Despite advances in the diagnosis and management of coronary artery disease (CAD) in developed countries, a significant proportion of CAD patients develop heart failure, which is associated with a tremendous economic and societal burden.1,2 With increasing industrialisation, changes in diet and a rapidly ageing population, there has been an enormous increase in the prevalence of heart failure due to CAD in South Asia and China. This has led to huge healthcare expenditure each year in these developing countries.3 It is well-known that heart failure progresses through different stages, and optimal medical therapy in the early stage of disease can slow its progression.4 Furthermore, early diagnosis and recognition of reversible elements that lead to heart failure can further improve long-term outcome. Cardiac magnetic resonance imaging (cMRI) is unique in that it has an unlimited imaging window, free from radiation exposure, little inter- and intra-observer variability and excellent tissue characterisation. This article reviews the current role of cMRI in the diagnosis and management of ischaemic cardiomyopathy.
Previous clinical studies have shown that assessment of left ventricular (LV) function provides important information and is a powerful independent prognostic index for patients with heart failure.5 Currently, transthoraic echocardiography is the most widely used technique for measuring LV chamber dimension and function as it is easily available. Nevertheless, it is limited by several technical problems, including poor echo windows, unclear endocardial definition and unusual chamber geometry in some patients, which causes significant inter- and intra-observer variability. In contrast, cMRI provides highly reproducible LV volumetric measurements due to unlimited imaging windows and the high tissue contrast between the endocardial border and the blood pool.6 Furthemore, cMRI acquires chamber volumes in a 3D fashion. The endocardial contours at the end-systolic and end-diastolic phase of each contiguous LV short-axis level of the whole heart are traced manually. The chamber volumes are obtained simply by adding the volume of all of the slice levels. As a result, unlike echocardiography, no geometry assumption is required. Since cMRI is more sensitive in detecting the temporal changes in myocardial size, mass and function, it has been increasingly used in clinical practice and trials for the assessment of disease progression as well as the response to therapy. In addition, by using semi-quantitative methods (American College of Cardiologists [ACC]/American Heart Association [AHA] 17 Segments Guideline), the functional recovery regarding regional wall contractility can be compared in patients with CAD before and after revascularisation.7
Although a variety of non-invasive methods, including treadmill exercise test, stress echocardiography and single-photon-emission computed tomography (SPECT) scan, are available for the diagnosis of CAD, up to 40–60% of all patients who subsequently undergo invasive coronary angiography do not require a revascularisation procedure.8,9 cMRI has evolved into a new technique for the non-invasive detection of significant obstructive CAD. Recent developments in the use of the first-pass cMRI perfusion imaging technique have allowed the identification of ischaemic myocardial segments. In principle, regions supplied by a significantly diseased coronary artery (>70% stenosis) will be shown as hypoperfused area during cMRI, and can be determined by the rate of a bolus of contrast arrival in the myocardium. Apart from performing visual interpretation on the myocardial perfusion, objective methods including semi-quantitative and full quantitative analysis are also feasible. On the other hand, some patients with CAD may have sufficient blood flow at rest due to intrinsic autoregulation mechanism; however, during stress the normal four- to five-fold increase in coronary blood flow will be impeded. As such, pharmacological stress is commonly performed using vasodilators such as adenosine or dipyridamole. Dobutamine is also used as a stress agent to induce an increase in myocardial oxygen consumption through increased heart rate and contractility. By measurement of the change of signal intensity over time in first-pass perfusion at rest and during pharmacological stress, myocardial perfusion reserve can be determined. Al Saadi et al. have shown that dipyridamole cMRI perfusion had a sensitivity of 90% and a specificity of 83% for detecting significant coronary artery stenosis (>75%) with reference to coronary angiogram.10 Furthermore, by combining the detection of inducible wall motion abnormalities and myocardial perfusion defect, dobutamine stress MR identifies patients at risk of myocardial infarction and cardiac death independent of the presence of traditional risk factors for CAD.11
Therapeutic responses and long-term prognosis among CAD patients are influenced by myocardial scar burden and the amount of hibernating and stunned myocardium.12,13 Several cMRI techniques have been developed to detect myocardial viability, including cMRI spectroscopy, low-dose dobutamine cMRI and contrast-enhanced myocardial imaging. While cMRI spectroscopy can provide a more physiological assessment by detecting the preserved myocardial metabolism,14 it is still available for research studies only.
