RESUMO
AIMS: Activation mapping of premature atrial complexes (PACs) proves challenging due to interference by mechanical bumping and non-targeted ectopies. This study aims to compare the mapping efficacy, instant success, and long-term recurrence of catheter ablation for PACs with non-pulmonary vein (PV) and non-superior vena cava (SVC) origins between the novel dual-reference approach (DRA) and the routine single-reference approach (SRA) of mapping. METHODS AND RESULTS: Patients with symptomatic, drug-refractory PACs, or frequent residual PACs after atrial tachyarrhythmia ablation were enrolled. During activation mapping, the coronary sinus (CS) catheter was used as the only timing reference in the SRA group. In the DRA group, another catheter, which was spatially separated from the CS catheter, was used as the second reference. The timing difference between the two references was used to discriminate the targeted PACs from the uninterested rhythms. Procedural parameters and long-term recurrence were compared. A total of 188 patients (109 in SRA and 79 in DRA) were enrolled. The baseline characteristics were similar. Compared with the SRA group, the DRA group had less repeated mapping (1.2 ± 0.4 vs. 1.4 ± 0.5, P = 0.004), shorter mapping (15 ± 6 vs. 23 ± 7 min, P < 0.001) and procedural time (119 ± 28 vs. 132 ± 22 min, P = 0.001), similar procedural complication rates (3.6 vs. 3.8%, P > 0.999), higher instant success (96.2 vs. 87.2%, P = 0.039), and lower recurrence rate (15.2 vs. 29.3%, hazard ratio 1.943, P = 0.033) during a 24-month follow-up. CONCLUSION: As a novel strategy, the DRA shortens the procedural time and improves both instant and long-term success of PAC ablation, serving as a promising approach in mapping PACs with non-PV and non-SVC origins.
Assuntos
Fibrilação Atrial , Complexos Atriais Prematuros , Ablação por Cateter , Veias Pulmonares , Humanos , Fibrilação Atrial/cirurgia , Resultado do Tratamento , Veias Pulmonares/cirurgia , Complexos Atriais Prematuros/diagnóstico , Complexos Atriais Prematuros/cirurgia , Ablação por Cateter/efeitos adversos , Ablação por Cateter/métodos , RecidivaRESUMO
Glycerol is an abundant byproduct of biodiesel production that has significant industrial value and can be converted into dihydroxyacetone (DHA). DHA is widely used for the production of various chemicals, pharmaceuticals, and food additives. Gluconobacter can convert glycerol to DHA through two different pathways, including membrane-bound dehydrogenases with pyrroloquinoline quinone (PQQ) and NAD(P)+ -dependent enzymes. Previous work has indicated that membrane-bound dehydrogenases are present in Gluconobacter oxydans and Gluconobacter frateurii, but the metabolic mechanism of Gluconobacter thailandicus's glycerol conversion is still not clear. Through in-depth analysis of the G. thailandicus genome and annotation of its metabolic pathways, we revealed the existence of both PQQ and NAD(P)+ -dependent enzymes in G. thailandicus. In addition, this study provides important information related to the tricarboxylic acid cycle, glycerol dehydrogenase level, and phylogenetic relationships of this important species.
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Genoma Bacteriano , Gluconobacter , Glicerol , Microrganismos Geneticamente Modificados , Ciclo do Ácido Cítrico/genética , Di-Hidroxiacetona/metabolismo , Engenharia Genética , Genoma Bacteriano/genética , Gluconobacter/genética , Gluconobacter/metabolismo , Glicerol/metabolismo , Microrganismos Geneticamente Modificados/genética , Microrganismos Geneticamente Modificados/metabolismo , NAD/metabolismo , NADP/metabolismo , Cofator PQQ/metabolismo , Filogenia , Desidrogenase do Álcool de Açúcar/análiseRESUMO
Cercis glabra is a plant belonging to the legume family, whose flowers and barks are commonly used as food and traditional Chinese medicines. However, its leaves are usually disposed of as wastes. This research comprehensively investigated the bioactive constituents of C. glabra leaves, and two new phenolic, ceroffesters A-B (1-2) and thirteen known compounds (3-15) were isolated. Their structures were elucidated by spectroscopic methods such as nuclear magnetic resonance (1D NMR and 2D NMR), high-resolution electrospray ionization mass spectra (HR-ESI-MS), optical rotatory dispersion (ORD) and electronic circular dichroism (ECD). All of them were assessed for their antioxidant activities through ABTS, DPPH and PTIO methodologies, and evaluated for inhibitory activities against two enzymes (mushroom tyrosinase and acetylcholinesterase). As a result, compounds 3-6, 10 and 13 exhibited evident antioxidant activities. Meanwhile, compounds 5, 10 and 13 showed the most potent tyrosinase inhibitory activities, with IC50 of 0.64, 0.65 and 0.59 mM, and compared with the positive control of 0.63 mM (kojic acid). In the initial concentration of 1 mg/mL, compounds 3, 5 and 6 demonstrated moderate inhibitory activities against acetylcholinesterase with 85.27 ± 0.06%, 83.65 ± 0.48% and 82.21 ± 0.09%, respectively, compared with the positive control of 91.17 ± 0.23% (donepezil). These bioactive components could be promising antioxidants, tyrosinase and acetylcholinesterase inhibitors.
