Clinical Outcomes Associated With Various Microvascular Injury Patterns Identified by CMR After STEMI.

BACKGROUND: The prognostic significance of various microvascular injury (MVI) patterns after ST-segment elevation myocardial infarction (STEMI) is not well known. OBJECTIVES: This study sought to investigate the prognostic implications of different MVI patterns in STEMI patients. METHODS: The authors analyzed 1,109 STEMI patients included in 3 prospective studies. Cardiac magnetic resonance (CMR) was performed 3 days (Q1-Q3: 2-5 days) after percutaneous coronary intervention (PCI) and included late gadolinium enhancement imaging for microvascular obstruction (MVO) and T2∗ mapping for intramyocardial hemorrhage (IMH). Patients were categorized into those without MVI (MVO-/IMH-), those with MVO but no IMH (MVO+/IMH-), and those with IMH (IMH+). RESULTS: MVI occurred in 633 (57%) patients, of whom 274 (25%) had an MVO+/IMH- pattern and 359 (32%) had an IMH+ pattern. Infarct size was larger and ejection fraction lower in IMH+ than in MVO+/IMH- and MVO-/IMH- (infarct size: 27% vs 19% vs 18% [P < 0.001]; ejection fraction: 45% vs 50% vs 54% [P < 0.001]). During a median follow-up of 12 months (Q1-Q3: 12-35 months), a clinical outcome event occurred more frequently in IMH+ than in MVO+/IMH- and MVO-/IMH- subgroups (19.5% vs 3.6% vs 4.4%; P < 0.001). IMH+ was the sole independent MVI parameter predicting major adverse cardiovascular events (HR: 3.88; 95% CI: 1.93-7.80; P < 0.001). CONCLUSIONS: MVI is associated with future adverse outcomes only in patients with a hemorrhagic phenotype (IMH+). Patients with only MVO (MVO+/IMH-) had a prognosis similar to patients without MVI (MVO-/IMH-). This highlights the independent prognostic importance of IMH in assessing and managing risk after STEMI.

Microvascular Obstruction and Intramyocardial Hemorrhage in Reperfused Myocardial Infarctions: Pathophysiology and Clinical Insights From Imaging.

Microvascular injury immediately following reperfusion therapy in acute myocardial infarction (MI) has emerged as a driving force behind major adverse cardiovascular events in the postinfarction period. Although postmortem investigations and animal models have aided in developing early understanding of microvascular injury following reperfusion, imaging, particularly serial noninvasive imaging, has played a central role in cultivating critical knowledge of progressive damage to the myocardium from the onset of microvascular injury to months and years after in acute MI patients. This review summarizes the pathophysiological features of microvascular injury and downstream consequences, and the contributions noninvasive imaging has imparted in the development of this understanding. It also highlights the interventional trials that aim to mitigate the adverse consequences of microvascular injury based on imaging, identifies potential future directions of investigations to enable improved detection of disease, and demonstrates how imaging stands to play a major role in the development of novel therapies for improved management of acute MI patients.

Intramyocardial Hemorrhage Leads to Higher MACE Rate by Increasing Myocardial Infarction Volume in Patients with STEMI.

Background and Aims: Whether IMH can directly cause persistent myocardial necrosis after reperfusion therapy in STEMI patients is still unclear. We conducted a prospective study to compare the cardiovascular parameters in patients with STEMI with and without IMH to explore the potential correlations between IMH and poor outcomes. Methods and Results: We prospectively enrolled 65 consecutive patients with newly diagnosed STEMI admitted to the CCU of the Second Xiangya Hospital of Central South University between April 2019 and November 2021, all of whom underwent primary PCI. Of these, 38 (58.5%) and 27 (41.5%) patients were in the IMH-absent and IMH-present groups, respectively. At a mean time of 5-7 days after reperfusion therapy, the volume of MI measured using LGE sequence was larger in STEMI patients with IMH than in patients without IMH (34.2 ± 12.7 cm3 vs 21.1 ± 13.1 cm3, P<0.001). HsTNT levels were significantly higher in the IMH-present group than in the IMH-absent [2500.0 (1681.5-4307.0) pg/mL vs 1710.0 (203.0-3363.5) pg/mL, P=0.021] group during hospitalization. The LVEF measured using CMR in the IMH-present group was lower than that in the IMH-absent group (30.7 ± 9.8% vs 42.3 ± 11.0%, P < 0.001). The rate of MACE at 12 months in IMH-present group was significantly higher than in the IMH-absent group (9/27 VS 2/38, P = 0.012). Conclusion: IMH can lead to further expansion of MI volumes in patients with STEMI, resulting in lower LVEF and higher MACE rate in the post-discharge follow-up.