The use of dobutamine MRI is also limited to a few experienced centres over the world. In contrast, contrast-enhanced imaging implemented with an inversion recovery technique has been applied in clinical practice for the detection of infarcted myocardium. The kinetics of gadolinium is different between infarcted myocardium and viable myocardium. The infarcted myocardium has delay in gadolinium washout. Therefore, 10–15 minutes after injection of intravenous gadolinium, infarcted myocardium appears bright or hyperenhanced compared with viable myocardium by adjustment of imaging parameters. As validated by numerous animal studies, contrastenhanced MRI can accurately identify small subendocardial or subepicardial infarcts to large transmural myocardial damage.15 Ibrahim et al. have demonstrated that contrast-enhanced cMRI was superior to SPECT in detecting myocardial necrosis after reperfusion therapy in patients with acute myocardial infarction.16 Indeed, with such a high-resolution imaging technique, the likelihood of functional improvement after revascularisation increased as the percentage of transmural hyperenhancement detected by cMRI decreased.17 More importantly, data obtained from cMRI have potential implications for long-term prognosis in CAD patients. Kwong et al. showed that the use of high-resolution cMRI imaging allows quantification of the extent of the peri-infarct zone, and also provides an incremental predictive value for LV remodelling and future cardiovascular events.18
Prediction of Clinical Response to Cardiac Resynchronisation Therapy in Heart Failure
Clinical trials have proved the clinical benefit of cardiac resynchronisation therapy (CRT) among heart failure patients with inter-ventricular conduction delays and myocardial dyssynchrony.19,21 Nevertheless, appropriate patient selection is vital to the success of CRT. Apart from tissue Doppler imaging, tagging techniques with cMRI provide an alternative method for quantitative analysis of regional LV function and dyssynchrony.22,23 During tagging cMRI, some temporary lines or grids are applied non-invasively during the imaging process by the spatial modulation of magnetisation (SPAMM) technique. These lines move along with the myocardial deformation during the cardiac cycle. By tracking the deformation of these tag lines, regional myocardial function and 3D myocardial strains will be available.24 Furthermore, a comprehensive 3D strain map of the entire left ventricle can be reconstructed and the magnitude of strains at different times can be displayed using a colour-coded map. cMRI tagging was not widely used in the past due to tedious post-processing analysis.
Recent improvements in cMRI techniques (for example using harmonic phase [HARP] MRI) have facilitated its clinical applications for study on myocardial dyssynchrony.25 Despite the use of tissue Doppler to document mechanical dyssynchrony, some patients still failed to respond after CRT.26 White et al.27 have shown that delay contrast cMRI imaging can accurately predict clinical response to CRT. Patients with a higher percentage of total LV scar failed to respond to CRT. Furthermore, the presence of an LV infarct area also predicted a poorer response to CRT.28
Cell Therapy in Heart Failure
Stem cell therapies have been investigated as a new treatment option for treating heart failure, mitigating post-infarction ventricular remodelling and enhancing neovascularisation.29 With its good spatial and temporal characteristics, cMRI is a promising tool in tracking the distribution, differentiation and survival of the delivered cells in the myocardial and vascular wall after stem cell therapy. Several cell-tracking techniques, such as labelling of stem cells with iron oxides or gadolinium to allow imaging of the transplanted cells, have shown encouraging results.30 Furthermore, comprehensive cMRI assessment may also provide further insight into the underlying mechanisms of beneficial effects with stem cell therapy.
The world of heart failure is ripe with new drugs and novel treatment ideas. Nevertheless, what seems to be more urgent is the identification of patients who are at risk of developing heart failure and the prevention of its progression and development. cMRI has emerged as a robust imaging modality able to assess anatomy, function and myocardial perfusion and identify myocardial infarction. It promises to become a non-invasive imaging modality in both daily clinical practice and high-end research.
- American Heart Association, Heart and Stroke Statistical Update. American Heart Association, 2001.
- Haldeman GA, Croft JB, Giles WH, Rashidee A, Hospitalisation of patients with heart failure: National hospital discharge survey, 1985–1995, Am Heart J, 1999;137:352–60.
- Yusuf S, et al., Global burden of cardiovascular diseases: part I: general considerations, the epidemiologic transition, risk factors and impact of urbanisation, Circulation, 2001;104:2746–53.
- Hunt SA, Abraham WT, et al., ACC/AHA 2005 guideline update for the diagnosis and management of chronic heart failure in the adult: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Update the 2001 Guidelines for the Evaluation and Management of Heart Failure), J Am Coll Cardiol, 2005;46:e1–82.
