Original Articles

Prognostic Value and Determinants of a Hypointense Infarct Core in T2-Weighted Cardiac Magnetic Resonance in Acute Reperfused ST-Elevation–Myocardial InfarctionClinical Perspective

Ingo Eitel, Konrad Kubusch, Oliver Strohm, Steffen Desch, Yoko Mikami, Suzanne de Waha, Matthias Gutberlet, Gerhard Schuler, Matthias G. Friedrich, Holger Thiele
https://doi.org/10.1161/CIRCIMAGING.110.960500
Circulation: Cardiovascular Imaging. 2011;4:354-362
Originally published July 19, 2011

Jump to

Abstract

Background—A hypointense core of infarcted myocardium in T2-weighted cardiovascular MRI (CMR) has been used as a noninvasive marker for intramyocardial hemorrhage. However, the clinical significance of such findings not yet been established. The aim of this study was to evaluate determinants and prognostic impact of a hypointense infarct core in T2-weighted CMR images, studied in patients after acute, reperfused ST-elevation–myocardial infarction.

Methods and Results—We analyzed 346 patients with ST-elevation–myocardial infarction undergoing primary angioplasty <12 hours after symptoms onset. T2-weighted, contrast-enhanced CMR was used for assessment of the area at risk, myocardial salvage, infarct size, hypointense core in T2-weighted images, and late microvascular obstruction. Patients were categorized into 2 groups defined by the presence or absence of a hypointense core. The primary end point of the study was occurrence of major adverse cardiovascular events defined as death, reinfarction, and congestive heart failure within 6 months after infarction. A hypointense core was present in 122 (35%) patients and was associated with larger infarcts, greater amount of microvascular obstruction, less myocardial salvage, and impaired left ventricular function (P<0.001, respectively). The presence of a hypointense core was a strong univariable predictor of major adverse cardiovascular events (hazard ratio, 2.59; confidence interval, 1.27 to 5.27) and was significantly associated with an increased major adverse cardiovascular events rate (16.4% versus 7.0%, P=0.006) 6 months after infarction.

Conclusions—A hypointense infarct core within the area at risk of reperfused infarcted myocardium in T2-weighted CMR is closely related to infarct size, microvascular obstruction, and impaired left ventricular function, with subsequent adverse clinical outcome.

Introduction

Early administration of reperfusion therapy improves survival in patients with ST-elevation–myocardial infarction (STEMI) by reestablishing coronary blood flow within the occluded infarct-related artery (IRA). When available, rapid primary percutaneous coronary intervention (PPCI) is the recommended therapy for patients with acute STEMI.1 The process of restoring blood flow to the ischemic myocardium, however, can induce additional endothelial and myocardial damage, which is also known as reperfusion injury.2

Clinical Perspective on p 362

Intramyocardial hemorrhage (IMH) is a phenomenon that reflects severe reperfusion injury, resulting in extravasation of erythrocytes into reperfused myocardium caused by loss of structural and functional integrity of the microcirculation.3–5 Animal studies4–8 and limited studies in humans3,9–14 have shown that IMH occurs frequently in reperfused STEMI and is localized predominantly within the infarct core. Although the relationship of IMH with adverse left ventricular (LV) remodeling and infarct size has been shown in relatively small studies in humans,9,10 the clinical significance of IMH is still unclear, largely because of the lack of methods for detecting IMH in vivo.

Cardiovascular MRI (CMR) allows for high-resolution assessment of the area at risk (AAR), myocardial necrosis (infarct size), and microvascular damage (microvascular obstruction [MO]), providing in vivo tissue characterization in patients with myocardial infarction.15–18 Although histological proof of the specificity of hypointense cores for IMH is still awaited, hypointense core regions of infarcted myocardium in T2-weighted and T2*-weighted CMR have been associated with hemorrhagic infarcts, because breakdown products of hemoglobin have paramagnetic effects and thereby shorten T2-relaxation times.7–11,13,14,19,20 Thus, CMR might be a powerful tool to assess the occurrence and extent of reperfusion injury in humans and to determine its relation to the AAR, salvaged myocardium, infarct size, and MO.

The aim of this study was to evaluate determinants and the clinical impact of a hypointense core in T2-weighted CMR in a large series of STEMI patients reperfused by PPCI.

Methods

Study Population

This prospective study was conducted at 2 tertiary care centers between February 2006 and October 2009 (University of Leipzig–Heart Center, Leipzig, Germany [center A]; and Stephenson CMR Center at the Libin Cardiovascular Institute of Alberta, University of Calgary, Calgary, Canada [center B]). The study protocol was approved by the local ethics committees, and all patients gave written informed consent. Patients were eligible if the onset of symptoms was <12 hours before PPCI and if they had ST-segment elevation of ≥0.1 mV in ≥2 extremity leads or ≥0.2 mV in ≥2 precordial leads. Exclusion criteria were prior fibrinolysis and patients with contraindications to CMR at study entry such as implanted pacemakers, defibrillators, claustrophobia, or metallic intracranial implants.

