After Acute Myocardial Infarction Research Articles

Rates of Sudden Death After Myocardial Infarction-Insights From the VALIANT and PARADISE-MI Trials.

Sudden death is a leading cause of death after acute myocardial infarction (AMI). The Prospective ARNi vs ACE Inhibitor Trial to Determine Superiority in Reducing Heart Failure Events After MI (PARADISE-MI) and Valsartan in Acute Myocardial Infarction (VALIANT) trials enrolled patients with pulmonary congestion and/or left ventricular dysfunction after AMI. Whether the prognosis in such patients has changed over time has not been examined. To compare the rate of sudden death/resuscitated cardiac arrest (RCA) after AMI in the PARADISE-MI and VALIANT trials. This was a secondary analysis of multicenter randomized clinical trials enrolling patients after AMI. In the primary analysis, the VALIANT cohort was restricted to patients with "PARADISE-MI-like" characteristics (eg, at least 1 augmenting risk factor and no history of heart failure). The baseline characteristics of people in both trials were compared. The VALIANT trial enrolled from December 1998 to June 2001, and the PARADISE-MI trial enrolled between December 2016, and March 2020. The median follow-up in the VALIANT and PARADISE-MI trials was 24.7 and 22 months, respectively. People with AMI, complicated by pulmonary congestion and/or left ventricular dysfunction, were included in the analysis. Sudden death after AMI. A total of 5661 patients were included in the PARADISE-MI cohort (mean [SD] age, 63.7 [11.5] years; 4298 male [75.9%]), 9617 were included in the VALIANT (PARADISE-MI-like) cohort (mean [SD] age, 66.1 [11.5] years; 6504 male [67.6%]), and 14 703 patients were included in the VALIANT (total) cohort (mean [SD] age, 64.8 [11.8] years; 10 133 male [68.9%]). In the PARADISE-MI-like cohort of the VALIANT trial, 707 of 9617 participants (7.4%) experienced sudden death/RCA. A total of 148 of 5661 people (2.6%) in the PARADISE-MI trial experienced sudden death/RCA. Sudden death rates were highest in the first month after infarction in both trials: 19.3 (95% CI, 16.4-22.6) per 100 person-years in the VALIANT trial and 9.5 (95% CI, 7.0-12.7) per 100 person-years in the PARADISE-MI trial, and these rates declined steadily thereafter. Compared with the VALIANT cohort, people in the PARADISE-MI trial were more often treated with percutaneous coronary intervention for their qualifying AMI and received a β-blocker, statin, and mineralocorticoid receptor antagonist more frequently. After AMI, the risk of sudden death/RCA was highest in the first month, declining rapidly thereafter. Results revealed that compared with counterparts from 20 years ago, the rate of sudden death/RCA in patients with a reduced left ventricular ejection fraction and/or pulmonary congestion was 2- to 3-fold lower in people receiving contemporary management. Interventions to further protect people in the highest risk first month after infarction are needed. ClinicalTrials.gov Identifier: NCT02924727.

Trends and Disparities in Ambulatory Follow-Up After Cardiovascular Hospitalizations : A Retrospective Cohort Study.

Timely follow-up after cardiovascular hospitalization is recommended to monitor recovery, titrate medications, and coordinate care. To describe trends and disparities in follow-up after acute myocardial infarction (AMI) and heart failure (HF) hospitalizations. Retrospective cohort study. Medicare. Medicare fee-for-service beneficiaries hospitalized between 2010 and 2019. Receipt of a cardiology visit within 30 days of discharge. Multivariable logistic regression models were used to estimate changes over time overall and across 5 sociodemographic characteristics on the basis of known disparities in cardiovascular outcomes. The cohort included 1 678 088 AMI and 4 245 665 HF hospitalizations. Between 2010 and 2019, the rate of cardiology follow-up increased from 48.3% to 61.4% for AMI hospitalizations and from 35.2% to 48.3% for HF hospitalizations. For both conditions, follow-up rates increased for all subgroups, yet disparities worsened for Hispanic patients with AMI and patients with HF who were Asian, Black, Hispanic, Medicaid dual eligible, and residents of counties with higher levels of social deprivation. By 2019, the largest disparities were between Black and White patients (AMI, 51.9% vs. 59.8%, difference, 7.9 percentage points [pp] [95% CI, 6.8 to 9.0 pp]; HF, 39.8% vs. 48.7%, difference, 8.9 pp [CI, 8.2 to 9.7 pp]) and Medicaid dual-eligible and non-dual-eligible patients (AMI, 52.8% vs. 60.4%, difference, 7.6 pp [CI, 6.9 to 8.4 pp]; HF, 39.7% vs. 49.4%, difference, 9.6 pp [CI, 9.2 to 10.1 pp]). Differences between hospitals explained 7.3 pp [CI, 6.7 to 7.9 pp] of the variation in follow-up for AMI and 7.7 pp [CI, 7.2 to 8.1 pp]) for HF. Generalizability to other payers. Equity-informed policy and health system strategies are needed to further reduce gaps in follow-up care for patients with AMI and patients with HF. National Institute on Aging.

