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1.
Semin Thorac Cardiovasc Surg ; 33(1): 49-58, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33242613

RESUMO

Intraoperative conversion to cardiopulmonary bypass with its subsequent high mortality is a major concern associated with off-pump coronary artery bypass grafting (OPCAB). The impact of procedure volume on the incidence of intraoperative conversion, however, is poorly defined. This study therefore evaluated the effect of procedure volume on the incidence of conversion in OPCAB using nationwide data. We analyzed 31,361 patients who underwent primary, nonemergent, isolated OPCAB during 2013-2016 reported in the Japan Cardiovascular Surgery Database. Hospitals (n = 548) and surgeons (n = 1315) were divided into tertile categories (low-, medium-, and high volumes) based on the total number of isolated coronary artery bypass grafting (CABG). Hierarchical logistic regression analysis, including 22 preoperative factors and hospital and surgeon CABG volumes, was used to assess the relation between procedure volume and the risk of conversion due to bleeding/hemodynamic instability. There were 797 (2.5%) intraoperative conversions due to bleeding/hemodynamic instability. Risk-adjusted odds ratios for conversion were significantly lower in some combined hospital/surgeon CABG volume categories than in the reference category. Hospital/surgeon volumes and their odds ratio (95% confidence interval) were as follows: low/low 1.00 (reference); medium/low 0.62 (0.39-0.96); high/low 0.47 (0.27-0.81); high/high 0.58 (0.38-0.89). There was a lower risk of conversion in medium- and high-volume than low-volume hospitals, especially among low-volume surgeons. Procedure volume is associated with the incidence of conversion during OPCAB. Among low-volume surgeons, hospital CABG volume significantly reduces conversion in a volume-dependent manner. These findings will be useful for safety training of OPCAB surgeons.


Assuntos
Ponte de Artéria Coronária , Cirurgiões , Ponte de Artéria Coronária/efeitos adversos , Hospitais , Humanos , Incidência , Japão/epidemiologia , Resultado do Tratamento
2.
Gen Thorac Cardiovasc Surg ; 69(4): 766-769, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33222090

RESUMO

A 32-year-old male patient was initially diagnosed with fibrosing mediastinitis. The patient subsequently developed severe dyspnea and was further diagnosed with constrictive pericarditis due to the extent of fibrosing mediastinitis around the heart. Therefore, the patient underwent surgical resection of the fibrotic tissue in the anterior mediastinum including the pericardium and the pleura. Postoperative histological and immunohistochemical analyses revealed angiosarcoma. Seven years after the diagnosis, he is still alive. Herein, we report a case of atypical primary angiosarcoma of the anterior mediastinum causing constrictive pericarditis and restrictive pulmonary dysfunction.


Assuntos
Hemangiossarcoma , Mediastinite , Pericardite Constritiva , Adulto , Hemangiossarcoma/diagnóstico , Hemangiossarcoma/cirurgia , Humanos , Masculino , Mediastino , Pericardite Constritiva/diagnóstico por imagem , Pericardite Constritiva/cirurgia , Pericárdio
3.
J Card Surg ; 36(2): 739-742, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33305858

RESUMO

A 40-year-old male with Becker muscular dystrophy presented with severe mitral regurgitation and underwent mitral valve repair. Following the surgery, the patient became tachycardic and developed a continuous high-grade fever and hyperbilirubinemia. The patient's condition worsened and we eventually tested his thyroid levels and discovered abnormally high thyroid levels. After diagnosing a severe thyroid storm, the patient was treated with oral administration of Lugol's iodine and thiamazole, as well as an intravenous steroid, which led to an immediate improvement of symptoms. The incidence of thyroid storm after open-heart surgery is extremely rare but highly life-threatening if unrecognized.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Insuficiência da Valva Mitral , Distrofia Muscular de Duchenne , Crise Tireóidea , Adulto , Humanos , Masculino , Valva Mitral/cirurgia , Insuficiência da Valva Mitral/etiologia , Insuficiência da Valva Mitral/cirurgia , Distrofia Muscular de Duchenne/complicações , Crise Tireóidea/diagnóstico , Crise Tireóidea/tratamento farmacológico , Crise Tireóidea/etiologia
4.
Surg Case Rep ; 6(1): 280, 2020 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-33151421

RESUMO

BACKGROUND: Staphylococcus lugdunensis is a coagulase-negative Staphylococcus species, which are weak pathogenic bacteria generally. However, the acute and severe pathogenicity of Staphylococcus lugdunensis infective endocarditis may be due to the rapid growth of large vegetation and consequent valve destruction. CASE PRESENTATION: The patient was an 81-year-old male who visited our hospital with chief complaints of low back pain and high fever. Four years before this visit, he had undergone aortic valve replacement for aortic regurgitation. He was found to be hypotensive. Although there is no heart murmur on auscultation and echocardiography revealed negative findings with aortic valve, a blood test showed increases in the white blood cell count and C-reactive protein concentration. On the next day, Gram-positive cocci were detected in a blood culture and echocardiography detected a large vegetation on the prosthetic valve with increased flow velocity. Therefore, he underwent redo aortic valve replacement emergently. Staphylococcus lugdunensis was identified in blood samples and vegetation culture. Consequently, the patient was treated with antibiotics for 5 weeks after the operation and discharged home. CONCLUSIONS: We experienced rapidly progressive prosthetic valve endocarditis caused by Staphylococcus lugdunensis. Hence, Staphylococcus lugdunensis infective endocarditis requires aggressive treatment, and the pathogenicity of this coagulase-negative Staphylococcus with high drug susceptibility should not be underestimated.

