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Background: Transcatheter aortic valve implantation (TAVI) has emerged as an effective and safe treatment for severe aortic stenosis in the last decades compared for surgical aortic valve replacement. However, it stills associated with high risk of conduction abnormalities requiring pacemaker implantation. Our study aimed to examine factors associated with transient conduction abnormities that don’t require pacemaker on long term. Methods: Retrospective analysis of all consecutive patients who underwent TAVI between 2010 and 2019 in Kaplan Medical Center, Rehovot, Israel. Results: Pre-TAVI haemoglobin levels were significantly lower in patients who developed transient CA compared to patients who develop persistent conduction abnormalities and were pacemaker dependent on follow up. Similarly, urea levels were higher in in patients with transient conduction abnormalities. Conclusion: Transient conduction abnormalities following TAVI are not uncommon. Correction of anaemia and volume depletion prior to TAVI may decrease the incidence of these transient conduction abnormalities and hence, decrease the fraction of unnecessary permanent pacemaker implantations in the long term. Watchful waiting may be wise in anaemic patients who develop CA after TAVI. The cut-off for haemoglobin levels prior to TAVI is yet to be determined.

Aims To evaluate the benefit of speckle tracking radial strain imaging (STRSI)-guided left ventricular (LV) lead (LVL) positioning in cardiac resynchronization therapy (CRT) in patients (pts) with ischaemic cardiomyopathy with CRT indication. Methods and results We conducted a prospective randomized controlled trial. Patients were enrolled in nine centres with 2:1 randomization into two groups (guided vs. control). Patients underwent STRSI to identify the optimal LV position from six LV segments at midventricular level. Implantation via STRSI was attempted for recommended segment in the guided group only. Follow-up included echocardiography (6 months) and clinical evaluation (6 and 12 months). The primary endpoint was comparison % reduction in LV end-systolic volume at 6 months with baseline. Secondary endpoints included hospitalizations for heart failure and death, and improvement in additional echocardiographic measurements and quality of life score. A total of 172 patients (115 guided vs. 57 control) were enrolled. In the guided group, 60% of the implanted LV leads were adjudicated to be successfully located at the recommended segment, whereas in the control group 44% reached the best STRSI determined segment. There was no difference between the groups in any of the primary or secondary endpoints at 6 and 12 months. Conclusion Our findings suggest that echo-guided implantation of an LV lead using STRSI does not improve the clinical or echocardiographic response compared with conventional implantation.

Early detection of atrial fibrillation (AF) is desirable but challenging due to the often-asymptomatic nature of AF. Known screening methods are limited and most of them depend of electrocardiography or other techniques with direct contact with the skin. Analysis of voice signals from natural speech has been reported for several applications in medicine. The study goal was to evaluate the usefulness of vocal features analysis for the detection of AF.This prospective study was performed in two medical centers. Patients with persistent AF admitted for cardioversion were enrolled. The patients pronounced the vowels "Ahh" and "Ohh" were recorded synchronously with an ECG tracing. An algorithm was developed to provide an "AF indicator" for detection of AF from the speech signal.A total of 158 patients were recruited. The final analysis of "Ahh" and "Ohh" syllables was performed on 143 and 142 patients, respectively. The mean age was 71.4 ± 9.3 and 43% of patients were females. The developed AF indicator was reliable. Its numerical value decreased significantly in sinus rhythm (SR) after the cardioversion ("Ahh": from 13.98 ± 3.10 to 7.49 ± 1.58; "Ohh": from 11.39 ± 2.99 to 2.99 ± 1.61). The values at SR were significantly more homogenous compared to AF as indicated by a lower standard deviation. The area under the receiver operating characteristic curve was0.98 and0.89 ("Ahh" and "Ohh," respectively, p .001). The AF indicator sensitivity is 95% with 82% specificity.This study is the first report to demonstrate feasibility and reliability of the identification of AF episodes using voice analysis with acceptable accuracy, within the identified limitations of our study methods. The developed AF indicator has higher accuracy using the "Ahh" syllable versus "Ohh."

Atrial fibrillation (AF) has become a major health and economic burden. Pulmonary veins isolation (PVI) based ablation for rhythm control of AF is well established. Furthermore, recent studies show its superiority over anti-arrhythmic therapy. However, most of these studies were performed in highly experienced centers, that may not necessarily reflect real world outcomes. We evaluated the outcome (success rate and complications) of 300 consecutive procedures, performed on 291 patients (during 2014-2015) of a major HMO. All had undergone PVI for AF by experienced electrophysiologists in 8 medical centers (85% RF technique). Data were retrospectively collected using computerized medical records. Variables included demographic and clinical characteristics, acute procedural success and complications, long term success rate based on multiple ECGs and Holter monitoring. The average age was 63 years, 61% were male, 79% had paroxysmal AF. Sinus rhythm at 2 years was considered success. The overall success rate of maintaining sinus rhythm at 2 years was 56%. Success rate correlated significantly with age and standard risk factors. Those patients in whom the index procedure was the first ablation, success rate was 78%. Sixty-one patients underwent a second ablation with success rate of 64%, 32 underwent a 3rd/4th procedure with success rate of 56%. The probability to be in sinus rhythm after 2 years regardless of the number of ablations was 78%. Thirty-five percent of the patients were still on anti-arrhythmic therapy at 2 years post procedure. Complication rate was 6.6% (2.5% serious), among them 2 deaths, 1 procedure related. PVI in a real-world large unselected population is a valid therapeutic option for AF with an overall 2-year success rate of 56%. In our group higher complication rate was observed compared to the reported rate in the literature. The use of cryo-ablation for PVI and further improvements in both technique and experience may improve both efficacy and safety profile.

