RESUMO
BACKGROUND: Mitochondrial DNA (mtDNA)-induced myocardial inflammation is intimately involved in cardiac remodeling. ZBP1 (Z-DNA binding protein 1) is a pattern recognition receptor positively regulating inflammation in response to mtDNA in inflammatory cells, fibroblasts, and endothelial cells. However, the role of ZBP1 in myocardial inflammation and cardiac remodeling remains unclear. The aim of this study was to elucidate the role of ZBP1 in mtDNA-induced inflammation in cardiomyocytes and failing hearts. METHODS: mtDNA was administrated into isolated cardiomyocytes. Myocardial infarctionwas conducted in wild type and ZBP1 knockout mice. RESULTS: We here found that, unlike in macrophages, ZBP1 knockdown unexpectedly exacerbated mtDNA-induced inflammation such as increases in IL (interleukin)-1ß and IL-6, accompanied by increases in RIPK3 (receptor interacting protein kinase 3), phosphorylated NF-κB (nuclear factor-κB), and NLRP3 (nucleotide-binding domain and leucine-rich-repeat family pyrin domain containing 3) in cardiomyocytes. RIPK3 knockdown canceled further increases in phosphorylated NF-κB, NLRP3, IL-1ß, and IL-6 by ZBP1 knockdown in cardiomyocytes in response to mtDNA. Furthermore, NF-κB knockdown suppressed such increases in NLRP3, IL-1ß, and IL-6 by ZBP1 knockdown in response to mtDNA. CpG-oligodeoxynucleotide, a Toll-like receptor 9 stimulator, increased RIPK3, IL-1ß, and IL-6 and ZBP1 knockdown exacerbated them. Dloop, a component of mtDNA, but not Tert and B2m, components of nuclear DNA, was increased in cytosolic fraction from noninfarcted region of mouse hearts after myocardial infarction compared with control hearts. Consistent with this change, ZBP1, RIPK3, phosphorylated NF-κB, NLRP3, IL-1ß, and IL-6 were increased in failing hearts. ZBP1 knockout mice exacerbated left ventricular dilatation and dysfunction after myocardial infarction, accompanied by further increases in RIPK3, phosphorylated NF-κB, NLRP3, IL-1ß, and IL-6. In histological analysis, ZBP1 knockout increased interstitial fibrosis and myocardial apoptosis in failing hearts. CONCLUSIONS: Our study reveals unexpected protective roles of ZBP1 against cardiac remodeling as an endogenous suppressor of mtDNA-induced myocardial inflammation.
Assuntos
Infarto do Miocárdio , NF-kappa B , Camundongos , Animais , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Inflamassomos/metabolismo , DNA Mitocondrial/genética , Interleucina-6/metabolismo , Remodelação Ventricular , Células Endoteliais/metabolismo , Infarto do Miocárdio/genética , Infarto do Miocárdio/prevenção & controle , Infarto do Miocárdio/patologia , Inflamação/metabolismo , Camundongos Knockout , Interleucina-1beta/metabolismo , Proteínas de Ligação a RNARESUMO
The 87thAnnual Meeting of the Japanese Circulation Society (JCS2023) was held in March 2023 in Fukuoka, Japan, marking the first in-person gathering after the COVID-19 pandemic. With the theme of "New Challenge With Next Generation" the conference emphasized the development of future cardiovascular leaders and technologies such as artificial intelligence (AI). Notable sessions included the Mikamo Lecture on heart failure and the Mashimo Lecture on AI in medicine. Various hands-on sessions and participatory events were well received, promoting learning and networking. Post-event surveys showed high satisfaction among participants, with positive feedback on face-to-face interactions and the overall experience. JCS2023, attended by 17,852 participants, concluded successfully, marking a significant milestone in post-pandemic meetings, and advancing cardiovascular medicine.
