Tuberous sclerosis complex is syndrome that affects several organs. Cardiac manifestations include rhabdomyoma, which could lead to intracardiac obstruction of blood flow. In the present case, the so far lowest documented Everolimus blood level of 2-3 ng/ml led to tumour regression. Repeated Everolimus stopping and restarting for clinical reasons serves as a proof-of-concept for Everolimus therapy in tuberous sclerosis complex.

Background: A subgroup of CHDs can only be treated palliatively through a Fontan circulation. In case of a failing Fontan situation, serum proteins are lost unspecifically and can also lead to a loss of vaccine antibodies. In a failing Fontan situation, heart transplantation may be the only feasible option. Patient: We describe a 17-year-old patient born with a hypoplastic left heart complex, who underwent Fontan completion at the age of 4 years and developed a failing Fontan physiology. Therefore, a Fontan takedown with creation of a reverse 11/2-circulation was performed. Multiple exacerbations of protein losing enteropathy occurred with a hypoproteinaemia, hypalbuminaemia, and hypogammaglobulinaemia. The patient was hospitalised several times and treated with intravenous application of immunoglobulins and albumin for symptom control. Before one of this substitutions, the immunoglobulin G against measles, mumps, and rubella was determined: the patient's serum demonstrated a positive measles and rubella, but mumps was negative. After administration of the iv-therapy, the lacking antibodies were replenished, and there was a positive test for mumps. Method: Serum samples were analysed by neutralisation test and enzyme-linked immunosorbent assay (ELISA). Conclusion: Although the patient had been vaccinated according to national guidelines, we saw an intermittent immune deficiency for mumps, but not for rubella and measles. For patient with a failing Fontan circulation, we recommend to test to vaccine antibodies for mumps, measles, and rubella with an ELISA an if its negative with a neutralisation test, especially in view of a possible heart to find a immune

Background: Accurate measurement of transcutaneous oxygen saturation is important for the assessment of cyanosis in CHD. Aim of this study was the evaluation of a supplementary transcutaneous oxygen saturation measurement with an Apple watch (R) in children with cyanotic heart disease. Material and methods: During a six-minute walk test, measurement of transcutaneous oxygen saturation was performed simultaneously with an Oximeter (Nellcor, Medtronic, USA) and an Apple watch (R) Series 7 (Apple inc, USA) in 36 children with cyanotic heart disease. Results: Median age was 9.2 (IQR 5.7-13.8) years. Transcutaneous oxygen saturation measurement with the Apple watch (R) was possible in 35/36 and 34/36 subjects before and after six-minute walk test. Children, in whom Apple watch (R) measurement was not possible, had a transcutaneous oxygen saturation < 85% on oximeter. Before six-minute walk test, median transcutaneous oxygen saturation was 93 (IQR 91-97) % measured by oximeter and 95 (IQR 93-96) % by the Apple watch (R). After a median walking distance of 437 (IQR 360-487) m, transcutaneous oxygen saturation dropped to 92 (IQR 88-95, p < 0.001) % by oximeter and to 94 (IQR 90-96, p = 0.013) % measured with the Apple watch (R). Conclusion: In children with mild cyanosis measurement of transcutaneous oxygen saturation with an Apple watch (R) showed only valid results if transcutaneous oxygen saturation was > 85%, with higher values being measured with the smart watch. In children with moderate or severe cyanosis transcutaneous oxygen saturation, measurement with the Apple watch (R) was not reliable and cannot be recommended to monitor oxygen saturation at home.