Background Limited fluoroscopy ablation using 3D electro-anatomical system (3DS) has been used for arrhythmias in children, however it is not a common practice. We aimed to facilitate a fluoroscopy limited approach for ablation of accessory pathways (AP) in children. Methods Following electrophysiologic (EP) catheter placement a single dual-plane fluoroscopic image (right anterior oblique-30° and left anterior oblique-60° views) was acquired and the 3DS views were rotated to be a perfect match to the fluoroscopy. Ninety-four consecutive pediatric patients [mean age 11.8 ± 4.1 (4.2–18) years, 61.7% males] with Wolf–Parkinson–White syndrome underwent ablation of an AP. Fifty-seven had manifest AP, 54 had left-sided AP (LSAP) and 40 had right-sided AP (RSAP). Results The acute success rate was 95.7% (90/94), with a recurrence rate of 1.1% (1/90) at a mean follow-up of 13 ± 5.5 (4.4–22.9) months. Mean procedure and fluoroscopy times were 144 ± 45 (55–262) min and 1.8 ± 1.4 (0.1–5.6) min, respectively. Comparison of the first 20 procedures to the next 74 procedures demonstrated an extended procedure time (171 ± 53 min vs 135 ± 38 min, p

Introduction Aortic Stenosis (AS) is the most common valvular heart disease in the Western world. Transcatheter aortic valve implantation (TAVI) is an alternative to surgical valve replacement in medium and high-risk patients. One of the most common complications after TAVI is conduction system disturbances including bundle branch block, complete heart block and need for permanent pacemaker implantation. Transthyretin cardiac amyloidosis (TTR–CA) is an increasingly recognized cause of heart failure that almost exclusively affects older adults. Diagnosis of TTR-CA in patients undergoing valvular intervention is relevant to understand their clinical outcomes and to discuss specific management. Objectives Occult amyloid may account for the frequent need for pacemakers among TAVR patients. We aimed to assess the correlation between intervention induced conduction abnormalities and the need for a pacemaker insertion and the presence of TTR-CA. Methods The study population included patients who had aortic valve intervention between 2011–2018. The patients underwent Tc99m-PYP scan using SPECT technology which has been shown to be valid for the diagnosis of TTR-CA. We examined the rate of conduction disorders and the need for a permanent pacemaker from patient files at the time of hospitalization and during a 24-month follow-up. Results The study population included 86 patients, mean age 78±6 years, 55% women. Twenty-nine (33%) of the participants were diagnosed as positive (VAS 2 and 3) for transthyretin cardiac amyloidosis. There were no differences in baseline characteristics with regard to age, gender, risk factors, hemoglobin and renal function between patients positive and negative for TTR CA. Conduction disorders were seen in 35 (40%) patients. Patients with TTR CA had a statistically higher prevalence of conduction disorders. Forty-two percent of TTR CA positive patients underwent peri-procedural permanent pacemaker implantation compared to 28% peri-procedural pacemaker implantations in the negative group (p=0.043). Development of a new left bundle branch block during the follow-up period was observed in 14.1% of all patients. There was a statistically significant higher rate in the positive group compared to TTR CA negative group (39.1% vs 10.9% p=0.03). Conclusions We observed a high prevalence of occult TTR-CA in older adults with aortic stenosis who underwent TAVI. We also found a high prevalence of conduction abnormalities following TAVI in patients with TTR CA. These findings suggest a need for more careful observation for possible conduction abnormalities and requirement for pacemaker insertion in these patients. Acknowledgement/Funding None

Background We previously demonstrated that elevated levels of antiendothelial cell antibodies are associated with improved survival of patients undergoing coronary angiography. However, renal insufficiency, which is associated with decreased survival, leads to increased level of the antiendothelial cell antibodies. The purpose of this study was to evaluate the correlation of the levels of these antibodies with survival in patients with normal versus reduced renal function. Patients and methods This was a single center prospective study. Eight hundred thirty eight consecutive patients undergoing coronary angiography with detectable antibody levels were enrolled. The levels of antiendothelial antibodies were determined by ELISA and measured in optical density units. Renal insufficiency was defined as adjusted GFR Results Of total 838 patients, 481 (57%) had normal and 357 (42.6%) had reduced renal function. Total mortality was 13.6%, being significantly higher in patients with reduced (23.2%) versus normal (6.4%) renal function (p Conclusions Renal insufficiency leads to mild decrease in the antiendothelial cell antibodies' levels. Higher levels of antiendothelial cell antibodies are associated with improved survival in patients undergoing coronary angiography. This association is significant in patients with normal but not reduced renal function. Thus, the effect of the higher levels of these antibodies on survival cannot be explained by its association with renal dysfunction.

