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1.
Artigo em Inglês | MEDLINE | ID: mdl-39132971

RESUMO

BACKGROUND AND AIMS: Successful left atrial posterior wall isolation (LAPWI) using only the cryoballoon (CB) is technically challenging for the treatment of atrial fibrillation (AF). This study aimed to evaluate the efficacy of the cross-over technique, wherein an overlapped ablation is performed by placing the CB from both directions in contact with the LAPW. METHODS: This was a single-center, retrospective, observational study of 194 consecutive patients with persistent atrial fibrillation (PerAF) who underwent a first-time procedure of pulmonary vein isolation (PVI) + PWI (108 patients) or PVI-only (86 patients) using the CB. The cross-over technique was applied in all LAPWI. RESULTS: For ablation of the LA roof and bottom, respectively, a mean of 8.6 ± 1.0 (right to left [R→L] 4.3 ± 1.1 and left to right [L→R] 4.3 ± 1.1) and 9.1 ± 1.2 (R→L 4.6 ± 1.6 and L→R 4.5 ± 1.2) CB applications were delivered. LAPW was successfully isolated solely using the CB in 99.1% of patients. Although the PVI + PWI group had significantly longer procedure time, no severe adverse events were observed in either group. During a median follow-up of 19 months, freedom from recurrence of all atrial tachyarrhythmias was achieved in 93.5% of the PVI + PWI group and 72.9% of the PVI-only group (p = .011). CONCLUSIONS: LAPWI performed solely with the CB using the cross-over technique is feasibly, safe, and was independently associated with a significantly higher freedom from recurrence of atrial tachyarrhythmias compared with PVI alone in patients with PerAF.

2.
JAMA Netw Open ; 7(8): e2428032, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39145976

RESUMO

Importance: The characteristics and treatment strategies of atrial functional mitral regurgitation (AFMR) are poorly understood. Objective: To investigate the prevalence, clinical characteristics, and outcomes of mitral valve (MV) surgery in AFMR. Design, Setting, and Participants: This retrospective cohort study, called the Real-World Observational Study for Investigating the Prevalence and Therapeutic Options for Atrial Functional Mitral Regurgitation (REVEAL-AFMR), was conducted across 26 Japanese centers (17 university hospitals, 1 national center, 3 public hospitals, and 5 private hospitals). All transthoracic echocardiography procedures performed from January 1 to December 31, 2019, were reviewed to enroll adult patients (aged ≥20 years) with moderate or severe AFMR, defined by preserved left ventricular function, a dilated left atrium, and an absence of degenerative valvular changes. Data were analyzed from May 8, 2023, to May 16, 2024. Exposures: Mitral valve surgery, with or without tricuspid valve intervention. Main Outcomes and Measures: The primary composite outcome included heart failure hospitalization and all-cause mortality. Results: In 177 235 patients who underwent echocardiography, 8867 had moderate or severe MR. Within this group, 1007 (11.4%) were diagnosed with AFMR (mean [SD] age, 77.8 [9.5] years; 55.7% female), of whom 807 (80.1%) had atrial fibrillation. Of these patients, 113 underwent MV surgery, with 92 (81.4%) receiving concurrent tricuspid valve surgery. Patients who underwent surgery were younger but had more severe MR (57.5% [n = 65] vs 9.4% [n = 84]; P < .001), a larger mean (SD) left atrial volume index (152.5 [97.8] mL/m2 vs 87.7 [53.1] mL/m2; P < .001), and a higher prevalence of heart failure (according to the New York Heart Association class III [marked limitation of physical activity] or class IV [symptoms of heart failure at rest], 26.5% [n = 30] vs 9.3% [n = 83]; P < .001) than those who remained under medical therapy. During a median follow-up of 1050 days (IQR, 741-1188 days), 286 patients (28.4%) experienced the primary outcome. Despite a more severe disease status, only the surgical group showed a decrease in natriuretic peptide levels at follow-up and had a significantly lower rate of the primary outcome (3-year event rates were 18.3% vs 33.3%; log-rank, P = .03). Statistical adjustments did not alter these findings. Conclusions and Relevance: The findings of this cohort study suggest that in patients with AFMR, who were typically older and predominantly had atrial fibrillation, MV surgery was associated with lower rates of adverse clinical outcomes. Future studies are warranted to investigate a possible causal relationship to better regulate cardiovascular medicine.


