Post-acute Myocardial Infarction Research Articles

Average and Interindividual Effects to a Comprehensive Cardiovascular Rehabilitation Program.

Background: To describe the average effects and the interindividual variability after a comprehensive outpatient cardiovascular rehabilitation (CCR) program using concurrent exercise training prescribed according to cardiovascular risk stratification on cardiorespiratory fitness (CRF), anthropometric/body composition, quality of life and emotional health in patients of four cardiovascular disease profiles. Methods: CRF, anthropometric/body composition, quality of life, and emotional health were measured before and after a CCR and analyzed in heart valve surgery (HVS), heart failure with reduced ejection fraction (HFrEF), post-acute myocardial infarction (post-AMI), and in coronary artery disease (CAD) patients. Twenty, twenty-four, and thirty-two exercise sessions were prescribed according to mild, moderate, and severe baseline cardiovascular risk, respectively. In addition to concurrent exercise training, nutritional counseling, psychological support, and lifestyle education programs were performed. Results: The main outcomes by delta changes comparisons (Δ) revealed no significant differences at anthropometric/body composition as ΔBody fat decreases (HVS Δ−1.1, HFrEF Δ−1.0, post-AMI Δ−1.4, CAD Δ−1.2 kg) and ΔSkeletal muscle mass increases (HVS Δ+1.4, HFrEF Δ+0.8, post-AMI Δ+0.9, CAD Δ+0.9 kg), and CRF performance as ΔVO2peak increases (HVS Δ+4.3, HFrEF Δ+4.8, post-AMI Δ+4.1, CAD Δ+5.1 mL/kg/min) outcomes among HVS, HFrEF, post-AMI, and CAD (p > 0.05). Secondary outcomes showed significant pre-post delta changes in METs (HVS Δ+1.8, HFrEF Δ+0.7, post-AMI Δ+1.4, CAD Δ+1.4), and maximal O2pulse (HVS Δ+3.1, post-AMI Δ+2.1, CAD Δ+1.9). In addition, quality of life had a significant improvement in physical functioning (HVS Δ+17.0, HFrEF Δ+12.1, post-AMI Δ+9.8, CAD Δ+11.2), physical role (HVS Δ+28.4, HFrEF Δ+26.8, post-AMI Δ+25.6, CAD Δ+25.3), vitality (HVS Δ+18.4, HFrEF Δ+14.3, post-AMI Δ+14.2, CAD Δ+10.6) and social functioning (HVS Δ+20.4, HFrEF Δ+25.3, post-AMI Δ+20.4, CAD Δ+14.8) in all cardiovascular disease. For anxiety (HVS Δ−3.6, HFrEF Δ−2.3, post-AMI Δ−3.0, CAD Δ−3.1) and depression (HVS Δ−2.8, HFrEF Δ−3.4, post-AMI Δ−3.2, CAD Δ−2.3) significant changes were also observed. Conclusions: A CCR program that prescribes the number of exercise sessions using a cardiovascular risk stratification improves CRF, QoL, and emotional health, and the average results show a wide interindividual variability (~25% of non-responders) in this sample of four CVD profile of patients.

Beta-blockers in post-acute myocardial infarction patients: Drug prescription patterns from 2018 to Italy's first wave of the COVID-19 pandemic.

Background: Major guidelines recommend the initiation of a beta-blocker therapy after an acute myocardial infarction (AMI). We aimed to map the treatment pathway of beta-blockers for AMI survivors during the first wave of COVID-19 pandemic in Italy and to investigate predictors for treatment non-initiation. Methods: Healthcare utilization databases of Lombardy Region were investigated. Subjects aged ≥18 years who were hospitalised with AMI in the period February-March-April of 2018, 2019, and 2020 were included, and followed for 30 days from the discharge date, to investigate whether they presented a first prescription of beta-blockers. A multivariate logistic model was performed to evaluate the effect of several covariates on the probability of not receiving a post-AMI beta-blocker therapy. Results: The cohorts comprised 2259, 2383, and 1932 individuals who were hospitalised with AMI in the 3-month period in 2018, 2019, and 2020, respectively. Overall in 2020, about 58-60% of individuals with AMI received a prescription of beta-blockers within 1month after the discharge. A continuous decreasing trend over time was observed. Men were 30% more likely to start the treatment than women, increasing age was associated with significant increasing probability of not receiving a post-infarction beta-blocker therapy, while having received an antihypertensive or lipid-lowering treatment, or having been hospitalized for heart failure prior to the AMI hospitalization reduced the likelihood of not being treated with beta-blockers. Conclusion: The initiation of beta-blocker treatment after AMI remains an under-prescribed practice, that does not seem to have been further affected by the first wave of the COVID-19 pandemic.

