maredia, Julia M. Brown, Colin C. Everett, Jane Nixon, Petra Bijsterveld, Catherine J. Dickinson, Stephen G. Ball, Sven Plein
Journal: Circulation (2014)

Evaluation of Magnetic Resonance Imaging in Coronary HeartDisease (CE-MARC) study. 2,3instein 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 0.67; P<0.0001).We reject the inferences that we compared state-of-the-art CMR with an inferior SPECT protocol.In fact, we used a 7-year-old 1•5T MRI scanner with standard perfusion pulse sequences, contemporary SPECT equipment, and comparable protocols for both techniques that were standard at the time of patient recruitment.Inevitably, both CMR and SPECT have undergone technological improvements in the interim, but this cannot fairly be used as criticism.Einstein also implies that an imbalance of expertise at Leeds General Infirmary favored CMR, but, in fact, the nuclear cardiology department is also a high-volume, highly specialized unit and its members were a key component of the CE-MARC collaboration.CE-MARC compared diagnostic accuracy, and, therefore, the comments regarding prognostic data from exercise SPECT are not relevant in this context.Einstein also oversimplifies the 2013 European Society of Cardiology guidelines on the management of stable coronary artery disease regarding the statement that exercise is always the preferred stressor.In fact, the guidelines only assign level C evidence to this recommendation.Despite conceding that SPECT performance is known to be poorer in women because of sex differences in heart size, Einstein dismisses this as an explanation for our results.This is surprising, because we clearly demonstrated that the females in our study had smaller hearts, and that there was a significant difference in sensitivity across tertiles of left ventricular mass.The argument that the magnitude of difference between SPECT and CMR is larger than in previous studies has also been previously addressed.Einstein supports his argument with selected data from a recent meta-analysis that excludes studies subjected to posttest referral bias (only positive cases referred for coronary angiography), but still makes no allowance for pretest selection bias (only patients warranting coronary angiography enrolled).In fact, when Miller et al used methods to correct for both types of bias in a SPECT cohort of 1853 patients, the adjusted sensitivity and specificity were 65% and 67%, respectively (ie, similar to CE-MARC values: sensitivity, 67%; specificity, 83%), which vindicates our prospective study design. 3,4inally, we concur that local expertise is paramount in diagnostic test selection.However, coronary artery disease remains the leading cause of death in women, and underdiagnosis contributes to their high mortality.For too long, the substantial underrepresentation of women in trials has limited their evidence-based assessment.It would therefore be remiss of us to ignore the evidence that is finally emerging, not just from our own study, but also from others such as Magnetic Resonance Imaging for Myocardial Perfusion Assessment in Coronary Artery Disease Trial (MR-IMPACT-II). 5