Assuntos
Cardiologia , Sistema Cardiovascular , Humanos , Japão , Inteligência Artificial , PandemiasRESUMO
Although anemia is a common comorbidity that often coexists with heart failure (HF), its clinical impact in patients with advanced HF remains unclear. We investigated the impact of hemoglobin levels on clinical outcomes in patients with advanced HF listed for heart transplantation without intravenous inotropes or mechanical circulatory support.We retrospectively reviewed the clinical data of patients listed for heart transplantation at our institute who did not receive intravenous inotropes or mechanical circulatory support between 2011 and 2022. We divided the patients into those with hemoglobin levels lower or higher than the median value and compared the composite of all-cause death and HF hospitalization within 1 year from the listing date.We enrolled consecutive 38 HF patients (27 males, 49.1 ± 10.8 years old). The median hemoglobin value at the time of listing for heart transplantation was 12.9 g/dL, and 66.7% of the patients had iron deficiency. None of the patients in either group died within 1 year. The HF hospitalization-free survival rate was significantly lower in the lower hemoglobin group (40.9% versus 81.9% at 1 year, P = 0.020). Multivariate Cox proportional hazards model analysis showed that hemoglobin as a continuous variable was an independent predictor for HF hospitalization (odds ratio 0.70, 95% confidence interval 0.49-0.97, P = 0.030).Hemoglobin level at the time of listing for heart transplantation was a predictor of hospitalization in heart-transplant candidates without intravenous inotropes or mechanical circulatory support.
Assuntos
Insuficiência Cardíaca , Transplante de Coração , Hemoglobinas , Hospitalização , Humanos , Masculino , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/terapia , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/mortalidade , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Hospitalização/estatística & dados numéricos , Hemoglobinas/metabolismo , Hemoglobinas/análise , Adulto , Listas de Espera/mortalidadeRESUMO
BACKGROUND: Japan became the world's first country to cover Helicobacter pylori eradication for chronic gastritis under its National Health Insurance (NHI) system in February 2013. Thereafter, H. pylori eradication dramatically increased and gastric cancer deaths began to decrease in Japan. However, the details of gastric cancer deaths and its prevention in the very elderly have not been fully elucidated. METHODS: We analyzed the temporal trend of gastric cancer deaths referencing data from Ministry of Health, Labour and Welfare reports and "Cancer Statistics in Japan-2021" and assessed the numbers of H. pylori test and gastric cancer screening using a national database and a report of cancer screening in Shimane Prefecture, respectively. RESULTS: Although gastric cancer deaths in total population have clearly decreased since 2013, those in people aged 80 years and older are still increasing. People aged 80 years and older represent 9% of the total population and accounted for half of all gastric cancer deaths in 2020. The numbers of H. pylori eradication and gastric cancer screening in people aged 80 years and older were 25% and 25% of those in other generations, respectively. CONCLUSION: In spite of a dramatic increase in H. pylori eradication and a clear decrease in gastric cancer deaths in Japan, gastric cancer deaths in people aged 80 years and older are increasing. This might be due to fewer H. pylori eradication in the elderly than in other generations, indicating the difficulty of gastric cancer prevention in the very elderly.
Assuntos
Infecções por Helicobacter , Helicobacter pylori , Neoplasias Gástricas , Idoso , Humanos , Adulto , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/prevenção & controle , Neoplasias Gástricas/diagnóstico , Infecções por Helicobacter/complicações , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/epidemiologia , Japão/epidemiologia , Detecção Precoce de Câncer , Antibacterianos/uso terapêuticoRESUMO
BACKGROUND: The present study aimed to clarify the regional variations in clinical practice and the prognosis of patients with heart failure with reduced ejection fraction (HFrEF) in Japan using the Japanese Registry of Acute Decompensated Heart Failure (JROADHF).MethodsâandâResults: We recruited data of hospitalized patients with HFrEF (n=4,329) from the JROADHF. The patients were divided into 6 groups based on the region of Japan where they were hospitalized: Hokkaido-Tohoku (n=504), Kanto (n=958), Chubu (n=779), Kinki (n=902), Chugoku-Shikoku (n=446), and Kyushu (n=740). We compared the patients' characteristics, including etiology of HF and prognosis after discharge. The age of the patients was lowest in the Kanto and Kinki regions. In contrast, there were no differences in the prevalence of comorbidities, levels of B-type natriuretic peptide, or left ventricular EF among the 6 groups. Post-discharge cardiospecific prognosis, specifically, the composite of cardiac death or HF hospitalization, cardiac death, and HF hospitalization, was comparable among the 6 regions. CONCLUSIONS: There were no differences in cardiospecific prognosis in patients with HFrEF among the 6 regions in Japan.
