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1.
Biochem Biophys Res Commun ; 710: 149910, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38593619

RESUMO

Ginsenoside Rb1 (Rb1), an active component isolated from traditional Chinese medicine Ginseng, is beneficial to many cardiovascular diseases. However, whether it can protect against doxorubicin induced cardiotoxicity (DIC) is not clear yet. In this study, we aimed to investigate the role of Rb1 in DIC. Mice were injected with a single dose of doxorubicin (20 mg/kg) to induce acute cardiotoxicity. Rb1 was given daily gavage to mice for 7 days. Changes in cardiac function, myocardium histopathology, oxidative stress, cardiomyocyte mitochondrion morphology were studied to evaluate Rb1's function on DIC. Meanwhile, RNA-seq analysis was performed to explore the potential underline molecular mechanism involved in Rb1's function on DIC. We found that Rb1 treatment can improve survival rate and body weight in Dox treated mice group. Rb1 can attenuate Dox induced cardiac dysfunction and myocardium hypertrophy and interstitial fibrosis. The oxidative stress increase and cardiomyocyte mitochondrion injury were improved by Rb1 treatment. Mechanism study found that Rb1's beneficial role in DIC is through suppressing of autophagy and ferroptosis. This study shown that Ginsenoside Rb1 can protect against DIC by regulating autophagy and ferroptosis.


Assuntos
Cardiotoxicidade , Ferroptose , Ginsenosídeos , Camundongos , Animais , Cardiotoxicidade/tratamento farmacológico , Cardiotoxicidade/prevenção & controle , Cardiotoxicidade/metabolismo , Miócitos Cardíacos/metabolismo , Doxorrubicina/efeitos adversos , Doxorrubicina/metabolismo , Autofagia , Estresse Oxidativo , Apoptose
2.
JACC Clin Electrophysiol ; 10(4): 685-694, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38658060

RESUMO

BACKGROUND: Reconnection after mitral isthmus (MI) block with radiofrequency ablation is common. OBJECTIVES: The aim of this study was to investigate the effects of ethanol infusion in the vein of Marshall (EIVOM) on acute reconnection after MI bidirectional block. METHODS: Patients with persistent atrial fibrillation who were scheduled to receive radiofrequency ablation for the first time were randomly assigned to the radiofrequency catheter ablation (RFCA) group (n = 44) or the EIVOM group (n = 45). The RFCA group's strategy was bilateral pulmonary vein ablation and linear ablation; in the EIVOM group, EIVOM was performed first. The primary endpoint was acute reconnection 30 minutes after MI bidirectional block. RESULTS: A total of 89 patients (average age 62.9 years; 57.3% male) were enrolled. The average duration for persistent atrial fibrillation was 2.3 years. Before observation, all patients in the EIVOM group achieved MI bidirectional block (45 of 45 [100%]), compared with 84.1% (37 of 44) in the RFCA group. After the observation, 3 cases of MI reconnection occurred in the EIVOM group and 13 cases in the RFCA group (6.7% vs 35.1%; P < 0.05). After additional ablation, the final MI block rates in the EIVOM and RFCA groups were 97.8% (44 of 45) and 72.7% (32 of 44), respectively. During a 1-year follow-up, 8 of 45 patients who underwent EIVOM had recurrent atrial fibrillation, compared with 14 of 44 in the RFCA group (17.8% vs 31.8%; P < 0.01). CONCLUSIONS: EIVOM can reduce acute reconnection after MI bidirectional block and significantly increase first-pass MI block.


Assuntos
Fibrilação Atrial , Ablação por Cateter , Valva Mitral , Veias Pulmonares , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Fibrilação Atrial/cirurgia , Ablação por Cateter/métodos , Idoso , Valva Mitral/cirurgia , Veias Pulmonares/cirurgia , Etanol/administração & dosagem , Recidiva , Resultado do Tratamento
3.
Cell Death Discov ; 10(1): 142, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38490981

