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1.
BMJ ; 366: l4563, 2019 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-31405902

RESUMO

OBJECTIVE: To determine any changes in total hospital revisits within 30 days of discharge after a hospital stay for medical conditions targeted by the Hospital Readmissions Reduction Program (HRRP). DESIGN: Retrospective cohort study. SETTING: Hospital stays among Medicare patients for heart failure, acute myocardial infarction, or pneumonia between 1 January 2012 and 1 October 2015. PARTICIPANTS: Medicare fee-for-service patients aged 65 or over. MAIN OUTCOMES: Total hospital revisits within 30 days of discharge after hospital stays for medical conditions targeted by the HRRP, and by type of revisit: treat-and-discharge visit to an emergency department, observation stay (not leading to inpatient readmission), and inpatient readmission. Patient subgroups (age, sex, race) were also evaluated for each type of revisit. RESULTS: Our study cohort included 3 038 740 total index hospital stays from January 2012 to September 2015: 1 357 620 for heart failure, 634 795 for acute myocardial infarction, and 1 046 325 for pneumonia. Counting all revisits after discharge, the total number of hospital revisits per 100 patient discharges for target conditions increased across the study period (monthly increase 0.023 visits per 100 patient discharges (95% confidence interval 0.010 to 0.035)). This change was due to monthly increases in treat-and-discharge visits to an emergency department (0.023 (0.015 to 0.032) and observation stays (0.022 (0.020 to 0.025)), which were only partly offset by declines in readmissions (-0.023 (-0.035 to -0.012)). Increases in observation stay use were more pronounced among non-white patients than white patients. No significant change was seen in mortality within 30 days of discharge for target conditions (-0.0034 (-0.012 to 0.0054)). CONCLUSIONS: In the United States, total hospital revisits within 30 days of discharge for conditions targeted by the HRRP increased across the study period. This increase was due to a rise in post-discharge emergency department visits and observation stays, which exceeded the decline in readmissions. Although reductions in readmissions have been attributed to improvements in discharge planning and care transitions, our findings suggest that these declines could instead be because hospitals and clinicians have intensified efforts to treat patients who return to a hospital within 30 days of discharge in emergency departments and as observation stays.


Assuntos
Readmissão do Paciente/estatística & dados numéricos , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Unidades de Observação Clínica/estatística & dados numéricos , Serviço Hospitalar de Emergência/estatística & dados numéricos , Feminino , Pesquisa sobre Serviços de Saúde/métodos , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/terapia , Humanos , Masculino , Medicare/estatística & dados numéricos , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/terapia , Alta do Paciente , Readmissão do Paciente/tendências , Pneumonia/epidemiologia , Pneumonia/terapia , Estudos Retrospectivos , Fatores Sexuais , Fatores de Tempo , Estados Unidos/epidemiologia
2.
Angiology ; 70(10): 908-915, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31256614

RESUMO

The optimal treatment strategy for coronary chronic total occlusion (CTO) has not been well established. The benefit of percutaneous coronary intervention (PCI) was inferred mainly from observational studies comparing successful versus failed PCI without a control group receiving optimal medical therapy (OMT). We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) and observational studies comparing PCI using drug-eluting stent (DES) versus OMT alone in patients with CTO. Eight studies were identified: 3 RCTs and 5 observational studies. Among a total of 4784 included patients, 2461 patients underwent PCI and 2323 patients received OMT. There was a significant association between PCI and lower cardiac mortality (odds ratio = 0.62; 95% confidence interval 0.42-0.93; P = .02). There was no significant difference between PCI and OMT regarding major adverse cardiac events, recurrent myocardial infarction (MI), repeat revascularization, or stroke. In the RCT subset (1399 patients), there was no significant difference between PCI and OMT regarding clinical outcomes. Compared with OMT alone, PCI with DES for CTO was associated with lower cardiac mortality, mainly driven by observational studies, without significant difference in recurrent MI or repeated revascularization. Further RCTs are needed to investigate the role of PCI for management of patients with CTO.


Assuntos
Oclusão Coronária/terapia , Stents Farmacológicos , Infarto do Miocárdio/terapia , Intervenção Coronária Percutânea , Oclusão Coronária/mortalidade , Stents Farmacológicos/efeitos adversos , Humanos , Infarto do Miocárdio/etiologia , Intervenção Coronária Percutânea/efeitos adversos , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/terapia , Resultado do Tratamento
3.
Br J Anaesth ; 123(4): 421-429, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31256916

RESUMO

BACKGROUND: The National Surgical Quality Improvement Program Myocardial Infarction & Cardiac Arrest (NSQIP MICA) calculator and the Revised Cardiac Risk Index (RCRI) were derived using currently outdated methods of diagnosing perioperative myocardial infarctions. We tested the external validity of these tools in a setting of a systematic perioperative cardiac biomarker measurement. METHODS: Analysis of routinely collected data nested in the Vascular Events In Noncardiac Surgery Patients Cohort Evaluation Study. A consecutive sample of patients ≥45 yr old undergoing in-hospital noncardiac surgery in a single tertiary care centre was enrolled. The predictive performance of the models was tested in terms of the occurrence of major cardiac complications defined as a composite of a nonfatal myocardial infarction, a nonfatal cardiac arrest, or a cardiac death within 30 days after surgery. The plasma concentration of high-sensitivity troponin T was measured before surgery, 6-12 h after operation, and on the first, second, and third days after surgery. Myocardial infarction was diagnosed according to the Third Universal Definition. RESULTS: The median age was 65 (59-72) yr, and 704/870 (80.9%) subjects were male. The primary outcome occurred in 76/870 (8.7%; 95% confidence interval [CI], 6.9-10.8%) patients. The c-statistic was 0.64 (95% CI, 0.57-0.70) for the NSQIP MICA and 0.60 (95% CI, 0.54-0.65) for the RCRI. Predicted risks were systematically underestimated in calibration belts (P<0.001). The RCRI and the NSQIP MICA showed no clinical utility before recalibration. CONCLUSIONS: The NSQIP and RCRI models had limited predictive performance in this at-risk population. The recently updated version of the RCRI was more reliable than the original index.


