Areas Of Microvascular Obstruction Research Articles

Cardiac extracellular matrix at microvascular obstruction area after reperfused myocardial infarction: a morphometric study

Abstract Background Extracellular matrix (ECM), a structural and biomechanical support to cardiomyocytes, suffers substantial alterations after myocardial infarction (MI). Despite a complete reopening at epicardial level, hypoperfusion within the infarcted myocardium, known as microvascular obstruction (MVO), occurs. Extensive clinical studies and meta-analysis reported the association between the magnitude of MVO and the appearance of adverse remodeling; thus, scrutinizing ECM composition within the infarcted areas with impaired tissue-level reperfusion could provide fundamental insight regarding MVO pathophysiology. Purpose To histologically compare ECM composition within the infarct zone regarding the presence or absence of MVO using an experimental swine model of reperfused MI. Methods MI was induced in swine (n=10) by transitory 90-min coronary occlusion followed by 7 days of reperfusion. Prior to euthanasia, intracoronary thioflavin-S was infused. Within the infarcted myocardium, regions displaying MVO (thioflavin-S-) or no MVO (thioflavin-S+) were isolated and stained to morphometrically compare ECM composition. Results Regarding cellularity, areas with MVO displayed an enlarged presence of neutrophils and lymphocytes, whilst no differences in the amount of macrophages and myofibroblasts were detected in comparison to no MVO-myocardium. Those regions with macroscopic MVO showed lower capillary density than those without MVO. According to the fibers and ground substance, a significant reduction in the extension of type I collagen, laminin, and fibronectin together with an augmentation of glycosaminoglycan were noted in areas showing MVO compared to those without microvascular injury. No changes in the amount of type III collagen was observed. Conclusion The ECM composition in infarcted regions with MVO displays a higher presence of inflammatory infiltrate and glycosaminoglycans as well as a reduced amount of microvessels and fibers compared to those areas without microvascular hypoperfusion. These characteristics might underlie the development of adverse ventricular remodeling in MI patients with extensive MVO.

Changes in the extracellular matrix at microvascular obstruction area after reperfused myocardial infarction: A morphometric study

BackgroundExtracellular matrix (ECM) suffers substantial alterations after myocardial infarction (MI), including the invasion of leukocyte subtypes. Despite a complete reopening at epicardial level, hypoperfusion within the infarcted myocardium, known as microvascular obstruction (MVO), occurs and exerts a negative impact on ventricular remodeling. In this study, ECM composition at MVO regions was described using a morphometric analysis. MethodsMI was induced in female swine (n = 10) by transitory 90-minute coronary occlusion followed by seven days of reperfusion. Prior to euthanasia, intracoronary thioflavin-S was infused. Within the infarcted myocardium, regions displaying MVO (thioflavin-S-) or no MVO (thioflavin-S+) were isolated and stained to morphometrically compare ECM composition. ResultsAs reflected by cell invasion through ECM, areas with MVO displayed an enlarged presence of neutrophils and lymphocytes, whilst no differences in the amount of macrophages and myofibroblasts were detected compared to infarcted myocardium without MVO. Indeed, those regions with macroscopic MVO showed lower capillary density than areas without MVO. Lastly, a significant reduction in the extension of total collagen, type I, but not type III, collagen, laminin, and fibronectin together with an augmentation of polysaccharides were noted in areas showing MVO compared to those without microvascular injury. ConclusionsECM composition in infarcted regions with MVO isolated from female swine displays a higher presence of inflammatory infiltrate and polysaccharides as well as reduced number of microvessels and collagen content compared to those areas without microvascular hypoperfusion. These characteristics might underlie the development of adverse ventricular remodeling in MI patients with extensive MVO.