CO79 Post-Acute Myocardial Infarction: 90-Day Outcomes Assessment Becoming More Relevant and Critical Due to Patient Burden and Poor Outcomes

CO79 Post-Acute Myocardial Infarction: 90-Day Outcomes Assessment Becoming More Relevant and Critical Due to Patient Burden and Poor Outcomes

Stress hyperglycemia ratio and neutrophil to lymphocyte ratio are reliable predictors of new-onset atrial fibrillation in patients with acute myocardial infarction.

The occurrence of new-onset atrial fibrillation (NOAF) post-acute myocardial infarction (AMI) is associated with worse outcomes. In this study, we sought to assess the predictive effect of stress hyperglycemia ratio (SHR) and neutrophil to lymphocyte ratio (NLR) to predict NOAF in patients with AMI. We recruited 3,194 individuals with AMI but free of atrial fibrillation (AF). AMI cases were stratified into groups according to SHR and NLR quartiles and were further categorized based on diabetes status. High SHR and high NLR were defined as the highest quartile of SHR and NLR. A nomogram incorporating risk factors for NOAF was constructed using multivariate logistic regression analyses. The performance of the novel nomogram was tested for predictive performance, agreement between the actual and predicted probability, and clinical utility using area under the curve (AUC), bootstrapped calibration curves, and decision curve analysis, respectively. A total of 245 (7.67%) patients developed NOAF post-AMI. The NOAF cases had higher values of SHR and NLR than non-NOAF patients after AMI regardless of diabetes status. After adjusting for potential confounders, high SHR and NLR were independently associated with NOAF post-AMI. Moreover, the novel nomogram incorporating high NLR and high SHR for NOAF risk estimation in patients with AMI showed satisfactory performance assessed by the AUC, calibration curves, decision curve analysis. SHR and NLR were independently associated with NOAF in AMI patients. The constructed novel nomogram that incorporates SHR and NLR might assist in NOAF risk stratification post-AMI.

Abstract 14479: Prolonged Decrease in Endothelial Cell (EC)-Specific Mitochondrial ROS Results in Mitochondrial Dysfunction in Coronary EC and Cardiac Hypertrophy in Post-AMI Animals

Introduction: Reducing mitochondrial ROS (mito-ROS) has been a novel approach for improving cardiac function. Here, we evaluated the effect of prolonged decrease in EC-specific mito-ROS on post-acute myocardial infarction (AMI) coronary angiogenesis and cardiac function. Hypothesis: We hypothesized that a prolonged decrease in EC-specific mito-ROS contributes to mitochondrial dysfunction in coronary EC resulting in post-AMI maladaptive cardiac remodeling. Methods: We used an EC-specific, tetracycline-controlled, transgenic MnSOD overexpression (MnSOD-OE) model. After 16 weeks of MnSOD-OE, mice underwent ligation of left anterior coronary artery (AMI). 28 days post-AMI, ejection fraction (EF), fractional shortening (FS), and left ventricle (LV) mass were determined by echocardiography (n=8/group). Isolated mouse heart ECs (MHEC) were evaluated by Seahorse for mitochondrial function and by western blot for cell signaling. Data were analyzed by Student’s t test. A p -value ≤0.05 was considered statistically significant. Results: MnSOD-OE mice showed 33% decrease (44.4±2.3 vs. 29.7±3.5) in EF and 35% decrease (21.7±1.2 vs. 14.2±1.7) in FS, compared to control. LV mass was increased by 51% (76.4±1.8 vs. 115.1±12.33 mg) in MnSOD-OE heart. LV end systolic and diastolic areas were increased in MnSOD-OE, by 2-fold (5.8±0.4 vs. 12.6±1.8) and 1.7-fold (9.8±0.5 vs. 16.8±1.6 mm 2 ), respectively. MnSOD-OE MHEC showed a reduction in mitochondrial maximal and spare respiration capacities, and decreased activation of Akt by 25% and ERK by 23%. Conclusions: Prolonged MnSOD-OE impaired mitochondrial respiration and inhibited Akt and ERK signaling in MHEC. These changes were associated with maladaptive remodeling post-AMI, including cardiac hypertrophy, LV dilatation, and systolic dysfunction. Together, these findings suggest that prolonged decrease in mito-ROS has detrimental effects on coronary EC resulting in maladaptive post-AMI cardiac remodeling.