RESUMO

Pleckstrin homology domain-containing family M member 2 (PLEKHM2) is an essential adaptor for lysosomal trafficking and its homozygous truncation have been reported to cause early onset dilated cardiomyopathy (DCM). However, the molecular mechanism of PLEKHM2 deficiency in DCM pathogenesis and progression is poorly understood. Here, we generated an in vitro model of PLEKHM2 knockout (KO) induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) to elucidate the potential pathogenic mechanism of PLEKHM2-deficient cardiomyopathy. PLEKHM2-KO hiPSC-CMs developed disease phenotypes with reduced contractility and impaired calcium handling. Subsequent RNA sequencing (RNA-seq) analysis revealed altered expression of genes involved in mitochondrial function, autophagy and apoptosis in PLEKHM2-KO hiPSC-CMs. Further molecular experiments confirmed PLEKHM2 deficiency impaired autophagy and resulted in accumulation of damaged mitochondria, which triggered increased reactive oxygen species (ROS) levels and decreased mitochondrial membrane potential (Δψm). Importantly, the elevated ROS levels caused oxidative stress-induced damage to nearby healthy mitochondria, resulting in extensive Δψm destabilization, and ultimately leading to impaired mitochondrial function and myocardial contractility. Moreover, ROS inhibition attenuated oxidative stress-induced mitochondrial damage, thereby partially rescued PLEKHM2 deficiency-induced disease phenotypes. Remarkably, PLEKHM2-WT overexpression restored autophagic flux and rescued mitochondrial function and myocardial contractility in PLEKHM2-KO hiPSC-CMs. Taken together, these results suggested that impaired mitochondrial clearance and increased ROS levels play important roles in PLEKHM2-deficient cardiomyopathy, and PLEKHM2-WT overexpression can improve mitochondrial function and rescue PLEKHM2-deficient cardiomyopathy.

4.
Clin Cardiol ; 47(2): e24233, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38375935

RESUMO

BACKGROUND: There is great heterogeneity in the quality of care among hospitals in China, but studies on the performance measures and prognosis of patients with heart failure (HF) are still deficient. HYPOTHESIS: Performance measures have been used as a guideline to clinicans, however, the association between them and outcomes among HF patients in China remains unclear. METHODS: We analyzed 4497 patients with HF from the Heart Failure Registry of Patient Outcomes study. Performance measures were determined according to the guidelines, and the patients were divided into four groups based on a composite performance score. Multiple imputation and Cox proportional-hazard regression models were used to assess the association between the performance measures and clinical outcomes. RESULTS: Overall, only 12.5% of patients met the top 25% of the performance measures, whereas 33.5% of patients met the bottom 25% of the measures. A total of 992 (22.2%) patients died within 1 year, involving a larger proportion of patients who had met only the bottom 25% of the performance measures than had met the top 25% (27.0% vs. 16.3%, respectively). The patients who met the top 25% of the measures had a lower 1-year mortality rate (adjusted hazard ratio: 0.78, 95% confidence interval: 0.61-0.98). CONCLUSIONS: The association between performance measures and mortality appeared to follow a dose-response pattern with a larger degree of compliance with performance measures being associated with a lower mortality rate in patients with HF. Accordingly, the quality of care for patients with HF in China needs to be further improved.


Assuntos
Fidelidade a Diretrizes , Insuficiência Cardíaca , Humanos , Hospitais , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/terapia , Modelos de Riscos Proporcionais , China/epidemiologia , Sistema de Registros
5.
Pacing Clin Electrophysiol ; 47(4): 511-517, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38407298

RESUMO

BACKGROUND: Wearable devices based on the PPG algorithm can detect atrial fibrillation (AF) effectively. However, further investigation of its application on long-term, continuous monitoring of AF burden is warranted. METHOD: The performance of a smartwatch with continuous photoplethysmography (PPG) and PPG-based algorithms for AF burden estimation was evaluated in a prospective study enrolling AF patients admitted to Beijing Anzhen Hospital for catheter ablation from September to November 2022. A continuous Electrocardiograph patch (ECG) was used as the reference device to validate algorithm performance for AF detection in 30-s intervals. RESULTS: A total of 578669 non-overlapping 30-s intervals for PPG and ECG each from 245 eligible patients were generated. An interval-level sensitivity of PPG was 96.3% (95% CI 96.2%-96.4%), and specificity was 99.5% (95% CI 99.5%-99.6%) for the estimation of AF burden. AF burden estimation by PPG was highly correlated with AF burden calculated by ECG via Pearson correlation coefficient (R2 = 0.996) with a mean difference of -0.59 (95% limits of agreement, -7.9% to 6.7%). The subgroup study showed the robust performance of the algorithm in different subgroups, including heart rate and different hours of the day. CONCLUSION: Our results showed the smartwatch with an algorithm-based PPG monitor has good accuracy and stability in continuously monitoring AF burden compared with ECG patch monitors, indicating its potential for diagnosing and managing AF.


Assuntos
Fibrilação Atrial , Humanos , Fibrilação Atrial/diagnóstico , Fotopletismografia/métodos , Estudos Prospectivos , Sensibilidade e Especificidade , Algoritmos , Eletrocardiografia/métodos
6.
Pacing Clin Electrophysiol ; 47(4): 518-524, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38407374

