MAGNETIC RESONANCE

The role of cardiac magnetic resonance imaging followingacute myocardial infarction

Dennis T. L. Wong & James D. Richardson & Rishi Puri &Adam J. Nelson & Angela G. Bertaso & Karen S. L. Teo &

Matthew I. Worthley & Stephen G. Worthley

Received: 4 November 2011 /Revised: 8 January 2012 /Accepted: 25 January 2012 /Published online: 25 March 2012# European Society of Radiology 2012

AbstractBackground Advances in the management of myocardialinfarction have resulted in substantial reductions in morbid-ity and mortality.Methods However, after acute treatment a number of diag-nostic and prognostic questions often remain to be answered,whereby cardiac imaging plays an essential role.Results For example, some patients will sustain early mechan-ical complications after infarction, while others may developsignificant ventricular dysfunction. Furthermore, many individ-uals harbour a significant burden of residual coronary diseasefor which clarification of functional ischaemic status and/orviability of the suspected myocardial territory is required.Conclusion Cardiac magnetic resonance (CMR) imaging iswell positioned to fulfil these requirements given its unparal-leled capability in evaluating cardiac function, stress ischaemiatesting and myocardial tissue characterisation. This reviewwillfocus on the utility of CMR in resolving diagnostic uncertainty,evaluating early complications following myocardial infarc-tion, assessing inducible ischaemia, myocardial viability, ven-tricular remodelling and the emerging role of CMR-derivedmeasures as endpoints in clinical trials.

Key Points• Cardiac magnetic resonance (CMR) imaging identifiesearly complications after myocardial infarction.

• Adenosine stress CMR can reliably assess co-existingdisease in non-culprit arteries.

• Assessment of infarct size and microvascular obstruction arobust prognostic indicator.

• Assessment of myocardial viability is important to guiderevascularisation decision-making.

Keywords Magnetic resonance imaging .Myocardial .

Infarction . Ischemia . Viability

Introduction

Myocardial infarction (MI) remains one of the most fre-quently encountered medical emergencies. Advances in themanagement of acute ST segment elevation myocardialinfarction (STEMI), particularly with the advent of round-the-clock availability of primary percutaneous intervention(PCI), have led to significant reductions in morbidity andmortality associated with this condition. However somepatients sustain early mechanical complications after MI,while others may develop significant ventricular dysfunc-tion. Furthermore, many individuals harbour a significantburden of residual coronary disease for which clarificationof functional ischaemic status and/or viability of the sus-pected myocardial territory is required. For other patients,diagnostic doubt remains about the underlying aetiology incases presenting with raised biomarkers but unobstructedcoronary arteries. In this review we explore the role of CMRimaging in patients post-MI. The review will focus on theutility of CMR in resolving diagnostic uncertainty, the evalua-tion of early complications, assessment of inducible ischaemia,

D. T. L. Wong : J. D. Richardson : R. Puri :A. J. Nelson :A. G. Bertaso :K. S. L. Teo :M. I. Worthley : S. G. WorthleyCardiovascular Research Centre, Royal Adelaide Hospital,Adelaide, Australia

D. T. L. Wong : J. D. Richardson : R. Puri :A. J. Nelson :K. S. L. Teo :M. I. Worthley : S. G. WorthleyDepartment of Medicine, University of Adelaide,Adelaide, Australia

S. G. Worthley (*)Cardiovascular Investigational Unit,Level 6 Theatre Block, North Terrace,Adelaide, South Australia 5000e-mail: stephen.worthley@adelaide.edu.au

Eur Radiol (2012) 22:1757–1768DOI 10.1007/s00330-012-2420-7

myocardial viability and ventricular remodelling, as well as theemerging role of CMR-derived measures as endpoints in clin-ical trials.

