Percutaneous Coronary Revascularization Strategies After Myocardial Infarction: A Systematic Review and Network Meta-Analysis.

BACKGROUND: Complete revascularization with percutaneous coronary intervention improves outcomes compared with culprit revascularization following myocardial infarction (MI) with multivessel coronary artery disease. An all-cause mortality reduction has never been demonstrated. Debate also remains regarding the optimal timing of complete revascularization (immediate or staged), and method of evaluation of nonculprit lesions (physiology or angiography). OBJECTIVES: This study aims to perform an updated systematic review with frequentist and Bayesian network meta-analyses including the totality of randomized data investigating revascularization strategies in patients presenting with MI and multivessel coronary artery disease. METHODS: The primary comparison tested complete vs culprit revascularization. Timing and methods of achieving complete revascularization were assessed. The prespecified primary outcome was all-cause mortality. Outcomes were expressed as relative risk (RR) (95% CI). RESULTS: Twenty-four eligible trials randomized 16,371 patients (weighted mean follow-up: 26.4 months). Compared with culprit revascularization, complete revascularization reduced all-cause mortality in patients with any MI (RR: 0.85; 95% CI: 0.74-0.99; P = 0.04). Cardiovascular mortality, MI, major adverse cardiac events and repeat revascularization were also significantly reduced. In patients presenting with ST-segment elevation myocardial infarction, the point estimate for all-cause mortality with complete revascularization was RR: 0.91 (95% CI: 0.78-1.05; P = 0.18). Rates of stent thrombosis, major bleeding, and acute kidney injury were similar. Immediate complete revascularization ranked higher than staged complete revascularization for all endpoints. CONCLUSIONS: Complete revascularization following MI reduces all-cause mortality, cardiovascular mortality, MI, major adverse cardiac events, and repeat revascularization. There may be benefits to immediate complete revascularization, but additional head-to-head trials are needed.

Analysis of barriers associated with emergency medical service activation in patients with acute stroke and acute myocardial infarction from Zhongjiang County of Sichuan Province in China.

OBJECTIVES: The purpose of this study was to investigate the preferred modes of transportation to the hospital among patients with acute stroke and acute myocardial infarction (AMI), as well as to identify the factors that influence the utilization of ambulances. METHODS: We conducted a cross-sectional study, including patients who were diagnosed with acute stroke and AMI, at the people's hospital of Zhongjiang, from September 30th, 2022 to August 30th, 2023. All patients were divided into emergency medical service (EMS)-activation group and self-transportation group. Chi-square and t-tests were utilized to discern differences between groups at baseline. To screen relevant variables, we employed the Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis using R package glmnet. Subsequently, we performed a logistic regression analysis to identify predictors of EMS activation according the results of LASSO regression. RESULTS: we collected 929 valid questionnaires. 26.16% of the patients required the services of EMS. 90.9% of individuals have not received any formal first aid education. 42.1% of them reported that they had no understanding of cardiovascular and cerebrovascular diseases. Diagnosed as AMI (OR 0.22, 95%CI 0.06 to 0.88) or acute cerebral infarction (OR 0.26, 0.10 to 0.68), the distance between the patient and the nearest 120 network hospital when the patient had these symptoms (OR 0.97, 0.94 to 0.99), the patient's son or daughter was there when the patient was symptomatic (OR 0.58, 0.37 to 0.94), the patient (OR 0.19, 0.05 to 0.72) and the patient's partner (wife or husband) (OR 0.36, 0.16 to 0.85) had decided that the patient needed further medical help, Among patients who did not seek immediate help after symptom onset, thinking that the symptoms will disappear spontaneously (OR 0.34, 0.13 to 0.92) or not wanting to disturb others (OR 0.06, 0.01 to 0.66) or believing that they are not important symptoms (OR 0.15, 0.05 to 0.42) were factors independently associated with less ambulance use. Age (OR 1.02, 1.00 to 1.04), Stroke patients have experienced symptoms of disturbance of consciousness or convulsions (OR 2.99, 1.72 to 5.2) were independent factors associated with increased ambulance use. CONCLUSION: There is still ambulance underutilization among patients with acute stroke and AMI in county territory of China. Moreover, it is needed to raise the level of first aid education and awareness about EMS. Additionally, private clinic doctors and the public should gain adequate understanding of the severity of acute stroke and AMI, as well as their common symptoms, the crucial importance of prompt medical intervention. Finally, we propose that all township hospitals should be integrated into the 120 emergency networks and equipped with emergency first aid capabilities, pre-hospital care, and transportation abilities.