RESUMO

BACKGROUND: Left bundle branch block (LBBB) and atrial fibrillation (AF) are commonly coexisting conditions. The impact of LBBB on catheter ablation of AF has not been well determined. This study aims to explore the long-term outcomes of patients with AF and LBBB after catheter ablation. METHODS: Forty-two patients with LBBB of 11,752 patients who underwent catheter ablation of AF from 2011 to 2020 were enrolled as LBBB group. After propensity score matching in a 1:4 ratio, 168 AF patients without LBBB were enrolled as non-LBBB group. Late recurrence and a composite endpoint of stroke, all-cause mortality, and cardiovascular hospitalization were compared between the two groups. RESULTS: Late recurrence rate was significantly higher in the LBBB group than that in the non-LBBB group (54.8% vs. 31.5%, p = .034). Multivariate analysis showed that LBBB was an independent risk factor for late recurrence after catheter ablation of AF (hazard ratio [HR] 2.19, 95% confidence interval [CI] 1.09-4.40, p = .031). LBBB group was also associated with a significantly higher incidence of the composite endpoint (21.4% vs. 6.5%, HR 3.98, 95% CI 1.64-9.64, p = .002). CONCLUSIONS: LBBB was associated with a higher risk for late recurrence and a higher incidence of composite endpoint in the patients underwent catheter ablation.


Assuntos
Fibrilação Atrial , Ablação por Cateter , Acidente Vascular Cerebral , Humanos , Bloqueio de Ramo/etiologia , Fatores de Risco , Acidente Vascular Cerebral/etiologia , Ablação por Cateter/efeitos adversos , Resultado do Tratamento , Recidiva
7.
J Cardiovasc Electrophysiol ; 35(4): 811-820, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38424601

RESUMO

INTRODUCTION: Various left atrial (LA) anatomical structures are correlated with postablative recurrence for atrial fibrillation (AF) patients. Comprehensively integrating anatomical structures, digitizing them, and implementing in-depth analysis, which may supply new insights, are needed. Thus, we aim to establish an interpretable model to identify AF patients' phenotypes according to LA anatomical morphology, using machine learning techniques. METHODS AND RESULTS: Five hundred and nine AF patients underwent first ablation treatment in three centers were included and were followed-up for postablative recurrent atrial arrhythmias. Data from 369 patients were regarded as training set, while data from another 140 patients, collected from different centers, were used as validation set. We manually measured 57 morphological parameters on enhanced computed tomography with three-dimensional reconstruction technique and implemented unsupervised learning accordingly. Three morphological groups were identified, with distinct prognosis according to Kaplan-Meier estimator (p < .001). Multivariable Cox model revealed that morphological grouping were independent predictors of 1-year recurrence (Group 1: HR = 3.00, 95% CI: 1.51-5.95, p = .002; Group 2: HR = 4.68, 95% CI: 2.40-9.11, p < .001; Group 3 as reference). Furthermore, external validation consistently demonstrated our findings. CONCLUSIONS: Our study illustrated the feasibility of employing unsupervised learning for the classification of LA morphology. By utilizing morphological grouping, we can effectively identify individuals at different risks of postablative recurrence and thereby assist in clinical decision-making.


Assuntos
Apêndice Atrial , Fibrilação Atrial , Ablação por Cateter , Humanos , Fibrilação Atrial/diagnóstico por imagem , Fibrilação Atrial/cirurgia , Resultado do Tratamento , Átrios do Coração/diagnóstico por imagem , Átrios do Coração/cirurgia , Ablação por Cateter/efeitos adversos , Ablação por Cateter/métodos , Recidiva
8.
Hypertension ; 81(3): 620-628, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38164752

RESUMO

BACKGROUND: To evaluate whether cancer modifies the effect of intensive blood pressure control on major cardiovascular outcomes. METHODS: Using data of the SPRINT (Systolic Blood Pressure Intervention Trial), we compared the risk of the composite outcomes of myocardial infarction, other acute coronary syndromes, stroke, heart failure, and cardiovascular death in patients with and without a history of cancer. Using Cox proportional hazards regression, we tested interactions between history of cancer and intensive blood pressure control on major cardiovascular outcomes. RESULTS: The study included a total of 9336 patients, with a mean age of 67.9±9.4 years, among whom 2066 (22.2%) were cancer survivors. Over a median follow-up of 3.2 years, 561 primary cardiovascular outcomes were observed. Cancer survivors had a similar risk of experiencing the primary outcome compared with patients without cancer after multivariable adjustment (adjusted hazard ratio, 0.94 [95% CI, 0.77-1.15]). Intensive blood pressure control reduced risk of the primary cardiovascular outcome similarly for cancer survivors (hazard ratio, 0.70 [95% CI, 0.51-0.97]) and patients without cancer (HR, 0.76 [95% CI, 0.63-0.93]; P for interaction 0.74). CONCLUSIONS: In SPRINT study, intensive blood pressure treatment reduced the risk of major cardiovascular events in cancer survivors to a similar extent to that of patients without cancer. Cancer history not requiring active treatment in last 2 years should not be an obstacle to intensive treatment of hypertension. This post hoc analysis should be considered as hypothesis-generating and merit further clinical trial. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01206062.


