Intracardiac Electrophysiologic Studies Research Articles

Rare Variant in MRC2 Associated With Familial Supraventricular Tachycardia and Wolff-Parkinson-White Syndrome.

Accessory pathways are a common cause of supraventricular tachycardia (SVT) and can lead to sudden cardiac death in otherwise healthy children and adults when associated with Wolff-Parkinson-White syndrome. The goal of this study was to identify genetic variants within a large family with structurally normal hearts affected by SVT and Wolff-Parkinson-White syndrome and determine causality of the gene deficit in a corresponding mouse model. Whole exome sequencing performed on 2 distant members of a 3-generation family in which multiple members were affected by SVT or Wolff-Parkinson-White pattern (preexcitation) on ECG identified MRC2 as a candidate gene. Serial electrocardiograms, intracardiac electrophysiology studies, echocardiography, optical mapping studies, and histology were performed on both Mrc2 mutant and WT (wild-type) mice. A rare HET (heterozygous) missense variant c.2969A>G;p.Glu990Gly (E990G) in MRC2 was identified as the leading candidate gene variant segregating with the cardiac phenotype following an autosomal-dominant Mendelian trait segregation pattern with variable expressivity. In vivo electrophysiology studies revealed reentrant SVT in E990G mice. Optical mapping studies in E990G mice demonstrated abnormal retrograde conduction, suggesting the presence of an accessory pathway. Histological analysis of E990G mouse hearts showed a disordered ECM (extracellular matrix) in the annulus fibrosus. Finally, Mrc2 knockdown in human cardiac fibroblasts enhanced accelerated cell migration. This study identified a rare nonsynonymous variant in the MRC2 gene in individuals with familial reentrant SVT, Wolff-Parkinson-White ECG pattern, and structurally normal hearts. Furthermore, Mrc2 knock-in mice revealed an increased incidence of reentrant SVT and bypass tract formation in the setting of preserved cardiac structure and function.

Gq-Mediated Arrhythmogenic Signaling Promotes Atrial Fibrillation

Atrial fibrillation (AF) is promoted by various stimuli like angiotensin II, endothelin-1, epinephrine/norepinephrine, vagal activation, or mechanical stress, all of which activate receptors coupled to G-proteins of the Gαq/Gα11-family (Gq). Besides pro-fibrotic and pro-inflammatory effects, Gq-mediated signaling induces inositol trisphosphate receptor (IP3R)-mediated intracellular Ca2+ mobilization related to delayed after-depolarisations and AF. However, direct evidence of arrhythmogenic Gq-mediated signaling is absent. To define the role of Gq in AF, transgenic mice with tamoxifen-inducible, cardiomyocyte-specific Gαq/Gα11-deficiency (Gq-KO) were created and exposed to intracardiac electrophysiological studies. Baseline electrophysiological properties, including heart rate, sinus node recovery time, and atrial as well as AV nodal effective refractory periods, were comparable in Gq-KO and control mice. However, inducibility and mean duration of AF episodes were significantly reduced in Gq-KO mice-both before and after vagal stimulation. To explore underlying mechanisms, left atrial cardiomyocytes were isolated from Gq-KO and control mice and electrically stimulated to study Ca2+-mobilization during excitation-contraction coupling using confocal microscopy. Spontaneous arrhythmogenic Ca2+ waves and sarcoplasmic reticulum content-corrected Ca2+ sparks were less frequent in Gq-KO mice. Interestingly, nuclear but not cytosolic Ca2+ transient amplitudes were significantly decreased in Gq-KO mice. Gq-signaling promotes arrhythmogenic atrial Ca2+-release and AF in mice. Targeting this pathway, ideally using Gq-selective, biased receptor ligands, may be a promising approach for the treatment and prevention of AF. Importantly, the atrial-specific expression of the Gq-effector IP3R confers atrial selectivity mitigating the risk of life-threatening ventricular pro-arrhythmic effects.

Reduction in Junctophilin 2 Expression in Cardiac Nodal Tissue Results in Intracellular Calcium-Driven Increase in Nodal Cell Automaticity.

