Cardiovascular magnetic resonance and single-photon emission computed tomography for diagnosis of coronary heart disease (CE-MARC): a prospective trial1
The 2010 NICE guidelines on stable chest pain of recent origin2 have revolutionised its management. The current UK management strategy is based on the estimated likelihood of coronary artery disease (CAD) using age, sex, risk factors and the typicality of chest pain. Functional imaging (for e.g. stress cardiovascular magnetic resonance/ stress echo/ Single-photon emission computed tomography) is only recommended in the group with predicted risk between 30-60%. In UK SPECT has been rapidly adopted as the default functional imaging modality mainly due to its easy availability. But its diagnostic accuracy is reported to be variable and it exposes patients to ionising radiation3-5.
Establish the diagnostic accuracy of CMR compared to invasive coronary angiography as the reference standard, and to compare CMR with SPECT, in patients with suspected coronary heart disease.
It was a prospective study from two North England hospitals and the patients were recruited between March 2006 - August 2009. Consecutive patients with suspected angina pectoris were screened and enrolled if they had at least one major cardiovascular risk factor and a cardiologist judged them to have stable angina needing investigation, in accordance with contemporary clinical practice.
Study patients were derived as shown in the following flow diagram.
CMR yields higher diagnostic performance than SPECT, using X-ray angiography as the reference standard.
The primary outcome was diagnostic accuracy of CMR.
The main secondary outcome was a comparison of multiparametric CMR (rest and stress perfusion, left ventricular function, coronary magnetic resonance angiography, and late gadolinium enhancement) and SPECT (rest and stress perfusion, left ventricular function) with x-ray angiography as the reference.
Previous coronary artery bypass surgery;
Crescendo angina or acute coronary syndrome;
Contraindication to CMR (eg, pacemaker) or adenosine infusion (eg, reversible airways disease, atrioventricular block);
Inability to lie supine; and
Glomerular filtration rate of 30 ml/min per 173m2 or less
Predetermined cardiovascular magnetic resonance imaging parameters used - rest and stress perfusion, left ventricular function, coronary magnetic resonance angiography, and late gadolinium enhancement.
Criteria for a positive CMR (any of the following)
1. Any evidence of regional wall motion abnormality
2. Hypoperfusion (ischaemia) assessed by visual comparison of stress and rest CMR perfusion scans
3. Visual severity (percentage luminal narrowing) of coronary artery stenosis in the coronary MR angiogram
4. Any infarct (scar) on late gadolinium-enhancement
SPECT radionuclide imaging was done with a cardiac gamma camera and patients underwent a standard 2-day protocol with 99mTc tetrofosmin (Myoview). Evidence of ischaemia was recorded by visual comparison of rest and stress SPECT perfusion scans. QGS software was used to calculate end diastolic and end systolic volumes and wall motion scores.
Stenosis ≥70% of a first order coronary artery measuring 2 mm or greater in diameter, or left main stem stenosis ≥50% as measured by quantitative coronary angiography with use of QCAPlus software was considered clinically significant.
In the 752 recruited patients, 39% had significant CAD as identified by x-ray angiography. The sensitivity of CMR was 865% (95% CI 818901), specificity 834% (795867), positive predictive value 772% (721816), and negative predictive value 905% (871930) - the primary outcome measure. In the secondary outcome measure, the sensitivity of SPECT was 665% (604721), specificity 826% (785861), positive predictive value 714% (653769), and negative predictive value 791% (748828). The sensitivity and negative predictive value of CMR and SPECT differed significantly (p<00001 for both) but specificity and positive predictive value did not (p=0916 and p=0061, respectively).
1. Extrapolation should be made with caution as patients were mostly Caucasians without any previous CABG and underwent the investigations in a high volume centre.
2. Two functional tests (CMR and SPECT) tests were compared with an imperfect reference standard anatomical test (angiography). Thus, false-negative results could occur if lesions not causing ischaemia (as assessed by CMR or SPECT) were judged clinically significant on the basis of angiographic stenosis severity. Results from the FAME trial6 showed a wide difference between angiographic stenosis and fractional flow reserve measurements. FFR measurements would have provided a more accurate result.
3. As a component of the multiparametric CMR assessment 3D coronary magnetic resonance angiography was used which is not part of the routine stress CMR protocol used in most hospitals. This may have improved the accuracy.
CE-MARC is the largest, prospective, real world assessment of CMR in stable chest pain. The CE-MARC study support the wider adoption of CMR for the assessment of stable coronary heart disease patients, in view of the growing concern of the cancer risk associated with medical-source ionising radiation.
The overall X-ray angiography proven CAD prevalence was 39% in the study group (average age of 60years and atleast 1 risk factor). The age, risk factor and typicality of chest pain would put their estimated pretest likelihood of CAD >60% where the recommended investigation is x-ray angiography. Hence the study hints toward a possible role of CMR in assessment of patients with predicted CAD risk >60% thereby avoiding unnecessary invasive angiography. Further sub-study is needed to confirm this observation.
1. Greenwood JP, Maredia N, Younger JF, et al. Cardiovascular magnetic resonance and single-photon emission computed tomography for diagnosis of coronary heart disease (CE-MARC): a prospective trial. Lancet 2011; 379(9814): 453460.
2. NICE. Chest pain of recent onset: assessment and diagnosis of recent onset chest pain or discomfort of suspected cardiac origin NICE clinical guideline (2010). http://www.nice.org.uk/guidance/CG95
4. Mowatt G, Vale L, Brazzelli M. Systematic review of the effectiveness and cost-effectiveness, and economic evaluation, of myocardial perfusion scintigraphy for the diagnosis and management of angina and myocardial infarction. Health Technol Assess. 2004;8:1207.
5. Shaw LJ, Bairey Merz CN, Pepine CJ., for the WISE investigators Insights from the NHLBI-sponsored women's ischemia syndrome evaluation (WISE) study: part I: gender differences in traditional and novel risk factors, symptom evaluation, and gender-optimized diagnostic strategies. J Am Coll Cardiol. 2006;47(3 suppl):S420.
6. Tonino PA, Fearon WF, De Bruyne B et al. Angiographic versus functional severity of coronary artery stenoses in the FAME study fractional flow reserve versus angiography in multivessel evaluation. J Am Coll Cardiol 2010; 55: 28162821