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1.
Int J Biol Sci ; 20(6): 2072-2091, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38617528

RESUMO

Background: It had been shown that selective cardiac vagal activation holds great potential for heart regeneration. Optogenetics has clinical translation potential as a novel means of modulating targeted neurons. This study aimed to investigate whether cardiac vagal activation via optogenetics could improve heart regenerative repair after myocardial infarction (MI) and to identify the underlying mechanism. Methods: We used an adeno-associated virus (AAV) as the vector to deliver ChR2, a light-sensitive protein, to the left nodose ganglion (LNG). To assess the effects of the cardiac vagus nerve on cardiomyocyte (CM) proliferation and myocardial regeneration in vivo, the light-emitting diode illumination (470 nm) was applied for optogenetic stimulation to perform the gain-of-function experiment and the vagotomy was used as a loss-of-function assay. Finally, sequencing data and molecular biology experiments were analyzed to determine the possible mechanisms by which the cardiac vagus nerve affects myocardial regenerative repair after MI. Results: Absence of cardiac surface vagus nerve after MI was more common in adult hearts with low proliferative capacity, causing a poor prognosis. Gain- and loss-of-function experiments further demonstrated that optogenetic stimulation of the cardiac vagus nerve positively regulated cardiomyocyte (CM) proliferation and myocardial regeneration in vivo. More importantly, optogenetic stimulation attenuated ventricular remodeling and improved cardiac function after MI. Further analysis of sequencing results and flow cytometry revealed that cardiac vagal stimulation activated the IL-10/STAT3 pathway and promoted the polarization of cardiac macrophages to the M2 type, resulting in beneficial cardiac regenerative repair after MI. Conclusions: Targeting the cardiac vagus nerve by optogenetic stimulation induced macrophage M2 polarization by activating the IL-10/STAT3 signaling pathway, which obviously optimized the regenerative microenvironment and then improved cardiac function after MI.


Assuntos
Interleucina-10 , Infarto do Miocárdio , Adulto , Humanos , Interleucina-10/genética , Optogenética , Infarto do Miocárdio/terapia , Nervo Vago , Miócitos Cardíacos
2.
Bratisl Lek Listy ; 125(5): 289-298, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38624053

RESUMO

Cardio-cerebral infarction (CCI) is a term coined to describe concomitant myocardial infarction and acute ischemic stroke. Acute myocardial infarction and stroke, as separate events, constitute some of the most important causes for disability and mortality in aging societies. Stroke can either occur simultaneously with myocardial infarction or become a serious complication of myocardial infarction and/or its treatment. The frequency of CCI has been reported at a 0.009% incidence rate in stroke patients and is associated with an extremely high mortality. Because of the rare occurrence of CCI, there are currently no guidelines for assessing its diagnosis and optimal treatment. Therefore, currently, the management of CCI cases needs to be individualized. Hopefully, in the future, the results of large clinical trials or prospective registries are expected to enhance our understanding of managing concomitant acute MI and stroke. In this review we have focused on the current literacy in the diagnosis and treatment of CCIs. The paper illustrates potential distinct scenarios of CCI through the analysis of three patient cases (Fig. 5, Ref. 65). Text in PDF www.elis.sk Keywords: myocardial infarction, stroke, cardio-cerebral infarction, carotid artery stenting, cardiac surgery.


Assuntos
Estenose das Carótidas , AVC Isquêmico , Infarto do Miocárdio , Acidente Vascular Cerebral , Humanos , Estudos Prospectivos , AVC Isquêmico/complicações , Resultado do Tratamento , Stents/efeitos adversos , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/diagnóstico , Infarto do Miocárdio/complicações , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/terapia , Infarto Cerebral/complicações , Fatores de Risco
3.
Int J Nanomedicine ; 19: 3295-3314, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38606373

RESUMO

Background: Cardiac repair remains a thorny issue for survivors of acute myocardial infarction (AMI), due to the regenerative inertia of myocardial cells. Cell-free therapies, such as exosome transplantation, have become a potential strategy for myocardial injury. The aim of this study was to investigate the role of engineered exosomes in overexpressing Growth Differentiation Factor-15 (GDF-15) (GDF15-EVs) after myocardial injury, and their molecular mechanisms in cardiac repair. Methods: H9C2 cells were transfected with GDF-15 lentivirus or negative control. The exosomes secreted from H9C2 cells were collected and identified. The cellular apoptosis and autophagy of H2O2-injured H9C2 cells were assessed by Western blotting, TUNEL assay, electron microscopy, CCK-8 and caspase 3/7 assay. A rat model of AMI was constructed by ligating the left anterior descending artery. The anti-apoptotic, pro-angiogenic effects of GDF15-EVs treatment, as well as ensuing functional and histological recovery were evaluated. Then, mRNA sequencing was performed to identify the differentially expressed mRNAs after GDF15-EVs treatment. Results: GDF15-EVs inhibited apoptosis and promoted autophagy in H2O2 injured H9C2 cells. GDF15-EVs effectively decreased the infarct area and enhanced the cardiac function in rats with AMI. Moreover, GDF15-EVs hindered inflammatory cell infiltration, inhibited cell apoptosis, and promoted cardiac angiogenesis in rats with AMI. RNA sequence showed that telomerase reverse transcriptase (TERT) mRNA was upregulated in GDF15-EVs-treated H9C2 cells. AMPK signaling was activated after GDF15-EVs. Silencing TERT impaired the protective effects of GDF15-EVs on H2O2-injured H9C2 cells. Conclusion: GDF15-EVs could fulfil their protective effects against myocardial injury by upregulating the expression of TERT and activating the AMPK signaling pathway. GDF15-EVs might be exploited to design new therapies for AMI.