Cardiac magnetic resonance imaging detection of intramyocardial hemorrhage in patients with ST-elevated myocardial infarction: comparison between susceptibility-weighted imaging and T1/T2 mapping techniques.

Background: Susceptibility-weighted imaging (SWI) and T1/T2 mapping can be used to detect reperfusion intramyocardial hemorrhage (IMH) in ST-segment elevation myocardial infarction (STEMI) patients. However, the sensitivity and accuracy of the SWI and T1/T2 mapping sequences were not systematically compared. The study aimed to evaluate image quality and diagnostic performance of SWI in patients with IMH, compared with T1/T2 mapping. Methods: A prospective study was conducted on consecutive acute STEMI patients who were recruited from January to July 2022. Within 2-6 days after reperfusion treatment, all patients underwent a 3T cardiac magnetic resonance (CMR) examination, including T2-weighted short-tau inversion recovery (T2W-STIR), T1/T2 mapping, and SWI. A total of 36 patients [age, 56.50±17.25 years; males, 83.33% (30/36)] were enrolled. The relative infarct-remote myocardium signal intensity ratio (SIinfarct-remote) and contrast-to-noise ratio (CNR) were calculated for each patient on T1/T2 mapping and SWI, and the difference between relative signal intensity-to-noise ratio (rSNR) in the IMH (rSNRIMH) was measured for IMH patients on T1/T2 mapping and SWI. SIinfarct-remote, CNR, and rSNRIMH were compared among the three sequences. Receiver operating characteristic (ROC) analyses were used to evaluate the diagnostic performance of three sequences by SIinfarct-remote and visual assessment. Results: A total of 26 (72.22%) patients had IMH. Quantitatively, the SIinfarct-remote of three sequences had excellent diagnostic performance for detecting IMH [SWI area under the curve (AUC) =1.000, 95% confidence interval (CI): 1.000-1.000 vs. T1 mapping AUC =0.954, 95% CI: 0.885-1.000 vs. T2 mapping AUC =0.985, 95% CI: 0.955-1.000; SWI vs. T1 mapping, P=0.300; SWI vs. T2 mapping, P=0.188; T1 mapping vs. T2 mapping, P=0.302). Qualitatively, three sequences had similar performance on detecting IMH (SWI AUC =0.895, 95% CI: 0.784-1.000; T1 mapping AUC =0.835, 95% CI: 0.711-0.958; and T2 mapping AUC =0.855, 95% CI: 0.735-0.974; SWI vs. T1 mapping, P=0.172; SWI vs. T2 mapping, P=0.317; T1 mapping vs. T2 mapping, P=0.710). The rSNRIMH was highest in T1 mapping, followed by T2 mapping and SWI, but SWI had the highest CNR. Conclusions: SWI, as well as T1/T2 mapping, is a feasible and accurate approach for clinical diagnosis of IMH with excellent performance.

Association of dysglycaemia with persistent infarct core iron in patients with acute ST-segment elevation myocardial infarction.