Assuntos
Insuficiência da Valva Mitral , Valva Mitral , Sistema de Registros , Humanos , Insuficiência da Valva Mitral/cirurgia , Insuficiência da Valva Mitral/fisiopatologia , Feminino , Masculino , Idoso , Estudos Retrospectivos , Valva Mitral/cirurgia , Valva Mitral/diagnóstico por imagem , Idoso de 80 Anos ou mais , Resultado do Tratamento , Pessoa de Meia-Idade , Japão/epidemiologia , Ecocardiografia , Átrios do Coração/fisiopatologia , Átrios do Coração/diagnóstico por imagem
3.
Heart Vessels ; 2024 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-39107635

RESUMO

BACKGROUND: Bleeding events are one of the major concerns in patients using oral anticoagulants (OACs). We aimed to evaluate the association between major bleeding and long-term clinical outcomes in atrial fibrillation (AF) patients taking OACs. METHODS: We analyzed a database comprising two large-scale prospective registries of patients with documented AF: the RAFFINE and SAKURA registries. The primary outcome was major adverse cardiac and cerebrovascular events (MACCE), defined as the composite of all-cause death, ischemic stroke, and myocardial infarction. Major bleeding was defined in accordance with the criteria of the International Society on Thrombosis and Hemostasis. Cox multivariate analysis was used to determine the impact of major bleeding on the incidence of MACCE. RESULTS: The median follow-up period was 39.7 (interquartile range, 33.1-48.1) months. Among 6,633 patients with AF who were taking OAC, 298 (4.5%) had major bleeding and 737 (11.1%) had MACCE. The incidence of MACCE was higher in patients with bleeding than in those without (18.33 and 3.22, respectively, per 100 patient-years; log-rank p < 0.0001). Multivariate logistic regression analysis revealed older age, vitamin K antagonist use, and antiplatelet drug use as independent predictors of major bleeding. Median duration of MACCE occurrence after major bleeding was 41 (interquartile range, 3-300) days. Multivariate Cox hazard regression analysis showed that the risk of MACCE was significantly higher in patients with major bleeding compared to those without (hazard risk, 4.64; 95% confidence interval, 3.62-5.94; p < 0.0001). CONCLUSIONS: Major bleeding was associated with long-term adverse cardiovascular events among AF patients taking OAC. Therefore, reducing the risk of bleeding is important for improving clinical outcomes in patients with AF.

4.
Cell ; 187(16): 4150-4175, 2024 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-39121846

RESUMO

Cellular senescence is a cell fate triggered in response to stress and is characterized by stable cell-cycle arrest and a hypersecretory state. It has diverse biological roles, ranging from tissue repair to chronic disease. The development of new tools to study senescence in vivo has paved the way for uncovering its physiological and pathological roles and testing senescent cells as a therapeutic target. However, the lack of specific and broadly applicable markers makes it difficult to identify and characterize senescent cells in tissues and living organisms. To address this, we provide practical guidelines called "minimum information for cellular senescence experimentation in vivo" (MICSE). It presents an overview of senescence markers in rodent tissues, transgenic models, non-mammalian systems, human tissues, and tumors and their use in the identification and specification of senescent cells. These guidelines provide a uniform, state-of-the-art, and accessible toolset to improve our understanding of cellular senescence in vivo.


Assuntos
Senescência Celular , Humanos , Animais , Biomarcadores/metabolismo , Guias como Assunto , Neoplasias/patologia
6.
PLoS Biol ; 22(8): e3002731, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39102375

RESUMO

Bacterial pathogens utilize the factors of their hosts to infect them, but which factors they exploit remain poorly defined. Here, we show that a pathogenic Salmonella enterica serovar Typhimurium (STm) exploits host polyamines for the functional expression of virulence factors. An STm mutant strain lacking principal genes required for polyamine synthesis and transport exhibited impaired infectivity in mice. A polyamine uptake-impaired strain of STm was unable to inject effectors of the type 3 secretion system into host cells due to a failure of needle assembly. STm infection stimulated host polyamine production by increasing arginase expression. The decline in polyamine levels caused by difluoromethylornithine, which inhibits host polyamine production, attenuated STm colonization, whereas polyamine supplementation augmented STm pathogenesis. Our work reveals that host polyamines are a key factor promoting STm infection, and therefore a promising therapeutic target for bacterial infection.


