Ibrutinib Contributes to Atrial Arrhythmia through the Autophagic Degradation of Connexins by Inhibiting the PI3K-AKT-mTOR Signaling Pathway.

BACKGROUND: Ibrutinib could increase the risk of atrial fibrillation (AF) in chronic lymphocytic leukemia (CLL) patients. However, the precise mechanism underlying ibrutinib-induced AF remains incompletely elucidated. METHODS: We investigated the proportion of ibrutinib-treated CLL patients with new-onset AF. Optical mapping was conducted to reveal the proarrhythmic effect of ibrutinib on HL-1 cells. Fluorescence staining and western blot were used to compare connexins 43 and 40 expression in ibrutinib-treated and control groups. To identify autophagy phenotypes, we used western blot to detect autophagy-related proteins, transmission electron microscopy to picture autophagosomes, and transfected mCherry-GFP-LC3 virus to label autophagosomes and lysosomes. Hydroxychloroquine as an autophagy inhibitor was administered to rescue ibrutinib-induced Cx43 and Cx40 degradation. RESULTS: About 2.67% of patients developed atrial arrhythmias after ibrutinib administration. HL-1 cells treated with ibrutinib exhibited diminished conduction velocity and a higher incidence of reentry-like arrhythmias compared to controls. Cx43 and Cx40 expression reduced along with autophagy markers increased in HL-1 cells treated with ibrutinib. Inhibiting autophagy upregulated Cx43 and Cx40. CONCLUSIONS: The off-target effect of ibrutinib on the PI3K-AKT-mTOR signaling pathway caused connexin degradation and atrial arrhythmia via promoting autophagy. CLINICAL TRIAL REGISTRATION: ChiCTR2100046062, https://clin.larvol.com/trial-detail/ChiCTR2100046062.

Symptom-to-balloon time and risk of ventricular arrhythmias in patients with STEMI undergoing percutaneous coronary intervention: The VERY-STEMI study.

Background: Ventricular arrhythmias (VAs) mainly occur in the early post-myocardial infarction (MI) period. However, studies examining the association between total myocardial ischemia time interval and the risk of new-onset VAs during a long-term follow-up are scarce. Methods: This study (symptom-to-balloon time and VEntricular aRrhYthmias in patients with STEMI, VERY-STEMI study) was a multicenter, observational cohort and real-world study, which included patients with ST-segment elevation MI (STEMI) undergoing percutaneous coronary intervention (PCI). The primary endpoint was cumulative new-onset VAs during follow-up. The secondary endpoints were the major adverse cardiovascular events (MACE) and changes in left ventricular ejection fraction (ΔLVEF, %). Results: A total of 517 patients with STEMI were included and 236 primary endpoint events occurred. After multivariable adjustments, compared to patients with S2BT of 24 h-7d, those with S2BT ≤ 24 h and S2BT > 7d had a lower risk of primary endpoint. RCS showed an inverted U-shaped relationship between S2BT and the primary endpoint, with an S2BT of 68.4 h at the inflection point. Patients with S2BT ≤ 24 h were associated with a lower risk of MACE and a 4.44 increase in LVEF, while there was no significant difference in MACE and LVEF change between the S2BT > 7d group and S2BT of 24 h-7d group. Conclusions: S2BT of 24 h-7d in STEMI patients was associated with a higher risk of VAs during follow-up. There was an inverted U-shaped relationship between S2BT and VAs, with the highest risk at an S2BT of 68.4 h.

Effects of Different Pre-Harvest Bagging Times on Fruit Quality of Apple.

Pre-harvest bagging can improve fruit color and protects against diseases. However, it was discovered that improper bagging times could lead to peel browning in production. Using the Ruixue apple variety as the research model, a study was conducted to compare the external and internal quality of fruits bagged at seven different timings between 50 and 115 days after full bloom (DAFB). Our findings indicate that delaying the bagging time can reduce the occurrence of peel browning in Ruixue apples. Compared to the control, the special bag reduced the browning index by 22.95%. However, the fruit point index of Ruixue fruits increased by 65.05% at 115 DAFB compared to 50 DAFB when bagging was delayed. The chlorophyll content of Ruixue fruits in special bags generally increased and then decreased, with the highest chlorophyll content of Ruixue fruits in special bags at 90 DAFB, which was 26.02 mg·kg-1. When the bagging process was delayed, the soluble solids, total phenols, and flavonoids content in the fruits increased, while the number of control volatiles decreased by 10. After two years of testing, results show that using special fruit bags at 90 DAFB bagging can significantly improve the fruit quality of Ruixue apple.