Assuntos
Antioxidantes , Fabaceae , Antioxidantes/química , Inibidores da Colinesterase/farmacologia , Inibidores da Colinesterase/análise , Monofenol Mono-Oxigenase , Acetilcolinesterase , Extratos Vegetais/química , Folhas de Planta/químicaRESUMO
OBJECTIVES: To explore the value of detecting the peri-device leak (PDL) and device endothelialization after left atrial appendage closure (LAAC) by cardiac computed tomography (CT) in patients with atrial fibrillation (AF), who underwent Watchman LAAC combined with radiofrequency ablation of atrial fibrillation (AFCA). METHODS: Patients with symptomatic drug-refractory atrial fibrillation at high risk of stroke (CHA2 DS2 -VASc Score ≥ 2), who underwent Watchman LAAC combined with AFCA in our center from March 2017 to December 2018 were enrolled. Maximum diameter of LAA orifice was determined by preoperative CCTA. A standardized view of Watchman device was obtained by postoperative CCTA multiplannar reconstruction to evaluate the PDL and device endothelialization. RESULTS: Approximately 84 patients post successful LAAC and AFCA were enrolled in this study. The satisfactory LAA occlusion rate was 100%. There was no death, bleeding, stroke, and device-related thrombus (DRT) events. At 6-month postprocedure, CCTA images evidenced complete endothelialization in 44 patients (no contrast enhancement in LAA); contrast enhancement in LAA and visible PDL in 33 patients; contrast enhancement in LAA but without PDL in seven patients (incomplete device endothelialization). Maximum diameter of LAA orifice could independently predict the occurrence of PDL (odds ratio, 1.31; 95% confidence interval, 1.11-1.55; p = .002), sensitivity was 69.7% and specificity was 80.4% with the cutoff value of maximum diameter of LAA orifice more than 28.2 mm on predicting PDL. CONCLUSIONS: CCTA is feasible to evaluate PDL and device endothelialization after LAAC. The maximum diameter of LAA orifice derived from CT can independently predict the occurrence of post-LAAC PDL.
Assuntos
Apêndice Atrial , Fibrilação Atrial , Ablação por Radiofrequência , Apêndice Atrial/diagnóstico por imagem , Apêndice Atrial/cirurgia , Fibrilação Atrial/diagnóstico por imagem , Fibrilação Atrial/cirurgia , Angiografia por Tomografia Computadorizada , Ecocardiografia Transesofagiana , Humanos , Estudos Prospectivos , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
BACKGROUND: Premature ventricular complexes (PVCs) exhibit circadian fluctuation. We determine if PVCs of different origin exhibit specific circadian patterns. METHODS: We analyzed Holter recordings from patients with monomorphic PVCs who underwent catheter ablation. PVC circadian patterns were classified as fast-heart rate- (HR-) dependent (F-PVC), slow-HR-dependent (S-PVC), or HR-independent (I-PVC). PVC origins were determined intraprocedurally. RESULTS: In a retrospective cohort of 407 patients, F-PVC and S-PVC typically exhibited diurnal and nocturnal predominance, respectively. Despite decreased circadian fluctuation, I-PVC generally had heavier nocturnal than diurnal burden. PVCs of left anterior fascicle origin were predominantly S-PVC, while those of posterior hemibranch origin were mostly F-PVC. PVCs originating from the aortic sinus of Valsalva (ASV) were predominantly I-PVC, while most PVCs arising from the left ventricular outflow tract (LVOT) were F-PVC. Using a diurnal/nocturnal PVC burden ratio of 0.92 as the cutoff value to distinguish LVOT from ASV origin achieved 97% sensitivity and, as further verification, an accuracy of 89% (16/18) in a prospective cohort of patients with PVCs originating from either ASV or LVOT. In contrast, PVCs originating from right ventricles, such as right ventricular outflow tract, did not show distinct circadian patterns. CONCLUSIONS: The circadian patterns exhibit origin specificity for PVCs arising from left ventricles. An analysis of Holter monitoring provides useful information on PVC localization in ablation procedure planning.