Electroacupuncture Improves Cardiac Function via Inhibiting Sympathetic Remodeling Mediated by Promoting Macrophage M2 Polarization in Myocardial Infarction Mice.

Electroacupuncture (EA) at the Neiguan acupoint (PC6) has shown significant cardioprotective effects. Sympathetic nerves play an important role in maintaining cardiac function after myocardial infarction (MI). Previous studies have found that EA treatment may improve cardiac function by modulating sympathetic remodeling after MI. However, the mechanism in how EA affects sympathetic remodeling and improves cardiac function remains unclear. The aim of this study is to investigate the cardioprotective mechanism of EA after myocardial ischemic injury by improving sympathetic remodeling and promoting macrophage M2 polarization. We established a mouse model of MI by occluding coronary arteries in male C57/BL6 mice. EA treatment was performed at the PC6 with current intensity (1 mA) and frequency (2/15 Hz). Cardiac function was evaluated using echocardiography. Heart rate variability in mice was assessed via standard electrocardiography. Myocardial fibrosis was evaluated by Sirius red staining. Levels of inflammatory factors were assessed using RT-qPCR. Sympathetic nerve remodeling was assessed through ELISA, western blotting, immunohistochemistry, and immunofluorescence staining. Macrophage polarization was evaluated using flow cytometry. Our results indicated that cardiac systolic function improved significantly after EA treatment, with an increase in fractional shortening and ejection fraction. Myocardial fibrosis was significantly mitigated in the EA group. The sympathetic nerve marker tyrosine hydroxylase and the nerve sprouting marker growth-associated Protein 43 were significantly reduced in the EA group, indicating that sympathetic remodeling was significantly reduced. EA treatment also promoted macrophage M2 polarization, reduced levels of inflammatory factors TNF-α, IL-1ß, and IL-6, and decreased macrophage-associated nerve growth factor in myocardial tissue. To sum up, our results suggest that EA at PC6 attenuates sympathetic remodeling after MI to promote macrophage M2 polarization and improve cardiac function.

The Influence of Metabolic Risk Factors on the Inflammatory Response Triggered by Myocardial Infarction: Bridging Pathophysiology to Treatment.

Myocardial infarction (MI) sets off a complex inflammatory cascade that is crucial for effective cardiac healing and scar formation. Yet, if this response becomes excessive or uncontrolled, it can lead to cardiovascular complications. This review aims to provide a comprehensive overview of the tightly regulated local inflammatory response triggered in the early post-MI phase involving cardiomyocytes, (myo)fibroblasts, endothelial cells, and infiltrating immune cells. Next, we explore how the bone marrow and extramedullary hematopoiesis (such as in the spleen) contribute to sustaining immune cell supply at a cardiac level. Lastly, we discuss recent findings on how metabolic cardiovascular risk factors, including hypercholesterolemia, hypertriglyceridemia, diabetes, and hypertension, disrupt this immunological response and explore the potential modulatory effects of lifestyle habits and pharmacological interventions. Understanding how different metabolic risk factors influence the inflammatory response triggered by MI and unraveling the underlying molecular and cellular mechanisms may pave the way for developing personalized therapeutic approaches based on the patient's metabolic profile. Similarly, delving deeper into the impact of lifestyle modifications on the inflammatory response post-MI is crucial. These insights may enable the adoption of more effective strategies to manage post-MI inflammation and improve cardiovascular health outcomes in a holistic manner.

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.

