Zbtb16 increases susceptibility of atrial fibrillation in type 2 diabetic mice via Txnip-Trx2 signaling.

Atrial fibrillation (AF) is the most prevalent sustained cardiac arrhythmia, and recent epidemiological studies suggested type 2 diabetes mellitus (T2DM) is an independent risk factor for the development of AF. Zinc finger and BTB (broad-complex, tram-track and bric-a-brac) domain containing 16 (Zbtb16) serve as transcriptional factors to regulate many biological processes. However, the potential effects of Zbtb16 in AF under T2DM condition remain unclear. Here, we reported that db/db mice displayed higher AF vulnerability and Zbtb16 was identified as the most significantly enriched gene by RNA sequencing (RNA-seq) analysis in atrium. In addition, thioredoxin interacting protein (Txnip) was distinguished as the key downstream gene of Zbtb16 by Cleavage Under Targets and Tagmentation (CUT&Tag) assay. Mechanistically, increased Txnip combined with thioredoxin 2 (Trx2) in mitochondrion induced excess reactive oxygen species (ROS) release, calcium/calmodulin-dependent protein kinase II (CaMKII) overactivation, and spontaneous Ca2+ waves (SCWs) occurrence, which could be inhibited through atrial-specific knockdown (KD) of Zbtb16 or Txnip by adeno-associated virus 9 (AAV9) or Mito-TEMPO treatment. High glucose (HG)-treated HL-1 cells were used to mimic the setting of diabetic in vitro. Zbtb16-Txnip-Trx2 signaling-induced excess ROS release and CaMKII activation were also verified in HL-1 cells under HG condition. Furthermore, atrial-specific Zbtb16 or Txnip-KD reduced incidence and duration of AF in db/db mice. Altogether, we demonstrated that interrupting Zbtb16-Txnip-Trx2 signaling in atrium could decrease AF susceptibility via reducing ROS release and CaMKII activation in the setting of T2DM.

ISE/ISHNE expert consensus statement on the ECG diagnosis of left ventricular hypertrophy: The change of the paradigm.

The ECG diagnosis of LVH is predominantly based on the QRS voltage criteria. The classical paradigm postulates that the increased left ventricular mass generates a stronger electrical field, increasing the leftward and posterior QRS forces, reflected in the augmented QRS amplitude. However, the low sensitivity of voltage criteria has been repeatedly documented. We discuss possible reasons for this shortcoming and proposal of a new paradigm. The theoretical background for voltage measured at the body surface is defined by the solid angle theorem, which relates the measured voltage to spatial and non-spatial determinants. The spatial determinants are represented by the extent of the activation front and the distance of the recording electrodes. The non-spatial determinants comprise electrical characteristics of the myocardium, which are comparatively neglected in the interpretation of the QRS patterns. Various clinical conditions are associated with LVH. These conditions produce considerable diversity of electrical properties alterations thereby modifying the resultant QRS patterns. The spectrum of QRS patterns observed in LVH patients is quite broad, including also left axis deviation, left anterior fascicular block, incomplete and complete left bundle branch blocks, Q waves, and fragmented QRS. Importantly, the QRS complex can be within normal limits. The new paradigm stresses the electrophysiological background in interpreting QRS changes, i.e., the effect of the non-spatial determinants. This postulates that the role of ECG is not to estimate LV size in LVH, but to understand and decode the underlying electrical processes, which are crucial in relation to cardiovascular risk assessment.

Novel dual-reference approach facilitates the activation mapping and catheter ablation of premature atrial complexes with non-pulmonary vein and non-superior vena cava origins.

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.

ISE/ISHNE Expert Consensus Statement on ECG Diagnosis of Left Ventricular Hypertrophy: The Change of the Paradigm. The joint paper of the International Society of Electrocardiology and the International Society for Holter Monitoring and Noninvasive Electrocardiology.

The ECG diagnosis of LVH is predominantly based on the QRS voltage criteria, i.e. the increased QRS complex amplitude in defined leads. The classical ECG diagnostic paradigm postulates that the increased left ventricular mass generates a stronger electrical field, increasing the leftward and posterior QRS forces. These increased forces are reflected in the augmented QRS amplitude in the corresponding leads. However, the clinical observations document increased QRS amplitude only in the minority of patients with LVH. The low sensitivity of voltage criteria has been repeatedly documented. We discuss possible reasons for this shortcoming and proposal of a new paradigm.

Current evidence on the safety and efficacy of combined atrial fibrillation ablation and left atrial appendage closure.

