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PURPOSE: To evaluate the ventricular electrophysiologic effects of long-term stimulation of the left dorsal branch of thoracic nerve (LDTN) derived from the left stellate ganglion (LSG) in a canine model of chronic myocardial infarction (MI). METHODS: Seventeen adult male beagles were randomly divided into three groups: the sham group (sham operated, n = 6), the MI group (n = 6), and the MI + LDTN group (MI plus LDTN stimulation, n = 5). The canine model of chronic MI was induced by the occlusion of the left anterior descending artery (LADO). The LDTN was separated and intermittently stimulated immediately after LADO for 2 months. The heart rate variability (HRV) analysis, in vivo electrophysiology, the evaluation of LSG function and neural activity, histological staining, and western blotting (WB) assay were performed to evaluate the effect of LDTN stimulation on the heart. RESULTS: The canine MI model was successfully established by LADO, and the LDTN was separated and stimulated immediately after LADO. The HRV analysis showed that LDTN stimulation reversed the increased LF value and LF/HF ratio of the MI group. LDTN stimulation prolonged the shortening ERP and APD90, decreased the dispersion of ERP and APD90, and increased the VFT. Additionally, LDTN stimulation inhibits the LSG function and neural activity. Furthermore, LDTN stimulation suppressed the activation of Wnt/ß-catenin signaling, which contributed to the LSG neuronal apoptosis by upregulation of pro-apoptotic Bax and downregulation of anti-apoptotic Bcl-2. CONCLUSION: LDTN stimulation could attenuate cardiac sympathetic remodeling and improve ventricular electrical remodeling, which may be mediated by suppressing the activated Wnt/ß-catenin signaling pathway and then promoting the LSG neuronal apoptosis.
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BACKGROUND: This study aimed to assess the safety of left bundle branch area pacing (LBBAP) by measuring the distance from the tip of the electrode to the nearby coronary artery with a nine-partition grid method. METHODS: From January 2019 to October 2020, patients who underwent LBBAP and postoperative coronary angiography in the Second Affiliated Hospital of Nanchang University were included in the study. The patients' fluoroscopic images of LBBAP and coronary angiography were collected and analyzed. Changes in the STT segment in the electrocardiogram (ECG), serum troponin, and myocardial enzyme profiles were observed before and after the LBBAP procedure. RESULTS: A total of 50 patients were included in this study, of whom 46 patients underwent implantation with a pacemaker and 4 patients received an implantable cardioverter defibrillator (ICD). The pacing electrodes were confined to the posterior-middle (PM), median (M), Posterior inferior (PI), and middle inferior (MI) positions of the two-dimensional nine-square grid or in the junction area of the above positions, and were concentrated in the rectangle formed by the line of the center points of the four positions. The average vertical distances from the electrode tip to the left anterior descending branch artery (LAD), posterior descending branches (PD) and the left posterior ventricular branches (PL) were 19.69⯱ 8.72â¯mm, 26.09⯱ 8.02â¯mm, and 21.11⯱ 7.86â¯mm, respectively; the minimum was 5.28â¯mm, 9.51â¯mm, and 8.69â¯mm, respectively. Coronary angiography in all patients showed no significant injury to the ventricular septal branch; however, we observed elevated serum troponin and changes in STT segment in ECG. CONCLUSION: The study demonstrates that pacing electrodes in LBBAP can be safely implanted over a wide range. Coronary arteries are likely to be safe when the pacing electrodes are located within the rectangle formed by the line connecting the PM, M, PI, and MI zone centroids. The left bundle branch can be quickly captured and the safety of the coronary artery can be improved by locating the electrode in the posterior-mid zone. The potential risk of injury to the LAD from the electrode is greater compared with the PD.
