Project description:Acute myocardial infarction (AMI) is one of the leading causes of death. It is particularly important to predict malignant ventricular arrhythmia (MVA) timely and accurately in patients with AMI. This study aimed to explore biomarkers and to reveal possible mechanisms of MVA in AMI for clinical diagnosis. Blood samples from 190 human subjects were collected to reveal the differentially expressed proteins (DEPs) in three comparisons (AMI/control, AMI+MVA/control, and AMI+MVA/AMI) in proteomics with bioinformatics analysis and validated in new cohorts. The diagnostic value of candidate DEPs predicting AMI+MVA was also evaluated by the receiver operating characteristic curve (ROC). A total of 8,365 peptides and 460 proteins from the LC-MS/MS analysis were identified with 90 in AMI/control, 94 in AMI+MVA/control, and 43 in AMI+MVA/AMI identified as DEPs. TGFBI level had notable decreasing trend in AMI+MVA (161.9 ± 19.0 ng/ml) compared with AMI (P<0.0001) or control (P<0.0001). vWF level in AMI+MVA patients was significantly higher than that in AMI patients (P<0.01) and control (P<0.0001). ROC analysis showed that TGFBI and vWF had the strong and potential value of predicting MVA in AMI. By constructing proteomics profile to identify the protein characteristics this study found that decreased TGFBI and increased vWF are the characteristics of proteins in the MVA patients with AMI. These findings provide new insight into the diagnosis and pathogenesis of the development of MVA. Further, decreased TGFBI and increased vWF are potential predicting biomarkers for diagnosis of MVA in AMI patients.
Project description:BackgroundAcute myocardial infarction (AMI) complicated by tachyarrhythmias or high-grade atrioventricular block (HAVB) may lead to increased mortality.PurposeTo evaluate the sex differences in patients with AMI complicated by tachyarrhythmias and HAVB and their associated outcomes.Materials and methodsWe analyzed the incidence rates of arrhythmias following AMI from the Acute Coronary Syndrome Israeli Survey database from 2000 to 2018. We assessed the differences in arrhythmias incidence and the associated mortality risk between men and women.ResultsThis cohort of 14,280 consecutive patients included 3,159 (22.1%) women and 11,121 (77.9%) men. Women were less likely to experience early ventricular tachyarrhythmia (VTA), (1.6% vs. 2.3%, p = 0.034), but had similar rates of late VTA (2.3% vs. 2.2%, p = 0.62). Women were more likely to experience atrial fibrillation (AF) (8.6% vs. 5.0%, p < 0.001) and HAVB (3.7% vs. 2.3%, p < 0.001). The risk of early VTAs was similar in men and women [adjusted Odds Ratio (aOR) = 0.76, p = 0.09], but women had a higher risk of AF (aOR = 1.27, p = 0.004) and HAVB (aOR = 1.30, p = 0.03). Early [adjusted hazard ratio (aHR) = 2.84, p < 0.001] and late VTA (aHR =- 4.59, p < 0.001), AF (aHR = 1.52, p < 0.001) and HAVB (aHR = 2.83, p < 0.001) were associated with increased 30-day mortality. Only late VTA (aHR = 2.14, p < 0.001) and AF (aHR = 1.44, p = 0.002) remained significant in the post 30 days period.ConclusionsDuring AMI women experienced more AF and HAVB but fewer early VTAs than men. Early and late VTAs, AF, and HAVB were associated with increased 30-day mortality. Only late VTA and AF were associated with increased post-30-day mortality.
Project description:BackgroundRenal denervation (RDN) can reduce ventricular arrhythmia after acute myocardial infarction (AMI), but the mechanism is not clear. The purpose of this study is to study its mechanism.MethodsThirty-two Sprague-Dawley rats were divided into four groups: control group, AMI group, RDN-1d + AMI group, RDN-2w + AMI group. The AMI model was established 1 day after RDN in the RDN-1d + AMI group and 2 weeks after RDN in the RDN-2w + AMI group. At the same time, 8 normal rats were subjected to AMI modelling (the AMI group). The control group consisted of 8 rats without RDN intervention or AMI modelling.ResultsThe study confirmed that RDN can reduce the occurrence of ventricular tachycardia in AMI rats, reduce renal sympathetic nerve discharge, and inhibit the activity of local sympathetic nerves and cell growth factor (NGF) protein expression in the heart after AMI. In addition, RDN decreased the expression of norepinephrine (NE) and glutamate in the hypothalamus,and NE in cerebrospinal fluid, and increased the expression level of γ aminobutyric acid (GABA) in the hypothalamus after AMI.ConclusionRDN can effectively reduce the occurrence of ventricular arrhythmia after AMI, and its main mechanism may be via the inhibition of central sympathetic nerve discharge.
