MSCs biomimetic ultrasonic phase change nanoparticles promotes cardiac functional recovery after acute myocardial infarction.

Acute Myocardial Infarction (AMI) has seen rising cases, particularly in younger people, leading to public health concerns. Standard treatments, like coronary artery recanalization, often don't fully repair the heart's microvasculature, risking heart failure. Advances show that Mesenchymal Stromal Cells (MSCs) transplantation improves cardiac function after AMI, but the harsh microenvironment post-AMI impacts cell survival and therapeutic results. MSCs aid heart repair via their membrane proteins and paracrine extracellular vesicles that carry microRNA-125b, which regulates multiple targets, preventing cardiomyocyte death, limiting fibroblast growth, and combating myocardial remodeling after AMI. This study introduces ultrasound-responsive phase-change bionic nanoparticles, leveraging MSCs' natural properties. These particles contain MSC membrane and microRNA-125b, with added macrophage membrane for stability. Using Ultrasound Targeted Microbubble Destruction (UTMD), this method targets the delivery of MSC membrane proteins and microRNA-125b to AMI's inflamed areas. This aims to enhance cardiac function recovery and provide precise, targeted AMI therapy.

Mid- to long-term efficacy and safety of stem cell therapy for acute myocardial infarction: a systematic review and meta-analysis.

BACKGROUND: This comprehensive systematic review and meta-analysis investigated the mid- to long-term efficacy and safety of stem cell therapy in patients with acute myocardial infarction (AMI). METHODS: The study encompassed 79 randomized controlled trials with 7103 patients, rendering it the most up-to-date and extensive analysis in this field. This study specifically focused on the impact of stem cell therapy on left ventricular ejection fraction (LVEF), major adverse cardiac events (MACE), and infarct size. RESULTS: Stem cell therapy significantly improved LVEF at 6, 12, 24, and 36 months post-transplantation compared to control values, indicating its potential for long-term cardiac function enhancement. A trend toward reduced MACE occurrence was observed in the intervention groups, suggesting the potential of stem cell therapy to lower the risk of cardiovascular death, reinfarction, and stroke. Significant LVEF improvements were associated with long cell culture durations exceeding 1 week, particularly when combined with high injected cell quantities (at least 108 cells). No significant reduction in infarct size was observed. CONCLUSIONS: This review highlights the potential of stem cell therapy as a promising therapeutic approach for patients with AMI, offering sustained LVEF improvement and a potential reduction in MACE risk. However, further research is required to optimize cell culture techniques, determine the optimal timing and dosage, and investigate procedural variations to maximize the efficacy and safety of stem cell therapy in this context.

Do DanGer-SHOCK-like patients benefit from VA-ECMO treatment in infarct-related cardiogenic shock? results of an individual patient data meta-analysis.

AIMS: In a recent meta-analysis of randomized controlled trials, routine use of veno-arterial ECMO (VA-ECMO) did not improve outcomes in patients with acute myocardial infarction-related cardiogenic shock (AMI-CS), while a microaxial flow pump reduced mortality in a selected group of patients with AMI-CS in the DanGer-Shock trial. METHODS AND RESULTS: Individual patient data of patients included in four randomized clinical trials investigating the routine use of VA-ECMO in AMI-CS were centrally analysed. For the purpose of this sub-analysis, DanGer-Shock-like patients were analysed (STEMI only, presumed low likelihood of brain injury). The primary endpoint was 180-day all-cause mortality. A total of 202 patients (106 randomized to VA-ECMO and 96 to control) were included. There were no differences in baseline characteristics, angiographic and interventional features between the two groups. Mortality after 6 months was numerically lower with VA-ECMO between the groups [45% in VA-ECMO group vs. 51% in control group; hazard ratio, 0.84; 95% confidence interval (CI), 0.56-1.26], while major bleeding (OR, 2.24; 95% CI, 1.08-4.64) and peripheral vascular complications (OR, 3.65; 95% CI, 1.15-11.56) were increased with the use of VA-ECMO. CONCLUSION: In this exploratory subgroup analysis in patients with CS, STEMI, and a low likelihood of brain injury, there was no mortality benefit with the routine use of VA-ECMO. However, as indicated by the large confidence intervals, the statistical power was limited to draw definite conclusions.

Support network: the challenges of ensuring myocardial infarction patients comfort in the critical care unit: a qualitative study.