Background Coronary artery disease (CAD) is the leading cause of diastolic dysfunction. Diastolic dysfunction is associated with adverse outcomes. Renal insufficiency is also associated with adverse outcomes in CAD patients. The interaction between diastolic dysfunction and renal insufficiency is not completely elucidated. Aims We evaluated the prognostic value of diastolic function assessed by echocardiography in patients with and without renal failure undergoing coronary angiography. Patients and methods An observational prospective study of 547 consecutive patients undergoing coronary angiography. The median follow up was 30 months. Significant diastolic dysfunction was defined as elevated LV filling pressure with e/e'>12. Renal insufficiency was defined as adjusted GFR Results Significant diastolic dysfunction and renal insufficiency had additive effect on mortality (Table 1). A significant association was observed between diastolic dysfunction and mortality in patients with and without renal insufficiency (p Table 1. Patients divided into 4 groups according to the presence of the significant diastolic dysfunction and renal insufficiency Patients' group N (%) Mortality Normal LV filling pressure / Normal renal function 230 (42.0%) 4.8% Elevated LV filling pressure / Normal renal function 58 (10.6%) 15.5% Normal LV filling pressure / Renal insufficiency 138 (25.2%) 15.9% Elevated LV filling pressure / Renal insufficiency 121 (22.1%) 38.8% P Fugure 1 Conclusions In patients undergoing coronary angiography, significant diastolic dysfunction with elevated filling pressure is associated with mortality in patients both with and without renal insufficiency. Both significant diastolic dysfunction and renal insufficiency are independent predictors of mortality.

Background Early identification of atrial fibrillation (AF) has been a long-standing clinical challenge and an unmet need. AF may be present without the patient being aware of any symptoms, leading to a delay in or failure of diagnosis. ESC guidelines recommend opportunistically screening patients >65 years of age using pulse palpation or an ECG rhythm strip, however these methods have limited effectivity. Analysis of natural speech signals has been used as a monitoring tool for various medical conditions and has recently been reported to enable estimation of heart rate. In this study we evaluated the efficacy of vocal features analysis in the detection of AF and in discriminating between sinus rhythm (SR) and episodes of AF. Methods In this prospective multicenter study, patients with persistent AF admitted for cardioversion were enrolled. A total of 86 patients in 2 centers were included. Prior to cardioversion, the patients spoke specific vowels and words according to a pre-specified protocol; an ECG tracing was simultaneously recorded. Following successful cardioversion and recovery from sedation, these recordings were repeated in SR. The recordings of the first 34 patients were used to develop an algorithm of AF detection based on analysis of acoustic features in SR and AF conditions. The algorithm was then validated in all of the patients (n=86) in the following manner: 25% of SR recordings were used to train the algorithm while the remaining 75% of SR and 100% of AF data from every patient were tested with the algorithm to distinguish between AF and SR. Results A total of 513 recordings from 86 patients were analyzed. Classification of the recordings as AF or SR was performed using varying cutoff values of the separation parameter. The resulting curve showing the specificity and sensitivity of the developed algorithm for distinguishing AF from SR is presented. Two specific examples of working points are a specificity of 92% and sensitivity of 83%, and a specificity of 82% and sensitivity of 92%. Conclusions This study demonstrates the feasibility of detecting AF and discriminating it from SR using analysis of acoustic features extracted from spoken vowels. The potential use of this method for wider population screening should be further evaluated.

Limited information exists about detailed clinical characteristics and management of the small subset of Brugada syndrome (BrS) patients who had an arrhythmic event (AE).To conduct the first nationwide survey focused on BrS patients with documented AE.Israeli electrophysiology units participated if they had treated BrS patients who had cardiac arrest (CA) (lethal/aborted; group 1) or experienced appropriate therapy for tachyarrhythmias after prophylactic implantable cardioverter defibrillator (ICD) implantation (group 2).The cohort comprised 31 patients: 25 in group 1, 6 in group 2. Group 1: 96% male, mean CA age 38 years (range 13-84). Nine patients (36%) presented with arrhythmic storm and three had a lethal outcome; 17 (68%) had spontaneous type 1 Brugada electrocardiography (ECG). An electrophysiology study (EPS) was performed on 11 patients with inducible ventricular fibrillation (VF) in 10, which was prevented by quinidine in 9/10 patients. During follow-up (143 ± 119 months) eight patients experienced appropriate shocks, none while on quinidine. Group 2: all male, age 30-53 years; 4/6 patients had familial history of sudden death age50 years. Five patients had spontaneous type 1 Brugada ECG and four were asymptomatic at ICD implantation. EPS was performed in four patients with inducible VF in three. During long-term follow-up, five patients received ≥ 1 appropriate shocks, one had ATP for sustained VT (none taking quinidine). No AE recurred in patients subsequently treated with quinidine.CA from BrS is apparently a rare occurrence on a national scale and no AE occurred in any patient treated with quinidine.

Atrial ablation has been recently utilized for curing atrial fibrillation. The success rate of empirical ablation is relatively low as often the exact locations of the arrhythmogenic sources remain elusive. Guided ablation has been proposed to improve ablation technique by providing guidance regarding the potential localization of the sources; yet to date no main technological solution has been widely adopted as an integral part of the ablation process. Here we propose a genetic algorithm optimization technique to map a major arrhythmogenic substance-non-conducting regions (NCRs). Excitation delays in a set of electrodes of known locations are measured following external tissue stimulation, and the spatial distribution of obstacles that is most likely to yield the measured delays is reconstructed. A forward problem module was solved to provide synthetic time delay measurements using a 2D human atrial model with known NCR distribution. An inverse genetic algorithm module was implemented to optimally reconstruct the locations of the now unknown obstacle distribution using the synthetic measurements. The performance of the algorithm was demonstrated for several distributions varying in NCR number and shape. The proposed algorithm was found robust to measurements with a signal-to-noise ratio of at least -20 dB, and for measuring electrodes separated by up to 3.2 mm. Our results support the feasibility of the proposed algorithm in mapping NCRs; nevertheless, further research is required prior to clinical implementation for incorporating more complex atrial tissue geometrical configurations as well as for testing the algorithm with experimental data.

