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Objective: We aimed to relate the amount of jeopardized myocardium to mortality in shocked patients presenting to the catheterization laboratory with ST-elevation myocardial infarction (STEMI) and cardiogenic shock., Background: In contrast with historical data and previous professional guidance, contemporary randomized data suggest that multi-vessel revascularization in such patients does not improve survival; mechanistic insight is incomplete., Methods: Clinical databases identified cases of STEMI and shock triaged for primary percutaneous coronary intervention (PPCI) in Eastern Denmark from June 2011 to December 2014 (n = 128). British Cardiovascular Intervention Society (BCIS)-1 jeopardy scores were calculated from angiography. The study endpoint was 30-day mortality., Results: Median lactate values were 6.0 [2.9-10.7] mmol/L. 30-day mortality was 53.9%. 68% of patients had multi-vessel coronary disease. Median pre-PCI BCIS-1 myocardial jeopardy scores were 8 [6-10]. After multiple logistic regression increasing age (p = 0.008; odds ratio [OR] 1.06), lactate values (p = 0.017; OR 1.02), mechanical ventilation (p = 0.011; OR 1.25) and a systolic blood pressure ≤ 90 mmHg at end-case (p = 0.005; OR 1.26) were predictive of 30-day mortality. Post-PPCI culprit vessel TIMI 3 flow was associated with reduced mortality (p < 0.001; OR 0.66). There was no association between pre-PCI jeopardy scores and the primary endpoint., Conclusions: In patients with STEMI and shock, myocardial jeopardy scores do not relate to patient outcomes. Jeopardy scores may be applied to existing datasets in order to understand why multi-vessel revascularization does not lead to the anticipated clinical benefits in cardiogenic shock., Competing Interests: Declaration of competing interest The authors have no relevant conflict of interest to declare., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Although some studies found improved coronary flow and myocardial salvage when stent implantation was deferred, the DANAMI-3-DEFER (Third DANish Study of Optimal Acute Treatment of Patients With ST-elevation Myocardial Infarction) did not show any improvement in clinical outcome in patients with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI) and deferred stenting., Objectives: This study sought to evaluate the effect of deferred stent implantation on infarct size, myocardial salvage, and microvascular obstruction (MVO) in patients with STEMI., Methods: In the present DANAMI-3 substudy, a total of 510 patients with STEMI were randomized to PCI with deferred versus immediate stent implantation. The patients underwent a cardiac magnetic resonance examination before discharge after the index procedure and again 3 months later. The primary endpoint was final infarct size., Results: Deferred stenting did not reduce final infarct size (9% left ventricle [LV]; interquartile range [IQR]: 3% to 18% vs. 10% LV; IQR: 3% to 18%; p = 0.67). Similarly, deferred stenting was not associated with myocardial salvage index (66%; IQR: 50% to 89% vs. 67%; IQR: 49% to 88%; p = 0.80) or presence of MVO (43% vs. 42%; p = 0.78). In a post hoc analysis, stent length was the only subgroup of 7 that had an effect on outcome. In patients with a stent length ≥24 mm, deferred stenting reduced the final infarct size (6% LV; IQR: 2% to 18% vs. 13% LV; IQR: 7% to 23%; p = 0.006; and p for interaction = 0.005)., Conclusions: In the DANAMI-3-DEFER cardiac magnetic resonance substudy, routine deferred stenting did not reduce infarct size or MVO and did not increase myocardial salvage. These results do not support the use of routine deferred stenting in STEMI patients treated with primary PCI. (DANish Study of Optimal Acute Treatment of Patients With ST-elevation Myocardial Infarction [DANAMI-3]; NCT01435408)., (Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Importance: Ischemic postconditioning of the heart during primary percutaneous coronary intervention (PCI) induced by repetitive interruptions of blood flow to the ischemic myocardial region immediately after reopening of the infarct-related artery may limit myocardial damage., Objective: To determine whether ischemic postconditioning can improve the clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI)., Design, Setting, and Participants: In this multicenter, randomized clinical trial, patients with onset of symptoms within 12 hours, STEMI, and thrombolysis in myocardial infarction (TIMI) grade 0-1 flow in the infarct-related artery at arrival were randomized to conventional PCI or postconditioning. Inclusion began on March 21, 2011, through February 2, 2014, and follow-up was completed on February 2, 2016. Analysis was based on intention to treat., Interventions: Patients were randomly allocated 1:1 to conventional primary PCI, including stent implantation, or postconditioning performed as 4 repeated 30-second balloon occlusions followed by 30 seconds of reperfusion immediately after opening of the infarct-related artery and before stent implantation., Main Outcome and Measures: A combination of all-cause death and hospitalization for heart failure., Results: During the inclusion period, 1234 patients (975 men [79.0%] and 259 women [21.0%]; mean [SD] age, 62 [11] years) underwent randomization in the trial. Median follow-up was 38 months (interquartile range, 24-58 months). The primary outcome occurred in 69 patients (11.2%) who underwent conventional primary PCI and in 65 (10.5%) who underwent postconditioning (hazard ratio, 0.93; 95% CI, 0.66-1.30; P = .66). The hazard ratios were 0.75 (95% CI, 0.49-1.14; P = .18) for all-cause death and 0.99 (95% CI, 0.60-1.64; P = .96) for heart failure., Conclusions and Relevance: Routine ischemic postconditioning during primary PCI failed to reduce the composite outcome of death from any cause and hospitalization for heart failure in patients with STEMI and TIMI grade 0-1 flow at arrival., Trial Registration: clinicaltrials.gov Identifier: NCT01435408.

