RESUMO
BACKGROUND: Macrophages are key players in obesity-associated cardiovascular diseases, which are marked by inflammatory and immune alterations. However, the pathophysiological mechanisms underlying macrophage's role in obesity-induced cardiac inflammation are incompletely understood. Our study aimed to identify the key macrophage population involved in obesity-induced cardiac dysfunction and investigate the molecular mechanism that contributes to the inflammatory response. METHODS: In this study, we used single-cell RNA-sequencing analysis of Cd45+CD11b+F4/80+ cardiac macrophages to explore the heterogeneity of cardiac macrophages. The CCR2+ (C-C chemokine receptor 2) macrophages were specifically removed by a dual recombinase approach, and the macrophage CCR2 was deleted to investigate their functions. We also performed cleavage under target and tagmentation analysis, chromatin immunoprecipitation-polymerase chain reaction, luciferase assay, and macrophage-specific lentivirus transfection to define the impact of lysozyme C in macrophages on obesity-induced inflammation. RESULTS: We find that the Ccr2 cluster undergoes a functional transition from homeostatic maintenance to proinflammation. Our data highlight specific changes in macrophage behavior during cardiac dysfunction under metabolic challenge. Consistently, inducible ablation of CCR2+CX3CR1+ macrophages or selective deletion of macrophage CCR2 prevents obesity-induced cardiac dysfunction. At the mechanistic level, we demonstrate that the obesity-induced functional shift of CCR2-expressing macrophages is mediated by the CCR2/activating transcription factor 3/lysozyme 1/NF-κB (nuclear factor kappa B) signaling. Finally, we uncover a noncanonical role for lysozyme 1 as a transcription activator, binding to the RelA promoter, driving NF-κB signaling, and strongly promoting inflammation and cardiac dysfunction in obesity. CONCLUSIONS: Our findings suggest that lysozyme 1 may represent a potential target for the diagnosis of obesity-induced inflammation and the treatment of obesity-induced heart disease.
Assuntos
Macrófagos , Muramidase , Obesidade , Receptores CCR2 , Animais , Obesidade/complicações , Obesidade/metabolismo , Macrófagos/metabolismo , Receptores CCR2/metabolismo , Receptores CCR2/genética , Camundongos , Muramidase/metabolismo , Muramidase/genética , Camundongos Endogâmicos C57BL , Masculino , Camundongos Knockout , Transdução de Sinais , Inflamação/metabolismo , Inflamação/genética , Cardiopatias/etiologia , Cardiopatias/metabolismo , Cardiopatias/genéticaRESUMO
Peel browning is a natural phenomenon that adversely affects the appearance of fruits. Research on the regulation of browning in apples (Malus × domestica Borkh.) has mainly focused on postharvest storage, while studies at the preharvest stage are relatively rare. Apple is an economically important horticultural crop prone to peel browning during growth, especially when the fruits are bagged (dark conditions). The present study's integrated transcriptomics and metabolomics analysis revealed that preharvest apple peel browning was primarily due to changes in phenolics and flavonoids. The detailed analysis identified MdLAC7's (laccase 7) role in the preharvest apple peel browning process. Transient injection, overexpression, and CRISPR/Cas9 knockout of the MdLAC7 gene in apple fruit and calli identified vallinic acid, anthocyanidin, tannic acid, sinapic acid, and catechinic acid as its catalytic substrates. In addition, yeast one-hybrid assay, electrophoretic mobility shift assay, luciferase reporter assay, and ChIP-PCR analysis revealed that MdWRKY31 binds to the promoter of MdLAC7 and positively regulates its activity to promote peel browning of bagged fruits (dark conditions). Interestingly, upon light exposure, the light-responsive transcription factor MdHY5 (ELONGATED HYPOCOTYL 5) bound to the promoter of MdWRKY31 and inhibited the gene's expression, thereby indirectly inhibiting the function of MdLAC7. Subsequent analysis showed that MdHY5 binds to the MdLAC7 promoter at the G-box1/2 site and directly inhibits its expression in vivo. Thus, the study revealed the MdLAC7-mediated mechanism regulating preharvest apple peel browning and demonstrated the role of light in inhibiting MdLAC7 activity and subsequently reducing peel browning. These results provide theoretical guidance for producing high-quality apple fruits.