Assuntos
Parada Cardíaca/etiologia , Parada Cardíaca/terapia , Cardiopatias/epidemiologia , Complicações Intraoperatórias/terapia , Infarto do Miocárdio/etiologia , Infarto do Miocárdio/terapia , Complicações Pós-Operatórias/terapia , Medição de Risco/normas , Procedimentos Cirúrgicos Vasculares/métodos , Idoso , Estudos de Coortes , Morte Súbita Cardíaca/prevenção & controle , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Valor Preditivo dos Testes , Melhoria de Qualidade , Resultado do Tratamento , Procedimentos Cirúrgicos Vasculares/efeitos adversos
4.
Life Sci ; 231: 116554, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31194992

RESUMO

AIMS: Several adipokines have been proven to improve the therapeutic efficacy of mesenchymal stromal cells (MSCs) when used to treat ischemic heart disease. Asprosin (ASP) is a newly-discovered adipokine. ASP might also predict the severity of coronary pathology. We investigated the role of ASP on MSCs and the effects of ASP-pretreated MSCs on myocardial infarction (MI). MAIN METHODS: MSCs were labelled with a lentivirus carrying green fluorescent protein (GFP). For in vivo study, after pretreatment with vehicle or ASP, MSCs were injected into infarcted hearts. Cardiac function and fibrosis were then evaluated 4 weeks after the induction of MI and survival of MSCs evaluated after 1 week. MSCs proliferation and migration were investigated after ASP treatment in vitro. MSCs apoptosis induced by hydrogen peroxide (H2O2) was assessed using flow cytometry. KEY FINDINGS: Compared to vehicle-pretreated MSCs, ASP-pretreated MSCs significantly improved the left ventricular ejection fraction (LVEF), and inhibited myocardial fibrosis 4 weeks after MI. ASP pretreatment may have promoted homing of transplanted MSCs. In vitro results showed that ASP had no significant effect on MSC proliferation and migration, but protected these cells from H2O2-induced apoptosis. Among 21 molecules associated with antioxidation and cell death, the antioxidant enzyme SOD2 was significantly upregulated by ASP. Furthermore, ASP treatment inhibited H2O2-induced ROS generation and apoptosis via the activated ERK1/2-SOD2 pathway. SIGNIFICANCE: This is the first evidence that ASP can regulate MSCs function and enhance MSCs therapy for ischemic heart disease. Furthermore, we demonstrate that ASP protects MSCs from oxidative stress-induced apoptosis via the ERK1/2-SOD2 pathway.


Assuntos
Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Células-Tronco Mesenquimais/efeitos dos fármacos , Proteínas dos Microfilamentos/metabolismo , Infarto do Miocárdio/terapia , Fragmentos de Peptídeos/metabolismo , Hormônios Peptídicos/metabolismo , Superóxido Dismutase/metabolismo , Animais , Apoptose/fisiologia , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Coração/fisiopatologia , Peróxido de Hidrogênio/farmacologia , Masculino , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/patologia , Camundongos , Camundongos Endogâmicos C57BL , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/patologia , Isquemia Miocárdica/metabolismo , Isquemia Miocárdica/patologia , Espécies Reativas de Oxigênio/metabolismo , Função Ventricular Esquerda
5.
Cell Physiol Biochem ; 52(6): 1309-1324, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31050280

RESUMO

BACKGROUND/AIMS: Different approaches have been considered to improve heart reconstructive medicine and direct delivery of pluripotent stem cell-derived cardiomyocytes (PSC-CMs) appears to be highly promising in this context. However, low cell persistence post-transplantation remains a bottleneck hindering the approach. Here, we present a novel strategy to overcome the low engraftment of PSC-CMs during the early post-transplantation phase into the myocardium of both healthy and cryoinjured syngeneic mice. METHODS: Adult murine bone marrow mesenchymal stem cells (MSCs) and PSC-CMs were co-cultured on thermo-responsive polymers and later detached through temperature reduction, resulting in the protease-free generation of cell clusters (micro-tissues) composed of both cells types. Micro-tissues were transplanted into healthy and cryo-injured murine hearts. Short term cell retention was quantified by real-time-PCR. Longitudinal cell tracking was performed by bioluminescence imaging for four weeks. Transplanted cells were further detected by immunofluorescence staining of tissue sections. RESULTS: We demonstrated that in vitro grown micro-tissues consisting of PSC-CMs and MSCs can increase cardiomyocyte retention by >10fold one day post-transplantation, but could not fully rescue a further cell loss between day 1 and day 2. Neutrophil infiltration into the transplanted area was detected in healthy hearts and could be attributed to the cellular implantation rather than tissue damage exerted by the transplantation cannula. Injected PSC-CMs were tracked and successfully detected for up to four weeks by bioluminescence imaging. CONCLUSION: This approach demonstrated that in vitro grown micro-tissues might contribute to the development of cardiac cell replacement therapies.


