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Catheter ablation (CA) is an essential method for the interventional treatment of atrial fibrillation (AF), and it is very important to reduce long-term recurrence after CA. The mechanism of recurrence after CA is still unclear. We established a long-term model of beagle canines after circumferential pulmonary vein ablation (CPVA). The transcriptome and proteome were obtained using high-throughput sequencing and TMT-tagged LC-MS/LC analysis, respectively. Differentially expressed genes and proteins were screened and enriched, and the effect of fibrosis was found and verified in tissues. A downregulated protein, neuropeptide Y (NPY), was selected for validation and the results suggest that NPY may play a role in the long-term reinduction of AF after CPVA. Then, the molecular mechanism of NPY was further investigated. The results showed that the atrial effective refractory period (AERP) was shortened and fibrosis was increased after CPVA. Atrial myocyte apoptosis was alleviated by NPY intervention, and Akt activation was inhibited in cardiac fibroblasts. These results suggest that long-term suppression of NPY after CPVA may lead to induction of AF through promoting cardiomyocyte apoptosis and activating the Akt pathway in cardiac fibroblasts, which may make AF more likely to reinduce.
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Apoptose , Fibrilação Atrial , Ablação por Cateter , Miocárdio , Neuropeptídeo Y , Veias Pulmonares , Animais , Cães , Apoptose/efeitos dos fármacos , Fibrilação Atrial/metabolismo , Fibrilação Atrial/cirurgia , Fibrilação Atrial/patologia , Ablação por Cateter/métodos , Modelos Animais de Doenças , Fibrose , Átrios do Coração/metabolismo , Átrios do Coração/patologia , Multiômica , Miocárdio/metabolismo , Miocárdio/patologia , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/patologia , Neuropeptídeo Y/metabolismo , Proteoma/metabolismo , Proteômica/métodos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Veias Pulmonares/metabolismo , Veias Pulmonares/cirurgia , TranscriptomaRESUMO
OBJECTIVE: The purpose of this study was to assess the utility of information generated by ChatGPT for residency education in China. METHODS: We designed a three-step survey to evaluate the performance of ChatGPT in China's residency training education including residency final examination questions, patient cases, and resident satisfaction scores. First, 204 questions from the residency final exam were input into ChatGPT's interface to obtain the percentage of correct answers. Next, ChatGPT was asked to generate 20 clinical cases, which were subsequently evaluated by three instructors using a pre-designed Likert scale with 5 points. The quality of the cases was assessed based on criteria including clarity, relevance, logicality, credibility, and comprehensiveness. Finally, interaction sessions between 31 third-year residents and ChatGPT were conducted. Residents' perceptions of ChatGPT's feedback were assessed using a Likert scale, focusing on aspects such as ease of use, accuracy and completeness of responses, and its effectiveness in enhancing understanding of medical knowledge. RESULTS: Our results showed ChatGPT-3.5 correctly answered 45.1% of exam questions. In the virtual patient cases, ChatGPT received mean ratings of 4.57 ± 0.50, 4.68 ± 0.47, 4.77 ± 0.46, 4.60 ± 0.53, and 3.95 ± 0.59 points for clarity, relevance, logicality, credibility, and comprehensiveness from clinical instructors, respectively. Among training residents, ChatGPT scored 4.48 ± 0.70, 4.00 ± 0.82 and 4.61 ± 0.50 points for ease of use, accuracy and completeness, and usefulness, respectively. CONCLUSION: Our findings demonstrate ChatGPT's immense potential for personalized Chinese medical education.
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BACKGROUND: Autoimmune disorder is the emerging mechanism of atrial fibrillation (AF). The ß1-adrenergic receptor antibody (ß1-AAb) is associated with AF progress. Our study aims to investigate whether ß1-AAbs involves in atrial vulnerable substrate by mediating Ca2+ mishandling and atrial fibrosis in autoimmune associated AF. METHODS: Active immunization models were established via subcutaneous injection of the second extracellular loop (ECL2) peptide for ß1 adrenergic receptor (ß1AR). Invasive electrophysiologic study and ex vivo optical mapping were used to evaluate the changed electrophysiology parameters and calcium handling properties. Phospho-proteomics combined with molecular biology assay were performed to identify the potential mechanisms of remodeled atrial substrate elicited by ß1-AAbs. Exogenous ß1-AAbs were used to induce the cellular phenotypes of HL-1 cells and atrial fibroblasts to AF propensity. RESULTS: ß1-AAbs aggravated the atrial electrical instability and atrial fibrosis. Bisoprolol alleviated the alterations of action potential duration (APD), Ca2+ transient duration (CaD), and conduction heterogeneity challenged by ß1-AAbs. ß1-AAbs prolonged calcium transient refractoriness and promoted arrhythmogenic atrial alternans and spatially discordant alternans, which were partly counteracted through blocking ß1AR. Its underlying mechanisms are related to ß1AR-drived CaMKII/RyR2 activation of atrial cardiomyocytes and the myofibroblasts phenotype formation of fibroblasts. CONCLUSION: Suppressing ß1-AAbs effectively protects the atrial vulnerable substrate by ameliorating intracellular Ca2+ mishandling and atrial fibrosis, preventing the process of the autoimmune associated AF.