Prognostic impact of High-intensity Lipid-Lowering Therapy Under-Prescription after Acute Myocardial Infarction in Women

Abstract Aims Women are less likely to receive lipid-lowering therapy(LLT) after acute myocardial infarction(AMI). We analysed whether this under-prescription currently persists and has an impact on long-term outcomes. Methods The FAST-MI program consists in nationwide registries including all patients admitted for AMI ≤48 hours from onset over a one-month period in 2005, 2010 and 2015, with long-term follow-up. This analysis focused on high-intensity LLT (atorvastatin≥40 mg or equivalent, or any combination of statin and ezetimibe) in women and men. Results Women accounted for 28% (N=3547) of the 12659 patients. At discharge, high-intensity LLT was significantly less prescribed in women (54% vs. 68% in men, p<0.001, adjusted OR 0.78[95% CI 0.71-0.87]), a trend that did not improve over time: 2005, 25% versus 35% (P=0.14); 2010, 66% versus 79% (P<0.001); 2015, 67% versus 79.5% (P=0.001). In contrast, female sex was not associated with a lack of other recommended treatments at discharge: beta-blockers (adjusted OR 0.98[95% CI 0.88-1.10], P=0.78), or renin-angiotensin blockers (adjusted OR 0.94[95% CI 0.85-1.03], P=0.18). High-intensity LLT at discharge was significantly associated with improved five-year survival and infarct- and stroke-free survival in women (adjusted HR 0.74[95%CI 0.64-0.86], P<0.001 and adjusted HR: 0.81[95% CI: 0.74−0.89]; P<0.001, respectively). Similar results were found using a propensity score-matched analysis (HR for 5-year survival in women with high intensity LLT: 0.82[95%CI 0.70-0.98], P=0.03). Conclusion Women suffer from a bias regarding prescription of high-intensity LLT after AMI, which did not attenuate between 2005 and 2015, with potential consequences on both survival and risk of cardiovascular events.

Cardiac rehabilitation patient perspectives during COVID-19 pandemic: quantitative and qualitative study

BackgroundThis study aimed to quantitatively assess stress, anxiety and obsessive thinking related to coronavirus disease-19 (COVID-19) and qualitatively appraise perceptions in patients after acute myocardial infarction (AMI) undergoing cardiac rehabilitation (CR) during the COVID-19 pandemic.MethodsWe used mixed-methods design in patients referred for CR in 2 centres which delivered uninterrupted service during COVID-19 pandemic. Coronavirus Anxiety Scale (CAS), Obsession with COVID-19 Scale (OCS), COVID-19 Stress Scale (CSS), Hospital Anxiety and Depression Scale (HADS), and in-person interviews (combination of a priori questions and probing) were used to evaluate patient experience and perceptions with COVID-19 and the healthcare services during pandemic.ResultsIn total, 109 patients (mean age 59 ± 10, 20% women) were included in quantitative part and in 30 of them we conducted the in-person interviews. About a quarter of patients met HADS threshold for anxiety and depression while CAS and OCS results demonstrated extremely low possibility of coronavirus related dysfunctional thinking (3%) and anxiety (2%). The CSS indicated the most prevalent concerns were related to COVID-19 vaccines safety (60%) and fear of getting infected (60%). During interviews, patients perceived the CR as well as health care providers as safe, trustworthy and with enough support to avoid or manage COVID-19 related health risks.ConclusionsOverall, patients reported AMI affected their lives more than the COVID-19 pandemic. The COVID-19 related stress and anxiety were relatively low and mostly related to general views of infectious disease. CR was perceived safe and trustworthy in terms of primary disease and COVID-19.Lay summaryThis mixed-method study included 109 patients with acute myocardial infarction who underwent cardiac rehabilitation during the COVID-19 and focused on their experience and perceptions with COVID-19 and the healthcare services during pandemic.-Patients reported acute myocardial infarction affected their lives more than the COVID-19 pandemic.-The COVID-19 related concerns were mostly related to general views of infectious disease (vaccine safety, fear of getting infected) whilst cardiac rehabilitation was perceived safe and trustworthy environment during COVID-19.

