Acute Phase Of Myocardial Infarction Research Articles

Is It Safe to Use Arterial Grafts in Patients with Acute Myocardial Infarction? Short-Mid-Term Propensity Analysis.

The use of multiple arterial grafts (MAGs) has an impact on patient survival; however, preference for its use in the acute phase of myocardial infarction (AMI) has not yet been established. This study aimed to compare the short-mid-term clinical results of AMI patients undergoing coronary artery bypass grafting (CABG) with a single arterial graft (SAG) vs. MAGs. This is a cross-sectional cohort study of 4,053 patients from the Registro Paulista de Cirurgia Cardiovascular II (REPLICCAR II). CABG in the AMI was considered when performed between one and seven days after diagnosis (n=238). Thirty-five patients underwent surgery with ≥ 2 arterial grafts (MAG group), population adjustment in SAG group was performed using the propensity score matching (PSM). Clinical follow-up was performed by telephone to assess need for readmission, new AMI, reoperation, and death. After PSM, 70 patients were evaluated. During hospitalization, a significant statistical difference was observed in the surgery duration: the MAG group had a median of 4.78 hours while the SAG group had 4.11 hours (P=0.040). Within the MAG group, there was a predominance use of bilateral internal thoracic artery (62.86%), followed by radial graft associated with the use of left internal thoracic artery (28.57%) and the combination of the three grafts (8.57%). There were no significant differences between the groups in terms of outcomes up to 30 days after CABG or up to five years after CABG. In REPLICCAR II, usage of MAGs in the AMI was not associated with clinical worsening of patients until the mid-term follow-up.

Anti-inflammatory effects of proprotein convertase subtilisin/kexin 9 inhibitor therapy in the early phase of acute myocardial infarction.

This study examined the anti-inflammatory and endothelial function-enhancing effects of proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitor therapy in the early phase after acute myocardial infarction (AMI) by assessing changes in tumor necrosis factor-α (TNF-α) levels and the L-arginine/asymmetric-dimethylarginine (ADMA) ratio. This retrospective, single-center cohort study included patients who underwent successful timely primary percutaneous coronary intervention (PCI) for first-onset AMI between September 2017 and March 2018. The PCSK9 inhibitor group comprised patients who received 75mg alirocumab up to 7days after AMI, while the standard therapy group comprised patients who did not. We evaluated the change in TNF-α levels and the L-arginine/ADMA ratio at the time of hospital admission and prior to discharge. PCSK9 inhibitor therapy in the early phase after AMI suppressed TNF-α levels (standard therapy group, 1.64 ± 2.14pg/mL vs. PCSK9 inhibitor group, 0.26 ± 0.33pg/mL; p = 0.033) and increased the L-arginine/ADMA ratio (standard therapy group, -13.0 ± 39.7 vs. PCSK9 inhibitor group, 23.2 ± 39.7; p = 0.042). Upon multiple regression analysis adjusted for sex, age, and peak creatine kinase levels, PCSK9 inhibitor therapy was associated with TNF-α suppression (p = 0.025; β = -0.235, 95% confidence interval [CI], -0.436 to -0.033). The L-arginine/ADMA ratio was also analyzed using multiple regression, adjusted for sex, age, peak creatine kinase levels, and smoking, showing a significant improvement in the ratio (p = 0.018; β = 41.913, 95% CI, 10.337-73.491). Moreover, a weak negative correlation was suggested between the change in TNF-α levels and the change in L-arginine/ADMA ratio (r = -0.393, p = 0.058). PCSK9 inhibitor therapy in the early phase after AMI suppresses TNF-α levels and improves the L-arginine/ADMA ratio, potentially indicating anti-inflammatory and endothelial function-enhancing effects.

Cardioprotective Action of the JNK Inhibitor Tryptanthrin Oxime in the Late Period after Myocardial Infarction.

In experiments on Wistar rats, the effect of a new selective JNK inhibitor tryptanthrin oxime (TR-Ox) on parameters of systemic hemodynamics, cardiohemodynamics, and post-infarction fibrosis was studied 4 months after acute myocardial ischemia (1 h) followed by reperfusion. TR-Ox was administered intraperitoneally at a dose of 12 mg/kg 20 min before reperfusion, and then once a day for the next 4 days. Administration of TR-Ox to animals in the acute phase of myocardial infarction contributed to more complete preservation of myocardial viability in the delayed period: a relative increase of muscle elements proportion in the scar, a decrease in the formation of connective tissue areas with complete and >50% replacement of the myocardium, and deceleration of fibrotic scarring in myocardium areas distant from the focus of injury, resulting in improved systolic and diastolic myocardial function. Four months after myocardial infarction, significant improvement in systemic hemodynamics and cardiohemodynamics parameters was observed in the group treated with TR-Ox: stroke volume, cardiac output, left ventricular systolic pressure, maximum rates of left ventricle pressure rise and fall significantly increased and the left ventricle end-diastolic pressure decreased in comparison with the corresponding parameters in the control group.