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Left bundle branch area pacing (LBBAP) has developed in an effort to improve cardiac resynchronization therapy (CRT). We aimed to compare the long-term clinical outcomes between LBBAP and biventricular pacing (BIVP) in patients with heart failure (HF) and complete left bundle branch block (CLBBB). Consecutive patients with HF and CLBBB requiring CRT received either LBBAP or BIVP were recruited at the Second Affiliated Hospital of Nanchang University from February 2018 to May 2019. We assessed their implant parameters, electrocardiogram (ECG), clinical outcomes at implant and during follow-up at 1, 3, 6, 12, and 24 months. Forty-one patients recruited including 21 for LBBAP and 20 for BIVP. Mean follow-up duration was 23.71 ± 4.44 months. LBBAP produced lower pacing thresholds, shorter procedure time and fluoroscopy duration compared to BIVP. The QRS duration was significantly narrower after LBBAP than BIVP (129.29 ± 31.46 vs. 156.85 ± 26.37 ms, p = 0.005). Notably, both LBBAP and BIVP significantly improved LVEF, LVEDD, NYHA class, and BNP compared with baseline. However, LBBAP significantly lowered BNP compared with BIVP (416.69 ± 411.39 vs. 96.07 ± 788.71 pg/ml, p = 0.007) from baseline to 24-month follow-up. Moreover, patients who received LBBAP exhibited lower number of hospitalizations than those in the BIVP group (p = 0.019). In addition, we found that patients with moderately prolonged left ventricular activation time (LVAT) and QRS notching in limb leads in baseline ECG respond better to LBBAP for CLBBB correction. LBBAP might be a relative safe and effective resynchronization therapy and as a supplement to BIVP for patients with HF and CLBBB.
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Terapia de Resincronización Cardíaca , Insuficiencia Cardíaca , Fascículo Atrioventricular , Bloqueo de Rama/diagnóstico , Bloqueo de Rama/terapia , Estimulación Cardíaca Artificial/métodos , Terapia de Resincronización Cardíaca/efectos adversos , Terapia de Resincronización Cardíaca/métodos , Electrocardiografía/métodos , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/terapia , Humanos , Resultado del TratamientoRESUMEN
Autophagy plays a deleterious role in ischemic myocardial injury. The deacetylase SIRT1 is a well-established regulator of autophagy that can be modified by the ubiquitin-like protein SUMO1. Our previous work demonstrated that another ubiquitin-like protein, FAT10, exerts cardioprotective effects against myocardial ischemia by stabilizing the caveolin-3 protein; however, the effects of FAT10 on autophagy through SIRT1 are unclear. Here, we constructed a Fat10-knockout rat model to evaluate the role of FAT10 in autophagy. In vivo and in vitro assays confirmed that FAT10 suppressed autophagy to protect the heart from ischemic myocardial injury. Mechanistically, FAT10 was mainly involved in the regulation of the autophagosome formation process. FAT10 affected autophagy through modulating SIRT1 degradation, which resulted in reduced SIRT1 nuclear translocation and inhibited SIRT1 activity via its C-terminal glycine residues. Notably, FAT10 competed with SUMO1 at the K734 modification site of SIRT1, which further reduced LC3 deacetylation and suppressed autophagy. Our findings suggest that FAT10 inhibits autophagy by antagonizing SIRT1 SUMOylation to protect the heart from ischemic myocardial injury. This is a novel mechanism through which FAT10 regulates autophagy as a cardiac protector.
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Autofagia , Daño por Reperfusión Miocárdica/prevención & control , Sustancias Protectoras/metabolismo , Sirtuina 1/metabolismo , Ubiquitinas/metabolismo , Animales , Masculino , Daño por Reperfusión Miocárdica/metabolismo , Daño por Reperfusión Miocárdica/patología , Ratas , Ratas Sprague-Dawley , Sirtuina 1/genética , Ubiquitinas/genéticaRESUMEN
Whether the presence of SCN5A mutation is a predictor of BrS risk remains controversial, and patient selection bias may have weakened previous findings. Therefore, we performed this study to clarify the clinical characteristics and outcomes of BrS probands with SCN5A mutations. We systematically retrieved eligible studies published through October 2018. A total of 17 studies enrolling 1780 BrS patients were included. Overall, our results found that compared with BrS patients without SCN5A mutations, patients with SCN5A mutations exhibited a younger age at the onset of symptoms and higher rate of the spontaneous type-1 electrocardiogram pattern, more pronounced conduction or repolarization abnormalities, and increased atrial vulnerability. In addition, the presence of SCN5A mutations was associated with an elevated risk of major arrhythmic events in both Asian (odds ratio [OR] = 1.82, 95% confidence interval [CI] 1.07-3.11; P = .03) and Caucasian (OR = 2.24, 95% CI 1.02-4.90; P = .04) populations. In conclusions, patients with SCN5A mutations exhibit more pronounced electrophysiological defects and more severe prognosis. Clinicians should be cautious when utilizing genetic testing for risk stratification or treatment guidance before determining whether the causal relationship regarding SCN5A mutation status is an independent predictor of risk.
