Injury In ST-elevation Myocardial Infarction Research Articles

Combined activation of complement and coagulation is associated with myocardial injury in ST-elevation myocardial infarction

Abstract Introduction Experimental data indicates that the complement system and the coagulation cascade can activate each other. The magnitude of this interaction in acute myocardial infarction is not known. We aimed to investigate a possible association between complement activation and coagulation activation in patients with acute ST-elevation myocardial infarction (STEMI), as well as how they relate to myocardial injury estimated by troponin T (TnT) and myocardial function assessed by echocardiography. Purpose To increase the understanding of the interaction between complement activation and coagulation activation in STEMI, and the clinical relevance to myocardial injury. Methods Blood samples were drawn after percutaneous coronary intervention (PCI) in 864 patients with STEMI. Myocardial function was measured as left ventricular ejection fraction (LVEF), estimated by visual approximation or Simpson biplane method within 3 months. Complement activation was assessed by ELISA of circulating levels of the terminal complement complex (TCC). Activation of coagulation was assessed by ELISA of prothrombin fragment 1+2 (F1+2) and D-dimer, and endogenous thrombin potential (ETP), analyzed by calibrated automated thrombogram assay. Results TCC was weakly correlated to F1+2 (r=0.086, p=0.012), D-dimer (r=0.176, p<0.001) and ETP (r=0.144, p<0.001). In univariate linear regression analysis, this association persisted for D-dimer and ETP. When adjusting for associated covariables, the association only persisted for ETP (Table 1). Patients with above-median TCC and D-dimer had significantly higher peak TnT (Figure 1). In logistic regression, having combined above-median TCC and D-dimer was predictive of an LVEF ≤40% (Table 2). Conclusion In this large STEMI cohort, complement activation by TCC was weakly associated with coagulation activation. Combined high levels of TCC and D-dimer were linked to higher peak TnT and lower LVEF, possibly reflecting greater myocardial injury. The interaction between complement and coagulation activation might be relevant for clinical outcomes in STEMI patients and warrants further investigation.

Effect of ischaemic postconditioning on markers of myocardial injury in ST-elevation myocardial infarction: a meta-analysis

ObjectivesThis study aimed to perform a meta-analysis of the short-term impact of ischaemic postconditioning (IPoC) on myocardial injury in ST elevation myocardial infarction (STEMI) using surrogate cardiac biomarkers.MethodsEligible studies were...

Cytokine pattern in patients with ST-elevation myocardial infarction treated with the interleukin-6 receptor antagonist tocilizumab

BackgroundTocilizumab improves myocardial salvage index (MSI) in patients with ST-elevation myocardial infarction (STEMI), but its mechanisms of action are unclear. Here, we explored how cytokines were affected by tocilizumab and...

Predictive Value of the Naples Prognostic Score for Acute Kidney Injury in ST-Elevation Myocardial Infarction Patients Undergoing Primary Percutaneous Coronary Intervention.

The purpose of this investigation was to investigate whether there was an association between the Naples prognostic score and the development of acute kidney injury (AKI) in ST-elevation myocardial infarction (STEMI) patients following primary percutaneous coronary intervention (pPCI). The study comprised 2901 consecutive STEMI patients who had pPCI. For each patient, the Naples prognostic score was determined. To evaluate the predictive performance of the Naples score (which included either continuous and categorical variables), we developed a Nested model and a nested model combined with the Naples score. The Naples prognostic score was the most significant predictor of AKI occurrence after admission creatinine, age, and contrast volume. The continuous Naples prognostic score model provided the best prediction performance and discriminative ability. The C-index of the Nested and full models with continuous Naples prognostic score were significantly higher than that of the Nested model. The decision curve analysis found that the overall model had a higher full range of probability of clinical net benefit than the baseline model, with a 10% AKI likelihood. The present study found that the Naples prognostic score may be useful to predict the risk of AKI in STEMI patients undergoing pPCI.