Epicardial adipose tissue, infarct size, microvascular obstruction and ventricular remodelling after ST-segment elevation myocardial infarction

Abstract Background Epicardial adipose tissue (EAT) is a biologically active fat deposit contained beneath the pericardium promoting coronary atherosclerosis. EAT can be accurately measured through cardiac magnetic resonance (CMR), which also enables an accurate quantification of infarct size, microvascular obstruction (MVO), left ventricular (LV) ejection fraction (EF) and volumes in patients with ST-elevation myocardial infarction (STEMI). Purpose We performed a systematic assessment of the correlates of EAT volume at baseline and after 6 months in a homogeneous cohort of patients with STEMI. Methods We prospectively enrolled patients with a first anterior STEMI reperfused within 12 hours from symptom onset. These patients underwent a first CMR exam after 1 week from the MI and after 6 months. Results Patients (n=138) were more often men (81%), with a median age of 58 years (interquartile range 48–66). EAT volume was 30 mL/m2 (23–41). Patients with EAT >30 mL/m2 (n=69) were older (60±12 vs. 55±11 years, p=0.02), more often diabetic (26% vs. 12%, p=0.03), and showed a worse baseline risk profile (Thrombolysis in Myocardial Infarction risk score 3 [2–5] vs. 2 [1–4], p=0.05). Patients with EAT >30 mL/m2 also displayed a larger IS (33±15 vs. 23±16% of LV mass, p=0.001) and MVO (1.5 [0–6.8] vs. 0% [0–2.2], p=0.008). Again in patients with EAT >30 mL/m2, EAT volume independently predicted infarct size (standardized beta coefficient=0.30, p<0.001) and MVO area (standardized beta coefficient=0.36, p<0.001) after adjusting for age, sex and infarct characteristics at 1 week (Figure 1). Despite these correlations with infarct size and MVO, patients with EAT >30 mL/m2 did not display more depressed LVEF or larger LV volumes than those with EAT ≤30 mL/m2, either at 1 week or at 6-month CMR (p>0.1 for all comparisons). Conclusions In a cohort of patients with first anterior STEMI undergoing timely reperfusion, those with a greater EAT volume have a larger infarct size and a larger area of MVO. Despite these correlates of EAT volume size, patients with larger EAT do not have a higher risk of adverse LV remodelling. Funding Acknowledgement Type of funding sources: None.

Myocardial Infarction Quantification from Late Gadolinium Enhancement MRI Using Top-Hat Transforms and Neural Networks

Late gadolinium enhancement (LGE) MRI is the gold standard technique for myocardial viability assessment. Although the technique accurately reflects the damaged tissue, there is no clinical standard to quantify myocardial infarction (MI). Moreover, commercial software used in clinical practice are mostly semi-automatic, and hence require direct intervention of experts. In this work, a new automatic method for MI quantification from LGE-MRI is proposed. Our novel segmentation approach is devised for accurately detecting not only hyper-enhanced lesions, but also microvascular obstruction areas. Moreover, it includes a myocardial disease detection step which extends the algorithm for working under healthy scans. The method is based on a cascade approach where firstly, diseased slices are identified by a convolutional neural network (CNN). Secondly, by means of morphological operations a fast coarse scar segmentation is obtained. Thirdly, the segmentation is refined by a boundary-voxel reclassification strategy using an ensemble of very light CNNs. We tested the method on a LGE-MRI database with healthy (n = 20) and diseased (n = 80) cases following a 5-fold cross-validation scheme. Our approach segmented myocardial scars with an average Dice coefficient of 77.22 ± 14.3% and with a volumetric error of 1.0 ± 6.9 cm3. In a comparison against nine reference algorithms, the proposed method achieved the highest agreement in volumetric scar quantification with the expert delineations (p< 0.001 when compared to the other approaches). Moreover, it was able to reproduce the scar segmentation intra- and inter-rater variability. Our approach was shown to be a good first attempt towards automatic and accurate myocardial scar segmentation, although validation over larger LGE-MRI databases is needed.

Impact of various types of microvascular injury on area at risk in patients with primary myocardial infarction with ST segment elevation (STEMI)