Efficacy and safety of extracorporeal membrane oxygenation for cardiogenic shock complicating myocardial infarction: a systematic review and meta-analysis.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) has been presented as a potential therapeutic option for patients with cardiogenic shock complicating myocardial infarction (CS-MI). We aimed to investigate the efficacy and safety of ECMO in CS-MI. METHODS: A systematic review and meta-analysis synthesizing evidence from randomized controlled trials obtained from PubMed, Embase, Cochrane, Scopus, and Web of Science until September 2023. We used the random-effects model to report dichotomous outcomes using risk ratio and continuous outcomes using mean difference with a 95% confidence interval. Finally, we implemented a trial sequential analysis to evaluate the reliability of our results. RESULTS: We included four trials with 611 patients. No significant difference was observed between ECMO and standard care groups in 30-day mortality with pooled RR of 0.96 (95% CI: 0.81-1.13, p = 0.60), acute kidney injury (RR: 0.65, 95% CI: 0.41-1.03, p = 0.07), stroke (RR: 1.16, 95% CI: 0.38-3.57, p = 0.80), sepsis (RR: 1.06, 95% CI: 0.77-1.47, p = 0.71), pneumonia (RR: 0.99, 95% CI: 0.58-1.68, p = 0.96), and 30-day reinfarction (RR: 0.95, 95% CI: 0.25-3.60, p = 0.94). However, the ECMO group had higher bleeding events (RR: 2.07, 95% CI: 1.44-2.97, p < 0.0001). CONCLUSION: ECMO did not improve clinical outcomes compared to the standard of care in patients with CS-MI but increased the bleeding risk.

Long-term clinical outcomes of image-guided percutaneous coronary intervention in acute myocardial infarction from the Korea Acute Myocardial Infarction Registry.

Imaging modalities for percutaneous coronary intervention (PCI), such as intravascular ultrasound (IVUS) or optical coherence tomography (OCT), have increased in the current PCI era. However, their clinical benefits in acute myocardial infarction (AMI) have not been fully elucidated. This study investigated the long-term outcomes of image-guided PCI in patients with AMI using data from the Korean Acute Myocardial Infarction Registry. A total of 9,271 patients with AMI, who underwent PCI with second-generation drug-eluting stents between November 2011 and December 2015, were retrospectively examined, and target lesion failure (TLF) at 3 years (defined as the composite of cardiac death, target vessel myocardial infarction, and ischemia-driven target lesion revascularization) was evaluated. From the registry, 2,134 patients (23.0%) underwent image-guided PCI (IVUS-guided: n = 1,919 [20.6%]; OCT-guided: n = 215 patients [2.3%]). Based on propensity score matching, image-guided PCI was associated with a significant reduction in TLF (hazard ratio: 0.76; 95% confidence interval: 0.59-0.98, p = 0.035). In addition, the TLF incidence in the OCT-guided PCI group was comparable to that in the IVUS-guided PCI group (5.3% vs 4.7%, p = 0.903). Image-guided PCI, including IVUS and OCT, is associated with favorable clinical outcomes in patients with AMI at 3 years post-intervention. Additionally, OCT-guided PCI is not inferior to IVUS-guided PCI in patients with AMI.

Extracorporeal Life Support in Myocardial Infarction: New Highlights.

Background and Objectives: Cardiogenic shock (CS) is a potentially severe complication following acute myocardial infarction (AMI). The use of veno-arterial extracorporeal membrane oxygenation (VA-ECMO) in these patients has risen significantly over the past two decades, especially when conventional treatments fail. Our aim is to provide an overview of the role of VA-ECMO in CS complicating AMI, with the most recent literature highlights. Materials and Methods: We have reviewed the current VA-ECMO practices with a particular focus on CS complicating AMI. The largest studies reporting the most significant results, i.e., overall clinical outcomes and management of the weaning process, were identified in the PubMed database from 2019 to 2024. Results: The literature about the use of VA-ECMO in CS complicating AMI primarily has consisted of observational studies until 2019, generating the need for randomized controlled trials. The EURO-SHOCK trial showed a lower 30-day all-cause mortality rate in patients receiving VA-ECMO compared to those receiving standard therapy. The ECMO-CS trial compared immediate VA-ECMO implementation with early conservative therapy, with a similar mortality rate between the two groups. The ECLS-SHOCK trial, the largest randomized controlled trial in this field, found no significant difference in mortality at 30 days between the ECMO group and the control group. Recent studies suggest the potential benefits of combining left ventricular unloading devices with VA-ECMO, but they also highlight the increased complication rate, such as bleeding and vascular issues. The routine use of VA-ECMO in AMI complicated by CS cannot be universally supported due to limited evidence and associated risks. Ongoing trials like the Danger Shock, Anchor, and Recover IV trials aim to provide further insights into the management of AMI complicated by CS. Conclusions: Standardizing the timing and indications for initiating mechanical circulatory support (MCS) is crucial and should guide future trials. Multidisciplinary approaches tailored to individual patient needs are essential to minimize complications from unnecessary MCS device initiation.

