MRI predictors in coronary artery disease

Ischaemic heart disease (IHD) is the leading cause of morbidity and mortality in industrialised countries and poses an enormous financial burden on our society. As a consequence, rational evidence-based use of diagnostic and therapeutic means are required to prevent financial lapses and to guarantee affordable care in the coming years. Accurate diagnosis, prediction of clinical outcome and prognosis assessment are important in patients with suspected or known coronary artery disease (CAD). Although traditional risk factor assessment enables stratification of patients in low-, intermediate- and high-risk groups, the majority of patients in high-risk groups will never experience a major adverse cardiac event (MACE), such as myocardial infarction or sudden cardiac death, while patients having a low or intermediate risk are not risk free for future cardiac events. There is accumulating evidence that magnetic resonance imaging (MRI) is an increasingly important tool in the management of cardiovascular disease.(1,2) This technique brings together information regarding myocardial perfusion, function and tissue characteristics.

Cardiac MRI studies are usually performed on a 1.5 or 3 T field magnet equipped with a cardiac phase-array coil and dedicated cardiac MRI sequences. Commercially available paramagnetic contrast agents are routinely used for myocardial perfusion assessment and tissue characterisation. To depict whether CAD is clinically significant, the perfusion and/or function of the myocardium is usually evaluated during stress conditions such as during administration of a coronary vasodilator (dipyridamole or adenosine) or a myocardial stressor (dobutamine ± atropine).

A comprehensive cardiac MRI study in a patient with IHD aims to evaluate myocardial function, myocardial perfusion and myocardial tissue characteristics. 

The heart is, in essence, a pump, so assessment of its performance is essential in IHD. Cine imaging using steady-state free precession sequences has become the reference to quantify ventricular volumes and function, to calculate myocardial mass and to assess myocardial wall thickening and wall motion patterns. Ejection fraction and end-systolic volumes represent two important functional parameters predicting outcome in patients with a recent myocardial infarction or in those presenting symptoms of ischaemic heart failure. In addition, increased myocardial mass independently predicts adverse outcome in patients with systemic arterial hypertension. In patients with stable CAD, resting (regional) myocardial function is often within normal limits, but when stressed (during increased myocardial oxygen consumption and thus oxygen need) myocardium supplied by a stenotic coronary artery may become dysfunctional. This is generally achieved by a stepwise increase of the dose of dobutamine. Moreover, additional information is or can be provided regarding concomitant valve dysfunction and atrial enlargement.

The myocardium has a short-lived capacity to sustain myocardial ischaemia, and a continuous myocardial perfusion is an essential condition to guarantee a normal myocardial function. As a consequence, a coronary artery occlusion triggers an ‘ischaemic cascade’ in the perfusion territory distal to the occluded coronary artery. To evaluate myocardial perfusion, MRI uses the first pass of a small intravenous bolus of contrast medium through the heart. Whereas normally perfused myocardium brightly enhances during first pass of contrast, hypoperfused myocardium presents as a non-enhancing subendocardial/transmural ‘defect’ typically located in one of the three coronary artery perfusion territories. MRI perfusion studies are performed at rest and during stress conditions, and they can be analysed visually or (semi)-quantitatively (see Figure 1).

Whereas the metabolic, morphologic and functional alterations in ischaemic myocardium are initially reversible, irreversible myocardial damage (‘necrosis’) soon occurs. Current state of the art treatment aims to restore myocardial perfusion as soon as possible to stop irreversible myocardial damage, to limit adverse ventricular remodelling and to improve patient outcome. T2-weighted MRI sequences can be used to depict myocardial oedema reflecting the area at risk, while inversion-recovery contrast-enhanced MRI sequences reliably depict the irreversibly damaged myocardium. The difference in extent between the area at risk and the irreversibly damaged myocardium reflects the salvaged myocardium. However, (new) myocardial damage, like microvascular obstruction (MVO) and post-reperfusion myocardial haemorrhage, can be caused or worsened by reopening of the coronary artery (‘reperfusion injury’). A comprehensive MRI exam can precisely determine the infarct composition in terms of infarct volume, transmural extent, MVO and area at risk, amongst others (see Figure 2).