5.
Circ J ; 83(10): 2061-2069, 2019 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-31434812

RESUMO

BACKGROUND: In patients with severe coronary artery disease (CAD) requiring coronary revascularization, the prevalence of surgical ineligibility and its clinical effect on long-term outcomes remain unclear.Methods and Results:Among 15,939 patients with first coronary revascularization in the CREDO-Kyoto percutaneous coronary intervention (PCI)/coronary artery bypass grafting (CABG) registry cohort-2, we identified 3,982 patients with triple-vessel or left main disease (PCI: n=2,188, and CABG: n=1,794). Surgical ineligibility as documented in hospital charts was present in 142 (6.5%) of 2,188 PCI-patients, which was mainly related to comorbidities and advanced age. The cumulative 5-year incidence of the primary outcome measure (all-cause death/myocardial infarction/stroke) was much higher in PCI-patients with surgical ineligibility than in PCI-patients without surgical ineligibility and in CABG-patients (52.5%, 27.6%, and 24.0%, respectively, log-rank P<0.001). After adjusting for confounders, the excess risk of PCI-patients with surgical ineligibility relative to CABG-patients was substantial (hazard ratio [HR] 1.97, 95% CI 1.51-2.58, P<0.001), while the excess risk of PCI-patients without surgical ineligibility relative to CABG-patients was modest, but remained significant (HR 1.37, 95% CI 1.19-1.59, P<0.001). CONCLUSIONS: Among patients with severe CAD, PCI-patients with surgical ineligibility had worse long-term outcomes as compared with those without surgical ineligibility and CABG-patients.


Assuntos
Contraindicações de Procedimentos , Ponte de Artéria Coronária/efeitos adversos , Doença da Artéria Coronariana/terapia , Definição da Elegibilidade , Intervenção Coronária Percutânea , Idoso , Idoso de 80 Anos ou mais , Causas de Morte , Ponte de Artéria Coronária/mortalidade , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/mortalidade , Progressão da Doença , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/mortalidade , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/mortalidade , Sistema de Registros , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Acidente Vascular Cerebral/mortalidade , Fatores de Tempo , Resultado do Tratamento
6.
J Thorac Cardiovasc Surg ; 156(6): 2088-2096.e3, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30195600

RESUMO

OBJECTIVES: The postoperative left ventricular end-systolic volume index and ejection fraction are benchmarks of surgical ventricular reconstruction but remain unpredictable. This study aimed to identify who could be associated with a higher long-term survival by adding surgical ventricular reconstruction to coronary artery bypass grafting than coronary artery bypass grafting alone (responders to surgical ventricular reconstruction). METHODS: The subjects were 293 patients (median age, 63 years; 255 men) who underwent coronary artery bypass grafting for ischemic heart disease with left ventricular dysfunction in 16 cardiovascular centers in Japan. The relationships among surgical ventricular reconstruction, postoperative end-systolic volume index, ejection fraction, and survival were analyzed to identify responders to surgical ventricular reconstruction. RESULTS: Surgical ventricular reconstruction was performed in 165 patients (56%). The end-systolic volume index and ejection fraction significantly improved (end-systolic volume index, 91 to 64 mL/m2; ejection fraction, 28% to 35%) for all patients. The postoperative end-systolic volume index and ejection fraction were estimated, and surgical ventricular reconstruction was found to be significantly associated with both end-systolic volume index (14.5 mL/m2 reduction, P < .001) and ejection fraction (3.1% increase, P = .003). During the median follow-up of 6.8 years, 69 patients (24%) died. Only the postoperative ejection fraction was significantly associated with survival (hazard ratio, 0.925; 95% confidence interval, 0.885-0.968), although this effect was limited to those with postoperative end-systolic volume index of 40 to 80 mL/m2 in the subgroup analysis (hazard ratio, 0.932; 95% confidence interval, 0.894-0.973). CONCLUSIONS: Adding surgical ventricular reconstruction to coronary artery bypass grafting could reduce the mortality risk by increasing ejection fraction for those with a postoperative end-systolic volume index within a specific range. The postoperative end-systolic volume index could demarcate responders to surgical ventricular reconstruction, and its estimation can help in surgical decision making.