Assuntos
Exossomos , MicroRNAs , Infarto do Miocárdio , Ratos , Animais , Exossomos/metabolismo , Fator 15 de Diferenciação de Crescimento/genética , Fator 15 de Diferenciação de Crescimento/metabolismo , Fator 15 de Diferenciação de Crescimento/farmacologia , Proteínas Quinases Ativadas por AMP/metabolismo , Proteínas Quinases Ativadas por AMP/farmacologia , Peróxido de Hidrogênio/farmacologia , Peróxido de Hidrogênio/metabolismo , Miócitos Cardíacos , Infarto do Miocárdio/genética , Infarto do Miocárdio/terapia , Infarto do Miocárdio/patologia , RNA Mensageiro/metabolismo , Apoptose , MicroRNAs/genética
5.
Dtsch Med Wochenschr ; 149(9): 496-501, 2024 Apr.
Artigo em Alemão | MEDLINE | ID: mdl-38621683

RESUMO

Dual antiplatelet therapy (DAPT) is the cornerstone of maintenance medication following acute coronary syndromes (ST elevation myocardial infarction, non-ST elevation myocardial infarction, unstable angina). Over the last decade, P2Y12 inhibition in addition to low-dose acetylsalicylic acid has been intensively debated. In patients with acute coronary syndromes, balancing the reduction in cardiovascular events and increase in major bleeding during treatment with more potent P2Y12 inhibitors such as prasugrel and ticagrelor is still an issue. A special focus is on patients already treated with oral anticoagulants for stroke prevention in atrial fibrillation who require additional platelet inhibition following coronary stenting. This article summarizes the major recommendations given in the most recent Guideline for "Acute Coronary Syndromes" published by the European Society of Cardiology (ESC). The recommendations finally address strategies to reduce an increased bleeding risk based on clinical predictors.


Assuntos
Síndrome Coronariana Aguda , Infarto do Miocárdio , Intervenção Coronária Percutânea , Humanos , Síndrome Coronariana Aguda/tratamento farmacológico , Inibidores da Agregação Plaquetária/efeitos adversos , Infarto do Miocárdio/terapia , Fibrinolíticos/efeitos adversos , Aspirina/uso terapêutico , Cloridrato de Prasugrel/uso terapêutico , Hemorragia/induzido quimicamente , Hemorragia/tratamento farmacológico , Resultado do Tratamento
6.
A A Pract ; 18(4): e01741, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38572854

RESUMO

ST-elevation myocardial infarction (STEMI) in a trauma patient with solid abdominal organ or vascular injuries can present complex diagnostic and therapeutic challenges. Evidence for managing such demanding cases is scarce, and isolated case reports remain the source of information in treating these patients. We present a patient with traumatic mesenteric and hepatic injuries who developed acute STEMI in the immediate postoperative period.


Assuntos
Infarto do Miocárdio , Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST , Humanos , Infarto do Miocárdio com Supradesnível do Segmento ST/etiologia , Infarto do Miocárdio com Supradesnível do Segmento ST/cirurgia , Infarto do Miocárdio/complicações , Infarto do Miocárdio/terapia , Infarto do Miocárdio/diagnóstico
7.
Scand Cardiovasc J ; 58(1): 2335905, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38557164

RESUMO

Background. Sudden cardiac arrest (SCA), often also leading to sudden cardiac death (SCD), is a common complication in coronary artery disease. Despite the effort there is a lack of applicable prediction tools to identify those at high risk. We tested the association between the validated GRACE score and the incidence of SCA after myocardial infarction. Material and methods. A retrospective analysis of 1,985 patients treated for myocardial infarction (MI) between January 1st 2015 and December 31st 2018 and followed until the 31st of December of 2021. The main exposure variable was patients' GRACE score at the point of admission and main outcome variable was incident SCA after hospitalization. Their association was analyzed by subdistribution hazard (SDH) model analysis. The secondary endpoints included SCA in patients with no indication to implantable cardioverter-defibrillator (ICD) device and incident SCD. Results. A total of 1985 patients were treated for MI. Mean GRACE score at baseline was 118.7 (SD 32.0). During a median follow-up time of 5.3 years (IQR 3.8-6.1 years) 78 SCA events and 52 SCDs occurred. In unadjusted analyses one SD increase in GRACE score associated with over 50% higher risk of SCA (SDH 1.55, 95% CI 1.29-1.85, p < 0.0001) and over 40% higher risk for SCD (1.42, 1.12-1.79, p = 0.0033). The associations between SCA and GRACE remained statistically significant even with patients without indication for ICD device (1.57, 1.30-1.90, p < 0.0001) as well as when adjusting with patients LVEF and omitting the age from the GRACE score to better represent the severity of the cardiac event. The association of GRACE and SCD turned statistically insignificant when adjusting with LVEF. Conclusions. GRACE score measured at admission for MI associates with long-term risk for SCA.