Assuntos
Insuficiência Cardíaca , Disfunção Ventricular Esquerda , Humanos , Assistência ao Convalescente , Morte , População do Leste Asiático , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/terapia , Hospitalização , Japão/epidemiologia , Alta do Paciente , Prognóstico , Sistema de Registros , Volume Sistólico , Função Ventricular EsquerdaRESUMO
BACKGROUND: Little is known about nationwide temporal trends in the clinical characteristics and treatment of dilated cardiomyopathy (DCM) in Japan.MethodsâandâResults: We collected data regarding demographics, echocardiography, and treatment of DCM between 2003 to 2013 from Clinical Personal Records, a national registry organized by the Japanese Ministry of Health, Labour, and Welfare. Among the 40,794 DCM patients screened, 27,702 with left ventricular ejection fraction (LVEF) <50% and age ≥18 years were enrolled in this study and divided into 3 groups according to registration year: Group 1, 2003-2005 (10,006 patients); Group 2, 2006-2010 (11,252 patients); and Group 3, 2011-2013 (6,444 patients). Over time, there were decreases in age at registration (mean [±SD] 58.6±13.0 vs. 56.8±13.8 vs. 56.2±13.8 years; P<0.001) and LVEF (33.5±10.0% vs. 31.1±9.9% vs. 29.2± 9.7%; P<0.001), and an increase in patients with New York Heart Association Class III-IV (28.2% vs. 35.2% vs. 41.0%; P<0.001). The use of ß-blockers (59.1% vs. 79.3% vs. 87.8%; P<0.001) and mineralocorticoid receptor antagonists (30.6% vs. 35.8% vs. 39.7%; P<0.001) increased over time. In multivariate analysis, male sex, systolic blood pressure, chronic kidney disease, hemoglobin, and registration year were positively associated, whereas age and LVEF were negatively associated, with ß-blocker prescription. CONCLUSIONS: Although the clinical characteristics of DCM changed, the implementation of optimal medical therapy for DCM increased from 2003 to 2013 in Japan.
Assuntos
Cardiomiopatia Dilatada , Humanos , Masculino , Adolescente , Cardiomiopatia Dilatada/diagnóstico por imagem , Cardiomiopatia Dilatada/tratamento farmacológico , Cardiomiopatia Dilatada/complicações , Volume Sistólico , Função Ventricular Esquerda , Japão/epidemiologia , Antagonistas Adrenérgicos beta/uso terapêuticoRESUMO
ABSTRACT: Doxorubicin (DOX) is an effective anti-cancer agent for various malignancies. Nevertheless, it has a side effect of cardiotoxicity, referred to as doxorubicin-induced cardiomyopathy (DIC), that is associated with a poorer prognosis. This cardiotoxicity limits the clinical use of DOX as a therapeutic agent for malignancies. Recently, ferroptosis, a form of regulated cell death induced by the accumulation of lipid peroxides, has been recognized as a major pathophysiology of DIC. Ethoxyquin is a lipophilic antioxidant widely used for food preservation and thus may be a potential therapeutic drug for preventing DIC. However, the efficacy of ethoxyquin against ferroptosis and DIC remains to be fully elucidated. Here, we investigated the inhibitory action of ethoxyquin against GPx4-deficient ferroptosis and its therapeutic efficacy against DOX-induced cell death in cultured cardiomyocytes and cardiotoxicity in a murine model of DIC. In cultured cardiomyocytes, ethoxyquin treatment effectively prevented GPx4-deficient ferroptosis. Ethoxyquin also prevented DOX-induced cell death, accompanied by the suppression of malondialdehyde (MDA) and mitochondrial lipid peroxides, which were induced by DOX. Furthermore, ethoxyquin significantly prevented DOX-induced cell death without any suppression of caspase cleavages representing apoptosis. In DIC mice, ethoxyquin treatment ameliorated cardiac impairments, such as contractile dysfunction and myocardial atrophy, and lung congestion. Ethoxyquin also suppressed serum lactate dehydrogenase and creatine kinase activities, decreased the levels of lipid peroxides such as MDA and acrolein, inhibited cardiac fibrosis, and reduced TUNEL-positive cells in the hearts of DIC mice. Collectively, ethoxyquin is a competent antioxidant for preventing ferroptosis in DIC and can be its prospective therapeutic drug.