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Malus , Malus/genética , Malus/metabolismo , Transcriptoma/genética , Frutas/genética , Frutas/metabolismo , Perfilação da Expressão Gênica , MetabolômicaRESUMO
INTRODUCTION: Endovascular left atrial appendage occlusion (LAAO) is associated with a high incidence of peri-procedure silent cerebral embolism (SCE), while the recommended activated clotting time (ACT) level by the expert consensus is lower than that in atrial fibrillation (AF) ablation. The aim of our study was to investigate whether raising the targeted ACT level during LAAO to the same level as AF ablation could decrease the incidence of SCE. METHODS: It was a prospective observational cohort study. Consecutive AF patients receiving LAAO between January 2021 and December 2022 were included and categorized into two groups based on the time of enrollment. Patients enrolled in 2021 (group 250) maintained a target ACT level of ≥250 s during LAAO procedure, while patients enrolled in 2022 (group 300) maintained the peri-procedure ACT ≥300 s. All patients underwent cerebral magnetic resonance imaging before and after the procedure. RESULTS: A total of 81 patients were included (38 in the group 250 and 43 in the group 300). After inverse probability of treatment weighting (IPTW), patients in the group 250 showed a significantly lower incidence of SCE than group 300 (IPTW p = 0.038). Only a stable high ACT pattern could decrease the risk of SCE. No significant differences were found between other ACT change patterns on the SCE incidence. CONCLUSION: Raising the peri-procedure ACT level to a stable 300 s could decrease the risk of the SCE without increasing the major bleeding events.
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Anticoagulantes , Apêndice Atrial , Fibrilação Atrial , Embolia Intracraniana , Humanos , Masculino , Feminino , Fibrilação Atrial/complicações , Embolia Intracraniana/prevenção & controle , Embolia Intracraniana/etiologia , Embolia Intracraniana/diagnóstico por imagem , Estudos Prospectivos , Apêndice Atrial/cirurgia , Apêndice Atrial/diagnóstico por imagem , Idoso , Anticoagulantes/uso terapêutico , Anticoagulantes/administração & dosagem , Pessoa de Meia-Idade , Incidência , Tempo de Coagulação do Sangue Total , Imageamento por Ressonância Magnética , Procedimentos EndovascularesRESUMO
BACKGROUND: Atrial tachycardias (ATs) frequently develop after a surgical Maze procedure. We aimed to elucidate the electrophysiologic mechanisms and their arrhythmogenic substrates of these ATs. METHODS AND RESULTS: We retrospectively reviewed 20 patients (14 females, mean age of 55.5 ± 8.6 years) with post-Maze ATs who underwent high-resolution mapping at three institutions. The slow conduction areas, reentry circuits, voltage signals, complex electrograms, and their correlation with the surgical incisions and lesions placed in the surgical Maze procedures were analyzed. Thirty-six ATs with a mean cycle length of 260.0 ± 67.6 ms were mapped in these patients. Among them, 22 (61.1%) were anatomical macro-reentrant ATs (AMAT), 12 (33.3%) non-AMATs (localized ATs), and 2 (5.6%) focal ATs, respectively. Epicardial conduction bridges were observed in 6/20 (30.0%) patients and 7/36 (19.4%) ATs. Different arrhythmogenic substrates were identified in these ATs, including slow conduction regions within the previous lesion areas or between the incisions and anatomical structures, the prolonged activation pathways caused by the short lesions connecting the tricuspid annulus, and the circuits around the long incisions and/or lesions. CONCLUSIONS: Reentry is the main mechanism of the post-Maze ATs. The pro-arrhythmic substrates are most likely caused by surgical incisions and lesions. The slow conduction regions and the protected channels yielded from these areas are the major arrhythmogenic factors.
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Fibrilação Atrial , Ablação por Cateter , Ferida Cirúrgica , Taquicardia Supraventricular , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Ablação por Cateter/efeitos adversos , Ablação por Cateter/métodos , Taquicardia Supraventricular/diagnóstico , Taquicardia Supraventricular/etiologia , Taquicardia Supraventricular/cirurgia , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/cirurgia , Fibrilação Atrial/complicaçõesRESUMO
BACKGROUND: Previous studies revealed a relationship between 8-hydroxy-2'-deoxyguanosine (8-OHdG) and the occurrence/recurrence of atrial fibrillation (AF). This 2-part study aimed to validate whether DNA damage related to 8-OHdG is associated with left atrial (LA) fibrosis in AF patients quantified by voltage mapping (Part I), and to identify the underlying genetic components regulating the 8-OHdG level (Part II).MethodsâandâResults: Plasma 8-OHdG determination, DNA extraction, and genotyping were conducted before catheter ablation. LA voltage mapping was performed under sinus rhythm. According to the percentage of low voltage area (LVA), patients were categorized as stage I (<5%), stage II (5-10%), stage III (10-20%), and stage IV (>20%). Part I included 209 AF patients. The 8-OHdG level showed an upward trend together with advanced LVA stage (stage I 8.1 [6.1, 10.5] ng/mL, stage II 8.5 [5.7, 14.1] ng/mL, stage III 14.3 [12.1, 16.5] ng/mL, stage IV 13.9 [10.5, 16.0] ng/mL, P<0.000). Part II included 175 of the 209 patients from Part I. Gene-set analysis based on genome-wide association study summary data identified that the gene set named 'DNA methylation on cytosine' was the only genetic component significantly associated with 8-OHdG concentration. CONCLUSIONS: Higher 8-OHdG levels may predict more advanced LVA of the LA in AF patients. DNA methylation is the putative genetic component underlying oxidative DNA damage in AF patients.