What is already known about this subject?Nearly 50% of cardiac mortality is caused by sudden cardiac death, often due to sudden cardiac arrest.Despite the effort, there is a lack of applicable prediction tools to identify those at high risk.What does this study add?This study shows that GRACE score measured at the point of admission for myocardial infarction can be used to evaluate patients' risk for sudden cardiac arrest in a long-term follow-up.How might this impact on clinical practice?Based on our findings, the GRACE score at the point of admission could significantly affect the patients' need for an ICD device after hospitalization for MI and should be considered as a contributing factor when evaluating the patients' follow-up care.


Assuntos
Desfibriladores Implantáveis , Parada Cardíaca , Infarto do Miocárdio , Humanos , Seguimentos , Incidência , Estudos Retrospectivos , Fatores de Risco , Morte Súbita Cardíaca/epidemiologia , Morte Súbita Cardíaca/prevenção & controle , Morte Súbita Cardíaca/etiologia , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/terapia , Hospitalização
8.
BMC Cardiovasc Disord ; 24(1): 187, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38561678

RESUMO

BACKGROUND: A coronary artery aneurysm (CAA) is an abnormal dilation of a coronary artery segment often accompanied by coronary artery fistula (CAF), leading to communication between a coronary artery and a cardiac chamber or a part of the coronary venous system. Both CAAs and CAFs can present with symptoms and signs of myocardial ischemia and infarction. CASE PRESENTATION: We describe the case of a 46-year-old woman with non-ST-elevation myocardial infarction (NSTEMI) caused by a "giant" CAA. Various imaging modalities revealed a thrombus-containing aneurysm located at the right-posterior cardiac border, with established arteriovenous communication with the distal part of left circumflex artery (LCx). After initial treatment with dual antiplatelet therapy, a relapse of pain was reported along with a new increase in troponin levels, electrocardiographic abnormalities, reduced left ventricular ejection fraction (LVEF) and thrombus enlargement. Surgical excision of the aneurysm was favored, revealing its true size of 6 cm in diameter. Τhe aneurysm was excised without complications. The patient remained asymptomatic during follow-up. CONCLUSIONS: Management of rare entities such as "giant" CAAs and CAFs can be challenging. Cases such as this can serve as precedents to facilitate treatment plans and develop consistent recommendations, emphasizing the importance of personalized strategies for future patients.


Assuntos
Fístula Arteriovenosa , Aneurisma Coronário , Doença da Artéria Coronariana , Infarto do Miocárdio , Trombose , Feminino , Humanos , Pessoa de Meia-Idade , Volume Sistólico , Função Ventricular Esquerda , Infarto do Miocárdio/diagnóstico por imagem , Infarto do Miocárdio/etiologia , Infarto do Miocárdio/terapia , Aneurisma Coronário/complicações , Aneurisma Coronário/diagnóstico por imagem , Doença da Artéria Coronariana/diagnóstico , Fístula Arteriovenosa/complicações , Fístula Arteriovenosa/diagnóstico por imagem , Trombose/complicações , Angiografia Coronária/métodos
9.
J Nanobiotechnology ; 22(1): 149, 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38570846

RESUMO

BACKGROUND: Myocardial infarction (MI), a representative form of ischemic heart disease, remains a huge burden worldwide. This study aimed to explore whether extracellular vesicles (EVs) secreted from hyaluronic acid (HA)-primed induced mesenchymal stem cells (HA-iMSC-EVs) could enhance the cardiac repair after MI. RESULTS: HA-iMSC-EVs showed typical characteristics for EVs such as morphology, size, and marker proteins expression. Compared with iMSC-EVs, HA-iMSC-EVs showed enhanced tube formation and survival against oxidative stress in endothelial cells, while reduced reactive oxygen species (ROS) generation in cardiomyocytes. In THP-1 macrophages, both types of EVs markedly reduced the expression of pro-inflammatory signaling players, whereas HA-iMSC-EVs were more potent in augmenting anti-inflammatory markers. A significant decrease of inflammasome proteins was observed in HA-iMSC-EV-treated THP-1. Further, phospho-SMAD2 as well as fibrosis markers in TGF-ß1-stimulated cardiomyocytes were reduced in HA-iMSC-EVs treatment. Proteomic data showed that HA-iMSC-EVs were enriched with multiple pathways including immunity, extracellular matrix organization, angiogenesis, and cell cycle. The localization of HA-iMSC-EVs in myocardium was confirmed after delivery by either intravenous or intramyocardial route, with the latter increased intensity. Echocardiography revealed that intramyocardial HA-iMSC-EVs injections improved cardiac function and reduced adverse cardiac remodeling and necrotic size in MI heart. Histologically, MI hearts receiving HA-iMSC-EVs had increased capillary density and viable myocardium, while showed reduced fibrosis. CONCLUSIONS: Our results suggest that HA-iMSC-EVs improve cardiac function by augmenting vessel growth, while reducing ROS generation, inflammation, and fibrosis in MI heart.