PPCI and Subsequent Treatment

PPCI was performed according to standard clinical practice. The use of bare metal or drug-eluting stents was left to the discretion of the interventional cardiologist. Additional use of intra-aortic balloon counterpulsation or thrombectomy was performed, depending on hemodynamic instability and thrombus in the IRA. All patients received 500 mg of aspirin and heparin (60 IU/kg body weight) intravenously before PPCI. Clopidogrel (loading dose of 600 mg orally during PCI, if not administered before, followed by 75 mg/d for at least 12 months) was mandatory. Aspirin was given indefinitely at a dose of 100 mg/d (center A) or 81 mg/d (center B). The use of glycoprotein IIb/IIIa-inhibitors, angiotensin-converting enzyme inhibitors, β-blockers, and statins was strongly recommended.

Angiographic Analysis

Coronary angiography of the target lesion was performed before and after PPCI with the same standard projections. Angiographic projections used were those that allowed optimal evaluation of the IRA Thrombolysis In Myocardial Infarction (TIMI) flow. Angiographic analysis included initial and final flow of the culprit vessel. Visual assessments were performed offline in the angiographic core laboratory by 2 blinded observers.

CMR Acquisition

Image acquisition was performed on a 1.5-T whole-body system in both centers (center A: Intera CV, Philips Medical Systems, Best, The Netherlands; center B: Avanto, Siemens Medical Solutions, Erlangen, Germany). A 12- or 32-element cardiac phased-array surface coil was utilized for all sequences except T2-weighted imaging, for which a body coil was used.

Localizers and LV functional assessment were performed using steady-state, free-precession images. In the short-axis orientation, the LV was completely encompassed by contiguous slices. A triple inversion-recovery T2-weighted sequence (short-TI inversion recovery) was used to assess edema in short-axis slices covering the whole ventricle (center A: repetition-time (TR), 2×R-R interval; echo time (TE), 80 ms; voxel-size, 0.7×0.7×8.0 mm; center B: TR, 2×R-R interval; TE, 61 ms; voxel size, 1.5×1.5×10 mm). Late gadolinium enhancement (LGE) images covering the entire LV were acquired approximately 10 to 15 minutes after intravenous administration of 0.2 mmol/kg gadolinium-based contrast agents (center A: Gadovist, BayerSchering, Germany; center B: Magnevist, Bayer Healthcare, Canada). A breath-hold 3D (Intera CV, Phillips) or 2D (Avanto, Siemens) inversion recovery gradient-echo pulse sequence (center A: TR, 2.9 ms; TE, 1.5 ms; flip angle, 15°; typical spatial resolution, 0.9×0.9×10 mm; center B: TR, 1.0 ms; TE, 3.4 ms; flip angle, 20°; typical spatial resolution, 1.4×1.4×10 mm) was used for image acquisition. Inversion times were individually adjusted to optimize nulling of apparently normal myocardium (typical values, 200 to 300 ms).

Image Analysis

For all quantitative analyses, certified CMR evaluation software was used (cmr,42 Circle Cardiovascular Imaging Inc, Calgary, Alberta, Canada). Off-line image analysis was performed by fully blinded observers. Semiautomated computer-aided threshold detection was used to identify regions of edema, hypointense cores, and infarcted myocardium. A myocardial region was regarded as affected if at least 10 adjacent myocardial pixels revealed a signal intensity of >2 standard deviations (SD) of remote myocardium for edema and >5 SD in LGE images.21 A hypointense core was defined as an area in the center of the AAR/edema having a mean signal intensity of at least 2 SD below the signal intensity of the periphery of the AAR and having a minimal volume of 1 mL (1 cm3), as previously described.9 The hypointense signal within the area of increased T2-signal intensity was included in the AAR assessment. Infarct size, AAR, hypointense cores, and MO were expressed as percentage of LV mass volume, given by the sum of the volume of edema, LGE, and MO regions for all slices divided by the sum of the LV myocardial cross-sectional volumes (%LV). In patients with MO, these dark areas were included for infarct size analysis and the area of MO was assessed separately. Salvaged myocardium was quantified as the difference between the volume of increased T2-signal (AAR) and the volume of LGE (infarct size), as previously described.15–17 The CMR core laboratory has excellent reproducibility and low interobserver and intraobserver variability for infarct size and myocardial salvage assessment.22

Interobserver and intraobserver variability for the assessment of hypointense infarct cores was also low in 15 randomly chosen patients of the current study (mean bias of 0.4%LV; limits of agreement, ±1.1%LV and 0.7%LV; limits of agreement, ±1.4%LV, respectively).

Clinical End Points

The primary study end point was the occurrence of major adverse cardiovascular events (MACE), defined as a composite of death, reinfarction, and new congestive heart failure within 6 months after the index event. Posthospital follow-up included 1 outpatient visit at 6 months. The diagnosis of reinfarction during the index hospitalization was based on clinical symptoms, new ST-segment changes, and an increase in the creatine kinase-MB levels above the reference limits in patients with normalized values or if there was an increase of >20% from the last non-normalized measurement.23 At follow-up, any new ischemic symptoms leading to hospital admission accompanied by elevated troponin were defined as recurrent myocardial infarction. New heart failure was defined as congestive heart failure requiring medical attention and treatment with diuretics occurring >24 hours after the index event. The diagnosis consisted of at least 1 of the following conditions: (1) pulmonary edema or congestion on chest radiograph without suspicion of a noncardiac cause; (2) rales of more than one-third up from the lung base (Killip class ≥2); (3) pulmonary capillary wedge pressure of >25 mm Hg; or (4) dyspnea with an oxygen pressure of <80 mm Hg or oxygen saturation of <90% without supplemental oxygen and in the absence of known lung disease. If a patient had more than 1 event during follow-up, then only the first was recorded, and no additional data were used for survival analysis. If 2 events occurred simultaneously, then the more severe event was recorded.