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Fibrilação Atrial , Ablação por Cateter , Humanos , 8-Hidroxi-2'-Desoxiguanosina , Metilação de DNA , Estudo de Associação Genômica Ampla , Átrios do Coração , Biomarcadores , Fibrose , Ablação por Cateter/métodos , Recidiva , Resultado do TratamentoRESUMO
BACKGROUND: It is inevitable for patients to have a temporary or permanent pacemaker implanted during or after radiofrequency catheter ablation (RFCA) for treatment of atrial fibrillation (AF) in some cases. The aim of our study was to evaluate the incidence of pacemaker implantation (PMI) during or within 3 months of RFCA for AF and to identify the risk factors that were associated with PMI. METHODS: We performed a retrospective analysis of consecutive AF patients who underwent RFCA between August 2018 and October 2020 at our center. The incidence of PMI within 3 months during or after RFCA were assessed. A multivariate logistic regression model was performed to identify predictors of PMI. RESULTS: One thousand and five patients (mean age, 60.2 ± 10.3 years; 37.6% women) were included in this analysis. PVI was performed in all patients. A total of 23 (2.3%) patients had a pacemaker implanted within 3 months during or after ablation. Multivariable logistic regression analysis revealed that older age (OR: 1.08 [95% CI 1.03-1.13], p = .003), female sex (OR: 3.08 [95% CI 1.28-7.45], p = .012), paroxysmal AF (OR: 4.71 [95% CI 1.09-20.45], p = .038) and repeated ablation (OR: 2.78 [95% CI 1.04-7.40], p = .041) were the independent predictors for PMI. CONCLUSIONS: Older age, female sex, paroxysmal AF and repeated ablation were identified as predictive risk factors for PMI after RFCA in patients with AF. A "watch and wait" strategy could be taken for patients with temporary PMI after ablation, especially for those with prolonged sinus pause after AF termination.
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Fibrilação Atrial , Ablação por Cateter , Marca-Passo Artificial , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Masculino , Estudos Retrospectivos , Resultado do Tratamento , Ablação por Cateter/efeitos adversos , RecidivaRESUMO
BACKGROUND: Persistent left superior vena cava (PLSVC) is the most prevalent form of thoracic venous abnormality and can serve as a significant arrhythmogenic source in atrial fibrillation (AF). METHODS AND RESULTS: Among the 3950 patients who underwent radiofrequency ablation for AF between September 2014 to April 2020, 17 patients (mean age 59.4 ± 8.0 years, 64.7% male) with PLSVC were identified. Among them, nine patients (52.9%) had a prior history of pulmonary vein isolation (PVI) alone. Eight out of nine patients who experienced AF recurrence underwent PLSVC isolation with or without pulmonary vein (PV) reconnection. For the remaining eight patients (47.1%), PVI plus PLSVC isolation were performed during the index procedure. Ectopy originating from PLSVC was documented in 11 patients (64.7%) and successful PLSVC isolation was achieved in 16 patients (94.1%). After a median follow-up of 28.3 months, freedom from AF/ atrial tachycardia (AT) was observed in 13 patients (76.5%). CONCLUSION: Empirical PLSVC isolation beyond PVI appears to be a feasible and safe strategy to prevent AF recurrence in patients with concomitant PLSVC.