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Grants Council of the Russian President for state support of young Russian scientists and state support of leading scientific schools of the Russian Federation CMR can quantify the area at risk (AAR). It includes both salvaged and infarcted myocardium. Furthermore, CMR permits to determine with high sensitivity the presence of microvascular injury phenomena: intramyocardial haemorrhage (IMH) and microvascular obstruction (MVO) in patients with STEMI. There is not enough known about the relation of AAR and different types of microvascular injury. Aim. To analyze the correlation between the risk zone and the phenomena of microvascular injury in patients with primary STEMI . Materials and methods. The study included 60 patients with primary STEMI, admitted within the first 12 hours after the onset of disease, who underwent stenting of the infarct-associated coronary artery. Exclusion criteria: pulmonary edema, cardiogenic shock, estimated glomerular filtration rate <30 mL/min/1,73 m2 or dialysis, severe comorbidity, acute psychotic disorders and inability to undergo or contra-indications for CMR. Each patient included in the study underwent CMR imaging at day 2 post-STEMI. The AAR extent was quantified on short-axis T2-STIR images. MVO and IMH were assessed using late gadolinium enhancement and T2-weighted CMR imaging. Results. It was demonstrated that the AAR occupies 12% (7,8-17,7%) of the total myocardium. Evidence of microvascular injury phenomena was present in 41 patients (68.3%), the combination of MVO and IMH - in 22 patients (36.6%). The isolated IMH phenomenon was visualized in 9 patients (15%). The isolated MVO phenomenon was visualized in 10 patients (16,7%). Relation between of size of ARR, MVO and IMH areas is demonstrated in Table 1. A comparison study showed that the ARR was larger in patients a combination of IMH and MVO. Patients with isolated IMH and isolated MVO had an ARR similar with to a group without microvascular injury. Correlation analysis showed a moderate direct correlation between the IMH and MVO sizes, and ARR (R = 0,42; p = 0,0007 and R = 0,55, p = 0,000004). Conclusions. The analysis of the influence of different microvascular injury phenotypes on the ARR of the myocardium as assessed by CMR in the early postinfarction period in patients with primary STEMI has shown that the combination of IMH with MVO associate with a large ARR. Correlations between the IMH and MVO sizes and increased ARR have been demonstrated. Table 1. CMR parametersArea at risk, %No phenomena MVO and IMH, n = 198,1 (5-17)Isolated MVO, n = 1010,1 (9-13)Isolated IMH, n = 911 (8-12)Combination of IMH and MVO, n = 2217,3 (10-27)

The effect of microvascular obstruction on the myocardial microstructure: a diffusion tensor imaging study

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Heart Research UK Background Diffusion tensor cardiac magnetic resonance (DT-CMR) imaging allows for characterising myocardial microstructure in-vivo using mean diffusivity (MD), fractional anisotropy (FA), secondary eigenvector angle (E2A) and helix angle (HA) maps. Following myocardial infarction (MI), alterations in MD, FA and HA proportions have previously been reported. E2A depicts the contractile state of myocardial sheetlets, however the behaviour of E2A in infarct segments, and all DTI markers in areas of microvascular obstruction (MVO) is also not fully understood. Purpose We performed spin echo DTI in patients following ST-elevation MI (STEMI) in order to investigate acute changes in DTI parameters in remote and infarct segments both with and without MVO. Method Twenty STEMI patients (16 men, 4 women, mean age 59) had acute (5 ± 2d) 3T CMR scans. CMR protocol included: second order motion compensated (M012) free-breathing spin echo DTI (3 slices, 18 diffusion directions at b-values 100s/mm2[3], 200s/mm2[3] and 500s/mm2[12], reconstructed resolution was 1.66x1.66x8mm); cine and late gadolinium enhancement (LGE) imaging. Average MD, FA, E2A HA parameters were calculated on a 16 AHA segmental level. HA maps were described by dividing values into left-handed HA (LHM, -90° < HA < -30°), circumferential HA (CM, -30° < HA < 30°), and right-handed HA (RHM, 30° < HA < 90°) and reported as relative proportions. Segments were defined as infarct (positive for LGE) and remote (opposite to the infarct). Results DTI acquisition was successful in all patients (acquisition time 13 ± 5mins). Ten patients had evidence of MVO on LGE images. MD was significantly higher in infarct regions in comparison to remote; MVO-ve infarct segments had significantly higher MD than MVO + ve infarct segments (MD remote= 1.46 ± 0.12x10-3mm2/s, MD MVO + ve = 1.59 ± 0.12x10-3mm2/s, MD MVO-ve = 1.75 ± 0.12x10-3mm2/s, ANOVA p < 0.01). FA was reduced in infarct segments in comparison to remote; MVO-ve infarct segments had significantly lower FA than MVO + ve infarct segments (FAremote= 0.37 ± 0.02, FA MVO + ve = 0.31 ± 0.02 x 10-3mm2/s, MD MVO-ve =0.25 ± 0.02, ANOVA p < 0.01). E2A values were significantly lower in infarct segments compared to remote; MVO + ve infarct segments had significantly lower values than MVO-ve. (E2A remote= 57.4 ± 5.2°, E2A MVO-ve = 46.8 ± 2.5°, E2A MVO + ve = 36.8 ± 3.1°, ANOVA p < 0.001). RHM% (corresponding to subendocardium) was significantly lower in infarct segments compared to remote; MVO + ve infarct segments had significantly lower RHM% than MVO-ve. (RHM remote= 37 ± 3%, RHM RHM MVO-ve= 28 ± 7%, MVO + ve= 8 ± 5%, ANOVA p < 0.001). Conclusion The presence of MVO results in a decrease in MD and increase in FA in comparison to surrounding infarct segments. However, the reduction in E2A and right-handed myocytes on HA in infarct segments is further exacerbated by the presence of MVO. Further study is required to investigate the underlying mechanisms for such alterations in signal intensity. Abstract Figure. A case of transmural septal MI with MVO

