Beware of atrial pacing-induced ventricular depolarization: A case of lead malfunction.

Although ventricular capture during the atrial threshold test is possible, there are rare reports on the insulation defect and inactive leads thereof. In this case, we present a pacemaker-dependent patient with a history of pacemaker generator replacements. The patient experienced ventricular capture induced by atrial pacing due to adhesion of the atrial and ventricular leads with an insulation defect. The atrial lead was abandoned and a new lead was implanted. However, there was a significant decrease in ventricular impedance detected shortly after the new lead was implanted. When observing the phenomenon of atrial pacing-induced ventricular depolarization, one uncommon reason to consider is lead adhesive wear. It is important to pay attention to the contact and bending sites of the leads.

Predictors of pacing-induced cardiomyopathy detection and outcomes demonstration after conduction system pacing upgrade on patients with long-term persistent atrial fibrillation.

OBJECTIVE: To identify the predictors of pacing-induced cardiomyopathy (PICM) and illustrate the safety and feasibility of conduction system pacing (CSP) upgrade on patients with long-term persistent atrial fibrillation (AF). METHODS: All patients with long-term persistent AF and normal left ventricular ejection fraction (LVEF) ≥50% were consecutively enrolled from January 2008 to December 2017, and all the patients with atrioventricular block (AVB) and high right ventricular pacing (RVP) percentage of at least 40%. The predictors of PICM were identified, and patients with PICM were followed up for at least 1 year regardless of CSP upgrade. Cardiac performances and lead outcomes were investigated in all patients before and after CSP upgrade. RESULTS: The present study included 139 patients, out of which 37 (26.62%) developed PICM, resulting in a significant decrease in the left ventricular ejection fraction (LVEF) from 56.11 ± 2.56% to 38.10 ± 5.81% (p< .01). The median duration for the development of PICM was 5.43 years. Lower LVEF (≤52.50%), longer paced QRS duration (≥175 ms), and higher RVP percentage (≥96.80%) were identified as independent predictors of PICM. Furthermore, the morbidity of PICM progressively increased with an increased number of predictors. The paced QRS duration (183.90 ± 22.34 ms vs. 136.57 ± 20.71 ms, p < .01), LVEF (39.35 ± 2.71% vs. 47.50 ± 7.43%, p < .01), and left ventricular end-diastolic diameter (LVEDD) (55.53 ± 5.67 mm vs. 53.20 ± 5.78 mm, p = .03) improved significantly on patients accepting CSP upgrade. CSP responses and complete reverse remodeling (LVEF ≥50% and LVEDD < 50 mm) were detected in 80.95% (17/21) and 42.9% (9/21) of patients. The pacing threshold (1.52 ± 0.78 V/0.4 ms vs. 1.27 ± 0.59 V/0.4 ms, p = .16) was stable after follow-up. CONCLUSION: PICM is very common in patients with long-term persistent AF, and CSP upgrade was favorable for better cardiac performance in this patient population.

Effects of temperature control on hyperthermia-related cardiac dysfunction in a porcine model of cardiac arrest.

The outcome of cardiac arrest is worse when there is fever after spontaneous circulation is restored (ROSC). The purpose of this study was to investigate the mechanism of post-ROSC cardiac dysfunction after hyperthermia treatment and the effects of temperature control. Twenty-four male Bama minipigs were randomized into 3 groups (8 per group): CPR + controlled normothermia (CN), CPR + hyperthermia (HT), and CPR + therapeutic mild hypothermia (TMH). Defibrillation was given to pigs with ventricular fibrillation after 8 min of untreated fibrillation. Subsequently, these animals received the post-ROSC treatments of hyperthermia (38 °C), controlled normothermia (37 °C) or hypothermia (33 °C) according to the groups. Hemodynamic parameters, left ventricular ejection fraction, blood samples and myocardial tissues were assessed. At 24 h after the post-ROSC treatments, the pigs treated with hyperthermia showed increments in heart rate and plasma cardiac troponin I, and decreases in mean arterial pressure, cardiac index, and left ventricular ejection fraction, compared to those with the controlled normothermia pigs. However, the deterioration of the above parameters can be attenuated by TMH. The pigs in the TMH group also had a reduced percentage of apoptotic cardiomyocytes, an increased anti-apoptotic Bcl-2/Bax ratio and a decreased caspase-3 activity in myocardium, as compared with both controlled normothermia and hyperthermia pigs. In conclusion, hyperthermia is associated with a worse myocardial dysfunction. TMH improves hyperthermia-induced myocardial dysfunction by attenuating apoptosis in a porcine model of cardiac arrest.