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Fibrilação Atrial , Ablação por Cateter , Veia Cava Superior Esquerda Persistente , Veias Pulmonares , Taquicardia Supraventricular , Humanos , Masculino , Pessoa de Meia-Idade , Idoso , Feminino , Veia Cava Superior Esquerda Persistente/complicações , Veia Cava Superior , Ablação por Cateter/métodos , Veias Pulmonares/cirurgia , Recidiva , Resultado do TratamentoRESUMO
BACKGROUND: Catheter ablation is an established therapeutic strategy to treat scar-related macroreentry atrial tachycardia (MAT). However, the scar properties and arrhythmogenicity and the reentry type have not been clearly defined. METHODS AND RESULTS: A total of 122 patients with scar-related MAT were enrolled in this study. The atrial scars were classified into two categories: spontaneous scars (Group A: n = 28) and iatrogenic scars (Group B: n = 94). According to the relationship between scar location and the reentry circuit, MAT was described as scar pro-flutter MAT, scar-dependent MAT, and scar-mediated MAT. The reentry type of MAT was significantly different between Groups A and B: pro-flutter (40.5% vs. 62.0%, p = 0.02), scar-dependent AT (40.5% vs. 13.0%, p < 0.001), and scar-mediated AT (19.0% vs. 25.0%, p = 0.42). After a median follow-up of 25 months, 21 patients with AT recurrence were observed. Compared with the spontaneous group, there was a lower recurrence rate of MAT in the iatrogenic group (28.6% vs. 10.6%, p = 0.03). CONCLUSION: Scar-related MAT has three reentry types, and the proportion of each type varies with the scar properties and its arrhythmogenic basis. Optimization of the ablation strategy based on the scar properties to improve the long-term outcome of catheter ablation of MAT is necessary.
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Flutter Atrial , Ablação por Cateter , Taquicardia Supraventricular , Humanos , Cicatriz/cirurgia , Resultado do Tratamento , Átrios do Coração/cirurgia , Ablação por Cateter/métodos , Doença Iatrogênica , Flutter Atrial/cirurgiaRESUMO
RATIONALE: Doxorubicin-induced cardiomyopathy (DiCM) is a primary cause of heart failure and mortality in cancer patients, in which macrophage-orchestrated inflammation serves as an essential pathological mechanism. However, the specific roles of tissue-resident and monocyte-derived macrophages in DiCM remain poorly understood. OBJECTIVE: Uncovering the origins, phenotypes, and functions of proliferative cardiac resident macrophages and mechanistic insights into the self-maintenance of cardiac macrophage during DiCM progression. METHODS AND RESULTS: Mice were administrated with doxorubicin to induce cardiomyopathy. Dynamic changes of resident and monocyte-derived macrophages were examined by lineage tracing, parabiosis, and bone marrow transplantation. We found that the monocyte-derived macrophages primarily exhibited a proinflammatory phenotype that dominated the whole DiCM pathological process and impaired cardiac function. In contrast, cardiac resident macrophages were vulnerable to doxorubicin insult. The survived resident macrophages exhibited enhanced proliferation and conferred a reparative role. Global or myeloid specifically ablation of SR-A1 (class A1 scavenger receptor) inhibited proliferation of cardiac resident reparative macrophages and, therefore, exacerbated cardiomyopathy in DiCM mice. Importantly, the detrimental effect of macrophage SR-A1 deficiency was confirmed by transplantation of bone marrow. At the mechanistic level, we show that c-Myc (Avian myelocytomatosis virus oncogene cellular homolog), a key transcriptional factor for the SR-A1-P38-SIRT1 (Sirtuin 1) pathway, mediated the effect of SR-A1 in reparative macrophage proliferation in DiCM. CONCLUSIONS: The SR-A1-c-Myc axis may represent a promising target to treat DiCM through augmentation of cardiac resident reparative macrophage proliferation.
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Cardiomiopatia Dilatada/enzimologia , Proliferação de Células , Autorrenovação Celular , Macrófagos/enzimologia , Miocárdio/enzimologia , Proteínas Proto-Oncogênicas c-myc/metabolismo , Receptores Depuradores Classe A/metabolismo , Animais , Receptor 1 de Quimiocina CX3C/genética , Receptor 1 de Quimiocina CX3C/metabolismo , Cardiomiopatia Dilatada/induzido quimicamente , Cardiomiopatia Dilatada/patologia , Cardiomiopatia Dilatada/prevenção & controle , Células Cultivadas , Modelos Animais de Doenças , Doxorrubicina , Feminino , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Humanos , Macrófagos/patologia , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Miocárdio/patologia , Fenótipo , Proteínas Proto-Oncogênicas c-myc/genética , Receptores Depuradores Classe A/deficiência , Receptores Depuradores Classe A/genética , Transdução de Sinais , Remodelação VentricularRESUMO
INTRODUCTION: For those cardiac resynchronization therapy (CRT) candidates who experience left-ventricular (LV) lead placement failure or underwent concomitant cardiac surgeries, surgical placement of epicardial LV lead guided by electroanatomic mapping may be a promising alternative. METHODS: Electroanatomic mapping was used to guide positioning of the LV lead through a surgical approach. The LV lead was placed at the region with the latest local LV activation and normal voltage, away from the scar. RESULTS: From April 2010 to September 2018, 10 consecutive patients (3 female) underwent surgical epicardial LV lead implantation. Among them, 3 had other surgical indications simultaneously (including 1 CRT non-responder), and 7 had failed transvenous LV lead placement. After CRT, the QRS duration was shortened from 149.3 ± 20.4 ms to 125.1 ± 15.2 ms (p = 0.01). At 6 months, the LV ejection fraction was significantly improved and remained stable in the follow-up (FU) period thereafter (baseline vs. 6 months, 31.0 ± 8.3% vs. 42.2 ± 13.4%, p = 0.006). Other parameters, including the threshold and impedance of the LV lead, were also stable at a mean FU of 755 ± 406 days, and the NYHA functional classification decreased from 2.9 ± 0.7 to 1.8 ± 0.8 (p = 0.002). CONCLUSIONS: Placement of an epicardial LV lead guided by electroanatomic mapping could be used as an adjunctive strategy in patients who were unable or refractory to conventional CRT therapy. This approach could also be applied in patients who had other surgical indications at the same time.
