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1.
Circ Cardiovasc Interv ; : e013579, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38629273

RESUMO

BACKGROUND: The prognostic impact of left atrial appendage (LAA) patency, including those with and without visible peri-device leak (PDL), post-LAA closure in patients with atrial fibrillation, remains elusive. METHODS: Patients with atrial fibrillation implanted with the WATCHMAN 2.5 device were prospectively enrolled. The device surveillance by cardiac computed tomography angiography was performed at 3 months post-procedure. Adverse events, including stroke/transient ischemic attack (TIA), major bleeding, cardiovascular death, all-cause death, and the combined major adverse events (MAEs), were compared between patients with complete closure and LAA patency. RESULTS: Among 519 patients with cardiac computed tomography angiography surveillance at 3 months post-LAA closure, 271 (52.2%) showed complete closure, and LAA patency was detected in 248 (47.8%) patients, including 196 (37.8%) with visible PDL and 52 (10.0%) without visible PDL. During a median of 1193 (787-1543) days follow-up, the presence of LAA patency was associated with increased risks of stroke/TIA (adjusted hazard ratio for baseline differences, 3.22 [95% CI, 1.17-8.83]; P=0.023) and MAEs (adjusted hazard ratio, 1.12 [95% CI, 1.06-1.17]; P=0.003). Specifically, LAA patency with visible PDL was associated with increased risks of stroke/TIA (hazard ratio, 3.66 [95% CI, 1.29-10.42]; P=0.015) and MAEs (hazard ratio, 3.71 [95% CI, 1.71-8.07]; P=0.001), although LAA patency without visible PDL showed higher risks of MAEs (hazard ratio, 3.59 [95% CI, 1.28-10.09]; P=0.015). Incidences of stroke/TIA (2.8% versus 3.0% versus 6.7% versus 22.2%; P=0.010), cardiovascular death (0.9% versus 0% versus 1.7% versus 11.1%; P=0.005), and MAEs (4.6% versus 9.0% versus 11.7% versus 22.2%; P=0.017) increased with larger PDL (0, >0 to ≤3, >3 to ≤5, or >5 mm). Older age and discontinuing antiplatelet therapy at 6 months were independent predictors of stroke/TIA and MAEs in patients with LAA patency. CONCLUSIONS: LAA patency detected by cardiac computed tomography angiography at 3 months post-LAA closure is associated with unfavorable prognosis in patients with atrial fibrillation implanted with WATCHMAN 2.5 device. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03788941.

2.
Diagnostics (Basel) ; 13(21)2023 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-37958221

RESUMO

BACKGROUND: Managing patients with atrial fibrillation (AF) and comorbid heart failure (HF) with reduced (HFrEF) or mildly reduced ejection fraction (HFmrEF) is of clinical importance but a great challenge. This study aimed to evaluate the clinical benefit of the combined radiofrequency catheter ablation (RFCA) and left atrial appendage closure (LAAC) procedure in AF patients complicated with systolic HF. METHODS: AF patients with HFrEF or HFmrEF who underwent the combined RFCA and LAAC procedure were prospectively enrolled in the LAACablation registry. The procedural complications and long-term outcomes were evaluated. Another cohort of AF patients with systolic HF who did not undergo either RFCA or LAAC were used for prognosis comparison. RESULTS: Among 802 AF patients who underwent the combined procedure, 65 patients were comorbid with systolic HF (25 with HFrEF and 40 with HFmrEF). The overall procedural complication rate was 9.2%, which was mainly attributed to acute decompensated HF (6.2%). Accompanied with markedly reduced AF burden (from median [25th, 75th percentile]: 100 [100, 100] to 0 [0, 1.2]%, p < 0.001), upward trajectories of cardiac function were observed in 51 (78.4%) patients, showing improvement in New York Heart Classification (p < 0.01), natriuretic peptide levels (from 1492 [809, 3259] to 413 [163, 880] pg/mL, p < 0.001) and left ventricular EF (from 42.6 ± 5.3 to 53.8 ± 8.2%, p < 0.001). During the 27-month follow-up period, death, thromboembolism, major bleeding, and HF rehospitalization were observed in three, one, one, and four patients, respectively. The observed event rates showed a significant reduction compared with the non-procedure AF-HF cohort (n = 138; for composite endpoint: hazard ratio: 2.509, 95% confidence interval: 1.415-4.449, p = 0.002) and with the respective rates predicted by risk scores. CONCLUSIONS: Combining RFCA and LAAC achieves acceptable safety and credible long-term efficacy in AF patients with systolic HF. Further randomized studies are warranted in a larger patient cohort.