Assuntos
Sobreviventes de Câncer , Hipertensão , Infarto do Miocárdio , Neoplasias , Humanos , Pessoa de Meia-Idade , Idoso , Pressão Sanguínea/fisiologia , Anti-Hipertensivos/farmacologia , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Hipertensão/induzido quimicamente , Infarto do Miocárdio/tratamento farmacológico , Resultado do Tratamento , Fatores de Risco , Neoplasias/epidemiologia , Neoplasias/tratamento farmacológico
9.
Clin Cardiol ; 47(2): e24194, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38054342

RESUMO

BACKGROUND: Evidence was lacking for the early choice of radiofrequency ablation (RFA) among patients with early-onset atrial fibrillation (AF). HYPOTHESIS: This study aimed to explore whether earlier RFA was associated with better clinical outcomes among early-onset AF patients. METHODS: Patients, who were diagnosed with AF before 45 years and underwent their first RFA procedures at baseline of the China Atrial Fibrillation registry, were enrolled and divided into four diagnosis-to-ablation time (DAT) groups: DAT ≤ 1 year, 1 year < DAT ≤ 3 years, 3 years < DAT ≤ 6 years, and DAT > 6 years. Another group of nonablation patients, who were newly diagnosed with AF and younger than 45 years, were also included. Adjusted associations of groups with composite cardiovascular events (cardiovascular death, embolism, major hemorrhages, or cardiac rehospitalization) or recurrent AF were analyzed using Cox proportional hazards models. RESULTS: Among 1694 patients who underwent their first RFA at enrollment, incidences of composite cardiovascular outcomes were increasing with extension of DAT (DAT ≤ 1 year: 6.1/100 person-years, 1 year < DAT ≤ 3 years: 7.9/100 person-years, 3 years < DAT ≤ 6 years: 7.6/100 person-years, DAT > 6 years: 10.5/100 person-years; p < .001). In comparison with DAT > 6 years group, the DAT ≤ 1 year group was associated with reduced risk of cardiovascular events (adjusted hazard ratio, HR [95% confidence interval, CI] = 0.64 [0.47-0.87], p = .005) and AF recurrence (adjusted HR [95% CI] = 0.70 [0.57-0.88], p = .002). Associations remained similar after stratified by AF types. Compared to nonablation group (n = 413), DAT ≤ 1year patients tended to show lower cardiovascular risk (adjusted HR [95% CI] = 0.78 [0.58-1.05], p = .099) and lower risk of recurrent AF (adjusted HR [95% CI] = 0.46 [0.38-0.55], p < .001). CONCLUSIONS: A shorter DAT was associated with a lower risk of cardiovascular events and recurrent AF for early-onset AF patients.


Assuntos
Fibrilação Atrial , Ablação por Cateter , Humanos , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/cirurgia , Resultado do Tratamento , Fatores de Risco , Ablação por Cateter/efeitos adversos , Ablação por Cateter/métodos , Frequência Cardíaca , Recidiva
10.
Pacing Clin Electrophysiol ; 47(1): 58-65, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38010824

RESUMO

BACKGROUND: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) is reported to reduce incident atrial fibrillation (AF) in patients with or without diabetes; however, its cardiovascular (CV) benefit for AF patients remains unclear. SS AIMS: To investigate the effect of SGLT2i on the incidence of CV events in patients with AF. METHODS: Six randomized controlled trials (RCTs) assessing the effects of SGLT2i on CV outcomes in patients with or without AF were included (PROSPERO: CRD 42023431535). The primary endpoint was the composite outcome of heart failure (HF) hospitalization and CV death. Additionally, we assessed the effects of treatment in prespecified subgroups on HF hospitalization, CV death, and all-cause mortality. RESULTS: Among 38,529 participants from all trials, 5018 patients with AF were treated with SGLT2i. The follow-up period of these trials ranged from 2.3 to 3.3 years. SGLT2i treatment was significantly associated with the risk reduction of primary endpoint in patients with AF (risk ratio [RR] 0.81, 95% confidence interval [CI] 0.74-0.88; p < 0.001), consistent with the finding in the general population (p for interaction = 0.76). SGLT2i was also associated with a consistent reduction in the risk of HF hospitalization in patients with AF (RR 0.76, 95% CI 0.69-0.84; p < 0.001) or not (RR 0.72, 95% CI 0.64-0.80; p < 0.0001), with no statistical difference between them (p for interaction = 0.41). Meta-regression further revealed no significant association between the prevalence of HF with reduced ejection fraction or diabetes and the effect size of SGLT2i. CONCLUSIONS: The treatment effects of SGLT2i were associated with a lower incidence of CV events, especially HF hospitalization, in patients with AF.