Because of its safety profile, cryoablation has become an alternative therapy for septal arrhythmias, including parahisian accessory pathways (APs). Data regarding its efficacy, safety, and late outcome for parahisian APs in children are limited.The purpose of this study was to evaluate the safety and efficacy of cryoablation of parahisian APs in children.Fifty-nine cryoablations of parahisian APs were performed in 50 patients [76% males; median age 16.5 years (range 5.3-20 years)]. Thirty-three had manifest APs and 17 had concealed APs. The time to effect was defined as the duration of time from reaching -30°C to the disappearance of AP during the cryomapping phase. The acute success rate for the first ablation was 94% (47/50).Mean fluoroscopy time and number of cryoablations were 28.5 ± 23.3 minutes and 2.6 ± 1.2 seconds, respectively. The time to effect was 8.5 ± 7.1 seconds. The overall recurrence rate was 14.9%, decreasing from 40% in the first 10 cases to 8.1% in the next 37 (P.02). Multivariate analysis showed that the only independent predictor for recurrence rate was time to effect10 seconds (P.001). A high recurrence rate was also associated with concealed APs and ablation during supraventricular tachycardia (P.03 and P.05, respectively). The patients who had recurrence underwent a second successful cryoablation. During median follow-up of 59.7 months (range 6-102 months), a long-term success rate of 94% was achieved. No permanent ablation-related complications occurred.Cryoablation of parahisian APs has excellent short- and long-term efficacy and safety profile. Increased physician experience is associated with a reduced recurrence rate.

ICD Programming in Ischemic and Nonischemic Cardiomyopathy Introduction The MADIT-RIT trial demonstrated reduction of inappropriate and appropriate ICD therapies and mortality by high-rate cut-off and 60-second-delayed VT therapy ICD programming in patients with a primary prophylactic ICD indication. The aim of this analysis was to study effects of MADIT-RIT ICD programming in patients with ischemic and nonischemic cardiomyopathy. Methods and Results First and total occurrences of both inappropriate and appropriate ICD therapies were analyzed by multivariate Cox models in 791 (53%) patients with ischemic and 707 (47%) patients with nonischemic cardiomyopathy. Patients with ischemic and nonischemic cardiomyopathy had similar incidence of first inappropriate (9% and 11%, P = 0.21) and first appropriate ICD therapy (11.6% and 14.1%, P = 0.15). Patients with ischemic cardiomyopathy had higher mortality rate (6.1% vs. 3.3%, P = 0.01). MADIT-RIT high-rate cut-off (arm B) and delayed VT therapy ICD programming (arm C) compared with conventional (arm A) ICD programming were associated with a significant risk reduction of first inappropriate and appropriate ICD therapy in patients with ischemic and nonischemic cardiomyopathy (HR range 0.11–0.34, P < 0.001 for all comparisons). Occurrence of total inappropriate and appropriate ICD therapies was significantly reduced by high-rate cut-off ICD programming and delayed VT therapy ICD programming in both ischemic and nonischemic cardiomyopathy patients. Conclusion High-rate cut-off and delayed VT therapy ICD programming are associated with significant reduction in first and total inappropriate and appropriate ICD therapy in patients with ischemic and nonischemic cardiomyopathy.

Adenosine can produce arrhythmias, which are generally short living. It may induce PACs and PVCs, sinus bradycardia, and atrial fibrillation. There have been reports of transient polymorphic VT (torsades de pointes) in patients with LQTS and others in people with normal QT interval. We report a case of a long episode of polymorphic VT induced by adenosine. A 27 year old woman received 6 mg adenosine for PSVT, which terminated and torsades de pointes developed, persisting for 17 seconds and terminated spontaneously. This is the longest described duration of the torsades after adenosine administration in patients with normal QT interval.

Introduction Exercise is considered a valuable nonpharmacological intervention modality in cardiac rehabilitation (CR) programs in patients with ischemic heart disease. The effect of aerobic interval exercise combined with alternating sets of resistance training (super-circuit training, SCT) on cardiac patients' with reduced left ventricular function, post-myocardial infarction (MI) has not been thoroughly investigated. Aim of study to improve cardiac function with a novel method of combined aerobic-resistance circuit training in a randomized control trial by way of comparing the effectiveness of continuous aerobic training (CAT) to SCT on mechanical cardiac function. Secondary to compare their effect on aerobic fitness, manual strength, and quality of life in men post MI. Finally, to evaluate the safety and feasibility of SCT. Methods 29 men post-MI participants were randomly assigned to either 12-weeks of CAT (n = 15) or SCT (n = 14). Both groups, CAT and SCT exercised at 60%-70% and 75–85% of their heart rate reserve, respectively. The SCT group also engaged in intermittently combined resistance training. Primary outcome measure was echocardiography. Secondary outcome measures were aerobic fitness, strength, and quality of life (QoL). The effectiveness of the two training programs was examined via paired t-tests and Cohen's d effect size (ES). Results Post-training, only the SCT group presented significant changes in echocardiography (a reduction in E/e' and an increase in ejection fraction, P