Assuntos
Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , Miocárdio/patologia , Miócitos Cardíacos/transplante , Animais , Células da Medula Óssea/citologia , Linhagem Celular , Rastreamento de Células , Técnicas de Cocultura , Imunidade Inata , Masculino , Células-Tronco Mesenquimais/metabolismo , Camundongos , Microscopia de Fluorescência , Infarto do Miocárdio/patologia , Infarto do Miocárdio/terapia , Miocárdio/imunologia , Miócitos Cardíacos/citologia , Miócitos Cardíacos/metabolismo , Infiltração de Neutrófilos , Imagem Óptica , Células-Tronco Pluripotentes/citologia , Polímeros/química
6.
Medicine (Baltimore) ; 98(19): e15621, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31083259

RESUMO

RATIONAL: Plaque rapid progression prior to acute myocardial infarction is not a common phenomenon, and its mechanism remains unknown. Intracoronary imaging may help to assess the plaque characteristics and progression. PATIENT CONCERN: A 37-year-old male patient suffered an acute myocardial infarction (AMI) 1 month after the diagnosis of a mildly stenosed coronary artery. Intracoronary imaging was done to seek the underlying causes and guide further treatment. DIAGNOSIS: Two coronary angiograms in 1 month showed plaque rapid progressing prior to the AMI. Intracoronary optical coherence tomography (OCT) post-AMI showed plaque erosion and heavy burden of thrombus. INTERVENTION: The patient was advised to defer stent deployment. The patient was then given intensified antithrombotic therapy. Three weeks later, OCT imaging revealed sufficient lumen area and the intact endothelium without remaining thrombus. Fractional flow reverse (FFR) showed no functional ischemia. Dual-antiplatelet therapy without stenting was recommended for 12 months. OUTCOMES: The 6-month follow-up showed good recovery and normal cardiac function. LESSONS: First, for patients with mild coronary stenosis and typical angina symptoms, further intracoronary assessment should be performed. Second, OCT can not only help to determine the plaque characteristics but can also help to develop patient-tailored strategies for AMI patients.


Assuntos
Estenose Coronária/diagnóstico por imagem , Estenose Coronária/terapia , Infarto do Miocárdio/diagnóstico por imagem , Infarto do Miocárdio/terapia , Placa Aterosclerótica/diagnóstico por imagem , Placa Aterosclerótica/terapia , Adulto , Estenose Coronária/complicações , Vasos Coronários/diagnóstico por imagem , Progressão da Doença , Humanos , Masculino , Infarto do Miocárdio/etiologia , Placa Aterosclerótica/complicações
7.
Zhonghua Xin Xue Guan Bing Za Zhi ; 47(4): 278-283, 2019 Apr 24.
Artigo em Chinês | MEDLINE | ID: mdl-31060186

RESUMO

Objective: To investigate the short-term outcome of patients with acute myocardial infarction complicating cardiogenic shock due to left main disease. Methods: A total of 24 patients with acute myocardial infarction complicating cardiogenic shock due to left main artery disease hospitalized in Fuwai hospital from June 2012 to May 2018 were included. The clinical data were analyzed,and the patients were divided into survivor group (11 cases) and death group (13 cases) according to survival status at 28 days post the diagnosis of shock. The patients were further divided into thrombolysis in myocardial infarction(TIMI) flow grade 0-2 group (11 cases) and TIMI flow grade 3 group (13 cases) according to TIMI flow grade after the procedure. The patients were then divided into non-three-vessel lesions group (14 cases) and three-vessel lesions group (10 cases) according to coronary angiography results. Results: Compared with survivor group, patients in death group presented with lower worst systolic blood pressure within 24 hours after admission (50(48, 70) mmHg (1 mmHg=0.133 kPa) vs. 73(70, 80) mmHg, P<0.01), lower worst diastolic blood pressure with in 24 hours after admission ((33.5±12.4) mmHg vs. (48.9±9.4) mmHg, P<0.01), higher respiratory rates ((27.3±2.5) times/min vs. (21.5±4.0) times/min, P<0.01), less 24 hours urine output ((422±266) ml vs. (1 680±863) ml, P<0.01), lower platelet counts ((161.9±81.9)×10(9)/L vs. (241.6±94.0)×10(9)/L, P=0.03), higher serum creatinine ((250.0±36.8) µmol/L vs. (132.7±34.2) µmol/L, P<0.01), higher alanine aminotransferase (288(76,846) IU/ml vs. 81(42, 109) IU/ml, P=0.04), lower artery pH (7.11±0.17 vs. 7.39±0.09, P<0.01), higher lactic acid ((10.29±3.62) mmol/L vs. (4.21±2.85) mmol/L, P<0.01), higher incidence of invasive ventilation (7/13 vs. 2/11, P=0.02), higher scores of acute physiology and chronic health evaluation (APACHE) Ⅱ (35.4±6.8 vs. 18.7±1.7, P<0.01) and simplified acute physiology score (SAPS) Ⅱ (73.5±17.4 vs. 47.0±4.3, P<0.01), and higher incidence of target vessel TIMI flow grade 0-2 (10/13 vs. 1/11, P<0.01). Kaplan-Meier survival curve analysis showed that survival rate at 28 days post the diagnosis of shock in TIMI flow grade 3 group was higher than that in TIMI flow grade 0-2 group (76.9% vs. 9.1%, log-rank test, P<0.01), and mortality rate was similar at 28 days post the diagnosis of shock between non-three-vessel lesions group and three-vessel lesions group (35.7% vs. 60.0%, log-rank test, P=0.14). Multivariate logistic regression analysis showed that compared with TIMI flow grade 0-2 group, the OR value of death at 28 days post the diagnosis of shock in TIMI flow grade 3 patients with acute myocardial infarction complicating cardiogenic shock due to left main disease was 0.030(95%CI 0.003-0.340, P<0.01). Conclusion: Short-term outcomeof patients with acute myocardial infarction complicating cardiogenic shock due to left main disease remains poor, and final flow of TIMI grade 3 is confirmed as independent protective factor of death at 28 days post the diagnosis of shock in these patients.


