Fasciculoventricular and atrioventricular accessory pathways in patients with Danon disease and preexcitation: A multicenter experience.

BACKGROUND: Studies have suggested that a fasciculoventricular pathway (FVP) may be the cause of preexcitation in patients with Danon disease, a rare X-linked dominant genetic disorder of hypertrophic cardiomyopathy. OBJECTIVE: The purpose of this study was to describe the prevalence of ventricular preexcitation on resting 12-lead electrocardiogram (ECG) in patients with Danon disease and the electrophysiological study (EPS) results of those with preexcitation. METHODS: Patients with confirmed Danon disease diagnosed with preexcitation (PR ≤120 ms, delta wave, QRS >110 ms) on ECG were included from a multicenter registry. The incidence of arrhythmias, implantable cardioverter-defibrillator (ICD) procedures, ICD shocks, and EPS results were collected. RESULTS: Thirteen of 40 patients (32.5%) with Danon disease were found to have preexcitation (mean age 17.3 years; 38% women). EPS performed in 9 of 13 patients (69%) demonstrated FVP only in 2 (22.2%), extranodal pathway without exclusion of FVP in 2 (22.2%), and both FVP and extranodal pathway in 5 (55.6%). Two patients had malignant accessory pathway (AP) properties. Over median follow-up of 842 days (interquartile range 138-1678), 11 patients (85%) had ICD placement, and 6 (46.1%) underwent heart transplantation. No patients required therapy for ventricular tachycardia, and 2 patients (15%) had paroxysmal atrial fibrillation. CONCLUSION: In a large multicenter cohort of patients with Danon disease, there was a high prevalence of FVP and extranodal pathways diagnosed on EPS in those with preexcitation. These findings suggest patients with preexcitation and Danon disease should undergo EPS to assess for FVP and potentially malignant extranodal AP.

Long-Term Follow-Up After Radiofrequency Catheter Ablation of Accessory Atrioventricular Pathways in Children.

OBJECTIVES: The purpose of this study was to evaluate long-term safety and efficacy of catheter ablation of accessory atrioventricular pathways (AP) in a pediatric cohort. BACKGROUND: Radiofrequency catheter ablation of accessory AP is the recommended treatment for patients with atrioventricular re-entrant tachycardia. Data on long-term results ≥1 year after AP ablation in pediatric patients is sparse. METHODS: A total of 296 patients <18 years of age who had undergone radiofrequency-AP ablation between October 2002 and June 2015 were included into the study. Follow-up was >1 year in all patients. Median age at ablation had been 11.6 years, and median follow-up was 5.6 years. Recurrence of AP conduction after ablation was defined as documentation of pre-excitation, supraventricular tachycardia attributable to AP, or proof of AP conduction during repeat electrophysiological study. RESULTS: AP ablation succeeded in 268 of 296 individuals (91%). After successful ablation, recurrence of AP conduction was observed in 29 of 268 individuals (10.8%). Of those 29, 23 (79%) had AP recurrence within the first year after ablation, whereas 13 (45%) had recurrence of AP conduction already within the first month. Six patients had late recurrence of AP conduction >1 year post-ablation. Procedural success and freedom from AP conduction after a single ablation procedure was 86% at 1 month, 83% at 1 year, and 81% at 5 years after ablation. CONCLUSIONS: After radiofrequency ablation of AP in children, recurrence of AP conduction occurred in 23 subjects (8% of the study cohort) within the first year after ablation. Late recurrences >1 year after ablation were noticed in 6 children (2% of the study group), highlighting the need for longer follow-up >1 year. Results of the present study on late AP recurrence should be taken into account whenever families are counselled for pediatric AP ablation.

Correlation of accessory pathway location with gender and their manifest or concealed presentation.

BACKGROUND: Atrioventricular reentrant tachycardias account for approximately one third of cases referred for electrophysiological study (EPS). The anatomical substrate responsible for the reentry is an accessory pathway (AP) able to conduct the electrical stimulus in an anterograde, retrograde or bidirectional manner. OBJECTIVE: To evaluate the correlation of AP location with the male and female genders and AP clinical presentation, whether manifest or concealed. METHODS: Retrospective observational study including 942 consecutive patients, all diagnosed with EPS-confirmed AP from January 1994 to December 2008. APs were classified into eight anatomical groups: left lateral (LL), left posterior (LP), left posteroseptal (LPS), right posteroseptal (RPS), right midseptal (RMS), right anteroseptal (RAS), right lateral (RL), and right posterior (RP). RESULTS: Of the 942 patients, 52.6% were males. The mean age was 31.2±13.8years. As regards gender, APs were more prevalent among men. However, a statistically significant difference was observed only in the LPS (p=0.029) and RL (p=0.003) regions. In relation to the form of presentation of AP, the manifest form was more frequent than the concealed form in six of the eight regions studied, except for the LL and LPS regions. CONCLUSION: AP predominated in males and the manifest form was more frequent than the concealed form in most of the regions studied.

