Type 3 long QT syndrome: Is the effectiveness of treatment with beta-blockers population-specific?

BACKGROUND: The efficacy of beta-blocker treatment in type 3 long QT syndrome (LQT3) remains debated. OBJECTIVES: The purpose of this study was to test the hypothesis that beta-blocker use is associated with cardiac events (CEs) in a French cohort of LQT3 patients. METHODS: All patients with a likely pathogenic/pathogenic variant in the SCN5A gene (linked to LQT3) were included and followed-up. Documented ventricular tachycardia/ventricular fibrillation, torsades de pointes, aborted cardiac arrest, sudden death, and appropriate shocks were considered as severe cardiac events (SCEs). CEs also included syncope. RESULTS: We included 147 patients from 54 families carrying 23 variants. Six of the patients developed symptoms before the age of 1 year and were analyzed separately. The 141 remaining patients (52.5% male; median age at diagnosis 24.0 years) were followed-up for a median of 11 years. The probabilities of a CE and an SCE from birth to the age of 40 were 20.5% and 9.9%, respectively. QTc prolongation (hazard ratio [HR] 1.12 [1.0-1.2]; P = .005]) and proband status (HR 4.07 [1.9-8.9]; P <.001) were independently associated with the occurrence of CEs. Proband status (HR 8.13 [1.7-38.8]; P = .009) was found to be independently associated with SCEs, whereas QTc prolongation (HR 1.11 [1.0-1.3]; P = .108) did not reach statistical significance. The cumulative probability of the age at first CE/SCE was not lower in patients treated with a beta-blocker. CONCLUSION: In agreement with the literature, proband status and lengthened QTc were associated with a higher risk of CEs. Our data do not show a protective effect of beta-blocker treatment.

Catheter ablation of atrial tachyarrhythmias in patients with atrioventricular septal defect.

AIMS: The incidence of atrial tachyarrhythmias is high in patients with atrioventricular septal defect (AVSD). No specific data on catheter ablation have been reported so far in this population. We aimed to describe the main mechanisms of atrial tachyarrhythmias in patients with AVSD and to analyse outcomes after catheter ablation. METHODS AND RESULTS: This observational multi-centric cohort study enrolled all patients with AVSD referred for catheter ablation of an atrial tachyarrhythmia at six tertiary centres from 2004 to 2022. The mechanisms of the different tachyarrhythmias targeted were described and outcomes were analysed. Overall, 56 patients (38.1 ± 17.4 years, 55.4% females) were included. A total of 87 atrial tachyarrhythmias were targeted (mean number of 1.6 per patient). Regarding main circuits involved, a cavo-annular isthmus-dependent intra-atrial re-entrant tachycardia (IART) was observed in 41 (73.2%) patients and an IART involving the right lateral atriotomy in 10 (17.9%) patients. Other tachyarrhythmias with heterogeneous circuits were observed in 13 (23.2%) patients including 11 left-sided and 4 right-sided tachyarrhythmias. Overall, an acute success was achieved in 54 (96.4%) patients, and no complication was reported. During a mean follow-up of 2.8 ± 3.8 years, 22 (39.3%) patients had at least one recurrence. Freedom from atrial tachyarrhythmia recurrences was 77.5% at 1 year. Among 15 (26.8%) patients who underwent repeated ablation procedures, heterogeneous circuits including bi-atrial and left-sided tachyarrhythmias were more frequent. CONCLUSION: In patients with AVSD, most circuits involve the cavo-annular isthmus, but complex mechanisms are frequently encountered in patients with repeated procedures. The acute success rate is excellent, although recurrences remain common during follow-up.

Subcutaneous Implantable Cardioverter-Defibrillators in Patients With Congenital Heart Disease.