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Ablação por Cateter/métodos , Ritmo Circadiano/fisiologia , Eletrocardiografia Ambulatorial/métodos , Complexos Ventriculares Prematuros , Feminino , Frequência Cardíaca , Ventrículos do Coração/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Planejamento de Assistência ao Paciente , Estudos Retrospectivos , Complexos Ventriculares Prematuros/diagnóstico , Complexos Ventriculares Prematuros/fisiopatologia , Complexos Ventriculares Prematuros/cirurgiaRESUMO
AIM: The feasibility and safety of performing the combined procedure of catheter ablation (CA) and left atrial appendage closure (LAAC) for atrial fibrillation (AF) have been reported by observational studies without controls. The aim of this study was to compare the procedural and long-term outcomes of combined procedures with isolated CA or LAAC. METHODS AND RESULTS: This study included patients who underwent combined CA and LAAC (combined group), CA alone (CA-only group), or LAAC alone (LAAC-only group). Propensity score matching was used to select controls from the CA-only and LAAC-only groups. Each group contained 76 subjects. The procedures were successfully performed in all the patients. Procedure-related complications of the combined group included one pericardial effusion and two groin haematomas, which did not differ significantly with those of the CA-only group (3.9% vs. 2.6%, P=0.650) or the LAAC-only group (3.9% vs. 2.6%, P=0.650), respectively. The AF-free rate of the combined group was comparable with that of the CA-only group after a mean of 2 years follow-up (67.1% vs. 69.7%, P=0.727). Compared with the LAAC-only group, the combined group achieved similar complete occlusion rate at implant (94.7% vs. 93.4%) and at 45 days (82.9% vs. 85.5%). At the end of follow-up, ischemic stroke and bleeding events of the combined group were low (3.9%) and were comparable with those of the CA-only group (5.3%) and the LAAC-only group (2.6%). CONCLUSIONS: The combination of AF-CA and LAAC is safe and efficacious compared with single procedures alone.
Assuntos
Apêndice Atrial/cirurgia , Fibrilação Atrial/cirurgia , Ablação por Cateter , Complicações Pós-Operatórias , Implantação de Prótese , Dispositivo para Oclusão Septal , Idoso , Fibrilação Atrial/complicações , Estudos de Casos e Controles , Ablação por Cateter/efeitos adversos , Ablação por Cateter/métodos , Feminino , Humanos , Masculino , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/etiologia , Implantação de Prótese/efeitos adversos , Implantação de Prótese/instrumentação , Implantação de Prótese/métodos , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Resultado do TratamentoRESUMO
BACKGROUND: Recently, left bundle branch area pacing (LBBAP) has been shown to be feasible. However, the right ventricular (RV) implantation site for LBBAP remains elusive. We believe that the RV implantation site should be located at the posteromedial basal septum, and in this paper, we propose a new method to help guide lead implantation. The aim of this study is to demonstrate the feasibility of the proposed method. METHODS: The RV implantation site was positioned by a combination of a nine-grid system on fluoroscopy and the use of intracardiac echocardiogram (ICE) and then verified by ICE. RESULTS: Fifteen patients were enrolled for LBBAP using our method. The acute success rate was 86.7% (13/15), which demonstrated that our method is useful for assisting with lead implantation. According to ICE, the distance between the implantation site and apex (the front) and the distance between the implantation site and tricuspid annulus (the back) were 44.9 ± 10.7 and 33.2 ± 10.4 mm, respectively, and the ratio of the front and the back was 1.57 ± 0.80. The distance between the implantation site and the front junction point of the left-right ventricle (the upper) and the distance between the implantation site and the back junction point (the lower) were 33.4 ± 10.6 and 24.5 ± 10.2 mm, respectively. The ratio of the upper to the lower was 1.76 ± 1.36. These results suggest that the implantation site was at the posteromedial basal septum. The width of the QRS duration increased from 110.4 ± 33.1 ms at baseline to 114.1 ± 16.1 ms post LBBAP (P > 0.05). The operation time was 133 ± 32.9 min. The time of X-ray fluoroscopy was 21.2 ± 5.9 min. The mean time for lead positioning during LBBAP was 33.8 ± 16.6 min. During a follow-up of 3 months, the LBB capture threshold remained stable in 12 patients, except for one patient who had an increase in the LBB capture threshold to 3.0 v/0.4 ms. CONCLUSIONS: Our preliminary results indicate that the posteromedial basal septum could be seen as the implantation site for LBBAP. As a technique for LBBAP, ICE is a useful method for assisting with lead implantation. It is feasible and safe to use a nine-grid system combined with ICE for LBBAP.