Assuntos
Ponte de Artéria Coronária , Doença da Artéria Coronariana/cirurgia , Ventrículos do Coração/cirurgia , Procedimentos de Cirurgia Plástica , Volume Sistólico , Disfunção Ventricular Esquerda/cirurgia , Função Ventricular Esquerda , Remodelação Ventricular , Idoso , Ponte de Artéria Coronária/efeitos adversos , Ponte de Artéria Coronária/mortalidade , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/mortalidade , Doença da Artéria Coronariana/fisiopatologia , Feminino , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/fisiopatologia , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Procedimentos de Cirurgia Plástica/efeitos adversos , Procedimentos de Cirurgia Plástica/mortalidade , Recuperação de Função Fisiológica , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/mortalidade , Disfunção Ventricular Esquerda/fisiopatologia
7.
PLoS One ; 13(8): e0201650, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30071102

RESUMO

To realize human induced pluripotent stem cell (hiPSC)-based cardiac regenerative therapy, evidence of therapeutic advantages in human-sized diseased hearts are indispensable. In combination with an efficient and simultaneous differentiation of various cardiac lineages from hiPSCs and cell sheet technology, we aimed to generate clinical-sized large cardiac tissue sheets (L-CTSs) and to evaluate the therapeutic potential in porcine infarct heart. We simultaneously induced cardiomyocytes (CMs) and vascular cells [vascular endothelial cells (ECs) and vascular mural cells (MCs)] from hiPSCs. We generated L-CTSs using 10cm-sized temperature-responsive culture dishes. We induced myocardial infarction (MI) in micromini-pigs (15-25 kg) and transplanted the L-CTSs (Tx) 2 weeks after MI induction (4 sheets/recipient) under immunosuppression (Tx: n = 5, Sham: n = 5). Self-pulsating L-CTSs were approximately 3.5cm in diameter with 6.8×106±0.8 of cells containing cTnT+-CMs (45.6±13.2%), VE-cadherin+-ECs (5.3±4.4%) and PDGFRß+-MCs (14.4±20.7%), respectively (n = 5). In Tx group, echocardiogram indicated a significantly higher systolic function of the left ventricle (LV) compared to that in sham control (Sham vs Tx: fractional shortening: 24.2±8.6 vs 40.5±9.7%; p<0.05). Ejection fraction evaluated by left ventriculogram was significantly higher in Tx group (25.3±6.2% vs 39.8±4.2%; p<0.01). Speckle tracking echocardiogram showed a significant increase of circumference strain in infarct and border regions after transplantation. Fibrotic area was significantly lower in Tx group (23.8±4.5 vs 15.9±3.8%; P<0.001). Capillary density in the border region was significantly higher in Tx group (75.9±42.6/mm2 vs 137.4±44.8/mm2, p<0.001). These data indicate that the L-CTS transplantation attenuated LV remodeling. L-CTSs potentially restore cardiac dysfunction of human-sized infarct heart.


Assuntos
Coração/fisiologia , Infarto do Miocárdio/terapia , Miócitos Cardíacos/transplante , Alicerces Teciduais/química , Animais , Caderinas/metabolismo , Cálcio/metabolismo , Células Cultivadas , Modelos Animais de Doenças , Ecocardiografia , Humanos , Células-Tronco Pluripotentes Induzidas/citologia , Microscopia de Fluorescência , Infarto do Miocárdio/patologia , Miocárdio/metabolismo , Miocárdio/patologia , Miócitos Cardíacos/citologia , Miócitos Cardíacos/metabolismo , Regeneração , Suínos , Engenharia Tecidual , Troponina T/metabolismo , Função Ventricular , Remodelação Ventricular
8.
Heart Vessels ; 33(10): 1251-1257, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29761379

RESUMO

This study investigated the safety and efficacy of a sustained release of basic fibroblast growth factor (bFGF) with biodegradable gelatin hydrogel sheets as therapeutic angiogenesis in canine chronic myocardial infarction (MI) models. Canine chronic MI model was induced by ligating the left anterior descending coronary artery and its diagonal branches. At 4 week post-induction, we applied either saline (Control group, n = 5) or 200 µg of bFGF (Treatment group, n = 6) soaked gelatin hydrogel sheets on the ischemic area of the left ventricular (LV) wall. At 6 weeks after the procedure, we evaluated the efficacy by echocardiography and immunohistochemical study. There were no procedure-related adverse events or deaths. The serum bFGF level was under detectable levels in all animals at any sampling points. In terms of efficacy, echocardiographic evaluation demonstrated that fractional shortening was significantly improved in the treatment group. In addition, immunohistochemical study showed that the capillary density in the border zone of the MI area, as well as the MI area, significantly increased in the treatment group. Therapeutic angiogenesis by bFGF using biodegradable gelatin hydrogel sheets was safe, increased the capillary density, and improved LV function in canine chronic MI models.


