Experimental evidence suggests that exenatide, a glucagon-like peptide 1 receptor analogue, has significant cardiovascular protective effects in various conditions. We examined whether routine use of ...exenatide at the time of primary percutaneous coronary intervention would reduce infarct size in patients with ST-segment-elevation myocardial infarction.
Fifty-eight patients with ST-segment-elevation myocardial infarction and thrombolysis in myocardial infarction flow 0 were enrolled in the study and randomly assigned to receive either exenatide or placebo (saline) subcutaneously. Infarct size was assessed by measuring the release of creatine kinase-MB and troponin I during 72 hours and by performing cardiac magnetic resonance imaging at 1 month after infarction. Routine and speckle tracking echocardiography was performed at initial presentation and at 3 days and 6 months after primary percutaneous coronary intervention. The exenatide and control groups had similar results with respect to ischemia time, demographic characteristics, and ejection fraction before primary percutaneous coronary intervention. The releases of creatine kinase-MB and troponin I were significantly reduced in the exenatide group. In 58 patients evaluated with cardiac magnetic resonance, the absolute mass of delayed hyperenhancement was significantly reduced in the exenatide group as compared with the control group (12.8±11.7 versus 26.4±11.6 g; P<0.01). At 6 months, the exenatide group showed a significantly lower value of E/E' with improved strain parameters. No significant adverse effects of exenatide administration were detected.
In patients with ST-segment-elevation myocardial infarction, adjunctive exenatide therapy with primary percutaneous coronary intervention was associated with reduction of infarct size and improvement of subclinical left ventricular function.
Soluble suppression of tumorigenicity 2 (sST2), a biomarker representing myocardial fibrosis and inflammation, has been applied in risk stratification of patients with myocardial infarction (MI). ...However, whether primary PCI (PPCI) will eliminate the predictive value of sST2 in STEMI patients has not been well studied. Here, we conducted a prospective clinical trial to evaluate the correlation between sST2 and prognosis in STEMI patients undergoing PPCI. sST2 levels were measured in 295 STEMI patients (60.2 ± 10.8 years) at admission using a high sensitivity assay. Baseline sST2 levels were significantly associated with heart function, biomarkers of inflammation, and myocardial injury. During a 12-month follow-up, 19 patients had major adverse cardiovascular events (MACEs). Greater sST2 was continuously associated with a higher risk of incident MACEs. Such association remained even after adjusting for other risk factors in a multivariate Cox analysis. A baseline sST2 level in the highest quartile (≥ 58.7 ng/mL) was independently associated with mortality (HR: 5.01, 95%CI: 1.02-16.30, P = 0.048). More incident heart failure was seen in the group with greater sST2, however, the association was not significant after adjustment. Therefore, baseline sST2 may be useful to predict MACEs, especially mortality, in STEMI patients receiving PPCI.
Among patients with clinically manifest vascular disease, the risk of recurrent vascular events is likely to vary. We assessed the distribution of estimated 10-year risk of recurrent vascular events ...in a secondary prevention population. We also estimated the potential risk reduction and residual risk that can be achieved if patients reach guideline-recommended risk factor targets.
The SMART score (Second Manifestations of Arterial Disease) for 10-year risk of myocardial infarction, stroke, or vascular death was applied to 6904 patients with vascular disease. The risk score was externally validated in 18 436 patients with various manifestations of vascular disease from the TNT (Treating to New Targets), IDEAL (Incremental Decrease in End Points Through Aggressive Lipid Lowering), SPARCL (Stroke Prevention by Aggressive Reduction in Cholesterol Levels), and CAPRIE (Clopidogrel Versus Aspirin in Patients at Risk of Ischemic Events) trials. The residual risk at guideline-recommended targets was estimated by applying relative risk reductions from meta-analyses to the estimated risk for targets for systolic blood pressure, low-density lipoprotein cholesterol, smoking, physical activity, and use of antithrombotic agents.
The external performance of the SMART risk score was reasonable, apart from overestimation of risk in patients with 10-year risk >40%. In patients with various manifestations of vascular disease, median 10-year risk of a recurrent major vascular event was 17% (interquartile range, 11%-28%), varying from <10% in 18% to >30% in 22% of the patients. If risk factors were at guideline-recommended targets, the residual 10-year risk would be <10% in 47% and >30% in 9% of the patients (median, 11%; interquartile range, 7%-17%).
Among patients with vascular disease, there is very substantial variation in estimated 10-year risk of recurrent vascular events. If all modifiable risk factors were at guideline-recommended targets, half of the patients would have a 10-year risk <10%. These data suggest that even with optimal treatment, many patients with vascular disease will remain at >20% and even >30% 10-year risk, clearly delineating an area of substantial unmet medical need.