Statistical Analysis

Each categorical variable is expressed as number and percentage of patients. Most continuous variables had non-normal distribution and are therefore presented as medians together with interquartile range. Differences between groups were assessed by Fisher exact or the χ2 test for categorical variables and by the Student t test for continuous data with normal distribution. Otherwise, the nonparametric Wilcoxon rank sum test was used. Correlation analyses were done by Pearson or Spearman tests, as indicated.

Univariable and stepwise multivariable logistic regression analyses were performed to identify predictors of the occurrence of a hypointense core. Multivariable regression was performed using only variables with a probability value <0.05 in univariable regression analyses. For univariable analyses, all variables of Table 1 and Table 2 were tested.

View this table:
Table 1.

Patient Characteristics

View this table:
Table 2.

CMR Results

For the combined clinical end point, the Kaplan-Meier method was applied, and differences were assessed by the log rank test. Simple Cox-regression analysis using the same variables as defined above was used to identify predictors of MACE during 6 months. Hazard ratios with corresponding 95% confidence intervals are reported. All significant variables were then tested in a multiple Cox regression analysis, based on a stepwise algorithm with the probability value set at 0.05 for entering and 0.1 for exclusion. Myocardial salvage was not included in the model to avoid multicollinearity because infarct size is included in the formula for calculation of myocardial salvage.

The incremental additive information associated with the presence of hypointense infarct cores over preimaging variables (age, infarct location, and time to reperfusion), LV function, and infarct size for the prediction of MACE was assessed using c-statistics. c-Statistic results were compared using the nonparametric method previously described by De Long et al.24 All statistical tests were performed with SPSS software, version 15.0. A 2-tailed probability value <0.05 was considered statistically significant.

Results

Of 407 eligible consecutive STEMI patients, this prospective study included 346 patients (Figure 1). The main reason for exclusion of the study was a lacking CMR examination (n=51). Reasons for not pursuing CMR are listed in Figure 1. Complete clinical outcome data at 6 months were available in 333 patients.

Patient Characteristics

Demographic and clinical characteristics are shown in Table 1. There were no significant differences between groups regarding baseline characteristics and reperfusion times. Patients with a hypointense core in T2 imaging had a significantly higher frequency of anterior infarction and TIMI flow ≤1 before PPCI. After PPCI, the majority of patients had TIMI-flow 3 in both groups. However, patients with a hypointense core in T2-weighted CMR had a significantly higher occurrence of TIMI flow <3 after PPCI (15% versus 7%, P=0.03). The main reason for the absence of TIMI-flow 3 after PCI was no-reflow caused by distal coronary microembolization of atherosclerotic debris or thrombotic material.

Cardiovascular Magnetic Resonance Imaging

The median time between the index event and CMR was 3 days (interquartile range, 2 to 4) for both groups (P=0.39). In all patients, a regional T2-signal increase (AAR) was observed in the infarct region (Figure 2A through 2C and Figure 3A through 3C). A hypointense core within the increased T2 signal was detected in 122 patients (35%) (Figure 3A through 3C). The mean extent of such core was 1.3±2.0%LV. The localization of LGE was in the same region as the edema in all cases (Figure 2D and Figure 3D). In 21 (6%) patients, CMR detected no LGE consistent with an aborted infarction.25

Figure 2.
Figure 2.

A, T2-weighted CMR show homogenous high signal intensity (SI) of the anteroseptal segment. B, Computer-aided SI analysis with color-coded display of relative SI, normalized to normal myocardium. Red indicates a SI of ≥5 SD above remote myocardium. Computer-aided SI analysis with color-coded display of relative SI normalized to skeletal muscle. Blue indicates a SI ratio of myocardium/skeletal muscle of ≥2, indicating edema, green/yellow indicates normal SI (1.4 to 1.9). C, This image is displayed to further demonstrate the robustness of CMR for detection of a hypointense core in T2-weighted imaging and was not the method used in this study. D, Contrast-enhanced image showing transmural necrosis on the same myocardial segments.

Figure 3.
Figure 3.

A, T2 images showing a hypointense core within the area of myocardial edema (arrow). Computer-aided SI analysis normalized to normal myocardium (B) and to skeletal muscle (C). Contrast-enhanced image showing a transmural necrosis with a core of late MO (arrow) (D).

In all patients with presence of a hypointense core, late MO was detected (Figure 3A through 3D and Table 2). However, in 108 (48%) patients with late MO, no hypointense core was present (Figure 4). Patients with hypointense cores had significantly larger LV volumes and lower LV ejection fraction than patients without hypointense cores (Table 2). The amount of the AAR, infarct size, and the presence and extent of late MO were significantly larger in patients with a hypointense core (P<0.001, respectively, Table 2). Significantly less myocardium at risk could be salvaged in patients with hypointense cores (P<0.001).

Figure 4.
Figure 4.

Patient with anteroseptal infarction with homogenous increased T2-signal (A and B) despite the presence of late MO (arrow) (C and D).

