Murray law-based quantitative flow ratio for assessment of nonculprit lesions in patients with ST-segment elevation myocardial infarction.

INTRODUCTION: Revascularization of nonculprit arteries in patients with ST-Segment Elevation Myocardial Infarction (STEMI) is now recommended based on several trials. However, the optimal therapeutic strategy of nonculprit lesions remains unknown. Murray law-based Quantitative Flow Ratio (µQFR) is a novel, non-invasive, vasodilator-free method for evaluating the functional severity of coronary artery stenosis, which has potential applications for nonculprit lesion assessment in STEMI patients. MATERIAL AND METHODS: Patients with STEMI who received staged PCI before hospital discharge were enrolled retrospectively. µQFR analyses of nonculprit vessels were performed based on both acute and staged angiography. RESULTS: Eighty-one patients with 110 nonculprit arteries were included. The mean acute µQFR was 0.76 ± 0.18, and the mean staged µQFR was 0.75 ± 0.19. The average period between acute and staged evaluation was 8 days. There was a good correlation (r = 0.719, P < 0.001) between acute µQFR and staged µQFR. The classification agreement was 89.09%. The area under the receiver operator characteristic (ROC) curve for detecting staged µQFR ≤ 0.80 was 0.931. CONCLUSIONS: It is feasible to calculate the µQFR during the acute phase of STEMI patients. Acute µQFR and staged µQFR have a good correlation and agreement. The µQFR could be a valuable method for assessing functional significance of nonculprit arteries in STEMI patients.

Prognostic Value of Coronary Microvascular Dysfunction Assessed by Coronary Angiography-Derived Index of Microcirculatory Resistance in Patients With ST-Segment Elevation Myocardial Infarction.

BACKGROUND: CaIMR is proposed as a novel angiographic index designed to assess microcirculation without the need for pressure wires or hyperemic agents. We aimed to investigate the impact of caIMR on predicting clinical outcomes in STEMI patients. METHODS: One hundred and forty patients with STEMI who received PCI in Putuo Hospital of Shanghai from October 2021 to September 2022 were categorized into CMD and non-CMD groups according to the caIMR value. The baseline information, patient-related examinations, and the occurrence of MACE at the 12-month follow-up were collected to investigate risk factors in patients with STEMI. RESULTS: We divided 140 patients with STEMI enrolled into two groups according to caIMR results, including 61 patients diagnosed with CMD and 79 patients diagnosed with non-CMD. A total of 21 MACE occurred during the 1 year of follow-up. Compared with non-CMD group, patients with CMD showed a significantly higher risk of MACE. A multivariate Cox regression model was conducted for the patients, and it was found thatcaIMR was a significant predictor of prognosis in STEMI patients (HR: 8.921). Patients with CMD were divided into culprit vascular CMD and non-culprit vascular CMD, and the result found that culprit vascular CMD was associated with the incidence of MACE (OR: 4.75) and heart failure (OR: 7.50). CONCLUSION: CaIMR is a strong predictor of clinical outcomes and can provide an objective risk stratification for patients with STEMI. There is a strong correlation among leukocyte index, the use of furosemide, Killips classification, and clinical outcomes.

Advanced Nanomedicine Approaches for Myocardial Infarction Treatment.

Myocardial infarction, usually caused by the rupture of atherosclerotic plaque, leads to irreversible ischemic cardiomyocyte death within hours followed by impaired cardiac performance or even heart failure. Current interventional reperfusion strategies for myocardial infarction still face high mortality with the development of heart failure. Nanomaterial-based therapy has made great progress in reducing infarct size and promoting cardiac repair after MI, although most studies are preclinical trials. This review focuses primarily on recent progress (2016-now) in the development of various nanomedicines in the treatment of myocardial infarction. We summarize these applications with the strategy of mechanism including anti-cardiomyocyte death strategy, activation of neovascularization, antioxidants strategy, immunomodulation, anti-cardiac remodeling, and cardiac repair.

Inhibition of proline-rich tyrosine kinase 2 restores cardioprotection by remote ischaemic preconditioning in type 2 diabetes.