CMR in cases of diagnostic uncertainty

The increasing use of an early invasive strategy for MI hasrevealed that 10% of patients with STEMI and 30% ofbiomarker-negative non-ST elevation acute coronary syn-drome (ACS) cases display near-normal epicardial coronaryarteries [1, 2]. There often remains considerable diagnosticuncertainty regarding the underlying aetiology in this group.Alternative diagnoses including myocarditis, Takotsubo car-diomyopathy, pulmonary embolism and coronary spasmmakethe differentiation from a plaque-based event challenging. Adetailed clinical history together with selected investigations(inflammatory markers, regional wall motion abnormalities,D-dimer) can elucidate the likely diagnosis in some. In others,non-invasive imaging can provide robust objective evidencethat aids the clarification of the underlying aetiology, hence itsincorporation into consensus guidelines [3].

Of the non-invasive imaging options, CMR is particularlyadept in accomplishing this task. High-resolution images candetect even subtle regional wall motion abnormalities thatmay be missed by echocardiography, particularly in patientswith poor acoustic windows. CMR can also provide importanttissue characterisation information. Increased myocardial wa-ter content increases signal on T2-weighted images, such asinflammation. The acute inflammatory response seen in myo-carditis is easily identified using fat-suppressed T2-weightedimages [4]. Myocardial oedema in the acute phase of myocar-dial infarction can also be visualised as a bright signal on T2-weighted images, defining myocardium at risk. However themajor advantage of CMR in this scenario is the informationprovided by late gadolinium enhancement (LGE). This tech-nique involves the injection of the contrast agent gadolinium,an extracellular molecule that rapidly extravasates into theinterstitium. The clearance of gadoliniumwithin normal tissueis relatively fast (1–2min), whilst the clearance within infarctedtissue is far slower (~30 min). The consequence of thesedivergent tissue kinetics is that infarcted myocardium appearshyperenhanced, or ‘bright’, compared with normal myocardialtissue when imaged late (10–15 min) following contrast medi-um administration [5]. Inversion recovery images accuratelyidentify these abnormal areas of enhancement, and the presenceand moreover the pattern of distribution greatly enhances thediagnostic yield. Myocardial necrosis caused by interruption ofcoronary flow produces subendocardial late enhancement, withvarying degrees of transmural extent, localised to a specificcoronary territory. This reflects the ischaemic wavefront of myo-cardial necrosis that extends outwards from the subendocardium[6]. Myocarditis, on the other hand has a patchy diffuse

distribution within the sub-epicardium, with certain patternsalmost pathognomonic for particular culprit viruses (Fig. 1).Takotsubo cardiomyopathy often has no LGE present (Fig. 1),but if observed usually has a diffuse morphological pattern.The LGE in this instance may reflect acute microcirculatoryinjury, which is only temporary and mirrors the resolution inwall motion noted over subsequent weeks, which definesTakotsubo cardiomyopathy [7]. Studies have shown thatCMR can make a specific diagnosis in two thirds of caseswith elevated biomarkers but normal epicardial coronary ar-teries, with exclusion of significant pathological features inthe remainder [8]. When CMR is not available, some centresrely on echocardiography to assess for regional wall motionabnormalities, on the basis that the absence of impaired wallmotion may exclude MI. However, normokinesia may beobserved in myocardium associated with significant LGE[9]. Microinfarctions of <1 g of tissue can be detected byLGE [10], while 10 g of myocardial necrosis is requiredbefore a defect is apparent on single positron emission tomog-raphy (SPECT) [11] and even greater myocardial necrosisbefore regional wall motion abnormalities become evidenton echocardiography.

Assessment of complications post-STEMI

Cardiac imaging after MI can identify early mechanical com-plications such as left ventricular free wall rupture, ventricularseptal defect and papillary muscle rupture. Half of such casesoccur within the first 5 days following infarction, and 90%within the first 2 weeks [12]. Usually mechanical complica-tions will be demonstrated in acutely sick patients, whereassome will be identified through screening of asymptomaticpatients. Echocardiography remains the most frequently usedimaging technique for this purpose in most centres by natureof its availability and portable characteristics. However, CMRis used increasingly early post-MI inmany centres owing to itshigher resolution and additional diagnostic abilities.