Predictors of a Hypointense Core in T2-Weighted Images

The extent of infarct size (r=0.61) and late MO (r=0.74) correlated significantly with the volumetric extent of the hypointense core (P<0.001, respectively). In a multivariable regression model adjusted for significant variables in univariable regression analysis, the extent of late MO (P<0.001), infarct size (P=0.01), and impaired LV ejection fraction (P=0.02) were the strongest predictors of hypointense cores.

Clinical Outcome

At 6-month follow-up, there were 35 MACE (10%), including 12 cardiac deaths, 10 nonfatal reinfarctions, and 13 readmissions for congestive heart failure. Patients with the presence of hypointense cores had significantly more MACE compared with patients without this finding (16.4% versus 7.0%, P=0.006; Figure 5A). The presence of late MO was also associated with a significantly increased MACE rate (13.8% versus 3.6%, P=0.004).

Figure 5.
Figure 5.

Unadjusted survival curves of the cumulative incidence of death, reinfarction, and new congestive heart failure during the first 6 months after infarction in patients with and without the presence of a hypointense core in T2-weighted imaging (A) and in patients with hypointense core and MO both present (IMH), MO only present, and patients with neither MO nor hypointense core (B).

When using a 3-level categorical variable including (1) late MO and hypointense core both present, (2) late MO only present, and (3) no late MO and no hypointense core present, a risk gradient across the 3 groups could be observed (16.4% versus 10.8% versus 3.6%, P=0.002; Figure 5B).

The presence of a hypointense core demonstrated a strong unadjusted association with MACE (hazard ratio, 2.59; 95% confidence interval, 1.27 to 5.27). In addition to hypointense cores, several established markers of increased patient risk were associated with increased MACE at 6-month follow-up by simple Cox-regression analysis. Using stepwise multiple Cox-regression analysis, only the presence of hypointense infarct cores, LV ejection fraction less than median, and age remained independent predictors of MACE (Table 3). Although the presence of late MO only was able to predict 6-month MACE in univariable analysis, it was no independent predictor in stepwise multivariable Cox regression analysis.

View this table:
Table 3.

Predictors of MACE in Univariable and Stepwise Multivariable Cox Regression Analysis

The results of 4 separate models for the prediction of MACE are presented in Table 4 and Figure 6. The inclusion of hypointense infarct cores in addition to preimaging variables (age, infarct location, and time to treatment), LV function, and infarct size resulted in an increase of the c-statistics from 0.76 to 0.80 (P=0.046), thus demonstrating an additive prognostic value of hypointense infarct cores.

View this table:
Table 4.

c-Statistics: Additive Prognostic Value of the Presence of Hypointense Infarct Cores

Figure 6.
Figure 6.

Receiver operator characteristic curves demonstrating the ability of 4 models to predict MACE at 6 months.

Discussion

The present study is the largest study thus far to assess determinants and the prognostic significance of a hypointense infarct core in T2-weighted CMR in acutely reperfused STEMI patients. The major findings are as follows: (1) A hypointense core detected by CMR is a frequent finding in STEMI patients reperfused by PPCI; (2) The occurrence of a hypointense core is mainly associated with the presence and extent of late MO together with large infarcts and impaired LV function; and (3) A hypointense infarct core is a strong indicator of MACE at 6-month follow-up.

Hypointense Infarct Core in T2-Weighted CMR

CMR can provide a wide range of prognostic information in acute STEMI by detecting infarct size, MO, and myocardial salvage.15–18 Additionally, T2-weighted CMR has been introduced as a method for detection of IMH.7–10,12,19,20,26 Because IMH occurs only in acutely reperfused, infarcted myocardium, T2 values in these regions are determined by the relative contribution of 2 opposing mechanisms: (1) increase in T2 caused by tissue edema/injured myocardium and (2) decrease in T2 induced by the paramagnetic effect of deoxyhemoglobin or degradation products of hemoglobin as found in hemorrhage or thrombus.7,19 The resulting hypointense core within the area of tissue edema seen on T2-weighted images has been demonstrated to correspond to histological evidence of IMH in animals7,8 and in limited patients.7,26

Even though several studies have used T2-weighted imaging to detect IMH,9,10,12 further validation is necessary to conclusively ascertain this relationship. Late MO, even in the absence of IMH, may also be represented by a signal drop within the area of edema and therefore a hypointense core in T2-weighted images may not be specific for IMH.27 The close relationship between late MO and hypointense cores that we and others observed9,10,12,13 may indicate that hypointense cores represent late MO. In the current study, however, a significant proportion of patients with presence of late MO had no signal abnormalities in T2-weighted CMR (Figure 4).

To more comprehensively assess for the presence of hemorrhage within the infarction zone, a T2* mapping technique, which has also been shown to detect the paramagnetic effects of iron and thereby IMH, might be useful in addition to T2-weighted imaging.11 The technique of T2* imaging has been validated histopathologically in animal and ex vivo studies as an effective method for quantifying reperfusion hemorrhage as well as myocardial iron overload and has been successfully applied in humans.11,14,28–31 Advantages of T2*-CMR include its more sensitive detection of the susceptibility effects of IMH than spin-echo imaging. However, T2* imaging requires relatively long echo times that may degrade image quality and, especially in the STEMI setting, stents can induce susceptibility artifacts.