3.
JACC Clin Electrophysiol ; 9(12): 2477-2490, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37831033

RESUMO

BACKGROUND: Multifocal ectopic Purkinje-related premature contractions (MEPPCs) are associated with SCN5A variants. However, it is not well understood why Purkinje fibers, but not ventricular myocardium, play a predominant role in arrhythmogenesis. OBJECTIVES: This study sought to explore the underlying mechanisms of MEPPC. METHODS: Whole-cell patch-clamp and molecular biology techniques were used in the present study. RESULTS: Clinical data from one patient with R814W variant showed MEPPC syndrome, which is well responsive to amiodarone. Compared with canine ventricular myocytes, Purkinje cells (PCs) had significantly larger sodium current (INa), leftward shift of INa activation and inactivation curves, suggesting higher sodium channel excitability in PCs. Real-time polymerase chain reaction and Western blot analysis showed that the mRNA and protein expression of NaVß1 and NaVß3 was higher in canine Purkinje fibers than in ventricular myocardium. INa in heterologous Chinese hamster ovary cell expression system co-expressing NaV1.5 and NaVß1/NaVß3 exhibited similar biophysical properties of INa in PCs. R814W variant shifted INa activation in a hyperdepolarized direction, caused a larger window current, and generated an outward-gating pore current at depolarized voltages. Coexpression of NaVß1/NaVß3 with Nav1.5-R814W further left-shifted INa activation and caused an even larger window current and gating pore current, suggesting higher susceptibility of Purkinje fibers to R814W variant. Amiodarone inhibited INa, shifted its inactivation to more negative voltages, and significantly decreased the window current. CONCLUSIONS: A higher expression of ß1 and ß3 subunits contributes to higher sodium channel excitability in cardiac Purkinje fibers, making them more susceptible to MEPPC.


Assuntos
Amiodarona , Ramos Subendocárdicos , Cricetinae , Humanos , Animais , Cães , Células CHO , Cricetulus , Arritmias Cardíacas/metabolismo
4.
Am J Cardiol ; 204: 312-319, 2023 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-37567023

RESUMO

Left atrial appendage closure (LAAC) proved to be noninferior to oral anticoagulation (OAC) in nonablated patients with atrial fibrillation (AF). This study aimed to compare the efficacy and safety of LAAC with those of OAC therapy in patients after AF ablation. This study included patients who underwent catheter ablation (CA) of AF between January 2016 and December 2020. The cohort was divided into CA + LAAC and CA + OAC, where propensity score matching was used to select controls, and each group contained 682 subjects. The enrolled patients' mean age was 70.34 ± 8.32 years, and 47.3% were female; their CHA2DS2-VASc score was 3.48 ± 1.17. Baseline characteristics were similar between groups. After a 3-year mean follow-up, the incidence of thromboembolic events was 1.25 and 1.10 and that of major bleeding events was 0.65 and 1.72 per 100 patient-years in the CA + LAAC, and CA + OAC groups, respectively. The rate of thromboembolisms and major adverse cardiovascular events was similar between the 2 groups (hazard ratio [HR] 1.162, 95% confidence interval [CI] 0.665 to 2.030, p = 0.598, HR 0.711, 95% CI 0.502 to 1.005, p = 0.053); however, that of major bleeding and all-cause death was significantly reduced with LAAC (HR 0.401, 95% CI 0.216 to 0.746, p = 0.004, HR 0.528, 95% CI 0.281 to 0.989, p = 0.046). There was no significant difference in periprocedural complications (p >0.05) and the rate of AF recurrence (OAC vs LAAC: 39.44% vs 40.62%, p = 0.658). LAAC is a reasonable and safer alternative to OAC therapy in high-risk patients after AF ablation.