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Fibrilação Atrial , Animais , Coelhos , Fibrilação Atrial/genética , Cálcio , Átrios do Coração/patologia , Fibrose , Receptores AdrenérgicosRESUMO
BACKGROUND: Weight-adjusted waist index (WWI) is a new anthropometric indicator to assess adiposity. Current knowledge regarding its association with type 2 diabetes mellitus (T2DM) is limited. This present study aims to evaluate the association of WWI with the risk of T2DM in the Japanese population, and to compare its predictive ability with body mass index (BMI) and waist circumference (WC). METHODS: This was a secondary analysis of a retrospective cohort study involving 15,464 participants. Participants were divided into quartiles based on baseline WWI levels. Cox regression model, Kaplan-Meier curve, and smooth curve fitting were used to explore the relationship between WWI and T2DM. The discriminative ability of obesity indices in predicting T2DM was compared by the receiver operating characteristic (ROC) curve. RESULTS: After a mean follow-up of 6.05 years, 373 participants were diagnosed with T2DM. In fully adjusted models, the risk of incident T2DM was 1.96 times higher for each 1-unit increment in WWI levels (95% CI: 1.61-2.39, P < 0.001). Smooth curve fitting analysis showed a linear positive association between baseline WWI and new-onset T2DM. Subgroup analysis showed consistent results which subjects in the 4th WWI quartile had the highest risk of developing T2DM in different age, gender, and BMI groups. WWI did not exhibit better predictive ability compared with BMI and WC in the results of ROC curve. CONCLUSION: WWI, a new metabolic index, can be used to predict new-onset T2DM in the Japanese population. However, its predictive capability was not superior to conventional anthropometric indices.
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Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Fatores de Risco , Estudos Retrospectivos , Antropometria/métodos , Obesidade/diagnóstico , Índice de Massa Corporal , Circunferência da CinturaRESUMO
AIM: Increasing evidence supports the hypothesis that high serum uric acid (SUA) levels are related to atrial fibrillation (AF). However, the incidence of AF in patients with hyperuricemia and SUA levels in different types of AF is not entirely clear. This meta-analysis was designed to evaluate the relationship between SUA and incidence of AF, and the variation in SUA levels in different types of AF. DATA SYNTHESIS: Relevant reports were searched for in Embase, PubMed and the Cochrane Library. A fixed-effects model combining relative risk (RR) and the corresponding 95% confidence interval (95% CI) was used to evaluate the correlation between SUA and AF. The standardized mean differences (SMDs) of SUA values were calculated using a random-effects model to evaluate the differences in SUA levels among different types of AF. A total of 31 studies with 504,958 participants were included in this research. The results from 8 cohort studies showed that high SUA levels significantly increased the incidence of AF [RR (95% CI): 1.92 (1.68-2.20); P < 0.01]. The results from 29 studies revealed that SUA levels elevated in patients with AF [SMD (95% CI): 0.55 (0.43-0.66); P < 0.001]. Meanwhile, SUA levels in new-onset AF [SMD (95%CI): 0.24 (0.10-0.38); P = 0.001], paroxysmal AF [SMD (95%CI): 0.52 (0.33-0.72); P < 0.001] and persistent AF [SMD (95%CI): 1.23 (0.98-1.48); P < 0.001] were significantly higher than that in patients without AF. CONCLUSIONS: High SUA levels had an obvious correlation with the occurrence rate of AF. In addition, SUA levels were significantly different among patients with new-onset, paroxysmal and persistent AF.