BACKGROUND: Very few data have been published on the use of subcutaneous implantable cardioverter-defibrillators (S-ICDs) in patients with congenital heart disease (CHD). OBJECTIVES: The aim of this study was to analyze outcomes associated with S-ICDs in patients with CHD. METHODS: This nationwide French cohort including all patients with an S-ICD was initiated in 2020 by the French Institute of Health and Medical Research. Characteristics at implantation and outcomes were analyzed in patients with CHD. RESULTS: From October 12, 2012, to December 31, 2019, among 4,924 patients receiving an S-ICD implant in 150 centers, 101 (2.1%) had CHD. Tetralogy of Fallot, univentricular heart, and dextro-transposition of the great arteries represented almost one-half of the population. Patients with CHD were significantly younger (age 37.1 ± 15.4 years vs 50.1 ± 14.9 years; P < 0.001), more frequently female (37.6% vs 23.0%; P < 0.001), more likely to receive an S-ICD for secondary prevention (72.3% vs 35.9%; P < 0.001), and less likely to have severe systolic dysfunction of the systemic ventricle (28.1% vs 53.1%; P < 0.001). Over a mean follow-up period of 1.9 years, 16 (15.8%) patients with CHD received at least 1 appropriate shock, with all shocks successfully terminating the ventricular arrhythmia. The crude risk of appropriate S-ICD shock was twice as high in patients with CHD compared with non-CHD patients (annual incidences of 9.0% vs 4.4%; HR: 2.1; 95% CI: 1.3-3.4); however, this association was no longer significant after propensity matching (especially considering S-ICD indication, P = 0.12). The burden of all complications (HR: 1.2; 95% CI: 0.7-2.1; P = 0.4) and inappropriate shocks (HR: 0.9; 95% CI: 0.4-2.0; P = 0.9) was comparable in both groups. CONCLUSIONS: In this nationwide study, patients with CHD represented 2% of all S-ICD implantations. Our findings emphasize the effectiveness and safety of S-ICD in this particularly high-risk population. (S-ICD French Cohort Study [HONEST]; NCT05302115).

Systematic Electrophysiological Study Prior to Pulmonary Valve Replacement in Tetralogy of Fallot: A Prospective Multicenter Study.

BACKGROUND: Ventricular arrhythmias and sudden death are recognized complications in tetralogy of Fallot. Electrophysiological studies (EPS) before pulmonary valve replacement (PVR), the most common reintervention in tetralogy of Fallot, could potentially inform therapy to improve arrhythmic outcomes. METHODS: A prospective multicenter study was conducted to systematically assess EPS with programmed ventricular stimulation in patients with tetralogy of Fallot referred for PVR from January 2020 to December 2021. A standardized stimulation protocol was used across all centers. RESULTS: A total of 120 patients were enrolled, mean age 39.2±14.5 years, 53.3% males. Sustained ventricular tachycardia was induced in 27 (22.5%) patients. When identifiable, the critical isthmus most commonly implicated (ie, in 90.0%) was between the ventricular septal defect patch and pulmonary annulus. Factors independently associated with inducible ventricular tachycardia were history of atrial arrhythmia (odds ratio, 8.56 [95% CI, 2.43-34.73]) and pulmonary annulus diameter >26 mm (odds ratio, 5.05 [95% CI, 1.47-21.69]). The EPS led to a substantial change in management in 23 (19.2%) cases: 18 (15.0%) had catheter ablation, 3 (2.5%) surgical cryoablation during PVR, and 9 (7.5%) defibrillator implantation. Repeat EPS 5.1 (4.8-6.2) months after PVR was negative in 8 of 9 (88.9%) patients. No patient experienced a sustained ventricular arrhythmia during 13 (6.1-20.1) months of follow-up. CONCLUSIONS: Systematically performing programmed ventricular stimulation in patients with tetralogy of Fallot referred for PVR yields a high rate of inducible ventricular tachycardia and carries the potential to alter management. It remains to be determined whether a standardized treatment approach based on the results of EPS will translate into improved outcomes. REGISTRATION: URL: https://clinicaltrials.gov/ct2/show/NCT04205461; Unique identifier: NCT04205461.

Epicardial vs. transvenous implantable cardioverter defibrillators in children.

