[Retracted] Exogenous hydrogen sulfide protects against high glucose­induced apoptosis and oxidative stress by inhibiting the STAT3/HIF­1α pathway in H9c2 cardiomyocytes.

[This retracts the article DOI: 10.3892/etm.2019.8036.].

The correlation between gut microbiome and atrial fibrillation: pathophysiology and therapeutic perspectives.

Regulation of gut microbiota and its impact on human health is the theme of intensive research. The incidence and prevalence of atrial fibrillation (AF) are continuously escalating as the global population ages and chronic disease survival rates increase; however, the mechanisms are not entirely clarified. It is gaining awareness that alterations in the assembly, structure, and dynamics of gut microbiota are intimately engaged in the AF progression. Owing to advancements in next-generation sequencing technologies and computational strategies, researchers can explore novel linkages with the genomes, transcriptomes, proteomes, and metabolomes through parallel meta-omics approaches, rendering a panoramic view of the culture-independent microbial investigation. In this review, we summarized the evidence for a bidirectional correlation between AF and the gut microbiome. Furthermore, we proposed the concept of "gut-immune-heart" axis and addressed the direct and indirect causal roots between the gut microbiome and AF. The intricate relationship was unveiled to generate innovative microbiota-based preventive and therapeutic interventions, which shed light on a definite direction for future experiments.

Valor do Diâmetro do Átrio Esquerdo com Escore CHA2DS2-Vasc na Predição da Trombose Atrial Esquerda/Trombose de Apêndice Atrial Esquerdo na Fibrilação Atrial Não Valvar / Value of left atrial diameter with CHA2DS2-VASc score in predicting left atrial/left atrial appendage thrombosis in non-valvular atrial fibrillation

Resumo Fundamentos A fibrilação atrial é a arritmia persistente mais comum e é o principal fator que leva ao tromboembolismo. Objetivo Investigar o valor do diâmetro do átrio esquerdo combinado com o escore CHA2DS2-VASc na predição da trombose atrial esquerda/trombose de apêndice atrial esquerdo na fibrilação atrial não valvar. Métodos Trata-se de estudo retrospectivo. 238 pacientes com fibrilação atrial não valvar foram selecionados e divididos em dois grupos: trombose e não trombose. Determinou-se o escore CHA2DS2-VASc. Valores de p<0,05 foram considerados estatisticamente significativos. Resultados A análise de regressão logística multivariada revelou que histórico de acidente vascular cerebral/ataque isquêmico transitório, doença vascular, escore CHA2DS2-VASc, DAE, DDFVE e FEVE foram fatores de risco independentes para trombose atrial esquerda/trombose de apêndice atrial esquerdo (p<0,05). A análise da curva ROC ( Receiver Operating Characteristic ) revelou que a área sob a curva para o escore CHA2DS2-VASc na predição de trombose atrial esquerda/trombose de apêndice atrial esquerdo foi de 0,593 quando o escore CHA2DS2-VASc foi ≥3 pontos, e a sensibilidade e especificidade foram 86,5% e 32,6%, respectivamente, enquanto a área sob a curva para o DAE na predição de trombose atrial esquerda/trombose de apêndice atrial esquerdo foi 0,786 quando o DAE foi ≥44,17 mm, e a sensibilidade e especificidade foram 89,6% e 60,9%, respectivamente. Entre os diferentes grupos CHA2DS2-VASc, a taxa de incidência de trombose atrial esquerda/trombose de apêndice atrial esquerdo em pacientes com DAE ≥44,17 mm foi maior do que em pacientes com DAE <44,17 mm (p <0,05). Conclusão O escore CHA2DS2-VASc e o DAE estão correlacionados com a trombose atrial esquerda/trombose de apêndice atrial esquerdo na fibrilação atrial não valvar. Para pacientes com escore CHA2DS2-VASc de 0 ou 1, quando o DAE é ≥44,17 mm, o risco de trombose atrial esquerda/trombose de apêndice atrial esquerdo permaneceu alto. (Arq Bras Cardiol. 2020; [online].ahead print, PP.0-0)

