Novel applications of cardiovascular magnetic resonance in acute myocardial injury

Acute myocardial injury, defined as an acute rise and fall in cardiac Troponin, is a common reason for hospital admission, and can be triggered by ischaemic and non-ischaemic pathologies. Accordingly, most patients admitted to hospital with clinically significant acute myocardial injury undergo an invasive coronary angiogram (ICA) to screen for coronary artery disease (CAD). However, there are clinically-important limitations with this approach and it is likely that cardiovascular magnetic resonance imaging (CMR), given its status as the gold standard imaging test in the assessment of the causes and the extent of myocardial disease, can add clinical value as a non-invasive approach, either alone or in conjunction with ICA. However, at present, CMR’s use is mostly confined to stable outpatients. In this Thesis, I examine the role of acute CMR in four different cohorts of acutely ill hospitalised patients with acute myocardial injury.
Firstly, a significant proportion of patients admitted to hospital with acute myocardial injury and suspected Non-ST-segment Elevation Myocardial Infarction (NSTEMI) are found to have unobstructed coronary arteries, suggestive of either a non-ischaemic acute myocardial injury such as myocarditis or MI with non-obstructive coronary arteries (MINOCA). At present an early Cardiovascular magnetic resonance imaging (CMR) is recommended in patients with unobstructed coronary arteries within twenty-eight days of discharge from hospital to reach a clinical diagnosis, which has therapeutic and prognostic implications. On the other hand, some patients with confirmed MI on ICA are found to have stenosis in more than one coronary artery, which can render it difficult to identify the infarct related artery (IRA). Taken together, diagnosing non-ischaemic pathologies upfront may obviate the need for ICA whilst identifying the IRA can offer precise management of MI. In Chapter 3, I investigated if a CMR-first strategy in patients with acute myocardial injury has the potential to change management in patients waiting to have ICA for suspected NSTEMI. I found that a such a strategy could have changed the clinical management in at least 31% of of patients by reclassifying diagnosis in those with non-obstructed coronary arteries (17%) and in MI (7%) and offering a new IRA in MI (7%).
Secondly, acute myocardial injury was reported in approximately one fifth of hospitalised and unvaccinated patients with COVID-19 infection at the beginning of the current pandemic and it was associated with reduced survival. However, the cause of the myocardial injury remained unclear as these patients were not systematically evaluated with CMR at the time of the injury due to pandemic restrictions. Interestingly, CMR scans of unselected survivors of COVID-19, performed a few months after the acute illness, had reported myocardial inflammation and infarction in some patients, but the clinical implication to acutely-hospitalized patients with acute COVID-19 remained unclear. Chapter 4 investigated for the presence of myocardial abnormalities on CMR in unvaccinated, acutely ill and hospitalised COVID-19 patients with and without acute myocardial injury when compared to uninfected and asymptomatic controls from the community. I observed that acute COVID-19 induces mild myocardial oedema in some patients, but it returns to normal levels at six months after the acute illness.
Thirdly, some patients with acute myocardial injury due to with ST-segment elevation myocardial infarction (STEMI) present late, when the injury may already be established. Characterising of the extent and nature of acute myocardial injury in these patients (presenting twelve to forty-eight hours after the onset of chest pain) prior to ICA may of be of use when deciding whether to revascularise. Chapter 5 reports the investigation that involved performing CMR in patients with late-presenting STEMI just before and three days after revascularisation. I found no significant changes in ventricular function, area at risk and infarct size between the two scans except a reduction in the size of microvascular obstruction. The study’s findings suggest that it is feasible to safely conduct acute CMR scans in patients with late-presenting STEMI prior to ICA and that revascularisation appears to confer neither a positive or negative immediate impact on the magnitude of the acute myocardial injury.
Finally, the degree of acute myocardial injury in the infarcted myocardium in patients with revascularised STEMI has been shown to be strongly associated with long-term clinical outcomes. However, less is known about the prognostic relevance of the changes that are known to take place in the non-infarcted myocardium immediately after STEMI; acute injury to the remote non-infarcted myocardium is believed to represent an adverse inflammatory reaction secondary to a response to the MI from the innate immune system and it has been detected with CMR T1-mapping. In Chapter 6, I used CMR T1 mapping to detect the injuries in the entire heart including both the infarcted and the non-infarcted myocardium at two days after timely reperfused STEMI. I found that non-infarcted myocardial injury is an independent predictor of the risk of developing heart failure and related cardiac events at long-term, justifying further research into therapeutic modulation of myocardial inflammation post-STEMI. Moreover, I found that the T1 values in the infarcted and non-infarcted myocardium provided superior risk prediction than the conventional CMR indices of the infarcted myocardium (intramyocardial haemorrhage, area at risk, infarct size and microvascular obstruction) and of global left ventricular function (left ventricular ejection fraction). My findings indicate that non-contrast T1-mapping offers a more complete assessment of the pan-myocardial injury post-STEMI than the traditional contrast-based metrics of the infarcted myocardium and perhaps could be used as a biomarker in future clinical trials of patients with MI.
Overall, this Thesis presents fresh evidence to support the clinical application of acute CMR in acutely ill hospitalised patients with acute myocardial injury, as it can accurately diagnose both non-ischaemic and ischaemic pathologies, enable avoidance of unnecessary invasive testing and guide treatment pathways. Moreover, it provides new and highly promising evidence that an acute CMR (in particular T1 mapping) can help identify patients at long-term risk of heart failure after a revascularised STEMI. Both of these findings lay the foundation to build clinical trials to test the clinical and cost-effectiveness of acute CMR in patients admitted to hospital with acute myocardial injury.

Keywords: prognosis
T1 mapping
cardiovascular magnetic resonance imaging
CMR
myocardial infarction
acute myocardial injury
Advisor: Ferreira, V
Channon, K
Piechnik, S