Cardiovascular magnetic resonance-derived intramyocardial hemorrhage after STEMI: Influence on long-term prognosis, adverse left ventricular remodeling and relationship with microvascular obstruction

doi:10.1016/j.ijcard.2012.05.055

International Journal of Cardiology

Volume 167, Issue 5, 1 September 2013, Pages 2047-2054

https://doi.org/10.1016/j.ijcard.2012.05.055 Get rights and content

Abstract

Background

T2 weighted cardiovascular magnetic resonance (CMR) can detect intramyocardial hemorrhage (IMH) after ST-elevation myocardial infarction (STEMI). The long-term prognostic value of IMH beyond a comprehensive CMR assessment with late enhancement (LE) imaging including microvascular obstruction (MVO) is unclear. The value of CMR-derived IMH for predicting major adverse cardiac events (MACE) and adverse cardiac remodeling after STEMI and its relationship with MVO was analyzed.

Methods

CMR including LE and T2 sequences was performed in 304 patients 1 week after STEMI. Adverse remodeling was defined as dilated left ventricular end-systolic volume indexes (dLVESV) at 6 months CMR.

Results

During a median follow-up of 140 weeks, 47 MACE (10 cardiac deaths, 16 myocardial infarctions, 21 heart failure episodes) occurred. Predictors of MACE were ejection fraction (HR .95 95% CI [.93–.97], p = .001, per %) and IMH (HR 1.17 95% CI [1.03–1.33], p = .01, per segment). The extent of MVO and IMH significantly correlated (r = .951, p < .0001). dLVESV was present in 40% of patients. CMR predictors of dLVESV were: LVESV (OR 1.11 95% CI [1.07–1.15], p < .0001, per ml/m²), infarct size (OR 1.05 95% CI [1.01–1.09], p = .02, per %) and IMH (OR 1.54 95% CI [1.15–2.07], p = .004, per segment). Addition of T2 information did not improve the LE and cine CMR-model for predicting MACE (.744 95% CI [.659–.829] vs. .734 95% CI [.650–.818], p = .6) or dLVESV (.914 95% CI [.875–.952] vs. .913 95% CI [.875–.952], p = .9).

Conclusions

IMH after STEMI predicts MACE and adverse remodeling. Nevertheless, with a strong interrelation with MVO, the addition of T2 imaging does not improve the predictive value of LE-CMR.

Introduction

In ST-segment elevation myocardial infarction (STEMI) timely reperfusion is the primary therapeutic goal [1]. Nevertheless, despite re-established epicardial blood flow in the infarct related artery, microvascular perfusion might still be impaired, a phenomenon referred to as microvascular obstruction (MVO) [2]. Moreover reperfusion itself may cause additional myocardial damage termed reperfusion injury with intramyocardial hemorrhage (IMH) [3].

These phenomena can be readily assessed using cardiovascular magnetic resonance imaging (CMR) allowing for a state of the art assessment of the post-infarction patient [4], [5]. Using T2 weighted sequences, CMR allows for the appreciation of myocardial edema representing the area at risk in an acute STEMI [6]. Within these hyperdense areas of myocardial edema, hypodense cores can appear and are suspected to reflect IMH [7], [8].

Additionally, CMR allows for an exact delineation of infarct size in late gadolinium enhancement (LGE) sequences. Dark areas within the core of the infarct zone have been described as MVO resulting from impaired microvascular perfusion due to multifactorial causes including edema, microembolization and inflammatory response [9], [10].

MVO has been linked to adverse outcome and left ventricular (LV) remodeling [5], [11], [12]. Emerging data indicates that the presence of IMH also brings about a higher rate of cardiovascular events [13], nevertheless the existing prognostic data are scarce and it is unclear whether or not both phenomena represent different entities or are representations of the same pathology in different imaging sequences.

In the present study we aimed to assess [1] the long-term prognostic value of CMR-derived IMH in a large unselected population of STEMI patients, [2] the influence of IMH on LV remodeling at the 6th month, [3] to compare the additional value of T2 imaging beyond LGE imaging for these purposes and [4] to assess the relationship of IMH with MVO.

Section snippets

Study group

We prospectively included patients admitted to our institution with a first STEMI from November 2001 to December 2010. Patients who died or had a reinfarction or otherwise complicated clinical course or cardiac surgery as well as those who denied participation in the registry, were transferred to other hospitals after reperfusion or those who had contraindications to CMR were not included in the study. Patients underwent CMR at 1 week and, in order to evaluate LV remodeling, at 6 months after

Results

The clinical, angiographic and CMR characteristics of the study group are shown in Table 1. IMH was present in 102 patients (34%) and was associated with younger age (57 ± 12 years vs. 59 ± 12, p = .03), a higher heart rate on admission (84 ± 20 bpm vs. 79 ± 19, p = .04), diabetes (25% vs. 14%, p = .02) and a higher rate of Killip class > 1 (18% vs. 6%, p = .002). Patients with IMH more often had received rescue angioplasty (23% vs. 7%, p < .0001) and had a higher rate of anterior infarctions with involvement of

Discussion

The present study investigates the prognostic value of a comprehensive state-of-the-art CMR examination including T2 imaging-derived IMH in a large population of STEMI patients. It shows that the presence of IMH in the 1st week CMR scan after STEMI indicated a higher rate of MACE and was an independent predictor of MACE during follow up. Additionally, evidence of IMH on the 1st week CMR scan was also an independent prognosticator of adverse LV remodeling in terms of dLVESV at the 6th month.