Assuntos
Fibrilação Atrial , Diabetes Mellitus , Insuficiência Cardíaca , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Fibrilação Atrial/tratamento farmacológico , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/epidemiologia
11.
Chin Med J (Engl) ; 137(2): 172-180, 2024 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-38146256

RESUMO

BACKGROUND: Oral anti-coagulants (OAC) are the intervention for the prevention of stroke, which consistently improve clinical outcomes and survival among patients with atrial fibrillation (AF). The main purpose of this study is to identify problems in OAC utilization among hospitalized patients with AF in China. METHODS: Using data from the Improving Care for Cardiovascular Disease in China-Atrial Fibrillation (CCC-AF) registry, guideline-recommended OAC use in eligible patients was assessed. RESULTS: A total of 52,530 patients with non-valvular AF were enrolled from February 2015 to December 2019, of whom 38,203 were at a high risk of stroke, 9717 were at a moderate risk, and 4610 were at a low risk. On admission, only 20.0% (6075/30,420) of patients with a diagnosed AF and a high risk of stroke were taking OAC. The use of pre-hospital OAC on admission was associated with a lower risk of new-onset ischemic stroke/transient ischemic attack among the diagnosed AF population (adjusted odds ratio: 0.54, 95% confidence interval: 0.43-0.68; P  <0.001). At discharge, the prescription rate of OAC was 45.2% (16,757/37,087) in eligible patients with high stroke risk and 60.7% (2778/4578) in eligible patients with low stroke risk. OAC utilization in patients with high stroke risk on admission or at discharge both increased largely over time (all P  <0.001). Multivariate analysis showed that OAC utilization at discharge was positively associated with in-hospital rhythm control strategies, including catheter ablation (adjusted odds ratio [OR] 11.63, 95% confidence interval [CI] 10.04-13.47; P <0.001), electronic cardioversion (adjusted OR 2.41, 95% CI 1.65-3.51; P <0.001), and anti-arrhythmic drug use (adjusted OR 1.45, 95% CI 1.38-1.53; P <0.001). CONCLUSIONS: In hospitals participated in the CCC-AF project, >70% of AF patients were at a high risk of stroke. Although poor performance on guideline-recommended OAC use was found in this study, over time the CCC-AF project has made progress in stroke prevention in the Chinese AF population.Registration:ClinicalTrials.gov, NCT02309398.


Assuntos
Fibrilação Atrial , Acidente Vascular Cerebral , Humanos , Administração Oral , Anticoagulantes/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/complicações , Alta do Paciente , Pacientes , Sistema de Registros , Fatores de Risco , Acidente Vascular Cerebral/tratamento farmacológico
12.
ESC Heart Fail ; 11(2): 709-718, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38131256

RESUMO

AIMS: Relationship between body mass index (BMI), frailty, and clinical adverse events remains unclear in patients with heart failure (HF) with preserved ejection fraction (HFpEF) in different patient populations. We aimed to compare the association of BMI, frailty, and clinical adverse events between a US cohort from the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) study and a Chinese cohort from the Heart Failure Registry of Patient Outcomes (HERO) study. METHODS AND RESULTS: We used data of 1715 participants enrolled from America in the TOPCAT study and 1487 patients with HFpEF in the Chinese registry study, the HERO. We evaluated the relationship between BMI and frailty using multivariate restricted cubic spline logistic regression. Association between frailty and BMI categories and primary outcomes including HF hospitalization, aborted sudden death, and cardiovascular death, all-cause mortality, and HF hospitalization were analysed by Cox proportional hazards models. The patients' mean age was 72 ± 11 years for both study populations, with 50% and 46% female for the TOPCAT study and the HERO study, respectively. Patients in the TOPCAT study had a higher mean BMI (33.9 vs. 24 kg/m2), with 72.3% vs. 52.9% defined as moderately to severely frail (frailty index > 0.3). In the TOPCAT study, risk of frailty rose as BMI increased, but not in the HERO study. Patients with frailty were at significant higher risk for the primary composite outcomes [hazard ratio (HR) 1.84 (95% confidence interval: 1.46-2.32)], all-cause mortality [HR 1.73 (1.34-2.25)], and HF hospitalization [HR 1.83 (1.40-2.40)] in the TOPCAT study. The corresponding numbers in the HERO study were 1.26 (1.01-1.57), 2.21 (1.45-3.35), and 1.15 (0.81-1.37), respectively. The association of frailty with clinical outcomes did not vary with BMI categories in the two studies. CONCLUSIONS: BMI distribution and association between BMI and frailty risk were different between the two study populations. Frailty was associated with clinical adverse events and this association was consistent across different BMI categories in both studies.