Abstract 14875: Topological Data Analysis of Electronic Health Record Features Predicts Major Cardiovascular Outcomes After Revascularization for Acute Myocardial Infarction

Introduction: Topological data analysis (TDA) is an emerging mathematical technique that imposes structure on a dataset and examines the shapes (or topological features) that arise. The TDA algorithm Mapper Plus is proposed to study the spatial characteristics of clinical data for the purpose of patient classification. This is a data-driven and hypothesis-free approach to clinical risk stratification. Hypothesis: The hypothesis is that Mapper Plus can classify distinctive subsets of patients receiving optimal treatments post-acute myocardial infarction (AMI). Our goal is to identify subgroups who remained at risk of having a future adverse event (AE) i.e., death, heart failure hospitalization, or recurrent MI Methods: A single-center, retrospective analysis of 31 clinical variables from the electronic health record (EHR) was conducted on 798 AMI subjects. Risk was defined as high or low in relation to the average probability of survival without AE for the entire cohort at the 1 year mark. Results: TDA identified six subsets of patients. Four subsets (n=597) had > 1-fold change on the probability of survival free of AEs; these became the low-risk subgroup. Two subsets (n=344) had < 1-fold change on the probability of survival free of AEs; these became the high-risk subgroup. Because Mapper Plus allows for subject overlap across subgroups, 143 subject (18%) were shared between the high (n=201, 25%)- and low-risk (n=454, 57%) subgroups and were extracted into a 3rd intermediate risk subgroup (see figure). Conclusions: TDA significantly stratified AMI patients into 3 subgroups with distinctive incidences of AE up to 3 years post AMI. This is a new framework for EHR-based risk stratification that requires no additional patient interaction, is agnostic to prior knowledge, and is driven by the topological features of the included data. Further studies will be needed to validate TDA across different patient cohorts before it can be applied to clinical practice.

TREML4 polymorphisms increase the mRNA in blood leukocytes in the progression of atherosclerosis

TREML4 and other members of the triggering receptor expressed in the myeloid cell family are associated with a risk of atherosclerosis and progression in coronary artery disease, acute coronary syndrome, and coronary artery calcification. Herein, the relationship between TREML4 expression and its polymorphisms (rs2803495 and rs280396) was evaluated in patients with subclinical atherosclerosis (n = 340) and heart failure post-acute myocardial infarction (MI) (n = 68) for the first time. TREML4 variants rs2803495 (A > G) and rs2803496 (T > C) and leukocyte mRNA expression was analyzed by qRT–PCR. The rs2803495 G allele was associated with TREML4 expression (OR 8.01, CI 3.78–16.99, p < 0.001). Patients carrying the rs2803496 C minor allele (TC/CC genotypes) were more likely to express TREML4 than those without the C allele (OR 10.42, CI 4.76–22.78, p < 0.001), as well as having higher levels of TREML4 expression (OR 4.88, CI 2.35–10.12, p < 0.001). Thus, we report for the first time that TREML4 is not associated with the early stages of atherosclerotic plaque formation and later stages after MI. In conclusion, TREML4 mRNA expression in blood leukocytes is influenced by minor alleles (G and C) and may regulate differently during the atherosclerosis progression stages, but not in asymptomatic atherosclerosis disease and post-MI.

Sphingosine-1-phosphate improves outcome of no-reflow acute myocardial infarction via sphingosine-1-phosphate receptor 1.

Therapeutic options targeting post-ischaemic cardiac remodelling are sparse. The bioactive sphingolipid sphingosine-1-phosphate (S1P) reduces ischaemia/reperfusion injury. However, its impact on post-ischaemic remodelling independently of its infarct size (IS)-reducing effect is yet unknown and was addressed in this study. Acute myocardial infarction (AMI) in mice was induced by permanent ligation of the left anterior descending artery (LAD). C57Bl6 were treated with the S1P lyase inhibitor 4-deoxypyridoxine (DOP) starting 7days prior to AMI to increase endogenous S1P concentrations. Cardiac function and myocardial healing were assessed by cardiovascular magnetic resonance imaging (cMRI), murine echocardiography, histomorphology, and gene expression analysis. DOP effects were investigated in cardiomyocyte-specific S1P receptor 1 deficient (S1PR1 Cardio Cre+) and Cre- control mice and S1P concentrations measured by LC-MS/MS. IS and cardiac function did not differ between control and DOP-treated groups on day one after LAD-ligation despite fourfold increase in plasma S1P. In contrast, cardiac function was clearly improved and myocardial scar size reduced, respectively, on Day 21 in DOP-treated mice. The latter also exhibited smaller cardiomyocyte size and reduced embryonic gene expression. The benefit of DOP treatment was abolished in S1PR1 Cardio Cre+. S1P improves cardiac function and myocardial healing post AMI independently of initial infarct size and accomplishes this via the cardiomyocyte S1PR1. Hence, in addition to its beneficial effects on I/R injury, S1PR1 may be a promising target in post-infarction myocardial remodelling as adjunctive therapy to revascularization as well as in patients not eligible for standard interventional procedures.