Timely detection of left ventricular (LV) mural thrombusafter MI is important to avoid systemic embolisation, a seriouscomplication that needs to be treated with urgent anticoagula-tion. Mural thrombus is most frequently encountered in thosewith the greatest degree of LV impairment, with as many as 7%patients developing LV thrombus early after anterior MI [13].Transthoracic echocardiography remains the workhorse imag-ing technique for detecting LV thrombus. Occasionally identi-fication or exclusion of thrombus, particularly in the artefact-prone apical ventricular regions, can be challenging. Further-more, patient-related factors such as poor acoustic windows inpatients who are obese or have hyperinflated lungs amplify thechallenge. Myocardial contrast echocardiography can over-come this difficulty in some, but with the combination of highspatial resolution and gadolinium-enhanced evaluation, CMR

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is superior in detecting and defining thrombus. On cine imag-ing, thrombus is often hyperintense in comparison to theadjacent myocardium, though the signal intensity will alteras the thrombus ages. Inversion recovery images post-contrastallow tissue characterisation with thrombus typically demon-strating a dark hypointense signal reflecting the absence ofgadolinium uptake (Fig. 2). Cardiac MRI has high sensitivity(88%) and high specificity (99%) in comparison to transthoracic

echocardiography (27% and 96% respectively) and transoeso-phageal echocardiography (40% and 96% respectively) [14]. Itis particularly suited to detection of small mural thrombi inapical aneurysms, and is superior to contrast echo in this regard[15]. Usually, owing to the greater availability of echocardiog-raphy, CMR is often used in equivocal cases as the secondimaging technique, or as the first investigation where clinicalsuspicion is high.

Fig. 1 Alternative diagnoses to MI. The appearance of myocarditis(top panel); a late gadolinium enhancement showing subepicardialenhancement in the distal lateral wall. b T2-weighted imaging showingenhancement in the distal lateral wall consistent with myocardialoedema. c Late gadolinium enhancement in the short axis showing

sub-epicardial enhancement in the inferior wall. Takotsubo cardiomy-opathy (lower panel), with cine imaging at end-diastole (d) and end-systole (e) illustrating apical ballooning. No evidence of late gadolin-ium enhancement (f)

Fig. 2 Left ventricular thrombus detection by CMR. a Large apicalthrombus on a cine image. b Late gadolinium enhancement inversionrecovery image in the same patient clearly demonstrates the thrombus(large, dark, hypointense mass) and the associated antero-apical

infarction. c In a different patient, a small apical LV thrombus is readilyidentified on an early gadolinium enhancement image, yet was barelyapparent on cine imaging

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Right ventricular dysfunction may occur soon after MIand is associated with an adverse short and long-term prog-nosis. This is sometimes difficult to identify with echocar-diography and in those situations CMR can be a usefulalternative technique. Cine assessment of right ventricularfunction and late enhancement evaluation of RV infarctioncan be readily accomplished.

Assessment of ischaemia

Many patients presenting with acute MI have co-existentdisease in non-culprit coronary arteries. Approximately halfof patients presenting with STEMI have evidence of multi-vessel disease and this group experience an adverse prognosis[16, 17]. The default management strategy in these patientshas focussed on the infarct-related artery only with targeted,staged symptom-driven revascularisation of non-culprit ves-sels. There is emerging evidence that non-infarct-related arteryintervention may actually be harmful in the acute setting ofSTEMI [18–20]. New and delayed clinically evident ischae-mia not related to the culprit vessel may be treated optimallywith staging of non-culprit vessels and appropriate revascu-larisation, particularly as it is now established that in the 20%of patients that have a new acute ACS following the indexacute MI, 50% are the result of a non-culprit lesion [21].

