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Introduction: Stem cell-based therapies have shown promise in adults with ischemic cardiomyopathy and children with congenital heart diseases, especially those without available therapeutic options. Human neonatal mesenchymal stem cells (nMSCs) have greater regenerative potential than adult stem cells. Aim: To describe our experience with a novel catheter system for transcoronary delivery of cell-based therapies (CIRCULATE catheter) in the intra-coronary delivery of nMSCs in a swine acute myocardial infarct model. Material and methods: A newly developed catheter system (CIRCULATE catheter) with several unique features, including an expandable intra-coronary reservoir with spirally placed side holes of varying diameter, was used. nMSCs together with their secretome were used for the treatment. Pigs underwent myocardial infarction by inflating a 2.5 mm angioplasty balloon in the left anterior descending artery for 60 min. After reperfusion, stem cell therapy or placebo was administered via the novel catheter. TTE was performed at baseline, 1 h after the procedure, and before the euthanasia. Troponin blood concertation was evaluated at baseline, and after 48 h. The heart was harvested, sliced, and stained with triphenyl tetrazolium chloride (TTC). Infarct size to area-at-risk ratio was calculated. Troponin was assessed at baseline and after 48 h. Results: Thirty-nine pigs were operated with the mortality rate of 5.13% (exclusively malignant arrhythmia). Infarct size to areaat-risk ratio was significantly lower in the treatment group. Treated animals had higher ejection fraction than controls. Conclusions: Intra-coronary delivery of neonatal mesenchymal stem cells reduces the infarct size and restores myocardial function in a swine model. The novel catheter system (CIRCULATE catheter) tested in this study was safe and effective in transcoronary cell delivery of human neonatal mesenchymal stem cells. [ABSTRACT FROM AUTHOR]

AimsMyocardial salvage index (MSI) is attracting increasing attention for predicting prognosis in acute myocardial infarction (AMI); however, the evaluation of MSI is mainly based on contrast agent-dependent cardiac magnetic resonance (CMR) scanning sequences. This study aims to investigate the prognostic value of MSI in reperfused ST-segment elevation myocardial infarction (STEMI) through the contrast agent-free CMR technique.Methods and resultsNighty-two patients with acute STEMI, who underwent CMR after primary percutaneous coronary intervention (PPCI), were finally enrolled. Patients were subcategorized into two groups according to median MSI. T1 and T2 mapping were conducted for measuring infarct size (IS) and area at risk (AAR). IS was significantly larger in < median MSI group than ≥ median MSI group (P < 0.001). AAR between the two groups showed no obvious differences (P = 0.108). Left ventricular ejection fraction (LVEF) was lower in < median MSI group than ≥ median MSI group (P = 0.014). There was an obvious inverse correlation between MSI and reperfusion time (R = –0.440, P < 0.001) and a strong inverse correlation between MSI and IS (R = –0.716, P = 0.011). As for the relationship LVEF, MSI showed positive but weak correlation (R = 0.2265, P < 0.001). Over a median follow-up period of 263 (227–238) days, prevalence of MACEs was significantly higher in the < median MSI group [HR: 0.15 (0.04–0.62); Log-rank P = 0.008]. The univariate Cox regression analysis revealed that LVEF, IS, and MSI were significant predictors for major adverse cardiovascular events (MACEs) (all P < 0.05). In the stepwise multivariate Cox regression analysis, LVEF and MSI were identified as independent parameters for predicting MACEs (both P < 0.05). In the receiver-operating characteristic analysis, LVEF, IS, and MSI showed prognostic value in predicting MACEs with AUCs of 0.809, 0.779, and 0.896, respectively, all (P < 0.05). A combination of MSI with LVEF showed the strongest prognostic value of MACEs (AUC: 0.901, sensitivity: 77.78%, specificity: 98.80%, P < 0.001). Delong’s test showed that the combination of LVEF with MSI had an incremental value than LVEF itself in predicting MACEs (P = 0.026).ConclusionContrast agent-free CMR technique provides a reliable evaluation of MSI, which contributes to assessing the efficacy of reperfusion therapy and predicting the occurrence of MACEs.

Background: Better survival for overweight and obese patients after ST-segment elevation myocardial infarction (STEMI) has been demonstrated. The association between body mass index (BMI), microvascular obstruction (MVO), and area at risk (AAR) after STEMI was evaluated. Methods: A prospective observational study was performed to enrolled patients undergoing primary percutaneous coronary intervention (pPCI) for STEMI and cardiac magnetic resonance was performed within 5– 7 days. Patients were classified as normal weight (18.5 ≤BMI < 24.0 kg/m2), overweight (24.0 ≤BMI < 28.0 kg/m2), or obese (BMI ≥ 28 kg/m2). Results: Among 225 patients undergoing pPCI, 67 (30.00%) were normal weight, 113 (50.22%) were overweight, and 45 (20.00%) were obese. BMI ≥ 28 kg/m2 was significantly associated with less risk of MVO when compared with a normal BMI after multivariable adjustment (overweight: HR 0.29, 95% CI 0.13– 0.68, p = 0.004). Compared with normal weight patients, obese and overweight patients tend to have larger hearts (greater left ventricular end-diastolic volume [LVEDV] and left ventricular [LV] mass). In adjusted analysis, increased BMI was significantly associated with a smaller AAR. In addition, obese patients had a smaller AAR (β = − 0.252, 95% CI − 20.298- − 3.244, p = 0.007) and AAR, % LV mass (β = − 0.331, 95% CI − 0.211- − 0.062, p < 0.001) than normal weight patients. Conclusion: Obesity (BMI ≥ 28 kg/m2) is independently associated with lower risks of MVO and a smaller AAR, % LV mass than normal weight patients among subjects undergoing pPCI for STEMI. [ABSTRACT FROM AUTHOR]