Assuntos
Poliaminas , Salmonella typhimurium , Sistemas de Secreção Tipo III , Fatores de Virulência , Salmonella typhimurium/metabolismo , Salmonella typhimurium/patogenicidade , Salmonella typhimurium/genética , Animais , Poliaminas/metabolismo , Camundongos , Sistemas de Secreção Tipo III/metabolismo , Sistemas de Secreção Tipo III/genética , Fatores de Virulência/metabolismo , Fatores de Virulência/genética , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Interações Hospedeiro-Patógeno , Humanos , Infecções por Salmonella/metabolismo , Infecções por Salmonella/microbiologia , Feminino
8.
ESC Heart Fail ; 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38984563

RESUMO

AIMS: In heart failure (HF), inflammation is linked to malnutrition and impaired physical function. In this study, we aimed to assess how novel nutritional-inflammatory markers and lymphocyte-to-C-reactive protein ratio (LCR) and score (LCS) are associated with the nutritional status, physical function, and prognosis of patients with HF. METHODS AND RESULTS: This study was a secondary analysis of the FRAGILE-HF study, a prospective observational study conducted across 15 hospitals in Japan. We included 1212 patients (mean age, 80.2 ± 7.8 years; 513 women) hospitalized with HF, who were classified into three groups according to their LCS score: 0 (n = 498), 1 (n = 533), and 2 (n = 181). Baseline data on physical examination, echocardiography, blood test results (including lymphocyte counts and CRP levels), and oral medication usage were collected in a clinically compensated state before discharge. Nutritional status and physical function were evaluated using several indices and tests. The primary outcome of this study was all-cause death within 2 years. Univariate and multivariate linear regression analyses were performed to evaluate the associations among the nutritional status, physical function, and LCR/LCS. Patients with an LCS score of 2 were older and had a lower body mass index than those in the other two groups. Multivariate linear regression analysis revealed that lower LCR and higher LCS were independently associated with worse nutritional status, lower handgrip strength, shorter physical performance battery score, and shorter 6-min walk distance. At 2 years, all-cause death occurred in 254 patients: 86 (17.6%), 113 (21.5%), and 55 (30.9%) with LCS scores of 0, 1, and 2, respectively (P = 0.001). Cox proportional hazards analysis revealed that LCR and LCS were significantly associated with 2-year mortality even after adjusting for the conventional risk model (LCS score, 0 vs. 2: hazard ratio, 1.64; 95% confidence interval [CI]; 1.14-2.35; P = 0.007; log-transformed LCR: hazard ratio, 0.88; 95% CI, 0.81-0.95; P = 0.002). LCR yielded additional prognostic predictability compared with the conventional risk model (continuous net reclassification improvement, 0.153; 95% CI, 0.007-0.299; P = 0.041). CONCLUSIONS: LCR and LCS emerge as potential predictors of nutritional status, physical function, and prognosis in older patients with HF.

9.
PLoS One ; 19(7): e0306822, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38980861

RESUMO

Studies have reported that health care professionals experienced a lack of sleep during the coronavirus disease 2019 (COVID-19) pandemic and that such lack of sleep and working environment affect their performance. However, to the authors' knowledge, no study has yet investigated the relationship between sleep duration and working environment among Japanese physiotherapists during the COVID-19 pandemic. This study retrospectively investigated the sleep duration of physiotherapists directly providing physiotherapy to patients with COVID-19 within the red zone and analyzed the association between sleep duration and working environment using logistic regression analysis. Among the 565 physiotherapists studied, the average sleep duration was 6 (6-7) h, and 381 (67.4%) had an average sleep duration of ≤6 h. Less experienced physiotherapists were 1.03 times more likely to sleep ≤6 h, and those in charge of patients with COVID-19 as the supervisor ordered were 0.64 times more likely to sleep ≤6 h. Moreover, physiotherapists with a significant increase in the frequency of internal online meetings and those who had been providing physiotherapy to patients with COVID-19 for >6 months were 2.34 and 2.05 times more likely to sleep ≤6 h, respectively. During the COVID-19 pandemic in Japan, two-thirds of the physiotherapists directly providing physiotherapy to patients with COVID-19 slept less than the recommended duration. This study highlights the need for appropriate workload and work hour management for physiotherapists according to their experience and workload, as well as establishing a medical care system that includes work rotation to ensure that the recommended sleep duration is satisfied.