Background Moderate exercise training has been shown to decrease sudden cardiac death post myocardial infarction. However, the effects of intensive exercise are still controversial. Methods and Results Fourteen myocardial‐infarcted rats were divided into sedentary (n=8) and intensive training groups (n=6) and 18 sham control rats to sedentary (n=10) and intensive training groups (n=8). Heart rate variability was obtained at weeks 1 and 8. The inducibility of ventricular tachycardia/fibrillation was assessed in a Langendorff system. Fast Fourier transforms were applied on the recorded ventricular tachycardia/fibrillations. Training reduces low to high frequency ratio of heart rate variability at week 8 compared with that at week 1 ( P P P P ECG findings revealed an exercise‐induced ventricular fibrillation transition from a narrow, single‐peak spectrum at 17 Hz in sedentary controls to a broader range of peaks ranging from 13 to 22 Hz in the intensive training controls. Conclusions Intensive exercise in infarcted rats leads to reduced ventricular fibrillation propensity and is associated with normalization of refractoriness and intrinsic spatiotemporal electrical variations.

Elderly patients are underrepresented in clinical trials of device therapy.To provide real-world data regarding outcomes associated with device-based therapy in a large cohort of elderly patients enrolled in the Israeli ICD Registry.Between July 2010 and June 2012, a total of 2807 consecutive patients undergoing implanted cardioverter-defibrillator/cardiac resynchronization therapy-defibrillator (ICD/CRT-D) implantation were prospectively enrolled in the Israeli ICD Registry. For the present analysis, patients were categorized into 3 age groups: ≤60 years (n = 1378 [49%]), 61-75 years (n = 863 [31%]), and75 years (n = 566 [20%]).Elderly patients (75 years of age) had more comorbid conditions and were more likely to undergo CRT-D implantation (all P.01). However, the rate of device-related complications associated with surgical reinterventions at 1 year was3% regardless of age (P = .70 for the comparison among the 3 age groups). Multivariate analysis showed that the risk of heart failure or death and of appropriate ICD therapy for ventricular arrhythmias was significantly increased with increasing age among patients who received an ICD. In contrast, the age-related increase in the risk of all end points was attenuated among patients who received CRT-D devices (all P values for age-by-device-type interactions are.05).In a real-world scenario, elderly patients (75 years of age) comprise approximately 20% of the ICD/CRT-D recipients and experience a device reintervention rate similar to that of their younger counterparts. Our data suggest that the association between advanced age and adverse clinical outcomes is attenuated in elderly patients implanted with CRT-D devices.

Aims There are limited data regarding the effect of diabetes mellitus (DM) on the risks of both appropriate and inappropriate implantable cardioverter defibrillator (ICD) therapy. The present study was designed to compare the outcome of appropriate and inappropriate ICD therapy in patients with or without DM. Methods and results The risk of a first appropriate ICD therapy for ventricular tachyarrhythmias (including anti tachycardia pacing and shock) was compared between 764 DM and 1346 non-DM patients enrolled in the national Israeli ICD registry. We also compared the risks of inappropriate ICD therapy, and death or cardiac hospitalization between diabetic and non-diabetic patients. Diabetic patients were older, were more likely to have ischemic cardiomyopathy, lower ejection fraction, atrial fibrillation, and other co-morbidities. The 3-year cumulative incidence of appropriate ICD therapy was similar in the DM and non-DM groups (12 and 13%, respectively, p = 0.983). Multivariate analysis showed that DM did not affect the risk of appropriate ICD therapy (HR = 1.07, 95% CI 0.78–1.47, p = 0.694) or inappropriate therapy (HR = 0.72, 95% CI 0.42–1.23, p = 0.232). However, DM was associated with a 31% increased risk for death or cardiac hospitalization (p = 0.005). Results were similar in subgroup analyses including ICD and defibrillators with cardiac resynchronization therapy function recipients, primary or secondary prevention indication for an ICD. Conclusions Despite a significant excess of cardiac hospitalizations and mortality in the diabetic population, there was no difference in the rate of ICD treatments, suggesting that the outcome difference is not related to arrhythmias.

Background Limited fluoroscopy cryo-ablation using a 3D electro-anatomical system (3DS) has been used for AVNRT in children. We aimed to facilitate a fluoroscopy limited approach of RF ablation of AVNRT in children. Methods A retrospective study was performed of procedure parameters in children undergoing RF ablation of AVNRT in 75 consecutive children (June 2011 to November 2013 — Group A) using standard fluoroscopy techniques compared to those of 64 consecutive children (December 2013 to May 2015 — Group B), using a fluoroscopy limited approach with 3DS. Results The acute success rate was 98.7% (74/75) and 98.4% (63/64) for groups A and B, respectively. The recurrence rate was 2.7% (2/74) and 0% (0/63) with a mean follow-up period of 45.5±12.1 and 14.3±6.1months for group A and group B, respectively. The mean procedure and fluoroscopy times were significantly lower for group B compared to group A (119±37 (43–203) and 0.83±1.04 (0.05–3.83) minutes versus 146±53 (72–250) and 16.1±8.9 (4.39–55) minutes, p p Conclusions A fluoroscopy limited approach for RF ablation of AVNRT in children using a 3DS is easily acquired and adapted, and significantly reduces the fluoroscopy and procedure time with excellent efficacy, safety and low recurrence rate. Condensed ABSTRACT This study confirmed that a 3D mapping system (3DS) to guide ablations of AVNRT in children reduces radiation exposure. Combined, limited fluoroscopy and 3DS in a methodology that resembles the familiar conventional fluoroscopy approach for RF ablation of AVNRT in children is proposed. Combined limited fluoroscopy and RF-energy in children with AVNRT are associated with a shorter procedure time, minimal fluoroscopy time, a high success rate and a low recurrence rate.