Assuntos
Fragilidade , Insuficiência Cardíaca , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Masculino , Índice de Massa Corporal , Fragilidade/complicações , Volume Sistólico , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico
13.
J Intern Med ; 295(4): 557-568, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38111091

RESUMO

BACKGROUND: Effects of intensive blood pressure (BP) control on cognitive outcomes in patients with excess orthostatic BP changes are unclear. We aimed to evaluate whether orthostatic BP changes modified the effects of BP intervention on cognitive impairment. METHODS: We analyzed 8547 participants from the Systolic Blood Pressure Intervention Trial Memory and cognition IN Decreased Hypertension. Associations between orthostatic BP changes and incident cognitive outcomes were evaluated by restricted cubic spline curves based on Cox models. The interactions between orthostatic BP changes and intensive BP intervention were assessed. RESULTS: The U-shaped associations were observed between baseline orthostatic systolic BP changes and cognitive outcomes. However, there were insignificant interactions between either change in orthostatic systolic BP (P for interaction = 0.81) or diastolic BP (P for interaction = 0.32) and intensive BP intervention for the composite outcome of probable dementia or mild cognitive impairment (MCI). The hazard ratio of intensive versus standard target for the composite cognitive outcome was 0.82 (95% CI 0.50-1.35) in those with an orthostatic systolic BP reduction of >20 mmHg and 0.41 (95% CI 0.21-0.80) in those with an orthostatic systolic BP increase of >20 mmHg. Results were similar for probable dementia and MCI. The annual changes in global cerebral blood flow (P for interaction = 0.86) consistently favored intensive BP treatment across orthostatic systolic BP changes. CONCLUSION: Intensive BP control did not have a deteriorating effect on cognitive outcomes among hypertensive patients experiencing significant postural BP changes.


Assuntos
Disfunção Cognitiva , Demência , Hipertensão , Hipotensão Ortostática , Humanos , Pressão Sanguínea , Hipotensão Ortostática/psicologia , Hipertensão/tratamento farmacológico , Cognição
14.
Stem Cell Res ; 74: 103284, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38118206

RESUMO

TGF-ß-activated kinase 1 binding protein 2 (TAB2) is an intermediate protein that connects TNFR1 and other receptor signals to the TGF-ß-activated kinase 1 (TAK1) signaling complex. TAB2 has been proved clinically relevant to congenital heart defects (CHD) and cardiomyopathy. In this study, we created a TAB2 knockout human embryonic stem cell line by CRISPR/Cas9 technology. The WAe009-A-Z cell line displayed stem cell morphology, pluripotency and normal karyotype, which could develop into three germ layers in vitro.


Assuntos
Células-Tronco Embrionárias Humanas , Humanos , Células-Tronco Embrionárias Humanas/metabolismo , Sistemas CRISPR-Cas/genética , Linhagem Celular , Transdução de Sinais , Proteínas Adaptadoras de Transdução de Sinal/genética
15.
Cell Calcium ; 117: 102822, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38101154

RESUMO

Hypertrophic cardiomyopathy (HCM), the most common inherited heart disease, is frequently caused by mutations in the ß-cardiac myosin heavy chain gene (MYH7). Abnormal calcium handling and diastolic dysfunction are archetypical features of HCM caused by MYH7 gene mutations. However, the mechanism of how MYH7 mutations leads to these features remains unclear, which inhibits the development of effective therapies. Initially, cardiomyocytes were generated from induced pluripotent stem cells from an eight-year-old girl diagnosed with HCM carrying a MYH7(C.1063 G>A) heterozygous mutation(mutant-iPSC-CMs) and mutation-corrected isogenic iPSCs(control-iPSC-CMs) in the present study. Next, we compared phenotype of mutant-iPSC-CMs to that of control-iPSC-CMs, by assessing their morphology, hypertrophy-related genes expression, calcium handling, diastolic function and myofilament calcium sensitivity at days 15 and 40 respectively. Finally, to better understand increased myofilament Ca2+ sensitivity as a central mechanism of central pathogenicity in HCM, inhibition of calcium sensitivity with mavacamten can improveed cardiomyocyte hypertrophy. Mutant-iPSC-CMs exhibited enlarged areas, increased sarcomere disarray, enhanced expression of hypertrophy-related genes proteins, abnormal calcium handling, diastolic dysfunction and increased myofilament calcium sensitivity at day 40, but only significant increase in calcium sensitivity and mild diastolic dysfunction at day 15. Increased calcium sensitivity by levosimendan aggravates cardiomyocyte hypertrophy phenotypes such as expression of hypertrophy-related genes, abnormal calcium handling and diastolic dysfunction, while inhibition of calcium sensitivity significantly improves cardiomyocyte hypertrophy phenotypes in mutant-iPSC-CMs, suggesting increased myofilament calcium sensitivity is the primary mechanisms for MYH7 mutations pathogenesis. Our studies have uncovered a pathogenic mechanism of HCM caused by MYH7 gene mutations through which enhanced myofilament calcium sensitivity aggravates abnormal calcium handling and diastolic dysfunction. Correction of the myofilament calcium sensitivity was found to be an effective method for treating the development of HCM phenotype in vitro.