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Terapia de Ressincronização Cardíaca , Insuficiência Cardíaca , Dispositivos de Terapia de Ressincronização Cardíaca , Feminino , Insuficiência Cardíaca/terapia , Ventrículos do Coração , Humanos , Resultado do TratamentoRESUMO
BACKGROUND AND PURPOSE: Complete P wave disappearance (CPWD) in patients without atrial fibrillation is an uncommon clinical phenomenon. We aimed to study the relationship between CPWD and thromboembolism. METHODS: Between July 2007 and December 2018, consecutive patients with CPWD on surface ECG and 24-hour Holter recording were recruited into the study from 4 centers in China. All recruited patients underwent transesophageal echocardiography or cardiac computed tomography to screen for atrial thrombus. Atrial electrical activity and scar were assessed by electrophysiological study (EPS) and 3-dimensional electroanatomic mapping. Cardiac structure and function were assessed by multimodality cardiac imaging. RESULTS: Twenty-three consecutive patients (8 male; mean age 48.5±14.7 years) with CPWD were included. Only 3 patients demonstrated complete atrial electrical silence with atrial noncapture. Thirteen patients who had invasive atrial endocardial mapping demonstrated extensive scar. Pulse-wave mitral inflow Doppler demonstrated absent and dampened A waves in 18 and 5 patients, respectively. Pulse-wave tricuspid inflow Doppler showed absent and dampened A waves in 19 and 4 patients, respectively. Upon recruitment, 8 patients had previous stroke and 3 patients had atrial thrombus. Warfarin was prescribed to all patients. During median follow-up of 42.0 months, 2 patients developed massive ischemic stroke due to warfarin discontinuation. CONCLUSIONS: Our study suggested that CPWD reflects extensive atrial electrical silence and significantly impaired atrial mechanical function. It was strongly associated with thromboembolism and the clinical triad of CPWD-atrial paralysis-stroke was proposed. Anticoagulation should be recommended in such patients.
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Fibrilação Atrial/fisiopatologia , Eletrocardiografia , Adulto , Idoso , Anticoagulantes/uso terapêutico , Fibrilação Atrial/congênito , Fibrilação Atrial/diagnóstico por imagem , China , Trombose Coronária/complicações , Trombose Coronária/diagnóstico por imagem , Ecocardiografia Transesofagiana , Eletrocardiografia Ambulatorial , Feminino , Seguimentos , Humanos , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Valva Mitral/diagnóstico por imagem , Risco , Acidente Vascular Cerebral/fisiopatologia , Tromboembolia/fisiopatologia , Tomografia Computadorizada por Raios X , Valva Tricúspide/diagnóstico por imagem , Varfarina/uso terapêuticoRESUMO
BACKGROUND/AIMS: Heart failure induced by tachycardia, the most common arrhythmia, is frequently observed in clinical practice. This study was designed to investigate the underlying mechanisms. METHODS: Rapid electrical stimulation (RES) at a frequency of 3 Hz was applied on human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) for 7 days, with 8 h/day and 24 h/day set to represent short-term and long-term tachycardia, respectively. Age-matched hiPSC-CMs without electrical stimulation or with slow electrical stimulation (1 Hz) were set as no electrical stimulation (NES) control or low-frequency electrical stimulation (LES) control. Following stimulation, JC-1 staining flow cytometry analysis was performed to examine mitochondrial conditions. Apoptosis in hiPSC-CMs was evaluated using Hoechst staining and Annexin V/propidium iodide (AV/PI) staining flow cytometry analysis. Calcium transients and L-type calcium currents were recorded to evaluate calcium homeostasis. Western blotting and qPCR were performed to evaluate the protein and mRNA expression levels of apoptosis-related genes and calcium homeostasis-regulated genes. RESULTS: Compared to the controls, hiPSC-CMs following RES presented mitochondrial dysfunction and an increased apoptotic percentage. Amplitudes of calcium transients and L-type calcium currents were significantly decreased in hiPSC-CMs with RES. Molecular analysis demonstrated upregulated expression of Caspase3 and increased Bax/Bcl-2 ratio. Genes related to calcium re-sequence were downregulated, while phosphorylated Ca2+/calmodulin-dependent protein kinase II (CaMKII) was significantly upregulated following RES. There was no significant difference between the NES control and LES control groups in these aspects. Inhibition of CaMKII with 1 µM KN93 partly reversed these adverse effects of RES. CONCLUSION: RES on hiPSC-CMs disturbed calcium homeostasis, which led to mitochondrial stress, promoted cell apoptosis and caused electrophysiological remodeling in a time-dependent manner. CaMKII played a central role in the damages induced by RES, pharmacological inhibition of CaMKII activity partly reversed the adverse effects of RES on both structural and electrophysiological properties of cells.