BackgroundCatecholaminergic polymorphic ventricular tachycardia (CPVT) may cause sudden cardiac death (SCD) despite medical therapy. Therefore, implantable cardioverter defibrillators (ICDs) are commonly advised. However, there are limited data on the outcomes of ICD use in children.ObjectiveTo compare the risk of arrhythmic events in pediatric CPVT patients with and without ICDs.MethodsWe compared the risk of SCD in RYR2 variant and phenotype positive symptomatic CPVT patients with and without ICDs, who were <19 years of age and had no history of sudden cardiac arrest (SCA) at phenotype diagnosis. The primary outcome was SCD; secondary outcomes were composite incidences of SCD, SCA, appropriate ICD shocks, with/without arrhythmic syncope.ResultsThe study included 235 patients, 73 (31.1%) with ICDs and 162 (68.9%) without ICDs. Over a median follow-up of 8.0 years (IQR 4.3-13.4), SCD occurred in 7 (3.0%) patients, of which 4 (57.1%) were non-compliant with medications and none had an ICD. ICD patients had a higher risk of both secondary composite outcomes (without syncope: HR 5.85 (CI 3.40-10.09); p<0.0001; with syncope: HR 2.55 (CI 1.50-4.34); p=0.0005). Thirty-one (42.5%) patients with an ICD experienced appropriate shocks, 18 (24.7%) inappropriate shocks, and 21 (28.8%) device-related complications.ConclusionsSCD events occurred only in the no ICD group, in those not on optimal medical therapy. ICD patients had a high risk of appropriate and inappropriate shocks, which may be reduced with appropriate device programming. Severe ICD complications were common and risks versus benefits of ICDs need to be considered.

D-Transposition of the great arteries (d-TGA) is the most common congenital heart disease requiring surgical correction within the neonatal period. Sinus tachycardia often persists postoperatively, potentially affecting cardiac function. This study aimed to investigate the efficacy and safety of the short-acting beta-1-selective beta-blocker esmolol in controlling heart rate in neonatal cardiac surgery with cardiopulmonary bypass (CPB). A retrospective cohort study was conducted on neonates undergoing surgery for d-TGA. The study cohort included 112 patients, divided into an esmolol intervention group (n = 57) and a control group (n = 55). Baseline characteristics, hemodynamic parameters and outcome measures were assessed. In the esmolol group, median heart rate at ICU admission was significantly higher compared to the control group (155 vs. 147 bpm, p = 0.018). After a median time of 11 h, heart rate was lower among the esmolol patients (135 vs. 144 bpm, p < 0.001). There were no differences in other hemodynamic parameters between the two groups. Patients treated with esmolol required longer catecholamine support while no difference regarding survival, duration of invasive ventilation and ICU stay were noticed. No relevant hemodynamic difference was seen between neonates treated with perioperative esmolol and the control group and outcome did not differ. This indicates non-inferiority of perioperative betablocker therapy in young age. Prospective and placebo-controlled assessment of perioperative esmolol therapy in neonates is needed.

In patients with AV-block (AVB), His bundle pacing (HBP) allows physiological ventricular depolarisation and may prevent pacemaker-induced cardiomyopathy. Selective and non-selective HBP is a feasible procedure in pediatric patients with and without congenital heart disease (CHD).

Background: Sex-specific differences in heart disease outcomes are influenced by the levels of the steroid hormones, estrogen and testosterone. While the roles of estrogen receptors in cardiac disease are well-studied in animals and humans, respective research on androgen receptors (AR) is limited. Here we investigate AR protein and mRNA expression in human myocardium of various cardiac diseases. Methods: AR expression was analyzed by western blotting in myocardium from human non-failing hearts (NF, n = 6) and patients with aortic stenosis (AS, n = 6), hypertrophic cardiomyopathy (HCM, n = 7), dilated cardiomyopathy (DCM, n = 7), and ischemic cardiomyopathy (ICM, n = 7). Using an AR45-specific antibody, a subsequent western blot assessed samples from male and female patients with HCM (n = 10) and DCM (n = 10). The same sample set was probed for full-length AR and AR45 mRNA expression. Immunohistochemistry (IHC) localized AR in myocardium from HCM and AS hearts. Results: Full-length AR was notably enriched in AS and HCM hearts compared to ICM, DCM, and NF. Similarly, AR45 was more abundant in HCM than in DCM. In contrast to the pattern observed for AR protein, full-length AR mRNA levels were lower in HCM compared to DCM, with no discernible difference for the AR45 isoform. Although gender differences in AR expression were not detected in western blots or qRT-PCR, IHC showed stronger nuclear AR signals in males than in females. Conclusions: Our findings indicate disease-specific regulation of AR mRNA and/or AR protein in cardiac hypertrophy, underscoring a potential role in this cardiac pathology.