Intracoronary Administration of Allogeneic Cardiosphere-Derived Cells Immediately Prior to Reperfusion in Pigs With Acute Myocardial Infarction Reduces Infarct Size and Attenuates Adverse Cardiac Remodeling.

Allogeneic cardiosphere-derived cells (CDCs) exert cardioprotective effects when administered intracoronarily after reperfusion in animal models of acute myocardial infarction (AMI). The "no-reflow" phenomenon develops rapidly post-reperfusion and may undermine the efficacy of cell therapy, due to poor cell delivery in areas of microvascular obstruction (MVO). We hypothesized that CDC-induced cardioprotection would be enhanced by cell administration prior to reperfusion, when microvasculature is still relatively intact, to facilitate widespread cell delivery within the ischemic area. We studied 81 farm pigs; 55 completed the specified protocols. A dose-optimization study in infarcted pigs demonstrated that the doses of 5 million and 10 million CDCs are the maximum safe doses that can be administered intracoronarily at 5 minutes prior to and at 5 minutes post-reperfusion, respectively, without aggravating MVO. Quantification of acute cell retention by polymerase chain reaction demonstrated that cell delivery prior to reperfusion resulted in higher cardiac cell retention compared to delivery post-reperfusion. We then performed a randomized, placebo-controlled study to assess the long-term efficacy of intracoronary infusion of 5 million allogeneic CDCs, delivered at 5 minutes prior to reperfusion, in a porcine model of AMI. The CDC therapy resulted in decreased scar size, improved regional systolic function, and attenuation of adverse cardiac remodeling (manifested as preserved global systolic function, preserved end-systolic volume, and decreased interstitial fibrosis) compared to placebo at 30 days post-MI. Dose-optimized intracoronary infusion of allogeneic CDCs prior to reperfusion in a porcine model of AMI is feasible, safe and confers long-term benefits.

Quantitative T1 Mapping for Detecting Microvascular Obstruction in Reperfused Acute Myocardial Infarction: Comparison with Late Gadolinium Enhancement Imaging.

ObjectiveTo compare native and post-contrast T1 mapping with late gadolinium enhancement (LGE) imaging for detecting and measuring the microvascular obstruction (MVO) area in reperfused acute myocardial infarction (MI).Materials and MethodsThis study included 20 patients with acute MI who had undergone 1.5T cardiovascular magnetic resonance imaging (CMR) after reperfusion therapy. CMR included cine imaging, LGE, and T1 mapping (modified look-locker inversion recovery). MI size was calculated from LGE by full-width at half-maximum technique. MVO was defined as an area with low signal intensity (LGE) or as a region of visually distinguishable T1 values (T1 maps) within infarcted myocardium. Regional T1 values were measured in MVO, infarcted, and remote myocardium on T1 maps. MVO area was measured on and compared among LGE, native, and post-contrast T1 maps.ResultsThe mean MI size was 27.1 ± 9.7% of the left ventricular mass. Of the 20 identified MVOs, 18 (90%) were detected on native T1 maps, while 10 (50%) were recognized on post-contrast T1 maps. The mean native T1 values of MVO, infarcted, and remote myocardium were 1013.5 ± 58.5, 1240.9 ± 55.8 (p < 0.001), and 1062.2 ± 55.8 ms (p = 0.169), respectively, while the mean post-contrast T1 values were 466.7 ± 26.8, 399.1 ± 21.3, and 585.2 ± 21.3 ms, respectively (p < 0.001). The mean MVO areas on LGE, native, and post-contrast T1 maps were 134.1 ± 81.2, 133.7 ± 80.4, and 117.1 ± 53.3 mm2, respectively. The median (interquartile range) MVO areas on LGE, native, and post-contrast T1 maps were 128.0 (58.1–215.4), 110.5 (67.7–227.9), and 143.0 (76.7–155.3) mm2, respectively (p = 0.002). Concordance correlation coefficients for the MVO area between LGE and native T1 maps, LGE and post-contrast T1 maps, and native and post-contrast T1 maps were 0.770, 0.375, and 0.565, respectively.ConclusionMVO areas were accurately delineated on native T1 maps and showed high concordance with the areas measured on LGE. However, post-contrast T1 maps had low detection rates and underestimated MVO areas. Collectively, native T1 mapping is a useful tool for detecting MVO within the infarcted myocardium.