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Sinalização do Cálcio , Cálcio/metabolismo , Terapia por Estimulação Elétrica/efeitos adversos , Células-Tronco Pluripotentes Induzidas/metabolismo , Mitocôndrias Cardíacas/metabolismo , Miócitos Cardíacos/metabolismo , Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/patologia , Insuficiência Cardíaca/terapia , Humanos , Células-Tronco Pluripotentes Induzidas/patologia , Mitocôndrias Cardíacas/patologia , Miócitos Cardíacos/patologia , Taquicardia/metabolismo , Taquicardia/patologia , Taquicardia/terapiaRESUMO
BACKGROUND: Right atrial tachycardia (AT) is a common arrhythmia postsurgical valve replacement in patients with rheumatic heart disease (RHD). However, the substrate and the mechanism of left AT in such patients and the ablation efficacy is less known. METHODS AND RESULTS: Twenty-seven RHD patients with AT were enrolled in this study; nine of them (33%) had left AT. Five and four patients had left AT during the first and second procedure, respectively. A spontaneous scar in the left posterior wall was identified in all patients, and obvious anterior scar in three patients. Dual-roof-dependent AT was found in three patients and macroreentry AT surrounding right pulmonary vein was identified in one patient, two of whom had left anterior scar. Three patients had AT circuit going around the mitral annulus, one of whom had left anterior scar. Entrainment pacing at different sites confirmed the mechanism of these macroreentries. Two patients had a focal origin, one was localized in posterior wall at the edge of the scar and the other one was originated from the left septum with normal voltage. After a mean follow-up of 27.4 ± 7.9 months, the left AT group had a similar recurrence rate compared with the right AT group alone (67% vs 56%, P = 0.58). In the left AT group, 11% of patients had AT recurrence and 56% of patients developed atrial fibrillation. CONCLUSION: Left atrial AT can occur in RHD patients postmitral valve replacement. Catheter ablation is feasible with high acute success rate. The incidence of late development atrial fibrillation is considerable after successful ablation.
Assuntos
Ablação por Cateter , Complicações Pós-Operatórias/cirurgia , Taquicardia/cirurgia , Adulto , Idoso , Feminino , Átrios do Coração , Doenças das Valvas Cardíacas/etiologia , Doenças das Valvas Cardíacas/cirurgia , Implante de Prótese de Valva Cardíaca , Humanos , Masculino , Pessoa de Meia-Idade , Valva Mitral/cirurgia , Estudos Retrospectivos , Cardiopatia Reumática/complicações , Resultado do TratamentoRESUMO
Pre-harvest bagging can improve fruit color and protects against diseases. However, it was discovered that improper bagging times could lead to peel browning in production. Using the Ruixue apple variety as the research model, a study was conducted to compare the external and internal quality of fruits bagged at seven different timings between 50 and 115 days after full bloom (DAFB). Our findings indicate that delaying the bagging time can reduce the occurrence of peel browning in Ruixue apples. Compared to the control, the special bag reduced the browning index by 22.95%. However, the fruit point index of Ruixue fruits increased by 65.05% at 115 DAFB compared to 50 DAFB when bagging was delayed. The chlorophyll content of Ruixue fruits in special bags generally increased and then decreased, with the highest chlorophyll content of Ruixue fruits in special bags at 90 DAFB, which was 26.02 mg·kg-1. When the bagging process was delayed, the soluble solids, total phenols, and flavonoids content in the fruits increased, while the number of control volatiles decreased by 10. After two years of testing, results show that using special fruit bags at 90 DAFB bagging can significantly improve the fruit quality of Ruixue apple.