A number of non-invasive investigation options are avail-able, including exercise ECG, nuclear SPECT, dobutaminestress echocardiography (DSE), cardiac computed tomogra-phy, and adenosine or dobutamine stress CMR. There isconvincing evidence that imaging-based stress tests are betterthan exercise ECG investigations [22, 23]. There is substantialevidence in favour of these imaging techniques in the generalpopulation with suspected ischaemic symptoms, and in thepost-MI setting. However, a large proportion of the post-MIdata relate to the thrombolytic era in patients with unknowncoronary anatomy at the time of evaluation, with non-invasive

tests being utilised as risk-predictive tools for triaging patientstowards an invasive versus non-invasive approach to furthermanagement. Therefore the applicability of these data to con-temporary clinical practice in the current era of primary PCI inpatients with defined coronary anatomy is unclear. In thebroader general population undergoing assessment for revers-ible ischaemia, meta-analyses of each imaging technique havedemonstrated variable diagnostic performance. Sensitivityand specificity have been documented for DSE (81.0% and84.1%) [24], nuclear SPECT (88.1% and 73.0%) [24], dobut-amine stress CMR (83.0% and 86.0%) [25] and adenosinestress perfusion CMR (91.0% and 81.0%) [25]. These meas-ures of diagnostic ability have been evaluated against a goldstandard of coronary angiography, with stenoses of either 50%or 70% used as a cutoff value for clinical significance. Where-as when adenosine stress CMR is assessed against the alter-native—and likely more accurate—gold standard of fractionalflow reserve (FFR) a significant increase in specificity (94%) isobserved whilst retaining high sensitivity [26, 27]. Thereforeconsiderable evidence exists confirming the superior diagnos-tic ability of stress perfusion CMR, though this is yet totranslate into a prominent position in international guidelines.

To be confident that a negative imaging procedure cansafely allow the deferral of coronary revascularisation, thediagnostic performance of the imaging technique must trans-late into a clear prognostic ability. Considerable experienceand evidence are available for nuclear imaging and stressecho; a negative SPECT or DSE is associated with an excel-lent prognosis with death/MI rates of <1% at 2 years’ follow-up. Stress CMR has recently been proven to provide compa-rable prognostic data at medium-term follow-up [28, 29] incohorts with a high proportion of patients with previous MI.

The proposed advantage of CMR lies in its superiorspatial resolution with the ability to detect subendocardialdefects (Fig. 3) and in additional diagnostic informationsuch as the evaluation of valvular disease and assessmentof left ventricular structure, function and viability [30–32].

Fig. 3 Adenosine stress CMR early after STEMI. a Perfusion defect(yellow arrow) in the anteroseptal wall on the left ventricular short axisat stress. b No perfusion defect at rest in the anteroseptal wall of the left

ventricle. c Severe stenosis in proximal LAD at subsequent coronaryangiography

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Adenosine stress CMR early after primary PCI for STEMI hasbeen shown to be safe and feasible, with good diagnosticperformance through visual assessment [33]. More recently,semi-quantitative assessment based on the myocardial perfu-sion reserve index (MPRI) has also been validated in patientswith STEMI and coronary artery disease [32, 34, 35]. Besidesbeing more accurate than visual assessment for identifyingand quantifying ischaemia, semi-quantitative assessment alsoprovides the ability to assess myocardial blood flow in theinfarct territory for assessment of microvascular obstruction.Therefore, CMR is likely to assume an increasing role in theevaluation of patients with co-existent non-infarct-related dis-ease following MI.

Assessment of left ventricular remodelling post-STEMI

Soon after the onset of ischaemia the myocardium becomesoedematous and is accompanied by a profound inflammatorycell infiltrate. In the absence of reperfusion therapy, necrosisof cardiomyocytes in the direct distribution of the infarctterritory occurs within the first hour. Upregulation of matrixmetalloproteinases in the infarct and adjoining border zone ofinfarction soon follows. Apoptosis in the border zone ofinfarction contributes to continuing cardiomyocyte loss inthe subacute period and together with the extracellular matrixchanges, contributes to the process of infarct expansion andsubsequent negative remodelling observed following MI.