Complement activation in association with clinical outcomes in ST-elevation myocardial infarction

IntroductionThe complement system and neutrophil extracellular traps (NETs) might contribute to ischemia-reperfusion injury in ST-elevation myocardial infarction (STEMI). We aimed to estimate associations between complement activation and NETs in STEMI, and their prognostic value on clinical endpoints. MethodsIn this cohort study, 864 patients admitted for PCI during STEMI were included. Complement activation was analyzed by the terminal complement complex (TCC), while NETs were analyzed by myeloperoxidase-DNA, citrullinated histone 3 (CitH3) and dsDNA. The composite endpoint was reinfarction, unscheduled revascularization, stroke, hospitalization due to heart failure, or death, and the secondary endpoint was total mortality. The association between TCC and clinical endpoints was assessed by Cox regression and ROC curve analysis. ResultsTCC was weakly correlated to dsDNA (r = 0.127, p < 0.001) and CitH3 (r = 0.102, p = 0.003). After a median follow-up time of 4.6 years, 184 (21.3 %) patients had reached a clinical endpoint. TCC was not associated with the composite endpoint, but with total mortality (HR: 1.673, 95 % CI: [1.014, 2.761], p = 0.044). The significant association was lost when adjusting for CRP, NT-proBNP, LVEF and time from symptoms to PCI. In ROC curve analysis of total mortality, the AUC for TCC alone was 0.549 (95 % CI: [0.472, 0.625]), AUC for dsDNA alone was 0.653 (95 % CI: [0.579, 0.720]), while AUC for TCC and dsDNA combined was 0.660 (95 % CI: [0.590, 0.730]). ConclusionsIn this STEMI cohort, TCC was not associated with the composite endpoint, but somewhat with total mortality. Combining TCC and dsDNA did not increase the prognostic value compared to dsDNA alone.

The role of IL-6 receptor trans-signalling in ischemia-reperfusion injury, infarct healing and future adverse events in patients with ST-Elevation Myocardial Infarction

Abstract Background Inflammation has emerged as a new treatment target in patients with coronary artery disease, and inflammation seems to play an important role in the ischemia/reperfusion injury in ST-elevation myocardial infarction (STEMI). The pro-inflammatory cytokine interleukin-6 (IL-6) has been shown to be associated with myocardial injury and poor prognosis in patients with STEMI. Purpose The aim of the study was to further elucidate possible associations between the IL-6 trans-signalling system and final infarct size, myocardial function, adverse remodelling, and future cardiovascular events in patients with STEMI. Methods A total of 272 patients with first-time STEMI included in the POSTEMI study on ischaemic postconditioning, with symptom duration &amp;lt;6 hours and treated with percutaneous coronary intervention (PCI), were included. Blood samples for analysis of IL-6 and IL-6 receptor (IL-6R) were collected before PCI, immediately after PCI, at day 1 (median 18.3 hours after PCI), and at 4 months follow-up. Cardiac magnetic resonance imaging (CMR) was performed in the acute phase, median 2 days after admission, and repeated after 4 months. Clinical events and all-cause mortality were registered during 12 months' and 70 months' follow-up, respectively. Results There was a significant increase in IL-6 levels from admission to day 1 with a subsequent decline from day 1 to 4 months (Figure 1A). No significant change in IL-6R levels were found from admission to day 1 (Figure 1B). There was no difference between patients treated by postconditioning compared to routine PCI. High levels of IL-6 (&amp;gt; median) at all sampling points were significantly associated with increased infarct size and reduced left ventricular ejection fraction (LVEF) measured by CMR. Additionally, high levels of IL-6 (&amp;gt; median) at day 1 were associated with lower myocardial salvage, more presence of microvascular obstruction and larger increase in indexed LV end diastolic volume (LVEDVi). IL-6R measured during hospitalisation was significantly associated with change in LVEDVi, but did not associate with infarct size, LVEF or myocardial salvage. High levels of IL-6 (&amp;gt;75th percentile) at all sampling points were associated with an increased risk of having an adverse clinical event during the first year and with long-term all-cause mortality (Figure 2), whereas there was no association between IL-6R and adverse clinical events. Conclusion Patients with high IL-6 levels during the acute phase of STEMI had larger infarct size, reduced myocardial salvage, reduced LV function and worse clinical outcome than patients with lower levels of IL-6. High levels of IL-6 measured after 4 months were associated with larger infarct size, reduced LVEF and increased all-cause mortality. IL-6R was significantly associated with increase in LVEDVi. The results add important information to the role of IL-6 in myocardial injury in acute STEMI and the IL-6 pathway as a potential treatment target. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Stein Erik Hagen Foundation for Clinical Heart Research, Oslo, Norway. Figure 1Figure 2