Anticoagulation Intensity during Appendage Occlusion:Lessons from Silent Cerebral Embolism.

INTRODUCTION: Endovascular left atrial appendage occlusion (LAAO) is associated with a high incidence of peri-procedure silent cerebral embolisms (SCE), while the recommended activated clotting time (ACT) level by the expert consensus is lower than that in atrial fibrillation (AF) ablation. The aim of our study is to investigate whether raising the targeted ACT level during LAAO to the same level as AF ablation could decrease the incidence of SCE. METHODS: It was a prospective observational cohort study. Consecutive AF patients receiving LAAO between January 2021 and December 2022 were included and categorized into two groups based on the time of enrollment. Patients enrolled in 2021 (group 250) maintained a target ACT level of ≥250 s during LAAO procedure, while patients enrolled in 2022 (group 300) maintained the peri-procedure ACT ≥300 s. All patients underwent cerebral magnetic resonance imaging (MRI) before and after the procedure. RESULTS: A total of 81 patients were included (38 in the group 250 and 43 in the group 300). After inverse probability of treatment weighting (IPTW), patients in the group 250 showed a significantly lower incidence of SCE than group 300 (IPTW p = 0.038). Only a stable high ACT pattern could decrease the risk of SCE. No significant differences were found between other ACT change patterns on the SCE incidence. CONCLUSION: Raising the peri-procedure ACT level to a stable 300 seconds could decrease the risk of the SCE without increasing the major bleeding events.

General anesthesia enhances lesion quality and ablation efficiency of circumferential pulmonary vein isolation.

Background: Pulmonary vein isolation (PVI) is the cornerstone of atrial fibrillation (AF) ablation. General anesthesia (GA) resolves the problem of pain intolerability and provides regular respiratory mode which might improve the catheter maneuverability of AF ablation. This study aims to compare the procedural performance of PVI under GA versus conscious sedation (CS) from multiple perspectives. Methods: A total of 36 consecutive patients undergoing first AF ablation under GA were enrolled in GA group. Another 109 patients receiving AF ablation under CS in the same period were selected as the control group. After propensity score matching, 29 matched pairs with similar baseline characteristics were available for further analysis. The AIFV (using AI to analyze the raw data from CARTO3 system) system was used to evaluate six procedural parameters in each PVI procedure. Results: Compared with CS, PVI under GA had a significantly shorter total PVI time (51.4 min vs. 67.8 min; p = .003) and higher radiofrequency ratio (62.6% vs. 55.8%; p = .032). The number of gaps (1.0 vs. 3.0; p < .001) and the rate of break point were significantly lower in the GA group. GA was also associated with a higher effective ablation-index ratio (87.5% vs. 74.1%; p < .001) and effective force-over-time ratio (85.3% vs. 69.2%; p = .001). After a medium follow-up time of 24 months, 12/29 (41.4%) patients in the CS group and 6/29 (20.7%) patients in the GA group suffered from AF recurrence (p = .156). Conclusions: GA improves the lesion quality and procedural efficiency of PVI from multiple perspectives evaluated by the AIFV system.

Persistent left superior vena cava isolation in patients with atrial fibrillation: Selective or empirical?

BACKGROUND: Persistent left superior vena cava (PLSVC) is the most prevalent form of thoracic venous abnormality and can serve as a significant arrhythmogenic source in atrial fibrillation (AF). METHODS AND RESULTS: Among the 3950 patients who underwent radiofrequency ablation for AF between September 2014 to April 2020, 17 patients (mean age 59.4 ± 8.0 years, 64.7% male) with PLSVC were identified. Among them, nine patients (52.9%) had a prior history of pulmonary vein isolation (PVI) alone. Eight out of nine patients who experienced AF recurrence underwent PLSVC isolation with or without pulmonary vein (PV) reconnection. For the remaining eight patients (47.1%), PVI plus PLSVC isolation were performed during the index procedure. Ectopy originating from PLSVC was documented in 11 patients (64.7%) and successful PLSVC isolation was achieved in 16 patients (94.1%). After a median follow-up of 28.3 months, freedom from AF/ atrial tachycardia (AT) was observed in 13 patients (76.5%). CONCLUSION: Empirical PLSVC isolation beyond PVI appears to be a feasible and safe strategy to prevent AF recurrence in patients with concomitant PLSVC.