Assuntos
Cardiomiopatias , Cardiomiopatia Hipertrófica , Células-Tronco Pluripotentes Induzidas , Criança , Feminino , Humanos , Cálcio/metabolismo , Miosinas Cardíacas/genética , Miosinas Cardíacas/metabolismo , Cardiomiopatias/metabolismo , Cardiomiopatia Hipertrófica/genética , Cardiomiopatia Hipertrófica/patologia , Hipertrofia/metabolismo , Hipertrofia/patologia , Células-Tronco Pluripotentes Induzidas/metabolismo , Mutação/genética , Miócitos Cardíacos/metabolismo , Miofibrilas/metabolismo , Miofibrilas/patologia , Cadeias Pesadas de Miosina/genética , Cadeias Pesadas de Miosina/metabolismo
16.
JACC Asia ; 3(5): 790-801, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38095000

RESUMO

Background: Data on the performance of risk scores in predicting mortality risk after atrial fibrillation (AF) ablations are limited. Objectives: The purpose of this study was to investigate the associations of mortality with preablation biomarkers and evaluate the performance of age, biomarker, and clinical history (ABC)-death score in patients with AF undergoing catheter ablation. Methods: Patients with AF undergoing catheter ablations between 2013 and 2019 in the Chinese Atrial Fibrillation Registry were enrolled. Biomarkers associated with ABC-death score were quantified from baseline blood samples collected before AF ablation. Clinical outcomes were all-cause mortality and cardiac mortality. Discrimination, reclassification, clinical use, and calibration were further evaluated. Results: We identified 4,218 patients with AF undergoing catheter ablations. During a median follow-up period of 4.0 years, 119 patients died due to all causes, with 49 dying due to cardiac causes. Biomarker levels were all independently associated with an increased risk of all-cause death and cardiac death. The ABC-death score was superior to the CHA2DS2-VASc score in predicting all-cause death (C index 0.73 vs 0.63; P = 0.001) and cardiac death (C index 0.83 vs 0.71; P = 0.007). Reclassification analysis revealed significant reclassification improvements of the ABC-death score compared with the CHA2DS2-VASc (cardiac failure or dysfunction, hypertension, age ≥75 [doubled], diabetes mellitus, stroke [doubled]-vascular disease, age 65 to 74 years and sex category [female]) score. Decision curve analysis showed the greater net benefit of use of the ABC-death score. Calibration plots presented an overestimation of the observed mortality event rate by ABC-death score. Conclusions: Preablation biomarkers associated with ABC-death score were independently related to increased all-cause and cardiac mortality risk. Despite the overestimation of the event rate, the ABC-death score outperformed the CHA2DS2-VASc score in discriminating and reclassifying mortality risk, especially for cardiac mortality.

17.
J Multidiscip Healthc ; 16: 3873-3885, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38084122

RESUMO

Objective: To describe the effects of various fluid strategies on mechanical ventilation time and other outcomes in patients with diastolic dysfunction undergoing non-cardiac surgery. Methods: After evaluation, 192 Intensive Care patients met the inclusion criteria. Based on infusion volume and fluid balance, we categorized patients into quartiles using two grouping methodologies. The first quartiles for total infusion volume on day one of ICU admission after surgery were as follows: Q1 ≤ 2.02 mL/kg/h; Q2 > 2.02 to 2.69 mL/kg/h; Q3 > 2.69 to 3.86 mL/kg/h; Q4 > 3.86 mL/kg/h. The second quartiles for fluid balance divided by actual body weight multiplied by the corresponding number of hours were as follows: G1 ≤ -0.07 mL/kg/h; G2 > -0.07 to 0.56 mL/kg/h; G3 > 0.56 to 1.54 mL/kg/h; G4>1.54 mL/kg/h. The primary outcome was mechanical ventilation time. The research utilized both univariate and multivariate negative binomial regression models. Results: The fourth group (Q4 and G4) had a significant impact on mechanical ventilation time(P<0.05).There were also significant differences between Q4 or G4 and some other groups in terms of ICU time, ICU cost, total hospital time, and total hospital cost (P < 0.05).After negative binomial regression analysis,Q2 and Q4 were approximately 2.406 times (95% CI 1.153-5.017, P = 0.019) and 3.532 times (95% CI 1.812-6.883, P < 0.01) longer than Q1 respectively, when grouped by infusion volume, but there was no significant difference between G groups. And Q4 or G4 also differed significantly from other parameters of clinical outcomes (P < 0.05). Conclusion: For patients admitted to the ICU following non-cardiac surgery with left ventricular diastolic dysfunction, the greater the fluid infusion or fluid balance, the greater the mechanical ventilation time, ICU or hospital time, and cost.