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BACKGROUND: Ibrutinib could increase the risk of atrial fibrillation (AF) in chronic lymphocytic leukemia (CLL) patients. However, the precise mechanism underlying ibrutinib-induced AF remains incompletely elucidated. METHODS: We investigated the proportion of ibrutinib-treated CLL patients with new-onset AF. Optical mapping was conducted to reveal the proarrhythmic effect of ibrutinib on HL-1 cells. Fluorescence staining and western blot were used to compare connexins 43 and 40 expression in ibrutinib-treated and control groups. To identify autophagy phenotypes, we used western blot to detect autophagy-related proteins, transmission electron microscopy to picture autophagosomes, and transfected mCherry-GFP-LC3 virus to label autophagosomes and lysosomes. Hydroxychloroquine as an autophagy inhibitor was administered to rescue ibrutinib-induced Cx43 and Cx40 degradation. RESULTS: About 2.67% of patients developed atrial arrhythmias after ibrutinib administration. HL-1 cells treated with ibrutinib exhibited diminished conduction velocity and a higher incidence of reentry-like arrhythmias compared to controls. Cx43 and Cx40 expression reduced along with autophagy markers increased in HL-1 cells treated with ibrutinib. Inhibiting autophagy upregulated Cx43 and Cx40. CONCLUSIONS: The off-target effect of ibrutinib on the PI3K-AKT-mTOR signaling pathway caused connexin degradation and atrial arrhythmia via promoting autophagy. CLINICAL TRIAL REGISTRATION: ChiCTR2100046062, https://clin.larvol.com/trial-detail/ChiCTR2100046062.
Assuntos
Adenina , Fibrilação Atrial , Autofagia , Conexina 43 , Conexinas , Fosfatidilinositol 3-Quinases , Piperidinas , Proteínas Proto-Oncogênicas c-akt , Transdução de Sinais , Serina-Treonina Quinases TOR , Humanos , Adenina/análogos & derivados , Adenina/farmacologia , Adenina/efeitos adversos , Serina-Treonina Quinases TOR/metabolismo , Autofagia/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Piperidinas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Conexina 43/metabolismo , Conexina 43/genética , Feminino , Fibrilação Atrial/metabolismo , Fibrilação Atrial/induzido quimicamente , Conexinas/metabolismo , Conexinas/genética , Masculino , Idoso , Pessoa de Meia-Idade , Proteína alfa-5 de Junções Comunicantes , Arritmias Cardíacas/metabolismo , Arritmias Cardíacas/induzido quimicamenteRESUMO
Background: Pulmonary vein isolation (PVI) is the cornerstone of atrial fibrillation (AF) ablation. General anesthesia (GA) resolves the problem of pain intolerability and provides regular respiratory mode which might improve the catheter maneuverability of AF ablation. This study aims to compare the procedural performance of PVI under GA versus conscious sedation (CS) from multiple perspectives. Methods: A total of 36 consecutive patients undergoing first AF ablation under GA were enrolled in GA group. Another 109 patients receiving AF ablation under CS in the same period were selected as the control group. After propensity score matching, 29 matched pairs with similar baseline characteristics were available for further analysis. The AIFV (using AI to analyze the raw data from CARTO3 system) system was used to evaluate six procedural parameters in each PVI procedure. Results: Compared with CS, PVI under GA had a significantly shorter total PVI time (51.4 min vs. 67.8 min; p = .003) and higher radiofrequency ratio (62.6% vs. 55.8%; p = .032). The number of gaps (1.0 vs. 3.0; p < .001) and the rate of break point were significantly lower in the GA group. GA was also associated with a higher effective ablation-index ratio (87.5% vs. 74.1%; p < .001) and effective force-over-time ratio (85.3% vs. 69.2%; p = .001). After a medium follow-up time of 24 months, 12/29 (41.4%) patients in the CS group and 6/29 (20.7%) patients in the GA group suffered from AF recurrence (p = .156). Conclusions: GA improves the lesion quality and procedural efficiency of PVI from multiple perspectives evaluated by the AIFV system.