Spontaneously depolarizing nodal cells comprise the pacemaker of the heart. Intracellular calcium (Ca2+) plays a critical role in mediating nodal cell automaticity and understanding this so-called Ca2+ clock is critical to understanding nodal arrhythmias. We previously demonstrated a role for Jph2 (junctophilin 2) in regulating Ca2+-signaling through inhibition of RyR2 (ryanodine receptor 2) Ca2+ leak in cardiac myocytes; however, its role in pacemaker function and nodal arrhythmias remains unknown. We sought to determine whether nodal Jph2 expression silencing causes increased sinoatrial and atrioventricular nodal cell automaticity due to aberrant RyR2 Ca2+ leak. A tamoxifen-inducible, nodal tissue-specific, knockdown mouse of Jph2 was achieved using a Cre-recombinase-triggered short RNA hairpin directed against Jph2 (Hcn4:shJph2). In vivo cardiac rhythm was monitored by surface ECG, implantable cardiac telemetry, and intracardiac electrophysiology studies. Intracellular Ca2+ imaging was performed using confocal-based line scans of isolated nodal cells loaded with fluorescent Ca2+ reporter Cal-520. Whole cell patch clamp was conducted on isolated nodal cells to determine action potential kinetics and sodium-calcium exchanger function. Hcn4:shJph2 mice demonstrated a 40% reduction in nodal Jph2 expression, resting sinus tachycardia, and impaired heart rate response to pharmacologic stress. In vivo intracardiac electrophysiology studies and ex vivo optical mapping demonstrated accelerated junctional rhythm originating from the atrioventricular node. Hcn4:shJph2 nodal cells demonstrated increased and irregular Ca2+ transient generation with increased Ca2+ spark frequency and Ca2+ leak from the sarcoplasmic reticulum. This was associated with increased nodal cell AP firing rate, faster diastolic repolarization rate, and reduced sodium-calcium exchanger activity during repolarized states compared to control. Phenome-wide association studies of the JPH2 locus identified an association with sinoatrial nodal disease and atrioventricular nodal block. Nodal-specific Jph2 knockdown causes increased nodal automaticity through increased Ca2+ leak from intracellular stores. Dysregulated intracellular Ca2+ underlies nodal arrhythmogenesis in this mouse model.

The first experience of a hybrid approach in the surgical treatment of atrial fibrillation

Background: Atrial fibrillation (AF) is the most common arrhythmia in clinical practice and is associated with an increased risk of death, progression of heart failure, and the development of cardiogenic thromboemboli. Despite the significant success in the management of AF in the paroxysmal form, the results of the treatment for patients with persistent forms of AF remain unsatisfactory. Though the surgical approach provides higher rates of efficiency regarding the restoration of a sinus rhythm, transmural lesions are not always attainable, as a result, the rate of AF recurrence in the long-term period remains fairly high. It is also impossible to create ablative patterns to the mitral and tricuspid valves during thoracoscopic epicardial ablation, which can cause the development of recurrent AF, perimitral and typical atrial flutter. Therefore, the development of hybrid approaches combining the advantages of catheter and thoracoscopic techniques is an urgent task of contemporary surgical and interventional arrhythmology.
 Aims: to estimate the immediate results of a hybrid approach in the management of patients with persistent AF.
 Methods: We report the first experience of a hybrid treatment of patients with persistent AF. 6 patients aged 53-64 years (1 female, 5 males) were included in the study. At the first stage, thoracoscopic epicardial bipolar ablation was performed (modified GALAXY protocol); the second stage (in 3 to 6 months after the thoracoscopic stage) included an intracardiac electrophysiological study with three-dimensional endocardial mapping followed by endocardial ablation.
 Results: The thoracoscopic stage of the hybrid treatment included ablation according to the box lesion scheme using a bipolar irrigation equipment. No lethal outcomes and severe, life-threatening complications were registered. The duration of the inpatient period was 510 hospital-days. The 2nd stage of the hybrid treatment was limited to intracardiac electrophysiological examination only in 2 patients. In 4 patients, epicardial radiofrequency ablation was complemented by endocardial radiofrequency exposure. In 3 of the 4 patients who underwent endocardial radiofrequency ablation, catheter ablation of the mitral and cavotricuspid isthmus was required because of the induction of perimitral and typical flutter, respectively. After the 2nd stage of the hybrid treatment, at the time of discharge all the patients maintained a stable sinus rhythm. There were no severe complications or lethal outcomes.
 Conclusion: a hybrid approach in the AF management is a safe and effective method of treatment, which combines the advantages of minimally invasive surgery and endocardial intervention in patients with persistent AF. The technique is safe and has acceptable short-term results.

Sodium-glucose cotransporter-2 inhibitor alleviated atrial remodeling in STZ-induced diabetic rats by targeting TLR4 pathway.