P3095Left ventricular thrombus formation after ST-elevation myocardial infarction: a prospective observational CMR study

Abstract Background Left ventricular (LV) thrombus formation is a severe complication after acute ST-segment elevation myocardial infarction (STEMI). The incidence and determinants of LV thrombus formation are still a matter of controversy. Purpose We aimed to assess the incidence as detected by cardiac magnetic resonance (CMR) imaging as well as the determinants of LV thrombus formation in contemporary reperfused STEMI patients. Methods This prospective observational study included 530 consecutive STEMI patients treated with primary percutaneous coronary intervention (PCI). Comprehensive CMR was performed at a median of 3 days (interquartile range 2–4 days) after symptom onset for the evaluation of LV thrombus formation as well as LV function and infarct severity. Results LV thrombi were detected in 17 patients (3.2% of the overall cohort). The incidence of LV thrombi in anterior STEMI patients (n=247) was 6.9%. In all patients presenting with LV thrombus left anterior descending artery (LAD) was identified as culprit lesion. The occurrence of thrombi was significantly associated with reduced LV ejection fraction (LVEF) (p&lt;0.001), larger LV end-diastolic volume (p&lt;0.001) and LV end-systolic volume (p&lt;0.001), larger areas of microvascular obstruction (MVO) (p=0.003) and larger infarct size (IS) (p&lt;0.001). Furthermore, increased levels of peak high sensitivity cardiac Troponin T (p&lt;0.001) and hyperlipidaemia (p=0.038) were significantly related to LV thrombi. In multivariable analysis including IS, LVEF and MVO, only LVEF (odds ratio: 0.91 (95% confidence interval: 0.87–0.96); p=0.001) emerged as independent predictor of LV thrombus formation. Conclusion The risk of LV thrombus formation remains considerable in contemporary treated STEMI patients, especially in those with LAD as culprit lesion. Among CMR parameters of LV dysfunction and infarct severity, only baseline LVEF, but not IS or MVO, independently predicted LV thrombus formation after STEMI.

The Value of Low-Dose Dynamic Myocardial Perfusion CT for Accurate Evaluation of Microvascular Obstruction in Patients With Acute Myocardial Infarction.

OBJECTIVE. The purpose of this study was to investigate the diagnostic performance of quantitative parameters generated from dynamic myocardial perfusion CT for assessment of acute myocardial infarction (AMI) and microvascular obstruction (MVO) using cardiac MRI as a reference standard. SUBJECTS AND METHODS. Patients who underwent successful reperfusion treatment within 1 week after AMI between January 1, 2018, and May 31, 2018, were prospectively enrolled. All patients were referred for cardiac MRI and dynamic myocardial perfusion CT on the same day. Various quantitative parameters and late iodine enhancement (LIE) were analyzed for the evaluation of AMI and MVO using cardiac MRI findings as a reference standard. RESULTS. Twenty-seven patients with 442 vascular segments were ultimately included in the analysis. The mean radiation doses ± SD for dynamic myocardial perfusion CT and LIE were 3.3 ± 1.1 mSv and 2.0 ± 0.6 mSv, respectively. Myocardial blood flow (MBF) was significantly lower in segments with MVO than in those without MVO and in reference segments (23.08 ± 7.95 mL/min/100 mL vs 44.60 ± 14.97 mL/min/100 mL and 75.07 ± 7.34 mL/min/100 mL; p < 0.001). According to ROC curve analysis, MBF had the largest AUC of all parameters for identifying AMI with and without MVO as determined by late gadolinium enhancement (LGE) (AUC = 0.941 and 0.996; p < 0.001). The diagnostic accuracy of MBF-based assessment for identifying MVO was 99.2%, which outperformed other quantitative parameters and LIE. We found good correlation between the AMI area and MVO area estimated by MBF and LGE (r = 0.95 and 0.99; p < 0.001). CONCLUSION. MBF derived from dynamic myocardial perfusion CT is accurate and outperforms other quantitative parameters and LIE in diagnosis of AMI and MVO. Area of AMI and MVO can also be accurately estimated using MBF.