Abstract Background Atrial fibrillation is the most common persistent arrhythmia, and is the main factor that leads to thromboembolism. Objective To investigate the value of left atrial diameter combined with CHA2DS2-VASc score in predicting left atrial/left atrial appendage thrombosis in non-valvular atrial fibrillation. Methods This is a retrospective study. 238 patients with non-valvular atrial fibrillation were selected and divided into two groups: thrombosis and non-thrombosis. CHA2DS2-VASc score was determined. P<0.05 was considered statistically significant. Results Multivariate logistic regression analysis revealed that the history of stroke/transient ischemic attack, vascular disease, CHA2DS2-VASc score, left atrial diameter (LAD), left ventricular end-diastolic dimension (LVEDD) and left ventricular ejection fraction (LVEF) were independent risk factors for left atrial/left atrial appendage thrombosis (p<0.05). Receiver operating characteristic curve analysis revealed that the area under the curve for the CHA2DS2-VASc score in predicting left atrial/left atrial appendage thrombosis was 0.593 when the CHA2DS2-VASc score was ≥3 points, and sensitivity and specificity were 86.5% and 32.6%, respectively, while the area under the curve for LAD in predicting left atrial/left atrial appendage thrombosis was 0.786 when LAD was ≥44.17 mm, and sensitivity and specificity were 89.6% and 60.9%, respectively. Among the different CHA2DS2-VASc groups, the incidence rate of left atrial/left atrial appendage thrombosis in patients with LAD ≥44.17 mm was higher than patients with LAD <44.17 mm (p<0.05). Conclusion CHA2DS2-VASc score and LAD are correlated with left atrial/left atrial appendage thrombosis in non-valvular atrial fibrillation. For patients with a CHA2DS2-VASc score of 0 or 1, when LAD is ≥44.17 mm, the risk for left atrial/left atrial appendage thrombosis remained high. (Arq Bras Cardiol. 2020; [online].ahead print, PP.0-0)

Value of left atrial diameter with CHA2DS2-VASc score in predicting left atrial/left atrial appendage thrombosis in non-valvular atrial fibrillation. / Valor do Diâmetro do Átrio Esquerdo com Escore CHA2DS2-Vasc na Predição da Trombose Atrial Esquerda/Trombose de Apêndice Atrial Esquerdo na Fibrilação Atrial Não Valvar.

BACKGROUND: Atrial fibrillation is the most common persistent arrhythmia, and is the main factor that leads to thromboembolism. OBJECTIVE: To investigate the value of left atrial diameter combined with CHA2DS2-VASc score in predicting left atrial/left atrial appendage thrombosis in non-valvular atrial fibrillation. METHODS: This is a retrospective study. 238 patients with non-valvular atrial fibrillation were selected and divided into two groups: thrombosis and non-thrombosis. CHA2DS2-VASc score was determined. P<0.05 was considered statistically significant. RESULTS: Multivariate logistic regression analysis revealed that the history of stroke/transient ischemic attack, vascular disease, CHA2DS2-VASc score, left atrial diameter (LAD), left ventricular end-diastolic dimension (LVEDD) and left ventricular ejection fraction (LVEF) were independent risk factors for left atrial/left atrial appendage thrombosis (p<0.05). Receiver operating characteristic curve analysis revealed that the area under the curve for the CHA2DS2-VASc score in predicting left atrial/left atrial appendage thrombosis was 0.593 when the CHA2DS2-VASc score was ≥3 points, and sensitivity and specificity were 86.5% and 32.6%, respectively, while the area under the curve for LAD in predicting left atrial/left atrial appendage thrombosis was 0.786 when LAD was ≥44.17 mm, and sensitivity and specificity were 89.6% and 60.9%, respectively. Among the different CHA2DS2-VASc groups, the incidence rate of left atrial/left atrial appendage thrombosis in patients with LAD ≥44.17 mm was higher than patients with LAD <44.17 mm (p<0.05). CONCLUSION: CHA2DS2-VASc score and LAD are correlated with left atrial/left atrial appendage thrombosis in non-valvular atrial fibrillation. For patients with a CHA2DS2-VASc score of 0 or 1, when LAD is ≥44.17 mm, the risk for left atrial/left atrial appendage thrombosis remained high. (Arq Bras Cardiol. 2020; [online].ahead print, PP.0-0).