Background Although sex disparities in the diagnostic evaluation and revascularization of patients with acute myocardial infarction are well documented, no study has evaluated longitudinal trends in ...these disparities. Methods and Results Using the National Inpatient Sample from 2005 to 2019, 9 259 932 patients with acute myocardial infarction were identified. We divided 15 years into five 3-year periods. The primary objective was to evaluate sex-based trends in the use of diagnostic angiography, percutaneous coronary intervention, and coronary artery bypass graft (CABG) among patients with non-ST-segment-elevation myocardial infarction and ST-segment-elevation myocardial infarction (STEMI) over 15 years. The secondary objective was to evaluate sex disparities in mortality, length of stay, and cost. For non-ST-segment-elevation myocardial infarction, we saw a small reduction in sex disparity in the use of all diagnostic angiography in period 5 versus period 1 (4% versus 5.3%;
<0.01), no change in sex disparity in percutaneous coronary intervention use in period 5 versus period 1 (5.6% versus 5%;
=0.16), and a widening sex disparity in CABG in period 5 versus period 1 (5.4% versus 4.4%;
<0.01). However, we noted decreasing sex disparities in the use of diagnostic angiography, percutaneous coronary intervention, and CABG for ST-segment-elevation myocardial infarction in mostly all periods compared with period 1 (
<0.05, all comparisons), but differences still existed in period 5. Risk-adjusted in-hospital mortality was higher after CABG for non-ST-segment-elevation myocardial infarction and after percutaneous coronary intervention and CABG for ST-segment-elevation myocardial infarction in women than men. Conclusions Despite variable trends in sex disparities in diagnostic and revascularization procedures for acute myocardial infarction, disparities still exist.
Myocardial infarction (MI) is a leading cause of heart failure and death worldwide. Preservation of contractile function and protection against adverse changes in ventricular architecture (cardiac ...remodeling) are key factors to limiting progression of this condition to heart failure. Consequently, new therapeutic targets are urgently required to achieve this aim. Expression of the Runx1 transcription factor is increased in adult cardiomyocytes after MI; however, the functional role of Runx1 in the heart is unknown.
To address this question, we have generated a novel tamoxifen-inducible cardiomyocyte-specific
-deficient mouse. Mice were subjected to MI by means of coronary artery ligation. Cardiac remodeling and contractile function were assessed extensively at the whole-heart, cardiomyocyte, and molecular levels.
-deficient mice were protected against adverse cardiac remodeling after MI, maintaining ventricular wall thickness and contractile function. Furthermore, these mice lacked eccentric hypertrophy, and their cardiomyocytes exhibited markedly improved calcium handling. At the mechanistic level, these effects were achieved through increased phosphorylation of phospholamban by protein kinase A and relief of sarco/endoplasmic reticulum Ca
-ATPase inhibition. Enhanced sarco/endoplasmic reticulum Ca
-ATPase activity in Runx1-deficient mice increased sarcoplasmic reticulum calcium content and sarcoplasmic reticulum-mediated calcium release, preserving cardiomyocyte contraction after MI.
Our data identified Runx1 as a novel therapeutic target with translational potential to counteract the effects of adverse cardiac remodeling, thereby improving survival and quality of life among patients with MI.
The Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension conceived and designed an ad-hoc study aimed at searching for prognostic cut-off values of serum uric ...acid (SUA) in predicting fatal myocardial infaction (MI) in women and men.
The URic acid Right for heArt Health study is a nationwide, multicentre, observational cohort study involving data on individuals aged 18-95 years recruited on a regional community basis from all the territory of Italy under the patronage of the Italian Society of Hypertension with a mean follow-up period of 122.3 ± 66.9 months.
A total of 23 467 individuals were included in the analysis. Cut-off values of SUA able to discriminate MI status were identified by mean of receiver operating characteristic curves in the whole database (>5.70 mg/dl), in women (>5.26 mg/dl) and in men (>5.49 mg/dl). Multivariate Cox regression analyses adjusted for confounders (age, arterial hypertension, diabetes, chronic kidney disease, smoking habit, ethanol intake, BMI, haematocrit, LDL cholesterol and use of diuretics) identified an independent association between SUA and fatal MI in the whole database (hazard ratio 1.381, 95% confidence intervals, 1.096-1.758, P = 0.006) and in women (hazard ratio 1.514, confidence intervals 1.105-2.075, P < 0.01), but not in men.
The results of the current study confirm that SUA is an independent risk factor for fatal MI after adjusting for potential confounding variables, and demonstrate that a prognostic cut-off value associated to fatal MI can be identified at least in women.
Detection of cardiomyocyte death is crucial for the diagnosis and treatment of heart disease. Here we use comparative methylome analysis to identify genomic loci that are unmethylated specifically in ...cardiomyocytes, and develop these as biomarkers to quantify cardiomyocyte DNA in circulating cell-free DNA (cfDNA) derived from dying cells. Plasma of healthy individuals contains essentially no cardiomyocyte cfDNA, consistent with minimal cardiac turnover. Patients with acute ST-elevation myocardial infarction show a robust cardiac cfDNA signal that correlates with levels of troponin and creatine phosphokinase (CPK), including the expected elevation-decay dynamics following coronary angioplasty. Patients with sepsis have high cardiac cfDNA concentrations that strongly predict mortality, suggesting a major role of cardiomyocyte death in mortality from sepsis. A cfDNA biomarker for cardiomyocyte death may find utility in diagnosis and monitoring of cardiac pathologies and in the study of normal human cardiac physiology and development.