Assuntos
Doença da Artéria Coronariana , Infarto do Miocárdio , Angiografia Coronária , Doença da Artéria Coronariana/terapia , Humanos , Estimativa de Kaplan-Meier , Infarto do Miocárdio/terapia , Choque Cardiogênico
8.
Int J Mol Sci ; 20(9)2019 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-31052231

RESUMO

We investigated the antiarrhythmic effects of ischemic preconditioning (IPC) and postconditioning (PostC) by intracardiac electrocardiogram (ECG) and measured circulating microRNAs (miRs) that are related to cardiac conduction. Domestic pigs underwent 90-min. percutaneous occlusion of the mid left anterior coronary artery, followed by reperfusion. The animals were divided into three groups: acute myocardial infarction (AMI, n = 7), ischemic preconditioning-acute myocardial infarction (IPC-AMI) (n = 9), or AMI-PostC (n = 5). IPC was induced by three 5-min. episodes of repetitive ischemia/reperfusion cycles (rI/R) before AMI. PostC was induced by six 30-s rI/R immediately after induction of reperfusion 90 min after occlusion. Before the angiographic procedure, a NOGA endocardial mapping catheter was placed again the distal anterior ventricular endocardium to record the intracardiac electrogram (R-amplitude, ST-Elevation, ST-area under the curve (AUC), QRS width, and corrected QT time (QTc)) during the entire procedure. An arrhythmia score was calculated. Cardiac MRI was performed after one-month. IPC led to significantly lower ST-elevation, heart rate, and arrhythmia score during ischemia. PostC induced a rapid recovery of R-amplitude, decrease in QTc, and lower arrhythmia score during reperfusion. Slightly higher levels of miR-26 and miR-133 were observed in AMI compared to groups IPC-AMI and AMI-PostC. Significantly lower levels of miR-1, miR-208, and miR-328 were measured in the AMI-PostC group as compared to animals in group AMI and IPC-AMI. The arrhythmia score was not significantly associated with miRNA plasma levels. Cardiac MRI showed significantly smaller infarct size in the IPC-AMI group when compared to the AMI and AMI-PostC groups. Thus, IPC led to better left ventricular ejection fraction at one-month and it exerted antiarrhythmic effects during ischemia, whereas PostC exhibited antiarrhythmic properties after reperfusion, with significant downregulaton of ischemia-related miRNAs.


Assuntos
Exossomos/metabolismo , Pós-Condicionamento Isquêmico , Precondicionamento Isquêmico Miocárdico , MicroRNAs/metabolismo , Infarto do Miocárdio/metabolismo , Fibrilação Ventricular/metabolismo , Animais , Feminino , Ventrículos do Coração/metabolismo , MicroRNAs/genética , Infarto do Miocárdio/complicações , Infarto do Miocárdio/terapia , Suínos , Fibrilação Ventricular/etiologia , Fibrilação Ventricular/terapia , Função Ventricular
9.
Int J Mol Med ; 43(6): 2451-2461, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31017253

RESUMO

Ischemic postconditioning (IPoC) has been demonstrated to prevent myocardial ischemia­reperfusion injury (MIRI), but its cardioprotective effect is abrogated by hypercholesterolemia. The aim of the present study was to determine whether lycopene (LP), a type of carotenoid, can restore the cardioprotective effect of IPoC in hypercholesterolemic rats. Male Wistar rats were fed a cholesterol­enriched diet for 12 weeks to establish a hypercholesterolemic model. The rat hearts were isolated and subjected to 30 min ischemia and 60 min reperfusion using a Langendorff apparatus. LP was administered to the rats intraperitoneally for 5 consecutive days prior to ischemia and reperfusion. Myocardial pathological changes, infarct size and cell apoptosis were measured by hematoxylin and eosin, triphenyltetrazolium chloride and TUNEL staining, respectively. The changes in endoplasmic reticulum (ER) stress markers, the reperfusion injury salvage kinase (RISK) pathway and mitochondrial apoptosis­related proteins were detected by western blotting. Overall, the results demonstrated that low­dose LP in combination with IPoC ameliorated myocardial histopathological changes, reduced the infarct size and release of cardiac enzymes, and decreased cardiomyocyte apoptosis in hypercholesterolemic rats, but no beneficial effects were achieved by the same dose of LP or IPoC treatment were used alone. Furthermore, the combination of LP and IPoC inhibited the expression of glucose­regulated protein 78 and C/EBP homologous protein, increased the phosphorylation levels of AKT, ERK1/2 and glycogen synthase kinase­3ß, repressed mitochondrial permeability transition pore opening, and reduced the expression of cytochrome c, cleaved caspase­9 and cleaved caspase­3. Collectively, these findings demonstrated that LP can restore the cardioprotective effects of IPoC on MIRI in hypercholesterolemic rats, and this restoration by LP was mediated by inhibition of ER stress and reactivation of the RISK pathway in hypercholesterolemic rat myocardium.