Association between P-wave terminal force in lead V1 and extent of left atrial low-voltage substrate in older patients with paroxysmal atrial fibrillation.

BACKGROUND: The P-wave terminal force in lead V1 (PTFV1) is a marker of cardiomyopathy and risk of atrial fibrillation (AF). Low-voltage area (LVA) in the left atrium (LA), which indicates underlying atrial fibrosis, could predict AF recurrence. This study aimed to investigate the correlation between PTFV1 and LVA in older patients with paroxysmal AF. METHODS: From May 1, 2020, to October 31, 2021, a total of 162 patients aged 65-80 years with paroxysmal AF who underwent index ablation procedures were enrolled. PTFV1 was measured in sinus rhythm (SR) using 12-lead electrocardiograms prior to the ablation. Abnormal PTFV1 was defined as a ≥ 4 mVms depression. Additional LVA ablation beyond circumferential pulmonary vein isolation (CPVI) was performed if LVAs were found. RESULTS: Among the 162 patients, 88 had a normal PTFV1 and 74 had an abnormal PTFV1 prior to ablation. There was a significant difference in LVA in patients with and without an abnormal PTFV1 (LVA, 11.0 vs. 5.1 cm2, P < 0.001; LVA burden, 8.9% vs. 4.5%, P < 0.001). PTFV1 and PTAV1 were highest in the upper tertile with extensive LVAs (P < 0.001). Multivariate analysis revealed that abnormal PTFV1 was an independent predictor of LVAs (ß = 4.961; 95% CI, 2.135-7.788; P < 0.001). After a median follow-up of 23 months, the AF-free survival rate was similar between the normal PTFV1 group and the abnormal PTFV1 group (13/88 vs. 12/74, hazard ratio [HR], 0.933 [95% CI, 0.425-2.047]; P = 0.861). CONCLUSIONS: Abnormal PTFV1 at baseline was independently associated with the extent of LVA in older patients with paroxysmal AF.

Arrhythmogenic Right Ventricular Cardiomyopathy With Extensive Abnormal Substrate: Is Isolation Possible?

BACKGROUND: In arrhythmogenic right ventricular cardiomyopathy (ARVC) patients with extensive right ventricular free wall (RVFW) abnormal substrate, large-area homogenization with combined epicardial and endocardial approach is time consuming and often inadequate for modification. OBJECTIVES: This study aimed to explore the feasibility and efficacy of RVFW abnormal substrate isolation in such patients to control ventricular tachycardia (VT). METHODS: Eight consecutive ARVC patients with VT who had extensive abnormal RVFW substrate were included. VT induction was performed before substrate mapping and modification. Detailed voltage mapping was done during sinus rhythm. A circumferential linear lesion was deployed along the border zone of low-voltage area on the RVFW to achieve electrical isolation. Other small areas with fractionated or late potentials were further homogenized. RESULTS: All 8 patients had RVFW endocardial low-voltage area. The entire RV low-voltage area was 113.8 ± 84.1 cm2 (49.6% ± 29.8%) and the dense scar was 59.6 ± 39.8 cm2 (25.0% ± 14.1%). Electrical isolation of abnormal substrate was achieved in 5 of 8 (62.5%) patients via endocardial approach alone and 3 of 8 (37.5%) patients via a combination of endocardial and epicardial approach. Electrical isolation was verified by slow automaticity (5 of 8, 62.5%) or RV noncapture (3 of 8, 37.5%) during high-output pacing inside the encircled area. VTs were induced in 6 patients before ablation, and all patients were rendered noninducible after ablation. During a median follow-up of 43 months (range: 24-53 months), 7 of 8 (87.5%) patients remained free of sustained VT. CONCLUSIONS: Electrical isolation of RVFW is feasible and can be the option in ARVC patients with extensive abnormal substrate.

Scar-related atrial macroreentries: Different arrhymogenic basis generates different reentry type.