Association between carotid plaque progression and persistent endothelial dysfunction in an infarct-related coronary artery in STEMI survivors.

Persistent coronary endothelial dysfunction predicts future adverse events; however, performing multiple invasive endothelial function tests is difficult in actual clinical practice. This study examined the association between carotid plaque progression and persistent coronary endothelial dysfunction using serial assessments of the coronary vasomotor response to acetylcholine (ACh) in the infarct-related artery (IRA) among patients with ST-elevation acute myocardial infarction (STEMI). This study included 169 consecutive patients with a first STEMI due to the left anterior descending coronary artery (LAD) occlusion who underwent successful percutaneous coronary intervention. The vasomotor response to ACh in the LAD was measured within two weeks after acute myocardial infarction (AMI) (first test) and repeated at six months (second test) after AMI. Ultrasonography of the bilateral common carotid artery and internal carotid artery was performed during the acute phase, and the thickest intima-media thickness (IMT) of either artery was measured as the maximum IMT. After six months, the IMT at the site of maximal IMT was re-measured to determine the carotid plaque progression. Finally, 87 STEMI patients analyzed. At 6months, 25 patients (28.7%) showed carotid plaque progression. In a multivariable analysis, carotid plaque progression was identified as an independent predictor of persistent coronary endothelial dysfunction, both in terms of coronary diameter response [odd ratio (OR) 3.22, 95% confidence interval (95% CI) 1.13-9.15, p = 0.03] and coronary flow response [OR 2.65, 95% CI 1.01-7.00, p = 0.04]. Independently, carotid plaque progression is linked to persistent endothelial dysfunction in the IRA among STEMI survivors.

Treatment of sleep apnoea early after myocardial infarction with adaptive servo-ventilation - a proof-of-concept randomised controlled trial.

Sleep-disordered breathing has been associated with less myocardial salvage and smaller infarct size reduction after acute myocardial infarction (AMI). The Treatment of sleep apnoea Early After Myocardial infarction with Adaptive Servo-Ventilation (TEAM-ASV I) trial investigated the effects of adding adaptive servo-ventilation (ASV) for sleep-disordered breathing (SDB) to standard therapy on myocardial salvage index (MSI) and change in infarct size within 12 weeks after AMI. In this multicentre, randomised, open-label trial, patients with AMI and successful percutaneous coronary intervention within 24 h after symptom onset plus SDB (apnoea-hypopnoea index ≥15/h) were randomised to standard medical therapy alone (control) or plus ASV (starting 3.6±1.4 days post-AMI). The primary outcome was MSI at 12 weeks post-AMI. Cardiac magnetic resonance (CMR) imaging was performed at ≤5 days and 12 weeks after AMI. Seventy-six individuals were enrolled from February 2014 to August 2020; 39 had complete CMR data for analysis of the primary endpoint. MSI was significantly higher in the ASV versus control group (difference 14.6% of left ventricular mass [LVM]; 95% confidence interval 0.14-29.1; p=0.048). At 12 weeks, absolute [interquartile range] (6.6 [4.8-8.5] versus 2.8 [0.9-4.8] %LVM; p=0.003) and relative (44 [30-57] versus 21 [6-35] % of baseline; p=0.013) reductions in infarct size were greater in the ASV versus control group. No serious treatment-related adverse events occurred. Early treatment of SDB with ASV improved the MSI and decreased the infarct size at 12 weeks after AMI. Larger randomised trials are required to confirm these findings.

The relative impact of components of high residual risk on the long-term prognosis after AMI

BackgroundThe reduction in long-term mortality after acute myocardial infarction (AMI) is less pronounced than that of in-hospital mortality among patients with AMI complicated by heart failure (HF) and/or in those with a high residual thrombotic risk (HTR). AimTo investigate the relative prognostic significance of HTR and HF in AMI survivors. MethodsThis retrospective cohort study enrolled patients admitted for AMI in 2014–2015 in all Italian hospitals. HTR was defined as at least one of the following conditions: previous AMI, ischemic stroke or other vascular disease, type 2 diabetes, renal failure. Patients were classified into four categories: uncomplicated AMI; AMI with HTR; AMI with HF and AMI with both HTR and HF (HTR + HF). Cox proportional hazard model was used to evaluate the impact of HTR, HF and HTR + HF on the 5-year prognosis. A time-varying coefficient analysis was performed to estimate the 5-year trend of HR for major averse cardiac and cerebrovascular events (MACCE). Resultsa total of 174.869 AMI events were identified. The adjusted 5-year HR for MACCE was 1.74 (p < 0.0001) and 1.75 (p < 0.0001) in HTR and HF patients vs uncomplicated patients, respectively. The coexistence of HTR and HF furtherly increased the risk of MACCE (HR = 2.43, p < 0.0001) over the first 3 years after AMI. ConclusionEither HRT and HF confer an increased 5-year hazard of MACCE after AMI. The coexistence of HTR and HF doubled the overall 5-year risk of MACCE after AMI.