Cardiomyopathy induced by premature ventricular contractions with ventricular escape beats in the compensatory pause: A case report and brief review of the literature.

RATIONALE: We reported a case with cardiomyopathy induced by frequent premature ventricular contractions (PVCs) and followed ventricular escape beats (VEBs). PVCs with VEBs in the compensatory pause which induced cardiomyopathy is rarely reported. Also, the case exhibited many characteristics of PVCs which were more likely to induce cardiomyopathy, like the location of origin, the longer coupling interval, and the QRS wave companied with the P wave. PATIENT CONCERNS: A 53-year-old man with left ventricular (LV) dysfunction presented with palpation, chest distress, and dyspnea for 3 years. Holter revealed a high burden of ventricular rhythm of PVCs and another wide QRS patterns (96,562 total beats with 87,330 wide QRS beats in 24 hours). The LV ejection fraction decreased to 34% and the left ventricle, right and left atria all dilated. DIAGNOSIS: He was diagnosed with PVC-induced cardiomyopathy. INTERVENTIONS: The patient experienced intracardiac electrophysiological examination which revealed frequent PVCs followed by VEBs in the compensatory pause. Activation mapping of the PVCS and ablation were performed. OUTCOMES: PVCs and VEBs disappeared after ablation. The LV ejection fraction increased to 46% at 2 days after the procedure. The diameters of the right and left atria were also significantly reduced. LESSONS: VEBs may occur during the compensatory pause of PVCs. PVCs with VEBs can lead to a high burden of ventricular rhythm and LV dysfunction. Ablation of the PVCs can also eliminate VEBs and improve the LV function.

Evaluation of Left Ventricular Function in Patients with Coronary Slow Flow by the Dobutamine Stress Echocardiography.

BACKGROUND: The study aims to assess the changes to left ventricular (LV) function of patients with the coronary slow flow (CSF) in response to stress induced by low dose dobutamine. METHODS: Based on coronary angiography (CAG) results, a total of 186 patients undergoing CAG for chest pain and suspected coronary heart disease were assigned to the CSF group (n = 142) and control group (n = 44). Patients in the CSF group underwent two-dimensional speckle-tracking echocardiography (STE) during the dobutamine stress test to evaluate LV systolic and diastolic functions. RESULTS: At rest, there were no statistically significant differences in LV peak systolic longitudinal strain (LS), LV peak systolic longitudinal strain rate (LSRs), LV peak early diastolic longitudinal strain rate (LSRed), LV circumferential strain (CS), or LV circumferential strain rate (CSRed) between the CSF and control groups. In the CSF group, LS and LSRs first increased as the infusion rate was increased to 10 µg/kg/min (all, p < 0.05), before decreasing at infusion rates of 15 and 20 µg/kg/min (all, p < 0.05). CS and CSRed increased in the CSF group at infusion rates of 5, 10, and 15 µg/kg/min, (all, p < 0.05), but decreased significantly at 20 µg/kg/min (all, p < 0.05). CONCLUSION: At rest, LV systolic and diastolic functions were comparable between the CSF and control groups. However, when blood flow to the heart muscles was insufficient, LSRed decreased first, followed by LS. In terms of sensitivity to myocardial ischemia, LS is a better strain parameter than CS.

Impact of baseline impedance of pulmonary vein antrum on success of catheter ablation for paroxysmal atrial fibrillation guided by ablation index.