Assuntos
Cardiomiopatias , Ferroptose , Camundongos , Animais , Cardiotoxicidade/prevenção & controle , Antioxidantes/uso terapêutico , Etoxiquina/metabolismo , Etoxiquina/farmacologia , Etoxiquina/uso terapêutico , Peróxidos Lipídicos/metabolismo , Peróxidos Lipídicos/farmacologia , Estresse Oxidativo , Doxorrubicina/toxicidade , Miócitos Cardíacos , Apoptose , Cardiomiopatias/induzido quimicamente , Cardiomiopatias/prevenção & controle , Cardiomiopatias/metabolismoRESUMO
PURPOSE: Cardiac rupture is a fatal complication following myocardial infarction (MI). An increase in heart rate (HR) is reportedly an independent risk factor for cardiac rupture during acute MI. However, the role of HR reduction in cardiac rupture after MI remains to be fully elucidated. We aimed to evaluate the therapeutic efficacy of HR reduction with ivabradine (IVA) on post-MI cardiac rupture in mice. METHODS: We induced MI in mice by ligating the left anterior descending coronary artery. Subsequently, we subcutaneously implanted osmotic pumps filled with IVA solution or vehicle (Veh) in the surviving MI mice at 24 h postoperatively. We biochemically analyzed the myocardium on day 5, additionally observed the mice for 10 days, and analyzed the rates of cardiac rupture and non-cardiac rupture death, and survival after MI. RESULTS: HR was significantly lower in the IVA-treated mice, whereas blood pressure was comparable between the two groups. Compared to the Veh-treated mice, apoptosis was significantly reduced in the MI border zone in the IVA-treated mice. Although there were no differences in the infarct size of the surviving MI mice between the two groups, HR reduction with IVA significantly reduced cardiac rupture (rupture rate 26 and 8% in the Veh-treated and IVA-treated groups, respectively) and improved survival after MI. CONCLUSION: Our findings suggest that HR reduction with IVA prevents cardiac rupture after MI. This may be particularly effective in MI patients with a high HR who are either unable to adequately tolerate ß-blockers or whose HR remains high despite receiving ß-blockers.
Assuntos
Ruptura Cardíaca , Infarto do Miocárdio , Animais , Frequência Cardíaca , Ruptura Cardíaca/complicações , Ruptura Cardíaca/tratamento farmacológico , Humanos , Ivabradina/farmacologia , Ivabradina/uso terapêutico , Camundongos , Camundongos Endogâmicos C57BL , Infarto do Miocárdio/tratamento farmacológico , Miocárdio , Remodelação VentricularRESUMO
BACKGROUND: With aging population, the prevalence and incidence of heart failure (HF) have been increasing worldwide. However, the characteristics and outcomes of patients with HF in an era of aging are not well established in Japan.MethodsâandâResults:The Japanese Registry Of Acute Decompensated Heart Failure (JROADHF), a retrospective, multicenter, nationwide registry, was designed to study the clinical characteristics and outcomes of patients hospitalized with HF throughout Japan in 2013. One hundred and twenty-eight hospitals were selected by cluster random sampling and 13,238 hospitalized patients with HF were identified by medical record review. Demographics, medical history, severity, treatment, and in-hospital and long-term outcome data were collected from the Diagnostic Procedure Combination and medical charts. Data were analyzed using univariate and multivariate logistic regression or Cox regression analysis. The mean age of registered patients was 78.0±12.5 years and 52.8% were male. Elderly patients (age >75 years) accounted for 68.9%, and HF with preserved ejection fraction (HFpEF) accounted for 45.1%. Median length of hospital stay was 18 days and in-hospital mortality was 7.7%. The median follow-up period was 4.3 years, and the incidence rates for cardiovascular death and rehospitalization for HF were 7.1 and 21.1 per 100 person-years, respectively. CONCLUSIONS: A contemporary nationwide registry demonstrated that hospitalized HF patients were very elderly, HFpEF was common, and their prognosis was still poor in Japan.