AIMS: The implantable cardioverter defibrillator (ICD) has been increasingly used in children. Both epicardial and transvenous approaches are used, with controversy regarding the best option with no specific recommendations. We aimed to compare outcomes associated with epicardial vs. transvenous ICDs in children. METHODS AND RESULTS: Data were analysed from a retrospective study including all patients <18-year-old implanted with an ICD in a tertiary centre from 2003 to 2021. Outcomes were compared between epicardial and transvenous ICDs. A total of 122 children with an ICD (mean age 11.5 ± 3.8 years, 57.4% males) were enrolled, with 84 (64.1%) epicardial ICDs and 38 (29.0%) transvenous ICDs. Early (<30 days) ICD-related complications were reported in 17 (20.2%) patients with an epicardial ICD vs. 0 (0.0%) with a transvenous ICD (P = 0.002). Over a mean follow-up of 4.8 ± 4.0 years, 25 (29.8%) patients with an epicardial ICD and 9 (23.7%) patients with a transvenous ICD experienced at least one late ICD-related complication [hazard ratio (HR) 1.8, 95% confidence interval (CI) 0.8-4.0]. Implantable cardioverter defibrillator lead dysfunction occurred in 19 (22.6%) patients with an epicardial ICD vs. 3 (7.9%) with a transvenous ICD (HR 5.7, 95% CI 1.3-24.5) and was associated with a higher incidence of ICD-related reintervention (HR 3.0, 95% CI 1.3-7.0). After considering potential confounders, especially age and weight at implantation, this association was no longer significant (P = 0.112). The freedom from ICD lead dysfunction was greater in patients with pleural coils than in those with epicardial coils (HR 0.38, 95% CI 0.15-0.96). CONCLUSION: In children, after a consideration of patient characteristics at implantation, the burden of complications and ICD lead dysfunction appears to be similar in patients with epicardial and transvenous devices. Pleural coils seem to be associated with better outcomes than epicardial coils in this population. CLINICAL TRIAL REGISTRATION: NCT05349162.

The SIDECAR project: S-IcD registry in European paediatriC and young Adult patients with congenital heaRt defects.

AIMS: Subcutaneous-implantable cardiac defibrillators (S-ICDs) are used increasingly to prevent sudden cardiac death in young patients. This study was set up to gain insight in the indications for S-ICD, possible complications, and their predictors and follow-up results. METHODS AND RESULTS: A multicentre, observational, retrospective, non-randomized, standard-of-care registry on S-ICD outcome in young patients with congenital heart diseases (CHDs), inherited arrhythmias (IAs), idiopathic ventricular fibrillation (IVF), and cardiomyopathies (CMPs). Anthropometry was registered as well as implantation technique, mid-term device-related complications, and incidence of appropriate/inappropriate shocks (IASs). Data are reported as median (interquartile range) or mean ± standard deviation. Eighty-one patients (47% CMPs, 20% CHD, 21% IVF, and 12% IA), aged 15 (14-17) years, with body mass index (BMI) 21.8 ± 3.8 kg/m2, underwent S-ICD implantation (primary prevention in 59%). This was performed with two-incision technique in 81% and with a subcutaneous pocket in 59%. Shock and conditional zones were programmed at 250 (200-250) and 210 (180-240) b.p.m., respectively. No intraoperative complications occurred. Follow up was 19 (6-35) months: no defibrillation failure occurred, 17% of patients received appropriate shocks, 13% of patients received IAS (supraventricular tachycardias 40%, T-wave oversensing 40%, and non-cardiac oversensing 20%). Reprogramming, proper drug therapy, and surgical revision avoided further IAS. Complications requiring surgical revision occurred in 9% of patients, with higher risks in patients with three-incision procedures [hazard ratio (HR) 4.3, 95% confidence interval (95% CI) 0.5-34, P = 0.038] and BMI < 20 (HR 5.1, 95% CI 1-24, P = 0.031). CONCLUSION: This multicentre European paediatric registry showed good S-ICD efficacy and safety in young patients. Newer implantation techniques and BMI > 20 showed better outcome.

Cardiac tomography-echocardiography imaging fusion: a new approach to congenital heart disease.

INTRODUCTION AND OBJECTIVES: Diagnosis, management, and surgical decision-making in children and adults with congenital heart disease are largely based on echocardiography findings. A recent development in cardiac imaging is fusion of different imaging modalities. Our objective was to evaluate the feasibility of computed tomography (CT) and 3-dimensional (3D) transthoracic echocardiography (TTE) fusion in children and adults with congenital heart disease. METHODS: We prospectively included 14 patients, 13 of whom had congenital heart disease, and who underwent both CT and 3D TTE as part of their usual follow-up. We described the steps required to complete the fusion process (alignment, landmarks, and superimposition), navigation, and image evaluation. RESULTS: Median age was 9.5 [2.7-15.7] years, 57% were male, and median body surface area was 0.9 m2 [0.6-1.7]. Congenital heart disease was classified as simple (n=4, 29%), moderate (n=4, 29%), or complex (n=6, 42%). 3D TTE-CT fusion was successful in all patients. Median total time to complete the fusion process was 735 [628-1163] seconds, with no significant difference according to the degree of complexity of the defects. Landmarks were significantly modified in complex congenital heart disease. CONCLUSIONS: We established the feasibility and accuracy of 3D TTE-CT fusion in a population of children and adults with a variety of congenital heart diseases. The simultaneous visualization of many intracardiac structures may help to understand the anatomical features of congenital heart disease without limitations regarding age, weight, or complexity of the congenital defects.