FUNDAMENTOS: A fibrilação atrial é a arritmia persistente mais comum e é o principal fator que leva ao tromboembolismo. OBJETIVO: Investigar o valor do diâmetro do átrio esquerdo combinado com o escore CHA2DS2-VASc na predição da trombose atrial esquerda/trombose de apêndice atrial esquerdo na fibrilação atrial não valvar. MÉTODOS: Trata-se de estudo retrospectivo. 238 pacientes com fibrilação atrial não valvar foram selecionados e divididos em dois grupos: trombose e não trombose. Determinou-se o escore CHA2DS2-VASc. Valores de p<0,05 foram considerados estatisticamente significativos. RESULTADOS: A análise de regressão logística multivariada revelou que histórico de acidente vascular cerebral/ataque isquêmico transitório, doença vascular, escore CHA2DS2-VASc, DAE, DDFVE e FEVE foram fatores de risco independentes para trombose atrial esquerda/trombose de apêndice atrial esquerdo (p<0,05). A análise da curva ROC ( Receiver Operating Characteristic ) revelou que a área sob a curva para o escore CHA2DS2-VASc na predição de trombose atrial esquerda/trombose de apêndice atrial esquerdo foi de 0,593 quando o escore CHA2DS2-VASc foi ≥3 pontos, e a sensibilidade e especificidade foram 86,5% e 32,6%, respectivamente, enquanto a área sob a curva para o DAE na predição de trombose atrial esquerda/trombose de apêndice atrial esquerdo foi 0,786 quando o DAE foi ≥44,17 mm, e a sensibilidade e especificidade foram 89,6% e 60,9%, respectivamente. Entre os diferentes grupos CHA2DS2-VASc, a taxa de incidência de trombose atrial esquerda/trombose de apêndice atrial esquerdo em pacientes com DAE ≥44,17 mm foi maior do que em pacientes com DAE <44,17 mm (p <0,05). CONCLUSÃO: O escore CHA2DS2-VASc e o DAE estão correlacionados com a trombose atrial esquerda/trombose de apêndice atrial esquerdo na fibrilação atrial não valvar. Para pacientes com escore CHA2DS2-VASc de 0 ou 1, quando o DAE é ≥44,17 mm, o risco de trombose atrial esquerda/trombose de apêndice atrial esquerdo permaneceu alto. (Arq Bras Cardiol. 2020; [online].ahead print, PP.0-0).

Exogenous hydrogen sulfide protects against high glucose-induced apoptosis and oxidative stress by inhibiting the STAT3/HIF-1α pathway in H9c2 cardiomyocytes.

Hydrogen sulfide (H2S), an endogenous gasotransmitter, possesses multiple physiological and pharmacological properties including anti-apoptotic, anti-oxidative stress and cardiac protective activities in diabetic cardiomyopathy. An increasing body of evidence has suggested that signal transducer and activator of transcription 3 (STAT3) has beneficial effects in the heart. However, the effect of diabetes on the phosphorylation or activation of cardiac STAT3 appears to be controversial. The present study was designed to investigate the precise function of the STAT3/hypoxia-inducible factor-1α (HIF-1α) signaling pathway in high glucose (HG)-induced H9c2 cardiomyocyte injury and the function of the STAT3/HIF-1α pathway in the cardioprotective action of H2S. The results revealed that GYY4137 pretreatment substantially ameliorated the HG-induced decrease in cell viability and the increase in lactate dehydrogenase (LDH) release in H9c2 cells. Additionally, HG treatment resulted in the upregulation of the phosphorylated (p)-STAT3/STAT3 ratio and HIF-1α protein expression in H9c2 cells, indicating that the activation of the STAT3/HIF-1α pathway was induced by HG. STAT3/HIF-1α pathway inhibition induced by transfection with STAT3 small interfering (si)-RNA attenuated the HG-induced downregulation of cell viability and the upregulation of LDH release. Furthermore, STAT3 siRNA transfection and GYY4137 pretreatment combined attenuated HG-induced apoptosis as illustrated by the decrease in the number of terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells, caspase-3 activity, apoptosis ratio and BCL2 associated X, apoptosis regulator/BCL2 apoptosis regulator ratio in H9c2 cells. In addition, STAT3 siRNA transfection and GYY4137 blocked HG-induced oxidative stress as evidenced by the decrease in reactive oxygen species generation, malondialdehyde content and NADPH oxidase 2 expression, and the increase in superoxide dismutase activity and glutathione level. Notably, GYY4137 pretreatment was revealed to reduce the p-STAT3/STAT3 ratio and HIF-1α protein expression, resulting in the inhibition of the STAT3/HIF-1α signaling pathway in HG-treated H9c2 cells. Altogether, the present results demonstrated that H2S mitigates HG-induced H9c2 cell damage, and reduces apoptosis and oxidative stress by suppressing the STAT3/HIF-1α signaling pathway.

Association between PPAP2B gene polymorphisms and coronary heart disease susceptibility in Chinese Han males and females.