Assuntos
Hipercolesterolemia/complicações , Pós-Condicionamento Isquêmico , Licopeno/uso terapêutico , Traumatismo por Reperfusão Miocárdica/complicações , Traumatismo por Reperfusão Miocárdica/terapia , Substâncias Protetoras/uso terapêutico , Animais , Hipercolesterolemia/sangue , Hipercolesterolemia/patologia , Pós-Condicionamento Isquêmico/métodos , Lipídeos/sangue , Masculino , Infarto do Miocárdio/sangue , Infarto do Miocárdio/complicações , Infarto do Miocárdio/patologia , Infarto do Miocárdio/terapia , Traumatismo por Reperfusão Miocárdica/sangue , Traumatismo por Reperfusão Miocárdica/patologia , Miocárdio/patologia , Ratos Wistar
10.
Int J Mol Med ; 43(6): 2319-2328, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30942393

RESUMO

Exosomes serve important functions in cell­to­cell communication and biological functions by serving as a delivery cargo shuttle for various molecules. The application of an improved delivery method for microRNAs (miRNAs/miRs) may enhance their potential as a therapeutic tool in cardiac diseases. Thus, the present study investigated whether human peripheral blood­derived exosomes may be used as a delivery cargo system for miRNAs, and whether the delivery of miR­21 using a human peripheral blood derived­exosome may influence the degree of remodeling following myocardial infarction (MI). In H9C2 and HL­1 cells, miR­21 expression was successfully regulated by treatment with human peripheral blood derived­exosomes loaded with an miR­21 mimic or inhibitor compared with untreated cells. In addition, the mRNA and protein expression levels of SMAD family member 7 (Smad7), phosphatase and tensin homolog (PTEN) and matrix metalloproteinase 2 (MMP2), which are involved in cardiac fibrosis, were associated with the uptake of miR­21 mimic­ or inhibitor­loaded exosomes. Similarly, the in vivo mRNA and protein expression of Smad7, PTEN and MMP2 were altered following treatment with miR­21 mimic­ or inhibitor­loaded exosomes. Furthermore, miR­21 mimic­loaded exosomes enhanced fibrosis, whereas miR­21 inhibitor­loaded exosomes reduced fibrosis in a mouse MI model. These results suggested that miRNA­loaded human peripheral blood derived­exosomes may be used as a therapeutic tool for cardiac diseases.


Assuntos
Portadores de Fármacos/química , Exossomos/química , MicroRNAs/administração & dosagem , Infarto do Miocárdio/terapia , Idoso , Animais , Linhagem Celular , Feminino , Fibrose , Terapia Genética , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/uso terapêutico , Infarto do Miocárdio/genética , Infarto do Miocárdio/patologia , Miocárdio/patologia
11.
Biol Pharm Bull ; 42(4): 524-530, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30930411

RESUMO

Myocardial infarction occurs as a result of acute arteriosclerotic plaque rupture in the coronary artery, triggering strong inflammatory responses. The necrotic cardiomyocytes are gradually replaced with noncontractile scar tissue that eventually manifests as heart failure. Pluripotent stem cells (PSCs) show great promise for widespread clinical applications, particularly for tissue regeneration, and are being actively studied around the world to help elucidate disease mechanisms and in the development of new drugs. Human induced PSCs also show potential for regeneration of the myocardial tissue in experiments with small animals and in in vitro studies. Although emerging evidence points to the effectiveness of these stem cell-derived cardiomyocytes in cardiac regeneration, several challenges remain before clinical application can become a reality. Here, we provide an overview of the present state of PSC-based heart regeneration and highlight the remaining hurdles, with a particular focus on graft survival, immunogenicity, posttransplant arrhythmia, maintained function, and tumor formation. Rapid progress in this field along with advances in biotechnology are expected to resolve these issues, which will require international collaboration and standardization.


Assuntos
Infarto do Miocárdio/terapia , Miócitos Cardíacos/transplante , Células-Tronco Pluripotentes/citologia , Animais , Diferenciação Celular , Humanos
12.
BMJ Case Rep ; 12(3)2019 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-30936331

RESUMO

Coronary artery disease managed by percutaneous coronary intervention (PCI) has been noted for profit-driven overuse medicine. Concerns mount over inappropriate use of PCI for patients in India. We describe the case of a 55-year-old Indian man who presented for a second opinion following an urgent recommendation for PCI by two cardiologists following a recent acute myocardial infarction even though the patient was symptom-free and out of the window period for primary PCI. The proposed intervention placed the patient at financial risk for insolvency. This case report highlights the challenges and consequences of inappropriate overuse of PCI. Also, we outline the current lack of shared decision-making among patients and physicians for the PCI procedure. The challenges, inherent in the assumptions that overuse of PCI is evidence-based, are discussed including recommendations for the practice of evidence based medicine for this intervention.