Assuntos
COVID-19 , Fisioterapeutas , Sono , Humanos , COVID-19/epidemiologia , Japão/epidemiologia , Estudos Retrospectivos , Feminino , Masculino , Adulto , Sono/fisiologia , Pessoa de Meia-Idade , Pandemias , SARS-CoV-2 , Local de Trabalho , Fatores de Tempo , Condições de Trabalho , Duração do Sono
10.
Heart Rhythm ; 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39019384

RESUMO

BACKGROUND: The coagulation response during vascular injury with uninterrupted administration of direct oral anticoagulants has not been elucidated. OBJECTIVE: Our aim was to evaluate differences in coagulation responses after vascular injury between uninterrupted direct thrombin inhibitor and direct factor Xa inhibitor recipients. METHODS: Patients scheduled for catheter ablation for atrial fibrillation were randomly assigned to receive dabigatran or apixaban in this prospective, randomized, comparative, parallel-group study. Venous blood was collected 3 times: 180 minutes after taking the anticoagulant on the day before the procedure, before vascular punctures of the ablation procedure, and 10-15 minutes after the start of vascular punctures. RESULTS: Forty-two patients were enrolled. The prothrombin fragment 1+2 level, the primary end point, was much larger after vascular puncture in the uninterrupted dabigatran recipients (median, 83 pmol/L; interquartile range, 56-133 pmol/L) than in the uninterrupted apixaban recipients (median, 1 pmol/L; interquartile range, -3 to 19 pmol/L; P < .001). Antithrombin levels decreased after vascular puncture in dabigatran recipients, and both protein C and antithrombin levels decreased after vascular puncture in apixaban recipients. CONCLUSION: Unlike uninterrupted apixaban, uninterrupted dabigatran does not inhibit thrombin generation in response to vascular injury.

11.
Juntendo Iji Zasshi ; 70(1): 29-43, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38854810

RESUMO

Objective: Due to the lack of information on the effects of nutritional guidance focused on leucine intake in patients undergoing maintenance cardiac rehabilitation, this study investigated on plasma leucine concentrations, lean body mass, and muscle strength. Methods: Nutritional guidance, focused on leucine (intervention group) or general nutritional guidance (control group), was provided for six months to patients participating in cardiac rehabilitation. Body composition, grip strength, hematological test results, and diet of both groups were compared before and after the intervention. Results: Seven patients in the intervention group (53.2 ±â€…18.2 years) and 7 patients in the control group (58.6 ±â€…15.3 years) were included. Dietary survey results showed that the six-month intervention significantly (p < 0.05) increased protein intake and estimated leucine intake only in the intervention group. There was no significant difference in the rate of change in plasma leucine concentration between the two groups. The rate of change in lean body mass was significantly higher in the intervention group compared to the control group (p = 0.035). The rate of change in plasma leucine concentration and that in lean body mass was positively correlated only in the intervention group (r = 0.777, p = 0.040), and the rate of change in plasma leucine concentration was also positively correlated with the rate of change in grip strength (ρ = 0.857, p = 0.014). Conclusions: In the patients undergoing maintenance cardiac rehabilitation, increased plasma leucine concentration by nutritional guidance focused on leucine increased lean body mass without any increasing the training load.