OBJECTIVE: Ablation index (AI) is an effective ablation quality marker. Impedance is also an important factor for lesion formation. The present study evaluated the influence of the baseline impedance in the effect of ablation for atrial fibrillation (AF) guided by AI. METHODS: This was a retrospective study. 101 patients with paroxysmal AF (PAF) were enrolled. All patients underwent radiofrequency ablation guided by the same AI strategy. The ablation strategy was pulmonary vein (PV) isolation with non-PV triggers ablation. The baseline impedance of the ablation points was recorded. The patients were followed up every 3 months or so. RESULTS: During a median follow-up of 12 (4-14) months, freedom from AF/atrial tachycardia recurrence were 82.2%. No difference existed in baseline characteristics between the success group and the recurrence group. The average baseline impedance was 124.3 ± 9.7 Ω. The baseline impedance of the ablation points in success group was lower compared to the recurrence group (122.9 ± 9.4 vs. 130.5 ± 8.8 Ω, P < 0.01). The ratio of impedance drop in the success group was higher than the recurrence group ([8.8 ± 1.4]% vs. [8.1 ± 1.2]%, P = 0.03). Multivariate analysis revealed that baseline impedance, PAF duration and AI were the independent predictors of AF recurrence. The cumulative free of recurrence rate of low-impedance group (≤ 124 Ω, n = 54) was higher than that of high-impedance group. CONCLUSION: Baseline impedance correlates with clinical outcome of radiofrequency ablation for PAF guided by AI. Higher impedance in the same AI strategy may result in an ineffective lesion which probably causes recurrence.

Single-Nucleotide Polymorphisms in the 3' Untranslated Region of CORIN Associated With Cardiovascular Diseases in a Chinese Han Population: A Case-Control Study.

Background: Corin is a transmembrane serine protease that activates pro-forms of atrial and brain natriuretic peptides. Numerous studies have indicated that corin played an important role in cardiovascular diseases (CVDs). However, there have been few studies about the correlation between single-nucleotide polymorphisms (SNPs) in the 3' untranslated region (3'UTR) of CORIN and CVDs. The aims of this study were to investigate the associations of three SNPs (rs3749585, rs4695253, and rs12641823) in the 3'UTR of CORIN with CVDs and to find the seed regions of microRNAs (miRNAs) that bind to SNPs of CORIN. Methods and Results: A case-control study (n = 3,537) was performed in a Han population of northeastern China. CVDs included essential hypertension (EH), atrial fibrillation (AF), heart failure (HF), and coronary artery disease (CAD). Genotyping was performed using high-resolution melt analysis. In the EH-control study, rs3749585T was significantly associated with the risk of EH after adjusting for sex and age in allelic (p adj = 0.049; OR: 1.113) and dominant (p adj = 0.015, OR: 1.233) models. Rs4695253T was significantly associated with the risk of EH in the recessive model after adjusting for sex and age (p adj = 0.005, OR: 2.084). Rs3749585T was significantly and negatively associated with AF in the dominant and additive models after adjusting for sex, age, EH, HF, T2DM, and CAD (dominant: p adj = 0.009, OR: 0.762; additive: p adj = 0.048, OR: 0.873). In the HF-control study and CAD-control study, none of the three SNPs was associated with HF and CAD after adjusting for covariates in any models (p adj > 0.05). The levels of high-density lipoprotein (HDL) in rs4695253CC+CT were lower than the levels of HDL in rs4695253TT (42.47 ± 10.30 vs. 48.0 ± 10.24 mg/dl, p adj = 0.008). The levels of total cholesterol (TC) in rs4695253CC+CT were lower than the levels of TC in rs4695253TT (164.01 ± 49.15 vs. 180.81 ± 43.92 mg/dl, p adj = 0.036). Luciferase assay revealed that the relative luciferase activity of rs3749585CC-transfected cells was significantly decreased by miR-494-3p, in comparison to cells transfected with rs3749585TT (p < 0.001). A significant decrease in the relative luciferase activity of rs3749585TT reporter was observed as compared with rs3749585CC reporter in the presence of miR-1323 or miR-548o-3p (p = 0.017 and 0.012, respectively). Conclusions: We found significant associations between rs3749585T and rs4695253T and EH, between rs4695253T and the levels of TC and HDL, and between rs3749585T and AF. Hsa-miR-494-3p may serve as a potential therapeutic target for EH and AF patients in the future.

Brady-arrhythmias in patients with atrial fibrillation and heart failure of reduced ejection fraction: is his-bundle pacing superior to biventricular pacing？.