Assuntos
Mau Uso de Serviços de Saúde/estatística & dados numéricos , Infarto do Miocárdio/diagnóstico , Intervenção Coronária Percutânea , Padrões de Prática Médica/estatística & dados numéricos , Procedimentos Desnecessários , Efeitos Psicossociais da Doença , Tomada de Decisões , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Índia , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/terapia , Satisfação do Paciente , Intervenção Coronária Percutânea/economia , Inibidores da Agregação de Plaquetas/uso terapêutico , Encaminhamento e Consulta , Resultado do Tratamento , Procedimentos Desnecessários/economia , Procedimentos Desnecessários/estatística & dados numéricos
13.
Emerg Med Clin North Am ; 37(2): 339-350, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30940376

RESUMO

Cardiovascular disease has overtaken all other causes of maternal death in the United States. The physiologic changes of pregnancy place a significant amount of stress on the cardiovascular system and put pregnant women at risk for potentially catastrophic complications, such as pulmonary embolism, aortic or coronary artery dissection, myocardial infarction, and peripartum cardiomyopathy. The diagnosis of these conditions is challenging because the symptoms can mimic those experienced in normal pregnancies. There are subtle differences in the diagnosis and treatment of cardiovascular emergencies in pregnant patients that clinicians must be aware of; however, the overall management goals are similar.


Assuntos
Serviço Hospitalar de Emergência , Complicações Cardiovasculares na Gravidez/diagnóstico , Aneurisma Dissecante/complicações , Aneurisma Dissecante/diagnóstico , Aneurisma Dissecante/terapia , Aneurisma Aórtico/complicações , Aneurisma Aórtico/diagnóstico , Aneurisma Aórtico/terapia , Cardiomiopatias/complicações , Cardiomiopatias/diagnóstico , Cardiomiopatias/terapia , Feminino , Humanos , Infarto do Miocárdio/complicações , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/terapia , Período Periparto , Gravidez , Complicações Cardiovasculares na Gravidez/terapia , Tromboembolia Venosa/complicações , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/terapia
14.
Nat Commun ; 10(1): 1735, 2019 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-30988291

RESUMO

Injectable biopolymer hydrogels have gained attention for use as scaffolds to promote cardiac function and prevent negative left ventricular (LV) remodeling post-myocardial infarction (MI). However, most hydrogels tested in preclinical studies are not candidates for minimally invasive catheter delivery due to excess material viscosity, rapid gelation times, and/or concerns regarding hemocompatibility and potential for embolism. We describe a platform technology for progelator materials formulated as sterically constrained cyclic peptides which flow freely for low resistance injection, and rapidly assemble into hydrogels when linearized by disease-associated enzymes. Their utility in vivo is demonstrated by their ability to flow through a syringe and gel at the site of MI in rat models. Additionally, synthetic functionalization enables these materials to flow through a cardiac injection catheter without clogging, without compromising hemocompatibility or cytotoxicity. These studies set the stage for the development of structurally dynamic biomaterials for therapeutic hydrogel delivery to the MI.


Assuntos
Hidrogéis/química , Infarto do Miocárdio/terapia , Peptídeos Cíclicos/química , Animais , Cateteres Cardíacos , Hidrogéis/administração & dosagem , Hidrogéis/uso terapêutico , Miocárdio/patologia , Peptídeos Cíclicos/administração & dosagem , Peptídeos Cíclicos/uso terapêutico , Ratos
15.
Medicine (Baltimore) ; 98(15): e15143, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30985685

RESUMO

RATIONALE: Takayasu arteritis (TA) is a chronic inflammatory disease involving the aorta and its major branches. Initial diagnosis is usually difficult due to the highly variable symptoms. Acute myocardial infarction (AMI) is a very rare presentation in patients with TA. Moreover, the choice of early management for these patients is not well established. PATIENT CONCERNS: A 34-year-old woman was taken to the Emergency Department of our hospital, presenting with a sudden onset and persistent retrosternal chest pain radiating to both upper extremities for 2 hours. Blood pressures were different between 2 arms with 151/115 mm Hg on the right arm and 140/100 mm Hg on the left arm. DIAGNOSES: The patient was diagnosed with TA according to the medical history, physical examination, and vascular imaging. INTERVENTIONS: Primary percutaneous coronary intervention (PPCI) was performed to restore the coronary flow of left anterior descending. Meanwhile, combination of oral glucocorticoids and immunosuppressive agents was administered to halt disease progression of TA. OUTCOMES: Chest pain was relieved without rest and exertional angina. The patient achieved long-term remission without symptom relapse during our follow-up. LESSONS: Percutaneous coronary intervention was essential and effective in AMI of TA. Timely immunosuppressive therapy could improve the long-term outcome.