Arginase 1 is upregulated at admission in patients with ST-elevation myocardial infarction.

The mechanisms underlying rupture of a coronary atherosclerotic plaque and development of myocardial ischemia-reperfusion injury in ST-elevation myocardial infarction (STEMI) remain unresolved. Increased arginase 1 activity leads to reduced nitric oxide (NO) production and increased formation of reactive oxygen species due to uncoupling of the NO-producing enzyme endothelial NO synthase (eNOS). This contributes to endothelial dysfunction, plaque instability and increased susceptibility to ischemia-reperfusion injury in acute myocardial infarction. The purpose of this study was to test the hypothesis that arginase gene and protein expression are upregulated in patients with STEMI. Two cohorts of patients with STEMI were included. In the first cohort (n = 51), expression of arginase and NO-synthases as well as arginase 1 protein levels were determined and compared to a healthy control group (n = 45). In a second cohort (n = 68), plasma arginase 1 levels and infarct size were determined using cardiac magnetic resonance imaging. Expression of the gene encoding arginase 1 was significantly elevated at admission and 24-48 h after STEMI but not 3 months post STEMI, in comparison with the control group. Expression of the genes encoding arginase 2 and endothelial NO synthase (NOS3) were unaltered. Arginase 1 protein levels were elevated at admission, 24 h post STEMI and remained elevated for up to 6 months. No significant correlation between plasma arginase 1 protein levels and infarct size was observed. The markedly increased gene and protein expression of arginase 1 already at admission indicates a role of arginase 1 in the development of STEMI.

East Asian variant aldehyde dehydrogenase type 2 genotype exacerbates ischemia/reperfusion injury with ST-elevation myocardial infarction in men: possible sex differences.

Mitochondrial aldehyde dehydrogenase 2 (ALDH2) detoxifies toxic aldehydes generated during ischemia/reperfusion (I/R) injury in ST-elevation myocardial infarction (STEMI). The deficient variant ALDH2 genotype (ALDH2*2) is prevalent among East Asians. Whether ALDH2*2 exacerbates I/R injury of in patients with STEMI is not known. The study subjects comprised 218 Japanese patients with STEMI (158 men and 60 women, mean age 67.9 ± 11.9) who underwent successful percutaneous coronary intervention. Of these, 120 (55.0%) were the carriers of variant ALDH2*2 and 98 (45.0%) those of wild ALDH2*1/*1 on genotyping. There were no differences in clinical characteristics between the ALDH2*2 and ALDH2*1/*1 group except lower alcohol habit (14.2% vs 46.3%, P < 0.001) in the ALDH2*2 group. The peak plasma levels of creatine phosphokinase myocardial binding (CKMB), a marker of myocardial injury, however, were significantly higher in the patients with ALDH2*2 than in those with ALDH2*1/*1 [a median 275.0 (175.8-407.5) vs 177.5 (126.9-344.3) U/L, P = 0.001] among men but not among women (P = 0.811). There was a significant interaction between men (male sex) and ALDH2*2 for I/R injury (χ2 = 4.425, P = 0.040). The variant ALDH2*2 was associated with more severe I/R injury than the wild ALDH2*1/*1 in STEMI patients in men with possible sex differences.