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Síndrome de Brugada/genética , Predisposición Genética a la Enfermedad , Canal de Sodio Activado por Voltaje NAV1.5/genética , Síndrome de Brugada/diagnóstico , Síndrome de Brugada/patología , Fenómenos Electrofisiológicos/genética , Pruebas Genéticas , Humanos , MutaciónRESUMEN
BACKGROUND: Pulsed field ablation (PFA) has emerged as a novel non-thermal modality with highly myocardium-specific. However, the PFA catheter based on contact force (CF)-sensing has not been reported. The study aimed to evaluate the efficacy and safety of a novel CF-sensing PFA catheter. METHODS: First, different CF (5, 15, 25, and 35 g) of the novel PFA catheter were evaluated on lesion dimensions during ablation on right and left ventricle in two pigs. Next, this catheter was further evaluated on four typical sites of superior vena cava (SVC), cavotricuspid isthmus (CTI), right superior pulmonary vein (RSPV), and right inferior pulmonary vein (RIPV) for atrial ablation in another six pigs. Electrical isolation was evaluated immediately after ablation and 30-day survival. Chronic lesions were assessed via histopathology after euthanasia. Acute and chronic safety outcomes were observed peri- and post-procedurally. RESULTS: In ventricular ablation, increased CF from 5 to 15 g produced significantly greater lesion depth but nonsignificant increases from 15 to 35 g. In atrial ablation, the novel CF-sensing PFA deliveries produced an acute attenuation of local electrograms and formation of a continuous line of block in all 6 pigs. The ablation line remained sustained blockage at the 30-day survival period. The CF of SVC, CTI, RSPV, and RIPV was 9.4 ± 1.5, 14.5 ± 3.2, 17.2 ± 2.6, and 13.4 ± 2.8 g, respectively. Moreover, no evidence of damage to esophagus or phrenic nerve was observed. CONCLUSION: The novel CF-sensing PFA catheter potentiated efficient, safe, and durable ablation, without causing damage to the esophagus or phrenic nerve.
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Ablación por Catéter , Vena Cava Superior , Humanos , Porcinos , Animales , Vena Cava Superior/cirugía , Catéteres , Ventrículos Cardíacos , MiocardioRESUMEN
Leadless pacemaker (LP) is a new type of pacemaker that integrates generator and leads, and has become an effective alternative to traditional transvenous pacemakers. It can be used for difficult or complicated situations of traditional pacemaker implantation, such as subclavian vein occlusion, traditional pacemaker pocket infection, lead fracture, and multiple pacemaker replacements. Because no pockets and leads are required, LPs eliminate pocket- and lead-related complications compared to traditional pacemakers. Multiple studies have demonstrated its reliable safety and efficacy. Compared with traditional pacemakers, due to the different implantation methods, the difficulties encountered during the implantation process are also different. This article reviews the difficulties that may be encountered during leadless implantation and looks forward to the future of leadless pacemakers.
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Cardiac resynchronization therapy (CRT) via biventricular pacing (BVP) improves morbidity, mortality, and quality of life, especially in subsets of patients with impaired cardiac function and wide QRS. However, the rate of unsuccessful or complicated left ventricular (LV) lead placement through coronary sinus is 5-7%, and the rate of "CRT non-response" is approximately 30%. These reasons have pushed physicians and engineers to collaborate to overcome the challenges of LV lead implantation. Thus, various alternatives to BVP have been proposed to improve CRT effectiveness. His bundle pacing (HBP) has been increasingly used by activating the His-Purkinje system but is constrained by challenging implantation, low success rates, high and often unstable thresholds, and low perception. Therefore, the concept of pacing a specialized conduction system distal to the His bundle to bypass the block region was proposed. Multiple clinical studies have demonstrated that left bundle branch area pacing (LBBAP) has comparable electrical resynchronization with HBP but is superior in terms of simpler operation, higher success rates, lower and stable capture thresholds, and higher perception. Despite their well-demonstrated effectiveness, the transvenous lead-related complications remain major limitations. Recently, leadless LV pacing has been developed and demonstrated effective for these challenging patient cohorts. This article focuses on the current state and latest progress in HBP, LBBAP, and leadless LV pacing as alternatives for failed or non-responsive conventional CRT as well as their limits and prospects.