Murine exosomal miR-30a aggravates cardiac function after acute myocardial infarction via regulating cell fate of cardiomyocytes and cardiac resident macrophages

After acute myocardial infarction (AMI), intercellular communication is crucial for maintaining cardiac homeostasis and patient survival. Exosomes secreted by cardiomyocytes serve as carriers for transporting microRNA(miRNAs), participating in intercellular signaling and the regulation of cardiac function. This study aims to investigate the role of exosomal microRNA-30a(miR-30a) during AMI and its underlying mechanisms. AMI was induced by permanent ligation of the left anterior descending (LAD) artery in C57BL/6 mice. The expression of miR-30a in mice was respectively enhanced and inhibited by administering agomiR-30a and antagomiR-30a. Using HL-1 cardiomyocytes and RAW264.7 macrophages for in vitro experiments, HL-1 cardiomyocytes were cultured under hypoxic conditions to induce ischemic injury. Following isolation and injection of exosomals, a variety of validation methods were utilized to assess the expression of miR-30a, and investigate the effects of enriched exosomal miR-30a on the state of cardiomyocytes. After AMI, the level of exosomal miR-30a in the serum of mice significantly increased and was highly enriched in cardiac tissue. Cardiomyocytes treated with agomiR-30a and miR-30a-enriched exosomes exhibited inhibition of cell autophagy, increased cell apoptosis, mice showed an larger myocardial infarct area and poorer cardiac function. Exosomes released from hypoxic cardiomyocytes transferred miR-30a to cardiac resident macrophages, promoting the polarization into pro-inflammatory M1 macrophages. In conclusion, murine exosomal miR-30a exacerbates cardiac dysfunction post-AMI by disrupting the autophagy-apoptosis balance in cardiomyocytes and polarizing cardiac resident macrophages into pro-inflammatory M1 macrophages. Modulating the expression of miR-30a may reduce cardiac damage following AMI, and targeting exosomal miR-30a could be a potential therapeutic approach for AMI.

The ischemia-enhanced myocardial infarction protection-related lncRNA protects against acute myocardial infarction.

Long non-coding RNA RP11-64B16.4 (myocardial infarction protection-related lncRNA [MIPRL]) is among the most abundant and the most upregulated lncRNAs in ischemic human hearts. However, its role in ischemic heart disease is unknown. We found MIPRL was conserved between human and mouse and its expression was increased in mouse hearts after acute myocardial infarction (AMI) and in cultured human and mouse cardiomyocytes after hypoxia. The infarcted size, cardiac cell apoptosis, cardiac dysfunction, and cardiac fibrosis were aggravated in MIPRL knockout mice after AMI. The above adverse results could be reversed by re-expression of MIPRL via adenovirus expressing MIPRL. Both in vitro and in vivo, we identified that heat shock protein beta-8 (HSPB8) was a target gene of MIPRL, which was involved in MIPRL-mediated anti-apoptotic effects on cardiomyocytes. We further discovered that MIPRL could combine with the messenger RNA (mRNA) of HSPB8 and increase its expression in cardiomyocytes by enhancing the stability of HSPB8 mRNA. In summary, we have found for the first time that the ischemia-enhanced lncRNA MIPRL protects against AMI via its target gene HSPB8. MIPRL might be a novel promising therapeutic target for ischemic heart diseases such as AMI.

Angiotensin-converting enzyme inhibitors provide a protective effect on hypoxia-induced injury in human coronary artery endothelial cells via Nrf2 signaling and PLVAP.