BACKGROUND: Catheter ablation is an established therapeutic strategy to treat scar-related macroreentry atrial tachycardia (MAT). However, the scar properties and arrhythmogenicity and the reentry type have not been clearly defined. METHODS AND RESULTS: A total of 122 patients with scar-related MAT were enrolled in this study. The atrial scars were classified into two categories: spontaneous scars (Group A: n = 28) and iatrogenic scars (Group B: n = 94). According to the relationship between scar location and the reentry circuit, MAT was described as scar pro-flutter MAT, scar-dependent MAT, and scar-mediated MAT. The reentry type of MAT was significantly different between Groups A and B: pro-flutter (40.5% vs. 62.0%, p = 0.02), scar-dependent AT (40.5% vs. 13.0%, p < 0.001), and scar-mediated AT (19.0% vs. 25.0%, p = 0.42). After a median follow-up of 25 months, 21 patients with AT recurrence were observed. Compared with the spontaneous group, there was a lower recurrence rate of MAT in the iatrogenic group (28.6% vs. 10.6%, p = 0.03). CONCLUSION: Scar-related MAT has three reentry types, and the proportion of each type varies with the scar properties and its arrhythmogenic basis. Optimization of the ablation strategy based on the scar properties to improve the long-term outcome of catheter ablation of MAT is necessary.

Plasma 8-Hydroxy-2'-Deoxyguanosine, a Potential Valuable Biomarker for Atrial Fibrosis Is Influenced by Polymorphism of DNA Methylation Gene.

BACKGROUND: Previous studies revealed a relationship between 8-hydroxy-2'-deoxyguanosine (8-OHdG) and the occurrence/recurrence of atrial fibrillation (AF). This 2-part study aimed to validate whether DNA damage related to 8-OHdG is associated with left atrial (LA) fibrosis in AF patients quantified by voltage mapping (Part I), and to identify the underlying genetic components regulating the 8-OHdG level (Part II).Methods and Results: Plasma 8-OHdG determination, DNA extraction, and genotyping were conducted before catheter ablation. LA voltage mapping was performed under sinus rhythm. According to the percentage of low voltage area (LVA), patients were categorized as stage I (<5%), stage II (5-10%), stage III (10-20%), and stage IV (>20%). Part I included 209 AF patients. The 8-OHdG level showed an upward trend together with advanced LVA stage (stage I 8.1 [6.1, 10.5] ng/mL, stage II 8.5 [5.7, 14.1] ng/mL, stage III 14.3 [12.1, 16.5] ng/mL, stage IV 13.9 [10.5, 16.0] ng/mL, P<0.000). Part II included 175 of the 209 patients from Part I. Gene-set analysis based on genome-wide association study summary data identified that the gene set named 'DNA methylation on cytosine' was the only genetic component significantly associated with 8-OHdG concentration. CONCLUSIONS: Higher 8-OHdG levels may predict more advanced LVA of the LA in AF patients. DNA methylation is the putative genetic component underlying oxidative DNA damage in AF patients.

Predictors of pacemaker implantation within three months after catheter ablation of atrial fibrillation.

BACKGROUND: It is inevitable for patients to have a temporary or permanent pacemaker implanted during or after radiofrequency catheter ablation (RFCA) for treatment of atrial fibrillation (AF) in some cases. The aim of our study was to evaluate the incidence of pacemaker implantation (PMI) during or within 3 months of RFCA for AF and to identify the risk factors that were associated with PMI. METHODS: We performed a retrospective analysis of consecutive AF patients who underwent RFCA between August 2018 and October 2020 at our center. The incidence of PMI within 3 months during or after RFCA were assessed. A multivariate logistic regression model was performed to identify predictors of PMI. RESULTS: One thousand and five patients (mean age, 60.2 ± 10.3 years; 37.6% women) were included in this analysis. PVI was performed in all patients. A total of 23 (2.3%) patients had a pacemaker implanted within 3 months during or after ablation. Multivariable logistic regression analysis revealed that older age (OR: 1.08 [95% CI 1.03-1.13], p = .003), female sex (OR: 3.08 [95% CI 1.28-7.45], p = .012), paroxysmal AF (OR: 4.71 [95% CI 1.09-20.45], p = .038) and repeated ablation (OR: 2.78 [95% CI 1.04-7.40], p = .041) were the independent predictors for PMI. CONCLUSIONS: Older age, female sex, paroxysmal AF and repeated ablation were identified as predictive risk factors for PMI after RFCA in patients with AF. A "watch and wait" strategy could be taken for patients with temporary PMI after ablation, especially for those with prolonged sinus pause after AF termination.