Beclin-1 overexpression regulates NLRP3 activation by promoting TNFAIP3 in microvascular injury following myocardial reperfusion

Innate immune response contributes significantly to ischemia reperfusion (I/R) injury. Targeting innate immunity seems to be a promising method for protecting the microvascular injury in ST-elevation myocardial infarction (STEMI) patients following myocardial I/R injury (MI/R). NLRP3 inflammasome is a central part of the innate immune system involved in the pathophysiological process of MI/R. However, the mechanisms regulating NLRP3 activation are yet to be clarified. Recently, autophagy has been related to the regulation of NLRP3 activation. Thus, how Beclin-1/Becn1 overexpression influences NLRP3 activation in microvascular endothelial cells (CMECs) after MI/R is yet to be investigated. The present study showed that Becn1 overexpression exhibits a significant increase in NLRP3 and IL-1β in CMEC responses to MI/R. Interestingly, Becn1 overexpression promoted TNFAIP3 expression, which restricted NLRP3 activation in vitro and in vivo. The current study also showed that inflammatory cells (CD68) and B (CDB220) lymphocytes were decreased in transgenic mice with overexpression of Beclin-1 (BECN1-Tg) in the spleen and heart. These findings highlighted Becn1 as a prospective target for treating NLRP3 mediated microvascular injury following MI/R.

Myocardial Extracellular Volume Fraction Allows Differentiation of Reversible Versus Irreversible Myocardial Damage and Prediction of Adverse Left Ventricular Remodeling of ST‐Elevation Myocardial Infarction

The relationship between dynamic changes of myocardial injury in ST-elevation myocardial infarction (STEMI) patients and long-term prognosis is still unclear. To evaluate the extracellular volume fraction (ECV) in the differentiation of reversible from irreversible myocardial injury and the prediction value of left ventricular adverse remodeling in patients with STEMI after reperfusion. Prospective. Twenty-four STEMI patients after reperfusion were included FIELD STRENGTH/SEQUENCE: 3.0 T, T1 mapping, ECV, T2 -STIR, and late gadolinium enhancement (LGE). All the patients underwent cardiac MRI at four timepoints (days 1, 3, and 7, and at 6 months). The regions of interest (ROIs) were selected at the infarcted myocardium (with/without intramyocardial hemorrhage [IMH] and microvascular obstruction [MVO]). One-way analysis of variance and the Kruskal-Wallis test were used for the statistical analysis. Native T1 of MI (without MVO/IMH) gradually decreased after reperfusion (P < 0.05). The ECV of MI increased during the first 3 days and then slowly declined. Native T1 of MI with MVO/IMH was the lowest (1184 msec; 1108.5-1266), while ECV (78%; 65.5-87%) was the highest, P < 0.001. Native T1 and ECV of salvageable myocardium were higher than those of the remote myocardium but lower than those of the MI without MVO or IMH (P < 0.001). ROC analysis revealed an area under the curve (AUC) of ECV (0.85, P < 0.001) for differentiating infarcted and salvageable myocardium was higher than that of native T1 mapping (AUC: 0.63, P < 0.001) in the first week after STEMI (P < 0.0001). T1 and ECV differed significantly between patients with and without left ventricle adverse remodeling (P < 0.05). Dynamic temporal changes in reversibly and irreversibly damaged myocardia were differentiated via native T1 and ECV mapping after primary percutaneous coronary intervention in STEMI patients. ECV may better reflect microvascular injury severity and myocardial viability. MI with higher native T1 and ECV or with severe microvascular injury (MVO and IMH) was correlated with adverse LV remodeling. 2 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2020. J. Magn. Reson. Imaging 2020;52:476-487.