Cryoablation with an 8-mm-Tip Catheter for Right-Sided Accessory Pathways in Children.

BACKGROUND: Cryoablation is increasingly utilized in children because of its safety profile. Recently, larger catheter tips have been more widely used to improve long-term success rates. The aim of this study was to assess the safety and efficacy of 8-mm-tip catheters for cryoablation of right-sided accessory pathways (APs) in children. METHODS: Electrophysiological procedures were performed using the EnSite™ system (St. Jude Medical Inc., St. Paul, MN, USA). RESULTS: Between July 2010 and July 2014, 54 patients (mean age: 13.1 ± 3.7 years) underwent cryoablation using an 8-mm-tip catheter. In 18 of 54 (33%) patients where an 8-mm-tip catheter was the first-choice catheter, the success rate was 18 of 18 (100%). There was a history of previous failed attempts or recurrence with radiofrequency ablation and/or 6-mm-tip cryoablation in 36 of 54 (67%) patients. The success rate in these patients was 24 of 36 (67%). No fluoroscopy was used in 34 of 54 procedures. The recurrence rate was six of 42 (14%) during a mean follow-up period of 32 ± 15 months. In one patient, transient atrioventricular block occurred. CONCLUSIONS: Cryoablation with an 8-mm-tip catheter for right-sided APs in children who weigh over 40 kg appears to be safe and acutely effective in cases where conventional ablation methods fail and also as a first choice for ablation procedure. However, the recurrence rate still seems to be high.

Long-term results of paediatric radiofrequency catheter ablation: a population-based study.

AIMS: We aimed to evaluate long-term utilization and results of paediatric radiofrequency catheter ablation (RFCA) in a population-based study. METHODS AND RESULTS: Data from all three centres performing paediatric RFCA for the whole population of the Czech Republic between 1993 and 2010 were retrospectively reviewed. A total of 708 ablation procedures in 633 consecutive patients <18 years for 716 different substrates were tracked, with accessory pathways = 439 (61.3%) and atrioventricular nodal reentry tachycardia (AVNRT) = 205 (28.6%) being most frequent. Incidence of RFCA reached 0.049 per 1000 children <18 years of age in the recent era (2006-10). Indications included patient preference (68.0%), drug refractoriness (15.5%), asymptomatic Wolff-Parkinson-White pre-excitation (8.4%), and malignant arrhythmia (6.1%). Median follow-up was 13.7 (interquartile range 5.7-21.5) months. Overall acute/long-term success of the primary procedure was 89.1/77.2% (accessory pathways 87.2/77.7%, AVNRT 98.5/84.4%). Re-ablation was performed in 73 of 163 substrates after a primary unsuccessful ablation resulting in a long-term cumulative efficacy of 96.3%. Between 1993-2005 and 2006-10, procedure/fluoroscopy time decreased from median 154/24 to 105/14 min. (P < 0.001 for both). Serious complications occurred in nine patients (1.4%). CONCLUSION: This population-based study could replicate data from previous single- or multi-centre reports confirming RFCA as a safe method of arrhythmia treatment in children with long-term cumulative efficacy exceeding 90% and significant decrease in the procedure and fluoroscopy time during the study period. The need for RFCA can be estimated at ∼0.05/1000 children <18 years using current indication criteria.

Ventricular fibrillation risk factors in over one thousand patients with accessory pathways.

BACKGROUND: Published data concerning risk factors of VF in WPW patients are inconsistent or contradictory. METHODS AND RESULTS: We included 1007 patient (pts) (mean age 35 years; 45% female) with an accessory pathway (AP) referred for non pharmacological treatment. Group 1 consisted of 56 pts (42M, aged 34 ± 15 yrs) with an AP and documented VF and Group 2-951 pts (513M, aged 35 ± 15 yrs) with an AP and without VF. Univariate predictors of VF were: overt pre-excitation, male gender, multiple AP, large AP. Multivariate predictors were: overt pre-excitation, male gender and MAP. The mean shortest pre-excited RR interval during AF was significantly shorter in Group 1: 205 ± 27 vs. 243 ± 64, P=0.019. VF as an end point of the first arrhythmia episode (AVRT or AF) was observed in 20 pts (15M, 5F). Primary VF (no documented arrhythmia prior to aborted SCD) occurred in 16 pts (13M, 3F). The mean age of primary VF pts was significantly lower than of pts with history of AVRT or AVRT and/or AF (24.5 vs. 36.5 vs. 38 yrs., P<0.005 and P=0.002, respectively). Age at VF occurrence shows a bi-modal distribution with peak occurrences in the 2-nd/3-rd and 5-th decades. CONCLUSION: In patients with an accessory pathway, overt pre-excitation, male gender and multiple AP constitute independent risk factors of VF episodes. Young patients in the 2-nd/3-rd and older patients in the 5-th decade might be at higher risk of VF occurrence.