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Potenciais de Ação , Fascículo Atrioventricular/diagnóstico por imagem , Bloqueio de Ramo/terapia , Estimulação Cardíaca Artificial , Ecocardiografia , Frequência Cardíaca , Ventrículos do Coração/diagnóstico por imagem , Marca-Passo Artificial , Adulto , Idoso , Idoso de 80 Anos ou mais , Pontos de Referência Anatômicos , Fascículo Atrioventricular/fisiopatologia , Bloqueio de Ramo/diagnóstico por imagem , Bloqueio de Ramo/fisiopatologia , Estudos de Viabilidade , Feminino , Ventrículos do Coração/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Resultado do TratamentoRESUMO
INTRODUCTION: Catheter ablation of atrial fibrillation (AFCA) and left atrial appendage closure (LAAC) exert opposite effects on left atrial (LA) size. We aim to observe the net impact of combined AFCA and LAAC strategy on LA size and explore those factors which might affect the postprocedure LA structural remodeling. METHODS: A total of 53 patients, who underwent combined AFCA and Watchman LAAC in our center from March to December 2017, were enrolled. Atrial fibrillation (AF) recurrence was monitored after the procedure. Left atrial volume (LAV) and left atrial appendage volume (LAAV) were measured by Mimics based on dual-source computed tomography images. RESULTS: At 6 months, sinus rhythm (SR) was maintained in 79.2% patients. LAV was significantly reduced (130.2 ± 36.3 mL to 107.1 ± 30.0 ml; P < .001) in SR maintenance group, but not in AF recurrence group (138.8 ± 39.3 mL to 137.9 ± 36.9 mL; P = .671). In SR group, preoperative LAAV/LAV ratio (B = -0.894; P = .015), NT-proBNP (B = 0.005; P = .019) and left ventricular ejection fraction (LVEF) (B = -0.778; P < .001) could interactively affect the extent of postoperative LA structural reverse remodeling, among which LAAV/LAV ratio could independently predict the significance of reverse remodeling (≥15% reduction in LAV) (OR, 0.56; 95% CI, 0.34-0.90; P = .018). A preoperative LAAV/LAV ratio less than 7.1% is indicative of significant LA structural reverse remodeling in this patient cohort. CONCLUSIONS: LA structural reverse remodeling could be evidenced in patients with maintained SR following combined AFCA and LAAC. Smaller LAAV/LAV ratio, higher NT-proBNP or lower LVEF at baseline are associated with more significant LA structural reverse remodeling, while LAAV/LAV ratio can predict the significance of the process after one-stop treatment.
Assuntos
Apêndice Atrial/cirurgia , Fibrilação Atrial/cirurgia , Função do Átrio Esquerdo , Remodelamento Atrial , Procedimentos Cirúrgicos Cardíacos , Ablação por Cateter , Potenciais de Ação , Idoso , Apêndice Atrial/diagnóstico por imagem , Apêndice Atrial/fisiopatologia , Fibrilação Atrial/diagnóstico por imagem , Fibrilação Atrial/fisiopatologia , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Procedimentos Cirúrgicos Cardíacos/instrumentação , Ablação por Cateter/efeitos adversos , Feminino , Fibrose , Frequência Cardíaca , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
AIMS: Ventricular arrhythmias (VAs) originating from the para-Hisian region represent a challenging location. The long-term success rate of catheter ablation above the septal leaflet of the tricuspid valve is not ideal. This study aimed to investigate the safety and efficacy of catheter ablation for para-Hisian VAs via a direct approach under the septal valve with reversed C-curve technique. METHODS AND RESULTS: Twenty-five consecutive patients with para-Hisian VAs were included. Systematic mapping was performed in the right ventricle septum, including both the regions above and under the septal valve. Radiofrequency (RF) ablation was preferentially performed under the valve with reversed C-curve technique in all patients. If the ablation failed under the valve, it was then performed above the valve and even in aortic sinus cusps. The earliest ventricular activation preceding surface QRS (V-QRS) under the valve was significantly larger than that above the valve (34.8 ± 5.3 vs 27.8 ± 5.7 ms, P < .01). RF ablation under the valve with reversed C-curve technique achieved acute success in 22 of 25 (88%) patients. Junctional rhythm developed during ablation in 3 of 25 (12%) patients and no atrioventricular block occurred. In the remaining three patients, RF application above the valve failed to eliminate the VAs and one of them achieved successful ablation in the right coronary cusp. During a mean follow-up of 17.8 ± 9.4 months, no patients presented with VAs recurrence and no postprocedure complications occurred. CONCLUSIONS: Catheter ablation under the valve with reversed C-curve technique shows to be effective and safe for para-Hisian VAs.