PurposeThe mechanism of sodium–glucose cotransporter-2 inhibitor (SGLT-2i) reducing the incidence of atrial fibrillation remains unclear. We hypothesize that sodium–glucose cotransporter-2 inhibitor alleviated atrial remodeling in STZ-induced diabetic rats by targeting TLR4 pathway.MethodsA total of 42 rats were randomly assigned into three groups: control group (CON group); diabetes group (DM group): diabetes mellitus rats were established by 65 mg/kg streptozotocin (STZ) intraperitoneal injection; and diabetes + dapagliflozin group (DM + DAPA group): diabetic rats were given DAPA gavage administration (DAPA 2mg/kg/d for 4 weeks by gavage administration), 14 rats in each group. Epicardial multiple-lead recording and intracardiac electrophysiology studies were performed to investigate the electrical remodeling in the heart and the atrial fibrillation inducibility in each group. Western blot analysis and real-time PCR were used to determine the protein and mRNA expression of toll-like receptor 4 (TLR4), interleukin receptor-associated kinase 1 (IRAK1), tumor necrosis factor receptor-associated factor 6 (TRAF6), nuclear factor-kappa B (NF-κB), and type I collagen (collagen I).ResultsCompared with rats in CON group, rats in DM group showed marked myocardial fibrosis, ectopic pacing excitement, reduced conduction velocity, decreased cardiac function. TLR4/IRAK1/TRAF6/NF-κB, collagen I proteins expressions and incidence of atrial fibrillation (27.3%) were increased in DM group. Parts of these changes were reversed by treatment of DAPA. Incidence of atrial fibrillation was decreased in DM + DAPA group (2.8%).ConclusionsSGLT-2i dapagliflozin may prevent diabetic rats' atrial remodeling and reduce the inducibility of atrial fibrillation partly by targeting TLR4/IRAK1/TRAF6/NF-κB inflammatory pathway.

Occurrence of high-grade conduction disorder after the onset of left bundle branch block in post-TAVI. The French multicenter LBBB-TAVI study

Transcatheter aortic valve implantation (TAVI) has revolutionized the management of severe aortic stenosis. The development of a new-onset complete left bundle branch block (LBBB) is, however, a frequent complication. The objective of the present study was to assess the impact of a new-onset LBBB after TAVI on the risk of high degree conduction disorder appearance. Patients were included in 10 centers in the French Multicenter LBBB-TAVI study. New-onset LBBB after TAVI persisting for more than 24 hours were stratified by intracardiac electrophysiological study. Patients at high-risk of conduction disturbances (≥ 70 ms His-ventricle interval (HV) or presence of infra-Hissian block) were implanted with a pacemaker with recording of disturbance episodes (Sorin Microport CRM, Clamart, France). Those at lower risk (HV < 70 ms) were implanted with a loop recorder with automatic remote monitoring (Biotronik, Berlin, Germany). The primary end point was the incidence (rate and time to onset) of high-grade conduction disturbances between the two groups at 12 months. From June 2015 to November 2018, 199 patients were included in the study (mean age 82.3 ± 5.9 years, 61.9% female sex). A self-expanding valve was implanted in 65.2% of the procedures. A pacemaker were implanted in 46 patients, 135 patients with a loop recorder. At 12 months, 46 (25.4%) patients displayed a high-grade conduction disorder. High-grade conduction disturbances were more frequent with HV ≥ 70 ms (46.2% vs. 17.1%, P < 0.001). The median time to conduction disorder occurrence was 100 [29–229] days. In multivariate analysis, adjusted for implantation center, an HV ≥ 70 ms was independently associated with the occurrence of a high-grade conduction disorder, HR 2.8 [1.3–6.1], P = 0.007 ( Fig. 1 ). Increased HV interval (≥ 70 ms) is independently associated with the occurrence of high-grade conduction disorder in new-onset LBBB after TAVI.

Predictive value of electrophysiological study for risk stratification of ventricular tachyarrhythmias in patients with non-ischemic cardiomyopathy and chronic systolic heart failure

A systematic review and meta-analysis of studies providing information on the use of intracardiac electrophysiological study (EPS) to stratify the risk of ventricular tachyarrhythmia (VT) in patients with non-ischemic chronic heart failure with low left ventricle ejection fraction (HFrEF). Relevant publications were searched until 20.01.2021 by two independent researchers in major search engines, electronic archives of clinical research, and open access preservatives repository. The end point considered was an episode of sudden cardiac death or sustained paroxysm of VT, or an appropriate electrotherapy of an implanted cardiac defibrillator. Ten clinical trials with 608 relevant patients (mean age: 51.5 ± 12 years; mean left ventricle EF: 26.8±8.5%, NYHA class: I - 17.7%; II - 33.7%; III - 35.9%, IV - 12.7%) were selected. The end point was registered in 92 patients (15.1%): in 47 patients (43.9%) with previously induced VT during EPS and in 45 patients (8.9%) without VT. The diagnostic odds ratio was 5.57 (2.27-13.63). The combined sensitivity and specificity of the EPS were 42% (26-61%) and 88% (83-92%) respectively. The results indicate the potential of EPS to stratify the arrhythmic risk in patients with non-ischemic HFrEF.