Characteristics, Thrombus Resolution, and Long-Term Outcomes in Patients with Nonvalvular Atrial Fibrillation and Atrial Thrombus.

To assess the prevalence and management of atrial thrombus in patients with nonvalvular atrial fibrillation (NVAF) and identify the risk factors of the nonresolution of atrial thrombus. This single-center retrospective observational study consecutively enrolled patients with NVAF and atrial thrombus detected using transesophageal echocardiography (TEE) or cardiac computed tomography angiography (CTA) from January 2012 to December 2020. Patients with prior left atrial appendage (LAA) intervention were excluded. The primary endpoint was the presence of atrial thrombus, while the secondary endpoint was the complete resolution of atrial thrombus. The prevalence of atrial thrombus in patients with NVAF was 1.4%. Ninety patients with atrial thrombus (mean age 62.8 ± 11.9 years and 61.1% men) were finally analyzed. Atrial thrombus was in the LAA in 82 (91.1%) patients. During follow up, 60% of the patients showed complete resolution of atrial thrombus. Congestive heart failure (odds ratio [OR]: 8.94; 95% confidence interval [CI]: 1.67-47.80) and a history of ischemic stroke (OR: 8.28; 95% CI: 1.48-46.42) were independently associated with the risk of the nonresolution of atrial thrombus. The presence of atrial thrombus in patients with NVAF who received anticoagulation therapy is non-negligible. Even in anticoagulated patients, TEE or cardiac CTA might still be needed. Congestive heart failure and a history of ischemic stroke are risk factors of the nonresolution of atrial thrombus.

Surgical and percutaneous left atrial appendage intervention: silent cerebral embolism considerations.

OBJECTIVES: Left atrial appendage intervention is an alternative to oral anticoagulation for thromboprophylaxis in atrial fibrillation. The aim of our study was to compare the incidence of silent cerebral embolisms after surgical and percutaneous intervention and to identify the risk factors for procedure-related silent cerebral embolisms after intervention. METHODS: This prospective observational study included consecutive atrial fibrillation patients from 2 independent cohorts (left atrial appendage excision (LAAE) cohort and left atrial appendage occlusion cohort) between September 2018 and December 2020. All patients underwent cerebral magnetic resonance imaging before and after the procedure. Silent cerebral embolism was defined as new focal hyperintense lesions detected only on postprocedural sequence. RESULTS: Thirty-two patients from the LAAE cohort and 42 patients from the occlusion cohort were enrolled. A significantly lower incidence of silent cerebral embolism was observed in the LAAE cohort as compared with occlusion (6.3% vs 54.8%, P < 0.001). In the left atrial appendage occlusion cohort, patients who developed silent cerebral embolism after the procedure had significantly higher CHA2DS2-VASc scores [odds ratio (OR) 2.172; 95% confidence interval (CI) 1.149-4.104; P = 0.017], longer occlusion placement time (OR 1.067; 95% CI 1.018-1.118; P = 0.006) and lower peak activated clotting time level after transseptal puncture (OR 0.976; 95% CI 0.954-0.998; P = 0.035). CONCLUSIONS: The incidence of procedure-related silent cerebral embolism was strikingly lower in patients with LAAE than in patients with occlusion. More cardiovascular comorbidities, longer occlusion placement time and lower activated clotting time level were significantly associated with the development of procedure-related silent cerebral embolism.

Progressive outcomes of bundle branch reentrant ventricular tachycardia in patients without structural heart disease.