Clinical Significance of Postinfarct Fever in ST-Segment Elevation Myocardial Infarction: A Cardiac Magnetic Resonance Imaging Study.

BackgroundLittle is known about causality and pathological mechanism underlying association of postinfarct fever with myocardial injury in patients with ST‐segment elevation myocardial infarction.Methods and ResultsIn 276 patients undergoing primary percutaneous coronary intervention for ST‐segment elevation myocardial infarction, cardiac magnetic resonance imaging was performed a median of 3.4 days after the index procedure. Forty‐five patients had postinfarct fever (peak body temperature within 4 days after primary percutaneous coronary intervention ≥37.7°C; Fever group) whereas 231 did not (no‐Fever group). Primary outcome was myocardial infarct size as assessed by cardiac magnetic resonance imaging. Secondary outcomes were extent of area at risk, myocardial salvage index, and microvascular obstruction area. In cardiac magnetic resonance imaging analysis, myocardial infarct size (25.6% [19.7–32.4] in the Fever group versus 17.2% [11.8–25.4] in the no‐Fever group; P<0.01), extent of area at risk (43.7% [31.9–54.9] versus 35.3% [24.0–43.7]; P<0.01), and microvascular obstruction area (4.4% [0.0–13.2] versus 1.2% [0.0–5.1]; P=0.02) were greater in the Fever group than in the no‐Fever group. Myocardial salvage index tended to be lower in the Fever group compared to the no‐Fever group (37.7 [28.5–56.1] versus 47.0 [34.1–56.8]; P=0.13). In multivariate analysis, postinfarct fever was associated with larger myocardial infarct (odds ratio, 3.48; 95% CI, 1.71–7.07; P<0.01) and lower MSI (odds ratio, 2.10; 95% CI, 1.01–4.08; P=0.03).ConclusionsPostinfarct fever could predict advanced myocardial injury and less salvaged myocardium in ST‐segment elevation myocardial infarction patients undergoing primary percutaneous coronary intervention.

Role of Non-Transferrin-Bound Iron in the pathogenesis of cardiotoxicity in patients with ST-elevation myocardial infarction assessed by Cardiac Magnetic Resonance Imaging

BackgroundHereditary hemochromatosis, thalassemia and myelodysplastic syndromes represent disease models with evidence of iron-related heart failure. Non-Transferrin Bound Iron (NTBI) induces cardiac toxicity through the production of reactive oxygen species and lipid peroxidation. In ST-elevation acute myocardial infarction (STEMI) with evidence of microvascular obstruction (MVO) and hemorrhage (HEM), HEM may be a source of iron-related cardiac toxicity through NTBI and pro-inflammatory mediators. Aim of the studyThe study aims to assess NTBI in patients with STEMI and its possible relationship with MVO and HEM. Methods and resultsNTBI, LPO–Malondialdehyde (MDA) and interleukin-6 (IL-6) were assessed in 15 patients with STEMI immediately before primary percutaneous coronary intervention (PPCI) and at 3, 6, 9, 12, and 24h post-PPCI. Cardiac Magnetic Resonance (CMR) was performed at 5days and 6months after STEMI. Myocardial edema and HEM were assessed by T2 and T2* mapping. MVO and necrotic area were assessed by early and late gadolinium enhancement (LGE). NTBI was detected in 13/15 patients with the highest values in 4 patients with evidence of MVO and HEM. NTBI levels were significantly related to CK-MB and troponin T values. NTBI kinetics appeared to be different in patients with MVO and HEM (7/15 patients), with a peak value at 6h after PCI, in comparison with those with no evidence of MVO and HEM, in whom NTBI values were lower and remained indeterminable after the first 24h. ConclusionsThe detection of elevated NTBI values in patients with STEMI, MVO and HEM suggests a possible role of iron cardiotoxicity in myocardial damage.