Cardiac imaging in the acute and subacute phases post-STEMI have provided significant insights into this remodel-ling process, including the impact of reperfusion treatment.The assessment of infarct size and microvascular obstructionhas proved to be a robust prognostic indicator, increasinglyutilised as an endpoint in clinical trials. Repeat imaging at 2–3 months following infarction aids the evaluation of the extentof post-infarct negative remodelling [36, 37]. Infarct remod-elling usually involves the progressive increase in end-diastolic and end-systolic volumes (EDV and ESV) in a par-allel fashion. Accordingly, initial changes in ejection fraction(EF) may appear to be minimal, despite significant alterationin LV chamber size. Although the definition of infarct remod-elling remains arbitrary, an increase in LV EDV of ≥20%compared with baseline is frequently used [38, 39]. There isextensive evidence regarding the prognostic significance ofLVEF following MI and the implications it holds for heartfailure and arrhythmic risk [40]. Cardiac magnetic resonanceimaging is considered the current gold-standard technique ofevaluating cardiac volumes and EF. This is especially relevantin patients with EFs that straddle important threshold cutoffpoints for determining clinical decision-making. More sophis-ticated imaging parameters can also be elucidated with CMR.It is well recognised that infarct size, transmural extent ofinfarction and microvascular obstruction (MVO) are strong

independent predictors of left ventricular remodelling [41,42]. All of these measures can be derived from gadoliniumenhanced CMR acquisitions [43].

Infarct size and transmurality

Late gadolinium enhancement imaging with CMR allowsassessment of infarct transmurality. Previous studies haveshown that LGE corresponds closely with area of necrosismeasured by triphenyltetrazolium chloride staining [44]. Thistechnique can depict the extent of scarring with impressivespatial resolution and high signal-to-noise ratio. Infarct sizemay be reported qualitatively or expressed quantitatively usingdedicated off-line software packages. The presence of four LVsegments with transmural LGE represents a powerful predictorof adverse LV remodelling following primary PCI, indepen-dent of the presence and extent of microvascular damage [45].In some studies, CMR-derived infarct size has been demon-strated to be the strongest predictor of LVremodelling, superiorto MVO [46]. It should be noted that the transmural extent oflate gadolinium enhancement may be affected by the timing ofimaging after MI. In the acute phase after infarction, myocar-dial enhancement will reflect a combination of the infarctedmyocardium and also myocardial oedema and inflammation.The contribution to myocardial enhancement provided byoedema and inflammation gradually subsides over the subse-quent 3-4 weeks, though the precise timing of resolution islikely to vary on an individual basis. Therefore there is thepotential to overestimate infarct size at early imaging timepoints and accordingly some units choose to defer imagingundertaken for clinical purposes until 4-6 weeks after MI.

Microvascular obstruction

Microvascular obstruction can be identified by two gadolinium-based techniques: first-pass-perfusion and LGE. First-pass-perfusion imaging is performed simultaneously with contrastmedium injection for the first 50 heart beats acquiring ≥3 shortaxis slices [41, 47]. A homogeneous increase in signal intensityin normal and infarcted myocardium is observed early aftercontrast medium administration, whereas MVO is seen as anarea of reduced signal intensity (hypoenhancement) in thecentral core of the infarct that persists for >2 min after contrastmedium administration. This is termed ‘early MVO’. With theLGE technique, MVO appears as a central hypoenhancedregion within a hyperenhanced region. This is termed ‘lateMVO’ (Fig. 4). The appearance observed is due to significantdamage within the microvasculature that prevents gadoliniumfrom entering the region.

There is ongoing debate about which methodology is su-perior for quantification ofMVO,with differences observed inthe sensitivity between first-pass and LGE for MVO quantifi-cation [48, 49]. It is however generally accepted that late

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MVO is less sensitive than early MVO because small ‘no-reflow’ zones become rapidly enhanced owing to diffusion ofthe extracellular contrast medium from adjacent regions with-out impaired microvasculature. As a result, late MVO mayunderestimate the extent of MVO [48]. Conversely, earlyMVO has limitations such as incomplete LV coverage, lowsignal-to-noise ratio and low spatial resolution, although novelimaging protocols with greater coverage aim to address thisissue [50]. Irrespective of the technique used, the extent orpresence ofMVO has beenwell validated as a strong predictorof LV remodelling. The categorical finding of the presence ofMVO, rather than the extent, has been suggested to be a betterpredictor of changes in EF and LV ESVat follow-up [49].