BACKGROUND: Ablation strategies to treat bundle branch reentrant ventricular tachycardia (BBRT) are well described. However, reports of long-term follow-up outcomes in BBRT patients without structural heart disease (SHD) are limited. OBJECTIVE: The purpose of this study was to investigate the long-term follow-up prognosis of BBRT patients without SHD. METHODS: Changes in electrocardiographic and echocardiographic parameters were used to evaluate progression during follow-up. Potential pathogenic candidate variants were screened using a specific gene panel. RESULTS: Eleven consecutive BBRT patients without obvious SHD based on echocardiographic and cardiovascular magnetic resonance imaging results were enrolled. Median age was 20 (11-48) years, and median follow-up time was 72 months. During follow-up, PR interval [206 (158-360) ms vs 188 (158-300) ms; P = .018] and QRS duration [187 (155-240) ms vs 164 (130-178) ms; P = .008] each increased significantly compared with postablation. Right- and left-sided chamber dilation and reduced left ventricular ejection fraction (LVEF) also were observed. Clinical deterioration or events occurred in 8 patients: 1 sudden death; 3 both complete heart block and reduced LVEF; 2 significantly reduced LVEF; and 2 prolonged PR interval. Genetic testing results showed that 6 of 10 patients (excluding the patient with sudden death) had ≥1 potential pathogenic candidate variants. CONCLUSION: Further deterioration of His-Purkinje system conduction was observed in young BBRT patients without SHD after ablation. The His-Purkinje system may be the first target of genetic predisposition.

Neurology care and the long-term outcomes of atrial fibrillation-related ischaemic stroke in China: median 3-year outcome from a high volume academic tertiary hospital.

OBJECTIVES: The initial medical contact of patients with atrial fibrillation (AF) and ischaemic stroke is often performed by neurologists. However, when stand care with oral anticoagulants (OACs) adherence and persistence was emphasised by cardiologists, data regarding the gap between current neurology care and standard care from Chinese tertiary hospitals is scarce and the long-term outcome is unknown. This study was to investigate the AF detection rate, the use of anticoagulation therapy and posthospital clinical outcomes associated with neurology care in patients with AF and ischaemic stroke in China. DESIGN: A retrospective cohort study. SETTING: Clinical data of all patients who had an ischaemic stroke discharged from the neurologic department of a high-volume academic hospital from 1 January 2013 to 31 December 2017 were analysed and patients were followed. PARTICIPANTS: Patients diagnosed with ischaemic stroke and AF were included. MAIN OUTCOME MEASURES: The usage of anticoagulation at discharge, the posthospital restroke rate and all-cause mortality. RESULTS: Among 5797 patients who had an ischaemic stroke, 373 (6.43%) patients were diagnosed with AF during hospitalisation. Among them, only 198 (53.66%) patients were on anticoagulation therapy at discharge. A total of 325 (88.08%) patients were accessible and received follow-up. After a median 3-year follow-up, 103 (31.69%) patients died due to all causes. Among them, 53 (16.31%) patients died from recurrent stroke. And 86 (26.46%) patients restroked. In multivariable analysis, patients without anticoagulation therapy, muscle strength

Transcriptomic and metabolomic analysis reveals a protein module involved in preharvest apple peel browning.

Peel browning is a natural phenomenon that adversely affects the appearance of fruits. Research on the regulation of browning in apples (Malus × domestica Borkh.) has mainly focused on postharvest storage, while studies at the preharvest stage are relatively rare. Apple is an economically important horticultural crop prone to peel browning during growth, especially when the fruits are bagged (dark conditions). The present study's integrated transcriptomics and metabolomics analysis revealed that preharvest apple peel browning was primarily due to changes in phenolics and flavonoids. The detailed analysis identified MdLAC7's (laccase 7) role in the preharvest apple peel browning process. Transient injection, overexpression, and CRISPR/Cas9 knockout of the MdLAC7 gene in apple fruit and calli identified vallinic acid, anthocyanidin, tannic acid, sinapic acid, and catechinic acid as its catalytic substrates. In addition, yeast one-hybrid assay, electrophoretic mobility shift assay, luciferase reporter assay, and ChIP-PCR analysis revealed that MdWRKY31 binds to the promoter of MdLAC7 and positively regulates its activity to promote peel browning of bagged fruits (dark conditions). Interestingly, upon light exposure, the light-responsive transcription factor MdHY5 (ELONGATED HYPOCOTYL 5) bound to the promoter of MdWRKY31 and inhibited the gene's expression, thereby indirectly inhibiting the function of MdLAC7. Subsequent analysis showed that MdHY5 binds to the MdLAC7 promoter at the G-box1/2 site and directly inhibits its expression in vivo. Thus, the study revealed the MdLAC7-mediated mechanism regulating preharvest apple peel browning and demonstrated the role of light in inhibiting MdLAC7 activity and subsequently reducing peel browning. These results provide theoretical guidance for producing high-quality apple fruits.