564 Controversial role of intracardiac eletrophysiology study in Brugada syndrome: analysis of a single-centre retrospective cohort study

Abstract Aims According to European guidelines, aborted sudden cardiac death (SCD) in Brugada syndrome (BrS) is regarded as a I class recommendation for secondary prevention implantable cardioverter defibrillator (ICD). However, the risk stratification of BrS patients for primary prevention ICD still represents a clinical conundrum. Although intracardiac electrophysiology (EP) study proved useful for the selection of high-risk patients in this setting. Therefore, aim of this study was to assess all clinical and EP variables associated with the induction of VA at EP study and the rate of appropriate/inappropriate ICD interventions and/or clinical SCD events in these patients occurring at follow-up. Methods and results From 2001 to 2021, all EP studies performed in symptomatic/asymptomatic patients (46 ± 14 years, M 88%) with/without family history of SCD spontaneous/drug-induced type I pattern (TIP) on ECG and no spontaneous ventricular arrhythmias were retrospectively considered at our study centre. Clinical variables, BrS pattern, EP study data (including right ventricular site and type of stimulation protocol), and ICD interventions (DC-shocks or Anti-Tachycardia Pacing events, ATP) and/or SCD events occurring at follow-up were all evaluated. EP study was deemed positive for any polymorphic VA induced during programmed ventricular stimulation; non-sustained episodes included. ICD was routinely implanted in all patients with a positive EP study. Follow-up data were detected by the collection of medical and home-monitoring recordings at study-site level. Follow-up data were available in 50 patients (9 ± 6 years on average). Patients were generally young with few cardiovascular comorbidities. SCD history was known in 21 (42%) with a significant number of asymptomatic patients (48%). Br patterns were equally distributed in the investigated population (spontaneous and drug-induced TIP in 52% and 48%, respectively) and AF history was fairly common (16%). In the study population, EP study tested positive in 30 patients (60%): spontaneous TIP (P = 0.0518), few extrastimuli during programmed ventricular stimulation (P = 0.0015), and right ventricular stimulation at the apical site (P ≤ 0.0001) were the only variables to be clearly associated with a positive EP study in the appraised patients. At follow-up, appropriate ICD shocks were documented in 4 out of 30 implanted patients (13%) at generally 5 ± 7 years from EP study evaluation. Although three ICD interventions (75%) occurred in patients with spontaneous TIP, one patient with drug-induced TIP pattern and positive EP study referred to Emergency Department for unrelenting VT storm after roughly 13 years from ICD implantation. Inappropriate ICD interventions for fast rate AF were detected in 10% of cases. Finally, no SCD events were documented at follow up in patients with a negative EP study. Conclusions In a retrospective analysis, EP study proved useful in the risk stratification of SCD in BrS patients. A few ventricular extrastimuli delivered at the right ventricular apex seem sufficient to prompt the induction of life-threatening VA in high-risk BrS patients during EP study. Moreover, in this setting, a negative EP study seems protective against the development of VA/SCD events at follow-up. However, not only is spontaneous TIP associated with an increased risk of arrhythmic death, but a drug-induced TIP, generally regarded as a low-risk condition, might also be associated with a long-term hazard of SCD in these patients.

Dyssynchronous cardiomyopathy in patients with WPW syndrome and its reversibility after RFA of accessory pathway

Abstract Introduction In some cases accessory pathway-mediated ventricular preexcitation can be associated with electro-mechanical dyssynchrony and, consequently, with dyssynchrony-related dilated cardiomyopathy, even in the absence of supraventricular tachycardia (SVT). Sometimes rapid progression of ventricular dysfunction developed in such patients after birth. Methods and materials 8 patients with asymptomatic WPW and dyssynchronous cardiomyopathy were examined in our Institute from 2017 till 2019. Four patients of the group were observed in other clinics with dilated cardiomyopathy (DCM) and prescribed appropriate therapy without significant clinical effect. The absence of complaints of heartbeat and episodes of tachycardia at the scheduled Holter monitoring allowed eliminating incessant tachycardia as a possible cause of cardiomyopathy. After radiofrequency ablation (RFA) all patients were performed ECG to assess QRS duration, Holter monitoring, echocardiography (Echo) for assessment of heart chamber volume and left ventricle (LV) contractile function and Speckle tracking – Echo with LV longitudinal strain assessment. The average age of the patients was 9.5 years (from 2 to 14 years). 6 children had heart failure (NYHA Class II). Results According to Echo all patients had widened QRS complex. Dilatation and enlargement of LV volume were marked in 6 pts. According to Echo7 patients had decrease of LV contractile function. According to Speckle tracking – Echo all patients had intraventricular dyssynchrony, decrease of longitudinal strain indices. At intracardiac electrophysiology study right-sided accessory pathways was diagnosed in all patients, successful RFA was performed. Preexitation relapsed, and the repeated RFA was performed in 2 pts. Complications caused by RFA were not marked. After RFA all patients showed a regular normalization of QRS duration. At the 5th day after RFA Echo was performed to all patients. The patients with initially decreased LV ejection fraction had it increased. The patients with initial dilatation and LV volume enlargement had normalization of the given indices. According to Speckle tracking – Echo normalization of global and regional myocardial function, LV longitudinal strain, disappearance of intraventricular and interventricular dyssynchrony were marked in all patients. The index of longitudinal strain was 17,0±0,64% before RFA, after RFA - 23,75±0,92% (p=0,ehab724.035946). Conclusion As a result of RFA of accessory pathways electromechanical resynchronization causes LV demodeling and restoration of its contractile ability. The presented clinical examples are an additional indication for RFA of accessory pathways even in the absence of SVT in patients regardless of age. Funding Acknowledgement Type of funding sources: None.