Assuntos
Células-Tronco Mesenquimais , Infarto do Miocárdio , Humanos , Ácido Hialurônico/farmacologia , Células Endoteliais/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Proteômica , Infarto do Miocárdio/terapia , Infarto do Miocárdio/patologia , Miócitos Cardíacos/metabolismo , Células-Tronco Mesenquimais/metabolismo , Fibrose
10.
ACS Appl Mater Interfaces ; 16(14): 17323-17338, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38556990

RESUMO

Electroactive hydrogels have garnered extensive interest as a promising approach to myocardial tissue engineering. However, the challenges of spatiotemporal-specific modulation of individual pathological processes and achieving nontoxic bioresorption still remain. Herein, inspired by the entire postinfarct pathological processes, an injectable conductive bioresorbable black phosphorus nanosheets (BPNSs)-loaded hydrogel (BHGD) was developed via reactive oxide species (ROS)-sensitive disulfide-bridge and photomediated cross-linking reaction. Significantly, the chronologically programmed BHGD hydrogel can achieve graded modulation during the inflammatory, proliferative, and maturation phases of myocardial infarction (MI). More details, during early infarction, the BHGD hydrogel can effectively reduce ROS levels in the MI area, inhibit cellular oxidative stress damage, and promote macrophage M2 polarization, creating a favorable environment for damaged myocardium repair. Meanwhile, the ROS-responsive structure can protect BPNSs from degradation and maintain good conductivity under MI microenvironments. Therefore, the BHGD hydrogel possesses tissue-matched modulus and conductivity in the MI area, facilitating cardiomyocyte maturation and electrical signal exchange, compensating for impaired electrical signaling, and promoting vascularization in infarcted areas in the maturation phase. More importantly, all components of the hydrogel degrade into nontoxic substances without adverse effects on vital organs. Overall, the presented BPNS-loaded hydrogel offers an expandable and safe option for clinical treatment of MI.


Assuntos
Hidrogéis , Infarto do Miocárdio , Humanos , Hidrogéis/química , Espécies Reativas de Oxigênio , Infarto do Miocárdio/terapia , Miocárdio/patologia , Miócitos Cardíacos/metabolismo
11.
N Engl J Med ; 390(15): 1372-1381, 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38587241

RESUMO

BACKGROUND: Most trials that have shown a benefit of beta-blocker treatment after myocardial infarction included patients with large myocardial infarctions and were conducted in an era before modern biomarker-based diagnosis of myocardial infarction and treatment with percutaneous coronary intervention, antithrombotic agents, high-intensity statins, and renin-angiotensin-aldosterone system antagonists. METHODS: In a parallel-group, open-label trial performed at 45 centers in Sweden, Estonia, and New Zealand, we randomly assigned patients with an acute myocardial infarction who had undergone coronary angiography and had a left ventricular ejection fraction of at least 50% to receive either long-term treatment with a beta-blocker (metoprolol or bisoprolol) or no beta-blocker treatment. The primary end point was a composite of death from any cause or new myocardial infarction. RESULTS: From September 2017 through May 2023, a total of 5020 patients were enrolled (95.4% of whom were from Sweden). The median follow-up was 3.5 years (interquartile range, 2.2 to 4.7). A primary end-point event occurred in 199 of 2508 patients (7.9%) in the beta-blocker group and in 208 of 2512 patients (8.3%) in the no-beta-blocker group (hazard ratio, 0.96; 95% confidence interval, 0.79 to 1.16; P = 0.64). Beta-blocker treatment did not appear to lead to a lower cumulative incidence of the secondary end points (death from any cause, 3.9% in the beta-blocker group and 4.1% in the no-beta-blocker group; death from cardiovascular causes, 1.5% and 1.3%, respectively; myocardial infarction, 4.5% and 4.7%; hospitalization for atrial fibrillation, 1.1% and 1.4%; and hospitalization for heart failure, 0.8% and 0.9%). With regard to safety end points, hospitalization for bradycardia, second- or third-degree atrioventricular block, hypotension, syncope, or implantation of a pacemaker occurred in 3.4% of the patients in the beta-blocker group and in 3.2% of those in the no-beta-blocker group; hospitalization for asthma or chronic obstructive pulmonary disease in 0.6% and 0.6%, respectively; and hospitalization for stroke in 1.4% and 1.8%. CONCLUSIONS: Among patients with acute myocardial infarction who underwent early coronary angiography and had a preserved left ventricular ejection fraction (≥50%), long-term beta-blocker treatment did not lead to a lower risk of the composite primary end point of death from any cause or new myocardial infarction than no beta-blocker use. (Funded by the Swedish Research Council and others; REDUCE-AMI ClinicalTrials.gov number, NCT03278509.).