Liberal versus restrictive transfusion strategies in acute myocardial infarction: a systematic review and comparative frequentist and Bayesian meta-analysis of randomized controlled trials

BackgroundThe transfusion strategy in the acute phase of myocardial infarction (AMI) remains a debated topic with non-standardized guidelines. This study aimed to evaluate the impact of liberal versus restrictive transfusion strategies on mortality during AMI.MethodsA systematic search was conducted across MEDLINE, EMBASE, and the COCHRANE library databases, focusing on randomized controlled trials (RCTs). The primary endpoint was the latest measured mortality within 90 days following myocardial infarction (MI). Secondary endpoints included recurrence of MI, cardiovascular mortality, stroke occurrence, unplanned revascularization, and a composite endpoint of death or recurrent MI. Mixed and random-effects models were employed to estimate relative risks. Sensitivity analyses were conducted using two approaches: one incorporating only studies assessed as low risk of bias according to the Rob2 tool, and another employing a Bayesian analysis.ResultsFour RCTs including a total of 4324 participants were analyzed. Neither the fixed-effect nor random-effects models demonstrated a significant reduction in mortality, with risk ratios (RR) of 1.16 (95% CI 0.95–1.40) for the fixed-effect model and 1.13 (95% CI 0.67–1.91) for the random-effects model (GRADE: low certainty of evidence). Sensitivity analyses, including the exclusion of two high-risk-of-bias studies and a Bayesian analysis, were consistent with the primary analysis. For the composite outcome death or MI both fixed-effect and random-effects models showed a statistically significant RR of 1.18 (95% CI 1.01–1.37) with negligible heterogeneity (I2 = 0%, p = 0.46), indicating results unfavorable to restrictive transfusion (GRADE: very low certainty of evidence). However, this result was primarily driven by a single study. For cardiac mortality, the fixed-effects model indicated a significant RR of 1.42 (95% CI 1.07–1.88), whereas the random-effects model showed non-significant RR of 1.05 (95% CI 0.36–3.80). Analyses of other secondary endpoints did not show statistically significant results.ConclusionsOur analysis did not demonstrate a significant benefit in early mortality with a liberal transfusion strategy compared to a restrictive strategy for AMI, low certainty of evidence. Liberal transfusion may reduce the risk of the composite outcome death or MI, with very low certainty of evidence. These findings should be interpreted with caution in critically ill patients.

Targeting Cardiac Resident CCR2+ Macrophage-Secreted MCP-1 to Attenuate Inflammation After Myocardial Infarction

After myocardial infarction (MI), cardiac resident CCR2+ macrophages release various cytokines and chemokines, notably monocyte chemoattractant protein-1 (MCP-1). MCP-1 is instrumental in recruiting CCR2+ monocytes to the damaged region. The excessive arrival of these monocytes, which then become macrophages, perpetuates inflammation at the site of injury. This continuous inflammation leads to adverse tissue remodeling and compromises cardiac function over time. We hypothesized that neutralizing the MCP-1 secreted by cardiac resident CCR2+ macrophages can mitigate post-MI inflammation by curtailing the recruitment of monocytes and their differentiation into macrophages. In this work, we developed nanoparticles that target the infarcted heart, specifically accumulating in the damaged area after intravenous (IV) administration, and docking onto CCR2+ macrophages. These nanoparticles were designed to slowly release an MCP-1 binding peptide, HSWRHFHTLGGG (HSW), which neutralizes the upregulated MCP-1. We showed that the HSW reduced monocyte migration, inhibited pro-inflammatory cytokine upregulation, and suppressed myofibroblast differentiation in vitro. After IV delivery, the released HSW significantly decreased monocyte recruitment and pro-inflammatory macrophage density, increased cardiac cell survival, attenuated cardiac fibrosis, and improved cardiac function. Taken together, our findings support the strategy of MCP-1 neutralization at the acute phase of MI as a promising way to alleviate post-MI inflammation. STATEMENT OF SIGNIFICANCE: After a myocardial infarction (MI), CCR2+ macrophages resident in the heart release various cytokines and chemokines, notably monocyte chemoattractant protein-1 (MCP-1). MCP-1 is instrumental in attracting CCR2+ monocytes to the damaged region. The excessive arrival of these monocytes, which then become macrophages, perpetuates inflammation at the site of injury. This continuous inflammation leads to adverse tissue remodeling and compromises cardiac function over time. In this work, we tested the hypothesis that neutralizing the MCP-1 secreted by cardiac CCR2+ macrophages can mitigate post-MI inflammation by curtailing the recruitment of monocytes.