18.
J Am Heart Assoc ; 12(24): e031269, 2023 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-38084708

RESUMO

BACKGROUND: The association between sodium-glucose cotransporter 2 inhibitors (SGLT2i) and atrial fibrillation (AF) recurrence after catheter ablation among patients with diabetes and AF remains unclear. METHODS AND RESULTS: Patients with AF undergoing initial catheter ablation with a history of diabetes from the China AF registry were included. Patients using SGLT2i were identified and matched by propensity score with non-SGLT2i patients in a 1:3 ratio. The main outcome was AF recurrence during the 18-month follow-up. A total of 138 patients with diabetes with SGLT2i therapy and 387 without SGLT2i were analyzed. AF recurrence occurred in 37 patients (26.8%) in the SGLT2i group and 152 patients (39.3%) in the non-SGLT2i group during a total of 593.3 person-years follow-up. The SGLT2i group was associated with lower AF recurrence compared with the non-SGLT2i group (hazard ratio, 0.63 [95% CI, 0.44-0.90], P=0.007). A total of 4 studies were analyzed in our meta-analysis demonstrating that SGLT2i was associated with lower AF recurrence after catheter ablation (odds ratio, 0.61 [95% CI, 0.54-0.69]; P<0.001, I2=0.0%). CONCLUSIONS: Our prospective study coupled with a meta-analysis demonstrated a lower risk of AF recurrence with the use of SGLT2i among patients with diabetes after AF ablation.


Assuntos
Fibrilação Atrial , Ablação por Cateter , Diabetes Mellitus , Humanos , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/cirurgia , Fibrilação Atrial/complicações , Pontuação de Propensão , Estudos Prospectivos , Fatores de Risco , Resultado do Tratamento , Recidiva , Diabetes Mellitus/etiologia , Ablação por Cateter/efeitos adversos , Ablação por Cateter/métodos , Glucose , Sódio
19.
Circ J ; 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37914274

RESUMO

BACKGROUND: Epicardial adipose tissue (EAT) is recognized as a clinical diagnostic marker for cardiometabolic disease. Thicker EAT may be associated with recurrence of ventricular tachycardia after ablation. The association between EAT volume and recurrence of premature ventricular complexes (PVC) following ablation has not been clarified. We investigated the association between EAT volume and PVC recurrence following radiofrequency catheter ablation.Methods and Results: This retrospective study included 401 patients with PVC undergoing catheter ablation with preprocedural non-contrast computed tomography between 2017 and 2022. The impact of EAT volume in predicting PVC recurrence after ablation was analyzed. The mean (±SD) age of patients was 50.2±13.3 years. Multivariable Cox analysis revealed that a large EAT volume was an independent predictor of PVC recurrence after ablation during a median follow-up of 16.3 months. Kaplan-Meier analysis showed a difference in postablation PVC recurrence between the 2 groups dichotomized around the EAT volume cut-off. The risk of recurrence increased with increasing EAT volume according to restricted cubic spline regression. Furthermore, PVC originating from epicardial locations had larger EAT volumes than those originating from the right ventricular outflow tract. CONCLUSIONS: A large EAT volume was independently associated with PVC recurrence following ablation. Patients with PVC originating from epicardial sites had large EAT volumes. EAT volume may help stratify patients according to their risk of PVC recurrence after ablation.

20.
J Geriatr Cardiol ; 20(10): 707-715, 2023 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-37970223

RESUMO

BACKGROUND: Patients with atrial fibrillation (AF) and prior stroke history have a high risk of cardiovascular events despite anticoagulation therapy. It is unclear whether catheter ablation (CA) has further benefits in these patients. METHODS: AF patients with a previous history of stroke or systemic embolism (SE) from the prospective Chinese Atrial Fibrillation Registry study between August 2011 and December 2020 were included in the analysis. Patients were matched in a 1:1 ratio to CA or medical treatment (MT) based on propensity score. The primary outcome was a composite of all-cause death or ischemic stroke (IS)/SE. RESULTS: During a total of 4.1 ± 2.3 years of follow-up, the primary outcome occurred in 111 patients in the CA group (3.3 per 100 person-years) and in 229 patients in the MT group (5.7 per 100 person-years). The CA group had a lower risk of the primary outcome compared to the MT group [hazard ratio (HR) = 0.59, 95% CI: 0.47-0.74, P < 0.001]. There was a significant decreasing risk of all-cause mortality (HR = 0.43, 95% CI: 0.31-0.61, P < 0.001), IS/SE (HR = 0.73, 95% CI: 0.54-0.97, P = 0.033), cardiovascular mortality (HR = 0.32, 95% CI: 0.19-0.54, P < 0.001) and AF recurrence (HR = 0.33, 95% CI: 0.30-0.37, P < 0.001) in the CA group compared to that in the MT group. Sensitivity analysis generated consistent results when adjusting for time-dependent usage of anticoagulants. CONCLUSIONS: In AF patients with a prior stroke history, CA was associated with a lower combined risk of all-cause death or IS/SE. Further clinical trials are warranted to confirm the benefits of CA in these patients.

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