INTRODUCTION: Myocardial infarction (MI) is a critical emergency condition that affects all aspects of health. Patients with MI need specialized care in the Coronary care unit (CCU). The main goal of care is to ensure their comfort, which can be significantly affected by their illness and hospitalization. This study aims to explore MI patients' perceptions of support network challenges to ensure comfort in the CCU. METHODS: A qualitative approach was adopted, and semi-structured interviews and notes were used for collecting data between 2020 and mid-2021. The participants were 27 MI patients in our country who had been hospitalized in the CCU of the University Heart Hospital. They were selected using purposive sampling. The data were analyzed using conventional content analysis by Graneheim and Lundman. FINDINGS: The results of this research were revealed in the form of a "support network" theme comprising five categories: "Physical support", "Mental occupations", "Presence of peers", "relatives support "and "Spiritual strategies". CONCLUSION: The study results showed that MI patients, in critical condition, receiving care, and hospitalized in the CCU require continuity in their support network to ensure comfort. The inconsistency between the components of each dimension leads to the challenge of ensuring comfort.

Advancing Human iPSC-Derived Cardiomyocyte Hypoxia Resistance for Cardiac Regenerative Therapies through a Systematic Assessment of In Vitro Conditioning.

Acute myocardial infarction (MI) is a sudden, severe cardiac ischemic event that results in the death of up to one billion cardiomyocytes (CMs) and subsequent decrease in cardiac function. Engineered cardiac tissues (ECTs) are a promising approach to deliver the necessary mass of CMs to remuscularize the heart. However, the hypoxic environment of the heart post-MI presents a critical challenge for CM engraftment. Here, we present a high-throughput, systematic study targeting several physiological features of human induced pluripotent stem cell-derived CMs (hiPSC-CMs), including metabolism, Wnt signaling, substrate, heat shock, apoptosis, and mitochondrial stabilization, to assess their efficacy in promoting ischemia resistance in hiPSC-CMs. The results of 2D experiments identify hypoxia preconditioning (HPC) and metabolic conditioning as having a significant influence on hiPSC-CM function in normoxia and hypoxia. Within 3D engineered cardiac tissues (ECTs), metabolic conditioning with maturation media (MM), featuring high fatty acid and calcium concentration, results in a 1.5-fold increase in active stress generation as compared to RPMI/B27 control ECTs in normoxic conditions. Yet, this functional improvement is lost after hypoxia treatment. Interestingly, HPC can partially rescue the function of MM-treated ECTs after hypoxia. Our systematic and iterative approach provides a strong foundation for assessing and leveraging in vitro culture conditions to enhance the hypoxia resistance, and thus the successful clinical translation, of hiPSC-CMs in cardiac regenerative therapies.

Ischemic-Preconditioning Induced Serum Exosomal miR-133a-3p Improved Post-Myocardial Infarction Repair via Targeting LTBP1 and PPP2CA.

Background: Ischemic preconditioning-induced serum exosomes (IPC-exo) protected rat heart against myocardial ischemia/reperfusion injury. However, whether IPC-exo regulate replacement fibrosis after myocardial infarction (MI) and the underlying mechanisms remain unclear. MicroRNAs (miRs) are important cargos of exosomes and play an essential role in cardioprotection. We aim to investigate whether IPC-exo regulate post-MI replacement fibrosis by transferring cardioprotective miRs and its action mechanism. Methods: Exosomes obtained from serum of adult rats in control (Con-exo) and IPC groups were identified and analyzed, subsequently intracardially injected into MI rats following ligation. Their miRs profiles were identified using high-throughput miR sequencing to identify target miRs for bioinformatics analysis. Luciferase reporter assays confirmed target genes of selected miRs. IPC-exo transfected with selected miRs antagomir or NC were intracardially administered to MI rats post-ligation. Cardiac function and degree of replacement fibrosis were detected 4 weeks post-MI. Results: IPC-exo exerted cardioprotective effects against excessive replacement fibrosis. MiR sequencing and RT-qPCR identified miR-133a-3p as most significantly different between IPC-exo and Con-exo. MiR-133a-3p directly targeted latent transforming growth factor beta binding protein 1 (LTBP1) and protein phosphatase 2, catalytic subunit, alpha isozyme (PPP2CA). KEGG analysis showed that transforming growth factor-ß (TGF-ß) was one of the most enriched signaling pathways with miR-133a-3p. Comparing to injection of IPC-exo transfected with miR-133a-3p antagomir NC, injecting IPC-exo transfected with miR-133a-3p antagomir abolished protective effects of IPC-exo on declining excessive replacement fibrosis and cardiac function enhancement, while increasing the messenger RNA and protein expression of LTBP1, PPP2CA, and TGF-ß1in MI rats. Conclusion: IPC-exo inhibit excessive replacement fibrosis and improve cardiac function post-MI by transferring miR-133a-3p, the mechanism is associated with directly targeting LTBP1 and PPP2CA, and indirectly regulating TGF-ß pathway in rats. Our finding provides potential therapeutic effect of IPC-induced exosomal miR-133a-3p for cardiac repair.