Assuntos
Infarto do Miocárdio/diagnóstico , Arterite de Takayasu/diagnóstico , Adulto , Terapia Combinada , Diagnóstico Diferencial , Feminino , Humanos , Infarto do Miocárdio/terapia , Arterite de Takayasu/terapia
16.
Nat Commun ; 10(1): 1802, 2019 04 17.
Artigo em Inglês | MEDLINE | ID: mdl-30996254

RESUMO

The primary cause of heart failure is the loss of cardiomyocytes in the diseased adult heart. Previously, we reported that the miR-17-92 cluster plays a key role in cardiomyocyte proliferation. Here, we report that expression of miR-19a/19b, members of the miR-17-92 cluster, is induced in heart failure patients. We show that intra-cardiac injection of miR-19a/19b mimics enhances cardiomyocyte proliferation and stimulates cardiac regeneration in response to myocardial infarction (MI) injury. miR-19a/19b protected the adult heart in two distinctive phases: an early phase immediately after MI and long-term protection. Genome-wide transcriptome analysis demonstrates that genes related to the immune response are repressed by miR-19a/19b. Using an adeno-associated virus approach, we validate that miR-19a/19b reduces MI-induced cardiac damage and protects cardiac function. Finally, we confirm the therapeutic potential of miR-19a/19b in protecting cardiac function by systemically delivering miR-19a/19b into mice post-MI. Our study establishes miR-19a/19b as potential therapeutic targets to treat heart failure.


Assuntos
Terapia Genética/métodos , Insuficiência Cardíaca/patologia , MicroRNAs/administração & dosagem , MicroRNAs/metabolismo , Infarto do Miocárdio/terapia , Animais , Proliferação de Células/genética , Dependovirus/genética , Modelos Animais de Doenças , Perfilação da Expressão Gênica , Vetores Genéticos/administração & dosagem , Vetores Genéticos/genética , Insuficiência Cardíaca/terapia , Ventrículos do Coração/patologia , Humanos , Injeções Intralesionais , Masculino , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/genética , Infarto do Miocárdio/etiologia , Infarto do Miocárdio/patologia , Miócitos Cardíacos/fisiologia , Regeneração/genética
17.
Vasc Health Risk Manag ; 15: 57-67, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30936712

RESUMO

Background: Acute myocardial infarction (AMI) with no evidence of relevant stenosis of the coronary artery, known as myocardial infarction (MI) with nonobstructive coronary arteries (MINOCA), has a prevalence of up to 14%. The various causes of MINOCA lead to damage of the myocardium, and there are marked differences in diagnoses, prognoses, and treatments. Although the number of patients affected is considerable owing to the high prevalence of acute coronary syndrome (ACS), the causes of MINOCA have received little attention with the result that some patients may not receive appropriate treatment. Awareness of this disease among clinicians has started only to improve since the beginning of the current century. The aim of this study was to develop a score that enables patients with MINOCA to be distinguished from patients with MI with coronary artery disease (MI-CAD) and thus to facilitate appropriate diagnosis and therapy. Patients and methods: A multicenter observational cohort study was designed. All patients aged ≥18 years from the ARIAM-SEMICYUC (Analysis of Delay in AMI-Spanish Society of Intensive Care Medicine and Coronary Unit) registry, diagnosed with AMI, and admitted to critical care units or coronary care units (CCUs) were included. Patients were classified into two groups: MINOCA, comprising patients with no significant lesions on angiography, and MI-CAD, comprising patients with lesions of the coronary artery tree. Results: A score based on standard variables to assess the probability of MINOCA on admission was designed, showing a maximum value corresponding to a 40% probability of MINOCA. The discriminative power of the model was 0.756 (P-value for the Hosmer-Lemeshow test was >0.05). At 30-day follow-up, the mortality rate was higher for MI-CAD patients. Conclusion: Patients with MINOCA constitute a population that differs from other patients with AMI. Their differential characteristics require a certain diagnostic effort to align therapy with the disease causing the ischemic event. This score could prove useful in establishing additional diagnostic procedures.


Assuntos
Doença da Artéria Coronariana/diagnóstico , Estenose Coronária/diagnóstico , Técnicas de Apoio para a Decisão , Infarto do Miocárdio/diagnóstico , Fatores Etários , Idoso , Biomarcadores/sangue , Angiografia Coronária , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/epidemiologia , Doença da Artéria Coronariana/terapia , Estenose Coronária/sangue , Estenose Coronária/epidemiologia , Estenose Coronária/terapia , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/sangue , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/terapia , Valor Preditivo dos Testes , Prognóstico , Sistema de Registros , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais , Espanha/epidemiologia , Troponina/sangue , Regulação para Cima
18.
Int J Exp Pathol ; 100(2): 102-113, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-31017330

RESUMO

A major translational barrier to the use of stem cell (SC)-based therapy in patients with myocardial infarction (MI) is the lack of a clear understanding of the mechanism(s) underlying the cardioprotective effect of SCs. Numerous paracrine factors from SCs may account for reduction in infarct size, but myocardial salvage associated with transdifferentiation of SCs into vascular cells as well as cardiomyocyte-like cells may be involved too. In this study, bone marrow-derived rat mesenchymal SC (MSCs) were microencapsulated in alginate preventing viable cell release while supporting their secretory phenotype. The hypothesis on the key role of paracrine factors from MSCs in their cardioprotective activity was tested by comparison of the effect of encapsulated vs free MSCs in the rat model of MI. Intramyocardial administration of both free and encapsulated MSCs after MI caused reduction in scar size (12.1 ± 6.83 and 14.7 ± 4.26%, respectively, vs 21.7 ± 6.88% in controls, P = 0.015 and P = 0.03 respectively). Scar size was not different in animals treated with free and encapsulated MSC (P = 0.637). These data provide evidence that MSC-derived growth factors and cytokines are crucial for cardioprotection elicited by MSC. Administration of either free or encapsulated MSCs was not arrhythmogenic in non-infarcted rats. The consistency of our data with the results of other studies on the major role of MSC secretome components in cardiac protection further support the theory that the use of live, though encapsulated, cells for MI therapy may be replaced with heart-targeted-sustained delivery of growth factors/cytokines.