Assuntos
Vasos Coronários/diagnóstico por imagem , Fator 2 de Crescimento de Fibroblastos/administração & dosagem , Infarto do Miocárdio/tratamento farmacológico , Neovascularização Patológica/tratamento farmacológico , Animais , Doença Crônica , Vasos Coronários/efeitos dos fármacos , Preparações de Ação Retardada , Modelos Animais de Doenças , Cães , Implantes de Medicamento , Hidrogéis , Masculino , Microesferas , Infarto do Miocárdio/diagnóstico , Neovascularização Patológica/diagnóstico , Proteínas Recombinantes
9.
J Thorac Cardiovasc Surg ; 156(3): 976-983, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29753505

RESUMO

OBJECTIVES: Most randomized controlled trials of off-pump versus on-pump coronary artery bypass grafting (CABG) have included limited numbers of patients with preoperative renal failure. This study was performed to evaluate the association between the clinical benefit of the off-pump technique and chronic kidney disease stage. METHODS: We analyzed 38,051 patients with chronic kidney disease who underwent primary nonemergent isolated CABG from 2013 to 2015 as reported in the Japan Cardiovascular Surgery Database-Adult section. These patients were stratified into 4 categories according to their estimated glomerular filtration rate (eGFR) of 60 to 90, 30 to 59, and <30 mL/min/1.73 m2, and hemodialysis-dependent. The clinical outcomes were compared between patients undergoing off-pump and on-pump CABG in each stratum using inverse probability of treatment weighting. RESULTS: In total, 23,634 (62.1%) patients were intended for off-pump CABG. In patients with mildly reduced renal function (eGFR 60-89 mL/min/1.73 m2), there was no significant risk reduction effect of off-pump CABG for surgical mortality. Conversely, in patients with moderate or severe renal disease (eGFR <60 mL/min/1.73 m2), off-pump CABG was associated with a significantly lower incidence of surgical death (odds ratio with 95% confidence interval: eGFR 30-59 mL/min/1.73 m2, 0.66 [0.51-0.84]; eGFR <30 mL/min/1.73 m2, 0.51 [0.37-0.72]; and hemodialysis-dependent, 0.68 [0.51-0.90]). In addition, in patients with severe renal disease (eGFR of <30), off-pump CABG was associated with a significantly lower incidence of de novo dialysis. CONCLUSIONS: The off-pump technique significantly reduced surgical mortality in patients with moderate or severe preoperative renal dysfunction.


Assuntos
Ponte de Artéria Coronária sem Circulação Extracorpórea , Insuficiência Renal , Adulto , Ponte de Artéria Coronária , Humanos , Japão , Estudos Retrospectivos
10.
Interact Cardiovasc Thorac Surg ; 27(3): 322-327, 2018 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-29617819

RESUMO

OBJECTIVES: Little data are available with regard to valve selections in redo valvular surgery. We investigated the impact of valve types on late outcomes after redo mitral valve replacement (MVR). METHODS: We retrospectively reviewed 66 patients aged 50-69 (mean age 62.2 ± 5.1) years who underwent redo MVR over the past 25 years. In redo MVR, 46 (69.7%) redo procedures were the 1st redo valvular surgeries, 16 (24.2%) were 2nd redos, 3 (4.5%) were 3rd redos and 1 was a 4th (1.5%) redo. We classified 66 patients into 2 groups: mechanical MVR group (M-MVR, n = 44) and biological MVR group (B-MVR, n = 22). The mean follow-up period was 8.2 ± 6.3 years. RESULTS: Hospital mortality rates were 3.3% in M-MVR and 9.7% in B-MVR (P = 0.3328). Survival rates in M-MVR and B-MVR at 5 and 10 years were 93.0 ± 4.8% vs 76.0 ± 10.5% and 77.6 ± 9.1% vs 51.3 ± 13.7%, respectively (log-rank test, P = 0.0072). Late death occurred in 7 patients in M-MVR and 9 in B-MVR. Freedom rates from valve-related events in M-MVR and B-MVR at 5 and 10 years were 100.0 ± 0.0% vs 76.5 ± 10.3% and 93.3 ± 6.4% vs 52.4 ± 13.6%, respectively (log-rank test, P < 0.0001). No bleeding and thromboembolic events were observed in M-MVR, whereas gastrointestinal bleeding (n = 1), subarachnoid haemorrhage (n = 1) and cerebral infarction (n = 2) were observed in B-MVR. A predictor of late death was a biological valve in redo MVR (P = 0.0206, hazard ratio = 3.402, 95% confidence interval 1.207-9.591). CONCLUSIONS: It would seem that redo MVR using a mechanical valve was associated with better early and late outcomes in this age group.


Assuntos
Doenças das Valvas Cardíacas/cirurgia , Implante de Prótese de Valva Cardíaca/instrumentação , Próteses Valvulares Cardíacas , Valva Mitral , Reoperação , Fatores Etários , Idoso , Feminino , Doenças das Valvas Cardíacas/mortalidade , Implante de Prótese de Valva Cardíaca/efeitos adversos , Implante de Prótese de Valva Cardíaca/mortalidade , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Desenho de Prótese , Estudos Retrospectivos , Taxa de Sobrevida
11.
J Card Surg ; 33(2): 56-63, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29399899