P6599Upregulation of protein and gene expression of arginase-1 in patients with ST elevation myocardial infarction

Abstract Background The mechanisms underlying rupture of a coronary atherosclerotic plaque and development of myocardial ischemia-reperfusion injury in ST-elevation myocardial infarction (STEMI) remain unknown. Increased arginase-1 activity leads to reduced nitric oxide production and increased formation of reactive oxygen species due to uncoupling of the endothelial nitric oxide synthase (eNOS). These events lead to endothelial dysfunction, plaque instability and increased susceptibility to ischemia-reperfusion injury in acute myocardial infarction. Experimental studies have shown that arginase-1 expression and activity are increased in atherosclerosis and during myocardial ischemia-reperfusion. Accordingly, inhibition of arginase-1 reduces atherosclerotic lesion development and limits the extent of infarct size during ischemia-reperfusion via an eNOS-dependent mechanism. Furthermore, arginase-1 inhibition improves endothelial function in patients with coronary artery disease but the potential role of arginase-1 in patients with STEMI is poorly understood. Purpose The purpose of the current study was to test the hypothesis that arginase-1 is upregulated and correlate to infarct size in STEMI patients. Methods and results Two independent cohorts of STEMI patients were included. In cohort 1, plasma and buffy coat leukocytes were collected from 53 STEMI patients at the time of arterial puncture for percutaneous coronary intervention, at 24–48 hours post STEMI and at 3 months post STEMI. Gene expression in leukocytes was determined in 51 patients with Affymetrix Human Transcriptome Array 2.0. In cohort 2, plasma was collected from 82 STEMI patients at admission and at 6 months for determination of plasma arginase-1. These patients underwent cardiac magnetic resonance imaging performed at day 4–7 and at 6 months post STEMI. Plasma arginase-1 levels were quantified with ELISA. Control blood samples were collected from 56 healthy age matched subjects. In cohort 1, ARG1 gene expression was four-fold higher in STEMI patients at admission compared to controls (Figure A). This expression returned to control levels within 3 months. Plasma arginase-1 levels were two times higher in STEMI patients at admission compared to controls, and remained elevated at 24–48 hours and at 3 months post STEMI (Figure B). The increase in plasma arginase-1 in STEMI patients was confirmed in cohort 2 (Figure C). Arginase-1 levels did not correlate with infarct size. Conclusions STEMI patients demonstrate increased gene expression and plasma levels of arginase-1 in the acute setting. In contrast to gene expression plasma arginase-1 levels remain significantly elevated over time. The markedly increased expression of arginase-1 already at admission may suggest a mechanistic role of arginase-1 in the development of STEMI. Further studies are needed to elucidate whether increased expression, induction and activity of arginase-1 are contributing factors for the development of STEMI.

Remote ischemic conditioning protects against endothelial ischemia-reperfusion injury via a glucagon-like peptide-1 receptor-mediated mechanism in humans

BackgroundRemote ischemic conditioning (RIC), i.e. short cycles of ischemia and reperfusion in remote tissue, is a novel approach to protect against myocardial ischemia-reperfusion injury in ST-elevation myocardial infarction. The nature of the factors transmitting the protective effect of RIC remains unknown, and both neuronal and hormonal mechanisms appear to be involved. A recent study indicated involvement of glucagon-like peptide-1 (GLP-1) regulated by the vagal nerve in RIC in rats. In the present study we aimed to investigate whether the protective effect of RIC is mediated by a GLP-1 receptor-dependent mechanism in humans. MethodsEndothelial function was determined from flow-mediated dilatation (FMD) of the brachial artery before and after 20 min of forearm ischemia and 20 min of reperfusion in twelve healthy subjects on three occasions: (A) ischemia-reperfusion without intervention, (B) ischemia-reperfusion + RIC and (C) iv administration of the GLP-1 receptor antagonist exendin(9-39) + ischemia-reperfusion + RIC. ResultsIschemia-reperfusion reduced FMD from 4.7 ± 0.8% at baseline to 1.5 ± 0.4% (p < 0.01). RIC protected from the impairment in FMD induced by ischemia-reperfusion (4.6 ± 1.1% at baseline vs. 5.0 ± 1.1% following ischemia-reperfusion). Exendin(9-39) abolished the protection induced by RIC (FMD 4.9 ± 0.9% at baseline vs. 1.4 ± 1.3% following ischemia-reperfusion; p < 0.01) but did not affect basal FMD. Plasma GLP-1 levels did not change significantly between examinations. ConclusionThe present study is the first to suggest that RIC protects against endothelial ischemia-reperfusion injury via a GLP-1 receptor-mediated mechanism in humans.