The concept of MVO is not exclusive to CMR, as anassessment can also be performed by myocardial contrastechocardiography. This technique uses small microbubbles(<5 μm) from which peak opacification and replenishmentkinetics can be evaluated [51] (early MVO equivalent). Addi-tionally, the endocardial length of transmural contrast defect[51] provides an LGE/late MVO parallel. These methodscorrelate with MVO [52], including those with apparent resto-ration of TIMI flow grade [53]. Myocardial contrast-enhancedechocardiography-derivedMVO has been shown to be a great-er predictor of LV remodelling following STEMI comparedwith persistent ST-segment elevation and myocardial blushgrade [54]. This technique has some shortcomings in compar-ison to CMR, including moderate spatial resolution, operatordependency, incomplete LV coverage with suboptimal visual-isation of the lateral wall and semi-quantitative assessment ofMVO [55, 56].

Assessment of myocardial viability

A significant proportion of patients have co-existent disease innon-infarct-related arteries identified at the time of primaryPCI. A number of these ischaemic territories supply dysfunc-tional myocardial segments. The assessment of myocardialviability is therefore important to guide revascularisation deci-sions because studies have shown that revascularisation of

viable myocardial segments predicts functional recovery[57]. As reduced contractile performance may be secondaryto hibernating myocardium, if perfusion is restored, there ispotential for recovery of contractile function. Alternatively,the level of myocardial necrosis may be so severe that func-tional recovery is not possible, therefore indicating that revas-cularisation, which carries concomitant risks, would be futile.Accordingly, this explains the rationale for evaluating myo-cardial viability before possible revascularisation. Patientswith >4 viable segments on DSE have a survival benefit whentreated with a revascularisation strategy compared with med-ical therapy alone [58]. Wall thickness of ventricular myocar-dial segments may also predict viability with an end diastolicthickness of <6 mm strongly predictive of failure of functionalrecovery [59].

Additionally, it has been demonstrated that reverse remodel-ling of the left ventricle following revascularisation of viablemyocardium is not only restricted to improvement in EF and LVvolumes, but also diastolic function [60]. Furthermore, a meta-analysis has shown that revascularisation of viable myocardiumreduces mortality [61]. However the recent STITCH (SurgicalTreatment for Ischemic Heart Failure) trial [62] did not demon-strate a survival benefit with a viability-directed revascularisa-tion strategy as assessed by SPECT or DSE [63]. Therefore,these discrepant findings suggest that a complex relationshipbetween myocardial viability (and thus recovery of contractilefunction) and prognosis appears to exist. However viabilityassessment remains a routine clinical indication and can beperformed by multiple techniques including DSE, SPECT, pos-itron emission tomography (PET), dobutamine stress CMR andCMR-derived LGE. Utilising the tracers 201thallium, 99mtechne-tium sestamibi or 99mtechnetium tetrofosmin, SPECT has tradi-tionally been the most widely applied technique for myocardialviability assessment. This provides information on perfusionand viability, with reported viability sensitivity of 81% andspecificity of 66% [64]. The most accurate results are achievedwith PET, with sensitivity and specificity rates of 93% and 58%respectively, when undertaken during stimulation of glucosemetabolism during simultaneous glucose and insulin infusion

Fig. 4 Microvascularobstruction. a Late gadoliniumenhancement image showingregions of scar tissue (white)and microvascular obstructionarea ‘late MVO’ (black bloodlakes within scar tissue,highlighted in orange andpurple) after acute MI. b First-pass perfusion imaging on car-diac MRI showing microvascu-lar obstruction area ‘earlyMVO’, highlighted in orange

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(‘hyperinsulinaemic euglycaemic clamp’) [64]. However, thisparticular technique is costly and not widely available. Con-versely, low-dose DSE is widely available and relatively cheap,and can be used to assess contractile reserve. Studies haveshown that contractile reserve for chronically ischaemic hiber-nating myocardium is best elicited by low-dose dobutamine[65], with a high-dose evaluation for a biphasic response addinggreater specificity for functional recovery.