Project description:ObjectiveWe carried out a secondary analysis in high-risk patients with a previous myocardial infarction (MI) and diabetes in the Alpha Omega Trial. We tested the hypothesis that in these patients an increased intake of the n-3 fatty acids eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and α-linolenic acid (ALA) will reduce the incidence of ventricular arrhythmias and fatal MI.Research design and methodsA subgroup of 1,014 post-MI patients with diabetes aged 60-80 years was randomly allocated to receive one of four trial margarines, three with an additional amount of n-3 fatty acids and one placebo for 40 months. The end points were ventricular arrhythmia-related events and fatal MI. The data were analyzed according to the intention-to-treat principle, using multivariable Cox proportional hazards models.ResultsThe patients consumed on average 18.6 g of margarine per day, which resulted in an additional intake of 223 mg EPA plus 149 mg DHA and/or 1.9 g ALA in the active treatment groups. During follow-up, 29 patients developed a ventricular arrhythmia-related events and 27 had a fatal MI. Compared with placebo patients, the EPA-DHA plus ALA group experienced less ventricular arrhythmia-related events (hazard ratio 0.16; 95% CI 0.04-0.69). These n-3 fatty acids also reduced the combined end-point ventricular arrhythmia-related events and fatal MI (0.28; 0.11-0.71).ConclusionsOur results suggest that low-dose supplementation of n-3 fatty acids exerts a protective effect against ventricular arrhythmia-related events in post-MI patients with diabetes.
Project description:Acute myocardial infarction (AMI) is the one of the main cause of death worldwide. Exosomes carry important information about intercellular communication and could be diagnostic marker for many diseases. Here, we aimed to find potential key proteins for the early diagnosis of AMI. A label free proteomics strategy was used to identify the differentially expressed proteins (DEPs) of AMI patients' plasma exosome. By bioinformatics analysis and enzyme-linked immunosorbent assay to validate the candidate proteins. Compared to healthy control plasma exosome, we totally identified 72 differentially expressed proteins (DEPs) in AMI patients. Also, we found that complement and coagulation cascades was activated by KEGG analysis and GSEA. PLG, C8B and F2 were selected as candidate molecules for further study, and then validated another 40 plasma samples using enzyme-linked immunosorbent assay. Finally, we found that the expression levels of these three proteins (PLG, C8B and F2) were significantly higher than those of healthy controls (P < 0.05). ROC analysis revealed that PLG, C8B and F2 had potential value for AMI early diagnosis. In conclusion, our study identified three potential biomarkers for AMI diagnosis. But there remains a need to further study the mechanism of the biomarkers.
Project description:ObjectivesThe purpose of this study was to investigate the effects of enhancing gap junction (GJ) coupling during acute myocardial infarction (MI) on the healed infarct scar morphology and late post-MI arrhythmia susceptibility.BackgroundIncreased heterogeneity of myocardial scarring after MI is associated with greater arrhythmia susceptibility. We hypothesized that short-term enhancement of GJ coupling during acute MI can produce more homogeneous infarct scars, reducing late susceptibility to post-MI arrhythmias.MethodsFollowing arrhythmic characterization of a rat 4-week post-MI model (n = 24), another 27 Sprague-Dawley rats were randomized to receive rotigaptide to enhance GJ coupling (n = 13) or to saline control (n = 14) by osmotic minipump immediately prior to and for the first 7 days following surgically induced MI. At 4 weeks post-MI, hearts were explanted for ex vivo programmed electrical stimulation (PES) and optical mapping. Heterogeneity of infarct border zone (IBZ) scarring was quantified by histomorphometry.ResultsDespite no detectable differences in infarct size at 4 weeks post-MI, rotigaptide-treated hearts had reduced arrhythmia susceptibility during PES (inducibility score for rotigaptide: 2.4 ± 0.8; for control: 5.0 ± 0.6; p = 0.02) and less heterogeneous IBZ scarring (dispersion of IBZ complexity score: rotigaptide: 1.1 ± 0.1; control: 1.4 ± 0.1; p = 0.04), associated with an improvement in IBZ conduction velocity (rotigaptide: 43.1 ± 3.4 cm/s; control: 34.8 ± 2.0 cm/s; p = 0.04).ConclusionsEnhancement of GJ coupling for only 7 days at the time of acute MI produced more homogeneous IBZ scarring and reduced arrhythmia susceptibility at 4 weeks post-MI. Short-term GJ modulation at the time of MI may represent a novel treatment strategy to modify the healed infarct scar morphology and reduce late post-MI arrhythmic risk.