Person-centred care intervention to promote self-efficacy in patients following a myocardial infarction (P2MIR): a protocol of a qualitative study for cultural adaptation within a Portuguese healthcare context.

INTRODUCTION: Cardiovascular diseases remain a leading cause of death worldwide. Recovery from myocardial infarction is challenging as the causes of symptoms span multiple aspects of health not just physical conditions. Evidence has shown a gap between the waycare is provided in the clinical setting and the person's needs and preferences. The implementation of person-centred care (PCC) interventions can promote recovery from myocardial infarction by allowing a greater understanding of the person's perception and its role on the overall recovering process. This study aims to culturally adapt an evidence-based PCC intervention to enhance self-efficacy in patients after myocardial infarction within a Portuguese healthcare context. METHODS AND ANALYSIS: The Portuguese person-centred care for myocardial infarction recovery (P2MIR) intervention is set to be developed from an evidence-based intervention, rooted in the ethics of PCC. An intervention of PCC for patients with acute coronary syndrome, which has been successfully implemented and evaluated in the Swedish healthcare context will be validated, culturally adapted and harmonised to the Portuguese healthcare context by using qualitative methods. To evaluate its acceptability, appropriateness and feasibility, a sample of stakeholders, consisting of a sample of healthcare professionals and a sample of people who suffered a myocardial infarction, will be recruited from a hospital, including both inpatient and outpatient departments. The stakeholders will be invited to semistructured focus group discussions, aiming to gather their perceptions about the P2MIR intervention, which will be previously presented to them. Data analysis will be conducted using content analysis following a deductive-inductive approach to further inform the intervention adaptation process to its final intervention in a Portuguese healthcare context. ETHICS AND DISSEMINATION: The study has been reviewed and approved by the Health Ethics' Committees of the Centro Hospitalar Lisboa Ocidental, Lisbon, Portugal (registry number 20170700050). The results will be disseminated through peer-reviewed journals and conference presentations.

Automated control of Impella maintains optimal left ventricular unloading during periods of unstable hemodynamics and prevents myocardial damage in acute myocardial infarction.

BACKGROUND: Left ventricular (LV) unloading by Impella, an intravascular microaxial pump, has been shown to exert dramatic cardioprotective effects in acute clinical settings of cardiovascular diseases. Total Impella support (no native LV ejection) is far more efficient in reducing LV energetic demand than partial Impella support, but the manual control of pump speed to maintain stable LV unloading is difficult and impractical. We aimed to develop an Automatic IMpella Optimal Unloading System (AIMOUS), which controls Impella pump speed to maintain LV unloading degree using closed-feedback control. We validated the AIMOUS performance in an animal model. METHODS: In dogs, we identified the transfer function from pump speed to LV systolic pressure (LVSP) under total support conditions (n = 5). Using the transfer function, we designed the feedback controller of AIMOUS to keep LVSP at 40 mmHg and examined its performance by volume perturbations (n = 9). Lastly, AIMOUS was applied in the acute phase of ischemia-reperfusion in dogs. Four weeks after ischemia-reperfusion, we assessed LV function and infarct size (n = 10). RESULTS: AIMOUS maintained constant LVSP, thereby ensuring a stable LV unloading condition regardless of volume withdrawal or infusion (±8 ml/kg from baseline). AIMOUS in the acute phase of ischemia-reperfusion markedly improved LV function and reduced infarct size (No Impella support: 13.9 ± 1.3 vs. AIMOUS: 5.7 ± 1.9%, P < 0.05). CONCLUSIONS: AIMOUS is capable of maintaining optimal LV unloading during periods of unstable hemodynamics. Automated control of Impella pump speed in the acute phase of ischemia-reperfusion significantly reduced infarct size and prevented subsequent worsening of LV function.