Assuntos
Antagonistas Adrenérgicos beta , Bisoprolol , Metoprolol , Infarto do Miocárdio , Humanos , Antagonistas Adrenérgicos beta/efeitos adversos , Antagonistas Adrenérgicos beta/uso terapêutico , Bisoprolol/efeitos adversos , Bisoprolol/uso terapêutico , Insuficiência Cardíaca/etiologia , Infarto do Miocárdio/complicações , Infarto do Miocárdio/diagnóstico por imagem , Infarto do Miocárdio/mortalidade , Infarto do Miocárdio/terapia , Volume Sistólico , Resultado do Tratamento , Função Ventricular Esquerda , Metoprolol/efeitos adversos , Metoprolol/uso terapêutico , Prevenção Secundária
12.
Circ Cardiovasc Qual Outcomes ; 17(4): e010090, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38597091

RESUMO

BACKGROUND: Socioeconomically disadvantaged communities in the United States disproportionately experience poor cardiovascular outcomes. Little is known about how hospitalizations and mortality for acute cardiovascular conditions have changed among Medicare beneficiaries in socioeconomically disadvantaged and nondisadvantaged communities over the past 2 decades. METHODS: Medicare files were linked with the Centers for Disease Control and Prevention's social vulnerability index to examine age-sex standardized hospitalizations for myocardial infarction, heart failure, ischemic stroke, and pulmonary embolism among Medicare fee-for-service beneficiaries ≥65 years of age residing in socioeconomically disadvantaged communities (highest social vulnerability index quintile nationally) and nondisadvantaged communities (all other quintiles) from 2003 to 2019, as well as risk-adjusted 30-day mortality among hospitalized beneficiaries. RESULTS: A total of 10 942 483 Medicare beneficiaries ≥65 years of age were hospitalized for myocardial infarction, heart failure, stroke, or pulmonary embolism (mean age, 79.2 [SD, 8.7] years; 53.9% female). Although age-sex standardized myocardial infarction hospitalizations declined in socioeconomically disadvantaged (990-650 per 100 000) and nondisadvantaged communities (950-570 per 100 000) from 2003 to 2019, the gap in hospitalizations between these groups significantly widened (adjusted odds ratio 2003, 1.03 [95% CI, 1.02-1.04]; adjusted odds ratio 2019, 1.14 [95% CI, 1.13-1.16]). There was a similar decline in hospitalizations for heart failure in socioeconomically disadvantaged (2063-1559 per 100 000) and nondisadvantaged communities (1767-1385 per 100 000), as well as for ischemic stroke, but the relative gap did not change for both conditions. In contrast, pulmonary embolism hospitalizations increased in both disadvantaged (146-184 per 100 000) and nondisadvantaged communities (153-184 per 100 000). By 2019, risk-adjusted 30-day mortality was similar between hospitalized beneficiaries from socioeconomically disadvantaged and nondisadvantaged communities for myocardial infarction, heart failure, and ischemic stroke but was higher for pulmonary embolism (odds ratio, 1.10 [95% CI, 1.01-1.20]). CONCLUSIONS: Over the past 2 decades, hospitalizations for most acute cardiovascular conditions decreased in both socioeconomically disadvantaged and nondisadvantaged communities, although significant disparities remain, while 30-day mortality is now similar across most conditions.


Assuntos
Insuficiência Cardíaca , AVC Isquêmico , Infarto do Miocárdio , Embolia Pulmonar , Humanos , Feminino , Idoso , Estados Unidos/epidemiologia , Masculino , Medicare , Hospitalização , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/terapia , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/terapia , Classe Social
14.
Int J Mol Sci ; 25(6)2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38542439