BACKGROUND: Dysglycaemia increases the risk of myocardial infarction and subsequent recurrent cardiovascular events. However, the role of dysglycaemia in ischemia/reperfusion injury with development of irreversible myocardial tissue alterations remains poorly understood. In this study we aimed to investigate the association of ongoing dysglycaemia with persistence of infarct core iron and their longitudinal changes over time in patients undergoing primary percutaneous coronary intervention (PCI) for acute ST-segment elevation myocardial infarction (STEMI). METHODS: We analyzed 348 STEMI patients treated with primary PCI between 2016 and 2021 that were included in the prospective MARINA-STEMI study (NCT04113356). Peripheral venous blood samples for glucose and glycated hemoglobin (HbA1c) measurements were drawn on admission and 4 months after STEMI. Cardiac magnetic resonance (CMR) imaging including T2 * mapping for infarct core iron assessment was performed at both time points. Associations of dysglycaemia with persistent infarct core iron and iron resolution at 4 months were calculated using multivariable regression analysis. RESULTS: Intramyocardial hemorrhage was observed in 147 (42%) patients at baseline. Of these, 89 (61%) had persistent infarct core iron 4 months after infarction with increasing rates across HbA1c levels (<5.7%: 33%, ≥5.7: 79%). Persistent infarct core iron was independently associated with ongoing dysglycaemia defined by HbA1c at 4 months (OR: 7.87 [95% CI: 2.60-23.78]; p < 0.001), after adjustment for patient characteristics and CMR parameters. The independent association was present even after exclusion of patients with diabetes (pre- and newly diagnosed, n = 16). CONCLUSIONS: In STEMI patients treated with primary PCI, ongoing dysglycaemia defined by HbA1c is independently associated with persistent infarct core iron and a lower likelihood of iron resolution. These findings suggest a potential association between ongoing dysglycaemia and persistent infarct core iron, which warrants further investigation for therapeutic implications.

On the loss of image contrast in double-inversion-recovery prepared T2* MRI of Intramyocardial hemorrhage.

PURPOSE: Studies have shown that double-inversion-recovery (DIR) prepared dark-blood T2*-weighted images result in lower SNR, CNR and diagnostic accuracy for intramyocardial hemorrhage (IMH) detection compared to non-DIR-prepared (bright-blood) T2*-weighted images; however, the mechanism contributing to this observation has not been investigated and explained in detail. This work tests the hypothesis that the loss of SNR on dark-blood cardiac T2*-weighted images of IMH stems from spin-relaxation during the long RF pulses in double inversion preparation, as a result, compromising image contrast for intramyocardial hemorrhage detection. METHODS: Phantom and in-vivo animal studies were performed to test the hypothesis of the study. An agar phantom was imaged with multi-gradient-echo T2* imaging protocols with and without double-inversion-recovery (DIR) preparation. Image acquisitions were placed at different delay times (TD) after DIR preparation. SNR, T2* and Coefficient of Variation (COV) were measured and compared between DIR-prepared and non-DIR-prepared images. Canines with hemorrhagic myocardial infarctions were scanned at 3.0 T with DIR-prepared (dark-blood) and non-DIR-prepared (bright-blood) T2* imaging protocols. DIR-prepared T2* images were acquired with short, medium, and long delay times (TD). SNR, CNR, intramyocardial hemorrhage (IMH) extent, T2* and COV were measured and compared between DIR-prepared T2* images with short, medium, and long delay times (TD) to non-DIR-prepared bright-blood T2* images. RESULTS: Phantom studies confirmed the hypothesis that the SNR loss on DIR-prepared T2* images originated from signal loss during DIR preparation. SNR followed T1 recovery curve with increased delay times (TD) indicating that SNR can be recovered with longer time delay between DIR and image acquisition. Myocardial T2* values were not affected by DIR preparation but COV of T2* was elevated. Animal studies supported the hypothesis and showed that DIR-prepared T2* images with insufficient delay time (TD) had impaired sensitivity for IMH detection due to lower SNR and CNR, and higher COV. CONCLUSION: We conclude that lower SNR and CNR on DIR-prepared T2* images originate from signal loss during DIR preparation and insufficient recovery between DIR preparation and image acquisition. Although, the impaired sensitivity can be recovered by extending delay time (TD), it will extend the scan time. Bright-blood T2* imaging protocols should remain the optimal choice for assessment of intramyocardial hemorrhage. DIR-prepared dark-blood T2* imaging protocols should be performed with extra attention on image signal-to-noise ratio when used for intramyocardial hemorrhage detection.

Chronic heart failure following hemorrhagic myocardial infarction: mechanism, treatment and outlook.

Myocardial infarction (MI), the blockage of arterial blood supply of the heart, is among the most common causes of death worldwide. Even when patients receive immediate treatment by re-opening blocked arteries, they often develop chronic heart failure (CHF) in the aftermath of MI events. Yet, the factors that contribute to the development of MI-associated CHF are poorly understood. In our recent study (Nat Commun 13:6394), we link intramyocardial hemorrhage, an injury which can occur during reperfusion of areas affected by MI, to an increased risk of CHF. Mechanistically, our data suggest that an iron-induced adverse cascade of events after hemorrhagic MI drives fatty degeneration of infarcted tissue, which ultimately contributes to negative cardiac remodeling. In this Microreview, we discuss the implications of our findings regarding the molecular mechanism, more targeted treatment options as well as perspectives in the clinical care of CHF after hemorrhagic MI.