Both autonomic nerve activity and electrical remodeling are important in atrial arrhythmogenesis. Therefore, dogs with sympathetic hyperinnervation, myocardial infarction (MI), and complete atrioventricular block (CAVB) may have a high incidence of atrial arrhythmias. We studied eight dogs (experimental group) with MI, CAVB, and sympathetic hyperinnervation induced either by nerve growth factor infusion ( n = 4 dogs) or subthreshold electrical stimulation ( n = 4 dogs) of the left stellate ganglion. Cardiac rhythm was continuously monitored by a Data Sciences International transmitter for 48 (SD 27) days. Three normal control dogs were also monitored. Six additional normal dogs were used for histology control. Paroxysmal atrial fibrillation (PAF) and paroxysmal atrial tachycardia (PAT) were documented in all dogs in the experimental group, with an average of 3.8 (SD 3) episodes/day, including 1.3 (SD 1.6) episodes of PAF and 2.5 (SD 2.2) episodes of PAT. The duration averaged 298 (SD 745) s (range, 7–4,000 s). There was a circadian pattern of arrhythmia onset ( P < 0.01). Of 576 episodes of PAF and PAT, 236 (41%) episodes occurred during either sustained or nonsustained ventricular tachycardia (VT). Among these 236 episodes, 53% started before VT, whereas 47% started after the onset of VT. Normal dogs did not have either PAF or PAT. The hearts from the experimental group had a higher density of nerve structures immunopositive ( P < 0.01) for three different nerve specific markers in both right and left atria than those of the control dogs. We conclude that the induction of nerve sprouting and sympathetic hyperinnervation in dogs with CAVB and MI creates a high yield model of PAF and PAT.

Introduction: We previously demonstrated the relationship between sympathetic nerve density in myocardium and the occurrences of ventricular arrhythmia. Nerve growth factor (NGF) regulates myocardial sympathetic innervation. However, it is unclear whether the NGF high-affinity receptor tyrosine kinase A (TrkA) and the NGF low-affinity receptor p75NTR are altered in the state of sympathetic hyperinnervation in the heart. The aim of this study was to determine the density and location of TrkA and p75NTR in canine ventricles with sympathetic hyperinnervation. Methods and Results: Myocardial sympathetic hyperinnervation was induced by local infusion of NGF into myocardium or left stellate ganglia, or chronic subthreshold electric stimulation to the left stellate ganglia. The results showed that TrkA immunoreactivity was absent in the myocardium. Low-affinity receptor p75NTR immunoreactivity was present in axons, Schwann cells, and interstitial cells of sympathetic nerves, as well as in interstitial cells of the myocardium. The density of p75NTR immunolabeled myocardial interstitial cells at the NGF infusion site was lower than that at the site remote from NGF infusion, yet the sympathetic nerve density was higher at the infusion site than the remote area. The density of p75NTR also was lower in the myocardium with high sympathetic nerve density, induced by NGF infusion or chronic electric stimulation of the left stellate ganglia, compared to control groups. Conclusion: The data indicate that p75NTR may be the main NGF receptor in the myocardium, and p75NTR immunopositive interstitial cells may have a role in regulating sympathetic nerve growth in canine heart. (J Cardiovasc Electrophysiol, Vol. 15, pp. 430-437, April 2004)

ObjectivesWe sought to develop a high-yield canine model of sudden cardiac death (SCD).BackgroundBecause electrical stimulation is a powerful means to elicit nerve sprouting, we hypothesize that subthreshold electrical stimulation is more effective than nerve growth factor (NGF) infusion in inducing nerve sprouting and SCD in dogs with myocardial infarction (MI) and complete atrioventricular block (CAVB).MethodsWe gave subthreshold electrical stimulation to the left stellate ganglion (LSG) in six normal dogs for 41 ± 9 days (protocol 1) and to six dogs with MI and CAVB for 41 ± 29 days, while continuously monitoring their cardiac rhythm (protocol 2). We also monitored the rhythm of two dogs with MI, CAVB, and NGF infusion to the LSG and determined the ventricular nerve density in six healthy control dogs.ResultsIn protocol 1, the hearts from dogs with LSG electrical stimulation had a higher density of nerve fibers immunopositive to tyrosine hydroxylase, synaptophysin, and growth-associated protein-43 than those of normal control dogs (p < 0.01). In protocol 2, there was a high magnitude of cardiac nerve sprouting in all dogs studied. Ventricular tachycardia ≥8 beats and ≥20 beats was more frequent in dogs with electrical stimulation than in dogs with NGF infusion to the LSG (36 ± 60 and 11 ± 17 vs. 4.7 ± 6.1 and 0.1 ± 0.33 episodes per day, p < 0.05 and p < 0.03, respectively). Four of six dogs in protocol 2 had SCD.ConclusionsSubthreshold electrical stimulation of the LSG induces cardiac nerve sprouting and sympathetic hyperinnervation and facilitates the development of a high-yield canine model of ventricular arrhythmia and SCD.