Assuntos
Fascículo Atrioventricular/cirurgia , Ablação por Cateter , Frequência Cardíaca , Taquicardia Ventricular/cirurgia , Complexos Ventriculares Prematuros/cirurgia , Potenciais de Ação , Idoso , Fascículo Atrioventricular/fisiopatologia , Ablação por Cateter/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taquicardia Ventricular/diagnóstico , Taquicardia Ventricular/fisiopatologia , Fatores de Tempo , Resultado do Tratamento , Complexos Ventriculares Prematuros/diagnóstico , Complexos Ventriculares Prematuros/fisiopatologiaRESUMO
Left atrial appendage (LAA) closure (LAAC) has emerged as an alternative therapeutic approach to medical therapy for stroke prevention in patients with nonvalvular atrial fibrillation (NVAF). However, complex LAA anatomy may preclude its use. LAmbre is a new, self-expanding LAA occluder, and is highly adaptable to different LAA morphologies. We explored the feasibility, safety, and efficacy of LAAC using LAmbre device in NVAF patients with or without prior catheter ablation (CA). LAAC using LAmbre device was applied in NVAF patients with (group C) or without (group N) prior CA. Transesophageal echocardiography (TEE) was performed at 3, and 12 months post-LAAC. Among 17 LAAC patients (group C, 6 & group N, 11), 4 cases were implanted with special type devices, 5 were implanted with large devices. Besides one case of cardiac tamponade (N group), there were two minor peri-procedural complications only. Successful sealing of the LAA was documented in all the patients (100%) by TEE both post LAAC and at 3 months. At 3 months, no residual flow was achieved in 11 patients (64.7%); six patients (35.3%) had residual flow < 5 mm. There was no device dislocation or leakage during the mean of 30 months follow up. At 545 days after LAAC, one patient in group C experienced sudden death. Baseline, peri-procedural, and follow-up characteristics were similar between two groups (P > 0.05). LAAC with LAmbre device, subsequent to prior CA for AF, can be performed successfully and safely. The design and distinguishing features of this device could be of help in patients with complex anatomy of LAA.
Assuntos
Apêndice Atrial/diagnóstico por imagem , Fibrilação Atrial/cirurgia , Procedimentos Cirúrgicos Cardíacos/instrumentação , Idoso , Apêndice Atrial/cirurgia , Fibrilação Atrial/diagnóstico por imagem , Ablação por Cateter , Ecocardiografia Transesofagiana , Estudos de Viabilidade , Feminino , Humanos , Masculino , Desenho de Prótese , Dispositivo para Oclusão Septal , Resultado do TratamentoRESUMO
BACKGROUND: Post cardiac injury syndrome (PCIS) is a troublesome but not uncommon complication following catheter ablation of arrhythmias. We aimed to study the clinical features of ablation-associated PCIS. METHODS: For this purpose, we conducted a computerised literature search that identified 19 published cases, and we additionally included another two new cases from our centres. Twenty-one (21) cases of PCIS following ablation were analysed. RESULTS: Among the 21 cases, PCIS most commonly occurred after atrial flutter/fibrillation (AFL/AF) ablation (71.4%), followed by atrioventricular re-entrant tachycardia (AVRT) ablation (9.5%), atrioventricular node (AVN) ablation (9.5%), atrioventricular nodal re-entrant tachycardia (AVNRT) ablation (4.8%) and ventricular tachycardia (VT) ablation (4.8%). Thirty-eight (38) per cent of PCIS was suggested to be secondary to cardiac perforation. Specific symptoms or features include pleuritic chest pain (76.2%), fever (76.2%), elevated markers of inflammation (76.2%), pericardial effusion (90.5%), pleural effusion (71.4%) and pulmonary infiltrates (28.6%). Interestingly, all the six cases with pulmonary infiltrates were following AFL/AF ablation (6/15, 40%). Serious clinical manifestations include cardiac tamponade, massive pleural effusion with hypoalbuminaemia and hyponatraemia, and massive pulmonary infiltrates with hypoxaemia. Notably, empiric antibiotic therapy was used in seven cases including five with pulmonary infiltrates but failed to work. No mortality occurred during a mean follow-up of 4.1±5.3 (1 to 19) months. CONCLUSIONS: Catheter ablation of AFL/AF was most commonly involved in ablation-associated PCIS. Pulmonary infiltrate is an important feature of PCIS following AFL/AF ablation and may be misdiagnosed as pneumonia. Although PCIS is troublesome and even dangerous, it does carry a benign prognosis.