BACKGROUND AND PURPOSE: Remote ischaemic preconditioning (rIPC) for cardioprotection is severely impaired in diabetes, and therapeutic options to restore it are lacking. The vascular endothelium plays a key role in rIPC. Given that the activity of endothelial nitric oxide synthase (eNOS) is inhibited by proline-rich tyrosine kinase 2 (Pyk2), we hypothesized that pharmacological Pyk2 inhibition could restore eNOS activity and thus restore remote cardioprotection in diabetes. EXPERIMENTAL APPROACH: New Zealand obese (NZO) mice that demonstrated key features of diabetes were studied. The consequence of Pyk2 inhibition on endothelial function, rIPC and infarct size after myocardial infarction were evaluated. The impact of plasma from mice and humans with or without diabetes was assessed in isolated buffer perfused murine hearts and aortic rings. KEY RESULTS: Plasma from nondiabetic mice and humans, both subjected to rIPC, caused remote tissue protection. Similar to diabetic humans, NZO mice demonstrated endothelial dysfunction. NZO mice had reduced circulating nitrite levels, elevated arterial blood pressure and a larger infarct size after ischaemia and reperfusion than BL6 mice. Pyk2 increased the phosphorylation of eNOS at its inhibitory site (Tyr656), limiting its activity in diabetes. The cardioprotective effects of rIPC were abolished in diabetic NZO mice. Pharmacological Pyk2 inhibition restored endothelial function and rescued cardioprotective effects of rIPC. CONCLUSION AND IMPLICATIONS: Endothelial function and remote tissue protection are impaired in diabetes. Pyk2 is a novel target for treating endothelial dysfunction and restoring cardioprotection through rIPC in diabetes.

Impact of Complete Revascularization for Acute Myocardial Infarction In Multivessel Coronary Artery Disease Patients With Diabetes Mellitus.

BACKGROUND AND OBJECTIVES: The clinical benefits of complete revascularization (CR) in acute myocardial infarction (AMI) patients are unclear. Moreover, the benefit of CR is unknown in AMI with diabetes mellitus (DM) patients. We sought to compare the prognosis of CR and incomplete revascularization (IR) in patients with AMI and multivessel disease, according to the presence of DM. METHODS: A total of 2,150 AMI patients with multivessel coronary artery disease were analyzed. CR was defined based on the angiographic image. The primary endpoint of this study was the patient-oriented composite outcome (POCO) defined as a composite of all-cause death, any myocardial infarction, and any revascularization within 3 years. RESULTS: Overall, 3-year POCO was significantly lower in patients receiving angiographic CR (985 patients, 45.8%) compared with IR (1,165 patients, 54.2%). When divided into subgroups according to the presence of DM, CR reduced 3-year clinical outcomes in the non-DM group but not in the DM group (POCO: 11.7% vs. 23.2%, p<0.001, any revascularization: 7.2% vs. 10.8%, p=0.024 in the non-DM group, POCO: 24.3% vs. 27.8%, p=0.295, any revascularization: 13.3% vs. 11.3%, p=0.448 in the DM group, for CR vs. IR). Multivariate analysis showed that CR significantly reduced 3-year POCO (hazard ratio, 0.52; 95% confidence interval, 0.36-0.75) only in the non-DM group. CONCLUSIONS: In AMI patients with multivessel disease, CR may have less clinical benefit in DM patients than in non-DM patients.

Prognostic Implications of Coronary Artery Sclerosis in Troponin-Positive Patients with Non-Obstructive Coronary Arteries.