Angiotensin-converting enzyme inhibitors (ACEIs) were reported to protect from hypoxia-induced oxidative stress in coronary endothelial cells (CECs) after acute myocardial infarction (AMI). Nrf2 shows a protective effect in hypoxia-induced CECs after AMI. Plasmalemma vesicle-associated protein (PLVAP) plays a pivotal role in angiogenesis after AMI. To explore the protective effect of ACEIs and the involved mechanisms under hypoxia challenge. Human coronary endothelial cells (HCAECs) were used to establish hypoxia-induced oxidative stress injury in vitro. Flow cytometry was used to evaluate the protective effect of ACEI on hypoxia conditions.ET-1, NO, ROS, and VEGF were detected by ELISA. HO-1, Nrf2, and Keap-1, the pivotal member in the Nrf2 signaling pathway, eNOS and PLVAP were detected in HEAECs treated with ACEI by immunofluorescence, qPCR, and western blotting. The hypoxia ACEI or Nrf2 agonist groups showed higher cell viability compared with the hypoxia control group at 24 (61.75±1.16 or 61.23±0.59 vs. 44.24±0.58, both P < 0.05) and 48 h (41.85±1.19 or 59.64±1.13 vs. 22.98±0.25, both P < 0.05). ACEI decreased the levels of ET-1 and ROS under hypoxia challenge at 24 and 48 h (all P < 0.05); ACEI increased the VEGF and NO levels (all P < 0.05). ACEI promoted the expression level of eNOS, HO-1, Nrf2 and PLVAP but inhibited Keap-1 expression at the mRNA and protein levels (all P < 0.05). Blockade of the Nrf2 signaling pathway significantly decreased the expression level of PLVAP. ACEI protects hypoxia-treated HEAECs by activating the Nrf2 signaling pathway and upregulating the expression of PLVAP.

Determinants of 1-year mortality after acute myocardial infarction in patients with and without diabetes

The gap in excess mortality between patients with and without diabetes has not decreased over time. The aim of this study was to investigate the determinants of mortality after acute myocardial infarction (AMI) in patients with diabetes and without diabetes in a contemporary population. A retrospective analysis of a cohort of 266 patients with a diagnosis of AMI during 2022 was carried out. Patients living with diabetes had higher 1-year mortality, even after adjustment for covariates. Estimated glomerular filtration (eGFR) rate was independently associated with increased mortality in patients with diabetes. Plasma glucose was independently associated with peak troponin in patients both with and without diabetes. These data suggest that patients living with diabetes and with a low eGFR warrant more aggressive risk reduction and use of nephroprotective medications. Further studies are needed to assess whether early blood glucose control improves cardiovascular outcomes in all patients with AMI.

Sex differences in cardiac ferroptosis after acute myocardial infarction in wild type and aryl hydrocarbon receptor knockout mice

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): MICIN/Agencia Estatal de Investigación (DOI: 10.13039/50110001103) (NextGeneration, EU/PRTR) Background and Purpose Ferroptosis is a new regulated programmed cell death pathway, driven by iron-dependent phospholipid peroxidation, that plays an important role in the development of cardiovascular diseases. The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor of the basic Helix-Loop-Helix-PER-ARNT-SIM superfamily. Upon ligand binding, AhR translocates into the nucleus and dimerizes with the AhR nuclear translocator; the heterodimer then binds to dioxin-response elements located in the promoter region of receptor-regulated genes, most of which are involved in xenobiotic metabolism. Beyond its role in metabolizing exogenous toxins as part of an adaptive chemical response, it is well known that AhR is activated by endogenous ligands and it has been postulated that AhR has important functions in physiological and/or pathological conditions. Here we studied sex differences in cardiac ferroptosis after acute myocardial infarction (AMI) in mice and the implication of defective AhR signalling on this process. Methods and Results AMI was induced in 8–10-weeks-old males and females AhR+/+ and AhR-/- mice by ligation of the left anterior descending coronary artery. Animal care and experimental procedures followed the principles of animal care (NIH publication Nº85-23 revised 1985) and the guidelines for ethical care of experimental animals of the European Union (2010/63/EU). Survival analysis showed that 16% of AhR+/+male mice and 14% of AhR+/+ female mice died 72 h after AMI surgery whereas the mortality was 100% in AhR-/-male mice and only 17% in AhR-/- female mice group. The treatment of AhR-/- AMI male mice with ferrostatin (1 mg/kg i.p) increased survival to 40%. Immunofluorescence analysis of cardiac staining levels of 8-hydroxy-2’-deoxyguanosine revealed higher oxidative stress in AhR+/+AMI male mice compared with AhR+/+AMI females, 24 h after surgery. The absence of AhR in AMI males showed an increased oxidative stress that was similar to that obtained in AMI AhR+/+ males but significantly greater than that observed in AhR-/- AMI females. Finally, analysis of differential expressions of classical genes related to ferroptosis in AhR-/- AMI male and AMI female mice, 24 h after surgery, showed, only in males, a reduced expression of ferritin heavy chain 1 and ferroportin, and an increased expression of phospholipase A2. Conclusion Our results show that loss of AhR in males but not in females favours the ferroptosis process associated with myocardial ischemia, highlighting a possible role for this nuclear receptor in cardiac remodelling and survival after AMI.

Acute myocardial infarction prognosis prediction with reliable and interpretable artificial intelligence system.