Health Outcomes of 215 Mothers of Children With Autoimmune Congenital Heart Block: Analysis of the French Neonatal Lupus Syndrome Registry.

OBJECTIVE: Transplacental passage of maternal anti-SSA and anti-SSB antibodies, potentially associated with maternal autoimmune diseases, can cause neonatal lupus syndrome. Given the paucity of data in this setting, we report short- and long-term outcomes of mothers of offspring with congenital heart block (CHB). METHODS: This retrospective study included anti-SSA/SSB antibody-positive mothers of fetuses with high-degree CHB and focused on their health status before pregnancy, at CHB diagnosis, and thereafter. RESULTS: We analyzed 215 women with at least 1 pregnancy with CHB. Prior to this diagnosis, only 52 (24%) mothers had been diagnosed with an autoimmune disease, mainly systemic lupus erythematosus (SLE; n = 26, 12%) and Sjögren syndrome (SS; n = 16, 7%). Six more were diagnosed with an autoimmune disease during the index pregnancy. Of the 157 mothers (73%) with no such diagnosis at childbirth, 77 (49%) developed one after a median follow-up of 11 years (range: 21 days to 54 years). By the end of follow-up, 135 women (63%) had an autoimmune disease diagnosis, mainly SLE (n = 54, 25%) and SS (n = 72, 33%). Three patients with SLE had renal involvement, and only 6 (3%) had required an immunosuppressive drug at any point. The symptoms best predicting autoimmune disease development were arthralgia and myalgia (P < 0.001), dry syndrome (P = 0.01), and parotid swelling (P = 0.05). CONCLUSION: One-quarter of the patients had an autoimmune disease diagnosis at the time of the fetal CHB diagnosis. Nearly half of those without an initial diagnosis progressed during follow-up, most without severe manifestations. Severe diseases such as lupus nephritis were rarely seen, and immunosuppressive drugs were rarely required.

Incidence, Risk Factors, and Outcomes of Atrial Arrhythmias in Adult Patients With Atrioventricular Septal Defect.

OBJECTIVES: This study aimed to assess the incidence, associated factors, and outcomes of atrial arrhythmias in adults with atrioventricular septal defect (AVSD). BACKGROUND: Data regarding atrial arrhythmias in adults with AVSD are particularly scarce. METHODS: Data were analyzed from a multicentric cohort of adult patients with AVSD. Lifetime cumulative incidences of atrial arrhythmias were studied. Multiple logistic regression models were used to identify risk factors. RESULTS: A total of 391 patients (61.6% women) were enrolled with a mean age of 36.3 ± 16.3 years and a mean follow-up of 17.3 ± 14.2 years after initial surgical repair. Overall, 98 patients (25.1%) developed at least 1 episode of atrial arrhythmia at a mean age of 39.2 ± 17.2 years. The mean ages of patients at first episode of intra-atrial re-entrant tachycardia (IART)/ focal atrial tachycardia (FAT) and atrial fibrillation were 33.7 ± 15.3 and 44.3 ± 16.5 years, respectively. The lifetime risks for developing atrial arrhythmia to ages 20, 40, and 60 years were 3.7%, 17.8%, and 55.3%, respectively. IART/FAT was the leading arrhythmia until the age of 45, then atrial fibrillation surpassed IART/FAT. Age (odds ratio [OR]: 1.4; 95% confidence interval [CI]: 1.2-1.6), number of cardiac surgeries (OR: 4.1; 95% CI: 2.5-6.9), left atrial dilatation (OR: 3.1; 95% CI: 1.4-6.8), right atrial dilatation (OR: 4.1; 95% CI: 1.7-10.3), and moderate or severe left atrioventricular valve regurgitation (OR: 3.7; 95% CI: 1.2-11.7) were independently associated with a higher risk of atrial arrhythmias, whereas the type of AVSD and the age at repair were not. The occurrence of atrial arrhythmias was associated with pacemaker implantation (41.8% vs. 8.5%; P < 0.001), heart failure (24.5% vs. 1.0%; P < 0.001), and cerebrovascular accidents (11.2% vs. 3.4%; P = 0.007). CONCLUSIONS: The lifetime risk of atrial arrhythmias in patients with AVSD is considerable with more than half of patients developing ≥1 atrial arrhythmia by the age of 60 and is associated with a significant morbidity. The risk in partial/intermediate AVSD is as high as in complete AVSD and is not impacted by age at repair.