OBJECTIVE: To investigate the efficacy and safety of His-bundle pacing (HBP) compared with the traditional biventricular pacing (BVP) on patients with brady-arrhythmias, who suffer from permanent atrial fibrillation (AF) and heart failure with reduced ejection fraction (HFrEF). METHODS: All patients with brady-arrhythmias, permanent AF and HFrEF were continuously enrolled from January 2017 to July 2019 and followed up for at least 12 months. The differences in QRS duration (QRSd), New York Heart Association (NYHA) classification, left ventricular ejection fraction (LVEF), tricuspid regurgitation grade, mitral regurgitation grade, left ventricular end-diastolic diameter (LVEDD), and left atrial size were compared. RESULTS: A total of 52 patients were enrolled: 37 patients were with HBP and 15 patients with BVP. There was no electrode dislodged, perforation, infection or thrombosis during the follow-up of 18.12 ± 4.45 months. The success rate for HBP implantation was 88.10%. The capture threshold of his-bundle and the threshold of the left ventricular lead remained stable during follow-up. LVEF increased to higher than 50% in 11 patients with HBP (29.73%). The NYHA classification (both p < .001), LVEF (both p < .001) and LVEDD improved significantly during the follow-up in both groups. NYHA (p = .030), LVEF (p = .013), and LVEDD (p = .003) improved in patients with HBP compared with BVP. CONCLUSION: HBP was safe and more effective in improving the cardiac function and remodeling in patients with brady-arrhythmias, permanent AF and HFrEF compared with BVP.

E/E' Is a New Independent Predictor of Recovered Ejection Fraction in Patients With Systolic Heart Failure Undergoing Ablation for Atrial Fibrillation.

Aims: Catheter ablation should be considered in patients with atrial fibrillation (AF) and with heart failure (HF) with reduced ejection fraction (EF; HFrEF) to improve survival and reduce heart failure hospitalization. Careful patient selection for AF ablation is key to achieving similar outcome benefits. However, limited data exist regarding predictors of recovered ejection fraction. We aimed to evaluate the predictors of recovered ejection fraction in consecutive patients with HF undergoing AF ablation. Methods and Results: A total of 156 patients [67.3% men, median age 63 (11)] with AF and HF underwent initial catheter ablation between September 2017 and October 2019 in the First Affiliated Hospital of Dalian Medical University. Overall, the percentage of recovered ejection fractions was 72.3%. Recovered EFs were associated with a 39% reduction in all-cause hospitalization compared to non-recovered EFs at the 1-year follow-up [23.8 vs. 62.8 (odds ratio) OR 2.09 (1.40-3.12), P < 0.001]. Univariate analysis for recovered EFs showed that diabetes (P = 0.083), prevalent HF (P = 0.014), prevalent AF (P = 0.051), LVEF (P = 0.022), and E/E' (P = 0.001) were associated with EF improvement. Multivariate analysis showed that the only independent predictor of EF recovery was E/E' [OR 1.13 (1.03-1.24); P = 0.011]. A receiver operating characteristic analysis determined that the suitable cut-off value for E/E' was 15 (sensitivity 38.7%, specificity 89.2%, the area under curve 0.704). Conclusions: Ejection fraction (EF) recovery occurred in 72.3% of patients, associated with a 39% reduction in all-cause hospitalization compared to the non-recovered EFs in our cohort. The only independent predictor of recovered EF was E/E' < 15 in our series.

Long-term observation of catheter ablation vs. pharmacotherapy in the management of persistent and long-standing persistent atrial fibrillation (CAPA study).

AIMS: The roles of radiofrequency catheter ablation (RFCA) and pharmacotherapy in treating persistent and long-standing persistent atrial fibrillation (AF) have not been sufficiently investigated. We conducted a multicentre, randomized, controlled trial to compare the effects of RFCA and pharmacotherapy on the prognosis of these patients. METHODS AND RESULTS: A total of 648 patients with persistent and long-standing persistent AF were enrolled from 30 centres and randomized to either the ablation group (n = 327) or the pharmacotherapy group (n = 321). After 54.2 ± 10.6 months of follow-up, the primary endpoints occurred significantly more rarely in the ablation group than in the pharmacotherapy group (10.4% vs. 17.4%; hazard ratio 0.59, 95% confidence interval 0.48-0.75; P < 0.001). The incidence of stroke/transient ischaemic attack (TIA) was significantly lower in the ablation group (4.2% vs. 7.2%, P < 0.001). Likewise, the incidence of new-onset congestive heart failure (CHF) was lower in the ablation group (2.8% vs. 7.2%, P < 0.001). More patients had sinus rhythm in the ablation group than in the pharmacotherapy group (60.6% vs. 20.9%, P < 0.001), but fewer patients were on antiarrhythmic drugs (24.4% vs. 41.6%, P < 0.001) and warfarin (60.8% vs. 83.9%, P = 0.001). Both the 6-min walk distance and the quality of life (QoL) were improved in the ablation group at the end of follow-up. CONCLUSION: In patients with persistent and long-standing persistent AF, RFCA-based treatment was superior to pharmacotherapy in decreasing stroke/TIA and new-onset CHF and improving QoL.