RESUMO

AIM: We reviewed our experience in redo valvular surgery to evaluate trends in short- and long-term outcomes. METHODS: We reviewed 414 patients (mean age, 62.8 ± 13.6 years) who underwent redo valvular surgery in the past 25 years. A total of 301 patients (54.2%) underwent first-time redo valvular surgeries; 178 (32.1%) were second redos, 60 (10.8%) were third redos, and 16 were fourth redos (2.9%). The mean follow-up period was 6.8 ± 6.3 years. RESULTS: Hospital mortality was 5.8%. New York Heart Association (NYHA) class III/IV (P = 0.0007, odds ratio = 4.403) and hemodialysis (P = 0.0383, odds ratio = 7.196) were risk factors for hospital death. Long-term survival rates at 15 and 20 years were 64.7% ± 4.3% and 59.1% ± 5.0%, respectively. Predictors of late death were first time redo (P = 0.0076, hazard ratio = 0.422) and age younger than 61 years (P = 0.0005, hazard ratio = 0.229). There were significant differences in long-term survival between NYHA classes I/II and III/IV (log-rank test, P = 0.0419) and between the time from redo surgery (log-rank test, P = 0.0189) and age (log-rank test, P = 0.0001). CONCLUSIONS: The hospital mortality rate for redo valve surgery has improved. Early referral for redo surgery can contribute to improving early and late outcomes.


Assuntos
Doenças das Valvas Cardíacas/cirurgia , Implante de Prótese de Valva Cardíaca , Valvas Cardíacas/cirurgia , Reoperação , Idoso , Idoso de 80 Anos ou mais , Anuloplastia da Valva Cardíaca , Feminino , Seguimentos , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Reoperação/estatística & dados numéricos , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Fatores de Tempo , Resultado do Tratamento
12.
Cardiovasc Revasc Med ; 19(5 Pt B): 597-606, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29366795

RESUMO

BACKGROUND: The contemporary medications for secondary prevention like statins and antithrombotic agents are targeting to delay the progression of atherothrombosis. However, there is limited data on the relation between death and progressive coronary atherothrombosis. This study sought to evaluate what proportion of death after coronary revascularization is related to documented progressive coronary atherothrombosis. METHODS: We reviewed the detailed causes of death among 15,231 patients receiving their first coronary revascularization enrolled in the CREDO-Kyoto PCI/CABG registry cohort-2, dividing into two groups; 13,839 patients with clinical success and without major complication (uncomplicated) and the other 1392 patients (complicated). Documented progressive coronary atherothrombosis as the cause of death was defined as preceding coronary revascularization within 30days before death or irreversible brain damage and/or proof of coronary thrombus by autopsy. RESULTS: During the median follow-up of 5.4years, 2837 patients died with cumulative 5-year incidence of 17.5%. The proportions of cardiac/non-cardiovascular death among all-cause death in uncomplicated patients and complicated patients were 36.6%/51.5% and 74.2%/17.4%, respectively. The numbers of patients died with documented progressive coronary atherothrombosis were 41 (1.9% of all-cause death) and 304 (47.3%). The number was only 51 (2.1%) among all post-discharge patients. Dominant causes of cardiac death in post-discharge patients included heart failure (10.0%) and sudden cardiac death (9.1%), both without apparent relation with progressive coronary atherothrombosis. CONCLUSIONS: Only about one-third of deaths were cardiac in origin during 5-year follow-up in post-discharge patients after coronary revascularization. Cardiac death after discharge was very infrequently related to documented progressive coronary atherothrombosis.


Assuntos
Ponte de Artéria Coronária/mortalidade , Doença da Artéria Coronariana/cirurgia , Trombose Coronária/mortalidade , Alta do Paciente , Intervenção Coronária Percutânea/mortalidade , Idoso , Idoso de 80 Anos ou mais , Autopsia , Causas de Morte , Angiografia Coronária , Ponte de Artéria Coronária/efeitos adversos , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/mortalidade , Trombose Coronária/diagnóstico por imagem , Trombose Coronária/etiologia , Bases de Dados Factuais , Progressão da Doença , Feminino , Humanos , Incidência , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/instrumentação , Sistema de Registros , Fatores de Risco , Stents , Fatores de Tempo , Resultado do Tratamento
13.
J Vasc Surg ; 68(4): 1209-1215, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29242072