Hyperglycemia upon hospital admission in patients with ST-segment elevation myocardial infarction (STEMI) occurs frequently and is associated with adverse outcomes. It is, however, unsettled as to whether an elevated blood glucose level is the cause or consequence of increased myocardial damage. In addition, whether the cardioprotective effect of exenatide, a glucose-lowering drug, is dependent on hyperglycemia remains unknown. The objectives of this substudy were to evaluate the association between hyperglycemia and infarct size, myocardial salvage, and area at risk, and to assess the interaction between exenatide and hyperglycemia. A total of 210 STEMI patients were randomized to receive intravenous exenatide or placebo before percutaneous coronary intervention. Hyperglycemia was associated with larger area at risk and infarct size compared with patients with normoglycemia, but the salvage index and infarct size adjusting for area at risk did not differ between the groups. Treatment with exenatide resulted in increased salvage index both among patients with normoglycemia and hyperglycemia. Thus, we conclude that the association between hyperglycemia upon hospital admission and infarct size in STEMI patients is a consequence of a larger myocardial area at risk but not of a reduction in myocardial salvage. Also, cardioprotection by exenatide treatment is independent of glucose levels at hospital admission. Thus, hyperglycemia does not influence the effect of the reperfusion treatment but rather represents a surrogate marker for the severity of risk and injury to the myocardium., (© 2014 by the American Diabetes Association.)

Background: The study assessed long-term safety and efficacy of intramyocardial injection of autologous bone-marrow derived mesenchymal stromal cells (BMMSCs) in patients with severe stable coronary artery disease (CAD) and refractory angina., Methods: Thirty-one patients with severe stable CAD and refractory angina were included. Patients had reversible myocardial ischemia and no further revascularization options. Autologous BMMSCs were isolated, culture expanded and stimulated with vascular endothelial growth-factor to facilitate endothelial differentiation. BMMSCs were injected into an ischemic, viable region of the myocardium. Patients were followed for 3 years., Results: We found significant clinical improvements in exercise time (p=0.0016), angina class (CCS) (p<0.0001), weekly number of angina attacks (p<0.0001) and use of nitroglycerine from (p=0.0017). In the Seattle Angina Questionnaire there were significant improvements in physical limitation score, angina stability score, angina frequency score and quality of life score (all p<0.0001). When comparing all hospital admissions from 3 years before to 3 years after treatment, we observed highly reduced admission rates for stable angina (p<0.0001), revascularization (p=0.003) and overall cardiovascular disease (p<0.0001). No early or late side-effects of the treatment were observed., Conclusions: The final 3-year follow-up data after intramyocardial injection of autologous BMMSCs, in patients with severe CAD and refractory angina, demonstrated sustained clinical effects, reduced hospital admissions for cardiovascular disease and excellent long-term safety. The results indicate that autotransplantation of BMMSCs to the heart does not only improve symptoms but also slows down disease progression., (© 2013.)