An International Multicenter Cohort Study on ß-Blockers for the Treatment of Symptomatic Children With Catecholaminergic Polymorphic Ventricular Tachycardia.

BACKGROUND: Symptomatic children with catecholaminergic polymorphic ventricular tachycardia (CPVT) are at risk for recurrent arrhythmic events. ß-Blockers decrease this risk, but studies comparing individual ß-blockers in sizeable cohorts are lacking. We aimed to assess the association between risk for arrhythmic events and type of ß-blocker in a large cohort of symptomatic children with CPVT. METHODS: From 2 international registries of patients with CPVT, RYR2 variant-carrying symptomatic children (defined as syncope or sudden cardiac arrest before ß-blocker initiation and age at start of ß-blocker therapy <18 years), treated with a ß-blocker were included. Cox regression analyses with time-dependent covariates for ß-blockers and potential confounders were used to assess the hazard ratio (HR). The primary outcome was the first occurrence of sudden cardiac death, sudden cardiac arrest, appropriate implantable cardioverter-defibrillator shock, or syncope. The secondary outcome was the first occurrence of any of the primary outcomes except syncope. RESULTS: We included 329 patients (median age at diagnosis, 12 [interquartile range, 7-15] years, 35% females). Ninety-nine (30.1%) patients experienced the primary outcome and 74 (22.5%) experienced the secondary outcome during a median follow-up of 6.7 (interquartile range, 2.8-12.5) years. Two-hundred sixteen patients (66.0%) used a nonselective ß-blocker (predominantly nadolol [n=140] or propranolol [n=70]) and 111 (33.7%) used a ß1-selective ß-blocker (predominantly atenolol [n=51], metoprolol [n=33], or bisoprolol [n=19]) as initial ß-blocker. Baseline characteristics did not differ. The HRs for both the primary and secondary outcomes were higher for ß1-selective compared with nonselective ß-blockers (HR, 2.04 [95% CI, 1.31-3.17]; and HR, 1.99 [95% CI, 1.20-3.30], respectively). When assessed separately, the HR for the primary outcome was higher for atenolol (HR, 2.68 [95% CI, 1.44-4.99]), bisoprolol (HR, 3.24 [95% CI, 1.47-7.18]), and metoprolol (HR, 2.18 [95% CI, 1.08-4.40]) compared with nadolol, but did not differ from propranolol. The HR of the secondary outcome was only higher in atenolol compared with nadolol (HR, 2.68 [95% CI, 1.30-5.55]). CONCLUSIONS: ß1-selective ß-blockers were associated with a significantly higher risk for arrhythmic events in symptomatic children with CPVT compared with nonselective ß-blockers, specifically nadolol. Nadolol, or propranolol if nadolol is unavailable, should be the preferred ß-blocker for treating symptomatic children with CPVT.

Cardiac resynchronization therapy in patients with congenital heart disease and systemic right ventricle.

BACKGROUND: Although patients with systemic right ventricle (SRV) represent a significant proportion of patients with congenital heart disease (CHD) implanted with cardiac resynchronization therapy (CRT), there are limited and conflicting data in this specific patient group. OBJECTIVE: We aimed to analyze outcomes of patients with SRV implanted with a CRT device. METHODS: Data were analyzed from an observational, retrospective, multicenter cohort study including all patients with CHD implanted with a CRT device from 6 French centers from 2004 to 2020. Response to CRT was defined as an increase in systemic ventricular ejection fraction of ≥10% and/or an improvement in New York Heart Association functional class by at least 1 grade. RESULTS: A total of 85 patients with CHD were enrolled (mean age 39.8 ± 20.0 years; 55 [64.7%] males; 25 defibrillators [29.4%]), including 31 patients with SRV (36.5%) (mean age 43.9 ± 19.8 years; 16 [51.6%] males). The mean change in QRS duration after implantation was similar as compared with patients with systemic left ventricle (-46 ± 26 ms vs -35 ± 32 ms; P = .16). During a mean follow-up of 5.1 ± 3.5 years, late complications included 2 lead dysfunctions (6.5%), 3 CRT-related infections (9.7%), and 1 inappropriate implantable cardioverter-defibrillator shock (3.2%). The proportion of CRT responders at 6, 12, and 24 months were 82.6%, 80.0%, and 77.8% in patients with SRV vs 66.7%, 64.3%, and 69.6% in patients with systemic left ventricle (P = NS). CONCLUSION: In this multicenter cohort, one-third of patients with CHD implanted with a CRT device had SRV. CRT in patients with SRV was associated with a high rate of responders, comparable to that of patients with systemic left ventricle.