SGLT2 inhibitor dapagliflozin alleviates intramyocardial hemorrhage and adverse ventricular remodeling via suppressing hepcidin in myocardial ischemia-reperfusion injury.

Intramyocardial hemorrhage (IMH), a reperfusion therapy-associated complication, is the extravasation of red blood cells caused by severe microvascular injury. IMH is an independent predictor of adverse ventricular remodeling (AVR) after acute myocardial infarction (AMI). Hepcidin, a major regulator of iron uptake and systemic distribution, is a key factor affecting AVR. However, the role of cardiac hepcidin in the development of IMH has not been completely elucidated. This study aimed to explore if sodium-dependent glucose co-transporter 2 inhibitor (SGLT2i) exerts therapeutic effects on IMH and AVR by suppressing hepcidin and to elucidate the underlying mechanisms. SGLT2i alleviated IMH and AVR in the ischemia-reperfusion injury (IRI) mouse model. Additionally, SGLT2i downregulated the cardiac levels of hepcidin in IRI mice, suppressed M1-type macrophage polarization, and promoted M2-type macrophage polarization. The effects of hepcidin knockdown on macrophage polarization were similar to those of SGLT2i in RAW264.7 cells. SGLT2i treatment or hepcidin knockdown inhibited the expression of MMP9, an inducer of IMH and AVR, in RAW264.7 cells. Regulation of macrophage polarization and reduction of MMP9 expression by SGLT2i and hepcidin knockdown is achieved through activation of pSTAT3. In conclusion, this study demonstrated that SGLT2i alleviated IMH and AVR by regulating macrophage polarization. The potential mechanism through which SGLT2i exerted its therapeutic effect seems to involve the downregulation of MMP9 via the hepcidin-STAT3 pathway.

Regulatory T Cell as Predictor of Intramyocardial Hemorrhage in STEMI Patients after Primary PCI.

Background: Intramyocardial hemorrhage (IMH) is a result of ischemia-reperfusion injury in ST-segment elevation myocardial infarction (STEMI) after primary percutaneous coronary intervention (PPCI). Despite patients with IMH show poorer prognoses, studies investigating predictors of IMH occurrence are scarce. This study firstly investigated the effectiveness of regulatory T cell (Treg), peak value of Creatine Kinase MB (pCKMB), high-sensitivity C-reactive protein (hsCRP), and left ventricular end-systolic diameter (LVESD) as predictors for IMH. Methods: In 182 STEMI patients received PPCI, predictors of IMH were analyzed by logistic regression analysis. The predictive ability of risk factors for IMH were determined by receiver operating characteristic curves, net reclassification improvement (NRI), integrated discrimination improvement (IDI) and C-index. Results: Overall, 80 patients (44.0%) developed IMH. All 4 biomarkers were independent predictors of IMH [odds ratio [OR] (95% confidence interval [CI]): 0.350 (0.202-0.606) for Treg, 1.004 (1.001-1.006) for pCKMB, 1.060 (1.022-1.100) for hsCRP, and 3.329 (1.346-8.236) for LVESD]. After propensity score matching (PSM), the biomarkers significantly predicted IMH with areas under the curve of 0.750 for Treg, 0.721 for pCKMB, 0.656 for hsCRP, 0.633 for LVESD, and 0.821 for the integrated 4-marker panel. The addition of integrated 4-marker panel to a baseline risk model had an incremental effect on the predictive value for IMH [NRI: 0.197 (0.039 to 0.356); IDI: 0.200 (0.142 to 0.259); C-index: 0.806 (0.744 to 0.869), all p < 0.05]. Conclusions: Treg individually or in combination with pCKMB, hsCRP, and LVESD can effectively predict the existence of IMH in STEMI patients received PPCI. Clinical Trial Registration: NCT03939338.

[The role of cardiac magnetic resonance imaging in defining the prognosis of patients with acute ST-segment elevation myocardial infarction. Part 2. Assessment of the disease prognosis].