Ablação por cateter: uma nova opção de tratamento da Fibrilação Atrial Crônica

Objetivo: Descrever as principais características da fibrilação atrial crônica e apresentar a ablação por cateter como alternativa terapêutica efetiva. Detalhamento do caso: Trata-se de um relato de caso de um paciente com aumento de átrio esquerdo e fibrilação atrial (FA) crônica de difícil controle, que após ser submetido ao tratamento medicamentoso otimizado e posterior cardioversão elétrica sem sucesso, obteve resposta eficiente com ablação por cateter após estudo eletrofisiológico intracardíaco (EEF) e consequente resolução do quadro de FA. O EEF é um método diagnóstico e terapêutico de cateterismo cardíaco, no qual é possível identificar o circuito responsável pela taquicardia e bloquear o foco por meio de uma lesão térmica discreta provocada pelo próprio cateter já inserido, proporcionando a eliminação dos estímulos impulsionadores da arritmia. Considerações finais: O trabalho expõe esta nova alternativa terapêutica, bem como suas vantagens em relação aos tratamentos convencionais já consagrados e a possibilidade de um maior benefício no prognóstico do paciente com FA de difícil controle.

Toll-like receptor 9 is a novel therapeutic target to prevent atrial fibrillation

Abstract Background Atrial fibrillation (AF) is the most common type of arrhythmia seen in clinical practice. Recent studies suggest that inflammation contributes to the pathogenesis of AF. On the other hand, several evidence suggests that toll-like receptor (TLR) 9 recognizes bacterial DNA, activating innate immunity, whereas it also provokes inflammation in response to fragmented DNA released from mammalian cells. Recently, we have reported that TLR 9 plays a pivotal role in the development of vascular inflammation and atherogenesis through proinflammatory activation of macrophages. Purpose This study aimed to assess whether TLR9 contributes to the AF arrhythmogenesis. Methods TLR9 deficient (TLR9−/−) and wild-type mice were infused with angiotensin II (Ang II) or vehicle via an osmotic minipump for 4 weeks. Blood pressure and body weight were measured serially. Then, we examined AF inducibility by intracardiac electrophysiological study and the inflammation-induced atrial remodeling by biochemical analysis after 4 weeks of Ang II infusion. Results There was no significant difference in blood pressure and pulse rate between TLR9−/− and wild-type mice both before and after Ang II infusion. Ang II-treated TLR9−/− mice showed lower incidence of AF compared with wild-type mice treated with Ang II. Genetic deletion of TLR9 significantly reduced the interstitial fibrosis in atrium of Ang II-treated mice. TLR9−/− mice also showed less mRNA expressions of inflammatory and fibrosis-related biomarkers (TNF-α, interleukin-6, TGF-β, collagen-1, collagen-3) in atrium compared with wild-type mice. Conclusions TLR9 might contribute to the AF arrhythmogenesis associated with atrial inflammation. TLR9 might serve as a potential therapeutic target for AF. Funding Acknowledgement Type of funding source: None

Assessment of the potential damaging effect of radiofrequency exposure in children in prospective follow-up (case report series)

Aim: To evaluate the electrical activity of the myocardium and the radiofrequency (RF) application zone resulting from radiofrequency ablation (RFA) performed at an early age.Material and Methods. A prospective follow-up study included three patients who underwent intracardiac electrophysiological study (EPS) and effective RFA of the tachycardia for the first time at an early age. A reintervention was required in one case 12 years after the procedure and in two cases six years after it due to recurrent and new-onset arrhythmias. During the reintervention, electroanatomical mapping was performed to assess the potential damaging effect of radiofrequency exposure in the area of the first ablation.Results. The intracardiac EPS and amplitude bipolar CARTO-reconstruction of primary ablation area were performed during repeated RFA procedure. The study showed that neither zones with a decrease in the amplitude of electrical signal from the myocardium nor silent electrical zones were present ruling out the cicatricial-sclerotic changes in the myocardium in children in the long-term period after RF exposure.Conclusion. The study showed that no increase in the coagulation necrosis zone in the area of primary ablation occurred during the growth of child when the sparing energy and temperature parameters of RFA and the limited number of RF applications were used. Further research in this area is required.