PURPOSE OF REVIEW: Combined atrial fibrillation (AF) ablation and left atrial (LA) appendage (LAA) closure (LAAC) has been practiced for management of both the symptoms and the high stroke risk of AF. The purpose of this review is to review recent evidence regarding the combined procedure. RECENT FINDINGS: Newly acquired long-term data of combined AF ablation and LAAC supplied satisfactory evidence on the safety and efficacy of the combined procedure. Studies also showed LA structural remodeling following combined procedure was mainly affected by sinus rhythm status post catheter ablation, not by LAAC. A cost-effectiveness study revealed that combined procedure was a cost-effective therapeutic option in symptomatic AF patients with high stroke and bleeding risk. Due to recent evidence of high incidences of LAA thrombus formation after LAA electrical isolation (LAAEI) and benefit of LAAC after LAAEI, an extended combined procedure of standard AF ablation plus LAAEI and LAAC was considered as a potential therapeutic option for persistent AF patients with high stroke risk. SUMMARY: In conclusion, combined AF ablation and LAAC serve as a promising option for patients with symptomatic AF and high risk of stroke and/or bleeding.

Effects of adaptive left bundle branch-optimized cardiac resynchronization therapy: a single centre experience.

BACKGROUND: Adaptive cardiac resynchronization therapy (aCRT) is associated with improved clinical outcomes. Left bundle branch area pacing (LBBAP) has shown encouraging results as an alternative option for aCRT. A technique that can be accomplished effectively using LBBAP combined with coronary venous pacing (LOT-aCRT). We aimed to assess the feasibility and outcomes of LOT-aCRT. METHODS: LOT-aCRT, capable of providing two pacing modes, LBBAP alone or LBBAP combined with LV pacing, was attempted in patients with CRT indications. Patients were divided into two groups: those with LBBAP and LV pacing (LOT-aCRT) and those with conventional biventricular pacing (BVP-aCRT). RESULTS: A total of 21 patients were enrolled in the study (10 in the LOT-aCRT group, 11 in the BVP-aCRT group). In the LOT-aCRT group, the QRS duration (QRSd) via BVP was narrowed from 158.0 ± 13.0 ms at baseline to 132.0 ± 4.5 ms (P = 0.019) during the procedure, and further narrowed to 123.0 ± 5.7 ms (P < 0.01) via LBBAP. After the procedure, when LOT-aCRT implanted and worked, QRSd was further changed to 121.0 ± 3.8 ms, but the change was not significant (P > 0.05). In the BVP-aCRT group, BVP resulted in a significant reduction in the QRSd from 176.7 ± 19.7 ms at baseline to 133.3 ± 8.2 ms (P = 0.011). However, compared with LOT-aCRT, BVP has no advantage in reducing QRSd and the difference was statistically significant (P < 0.01). During 9 months of follow-up, patients in both groups showed improvements in the LVEF and NT-proBNP levels (all P < 0.01). However, compared with BVP-aCRT, LOT-aCRT showed more significant changes in these parameters (P < 0.01). CONCLUSIONS: The study demonstrates that LOT-aCRT is clinically feasible in patients with systolic heart failure and LBBB. LOT-aCRT was associated with significant narrowing of the QRSd and improvement in LV function.

Mysterious window: A right coronary artery-left ventricular fistula diagnosed by multiple imaging approaches.

Prevalence of primary coronary cameral fistula (CCF) is extremely rare, especially for CCF with its drainage channel into the left ventricle (LV). We describe a 45-year-old male patient with giant aneurysm associated with proximal right coronary artery (RCA), and the distal end of RCA draining into the LV through a fistula, which was discovered by echocardiography. Dual-source computer tomography revealed only the CCF-related giant RCA aneurysm. The drainage site of the fistula and the above coexistent abnormality could not be visualized clearly by coronary artery angiography because of deficient contrast medium filling into the aneurysm. The patient underwent surgical resection of the giant aneurysm and occlusion of the fistula in 2015. Finally, the patient accepted another operation to occlude the residual coronary fistula in 2021.

The regulation of the small-conductance calcium-activated potassium current and the mechanisms of sex dimorphism in J wave syndrome.