Multiple accessory pathways in the young: the impact of structural heart disease.

BACKGROUND: The presence of multiple accessory pathways (MultAP) is described in structural heart disease (SHD) such as Ebstein's anomaly and cardiomyopathies. Structural defects can impact the tolerability of tachyarrhythmia and can complicate both medical management and ablation. In a large cohort of pediatric patients with and without SHD undergoing invasive electrophysiology study, we examined the prevalence of MultAP and the effect of both MultAP and SHD on ablation outcomes. METHODS: Accessory pathway number and location, presence of SHD, ablation success, and recurrence were analyzed in consecutive patients from our center over a 16-year period. RESULTS: In 1088 patients, 1228 pathways (36% retrograde only) were mapped to the right side (TV) in 18%, septum (S) in 39%, and left side (MV) in 43%. MultAP were present in 111 pts (10%), involving 250 distinct pathways. SHD tripled the risk of MultAP (26% SHD vs 8% no SHD, P < .001). Multivariable adjusted risk factors for MultAP included Ebstein's (OR 8.7[4.4-17.5], P < .001) and cardiomyopathy (OR 13.3[5.1-34.5], P < .001). Of 1306 ablation attempts, 94% were acutely successful with an 8% recurrence rate. Ablation success was affected by SHD (85% vs 95% for no SHD, P < .01) but not by MultAP (91% vs 94% for single, P = .24). Recurrence rate was higher for SHD (17% SHD vs 8% no SHD, P < .05) and MultAP (19% MultAP vs 8% single, P < .001). CONCLUSIONS: MultAP are found in 10% of pediatric patients, and are more common in SHD compared to those with normal hearts. Both the presence of MultAP and SHD negatively influence ablation outcomes.

Unusually high association of hypertrophic cardiomyopathy and complex heart defects in children with fasciculoventricular pathways.

INTRODUCTION: Fasciculoventricular pathways (FVPs) are rare causes of preexcitation that do not mediate tachycardias. We report a two-center experience of pediatric patients with FVP and an unexpectedly high association of complex congenital heart defects (CHDs), chromosomal anomalies, and hypertrophic cardiomyopathy. METHODS: A retrospective review of the electrophysiology database at two institutions was performed to identify patients with FVP from January 2000 to January 2011. Medical records of these patients were reviewed for clinical history and course, presence of comorbidities, and details of intracardiac electrophysiology (EP) study. RESULTS: A total of 17 patients were identified. The primary indication for EP study was a preexcitation pattern on electrocardiogram. The majority of patients, 12/17 (71%), were found to have associated cardiac and genetic anomalies. Hypertrophic cardiomyopathy was found in 5/17 (29%) patients, with genetic testing in two patients demonstrating the lysosomal-associated membrane protein 2 mutation (Danon syndrome). Underlying complex CHDs were present in 3/17 (18%) patients. One patient (6%) was status post (s/p) cardiac transplant, one patient had hypertension, and another had Trisomy 21. Other electrophysiologic substrates mediating tachycardia were found in 3/17 (18%) patients. Only 5/17 patients (29%) were otherwise healthy with structurally normal hearts. CONCLUSIONS: In this largest reported series of FVP in children, there is an unusually high association of FVP with complex CHDs, chromosomal anomalies, and hypertrophic cardiomyopathy. Any patient with such disorders and manifest preexcitation should be evaluated with a high index of suspicion for a FVP.

Aberrant pathway in an anomaly: pre-excitation syndrome in association with coronary sinus aneurysm.

Congenital coronary sinus anomalies are unusual and they rarely coexist with accessory atrio-ventricular pathways. These anomalies are generally symptomatic; however they can cause difficulty in mapping. The association between accessory pathway and coronary sinus anomalies may suggest an embryological link. Here, we report on a male patient with an accessory conducting pathway in the coronary sinus, leading to Wolff-Parkinson-White (WPW) syndrome.