RESUMO

OBJECTIVE: Recent studies demonstrate that microRNAs show promising potential, including angiogenesis, in therapeutic intervention. MicroRNA-126 (miR-126) is reported to regulate angiogenesis by blocking Sprouty-related EVH1 domain-containing protein 1 (SPRED1), an endogenous inhibitor of vascular endothelial cell growth factor. In this study, we investigated the angiogenic effects of the sustained release of miR-126 loaded with poly lactic-co-glycolic acid (PLGA) nanoparticles (NPs) in a murine hindlimb ischemia model. METHODS: We induced mice hindlimb ischemia through femoral artery excision. We randomly assigned the mice to two groups and performed an intramuscular injection of miR-126-loaded PLGA NPs (miR-126) or scrambled miR-loaded PLGA NPs (control) shortly after induction of ischemia. RESULTS: The miR-126 expression levels in the ischemic limb at 3 days after treatment were significantly higher in mice treated with miR-126-loaded PLGA NPs than in those with scrambled miR, indicating the fair efficiency of local miR transduction (control vs miR-126: 0.33 ± 0.12 vs 0.74 ± 0.42; P < .05; n = 6). Laser Doppler perfusion imaging revealed that limb blood flow in mice treated with miR-126-loaded PLGA NPs was significantly higher at 14 days after treatment (sham vs control vs miR-126: 0.62 ± 0.09 vs 0.58 ± 0.05 vs 0.72 ± 0.07; P < .001; n = 12). Immunohistochemical analysis indicated that CD31-positive cell density and α-smooth muscle actin-positive vessel density were significantly higher in miR-126-treated mice (control vs miR-126: 0.33 ± 0.12 vs 0.74 ± 0.42; P < .05; n = 6). SPRED1 messenger RNA expression levels were significantly lower in miR-126-treated mice (control vs miR-126: 1.00 ± 0.05 vs 0.81 ± 0.07; P < .05; n = 6). Western blotting indicated that protein levels of pERK/ERK mediated by SPRED1 were significantly higher in miR-126-treated mice (control vs miR-126: 0.29 ± 0.10 vs 0.54 ± 0.21; P < .05; n = 6). CONCLUSIONS: This study suggests that sustained release of miR-126-loaded PLGA NPs might be an effective method in therapeutic angiogenesis for hindlimb ischemia.


Assuntos
Isquemia/terapia , MicroRNAs/administração & dosagem , Músculo Esquelético/irrigação sanguínea , Nanopartículas , Neovascularização Fisiológica , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Actinas/metabolismo , Proteínas Adaptadoras de Transdução de Sinal , Animais , Velocidade do Fluxo Sanguíneo , Modelos Animais de Doenças , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Membro Posterior , Injeções Intramusculares , Isquemia/genética , Isquemia/metabolismo , Isquemia/fisiopatologia , Masculino , Camundongos Endogâmicos C57BL , MicroRNAs/genética , MicroRNAs/metabolismo , Fosforilação , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Fluxo Sanguíneo Regional , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Transdução de Sinais , Fatores de Tempo
15.
Sci Rep ; 7(1): 14723, 2017 11 07.
Artigo em Inglês | MEDLINE | ID: mdl-29116212

RESUMO

Whether patients with severe aortic stenosis (AS) die because of AS-related causes is an important issue for the management of these patients. We used data from CURRENT AS registry, a Japanese multicenter registry, to assess the causes of death in severe AS patients and to identify the factors associated with non-cardiac mortality. We enrolled 3815 consecutive patients with a median follow-up of 1176 days; the 1449 overall deaths comprised 802 (55.3%) from cardiac and 647 (44.7%) from non-cardiac causes. Heart failure (HF) (25.7%) and sudden death (13.0%) caused the most cardiac deaths, whereas infection (13.0%) and malignancy (11.1%) were the main non-cardiac causes. According to treatment strategies, infection was the most common cause of non-cardiac death, followed by malignancy, in both the initial aortic valve replacement (AVR) cohort (N = 1197), and the conservative management cohort (N = 2618). Both non-cardiac factors (age, male, body mass index <22, diabetes, prior history of stroke, dialysis, anemia, and malignancy) and cardiac factors (atrial fibrillation, ejection fraction <68%, and the initial AVR strategy) were associated with non-cardiac death. These findings highlight the importance of close monitoring of non-cardiac comorbidities, as well as HF and sudden death, to improve the mortality rate of severe AS patients.


Assuntos
Estenose da Valva Aórtica/mortalidade , Causas de Morte , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Japão , Masculino , Sistema de Registros
16.
Nat Commun ; 8(1): 1078, 2017 10 20.
Artigo em Inglês | MEDLINE | ID: mdl-29057872

RESUMO

Torsade de Pointes (TdP) is a lethal arrhythmia that is often drug-induced, thus there is an urgent need for development of models to test or predict the drug sensitivity of human cardiac tissue. Here, we present an in vitro TdP model using 3D cardiac tissue sheets (CTSs) that contain a mixture of human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes and non-myocytes. We simultaneously monitor the extracellular field potential (EFP) and the contractile movement of the CTSs. Upon treatment with IKr channel blockers, CTSs exhibit tachyarrhythmias with characteristics of TdP, including both a typical polymorphic EFP and meandering spiral wave re-entry. The TdP-like waveform is predominantly observed in CTSs with the cell mixture, indicating that cellular heterogeneity and the multi-layered 3D structure are both essential factors for reproducing TdP-like arrhythmias in vitro. This 3D model could provide the mechanistic detail underlying TdP generation and means for drug discovery and safety tests.