Currently the incidence of congestive heart failure after ST-segment elevation myocardial infarction (STEMI) tends to increase. Reperfusion therapy is still the only effective method to reduce an infarct size. Therefore, there is a high unmet need of novel cardioprotective treatments that would improve outcomes in such patients. Recent advances in cardiovascular magnetic resonance (CMR) methods enabled the identification of certain new infarct characteristics associated with the development of heart failure and sudden cardiac death. These characteristics can help identify new groups of high risk patients and used as a targets for novel cardioprotective treatments. This part of the review summarizes novel CMR-based characteristics of myocardial infarction and their role in the prognostic stratification of STEMI patients.

Hyperglycemia and intramyocardial hemorrhage in patients with ST-segment elevation myocardial infarction.

BACKGROUND: Hyperglycemia at admission and intramyocardial hemorrhage (IMH) are associated with poor prognosis in patients with ST-segment elevation myocardial infarction (STEMI). Little is known about the relationship between glucose levels at admission and IMH. The association between matrix metalloproteinase-9 (MMP-9), which plays an important role in the development of IMH, and hyperglycemia is also unknown. This study aimed to investigate the relationship between hyperglycemia at admission and IMH in patients with STEMI. METHODS: We enrolled 174 patients with first STEMI who underwent primary percutaneous coronary intervention (PCI) and cardiovascular magnetic resonance (CMR) imaging. T2-weighted imaging and late gadolinium enhancement (LGE)-CMR were performed to detect IMH and microvascular obstruction (MVO), respectively. Two patient groups were created: IMH group and non-IMH group. MMP-9 levels were measured in the culprit coronary arteries of 13 patients. RESULTS: Glucose level at admission and the value of glycosylated hemoglobin were higher in the IMH group than in the non-IMH group [IMH group vs. non-IMH group; 208.5 (157.8-300.5) mg/dL vs. 157.0 (128.8-204.3) mg/dL, p < 0.001, and 6.2 (5.7-7.5) % vs. 5.8 (5.4-6.6) %, p = 0.030, respectively]. A multivariable logistic regression analysis revealed that only admission glucose level was an independent predictor of IMH (OR: 1.012; 95 % CI: 1.005-1.020, p = 0.001). The MMP-9 levels in patients with IMH were higher than those in patients without IMH [256.0 (161.0-396.0) ng/mL vs. 73.5 (49.5-131.0) ng/mL, p = 0.040]. There was a moderate positive correlation between glucose levels at admission and MMP-9 levels (r = 0.600, p = 0.030). CONCLUSIONS: Hyperglycemia at admission is associated with the occurrence of IMH in patients with STEMI.

Gradual Versus Abrupt Reperfusion During Primary Percutaneous Coronary Interventions in ST-Segment-Elevation Myocardial Infarction (GUARD).