S1P lyase inhibition improves post-ischemic cardiac remodeling independently of infarct size via S1P receptor 1

Abstract Background Revascularization of the infarct vessel is the golden standard in acute myocardial infarction (AMI). Even in Western countries, more than ten percent of AMI patients are so-called “latecomers” and it is controversial if revascularization of the infarct vessel is beneficial in these patients. Current guidelines even discourage revascularization of the infarcted artery if symptom onset was &amp;gt;48 hours and the patient is asymptomatic. These patients are at high risk for cardiovascular events and heart failure with reduced ejection fraction (HFrEF). HFrEF has an enormous socio-economic impact, high morbidity, and mortality. Purpose Therapeutic options targeting post-ischemic cardiac remodeling are sparse. The bioactive sphingolipid sphingosine-1-phosphate (S1P) reduces ischemia/reperfusion injury when administered in advance. However, its impact on post-ischemic remodeling independently of its infarct size (IS)-reducing effect is yet unknown. Methods Acute myocardial infarction (AMI) in mice was induced by permanent ligation of the left anterior descending artery (LAD). C57Bl/6J were treated with the S1P lyase inhibitor 4-deoxypyridoxine (DOP) starting seven days prior to AMI to increase endogenous S1P concentrations. Cardiac function and myocardial healing were assessed by cardiovascular magnetic resonance imaging (cMRI), histomorphology and gene expression analysis. DOP effects were investigated in cardiomyocyte-specific S1P receptor 1 deficient (S1PR1 Cardio Cre+ and Cre− control) mice, and S1P concentrations measured by LC-MS/MS. Results S1P concentrations in plasma before induction of AMI were increased fourfold by DOP (Control 0.97±0.09μM [n=6] vs. DOP 3,80±0,09μM [n=6]). Scar size determined by MRI, as well as ejection fraction (EF), did not differ 24 h post AMI. In contrast, after 21 days, there was a clear difference between the two groups (scar size vehicle: 19.3±6.2% vs. DOP 13.4±5.7%; EF: Vehicle: 26.4±8.7% vs. DOP 38.2±11.8%). In addition, in the remote area 21 days post AMI in the DOP-treated animals, a reduced gene expression of brain natriuretic peptide, atrial natriuretic peptide and collagen 1a2. Finally, cardiomyocyte diameter in the remote myocardium was 21% smaller in DOP-treated (Vehicle: 21.95±1.59μm vs. DOP 17.35±0.77μm). The benefit of DOP-treatment was abolished in cardiomyocyte-specific S1PR1-deficient mice. Conclusion S1P improves cardiac function and myocardial healing post AMI independently of initial infarct size via S1PR1. Hence, in addition to its beneficial effects on I/R injury, S1PR1 may be a promising target in post-infarction myocardial remodeling as adjunctive therapy to revascularization and in patients who are not eligible for standard interventional procedures. Funding Acknowledgement Type of funding sources: None.

Prognostic importance of NT-proBNP following high-risk myocardial infarction in the PARADISE-MI Trial