RESUMO
Background: Ventricular arrhythmias (VAs) mainly occur in the early post-myocardial infarction (MI) period. However, studies examining the association between total myocardial ischemia time interval and the risk of new-onset VAs during a long-term follow-up are scarce. Methods: This study (symptom-to-balloon time and VEntricular aRrhYthmias in patients with STEMI, VERY-STEMI study) was a multicenter, observational cohort and real-world study, which included patients with ST-segment elevation MI (STEMI) undergoing percutaneous coronary intervention (PCI). The primary endpoint was cumulative new-onset VAs during follow-up. The secondary endpoints were the major adverse cardiovascular events (MACE) and changes in left ventricular ejection fraction (ΔLVEF, %). Results: A total of 517 patients with STEMI were included and 236 primary endpoint events occurred. After multivariable adjustments, compared to patients with S2BT of 24 h-7d, those with S2BT ≤ 24 h and S2BT > 7d had a lower risk of primary endpoint. RCS showed an inverted U-shaped relationship between S2BT and the primary endpoint, with an S2BT of 68.4 h at the inflection point. Patients with S2BT ≤ 24 h were associated with a lower risk of MACE and a 4.44 increase in LVEF, while there was no significant difference in MACE and LVEF change between the S2BT > 7d group and S2BT of 24 h-7d group. Conclusions: S2BT of 24 h-7d in STEMI patients was associated with a higher risk of VAs during follow-up. There was an inverted U-shaped relationship between S2BT and VAs, with the highest risk at an S2BT of 68.4 h.
RESUMO
OBJECTIVES: The initial medical contact of patients with atrial fibrillation (AF) and ischaemic stroke is often performed by neurologists. However, when stand care with oral anticoagulants (OACs) adherence and persistence was emphasised by cardiologists, data regarding the gap between current neurology care and standard care from Chinese tertiary hospitals is scarce and the long-term outcome is unknown. This study was to investigate the AF detection rate, the use of anticoagulation therapy and posthospital clinical outcomes associated with neurology care in patients with AF and ischaemic stroke in China. DESIGN: A retrospective cohort study. SETTING: Clinical data of all patients who had an ischaemic stroke discharged from the neurologic department of a high-volume academic hospital from 1 January 2013 to 31 December 2017 were analysed and patients were followed. PARTICIPANTS: Patients diagnosed with ischaemic stroke and AF were included. MAIN OUTCOME MEASURES: The usage of anticoagulation at discharge, the posthospital restroke rate and all-cause mortality. RESULTS: Among 5797 patients who had an ischaemic stroke, 373 (6.43%) patients were diagnosed with AF during hospitalisation. Among them, only 198 (53.66%) patients were on anticoagulation therapy at discharge. A total of 325 (88.08%) patients were accessible and received follow-up. After a median 3-year follow-up, 103 (31.69%) patients died due to all causes. Among them, 53 (16.31%) patients died from recurrent stroke. And 86 (26.46%) patients restroked. In multivariable analysis, patients without anticoagulation therapy, muscle strengthAssuntos
Fibrilação Atrial
, Isquemia Encefálica
, AVC Isquêmico
, Neurologia
, Acidente Vascular Cerebral
, Humanos
, Acidente Vascular Cerebral/etiologia
, Acidente Vascular Cerebral/prevenção & controle
, Acidente Vascular Cerebral/diagnóstico
, Fibrilação Atrial/complicações
, Fibrilação Atrial/tratamento farmacológico
, Isquemia Encefálica/tratamento farmacológico
, Estudos Retrospectivos
, Centros de Atenção Terciária
, Anticoagulantes/uso terapêutico
, AVC Isquêmico/complicações
, Fatores de Risco
, Administração Oral
RESUMO
OBJECTIVES: Left atrial appendage intervention is an alternative to oral anticoagulation for thromboprophylaxis in atrial fibrillation. The aim of our study was to compare the incidence of silent cerebral embolisms after surgical and percutaneous intervention and to identify the risk factors for procedure-related silent cerebral embolisms after intervention. METHODS: This prospective observational study included consecutive atrial fibrillation patients from 2 independent cohorts (left atrial appendage excision (LAAE) cohort and left atrial appendage occlusion cohort) between September 2018 and December 2020. All patients underwent cerebral magnetic resonance imaging before and after the procedure. Silent cerebral embolism was defined as new focal hyperintense lesions detected only on postprocedural sequence. RESULTS: Thirty-two patients from the LAAE cohort and 42 patients from the occlusion cohort were enrolled. A significantly lower incidence of silent cerebral embolism was observed in the LAAE cohort as compared with occlusion (6.3% vs 54.8%, P < 0.001). In the left atrial appendage occlusion cohort, patients who developed silent cerebral embolism after the procedure had significantly higher CHA2DS2-VASc scores [odds ratio (OR) 2.172; 95% confidence interval (CI) 1.149-4.104; P = 0.017], longer occlusion placement time (OR 1.067; 95% CI 1.018-1.118; P = 0.006) and lower peak activated clotting time level after transseptal puncture (OR 0.976; 95% CI 0.954-0.998; P = 0.035). CONCLUSIONS: The incidence of procedure-related silent cerebral embolism was strikingly lower in patients with LAAE than in patients with occlusion. More cardiovascular comorbidities, longer occlusion placement time and lower activated clotting time level were significantly associated with the development of procedure-related silent cerebral embolism.