Assuntos
Arritmias Cardíacas/fisiopatologia , Células-Tronco Pluripotentes Induzidas/citologia , Torsades de Pointes/fisiopatologia , Células Cultivadas , Humanos , Miócitos Cardíacos/citologia , Miócitos Cardíacos/metabolismo , Taquicardia/fisiopatologia
17.
Heart ; 103(24): 1992-1999, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28684442

RESUMO

OBJECTIVE: To elucidate the factors associated with high left ventricular mass index (LVMI) and to test the hypothesis that high LVMI is associated with worse outcome in severe aortic stenosis (AS). METHODS: We analysed 3282 patients with LVMI data in a retrospective multicentre registry enrolling consecutive patients with severe AS in Japan. The management strategy, conservative or initial aortic valve replacement (AVR), was decided by the attending physician. High LVMI was defined as LVMI >115 g/m2 for males and >95 g/m2 for females. We compared the risk between normal and high LVMI in the primary outcome measures compromising aortic valve-related death and heart failure hospitalisation. RESULTS: Age was mean 77 (SD 9.6) years and peak aortic jet velocity (Vmax) was 4.1 (0.9) m/s. The factors associated with high LVMI (n=2374) included female, body mass index ≥22, absence of dyslipidemia, left ventricular ejection fraction <50%, Vmax ≥4 m/s, regurgitant valvular disease, hypertension, anaemia and end-stage renal disease. In the conservative management cohort (normal LVMI: n=691, high LVMI: n=1480), the excess adjusted 5-year risk of high LVMI was significant (HR: 1.53, 95% CI 1.26 to 1.85, p<0.001). In the initial AVR cohort (normal LVMI: n=217, high LVMI: n=894), the risk did not differ significantly between the two groups (HR: 0.96, 95% CI 0.60 to 1.55, p=0.88). There was a significant interaction between the initial treatment strategy and the risk of high LVMI (p=0.016). CONCLUSIONS: The deleterious impact of high LVMI on outcome was observed in patients managed conservatively, but not observed in patients managed with initial AVR. TRIAL REGISTRATION NUMBER: UMIN000012140; Post-results.


Assuntos
Estenose da Valva Aórtica/terapia , Implante de Prótese de Valva Cardíaca , Função Ventricular Esquerda , Remodelação Ventricular , Idoso , Idoso de 80 Anos ou mais , Estenose da Valva Aórtica/complicações , Estenose da Valva Aórtica/mortalidade , Estenose da Valva Aórtica/fisiopatologia , Distribuição de Qui-Quadrado , Bases de Dados Factuais , Feminino , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/radioterapia , Implante de Prótese de Valva Cardíaca/efeitos adversos , Implante de Prótese de Valva Cardíaca/mortalidade , Humanos , Japão , Masculino , Análise Multivariada , Razão de Chances , Readmissão do Paciente , Modelos de Riscos Proporcionais , Sistema de Registros , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Volume Sistólico , Fatores de Tempo , Resultado do Tratamento
18.
J Thorac Cardiovasc Surg ; 154(6): 1973-1983.e1, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28645823

RESUMO

BACKGROUND: Cardiopulmonary bypass (CPB) may induce systemic inflammatory responses causing acute lung injury. Recombinant human soluble thrombomodulin (rTM) is reported to attenuate the secretion of inflammatory cytokines and the high-mobility group box 1 (HMGB1) protein, which is critical in controlling systemic inflammation and apoptosis. We investigated the protective effects of rTM on CPB-induced lung injury in a rat model. METHODS: Eighteen male Sprague-Dawley rats were divided into 3 groups: sham, control (CPB alone), and rTM (CPB + rTM). CPB was conducted in the control group and the rTM group. A bolus of rTM (3 mg/kg) was administered to the rTM group rats before CPB establishment. RESULTS: The ratio of partial pressure of arterial oxygen to the fraction of inspired oxygen only dropped markedly from before CPB in the control group (P < .001). Serum tumor necrosis factor α, interleukin (IL) 6, and HMGB1 levels were significantly higher in the control group after CPB. Pathologic study revealed significantly more severe congestion, alveolar hemorrhage, neutrophil accumulation, and edema, and the number of lung cells expressing HMGB1 increased in the control group. The mRNA expression levels of tumor necrosis factor α, IL-6, IL-1ß, and HMGB1 in the control group were significantly higher than those in other groups. According to Western blot analysis, nuclear factor-κB p65 in lung tissue was significantly downregulated in the rTM group. The number of apoptotic cells and the protein of cleaved Caspase-3 were reduced in the rTM group. CONCLUSIONS: These results suggest that rTM prevents acute lung injury through attenuating inflammation and apoptosis during and after CPB in a rat model.