INTRODUCTION: Coronary sclerosis is a risk factor for the progression to obstructive coronary artery disease (CAD). However, understanding its impact on the outcomes of patients with myocardial infarction and non-obstructive coronary arteries is limited. This study aimed to explore the prognostic influence of coronary sclerosis on in- and out-of-hospital events in troponin-positive patients with non-obstructive coronary arteries. METHODS: This study was a retrospective cohort analysis based on prospectively collected data. A total of 24,775 patients who underwent coronary angiography from 2010 to 2021 in a German university hospital were screened, resulting in a final study cohort of 373 troponin-positive patients with non-obstructive coronary arteries and a follow-up period of 6.2 ± 3.1 years. Coronary sclerosis was defined as coronary plaques without angiographically detectable stenotic lesions of 50% or more in the large epicardial coronary arteries. The primary study endpoint was the occurrence of in-hospital events. Secondary endpoints included events during follow-up. RESULTS: Patients with coronary sclerosis were significantly older (70 ± 12 vs. 58 ± 16 years, p < 0.001), had ST-segment elevation less frequently on electrocardiogram (9.4% vs. 18.7%, p = 0.013), and suffered more often from diabetes mellitus (23.3% vs. 13.1%, p = 0.009), arterial hypertension (79.6% vs. 59.8%, p < 0.001), chronic obstructive pulmonary disease (17.1% vs. 9.4%, p = 0.028), chronic kidney disease (22.2% vs. 8.4%, p < 0.001), atrial fibrillation (19.8% vs. 12.2%, p = 0.045), and valvular diseases than patients without CAD. Patients with coronary sclerosis were more likely to receive medication for primary/secondary prevention on admission and at discharge. The incidence of in- and out-of-hospital events was significantly higher in patients with coronary sclerosis (in-hospital: 42.8% vs. 29.9%, p = 0.010; out-of-hospital: 46.0% vs. 26.1%, p < 0.001). Mortality rates tended to be higher in the coronary sclerosis group (29.4% vs. 20.0%, p = 0.066). CONCLUSION: Patients diagnosed with coronary sclerosis presented a higher incidence of comorbidities and increased medication use, and experienced higher rates of both in-hospital and out-of-hospital events, primarily due to the clustering of cardiovascular risk factors.

Exploring the Function of Epicardial Cells Beyond the Surface.

The epicardium, previously viewed as a passive outer layer around the heart, is now recognized as an essential component in development, regeneration, and repair. In this review, we explore the cellular and molecular makeup of the epicardium, highlighting its roles in heart regeneration and repair in zebrafish and salamanders, as well as its activation in young and adult postnatal mammals. We also examine the latest technologies used to study the function of epicardial cells for therapeutic interventions. Analysis of highly regenerative animal models shows that the epicardium is essential in regulating cardiomyocyte proliferation, transient fibrosis, and neovascularization. However, despite the epicardium's unique cellular programs to resolve cardiac damage, it remains unclear how to replicate these processes in nonregenerative mammalian organisms. During myocardial infarction, epicardial cells secrete signaling factors that modulate fibrotic, vascular, and inflammatory remodeling, which differentially enhance or inhibit cardiac repair. Recent transcriptomic studies have validated the cellular and molecular heterogeneity of the epicardium across various species and developmental stages, shedding further light on its function under pathological conditions. These studies have also provided insights into the function of regulatory epicardial-derived signaling molecules in various diseases, which could lead to new therapies and advances in reparative cardiovascular medicine. Moreover, insights gained from investigating epicardial cell function have initiated the development of novel techniques, including using human pluripotent stem cells and cardiac organoids to model reparative processes within the cardiovascular system. This growing understanding of epicardial function holds the potential for developing innovative therapeutic strategies aimed at addressing developmental heart disorders, enhancing regenerative therapies, and mitigating cardiovascular disease progression.

Effect of Elevated Neutrophil-to-Lymphocyte Ratio on Adverse Outcomes in Patients With Myocardial Infarction: A Systematic Review and Meta-Analysis.

Myocardial infarction (MI), a leading cause of morbidity and mortality globally, is characterized by an underlying inflammatory process driven by atherosclerosis. The neutrophil-to-lymphocyte ratio (NLR), a readily available and cost-effective marker of systemic inflammation, has emerged as a potential predictor of adverse outcomes in patients with MI. This meta-analysis aimed to evaluate the association between elevated NLR and the risk of major adverse cardiovascular events (MACE) and all-cause mortality in patients with MI. A comprehensive literature search was conducted across multiple databases, including Embase, Web of Science, PubMed, and OVID Medicine, to identify relevant studies published from January 1, 2011, onward. Studies reporting the effect of NLR values on MACE and mortality in adult patients with MI, including both ST-elevation (STEMI) and non-ST-elevation (NSTEMI) subtypes, were included. Data extraction and quality assessment were performed independently by multiple authors. The meta-analysis included 37 studies, comprising a total of 18 studies evaluating the risk of MACE and 30 studies assessing all-cause mortality. The pooled analysis revealed a significantly increased risk of MACE (odds ratio [OR] 1.86, 95% confidence interval [CI] 1.53-2.28, P < 0.01) and all-cause mortality (OR 2.29, 95% CI 1.94-2.70, P < 0.01) in patients with elevated NLR compared to those without elevated NLR. Subgroup analyses stratified by follow-up duration and study design further supported the consistent association between elevated NLR and adverse outcomes. In conclusion, this meta-analysis demonstrates a significant association between elevated NLR and an increased risk of MACE and all-cause mortality in patients with MI. These findings highlight the potential clinical utility of NLR as a prognostic marker and underscore the importance of further research to validate its predictive value and establish optimal cutoff values for risk stratification in this patient population.