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Fibrilação Atrial/fisiopatologia , Frequência Cardíaca , Hiperuricemia/sangue , Ácido Úrico/sangue , Adulto , Idoso , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/epidemiologia , Biomarcadores/sangue , Feminino , Humanos , Hiperuricemia/diagnóstico , Hiperuricemia/epidemiologia , Incidência , Masculino , Pessoa de Meia-Idade , Prognóstico , Medição de Risco , Fatores de Risco , Regulação para CimaRESUMO
BACKGROUND: Cholinergic anti-inflammatory pathway (CAP) is implicated in cardioprotection in chronic heart failure (CHF) by downregulating inflammation response. Mitochondrial injuries play an important role in ventricular remodeling of the CHF process. Herein, we aim to investigate whether CAP elicitation prevents ventricular remodeling in CHF by protecting myocardial mitochondrial injuries and its underlying mechanisms. METHODS AND RESULTS: CHF models were established by ligation of anterior descending artery for 5 weeks. Postoperative survival rats were assigned into 5 groups: the sham group (sham, n = 10), CHF group (CHF, n = 11), Vag group (CHF+vagotomy, n = 10), PNU group (CHF+PNU-282987 for 4 weeks, n = 11), and Vag+PNU group (CHF+vagotomy+PNU-282987 for 4 weeks, n = 10). The antiventricular remodeling effect of cholinergic elicitation was evaluated in vivo, and H9C2 cells were selected for the TNF-α gradient stimulation experiment in vitro. In vivo, CAP agitated by PNU-282987 alleviated the left ventricular dysfunction and inhibited the energy metabolism remodeling. Further, cholinergic elicitation increased myocardium ATP levels and reduced systemic inflammation. CAP induction alleviates macrophage infiltration and cardiac fibrosis, of which the effect is counteracted by vagotomy. Myocardial mitochondrial injuries were ameliorated by CAP activation, including the reserved ultrastructural integrity, declining ROS overload, reduced myocardial apoptosis, and enhanced mitochondrial fusion. In vitro, TNF-α intervention significantly exacerbated the mitochondrial damage in H9C2 cells. CONCLUSION: CAP elicitation effectively improves ischemic ventricular remodeling by suppressing systemic and cardiac inflammatory response, attenuating cardiac fibrosis and potentially alleviating the mitochondrial dysfunction linked to hyperinflammation reaction.
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Insuficiência Cardíaca/etiologia , Inflamação/prevenção & controle , Mitocôndrias Cardíacas/patologia , Isquemia Miocárdica/complicações , Remodelação Ventricular , Receptor Nicotínico de Acetilcolina alfa7/fisiologia , Animais , Benzamidas/farmacologia , Compostos Bicíclicos com Pontes/farmacologia , Doença Crônica , Citocinas/biossíntese , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
BACKGROUND Obesity increases the risk of atrial fibrillation (AF) recurrence after ablation. This study explored the relationship between various obesity indexes and risk of recurrence after cryoablation of paroxysmal AF (PAF). MATERIAL AND METHODS Our prospective study included 100 patients with PAF who underwent first cryoablation. Physical examination and fasting blood lipids levels were measured at baseline. Seven obesity indexes were determined: body mass index (BMI), waist circumference (WC), waist-to-height ratio (WHtR), waist-hip ratio (WHR), cardiometabolic index (CMI), lipid accumulation product (LAP), and body adiposity index (BAI). AF recurrence was confirmed by electrocardiograms and Holter monitor at follow-up visits after the initial 3-month blanking period. Receiver operating characteristic (ROC) curves were drawn to assess the abilities of obesity indicators in predicting AF recurrence. Multivariable Cox regression analysis was used to examine independent predictors of AF recurrence. RESULTS During a mean follow-up of 13.4 months, 31 patients (31.0%) had recurrent AF. Patients with recurrence had higher BMI, WC, WHtR, LAP, and BAI compared with those without recurrence. ROC analysis indicated the potential predictive value of BAI with an AUC of 0.657 (95% confidence interval [CI]: 0.534-0.779), followed by WC, WHtR, LAP, and BMI (all P<0.05). Diagnosis-to-ablation time (HR 1.034, 95% CI: 1.002-1.068), left atrial diameter (HR 1.147, 95% CI: 1.026-1.281), and WC (HR 1.026, 95% CI: 1.000-1.053) were independent predictive factors for AF recurrence after multivariable adjustment. CONCLUSIONS In this study population, WC appears to be a potential indicator for the prediction of recurrence in patients with PAF after cryoablation.