Differences between sexes in cardiac risk factors, perceptions of cardiac risk, and health care provider discussions about risk among young patients with acute myocardial infarction (AMI) are not ...well studied.
This study compared cardiac risk factor prevalence, risk perceptions, and health care provider feedback on heart disease and risk modification between young women and men hospitalized with AMI.
We studied 3,501 AMI patients age 18 to 55 years enrolled in the VIRGO (Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients) study in U.S. and Spanish hospitals between August 2008 and January 2012, comparing the prevalence of 5 cardiac risk factors by sex. Modified Poisson regression was used to assess sex differences in self-perceived heart disease risk and self-reported provider discussions of risk and modification.
Nearly all patients (98%) had ≥1 risk factor, and 64% had ≥3. Only 53% of patients considered themselves at risk for heart disease, and even fewer reported being told they were at risk (46%) or that their health care provider had discussed heart disease and risk modification (49%). Women were less likely than men to be told they were at risk (relative risk: 0.89; 95% confidence interval: 0.84 to 0.96) or to have a provider discuss risk modification (relative risk: 0.84; 95% confidence interval: 0.79 to 0.89). There was no difference between women and men for self-perceived risk.
Despite having significant cardiac risk factors, only one-half of young AMI patients believed they were at risk for heart disease before their event. Even fewer discussed their risks or risk modification with their health care providers; this issue was more pronounced among women.
In this paper, a novel technique on a multiscale energy and eigenspace (MEES) approach is proposed for the detection and localization of myocardial infarction (MI) from multilead electrocardiogram ...(ECG). Wavelet decomposition of multilead ECG signals grossly segments the clinical components at different subbands. In MI, pathological characteristics such as hypercute T-wave, inversion of T-wave, changes in ST elevation, or pathological Q-wave are seen in ECG signals. This pathological information alters the covariance structures of multiscale multivariate matrices at different scales and the corresponding eigenvalues. The clinically relevant components can be captured by eigenvalues. In this study, multiscale wavelet energies and eigenvalues of multiscale covariance matrices are used as diagnostic features. Support vector machines (SVMs) with both linear and radial basis function (RBF) kernel and K-nearest neighbor are used as classifiers. Datasets, which include healthy control, and various types of MI, such as anterior, anteriolateral, anterioseptal, inferior, inferiolateral, and inferioposterio-lateral, from the PTB diagnostic ECG database are used for evaluation. The results show that the proposed technique can successfully detect the MI pathologies. The MEES approach also helps localize different types of MIs. For MI detection, the accuracy, the sensitivity, and the specificity values are 96%, 93%, and 99% respectively. The localization accuracy is 99.58%, using a multiclass SVM classifier with RBF kernel.
Assess the relative incidence and compare characteristics and outcome of unstable angina (UA) and non-ST-elevation myocardial infarction (NSTEMI).
Two independent prospective multicentre diagnostic ...studies (Advantageous Predictors of Acute Coronary Syndromes Evaluation APACE and High-Sensitivity Troponin in the Evaluation of Patients With Acute Coronary Syndrome High-STEACS) enrolling patients with acute chest discomfort presenting to the emergency department. Central adjudication of the final diagnosis was done by two independent cardiologists using all clinical information including serial measurements of high-sensitivity cardiac troponin (hs-cTn). All-cause death and future non-fatal MI were assessed at 30 days and 1 year.
8992 patients were enrolled at 11 centres. UA was adjudicated in 8.9%(95% CI 8.0 to 9.7) and 2.8% (95% CI 2.3 to 3.3) patients in APACE and High-STEACS, respectively, and NSTEMI in 15.1% (95% CI 14.0 to 16.2) and 13.4% (95% CI 12.4 to 14.3). Coronary artery disease was pre-existing in 73% and 76% of patients with UA. At 30 days, all-cause mortality in UA was substantially lower as compared with NSTEMI (0.5% vs 3.7%, p=0.002 in APACE, 0.7% vs 7.4%, p=0.004 in High-STEACS). Similarly, at 1 year in UA all-cause mortality was 3.3% (95% CI 1.2 to 5.3) vs 10.4% (95% CI 7.9 to 12.9) in APACE, and 5.1% (95% CI 0.7 to 9.5) vs 22.9% (95% CI 19.3 to 26.4) in High-STEACS, and similar to non-cardiac chest pain (NCCP). In contrast, future non-fatal MI in APACE was comparable in UA and NSTEMI (11.2%, 95% CI 7.8 to 14.6 and 7.9%, 95% CI 5.7 to 10.2), and higher than in NCCP (0.6%, 95% CI 0.2 to 1.0).
The relative incidence and mortality of UA is substantially lower than that of NSTEMI, while the rate of future non-fatal MI is similar.
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