Predicting mortality after acute myocardial infarction (AMI) is crucial for timely prescription and treatment of AMI patients, but there are no appropriate AI systems for clinicians. Our primary goal is to develop a reliable and interpretable AI system and provide some valuable insights regarding short, and long-term mortality. We propose the RIAS framework, an end-to-end framework that is designed with reliability and interpretability at its core and automatically optimizes the given model. Using RIAS, clinicians get accurate and reliable predictions which can be used as likelihood, with global and local explanations, and "what if" scenarios to achieve desired outcomes as well. We apply RIAS to AMI prognosis prediction data which comes from the Korean Acute Myocardial Infarction Registry. We compared FT-Transformer with XGBoost and MLP and found that FT-Transformer has superiority in sensitivity and comparable performance in AUROC and F1 score to XGBoost. Furthermore, RIAS reveals the significance of statin-based medications, beta-blockers, and age on mortality regardless of time period. Lastly, we showcase reliable and interpretable results of RIAS with local explanations and counterfactual examples for several realistic scenarios. RIAS addresses the "black-box" issue in AI by providing both global and local explanations based on SHAP values and reliable predictions, interpretable as actual likelihoods. The system's "what if" counterfactual explanations enable clinicians to simulate patient-specific scenarios under various conditions, enhancing its practical utility. The proposed framework provides reliable and interpretable predictions along with counterfactual examples.

Patient knowledge about risk factors, achievement of target values, and guideline-adherent secondary prevention therapies 12 months after acute myocardial infarction.

The prospective GULLIVE-R study aimed to evaluate adherence to guideline-recommended secondary prevention, physicians' and patients' estimation of cardiac risk, and patients' knowledge about target values of risk factors after acute myocardial infarction (AMI). We performed a prospective study enrolling patients 9-12 months after AMI. Guideline-recommended secondary prevention therapies and physicians as well as patients' estimation about their risk and patients' knowledge about target values were prospectively collected. Between July 2019 and June 2021, a total of 2509 outpatients were enrolled in 150 German centres 10 months after AMI. The mean age was 66 years, 26.4% were women, 45.3% had ST elevation myocardial infarction, 54.7% had non-ST elevation myocardial infarction, and 93.6% had revascularization (84.0% percutaneous coronary intervention, 7.4% coronary artery bypass graft, 1.8% both). Guideline-recommended secondary drug therapies were prescribed in over 80% of patients, while only about 50% received all five recommended drugs (aspirin, P2Y12 inhibitors, statins, beta-blockers, renin-angiotensin-aldosterone system inhibitors), and regular exercise was performed by only one-third. About 90% of patients felt well informed about secondary prevention, but the correct target value for blood pressure was known in only 37.9% and for LDL-cholesterol in only 8.2%. Both physicians and patients underestimated the objective risk of future AMIs as determined by the thormbolysis in myocardial infarction (TIMI) risk score for secondary prevention. There is still room for improvement in patient education and implementation of guideline-recommended non-pharmacological and pharmacological secondary prevention therapies in patients in the chronic phase after AMI.

Clinical Outcomes in Type 2 Diabetes Patients After Acute Myocardial Infarction: AComparison of Sodium-Glucose Cotransporter 2 Inhibitors vs. Non-Users.

To compare clinical outcomes in patients with type 2 diabetes (T2D) after acute myocardial infarction (AMI) using sodium-glucose cotransporter-2 inhibitors (SGLT2i) vs. non-use of SGLT2i. A national cohort study based on the Taiwan National Health Insurance Research Database enrolled 944 patients with T2D who had experienced AMI and were treated with SGLT2i and 8,941 patients who did not receive SGLT2i, respectively, from May 1, 2016, to December 31, 2019. We used propensity score matching to balance covariates across study groups. The follow-up period was from the index date to the independent occurrence of the study outcomes, discontinuation of the index drug, or the end of the study period (December 31, 2020), whichever occurred first. The SGLT2i group exhibited a significantly lower incidence of cardiovascular death (0.865% per year vs. 2.048% per year; hazard ratio (HR): 0.42; 95% confidence interval (CI): 0.24-0.76; P = 0.0042), heart failure hospitalization (1.987% per year vs. 3.395% per year; HR: 0.59; 95% CI: 0.39-0.89; P = 0.0126), and all-cause mortality (3.406% per year vs. 4.981% per year, HR: 0.69; 95% CI: 0.50-0.95; P = 0.0225) compared with the non-SGLT2i group. There were no significant differences between the two groups in the incidence of AMI, ischemic stroke, coronary revascularization, major adverse cardiovascular events, composite renal outcomes, or lower limb amputation. These findings suggest that the use of SGLT2i may have favorable effects on clinical outcomes in patients with T2D after AMI.