Risk factors and prognostic value of endotoxemia in patients with acute myocardial infarction.

There is increasing evidence regarding the association between endotoxemia and the pathogenesis of atherosclerosis and myocardial infarction (MI). During the acute phase of MI, endotoxemia might increase inflammation and drive adverse cardiovascular (CV) outcomes. We aimed to explore the risk factors and prognostic value of endotoxemia in patients admitted for acute MI. Patients admitted to the coronary care unit of Dijon University Hospital for type 1 acute MI between 2013 and 2015 were included. Endotoxemia, assessed by plasma lipopolysaccharide (LPS) concentration, was measured by mass spectrometry. Major adverse CV events were recorded in the year following hospital admission. Data from 245 consecutive MI patients were analyzed. LPS concentration at admission markedly increased with age and diabetes. High LPS concentration was correlated with metabolic biomarkers (glycemia, triglyceride, and total cholesterol) but not with CV (troponin Ic peak and N-terminal pro-brain natriuretic peptide) or inflammatory biomarkers (C-reactive protein, IL6, IL8, and TNFα). LPS concentration was not associated with in-hospital or 1-year outcomes. In patients admitted for MI, higher levels of endotoxins were related to pre-existing conditions rather than acute clinical severity. Therefore, endotoxins measured on the day of MI could reflect metabolic chronic endotoxemia rather than MI-related acute gut translocation.

Association of H-FABP with cardiovascular events: A systematic review.

The research aimed to evaluate the association between heart-type fatty acid binding protein (H-FABP) and cardiovascular events. We systematically reviewed research that has been conducted to assess this relationship, aiming to determine how useful H-FABP could be as a biomarker for cardiovascular diseases, especially in the initial phases of acute myocardial infarction (AMI) and acute coronary syndrome (ACS). Our goal was to validate its diagnostic accuracy and clinical relevance. We systematically searched through PubMed, Web of Science, and Google Scholar databases to find pertinent publications related to cardiovascular diseases and H-FABP, using various permutations, abbreviations, and language variations of MeSH keywords. The final analysis included 12 studies in total. The final study comprised twelve studies, and it was concluded that H-FABP demonstrated high sensitivity (64.3-91.5) and specificity (73-100) for diagnosing Acute Myocardial Infarction (AMI) and Acute Coronary Syndrome (ACS), especially within the first hours of symptom onset. H-FABP demonstrates potential in enhancing the overall diagnostic accuracy during the initial hours following the manifestation of symptoms. However, the existing data do not provide sufficient evidence to recommend the regular utilization of H-FABP as a preliminary risk assessment approach in individuals who present with suspected cardiac events. Additional investigations, with well-defined prospective cohorts, are needed to validate the results observed.

Differences in Cardiac Troponin T Composition in Myocardial Infarction and End-Stage Renal Disease Patients: A Blood Tube Effect?

Cardiac troponin T (cTnT) is key in diagnosing myocardial infarction (MI) but is also elevated in end-stage renal disease (ESRD) patients. Specific larger cTnT proteoforms were identified for the acute phase of MI, while in serum of ESRD patients solely small cTnT fragments were found. However, others allocated this to a pre-analytic effect due to abundant thrombin generation in serum. Therefore, we investigated the effect of various anticoagulation methods on cTnT composition and concentration and compared the cTnT composition of MI and ESRD patients. The agreement of cTnT concentrations between simultaneously collected serum, lithium-heparin (LH) plasma, and ethylenediaminetetraacetic acid (EDTA) plasma was studied using the high-sensitivity (hs-)cTnT immunoassay. cTnT proteoform composition was investigated in a standardized time-dependent manner through spike experiments and in simultaneously collected blood matrixes of MI and ESRD patients. Excellent hs-cTnT concentration agreements were observed across all blood matrixes (slopes > 0.98; 95% CI, 0.96-1.04). Time-dependent degradation (40 kDa intact:29 kDa fragment:15 to 18 kDa fragments) was found in LH plasma and EDTA plasma, and serum in ratios (%) of 90:10:0, 0:5:95, and 0:0:100, respectively (48 h after blood collection). Moreover, gel filtration chromatography (GFC) profiles illustrated mainly larger cTnT proteoforms in MI patients, while in ESRD patients mainly 15 to 18 kDa fragments were found for all matrices. The extent of cTnT degradation in vitro is dependent on the (anti)coagulation method, without impacting hs-cTnT concentrations. Furthermore, mainly larger cTnT proteoforms were present in MI patients, while in ESRD patients mainly small 15 to 18 kDa cTnT fragments were found. These insights are essential when developing a novel hs-cTnT assay targeting larger cTnT proteoforms.