Background Intramyocardial edema and hemorrhage are key pathological mechanisms in the development of reperfusion-related microvascular damage in ST-segment-elevation myocardial infarction. These processes may be facilitated by abrupt restoration of intracoronary pressure and flow triggered by primary percutaneous coronary intervention. We investigated whether pressure-controlled reperfusion via gradual reopening of the infarct-related artery may limit microvascular injury in patients undergoing primary percutaneous coronary intervention. Methods and Results A total of 83 patients with ST-segment-elevation myocardial infarction were assessed for eligibility and 53 who did not meet inclusion criteria were excluded. The remaining 30 patients with totally occluded infarct-related artery were randomized to the pressure-controlled reperfusion with delayed stenting (PCRDS) group (n=15) or standard primary percutaneous coronary intervention with immediate stenting (IS) group (n=15) (intention-to-treat population). Data from 5 patients in each arm were unsuitable to be included in the final analysis. Finally, 20 patients undergoing primary percutaneous coronary intervention who were randomly assigned to either IS (n=10) or PCRDS (n=10) were included. In the PCRDS arm, a 1.5-mm balloon was used to achieve initial reperfusion with thrombolysis in myocardial infarction grade 3 flow and, subsequently, to control distal intracoronary pressure over a 30-minute monitoring period (MP) until stenting was performed. In both study groups, continuous assessment of coronary hemodynamics with intracoronary pressure and Doppler flow velocity was performed, with a final measurement of zero flow pressure (primary end point of the study) at the end of a 60-minute MP. There were no complications associated with IS or PCRDS. PCRDS effectively led to lower distal intracoronary pressures than IS over 30 minutes after reperfusion (71.2±9.37 mm Hg versus 90.13±12.09 mm Hg, P=0.001). Significant differences were noted between study arms in the microcirculatory response over MP. Microvascular perfusion progressively deteriorated in the IS group and at the end of MP, and hyperemic microvascular resistance was significantly higher in the IS arm as compared with the PCDRS arm (2.83±0.56 mm Hg.s.cm-1 versus 1.83±0.53 mm Hg.s.cm-1, P=0.001). The primary end point (zero flow pressure) was significantly lower in the PCRDS group than in the IS group (41.46±17.85 mm Hg versus 76.87±21.34 mm Hg, P=0.001). In the whole study group (n=20), reperfusion pressures measured at predefined stages in the early reperfusion period showed robust associations with zero flow pressure values measured at the end of the 1-hour MP (immediately after reperfusion: r=0.782, P<0.001; at the 10th minute: r=0.796, P<0.001; and at the 20th minute: r=0.702, P=0.001) and peak creatine kinase MB level (immediately after reperfusion: r=0.653, P=0.002; at the 10th minute: r=0.597, P=0.007; and at the 20th minute: r=0.538, P=0.017). Enzymatic myocardial infarction size was lower in the PCRDS group than in the IS group with peak troponin T (5395±2991 ng/mL versus 8874±1927 ng/mL, P=0.006) and creatine kinase MB (163.6±93.4 IU/L versus 542.2±227.4 IU/L, P<0.001). Conclusions In patients with ST-segment-elevation myocardial infarction, pressure-controlled reperfusion of the culprit vessel by means of gradual reopening of the occluded infarct-related artery (PCRDS) led to better-preserved coronary microvascular integrity and smaller myocardial infarction size, without an increase in procedural complications, compared with IS. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02732080.

Detection of Intramyocardial Iron in Patients Following ST-Elevation Myocardial Infarction Using Cardiac Diffusion Tensor Imaging.

BACKGROUND: Intramyocardial hemorrhage (IMH) following ST-elevation myocardial infarction (STEMI) is associated with poor prognosis. In cardiac magnetic resonance (MR), T2* mapping is the reference standard for detecting IMH while cardiac diffusion tensor imaging (cDTI) can characterize myocardial architecture via fractional anisotropy (FA) and mean diffusivity (MD) of water molecules. The value of cDTI in the detection of IMH is not currently known. HYPOTHESIS: cDTI can detect IMH post-STEMI. STUDY TYPE: Prospective. SUBJECTS: A total of 50 patients (20% female) scanned at 1-week (V1) and 3-month (V2) post-STEMI. FIELD STRENGTH/SEQUENCE: A 3.0 T; inversion-recovery T1-weighted-imaging, multigradient-echo T2* mapping, spin-echo cDTI. ASSESSMENT: T2* maps were analyzed to detect IMH (defined as areas with T2* < 20 msec within areas of infarction). cDTI images were co-registered to produce averaged diffusion-weighted-images (DWIs), MD, and FA maps; hypointense areas were manually planimetered for IMH quantification. STATISTICS: On averaged DWI, the presence of hypointense signal in areas matching IMH on T2* maps constituted to true-positive detection of iron. Independent samples t-tests were used to compare regional cDTI values. Results were considered statistically significant at P ≤ 0.05. RESULTS: At V1, 24 patients had IMH on T2*. On averaged DWI, all 24 patients had hypointense signal in matching areas. IMH size derived using averaged-DWI was nonsignificantly greater than from T2* (2.0 ± 1.0 cm2 vs 1.89 ± 0.96 cm2 , P = 0.69). Compared to surrounding infarcted myocardium, MD was significantly reduced (1.29 ± 0.20 × 10-3  mm2 /sec vs 1.75 ± 0.16 × 10-3  mm2 /sec) and FA was significantly increased (0.40 ± 0.07 vs 0.23 ± 0.03) within areas of IMH. By V2, all 24 patients with acute IMH continued to have hypointense signals on averaged-DWI in the affected area. T2* detected IMH in 96% of these patients. Overall, averaged-DWI had 100% sensitivity and 96% specificity for the detection of IMH. DATA CONCLUSION: This study demonstrates that the parameters MD and FA are susceptible to the paramagnetic properties of iron, enabling cDTI to detect IMH. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 2.