Limitations

The present study has some limitations. CMR studies were evaluated by a single expert observer, despite the excellent intraobserver variability; this might limit the generalizability of our results.

Patients who died on admission or early after or who had a complicated clinical course due to prolonged cardiogenic shock were not included into our registry. Also, some patients were transferred to other hospitals after successful PCI and also could not be included. Finally, and a limitation of

Conclusions

The presence of IMH on a post-STEMI CMR scan is an independent prognosticator of adverse prognosis and LV remodeling during follow-up. Nevertheless, addition of T2 information did not improve the predictive capability for these purposes beyond established LGE-derived and cine CMR parameters due to a strong interrelation of IMH and MVO. Nevertheless, T2 imaging remains a unique technique for evaluating the presence of IMH and its pathophysiological and clinical repercussions which might

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The Canadian Cardiovascular Society Classification of Acute Atherothrombotic Myocardial Infarction Based on Stages of Tissue Injury Severity: An Expert Consensus Statement
2024, Canadian Journal of Cardiology
Myocardial infarction (MI) remains a leading cause of morbidity and mortality. In atherothrombotic MI (ST-elevation MI and type 1 non-ST-elevation MI), coronary artery occlusion leads to ischemia. Subsequent cardiomyocyte necrosis evolves over time as a wavefront within the territory at risk. The spectrum of ischemia and reperfusion injury is wide: it can be minimal in aborted MI or myocardial necrosis can be large and complicated by microvascular obstruction and reperfusion hemorrhage. Established risk scores and infarct classifications help with patient management but do not consider tissue injury characteristics. This document outlines the Canadian Cardiovascular Society classification of acute MI. It is an expert consensus formed on the basis of decades of data on atherothrombotic MI with reperfusion therapy. Four stages of progressively worsening myocardial tissue injury are identified: (1) aborted MI (no/minimal myocardial necrosis); (2) MI with significant cardiomyocyte necrosis, but without microvascular injury; (3) cardiomyocyte necrosis and microvascular dysfunction leading to microvascular obstruction (ie, “no-reflow”); and (4) cardiomyocyte and microvascular necrosis leading to reperfusion hemorrhage. Each stage reflects progression of tissue pathology of myocardial ischemia and reperfusion injury from the previous stage. Clinical studies have shown worse remodeling and increase in adverse clinical outcomes with progressive injury. Notably, microvascular injury is of particular importance, with the most severe form (hemorrhagic MI) leading to infarct expansion and risk of mechanical complications. This classification has the potential to stratify risk in MI patients and lay the groundwork for development of new, injury stage-specific and tissue pathology-based therapies for MI.
L’infarctus du myocarde (IM) demeure l’une des principales causes de morbidité et de mortalité. En présence d’IM athérothrombotique (IM avec élévation du segment ST et IM sans élévation du segment ST type 1), l’occlusion de l’artère coronaire entraîne une ischémie et une nécrose des cardiomyocytes qui se propage tel un front de vague dans la zone à risque. L'étendue de l’ischémie et des lésions de reperfusion est large : les lésions peuvent être minimes dans le cas d’un IM avorté; en revanche, dans le cas d’une nécrose myocardique, elles peuvent être importantes et être associées à une obstruction microvasculaire et à une hémorragie de reperfusion. Les indices de risque et les outils de classification des infarctus du myocarde facilitent la prise en charge des patients, mais ne prennent pas en considération les caractéristiques des lésions tissulaires. Le présent document donne un aperçu de la classification de la Société cardiovasculaire du Canada pour l’IM aigu. Cette classification est le fruit d’un consensus d’experts reposant sur des décennies de données relatives à l’IM athérothrombotique avec traitement de reperfusion. Quatre stades d’aggravation progressive des lésions du tissu myocardique sont définis : 1) IM avorté (aucune/minime nécrose myocardique); 2) IM avec nécrose des cardiomyocytes importante, mais aucune lésion microvasculaire; 3) nécrose des cardiomyocytes et dysfonction microvasculaire entraînant une obstruction microvasculaire (“no-reflow”); 4) nécrose des cardiomyocytes et nécrose microvasculaire entraînant une hémorragie de reperfusion. Chaque stade reflète la progression de la pathologie tissulaire liée à l’ischémie myocardique et des lésions de reperfusion par rapport au stade précédent. Des recherches cliniques ont démontré qu’une progression des lésions se traduisait par un remodelage néfaste et une augmentation du nombre d'événements cliniques défavorables. Les lésions microvasculaires sont particulièrement importantes, et leur forme la plus grave (l’IM hémorragique) entraîne une expansion de l’infarctus et un risque de complications mécaniques. Cette classification permet de stratifier le risque des patients ayant subi un IM et de favoriser la mise au point de nouveaux traitements de l’IM adaptés au stade des lésions et de la pathologie des tissus.
SGLT2 inhibitor dapagliflozin alleviates intramyocardial hemorrhage and adverse ventricular remodeling via suppressing hepcidin in myocardial ischemia-reperfusion injury
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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.
Impact of Intramyocardial Hemorrhage on Clinical Outcomes in ST-Elevation Myocardial Infarction: A Systematic Review and Meta-analysis
2022, Journal of the Society for Cardiovascular Angiography and Interventions
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.
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.
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.
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.
Hyperglycemia and intramyocardial hemorrhage in patients with ST-segment elevation myocardial infarction
2022, Journal of Cardiology
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.
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.
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).
Hyperglycemia at admission is associated with the occurrence of IMH in patients with STEMI.
Implementing the risk stratification in STEMI by cardiovascular magnetic resonance: An academic exercise or real benefit?
2022, International Journal of Cardiology
Predictive value of major adverse cardiac events by T2-mapping texture analysis of the myocardial remote zone in patients with acute myocardial infarction
2022, Clinical Radiology
Citation Excerpt :
In another T1-and T2-mapping-based study conducted by Mordi et al. including 300 patients,18 it was found that T1-and T2-mapping were potentially significant for differentiating between athletes' hearts and patients with early dilated cardiomyopathy, and could be used whenever differentiation between these two phenotypes is inconclusive using standard imaging techniques. As reported previously, intramyocardial haemorrhage (IMH) often occurs after successful reperfusion in patients with AMI, and it is associated with more extensive myocardial necrosis.19,20 Reinstadler et al. demonstrated that T2-mapping might provide prognostic information for the incidence of MACEs.
To assess the predictive value of major adverse cardiac events (MACEs) in patients with acute myocardial infarction (AMI) by T2-mapping texture analysis (TA) of the myocardial remote zone.
Data from 155 patients, who were diagnosed with AMI and were treated with primary percutaneous coronary intervention (PPCI), and 32 healthy controls who underwent cardiac magnetic resonance imaging (CMRI) were analysed retrospectively. T2-mapping TA of the myocardial remote zone was conducted accordingly. The patients were divided into two subgroups according to the occurrence of MACEs. The primary outcome was a composite of MACEs.
Among 155 patients, 32 (20.6%) patients suffered MACEs, and the most common event was non-sustained ventricular tachycardia (84.3%). Five independent texture features on T2-mapping were selected: Perc.50%, S(4,-4)AngScMom, S(1,1)InvDfMom, S(0,2)DifEntrp, and Horzl_LngREmph. Among them, the mean value of Horzl_LngREmph in the myocardial remote zone among all patients, MACEsnegative, and MACEs-positive was 21.64, 19.12, and 34.52, respectively. Horzl_LngREmph provided the highest area under the receiver operating characteristic (ROC) curve (AUC) value, which enabled two subgroups to be distinguished (AUC = 0.914, p<0.05). According to the results of the univariate analysis, combined with late gadolinium enhancement (LGE) extent and the presence of left ventricular hypertrophy, Horzl_LngREmph, was strongly associated with the occurrence of MACEs (p<0.05, hazard ratio: 1.64, 95% confidence interval: 1.10–4.51).
Together with LGE extent, Horzl_LngREmph, a texture feature obtained from T2-mapping TA of the myocardial remote zone, could predict the occurrence of MACEs in AMI patients.

