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The growing use of cardiac magnetic resonance in ischaemic heart disease

Prof. C. Bucciarelli-Ducci, Chair of the CMR Section at the EACVI and co-director of the Clinical Research and Imaging Centre at Bristol Heart Institute, Bristol, UK.



Cardiac magnetic resonance imaging (CMR) is a non-invasive and radiation- free technique that is increasingly used in patients with chest pain, as it offers the ability to assess the causes of the symptom. Primarily, this means assessing the presence and extent of myocardial ischaemia, but the technique can also be used to rule out other causes of chest pain, such as myocarditis or pericarditis, among others.1

Increased clinical use of CMR in cardiology

The CMR service in Bristol, a city with 500,000 inhabitants, has grown to be one of the largest in the UK, performing ~3,000 scans a year in one dedicated scanner at the Bristol Heart Institute, of which 1,200 are stress CMR tests. Over the last 4 years, referrals for stress CMR have grown by 480%, reflecting the confidence that referring cardiologists have in the test, as well as patient preference for a test of ~1 hour versus a few hours spent in a nuclear medicine department for singlephoton emission computed tomography (SPECT).

CMR to detect myocardial viability

CMR was initially validated against histology for detecting the presence and extent of infarct size, and the latest gadolinium enhancement (LGE) technique very accurately reflects myocardial scarring. Gadoliniumchelate contrast agents are extracellular molecules that accumulate in increased extracellular space. In myocardial infarction, they accumulate inside infarcted myocytes due to membrane rupture, which increases the extracellular space.

Wagner et al. demonstrated that both CMR and SPECT could similarly detect transmural infarcts but that CMR could consistently detect subendocardial (partial thickness) infarctions missed on SPECT.2 Moon et al. also validated the use of CMR, showing that Q waves on ECG do not equate to transmural infarction, and are determined by total infarct size rather than transmural extent (i.e., a large subendocardial infarction could also lead to a Q wave).3

Imaging the presence and extent of myocardial infarction is important in relation to regional wall motion abnormality and the prediction of regional functional recovery. Indeed, myocardial segments that are very dysfunctional (akinesia or severe hypokinesia) but only minimally infarcted suggest myocardial hibernation and can show a degree of functional recovery following successful revascularization. 4 CMR can therefore be a valuable myocardial vitality test in ischemic heart disease patients who are candidates for revascularization.

CMR to detect myocardial ischemia

The stressors used in CMR are the same as those used in stress echo and SPECT, and the protocols are similar. The most commonly used agent is adenosine, given its very short half-life (<10 seconds) and ease of use in a patient being stressed in the scanner without the physician at their side. After 4–5 minutes of adenosine infusion, stress first-pass perfusion images are acquired dynamically. Myocardial segments with reduced perfusion identify a coronary artery territory with significant coronary artery disease (CAD).

Given the high spatial resolution of CMR (~2mm), the presence and extent of hypoperfused myocardium can be easily identified and related to a territory. Moreover, three-vessel myocardial ischemia is easily identified and the issue of ‘balanced-ischemia’ is not experienced.

Over the last 20 years, CMR has gone from being an experimental research tool to a robust clinical application (Figure 1). This began with the development of non-diagnostic images in 1990, the progressive accumulation of clinical evidence from single and then multicentre studies, and finally studies comparing stress CMR against invasive and non-invasive imaging techniques, such as positron emission tomography and coronary angiography.5 Lockie et al. validated stress CMR against fractional flow reserve, with a good sensitivity and specificity.6 A number of studies have also highlighted the high negative predictive value of CMR stress and very low event rates in patients with a normal stress CMR test.

In recent years, two randomized studies finally established stress CMR as a routine test in assessing patients with stable angina. In 2012, the CE-MARC single centre study established the higher diagnostic accuracy of stress CMR versus SPECT in 752 patients with stable angina undergoing both tests in addition to invasive angiography.7 Subset analysis confirmed these findings in patients with single, dual and triple vessel coronary artery disease and in women and men. At 5-year followup, CMR was a stronger predictor of risk for major adverse cardiac events, independent of cardiovascular risk factors, angiography results and initial patient treatment.8

Consequently, stress CMR was, for the first time, introduced to the 2014 ESC Guidelines on myocardial revascularization as a class IA recommendation in patients with intermediate CAD risk.