Apamin-sensitive small-conductance calcium-activated potassium (SK) current (IKAS) plays an important role in cardiac repolarization under a variety of physiological and pathological conditions. The regulation of cardiac IKAS relies on SK channel expression, intracellular Ca2+, and interaction between SK channel and intracellular Ca2+. IKAS activation participates in multiple types of arrhythmias, including atrial fibrillation, ventricular tachyarrhythmias, and automaticity and conduction abnormality. Recently, sex dimorphisms in autonomic control have been noticed in IKAS activation, resulting in sex-differentiated action potential morphology and arrhythmogenesis. This review provides an update on the Ca2+-dependent regulation of cardiac IKAS and the role of IKAS on arrhythmias, with a special focus on sex differences in IKAS activation. We propose that sex dimorphism in autonomic control of IKAS may play a role in J wave syndrome.

Value of detecting peri-device leak and incomplete endothelialization by cardiac CT angiography in atrial fibrillation patients post Watchman LAAC combined with radiofrequency ablation.

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.

Utility of Circadian Variability Patterns in Differentiating Origins of Premature Ventricular Complexes.

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.

Combined Therapy of Catheter Ablation and Left Atrial Appendage Closure for Patients with Atrial Fibrillation: A Case-Control Study.

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.

Permanent left bundle branch area pacing utilizing intracardiac echocardiogram.

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.

Efficacy and Safety of Adjunctive Substrate Modification During Pulmonary Vein Isolation for Atrial Fibrillation: A Meta-Analysis.

BACKGROUND: The efficacy and safety of adjuvant substrate modification (SM; either linear ablation [LA] or complex fractionated atrial electrogram [CFAE] ablation) in addition to pulmonary vein isolation (PVI) for the treatment of symptomatic, drug-refractory atrial fibrillation (AF), have still not been clarified and need further assessment. METHOD: We systematically searched the PubMed, MEDLINE, and Cochrane databases for studies comparing PVI with adjunctive SM versus PVI alone for treatment of drug-refractory AF. RESULTS: Twenty-six (26) studies including 3,409 patients (1,975 PVI + SM; 1,434 PVI alone) were included for further analysis. Atrial fibrillation/atrial tachycardia-free survival of patients with PVI + SM was comparable with that of PVI alone (relative risk [RR], 1.06; 95% confidence interval [CI], 0.98-1.14; p = 0.143). In line with this, the primary clinical outcomes were robust, irrespective of additional LA (RR, 1.07; 95% CI, 0.97-1.18; p = 0.194) or CFAE ablation (RR, 1.04; 95% CI, 0.93-1.16; p = 0.534). Adjuvant SM is associated with longer procedural time (weighted mean difference, 20.72; 95% CI, 10.25-31.20; p = 0.0) and fluoroscopy time (weighted mean difference, 6.66; 95% CI, 1.74-11.58; p = 0.000); surprisingly, it presented similar procedure-related complications as PVI alone during AF catheter ablation (RR, 1.01; 95% CI, 0.68-1.50; p = 0.946). CONCLUSIONS: Adjuvant LA or CFAE ablation do not provide incremental benefit over PVI alone. Although substrate-based ablation markedly prolonged procedural and fluoroscopic duration, there was no evidence of increased risk of procedure-related complications.

Catheter ablation of ventricular arrhythmias originating from the para-Hisian region with reversed C-curve technique.

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.

Determinants of postoperative left atrial structural reverse remodeling in patients undergoing combined catheter ablation of atrial fibrillation and left atrial appendage closure procedure.

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.

A novel mutation KCNQ1p.Thr312del is responsible for long QT syndrome type 1.

Patients with high-risk long QT syndrome (LQTS) mutations may experience life-threatening cardiac events. The present study sought to characterize a novel pathogenic mutation, KCNQ1p.Thr312del, in a Chinese LQT1 family. Clinical and genetic analyses were performed to identify this novel causative gene mutation in this LQTS family. Autosomal dominant inheritance of KCNQ1p.T312del was demonstrated in the three-generation pedigree. All mutation carriers presented with prolonged QT intervals and experienced recurrent syncope during exercise or emotional stress. The functional consequences of the mutant channel were investigated by computer homology modeling as well as whole-cell patch-clamp, western-blot and co-immunoprecipitation techniques using transfected mammalian cells. T312 is in the selectivity filter (SF) of the pore region of the KCNQ1-encoded channel. Homology modeling suggested that secondary structure was altered in the mutant SF compared with the wild-type (WT) SF. There were no significant differences in Kv7.1 expression, membrane trafficking or physical interactions with KCNE1-encoded subunits between the WT and mutant transfected channels. However, the KCNQ1p.T312del channels expressed in transfected cells were non-functional in the absence or presence of auxiliary KCNE1-subunits. Dominant-negative suppression of current density and decelerated activation kinetics were observed in cells expressing KCNQ1WT and KCNQ1p.T312del combined with KCNE1 (KCNQ1WT/p.T312del + KCNE1 channels). Those electrophysiological characteristics underlie the pathogenesis of this novel mutation and also suggest a high risk of cardiac events in patients carrying KCNQ1p.T312del. Although protein kinase A-dependent current increase was preserved, a significant suppression of rate-dependent current facilitation was noted in the KCNQ1WT/p.T312del + KCNE1 channels compared to the WT channels during 1- and 2-Hz stimulation, which was consistent with the patients' phenotype being triggered by exercise. Overall, KCNQ1p.Thr312del induces a loss of function in channel electrophysiology, and it is a high-risk mutation responsible for LQT1.