Abstract Background/Introduction N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a marker of ventricular wall stress and a potent predictor of death and heart failure (HF) across multiple populations (from healthy insurance applicants to various disease entities). Purpose To evaluate the prognostic importance of NT-proBNP in patients with acute myocardial infarction (AMI) complicated by left ventricular systolic dysfunction, pulmonary congestion, or both and ≥1 of 8 predefined risk-augmenting factors (age ≥70 years, diabetes, previous MI, eGFR &amp;lt;60 ml/min/1.73 m2, atrial fibrillation, LVEF &amp;lt;30%, Killip class III/IV, or ST elevation MI without reperfusion) enrolled in PARADISE-MI. Methods Patients were randomized to sacubitril/valsartan 200mg or ramipril 5mg twice daily within 0.5 to 7 days of presenting with an AMI. Patients with prior HF were excluded. NT-proBNP and high-sensitivity troponin T (hsTnT) were collected at randomization in a prespecified sub-study of 1129 patients. The primary endpoint of PARADISE-MI was a time-to-first composite of cardiovascular (CV) death or incident HF (hospitalization or outpatient symptomatic HF); secondary endpoints included all-cause death and the composite of fatal or non-fatal MI or stroke. Results Median NT-proBNP was 1757 pg/ml [interquartile range, 896–3462 pg/ml] at randomization (4.0±1.8 days after presentation with the index MI). Patients with higher NT-proBNP levels at baseline were older, more commonly women and more frequently had hypertension, atrial fibrillation, renal dysfunction, and pulmonary congestion at randomization (all p&amp;lt;0.001). NT-proBNP concentrations were only weakly correlated with levels of hsTnT at randomization (r=0.38, p&amp;lt;0.001). NT-proBNP at baseline was strongly associated with the primary composite endpoint (adjusted HR 1.45 per doubling NT-proBNP; 95% CI, 1.23–1.70), independent of clinical variables as well as hsTnT (Figure). NT-proBNP was also independently associated with all-cause death (aHR 1.74; 95% CI, 1.38–2.21) and fatal or non-fatal MI or stroke (aHR 1.24; 95% CI, 1.05–1.45). The relative effect of sacubitril/valsartan versus ramipril on the primary composite endpoint was not statistically different across the spectrum of NT-proBNP (p-interaction = 0.46). Conclusions When assessed within the first week of a high risk AMI NT-proBNP is not only associated with incident HF and death but also with atherosclerotic events and provides prognostic information that is independent of hsTnT in this post AMI population. Funding Acknowledgement Type of funding sources: None.

Low chronotropic index predicts rehospitalization in post-acute myocardial infarction patients with preserved or mildly reduced left ventricular ejection fraction

Abstract Background There are limited data about the clinical utility of combined stress echocardiography and cardiopulmonary exercise testing (CPET-ESE) in predicting prognosis in patients after acute myocardial infarction (AMI) with preserved left ventricular ejection fraction (LVEF). Aim To assess prognostic parameters using CPET-ESE in post-AMI patients with preserved or mildly reduced LVEF. Methods Eighty-seven patients after the first AMI with LVEF &amp;gt;40% were followed for 2 years (median 1.93 years IQR 1.16–2.41). The composite end-point was all-cause mortality or rehospitalization due to ischaemic heart disease (AMI, unstable angina, percutaneous coronary intervention/coronary artery bypass grafting) or heart failure exacerbation. All patients underwent symptom-limited CPET-ESE on a semi-supine cycle ergometer 3 to 5 weeks after AMI. The chronotropic index was calculated as the percent of heart rate reserve. Six patients refused to complete the survey and they were not included in the analysis. Results Follow-up was conducted in 81 consecutive patients (mean age 59±10 years, 62% males, 50% AMI with ST-segment elevation, 85% on beta-blockers). Mean LVEF was 56±9% and peak VO2 18.5±5.0 mL/kg/min. There were no deaths during follow-up. The composite end-point occurred in 13 patients. In multivariate Cox regression analysis after correction for demographic and clinical variables, only chronotropic index correlated with the composite end-point (HR 0.93, 95% CI 0.87–0.99, p=0.026). A positive predictive value of 33.3% and a negative predictive value of 91.3% (sensitivity 61.5%, specificity 76.5%, area under the curve, AUC 71%) for predicting the composite end-point was established for the chronotropic index ≤36.8% (Fig. 1). There was a statistically significant difference in the composite end-point occurrence (p&amp;lt;0.01) between subgroups with the chronotropic index above and below that threshold (Fig. 2). Conclusions In patients after the first AMI with preserved or mildly reduced left ventricular systolic function, a lower chronotropic index is a predictor of rehospitalization in 2-year follow-up. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Centre of Postgraduate Medical Education, Warsaw, Poland

Improve the Prevention of Sudden Cardiac Arrest in Patients With Post-Acute Myocardial Infarction