The role of 3D-high definition mapping systems in treating postoperative drug-resistant intra-atrial reentrant tachycardia

We report the case of a patient with recurrent episodes of postoperative intra-atrial reentrant tachycardia occurring after surgical patch closure of a sinus venosus atrial septal defect (SVASD). Arrhythmic episodes, as usually reported in scar-related arrhythmias, were resistant to antiarrhythmic therapy and worsened patient's quality of life. Therefore, we decided to perform an intracardiac electrophysiology study using a 3D-high definition mapping system to identify and treat the precise arrhythmic substrate with radiofrequency ablation. There is a growing evidence that this technique represents a valid therapeutic option in postoperative arrhythmias refractory to medical treatment in patients with repaired congenital heart disease.

Successful Ablation of Ventricular Arrhythmia Without Fluoroscopy Guided by Carto 3 System in Pregnant Woman Without Structural Heart Disease

Introduction: Arrhythmias can take place in any period of pregnancy. In addition, the incidence of life-threatening ventricular arrhythmias in a pregnant woman without the organic pathology of the heart is rare. Interventional treatment should be carried out in cases of severe arrhythmias and drug resistance. The radiation exposure during ablation carries a potentially harmful effect on the mother and fetus although data on the zero-fluoroscopy ablation of arrhythmias in pregnant women is limited. Case Presentation: A 26-year-old female without structural heart disease at the gestation period of 26-28 weeks was admitted to a hospital due to severe symptoms of ventricular tachycardia (VT) and premature ventricular contractions. In this regard, the conservative therapy of β-blockers was ineffective and accompanied by a decrease in blood pressure to 60/40 mm Hg. Results: An intracardiac electrophysiological study and non-fluoroscopic catheter ablation were carried out considering the drug refractory and severe symptoms of VT. The ablation of the arrhythmia substrate was successfully performed using the Carto 3 System without fluoroscopy. Based on the results, the procedure was not associated with any maternal or fetal complications. Conclusions: In general, the non-fluoroscopic catheter ablation guided by electro-anatomical mapping and navigation systems is safe and applicable in the treatment of pregnant women with severe types of arrhythmias.

P1010Electrophysiological characteristics of paroxysmal tachycardia in children with short PQ interval

Abstract Introduction It is well known that children with short PQ interval can have different types paroxysmal tachycardia (PT). Combination of short PQ interval with PT is called Lown-Ganong-Levine (LGL) syndrome. We have hypothesized that in children with short PQ interval electrophysiological types of PT do not correlate with shortening of PQ interval. Purpose The aim of the study was to assess the PT types based on results of the electrophysiological studies and radiofrequencycatheter ablation (RFA), and to estimate the AV conduction parameters and their dynamic changes before and after the procedure. Materials and methods of research: 55 children with supraventricular tachycardia (SVT) and short PQ interval were examined. The examination included:ECG, 24-hour Holter monitor, transesophageal pacing study (TEPS), intracardiac electrophysiological study (EPS). 22 children underwent RFA procedure. During the period of the study 55 children had 111 TEPS and 28 EPS studies. Results 21 (38,2%) children had orthodromic AV reentrant tachycardia with accessory pathway (AVRT), 27 (49,1%) had typical (slow-fast) AV nodal reentrant tachycardia (AVNRT), 2 (3,6%) had atypical AVNRT, 1 (1,8%) had combination of typical and atypical AVNRT, 1 (1,8%) had atrial ectopic tachycardia combined with atypical AVNRT, 4 (7,3%) had spontaneous atrial fibrillation or atrial flutter, 3 (5,4%) had combination with typical AVNRT and 1 child (1,8%) had AVRT. PQ interval measured 107,2 ms (83–120ms). 22 (40%) children underwent RFA-13 children with typical AVNRT, 9 with AVRT. In children with AVNRT tachycardia cycle length was 229–425 ms (309,8±67,6ms). Primary RFA was effective in 10 (76,9%) children. The AVNRT recurrence was found in 3 (13,6%) cases after 7,2±4,3 month from the time of procedure. After slow pathway ablation PQ interval length didn't change (107,1±9,1ms compared to 108,2±7,1ms; p=0,2). No change occurred with the maximal rate of 1:1 conduction through AV node (187,8±14,8 imp/min compared to187±12,5 imp/min; p=0,2). Effective refractory period of AV node (AVNERP) increased by a small amount (288,9±14ms, compared to 266±42,7ms; p=0,06). 9 (40,9%) children underwent RFA of the accessory pathway (AP). In all of the cases there were concealed AP with the left-sided localization. AVRT cycle length was 259–382 ms (304,2±41,2ms). After RFA of concealed AP maximal rate of 1:1 conduction through AV node increased by a small amount (220±26,4 imp/min compared to 191,2±23,6 imp/min) and AVNERP decreased (256,7±25,2ms compared to 268,6±38,9ms; p=0,09).After RFA of AP PQ interval length didn't change (110±5,9ms compared to 110±5ms; p=0,1). Conclusion In children with short PQ interval PT was associated with dual physiology of AV connection or with concealed AP. After the successful RFA in children with AVNRT and AVRT there was no PQ interval normalization, which remained short in all examinations. Thus, short PQ- interval is a co-existing phenomenon in children with AVNRT and AVRT.