Assuntos
Insuficiência Cardíaca , Idoso , Idoso de 80 Anos ou mais , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/terapia , Humanos , Japão/epidemiologia , Masculino , Sistema de Registros , Estudos Retrospectivos , Volume SistólicoRESUMO
BACKGROUND: The usefulness of electrocardiographic (ECG) voltage criteria for diagnosing hypertrophic cardiomyopathy (HCM) in pediatric patients is poorly defined.MethodsâandâResults:ECGs at the 1st grade (mean [±SD] age 6.6±0.3 years) were available for 11 patients diagnosed with HCM at around the 7th grade (13.2±0.3 years). ECGs were available for another 64 patients diagnosed with HCM in the 1st (n=15), 7th (n=32), and 10th (n=17) grades. Fifty-one voltage criteria were developed by grade and sex using 62,841 ECGs from the general population. Voltage criteria were set at the 99.95th percentile (1/2,000) point based on the estimated prevalence of childhood HCM (2.9 per 100,000 [1/34,483]) to decrease false negatives. Conventional criteria were from guidelines for school-aged children in Japan. Of 11 patients before diagnosis, 2 satisfied conventional criteria in 1st grade; 5 (56%) of the remaining 9 patients fulfilled 2 voltage criteria (R wave in limb-lead I [RI]+S wave in lead V3 [SV3] and R wave in lead V3 [RV3]+SV3). Robustness analysis for sensitivity showed RV3+SV3 was superior to RI+SV3. For all patients after diagnosis, RI+SV4 was the main candidate. However, conventional criteria were more useful than voltage criteria. CONCLUSIONS: Early HCM prediction was possible using RV3+SV3 in >50% of patients in 1st grade. Voltage criteria may help diagnose prediagnostic or early HCM, and prevent tragic accidents, although further prospective studies are required.
Assuntos
Cardiomiopatia Hipertrófica , Adolescente , Cardiomiopatia Hipertrófica/diagnóstico , Cardiomiopatia Hipertrófica/epidemiologia , Criança , Eletrocardiografia/métodos , Humanos , Japão , Estudos ProspectivosRESUMO
Angiotensin-converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARB) have been shown to prevent left ventricular remodeling and improve outcomes of patients with heart failure (HF). This study aimed to investigate whether the use of ACEi/ARB could be associated with HF with recovered ejection fraction (HFrecEF) in patients with dilated cardiomyopathy (DCM).We collected individual patient data regarding demographics, echocardiogram, and treatment in DCM between 2003 and 2014 from the clinical personal record, a national database of the Japanese Ministry of Health, Labour and Welfare. Patients with left ventricular ejection fraction (LVEF) < 40% were included. Eligible patients were divided into two groups according to the use of ACEi/ARB. A propensity score matching analysis was employed. The primary outcome was defined as LVEF ≥ 40% at 3 years of follow-up.Out of 5,955 patients with DCM and LVEF < 40%, propensity score matching yielded 830 pairs. The mean age was 58.8 years, and 1,184 (71.3%) of the patients were male. The primary outcome was observed more frequently in the ACEi/ARB group than in the no ACEi/ARB group (57.0% versus 49.3%; odds ratio 1.36; 95% confidence interval (CI) 1.12-1.65; P = 0.002). Subgroup analysis revealed that the use of ACEi and ARB was associated with recovery of LVEF regardless of atrial fibrillation. The change in LVEF from baseline to 3 years of follow-up was greater in the ACEi-ARB group (14.9% ± 0.6% versus 12.3% ± 0.5%; P = 0.001).The use of ACEi/ARB is associated with HFrecEF in patients with DCM and reduced LVEF.
Assuntos
Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Cardiomiopatia Dilatada/tratamento farmacológico , Sistema de Registros , Volume Sistólico/efeitos dos fármacos , Idoso , Antagonistas de Receptores de Angiotensina/farmacologia , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
A 61-year-old woman suffered chest pain and was admitted to a nearby hospital emergency department. She was diagnosed with acute myocardial infarction probably due to thromboembolism in the left anterior descending coronary artery and aspiration thrombectomy was performed. Afterwards, she developed refractory heart failure with severe global left ventricular dysfunction and was transferred to our hospital. An 18F-FDG-PET/CT scan revealed abnormal 18F-FDG uptake in non-infarcted regions of the left ventricle. Non-caseating granulomas were detected by biopsy from a skin eruption. She was diagnosed with cardiac sarcoidosis. In cases of refractory heart failure which cannot be explained only by myocardial infarction, evaluation of other undiagnosed cardiomyopathies is important for optimal management.