RESUMO

This study aims to investigate the induction effect of LncRNA-CIR6 on MSC differentiation into cardiogenic cells in vitro and in vivo. In addition to pretreatment with Ro-3306 (a CDK1 inhibitor), LncRNA-CIR6 was transfected into BMSCs and hUCMSCs using jetPRIME. LncRNA-CIR6 was further transfected into the hearts of C57BL/6 mice via 100 µL of AAV9-cTnT-LncRNA-CIR6-ZsGreen intravenous injection. After three weeks of transfection followed by AMI surgery, hUCMSCs (5 × 105/100 µL) were injected intravenously one week later. Cardiac function was evaluated using VEVO 2100 and electric mapping nine days after cell injection. Immunofluorescence, Evans blue-TTC, Masson staining, FACS, and Western blotting were employed to determine relevant indicators. LncRNA-CIR6 induced a significant percentage of differentiation in BMSCs (83.00 ± 0.58)% and hUCMSCs (95.43 ± 2.13)% into cardiogenic cells, as determined by the expression of cTnT using immunofluorescence and FACS. High cTNT expression was observed in MSCs after transfection with LncRNA-CIR6 by Western blotting. Compared with the MI group, cardiac contraction and conduction function in MI hearts treated with LncRNA-CIR6 or combined with MSCs injection groups were significantly increased, and the areas of MI and fibrosis were significantly lower. The transcriptional expression region of LncRNA-CIR6 was on Chr17 from 80209290 to 80209536. The functional region of LncRNA-CIR6 was located at nucleotides 0-50/190-255 in the sequence. CDK1, a protein found to be related to the proliferation and differentiation of cardiomyocytes, was located in the functional region of the LncRNA-CIR6 secondary structure (from 0 to 17). Ro-3306 impeded the differentiation of MSCs into cardiogenic cells, while MSCs transfected with LncRNA-CIR6 showed a high expression of CDK1. LncRNA-CIR6 mediates the repair of infarcted hearts by inducing MSC differentiation into cardiogenic cells through CDK1.


Assuntos
Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Infarto do Miocárdio , Quinolinas , RNA Longo não Codificante , Tiazóis , Animais , Camundongos , Proteína Quinase CDC2/genética , Proteína Quinase CDC2/metabolismo , Diferenciação Celular/genética , Células-Tronco Mesenquimais/metabolismo , Camundongos Endogâmicos C57BL , Infarto do Miocárdio/genética , Infarto do Miocárdio/terapia , Infarto do Miocárdio/metabolismo , Miócitos Cardíacos/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo
15.
BMC Health Serv Res ; 24(1): 393, 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38549108

RESUMO

BACKGROUND: Evidence-based care for acute myocardial infarction (AMI) reduces morbidity and mortality. Prior studies in Tanzania identified substantial gaps in the uptake of evidence-based AMI care. Implementation science has been used to improve uptake of evidence-based AMI care in high-income settings, but interventions to improve quality of AMI care have not been studied in sub-Saharan Africa. METHODS: Purposive sampling was used to recruit participants from key stakeholder groups (patients, providers, and healthcare administrators) in northern Tanzania. Semi-structured in-depth interviews were conducted using a guide informed by the Consolidated Framework for Implementation Research (CFIR). Interview transcripts were coded to identify barriers to AMI care, using the 39 CFIR constructs. Barriers relevant to emergency department (ED) AMI care were retained, and the Expert Recommendations for Implementing Change (ERIC) tool was used to match barriers with Level 1 recommendations for targeted implementation strategies. RESULTS: Thirty key stakeholders, including 10 patients, 10 providers, and 10 healthcare administrators were enrolled. Thematic analysis identified 11 barriers to ED-based AMI care: complexity of AMI care, cost of high-quality AMI care, local hospital culture, insufficient diagnostic and therapeutic resources, inadequate provider training, limited patient knowledge of AMI, need for formal implementation leaders, need for dedicated champions, failure to provide high-quality care, poor provider-patient communication, and inefficient ED systems. Seven of these barriers had 5 strong ERIC recommendations: access new funding, identify and prepare champions, conduct educational meetings, develop educational materials, and distribute educational materials. CONCLUSIONS: Multiple barriers across several domains limit the uptake of evidence-based AMI care in northern Tanzania. The CFIR-ERIC mapping approach identified several targeted implementation strategies for addressing these barriers. A multi-component intervention is planned to improve uptake of evidence-based AMI care in Tanzania.


Assuntos
Atenção à Saúde , Infarto do Miocárdio , Humanos , Tanzânia , Infarto do Miocárdio/terapia , Ciência da Implementação , Qualidade da Assistência à Saúde
16.
Eur Heart J ; 45(15): 1339-1351, 2024 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-38426727