P2867Vildagliptin reduces inducibility of atrial fibrillation in hypertensive rats complicated with diabetes mellitus

Abstract Background Atrial fibrillation (AF) is the most common arrhythmia in clinical practice, increasing the incidence of ischemic stroke. Diabetes mellitus (DM) is a predictor of stroke and thromboembolism, and it was reported to be an independent risk factor for AF. A recent study has shown that, in obese mice with diabetes, dipeptidyl peptidase-4 (DPP-4) inhibitor prevents myocardial fibrosis, active oxygen stress, weight loss and improves myocardial hypertrophy. However, the effects of DPP-4 inhibitors on atrial remodeling associated with diabetes and atrial fibrillation have not yet been clarified. Purpose This study was performed to assess whether a DPP-4 inhibitor (vildagliptin) ameliorates atrial remodeling in spontaneously hypertensive rats (SHR) with streptozotocin-induced diabetes. Methods Rats were divided into 3 groups: SHR without DM, SHR with DM treated with vehicle and SHR-DM treated with vildagliptin (3mg/kg/day; intragastric gavage). For each group, blood pressure, blood glucose level and body weight were measured serially. Cardiac function was also evaluated by echocardiography. Then, we examined AF inducibility by intracardiac electrophysiological study and the inflammation-induced atrial remodeling by biochemical analysis after 4 weeks of treatment. Results There was no significant difference in blood pressure and blood gucose level between vehicle and vildagliptin groups. Administration of vildagliptin significantly reduced AF inducibility compared with rats with vehicle. In DM rats treated with vehicle, rapid atrial pacing promoted the gene expression of inflammatory and fibrosis-related biomarkers (TNF-α, MCP-1, collagen-1) in atrium. Vildagliptin reduced these gene expression levels. In addition, administration of vildagliptin significantly reduced the interstitial fibrosis in atrium. Conclusions DPP-4 inhibitor, vildagliptin. could prevent atrial inflammation and reduce the AF inducibility in SHR complicated with DM.

LONG-TERM FOLLOW-UP ASSESSMENT OF POTENTIAL ADVERSE EFFECTS AFTER RADIOFREQUENCY ABLATION IN AN INFANT (A CLINICAL CASE)

The article presents a long-term follow-up of the patient who underwent an intracardiac electrophysiological study (EPS) and radiofrequency ablation (RFA) of focal tachycardia at the age of 2 months. 12 years after the indexed procedure, Wolff-Parkinson-White (WPW) syndrome was diagnosed and required repeat RFA procedure. The atrial map of the first ablated zone was reconstructed using non-fluroscopic mapping system. EPS reported the absence of myocardial electrical activity reduction zones. There were no damages after the indexed ablation. Our findings suggested the normal electrical activity of the atrial tissue in the long-term period following the indexed RFA. This clinical case reports the absence of post-ablation necrosis and successful restoration of the electrical activity of the myocardium with the child’s growth.

Advanced Cardiac Signal Recording

Implantable loop recorders allow prolonged and continuous single-lead electrocardiogram recording, with the pivotal addition of remote monitoring. They have significantly shortened time to electrocardiographic diagnosis and appropriate therapy of many bradyarrhythmias/tachyarrhythmias and proved helpful in arrhythmia burden definition, offering invaluable information in the diagnostic workup for syncope and atrial fibrillation. Advanced cardiac signal recording is also possible by transesophageal catheters. They have been used to orient diagnosis during wide and narrow QRS complex tachycardias and also to perform minimally invasive pacing. Intracardiac electrophysiologic study remains, however, essential for diagnosis of several arrhythmias in the perspective of curative catheter ablation.