High efficiency and workflow of His bundle pacing and atrioventricular node ablation guided by three-dimensional mapping system.

BACKGROUND: Atrioventricular node (AVN) ablation combined with His bundle pacing is an effective strategy for permanent atrial fibrillation (AF) with rapid ventricular rate refractory to pharmacological therapy. We aimed to access the feasibility and efficiency of His bundle pacing and AVN ablation guided by three-dimensional (3-D) mapping system throughout the procedure. METHODS: Eighteen patients with permanent AF with refractory rate and symptoms were referred for His bundle pacing and AVN ablation guided by 3-D mapping (CARTO3). Electroanatomic 3-D mapping of the right atrium and right ventricle was performed by the ablation catheter with CARTO 3 system, followed by the visualization of the leads for implantation and AVN ablation. RESULTS: Implantation of His bundle and ventricular leads and AVN ablation were achieved successfully with the help of 3-D mapping in 17 patients. Selective His bundle pacing was achieved in five patients (29.4%), and the other (70.6%) were nonselective His bundle pacing. The mean procedure duration was 99.4 ± 16.4 minutes. The mean fluoroscopy time was 7.0 ± 2.6 minutes. The time spent on His lead implantation was 6.1 ± 3.2 minutes. One patient experienced AVN ablation from left side under aortic valves due to no effect of ablation in right atrium. CONCLUSION: His bundle pacing and AVN ablation guided by throughout real-time 3-D mapping system are of high-efficiency and feasibility.

Benefit of Contact Force-Guided Catheter Ablation for Treating Premature Ventricular Contractions.

We evaluated whether an irrigated contact force-sensing catheter would improve the safety and effectiveness of radiofrequency ablation of premature ventricular contractions originating from the right ventricular outflow tract. We retrospectively reviewed the charts of patients with symptomatic premature ventricular contractions who underwent ablation with a contact force-sensing catheter (56 patients, SmartTouch) or conventional catheter (59 patients, ThermoCool) at our hospital from August 2013 through December 2015. During a mean follow-up of 16 ± 5 months, 3 patients in the conventional group had recurrences, compared with none in the contact force group. Complications occurred only in the conventional group (one steam pop; 2 ablations suspended because of significantly increasing impedance). In the contact force group, the median contact force during ablation was 10 g (interquartile range, 7-14 g). Times for overall procedure (36.9 ± 5 min), fluoroscopy (86.3 ± 22.7 s), and ablation (60.3 ± 21.4 s) were significantly shorter in the contact force group than in the conventional group (46.2 ± 6.2 min, 107.7 ± 30 s, and 88.7 ± 32.3 s, respectively; P <0.001). In the contact force group, cases with a force-time integral <560 gram-seconds (g-s) had significantly longer procedure and fluoroscopy times (both P <0.001) than did those with a force-time integral ≥560 g-s. These findings suggest that ablation of premature ventricular contractions originating from the right ventricular outflow tract with an irrigated contact force-sensing catheter instead of a conventional catheter shortens overall procedure, fluoroscopy, and ablation times without increasing risk of recurrence or complications.

Long-term effect of catheter ablation on tachycardia-bradycardia syndrome: evidenced by 10 years follow up.