Preconditioning with selective autoretroperfusion: In vivo and in silico evidence of washout hypothesis.

Prompt reperfusion of coronary artery after acute myocardial infarction (AMI) is crucial for minimizing heart injury. The myocardium, however, may experience additional injury due to the flow restoration itself (reperfusion injury, RI). The purpose of this study was to demonstrate that short preconditioning (10min) with selective autoretroperfusion (SARP) ameliorates RI, based on a washout hypothesis. AMI was induced in 23 pigs (3 groups) by occluding the left anterior descending (LAD) artery. In SARP-b (SARP balloon inflated) and SARP-nb (SARP balloon deflated) groups, arterial blood was retroperfused for 10min via the great cardiac vein before releasing the arterial occlusion. A mathematical model of coronary circulation was used to simulate the SARP process and evaluate the potential washout effect. SARP restored left ventricular function during LAD occlusion. Ejection fraction in the SARP-b group returned to baseline levels, compared to SARP-nb and control groups. Infarct area was significantly larger in the control group than in the SARP-b and SARP-nb groups. End-systolic wall thickness was preserved in the SARP-b compared to the SARP-nb and control groups. Analyte values (pH, lactate, glucose, and others), measured every 2min during retroperfusion, suggest a "washout" effect as one important mechanism of action of SARP in reducing infarct size. With SARP, the values progressively approached baseline levels. The mathematical model also confirmed a possible washout effect of tracers. RI can be ameliorated by delaying restoration of arterial flow for a brief period of time while pretreating the infarction with SARP to restore homeostasis via a washout mechanism.

MiR-30a-5p attenuates hypoxia/reoxygenation-induced cardiomyocyte apoptosis by regulating PTEN protein expression and activating PI3K/Akt signaling pathway

BackgroundThis study was designed to investigate the mechanism by which miR-30a-5p mediates cardiomyocyte apoptosis after acute myocardial infarction (AMI) induced by hypoxia/reoxygenation (H/R).MethodsDifferentially expressed miRNAs were analyzed by RNA high-throughput sequencing in acute myocardial infarction (ST-elevation myocardial infarction) patients versus healthy individuals (controls). The H/R model was used to assess the regulatory mechanism of miRNAs in AMI. Lentivirus-associated vectors were used to overexpress or knock down miR-30a-5p in cellular models. The pathological mechanisms of miR-30a-5p regulating the development of acute myocardial infarction were serially explored by qPCR, bioinformatics, target gene prediction, dual luciferase, enzyme-linked immunosorbent assays (ELISAs) and Western blotting.ResultsThe results showed that the expression of miR-30a-5p was significantly increased in AMI patients and H9C2 cells. Hypoxia decreased cardiomyocyte survival over time, and reoxygenation further reduced cell survival. Bax and Phosphatase and tensin homolog (PTEN)were suppressed, while Bcl-2 was upregulated. Additionally, miR-30a-5p specifically targeted the PTEN gene. According to the GO and KEGG analyses, miR-30a-5p may participate in apoptosis by interacting with PTEN. The miR-30a-5p mimic decreased the expression of apoptosis-related proteins and the levels of the proinflammatory markers IL-1β, IL-6, and TNF-α by activating the PTEN/PI3K/Akt signaling pathway. Conversely, anti-miR-30a-5p treatment attenuated these effects. Additionally, silencing PTEN and anti-miR-30a-5p had opposite effects on H/R-induced cell apoptosis.ConclusionsmiR-30a-5p plays a crucial role in cardiomyocyte apoptosis after hypoxia-induced acute myocardial infarction. Our findings provide translational evidence that miR-30a-5p is a novel potential therapeutic target for AMI.

Self-Administration of Aspirin After Chest Pain for the Prevention of Premature Cardiovascular Mortality in the United States: A Population-Based Analysis.

Aspirin, an effective, low-cost pharmaceutical, can significantly reduce mortality if used promptly after acute myocardial infarction (AMI). However, many AMI survivors do not receive aspirin within a few hours of symptom onset. Our aim was to quantify the mortality benefit of self-administering aspirin at chest pain onset, considering the increased risk of bleeding and costs associated with widespread use. We developed a population simulation model to determine the impact of self-administering 325 mg aspirin within 4 hours of severe chest pain onset. We created a synthetic cohort of adults ≥ 40 years old experiencing severe chest pain using 2019 US population estimates, AMI incidence, and sensitivity/specificity of chest pain for AMI. The number of annual deaths delayed was estimated using evidence from a large, randomized trial. We also estimated the years of life saved (YOLS), costs, and cost per YOLS. Initiating aspirin within 4 hours of severe chest pain onset delayed 13 016 (95% CI, 11 643-14 574) deaths annually, after accounting for deaths due to bleeding (963; 926-1003). This translated to an estimated 166 309 YOLS (149391-185 505) at the cost of $643 235 (633 944-653 010) per year, leading to a cost-effectiveness ratio of $3.70 (3.32-4.12) per YOLS. For <$4 per YOLS, self-administration of aspirin within 4 hours of severe chest pain onset has the potential to save 13 000 lives per year in the US population. Benefits of reducing deaths post-AMI outweighed the risk of bleeding deaths from aspirin 10 times over.