The focal source hypothesis of ventricular fibrillation (VF) posits that rapid activation from a focal source, rather than action potential duration (APD) restitution properties, is responsible for the maintenance of VF. We injected aconitine (100 μg) into normal isolated perfused swine right ventricles (RVs) stained with 4-{β-[2-(di- n-butylamino)-6-naphthyl]vinyl}pyridinium (di-4-ANEPPS) for optical mapping studies. Within 97 ± 163 s, aconitine induced ventricular tachycardia (VT) with a mean cycle length 268 ± 37 ms, which accelerated before converting to VF. Drugs that flatten the APD restitution slope, including diacetyl monoxime (10–20 mM, n = 6), bretylium (10–20 μg/ml, n = 3), and verapamil (2–4 μg/ml, n = 3), reversibly converted VF to VT in all cases. In two RVs, VF persisted despite of the excision of the aconitine site. Simulations in two-dimensional cardiac tissue showed that once VF was initiated, it remained sustained even after the “aconitine” site was eliminated. In this model of focal source VF, the VT-to-VF transition occurred due to a wave break outside the aconitine site, and drugs that flattened the APD restitution slope converted VF to VT despite continuous activation from aconitine site.

We tested the hypothesis that sildenafil, singly or in combination with nitric oxide (NO) donors, promotes ventricular tachycardia (VT) and ventricular fibrillation (VF). Vulnerability to VT/VF was tested by rapid pacing in eight isolated normal swine right ventricles (RV). The endocardial activation was optically mapped, and the dynamic action potential duration (APD) restitution curves were constructed with metal microelectrodes. At baseline, no VT/VF could be induced. Sildenafil (0.2 μg/ml) or NO donor singly or in combination did not alter VT/VF vulnerability. However, when 2 μg/ml sildenafil was combined with NO donors, the incidence of VT and VF rose significantly ( P < 0.01). VT with a single periodic wavefront was induced in five of eight RVs, and VF with multiple wavefronts was induced in all eight RVs. The sildenafil-NO donor pro-VT/VF combination significantly increased the maximum slope of the APD restitution curve and the amplitude of the APD alternans. The pro-VT/VF effects of sildenafil were reversible after drug-free Tyrode solution perfusion. We conclude that a sildenafil (2 μg/ml) and NO donor combination increases VT/VF vulnerability in the normal RV by a mechanism compatible with the restitution hypothesis.

Objective Hemodynamic forces are potential determinants of aortic atherosclerosis. Aortic regurgitation (AR) alters the flow pattern in the aorta. However, the association between AR and aortic atherosclerosis is not well known. Methods We assessed the presence, extent and distribution of atherosclerotic lesions in the aorta of 42 patients with chronic AR and compared them to 40 patients with similar risk factor profile for atherosclerosis and no valvular disease. Results There was no difference in the extent of atheroma in the ascending aorta and aortic arch between patients with and without AR. Descending aortic atheroma was evident in 25 patients with AR (60%) and 12 patients without AR (30%, p =0.01). AR was found to be the only predicting factor for the presence of aortic atherosclerosis in the descending aorta (odds ratio 4.1; 95% CI 1.2–14.3, p =0.03). Conclusions There is an increased prevalence of descending aortic atherosclerosis in patients with significant AR.

The MADIT-RIT trial demonstrated reduction of inappropriate and appropriate ICD therapies and mortality by high-rate cut-off and 60-second-delayed VT therapy ICD programming in patients with a primary prophylactic ICD indication. The aim of this analysis was to study effects of MADIT-RIT ICD programming in patients with ischemic and nonischemic cardiomyopathy.First and total occurrences of both inappropriate and appropriate ICD therapies were analyzed by multivariate Cox models in 791 (53%) patients with ischemic and 707 (47%) patients with nonischemic cardiomyopathy. Patients with ischemic and nonischemic cardiomyopathy had similar incidence of first inappropriate (9% and 11%, P = 0.21) and first appropriate ICD therapy (11.6% and 14.1%, P = 0.15). Patients with ischemic cardiomyopathy had higher mortality rate (6.1% vs. 3.3%, P = 0.01). MADIT-RIT high-rate cut-off (arm B) and delayed VT therapy ICD programming (arm C) compared with conventional (arm A) ICD programming were associated with a significant risk reduction of first inappropriate and appropriate ICD therapy in patients with ischemic and nonischemic cardiomyopathy (HR range 0.11-0.34, P0.001 for all comparisons). Occurrence of total inappropriate and appropriate ICD therapies was significantly reduced by high-rate cut-off ICD programming and delayed VT therapy ICD programming in both ischemic and nonischemic cardiomyopathy patients.High-rate cut-off and delayed VT therapy ICD programming are associated with significant reduction in first and total inappropriate and appropriate ICD therapy in patients with ischemic and nonischemic cardiomyopathy.