Spontaneous intercostal artery bleeding occurring simultaneously in numerous vessels during antithrombotic therapy with mechanical circulatory support: a case report.

BACKGROUND: Intercostal artery bleeding often occurs in a single vessel; in rare cases, it can occur in numerous vessels, making it more difficult to manage. CASE PRESENTATION: A 63-year-old Japanese man was admitted to the emergency department owing to sudden chest and back pain, dizziness, and nausea. Emergency coronary angiography revealed myocardial infarction secondary to right coronary artery occlusion. After intra-aortic balloon pumping, percutaneous coronary intervention was performed in the right coronary artery. At 12 hours following percutaneous coronary intervention, the patient developed new-onset left anterior chest pain and hypotension. Contrast-enhanced computed tomography revealed 15 sites of contrast extravasation within a massive left extrapleural hematoma. Emergency angiography revealed contrast leakage in the left 6th to 11th intercostal arteries; hence, transcatheter arterial embolization was performed. At 2 days after transcatheter arterial embolization, his blood pressure subsequently decreased, and contrast-enhanced computed tomography revealed the re-enlargement of extrapleural hematoma with multiple sites of contrast extravasation. Emergency surgery was performed owing to persistent bleeding. No active arterial hemorrhage was observed intraoperatively. Bleeding was observed in various areas of the chest wall, and an oxidized cellulose membrane was applied following ablation and hemostasis. The postoperative course was uneventful. CONCLUSION: We report a case of spontaneous intercostal artery bleeding occurring simultaneously in numerous vessels during antithrombotic therapy with mechanical circulatory support that was difficult to manage. As bleeding from numerous vessels may occur during antithrombotic therapy, even without trauma, appropriate treatments, such as transcatheter arterial embolization and surgery, should be selected in patients with such cases.

Canadian Cardiovascular Society/Canadian Women's Heart Health Alliance Clinical Practice Update on Myocardial Infarction With No Obstructive Coronary Artery Disease (MINOCA).

Myocardial infarction with no obstructive coronary artery disease (MINOCA) represents 6%-15% of all acute coronary syndromes, and women are disproportionately represented. MINOCA is an encompassing preliminary diagnosis, and emerging evidence supports a more expansive comprehensive diagnostic and therapeutic clinical approach. The current clinical practice update summarizes the latest evidence regarding the epidemiology, clinical presentation, and diagnostic evaluation of MINOCA. A cascaded approach to diagnostic workup is outlined for clinicians, for noninvasive and invasive diagnostic pathways, depending on clinical setting and local availability of diagnostic modalities. Evidence concerning the nonpharmacological and pharmacological treatment of MINOCA are presented and summarized according to underlying cause of MINOCA, with practical tips on the basis of expert opinion, outlining a real-life, evidence-based, comprehensive approach to management of this challenging condition.

M2 macrophage-derived exosomes promote angiogenesis and improve cardiac function after myocardial infarction.

BACKGROUND: Myocardial infarction (MI) is a major cause of mortality and morbidity worldwide. The intercellular communication in post-infarction angiogenesis remains unclear. METHODS: In this study, we explored the role and mechanism of action of M2 macrophage-derived exosomes (M2-exos) in angiogenesis after MI. M2-exos were harvested and injected intramyocardially at the onset of MI. Two distinct endothelial cells (ECs) were cultured with M2-exos to explore the direct effects on angiogenesis. RESULTS: We showed that M2-exos improved cardiac function, reduced infarct size, and enhanced angiogenesis after MI. Moreover, M2-exos promoted angiogenesis in vitro; the molecules loaded in the vesicles were responsible for its proangiogenic effects. We further validated that higher abundance of miR-132-3p in M2-exos, which recapitulate their functions, was required for the cardioprotective effects exerted by M2-exos. Mechanistically, miR-132-3p carried by M2-exos down-regulate the expression of THBS1 through direct binding to its 3´UTR and the proangiogenic effects of miR-132-3p were largely reversed by THBS1 overexpression. CONCLUSION: Our findings demonstrate that M2-exos promote angiogenesis after MI by transporting miR-132-3p to ECs, and by binding to THBS1 mRNA directly and negatively regulating its expression. These findings highlight the role of M2-exos in cardiac repair and provide novel mechanistic understanding of intercellular communication in post-infarction angiogenesis.