Assuntos
Fibrilação Atrial/cirurgia , Ablação por Cateter/efeitos adversos , Traumatismos Cardíacos/complicações , Pericardite/etiologia , Idoso , Idoso de 80 Anos ou mais , Diagnóstico Diferencial , Erros de Diagnóstico , Traumatismos Cardíacos/diagnóstico , Humanos , Masculino , Pericardite/diagnóstico , Radiografia Torácica , Síndrome , Tomografia Computadorizada por Raios XRESUMO
Atrial fibrosis, the hallmark of structural remodeling associated with atrial fibrillation (AF), is characterized by abnormal proliferation of atrial fibroblasts and excessive deposition of extracellular matrix. Transforming growth factor-ß1 (TGF-ß1)/activin receptor-like kinase 5 (ALK5)/Smad2/3/4 pathway has been reported to be involved in the process. Recent studies have implicated both activin A and its specific downstream component activin receptor-like kinase 4 (ALK4) in stimulating fibrosis in non-cardiac organs. We recently reported that ALK4 haplodeficiency attenuated the pressure overload- and myocardial infarction-induced ventricular fibrosis. However, the role of activin A/ALK4 in the pathogenesis of atrial fibrosis and vulnerability to AF remains unknown. Our study provided experimental and clinical evidence for the involvement of activin A and ALK4 in the pathophysiology of atrial fibrosis and AF. Patients with AF had higher activin A and ALK4 expression in atriums as compared to individuals devoid of AF. After angiotensin-II (Ang-II) stimulation which mimicked atrial fibrosis progression, ALK4-deficient mice showed lower expression of ALK4 in atriums, reduced activation of atrial fibroblasts, blunted atrial enlargement and atrial fibrosis, and further reduced AF vulnerability upon right atrial electrophysiological studies as compared to wild-type littermates. Moreover, we found that apart from the well-known TGF-ß1/ALK5 pathway, the activation of activin A/ALK4/smad2/3 pathway played an important role in the pathogenesis of Ang-II-mediated atrial fibrosis and inducibility of AF, suggesting that targeting ALK4 might be a potential therapy for atrial fibrosis and AF.
Assuntos
Receptores de Ativinas Tipo I/metabolismo , Ativinas/metabolismo , Fibrilação Atrial/metabolismo , Átrios do Coração/patologia , Adulto , Idoso , Angiotensina II/toxicidade , Animais , Fibrilação Atrial/patologia , Feminino , Fibrose , Átrios do Coração/metabolismo , Humanos , Masculino , Camundongos , Camundongos Knockout , Pessoa de Meia-IdadeRESUMO
AIMS: Myocardial infarction (MI) induces neural remodelling of the left stellate ganglion (LSG), which may contribute to ischaemia-induced arrhythmias. The neural chemorepellent Semaphorin 3a (Sema3a) has been identified as a negative regulator of sympathetic innervation in the LSG and heart. We previously reported that overexpression of Sema3a in the border zone could reduce the arrhythmogenic effects of cardiac sympathetic hyperinnervation post-MI. This study investigated whether Sema3a overexpression within the LSG confers an antiarrhythmic effect after MI through decreasing extra- and intra-cardiac neural remodelling. METHODS AND RESULTS: Sprague-Dawley rats were subjected to MI, and randomly allocated to intra-LSG microinjection of either phosphate-buffered saline (PBS), adenovirus encoding green fluorescent protein (AdGFP), or adenovirus encoding Sema3a (AdSema3a). Sham-operated rats served as controls. Two weeks after infarction, MI-induced nerve sprouting and sympathetic hyperinnervation in the LSG and myocardium were significantly attenuated by intra-LSG injection with AdSema3a, as assessed by immunohistochemistry and western blot analysis of growth-associated protein 43 and tyrosine hydroxylase. This was also confirmed by sympathetic nerve function changes assessed by cardiac norepinephrine content. Additionally, intra-LSG injection with AdSema3a alleviated MI-induced accumulation of dephosphorylated connexin 43 in the infarct border zone. Furthermore, Sema3a overexpression in the LSG reduced the incidence of inducible ventricular tachyarrhythmia by programmed electrical stimulation post-MI, and arrhythmia scores were significantly lower in the AdSema3a group than in the PBS and AdGFP groups. CONCLUSION: Semaphorin 3a overexpression in the LSG ameliorates the inducibility of ventricular arrhythmias after MI, mainly through attenuation of neural remodelling within the cardiac-neuraxis.