Little is known about gender-related differences in the association between PPAP2B single nucleotide polymorphisms (SNPs) and coronary heart disease (CHD) in Chinese Han males and females. We therefore conducted a case-control study with 456 cases and 685 healthy controls divided into male and female subgroups. Five PPAP2B polymorphisms (SNPs) were selected and genotyped using Sequenom Mass-ARRAY technology. Odds ratios (OR) and 95% confidence intervals (CIs) were calculated using unconditional logistic regression adjusting for age and gender. Allelic model analysis revealed that for PPAP2B rs1759752, allele frequency distributions differed between cases and controls in the male subgroup (p = 0.015, OR: 1.401, 95%CI: 1.066-1.481). Genetic model analysis revealed that in the male subgroup, rs1759752 was associated with increased CHD risk in the dominant model (p = 0.035) and overdominant model (p = 0.045). In the female subgroup, rs12566304 was associated with a decreased CHD risk in the codominant model (p = 0.038) and overdominant model (p = 0.031). Additionally, the "GC" haplotypes of rs1759752 and rs1930760 were protective against CHD in males. These observations shed new light on gender-related differences in the association between PPAP2B gene polymorphisms and CHD susceptibility in the Chinese Han population.

[Prevention of non-acute stent thrombosis after drug-eluting stent implantation].

OBJECTIVE: To decrease acute myocardial infarction (AMI) and incidence of other cardiovascular event after drug-eluting stent (DES) implantation, so as to prevent non-acute stent thrombosis. METHODS: Patients who had undergone percutaneous coronary intervention with DES from January 2005 to September 2008 were enrolled. All patients were randomly assigned into two groups with different treatment protocols for anti-thrombosis. The patients in control group were treated with aspirin and clopidogrel for anti-thrombosis (double anti-treatment), while those in observation group were treated with tirofiban and warfarin on top of basic treatment with double anti-thromotic drugs. The latter group of patients received warfarin in addition for 6 months, with the international normalized ratio (INR) maintained at 1.5-2.0. The patients in both groups were followed up at 1-3 months after the treatment, and the deadline was October 2012. Stent thrombosis was assessed by the definition of Dublin for Academic Research Consortium. The main ending point indexes were main adverse cardiac and cerebral events (MACCE), and the secondary ending point indexes were incidence of bleeding and other adverse events. RESULTS: A total of 505 consecutive patients treated with DES implantation were enrolled, 245 in the observation group while 260 in the control. The rates of MACCE at 1- 48 months after operation in observational group were significantly lower than those in control group (1 month: 0.41% vs. 3.08%, 2-6 months: 0 vs. 2.31%, 7-12 months: 0.82% vs. 4.23%, 13-24 months: 1.22% vs. 8.85%, 25- 48 months: 2.04% vs. 12.31%, all P<0.05). Cardiac death (13-24 months: 0.41% vs. 3.08%, 25-48 months: 0.82% vs. 4.23%), non-lethal acute myocardial infarction unrelated with target vessels (25-48 months: 0.41% vs. 3.08%), and rates of revascularization of target vessels (13-24 months: 0.41% vs. 3.08%, 25-48 months: 0.82% vs. 4.23%) in observation group were significantly lower than those in the control group (all P<0.05). The rates of sub-acute stent thrombosis, late stent thrombosis, and very late stent thrombosis in observation group were significantly lower than those in control group (0 vs. 2.31%, 0.82% vs. 4.23%, 1.63% vs. 8.46%, all P<0.05). The rate of bleeding in observational group was a litter higher than control group (3.27% vs. 1.54%, P=0.167) and no severe bleeding occurred. Other severe adverse events were not found in both groups. CONCLUSION: The results indicate that tirofiban and warfarin combined with aspirin and clopidogrel could reduce the rates of MACCE and bleeding, and it could prevent non-acute stent thrombosis safely and effectively after percutaneous coronary intervention with DES.

Long-term follow up of interventional therapy of secundum atrial septal defect.