Implementation of risk-based lipid-lowering therapies in older (age ≥ 65 years) and very-old adults (age ≥ 75 years) with ischemic heart disease in the greater Salzburg region.

Introduction: European guidelines recommend the implementation of lipid-lowering therapies (LLTs) in adults (≥ 65 years) with established atherosclerotic cardiovascular disease (ASCVD) and for risk-based primary prevention in older adults (≤ 75 years), yet their use in very-old adults (> 75 years) is controversial, discretionary, and oriented on the presence of risk factors. The aim of this retrospective study is to assess guideline-directed LLT implementation and low-density lipoprotein cholesterol (LDL-C) target achievement in high-/very-high-risk older/very-old adults (65-74 and ≥ 75 years) at presentation for ST-segment elevation myocardial infarction (STEMI) and also to assess evidence-based care delivery to older adults in our region. Methods: All STEMI patients with available LDL-C and total cholesterol presenting for treatment at a large tertiary center in Salzburg, Austria, 2018-2020, were screened (n = 910). High-risk/very-high-risk patients (n = 369) were classified according to European guidelines criteria and divided into cohorts by age: < 65 years (n = 152), 65-74 years (n = 104), and ≥ 75 years (n = 113). Results: Despite being at high-/very-high-risk, prior LLT use was < 40% in the total cohort, with no significant difference by age. Statin monotherapy predominated; 20%-23% of older/very-old adults in the entire cohort were using low-/moderate-intensity stains, 11%-13% were using high-intensity statins, 4% were on ezetimibe therapy, and none were taking proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors. In the secondary prevention cohort, 53% of older/very-old patients used prior LLTs. Significantly higher percentages of older/oldest ASCVD patients (43% and 49%) met LDL-C targets < 70 mg/dL compared to patients < 65 years (29%; p = 0.033), although just 22% and 30% of these older groups attained stricter LDL-C targets of < 55 mg/dL. Low LLT uptake (16%) among older adults aged 64-74 years for primary prevention resulted in 17% and 10% attainment of risk-based LDL-C targets < 70 mg/dL and < 55 mg/dL, respectively. Oldest adults (≥ 75 years) in both primary and secondary prevention groups more often met risk-based targets than older and younger adults, despite predominantly receiving low-/moderate-intensity statin monotherapy. Conclusion: Secondary prevention was sub-optimal in our region. Less than half of older/very-old adults with established ASCVD met LDL-C targets at the time of STEMI, suggesting severe care-delivery deficits in LLT implementation. Shortcomings in initiation of risk-based LLTs were also observed among high-/very-high-risk primary prevention patients < 75 years, with the achievement of risk-based LDL-C targets in 10%-48% of these patients.

The mechanisms underlying acute myocardial infarction in chronic kidney disease patients undergoing hemodialysis.

Cardiovascular disease (CVD) is a leading cause of death in chronic kidney disease (CKD). Hemodialysis is one of the main treatments for patients with end-stage kidney disease. Epidemiological data has shown that acute myocardial infarction (AMI) accounts for the main reason for death in patients with CKD under hemodialysis therapy. Immune dysfunction and changes in metabolism (including a high level of inflammatory cytokines, a disorder of lipid and mineral ion homeostasis, accumulation of uremic toxins et al.) during CKD can deteriorate stability of atherosclerotic plaque and promote vascular calcification, which are exactly the pathophysiological mechanisms underlying the occurrence of AMI. Meanwhile, the hemodialysis itself also has adverse effects on lipoprotein, the immune system and hemodynamics, which contribute to the high incidence of AMI in these patients. This review aims to summarize the mechanisms and further promising methods of prevention and treatment of AMI in CKD patients undergoing hemodialysis, which can provide an excellent paradigm for exploring the crosstalk between the kidney and cardiovascular system.

Prevalence of influenza and other acute respiratory illnesses in patients with acute myocardial infarction in Bangladesh: A cross-sectional study.