Cardiac MRI has considerable potential for the assessmentof viability, with two principle MRI techniques frequentlyapplied: dobutamine wall motion assessment (analogous toDSE protocols) and LGE. In comparison to 18F-deoxyglucosePET, dobutamine CMR has a sensitivity of 88% and specific-ity 87% with a positive predictive value of 92% [66]. Thistechnique shares the contractile reserve method with DSE, butCMR offers far greater spatial resolution that allows the de-tection of even subtle regional wall motion abnormalities.Greater diagnostic accuracy of viability was also observedagainst dobutamine transoesophageal echocardiography [67].

The second method is LGE quantification of scar trans-murality. This is usually graded into quartiles: <25%, 25–49%, 50–75% and >75%, and the probability of contractilerecovery following revascularisation has a graded relation tothe transmural extent of LGE [68]. As previously described,the extent of transmural enhancement may be overestimatedon imaging obtained in the acute phase after MI, and shouldtherefore be interpreted with caution with regard to assess-ment of viability. However, with deferred imaging, thistechnique has excellent sensitivity (90–97%) but limitedspecificity (52%) overall [69]. Specificity is far greater whenconsidering only the minimal (<25%) or transmural hyper-enhancement (>75%) categories as demonstrated by a 77%and 2% chance of recovery respectively [70]. However it isin the intermediate groups (segments with 25–75% hyper-enhancement) that functional recovery is most variable [70].Although dobutamine wall motion assessment of contractilereserve and LGE transmural extent are frequently consideredas separate investigations, they need not bemutually exclusiveas both can be readily accomplished in a single CMR exam-ination. A combination of both techniques has been proposedto improve the specificity of myocardial viability in patientswith intermediate LGE (25–75% transmural extent). In onestudy, low-dose dobutamine was shown to categorise 61% ofintermediate segments with and 39% without contractile re-serve [71], although the post-revascularisation imaging find-ings were not presented.

The presence of MVO on gadolinium imaging is a strongindicator of the absence of myocardial viability and portendsadverse outcomes independent from infarct size [41]. Recentlya comparison of viability indices (dobutamine response, MVOand LGE) was performed to estimate functional recovery in 69patients early after STEMI. Contractile response to low-dosedobutamine (10 μg/kg/min) was the best individual predictive

factor of segmental recovery with a probability of segmentalrecovery of 0.84.When other myocardial viability indexes suchas MVO and transmurality of enhancement were added, theprobability increased to 0.97 [72]. The excellent predictiveprobability reinforces CMR as a robust method for evaluatingmyocardial viability after acute myocardial infarction as thecombination of these viability indexes can be completed in asingle examination.

More recently, the utility of myocardial strain for assessingthe viability of functional recovery has been investigated.Initially this focussed on strain measured with speckle track-ing on transthoracic echocardiography [73, 74]. Myocardialstrain can also be assessed on CMR with grid-tagging. Thisinvolves a segmented k-space version of the spatial modula-tion of magnetisation (SPAMM) tagging sequence that satu-rates a grid into the CMR image (Fig. 5). This allows directevaluation of myocardial deformation, although images canbe limited by the relatively low spatial resolution and tagfading towards end-diastole, particularly with 1.5-T systems.Quantitative analysis off-line can provide a reproducible mea-sure of regional myocardial strain and can be used for detailedanalysis of regional ventricular function with high accuracy[75, 76]. In one study evaluating multiparametric strain in achronic ischaemic cardiomyopathy cohort, high diagnosticaccuracy was observed [77]. The utility of myocardial strainassessment with grid-tagged CMR has also been extended todiastolic function evaluation [78] as well as characterisation ofperi-infarct dysfunction [76]. However the value of grid-tagged-derived viability assessment in a post-STEMI cohortstill requires further appraisal.