Challenging indication of cardioverter defibrillator implantation after sudden cardiac arrest in the very young: a case series of catecholaminergic polymorphic ventricular tachycardia secondary to de novo calmodulin p.Asn98Ser.

BACKGROUND: Calmodulinopathy is an emerging group of primary electrical disease with various, severe, and early onset phenotype. Sudden cardiac arrest (SCA)/death can be the first symptom and current medical management seems insufficient to prevent recurrences. Implantable cardioverter-defibrillator (ICD) in the young is challenging and can be harmful. CASE SUMMARY: We report the management of two very young boys (aged 3.5 and 5.5 years old) who survived an SCA due to calmodulin mutation responsible of a catecholaminergic polymorphic ventricular tachycardia phenotype. In both case, SCA had an adrenergic trigger. Despite SCA, ICD implantation was denied by the parents. After thorough discussion with the family, the patients were managed with solely betablocker treatment and loop recorder implantation. At last follow-up of 30 and 23 months, respectively, there were no recurrence of any cardiac event. DISCUSSION: The benefits of ICD implantation at a very young age must be weighed against the risk complication. In the youngest, whom recreative activities are under constant supervision, the decision, jointly made with the parents, could be to postpone ICD.

Atrial flutter catheter ablation in adult congenital heart diseases.

The important increase in life expectancy of adult patients with congenital heart disease (ACHD) has generated new challenges, including arrhythmias that represent one of the main late complications. Reentrant atrial arrhythmias are by far the main mechanism encountered, and catheter ablation has been now presented as a first-line therapy in this patient population. The number of procedures is expected to continuously increase year after year. The heterogeneity and complexity of phenotypes encountered require these cases to be performed by highly experienced operators, in specialized centers with multidisciplinary competencies. A thorough knowledge and understanding of anatomic specificities, vascular access issues, and main circuits encountered according to underlying phenotype is essential. Acute success rates have significantly improved and are now excellent, but recurrences remain a common issue, with different mechanisms or circuits frequently encountered. Observational data have suggested the interest of systematically targeting all inducible atrial arrhythmias, whether previously documented or not, and a lot of hope and research is based on the prediction of arrhythmia substrate before arrhythmia development by imaging or electroanatomic mapping to deliver a prophylactic patient tailored ablation approach. In this review, we summarize those different points in the most common or distinctive defects to offer a didactic overview of atrial flutter catheter ablation in ACHD patients.

Outcomes of sustained fetal tachyarrhythmias after transplacental treatment.

BACKGROUND: Fetal tachyarrhythmia is a condition that may lead to cardiac dysfunction, hydrops, and death. Despite a transplacental treatment, failure to obtain or maintain sinus rhythm may occur. OBJECTIVE: We aimed to analyze the perinatal outcomes of sustained fetal tachyarrhythmias after in utero treatment. METHODS: We performed a retrospective evaluation of 69 cases with sustained fetal tachyarrhythmia. We compared the perinatal and long-term outcomes of prenatally converted and drug-resistant fetuses. Tachyarrhythmia subtypes were also evaluated. RESULTS: Conversion to sinus rhythm was obtained in 74% of cases; 26% of cases were drug-resistant and delivered arrhythmic. Three perinatal deaths occurred in both groups (6.7% vs 17%, P = .34). Neonates delivered arrhythmic were more frequently admitted to neonatal intensive care units (75% vs 31%, P < .01), and their hospital stay was longer (20.9 vs 6.64 days, P < .001). Multiple neonatal recurrences (81% vs 11%, P < .001), temporary hemodynamic dysfunction or heart failure (50% vs 6.7%, P < .001), and postnatal use of a combination treatment (44% vs 13%, P = .028) were also more frequent in this population. Beyond the neonatal period, rates of recurrences within the first 16 months were higher in drug-resistant fetuses (HR = 16.14, CI 95% [4.485; 193.8], P < .001). In this population, postnatal electrocardiogram revealed an overrepresentation of rare mechanisms, especially permanent junctional reciprocating tachycardia (PJRT) (31%). CONCLUSION: Prenatal conversion to stable sinus rhythm is a major determinant of perinatal and long-term outcomes in fetal tachyarrhythmias. The underlying electrophysiological mechanisms have a major role in predicting these differential outcomes with an overrepresentation of PJRT in the drug-resistant population.