Abstract Background The participation of long noncoding RNAs (lncRNAs) in myocardial infarction has recently been noted. However, their underlying roles in the border zone of myocardial infarction remain unclear. This study uses microarrays to determine the profiles of lncRNAs and mRNAs in the border zone. Methods Bioinformatics methods were employed to uncover their underlying roles. Highly dysregulated lncRNAs was further validated via PCR. Results Four hundred seven lncRNAs and 752 mRNAs were upregulated, while 132 lncRNAs and 547 mRNAs were downregulated in the border zone of myocardial infarction. A circos graph was constructed to visualize the chromosomal distribution and classification of the dysregulated lncRNAs and mRNAs. The upregulated mRNAs in the border zone were most highly enriched in cytokine activity, binding, cytokine receptor binding and related processes, as ascertained through Go analysis. Pathway analysis of the upregulated mRNAs showed the most significant changes were in the TNF signaling pathway, cytokine–cytokine receptor interaction and chemokine signaling pathway and similar pathways and interactions. An lncRNA–mRNA co-expression network was established to probe into the underlying functions of the 10 most highly dysregulated lncRNAs based on their co-expressed mRNAs. In the co-expression network, we found 16 genes directly involved in myocardial infarction, including Alox5ap, Itgb2 and B4galt1. The lncRNAs AY212271, EF424788 and MRAK088538, among others, might be associated with myocardial infarction. BC166504 is probably a key lncRNA in the border zone of myocardial infarction. Conclusions The results may have revealed some aberrantly expressed lncRNAs and mRNAs that contribute to the underlying pathophysiological mechanisms of myocardial infarction.

Abstract Background Infarct evolution rate and response to acute reperfusion therapy may differ between patients, which is important to consider for accurate management and treatment of patients with ST-elevation myocardial infarction (STEMI). The aim of this study was therefore to investigate the association of infarct size and myocardial salvage with gender, smoking status, presence of diabetes or history of hypertension in a cohort of STEMI-patients. Methods Patients (n = 301) with first-time STEMI from the three recent multi-center trials (CHILL-MI, MITOCARE and SOCCER) underwent cardiac magnetic resonance (CMR) imaging to determine myocardium at risk (MaR) and infarct size (IS). Myocardial salvage index (MSI) was calculated as MSI = 1-IS/MaR. Pain to balloon time, culprit vessel, trial treatments, age, TIMI grade flow and collateral flow by Rentrop grading were included as explanatory variables in the statistical model. Results Women (n = 66) had significantly smaller MaR (mean difference: 5.0 ± 1.5% of left ventricle (LV), p

Abstract Background It has recently been suggested that myocardial oedema follows a bimodal pattern early post ST-segment elevation myocardial infarction (STEMI). Yet, water content, quantified using tissue desiccation, did not return to normal values unlike oedema quantified by cardiovascular magnetic resonance (CMR) imaging. We studied the temporal changes in the extent and intensity of injured myocardium using T1-mapping technique within the first week after STEMI. Methods A first group (n = 31) underwent 3 acute 3 T CMR scans (time-point (TP)

Background: ST-segment elevation myocardial infarction (STEMI) is clinically diagnosed by significant ST-segment elevation (STE) in the electrocardiogram (ECG). The importance of the sum of significant ST-segment elevation (∑STE) before primary percutaneous coronary intervention (PPCI) - considered an indicator of the degree of ischemia - is sparse. We evaluated the association of ∑STE before PPCI with respect to area at risk, infarct size and myocardial salvage.Methods: A total of 503 patients with STEMI and available cardiac magnetic resonance (CMR) were included. CMR was performed at day 1 (interquartile range [IQR], 1-1) and at follow-up at day 92 (IQR, 88-96). The ECG before PPCI with the most prominent STE was used for analysis.Results: ∑STE divided into quartiles were progressive linearly associated with area at risk (p < 0.001), final infarct size (p < 0.001) and extent of microvascular obstruction (p < 0.001) and inverse linearly associated with final myocardial salvage (p < 0.001). Similar results were found for linear regression analyses. However, ∑STE was not associated with final myocardial salvage in patients with pre-PCI TIMI (thrombolysis in myocardial infarction) flow 0/1 (p = 0.24) in contrast to patients with pre-PCI TIMI flow 2/3 (p ≤ 0.001).Conclusion: In patients with STEMI presenting within 12 h of symptom onset, the degree of STE in the ECG before PPCI is a marker of the extent of myocardium at risk that in turn affects the infarct size in patients with pre-PCI TIMI flow 0/1, whereas the degree of STE in patients with pre-PCI TIMI flow 2/3 is a marker of the extent of the myocardium at risk as well as myocardial salvage - both affecting the myocardial damage. [ABSTRACT FROM AUTHOR]