Arrhythmogenesis of surgical atrial incisions and lesions in Maze procedure: insights from high-resolution mapping of atrial tachycardias.

BACKGROUND: Atrial tachycardias (ATs) frequently develop after a surgical Maze procedure. We aimed to elucidate the electrophysiologic mechanisms and their arrhythmogenic substrates of these ATs. METHODS AND RESULTS: We retrospectively reviewed 20 patients (14 females, mean age of 55.5 ± 8.6 years) with post-Maze ATs who underwent high-resolution mapping at three institutions. The slow conduction areas, reentry circuits, voltage signals, complex electrograms, and their correlation with the surgical incisions and lesions placed in the surgical Maze procedures were analyzed. Thirty-six ATs with a mean cycle length of 260.0 ± 67.6 ms were mapped in these patients. Among them, 22 (61.1%) were anatomical macro-reentrant ATs (AMAT), 12 (33.3%) non-AMATs (localized ATs), and 2 (5.6%) focal ATs, respectively. Epicardial conduction bridges were observed in 6/20 (30.0%) patients and 7/36 (19.4%) ATs. Different arrhythmogenic substrates were identified in these ATs, including slow conduction regions within the previous lesion areas or between the incisions and anatomical structures, the prolonged activation pathways caused by the short lesions connecting the tricuspid annulus, and the circuits around the long incisions and/or lesions. CONCLUSIONS: Reentry is the main mechanism of the post-Maze ATs. The pro-arrhythmic substrates are most likely caused by surgical incisions and lesions. The slow conduction regions and the protected channels yielded from these areas are the major arrhythmogenic factors.

Ventricular arrhythmias originating from the basal septum of the ventricle: Clinical and electrophysiological characteristics and a systematic ablation approach.

Background: There is a paucity of data about VAs clustered at the vicinity of the basal septum of the ventricle. We aimed to report and characterize the clinical and electrophysiological features of basal septum VAs and explore the systematic ablation approach. Methods: A consecutive series of 51 patients who had their VAs successfully ablated at the basal septum of the ventricle was enrolled in this study. The basal septum was defined as the area 2 cm away from the septal annulus, the upper boundary was the site of the left or right His-Purkinje system, and the lower boundary was the borderline that separated away from the septum. RFCA was performed based on detailed activation mapping or pace mapping. Patients who underwent VA ablation from other areas of the tricuspid annulus (TA) and mitral annulus (MA) during the same period were enrolled as the control group. Results: The patients with basal septum VAs were significantly older (p < 0.01) and had more comorbidities (hypertension and coronary artery disease) (p < 0.01). Meanwhile, the precordial R wave transition was significantly different in right side, left side and intramural foci group (p < 0.001). Acute procedural success was achieved in 44 patients (86.3%) in the study group and in 63 patients (95.5%) in the control group. After a median of 12 (6-36) months of follow-up, compared with VA recurrence in the control group (2 cases), 11 patients with basal septum VAs had recurrences (p = 0.002), while a delayed cure was observed in 3 in intramural foci group. Conclusion: Based on the unique anatomical and electrophysiological characteristics, a systematic approach for VAs originating from the basal septal area is warranted. Moreover, the follow-up data seemed to show a relative high recurrence rate for basal septal VAs during a period of time.

Rechallenge of immune checkpoint inhibitors in a case with adverse events inducing myasthenia gravis.

The mechanism(s) of immune checkpoint inhibitor (ICI)-induced myasthenia gravis (MG), an immune-related adverse event (irAE) that is fatal and limits subsequent ICI use, remain unexplored. Here, through comparative genomic analysis, we identified a pathogenic p.S467C germline variant in SLC22A5 in a thymoma case with ICI-induced MG, which was found to be associated with fatty acid oxidation through its regulation on L-carnitine levels. Remarkably, ICI rechallenge with L-carnitine pretreatment led to durable response without MG-related symptoms. Thus, we provide the first clinical evidence of genetic test-directed irAE management, which integrates individualized ICI treatment into the evolving paradigm of cancer management.