Circulating cluster miR-99b/let-7e/miR-125a expression associates with endothelial function, cytokine, and chemokine levels in myocardial infarction patients

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Spanish Ministry of Science and Innovation (ISCIII) co-financed by the European Regional Development Fund (ERDF), and by the Generalitat Valenciana Introduction During vascular remodelling following a myocardial infarction, miRNAs can modulate endothelial function in a post-transcriptional manner. Our study is focused on the cluster miR-99b/let-7e/miR-125a, examining its serum expression during the acute phase of a Non-ST-segment Elevation Myocardial Infarction (NSTEMI) and its expression one year later. Purpose All the miRNA miR-99b/let-7e/miR-125a cluster is hypothesized to impact endothelial function, specifically influencing cellular adhesion, proliferation, and vasculogenesis. Furthermore, it is hypothesized an association exists between the levels of miRNAs from this cluster during the acute phase of myocardial infarction and the serum levels of inflammatory cytokines and chemokines implicated in the pathology. Methods Serum RNA was extracted from control (n=41), acute NSTEMI phase (n=46), and one-year follow-up (n=24) patients. miRNA expression was quantified by qRT-PCR and miR-484 was used as endogenous control. Endothelial function was assessed by analyzing adhesion, proliferation, and vasculogenesis in human umbilical vein endothelial cells (HUVEC) and transfected with miRNA inhibitors and mimics. Serum levels of proinflammatory cytokines (IL-1β, IL-6, TNF-α, and VEGF-A), anti-inflammatory cytokines (IL-10 and IL-13), and chemokines (MCP-3, MDC, IL-8, and MIP-1α) were determined. Results The miRNA cluster components exhibited decreased expression during the acute phase of the infarction (p< 0.05) and returned to control levels after one year of follow-up. All the cluster components were high expressed in endothelial cells, and we determined the effect of these miRNAs or their inhibition on endothelial function. let-7e mimic increased (p< 0.05) cell adhesion, as well as the formation of tubular networks (p< 0.001). miR-125a inhibitor decreased cell proliferation (p< 0.05). Neither the mimic nor the inhibitor of miR-99b had effects on this endothelial function. let-7e exhibited a negative correlation with the proinflammatory cytokine TNF-α (r= -0.19, p= 0.0386) and a positive correlation with the levels of the anti-inflammatory cytokine IL-13 (r= 0.22, p= 0.0416). miR-99b showed a positive association with the chemokine MDC (r= 0.22, p= 0.0195), while the levels of miR-125a did not correlate with any of the analysed mediators. Conclusions miR-99b/let-7e/miR-125a cluster is implicated in NSTEMI and exhibits a consistent expression pattern in patients' serum, decreasing during the acute phase and returning to control levels one year after. Each of these miRNAs, especially let-7e and miR-125a, differentially affects cellular processes such as endothelial proliferation and angiogenesis. Additionally, let-7e and miR-99b miRNAs differentially impact the inflammation generated in NSTEMI. These results suggest the involvement of miRNAs from the same cluster in various processes that are coordinately activated in inflammatory situations, such as acute coronary syndrome.

Factors predicting resolution of left ventricular thrombus in different time windows after myocardial infarction

BackgroundLeft ventricular thrombus (LVT) is a serious complication after myocardial infarction. However, due to its asymptomatic nature, early detection is challenging. We aimed to explore the differences in clinical correlates of LVT found in acute to subacute and chronic phases of myocardial infarction.MethodsWe collected data from 153 patients who were diagnosed with LVT after myocardial infarction at the Affiliated Hospital of Qingdao University from January 2013 to December 2022. Baseline information, inflammatory markers, transthoracic echocardiograph (TTE) data and other clinical correlates were collected. Patients were categorized into acute to subacute phase group (< 30 days) and chronic phase group (30 days and after) according to the time at which echocardiograph was performed. The resolution of thrombus within 90 days is regarded as the primary endpoint event. We fitted logistic regression models to relating clinical correlates with phase-specific thrombus resolution.ResultsFor acute to subacute phase thrombus patients: C-reactive protein levels (OR: 0.95, 95% CI: 0.918–0.983, p = 0.003) were significantly associated with thrombus resolution. For chronic phase thrombus patients: anticoagulant treatment was associated with 5.717-fold odds of thrombus resolution (OR: 5.717, 95% CI: 1.543–21.18, p = 0.009).ConclusionsHigher levels of CRP were associated with lower likelihood of LVT resolution in acute phase myocardial infarction; Anticoagulant therapy is still needed for thrombus in the chronic stage of myocardial infarction.