Implantable cardioverter-defibrillator (ICD) implantation to prevent sudden cardiac death (SCD) in post-myocardial infarction (MI) patients varies by geography but remains low in many regions despite guideline recommendations. This study aimed to characterize the care pathway of post-MI patients and understand barriers to referral for further SCD risk stratification and management in patients meeting referral criteria. This prospective, nonrandomized, multi-nation study included patients≥18 years of age, with an acute MI≤30days and left ventricular ejection fraction<50%≤14days post-MI. The primary endpoint was defined as the physician's decision to refer a patient for SCD stratification and management. In total, 1,491 post-MI patients were enrolled (60.2 ± 12.0 years of age, 82.4% male). During the study, 26.7% (n=398) of patients met criteria for further SCD risk stratification; however, only 59.3% of those meeting criteria(n=236; 95%CI: 54.4%-64.0%) were referred for a visit. Of patients referred for SCD risk stratification and management, 94.9% (n=224) attended the visit of which 56.7% (n =127; 95%CI: 50.1%-63.0%) met ICD indication criteria. Of patients who met ICD indication criteria, 14.2% (n=18) were implanted. We found that ∼40% of patients meeting criteria were not referred for further SCD risk stratification and management and ∼85% of patients who met ICD indications did not receive a guideline-directed ICD. Physician and patient reasons for refusing referral to SCD risk stratification and management or ICD implant varied by geography suggesting that improvement will require both physician- and patient-focused approaches. (Improve Sudden Cardiac Arrest [SCA] Bridge Study; NCT03715790).

1 Reversing miRNA-Suppressed Cardioprotective Cardiokine Expression as a Novel Intervention Against Sleep Breathing Disorders-Exacerbated Post-MI Remodeling

Cardiovascular disease remains a leading cause of morbidity and mortality worldwide. Although technological and pharmaceutical advances have enhanced patient survival post-acute myocardial infarction (MI), both incidence and prevalence of post-MI leading to heart failure (HF) have continually climbed. Accordingly, it is important to identify treatable conditions potentially contributive to HF progression. Obstructive sleep apnea (OSA), a sleep breathing disorder in which chronic intermittent hypoxia (CIH) is the primary pathology, is associated with multiple cardiovascular diseases.

Plasma tissue factor coagulation activity in post-acute myocardial infarction patients.

IntroductionCoagulation is involved in fibroproliferative responses following acute myocardial infarction (AMI). Left ventricular (LV) remodeling following AMI is closely associated with progression to heart failure. This study aims to assess the association between plasma tissue factor activity and LV remodeling in post-AMI patients.MethodsWe studied 228 patients with AMI and 57 healthy subjects. Patients with AMI were categorized into two age- and sex-matched groups: patients with adverse LV remodeling or reverse LV remodeling, defined by an increase or decrease, respectively, in LV end systolic volume by ≥15% over 6 months. TF activity was measured in plasma collected at baseline (within 72 hours of revascularization), 1 month and 6 months post-AMI. Multiple level longitudinal data analysis with structural equation (ML-SEM) model was used to assess the impact of various clinical variables on TF activity in post-AMI.ResultsPlasma TF activity in post-AMI patients at baseline (29.05 ± 10.75 pM) was similar to that in healthy subjects but fell at 1 month (21.78 ± 8.23, p<0.001) with partial recovery by 6 months (25.84 ± 8.80, p<0.001) after AMI. Plasma TF activity at 6 month post-AMI was better restored in patients with reverse LV remodeling than those with adverse LV remodeling (27.35 ± 7.14 vs 24.34 ± 9.99; p=0.009) independent of gender, age and relevant cardiovascular risk factors.ConclusionsPlasma TF activity decreased after AMI but was better restored at 6 months in patients with reverse LV remodeling. The clinical significance of changes in post-AMI plasma TF activity needs further investigation.

The Clock Is Ticking: The Imminent Need to Re-evaluate the Standard of Care in the 90-Day High-Risk Post-Acute Myocardial Infarction Period

This CSL Behring-supported symposium took place during the European Society of Cardiology (ESC) 2021 Congress. Experts P. Gabriel Steg Cardiology Department, Hôpital Bichat-Claude-Bernard, Paris, France, and the Université de Paris, France; and Kausik Ray, Imperial Centre for Cardiovascular Disease Prevention, Imperial College London, UK; Imperial Clinical Trials Unit, Imperial College London, UK; and Commercial Trials, Imperial College London, UK, discussed the clinical significance of the early post-acute myocardial infarction (AMI) period and the risk of recurrent events despite optimal recommended standard of care. Steg highlighted data from a retrospective registry study as well as several randomised controlled trials, suggesting that recurrent cardiovascular (CV) events appeared to accrue quickly in the early post-AMI period. He proposed that this may be an important timeframe for additional therapeutic interventions and warrants further investigation. Ray highlighted guideline recommendations for secondary prevention, currently focused on lipid-lowering and antiplatelet therapies. Ray presented data from several randomised controlled trials of lipid-lowering therapies, demonstrating that despite therapeutic advances and guideline-recommended treatments, there is a residual risk of recurrent CV events post-AMI. Ray suggested that additional therapeutic targets should be explored to further reduce the incidence of recurrent CV events post-AMI.

