Bertrand Petit

Long-term follow-up of idiopathic ventricular fibrillation ablation: a multicenter study.

OBJECTIVES This multicenter study sought to evaluate the long-term follow-up of patients ablated for idiopathic ventricular fibrillation (VF). BACKGROUND Catheter ablation of idiopathic VF that targets ventricular premature beat (VPB) triggers has been shown to prevent VF recurrences on short-term follow-up. METHODS From January 2000, 38 consecutive patients from 6 different centers underwent ablation of primary idiopathic VF initiated by short coupled VPB. All patients had experienced at least 1 documented VF, with 87% having experienced > or =2 VF episodes in the preceding year. Catheter ablation was guided by activation mapping of VPBs or pace mapping during sinus rhythm. RESULTS There were 38 patients (21 men) age 42 +/- 13 years, refractory to a median of 2 antiarrhythmic drugs. Triggering VPBs originated from the right (n = 16), the left (n = 14), or both (n = 3) Purkinje systems and from the myocardium (n = 5). During a median post-procedural follow-up of 63 months, 7 (18%) of 38 patients experienced VF recurrence at a median of 4 months. Five of these 7 patients underwent repeat ablation without VF recurrence. Survival free of VF was predicted only by transient bundle-branch block in the originating ventricle during the electrophysiological study (p < 0.0001). The number of significant events (confirmed VF or aborted sudden death) was reduced from 4 (interquartile range 3 to 9) before to 0 (interquartile range 0 to 4) after ablation (p = 0.01). CONCLUSIONS Ablation for idiopathic VF that targets short coupled VPB triggers is associated with a long-term freedom from VF recurrence.

Impact of clinical and genetic findings on the management of young patients with Brugada syndrome

BACKGROUND Brugada syndrome (BrS) is an arrhythmogenic disease associated with sudden cardiac death (SCD) that seldom manifests or is recognized in childhood. OBJECTIVES The objectives of this study were to describe the clinical presentation of pediatric BrS to identify prognostic factors for risk stratification and to propose a data-based approach management. METHODS We studied 106 patients younger than 19 years at diagnosis of BrS enrolled from 16 European hospitals. RESULTS At diagnosis, BrS was spontaneous (n = 36, 34%) or drug-induced (n = 70, 66%). The mean age was 11.1 ± 5.7 years, and most patients were asymptomatic (family screening, (n = 67, 63%; incidental, n = 13, 12%), while 15 (14%) experienced syncope, 6(6%) aborted SCD or symptomatic ventricular tachycardia, and 5 (5%) other symptoms. During follow-up (median 54 months), 10 (9%) patients had life-threatening arrhythmias (LTA), including 3 (3%) deaths. Six (6%) experienced syncope and 4 (4%) supraventricular tachycardia. Fever triggered 27% of LTA events. An implantable cardioverter-defibrillator was implanted in 22 (21%), with major adverse events in 41%. Of the 11 (10%) patients treated with hydroquinidine, 8 remained asymptomatic. Genetic testing was performed in 75 (71%) patients, and SCN5A rare variants were identified in 58 (55%); 15 of 32 tested probands (47%) were genotype positive. Nine of 10 patients with LTA underwent genetic testing, and all were genotype positive, whereas the 17 SCN5A-negative patients remained asymptomatic. Spontaneous Brugada type 1 electrocardiographic (ECG) pattern (P = .005) and symptoms at diagnosis (P = .001) were predictors of LTA. Time to the first LTA event was shorter in patients with both symptoms at diagnosis and spontaneous Brugada type 1 ECG pattern (P = .006). CONCLUSION Spontaneous Brugada type 1 ECG pattern and symptoms at diagnosis are predictors of LTA events in the young affected by BrS. The management of BrS should become age-specific, and prevention of SCD may involve genetic testing and aggressive use of antipyretics and quinidine, with risk-specific consideration for the implantable cardioverter-defibrillator.

Sodium-channel blocker challenge in the familial screening of Brugada syndrome: Safety and predictors of positivity

BACKGROUND Sodium-channel blocker challenge (SCBC) is frequently performed to unmask Brugada syndrome. OBJECTIVE We aim to identify predictors of positivity and complications of SCBC in the setting of familial screening of Brugada syndrome. METHODS All consecutive patients from 2000 to 2014 who benefit from a sodium-channel blocker and belong to a family with at least 2 subjects affected by the syndrome were enrolled and followed prospectively. Data were reviewed by 2 physicians blinded to the clinical and genetic status. RESULTS Of the 672 SCBCs performed in 137 families, 337 (50%) were positive. Multivariate analysis identified ajmaline (odds ratio [OR] 2.98; 95% CI 1.65-4.91) and a significant S wave in lead DII (OR 3.11; 95% CI 2.12-4.58), DIII (OR 2.75; 95% CI 1.78-4.25), or V5 (OR 3.71; 95% CI 2.54-5.44) as predictors of a positive SCBC (P < .0001). Eleven patients (1.6%) presented complications (10 ventricular arrhythmias and 1 atrial flutter), but no deaths occurred. Familial history of complications (OR 41; lower quartile, upper quartile 10, 203; P < .0001), young age (P = .04), and decreased electrocardiographic conduction parameters at baseline (P = .04) were predictors of complications. QRS enlargement during SCBC was not associated with complications. During a median follow-up of 106 months (lower quartile, upper quartile 54, 143 months), 11 life-threatening arrhythmias occurred. CONCLUSION SCBC in the screening of familial Brugada syndrome is safe. The risk of complication is considerably increased in the case of familial history of complicated SCBC, in young patients, and in the presence of decreased electrocardiographic conduction parameters. However, QRS enlargement during the test is not directly related to complications and should not be used to prematurely stop the test unless leading to false-negative results.