12.
J Cardiol ; 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38876399

RESUMO

BACKGROUND: On-site computed tomography-derived fractional flow reserve (CT-FFR) is a feasible method for examining lesion-specific ischemia, and plaque analysis of coronary CT angiography (CCTA) is useful for predicting future cardiac events. However, their utility and association on a per-vessel level remain unclear. METHODS: We analyzed vessels showing 50-90 % stenosis on CCTA where planned revascularization was not performed after CCTA within 90 days. Relevant features, including CT-FFR and the plaque burden [necrotic core to the total plaque volume (% necrotic core), and non-calcified plaque (NCP) to vessel volume (% NCP)] using a novel algorithm for analyzing plaque to predict vessel-oriented composite outcomes (VOCO), including cardiac death, non-fatal myocardial infarction, and unplanned vessel-related revascularization, were assessed. RESULTS: In 256 patients (68.7 ±â€¯9.4 years; 73.8 % male) with 354 vessels (10.5 % CT-FFR ≤ 0.80), VOCO occurred in 24 vessels (6.8 %) during a median follow-up of 3.6 years. Multivariable Cox analysis revealed CT-FFR ≤ 0.80 had the pronounced impact on VOCO, and moreover, higher % necrotic core and % NCP were independently associated with VOCO [adjusted hazard ratio 3.43 (95 % confidence interval 1.42-8.29) and 4.05 (1.19-13.71), respectively], especially for vessels with CT-FFR > 0.80. CONCLUSIONS: In vessels without planned revascularization, per-vessel CT-FFR ≤ 0.80 was the notable predictor of future cardiac events. Additionally, necrotic core volume and NCP were identified as independent predictors along with CT-FFR.

13.
Cardiovasc Diabetol ; 23(1): 224, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38943159

RESUMO

BACKGROUND: Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of hospitalization for heart failure and cardiovascular death with type 2 diabetes; however, their effect on arrhythmias is unclear. The purpose of this study was to investigate the effects of empagliflozin on ventricular arrhythmias in patients with type 2 diabetes. METHODS: A total of 150 patients with type 2 diabetes who were treated with an implantable cardioverter-defibrillator or cardiac resynchronization therapy defibrillator (ICD/CRT-D) were randomized to once-daily empagliflozin or placebo for 24 weeks. The primary endpoint was the change in the number of ventricular arrhythmias from the 24 weeks before to the 24 weeks during treatment. Secondary endpoints included the change in the number of appropriate device discharges and other values. RESULTS: In the empagliflozin group, the number of ventricular arrhythmias recorded by ICD/CRT-D decreased by 1.69 during treatment compared to before treatment, while in the placebo group, the number increased by 1.79. The coefficient for the between-group difference was - 1.07 (95% confidence interval [CI] - 1.29 to - 0.86; P < 0.001). The change in the number of appropriate device discharges during and before treatment was 0.06 in the empagliflozin group and 0.27 in the placebo group, with no significant difference between the groups (P = 0.204). Empagliflozin was associated with an increase in blood ketones and hematocrit and a decrease in blood brain natriuretic peptide and body weight. CONCLUSIONS: In patients with type 2 diabetes treated with ICD/CRT-D, empagliflozin reduces the number of ventricular arrhythmias compared with placebo. Trial registration jRCTs031180120.


Assuntos
Compostos Benzidrílicos , Desfibriladores Implantáveis , Diabetes Mellitus Tipo 2 , Cardioversão Elétrica , Glucosídeos , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Glucosídeos/uso terapêutico , Glucosídeos/efeitos adversos , Compostos Benzidrílicos/uso terapêutico , Compostos Benzidrílicos/efeitos adversos , Masculino , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Feminino , Idoso , Pessoa de Meia-Idade , Resultado do Tratamento , Fatores de Tempo , Cardioversão Elétrica/instrumentação , Cardioversão Elétrica/efeitos adversos , Método Duplo-Cego , Japão , Terapia de Ressincronização Cardíaca/efeitos adversos , Glicemia/metabolismo , Glicemia/efeitos dos fármacos
14.
J Cardiol ; 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38839042