- Rogers WA, et al., on behalf of the SOLVD investigators. Studies of left ventricular dysfunction, Am J Cardiol, 1990;66:315–22.
- Semelka RC, Tomei E, et al., Interstudy variability in left ventricular mass measurement. Comparison between m-mode echocardiography and MRI, Eur Heart J, 1992;13:1011–19.
- Schiller NB, Shah PM, et al., American Society of Echocardiography Committee on Standards Subcommittee on Quantitation of Two Dimensional Echocardiograms. Recommendations for quantitation of the left ventricle by two-dimensional echocardiography, J American Soc Echocardio, 1989;2:358–67.
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- Al-Saadi N, Nagel E, et al., Non-invasive detection of myocardial ischaemia from perfusion reserve based on cardiovascular magnetic resonance, Circulation, 2000;101:1379–83.
- Hundley WG, et al., Magnetic resonance imaging determination of cardiac prognosis, Circulation, 2002;106:2328–33.
- Allman KC, Shaw LJ, Hachamovitch R, et al., Myocardial viability testing and impact of revascularisation on prognosis in patients with coronary artery disease and left ventricular dysfunction: a meta-analysis, J Am Coll Cardiol, 2002;39:1151–8.
- Mickleborough LL, et al., Results of revascularisation in patients with severe left ventricular dysfunction, Circulation, 1995;92:II73–9.
- Jansen MA, Van Emous JG, Nederhoff MG, et al., Assessment of myocardial viability by intracellular 23 Na magnetic resonance imaging, Circulation, 2004;110:3457–64.
- Kim RJ, et al., The use of contrast-enhanced MRI to identify reversible myocardial dysfunction, N Engl J Med, 2000;343:1445–53.
- Ibrahim T, et al., Diagnostic value of contrast-enhanced magnetic resonance imaging and single-photon emission computer tomography for detection of myocardial necrosis early after acute myocardial infarction, J Am Coll Cardiol, 2007;49:208–16.
- Kim RJ, Fieno DS, Parrish RB, et al., Relationship of MRI delayed contrast enhancement to irreversible injury, infarct age and contractile function, Circulation, 1999;100:185–92.
- Kwong RY, Chan AK, et al., Impact of unrecognised myocardial scar detected by cardiac magnetic resonance imaging on eventfree survival in patients presenting with signs or symptoms of coronary artery disease, Circulation, 2006;113:2733–43.
- Sogarrd, Egebald H, et al., Sequential versus simultaneous biventricular resynchronisation for severe heart failure: Evaluation by Tissue Doppler imaging, Circulation, 2002;106:2078–84.
- Bristow MR, et al., Comparison of Medical Therapy, Pacing and Defibrillation in Heart Failure (COMPANION) Investigators. Cardiac resynchronisation therapy with or without an implantable defibrillator in advanced chronic heart failure, N Engl J Med, 2004;350:2140–50.
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- Edvardsen T, Gerber BL, Garot J, et al., Quantitative assessment of intrinsic regional myocardial deformation by Doppler strain rate echocardiography in humans: validation against 3D tagged magnetic resonance imaging, Circulation, 2002;106:50–56.
- Castillo E, et al., Quantitative assessment of regional myocardial function with MRI-tagging in a multicentre study: interobserver and intraobserver agreement of fast strain analysis with Harmonic Phase (HARP) MRI, J Cardiovasc Magn Reson, 2005;7:783–91.
- Penicka M, et al., Improvement of left ventricular function after cardiac resynchronisation therapy is predicted by tissue Doppler imaging echocardiography, Circulation, 2004;109:978–83.
- White AJ, Yee R, Yuan X, et al., Delayed enhancement magnetic resonance imaging predicts response to cardiac resynchronisation therapy in patients with intraventricular dyssynchrony, J Am Coll Cardiol, 2006;48:1953–60.
- Bleeker GB, et al., Effect of post-erolateral scar tissue on clinical and echocardiographic improvement after cardiac resynchronisation therapy, Circulation, 2006;113:969–76.
- Tse HF, Yiu KH, Lau CP, Bone marrow stem cell therapy for myocardial angiogenesis, Curr Vasc Pharmacol, 2007;5:103–112.
- Beeres SL, Bengel FM, Bartunek J, et al., Role of imaging in cardiac stem cell therapy, JACC, 2007;49:1137–48.