0186 : Genotype/phenotype relationship in a large cohort of long QT syndrome patients

Introduction Congenital long QT syndrome (LQTS) is a hereditary disease characterized by prolonged QTc and a risk of cardiac arrest. The aim of this study is to report the experience of the referral center of Nantes hospital. Methods Patients were recruited from 19 tertiary centers in France between 1997 and 2014. Clinical data and 12-lead ECG were collected. The results of genetic screening were analyzed according to the symptoms and the length of QTc interval. Genetic screening was performed using dHPLC-DNA sequencing, HRM or NGS for at least KCNQ1 , KCNH2 and SCN5A . Results The population consisted in 456 probands affected by LQTS according to the Schwartz score (298 females, sex-ratio=1.9), mean age at diagnosis of 34±20 years. 214 patients (47%) were symptomatic: 54 patients (12%) experienced resuscitated SCD, 191 (42%) syncopes and 47 (10%) ventricular arrhythmias. Moreover, 73 patients (16%) had a history of familial SCD. An ICD was implanted in 62 of 456 patients (14%). Heart rate was 67±18 bpm, PR 151±51mm, QRS 87±17mm and QTc 486±55mm. Genetic screening was positive for 263 patients (58%): 122 mutations (27%) in KCNQ1 , 103 mutations (23%) in KCNH2 , 29 mutations (6%) in SCN5A and 10 mutations in minor genes of LQTS ( KCNE1, KCNE2, KCNJ2 and CACNA1C) . QTc duration was similar in asymptomatic patients with (483+/-45ms) or without mutation (QTc 476+/-49ms), NS. QTc duration was longer in symptomatic patients with (514+/-68ms) than without (470+/-47ms) mutations. Conclusion We identified a mutation in 58% of patients suspected for LQTS. The frequency of mutations are similar in all the different groups except for the symptomatic with QTc Table QTc QTc>480ms Number of patients Number of mutations % of mutated patients Number of patients Number of mutations % of mutated patients Asymptomatic 143 86 60% 99 69 70% Symptomatic 109 39 36% 105 69 66%

CO 2 The impact of clinical and genetic findings on the management of young Brugada syndrome patients

Aims - Brugada Syndrome (BrS) is an arrhythmogenic disease associated with sudden cardiac death (SCD) which seldom manifests and is recognized in childhood. We aim to describe the pediatric BrS clinical presentation to identify prognostic factors for risk stratification, and to propose a data-based approach management. Methods and results - We studied 106 patients, under 19 years of age at diagnosis with spontaneous (n=36) or drug-induced (n=70) BrS from 16 European hospitals. At diagnosis, mean age was 11.1±5.7 years and most patients were asymptomatic [family screening (n=67), incidental (n=13)] while 15 had experienced syncope, 6 aborted SCD or symptomatic ventricular tachycardia, 2 supraventricular tachycardia (SVT), 3 palpitations or presyncope. During follow-up (median: 54 months), 10 patients had life-threatening arrhythmias (LTA) including 3 deaths. Six experienced syncope and 4 SVT. Fever triggered 27% of LTA events. An ICD was implanted in 22 with major adverse events in 41%. Of the 11 patients treated with hydroquinidine, 8 remained asymptomatic. Genetic testing was performed in 75 patients and SCN5A rare variants were identified in 58; among the 32 pediatric probands tested 15 were genotype positive. Of the 10 patients with LTA the 9 with genetic testing were all genotype positive whereas the 17 SCN5A negative patients remained asymptomatic. Spontaneous BrS type 1 ECG (p=0.005) and symptoms at diagnosis (p=0.0015) were predictors of lta. Time to the first LTA event was shorter in patients with both symptoms at diagnosis and spontaneous BrS type 1 ECG pattern (p=0.01) (figure 1). Conclusions - Spontaneous type 1 ECG and symptoms at diagnosis are predictors of LTA events in the young affected by BrS. The management of BrS should become age-specific and prevention of SCD may involve genetic testing, aggressive use of anti-pyretics and quinidine with risk-specific consideration for the ICD

327 Clinical outcome and therapeutic strategies in non proband children with genetically confirmed LQTS

Results: AV block was asymptomatic in 119 (84.4%) and complete in 100 (70.9%) patients. Incomplete AV block progressed to complete in 29 (70.7%) patients with incomplete block over 2.8±3.4 years (1-155 months). Narrow QRS complex was present in 18 of 26 patients (69.2%) with congenital, and 106 of 115 (92.2%) with childhood AV block. Pacemakers were implanted in 112 children (79.4%), during the first year of life in 18 (16.1%) and before 10 years of age in 90 (80.4%). The mean delay between diagnosis of AVB and pacemaker implants was 2.6±3.9 years (0-300 months). The pacing indication was prophylactic in 70 children (62.5%). During a median follow-up of 11.6±6.7 years (1-32 years), no patient died or developed dilated cardiomyopathy. The long-term follow-up was uncomplicated in 127 children (90.1%).