RESUMO

BACKGROUND: The purpose of this study was to examine the relationship between responsiveness to prehabilitation and postoperative recovery of physical function in cardiac surgery patients. METHODS: Ninety-three cardiac surgery patients (mean age: 76.4 years) were included in this retrospective cohort study. Preoperative physical function was measured using the Short Physical Performance Battery (SPPB), and a prehabilitation exercise program was implemented for the SPPB domains with low scores. Among the patients, those whose SPPB score was over 11 from the start of prehabilitation and remained over 11 on the day before surgery were defined as the high-functioning group, and those whose SPPB score improved by 2 points or more from the start of prehabilitation and exceeded 11 points were defined as the responder group. Those whose SPPB score did not exceed 11 immediately before surgery were classified as non-responders. The characteristics of each group and postoperative recovery of physical function were investigated. RESULTS: There were no serious adverse events during prehabilitation. Mean days of prehabilitation was 5.4 days. The responder group showed faster improvement in postoperative physical function and shorter time to ambulatory independence than the non-responder group. The non-responder group had lower preoperative skeletal muscle index, more severe preoperative New York Heart Association classification, and a history of musculoskeletal disease or stroke. CONCLUSION: There were responders and non-responders to prehabilitation among cardiac surgery patients. Cardiac surgery patients who respond to prehabilitation had faster recovery of physical function. Further research is needed to determine what type of prehabilitation is more effective in postoperative recovery of physical function in cardiac surgery patients.

15.
J Cardiol ; 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38701945

RESUMO

BACKGROUND: Multi-parametric assessment, including heart sounds in addition to conventional parameters, may enhance the efficacy of noninvasive telemonitoring for heart failure (HF). We sought to assess the feasibility of self-telemonitoring with multiple devices including a handheld heart sound recorder and its association with clinical events in patients with HF. METHODS: Ambulatory HF patients recorded their own heart sounds, mono­lead electrocardiograms, oxygen saturation, body weight, and vital signs using multiple devices every morning for six months. RESULTS: In the 77 patients enrolled (63 ±â€¯13 years old, 84 % male), daily measurements were feasible with a self-measurement rate of >70 % of days in 75 % of patients. Younger age and higher Minnesota Living with Heart Failure Questionnaire scores were independently associated with lower adherence (p = 0.002 and 0.027, respectively). A usability questionnaire showed that 87 % of patients felt self-telemonitoring was helpful, and 96 % could use the devices without routine cohabitant support. Six patients experienced ten HF events of re-hospitalization and/or unplanned hospital visits due to HF. In patients who experienced HF events, a significant increase in heart rate and diastolic blood pressure and a decrease in the time interval from Q wave onset to the second heart sound were observed 7 days before the events compared with those without HF events. CONCLUSIONS: Self-telemonitoring with multiple devices including a handheld heart sound recorder was feasible even in elderly patients with HF. This intervention may confer a sense of relief to patients and enable monitoring of physiological parameters that could be valuable in detecting the deterioration of HF.

16.
Nat Aging ; 4(7): 926-938, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38816549

RESUMO

It has been reported that accumulation of senescent cells in various tissues contributes to pathological aging and that elimination of senescent cells (senolysis) improves age-associated pathologies. Here, we demonstrate that inhibition of sodium-glucose co-transporter 2 (SGLT2) enhances clearance of senescent cells, thereby ameliorating age-associated phenotypic changes. In a mouse model of dietary obesity, short-term treatment with the SGLT2 inhibitor canagliflozin reduced the senescence load in visceral adipose tissue and improved adipose tissue inflammation and metabolic dysfunction, but normalization of plasma glucose by insulin treatment had no effect on senescent cells. Canagliflozin extended the lifespan of mice with premature aging even when treatment was started in middle age. Metabolomic analyses revealed that short-term treatment with canagliflozin upregulated 5-aminoimidazole-4-carboxamide-1-ß-D-ribofuranoside, enhancing immune-mediated clearance of senescent cells by downregulating expression of programmed cell death-ligand 1. These findings suggest that inhibition of SGLT2 has an indirect senolytic effect by enhancing endogenous immunosurveillance of senescent cells.


Assuntos
Envelhecimento , Canagliflozina , Senescência Celular , Inibidores do Transportador 2 de Sódio-Glicose , Transportador 2 de Glucose-Sódio , Animais , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Senescência Celular/efeitos dos fármacos , Canagliflozina/farmacologia , Canagliflozina/uso terapêutico , Camundongos , Transportador 2 de Glucose-Sódio/metabolismo , Envelhecimento/efeitos dos fármacos , Envelhecimento/patologia , Obesidade/tratamento farmacológico , Obesidade/metabolismo , Obesidade/patologia , Humanos , Masculino , Camundongos Endogâmicos C57BL
18.
Eur J Prev Cardiol ; 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38573843