RESUMO

BACKGROUND AND AIMS: Patients with kidney failure have a higher risk of cardiovascular disease compared with the general population. Whilst temporal trends of myocardial infarction and stroke are declining in the general population, these have not been evaluated in patients with kidney failure. This study aimed to describe national trends in the incidence, treatment, and outcomes of myocardial infarction and stroke in patients with kidney failure (i.e. on dialysis or with a kidney transplant) over a 20-year period, stratified by age and sex. METHODS: In this retrospective national data linkage study, all patients with kidney failure in Scotland (UK) receiving kidney replacement therapy between January 1996 and December 2016 were linked to national hospitalization, prescribing, and death records. The primary outcomes were the incidence of myocardial infarction and stroke, and subsequent cardiovascular death. Generalized additive models were constructed to estimate age-standardized, sex-stratified incidence rates and trends in cardiovascular and all-cause death. RESULTS: Amongst 16 050 patients with kidney failure [52 (SD 15) years; 41.5% women], there were 1992 [66 (SD 12) years; 34.8% women] and 996 [65 (SD 13) years; 45.1% women] incident myocardial infarctions and strokes, respectively, between January 1996 and December 2016. During this period, the age-standardized incidence of myocardial infarction per 100 000 decreased in men {from 4376 [95% confidence interval (CI) 3998-4785] to 1835 (95% CI 1692-1988)} and women [from 3268 (95% CI 2982-3593) to 1369 (95% CI 1257-1491)]. Similarly, the age-standardized incidence of stroke per 100 000 also decreased in men [from 1978 (95% CI 1795-2175) to 799 (95% CI 729-875)] and women [from 2234 (95% CI 2031-2468) to 903 (95% CI 824-990)]. Compared with the general population, the incidence of myocardial infarction was four- to eight-fold higher in patients with kidney failure, whilst for stroke it was two- to four-fold higher. The use of evidence-based cardioprotective treatment increased over the study period, and the predicted probability of cardiovascular death within 1 year of myocardial infarction for a 66-year-old patient with kidney failure (mean age of the cohort) fell in men (76.6% to 38.6%) and women (76.8% to 38.8%), and also decreased in both sexes following stroke (men, from 63.5% to 41.4%; women, from 67.6% to 45.8%). CONCLUSIONS: The incidence of myocardial infarction and stroke has halved in patients with kidney failure over the past 20 years but remains significantly higher than in the general population. Despite improvements in treatment and outcomes, the prognosis of these patients following myocardial infarction and stroke remains poor.


Assuntos
Infarto do Miocárdio , Insuficiência Renal , Acidente Vascular Cerebral , Masculino , Humanos , Feminino , Idoso , Incidência , Estudos Retrospectivos , Diálise Renal/efeitos adversos , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/terapia , Infarto do Miocárdio/complicações , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/terapia , Acidente Vascular Cerebral/etiologia , Fatores de Risco
17.
Ann Glob Health ; 90(1): 21, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38495415

RESUMO

Background: Uptake of evidence-based care for acute myocardial infarction (AMI) is suboptimal in Tanzania, but there are currently no published interventions to improve AMI care in sub-Saharan Africa. Objectives: Co-design a quality improvement intervention for AMI care tailored to local contextual factors. Methods: An interdisciplinary design team consisting of 20 physicians, nurses, implementation scientists, and administrators met from June 2022 through August 2023. Half of the design team consisted of representatives from the target audience, emergency department physicians and nurses at a referral hospital in northern Tanzania. The design team reviewed multiple published quality improvement interventions focusing on ED-based AMI care. After selecting a multicomponent intervention to improve AMI care in Brazil (BRIDGE-ACS), the design team used the ADAPT-ITT framework to adapt the intervention to the local context. Findings: The design team audited current AMI care processes at the study hospital and reviewed qualitative data regarding barriers to care. Multiple adaptations were made to the original BRIDGE-ACS intervention to suit the local context, including re-designing the physician reminder system and adding patient educational materials. Additional feedback was sought from topical experts, including patients with AMI. Draft intervention materials were iteratively refined in response to feedback from experts and the design team. The finalized intervention, Multicomponent Intervention to Improve Myocardial Infarction Care in Tanzania (MIMIC), consisted of five core components: physician reminders, pocket cards, champions, provider training, and patient education. Conclusion: MIMIC is the first locally tailored intervention to improve AMI care in sub-Saharan Africa. Future studies will evaluate implementation outcomes and efficacy.


Assuntos
Infarto do Miocárdio , Médicos , Humanos , Tanzânia , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/terapia , Melhoria de Qualidade , Brasil
18.
Med Sci Monit ; 30: e943298, 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38449299

RESUMO

BACKGROUND Percutaneous coronary intervention (PCI) with angiography guidance is a common procedure. Optical coherence tomography (OCT) is a non-invasive imaging method that uses light waves. This study from a single center aimed to compare 1-year outcomes in 75 patients with acute ST-segment elevation myocardial infarction (STEMI) who underwent OCT-guided primary PCI, with 163 patients with acute STEMI who underwent PCI without OCT guidance from February 2019 to July 2021. MATERIAL AND METHODS Patients with acute STEMI were enrolled from February 2019 to July 2021. Seventy-five patients underwent OCT-guided PCI (OCT group), while 163 underwent PCI without OCT (control group). Baseline characteristics, in-hospital mortality, target lesion revascularization, post-MI heart failure, and 1-year all-cause mortality were compared between groups. RESULTS The OCT group had lower diabetes mellitus and hyperlipidemia prevalence. Additionally, they experienced longer procedures (OCT: 50.45±21.75 min; control: 33.80±14.44 min; P<0.001). After PCI, the control group had lower left ventricular ejection fractions (OCT: 53.4%±10.5%; control: 47.8%±12.4%; P<0.001) and higher post-MI heart failure rates (OCT: 2.7%; control: 11.0%; P=0.030). Notably, the 1-year all-cause mortality rate was significantly lower in the OCT group (OCT: 1.3%; control: 8.0%; P=0.043). CONCLUSIONS During the 1-year follow-up, patients who received OCT-guided primary PCI experienced a notably lower rate of post-MI heart failure than did those who underwent primary PCI without OCT guidance. Importantly, the application of OCT in primary PCI procedures did not result in a higher incidence of distal embolism, even in cases with a significant thrombus burden.