Abstract Background Cardioprotective value of ischemic post- (IPostC), remote (RIC) conditioning in acute myocardial infarction (AMI) is unclear in clinical trials. To evaluate cardioprotection, most translational animal studies and clinical trials utilize necrotic tissue referred to the area at risk (AAR) by magnetic resonance imaging (MRI). However, determination of AAR by MRI‚ may not be accurate, since MRI-indices of microvascular damage, i.e., myocardial edema and microvascular obstruction (MVO), may be affected by cardioprotection independently from myocardial necrosis. Therefore, we assessed the effect of IPostC, RIC conditioning and ischemic preconditioning (IPreC; positive control) on myocardial necrosis, edema and MVO in a clinically relevant, closed-chest pig model of AMI. Methods and results Acute myocardial infarction was induced by a 90-min balloon occlusion of the left anterior descending coronary artery (LAD) in domestic juvenile female pigs. IPostC (6 × 30 s ischemia/reperfusion after 90-min occlusion) and RIC (4 × 5 min hind limb ischemia/reperfusion during 90-min LAD occlusion) did not reduce myocardial necrosis as assessed by late gadolinium enhancement 3 days after reperfusion and by ex vivo triphenyltetrazolium chloride staining 3 h after reperfusion, however, the positive control, IPreC (3 × 5 min ischemia/reperfusion before 90-min LAD occlusion) did. IPostC and RIC attenuated myocardial edema as measured by cardiac T2-weighted MRI 3 days after reperfusion, however, AAR measured by Evans blue staining was not different among groups, which confirms that myocardial edema is not a measure of AAR, IPostC and IPreC but not RIC decreased MVO. Conclusion We conclude that IPostC and RIC interventions may protect the coronary microvasculature even without reducing myocardial necrosis.

After a reperfused myocardial infarction (MI), dynamic tissue changes occur (edema, inflammation, microvascular obstruction, hemorrhage, cardiomyocyte necrosis, and ultimately replacement by fibrosis). The extension and magnitude of these changes contribute to long-term prognosis after MI. Cardiac magnetic resonance (CMR) is the gold-standard technique for noninvasive myocardial tissue characterization. CMR is also the preferred methodology for the identification of potential benefits associated with new cardioprotective strategies both in experimental and clinical trials. However, there is a wide heterogeneity in CMR methodologies used in experimental and clinical trials, including time of post-MI scan, acquisition protocols, and, more importantly, selection of endpoints. There is a need for standardization of these methodologies to improve the translation into a real clinical benefit. The main objective of this scientific expert panel consensus document is to provide recommendations for CMR endpoint selection in experimental and clinical trials based on pathophysiology and its association with hard outcomes. [ABSTRACT FROM AUTHOR]

Aims Myocardial salvage following treatment for ST-segment elevation myocardial infarction is prognostic for morbidity and mortality. Studies with myocardial salvage as endpoint rely on valid assessment of the myocardial area at risk (AAR). T2-weighted cardiovascular magnetic resonance (CMR) imaging is the preferred method to assess the AAR. However, T2-weighted imaging can be of poor image quality and uninterpretable. Contrast-enhanced (CE) cine imaging can also show AAR and our aim was to investigate if CE-cine can replace T2-weighted imaging. Cine imaging is part of a standard CMR-protocol and implementing CE-cine imaging for assessment of the AAR would mean shorter investigation time. Methods and results As a DANAMI-3 substudy, we performed successful dual imaging of the AAR in 166 participants using both T2-weighted short tau inversion recovery (T2-STIR) and CE-cine imaging. T2-STIR imaging was non-diagnostic in nine and CE-cine in one scan during the period. CE-cine measured 4.7% of left ventricle (LV) [95% confidence interval 3.2–6.2%] smaller AAR compared with T2-STIR images (P  < 0.001). Visual analysis of a plot of infarct size vs. AAR showed an overestimation of the AAR when measured with T2-STIR images. There was no difference in AAR with CE-cine in an interobserver analysis of 46 scans [1.2 g (standard deviation 9.5), P  = 0.42]. Conclusions CE-cine imaging shows good internal consistency in assessment of the AAR. A visual inspection reveals possible overestimation of AAR with T2-STIR images. There is good interobserver agreement in the analysis of CE-cine imaging. CE-cine can replace T2-STIR imaging resulting in a more valid assessment of the myocardial AAR. [ABSTRACT FROM AUTHOR]