Clinical, electrocardiographic, and electrophysiologic characteristics of patients with a fasciculoventricular pathway: the role of PRKAG2 mutation.

BACKGROUND: The ECG, clinical, and electrophysiologic profiles of patients with a fasciculoventricular pathway are well described. Fasciculoventricular pathways occurring in the setting of glycogen storage cardiomyopathy possess unique features. OBJECTIVE: The purpose of this study was to compare the clinical, ECG, and electrophysiologic characteristics of patients with a fasciculoventricular pathway, with or without glycogen storage cardiomyopathy. METHODS: Two groups of patients with a fasciculoventricular pathway were compared: group A consisted of 10 patients with the PRKAG2 mutation (Arg302gln), and group B consisted of 9 patients without the mutation. RESULTS: Thirty percent of group A patients had left ventricular hypertrophy, and none had an additional accessory pathway. Group B patients had no structural heart disease, and 33% had an additional accessory pathway. Group A patients had a slower resting heart rate (56 ± 7 vs 75 ± 10 bpm, P <0.0001), a wider QRS complex (0.15 ± 0.01 vs 0.11 ± 0.02 ms, P = .0004), and a longer HV interval (34 ± 1 vs 25 ± 3 ms, P = .0003). During long-term follow-up, 50% of group A patients developed complete AV block versus none in group B. Eighty percent of group A patients developed atrial flutter and/or atrial fibrillation. No Group B patient had any arrhythmia during follow-up after successful ablation of additional arrhythmia circuits. No sustained ventricular arrhythmia was induced in any patient from either group. CONCLUSION: Patients with a fasciculoventricular pathway associated with the PRKAG2 mutation have distinct clinical, ECG, and electrophysiologic profiles and should be correctly identified because of their ominous long-term prognosis. Patients without the mutation have an excellent arrhythmia-free prognosis after treatment of additional circuits.

Gender differences of electrophysiologic characteristics in patients with accessory atrioventricular pathways.

BACKGROUND: Few epidemiologic data on the gender differences among patients with accessory atrioventricular pathways have been reported. OBJECTIVE: The purpose of this study was to investigate the explicit gender differences in electrophysiologic characteristics among patients with accessory atrioventricular pathways. METHODS: A total of 1,821 consecutive patients with accessory atrioventricular pathways were referred to our institution for electrophysiologic study and radiofrequency catheter ablation. A detailed electrophysiologic study was performed in all patients. RESULTS: Patient age at onset of atrioventricular reentrant tachycardia was 43 ± 17 years. There were 1,117 males (61.3%) with accessory atrioventricular pathways. Men had more manifest and left-sided but fewer multiple accessory pathways. Men had more antidromic atrioventricular reentrant tachycardia. Men had a shorter anterograde accessory pathway effective refractory period (ERP) and a higher prevalence of an anterograde accessory pathway ERP (<250 ms). Men with accessory atrioventricular pathways had a longer atrioventricular nodal ERP and atrial ERP and a shorter ventricular ERP. CONCLUSION: Gender differences in the clinical and electrophysiologic characteristics of patients with accessory atrioventricular pathways could be closely linked and may imply a different pathogenesis.

Differences in accessory pathway location by sex and race.

BACKGROUND: The etiology of accessory pathway (AP) formation is generally unknown. OBJECTIVE: The purpose of this study was to test the hypothesis that AP formation is genetically mediated by examining whether AP location differs by sex and/or race, using sex and race as proxies to distinguish genetically different individuals. METHODS: This was a single-center, retrospective cohort study of 282 consecutive patients undergoing their first electrophysiology study that revealed at least one AP between 2004 and 2008. Sex and race were compared with AP location determined by invasive electrophysiology study. RESULTS: Eighty-nine (52%) males and 40 (36%) females had a left posterior AP (P = .006). Sixty-four (57%) females had a right annular AP, compared with 55 (32%) males (P <.001). After adjusting for age and race, females had 2.8-fold greater odds of having a right annular AP compared with males (95% confidence interval [CI] 1.70-4.65 greater odds; P <.001). While right anterior (free-wall) pathways were rare in all other races (12%), a significantly larger proportion of Asians (n = 10, 26%) had a right anterior AP (P = .017). After adjusting for sex and age, Asians had 3.8-fold greater odds of having a right anterior AP compared with other races (95% CI 1.5-9.4 greater odds; P = .004). CONCLUSIONS: Females more commonly had right annular APs, and Asians had right anterior APs substantially more frequently than other races. These findings suggest that the pathogenesis of AP formation may have a genetic component.