Assuntos
Infarto do Miocárdio/complicações , Semaforina-3A/uso terapêutico , Gânglio Estrelado/metabolismo , Taquicardia Ventricular/terapia , Animais , Modelos Animais de Doenças , Ecocardiografia , Eletrocardiografia , Terapia Genética , Coração/inervação , Masculino , Miocárdio/metabolismo , Norepinefrina , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Semaforina-3A/genética , Gânglio Estrelado/efeitos dos fármacos , TransfecçãoRESUMO
Warfarin is yet the most widely used oral anticoagulant for thromboembolic diseases, despite the recently emerged novel anticoagulants. However, difficulty in maintaining stable dose within the therapeutic range and subsequent serious adverse effects markedly limited its use in clinical practice. Pharmacogenetics-based warfarin dosing algorithm is a recently emerged strategy to predict the initial and maintaining dose of warfarin. However, whether this algorithm is superior over conventional clinically guided dosing algorithm remains controversial. We made a comparison of pharmacogenetics-based versus clinically guided dosing algorithm by an updated meta-analysis. We searched OVID MEDLINE, EMBASE, and the Cochrane Library for relevant citations. The primary outcome was the percentage of time in therapeutic range. The secondary outcomes were time to stable therapeutic dose and the risks of adverse events including all-cause mortality, thromboembolic events, total bleedings, and major bleedings. Eleven randomized controlled trials with 2639 participants were included. Our pooled estimates indicated that pharmacogenetics-based dosing algorithm did not improve percentage of time in therapeutic range [weighted mean difference, 4.26; 95% confidence interval (CI), -0.50 to 9.01; P = 0.08], but it significantly shortened the time to stable therapeutic dose (weighted mean difference, -8.67; 95% CI, -11.86 to -5.49; P < 0.00001). Additionally, pharmacogenetics-based algorithm significantly reduced the risk of major bleedings (odds ratio, 0.48; 95% CI, 0.23 to 0.98; P = 0.04), but it did not reduce the risks of all-cause mortality, total bleedings, or thromboembolic events. Our results suggest that pharmacogenetics-based warfarin dosing algorithm significantly improves the efficiency of International Normalized Ratio correction and reduces the risk of major hemorrhage.