RESUMO

AIMS: This study aimed to investigate the prevalence, clinical characteristics, and prognostic value of bendopnea in older patients hospitalized for heart failure. METHODS: This post hoc analysis was performed using two prospective, multicenter, observational studies: the FRAGILE-HF (main cohort) and SONIC-HF (validation cohort) cohorts. Patients were categorized based on the presence of bendopnea, which was evaluated before discharge. The primary endpoint was 2-year all-cause mortality after discharge. RESULTS: Among the 1,243 patients (median age, 81 years; 57.2% male) in the FRAGILE-HF cohort and 225 (median age, 79 years; 58.2% men) in the SONIC-HF cohort, bendopnea was observed in 31 (2.5%) and 10 (4.4%) patients, respectively. Over a 2-year follow-up period, all-cause death occurred in 20.8% and 21.9% of the patients in the FRAGILE-HF and SONIC-HF cohorts, respectively. Kaplan-Meier survival curves demonstrated significantly higher mortality rates in patients with bendopnea than in those without bendopnea in the FRAGILE-HF (log-rank P = 0.006) and SONIC-HF cohorts (log-rank P = 0.014). Cox proportional hazard analysis identified bendopnea as an independent prognostic factor for all-cause mortality in both the FRAGILE-HF (hazard ratio [HR] 2.11, 95% confidence interval [CI] 1.18-3.78, P = 0.012) and SONIC-HF cohorts (HR 4.20, 95% CI 1.63-10.79, P = 0.003), even after adjusting for conventional risk factors. CONCLUSIONS: Bendopnea was observed in a relatively small proportion of older patients hospitalized for heart failure before discharge. However, its presence was significantly associated with an increased risk of all-cause mortality.


This study investigated how common it is for older patients with heart failure to have trouble breathing when they bend forward, and whether this affects their chances of survival. The study found that although this problem is not very common, it is linked to a higher risk of death. Key findings: Only a small number of older patients with heart failure have trouble breathing when they bend forward.However, those who do have this problem are more likely to die.

19.
J Am Heart Assoc ; 13(6): e032047, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38456399

RESUMO

BACKGROUND: Current guidelines recommend placing an implantable cardiac defibrillator for patients with cardiac sarcoidosis and a severely impaired left ventricular ejection fraction (LVEF) of ≤35%. In this study, we determined the association between mild or moderate LVEF impairment and fatal ventricular arrhythmic event (FVAE). METHODS AND RESULTS: We retrospectively analyzed 401 patients with cardiac sarcoidosis without sustained ventricular arrhythmia at diagnosis. The primary end point was an FVAE, defined as the combined endpoint of documented ventricular tachycardia or ventricular fibrillation and sudden cardiac death. Two cutoff points for LVEF were used: a sex-specific lower threshold of normal range of LVEF (52% for men and 54% for women) and an LVEF of 35%, which is used in the current guidelines. During a median follow-up of 3.2 years, 58 FVAEs were observed, and the 5- and 10-year estimated incidences of FVAEs were 16.8% and 23.0%, respectively. All patients were classified into 3 groups according to LVEF: impaired LVEF group, mild to moderate impairment of LVEF group, and maintained LVEF group. Multivariable competing risk analysis showed that both the impaired LVEF group (hazard ratio [HR], 3.24 [95% CI, 1.49-7.04]) and the mild to moderate impairment of LVEF group (HR, 2.16 [95% CI, 1.04-4.46]) were associated with a higher incidence of FVAEs than the maintained LVEF group after adjustment for covariates. CONCLUSIONS: Patients with cardiac sarcoidosis are at a high risk of FVAEs, regardless of documented ventricular arrhythmia at the time of diagnosis. In patients with cardiac sarcoidosis, mild to moderate impairment of LVEF is associated with FVAEs.


Assuntos
Desfibriladores Implantáveis , Miocardite , Sarcoidose , Masculino , Humanos , Feminino , Função Ventricular Esquerda , Volume Sistólico , Estudos Retrospectivos , Sarcoidose/complicações , Sarcoidose/diagnóstico , Arritmias Cardíacas/etiologia , Arritmias Cardíacas/complicações , Desfibriladores Implantáveis/efeitos adversos , Morte Súbita Cardíaca/epidemiologia , Morte Súbita Cardíaca/etiologia , Miocardite/complicações
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