Background: Catheter ablation has been used for the treatment of tachycardia-bradycardia syndrome (TBS). However, data on its long-term effect of rhythm control and stroke are limited.Method and results: Patients with TBS admitted in the First Affiliated Hospital of Dalian Medical University from 2002 to 2013 were reviewed in the present study. A total of 150 patients were enrolled. Seventy-nine patients underwent catheter ablation (CA group) and 71 patients chose implantation of pacemaker (PM group). The two groups were followed up for 123.01 ± 29.68 and 120.67 ± 31.05 months respectively. The CA group underwent 1.2 ± 0.5 procedure. Of the CA group, 70.9% patients exhibited sinus rhythm without long pauses or the need of anti-arrhythmia drugs (AADs). In contrast, no patient in the PM group was free of atrial fibrillation (AF). A higher proportion in the PM group progressed to persistent AF than in that in the CA group (9.9% vs. 1.3%, p < .05). The incidence of new-onset stroke in the PM group was significantly higher than that in the CA group (15.4% vs. 5.1%, p < .05).Conclusions: Even for long-term following up, catheter ablation is effective for preventing both the tachycardia and bradycardia components for the majority of patients with TBS without the need for further pacemaker implantation. Furthermore, ablation can reduce the stroke incidence of TBS through eliminating AF and reducing the progression to persistent AF.

Safety and efficacy of catheter ablation in atrial fibrillation patients with left ventricular dysfunction.

BACKGROUND: Catheter ablation (CA) for atrial fibrillation (AF) in heart failure (HF) patients reduced the mortality but may increase complications and raise the safety concern. HYPOTHESIS: CA for AF in HF patients may not increase the complications vs medical treatment, and it may reduce hospitalizations and mortality and improve heart function. METHODS: Three groups of AF patients were included in the study: 120 congestive HF for their first CA (AFHF-CA), 150 congestive HF who were undergoing medical therapy (AFHF-Med), and 150 patients with normal left ventricular (LV) ejection fraction (LVEF) (AF-CA). RESULTS: After 30 ± 6 months of follow up, 45.8% of patients in the AFHF-CA and 61.3% of patients in the AF-CA groups maintained sinus rhythm (SR) in comparison with 2.7% in AFHF-Med (P < .01). Hospitalization for HF was significantly lower in AFHF-CA than in AFHF-Med groups (P < .01). Death occurred in 7.5% of patients in the AFHF-CA group, which was lower than 18% in the AFHF-Med group (P < .01). Significant improvements in heart function were shown in the AFHF-CA group compared to the AFHF-Med group, including LVEF (P < .01), LV end-diastolic diameter (P < .01), and New York Heart Association classification (P < .01), as well as the left atrial diameter (P < .01). AFHF-CA patients required additional ablation more often (P < .05). CA had a better prognosis in paroxysmal AF and tachycardia-related diseases. CONCLUSION: CA for AF reduced hospitalizations and mortality and improved heart function, vs medical treatment, and was as safe as CA in those with normal heart function.

Stroke Risk Status, Anticoagulation Treatment, and Quality-of-Life in Chinese Patients with Atrial Fibrillation: China Registry of Atrial Fibrillation (CRAF).

Objective. To investigate the contemporary status of stroke risk profile, antithrombotic treatment, and quality-of-life (QoL) of patients with all types of atrial fibrillation (AF) in China. Design. This is a multicenter, cross-sectional study. Setting. Tertiary (80%) and Tier 2 hospitals (20%) were identified in different economic regions (Northeast, East, West, and Middle) by using a simple random sampling. Participants. A total of 3562 (85.6%) patients with nonvalvular atrial fibrillation (NVAF) and 599 (14.4%) with rheumatic valvular atrial fibrillation (VAF) were consecutively enrolled from 111 hospitals from July 2012 to December 2012. Data Collection. Patient information was collected and QoL was assessed using Short-Form 36 Health Survey (SF-36) questionnaire. Primary and Secondary Outcome Measures. The risk of stroke was assessed using the CHADS2 and CHA2DS2-VASc. QoL was assessed using Medical Outcomes Study SF-36 questionnaire. Results. Overall, 31.7% of the patients received anticoagulant treatment and 61.2% received antiplatelet treatment. The rate of anticoagulant treatment was higher in patients with VAF than in those with NVAF. The anticoagulant use was the lowest in Northeast and the highest in Middle regions. Independent risk factors associated with underuse of anticoagulants for NVAF were age, systolic blood pressure (SBP), non-Middle regions, nontertiary hospitals, and new-onset or paroxysmal AF. For VAF patients, the independent factors were age, paroxysmal AF, treatment in Tier 2 hospitals, SBP, diastolic blood pressure, history of coronary artery disease, and nonreceipt of antiarrhythmic therapy. Patients receiving anticoagulants fared significantly better in some QoL domains than those who received no antithrombotic therapy. Conclusions. These findings suggest that antiplatelet treatment is overused and anticoagulant treatment is underused both in Chinese patients with VAF and NVAF, even though usage of anticoagulants is associated with better QoL. Risk factors with underuse of anticoagulants were not identical in patients with NVAF and VAF.