Assuntos
Apêndice Atrial , Fibrilação Atrial , Ablação por Cateter , Acidente Vascular Cerebral , Tromboembolia , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Masculino , Fibrilação Atrial/complicações , Fibrilação Atrial/cirurgia , Resultado do Tratamento , Apêndice Atrial/cirurgia , Hemorragia/induzido quimicamente , Tromboembolia/epidemiologia , Tromboembolia/etiologia , Tromboembolia/prevenção & controle , Anticoagulantes/uso terapêutico , Ablação por Cateter/efeitos adversos , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle
5.
Clin Cardiol ; 46(10): 1202-1209, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37522390

RESUMO

BACKGROUND: Catheter ablation (CA) combined with left atrial appendage occlusion (LAAO) is a feasible approach for atrial fibrillation (AF) patients. Its role in octogenarians with AF is unclear. HYPOTHESIS: In AF patients over 80 years, CA combined with LAAO is a feasible way in restoring sinus rhythm and preventing stroke. METHODS: This is a single-center retrospective study. Patients who underwent CA and LAAO in a single procedure between March 2018 and December 2020 were included. Efficacy endpoints included procedural success rate, AF recurrence rate, and thromboembolic events. Safety endpoints included pericardial effusion/cardiac tamponade, device-related thrombus (DRT), all-cause death, and major bleeding. RESULTS: Five hundred and five patients (mean age 69.5 ± 7.7 years; 230 [45.5%] female) were included, with 46 (9.1%) patients aged ≥80 years old (octogenarian group). Prevalence of paroxysmal AF (25 [54.3%] vs. 207 [45.1%], p < 0.001) and CHA2DS2VASc score (4.1 ± 1.3 vs. 3.1 ± 1.4, p < 0.0001) were higher in octogenarian patients. There were six cases (1.2%) of pericardial effusion (all in nonoctogenarian patients). At 3 months postprocedure, 437 patients underwent TEE/CT. Thirty-two (80%) octogenarian patients and 308 (77.6%) nonoctogenarian patients had no peri-device leak. After a mean follow-up of 26.9 ± 9.1 months, AF was documented in 10 (21.7%) patients in octogenarian group and in 103 (22.4%) patients in nonoctogenarian group (p = 0.99). The annual thromboembolic risk was 2.1% and 0.8% in the octogenarian group and nonoctogenarian group, respectively. Death occurred in 16 nonoctogenarian patients. One major bleeding was recorded in the octogenarian group. CONCLUSIONS: The combination of CA and LAAO in a single procedure is a feasible treatment option in octogenarians with comparable efficacy and safety profile.


Assuntos
Apêndice Atrial , Fibrilação Atrial , Derrame Pericárdico , Acidente Vascular Cerebral , Tromboembolia , Idoso de 80 Anos ou mais , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Masculino , Fibrilação Atrial/complicações , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/cirurgia , Octogenários , Apêndice Atrial/diagnóstico por imagem , Apêndice Atrial/cirurgia , Derrame Pericárdico/diagnóstico , Derrame Pericárdico/epidemiologia , Derrame Pericárdico/etiologia , Estudos Retrospectivos , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Hemorragia , Resultado do Tratamento
6.
Enzyme Microb Technol ; 169: 110290, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37473696

RESUMO

Pullulanase (PulB) is a starch-debranching enzyme. In order to improve its catalytic performance, random mutagenesis was performed on the pullulanase gene derived from Bacillus thermoliquefaciens. Two rounds of error-prone PCR were carried out. Mutant T252S was screened in the first round of error-prone library, which had the highest catalytic activity. During the second round of mutations, mutant enzyme G250P/T252S/G253T/N255K was screened, which had further improved catalytic activity and the best thermostability. Compared with the parent enzyme, the specific activity of mutant enzyme G250P/T252S/G253T/N255K increased by 1.9 times, Km decreased by 22.7 %, kcat increased by 28.7 %, and kcat/Km increased by 68.4 %. The thermostability of the mutant enzyme improved significantly, showing that the half-life at 60 °C was extended to 7.5 h, which was 87.5 % higher than that of the parent enzyme. The mutation sites in these two rounds were concentrated in the 250-255 regions, indicating that this region was an important region affecting the catalytic activity and Thermostability. The reasons for the change of enzymtic properties was also preliminarily analyzed through three-dimensional simulation.