Risk factor analysis of device-related infections: value of re-sampling method on the real-world imbalanced dataset.

BACKGROUND: The incidence of cardiac implantable electronic device infection (CIEDI) is low and usually belongs to the typical imbalanced dataset. We sought to describe our experience on the management of the imbalanced CIEDI dataset. METHODS: Database from two centers of patients undergoing device implantation from 2001 to 2016 were reviewed retrospectively. Re-sampling technique was used to improve the classifier accuracy. RESULTS: CIEDI was identified in 28 out of 4959 procedures (0.56%); a high imbalance existed in the sizes of the patient profiles. In univariate analyses, replacement procedure and male were significantly associated with an increase in CIEDI: (53.6% vs. 23.4, 0.8% vs. 0.3%, P < 0.01). Multivariate logistic regression analysis showed that gender (odds ratio, OR = 3.503), age (OR = 1.032), replacement procedure (OR = 3.503), and use of antibiotics (OR = 0.250) remained as independent predictors of CIEDI (all P < 0.05) after adjustment for diabetes, post-operation fever, and device style, device company. There were 616 under-sampled cases and 123 over-sampled cases in the analyzed cohort after re-sampling. The re-sampling and bootstrap results were robust and largely like the analysis results prior re-sampling method, while use of antibiotics lost the predicting capacity for CIEDI after re-sampling technique (P > 0.05). CONCLUSION: The application of re-sampling techniques can generate useful synthetic samples for the classification of imbalanced data and improve the accuracy of predicting efficacy of CIEDI. The peri-operative assessment should be intensified in male and aged patients as well as patients receiving replacement procedures for the risk of CIEDI.

Feasibility and Safety of Left Atrial Appendage Closure Using the LAmbre Device in Patients with Nonvalvular Atrial Fibrillation with or Without Prior Catheter Ablation.

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.

Clinical Features of Post Cardiac Injury Syndrome Following Catheter Ablation of Arrhythmias: Systematic Review and Additional Cases.

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.

Development, safety and efficacy of a novel circular-irrigated deca-channel mapping and ablation catheter for pulmonary vein isolation.

BACKGROUND: Pulmonary vein isolation (PVI), a cornerstone for catheter ablation of atrial fibrillation (AF), remains a complex and time-consuming procedure. Present study introduces a novel, circular-irrigated, deca-channel mapping and ablation catheter (CIDMA), describes the in vitro test results on feasibility, safety, and acute efficacy of the CIDMA catheter. METHODS: An assembled CIDMA catheter was subjected to a number of in vitro tests. With this catheter, ablation procedures were first performed in a pig's myocardial strips in vitro to determine the effects in unipolar or bipolar configuration. RESULTS: Three catheters were assembled. The adjustable circular diameter was changed from initial state of 32.41 ± 0.61 mm into controlled state of 28.61 ± 0.47 mm (P = 0.013). In the plastic model, the push-ability, torque-ability, and kink resistance of CIDMA catheter were shown to be satisfactory. In vitro, our findings showed that ablation could produce obvious ablation lesions, and unipolar ablation (at length, width and depth of 5.0 ± 1.3, 4.6 ± 0.7, and 4.2 ± 0.6 mm, respectively) was more effective than bipolar (at length, width and depth of 2.8 ± 0.2, 4.2 ± 0.5, and 2.3 ± 0.4 mm, respectively) (P < 0.01). CONCLUSIONS: In vitro, our preliminary data suggest that the CIDMA catheter produced optimal ablation lesions, especially in the unipolar ablation mode. Future in vivo animal and clinical studies are warranted to test the efficacy of this catheter in real-world scenario.