Significant association of rare variant p.Gly8Ser in cardiac sodium channel ß4-subunit SCN4B with atrial fibrillation.

Atrial fibrillation (AF) affects 33.5 million individuals worldwide. It accounts for 15% of strokes and increases risk of heart failure and sudden death. The voltage-gated cardiac sodium channel complex is responsible for the generation and conduction of the cardiac action potential, and composed of the main pore-forming α-subunit Nav 1.5 (encoded by the SCN5A gene) and one or more auxiliary ß-subunits, including Nav ß1 to Nav ß4 encoded by SCN1B to SCN4B, respectively. We and others identified loss-of-function mutations in SCN1B and SCN2B and dominant-negative mutations in SCN3B in patients with AF. Three missense variants in SCN4B were identified in sporadic AF patients and small nuclear families; however, the association between SCN4B variants and AF remains to be further defined. In this study, we performed mutational analysis in SCN4B using a panel of 477 AF patients, and identified one nonsynonymous genomic variant p.Gly8Ser in four patients. To assess the association between the p.Gly8Ser variant and AF, we carried out case-control association studies with two independent populations (944 AF patients vs. 9,81 non-AF controls in the first discovery population and 732 cases and 1,291 controls in the second replication population). Significant association was identified in the two independent populations and in the combined population (p = 4.16 × 10-4 , odds ratio [OR] = 3.14) between p.Gly8Ser and common AF as well as lone AF (p = 0.018, OR = 2.85). These data suggest that rare variant p.Gly8Ser of SCN4B confers a significant risk of AF, and SCN4B is a candidate susceptibility gene for AF.

Preprodynorphin gene mutation causes progressive cardiac conduction disease: A whole-exome analysis of a pedigree.

AIMS: Progressive cardiac conduction disease (PCCD) is a rare heart disease that usually shows familial inheritance. Potential genetic risk factors for PCCD have been mostly limited to genes that encode ion channels, cardiac transcription factors, T-box transcription factors, gap junction proteins, energy metabolism regulators and structural proteins. MAIN METHODS: Subjects in the present study came from a family who exhibited the autosomal dominant inheritance of PCCD. The primary proband had syncope and an electrocardiogram typical for PCCD, which started in the left bundle branch block, and passed to the atrioventricular block. The patient received a permanent pacemaker in 2013. Pathogenic mutations in the proband's family were identified using whole-exome sequencing and Sanger sequencing. KEY FINDINGS: The results for the family members were verified using Sanger sequencing, while the results for healthy unrelated individuals were verified using SNaPShot. All patients in the family shared two adjacent missense mutations in the preprodynorphin (PDYN) gene (c.581A > T, c.580G > C; p.D194L). SIGNIFICANCE: The PDYN double mutation c.581A > T and c.580G > C (p.D194L) may be linked to the onset of familial PCCD. The effects of these mutations on electrophysiology require further investigation.

Comparison of cryoballoon ablation for atrial fibrillation guided by real-time three-dimensional transesophageal echocardiography vs. contrast agent injection.

BACKGROUND: Pulmonary vein (PV) occlusion generally depends on repetitive contrast agent injection when cryoballoon ablation for atrial fibrillation (AF). The present study was to compare the effect of cryoballoon ablation for AF guided by transesophageal echocardiography (TEE) vs. contrast agent injection. METHODS: Eighty patients with paroxysmal AF (PAF) were enrolled in the study. About 40 patients underwent cryoballoon ablation without TEE (non-TEE group) and the other 40 underwent cryoballoon ablation with TEE for PV occlusion (TEE group). In the TEE group during the procedure, PVs were displayed in 3-dimensional images to guide the balloon to achieve PV occlusion. The patients were followed up at regularly scheduled visits every 2 months. RESULTS: No differences were identified between the groups in regard to the procedure time and cryoablation time for each PV. The fluoroscopy time (6.7 ±â€Š4.2 min vs. 17.9 ±â€Š5.9 min, P < 0.05) and the amount of contrast agent (3.0 ±â€Š5.1 mL vs.18.1 ±â€Š3.4 mL, P < 0.05) in the TEE group were both less than the non-TEE group. At a mean of 13.0 ±â€Š3.3 mon follow-up, success rates were similar between the TEE group and non-TEE group (77.5% vs. 80.0%, P = 0.88). CONCLUSIONS: Cryoballoon ablation with TEE for occlusion of the PV is both safe and effective. Less fluoroscopy time and a lower contrast agent load can be achieved with the help of TEE for PV occlusion during procedure.