Assuntos
Lesão Pulmonar Aguda/prevenção & controle , Anti-Inflamatórios/farmacologia , Apoptose/efeitos dos fármacos , Ponte Cardiopulmonar/efeitos adversos , Pulmão/efeitos dos fármacos , Trombomodulina , Lesão Pulmonar Aguda/etiologia , Lesão Pulmonar Aguda/metabolismo , Lesão Pulmonar Aguda/patologia , Animais , Caspase 3/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Proteína HMGB1/metabolismo , Humanos , Mediadores da Inflamação/metabolismo , Pulmão/metabolismo , Pulmão/patologia , Masculino , Ratos Sprague-Dawley , Proteínas Recombinantes/farmacologia , Solubilidade , Fator de Transcrição RelA/metabolismo
19.
Interact Cardiovasc Thorac Surg ; 25(6): 912-917, 2017 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-28641394

RESUMO

OBJECTIVES: We reviewed reoperations following mitral valve repair (MVR) that used glutaraldehyde-treated autologous pericardium for mitral regurgitation (MR) to analyse the durability and risk factors for reoperation. METHODS: We retrospectively analysed 144 patients (mean age 57.9 years) who underwent MVR using glutaraldehyde-treated pericardium from March 1992 to December 2011. A total of 19 reoperations were necessary during the follow-up period (mean 6.9 years). The follow-up rate was 97.8%. RESULTS: At initial MVR, there were no differences in mitral leaflet augmentation applied to the anterior or posterior leaflets (P = 0.75 and P = 0.40) in both groups. Reoperations were required in 19 patients, and the mean interval between initial and redo operations was 6.7 years. Indications for reoperation included recurrent MR (n = 8), progressive mitral stenosis (n = 8) and recurrent infective endocarditis (n = 3). The rates of freedom from reoperation at 5, 10 and 15 years were 95.2 ± 1.9%, 83.5 ± 4.8% and 66.9 ± 8.5%, respectively. Four patients underwent redo MVR for recurrent MR, and the remaining 15 patients underwent mitral valve replacement. The freedom from reoperation rate in the group who underwent leaflet augmentation was statistically lower than that in the non-augmentation group (96.9 ± 2.2% vs 93.4 ± 3.2% at 5 years and 89.7 ± 4.5% vs 68.8 ± 13.7% at 10 years; log-rank, P = 0.008). Predictors of reoperation were absence of leaflet augmentation (P = 0.086, hazard ratio = 0.194) and persistent MR (P = 0.003, hazard ratio = 5.759). CONCLUSIONS: We must regularly pay careful attention to implanted pericardium, especially when augmented, as it constitutes a risk factor for reoperations. In addition, secure MVR is mandatory to control persistent MR.


Assuntos
Procedimentos Cirúrgicos Cardíacos/métodos , Previsões , Glutaral/farmacologia , Insuficiência da Valva Mitral/cirurgia , Valva Mitral/cirurgia , Pericárdio/transplante , Reoperação/estatística & dados numéricos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Ecocardiografia , Feminino , Fixadores/farmacologia , Seguimentos , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Insuficiência da Valva Mitral/diagnóstico , Insuficiência da Valva Mitral/mortalidade , Pericárdio/efeitos dos fármacos , Recidiva , Reoperação/normas , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida/tendências , Transplante Autólogo , Resultado do Tratamento , Adulto Jovem
20.
Interact Cardiovasc Thorac Surg ; 25(2): 246-253, 2017 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-28486683

RESUMO

OBJECTIVES: Although conventional open repair is our preference for patients with aortic arch aneurysms, we have often chosen thoracic endovascular aneurysm repair (TEVAR) with a handmade branched stent graft (bTEVAR) in high-risk patients. The aim of this study was to compare the midterm clinical outcomes of our bTEVAR technique to those of the open repair. METHODS: Between January 2007 and December 2014, we treated 129 patients with aortic arch aneurysm by means of either conventional open repair (OPEN, n = 61) or bTEVAR (n = 68) at our institution. RESULTS: The mean ages were 70.5 ± 12.7 years in the OPEN group and 72.7 ± 12.5 years in the bTEVAR group (P = 0.32). The aetiologies included true aneurysm in 101 patients (78.3%) and chronic dissection in 26 (20.1%). There were 2 (3.3%) in-hospital deaths in the OPEN group and 3 (4.4%) in the bTEVAR group. The mean follow-up duration was 3.0 ± 2.1 years (2.4 ± 1.9 years in the OPEN group and 3.6 ± 2.3 years in the bTEVAR group). There was no difference in 5-year aneurysm-related mortality between groups (10.7% in OPEN vs 12.8% in bTEVAR, P = 0.50). In terms of late additional procedures, however, none were required in the OPEN group, whereas 10 (15.4%) additional endovascular repairs and 4 (6.2%) open repairs were required in the bTEVAR group. CONCLUSIONS: Our bTEVAR could be performed with low early mortality, and it yielded similar midterm aneurysm-related mortality to that of conventional open repair. However, these patients undergoing this technique required more late additional procedures than those undergoing conventional open repair.


Assuntos
Aorta Torácica/cirurgia , Aneurisma da Aorta Torácica/cirurgia , Dissecção Aórtica/cirurgia , Implante de Prótese Vascular/métodos , Procedimentos Endovasculares/métodos , Stents , Idoso , Idoso de 80 Anos ou mais , Dissecção Aórtica/diagnóstico , Aorta Torácica/diagnóstico por imagem , Aneurisma da Aorta Torácica/diagnóstico , Aortografia , Prótese Vascular , Angiografia por Tomografia Computadorizada , Feminino , Seguimentos , Humanos , Imageamento Tridimensional , Masculino , Pessoa de Meia-Idade , Desenho de Prótese , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento
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