Assuntos
Insuficiência Cardíaca , Infarto do Miocárdio , Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST , Humanos , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico por imagem , Infarto do Miocárdio com Supradesnível do Segmento ST/cirurgia , Tomografia de Coerência Óptica , Arritmias Cardíacas , Infarto do Miocárdio/diagnóstico por imagem , Infarto do Miocárdio/terapia
19.
J Healthc Manag ; 69(2): 118-131, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38467025

RESUMO

GOAL: Patients engaged in self-care through information technology can potentially improve the quality of healthcare they receive. This study aimed to examine how electronic health record (EHR) system functionalities help hospitals mediate the impact of patient engagement on quality outcomes-notably, readmission rates. METHODS: A pooled cross-sectional study design employed data containing 3,547 observations from general acute care hospitals (2014-2018). The breadth of patient engagement functionalities adopted by a hospital was used as the independent variable and the degree of EHR presence was used as the mediating variable. Mean time to readmission for acute myocardial infarction (AMI), pneumonia, and heart failure were the dependent variables. The Baron and Kenny method was used to test mediation. PRINCIPAL FINDINGS: Patient engagement was associated with reduced AMI readmission rates both directly and via EHR system presence. Mediation effects were present, in that a 1-unit increase in patient engagement through EHR system presence was associated with a 0.33% decrease in AMI readmission rates (p < .05). For other disease categories (heart failure and pneumonia), a significant effect was not found. PRACTICAL APPLICATIONS: For hospitals with a comprehensive EHR system, patient engagement through information technology can potentially reduce readmission rates for some diseases. More research is needed to determine which specific clinical conditions are amenable to quality improvement through patient engagement. Synergies between patient engagement functionalities and an EHR system positively affect quality outcomes. Therefore, practitioners and hospital managers should leverage hospital investments made in their EHR system infrastructure and use it to engage patients in self-care.


Assuntos
Insuficiência Cardíaca , Infarto do Miocárdio , Pneumonia , Humanos , Estados Unidos , Participação do Paciente , Estudos Transversais , Hospitais , Infarto do Miocárdio/terapia , Insuficiência Cardíaca/terapia , Pneumonia/terapia , Readmissão do Paciente , Registros Eletrônicos de Saúde
20.
Kardiologiia ; 64(2): 3-17, 2024 Feb 29.
Artigo em Russo | MEDLINE | ID: mdl-38462799

RESUMO

AIM: Based on data from the Russian REGION-IM registry, to study the features of reperfusion therapy in patients with ST-segment elevation myocardial infarction (STEMI) in real-life clinical practice. MATERIAL AND METHODS: REGION-IM is a multicenter prospective observational study. The observational period is divided into 3 stages: during the stay in the hospital and at 6 and 12 months after inclusion in the registry. The patient's records contain demographic and history data; information about the present case of MI, including the time of the first symptom onset, first contact with medical personnel, and admission to the hospital; coronary angiography (CAG) data, percutaneous coronary intervention (PCI) data, and information about the thrombolytic therapy (TLT). RESULTS: Reperfusion therapy was performed in 88.9 % of patients with STEMI. Primary PCI (pPCI) was performed in 60.6 % of patients. The median time from the onset of symptoms to pPCI was 315 minutes [195; 720]. The median time from ECG to pPCI was 110 minutes [84;150]. Isolated TLT was performed in 7.4 %, pharmaco-invasive treatment tactics were used only in 20.9 % of cases. The median time from ECG to TLT (prehospital and in-hospital) was 30 minutes [10; 59], whereas the median time from ECG to prehospital TLT was 18 minutes [10; 39], and in 63 % of patients, TLT was performed more than 10 minutes after diagnosis. PCI followed TLT in 73 % of patients. CONCLUSION: The frequency of reperfusion therapy for STEMI in the Russian Federation has increased considerably in recent years. The high frequency of pPCI is noteworthy, but the timing of pPCI does not always comply with clinical guidelines. The results of this registry confirm the high demand for pharmaco-invasive strategies in real-life clinical practice. Taking into account geographical and logistical features, implementing timely myocardial reperfusion requires prehospital TLT. However, the TLT frequency in the Russian Federation is still insufficient despite its proven maximum effectiveness in the shortest possible time from the detection of acute MI.


Assuntos
Infarto do Miocárdio , Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST , Humanos , Infarto do Miocárdio/terapia , Reperfusão Miocárdica , Sistema de Registros , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Infarto do Miocárdio com Supradesnível do Segmento ST/tratamento farmacológico , Terapia Trombolítica , Resultado do Tratamento
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