Serum and salivary ferritin and Hepcidin levels in patients with chronic periodontitis and type 2 diabetes mellitus.

BACKGROUND: Iron disorder and abnormal expression of hepcidin play important roles in many diseases, but it is still unclear in chronic periodontitis (CP) and type 2 diabetes mellitus (T2DM). We aimed to assess ferritin and hepcidin levels in serum and saliva of CP patients with or without T2DM. METHODS: Serum and unstimulated whole saliva samples were collected from 88 participants, who were categorized into 4 groups based on the presence or absence of CP or T2DM. Demographics and general health parameters were recorded. Full-mouth clinical periodontal parameters including probing pocket depth, clinical attachment loss, bleeding index, and plaque index were recorded. Chemiluminescence microparticle immunoassay and enzyme-linked immunosorbent assay were used to detect ferritin and hepcidin concentrations, respectively, in serum and saliva. RESULTS: Serum ferritin and hepcidin levels in the CP and CP with T2DM groups were higher than in the control group (P < 0.05). Serum hepcidin and serum ferritin are linear correlated (P < 0.001). Serum hepcidin/ferritin values in the CP with T2DM group were significantly lower than those in the T2DM and control groups. Moreover, salivary ferritin levels in the CP and T2DM groups were higher than those in the control group (P < 0.05). There was positively correlation between salivary ferritin and serum ferritin (P = 0.017). Hepcidin concentrations were relatively low in saliva. CONCLUSIONS: These results suggest that iron overload and hepcidin inadequacy existed in CP with T2DM patients. Salivary ferritin might provide a reference for body iron load. TRIAL REGISTRATION: ChiCTR-ROC-17012780.

Novel Role for the Immunoproteasome Subunit PSMB10 in Angiotensin II-Induced Atrial Fibrillation in Mice.

Angiotensin II (Ang II) and inflammation are associated with pathogenesis of atrial fibrillation (AF), but the underlying molecular mechanisms of these events remain unknown. The immunoproteasome has emerged as a critical regulator of inflammatory responses. Here, we investigated its role in Ang II-induced AF in immunosubunit PSMB10 (also known as ß2i or LMP10) knockout (KO) mice. AF was induced by Ang II infusion (2000 ng/min per kg). PSMB10 expression and trypsin-like activity were increased in atrial tissues and serum from Ang II-treated mice or serum from patients with AF. Moreover, Ang II-infused wild-type (WT) mice had a higher AF and increased atrial fibrosis, reactive oxygen species production, and inflammation compared with saline-treated WT animals. These effects were attenuated in PSMB10 KO mice but were aggravated in recombinant adeno-associated virus serotype 9-PSMB10-treated mice. Administration of IKKß-specific inhibitor IMD 0354 reduced Ang II-induced AF, reactive oxygen species production, inflammation, and NF-kB (nuclear factor-kB) activation. Mechanistically, Ang II infusion upregulated PSMB10 expression to promote PTEN (phosphatase and tensin homolog deleted on chromosome ten) degradation and AKT1 activation, which not only activated TGF-ß-Smad2/3 signaling leading to cardiac fibrosis but also induced IKKß activation and ubiquitin-mediated degradation of IkBα ultimately resulting in activation of NF-kB target genes (IL [interleukin]-1ß, IL-6, NOX [NADPH oxidase] 2, NOX4, and CX43 [connexin 43]). Overall, our study identifies immunosubunit PSMB10 as a novel regulator that contributes to Ang II-induced AF and suggests that inhibition of PSMB10 may represent a potential therapeutic target for treating hypertensive AF.