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Background: Determining infarct size and myocardial salvage in patients with ST-segment elevation myocardial infarction (STEMI) is important when assessing the efficacy of new reperfusion strategies. We investigated whether rest 82Rb-PET myocardial perfusion imaging can estimate area at risk, final infarct size, and myocardial salvage index when compared to cardiac SPECT and magnetic resonance (CMR).Methods: Twelve STEMI patients were injected with 99mTc-Sestamibi intravenously immediate prior to reperfusion. SPECT, 82Rb-PET, and CMR imaging were performed post-reperfusion and at a 3-month follow-up. An automated algorithm determined area at risk, final infarct size, and hence myocardial salvage index.Results: SPECT, CMR, and PET were performed 2.2 ± 0.5, 34 ± 8.5, and 32 ± 24.4 h after reperfusion, respectively. Mean (± SD) area at risk were 35.2 ± 16.6%, 34.7 ± 11.3%, and 28.1 ± 16.1% of the left ventricle (LV) in SPECT, CMR, and PET, respectively, P = 0.04 for difference. Mean final infarct size estimates were 12.3 ± 15.4%, 13.7 ± 10.4%, and 11.9 ± 14.6% of the LV in SPECT, CMR, and PET imaging, respectively, P = .72. Myocardial salvage indices were 0.64 ± 0.33 (SPECT), 0.65 ± 0.20 (CMR), and 0.63 ± 0.28 (PET), (P = .78).Conclusions: 82Rb-PET underestimates area at risk in patients with STEMI when compared to SPECT and CMR. However, our findings suggest that PET imaging seems feasible when assessing the clinical important parameters of final infarct size and myocardial salvage index, although with great variability, in a selected STEMI population with large infarcts. These findings should be confirmed in a larger population. [ABSTRACT FROM AUTHOR]

Background: Assessment of the area at risk (AAR) associated with an acute myocardial infarction is crucial for evaluating prevention and revascularization strategies. The aim of this study was to evaluate whether 123I-metaiodobenzylguanidine (123I-MIBG) single-photon emission computed tomography (SPECT) provides a more widely available assessment of anatomical AAR than the established anatomical angiographic methods.Methods: Seventy patients with ST-segment elevation acute myocardial infarction (STEMI) underwent coronary angiography with percutaneous coronary intervention and subsequent 123I-MIBG myocardial scintigraphy with left myocardial relative radiotracer uptake evaluation 12 ± 10 days after STEMI. Patients were divided into two groups depending on whether the culprit artery was occluded (50 patients) or sub-occluded (20 patients). Two scores were calculated as a percentage of the left ventricular myocardium surface, the first using a standard 17-segment summed rest score derived from the relative quantitative evaluation of 123I-MIBG myocardial uptake (MAR) and the second using the modified APPROACH-score (ApAR).Results: For the patients with occluded artery, this study showed a high correlation between MAR and the angiographic score (Pearson r = .762 and P < .0001). For the patients with sub-occluded artery, for which the ApAR is not reliable, this study showed no correlation between MAR and the angiographic score (Pearson r = .18 and P = 0.45).Conclusions: 123I-MIBG myocardial scintigraphy provides ARR assessment similar to that of ApAR in patients with a single occluded coronary artery. However, MAR differs from ApAR when angiographic scores are known to be inaccurate (sub-occluded culprit artery) or impossible to use. Further studies are needed to evaluate the potential clinical interest of 123I-MIBG SPECT as an alternative for area at risk assessment after STEMI even when the culprit artery is sub-occluded or when the angiographic scores cannot be used. [ABSTRACT FROM AUTHOR]

Purpose of Review Cardiac magnetic resonance (CMR) has emerged in recent years as a reliable tool to assess, in a single examination after a reperfused myocardial infarction, the initially area at risk (AAR), the final infarct size (IS), and from their difference the salvaged myocardium (SM). The aim of the present review is to summarize recent advances in the CMR imaging of SM. Recent Findings While there is consensus on the use of late gadolinium enhancement (LGE) to calculate IS, how to assess the AAR is a debated topic. The use of T2-weighted short-TI inversion recovery (T2W-STIR) is to date supported by a large amount of data, but it is affected by several limitations. Newer techniques have been developed to overcome T2W-STIR limitations, some of them have been already used in randomized clinical trials (RCTs) while others are showing promising results. The use of CMR to generate surrogate endpoints in RCTs is gaining attention; in this context, analysis of data from recent RCTs suggests that the assessment of SM as outcome measure could be useful to reduce sample sizes and costs of trials. Summary CMR is a reliable technique for the assessment of SM. LGE is the gold standard for IS measurement, while which is the best technique for the evaluation ofAAR is still debated. When using CMR-derived endpoints in RCTs, the assessment of SM is advisable. [ABSTRACT FROM AUTHOR]

BackgroundPatients with recent non–ST‐segment elevation myocardial infarction commonly have heterogeneous characteristics that may be challenging to assess clinically. Methods and ResultsWe prospectively studied the diagnostic accuracy of 2 novel (T1, T2 mapping) and 1 established (T2‐weighted short tau inversion recovery [T2W‐STIR]) magnetic resonance imaging methods for imaging the ischemic area at risk and myocardial salvage in 73 patients with non–ST‐segment elevation myocardial infarction (mean age 57±10 years, 78% male) at 3.0‐T magnetic resonance imaging within 6.5±3.5 days of invasive management. The infarct‐related territory was identified independently using a combination of angiographic, ECG, and clinical findings. The presence and extent of infarction was assessed with late gadolinium enhancement imaging (gadobutrol, 0.1 mmol/kg). The extent of acutely injured myocardium was independently assessed with native T1, T2, and T2W‐STIR methods. The mean infarct size was 5.9±8.0% of left ventricular mass. The infarct zone T1 and T2 times were 1323±68 and 57±5 ms, respectively. The diagnostic accuracies of T1 and T2 mapping for identification of the infarct‐related artery were similar (P=0.125), and both were superior to T2W‐STIR (P