TO EXPLORE THE CLINICAL FRAILTY SCALE IN PREDICTING THE LONG TERM PROGNOSIS OF PATIENTS WITH ACUTE MYOCARDIAL INFARCTION AFTER IN-HOSPITAL CARDIAC REHABILITATION

Objective: Patients successfully revascularized after acute myocardial infarction (AMI) underwent in-hospital cardiac rehabilitation (CR) and were assessed for their state by the clinical frailty scale (CFS) to investigate the predictive value of the CFS score on the incidence rate of major cardiovascular events within one year. Design and method: A graded CR scheme was developed in a total of 501 patients with AMI, who were treated in the cardiology center of Shanghai Sixth People’s Hospital from May 2020 to May 2022, and the CFS score was assessed based on the CR condition of the patients before discharge. Patients were then categorized into three groups (norm group, vulnerable group, and frail group) according to their CFS score. The difference in one-year major cardiovascular event (all-cause death and re-hospitalization for heart failure) rates among these groups was compared. Logistic regression analysis was performed to explore risk factors affecting cardiovascular events, and an ROC curve was generated to analyze the risk factors in predicting one-year cardiovascular event rates. Finally, an optimal prediction model was developed. Results: The CFS score in AMI patients was positively correlated with age and peak proBNP and inversely correlated with gender difference (P &lt;= 0.001). There were significant differences in the incidence of all-cause death between the frail group and the norm group (P = 0.002), whereas there was no significant difference between the vulnerable group and the norm group (P &gt; 0.05). There was no significant difference in re-hospitalization for heart failure among the three groups (P = 0.710). The CFS score could sensitively predict the 1-year risk of all-cause death in AMI patients (β = 1.89, OR = 6.61, P = 0.001), and the risk model combined with the CFS score had the best predictive effect (AUC = 0.845, P = 0.000). Conclusions: In-hospital CR along with assessment using the CFS score can effectively identify AMI patients with a high risk of death.

Dapagliflozin Alleviates Myocardial Ischaemia Reperfusion Injury by Activating Mitophagy via the AMPK-PINK1/Parkin Signalling Pathway.

Myocardial ischaemia reperfusion injury (MIRI) determines infarct size and long-term outcomes after acute myocardial infarction (AMI). Dapagliflozin, a sodium-glucose cotransporter 2 inhibitor, alleviates MIRI in animal models. We investigated the potential mechanisms underlying the cardioprotective effect of dapagliflozin against MIRI, focusing on mitochondrial injury and mitophagy. MIRI mouse and H9C2 cell models were established. 2,3,5-Triphenyltetrazolium chloride (TTC) staining showed a significant alleviation of MIRI after pre-treatment of dapagliflozin compared to the model group (14.91±1.76 vs. 40.47±3.69%). Data from the pre-treatment dapagliflozin group showed a significant decrease in left ventricular ejection fraction (LVEF) (44.8±2.7 vs. 28.5±5.3%, P<0.01), left ventricular end-diastolic volume (LVEDV) (70.6±9.5 vs. 93.5±13.8 ul, P<0.05), and left ventricular end-systolic volume (LVESV) (39.0± 8.3 vs. 67.9±13.7 ul, P<0.05) compared to the model group. Dapagliflozin also reduced the levels of reactive oxygen species (ROS) and fragmented mitochondrial DNA, reversed the decrease in mitochondrial membrane potential, and suppressed apoptosis. Further study showed that dapagliflozin could protect against mitochondrial injury by rapidly clearing damaged mitochondria via mitophagy in a phosphatase and tensin homologue (PTEN)-induced putative kinase 1 (PINK1)/parkindependent manner. Dapagliflozin regulated mitophagy in cardiomyocytes by suppressing the adenosine 5'monophosphate-activated protein kinase (AMPK)-PINK1/parkin signalling pathway, resulting in attenuated MIRI. Dapagliflozin alleviated MIRI by activating mitophagy via the AMPK-PINK1/parkin signalling pathway.