Incidence, Determinants, and Prognostic Significance of Hypointense Infarct Cores

The true incidence of hypointense infarct cores within the area at risk of reperfused infarcted myocardium in T2-weighted CMR is unknown, but previous, relatively small studies in humans commonly observed hypointense cores after coronary artery reperfusion with a range from 25% to 49%.9,10,12,13 Our study, which is the largest patient population thus far, confirms that hypointense cores detected by T2-weighted CMR are frequently observed after PPCI, with an incidence of 35%. In contrast to animal studies, we and others9,13 could not find a relationship between the time from symptom onset to reperfusion and the occurrence of hypointense cores. This is somewhat surprising because hypointense infarct cores are closely related to microvascular injury/MO, infarct size, and the amount of the salvaged AAR, all parameters related to ischemic time in previous studies.15,17 However, it appears that ischemic time is not the only determinant of severe reperfusion injury, and hypointense cores are also influenced by other clinical factors such as presence or absence of residual flow in the IRA and/or infarct location with subsequent extent of the ischemic region as shown in our study. Other important factors might be the presence or absence of collateral flow, a history of ischemic preconditioning, distal coronary microembolization of atherosclerotic debris, or thrombotic material and/or the individual susceptibility of the coronary microcirculation to injury (eg, predisposed by diabetes and/or smoking).32

We found that similar to previous studies, infarct size and especially the presence and extent of late MO are the strongest predictors of the occurrence of hypointense cores.9,10,13,14 Late MO was detected in all patients with hypointense cores. However, late MO can occur without hypointense infarct cores in T2-weighted imaging. This is supported by our study, because 108 patients (48%) with late MO did not have a signal abnormality in T2-weighted CMR. Thus, we were able to differentiate our patients into 3 groups with different severity of reperfusion injury: (1) hypointense infarct core plus late MO present (severe reperfusion injury), (2) late MO only present (minor reperfusion injury), and (3) patients with neither late MO nor hypointense cores (no reperfusion injury). As a result, we were able to highlight important differences between patients with late MO only and those who also had hypointense cores. These observations indicate that the additional presence of hypointense cores confers a different outcome than late MO alone and that the known prognostic value of late MO32,33 mainly depends on the presence of both hypointense cores and late MO.

The clinical significance of hypointense cores regarding hard clinical end points has not yet been established. Ganame et al9 demonstrated that the presence of hypointense cores is an independent predictor of adverse LV remodeling. Two smaller studies could not confirm these results, and did not show prognostic significance of hypointense cores beyond late MO for prediction of functional changes at follow-up.10,12 The current study for the first time demonstrates the prognostic clinical relevance of the presence of hypointense infarct cores in STEMI patients reperfused by PPCI. Moreover, the presence of hypointense core together with late MO has additional prognostic value beyond the presence of late MO alone. Notably, we did not include myocardial salvage, which has been shown a strong predictor of clinical outcome15 in our Cox regression analysis. The main purpose of our study was to evaluate the relationship between infarct size, MO, and hypointense cores as well as to highlight differences in infarct characteristics and prognosis between patients with and without hypointense infarct cores. Interestingly, patients with a dark core in T2-weighted imaging also had significantly less myocardial salvage, indicating that the presence of hypointense cores might also carry prognostic information contained of this important outcome marker.15

However, the exact mechanism and contribution of hypointense infarct cores for reperfusion injury as well as IMH and any potential treatment interference or prevention strategy must be further explored.

Clinical Implications

The data of the present study and results of previous studies have shown that CMR provides intriguing incremental insights in postinfarct prognosis in STEMI patients by detecting AAR, infarct size, MO, and hypointense cores in T2-weighted images.9,15,18,33 A hypointense core in T2-weighted CMR, as a new CMR marker of severe reperfusion injury, predicts adverse LV remodeling9,14 and subsequent clinical prognosis, as shown in the present study. Thus, the presence of such a finding might help to select patients who may benefit from adjunctive therapy to promote the repair of infarcted myocardium and for the intensification of medical or device therapy. Because it can be detected in T2-weighted CMR without application of gadolinium-based contrast agents, this prognostic parameter might be especially useful in patients with relative contraindications against gadolinium compounds (eg, renal failure).

Limitations

The present study was conducted at 2 different centers using different CMR vendors. However, both centers carefully followed the same protocol, and all data were centrally analyzed. Second, infarct size and late MO are dynamic processes after acute infarction. Thus, imaging time after reperfusion is an important determinant for the presence and extent of late MO as well as infarct size. Because in our study both groups underwent CMR after a similar time delay, a potential bias is unlikely. Third, a main limitation of our study is the lack of pathological correlation with CMR results. Finally, a CMR protocol including a T2*-mapping sequence might be useful to comprehensively assess IMH.

Conclusions

A hypointense core within the AAR of reperfused infarcted myocardium in T2-weighted CMR is a frequent finding in reperfused STEMI patients and is closely related to infarct size, late MO, and adverse clinical outcome. However, larger multicenter studies are warranted to further investigate the prognostic significance of hypointense infarct cores.

Disclosures

Dr Eitel is supported by a research grant (BAYER scholarship) of the German Society of Cardiology. Dr Strohm was scientific advisor of Circle Cardiovascular Imaging Inc, and Dr Friedrich was shareholder and scientific advisor for Circle Cardiovascular Imaging Inc.