Short-term coronary physiology parameters evolution in acute coronary syndrome patients with multivessel disease treated with ticagrelor

Ticagrelor increases adenosine plasma concentration in acute coronary syndrome patients (ACS) by inhibiting adenosine uptake by red blood cells. Besides, ticagrelor treatment might be more effective than clopidogrel in reducing microvascular injury in ST-elevation myocardial infarction (STEMI) patients. However, the effects of ticagrelor on coronary physiology parameters in ACS patients with multivessel disease (MVD) remain uncertain. We designed a prospective study to assess the effects of ticagrelor treatment on microvascular resistance in ASC patients with MVD. Ten consecutive non-STE-ASC patients with no prior ticagrelor treatment and MVD, defined as the presence of at least one significant (> 50%) lesion in a non-infarct related artery, underwent intracoronary physiology parameters assessment immediately after primary percutaneous coronary intervention (PCI) of the culprit lesion. A second series of measurements was performed after 72 hours of ticagrelor treatment. The primary endpoint was the index of microvascular resistance (IMR) in a non-infarct related artery. The secondary endpoints were IMR in the culprit artery and the fractional flow reserve (FFR) both in a non-infarct related artery and in the culprit artery. IMR measured in a non-infarct related artery was significantly lower after 72 h of ticagrelor treatment (19.2 ± 11.2 vs. 14.2 ± 7.4, P = 0.02) whereas IMR in the culprit artery was not significantly different from baseline (13.1 ± 4.1 vs. 18.7 ± 11.4, P = 0.13). FFR measurements were not significantly different after ticagrelor treatment both in the non-infarct related artery and in the culprit artery after primary PCI (85 ± 0.15 vs. 0.86 ± 0.17, P = 0.80 and 0.98 ± 0.04 vs. 0.98 ± 0.04, P = 0.56 respectively) ( Table 1 ). Ticagrelor decreases microvascular resistance in non-infarct related artery in ASC patients with MVD.

Correlation between the Level of Serum Free Triiodothyronine and the Degree of Myocardial Injury in Patients with Acute ST Segment Elevation Myocardial Infarction

Background: Previous studies have suggested that hypothyroidism correlated with coronary artery diseases (CAD) mortality in long-term cohort studies, but whether the thyroid function status is associated with myocardial injury in acute ST-elevation myocardial infarction (STEMI) has not been investigated sufficiently. Aim: We aimed to investigate whether the lower free triiodothyronine level in acute STEMI is associated with more severe myocardial injury. Methods: This was a prospective observation cohort study that was conducted from August 2016 to April 2017 and included 50 patients presented to the coronary care Unit in Al Mataryia teaching hospital with acute STEMI and treated with thrombolysis. All patients were subjected to complete clinical assessment, serial ECGs, Echo, full labs, thyroid hormones, cardiac biomarkers, C-reactive protein (CRP). Results: There were 8 patients (16%) who had hypothyroidism including low-T3-syndrome (4 patients, 8%), subclinical hypothyroidism (3 patients, 6%) and clinical hypothyroidism (1 patient, 2%). After adjusting for conventional risk factors (age, gender, smoking, diabetes mellitus, dyslipidemia, hypertension), free triiodothyronine (FT3) was significantly and negatively correlated with CKMB (r=-0.294, P=0.038), cTnI (r=-0.368, P=0.009), and positively correlated with EF (r=0.385, P=0.006), indicating that the lower thyroid hormone level correlates with the more severe cardiac injury in STEMI patients. FT3 also had a negative correlation with CRP (r=-0.404, P=0.004), which might indicate that hypothyroidism may activate the inflammation response. Conclusion: The lower FT3 level correlates with higher level of cardiac biomarkers and lower left ventricular ejection fraction (LVEF), Low T3 syndrome may be a predictor for myocardial injury in STEMI. These results may warrant further study to investigate whether reversing the hypothyroidism could benefit the STEMI patients.