Optimizing cell therapy by sorting cells with high extracellular vesicle secretion.

Critical challenges remain in clinical translation of extracellular vesicle (EV)-based therapeutics due to the absence of methods to enrich cells with high EV secretion. Current cell sorting methods are limited to surface markers that are uncorrelated to EV secretion or therapeutic potential. Here, we utilize a nanovial technology for enrichment of millions of single cells based on EV secretion. This approach is applied to select mesenchymal stem cells (MSCs) with high EV secretion as therapeutic cells for improving treatment. The selected MSCs exhibit distinct transcriptional profiles associated with EV biogenesis and vascular regeneration and maintain high levels of EV secretion after sorting and regrowth. In a mouse model of myocardial infarction, treatment with high-secreting MSCs improves heart functions compared to treatment with low-secreting MSCs. These findings highlight the therapeutic importance of EV secretion in regenerative cell therapies and suggest that selecting cells based on EV secretion could enhance therapeutic efficacy.

Advanced Cardiac Patches for the Treatment of Myocardial Infarction.

Myocardial infarction is a cardiovascular disease characterized by a high incidence rate and mortality. It leads to various cardiac pathophysiological changes, including ischemia/reperfusion injury, inflammation, fibrosis, and ventricular remodeling, which ultimately result in heart failure and pose a significant threat to global health. Although clinical reperfusion therapies and conventional pharmacological interventions improve emergency survival rates and short-term prognoses, they are still limited in providing long-lasting improvements in cardiac function or reversing pathological progression. Recently, cardiac patches have gained considerable attention as a promising therapy for myocardial infarction. These patches consist of scaffolds or loaded therapeutic agents that provide mechanical reinforcement, synchronous electrical conduction, and localized delivery within the infarct zone to promote cardiac restoration. This review elucidates the pathophysiological progression from myocardial infarction to heart failure, highlighting therapeutic targets and various cardiac patches. The review considers the primary scaffold materials, including synthetic, natural, and conductive materials, and the prevalent fabrication techniques and optimal properties of the patch, as well as advanced delivery strategies. Last, the current limitations and prospects of cardiac patch research are considered, with the goal of shedding light on innovative products poised for clinical application.

Modified mRNA-Mediated CCN5 Gene Transfer Ameliorates Cardiac Dysfunction and Fibrosis without Adverse Structural Remodeling.

Modified mRNAs (modRNAs) are an emerging delivery method for gene therapy. The success of modRNA-based COVID-19 vaccines has demonstrated that modRNA is a safe and effective therapeutic tool. Moreover, modRNA has the potential to treat various human diseases, including cardiac dysfunction. Acute myocardial infarction (MI) is a major cardiac disorder that currently lacks curative treatment options, and MI is commonly accompanied by fibrosis and impaired cardiac function. Our group previously demonstrated that the matricellular protein CCN5 inhibits cardiac fibrosis (CF) and mitigates cardiac dysfunction. However, it remains unclear whether early intervention of CF under stress conditions is beneficial or more detrimental due to potential adverse effects such as left ventricular (LV) rupture. We hypothesized that CCN5 would alleviate the adverse effects of myocardial infarction (MI) through its anti-fibrotic properties under stress conditions. To induce the rapid expression of CCN5, ModRNA-CCN5 was synthesized and administrated directly into the myocardium in a mouse MI model. To evaluate CCN5 activity, we established two independent experimental schemes: (1) preventive intervention and (2) therapeutic intervention. Functional analyses, including echocardiography and magnetic resonance imaging (MRI), along with molecular assays, demonstrated that modRNA-mediated CCN5 gene transfer significantly attenuated cardiac fibrosis and improved cardiac function in both preventive and therapeutic models, without causing left ventricular rupture or any adverse cardiac remodeling. In conclusion, early intervention in CF by ModRNA-CCN5 gene transfer is an efficient and safe therapeutic modality for treating MI-induced heart failure.