Multicomponent Intervention to Improve Acute Myocardial Infarction Care in Tanzania: Protocol for a Pilot Implementation Trial.

BACKGROUND: Although the incidence of acute myocardial infarction (AMI) is rising in sub-Saharan Africa, the uptake of evidence-based care for the diagnosis and treatment of AMI is limited throughout the region. In Tanzania, studies have revealed common misdiagnosis of AMI, infrequent administration of aspirin, and high short-term mortality rates following AMI. OBJECTIVE: This study aims to evaluate the implementation and efficacy outcomes of an intervention, the Multicomponent Intervention to Improve Acute Myocardial Infarction Care (MIMIC), which was developed to improve the delivery of evidence-based AMI care in Tanzania. METHODS: This single-arm pilot trial will be conducted in the emergency department (ED) at a referral hospital in northern Tanzania. The MIMIC intervention will be implemented by the ED staff for 1 year. Approximately 400 adults presenting to the ED with possible AMI symptoms will be enrolled, and research assistants will observe their care. Thirty days later, a follow-up survey will be administered to assess mortality and medication use. The primary outcome will be the acceptability of the MIMIC intervention, which will be measured by the Acceptability of Intervention Measurement (AIM) instrument. Acceptability will further be assessed via in-depth interviews with key stakeholders. Secondary implementation outcomes will include feasibility and fidelity. Secondary efficacy outcomes will include the following: the proportion of participants who receive electrocardiogram and cardiac biomarker testing, the proportion of participants with AMI who receive aspirin, 30-day mortality among participants with AMI, and the proportion of participants with AMI taking aspirin 30 days following enrollment. RESULTS: Implementation of MIMIC began on September 1, 2023. Enrollment is expected to be completed by September 1, 2024, and the first results are expected to be published by December 31, 2024. CONCLUSIONS: This study will be the first to evaluate an intervention for improving AMI care in sub-Saharan Africa. If MIMIC is found to be acceptable, the findings from this study will inform a future cluster-randomized trial to assess effectiveness and scalability. TRIAL REGISTRATION: ClinicalTrials.gov NCT04563546; https://clinicaltrials.gov/study/NCT04563546. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/59917.

In silico evaluation of cell therapy in acute versus chronic infarction: role of automaticity, heterogeneity and Purkinje in human.

Human-based modelling and simulation offer an ideal testbed for novel medical therapies to guide experimental and clinical studies. Myocardial infarction (MI) is a common cause of heart failure and mortality, for which novel therapies are urgently needed. Although cell therapy offers promise, electrophysiological heterogeneity raises pro-arrhythmic safety concerns, where underlying complex spatio-temporal dynamics cannot be investigated experimentally. Here, after demonstrating credibility of the modelling and simulation framework, we investigate cell therapy in acute versus chronic MI and the role of cell heterogeneity, scar size and the Purkinje system. Simulations agreed with experimental and clinical recordings from ionic to ECG dynamics in acute and chronic infarction. Following cell delivery, spontaneous beats were facilitated by heterogeneity in cell populations, chronic MI due to tissue depolarisation and slow sinus rhythm. Subsequent re-entrant arrhythmias occurred, in some instances with Purkinje involvement and their susceptibility was enhanced by impaired Purkinje-myocardium coupling, large scars and acute infarction. We conclude that homogeneity in injected ventricular-like cell populations minimises their spontaneous beating, which is enhanced by chronic MI, whereas a healthy Purkinje-myocardium coupling is key to prevent subsequent re-entrant arrhythmias, particularly for large scars.

Prehospital emergency nurses' experiences of caring for patients with suspected acute myocardial infarction: an interview study.