Reliability and validity of sit-to-stand test protocols in patients with coronary artery disease.

BackgroundSit-To-Stand (STS) tests are reported as feasible alternatives for the assessment of functional fitness but the reliability of these tests in people with coronary artery disease (CAD) has not been reported. This study explored the test-retest reliability, convergent and known-groups validity of the five times, 30-sec and 1-min sit-to-stand test (FTSTS test, 30-s STS test and 1-min STS test respectively) in patients with CAD. The feasibility of applying these tests to distinguish the level of risk for cardiovascular events in CAD patients was also investigated.MethodsPatients with stable CAD performed a 6MWT and 3 STS tests in random order on the same day. Receiver operating characteristic (ROC) curve analyses were conducted using STS test data to differentiate patients with low or high risk of cardiovascular events based on the risk level determined by distance covered in the 6MWT as > or ≤ 419 m. Thirty patients repeated the 3 STS tests on the following day.Results112 subjects with diagnoses of atherosclerosis or post-percutaneous coronary intervention, or post-acute myocardial infarction (post-AMI) participated in the validity analysis. All 3 STS tests demonstrated moderate and significant correlation with the 6MWT (coefficient values r for the FTSTS, 30-s STS and 1-min STS tests were−0.53, 0.57 and 0.55 respectively). Correlations between left ventricular ejection fraction (LVEF) and all STS tests and between 6MWT and LVEF were only weak (r values ranged from 0.27 to 0.31). Subgroup analysis showed participants in the post-AMI group performed worse in all tests compared to non-myocardial infarction (non-MI) group. The area under the curve (AUC) was 0.80 for FTSTS (sensitivity: 75.0%, specificity: 73.8%, optimal cut-off: >11.7 sec), and the AUC, sensitivity, specificity and optimal cut-off for 30-s STS and 1-min STS test were 0.83, 75.0%, 76.2%, ≤ 12 repetitions and 0.80, 71.4%, 73.8%, ≤ 23 repetitions respectively. The intraclass correlation coefficients (ICC) for repeated measurements of the FTSTS, 30-s STS and 1-min STS tests were 0.96, 0.95 and 0.96 respectively, with the minimal detectable change (MDC95) computed to be 1.1 sec 1.8 repetitions and 3.9 repetitions respectively.ConclusionsAll STS tests demonstrated good test-retest reliability, convergent and known-groups validity. STS tests may discriminate low from high levels of risk for a cardiovascular event in patients with CAD.

Noninvasive Monitoring of Reparative Fibrosis after Myocardial Infarction in Rats Using 68Ga-FAPI-04 PET/CT.

Noninvasively monitoring activated fibroblasts is of great value for understanding the dynamic process of myocardial fibrosis after myocardial infarction (MI). This study aimed to evaluate the feasibility of 68Ga-labeled fibroblast activation protein inhibitor 04 (68Ga-FAPI-04) for monitoring reparative fibrosis and reactive fibrosis after MI. MI models were prepared by ligation of the left anterior descending (LAD) coronary artery and validated by electrocardiogram and 18F-FDG PET/CT 1 day after MI and hematoxylin and eosin (HE) staining. 68Ga-FAPI-04 PET/CT scans (1, 3, 6, 9, 12, 15, 18, 21, 28, and 35 days after MI) were carried out in MI rats and sham-operated rats without ligation of LAD. Blocking experiments were carried out on MI rats on day 7 after MI with 68Ga-FAPI-04 and excessive FAPI-04. Autoradiography, HE staining, Masson's trichrome staining, and immunofluorescence staining were carried out for ex vivo validation. The infarcted area with decreased or defective myocardial metabolic activity in 18F-FDG PET/CT correspondingly showed high 68Ga-FAPI-04 uptake in the MI rats. The myocardial tracer uptake was significantly different between MI and sham-operated rats from day 1 to 28 after MI and reached peak value 6 days after MI (0.806 ± 0.257%ID/cc vs 0.199 ± 0.012%ID/cc, P < 0.05). Tracer uptake at the infarcted myocardium and normal tissues in MI rats decreased significantly after blocking. Obvious tracer uptake was confirmed by autoradiography, and immunofluorescence staining showed FAP+ cells in the infarcted myocardium and border zone. Masson's trichrome staining of the heart sections of MI rats at different times suggested the presence of myocardial fibrosis. 68Ga-FAPI-04 uptake was not observed in the distal uninjured myocardium throughout the observation period. In conclusion, 68Ga-FAPI-04 PET could noninvasively monitor the activated fibroblasts in the early stage post acute MI and may be helpful for evaluating the degree of reparative fibrosis, while reactive fibrosis monitoring still needs further study.

