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Assessment of Myocardial Infarction Prognosis with Magnetic Resonance Imaging
In October 2018, a 56 year old woman presented to her GP to discuss her fears about returning to work following a myocardial infarction (MI) six months previously. She rarely visited the GP surgery before the MI, but since then she typically visits at least once a week. People typically return to work within two months after an MI. Her GP considers the patient physically fit to return to work, however the MI is clearly taking a psychological toll.
The prognosis of myocardial infarction depends on the extent of myocardial damage and the presence of ischaemia. Those who receive and survive hospital care have a much better prognosis, with an 85% 28-day survival rate. Those who survive an MI are at increased risk of recurrence (5% annual death rate vs 0.8% for those without coronary heart disease). Higher mortality is also associated with depression and social isolation. Returning to work is therefore an important step in the recovery from MI for people of working age.
Magnetic resonance imaging (MRI) provides a non-invasive means to investigate both cardiac structure and cardiac function. Assessment of myocardial infarction with MRI can therefore identify markers of prognosis and aid in risk stratification above and beyond indicators such as diet, smoking status and level of activity. In this article, the technical acquisition of cardiac MRI data will be briefly described and the use of MRI for the characterisation of MI extent and prognosis will be reviewed.
Since MRI acquisition of humans in vivo was first demonstrated in 197x, MRI has shown great capacity for imaging soft tissue structures with high resolution. Though the first MR images of the heart were produced in 1981, cardiac and respiratory motion posed a significant challenge to image quality and interpretation until the early 1990s.
Technical Overview of Cardiac MRI Sequences
A typical MRI investigation of suspected cardiac pathology takes upwards of 20 minutes, excluding the time spent preparing the patient for investigation. The MRI protocol consists of a number of sequences which each assess the heart via different physical and chemical mechanisms.
The cine MRI sequence is acquired over several heart beats to produce a short movie clip showing ventricular and valvular function throughout the cardiac cycle.
The most important sequence is delayed enhancement imaging. Delayed enhancement imaging involves the injection of the contrast agent gadolinium to identify structural abnormalities. Gadolinium is inert and does not normally cross cell membranes, leading to low volumes of distribution in healthy myocardium and its quick wash out. However, damaged myocardium takes up the gadolinium, leading to high volumes of distribution. This leads to hyper-enhancement and bright appearance of damaged tissue. Scar tissue also takes up gadolinium leading to a hyper-enhancement pattern. This phenomenon is illustrated in Figure 1.
MRI for MI Diagnosis
Cardiac MRI is of limited value for the diagnosis of myocardial infarction. Diagnosis is typically confirmed following investigation of typical clinical abnormalities with electrocardiography (ECG) and raised plasma cardiac biomarkers such as troponins T and I and the cardiac-specific isoform of creatine kinase. However, cardiac MRI is a useful diagnostic tool in patients whose ECG results or cardiac biomarker levels are inconclusive and in cases where a culprit lesion cannot be identified.
Cardiac MRI Markers of MI Prognosis and Risk Stratification
A landmark 1998 study by Wu et al. took advantage of the fact that areas of microvascular obstruction have low enhancement following gadolinium contrast enhancement. In the two weeks following an acute myocardial infarction, 44 patients had contrast enhanced cardiac MRI. Microvascular obstruction was predictive of future cardiovascular events and this was independent of myocardial infarct size.
Nijveldt et al. followed up Wu’s study by comparing microvascular obstruction estimates from cardiac MRI with the more commonly accepted angiography and ECG derived estimates. Cardiac MRI was performed following revascularisation and estimates of microvascular obstruction correlated with the left ventricular remodelling parameters such as end-diastolic and end-systolic volumes. Cardiac MRI was more predictive of functional recovery following acute MI than ECG and angiography.
Microvascular obstruction can be assessed following gadolinium contrast injection at either an early interval (one minute) or a late interval (15 minutes). Following reperfusion of an ST-elevated MI in 438 patients, de Wahl et al. observed that while late microvascular obstruction was independently related to cardiac related morbidity and mortality, early microvascular obstruction was not. De Wahl et al.’s results also indicated that late microvascular obstruction extent was a stronger predictor of prognosis than conventional estimates
Long-term prognostication using cardiac MRI assessment of microvascular obstruction following acute ST-elevated MI has also been presented. With a 52 month median follow up time, the presence of microvascular obstruction was related to reduced event free survival. Microvascular obstruction was again found to be the strongest independent predictor for morbidity following acute MI.
Prompt reperfusion and revascularisation is important for reducing infarct size. A recent meta-analysis comparing the relationship between infarct size and prognosis found that for each 5% increase in infarct size, there was a 20% greater risk of both mortality and heart failure within one year. In contrast, the overall 1-year rates for mortality, reinfarction and heart failure were 2.5%. The relationship between infarct size and increased risk was independent of confounding variables such as age, sex, diabetes and hypertension.
In a single centre study of 110 acute MI patients, Hombach et al. compared cardiac MRI indicators of cardiac structure and function with MI sequelae. The infarct size was predictive of adverse left ventricular remodelling and greater than 20% increases of end-diastolic volume. Left ventricular remodelling and end diastolic volume increases were predictive of major adverse cardiac events. However, there were only 16 major adverse cardiac events in the one year follow up period.
Kelle et al. investigated 177 patients with chronic MI with late gadolinium enhanced MRI. In the mean follow up period of 20 months, 6.2% of patients suffered an event. Myocardial infarct size was found to be a stronger predictor of high risk of future events than left ventricular ejection fraction and left ventricular volumes at rest.
Predicting Response to Revascularisation
While a range of cardiac MRI indicators of disease and prognosis are available, the clinical use of cardiac MRI remains limited. In many cases, the indices described are still only assessed in academic centres in the context of research studies. As such, cardiac MRI is yet to either be validated or demonstrate superiority over the other investigation methods available. This will require further clinical trials with both multiple centres participating and large study cohorts.
Cardiac MRI is also an expensive technique, which requires extensive experience from both radiographers for its acquisition and from radiologists for its interpretation. Depending on the sequences acquired, analysis of cardiac MRI data can also take upwards of 45 minutes to assess a single patient while still being prone to subjective errors. This level of evaluation is currently not feasible for radiologists working in the current NHS hospital climate where some radiology departments are already oversubscribed. In fact, over the last two decades there have been incredible volume increases of 540% and 1300% of MRI and CT content, without a concomitant increase in the number of radiologists. As such the use of the advanced techniques described here might only be available in specialist centres. The likelihood therefore is that cardiac MRI would be of limited value to the patient presenting at the GP surgery worried about returning to work.
Despite this cardiac MRI is not without value in the assessment of myocardial infarction. The literature presented in this article suggests that, if validated in larger trials, there is a wide range of potential applications of cardiac MRI despite the resource restrictions. These resource restrictions may even be overcome in the bourgeoning era of artificial intelligence and machine learning methods. In fact, in one recent study of automated cardiac MRI volume analysis using deep learning methods, evaluation of a typical cardiac MRI protocol could be completed in less than one second per patient. The licensing procedures required to enable these applications to be used in clinical practice could be lengthy, however they promise to help make cardiac MR imaging a much more viable prospect in future years.
Though prognostication and risk stratification using cardiac MRI techniques is promising for survivors of myocardial infarction, the methods described in this literature review are not yet sufficiently validated for clinical use. Cardiac MRI is therefore likely of limited benefit to the patient discussed in this article. However, with large scale multiple centre clinical trials planned and underway and the advent of the machine learning era, cardiac MRI may one day be a suitable modality for aiding risk stratification of myocardial infarction and assessing prognosis.
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