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Fibrilação Atrial/metabolismo , Criocirurgia/efeitos adversos , Obesidade/complicações , Adiposidade/fisiologia , Idoso , Fibrilação Atrial/sangue , Fibrilação Atrial/fisiopatologia , Índice de Massa Corporal , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/fisiopatologia , Estudos Prospectivos , Curva ROC , Recidiva , Fatores de Risco , Circunferência da Cintura , Razão Cintura-Estatura , Relação Cintura-QuadrilRESUMO
BACKGROUND: This study explored the relationships between the low-/high-density lipoprotein cholesterol ratio (LDL-C/HDL-C) and other clinical indicators and ischaemic stroke (IS) in patients with non-valvular atrial fibrillation (NVAF) in Xinjiang. The findings could provide a theoretical and therapeutic basis for NVAF patients. METHODS: NVAF patients who were admitted to 10 medical centres across Xinjiang were divided into stroke (798 patients) and control (2671 patients) groups according to the occurrence of first acute IS. Univariate and multivariate logistic regression analysis were used to examine the independent risk factors for IS in NVAF patients. Factor analysis and principal component regression analysis were used to analyse the main factors influencing IS. Receiver operating characteristic (ROC) curve analysis was used to evaluate the discriminatory ability of LDL-C/HDL-C for predicting the occurrence of IS. RESULTS: The stroke group had an average age of 71.64 ± 9.96 years and included 305 females (38.22%). The control group had a mean age of 67.30 ± 12.01 years and included 825 females (30.89%). Multivariate logistic regression showed that the risk of IS in the highest LDL-C/HDL-C quartile (≥2.73) was 16.23-fold that of the lowest quartile (< 1.22); IS risk was 2.27-fold higher in obese patients than in normal-weight subjects; IS risk was 3.15-fold higher in smoking patients than in non-smoking patients. The area under the ROC curve of LDL-C/HDL-C was 0.76, the optimal critical value was 2.33, the sensitivity was 63.53%, and the specificity was 76.34%. Principal component regression analysis showed that LDL-C/HDL-C, age, smoking, drinking, LDL-C and hypertension were risk factors for IS in NVAF patients. CONCLUSIONS: LDL-C/HDL-C > 1.22, smoking, BMI ≥24 kg/m2 and CHA2DS2-VASc score were independent risk factors for IS in NVAF patients; LDL-C/HDL-C was the main risk factor.
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Fibrilação Atrial/epidemiologia , AVC Isquêmico/epidemiologia , Obesidade/epidemiologia , Idoso , Fibrilação Atrial/sangue , Fibrilação Atrial/complicações , Fibrilação Atrial/patologia , Estudos de Casos e Controles , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Feminino , Humanos , AVC Isquêmico/sangue , AVC Isquêmico/complicações , AVC Isquêmico/patologia , Masculino , Obesidade/sangue , Obesidade/complicações , Obesidade/patologia , Fatores de RiscoRESUMO
BACKGROUND: Beta-1-adrenergic receptor antibodies (ß1-AAbs) function as arrhythmogenic molecules in autoimmune-related atrial fibrillation (AF). This study examined the potential impact of pioglitazone, an agonist for peroxisome proliferator-activated receptor-γ (PPAR-γ), on atrial remodeling induced by ß1-AAbs. METHODS: An in vivo study was performed to confirm the protective effects of pioglitazone on ß1- AAbs-induced atrial remodeling. GW9662, a PPAR-γ antagonist, was employed to identify the potential therapeutic target of pioglitazone. The rats were administered subcutaneous injections of the second extracellular loop peptide for 8 weeks to establish active immunization models. Pioglitazone was then administered orally for 2 weeks. Epicardial electrophysiologic studies, multielectrode array measurements, and echocardiography were conducted to examine atrial remodeling. Glucose metabolism products and key metabolic molecules were measured to evaluate the atrial substrate metabolism. Mitochondrial morphologies and function indices were tested to depict the underlying links between atrial metabolism and mitochondrial homeostasis under the pioglitazone treatment. RESULTS: Pioglitazone significantly reversed ß1-AAbs-induced AF susceptibility, ameliorated atrial structural remodeling, decreased the global insulin resistance reflected in the plasma glucose and insulin levels, and increased the protein expressions of glycolipid uptake and transportation (GLUT1, CD36, and CPT1a). These trends were counterbalanced by the GW9662 intervention. Mechanistically, pioglitazone mitigated the atrial mitochondrial network damage and partly renovated the mitochondrial biogenesis, even the mitochondrial dynamics, which were reversed by inhibiting the PPAR-γ target. CONCLUSION: Pioglitazone effectively reduced the AF vulnerability and recovered the atrial myocardial metabolism and mitochondrial damage. The potential anti-remodeling effect of pioglitazone on the atrium was associated with the moderately increased expression of key membrane proteins related to glucose transporter and fatty acid uptake, which may promote the increased myocardial preference for utilization of FA as the key cardiac oxidative fuel and ameliorate the atrial metabolic inflexibility.