BACKGROUND: The percutaneous transcatheter closure of secundum atrial septal defect (ASD) is increasingly a widespread alternative to surgical closure. The aim of this study was to assess long-term results of percutaneous closure of secundum-type atrial septal defect (ASDII). METHODS: Between January 2001 and December 2005, 61 patients underwent a successful percutaneous closure of ASDII; including 25 male and 36 female. All were included in the patient study and were followed up to monitor by electrocardiogram and echocardiography, at intervals of 3 days, 3 months, 6 months, 1 year, 2 years, and 5 years after operation. RESULTS: Three days after percutaneous transcatheter septal closure (PTSC), the right atrium diameter, right ventricular end-diastolic left-right diameter and right ventricular end-diastolic volume (RVEDV) decreased significantly (P < 0.05). Right ventricular end-diastolic anteroposterior diameter (RVEDD), right ventricular end-systolic volume (RVESV) and right ventricular ejection fraction (RVEF) also decreased (P < 0.01). During the period from 3 to 6 months, the size of the right atrium and right ventricle returned to normal range. Three days after PTSC, the left ventricular end-diastolic diameter (LVEDD), left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), left ventricular-systolic volume (LVSV) and left ventricular ejection fraction (LVEF) were significantly increased (P < 0.05). At 1 year, the size of the left atrium, left ventricle and left cardiac function returned to normal range (P < 0.01). There were no deaths or significant complications during the study. At five year follow-up, all defects were completely closed and remained closed thereafter. CONCLUSION: Transcatheter closure of ASDII effectively eliminated the abnormal shunt and, subsequently improved the dimensions of each chamber and cardiac function.

Ablation of right-sided accessory pathways with atrial insertion far from the tricuspid annulus using an electroanatomical mapping system.

BACKGROUND: It is difficult to ablate a right-sided accessory pathway (AP) with atrial insertion far from the tricuspid annulus (TA). We report our initial experience of ablating this rare AP by a 3-dimensional electroanatomical mapping system (CARTO). METHODS: From January of 2006 to April of 2008, 18 patients with right-sided APs who failed previous outside ablations were enrolled in this study. Retrograde AP conduction was mapped during pacing at the right ventricular apex by activation-mapping the right atrium (RA) using a 3-dimensional electroanatomical mapping system. AP atrial insertion was defined as the earliest retrograde atrial activations and successful ablation of the APs at this site. RESULTS: Among the 18 patients who had failed previous ablation, 10 patients (7 patients with right manifest APs and 3 patients with right conceal APs) had atrial insertions far from the TA. Of the 10 patients, the atrial insertions were found at the base of the RA appendage in 3 patients, at the high lateral RA in 5 patients, at the low lateral RA in other 2 patients. Ablation at the atrial insertions successfully abolished the AP conduction. The mean distance between the atrial insertion sites and the TA was 20.2 ± 2.7 mm. No patients reported recovered AP conduction or recurrent tachycardias after 6-month follow-up. CONCLUSIONS: The right-sided APs may have atrial insertion far from the TA. These uncommon variation of APs can be reliably identified and ablated using CARTO system.

[Comparison of amiodarone plus irbesartan regimen versus amiodarone alone on maintaining sinus rhythm in rheumatic heart disease patients with persistent atrial fibrillation post valve replacement and cardioversion].

OBJECTIVE: To compare the efficacy of combined amiodarone and irbesartan use versus amiodarone alone on maintaining sinus rhythm in rheumatic heart disease patients with persistent atrial fibrillation (AF) post valve replacement and cardioversion. METHODS: Patients were randomly divided into amiodarone group (A, n = 31) and amiodarone plus irbesartan group (AI, n = 32) and all patients received Warfarin (INR 2.0 - 3.0). For patients in group A, intravenous amiodarone (600 mg/d) was applied for 10 days and oral amiodarone (200 mg, b.i.d.) was given on the 7th day for 3 days. For patients in group AI, irbesartan (150 mg/d) was added on top of amiodarone at the study begin. Electric cardioversion was performed for patients still with AF on day 10. Amiodarone (200 mg, b.i.d. for 1 week, then 200 mg, q.d. till study end) with or without irbesartan (150 mg/d) was continued thereafter. Patients were followed up for 12 months after sinus rhythm recovery. The primary end points are first recurrence of symptomatic and asymptomatic AF. RESULTS: Twelve months post therapy, number of patients on sinus rhythm was significantly higher (68.7% vs. 41.9%, P<0.05) and left atrium diameter (LAD) was significantly smaller [(48.6 +/- 4.6) mm vs. (51.5 +/- 4.2) mm, P<0.05] in group AI than those in group A. LAD (OR 1.242) and use of irbesartan (OR 0.226) are associated with the AF recurrence. CONCLUSION: Combined amiodarone and irbesartan use is superior to amiodarone alone for maintaining sinus rhythm in rheumatic heart disease patients with persistent AF post valve replacement and cardioversion.