  • Received July 26, 2010.
  • Accepted April 15, 2011.

References

  1. 1.↵
    1. Huynh T,
    2. Perron S,
    3. O'Loughlin J,
    4. Joseph L,
    5. Labrecque M,
    6. Tu JV,
    7. Theroux P
    . Comparison of primary percutaneous coronary intervention and fibrinolytic therapy in ST-segment-elevation myocardial infarction: bayesian hierarchical meta-analyses of randomized controlled trials and observational studies. Circulation. 2009;119:3101–3109.
    OpenUrlAbstract/FREE Full Text
  2. 2.↵
    1. Yellon DM,
    2. Hausenloy DJ
    . Myocardial reperfusion injury. N Engl J Med. 2007;357:1121–1135.
    OpenUrlCrossRefPubMed
  3. 3.↵
    1. Asanuma T,
    2. Tanabe K,
    3. Ochiai K,
    4. Yoshitomi H,
    5. Nakamura K,
    6. Murakami Y,
    7. Sano K,
    8. Shimada T,
    9. Murakami R,
    10. Morioka S,
    11. Beppu S
    . Relationship between progressive microvascular damage and intramyocardial hemorrhage in patients with reperfused anterior myocardial infarction: myocardial contrast echocardiographic study. Circulation. 1997;96:448–453.
    OpenUrlAbstract/FREE Full Text
  4. 4.↵
    1. Higginson LA,
    2. White F,
    3. Heggtveit HA,
    4. Sanders TM,
    5. Bloor CM,
    6. Covell JW
    . Determinants of myocardial hemorrhage after coronary reperfusion in the anesthetized dog. Circulation. 1982;65:62–69.
    OpenUrlAbstract/FREE Full Text
  5. 5.↵
    1. Fishbein MC,
    2. Rit J,
    3. Lando U,
    4. Kanmatsuse K,
    5. Mercier JC,
    6. Ganz W
    . The relationship of vascular injury and myocardial hemorrhage to necrosis after reperfusion. Circulation. 1980;62:1274–1279.
    OpenUrlAbstract/FREE Full Text
  6. 6.↵
    1. Garcia-Dorado D,
    2. Theroux P,
    3. Solares J,
    4. Alonso J,
    5. Fernandez-Aviles F,
    6. Elizaga J,
    7. Soriano J,
    8. Botas J,
    9. Munoz R
    . Determinants of hemorrhagic infarcts: histologic observations from experiments involving coronary occlusion, coronary reperfusion, and reocclusion. Am J Pathol. 1990;137:301–311.
    OpenUrlPubMed
  7. 7.↵
    1. Lotan CS,
    2. Bouchard A,
    3. Cranney GB,
    4. Bishop SP,
    5. Pohost GM
    . Assessment of postreperfusion myocardial hemorrhage using proton NMR imaging at 1.5 T. Circulation. 1992;86:1018–1025.
    OpenUrlAbstract/FREE Full Text
  8. 8.↵
    1. Choi SH,
    2. Kang JW,
    3. Kim ST,
    4. Lee BH,
    5. Chun EJ,
    6. Schuleri KH,
    7. Choi SI,
    8. Lim TH
    . Investigation of T2-weighted signal intensity of infarcted myocardium and its correlation with delayed enhancement magnetic resonance imaging in a porcine model with reperfused acute myocardial infarction. Int J Cardiovasc Imaging. 2009;25(Suppl 1):111–119.
    OpenUrlCrossRefPubMed
  9. 9.↵
    1. Ganame J,
    2. Messalli G,
    3. Dymarkowski S,
    4. Rademakers FE,
    5. Desmet W,
    6. Van de Werf F,
    7. Bogaert J
    . Impact of myocardial haemorrhage on left ventricular function and remodelling in patients with reperfused acute myocardial infarction. Eur Heart J. 2009;30:1440–1449.
    OpenUrlAbstract/FREE Full Text
  10. 10.↵
    1. Beek AM,
    2. Nijveldt R,
    3. van Rossum AC
    . Intramyocardial hemorrhage and microvascular obstruction after primary percutaneous coronary intervention. Int J Cardiovasc Imaging. 2010;26:49–55.
    OpenUrlCrossRefPubMed
  11. 11.↵
    1. O'Regan DP,
    2. Ahmed R,
    3. Karunanithy N,
    4. Neuwirth C,
    5. Tan Y,
    6. Durighel G,
    7. Hajnal JV,
    8. Nadra I,
    9. Corbett SJ,
    10. Cook SA
    . Reperfusion hemorrhage following acute myocardial infarction: assessment with T2* mapping and effect on measuring the area at risk. Radiology. 2009;250:916–922.
    OpenUrlCrossRefPubMed
  12. 12.↵
    1. Bekkers SC,
    2. Smulders MW,
    3. Passos VL,
    4. Leiner T,
    5. Waltenberger J,
    6. Gorgels AP,
    7. Schalla S
    . Clinical implications of microvascular obstruction and intramyocardial haemorrhage in acute myocardial infarction using cardiovascular magnetic resonance imaging. Eur Radiol. 2010;20:2572–2578.
    OpenUrlCrossRefPubMed
  13. 13.↵
    1. Mather AN,
    2. Fairbairn TA,
    3. Ball SG,
    4. Greenwood JP,
    5. Plein S
    . Reperfusion haemorrhage as determined by cardiovascular MRI is a predictor of adverse left ventricular remodelling and markers of late arrhythmic risk. Heart. 2011;97:453–459.
    OpenUrlAbstract/FREE Full Text
  14. 14.↵
    1. O'Regan DP,
    2. Ariff B,
    3. Neuwirth C,
    4. Tan Y,
    5. Durighel G,
    6. Cook SA
    . Assessment of severe reperfusion injury with T2* cardiac MRI in patients with acute myocardial infarction. Heart. 2010;96:1885–1891.
    OpenUrlAbstract/FREE Full Text
  15. 15.↵
    1. Eitel I,
    2. Desch S,
    3. Fuernau G,
    4. Hildebrand L,
    5. Gutberlet M,
    6. Schuler G,
    7. Thiele H
    . Prognostic significance and determinants of myocardial salvage assessed by cardiovascular magnetic resonance in acute reperfused myocardial infarction. J Am Coll Cardiol. 2010;55:2470–2479.
    OpenUrlCrossRefPubMed
  16. 16.↵
    1. Friedrich MG,
    2. Abdel-Aty H,
    3. Taylor A,
    4. Schulz-Menger J,
    5. Messroghli D,
    6. Dietz R
    . The salvaged area at risk in reperfused acute myocardial infarction as visualized by cardiovascular magnetic resonance. J Am Coll Cardiol. 2008;51:1581–1587.
    OpenUrlCrossRefPubMed
  17. 17.↵
    1. Francone M,
    2. Bucciarelli-Ducci C,
    3. Carbone I,
    4. Canali E,
    5. Scardala L,
    6. Calabrese FA,