The use of MRI as a predictor in CAD applies to patients with suspected CAD, patients presenting with an acute coronary syndrome (ACS) and those presenting with ischaemic heart failure. First, in patients with suspected CAD, a negative stress perfusion MRI study yields a high negative predictive value for future MACE, whereas stress perfusion defects predict subsequent MACE.(3–5) Similarly, dobutamine stress-induced wall motion abnormalities are associated with future cardiac events.(6,7) In particular, the latter technique exhibits high prognostic utility for identifying women that may be at risk. Whereas a left ventricular ejection fraction (LVEF) <40% is associated with future MACE independent of traditional risk factors for CAD, a positive stress test in patients with mild to moderate reduction in LVEF (40–55%) forecasts future hard events.(8) In a recent study by Bingham and Hachamovitch,(2) 908 consecutive patients who underwent combined MRI (including stress perfusion, LV volumes and function, myocardial enhancement and aortic flow) for suspicion of CAD, and/or myocardial ischaemia were followed for 2.6 ± 1.2 years. A normal cardiac MRI study yielded a low risk of cardiac events, whereas all MRI parameters had incremental value for prediction of adverse events over pre-MRI data. Additional presence of LV hypertrophy (defined as LV wall thickness ≥12mm or LV mass >96g/m2 in men and >77 g/m2 in women) is an independent predictor of MACE and should be reported in those referred for stress MRI, particularly in those without inducible ischaemia.(9) Left ventricular hypertrophy bears a similar risk for future events as those patients presenting stress-induced wall motion abnormalities. Moreover, in patients without a history of MI but a clinical suspicion of CAD, presence of myocardial enhancement even in small amounts reflects ischaemia-related myocardial scarring and carries an increased risk for future MACE.(5) Second, in patients with ACS in whom MI is excluded by cardiac biomarkers and non-diagnostic electrocardiograms, adenosine stress perfusion MRI is a more accurate predictor of future cardiac events than traditional cardiac risk factors.(10) In acute MI, MRI has not only become the reference technique for infarct sizing, but because of its unique capability for characterisation of the infarct and jeopardised myocardium, MRI is rapidly emerging as the technique to evaluate which infarct characteristics bear poor prognosis. Although the extent of myocardial necrosis is a major determinant in predicting adverse remodelling and patient outcome,(11) it has become obvious that parameters other than purely infarct size should be taken into account. These include MVO, post-reperfusion myocardial haemorrhage, the peri-infarct area and myocardial salvage.(1) Also, in patients with non ST-segment elevation MI, persistent MVO is an independent predictor of MACE. Since some phenomena such as MVO and myocardial haemorrhage seem to be related to infarct size, further research in large patient trials is needed to elucidate whether these parameters are truly independent or should be considered as markers of infarct severity expression. Finally, in ischaemic cardiomyopathy patients presenting with severely reduced LVEF (‘ischaemic heart failure’), the extent of myocardial enhancement, reflecting myocardial replacement fibrosis, is associated with increased mortality or the need for cardiac transplantation.(12) In a study involving 857 consecutive patients with and without LV dysfunction and a median follow-up of 4.4 years, myocardial enhancement using a myocardial scar index (that is,  the sum of transmurality scores of all 17 segments divided by 17) was a strong and independent predictor of all cause mortality/cardiac transplantation even in the presence of traditional well-known prognosticators such as ejection fraction, congestive heart failure and age.(13)

Predicting which CAD patients are at risk for developing future adverse events is important for patient risk stratification and optimising treatment strategies. Since cardiac MRI provides substantial information in a brief time regarding the presence of haemodynamically significant stenoses, to depict and characterise acute or chronic ischaemically jeopardised myocardium and to evaluate the impact of the damaged myocardium on the cardiac performance as parameters that yield predictive value, cardiologists should consider cardiac MRI as a crucial tool for accurate decision making in CAD patients. 

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