Assuntos
Geobacillus stearothermophilus , Glicosídeo Hidrolases , Geobacillus stearothermophilus/genética , Geobacillus stearothermophilus/metabolismo , Temperatura , Glicosídeo Hidrolases/genética , Glicosídeo Hidrolases/metabolismo , Reação em Cadeia da Polimerase , Estabilidade Enzimática
8.
JACC Asia ; 3(1): 138-149, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36873751

RESUMO

Background: More than 40% of left atrial appendage closure (LAAC) procedures were combined with atrial fibrillation (AF) ablation in China. Objectives: This study aimed to assess the sex differences in the combined radiofrequency catheter ablation and LAAC procedures. Methods: Data from the LAACablation (Left Atrial Appendage Closure in Combination With Catheter Ablation) registry, which enrolled AF patients who underwent the combined procedure between 2018 and 2021, were analyzed. Procedural complications, long-term outcomes, and quality of life (QoL) were compared between sexes. Results: Of 931 patients, 402 (43.2%) were women. Compared with men, women were older (age 71.3 ± 7.4 years vs 68.7 ± 8.1 years; P < 0.001), presented more often with paroxysmal AF (52.5% vs 42.7%; P < 0.003), and had higher CHA2DS2-VASc scores (4.1 ± 1.5 vs 3.1 ± 1.5; P < 0.001), but received less often linear ablation and had shorter total procedural times and radiofrequency catheter ablation times. Women had similar rates of total and major procedural complications but presented with a higher incidence of minor complications than men (3.7% vs 1.3%; P = 0.027). Follow-up over 1,812 patient-years revealed similar adverse events between women and men, including all-cause death (HR: 0.89; 95% CI: 0.43-1.85; P = 0.754), thromboembolic events (HR: 1.17; 95% CI: 0.54-2.52; P = 0.697), major bleeding (HR: 0.96; 95% CI: 0.38-2.44; P = 0.935), and their composite (HR: 0.85; 95% CI: 0.56-1.28; P = 0.434). The recurrence rates of atrial tachyarrhythmia were also comparable between sexes presenting either paroxysmal or persistent AF. Women were seen with greater QoL impairment at baseline, but the sex gap narrowed at 1-year follow-up. Conclusions: In AF patients who underwent the combined procedure, women had similar procedural safety and long-term efficacy to men and presented greater QoL improvement. (Left Atrial Appendage Closure in Combination With Catheter Ablation [LAACablation]; NCT03788941).

9.
Heliyon ; 9(1): e12662, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36691523

RESUMO

Background: Left atrial appendage (LAA) closure (LAAC) in atrial fibrillation (AF) patients with the reversed chicken-wing (RCW) LAA is challenging. Aims: To elucidate the LAAC strategy of the RCW-LAA. Methods: A total of 802 AF patients who were enrolled in the LAACablation registry for LAAC procedure were included, 55 of whom presented with the RCW-LAA. The WATCHMAN device was implanted using the standard protocol when the sheath depth was no less than the device depth (the simple group). For those with a sheath depth of less than the device depth (the complex group), device deployment was attempted with acceptable protrusion or after a repeated atrial transseptal puncture (re-ATP) at a more inferior and anterior position. The anatomical and procedural features were compared between groups and before and after the re-ATP. Results: The success rate of LAAC was significantly lower in patients with the RCW-LAA than with the other morphologies (92.7% vs. 98.8%, p = 0.001). Compared with the simple group, the complex group had shorter root depth and shorter neck length, and more LAAs in the complex group were at lower position (all p < 0.05). The sheath depth after the re-ATP was significantly greater than that before the re-ATP (18.8 ± 3.4 mm vs. 14.7 ± 2.6 mm, p < 0.001). For the patients who underwent re-ATP, the sheath went significantly deeper in successful procedures than in aborted procedures (19.7 ± 3.3 mm vs. 15.8 ± 1.8 mm, p = 0.040). Conclusions: The anatomical features of the RCW-LAA were related to the complexity of the LAAC procedure. The re-ATP at an inferior and anterior location could increase the success rate of LAAC. ClinicalTrialsgov: NCT03788941.