Assuntos
Cálculos da Dosagem de Medicamento , Hemorragia , Tromboembolia/tratamento farmacológico , Varfarina , Algoritmos , Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Coagulação Sanguínea/efeitos dos fármacos , Hemorragia/induzido quimicamente , Hemorragia/diagnóstico , Hemorragia/prevenção & controle , Humanos , Coeficiente Internacional Normatizado , Farmacogenética/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto , Varfarina/administração & dosagem , Varfarina/efeitos adversosRESUMO
OBJECTIVE: To investigate the association between CHADS2 score and long-term ( ≥ 3 years) outcomes post catheter ablation in patients with atrial fibrillation (AF). METHODS: AF patients who received single catheter ablation in our hospital from January 2004 to March 2009 in our department were included and patients received regular follow-up. AF recurrence was defined as the occurrence of atrial arrhythmias (AF, atrial flutter and atrial tachycardia) recorded by electrocardiogram monitor ( ≥ 30 seconds) after ablation during follow-up period (after 3 months blanking period). The relationship between baseline clinical and echocardiographic characteristics and the time to recurrence during follow-up was evaluated using Cox multivariate analysis. RESULTS: A total of 280 patients who received single catheter ablation procedure were included in the study, 3 patients died and there were 50 patients lost to follow-up. A total of 227 patients with AF (163 paroxysmal and 64 non-paroxysmal ) were enrolled in the final analysis. During a median follow-up of 51 months (41-56 months), 109 patients experienced AF recurrences and the recurrence rate after catheter ablation ( ≥ 3 years) was 48.0% (109/227). Cox multivariate analysis showed that the high CHADS2 score (HR: 1.417, 95%CI 1.194-1.682, P < 0.001) and AF non-termination during ablation (HR: 2.077, 95%CI 1.380-3.126, P = 0.043) were risk factors of AF recurrence. AF recurrence rates in the termination and non-termination group were 41.0% (75/183) and 77.3% (34/44), respectively. In the AF termination group, the recurrence rates and the median recurrence free time in patients with CHADS2 score ≥ 3 were 80.0% (12/15) and 1 year, respectively. In the non-AF termination group, the recurrence rates in patients with CHADS2 score = 0, CHADS2 score = 1-2 and CHADS2 score ≥ 3 were 60.0% (6/10), 77.8% (21/27) and 100% (7/7), respectively; the median recurrence free time of patients with CHADS2 score = 0, CHADS2 score = 1-2 and CHADS2 score ≥ 3 were 30 months, 12 months and 6 months, respectively. CONCLUSIONS: CHADS2 score is a predictor of AF recurrences after catheter ablation. Patients with high CHADS2 score is associated with higher risk of long-term ( ≥ 3 years) AF recurrences.
Assuntos
Fibrilação Atrial/cirurgia , Ablação por Cateter/métodos , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Fatores de Risco , Resultado do TratamentoRESUMO
The management of brewery waste, particularly waste brewer's yeast, has posed a significant environmental and economic challenge. This study proposed an approach to valorize waste brewer's yeast by extracting ß-glucan. The key phases of the research included yeast autolysis, alkaline treatment and optimization of the ß-glucan purification conditions. The findings revealed that a 0.7 % NaOH concentration at 80 °C for 2.6 h was the most effective for impurity removal. In the comparative analysis, it was confirmed that extraction at 80 % DMSO concentration with a 30:1 solid-liquid ratio at 80 °C for 30 min was the optimal condition for obtaining high-purity ß-glucan. The process yielded a ß-glucan high purity of 95.84 ± 1.15 % and a yield of 5.56 ± 0.34 % based on the wet weight after centrifugation. The structure was analyzed using TLC, FTIR and NMR. The extracts are polysaccharides composed of glucose monomers linked by ß-glycosidic bonds. In addition, It has demonstrated significant anti-inflammatory properties in vitro and can be developed as a functional food. This study provides a feasible and efficient solution for the sustainable utilization of waste brewer's yeast, contributing to environmental sustainability and offering economic benefits for the brewing industry.
RESUMO
Background: Many patients with atrial fibrillation (AF) discontinued oral anticoagulation (OAC) therapy after successful catheter ablation. We aimed to determine the real-world risks and consequences of discontinuing OAC use after catheter ablation for AF. Methods: Patients who underwent successful catheter ablation for AF from January 2004 to December 2020 were divided into continued long-term OAC (On-OAC, n = 1062) and discontinued (Off-OAC, n = 1055) groups. The long-term outcomes including thromboembolic events, major bleeding, all-cause mortality and major adverse cardiovascular events (MACE), were compared between the two groups. Results: The CHA2DS2-VASc score was 3.44 ± 1.12. After a mean follow-up of 37.09 months, thromboembolism risk was higher and major bleeding risk was lower in the Off-OAC than in the On-OAC group (Both log-rank P < 0.001). CHA2DS2-VASc score-stratified subgroup analysis showed similar cumulative event rates between the two groups in men and women with scores of 2 and 3 (intermediate risk for stroke), respectively, (P > 0.05), except for a higher major bleeding rate in the On-OAC group (P = 0.002). Patients at high risk for stroke (men and women with scores ≥3 and ≥ 4) had better non-thromboembolic and non-MACE results (Both log-rank P < 0.05). Conclusion: Men with a CHA2DS2-VASc score of 2 and women with a score of 3 had a relatively low incidence of stroke events after successful catheter ablation for AF and may be safe for anticoagulation cessation. Greater benefits from long-term OAC were observed in men with CHA2DS2-VASc score ≥3 and women with score ≥4.