Microcirculation of intramyocardial hemorrhage caused by reperfused myocardial infarctions with ultrasmall superparamagnetic iron oxide cardiac magnetic resonance imaging.

BACKGROUND: The actual role of the coronary microcirculation, which is massively injured by myocardial infarction (MI), in intramyocardial hemorrhage (IMH) pathophysiology is still not fully understood. PURPOSE: To determine the change and distribution of microcirculation of myocardial edema (ME), IMH, MI, and the remote area of early reperfusion using 7.0-T cardiovascular magnetic resonance (CMR) in a rat model of acute MI. MATERIAL AND METHODS: Eight rats with 60-min myocardial ischemia followed by reperfusion were investigated. On days 2 and 7, after the acquisition of T2*-mapping and T2-mapping images, late gadolinium enhancement imaging was performed to evaluate the extent of myocardial ischemia after an injection of Gd-DTPA. On days 3 and 8, after the injection of ultrasmall superparamagnetic iron oxide (USPIO), T2*- and T2-mapping images were acquired. The R2 values of ME, IMH, MI, and remote areas were measured. RESULTS: From days 2 to 3, R2 values increased in the IMH, MI, ME, and remote area (all P < 0.05) following administration of USPIO, while the delta R2 value of IMH and MI was larger than remote area (P < 0.05). From day 7 to day 8, there was no significant difference in the IMH, MI, ME, and remote area (all P > 0.05). CONCLUSION: Microvascular injury of IMH and MI is the most severe among all the studied myocardial injuries in the early reperfusion of MI, while microvascular density decreased during follow-up.

Impact of Intramyocardial Hemorrhage on Clinical Outcomes in ST-Elevation Myocardial Infarction: A Systematic Review and Meta-analysis.

Background: Intramyocardial hemorrhage (IMH) occurs after ST-elevation myocardial infarction (STEMI) and has been documented using cardiac magnetic resonance imaging. The prevalence and prognostic significance of IMH are not well described, and the small sample size has limited prior studies. Methods: We performed a comprehensive literature search of multiple databases to identify studies that compared outcomes in STEMI patients with or without IMH. The outcomes studied were major adverse cardiovascular events (MACE), infarct size, thrombolysis in myocardial infarction (TIMI) flow after percutaneous coronary intervention (PCI), left ventricular end-diastolic volume (LVEDV), left ventricular ejection fraction (LVEF), and mortality. Odds ratios (ORs) and standardized mean differences with corresponding 95% CIs were calculated using a random effects model. Results: Eighteen studies, including 2824 patients who experienced STEMI (1078 with IMH and 1746 without IMH), were included. The average prevalence of IMH was 39%. There is a significant association between IMH and subsequent MACE (OR, 2.63; 95% CI, 1.79-3.86; P < .00001), as well as IMH and TIMI grade <3 after PCI (OR, 1.75; 95% CI, 1.14-2.68; P = .05). We also found a significant association between IMH and the use of glycoprotein IIb/IIIa inhibitors (OR, 2.34; 95% CI, 1.42-3.85; P = .0008). IMH has a positive association with infarct size (standardized mean difference, 2.19; 95% CI, 1.53-2.86; P < .00001) and LVEDV (standardized mean difference, 0.7; 95% CI, 0.41-0.99; P < .00001) and a negative association with LVEF (standardized mean difference, -0.89; 95% CI, -1.15 to -0.63; P = .01). Predictors of IMH include male sex, smoking, and left anterior descending infarct. Conclusions: Intramyocardial hemorrhage is prevalent in approximately 40% of patients who experience STEMI. IMH is a significant predictor of MACE and is associated with larger infarct size, higher LVEDV, and lower LVEF after STEMI.

Assessment of intramyocardial hemorrhage with dark-blood T2*-weighted cardiovascular magnetic resonance.