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Background and aims: Studies showed that elevated preoperative serum uric acid(SUA) levels are associated with recurrence of atrial fibrillation(AF) after catheter ablation. UA:creatinine ratio(UCR - UA normalised for renal function) has appeared as a new biomarker and is considered to reflect endogenous UA levels preferably because it eliminates the influence of renal function. This study aimed to investigate the correlation between UCR and recurrence of AF after catheter ablation. Methods and results: A total of 233 consecutive patients with symptomatic, drug-refractory AF underwent catheter ablation. All participants underwent history-taking, physical examination and blood biochemistry analysis at baseline. After a mean follow-up of 23.99 ± 0.76 months, recurrence ratios for each UCR quartile (from lowest quartile to highest) were 10.9%, 23.6%, 23.6%, and 41.8%, respectively (P = 0.005). Multivariate Cox regression analysis revealed that UCR was an independent predictor of AF recurrence (HR 1.217, 95%CI 1.008-1.468; P = 0.041). Subgroup analysis showed that UCR was associated with AF recurrence in paroxysmal AF (HR 1.426, 95% CI 1.092-1.8608; P = 0.009) and in male patients (HR 1.407, 95% CI 1.015-1.950; P = 0.04). A cut-off point of 4.475 for the UCR had sensitivity of 65.5% and specificity of 59.6% in predicting AF recurrence (P = 0.001). Conclusion: Our results demonstrate that elevated preoperative UCR is associated with recurrence of AF after catheter ablation, and it indicate UCR maybe a predictive factor for the recurrence of AF.
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Fibrilação Atrial , Ablação por Cateter , Humanos , Masculino , Fibrilação Atrial/cirurgia , Ácido Úrico , Creatinina , Resultado do Tratamento , Fatores de Risco , Ablação por Cateter/efeitos adversos , Ablação por Cateter/métodosRESUMO
Atrial fibrillation (AF) and subsequent stroke and death have become major public health problems in China. Oral anticoagulant (OAC) forms the backbone of prevention of AF-related stroke. However, the quality of OAC use in AF patients in China is not clear. The focus of this narrative review is to summarize the current status of OAC therapy in China and compare it with the studies conducted internationally. In general, most data of OAC use in China were reported around 10-50%, with an increasing proportion of high-risk patients receiving OACs, however, still much lower than those in other countries and regions. Moreover, the phenomenon of inappropriate OAC prescribing and poor long-term persistence and adherence with OAC therapy in AF patients in China have also been noted. The 1-year adherence and persistence of OACs are as low as 50%. Multiple factors from the physicians, patients, and OAC drugs contribute to these phenomena. The management of OACs in AF patients in China needs to be further improved by the joint efforts of healthcare administration (policy makers) and health systems including medical associations, hospitals, and physicians.
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Fibrilação Atrial , Acidente Vascular Cerebral , Humanos , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/induzido quimicamente , Anticoagulantes/uso terapêutico , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/prevenção & controle , Administração Oral , Fatores de RiscoRESUMO
BACKGROUND: Obesity is a well-known risk factor for type 2 diabetes mellitus (T2DM). Studies have shown that the Chinese visceral adiposity index (CVAI), a novel visceral adiposity indicator, is positive associated with the risk of T2DM in the Chinese population. This study aimed to investigate the correlation between CVAI and incident T2DM in a Japanese population. METHODS: We performed a secondary analysis of open-access data from a retrospective cohort study. This study included 15,464 participants who received regular medical examinations at Murakami Memorial Hospital. All participants underwent a questionnaire survey, physical examination, and blood biochemical testing at baseline. The main outcome was new-onset T2DM during follow-up. Cox regression analysis and Kaplan-Meier analysis were used to analyze the risk of CVAI on T2DM, and we conducted smooth curve fitting. Receiver operating characteristic (ROC) curve analysis was performed to assess the predictive value of CVAI, body mass index (BMI), and waist circumference (WC) for incident T2DM. RESULTS: During a median follow-up time of 5.39 years, 373 new-onset T2DM events were observed. Kaplan-Meier curves showed that the incidence of T2DM increased as the CVAI increased (log-rank χ 2 = 187.1076 and 129.6067 in males and females, respectively, both P <0.001). After adjustment for covariates, per 1 increase of CVAI was associated with a 1.0133-fold and 1.0246-fold higher risk of incident T2DM in males and females, respectively (both P <0.001). Those individuals in the top CVAI quartile group had the highest risk of new-onset T2DM (HR = 3.1568 and 5.8415 in males and females, respectively, both P <0.05). A nonlinear relationship was identified by the smooth fitting curve between CVAI and T2DM events in both genders. ROC analysis indicated that CVAI had better predictive power than BMI and WC in both genders. CONCLUSION: Our results demonstrate that CVAI was significantly associated with an increased risk of new-onset T2DM in Japanese adults.