Background: Exenatide has been demonstrated to be cardioprotective as an adjunct to primary percutaneous coronary intervention in patients with ST-segment-elevation myocardial infarction (STEMI). The aim of the post hoc analysis study was to evaluate the effect of exenatide in relation to system delay, defined as time from first medical contact to first balloon., Methods and Results: Patients with STEMI and Thrombolysis In Myocardial Infarction flow 0/1 were randomly assigned to intravenous exenatide or placebo continuous infusion. Study treatment was commenced 15 minutes before intervention and maintained for 6 hours after the procedure. The patients were stratified according to median system delay (132 minutes). Final infarct size and myocardial area at risk were measured by cardiovascular magnetic resonance. Among patients with a system delay ≤132 minutes (n=74), treatment with exenatide resulted in a smaller infarct size (9 grams [interquartile range (IQR), 4-13] versus 13 grams [IQR, 8-24], P=0.008, corresponding to 8% [IQR, 4-12] versus 11% [IQR, 7-17] of the left ventricle, P=0.015). In a regression analysis adjusting for myocardial area at risk the data points of the exenatide group lay significantly lower than for the placebo group (P=0.006). In the patients with system delay >132 minutes (n=74) no difference was observed in infarct size expressed as grams (P=0.49) or percentage (P=0.46). There was significant interaction between system delay (less than or equal to median versus greater than median) and treatment allocation in terms of infarct size (P=0.018)., Conclusions: In this post hoc analysis, exenatide treatment was associated with a 30% decrease in final infarct size in patients with short system delay, whereas no cardioprotective effect in patients with long system delay was seen. However, this finding must be confirmed in larger studies., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00835848.

Background: Ischemic postconditioning (IPost) during primary percutaneous coronary intervention (PPCI) is suggested to reduce myocardial damage. However, the association with ST-segment resolution (STR) and clinical outcome is not determined. The primary aim of this study was to evaluate the association of IPost with STR and clinical outcome. Secondly, we sought to determine the relationship between STR and cardiac magnetic resonance (CMR) parameters in these patients., Methods: One hundred eighteen patients referred for PPCI were randomly assigned to either conventional PPCI or PPCI with IPost. In a single electrocardiographic lead, STR was determined. Treatment modalities were compared as regards STR, ST-segment elevation, and the number of patients achieving complete-STR (≥70%), incomplete-STR (30%-70%), and no-STR (<30%). Patients were evaluated for clinical outcome after 15 months. Furthermore, patients with and without complete-STR were compared as regards CMR parameters., Results: There was a tendency toward a better outcome with IPost for the number of patients achieving complete-STR (55% vs 63%; P=.09), ST-segment elevation (1.41 vs 1.12 mm; P=.07), and New York Heart Association class (P=.06). No difference in other cardiac events was observed. Furthermore, data determine that patients with complete-STR have smaller infarct size (12.9% vs 21.1%; P<.01) and a better ejection fraction (55.7% vs 47.7%; P<.01)., Conclusions: Patients treated with IPost are suggested to have improved STR and New York Heart Association classification. Infarct size and the functional CMR parameters were better in the patients with complete-STR; as to this, single-lead STR remains an important predictor for successful treatment in patients treated with IPost., (Copyright © 2010 Mosby, Inc. All rights reserved.)

This pilot trial aimed to investigate the utilization of (111)In-labeling of mesenchymal stromal cells (MSC) for in vivo tracking after intramyocardial transplantation in a xenotransplantation model with gender mismatched cells. Human male MSC were expanded ex vivo and labeled with (111)In-tropolone. Ten female pigs were included. The labeled cells were transplanted intramyocardially using a percutaneous injection system. The (111)In activity was determined using gamma camera imaging. Excised hearts were analyzed by fluorescence in situ hybridization (FISH) and microscopy. Gamma camera imaging revealed focal cardiac (111)In accumulations up to 6 days after injection (N = 4). No MSC could be identified with FISH, and microscopy identified widespread acute inflammation. Focal (111)In accumulation, inflammation but no human MSC were similarly seen in pigs (N = 2) after immunosuppression. A comparable retention of (111)In activity was observed after intramyocardial injection of (111)In-tropolone (without cells) (N = 2), but without sign of myocardial inflammation. Injection of labeled non-viable cells (N = 1) also led to high focal (111)In activity up to 6 days after intramyocardial injection. As a positive control of the FISH method, we identified labeled cells both in culture and immediately after cell injection in one pig. This pilot trial suggests that after intramyocardial injection (111)In stays in the myocardium despite possible disappearance of labeled cells. This questions the clinical use of (111)In-labeled cells for tracking. The results further suggest that xenografting of human MSC into porcine hearts leads to inflammation contradicting previous studies implying a special immunoprivileged status for MSC.