10.
Europace ; 25(1): 146-155, 2023 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-35942655

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 , Recidiva
11.
Molecules ; 27(24)2022 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-36557801

RESUMO

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/química
12.
Int J Cardiol ; 368: 41-48, 2022 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-35952939

RESUMO

BACKGROUND: The combined procedure of catheter ablation and left atrial appendage closure (LAAC) aims to simultaneously control the heart rhythm and reduce the risk of strokes in patients with atrial fibrillation (AF). The study aims to evaluate the procedural safety and long-term outcome of the combined procedure in a large patient cohort. METHODS: Clinical data of AF patients who underwent the combined procedure was retrospectively analyzed. Procedural and imaging follow-up parameters were compared between the transesophageal echocardiography-guided standard process and fluoroscopy-guided modified process, and between the single-seal WATCHMAN and dual-seal LACBES devices. Long-term outcomes included all-cause mortality, thromboembolic events, major bleeding, and recurrence of atrial tachyarrhythmias. RESULTS: A total of 1114 patients were included. The rates of procedure-related major complications were comparable between the standard and modified processes (3.7% vs. 2.2%, p = 0.219), except for a higher incidence of respiratory depression in standard process group (0.9% vs 0%, p = 0.037), and between WATCHMAN and LACBES devices (2.4% vs. 3.3%, p = 0.535). The follow-up imaging evaluation revealed a high rate of satisfactory seals (99.7%) and a low rate of device related thrombus (1.9%), which were similar between two process groups and devices. The follow-up of over 1960 patient-years revealed low rates of mortality, thromboembolism, and nonprocedural major bleeding (1.8, 3.2, and 0.9 per 100 patient-years, respectively). Recurrent atrial tachyarrhythmias was observed in 23.9% patients. CONCLUSIONS: The results supported the safety and long-term efficacy of the combined procedure of catheter ablation and LAAC. Fluoroscopy-guided LAAC device implantation may be considered in experienced centers.


Assuntos
Apêndice Atrial , Fibrilação Atrial , Ablação por Cateter , Acidente Vascular Cerebral , Tromboembolia , Apêndice Atrial/diagnóstico por imagem , Apêndice Atrial/cirurgia , Fibrilação Atrial/complicações , Fibrilação Atrial/diagnóstico por imagem , Fibrilação Atrial/cirurgia , Ablação por Cateter/métodos , Hemorragia/etiologia , Humanos , Estudos Retrospectivos , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Tromboembolia/etiologia , Resultado do Tratamento
13.
J Cardiovasc Transl Res ; 15(5): 1010-1023, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35377130

RESUMO

Abnormal function of endothelial cells (ECs) is an important reason for vascular endothelial remodeling and atherosclerotic plaque formation in patients with atherosclerosis (AS). Here, we report for the first time that the vascular ECs with apoptosis resistance phenotype (ARECs) exist in peripheral blood of AS patients. Our research data showed that the switch of regulation modes between HIF-1α and Bax operated by lncRNA-ASLNC18810 is the direct cause for the formation of ARECs. When ASLNC18810 is low or missing, HIF-1α indirectly negatively regulates the Bax in post-transcription through HIF-1α/miR-559/Bax pathway which makes ECs acquire apoptosis resistance and form ARECs. The functional experiments results showed that ASLNC18810 could effectively eliminate the anti-apoptotic properties of ARECs by blocking the HIF-1α/miR559/Bax pathway and maintaining HIF-1α/Bax pathway. In a word, our study shows that ASLNC18810 has full potential to become a biological target for the prevention and treatment of atherosclerotic plaques by regulating ARECs. ASLNC18810 was significantly upregulated in ECs compared to ARECs. With high level of ASLNC18810 in ECs, ASLNC18810 binds to miR-559 as a miRNA sponge and suppresses the inhibition effect of miR-559 on Bax protein, this direct positive transcriptional regulation between HIF-1α and Bax endows the apoptotic property in ECs induced by Ox-LDL. However, with low expression of ASLNC18810 in ARECs, the post-transcriptional regulation of Bax by miR-559 dominates and the indirect negative regulation between HIF-1α and Bax endows the anti-apoptotic property of ARECs. To sum up, low ASLNC18810 expression-mediated switching of HIF-1α/Bax pathway to HIF-1α/miR-559/Bax pathway is the internal reason for ECs to obtain apoptosis resistance and the formation of ARECs under the ox-LDL induction.