Monitoring of Monocyte Recruitment in Reperfused Myocardial Infarction With Intramyocardial Hemorrhage and Microvascular Obstruction by Combined Fluorine 19 and Proton Cardiac Magnetic Resonance Imaging

Monocytes and macrophages are indispensable in the healing process after myocardial infarction (MI); however, the spatiotemporal distribution of monocyte infiltration and its correlation to prognostic indicators of reperfused MI have not been well described. With combined fluorine 19/proton ((1)H) magnetic resonance imaging, we noninvasively visualized the spatiotemporal recruitment of monocytes in vivo in a rat model of reperfused MI. Blood monocytes were labeled by intravenous injection of (19)F-perfluorocarbon emulsion 1 day after MI. The distribution patterns of monocyte infiltration were correlated to the presence of microvascular obstruction (MVO) and intramyocardial hemorrhage. In vivo, (19)F/(1)H magnetic resonance imaging performed in series revealed that monocyte infiltration was spatially inhomogeneous in reperfused MI areas. In the absence of MVO, monocyte infiltration was more intense in MI regions with serious ischemia-reperfusion injuries, indicated by severe intramyocardial hemorrhage; however, monocyte recruitment was significantly impaired in MVO areas accompanied by severe intramyocardial hemorrhage. Compared with MI with isolated intramyocardial hemorrhage, MI with MVO resulted in significantly worse pump function of the left ventricle 28 days after MI. Monocyte recruitment was inhomogeneous in reperfused MI tissue. It was highly reduced in MVO areas defined by magnetic resonance imaging. The impaired monocyte infiltration in MVO regions could be related to delayed healing and worse functional outcomes in the long term. Therefore, monocyte recruitment in MI with MVO could be a potential diagnostic and therapeutic target that could be monitored noninvasively and longitudinally by (19)F/(1)H magnetic resonance imaging in vivo.

Direct T2 Quantification of Myocardial Edema in Acute Ischemic Injury

To evaluate the utility of rapid, quantitative T2 mapping compared with conventional T2-weighted imaging in patients presenting with various forms of acute myocardial infarction. T2-weighted cardiac magnetic resonance (CMR) identifies myocardial edema before the onset of irreversible ischemic injury and has shown value in risk-stratifying patients with chest pain. Clinical acceptance of T2-weighted CMR has, however, been limited by well-known technical problems associated with existing techniques. T2 quantification has recently been shown to overcome these problems; we hypothesized that T2 measurement in infarcted myocardium versus remote regions versus zones of microvascular obstruction in acute myocardial infarction patients could help reduce uncertainty in interpretation of T2-weighted images. T2 values using a novel mapping technique were prospectively recorded in 16 myocardial segments in 27 patients admitted with acute myocardial infarction. Regional T2 values were averaged in the infarct zone and remote myocardium, both defined by a reviewer blinded to the results of T2 mapping. Myocardial T2 was also measured in a group of 21 healthy volunteers. T2 of the infarct zone was 69 ± 6 ms compared with 56 ± 3.4 ms for remote myocardium (p < 0.0001). No difference in T2 was observed between remote myocardium and myocardium of healthy volunteers (56 ± 3.4 ms and 55.5 ± 2.3 ms, respectively, p = NS). T2 mapping allowed for the detection of edematous myocardium in 26 of 27 patients; by comparison, segmented breath-hold T2-weighted short tau inversion recovery images were negative in 7 and uninterpretable in another 2 due to breathing artifacts. Within the infarct zone, areas of microvascular obstruction were characterized by a lower T2 value (59 ± 6 ms) compared with areas with no microvascular obstruction (71.6 ± 10 ms, p < 0.0001). T2 mapping provided consistent high-quality results in patients unable to breath-hold and in those with irregular heart rhythms, in whom short tau inversion recovery often yielded inadequate imaging. Quantitative T2 mapping reliably identifies myocardial edema without the limitations encountered by T2-weighted short tau inversion recovery imaging, and may therefore be clinically more robust in showing acute ischemic injury.