Background: Cardioprotective value of ischemic post- (IPostC), remote (RIC) conditioning in acute myocardial infarction (AMI) is unclear in clinical trials. To evaluate cardioprotection, most translational animal studies and clinical trials utilize necrotic tissue referred to the area at risk (AAR) by magnetic resonance imaging (MRI). However, determination of AAR by MRI' may not be accurate, since MRI-indices of microvascular damage, i.e., myocardial edema and microvascular obstruction (MVO), may be affected by cardioprotection independently from myocardial necrosis. Therefore, we assessed the effect of IPostC, RIC conditioning and ischemic preconditioning (IPreC; positive control) on myocardial necrosis, edema and MVO in a clinically relevant, closed-chest pig model of AMI.Methods and Results: Acute myocardial infarction was induced by a 90-min balloon occlusion of the left anterior descending coronary artery (LAD) in domestic juvenile female pigs. IPostC (6 × 30 s ischemia/reperfusion after 90-min occlusion) and RIC (4 × 5 min hind limb ischemia/reperfusion during 90-min LAD occlusion) did not reduce myocardial necrosis as assessed by late gadolinium enhancement 3 days after reperfusion and by ex vivo triphenyltetrazolium chloride staining 3 h after reperfusion, however, the positive control, IPreC (3 × 5 min ischemia/reperfusion before 90-min LAD occlusion) did. IPostC and RIC attenuated myocardial edema as measured by cardiac T2-weighted MRI 3 days after reperfusion, however, AAR measured by Evans blue staining was not different among groups, which confirms that myocardial edema is not a measure of AAR, IPostC and IPreC but not RIC decreased MVO.Conclusion: We conclude that IPostC and RIC interventions may protect the coronary microvasculature even without reducing myocardial necrosis. [ABSTRACT FROM AUTHOR]

Objectives The aim of this study was to determine whether early gadolinium enhancement (EGE) by cardiac magnetic resonance (CMR) in a canine model of reperfused myocardial infarction depicts the area at risk (AAR) as determined by microsphere blood flow analysis. Background It remains controversial whether only the irreversibly injured myocardium enhances when CMR is performed in the setting of acute myocardial infarction. Recently, EGE has been proposed as a measure of the AAR in acute myocardial infarction because it correlates well with T2-weighted imaging of the AAR, but this still requires pathological validation. Methods Eleven dogs underwent 2 h of coronary artery occlusion and 48 h of reperfusion before imaging at 1.5-T. EGE imaging was performed 3 min after contrast administration with coverage of the entire left ventricle. Late gadolinium enhancement imaging was performed between 10 and 15 min after contrast injection. AAR was defined as myocardium with blood flow <2 SD from remote myocardium determined by microspheres during occlusion. The size of infarction was determined with triphenyltetrazolium chloride. Results There was no significant difference in the size of enhancement by EGE compared with the size of AAR by microspheres (44.1 ± 15.8% vs. 42.7 ± 9.2%; p = 0.61), with good correlation (r = 0.88; p < 0.001) and good agreement by Bland-Altman analysis (mean bias 1.4 ± 17.4%). There was no difference in the size of enhancement by EGE compared with enhancement on native T1 and T2 maps. The size of EGE was significantly greater than the infarct by triphenyltetrazolium chloride (44.1 ± 15.8% vs. 20.7 ± 14.4%; p < 0.001) and late gadolinium enhancement (44.1 ± 15.8% vs. 23.5 ± 12.7%; p < 0.001). Conclusions At 3 min post-contrast, EGE correlated well with the AAR by microspheres and CMR and was greater than infarct size. Thus, EGE enhances both reversibly and irreversibly injured myocardium. [ABSTRACT FROM AUTHOR]

Background: Accurate assessment of myocardium at risk (MaR) after acute myocardial infarction (AMI) is necessary when assessing myocardial salvage. Contrast-enhanced steady-state free precession (CE-SSFP) is a recently developed cardiovascular magnetic resonance (CMR) method for assessment of MaR up to 1 week after AMI. Our aim was to validate CE-SSFP for determination of MaR in an experimental porcine model using myocardial perfusion single-photon emission computed tomography (MPS) as a reference standard and to test the stability of MaR-quantification over time after injecting gadolinium-based contrast. Methods: Eleven pigs were subjected to either 35 or 40 min occlusion of the left anterior descending artery followed by six hours of reperfusion. A technetium-based perfusion tracer was administered intravenously ten minutes before reperfusion. In-vivo and ex-vivo CE-SSFP CMR was performed followed by ex-vivo MPS imaging. MaR was expressed as % of left ventricular mass (LVM). Results: There was good agreement between MaR by ex-vivo CMR and MaR by MPS (bias: 1 ± 3% LVM, r² = 0.92, p < 0.001), between ex-vivo and in-vivo CMR (bias 0 ± 2% LVM, r² = 0.94, p < 0.001) and between in-vivo CMR and MPS (bias -2 ± 3% LVM, r² = 0.87, p < 0.001. No change in MaR was seen over the first 30 min after contrast injection (p = 0.95). Conclusions: Contrast-enhanced SSFP cine CMR can be used to measure MaR, both in vivo and ex vivo, in a porcine model with good accuracy and precision over the first 30 min after contrast injection. This offers the option to use the less complex ex-vivo imaging when determining myocardial salvage in experimental studies. [ABSTRACT FROM AUTHOR]