Background and Aims: Several studies imply that influenza and other respiratory illnesses could lead to acute myocardial infarction (AMI), but data from low-income countries are scarce. We investigated the prevalence of recent respiratory illnesses and confirmed influenza in AMI patients, while also exploring their relationship with infarction severity as defined by ST-elevation MI (STEMI) or high troponin levels. Methods: This cross-sectional study, held at a Dhaka tertiary hospital from May 2017 to October 2018, involved AMI inpatients. The study examined self-reported clinical respiratory illnesses (CRI) in the week before AMI onset and confirmed influenza using baseline real-time reverse transcription polymerase chain reaction (qRT-PCR). Results: Of 744 patients, 11.3% reported a recent CRI, most prominently during the 2017 influenza season (35.7%). qRT-PCR testing found evidence of influenza in 1.5% of 546 patients, with all positives among STEMI cases. Frequencies of CRI were higher in patients with STEMI and in those with high troponin levels, although these relationships were not statistically significant after adjusting for other variables. The risk of STEMI was significantly greater during influenza seasons in the unadjusted analysis (relative risk: 1.09, 95% confidence interval [CI]: 1.02-1.18), however, this relationship was not significant in the adjusted analysis (adjusted relative risk: 1.03, 95% CI: 0.91-1.16). Conclusion: In Bangladesh, many AMI patients had a recent respiratory illness history, with some showing evidence of influenza. However, these illnesses showed no significant relationship to AMI severity. Further research is needed to understand these relationships better and to investigate the potential benefits of infection control measures and influenza vaccinations in reducing AMI incidence.

Exosomal miRNA-21-5p and miRNA-21-3p as key biomarkers of myocardial infarction.

Objective: Coronary artery disease (CAD) is a debilitating condition that can lead to myocardial infarction (MI). Exosomal miRNAs (exo-miRNA) can be diagnostic biomarkers for detecting MI. Here, we conduct a study to evaluate the efficacy of exo-miRNA-21-5p/3p for early detection of MI. Methods: A total of 135 CAD patients and 150 healthy subjects participated in this study. Additionally, we randomly divided 26 male Wistar rats (12 weeks old) into two groups: control and induced MI. Angiographic images were used to identify patients and healthy individuals of all genders. In the following, serum exosomes were obtained, and exo-miRNA-21-5p/3p was measured by reverse-transcriptase polymerase chain reaction. Results: We observed an upregulation of exo-miRNA-21-5p/3p in CAD patient and MI-induced animal groups compared to controls. Analysis of the ROC curves defined 82% and 88% of the participants' exo-miRNA-21-5p and exo-miRNA-21-3p diagnostic power, respectively, which in the animal model was 92 and 82. Conclusion: This study revealed that the mean expression levels of exo-miRNA-21-5p/3p were significantly increased in CAD patients and animal models of induced MI. Also, these results are associated with the atherogenic lipid profile of CAD patients, which may play an important role in the progression of the disease. Therefore, they can be considered as novel biomarkers.

Targeting histone deacetylase in cardiac diseases.

Histone deacetylases (HDAC) catalyze the removal of acetylation modifications on histones and non-histone proteins, which regulates gene expression and other cellular processes. HDAC inhibitors (HDACi), approved anti-cancer agents, emerge as a potential new therapy for heart diseases. Cardioprotective effects of HDACi are observed in many preclinical animal models of heart diseases. Genetic mouse models have been developed to understand the role of each HDAC in cardiac functions. Some of the findings are controversial. Here, we provide an overview of how HDACi and HDAC impact cardiac functions under physiological or pathological conditions. We focus on in vivo studies of zinc-dependent classical HDACs, emphasizing disease conditions involving cardiac hypertrophy, myocardial infarction (MI), ischemic reperfusion (I/R) injury, and heart failure. In particular, we review how non-biased omics studies can help our understanding of the mechanisms underlying the cardiac effects of HDACi and HDAC.

Coronary Artery Ectasia: Case Reports and Literature Review.