BACKGROUND: Intramyocardial hemorrhage (IMH) within myocardial infarction (MI) is associated with major adverse cardiovascular events. Bright-blood T2*-based cardiovascular magnetic resonance (CMR) has emerged as the reference standard for non-invasive IMH detection. Despite this, the dark-blood T2*-based CMR is becoming interchangeably used with bright-blood T2*-weighted CMR in both clinical and preclinical settings for IMH detection. To date however, the relative merits of dark-blood T2*-weighted with respect to bright-blood T2*-weighted CMR for IMH characterization has not been studied. We investigated the diagnostic capacity of dark-blood T2*-weighted CMR against bright-blood T2*-weighted CMR for IMH characterization in clinical and preclinical settings. MATERIALS AND METHODS: Hemorrhagic MI patients (n = 20) and canines (n = 11) were imaged in the acute and chronic phases at 1.5 and 3 T with dark- and bright-blood T2*-weighted CMR. Imaging characteristics (Relative signal-to-noise (SNR), Relative contrast-to-noise (CNR), IMH Extent) and diagnostic performance (sensitivity, specificity, accuracy, area-under-the-curve, and inter-observer variability) of dark-blood T2*-weighted CMR for IMH characterization were assessed relative to bright-blood T2*-weighted CMR. RESULTS: At both clinical and preclinical settings, compared to bright-blood T2*-weighted CMR, dark-blood T2*-weighted images had significantly lower SNR, CNR and reduced IMH extent (all p < 0.05). Dark-blood T2*-weighted CMR also demonstrated weaker sensitivity, specificity, accuracy, and inter-observer variability compared to bright-blood T2*-weighted CMR (all p < 0.05). These observations were consistent across infarct age and imaging field strengths. CONCLUSION: While IMH can be visible on dark-blood T2*-weighted CMR, the overall conspicuity of IMH is significantly reduced compared to that observed in bright-blood T2*-weighted images, across infarct age in clinical and preclinical settings at 1.5 and 3 T. Hence, bright-blood T2*-weighted CMR would be preferable for clinical use since dark-blood T2*-weighted CMR carries the potential to misclassify hemorrhagic MIs as non-hemorrhagic MIs.

Prognostic value and clinical predictors of intramyocardial hemorrhage measured by CMR T2* sequences in STEMI.

Recent studies show that microvascular injury consists of microvascular obstruction (MVO) and intramyocardial hemorrhage (IMH). In patients with reperfused ST-segment elevation myocardial infarction (STEMI) quantitative assessment of IMH with T2* cardiovascular magnetic resonance imaging (CMR) appears to be useful in evaluation of microvascular damage. The current study aimed to investigate feasibility of this approach and to correlate IMH with clinical and CMR parameters. A single center observational cohort study was performed in reperfused STEMI patients with CMR examination 7 days (IQR: 5 to 8 days) after percutaneous coronary intervention. Infarct size (IS) and MVO were evaluated in short-axis late gadolinium enhancement sequences and IMH with whole LV volume T2* mapping sequences. Of the 94 patients, MVO was identified in 52% of patients and the median size of MVO was 3% of LV mass (IQR: 1.5 to 5.4%). IMH was present in 28% of patients and the median size of IMH was 1.1% of LV mass (IQR: 0.5 to 2.9%). IMH extent was independently associated with anterior myocardial infarction (p = 0.022) and thrombectomy (p = 0.049). IMH was correlated with MVO (R = 0.62, p < 0.001), necrosis (R = 0.58, p < 0.001) and LVEF (R = -0.21, p = 0.04). Patients with IMH presented higher incidence of MACE events, independently of LVEF (p = 0.022). T2* mapping is a novel imaging approach that proves useful to asses IMH in the setting of reperfused STEMI. T2* IMH extent was associated with anterior infarction and thrombectomy. T2* IMH was associated with higher incidence of MACE events regardless preserved or reduced LVEF.

An autopsy case report of extensive intramyocardial hemorrhage complicated with acute myocardial infarction.

Hemorrhagic myocardial infarction (HMI) is a complication associated with percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI). We carried out a successful PCI for a 59-year old Japanese man presenting with chest pain due to AMI over 5 h. The onset to balloon time was 363 min. The next morning, he suffered cardiogenic shock, even with an auxiliary circulating device, which eventually resulted in death. An autopsy revealed extensive HMI. The necrotic myocardium showed not only coagulation necrosis but also contraction band necrosis which suggests myocardial injury due to late reperfusion. Although the intramyocardial hemorrhage was confined to the necrotic area, it was beyond the perfusion area of the culprit artery. Here, we describe a case of death with severe HMI. HMI can be a serious complication and worsen prognosis. .