Aims Myocardial salvage, determined by cardiac magnetic resonance imaging (CMR), is used as end point in cardioprotection trials. To calculate myocardial salvage, infarct size is related to myocardium at risk (MaR), which can be assessed by T2-short tau inversion recovery (T2-STIR) and contrast-enhanced steady-state free precession magnetic resonance imaging (CE-SSFP). We aimed to determine how T2-STIR and CE-SSFP perform in determining MaR when applied in multicentre, multi-vendor settings. Methods and and results A total of 215 patients from 17 centres were included after percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction. CMR was performed within 1 -8 days. These patients participated in the MITOCARE or CHILL- MI cardioprotection trials. Additionally, 8 patients from a previous study, imaged 1 day post-CMR, were included. Late gadolinium enhancement, T2-STIR, and CE-SSFP images were acquired on 1.5T MR scanners (Philips, Siemens, or GE). In 65% of the patients, T2-STIR was of diagnostic quality compared with 97% for CE-SSFP. In diagnostic quality images, there was no difference in MaR by T2-STIR and CE-SSFP (bias: 0.02 ± 6%, P = 0.96, r² = 0.71, P, 0.001), or between treatment and control arms. No change in size or quality of MaR nor ability to identify culprit artery was seen over the first week after the acute event (P = 0.44). Conclusion In diagnostic quality images, T2-STIR and CE-SSFP provide similar estimates of MaR, were constant over the first week, and were not affected by treatment. CE-SSFP had a higher degree of diagnostic quality images compared with T2 imaging for sequences from two out of three vendors. Therefore, CE-SSFP is currently more suitable for implementation in multicentre, multi-vendor clinical trials. [ABSTRACT FROM AUTHOR]

Background-Hybrid positron emission tomography and magnetic resonance allows the advantages of magnetic resonance in tissue characterizing the myocardium to be combined with the unique metabolic insights of positron emission tomography. We hypothesized that the area of reduced myocardial glucose uptake would closely match the area at risk delineated by T2 mapping in ST-segment-elevation myocardial infarction patients. Methods and Results-Hybrid positron emission tomography and magnetic resonance using 18F-fluorodeoxyglucose (FDG) for glucose uptake was performed in 21 ST-segment-elevation myocardial infarction patients at a median of 5 days. Follow-up scans were performed in a subset of patients 12 months later. The area of reduced FDG uptake was significantly larger than the infarct size quantified by late gadolinium enhancement (37.2±11.6% versus 22.3±11.7%; P<0.001) and closely matched the area at risk by T2 mapping (37.2±11.6% versus 36.3±12.2%; P=0.10, R=0.98, bias 0.9±4.4%). On the follow-up scans, the area of reduced FDG uptake was significantly smaller in size when compared with the acute scans (19.5 [6.3%-31.8%] versus 44.0 [21.3%-55.3%]; P=0.002) and closely correlated with the areas of late gadolinium enhancement (R 0.98) with a small bias of 2.0±5.6%. An FDG uptake of ≥45% on the acute scans could predict viable myocardium on the follow-up scan. Both transmural extent of late gadolinium enhancement and FDG uptake on the acute scan performed equally well to predict segmental wall motion recovery. Conclusions-Hybrid positron emission tomography and magnetic resonance in the reperfused ST-segment-elevation myocardial infarction patients showed reduced myocardial glucose uptake within the area at risk and closely matched the area at risk delineated by T2 mapping. FDG uptake, as well as transmural extent of late gadolinium enhancement, acutely can identify viable myocardial segments. [ABSTRACT FROM AUTHOR]

Aims Cardiovascular magnetic resonance (CMR) imaging can measure the myocardial area at risk (AAR), but the technique has received criticism for inadequate validation. CMR commonly depicts an AAR that is wider than the infarct, which in turn would require a lateral perfusion gradient within the AAR. We investigated the presence of a lateral perfusion gradient within the AAR and validated CMR measures of AAR against three independent reference standards of high quality. Methods and results Computed tomography (CT) perfusion imaging, microsphere blood flow analysis, T1-weighted 3TCMR and fluorescent microparticle pathology were used to investigate the AAR in a canine model (n = 10) of ischaemia and reperfusion. AAR size by CMR correlated well with CT (R² = 0.80), microsphere blood flow (R² = 0.80), and pathology (R² = 0.74) with good limits of agreement [-0.79 ± 4.02% of the left ventricular mass (LVM) vs. CT; -1.49 ± 4.04% LVM vs. blood flow and -1.01 ± 4.18% LVM vs. pathology]. The lateral portion of the AAR had higher perfusion than the core of the AAR by CT perfusion imaging (40.7 ± 11.8 vs. 25.2 ± 17.7 Hounsfield units, P = 0.0008) and microsphere blood flow (0.11 ± 0.04 vs. 0.05 ± 0.02 mL/g/min, lateral vs. core, P = 0.001). The transmural extent of MI was lower in the lateral portion of the AAR than the core (28.2 ± 10.2 vs. 17.4 ± 8.4% of the wall, P = 0.001). Conclusion T1-weighted CMR accurately quantifies size of the AAR with excellent agreement compared with three independent reference standards. A lateral perfusion gradient results in lower transmural extent of infarction at the edges of the AAR compared with the core. [ABSTRACT FROM AUTHOR]