Assuntos
Aterosclerose , MicroRNAs , Placa Aterosclerótica , RNA Longo não Codificante , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Células Endoteliais/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo , Aterosclerose/genética , Aterosclerose/metabolismo , Apoptose , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/farmacologia
14.
Front Cardiovasc Med ; 9: 821960, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35445083

RESUMO

Background: Atrial fibrillation (AF) is the most common arrhythmia, and the incidence increases rapidly all over the world. The global prevalence of AF (age-adjusted) is 0.60% for men and 0.37% for women and the prevalence of AF in China is 0.65%. It is expected that the number of patients with AF will continue to rise in the future worldwide due to population aging. Objective: To explore the prevalence of AF in Chinese community population in 2019 and clarify the prevalence of AF complicated with other arrhythmias and myocardial ischemia (MI) events. Methods: The remote electrocardiogram (ECG) diagnosis system of Xinhua Hospital was assessed to the screen participants with ECG evidence of AF between January 1 and December 31, 2019. The prevalence rates of AF and its association with other arrhythmias and MI events were analyzed and subgroup analysis was performed between different sexes and age groups. Results: A total of 22,016 AF cases were identified out of all ECGs derived from the remote ECG diagnosis system in 2019. It is estimated that AF was presented in nearly 10.15 million people in China (age-adjusted standardized rate 0.72%, 95% CI 0.20-1.25%) in 2019 and 62% of the AF cases (6.27 million) affected people aged 65 years and above (age-adjusted standardized rate 3.56%, 95% CI 3.28-3.85%). The prevalence rate of AF in males was higher than that in females (p < 0.001), and the ventricular rate of AF patients was faster in females (p < 0.001) and younger patients (p < 0.001). AF patients with lower ventricular rate (under 60 beats per min) were associated with increased prevalence of ventricular escape/escape rhythm [p < 0.001, odds ratio (OR) 5.14] and third-degree atrioventricular block (p < 0.001, OR 32.05). Conclusion: The prevalence of AF is higher in the Chinese community population than that was previously reported. AF patients complicated with ECG patterns suggesting myocardial infarction is common in men, and stricter measures should be taken to control the common risk factors of AF and coronary heart disease. It is also important that more attention should be paid to recognize fatal arrhythmias, especially in elderly male patients with AF.

16.
Biotechnol Appl Biochem ; 69(3): 1190-1198, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34009642

RESUMO

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.


Assuntos
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/análise
17.
Heart Rhythm ; 19(3): 344-351, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34775069

RESUMO

BACKGROUND: Pulmonary vein isolation (PVI) for paroxysmal atrial fibrillation (AF) is associated with a non-negligible long-term recurrence rate. OBJECTIVES: The purpose of this study was to investigate whether PVI combined with 6 short ablation lines on the PVI circumferences (PVI+6L group) yields higher success rates than PVI alone (PVI group). METHODS: In this multicenter, single-blind, randomized trial, a total of 390 patients with paroxysmal AF were randomly assigned to the PVI group (n = 193) or the PVI+6L group (n = 197). The primary endpoint was freedom from AF/atrial tachycardia recurrence between 91 and 365 days. Secondary endpoints included AF burden, procedural parameters, and complications. RESULTS: Freedom from atrial tachyarrhythmia was achieved in 160 of 197 patients (81.2%) in the PVI+6L group and 142 of 193 patients (73.6%) in the PVI group (hazard ratio 0.61; 95% confidence interval 0.39-0.97; P = .040). Mean AF burden tended to be lower in the PVI+6L group compared to the PVI group (1.95% vs 0.53%, P = .097). Procedural and ablation times were slightly longer in the PVI+6L group than in the PVI group (130 ± 25 minutes vs 121 ± 28 minutes; P = .002; and 46 ± 14 minutes vs 41 ± 16 minutes, P = .001, respectively). X-ray exposure was similar (60 ± 54 seconds vs 61 ± 60 seconds; P = .964). Complications occurred in 3 patients (1.6%) in the PVI group and 3 patients (1.5%) in the PVI+6L group. CONCLUSION: In patients with paroxysmal AF undergoing catheter ablation, adding 6 short ablation lines on the PVI circumferences could reduce the AF recurrence rate.