Age-related difference in the impact of diabetes mellitus on all-cause mortality after acute myocardial infarction

Background and Aims : Little is known about the association of diabetes mellitus with clinical outcomes of post-acute myocardial infarction (AMI) in younger adults. We tested the hypothesis that the impact of diabetes on outcomes can vary by age.

Clinical Characteristics and Risk Factors of In-Hospital Mortality in Patients With Acute Myocardial Infarction With Subsequent Gastrointestinal Bleeding: A Single-Center Experience.

ObjectiveGastrointestinal bleeding (GIB) post acute myocardial infarction (AMI) is a severe clinical condition with a poor prognosis. The purpose of the study was to evaluate the rate of in-hospital mortality in patients with GIB post-AMI and to identify the potential risk factors of this situation.MethodsIn this single-center retrospective study, a total of 154 patients diagnosed with AMI who subsequently suffered GIB were enrolled from October 2013 to December 2021. Demographic, laboratory, and clinical data were collected. The in-hospital mortality was the outcome of interest. Logistic regression analysis was used to investigate the potential risk factors of in-hospital mortality.ResultsAmong the 154 subjects included in the final analysis, the mean age was 65.58 ± 11.20 years, and 104 (67.53%) were males. GIB occurred in 11 patients after thrombolytic therapy, 50 patients after percutaneous coronary intervention (PCI), and 93 patients during drug conservative treatment. A total of 41 patients died in the hospital. The in-hospital mortality rate of the thrombolysis group, PCI group, and drug conservative treatment group was 27.27% (3/11), 28.00% (14/50), and 25.81% (24/93), respectively. There was no difference in the in-hospital mortality among the three groups. The multivariate logistic regression analysis showed that the peak levels of TnI (OR 1.07, 95% CI 1.02–1.12, P = 0.011), condition of cardiogenic shock after admission (OR 14.52, 95% CI 3.36–62.62, P < 0.001), and the use of the mechanical ventilator (OR 8.14, 95% CI 2.03–32.59, P = 0.003) were significantly associated with in-hospital mortality.ConclusionRegardless of the treatment strategy for AMI, once GIB occurred, the prognosis was poor. High in-hospital mortality in patients with GIB post-AMI was independently associated with the peak levels of TnI, condition of cardiogenic shock, and the use of a mechanical ventilator.

Effects of Glucagon-Like Peptide-1 Receptor Agonist (GLP-1RA) on Cardiac Structure and Function: A Systematic Review and Meta-Analysis of Randomized-Controlled Trials.

Recent trials suggest glucagon-like peptide-1 receptor agonists (GLP-1RAs) may have a cardioprotective role by reducing major adverse cardiac events, stroke mortality and heart failure-related hospitalisations. We examined whether and how GLP-1RAs affect cardiac function in cardiovascular and metabolic diseases including type 2 diabetes, heart failure and post-myocardial infarction. In this PRISMA-adherent systematic review and meta-analysis, three databases were searched from inception to July 2021 and registered on PROSPERO (CRD42021259661). 20 reports of 19 randomized placebo-controlled trials including 2062 participants were meta-analyzed. Among type 2 diabetes patients, GLP-1RA resulted in improved systolic function measured by circumferential strain (mean difference [MD]= -5.48; 95% CI: -10.47 to -0.49; P= 0.03; I2= 89%) and diastolic dysfunction measured by E / A (MD= -0.15; 95% CI: -0.25 to -0.05; P= 0.003; I2= 0%). For post-myocardial infarction patients, GLP-1RA reduced infarct size (g) (MD= -5.36; 95% CI: -10.68 to -0.04; P= 0.05; I2= 78%). Liraglutide, but not exenatide, demonstrated improved systolic function, by increasing left ventricular ejection fraction (MD= 4.89; 95% CI: 3.62 to 6.16; P< 0.00001; I2= 0%) and reducing left ventricular end-systolic volume (MD= -4.15; 95% CI: -7.49 to -0.81; P = 0.01; I2= 0%). Among heart failure patients, no significant changes were noted. GLP-1RA drugs may improve systolic and diastolic function in type 2 diabetes and reduce infarct size post-acute myocardial infarction with no demonstrable effect on cardiac function in heart failure. Tailored recommendations for the use of GLP-1RAs for cardioprotection should be considered for each patient's condition.