    7. Sardella G,
    8. Mancone M,
    9. Catalano C,
    10. Fedele F,
    11. Passariello R,
    12. Bogaert J,
    13. Agati L
    . Impact of primary coronary angioplasty delay on myocardial salvage, infarct size, and microvascular damage in patients with ST-segment elevation myocardial infarction: insight from cardiovascular magnetic resonance. J Am Coll Cardiol. 2009;54:2145–2153.
    OpenUrlCrossRefPubMed
  18. 18.↵
    1. Kim HW,
    2. Farzaneh-Far A,
    3. Kim RJ
    . Cardiovascular magnetic resonance in patients with myocardial infarction: current and emerging applications. J Am Coll Cardiol. 2009;55:1–16.
    OpenUrlCrossRefPubMed
  19. 19.↵
    1. Lotan CS,
    2. Miller SK,
    3. Bouchard A,
    4. Cranney GB,
    5. Reeves RC,
    6. Bishop SP,
    7. Elgavish GA,
    8. Pohost GM
    . Detection of intramyocardial hemorrhage using high-field proton (1H) nuclear magnetic resonance imaging. Cathet Cardiovasc Diagn. 1990;20:205–211.
    OpenUrlPubMed
  20. 20.↵
    1. Payne AR,
    2. Berry C,
    3. Kellman P,
    4. Anderson R,
    5. Chen M,
    6. Watkins S,
    7. McPhaden A,
    8. Schenke W,
    9. Wright V,
    10. Lederman RJ,
    11. Aletras AH,
    12. Arai A
    . T2-weighted MRI has high diagnostic accuracy for myocardial hemorrhage in myocardial infarction: a preclinical validation study in swine (abstract). Circulation. 2009;120:321.
    OpenUrl
  21. 21.↵
    1. Bondarenko O,
    2. Beek AM,
    3. Hofman MB,
    4. Kuhl HP,
    5. Twisk JW,
    6. van Dockum WG,
    7. Visser CA,
    8. van Rossum AC
    . Standardizing the definition of hyperenhancement in the quantitative assessment of infarct size and myocardial viability using delayed contrast-enhanced CMR. J Cardiovasc Magn Reson. 2005;7:481–485.
    OpenUrlCrossRefPubMed
  22. 22.↵
    1. Thiele H,
    2. Kappl MJ,
    3. Conradi S,
    4. Niebauer J,
    5. Hambrecht R,
    6. Schuler G
    . Reproducibility of chronic and acute infarct size measurement by delayed enhancement-magnetic resonance imaging. J Am Coll Cardiol. 2006;47:1641–1645.
    OpenUrlCrossRefPubMed
  23. 23.↵
    1. Thygesen K,
    2. Alpert JS,
    3. White HD
    . Universal definition of myocardial infarction. Eur Heart J. 2007;28:2525–2538.
    OpenUrlFREE Full Text
  24. 24.↵
    1. DeLong ER,
    2. DeLong DM,
    3. Clarke-Pearson DL
    . Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. Biometrics. 1988;44:837–845.
    OpenUrlCrossRefPubMed
  25. 25.↵
    1. Eitel I,
    2. Desch S,
    3. Sareban M,
    4. Fuernau G,
    5. Gutberlet M,
    6. Schuler G,
    7. Thiele H
    . Prognostic significance and magnetic resonance imaging findings in aborted myocardial infarction after primary angioplasty. Am Heart J. 2009;158:806–813.
    OpenUrlCrossRefPubMed
  26. 26.↵
    1. Basso C,
    2. Corbetti F,
    3. Silva C,
    4. Abudureheman A,
    5. Lacognata C,
    6. Cacciavillani L,
    7. Tarantini G,
    8. Marra MP,
    9. Ramondo A,
    10. Thiene G,
    11. Iliceto S
    . Morphologic validation of reperfused hemorrhagic myocardial infarction by cardiovascular magnetic resonance. Am J Cardiol. 2007;100:1322–1327.
    OpenUrlCrossRefPubMed
  27. 27.↵
    1. Cannan C,
    2. Eitel I,
    3. Hare J,
    4. Kumar A,
    5. Friedrich M
    . Hemorrhage in the myocardium following infarction. J Am Coll Cardiol Cardiovasc Imaging. 2010;3:665–668.
    OpenUrl
  28. 28.↵
    1. van den Bos EJ,
    2. Baks T,
    3. Moelker AD,
    4. Kerver W,
    5. van Geuns RJ,
    6. van der Giessen WJ,
    7. Duncker DJ,
    8. Wielopolski PA
    . Magnetic resonance imaging of haemorrhage within reperfused myocardial infarcts: possible interference with iron oxide-labelled cell tracking? Eur Heart J. 2006;27:1620–1626.
    OpenUrlAbstract/FREE Full Text
  29. 29.↵
    1. Wood JC,
    2. Otto-Duessel M,
    3. Aguilar M,
    4. Nick H,
    5. Nelson MD,
    6. Coates TD,
    7. Pollack H,
    8. Moats R
    . Cardiac iron determines cardiac T2*, T2, and T1 in the gerbil model of iron cardiomyopathy. Circulation. 2005;112:535–543.
    OpenUrlAbstract/FREE Full Text
  30. 30.↵
    1. Ochiai K,
    2. Shimada T,
    3. Murakami Y,
    4. Ishibashi Y,
    5. Sano K,
    6. Kitamura J,
    7. Inoue S,
    8. Murakami R,
    9. Kawamitsu H,
    10. Sugimura K
    . Hemorrhagic myocardial infarction after coronary reperfusion detected in vivo by magnetic resonance imaging in humans: prevalence and clinical implications. J Cardiovasc Magn Reson. 1999;1:247–256.
    OpenUrlCrossRefPubMed
  31. 31.↵
    1. Anderson LJ,
    2. Holden S,
    3. Davis B,
    4. Prescott E,
    5. Charrier CC,
    6. Bunce NH,
    7. Firmin DN,
    8. Wonke B,
    9. Porter J,
    10. Walker JM,
    11. Pennell DJ
    . Cardiovascular T2-star (T2*) magnetic resonance for the early diagnosis of myocardial iron overload. Eur Heart J. 2001;22:2171–2179.
    OpenUrlAbstract/FREE Full Text
  32. 32.↵
    1. Niccoli G,
    2. Burzotta F,
    3. Galiuto L,
    4. Crea F
    . Myocardial no-reflow in humans. J Am Coll Cardiol. 2009;54:281–292.
    OpenUrlCrossRefPubMed
  33. 33.↵
    1. Nijveldt R,
    2. Beek AM,
    3. Hirsch A,
    4. Stoel MG,
    5. Hofman MB,
    6. Umans VA,
    7. Algra PR,
    8. Twisk JW,
    9. van Rossum AC
    . Functional recovery after acute myocardial infarction: comparison between angiography, electrocardiography, and cardiovascular magnetic resonance measures of microvascular injury. J Am Coll Cardiol. 2008;52:181–189.
    OpenUrlCrossRefPubMed