Assuntos
Fibrilação Atrial , Ablação por Cateter , Veias Pulmonares , Fibrilação Atrial/cirurgia , Ablação por Cateter/efeitos adversos , Ablação por Cateter/métodos , Átrios do Coração , Humanos , Veias Pulmonares/cirurgia , Recidiva , Método Simples-Cego , Resultado do Tratamento
18.
Dis Markers ; 2021: 8116633, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34853624

RESUMO

BACKGROUND: Neuropeptide levels are closely associated with the development and maintenance of atrial fibrillation (AF) after myocardial infarction (MI). This study was aimed at investigating the regulatory network that affects neuropeptide expression through transcription factor modulation. METHODS: We downloaded three datasets from the GEO database, and after performing differential and crosstabulation analyses, we screened out differentially expressed (DE) miRNAs and DEmRNAs coexpressed in AF and MI and performed DEmiRNA-DEmRNA pairing prediction; from which, we constructed a regulatory network. Subsequently, the hsa-miR-662-CREB1-VIP axis was obtained, and the role of CREB1 and VIP in the development of AF after MI was further revealed by single-cell analysis and prediction model construction. RESULTS: In this study, eight DEmRNAs and four miRNAs were screened. hsa-miR-662 was identified by database integration analysis to regulate the transcription factor CREB1, a potential transcriptional regulator in VIP. CREB1 and VIP are mainly enriched in pathways of energy metabolism, ion channels, and myocardial contraction. CREB1 and VIP were identified as biomarkers of the onset and prognosis of MI and AF. CONCLUSIONS: In this study, the miR-662/CREB1/VIP regulatory pathway was constructed through integrated analysis of datasets, thus providing new ideas to study the mechanisms of AF development.


Assuntos
Fibrilação Atrial/patologia , Biologia Computacional/métodos , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Regulação da Expressão Gênica , Infarto/complicações , MicroRNAs/genética , Peptídeo Intestinal Vasoativo/metabolismo , Idoso , Fibrilação Atrial/etiologia , Fibrilação Atrial/metabolismo , Biomarcadores/análise , Estudos de Casos e Controles , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/genética , Eletrofisiologia , Feminino , Seguimentos , Humanos , Masculino , Prognóstico
19.
Front Cardiovasc Med ; 8: 719755, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34722657

RESUMO

Background: The aim of this study was to investigate the efficacy of left atrial appendage closure (LAAC) for primary and secondary stroke prevention in patients with hypertrophic cardiomyopathy (HCM) and atrial fibrillation (AF). Methods: This pilot study enrolled 36 patients with HCM and AF who underwent LAAC between April 2017 and December 2019, of whom 22 were for primary stroke prevention and 14 were for secondary prevention. Results: The patients enrolled in this study had non-obstructive (86.1%) or mild obstructive (13.9%) HCM. Patients in the Secondary Prevention Group had higher CHA2DS2-VASc scores (5.1 ± 1.4 vs. 2.6 ± 1.6, P < 0.001) and higher HAS-BLED scores (2.8 ± 1.0 vs. 1.5 ± 0.9, P < 0.001) compared with those in the Primary Prevention Group. Successful closure with satisfactory seals (residual leak ≤ 5 mm) was achieved in all patients, with complete occlusion in 86.4% of the Primary Prevention Group and 92.9% of the Secondary Prevention Group. Procedural-related complications included one pericardial effusion and one groin hematoma. One device-related thrombus was identified in the Secondary Prevention Group and resolved after anticoagulation. During a mean follow-up time of 28.4 months, one bleeding event was recorded. There were no thromboembolic events or deaths in either group, with 97.2% of the patients achieving freedom from anticoagulation therapy. Conclusions: Initial results suggest that LAAC can be a safe and feasible alternative for primary and secondary stroke prevention in selected patients with HCM and AF. Further studies with larger samples are required.

20.
J Cardiovasc Electrophysiol ; 32(10): 2655-2664, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34428342

RESUMO

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 Tratamento
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