Assuntos
Peptídeos e Proteínas de Sinalização Intercelular/fisiologia , Transplante de Células-Tronco Mesenquimais/métodos , Infarto do Miocárdio/terapia , Alginatos , Animais , Arritmias Cardíacas/etiologia , Células Cultivadas , Cicatriz/patologia , Citoproteção/fisiologia , Composição de Medicamentos , Ecocardiografia , Imunofenotipagem , Masculino , Transplante de Células-Tronco Mesenquimais/efeitos adversos , Células-Tronco Mesenquimais/imunologia , Infarto do Miocárdio/diagnóstico por imagem , Infarto do Miocárdio/patologia , Infarto do Miocárdio/fisiopatologia , Comunicação Parácrina/fisiologia , Ratos Wistar , Função Ventricular Esquerda/fisiologia , Remodelação Ventricular/fisiologia
19.
ACS Appl Mater Interfaces ; 11(16): 14619-14629, 2019 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-30939870

RESUMO

Hydrogen sulfide (H2S) exhibits extensive protective actions in cardiovascular systems, such as anti-inflammatory and stimulating angiogenesis, but its therapeutic potential is severely discounted by the short half-life and the poorly controlled releasing behavior. Herein, we developed a macromolecular H2S prodrug by grafting 2-aminopyridine-5-thiocarboxamide (a small-molecule H2S donor) on partially oxidized alginate (ALG-CHO) to mimic the slow and continuous release of endogenous H2S. In addition, tetraaniline (a conductive oligomer) and adipose-derived stem cells (ADSCs) were introduced to form a stem cell-loaded conductive H2S-releasing hydrogel through the Schiff base reaction between ALG-CHO and gelatin. The hydrogel exhibited adhesive property to ensure a stable anchoring to the wet and beating hearts. After myocardial injection, longer ADSCs retention period and elevated sulfide concentration in rat myocardium were demonstrated, accompanied by upregulation of cardiac-related mRNA (Cx43, α-SMA, and cTnT) and angiogenic factors (VEGFA and Ang-1) and downregulation of inflammatory factors (tumor necrosis factor-α). Echocardiography and histological analysis strongly demonstrated an increase in the ejection fraction value and smaller infarction size, suggesting a remarkable improvement of the cardiac functions of Sprague-Dawley rats. The ADSC-loaded conductive hydrogen sulfide-releasing hydrogel dramatically promoted the therapeutic effects, offering a promising therapeutic strategy for treating myocardial infarction.


Assuntos
Tecido Adiposo/metabolismo , Hidrogéis , Sulfeto de Hidrogênio , Infarto do Miocárdio , Miocárdio/metabolismo , Transplante de Células-Tronco , Células-Tronco/metabolismo , Tecido Adiposo/patologia , Aloenxertos , Animais , Hidrogéis/química , Hidrogéis/farmacocinética , Hidrogéis/farmacologia , Sulfeto de Hidrogênio/química , Sulfeto de Hidrogênio/farmacocinética , Sulfeto de Hidrogênio/farmacologia , Masculino , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/patologia , Infarto do Miocárdio/terapia , Miocárdio/patologia , Ratos , Ratos Sprague-Dawley , Células-Tronco/patologia , Suínos
20.
Int J Mol Sci ; 20(6)2019 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-30909376

RESUMO

Myocardial tissue damage that occurs during an ischemic event leads to a spiraling deterioration of cardiac muscle structural and functional integrity. Reperfusion is the only known efficacious strategy and is the most commonly used treatment to reduce injury and prevent remodeling. However, timing is critical, and the procedure is not always feasible for a variety of reasons. The complex molecular basis for cardioprotection has been studied for decades but formulation of a viable therapeutic that can significantly attenuate myocardial injury remains elusive. In this review, we address barriers to the development of a fruitful approach that will substantially improve the prognosis of those suffering from this widespread and largely unmitigated disease. Furthermore, we proffer that ephrinA1, a candidate molecule that satisfies many of the important criteria discussed, possesses robust potential to overcome these hurdles and thus offers protection that surpasses the limitations currently observed.


Assuntos
Infarto do Miocárdio/terapia , Animais , Cardiotônicos , Terapia Combinada , Gerenciamento Clínico , Efrina-A1/genética , Efrina-A1/metabolismo , Efrina-A1/uso terapêutico , Efrina-A1/ultraestrutura , Humanos , Fragmentos Fc das Imunoglobulinas/uso terapêutico , Fragmentos Fc das Imunoglobulinas/ultraestrutura , Ligantes , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/etiologia , Infarto do Miocárdio/metabolismo , Proteínas Recombinantes de Fusão/uso terapêutico , Proteínas Recombinantes de Fusão/ultraestrutura , Pesquisa Médica Translacional , Resultado do Tratamento
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