Imaging markers as endpoints in clinical trials

The ability of CMR to accurately quantify various parameterswith minimal variation in reproducibility, particularly withregard to infarct size, has generated considerable interest inadopting CMR-derived indices as surrogate end points inclinical trials. The improved efficacy of current therapies forMI (particularly primary PCI and prompt restoration of ante-grade coronary flow) has meant that alternative or additionaltreatments offer the scope for only small incremental benefitsover current best medical practice. Accordingly the sample sizerequired for studies to evaluate such novel therapies in terms ofhard end points may be prohibitively large. Surrogate endpoints, such as CMR-derived infarct size, offer an alternativestrategy for evaluating therapies at various stages of develop-ment, provide mechanistic insights and generate hypothesesfor future research. Repeated measurements of LGE in patientswith acute MI have demonstrated a standard deviation of 1%of LV mass [79]. Accordingly, such precise reproducibilityoffers the prospect of substantial reductions in sample size. A2:1 relationship appears to exist [80], whereby for a given

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reduction in measurement variability, a reduction in samplesize of twice the magnitude is observed. For example, inseveral studies the standard deviation of infarct size has beenshown to be between 20 and 60% lower with CMR-LGE thanwith SPECT, which translates into a reduction of 40–120% inthe required sample size if CMR is used [81, 82].

More recently the myocardial salvage index (MSI) has beenproposed as an additional surrogate end point of reperfusiontreatment efficacy [83]. The myocardial salvage index (MSI) isdetermined by determining the area at risk (AAR) on T2-weighted images and infarct size on LGE imaging [84](Fig. 6):

Fig. 6 Infarct size. a T2-weighted image showing myo-cardial oedema with the area atrisk highlighted in red. b Lategadolinium enhancement imageshowing the extent of themyocardial infarct

Fig. 5 Myocardial grid-tagging. a Inversion recovery mid-LV shortaxis image demonstrating transmural late gadolinium enhancementwith areas of microvascular obstruction in the anterior, anteroseptumand inferoseptum. b Corresponding LV short axis tagged image using1.5-T MRI. c Bull’s eye plot of the same image slice with the ante-roseptum (infarcted region) and inferolateral wall (remote region)

highlighted in orange. d Circumferential strain: Red curve indicatesstrain in infarcted anteroseptum, green curve indicates strain in theremote inferolateral wall. e Circumferential strain rate: Red curveindicates strain rate in infarcted anteroseptum, green curve indicatesstrain rate in the remote inferolateral wall

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Myocardial salvage index (MSI) 0 area at risk minusinfarct size / area at risk

Friedrich et al. recently reported promising data on themyocardial salvage determination in acute MI patients [85],with further studies indicating that MSI may be a superiorsurrogate end point to infarct size [86–88]. One of the majorfactors that influence variation in infarct size is the AARwhereby even small differences in the AAR may result insignificant variation of the infarct size [89, 90]. Masci et al.recently showed that CMR-derived MSI was a major andindependent determinant of two important clinical and prog-nostic parameters, such as LV remodelling and early ST-segment resolution [83]. Although promising, this study wassmall and hence future larger studies are still required; how-ever CMR-derived indices of infarct size and area at riskwould appear particularly suited to the role of end point inclinical trials.

Conclusion

Patients post-MI have a number of ongoing important clinicalquestions that need to be addressed with cardiac imaging.These may include clarification of myocardial necrosis aeti-ology, assessment for early complications and evaluation forresidual ischaemia, adverse ventricular remodelling and myo-cardial viability. Each of these features has significant clinicalrelevance and has a direct impact upon prognosis and clinicalmanagement. Cardiac magnetic resonance imaging is wellsuited because of its ability to accurately determine myocar-dial structure, function, perfusion and viability in a singleexamination; CMR offers the prospect of studying left ven-tricular remodelling, ischaemia in the non-culprit territory andmyocardial viability after acute myocardial infarction, alsocalled “triple vital assessment”. It has also become the goldstandard for many cardiac parameters, hence the widespreadadoption of CMR-derived indices as surrogate end points inclinical trials. Accordingly CMR offers substantial incremen-tal value over the alternative imaging techniques available inpatients after myocardial infarction.

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