Objectives: The purpose of this study was to estimate the myocardial area at risk (MAAR) using coronary computed tomography angiography (CTA) and Voronoi algorithm-based myocardial segmentation in comparison with single-photon emission computed tomography (SPECT). Methods: Thirty-four patients with coronary artery disease underwent 128-slice coronary CTA, stress/rest thallium-201 SPECT, and coronary angiography (CAG). CTA-based MAAR was defined as the sum of all CAG stenosis (>50 %) related territories (the ratio of the left ventricular volume). Using automated quantification software (17-segment model, 5-point scale), SPECT-based MAAR was defined as the number of segments with a score above zero as compared to the total 17 segments by summed stress score (SSS), difference (SDS) score map, and comprehensive SPECT interpretation with either SSS or SDS best correlating CAG findings (SSS/SDS). Results were compared using Pearson's correlation coefficient. Results: Forty-nine stenoses were observed in 102 major coronary territories. Mean value of CTA-based MAAR was 28.3 ± 14.0 %. SSS-based, SDS-based, and SSS/SDS-based MAAR was 30.1 ± 6.1 %, 20.1 ± 15.8 %, and 26.8 ± 15.7 %, respectively. CTA-based MAAR was significantly related to SPECT-based MAAR ( r = 0.531 for SSS; r = 0.494 for SDS; r = 0.814 for SSS/SDS; P < 0.05 in each). Conclusions: CTA-based Voronoi algorithm myocardial segmentation reliably quantifies SPECT-based MAAR. Key points: • Voronoi algorithm allows for three-dimensional myocardial segmentation of coronary CT angiography • Stenosis-related CT myocardial territories correlate to SPECT based area at risk • CT angiography myocardial segmentation may assist in clinical decision-making [ABSTRACT FROM AUTHOR]

Background: A recent report demonstrated that early enhancement on contrast-enhanced cardiac magnetic resonance (CE-CMR) correlated with myocardial edema detected by T2-weighted CMR in reperfused acute myocardial infarction (AMI). However, the time at which the enhancement in salvaged myocardium disappears is yet to be determined. We aimed to examine the time course of the enhancement with the use of different quantification techniques and to compare the extent of enhancement with the myocardial edema. Methods and results: CE-CMR was performed at 2-20 min after gadolinium administration in 32 AMI patients. The extent of enhancement (% myocardium) was quantified by manual delineation and the threshold methods of 2-5 SDs above remote myocardium. In subendocardial infarct, the enhancement was greatest at 2 min regardless of the quantification techniques and decreased with time, particularly in the first 6 min. In transmural infarct, the change in the size of enhancement was modest although the time course of enhancement varied according to the quantification techniques. The sizes of enhancement were not significantly different between 15 and 20 min regardless of the techniques and infarct transmurality. The best agreement with myocardial edema was found at 2 min with average differences of 0.5% and -1.2% and limits of agreement of ±20.2% and ±21.2% for the manual and 2-SD techniques, respectively. Conclusions: The optimal timing for delineation of salvaged myocardium on CE-CMR is at 2 min when the manual or 2-SD technique was employed. Imaging needs to be completed in a short time (ideally within a minute) because of rapid reduction of enhancement in salvaged myocardium. [ABSTRACT FROM AUTHOR]

An introduction is presented in which the editor discusses the bimodal temporal course of myocardial T2 in patients after reperfused acute myocardial infarction (MI).

Area at risk (AAR) is an important parameter for the assessment of the salvage area after revascularization in acute myocardial infarction (AMI). By combining AAR assessment by T2-weighted imaging and scar quantification by late gadolinium enhancement imaging cardiovascular magnetic resonance (CMR) offers a promising alternative to the 'classical' modality of Tc99m-sestamibi single photon emission tomography (SPECT). Current T2 weighted sequences for edema imaging in CMR are limited by low contrast to noise ratios and motion artifacts. During the last years novel CMR imaging techniques for quantification of acute myocardial injury, particularly the T1-mapping and T2-mapping, have attracted rising attention. But no direct comparison between the different sequences in the setting of AMI or a validation against SPECT has been reported so far. We analyzed 14 patients undergoing primary coronary revascularization in AMI in whom both a pre-intervention Tc99m-sestamibi-SPECT and CMR imaging at a median of 3.4 (interquartile range 3.3-3.6) days after the acute event were performed. Size of AAR was measured by three different non-contrast CMR techniques on corresponding short axis slices: T2-weighted, fat-suppressed turbospin echo sequence (TSE), T2-mapping from T2-prepared balanced steady state free precession sequences (T2-MAP) and T1-mapping from modified look locker inversion recovery (MOLLI) sequences. For each CMR sequence, the AAR was quantified by appropriate methods (absolute values for mapping sequences, comparison with remote myocardium for other sequences) and correlated with Tc99m-sestamibi-SPECT. All measurements were performed on a 1.5 Tesla scanner. The size of the AAR assessed by CMR was 28.7 ± 20.9 % of left ventricular myocardial volume (%LV) for TSE, 45.8 ± 16.6 %LV for T2-MAP, and 40.1 ± 14.4 %LV for MOLLI. AAR assessed by SPECT measured 41.6 ± 20.7 %LV. Correlation analysis revealed best correlation with SPECT for T2-MAP at a T2-threshold of 60 ms (ms) (slope = 0.99, Pearson's r = 0.94), and for MOLLI at T1-threshold of 1,075 ms (slope 0.86, r = 0.91, Pearson's r = 0.45). For the assessment of AAR in AMI, the novel T2-mapping technique correlates best with SPECT size, T1-mapping with MOLLI and standard T2-weighted imaging showed similar good correlations. [ABSTRACT FROM AUTHOR]