Assuntos
Cardiomiopatias/complicações , Trombose Coronária/complicações , Insuficiência Cardíaca/etiologia , Infarto do Miocárdio/etiologia , Sarcoidose/complicações , Cardiomiopatias/diagnóstico , Trombose Coronária/diagnóstico , Diagnóstico Diferencial , Eletrocardiografia , Feminino , Insuficiência Cardíaca/diagnóstico , Humanos , Pessoa de Meia-Idade , Infarto do Miocárdio/diagnóstico , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Sarcoidose/diagnósticoRESUMO
BACKGROUND: Ischemic preconditioning (IPC) is an effective procedure to protect against ischemia/reperfusion (I/R) injury. Hypoxia-inducible factor-1α (Hif-1α) is a key molecule in IPC, and roxadustat (RXD), a first-in-class prolyl hydroxylase domain-containing protein inhibitor, has been recently developed to treat anemia in patients with chronic kidney disease. Thus, we investigated whether RXD pretreatment protects against I/R injury.MethodsâandâResults:RXD pretreatment markedly reduced the infarct size and suppressed plasma creatinine kinase activity in a murine I/R model. Analysis of oxygen metabolism showed that RXD could produce ischemic tolerance by shifting metabolism from aerobic to anaerobic respiration. CONCLUSIONS: RXD pretreatment may be a novel strategy against I/R injury.
Assuntos
Inibidores Enzimáticos/farmacologia , Glicina/análogos & derivados , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Prolina Dioxigenases do Fator Induzível por Hipóxia/antagonistas & inibidores , Isoquinolinas/farmacologia , Infarto do Miocárdio/prevenção & controle , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Miócitos Cardíacos/efeitos dos fármacos , Animais , Respiração Celular/efeitos dos fármacos , Células Cultivadas , Modelos Animais de Doenças , Glicina/farmacologia , Prolina Dioxigenases do Fator Induzível por Hipóxia/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/patologia , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/patologia , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Transdução de SinaisRESUMO
BACKGROUND: An inverse relationship exists between hospital case volume and mortality in patients with heart failure (HF). However, hospital performance factors associated with mortality in HF patients have not been examined. We aimed to identify these using exploratory factor analysis and assess the relationship between these factors and 7-day, 30-day, and in-hospital mortality among HF patients in Japan.MethodsâandâResults:We analyzed the records of 198,861 patients admitted to 683 certified hospitals of the Japanese Circulation Society between 2012 and 2014. Records were obtained from the nationwide database of the Japanese Registry Of All cardiac and vascular Diseases-Diagnostic Procedure Combination (JROAD-DPC). Using exploratory factor analysis, 90 hospital survey items were grouped into 5 factors, according to their collinearity: "Interventional cardiology", "Cardiovascular surgery", "Pediatric cardiology", "Electrophysiology" and "Cardiac rehabilitation". Multivariable logistic regression analysis was performed to determine the association between these factors and mortality. The 30-day mortality was 8.0%. Multivariable logistic regression analysis showed the "Pediatric cardiology" (odds ratio (OR) 0.677, 95% confidence interval [CI]: 0.628-0.729, P<0.0001), "Electrophysiology" (OR 0.876, 95% CI: 0.832-0.923, P<0.0001), and "Cardiac rehabilitation" (OR 0.832, 95% CI: 0.792-0.873, P<0.0001) factors were associated with lower mortality. In contrast, "Interventional cardiology" (OR 1.167, 95% CI: 1.070-1.272, P<0.0001) was associated with higher mortality. CONCLUSIONS: Hospital factors, including various cardiovascular therapeutic practices, may be associated with the early death of HF patients.
Assuntos
Insuficiência Cardíaca/mortalidade , Mortalidade Hospitalar , Hospitalização , Demandas Administrativas em Assistência à Saúde , Idoso , Idoso de 80 Anos ou mais , Análise por Conglomerados , Bases de Dados Factuais , Análise Fatorial , Feminino , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/terapia , Humanos , Japão/epidemiologia , Masculino , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Prognosis after acute decompensated heart failure (ADHF) is poor. An appropriate risk score that would allow for improved care and treatment of ADHF patients after discharge, however, is lacking. MethodsâandâResults: We used 2 HF cohorts, the NARA-HF study and JCARE-CARD, as derivation and validation cohorts, respectively. The primary endpoint was all-cause death during the 2-year follow-up, excluding in-hospital death. Age, hemoglobin (Hb), and brain natriuretic peptide (BNP) at discharge were identified as independent risk factors. We determined 3 categorizations on the basis of these parameters, termed A2B score: age (<65 years, 0; 65-74 years, 1; ≥75 years, 2), anemia (Hb <10 g/dL, 2; 10-11.9 g/dL, 1; ≥12 g/dL, 0) and BNP (<200 pg/mL, 0; 200-499 pg/mL, 1; ≥500 pg/mL, 2). We divided patients into 4 groups according to A2B score (extremely low, 0; low, 1-2; medium, 3-4; high, 5-6). For the extremely low-risk group, the 2-year survival rate was 97.8%, compared with 84.5%, 66.1%, and 45.2% for the low-, medium-, and high-risk groups, respectively. Using the JCARE-CARD as a validation model, for the extremely low-risk group, the 2-year survival was 95.4%, compared with 90.2%, 75.0%, and 55.6% for the low-, medium-, and high-risk groups, respectively. CONCLUSIONS: The user-friendly A2B score is useful for estimating survival rate in ADHF patients at discharge.