Evaluation of Change in Body Composition, including Phase Angle, in Post-Myocardial Infarction Patients Rehabilitated under the KOS-Zawał (MC-AMI) Programme.

Background: Ischaemic heart disease, including myocardial infarction, is one of the main causes leading to heart failure as a consequence of ischaemic myocardial damage. In recent years, survival in the acute phase of myocardial infarction has improved significantly, but the high mortality rate within 12 months of hospital discharge (reaching up to 9.8% in Poland) remains a challenge. Therefore, the KOS-Zawał (MC-AMI) comprehensive 12-month post-MI care programme was introduced in Poland in 2017. Aim: This study aimed to assess body composition (including, but not limited to, the phase angle, visceral fat, total body fat, redistribution between intracellular and extracellular fluid in the body, and metabolic age) using a bioelectrical impedance analysis (BIA) in post-MI patients before and after early post-MI rehabilitation who were participating in the KOS-Zawał (MC-AMI) programme. Methods: This study involved an examination (before rehabilitation) of 94 post-myocardial infarction patients who were referred to a cardiology appointment within 7-10 days of hospital discharge, during which a clinical assessment, electrocardiogram, and biochemical blood tests (complete blood count, CRP, and serum creatinine) were performed. For various reasons (death, qualification for device implantation, non-completion of rehabilitation, failure to attend a follow-up BIA), data from 55 patients who were examined twice (before and after rehabilitation) were used for the final analysis. Measurements were taken using a high-grade Tanita MC-780 BIA body composition analyser, which measured the resistance of tissues to a low-intensity electrical impulse (not perceptible to the subject). Results: Participation in rehabilitation as part of the KOS-Zawał (MC-AMI) programme was associated with a decrease in metabolic age in patients, with a reduction in visceral fat levels and levels of adipose tissue in the lower and upper limbs. Moreover, a clinically beneficial reduction in the ratio of extracellular water to total body water was also observed. These changes were statistically significant (p < 0.005). In contrast, there were no statistically significant differences in the change in phase angle values in the subjects before and after the 5-week post-infarction rehabilitation. Conclusions: Participation in early post-myocardial infarction rehabilitation as part of the KOS-Zawał (MC-AMI) programme (25 training sessions) is associated with significant improvements in body composition parameters, such as visceral adipose tissue, limb fat, and water redistribution, and, consequently, a reduction in metabolic age, despite no significant increase in phase angle values. It was hypothesised that the good baseline condition of the subjects might explain the lack of significant change in the phase angle over the short observation period. For further analysis, it would be worthwhile to increase the number of patients with baseline reduced phase angle values and monitor changes in this parameter throughout rehabilitation and the entire MC-AMI programme, because changes in the phase angle may also be influenced by other programme components such as dietary or psychological education. It is worth considering implementing a regular BIA assessment in patients in the programme as a motivating stimulus for diligent exercise and extending rehabilitation to be followed by telerehabilitation or hybrid telerehabilitation.

Importance of reassessment to identify trajectories of chronic transition of clinical indicators in post-myocardial infarction management.

Despite advances in multidisciplinary acute care for myocardial infarction (MI), the clinical need to manage heart failure and elevated mortality risks in the remote phase of MI remains unmet. Various prognostic models have been established using clinical indicators obtained during the acute phase of MI; however, most of these indicators also show chronic changes in the post-MI phase. Although relevant guidelines recommend follow-up assessments of some clinical indicators in the chronic phase, systematic reassessment has not yet been fully established and implemented in a real-world clinical setting. Therefore, clinical evidence of the impact of such chronic transitions on the post-MI prognosis is lacking. We speculate that post-MI reassessment of key clinical indicators and the impact of their chronic transition patterns on long-term prognoses can improve the quality of post-MI risk stratification and help identify residual risk factors. Several recent studies have investigated the impact of the chronic transition of some clinical indicators, such as serum albumin level, mitral regurgitation, and left-ventricular dysfunction, on post-MI prognosis. Interestingly, even in MI survivors with these indicators within their respective normal ranges in the acute phase of MI, chronic transition to an abnormal range was associated with worsening cardiovascular outcomes. On the basis of these recent insights, we discuss the clinical significance of post-MI reassessment to identify the trajectories of several clinical indicators and elucidate the potential residual risk factors affecting adverse outcomes in MI survivors.