Relationship Between Glucose Fluctuations and ST-Segment Resolution in Patients With ST-Elevation Acute Myocardial Infarction.

This study was conducted to assess whether any relationships exist between glucose fluctuations and electrocardiographic surrogate markers of reperfusion injury in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI).We prospectively studied 63 consecutive patients with STEMI undergoing primary PCI. Patients had either diabetes (n = 30), impaired glucose tolerance (n = 26), impaired fasting glucose (n = 1), or normal glucose tolerance (n = 6). STsegment resolution (STR, %) was measured using electrocardiograms recorded 60 minutes after PCI. STR was categorized as ≥ 30% and < 30%. Glucose fluctuations were assessed by the following parameters obtained from a continuous glucose monitoring system: mean amplitude of glucose excursion (MAGE, mg/dL); and area under curve with reference to mean blood glucose (AUCMBG, mg/ dL/day).Both MAGE and AUCMBG were significantly higher in STR < 30%. In univariate analysis, MAGE ≥ 70 mg/dL (OR = 17.0; 95%CI, 1.93-150.12; P < 0.01), AUCMBG ≥ 20 mg/dL/day (OR = 10.9; 95%CI, 1.92-61.77; P < 0.01), and reperfusion arrhythmias (OR = 7.6; 95%CI, 1.32-44.29; P < 0.05) were significantly associated with suboptimal STR. Multiple logistic regression analysis showed only MAGE ≥ 70 mg/dL was predictive of suboptimal STR (OR = 22.5; 95%CI, 2.43-208.66, P < 0.01).Parameters of glucose fluctuations correlated with electrocardiographic surrogate markers of impaired myocardial salvage in STEMI after reperfusion therapy. Our results suggest that glucose fluctuations may represent a potential therapeutic target to reduce myocardial reperfusion injury in STEMI.

Effect of supplemental oxygen exposure on myocardial injury in ST-elevation myocardial infarction

ObjectiveSupplemental oxygen therapy may increase myocardial injury following ST-elevation myocardial infarction (STEMI). In this study, we aimed to evaluate the effect of the dose and duration of oxygen exposure on...

Abstract 16276: A Web-based Tool for Predicting Acute Kidney Injury in ST-elevation Myocardial Infarction

ST-elevation myocardial infarction (STEMI) requires emergent diagnostic catheterization and therapeutic percutaneous coronary intervention. These therapies may cause acute kidney injury (AKI), a serious procedural complication that contributes to morbidity and mortality in STEMI patients. Identifying patients at risk for renal complications may save lives and reduce healthcare costs, but there is no validated tool for predicting AKI in STEMI patients. Methods: The UT-Methodist STEMI program is a racially diverse series of 1144 consecutive patients. We derived and validated the UT-AKI score to predict the risk of AKI in patients referred for STEMI (and not currently on dialysis). AKI was categorized by the modified AKI Network and RIFLE indices. The UT-AKI score was derived from logistic regression analysis performed on a randomly selected derivation dataset using variables with significant univariate relationships to AKI and markers of renal function. Receiver operator characteristic (ROC) curves for the UT-AKI were assessed in the derivation and validation datasets. Statistical significance was measured by appropriate parametric and non-parametric tests; a p&lt;0.05 was considered significant. Results: The incidence of AKI was similar in patients undergoing diagnostic catheterization with or without PCI (12% vs. 14%, p=0.34). ROC curve analysis of the validation data set showed that the UT-AKI score (AUC 0.76 (95% CI 0.70-0.82)) was significantly better at classifying patients at risk for AKI than the ACEF (AUC 0.65 (95% CI: 0.58-0.73)), AGEF (AUC 0.65 (95% CI: 0.58-0.72)), or Mehran (AUC 0.67 (95% CI: 0.59-0.75)). The classification accuracy for the UT-AKI index was comparable for milder and severe forms of AKI. Conclusions: In the largest analysis of STEMI patients to date, we found no significant difference in the risk of AKI from PCI vs. diagnostic catheterization. The validation study indicates that the UT-AKI index was significantly better than other scores at classifying which patients will develop AKI. Accurate prediction of AKI may help physicians to personalize therapies and develop novel strategies to reduce kidney injury in patients with STEMI.