Background: Knowledge of the natural course after an ST-elevation myocardial infarction (STEMI) treated according to guidelines is limited because comprehensive serial magnetic resonance imaging (MRI) of systolic left ventricular function, edema, perfusion, and infarct size after STEMI has not been undertaken. The aim of this study was to evaluate effects of therapy for STEMI on left ventricular function and perfusion and to test the hypothesis that myocardial perfusion by MRI predicts recovery of left ventricular function., Methods: Cine MRI, edema, first-pass perfusion, and late enhancement imaging were performed in 58 patients at day 2 and at 1 and 6 months after successful primary percutaneous coronary stent intervention for STEMI., Results: Ejection fraction increased 6.3% during the first month (P < .001) and 1.9% from 1 to 6 months (P < .06), indicating a maximal recovery very early after the infarction. The systolic wall thickening in the infarct area almost doubled (P < .001), the perfusion of infarcted myocardium increased approximately 50% (P = .02), and perfusion improved in 72% of patients. Edema decreased with a mean of 2 segments (P < .001) during the first month and another 2.5 segments from 1 to 6 months (P < .001). Infarct size decreased to 1 month (P = .01) and was unchanged from 1 to 6 months (P = .5). Baseline perfusion did not predict improvement in ejection fraction (r = 0.2, P = .2) but did predict regional systolic function (P = .03)., Conclusions: Left ventricular function, perfusion, and infarct mass recovered substantially after STEMI, with the main part of the change within the first month. First-pass perfusion at rest appeared to predict regional ventricular recovery.

Mobilization of stem cells into the peripheral circulation for myocardial regeneration using subcutaneous injections of granulocyte-colony-stimulating factor (G-CSF) has been tested in both patients with acute myocardial infarction (AMI) and patients with chronic myocardial ischaemia. G-CSF treatment seems to be safe and unblinded trials in patients with AMI were encouraging. However, larger double-blind placebo-controlled trials have not been able to demonstrate effect of G-CSF treatment. In patients with chronic myocardial ischaemia, small-unblinded G-CSF trials did not show effect on myocardial perfusion and function. In both patient populations, G-CSF did mobilize stem cells of known importance to myocardial regeneration, but there seemed to be a general lack of homing of the stem cells into the ischaemic myocardium. In AMI, factors of importance to homing of stem cells, stem cell derived factor-1, are maximally elevated in plasma 3 weeks after infarction, suggesting that this time point could be the optimal time for stem cell mobilization treatment. The known complex interaction of stem cells and cytokines for induction of vasculogenesis should be implemented in future clinical trials, to elucidate whether G-CSF mobilization of stem cells might be useful as a new regenerative treatment in patients with ischaemic heart disease.

Background--Pathological early Q waves (QW) are associated with adverse outcomes in patients with ST-segment-elevation myocardial infarction (STEMI). Primary percutaneous coronary intervention (PCI) may therefore be less beneficial in patients with QW than in patients without QW. Myocardial salvage index and microvascular obstruction (MVO) are markers for reperfusion success. Thus, to clarify the benefit from primary PCI in STEMI patients with QW, we examined the association between baseline QW and myocardial salvage index and MVO in STEMI patients treated with primary PCI. Methods and Results--The ECG was assessed before primary PCI for the presence of QW (early) in 515 STEMI patients. The patients underwent a cardiac magnetic resonance imaging scan at day 1 (interquartile range [IQR], 1-1) and again at day 92 (IQR, 89-96). Early QW was observed in 108 (21%) patients and was related to smaller final myocardial salvage index (0.59 [IQR, 0.39-0.69] versus 0.65 [IQR, 0.46-0.84]; P<0.001) and larger MVO (1.4 [IQR, 0.0-5.4] versus 0.0 [IQR, 0.0-2.4]; P<0.001) compared with non-QW. QW remained associated with both final myocardial salvage index (β=-0.12; P=0.03) and MVO (β=0.18; P=0.001) after adjusting for potential confounders. Conclusions--Patients presenting with their first STEMI and early QW in the ECG had smaller myocardial salvage index and more extensive MVO than non-QW despite treatment within 12 hours after symptom onset. However, final myocardial salvage index in patients with QW was substantial, and patients with QW still benefit from primary PCI. [ABSTRACT FROM AUTHOR]

The article evaluates the effect of ischemic postconditioning applied during primary percutaneous coronary intervention (PCCI) on the final infarct size using cardiac magnetic resonance (CMR). It is hypothesized that viable cardiomyocytes will benefit from postconditioning as long as they exist in the ischemic myocardium at the time of reperfusion. It is also suggested that myocardial damage during PCCI in patients with ST-segment-elevation myocardial infarction is reduced by postconditioning.