Coronary artery ectasia (CAE) is a rare condition, affecting 3%-8% of patients with atherosclerotic coronary artery disease, and is characterized by the abnormal dilatation of the coronary arteries. While the etiology of coronary artery ectasia encompasses a myriad of acquired and genetic factors, its pathogenesis still remains a subject of investigation. The clinical manifestations are varied, ranging from asymptomatic cases to chest angina and myocardial infarction. Coronary angiography remains the gold standard for diagnosing CAE. We herein report four cases of coronary ectasia: the first involving myocardial infarction, the second associated with bicuspid aortic valve with severe aortic regurgitation, the third detected during coronary angiography for moderate left ventricular dysfunction, and the last one detected during coronary angiography for stable angina. The aims of our study are to highlight the diversity of clinical presentations as well as the challenge of management, given that there are no universal treatments or guidelines.

Myocardial Infarction and Complete Heart Block in a Patient With Anomalous Origin of the Left Coronary Artery From the Pulmonary Artery (ALCAPA).

Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) is a rare congenital malformation. We present a case of an elderly patient with ALCAPA presenting with complete heart block and non-ST-elevation myocardial infarction years after diagnosis and surgical correction. An 81-year-old female with a history of ALCAPA presented to the emergency department with chest pain and progressive mental deterioration. She was bradycardic and hypotensive. An electrocardiogram revealed a complete heart block. Troponin was 4.04 ng/mL. She received atropine and underwent transcutaneous pacing. Left heart catheterization revealed complete occlusion of the mid-left circumflex artery, which was intervened with balloon angioplasty and chronic total occlusion of the right coronary artery. She was supported with temporary transvenous pacing, did not require further pacing support, and was discharged home. Previous records unearthed that in 1988 she had presented with syncope and was diagnosed with ALCAPA, filling from right-to-left collaterals with large and ectatic coronaries. At the time, she underwent surgical correction with excision of the left coronary from the pulmonary artery and reimplantation in the left coronary cusp along the posterior aorta. She had remained asymptomatic after her surgery until this presentation. ALCAPA is extremely rare in adults. Insufficient collaterals to the left ventricle cause inadequate blood supply, leading to ischemia in adults, predisposing them to arrhythmias and risk of sudden death. Adults with ALCAPA remain at increased risk of adverse cardiac events later in life, requiring long-term monitoring.

COVID-19 Infection and ST-Elevation Myocardial Infarction: Lessons in Disease Management During a Pandemic.

The emergence of the SARS-CoV-2 virus, causing the COVID-19 pandemic, has profoundly impacted global health, resulting in significant morbidity and mortality worldwide. This paper presents a case study highlighting the heightened risk of severe cardiovascular complications following COVID-19 infection. A 61-year-old male with hyperlipidemia was discharged after COVID-19 pneumonia treatment and experienced a severe ST-elevated myocardial infarction (STEMI) within a day of discharge. A retrospective chart review, supplemented by a literature review, revealed a pattern of increased severity in STEMI cases associated with COVID-19, particularly in patients with pre-existing cardiovascular comorbidities. SARS-CoV-2 induces a prothrombotic state, which causes endothelial dysfunction and systemic inflammation, potentially precipitating thrombotic events. Managing concurrent COVID-19 and STEMI poses unique challenges, emphasizing the critical role of timely intervention, such as percutaneous coronary intervention (PCI), in improving patient outcomes. Despite advancements, uncertainty persists regarding optimal thromboembolism prophylaxis post COVID-19, necessitating ongoing research and meticulous clinical management. While COVID-19 infection rates have declined since the pandemic, this case report hopes to emphasize the need for continued awareness in recognizing the potential thrombotic risks of COVID-19 infection and underscore the need for further investigation into cardiovascular risk as new viral strains develop in the future.

miR-590-3p Overexpression Improves the Efficacy of hiPSC-CMs for Myocardial Repair.

Recent evidence demonstrates that low engraftment rates limit the efficacy of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) for cardiac repair after myocardial infarction. In this study, we attempted to overcome this limitation by enhancing the proliferative capacity of transplanted hiPSC-CMs. We found that miR-590-3p overexpression increased the proliferative capacity of hiPSC-CMs. miR-590-3p overexpression increased the number of engrafted cells and had a higher efficacy for myocardial repair than control cells. Moreover, we confirmed the safety of using miR-590-3p-overexpressing hiPSC-CMs in pig hearts. These results indicated that miR-590-3p overexpression stimulated hiPSC-CM cell cycle re-entry to induce cell proliferation and increased the therapeutic efficacy in MI.