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BACKGROUND: The comparative effects of different types of cardiac resynchronization therapy (CRT) delivered by biventricular pacing (BVP), His bundle pacing (HBP), and left bundle branch area pacing (LBBAP) remain inconclusive. HYPOTHESIS: HBP and LBBAP may be advantageous over BVP for CRT. METHODS: PubMed, Embase, Web of Science, and the Cochrane Library were systematically searched for studies that reported the effects after BVP, HBP, and LBBAP for CRT. The effects between groups were compared by a frequentist random-effects network meta-analysis (NMA), by which the mean differences (MDs) and 95% confidence intervals (CIs) were calculated. RESULTS: Six articles involving 389 patients remained for the final meta-analysis. The mean follow-up of these studies was 8.03 ± 3.15 months. LBBAP resulted in a greater improvement in LVEF% (MD = 7.17, 95% CI = 4.31 to 10.04), followed by HBP (MD = 4.06, 95% CI = 1.09 to 7.03) compared with BVP. HBP resulted in a narrower QRS duration (MD = 31.58 ms, 95% CI = 12.75 to 50.40), followed by LBBAP (MD = 27.40 ms, 95% CI = 10.81 to 43.99) compared with BVP. No significant differences of changes in LVEF improvement and QRS narrowing were observed between LBBAP and HBP. The pacing threshold of LBBAP was significantly lower than those of BVP and HBP. CONCLUSION: The NMA first found that LBBAP and HBP resulted in a greater LVEF improvement and a narrower QRS duration compared with BVP. Additionally, LBBAP resulted in similar clinical outcomes but with lower pacing thresholds, and may therefore offer advantages than does HBP for CRT.
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Terapia de Resincronización Cardíaca , Fascículo Atrioventricular , Estimulación Cardíaca Artificial/métodos , Terapia de Resincronización Cardíaca/métodos , Electrocardiografía/métodos , Humanos , Metaanálisis en Red , Resultado del TratamientoRESUMEN
The Olinked ßNacetylglucosamine (OGlcNAc) modification and autophagy are associated with diabetic myocardial injury, however, the molecular mechanisms between the two processes remain to be fully elucidated. The purpose of the present study was to elucidate the molecular regulation of autophagy by OGlcNAcmodified synaptosomalassociated protein 29 (SNAP29) in diabetic myocardial injury. A rat model of type I diabetes was established via intraperitoneal injection of streptozotocin (STZ; 55 mg/kg). Significant increases in the OGlcNAc modification and accumulation of the autophagy markers microtubuleassociated protein 1 light chain 3α II/I and P62, which suggest that autophagic flux is inhibited, were observed in rats 8 weeks following STZ induction. Subsequently, the selective OGlcNAcase inhibitor, thiamet G, increased the level of OGlcNAc modification, which further disrupted autophagic flux; deteriorated cardiac diastolic function, as indicated by an increased left ventricular filling peak velocity/atrial contraction flow peak velocity ratio shown by echocardiography; and exacerbated myocardial abnormalities, as characterized by cardiomyocyte disorganization and fat and interstitial fibrosis accumulation. By contrast, 6diazo5oxoLnorleucine, an inhibitor of glucosamine fructose6phosphate aminotransferase isomerizing 1, acted as an OGlcNAc antagonist and reduced the level of OGlcNAc modification, which maintained autophagic flux and improved cardiac diastolic function. In vitro, high glucose (25 mM) was used to stimulate primary neonatal rat cardiomyocytes (NRCMs). Consistent with the myocardium of diabetic rats, it was also shown in the NRCMs that OGlcNAc modification of SNAP29 negatively regulated autophagic flux. The application of the short hairpin RNA interference lysosomeassociated membrane protein (LAMP2) and the autophagy inhibitor 3methyladenine demonstrated that high glucose inhibited autophagymediated degradation rather than affected the initial stage of autophagy. Finally, coimmunoprecipitation was used to determine the role of the OGlcNAcmodified substrate protein SNAP29, which acted as an SNAP29syntaxin17 (STX17)vesicleassociated membrane protein 8 (VAMP8) complex during disease progression. The present study is the first, to the best of our knowledge, to demonstrate that SNAP29 is an OGlcNAc substrate and that an increase in OGlcNAcmodified SNAP29 inhibits SNAP29STX17VAMP8 complex formation, thereby inhibiting the degradation of autophagy and exacerbating myocardial injury in type I diabetic rats.