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Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia worldwide and results in a significantly increased ischemic stroke (IS) risk. IS risk stratification tools are widely being applied to guide anticoagulation treatment decisions and duration in patients with non-valvular AF (NVAF). The CHA2DS2-VASc score is largely validated and currently recommended by renowned guidelines. However, this score is heavily dependent on age, sex, and comorbidities, and exhibits only moderate predictive power. Finding effective and validated clinical biomarkers to assist in personalized IS risk evaluation has become one of the promising directions in the prevention and treatment of NVAF. A number of studies in recent years have explored differentially expressed biomarkers in NVAF patients with and without IS, and the potential role of various biomarkers for prediction or early diagnosis of IS in patients with NVAF. In this review, we describe the clinical application and utility of AF characteristics, cardiac imaging and electrocardiogram markers, arterial stiffness and atherosclerosis-related markers, circulating biomarkers, and novel genetic markers in IS diagnosis and management of patients with NVAF. We conclude that at present, there is no consensus understanding of a desirable biomarker for IS risk stratification in NVAF, and enrolling these biomarkers into extant models also remains challenging. Further prospective cohorts and trials are needed to integrate various clinical risk factors and biomarkers to optimize IS prediction in patients with NVAF. However, we believe that the growing insight into molecular mechanisms and in-depth understanding of existing and emerging biomarkers may further improve the IS risk identification and guide anticoagulation therapy in patients with NVAF.
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RATIONALE: Long QT syndrome (LQTS) is an inheritable disease characterized by prolonged QT interval on the electrocardiogram. The pathogenesis of LQTS is related to mutations in LQTS-susceptible genes encoding cardiac ion channel proteins or subunits. PATIENT CONCERNS: Here, we reported a 37-year-old female Uygur patient with palpitation and loss of consciousness. DIAGNOSES: At the time of admission, a 12-lead electrocardiogram showed a QTc interval of 514âms. Genetic analysis revealed KCNQ1 G219E and TRPM4 T160M mutations. INTERVENTIONS: Although beta-blockers remain the mainstay in treating LQTS, the patient underwent implantation of an automatic cardioverter defibrillator due to life-threatening arrhythmias. OUTCOMES: To explore the effect of the calcium ion antagonist verapamil on ion channels, we generated human induced pluripotent stem cell cardiomyocytes (hiPSC-CMs) from the peripheral blood mononuclear cells of the patient. The changes of action potential duration in response to verapamil were observed. LESSONS: Our results showed that patient-derived hiPSC-CMs could recapitulate the electrophysiological features of LQTS and display pharmaceutical responses to verapamil.
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Canal de Potássio KCNQ1/genética , Síndrome do QT Longo/genética , Canais de Cátion TRPM/genética , Adulto , Bloqueadores dos Canais de Cálcio/farmacologia , Desfibriladores Implantáveis , Feminino , Humanos , Células-Tronco Pluripotentes Induzidas/efeitos dos fármacos , Síndrome do QT Longo/cirurgia , Verapamil/farmacologiaRESUMO
BACKGROUND AND AIM: Currently, the number of patients with coronavirus disease 2019 (COVID-19) infection is increasing rapidly worldwide. In this study, we aimed to assess whether diabetes mellitus (DM) would increase the risk of severe infection and death in patients with COVID-19. METHODS: We systematically searched the PubMed, Web of Science, MedRxiv and COVID-19 academic research communication platform for studies reporting clinical severity and/or overall mortality data on DM in patients with COVID-19 published up to July 10, 2020. The primary outcome was to compare the severe infection rate and mortality rate in COVID-19 patients with and without DM, and to calculate the odds ratio (OR) and 95% confidence interval (CI). RESULTS: A total of 76 studies involving 31,067 patients with COVID-19 were included in our meta-analysis. COVID-19 patients with DM had higher severe infection and case-mortality rates compared with those without DM (21.4 vs. 10.6% and 28.5 vs. 13.3%, respectively, all p <0.01). COVID-19 patients with DM were at significantly elevated risk of severe infection (OR = 2.38, 95% CI: 2.05-2.78, p <0.001) and mortality (OR = 2.21, 95% CI: 1.83-2.66, p <0.001). CONCLUSION: DM is associated with increased risk of severe infection and higher mortality in patients with COVID-19. Our study suggests that clinicians should pay more attention to the monitoring and treatment of COVID-19 patients with DM.