It has previously been shown that immunization with pathogenic anti-DNA idiotypes (Ids; e.g. 16/6 Id) leads to the induction of experimental system lupus erythematosus (SLF) in naive mice. The disease is characterized by serological (e.g. anti-double-strand DNA), clinical (elevation of erythrocyte sedimentation rate, leukopenia and proteinuria) and histological (immune complex deposition in kidneys) parameters. To determine whether the 16/6 Id carrying anti-DNA antibodies has unique pathogenic ability, in the current study we have employed diverse sources of anti-DNA antibodies to induce experimental SLE. An IgM anti-DNA antibody lacking the 16/6 Id was able to induce the production of the serological markers of experimental SLE, but not the clinico-histological findings. Furthermore, an IgA anti-DNA (16/6 Id derived from the serum of a patient with celiac disease was very effective in inducing the whole presentation of experimental SLE. Other anti-DNA antibodies failed to induce the autoimmune condition. Combined with our previous experience, the current study points to the diverse potential of various anti-DNA antibodies to induce SLE. The 16/6 Id is only one of a list of the potent pathogenic anti-DNA Ids. These facts may explain in part the diversity of clinical presentations of SLE, including asymptomatic subjects who carry high serum titers of anti-DNA antibodies.

The aim of this study was to compare the diagnostic value and safety of sublingual isosorbid dinitrate (ISDN) with intravenous isoproterenol (ISOP) during head-up tilt table testing (HUTT) in pediatric patients with suspected neurocardiogenic syncope.One hundred thirty-six consecutive pediatric patients complaining of presyncope or syncope were submitted to HUTT for the first time. Those who did not develop syncope or presyncope during passive HUTT for 20 minutes underwent repeated HUTT with either 1.25 to 2.5 mg sublingual ISDN or intravenous ISOP (1-3 mug/min) for 20 minutes. There were 54 boys and 82 girls, aged 10 to 18 years with an average of 15.5 +/- 2.4 years and a median of 16 years. Among the patients with cardioinhibition or mixed responses, the severity of the bradyarrhythmia was scored 1 to 3 (restoration of effective rhythm within 10 seconds, 10-20 seconds, and20 seconds while back to supine position, respectively).During the passive period, 24 (17.6%) of 136 patients had a positive response to HUTT. Syncope was observed in another 44 patients during either ISDN or ISOP period (14/58 [24.1%] and 30/54 [55.5%] with ISDN vs ISOP, respectively, P.05). The time to symptoms was shorter with both ISDN and ISOP compared with passive period (6.5 +/- 2.9, 6.3 +/- 5.9, and 10.3 +/- 4.4, minutes, respectively, P.05). The severity score for cardioinhibition response was significantly higher with ISDN compared with the passive period and ISOP (2 +/- 0.8, 1.25 +/- 0.45, and 1.26 +/- 0.45, respectively, P.01).Sublingual ISDN is less sensitive and less safe compared to intravenous ISOP in assessing pediatric age patients with suspected neurocardiogenic syncope and with a negative result in tilt test without provocation. The simplicity of ISDN use should be weighed against the risk of longer symptoms with ISDN.

A tilt table test (TTT) is an inexpensive, noninvasive tool for the differential diagnosis of syncope and orthostatic intolerance and has good diagnostic yield. The autonomic system malfunction which underlines the reflex syncope is manifested as either hypotension or bradycardia, while an orthostatic challenge is applied. The timing of the response to the orthostatic challenge, as well as the predominant component of the response help to differentiate between various forms of neurocardiogenic syncope, orthostatic hypotension and non-cardiovascular conditions (e.g., pseudosyncope). Medications, such as isoproterenol and nitrates, may increase TTT sensitivity. Sublingual nitrates are easiest to administer without the need of venous access. TTT can be combined with carotid sinus massage to evaluate carotid sinus hypersensitivity, which may not be present in supine position. TTT is not useful to access the response to treatment. Recently, implantable loop recorders (ILR) have been used to document cardioinhibitory reflex syncope, because pacemakers are beneficial in many of these patients, especially those over 45 years of age. The stepwise use of both TTT and ILR is a promising approach in these patients. Recently, TTT has been used for indications other than syncope, such as assessment of autonomic function in Parkinson’s disease and its differentiation from multiple system atrophy.

Subthreshold electrical stimulation of the left stellate ganglion (LSG) can induce nerve sprouting and sympathetic hyperinnervation in canine ventricles. It is unclear whether a similar neural plasticity involving both sympathetic and parasympathetic innervation also exists in the atria.We applied subthreshold electrical stimulation at 20 Hz (0.45 ms pulse width) or 5 Hz (1.9 ms pulse width) to the LSG in 6 normal mongrel dogs. After 41+/-9 days, the hearts were harvested and the right and left atrium stained for synaptophysin (SYN), growth-associated protein 43 (GAP43), sympathetic nerve markers tyrosine hydroxylase (TH), and parasympathetic marker choline acetyltransferase (ChAT). Tissues from 6 additional healthy dogs were used as controls. The hearts from dogs with LSG electrical stimulation had a higher density of nerve structures immunopositive to the SYN, GAP43, TH, and ChAT (P.01) in both right and left atria. Nerve density was equal in right and left atria. There were more TH-positive nerve structures than ChAT-positive nerve structures (P.01) for both right and left atria. No atrial arrhythmia was observed at the second surgery.Continuous subthreshold electrical stimulation to the LSG induces both sympathetic and parasympathetic hyperinnervation in both right and left atria in normal dogs.