Project description:AimsTo determine whether risk stratification tests can predict serious arrhythmic events after acute myocardial infarction (AMI) in patients with reduced left ventricular ejection fraction (LVEF < or = 0.40).Methods and resultsA total of 5869 consecutive patients were screened in 10 European centres, and 312 patients (age 65 +/- 11 years) with a mean LVEF of 31 +/- 6% were included in the study. Heart rate variability/turbulence, ambient arrhythmias, signal-averaged electrocardiogram (SAECG), T-wave alternans, and programmed electrical stimulation (PES) were performed 6 weeks after AMI. The primary endpoint was ECG-documented ventricular fibrillation or symptomatic sustained ventricular tachycardia (VT). To document these arrhythmic events, the patients received an implantable ECG loop-recorder. There were 25 primary endpoints (8.0%) during the follow-up of 2 years. The strongest predictors of primary endpoint were measures of heart rate variability, e.g. hazard ratio (HR) for reduced very-low frequency component (<5.7 ln ms(2)) adjusted for clinical variables was 7.0 (95% CI: 2.4-20.3, P < 0.001). Induction of sustained monomorphic VT during PES (adjusted HR = 4.8, 95% CI, 1.7-13.4, P = 0.003) also predicted the primary endpoint.ConclusionFatal or near-fatal arrhythmias can be predicted by many risk stratification methods, especially by heart rate variability, in patients with reduced LVEF after AMI.
Project description:BackgroundPatients with acute myocardial infarction (AMI) complicated by acute heart failure or cardiogenic shock have high mortality with conventional management.ObjectivesThis study evaluated outcomes of patients with AMI who received durable ventricular assist devices (VAD).MethodsPatients in the INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) registry who underwent VAD placement in the setting of AMI were included and compared with patients who received VAD for non-AMI indications.ResultsVAD were implanted in 502 patients with AMI: 443 left ventricular assist devices; 33 biventricular assist devices; and 26 total artificial hearts. Median age was 58.3 years, and 77.1% were male. At implantation, 66% were INTERMACS profile 1. A higher proportion of AMI than non-AMI patients had pre-operative intra-aortic balloon pumps (57.6% vs. 25.3%; p < 0.01), intubation (58% vs. 8.3%; p < 0.01), extracorporeal membrane oxygenation (17.9% vs. 1.7%, p < 0.01), cardiac arrest (33.5% vs. 3.3%, p < 0.01), and higher-acuity INTERMACS profiles. At 1 month post-VAD, 91.8% of AMI patients were alive with ongoing device support, 7.2% had died on device, and 1% had been transplanted. At 1-year post-VAD, 52% of AMI patients were alive with ongoing device support, 25.7% had been transplanted, 1.6% had left VAD explanted for recovery, and 20.7% had died on device. The AMI group had higher unadjusted early phase hazard (hazard ratio [HR]: 1.24; p = 0.04) and reduced late-phase hazard of death (HR: 0.57; p = 0.04) than the non-AMI group did. After accounting for established risk factors, the AMI group no longer had higher early mortality hazard (HR: 0.89; p = 0.30), but it had lower late mortality hazard (HR: 0.55; p = 0.02).ConclusionsPatients with AMI who receive VAD have outcomes similar to other VAD populations, despite being more critically ill pre-implantation. VAD therapy is an effective strategy for patients with AMI and acute heart failure or shock in whom medical therapy is failing.