Assuntos
Insuficiência Cardíaca , Modelos Cardiovasculares , Sistema de Registros , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Seguimentos , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Medição de Risco , Fatores de Risco , Taxa de SobrevidaRESUMO
A failing heart shows severe energy insufficiency, and it is presumed that this energy shortage plays a critical role in the development of cardiac dysfunction. However, little is known about the mechanisms that cause energy metabolic alterations in the failing heart. Here, we show that the novel RING-finger protein 207 (RNF207), which is specifically expressed in the heart, plays a role in cardiac energy metabolism. Depletion of RNF207 in neonatal rat cardiomyocytes (NRCs) leads to a reduced cellular concentration of adenosine triphosphate (ATP) and mitochondrial dysfunction. Consistent with this result, we observed here that the expression of RNF207 was significantly reduced in mice with common cardiac diseases including heart failure. Intriguingly, proteomic approaches revealed that RNF207 interacts with the voltage-dependent anion channel (VDAC), which is considered to be a key regulator of mitochondria function, as an RNF207-interacting protein. Our findings indicate that RNF207 is involved in ATP production by cardiomyocytes, suggesting that RNF207 plays an important role in the development of heart failure.
Assuntos
Metabolismo Energético , Miócitos Cardíacos/metabolismo , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Sequência de Aminoácidos , Animais , Animais Recém-Nascidos , Linhagem Celular , Expressão Gênica , Humanos , Camundongos , Mitocôndrias Cardíacas/metabolismo , Especificidade de Órgãos/genética , Ligação Proteica , Domínios e Motivos de Interação entre Proteínas , Ratos , Estresse Fisiológico , Ubiquitinação , Canal de Ânion 1 Dependente de Voltagem/química , Canal de Ânion 1 Dependente de Voltagem/metabolismoRESUMO
Modification of histones is one of the important mechanisms of epigenetics, in which genetic control is determined by factors other than an individual's DNA sequence. Sirtuin family proteins, which are class III histone deacetylases, were originally identified as gene silencers that affect the mating type of yeast, leading to the name "silent mating-type information regulation 2" (SIR2). They are characterized by their requirement of nicotinamide adenine dinucleotide for their enzyme activity, unlike other classes of histone deacetylases. Sirtuins have been traditionally linked to longevity and the beneficial effects of calorie restriction and DNA damage repair. Recently, sirtuins have been shown to be involved in a wide range of physiological and pathological processes, including aging, energy responses to low calorie availability, and stress resistance, as well as apoptosis and inflammation. Sirtuins can also regulate mitochondrial biogenesis and circadian clocks. Seven sirtuin family proteins (Sirt1-7) have been identified as mammalian SIR2 orthologs, localized in different subcellular compartments, namely, the cytoplasm (Sirt1, 2), the mitochondria (Sirt3, 4, 5), and the nucleus (Sirt1, 2, 6, 7). Sirt1 is evolutionarily close to yeast SIR2 and has been the most intensively investigated in the cardiovascular system. Endogenous Sirt1 plays a pivotal role in mediating the cell death/survival process and has been implicated in the pathogenesis of cardiovascular disease. Downregulation of Sirt2 is protective against ischemic-reperfusion injury. Increased Sirt3 expression has been shown to correlate with longevity in humans. In addition, Sirt3 protects cardiomyocytes from aging and oxidative stress and suppresses cardiac hypertrophy. Sirt6 has also recently been demonstrated to attenuate cardiac hypertrophy, and Sirt7 is known to regulate apoptosis and stress responses in the heart. On the other hand, the roles of Sirt4 and Sirt5 in the heart remain largely uncharacterized.