Catheter ablation in adults with congenital heart disease: A 15-year perspective from a tertiary centre.

BACKGROUND: With the growing adult congenital heart disease (ACHD) population, the number of catheter ablation procedures is expected to dramatically increase. Data reporting experience and evolution of catheter ablation in patients with ACHD, over a significant period of time, remain scarce. AIM: We aimed to describe temporal trends in volume and outcomes of catheter ablation in patients with ACHD. METHODS: This was a retrospective observational study including all consecutive patients with ACHD undergoing attempted catheter ablation in a large tertiary referral centre over a 15-year period. Acute procedural success rate and freedom from recurrence at 12 and 24 months were analysed. RESULTS: From November 2004 to November 2019, 302 catheter ablations were performed in 221 patients with ACHD (mean age 43.6±15.0 years; 58.9% male sex). The annual number of catheter ablations increased progressively from four to 60 cases per year (P<0.001). Intra-atrial reentrant tachycardia/focal atrial tachycardia was the most common arrhythmia (n=217, 71.9%). Over the study period, acute procedural success rate increased from 45.0% to 93.4% (P<0.001). Use of irrigated catheters (odds ratio [OR] 4.03, 95% confidence interval [CI] 1.86-8.55), a three-dimensional mapping system (OR 3.70, 95% CI 1.72-7.74), contact force catheters (OR 3.60, 95% CI 1.81-7.38) and high-density mapping (OR 3.69, 95% CI 1.82-8.14) were associated with acute procedural success. The rate of freedom from any recurrence at 12 months increased from 29.4% to 66.2% (P=0.001). Seven (2.3%) non-fatal complications occurred. CONCLUSIONS: The number of catheter ablation procedures in patients with ACHD has increased considerably over the past 15 years. Growing experience and advances in ablative technologies appear to be associated with a significant improvement in acute and mid-term outcomes.

Clinical and biological characterization of 20 patients with TANGO2 deficiency indicates novel triggers of metabolic crises and no primary energetic defect.

TANGO2 disease is a severe inherited disorder associating multiple symptoms such as metabolic crises, encephalopathy, cardiac arrhythmias, and hypothyroidism. The mechanism of action of TANGO2 is currently unknown. Here, we describe a cohort of 20 French patients bearing mutations in the TANGO2 gene. We found that the main clinical presentation was the association of neurodevelopmental delay (n = 17), acute metabolic crises (n = 17) and hypothyroidism (n = 12), with a large intrafamilial clinical variability. Metabolic crises included rhabdomyolysis (15/17), neurological symptoms (14/17), and cardiac features (12/17; long QT (n = 10), Brugada pattern (n = 2), cardiac arrhythmia (n = 6)) that required intensive care. We show previously uncharacterized triggers of metabolic crises in TANGO2 patients, such as some anesthetics and possibly l-carnitine. Unexpectedly, plasma acylcarnitines, plasma FGF-21, muscle histology, and mitochondrial spectrometry were mostly normal. Moreover, in patients' primary myoblasts, palmitate and glutamine oxidation rates, and the mitochondrial network were also normal. Finally, we found variable mitochondrial respiration and defective clearance of oxidized DNA upon cycles of starvation and refeeding. We conclude that TANGO2 disease is a life-threatening disease that needs specific cardiac management and anesthesia protocol. Mechanistically, TANGO2 disease is unlikely to originate from a primary mitochondrial defect. Rather, we suggest that mitochondrial defects are secondary to strong extrinsic triggers in TANGO2 deficient patients.