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COVID-19 , Complicações do Diabetes , COVID-19/complicações , COVID-19/epidemiologia , COVID-19/mortalidade , Complicações do Diabetes/complicações , Complicações do Diabetes/epidemiologia , Diabetes Mellitus/epidemiologia , Humanos , SARS-CoV-2RESUMO
OBJECTIVE: Beta 1-adrenergic receptor autoantibodies (ß1ARAbs) have been identified as a pathogenic factor in atrial fibrillation (AF), but the underlying pathogenetic mechanism is not well understood. We assessed the hypothesis that elevated ß1ARAb levels increase AF susceptibility by promoting atrial fibrosis. METHODS: A total of 70 patients with paroxysmal AF were continuously recruited. The serum levels of ß1ARAb and circulating fibrosis biomarkers were analyzed by ELISA. Linear regression was used to examine the correlations of ß1ARAb levels with left atrial diameter (LAD) and circulating fibrosis biomarker levels. Furthermore, we established a rabbit ß1ARAb overexpression model. We conducted electrophysiological studies and multielectrode array recordings to evaluate the atrial effective refractory period (AERP), AF inducibility and electrical conduction. AF was defined as irregular, rapid atrial beats > 500 bpm for > 1000 ms. Echocardiography, hematoxylin and eosin staining, Masson's trichrome staining, and picrosirius red staining were performed to evaluate changes in atrial structure and detect fibrosis. Western blotting and PCR were used to detect alterations in the protein and mRNA expression of TGF-ß1, collagen I and collagen III. RESULTS: Patients with a LAD ≥ 40 mm had higher ß1ARAb levels than patients with a smaller LAD (8.87 ± 3.16 vs. 6.75 ± 1.34 ng/mL, P = 0.005). ß1ARAb levels were positively correlated with LAD and circulating biomarker levels (all P < 0.05). Compared with the control group, the rabbits in the immune group showed the following: (1) enhanced heart rate, shortened AERP (70.00 ± 5.49 vs. 96.46 ± 3.27 ms, P < 0.001), increased AF inducibility (55% vs. 0%, P < 0.001), decreased conduction velocity and increased conduction heterogeneity; (2) enlarged LAD and elevated systolic dysfunction; (3) significant fibrosis in the left atrium identified by Masson's trichrome staining (15.17 ± 3.46 vs. 4.92 ± 1.72%, P < 0.001) and picrosirius red staining (16.76 ± 6.40 vs. 4.85 ± 0.40%, P < 0.001); and (4) increased expression levels of TGF-ß1, collagen I and collagen III. CONCLUSION: Our clinical and experiential studies showed that ß1ARAbs participate in the development of AF and that the potential mechanism is related to the promotion of atrial fibrosis.
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OBJECTIVE: The aim of this study was to assess the association between CHA2DS2-VASc score and carotid plaques in patients with non-valvular atrial fibrillation (NVAF). METHODS: We conducted a retrospective study including 3,435 NVAF patients who underwent carotid ultrasound examinations from January 2015 to December 2017.We collected the clinical data on the medical records system. Chi-square trend test was used to analyze trends between the prevalence of carotid plaques with an increasing CHA2DS2-VASc score. Univariate and multivariate logistic regression was also used to assess the association between carotid plaques and CHA2DS2-VASc scores. The area under the receiver operating characteristic (ROC) curve (AUC) was used to determine the optimal cutoff points of different CHA2DS2-VASc scores in NVAF patients. RESULTS: NVAF patients with carotid plaques had higher CHA2DS2-VASc scores compared with patients who did not have carotid plaques (3.01±1.36 vs. 2.55±1.28, P < 0.05). In all participants, male participants and female participants, the prevalence of carotid plaques increased significantly as the CHA2DS2-VASc score increased (P for trend < 0.001). Multivariate logistic regression analysis demonstrated that for each 1-point increase in the CHA2DS2-VASc score, there was an associated 37% increase in the prevalence of carotid plaques. ROC curve analysis revealed that a CHA2DS2-VASc score ≥ 2 in male patients (sensitivity, 44.67%; specificity, 75.64%; AUC, 0.639) or ≥ 3 in female patients (sensitivity, 47.24%; specificity, 72.40%; AUC, 0.634) were associated with carotid plaques. CONCLUSION: The prevalence of carotid plaques in patients with NVAF was associated with the CHA2DS2-VASc score.