Assuntos
Envelhecimento/genética , Senescência Celular/genética , Cardiopatias/genética , Histonas/metabolismo , Miócitos Cardíacos/metabolismo , Sirtuínas/genética , Animais , Apoptose/genética , Autofagia/genética , Cardiomegalia/genética , Cardiomegalia/metabolismo , Doenças Cardiovasculares , Sobrevivência Celular/genética , Metabolismo Energético/genética , Epigênese Genética , Cardiopatias/metabolismo , Insuficiência Cardíaca/genética , Insuficiência Cardíaca/metabolismo , Humanos , Longevidade/genética , Camundongos , Miócitos Cardíacos/citologia , Estresse Oxidativo/genética , Traumatismo por Reperfusão/genética , Traumatismo por Reperfusão/metabolismo , Sirtuínas/metabolismoRESUMO
BACKGROUND: Brain-derived neurotropic factor (BDNF) is involved in cardiovascular diseases as well as skeletal muscle energy metabolism and depression. We investigated whether serum BDNF level was associated with prognosis in patients with heart failure (HF). METHODS AND RESULTS: We measured the serum BDNF level in 58 patients with HF (59.2 ± 13.7 years old, New York Heart Association functional class I-III) at baseline, and adverse events, including all cardiac deaths and HF rehospitalizations, were recorded during the median follow-up of 20.3 months. In a univariate analysis, serum BDNF levels were significantly associated with peak oxygen capacity (ß = 0.547; P = .003), anaerobic threshold (ß = 0.929; P = .004), and log minute ventilation/carbon dioxide production slope (ß = -10.15; P = .005), but not Patient Health Questionnaire scores (ß = -0.099; P = .586). A multivariate analysis demonstrated that serum BDNF level was an independent prognostic factor of adverse events (hazard ratio 0.41, 95% confidence interval 0.20-0.84; P = .003). The receiver operating characteristic curve demonstrated that low levels of BDNF (<17.4 ng/mL) were associated with higher rates of adverse events compared with high levels of BDNF (≥17.4 ng/mL; log rank test: P < .001). CONCLUSIONS: Decreased serum BDNF levels were significantly associated with adverse outcomes in HF patients, suggesting that these levels can be a useful prognostic biomarker.
Assuntos
Fator Neurotrófico Derivado do Encéfalo/sangue , Insuficiência Cardíaca/sangue , Consumo de Oxigênio , Adulto , Idoso , Biomarcadores/sangue , Teste de Esforço , Feminino , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Curva ROC , Estudos Retrospectivos , Taxa de Sobrevida/tendências , Adulto JovemRESUMO
NEW FINDINGS: What is the central question of this study? Our aim was to examine whether sesamin can prevent a decline in exercise capacity in high-fat diet-induced diabetic mice. Our hypothesis was that maintenance of mitochondrial function and attenuation of oxidative stress in the skeletal muscle would contribute to this result. What is the main finding and its importance? The new findings are that sesamin prevents the diabetes-induced decrease in exercise capacity and impairment of mitochondrial function through the inhibition of NAD(P)H oxidase-dependent oxidative stress in the skeletal muscle. Sesamin may be useful as a novel agent for the treatment of diabetes mellitus. ABSTRACT: We previously reported that exercise capacity and skeletal muscle mitochondrial function in diabetic mice were impaired, in association with the activation of NAD(P)H oxidase. It has been reported that sesamin inhibits NAD(P)H oxidase-induced superoxide production. Therefore, we examined whether the antioxidant sesamin could prevent a decline in exercise capacity in mice with high-fat diet (HFD)-induced diabetes. C57BL/6J mice were fed a normal diet (ND) or HFD, then treated or not with sesamin (0.2%) to yield the following four groups: ND, ND+Sesamin, HFD and HFD+Sesamin (n = 10 each). After 8 weeks, body weight, fat weight, blood glucose, insulin, triglyceride, total cholesterol and fatty acid were significantly increased in HFD compared with ND mice. Sesamin prevented the increases in blood insulin and lipid levels in HFD-fed mice, but did not affect the plasma glucose. Exercise capacity determined by treadmill tests was significantly reduced in HFD mice, but almost completely recovered in HFD+Sesamin mice. Citrate synthase activity was significantly decreased in the skeletal muscle of HFD mice, and these decreases were also inhibited by sesamin. Superoxide anion and NAD(P)H oxidase activity were significantly increased in HFD mice compared with the ND mice and were ameliorated by sesamin. Sesamin prevented the decline in exercise capacity in HFD-induced diabetic mice via maintenance of mitochondrial function, fat oxidation and attenuation of oxidative stress in the skeletal muscle. Our data suggest that sesamin may be useful as a novel agent for the treatment of diabetes mellitus.