OBJECTIVE: Despite the prevalence of emergency medical service assignments related to chest discomfort, limited research delves into nurses' experiences of caring for such patients. This study aimed to illuminate prehospital emergency nurses' (PENs') experiences of caring for patients with suspected acute myocardial infarction (AMI). DESIGN: A qualitative interview study. SETTING: Two Swedish emergency medical service organisations in two different regions. PARTICIPANTS: Consecutive inclusion of 12 PENs. DATA ANALYSIS: An inductive content analysis according to Elo and Kyngäs. RESULTS: The results underline the active role of PENs in providing care for patients with AMI in the emergency medical service. They emphasise the ability to identify classic symptoms and the need for an open-minded approach to diffuse presentations. Ensuring patient security, projecting knowledge and composure are decisive for instilling a sense of safety. Healthcare providers feel profound responsibility and a fear of errors, especially in critical situations with potential patient deterioration. Prioritisation in time-sensitive cases leans towards medical interventions and immediate transportation. Continuing education is essential to enhance patient management and safety. Effective communication and trust are vital for urgent patient care, and prompt activation of the ST-elevation myocardial infarction pathway is recognised as imperative. Malfunctions result in frustration, underlining the importance of pathway functionality. CONCLUSIONS: PENs have immense responsibility for the swift and knowledgeable management of patients with suspected AMI. Balancing patient involvement and urgent medical measures is challenging, emphasising the critical role of mental preparedness and comprehensive education. The study underlines the significance of effective communication and trust between healthcare providers, particularly in time-sensitive scenarios. Establishing feedback mechanisms for prehospital staff is important for advancing prehospital emergency care in this patient category.

[The organisation of outpatient medical and nursing clinics for the follow-up of patients after hospitalization for a myocardial infarction or heart failure]. / L'organizzazione di ambulatori medico-infermieristici sul territorio per il follow-up dei pazienti dopo un ricovero per infarto miocardico o scompenso cardiaco.

. The organisation of outpatient medical and nursing clinics for the follow-up of patients after hospitalization for a myocardial infarction or heart failure. INTRODUCTION: Guidelines suggest careful monitoring of patients after acute heart failure (AHF) or acute myocardial infarction (AMI). OBJECTIVE: To describe the implementation of the 'accompanied discharge' (DIMACC) pathway for patients admitted for AHF or AMI in the Cardiology Department of the Pio XI hospital in Desio, and to evaluate its feasibility. METHODS: The DIMACC pathway was built following the recommendations of international guidelines and with the involvement of all the actors. RESULTS: At discharge, the health objectives to be achieved are defined, and outpatient visits during the first year after hospitalization in the District outpatient clinics with the cardiology doctor and family nurses are booked. The patient stays in the outpatient clinic about 1.5 hours to complete at first, in half an hour, questionnaires on measures, symptoms, adherence, quality of life; then, to receive the nursing visit lasting half an hour for the assessment of the questionnaires, measurement of clinical parameters and counseling; and finally, to be visited by the cardiologist. During the pilot phase (6 months of recruitment and 1 year of follow-up) 168 patients (129 AMI and 39 AHF) followed the pathway: 4 (2.4%) patients died during the follow-up, 14 (8.3%) abandoned the pathway and 150 (89.3%) completed it. CONCLUSIONS: The implementation of the DIMACC pathway required an investment of time (about a year) and resources but the follow-up is feasible. The next phase will be the evaluation of the patient outcomes.

Engineered model of heart tissue repair for exploring fibrotic processes and therapeutic interventions.

Advancements in human-engineered heart tissue have enhanced the understanding of cardiac cellular alteration. Nevertheless, a human model simulating pathological remodeling following myocardial infarction for therapeutic development remains essential. Here we develop an engineered model of myocardial repair that replicates the phased remodeling process, including hypoxic stress, fibrosis, and electrophysiological dysfunction. Transcriptomic analysis identifies nine critical signaling pathways related to cellular fate transitions, leading to the evaluation of seventeen modulators for their therapeutic potential in a mini-repair model. A scoring system quantitatively evaluates the restoration of abnormal electrophysiology, demonstrating that the phased combination of TGFß inhibitor SB431542, Rho kinase inhibitor Y27632, and WNT activator CHIR99021 yields enhanced functional restoration compared to single factor treatments in both engineered and mouse myocardial infarction model. This engineered heart tissue repair model effectively captures the phased remodeling following myocardial infarction, providing a crucial platform for discovering therapeutic targets for ischemic heart disease.

Highly-stable, injectable, conductive hydrogel for chronic neuromodulation.

Electroceuticals, through the selective modulation of peripheral nerves near target organs, are promising for treating refractory diseases. However, the small sizes and the delicate nature of these nerves present challenges in simplifying the fixation and stabilizing the electrical-coupling interface for neural electrodes. Herein, we construct a robust neural interface for fine peripheral nerves using an injectable bio-adhesive hydrogel bioelectronics. By incorporating a multifunctional molecular regulator during network formation, we optimize the injectability and conductivity of the hydrogel through fine-tuning reaction kinetics and multi-scale interactions within the conductive network. Meanwhile, the mechanical and electrical stability of the hydrogel is achieved without compromising its injectability. Minimal tissue damage along with low and stable impedance of the injectable neural interface enables chronic vagus neuromodulation for myocardial infarction therapy in the male rat model. Our highly-stable, injectable, conductive hydrogel bioelectronics are readily available to target challenging anatomical locations, paving the way for future precision bioelectronic medicine.