Five-Membered Nitrogen Heterocycles Angiotensin-Converting Enzyme (ACE) Inhibitors Induced Angioedema: An Underdiagnosed Condition.

Angiotensin-converting enzyme (ACE) inhibitors are used primarily in the treatment of hypertension, heart failure, and in the acute phase of myocardial infarction. Lisinopril [N2-[(1S)-1-car-boxy-3-phenylpropyl]-L-lysyl-L-proline], enalapril [(S)-1-[N-[1-(ethoxycarbonyl)-3-phenylpropyl]-L-alanyl]-L-proline] and ramipril [2-aza-bicyclo-[3.3.0]-octane-3-carboxylic acid] are all five-membered heterocycles and three of the most prevalent ACE inhibitors in clinical use worldwide. ACE inhibitor-induced angioedema (AE) is clinically characterized by self-limited edema of the dermis and subcutaneous lipid tissue, localized on face skin, oral mucosa and tongue in most cases. However, severe episodes of intestinal AE misdiagnosed as acute appendicitis and laryngeal AE requiring incubation have been reported. The pathophysiology of ACE inhibitor-induced angioedema is attributed to the accumulation of bradykinin, which is a potent vasodilator with proinflammatory activity that is normally degraded by angiotensin-converting enzyme (ACE) and aminopeptidase P; however, a small proportion of treated patients is affected. Given that patients do not respond to anti-H1 antihistamines and steroids, early clinical recognition and discontinuation of the ACE inhibitors are the treatments of choice for the long-term management of ACE inhibitor- induced angioedema. The search period of the present review was set up until November 2023, and its aim is to shed light on the broader context of ACE inhibitor-induced angioedema, exploring aspects such as clinical presentation, pathophysiology, and therapeutic considerations in this potentially life-threatening condition. The exploration of alternative drug options such as angiotensin II receptor blockers, the potential association of coadministration of DPP-4 inhibitors with ACE inhibitors, the presentation of angioedema and the significant clinical importance of this condition are also discussed. By focusing on the chemical structure of ACE inhibitors, specifically their nitrogen-based heterocycles-an attribute shared by over 880 drugs approved by the FDA within the pharmaceutical industry-this review emphasizes the pivotal role of nitrogen scaffolds in drug design and underscores their relevance in ACE inhibitor pharmacology.

In-Hospital Levels of Circulating MicroRNAs as Potential Predictors of Left Ventricular Remodeling Post-Myocardial Infarction.

Background and Objectives: Biochemical and molecular regulation of both adaptive and pathological responses of heart tissue to ischemic injury is widely investigated. However, it is still not fully understood. Several biomarkers are tested as predictors of left ventricle (LV) remodeling after myocardial infarction (MI). The aim of this study was to assess the relationship between selected microRNAs (miRNAs) and LV function and morphology in patients after MI. Materials and Methods: Selected miRNAs related to heart failure were assessed in the acute phase of MI: miR-150-3p, miR-21-5p, miR-19b-3p, miR-155-5p, miR-22-5p. Echocardiography with 3D imaging was performed at baseline and after 6 months. Remodeling was defined as >20% increase in LV end-diastolic volume, whereas reverse remodeling was defined as >10% reduction in LV end-systolic volume. Results: Eighty patients entered the registry. Remodeling occurred in 26% and reverse remodeling was reported in 51% of patients. In the presented study, none of the analyzed miRNAs were found to be a significant LV remodeling predictor. The observed correlations between miRNAs and other circulating biomarkers of myocardial remodeling were relatively weak. Conclusions: Our analysis does not demonstrate an association between the analyzed miRNAs and LV remodeling in patients with MI.

Influence of the Apelinergic System on Conduction Disorders in Patients after Myocardial Infarction.

There is a growing body of evidence for an important role of the apelinergic system in the modulation of cardiovascular homeostasis. The aim of our study was to (1) examine the relationship between apelin serum concentration at index myocardial infarction (MI) and atrioventricular conduction disorders (AVCDs) at 12-month follow-up, and (2) investigate the association between initial apelin concentration and the novel marker of post-MI scar (Q/QRS ratio) at follow-up. In 84 patients with MI with complete revascularization, apelin peptide serum concentrations for apelin-13, apelin-17, elabela (ELA) and apelin receptor (APJ) were measured on day one of hospitalization; at 12-month follow-up, 54 of them underwent thorough examination that included 12-lead electrocardiography (ECG), Holter ECG monitoring and echocardiography. The mean age was 58.9 years. At 12-month follow-up, AVCDs were diagnosed in 21.4% of subjects, with AV first-degree block in 16.7% and sinoatrial arrest in 3.7%. ELA serum concentration at index MI correlated positively with the occurrence of AVCD (p = 0.003) and heart rate (p = 0.005) at 12-month follow-up. The apelin-13 serum concentration at index MI correlated negatively with the Q/QRS ratio. The apelin peptide concentration during an acute phase of MI impacts the development of AVCD and the value of Q/QRS ratio in MI survivors.

