Cardiovascular magnetic resonance and single-photon emission computed tomography for diagnosis of coronary heart disease (CE-MARC): a prospective trial

Abstract

Background: In 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.

Methods: In 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 (99m)Tc tetrofosmin. The primary outcome was diagnostic accuracy of CMR. This trial is registered at controlled-trials.com, number ISRCTN77246133.

Findings: In 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<0·0001 for both) but specificity and positive predictive value did not (p=0·916 and p=0·061, respectively).

Interpretation: CE-MARC is the largest, prospective, real world evaluation of CMR and has established CMR's high diagnostic accuracy in coronary heart disease and CMR's superiority over SPECT. It should be adopted more widely than at present for the investigation of coronary heart disease.

Funding: British Heart Foundation.

Figure 1

Cardiovascular magnetic resonance protocol After a low-resolution survey scan and localisers to define the cardiac long and short axes, intravenous adenosine was administered for 4 min at 140 μg/kg per min, during which first-pass stress perfusion imaging was undertaken with 0·05 mmol/kg dimeglumine gadopentetate. 3D whole heart MR coronary angiography was done after the low resolution coronary survey and free-breathing four chamber cine (used to assess slice coverage and diastolic coronary rest period, respectively). Rest perfusion imaging was undertaken a minimum of 15 min after stress perfusion, with a further injection of 0·05 mmol/kg dimeglumine gadopentetate. A final injection of 0·1 mmol/kg dimeglumine gadopentetate was given after this sequence, bringing the overall gadolinium dose to 0·2 mmol/kg. Resting left ventricular function was then assessed, initially for three slices, planned identically to the perfusion slices, and then for the entire left ventricle with contiguous slices. A modified Look-Locker inversion time scout was done before late gadolinium enhancement imaging in short axis, vertical long axis, and horizontal long axis orientations. Times indicated are approximate and sequence blocks are not drawn to scale.

Figure 2

Trial profile *34 received SPECT before CMR. †56 received CMR before SPECT because of patient and logistic reasons.

Figure 3

Three examples of CMR, SPECT, and angiographic findings (A) Stress perfusion CMR shows inducible hypoperfusion (ischaemia) in the septum and anterior wall (arrow shows dark area of hypoperfusion), SPECT is concordant (arrows show lower signal counts during stress), indicating anteroseptal inducible ischaemia, and angiography confirms a stenosis (arrow) in the left anterior descending artery. (B) Late gadolinium-enhanced CMR (arrow shows hyperenhancement in the inferior wall) and SPECT (fixed defect; arrows show comparable inferior defect at rest and stress) are concordant, showing a transmural inferior myocardial infarct with the corresponding right coronary artery chronic total occlusion (arrow) seen at angiography. (C) Late gadolinium-enhanced CMR shows subendocardial inferior infarction (arrow), SPECT was reported as normal (no wall motion abnormality), and the angiogram shows coronary atheroma but no clinically significant stenosis (or occlusion). As per study protocol, CMR in this patient was classified as a false positive, showing the potential limitations of angiography as a reference test for the detection of coronary heart disease. The case also shows that SPECT can miss small subendocardial infarcts. CMR=cardiovascular magnetic resonance. SPECT=single-photon emission computed tomography.

Figure 4

Receiver operating characteristic curves of summed stress scores by population and coronary heart disease definition Generated using summed stress scores with the CMR stress perfusion component and from SPECT (n=647) for the whole cohort ([A] angiographic cutoff ≥50% LMS; ≥70% for LAD, LCx, and RCA; [B] angiographic cut-off ≥50% for LMS, LAD, LCx, and RCA), patients with single-vessel disease (C), and patients with multivessel (two or three vessel) disease (D). CMR=cardiovascular magnetic resonance. SPECT=single-photon emission computed tomography. AUC=area under the curve. LMS=left main stem. LAD=left anterior descending. LCx=left circumflex. RCA=right coronary artery.