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^☆: This work was supported by the “Instituto de Salud Carlos III” (PI1102323 grant), the Foundation Gent per Gent, and by the “Microcluster Proteccion Cardiovascular”. No conflicts of interests exist in the present study.

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Cardiovascular magnetic resonance-derived intramyocardial hemorrhage after STEMI: Influence on long-term prognosis, adverse left ventricular remodeling and relationship with microvascular obstruction☆

Abstract

Background

Methods

Results

Conclusions

Introduction

Section snippets

Study group

Results

Discussion

Limitations

Conclusions

Am Heart J

JACC Cardiovasc Imaging

J Am Coll Cardiol

Rev Esp Cardiol

J Am Coll Cardiol

J Am Coll Cardiol

Rev Esp Cardiol

J Am Coll Cardiol

Circulation

Detection of acutely impaired microvascular reperfusion after infarct angioplasty with magnetic resonance imaging

Circulation

Myocardial reperfusion injury

N Engl J Med

Determinants of hemorrhagic infarcts. Histologic observations from experiments involving coronary occlusion, coronary reperfusion, and reocclusion

Am J Pathol

Detection of intramyocardial hemorrhage using high-field proton (1H) nuclear magnetic resonance imaging

Cathet Cardiovasc Diagn

Recognition of the importance of embolization in atherosclerotic vascular disease

Circulation

The “no-reflow” phenomenon after temporary coronary occlusion in the dog

J Clin Invest

Prognostic significance of microvascular obstruction by magnetic resonance imaging in patients with acute myocardial infarction

Circulation