Abstract 12040: Acute-to-Chronic Assessment of Trajectory of Left Ventricular Ejection Fraction is Useful to Predict Long-Term Clinical Outcomes After Acute Myocardial Infarction

Aims: To determine the prognostic impact of left ventricular ejection fraction (LVEF) trajectories from acute to chronic phase of acute myocardial infarction (AMI). Materials and methods: Among 2,266 consecutive patients admitted for AMI from February 2008 to January 2016, 1,330 survivors with LV ejection fraction (LVEF) ≥40% during hospitalization who had LVEF data at 6 months after AMI were analyzed. Patients were divided into three subgroups based on LVEF at 6 months: reduced-LVEF (&lt;40%), mildly-reduced-LVEF (≥40% and &lt;50%) and preserved-LVEF (≥50%). Occurrence of a composite of hospitalization for heart failure or cardiovascular death after 6 months of AMI was the primary endpoint. The prognostic impact of LVEF at 6 months on primary endpoint was analyzed with a multivariate-adjusted Cox proportional hazards regression model. Results: Overall, the mean age was 67.5 ± 11.9 years, and LVEF during index hospitalization was 59.4 ± 9.1%. The individual trajectories of LVEF from index hospitalization to 6 months was dynamically changed. The median (interquartile range) duration of follow-up was 3.0 (1.5-4.8) years, and the primary endpoint occurred in 35/1,330 (2.6%) patients (13/69 [18.8%] in the reduced-LVEF, 9/265 [3.4%] in the mildly-reduced-LVEF, and 13/996 [1.3%] in the preserved-LVEF categories). The adjusted hazard ratio for the primary endpoint in the reduced-LVEF vs. mildly-reduced-LVEF categories and in the reduced-LVEF vs. preserved-LVEF categories was 4.71 (95% confidence interval [CI], 1.83 to 12.13; p &lt;0.001) and 14.37 (95% CI, 5.38 to 38.36; p &lt;0.001), respectively (Figure). Conclusion: Late-onset LV systolic dysfunction was significantly associated with long-term outcomes after AMI. Our findings suggest that, even in AMI survivors without LV systolic dysfunction at the acute phase of AMI, reassessment of LVEF and careful monitoring of its trajectories is useful to predict long-term clinical outcomes.

Changes in Physical Activity and Incidence of Nonfatal Cardiovascular Events in 47 153 Survivors of Myocardial Infarction.

Background The majority of patients survive the acute phase of myocardial infarction (MI) but have an increased risk of recurrent cardiovascular disease (CVD) events. To be regularly physically active or change activity level is associated with a lower risk of all-cause mortality. The objective was to explore to what extent physical activity (PA) levels or change in PA levels during the first year post-MI was associated with any recurrent nonfatal CVD events and specific CVD events (eg, MI, ischemic stroke, and vascular dementia). Methods and Results This cohort study among MI survivors was based on Swedish national registries between 2005 and 2020. PA levels were self-rated at 2 and 12 months post-MI, and patients were classified into remaining physically inactive, increasing, decreasing, or remaining active. A total of 6534 nonfatal CVD events occurred during 6 years of follow-up among the 47 153 included patients. In fully adjusted analyses, the risk of any nonfatal CVD event was lower (P<0.05) among patients remaining active (37%), increasing (22%), or decreasing (18%) PA level compared with remaining inactive. Compared with remaining inactive, the risk of recurring MI and stroke was lower (P>0.05) among remaining active (41% versus 52%, respectively), increasing (20% versus 35%, respectively), or decreasing PA level (24% versus 34%, respectively). For vascular dementia, patients remaining physically active had an 80% lower risk compared with remaining inactive (P<0.05). Conclusions Remaining physically active or change in PA levels during the first year post-MI was associated with a lower risk of recurrent nonfatal CVD events. This emphasizes the importance of supporting patients to continue to be or become physically active.

Activation of AHR by ITE improves cardiac remodelling and function in rats after myocardial infarction.