Components of the Atrial fibrillation Better Care pathway for holistic care of patients with atrial fibrillation: a win ratio analysis from the COOL-AF registry.

AIMS: Compliance with integrated care based on the Atrial fibrillation Better Care (ABC) pathway has been associated with improved clinical outcomes. The primary objective of this study was to compare clinical outcomes of AF patients according to the compliant status of each component of the ABC pathway in a hierarchical win ratio approach. METHODS AND RESULTS: We studied AF patients in the COOL-AF registry. Each patient was followed every 6 months until 3 years. A win ratio analysis was performed, as not all clinical outcomes are equivalent. The hierarchical outcomes were (1) all-cause death, (2) intracranial haemorrhage (ICH), (3) ischaemic stroke/systemic embolism, (4) non-ICH major bleedings, and (5) acute myocardial infarction or heart failure. We also assessed win ratio and win proportion variance over the follow-up time, and the variations over time. A total of 3405 patients (mean age 67.8 ± 11.3; 41.8% female) were studied. Win ratio of ABC-compliant (all three components) vs. ABC-not-compliant was 1.57 (1.35-1.83), P < 0.001. When adding time in therapeutic range (TTR) data for compliant criteria for those who were on warfarin, the win ratio increased to 2.28 (1.89-2.75), P < 0.001. The A-compliant group (plus TTR data), B-compliant, and C-compliant had the win ratio of 1.81 (1.51-2.12), 1.82 (1.53-2.16), and 1.39 (1.18-1.62), all P < 0.001, compared to not compliant group. CONCLUSION: Management of AF patients according to each component of the ABC pathway is associated with better clinical outcomes compared to those non-compliant to ABC pathway. This finding underscores the importance of a holistic management approach strategy for AF patients.

Surface engineering enhances the therapeutic potential of systemically delivered extracellular vesicles following acute myocardial infarction.

The objective of the study was to assess the therapeutic efficacy of targeting remote zone cardiomyocytes with cardiosphere-derived cell (CDC) extracellular vesicles (EVs) delivered via intramyocardial and intravenous routes following acute myocardial infarction (MI). Cardiomyocyte (CM) cell death plays a significant role in left ventricular (LV) remodeling and cardiac dysfunction following MI. While EVs secreted by CDCs have shown efficacy in promoting cardiac repair in preclinical models of MI, their translational potential is limited by their biodistribution and requirement for intramyocardial delivery. We hypothesized that engineering the surface of EVs to target cardiomyocytes would enhance their therapeutic efficacy following systemic delivery in a model of acute MI. CDC-derived EVs were engineered to express a CM-specific binding peptide (CMP) on their surface and characterized for size, morphology, and protein expression. Mice with acute MI underwent both intramyocardial and intravenous delivery of EVs, CMP-EVs and placebo in a double-blind study. LVEF was assessed by echo at 2- and 28-days post-MI and tissue samples processed for assessment of EV biodistribution and histological endpoints. CMP-EVs demonstrated superior cardiac targeting and retention when compared with unmodified EVs 24 h post-MI. Mice treated with IV delivered CMP-EVs demonstrated a significant improvement in LVEF and a significant reduction in remote zone cardiomyocyte apoptosis when compared with IV delivered non-targeted EVs at 28-day post-MI. Systemic administration of CMP-EVs improved cardiac function and reduced remote zone cardiomyocyte apoptosis compared with IV-administered unmodified EVs, demonstrating a strategy to optimize therapeutic EV delivery post-MI.

[Percutaneous treatment of post-acute myocardial infarction mechanical complications: state of the art]. / Trattamento percutaneo delle complicanze meccaniche dell'infarto miocardico acuto: stato dell'arte.

Left ventricular free wall rupture, ventricular pseudoaneurysm, papillary muscle rupture and ventricular septal rupture are life-threatening mechanical complications of acute myocardial infarction. Despite significant improvements over the last decades in overall mortality for patients with myocardial infarction, the outcome of subjects who develop post-infarction mechanical complications remains poor. Surgical treatment is considered the standard of care. However, percutaneous approaches (such as pericardial fibrin-glue injection for left ventricular free wall rupture, transcatheter edge-to-edge mitral repair for papillary muscle rupture and device closure for ventricular pseudoaneurysm or septal rupture) have been proposed in selected high-risk or inoperable patients, or in subjects with ideal characteristics for feasibility, as therapeutic alternatives to open surgery. The aim of the present review is to provide a comprehensive overview of the percutaneous strategies for the management of post-acute myocardial infarction mechanical complications.