Background The refinement of experimental stroke models is important for further development of neuroprotective interventions. Aims and/or hypothesis Our goal was to study the reproducibility of outcomes obtained in five rat models of middle cerebral artery ( MCA) ligation in order to identify the optimal model for the preclinical studies. Methods In Part 1 of the experiments, systolic blood flow velocity ( sBFV) and cerebral area at risk ( AR) were determined immediately after the onset of brain ischemia induced in different ways in Wistar rats. After that, another set of experiments was performed ( Part 2 of the experiments), now aimed at the assessment of the delayed outcome of five different models of cerebral ischemia designated as Versions 1-5. The versions were: Version 1 - 40-minute left MCA ( LMCA) occlusion with reperfusion; Version 2 - permanent LMCA ligation; Version 3 - permanent ligation of both LMCA and left common carotid artery ( CCA); Version 4 - permanent LMCA and bilateral CCA ( bCCA) ligation; Version 5 - permanent LMCA ligation and 40-minute bCCA occlusion. The infarct size ( IS) was quantified using triphenyltetrazolium chloride staining. The severity of neurological deficit was assessed by the Garcia score. The extent of brain edema was determined by calculating the difference in volumes of affected and contralateral hemispheres. Results Within a relatively big AR, Versions 1 and 2 resulted in a small IS [0·2 (0·0; 0·4)% and 0·3 (0·0; 0·7)%, respectively, P > 0·05]. Unlike that and comparable with AR, Version 3 resulted in a greater, albeit more variable IS [5·9 (2·1; 8·3)%, P < 0·0001 vs. Version 2]. Also comparable with AR, Versions 4 and 5 produced greatest values of IS [14·5 (11·4; 17·9)% and 11·3 (10·1; 14·2)%, respectively]; this parameter was most reproducible in Version 5. A significant decrease in neurological deficit score was found in Versions 4 and 5. Again, the reproducibility of the data on neurological outcome was higher in Version 5 versus Version 4. Conclusions Comparative analysis of several Versions of focal cerebral ischemia within a single study might be helpful in better understanding of the mechanisms underlying the development and aftermath of stroke. Permanent LMCA ligation plus transient bilateral CCA occlusion produced most consistent results and might be recommended for preclinical studies. [ABSTRACT FROM AUTHOR]

Myocardial in vivo tissue characterization is of great importance because it can provide meaningful information to understand pathophysiological processes underlying different cardiac diseases. Ex vivo histologic analyses of tissue samples have been classically considered the gold standard in the study of tissue properties and its composition. However, over the past decade, there has been a growing interest in the in vivo myocardial characterization with different imaging techniques, which can potentially be translated into the clinics in order to make an early diagnosis and evaluate serial changes, opening the possibility of dynamic evaluation. Animal models have become an essential tool to achieve this goal. This article aims at concisely reviewing recent and significant developments in the field of imaging techniques-mostly cardiac magnetic resonance-in relevant animal models of tissue characterization of area at risk, edema, and fibrosis. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Phosphatidylserine is translocated from the inner to the outer leaflet of the plasma membrane in the early stages of apoptosis and necrosis and in reversibly injured cells. In rabbit hearts, ischemia followed by reperfusion results in exposure of phosphatidylserine on myocytes unaffected by apoptosis or necrosis. Lactadherin was recently introduced as a highly sensitive phosphatidylserine ligand. We hypothesized that ischemic myocardial cell damage can be identified by radio-labeled lactadherin and that the ischemic area at risk (AAR) can be visualized retrospectively after reperfusion. Methods: Left anterior descending coronary artery in pigs was occluded for 20minutes, 45minutes or 45minutes preceded by ischemic preconditioning. In all three groups, 99mTc-lactadherin was injected intravenously 30minutes after reperfusion. The AAR was demarcated by Evans blue and the infarct size by 2,3,5,-triphenyltetrazodium chloride staining. Results: The regional myocardial uptake of 99mTc-lactadherin closely correlated with the AAR (r=.83, P = .001). The area of 99mTc–lactadherin uptake was unaltered by a shorter duration of ischemia and ischemic preconditioning (P=.23) despite significantly different infarct development (P=.001). Conclusion: The results suggest that 99mTc–lactadherin can be used as a sensitive marker for AAR imaging when injected 30minutes after reperfusion following acute ischemia. [Copyright &y& Elsevier]