Assuntos
Fibrilação Atrial , Doenças das Artérias Carótidas , Placa Aterosclerótica , Idoso , Fibrilação Atrial/complicações , Fibrilação Atrial/diagnóstico por imagem , Fibrilação Atrial/epidemiologia , Doenças das Artérias Carótidas/complicações , Doenças das Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Placa Aterosclerótica/complicações , Placa Aterosclerótica/diagnóstico por imagem , Placa Aterosclerótica/epidemiologia , Prevalência , Estudos Retrospectivos , Fatores Sexuais , UltrassonografiaRESUMO
BACKGROUND: Little is known about the risk factors for sudden cardiac death (SCD) in the overall hospitalized cardiac department population. This study was conducted to investigate the risk factors and develop a predictive model for SCD in a hospitalized cardiac department population. METHODS: We conducted a retrospective study of patients admitted to the cardiac department of the First Affiliated Hospital of Xinjiang Medical University from June 2015 to February 2017. We collected the clinical data from medical records. Multiple stepwise logistic regression analysis was carried out to confirm the risk factors for SCD and develop a predictive risk model. The risk score was assessed by the area under receiver operating characteristic (AUROC) curve and the Hosmer-Lemeshow goodness-of-fit test. RESULTS: A total of 262 patients with SCD and 4485 controls were enrolled in our study. Logistic regression modeling identified eight significant risk factors for in-hospital SCD: age, main admitting diagnosis, diabetes, corrected QT interval, QRS duration, ventricular premature beat burden, left ventricular ejection fraction, and estimated glomerular filtration rate. A predictive risk score including these variables showed an AUROC curve of 0.774 (95% confidence interval: 0.744-0.805). The Hosmer-Lemeshow goodness-of-fit test showed the chi-square value was 2.527 (Pâ=â0.640). The incidence of in-hospital SCD was 1.3%, 4.1%, and 18.6% for scores of 0 to 2, 3 to 5 and ≥6, respectively (Pâ<â0.001). CONCLUSIONS: Age, main admitting diagnosis, diabetes, QTc interval, QRS duration, ventricular premature beat burden, left ventricular ejection fraction, and estimated glomerular filtration rate are factors related to in-hospital SCD in a hospitalized cardiac department population. We developed a predictive risk score including these factors that could identify patients who are predisposed to in-hospital SCD.
Assuntos
Morte Súbita Cardíaca/epidemiologia , Pacientes Internados/estatística & dados numéricos , Idoso , Eletrocardiografia , Feminino , Taxa de Filtração Glomerular , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Fatores de RiscoRESUMO
BACKGROUND: Growing evidence suggests that second-generation cryoballoon ablation (2G-CB) is effective in patients with persistent atrial fibrillation (PerAF). The cornerstone of atrial fibrillation (AF) ablation is pulmonary vein isolation (PVI). The purpose of this study was to summarize the available data on the safety and mid-term (≥ 12 months) effectiveness of a 'PVI-only' strategy vs. a 'PVI-plus' strategy using 2G-CB in patients with PerAF. METHODS: We searched the PubMed, EMBASE and Cochrane library databases for studies on 2G-CB for PerAF. Group analysis was based on the ablation approach: 'PVI-only' versus 'PVI-plus', the latter of which involved PVI plus other substrate modifications. Studies showing clinical success rates at a follow-up (FU) of ≥ 12 months were included. Complication rates were also assessed. Data were analyzed by applying a fixed effects model. RESULTS: A total of 879 patients from 5 studies were analyzed. After a mid-term FU of 27 months, the overall success rate of 2G-CB for PerAF was 66.1%. In the 'PVI-plus' group, the success rate was 73.8%. In the 'PVI-only' group, the success rate was 53.6%. No heterogeneity was noted among studies (I2 = 0.0%, P = 0.82). Complications occurred in 5.2% of patients (P = 0.93), and the rate of phrenic nerve (PN) injury was 2.8% (P = 0.14). Vascular assess complications were the most frequent at 1.6% (P = 0.33). No death or myocardial infarction was reported. CONCLUSION: 'PVI-plus' involving 2G-CB seems to be safe and effective for treating PerAF.