Left ventricular remodelling subsequent to myocardial infarction (MI) constitutes a pivotal underlying cause of heart failure. Intervention with the nontoxic endogenous aryl hydrocarbon receptor (AHR) agonist 2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE) in the acute phase of MI has been shown to ameliorate cardiac function, but its role in the chronic phase remains obscured. This study explores the beneficial role of ITE in delaying the progression of heart failure in the chronic phase of MI. MI rats established by ligating the left anterior descending coronary artery were treated with the indicated concentration of the AHR agonist ITE or vehicle alone. Echocardiography was performed to determine cardiac structure and function; myocardial morphology and fibrosis were observed by haematoxylin and eosin and Masson's trichrome staining; serum biochemical indices, BNP, and inflammatory cytokine levels were detected by enzyme-linked immunosorbent assay; F4/80+ iNOS+ M1 macrophages and F4/80+ CD206+ M2 macrophages were detected by immunofluorescence; the terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling assay was used to detect the apoptosis of cardiomyocytes; ultrastructural changes in myocardial tissue were observed by transmission electron microscopy; and Cyp1a1, Akt, P-Akt, p70S6K, P-p70S6K, Bcl-2, Bax, caspase-3, and cleaved caspase-3 protein levels were determined via Western blotting. We found that therapy with the AHR agonist ITE rescued cardiac remodelling and dysfunction in rats with MI and attenuated myocardial fibrosis, inflammation, and mitochondrial damage. Further studies confirmed that ITE dose-dependently improved myocardial cell apoptosis after MI, as demonstrated by reduced levels of the apoptosis-related proteins cleaved caspase-3 and Bax but increased expression levels of Bcl-2. These effects were attributed to ITE-induced activation of AHR receptors, leading to the down-regulation of Akt and p70S6K phosphorylation. The AHR agonist ITE alleviates cardiomyocyte apoptosis through the Akt/p70S6K signalling pathway, thereby rescuing left ventricular adverse remodelling and cardiac dysfunction after MI.

Enzyme-Responsive Nanoparticles for the Targeted Delivery of an MMP Inhibitor to Acute Myocardial Infarction.

Herein, we have developed a drug-loaded matrix metalloproteinase (MMP)-responsive micellar nanoparticle (NP) intended for minimally invasive intravenous injection during the acute phase of myocardial infarction (MI) and prolonged retention in the heart for small-molecule drug delivery. Peptide-polymer amphiphiles (PPAs) bearing a small-molecule MMP inhibitor (MMPi), PD166793, were synthesized via ring-opening metathesis polymerization (ROMP) and formulated into spherical micelles by transitioning to aqueous solution. The resulting micellar NPs underwent MMP-induced aggregation, demonstrating enzyme responsiveness. Using a rat MI model, we observed that these NPs were capable of successfully extravasating into the infarcted region of the heart where they were retained due to the active, enzyme-mediated targeting, remaining detectable after 1 week post administration without increasing macrophage recruitment. Furthermore, in vitro studies show that these NPs demonstrated successful drug release following MMP treatment and maintained drug bioactivity as evidenced by comparable MMP inhibition to free MMPi. This work establishes a targeted NP platform for delivering small-molecule therapeutics to the heart after MI, opening possibilities for myocardial infarction treatment.

HESC-Derived Epicardial Cells Promote Repair of Infarcted Hearts in Mouse and Swine.

Myocardial infarction (MI) causes excessive damage to the myocardium, including the epicardium. However, whether pluripotent stem cell-derived epicardial cells (EPs) can be a therapeutic approach for infarcted hearts remains unclear. Here, the authors report that intramyocardial injection of human embryonic stem cell-derived EPs (hEPs) at the acute phase of MI ameliorates functional worsening and scar formation in mouse hearts, concomitantly with enhanced cardiomyocyte survival, angiogenesis, and lymphangiogenesis. Mechanistically, hEPs suppress MI-induced infiltration and cytokine-release of inflammatory cells and promote reparative macrophage polarization. These effects are blocked by a type I interferon (IFN-I) receptor agonist RO8191. Moreover, intelectin 1 (ITLN1), abundantly secreted by hEPs, interacts with IFN-β and mimics the effects of hEP-conditioned medium in suppression of IFN-β-stimulated responses in macrophages and promotion of reparative macrophage polarization, whereas ITLN1 downregulation in hEPs cancels beneficial effects of hEPs in anti-inflammation, IFN-I response inhibition, and cardiac repair. Further, similar beneficial effects of hEPs are observed in a clinically relevant porcine model of reperfused MI, with no increases in the risk of hepatic, renal, and cardiac toxicity. Collectively, this study reveals hEPs as an inflammatory modulator in promoting infarct healing via a paracrine mechanism and provides a new therapeutic approach for infarcted hearts.