Relation Between Signal Intensity on T2-Weighted MR Images and Presence of Microvascular Obstruction in Patients With Acute Myocardial Infarction

In experimental animal models and human autopsy studies, hemorrhagic infarction caused by microvascular injury has been detected after coronary reperfusion. The purpose of this study was to determine whether detection of myocardial edema with T2-weighted MRI is influenced by the presence of microvascular obstruction. Thirty-seven patients underwent black-blood fat-suppressed T2-weighted, rest perfusion, and late gadolinium-enhanced MRI 5.4 +/- 3.1 days after the onset of acute myocardial infarction. On T2-weighted MR images, the signal intensity in relation to that of remote myocardium was determined in the late gadolinium-enhanced and periinfarction areas. Segment-based analysis was performed to determine whether the presence of microvascular obstruction influences the detection of myocardial edema. The averaged signal intensity in the late gadolinium-enhanced area without microvascular obstruction was significantly higher than the signal intensity in remote normal myocardium (relative signal intensity, 1.83 +/- 0.50; p < 0.001). In contrast, the signal intensity in the microvascular obstruction area on T2-weighted images was not significantly different from the signal intensity in remote myocardium (relative signal intensity, 1.14 +/- 0.26). The percentages of late gadolinium-enhanced segments with high signal intensity on T2-weighted MR images were 95% (73/77) without microvascular obstruction and 30% (22/73) with microvascular obstruction. With T2-weighted MRI, infarction-associated edema can be reliably detected in infarct lesions without microvascular obstruction. Microvascular obstruction, however, does not necessarily exhibit high signal intensity on T2-weighted MRI. Careful attention is required in interpretation of cardiac MR images of patients who have experienced acute myocardial infarction and undergone percutaneous coronary intervention. The findings on T2-weighted MR images can be substantial underestimates of the extent of acute myocardial infarction.

Assessment of Microvascular Obstruction and Prediction of Short-term Remodeling after Acute Myocardial Infarction: Cardiac MR Imaging Study

To evaluate which cardiac magnetic resonance (MR) imaging technique for detection of microvascular obstruction (MVO) best predicts left ventricular (LV) remodeling after acute myocardial infarction (MI). This study had local ethics committee approval; all patients gave written informed consent. Sixty-three patients with first acute MI, treated with primary stent placement and optimal medical therapy, underwent cine MR imaging at 4-7 days and at 4 months after MI. Presence of MVO was qualitatively evaluated at baseline by using three techniques: (a) a single-shot saturation-recovery gradient-echo first-pass perfusion sequence (early hypoenhancement), mean time, 1.09 minutes +/- 0.07 (standard deviation) after contrast material administration; (b) a three-dimensional segmented saturation-recovery gradient-echo sequence (intermediate hypoenhancement), mean time, 2.17 minutes +/- 0.26; and (c) a two-dimensional segmented inversion-recovery gradient-echo late gadolinium enhancement sequence (late hypoenhancement), mean time, 13.32 minutes +/- 1.26. Contrast-to-noise ratios (CNRs) were calculated from the signal-to-noise ratios of the infarcted myocardium and MVO areas. Univariable linear regression analysis was used to identify the predictive value of each MR imaging technique. Early hypoenhancement was detected in 44 (70%) of 63 patients; intermediate hypoenhancement, in 39 (62%); and late hypoenhancement, in 37 (59%). Late hypoenhancement was the strongest predictor of change in LV end-diastolic and end-systolic volumes over time (beta = 14.3, r = 0.40, P = .001 and beta = 11.3, r = 0.44, P < .001, respectively), whereas intermediate and late hypoenhancement had comparable predictive values of change in LV ejection fraction (beta = -3.1, r = -0.29, P = .02 and beta = -2.8, r = -0.27, P = .04, respectively). CNR corrected for spatial resolution was significantly superior for late enhancement compared with the other sequences (P < .001). By using cardiac MR imaging, late hypoenhancement is the best prognostic marker of LV remodeling, with highest CNR between the infarcted myocardium and MVO regions.