Clinical analysis of right atrial appendage aneurysms complicated by atrial tachyarrhythmias in three children

Objective: To investigate the clinical features and results of treatment for right atrial appendage aneurysms complicated by atrial tachyarrhythmias in children. Methods: This retrospective study included three children with right atrial appendage aneurysm complicated by atrial tachyarrhythmias (aged 1.0 to 5.3 years, weight 10 to 17.1 kg) who were hospitalized at the Pediatric Cardiology Department (Heart Center) of the First Hospital of Tsinghua University (Beijing Huaxin Hospital) during the period from January 2016 through April 2018. The patients' clinical features, the results of electrocardiogram (ECG) and echocardiography, the effects of therapeutic interventions (antiarrhythmics, radiofrequency ablation, and surgical resection of right atrial appendage aneurysm) and the results of pathological assessment were analyzed. Results: Three cases of right atrial appendage aneurysm were diagnosed at 36 weeks of gestational age, 1 month and 4 months after birth respectively. In two cases, ECG showed alternating episodes of atrial tachyarrhythmias including atrial tachycardia, atrial flutter, and atrial fibrillation, and echocardiography showed aneurysmal dilatation of right atrial appendage. These two cases underwent right atrial appendage aneurysm resection. In the remaining one case of atrial tachycardia, echocardiography did not visualize important lesions in the right atrium, thus the intracardiac electrophysiologic study and radiofrequency ablation were performed; and focal atrial tachycardia originating from the apex of right atrial appendage was mapped but failed to be ablated; consequently, the patient received the right atrial appendage resection, in which the right atrial appendage aneurysm was found. Preoperative multiple antiarrhythmics showed only modest or no efficacy for all the three cases. The atrial tachyarrhythmias disappeared in all the three cases after right atrial appendage aneurysm resection. Postoperative atrial tachycardias associated with new foci of impulse formation developed in two cases. These two patients reverted to normal sinus rhythm and remained in this rhythm by using antiarrhythmics. Pathological assessment showed cystic dilation of parts of atrial cavity, fibrosis of cyst wall, generalized fibrosis of atrial myocardium combined with myocardial atrophy and cystic dilation, as well as uneven myocardial thickness with generalized myocardial interstitial fibrosis. Conclusions: For patients with congenital right atrial appendage aneurysm, atrial tachyarrhythmias might develop during fetal stage or early postpartum period. Reliance on echocardiography might often lead to the missed diagnosis. These patients with atrial tachyarrhythmias responded poorly to antiarrhythmics. Radiofrequency ablation might be associated with a high risk and limited efficacy. Surgical resection of right atrial appendage aneurysm showed satisfactory results and should be highly recommended.

EFFICACY OF CATHETER ABLATION FOR PERSISTENT ATRIAL FIBRILLATION IN PATIENTS WITH DIABETES MELLITUS PRESENT WITH TACHY-BRADY SYNDROME

Aim. To estimate the efficacy of catheter ablation in patients with type 2 diabetes mellitus (T2D) present with atrial fibrillation and sick sinus syndrome (SSS) undergoing permanent pacemaker implantation.Methods. 56 patients (34 females) with persistent AF and SSS were enrolled in the study. The mean age of patients was 67.7±10.7 years. Dual chamber cardiac pacemaker with remote monitoring function were implanted in all patients. All the patients were assigned to two groups: Group 1 comprised 31 patients aged 67.3±9.6 years, and Group 2 comprised 25 patients aged 72.6±9.9 years, including 22 (39.2%) diabetic patients. 2-3 days after pacemaker implantation, group 1 patients underwent intracardiac electrophysiology study and RFA of the pulmonary vein ostia, mitral isthmus and the left atrial posterior wall. Group 2 patients received antiarrhythmic drug therapy. Results. 3 patients (9%) in Group 1 had recurrent AF within the 6-month follow-up. The efficacy of the RFA for AF was 55% (n = 17) 1 year after the indexed hospitalization. 8 patients had short paroxysmal attacks which gradually lessened and stopped after. 5 patients (21%) in Group 2 did not have any AF paroxysms within the 1-year follow-up (Х2 = 5.52, р = 0.02). All these patients received amiodarone as antiarrhythmic drug therapy, whereas the others had paroxysmal attacks. Frequent attacks in 10 patients (40%) led to a change in antiarrhythmic drug use. Hospital readmission rates for AF were 16% and 52%, respectively (Х2 = 4.15, р = 0.04). The impact of atrial and ventricular stimulation on the development of recurrent AF was statistically insignificant (atrial stimulation – X2 = 0.01, cc = 1, p = 0.90; ventricular stimulation – X2 = 0.15, cc = 1, p = 0.69). None paroxysmal attacks were recorded in 10 diabetic patients (45%) after the RFA within the 1-year follow-up.Conclusion. Catheter ablation for persistent AF and SSS treated with permanent pacemakers is highly effective and safe method. In addition, it is superior to pharmacological approach. The presence of T2D likely did not significantly affect the efficacy of RFA for persistent form of AF.