Clinical Perspective

CMR can provide a wide range of prognostic information in acute STEMI by detecting infarct size, MO, and myocardial salvage. Additionally, a hypointense core of infarcted myocardium in T2-weighted CMR has been used as a noninvasive marker for IMH. However, the clinical significance of such findings has not yet been established. The present study is the largest study thus far to assess determinants and the prognostic significance of hypointense infarct cores in T2-weighted CMR. A hypointense core within the AAR of reperfused infarcted myocardium in T2-weighted CMR is a frequent finding in reperfused STEMI patients and is closely related to infarct size, impaired LV function, and late MO. Moreover, hypointense infarct cores are a strong indicator of MACE at 6-month clinical follow-up and may serve as a new CMR marker of severe reperfusion injury. However, further validation is necessary to conclusively ascertain the relationship between hypointense infarct cores and IMH, and large, multicenter studies are warranted to further investigate the prognostic significance of hypointense infarct cores.

View Abstract

This Issue

Jump to

Article Tools

Share this Article

  • Email
  • Prognostic Value and Determinants of a Hypointense Infarct Core in T2-Weighted Cardiac Magnetic Resonance in Acute Reperfused ST-Elevation–Myocardial InfarctionClinical Perspective
    Ingo Eitel, Konrad Kubusch, Oliver Strohm, Steffen Desch, Yoko Mikami, Suzanne de Waha, Matthias Gutberlet, Gerhard Schuler, Matthias G. Friedrich and Holger Thiele
    Circulation: Cardiovascular Imaging. 2011;4:354-362, originally published July 19, 2011
    https://doi.org/10.1161/CIRCIMAGING.110.960500
    del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo

Related Articles

Cited By...

Subjects