ST-segment depression resolution predicts infarct size and reperfusion injury in ST-elevation myocardial infarction

ObjectiveST-elevation myocardial infarction (STEMI) is frequently associated with reciprocal ST-segment depression in contralateral ECG leads. However, the relationship of the resolution of ST-segment depression (STD-R) with myocardial damage is unknown...

Effects of intracoronary melatonin on ischemia-reperfusion injury in ST-elevation myocardial infarction.

Acute coronary occlusion is effectively treated by primary percutaneous coronary intervention. However, myocardial ischemia-reperfusion injury is at the moment an unavoidable consequence of the procedure. Oxidative stress is central in the development of ischemia-reperfusion injury. Melatonin, an endogenous hormone, acts through antioxidant mechanisms and could potentially minimize the myocardial injury. The aim of the experimental study was to examine the cardioprotective effects of melatonin in a porcine closed-chest reperfused infarction model. A total of 20 landrace pigs were randomized to a dosage of 200 mg (0.4 mg/mL) melatonin or placebo (saline). The intervention was administered intracoronary and intravenous. Infarct size, area at risk and microvascular obstruction were determined ex vivo by cardiovascular magnetic resonance imaging. Myocardial salvage index was calculated. The plasma levels of high-sensitive troponin T were assessed repeatedly. The experimenters were blinded with regard to treatment regimen. Melatonin did not significantly increase myocardial salvage index compared with placebo [melatonin 21.8% (16.1; 24.8) vs. placebo 20.2% (16.9; 27.0), p = 1.00]. The extent of microvascular obstruction was similar between the groups [melatonin 3.8% (2.7; 7.1) vs. placebo 3.7% (1.3; 7.7), p = 0.96]. The area under the curve for high-sensitive troponin T release was insignificantly reduced by 32% in the melatonin group [AUC melatonin 12,343.9 (6,889.2; 20,147.4) ng h/L vs. AUC placebo 18,285.3 (5,180.4; 23,716.8) ng h/L, p = 0.82]. Combined intracoronary and intravenous treatment with melatonin did not reduce myocardial reperfusion injury. The lack of a positive effect could be due to an ineffective dose of melatonin, a type II error or the timing of administration.

The assessment of relationship between fragmented QRS complex and left ventricular wall motion score index in patients with ST elevation myocardial infarction who underwent primary percutaneous coronary intervention.

Fragmented QRS (fQRS) has been found to be associated with high mortality and arrhythmic events in acute coronary syndromes. Regional systolic function using wall motion score index (WMSI) is an alternative to left ventricular ejection fraction (LVEF) for the assessment of left ventricular systolic function. The aim of this study was to investigate the relation between the presence of fQRS on admission electrocardiogram (ECG) and WMSI in ST elevation myocardial infarction (STEMI) underwent primary coronary intervention (PCI). The in-hospital and long-term prognostic significance of persistent fQRS was also evaluated. In this retrospective study, 542 patients with a diagnose of STEMI underwent primary PCI were included. Study patients were divided into two groups according to the presence (n = 153) or absence (n = 389) of a fQRS on admission ECG. WMSI was found to be significantly higher in fQRS(+) group compared to the fQRS(-) group (P<0.001). In multivariete analysis, WMSI was found to be an independent predictor of fQRS, and fQRS was inversely associated with LVEF. The in-hospital reinfarction (P=0.003), MACE (P=0.024), intraaortic balloon pump use (P=0.014), and advanced heart failure (P<0.001) were found to be significantly more frequent in the fQRS(+) group. The presence of fQRS on admission was found to be associated with an increase in long-term cardiovascular mortality (P=0.028), and long-term all-cause mortality (P=0.022). WMSI was significantly related with the presence of the fQRS, which reflects the linking between impairment of regional left ventricular systolic function and the presence of severe myocardial injury in STEMI.