The multi-centre CE-MARC 2 was presented at the ESC Congress in 2016.9 It was a pragmatic comparative effectiveness study to determine whether care guided by CMR, National Institute for Health and Care Excellence (NICE) guidelines or myocardial perfusion scintigraphy (MPS) is superior in reducing unnecessary angiography in 1,202 patients with suspected CAD. There was a significant reduction in the proportion of patients undergoing unnecessary angiography with CMR-guided versus NICE guideline-guided care, suggesting that imaging can act as a ‘gatekeeper’ to angiography. From the patient perspective, this means avoiding an invasive test that is not without risk. While there was no significant difference in the rate of unnecessary angiography between CMR- and MPS-guided care, the prognostic impact of CMR was higher.

CMR has been well validated, and its use in clinical practice in patients with known or suspected ischemic heart disease is increasing. While its use may be limited by the availability of the equipment and expertise and costs, the literature suggests it is increasingly being used in cardiology over other imaging modalities.

To learn more about CMR, how it can be used in clinical practice and what it can offer to your patients, join us at EuroCMR 2017 (25–27 May; Prague, Czech Republic). This year, a CMR level 1 course has been designed for CMR novice colleagues as a special track to follow through the meeting, at no extra cost. For more information, visit: http://www.escardio.org/ Congresses-&-Events/EuroCMR

References

  1. Dastidar AG, Rodrigues JC, Baritussio A et al. MRI in the assessment of ischaemic heart disease. Heart 2016; 102: 239–252.
  2. Wagner A, Mahrholdt H, Holly TA et al. Contrast- enhanced MRI and routine single photon emission computed tomography (SPECT) perfusion imaging for detection of subendocardial myocardial infarcts: an imaging study. Lancet 2003; 361: 374–379.
  3. Moon JC, De Arenaza DP, Elkington AG et al. The pathologic basis of Q-wave and non-Qwave myocardial infarction: a cardiovascular magnetic resonance study. J Am Coll Cardiol 2004; 44: 554–560.
  4. Kim RJ, Wu E, Rafael A et al. The use of contrast- enhanced magnetic resonance imaging to identify reversible myocardial dysfunction. N Engl J Med 2000; 343: 1445–1453.
  5. Schwitter J, Nanz D, Kneifel S et al. Assessment of myocardial perfusion in coronary artery disease by magnetic resonance: a comparison with positron emission tomography and coronary angiography. Circulation 2001; 103: 2230–2235.
  6. Lockie T, Ishida M, Perera D et al. High-resolution magnetic resonance myocardial perfusion imaging at 3.0-Tesla to detect hemodynamically significant coronary stenoses as determined by fractional flow reserve. J Am Coll Cardiol 2011; 57: 70–75.
  7. Greenwood JP, Maredia N, Younger JF et al. Cardiovascular magnetic resonance and single- photon emission computed tomography for diagnosis of coronary heart disease (CEMARC): a prospective trial. Lancet 2012; 379: 453–460.
  8. Greenwood JP, Herzog BA, Brown JM et al. Prognostic Value of Cardiovascular Magnetic Resonance and Single-Photon Emission Computed Tomography in Suspected Coronary Heart Disease: Long-Term Follow-up of a Prospective, Diagnostic Accuracy Cohort Study. Ann Intern Med 2016; 165: 1–9.
  9. Greenwood JP, Ripley DP, Berry C et al. Effect of Care Guided by Cardiovascular Magnetic Resonance, Myocardial Perfusion Scintigraphy, or NICE Guidelines on Subsequent Unnecessary Angiography Rates: The CEMARC 2 Randomized Clinical Trial. JAMA 2016; 316: 1051–1060.