Abstract Aims State-of-the-art pacemaker implantation technique in infants and small children consists of pace/sense electrodes attached to the epicardium and a pulse generator in the abdominal wall with a significant rate of dysfunction during growth, mostly attributable to lead failure. In order to overcome lead-related problems, feasibility of epicardial implantation of a leadless pacemaker at the left ventricular apex in a growing animal model was studied. Methods and results Ten lambs (median body weight 26.8 kg) underwent epicardial implantation of a Micra transcatheter pacing system (TPS) pacemaker (Medtronic Inc., Minneapolis, USA). Using a subxyphoid access, the Micra was introduced through a short, thick-walled tube to increase tissue contact and to prevent tilting from the epicardial surface. The Micra's proprietary delivery system was firmly pressed against the heart, while the Micra was pushed forward out of the sheath allowing the tines to stick into the left ventricular apical epimyocardium. Pacemakers were programmed to VVI 30/min mode. Pacemaker function and integrity was followed for 4 months after implantation. After implantation, median intrinsic R-wave amplitude was 5 mV [interquartile range (IQR) 2.8–7.5], and median pacing impedance was 2235 Ω (IQR 1725–2500), while the median pacing threshold was 2.13 V (IQR 1.25–2.9) at 0.24 ms. During follow-up, 6/10 animals had a significant increase in pacing threshold with loss of capture at maximum output at 0.24 ms in 2/10 animals. After 4 months, median R-wave amplitude had dropped to 2.25 mV (IQR 1.2–3.6), median pacing impedance had decreased to 595 Ω (IQR 575–645), and median pacing threshold had increased to 3.3 V (IQR 1.8–4.5) at 0.24 ms. Explantation of one device revealed deep penetration of the Micra device into the myocardium. Conclusion Short-term results after epicardial implantation of the Micra TPS at the left ventricular apex in lambs were satisfying. During mid-term follow-up, however, pacing thresholds increased, resulting in loss of capture in 2/10 animals. Penetration of one device into the myocardium was of concern. The concept of epicardial leadless pacing seems very attractive, and the current shape of the Micra TPS makes the device unsuitable for epicardial placement in growing organisms.

Background: In neonates, sinus tachycardia frequently occurs after cardiac surgery despite correction of usual causes, such as stress, pain, fever, hypovolemia or anemia. Tachycardia-induced additional myocardial oxygen consumption may even deteriorate function of postoperative hearts. Beta-1-selective, short-acting β-blockers are useful to control the heart rate but data on their efficacy and safety in newborn cardiac surgery with CPB are lacking.

INTRODUCTION:Catheter contact is a key determinant for lesion size in radiofrequency catheter ablation (RFA). Monitoring of contact force (CF) during RFA has been shown to improve efficacy of RFA in experimental settings as well as in adult patients. Coronary artery narrowing after RFA has been described in experimental settings as well as in children and adults and may be dependent from catheter contact. The value of CF monitoring concerning these issues has not been systematically studied yet. Value of high versus low CF during RFA in piglets was studied to assess lesion size and potential coronary artery involvement mimicking RFA in small children.METHODS:RFA with continuous CF monitoring was performed in 24 piglets (median weight 18.5 kg) using a 7 F TactiCath Quartz radiofrequency (RF) ablation catheter (Abbott). A total of 7 lesions were induced in each animal applying low (10-20 g) or high (40-60 g) CF. RF energy was delivered with a target temperature of 65°C at 30 W for 30 s. Coronary angiography was performed prior and immediately after RF application. Animals were assigned to repeat coronary angiography followed by heart removal after 48 h (n = 12) or 6 months (n = 12). Lesions with surrounding myocardium were excised, fixated, and stained. Lesion volumes were measured by microscopic planimetry.RESULTS:A total of 148 RF lesions were identified in the explanted hearts. Only in the subset of lesions at the AV annulus 6 month after ablation, lesion size and number of lesions exhibiting transmural extension were higher in the high CF group compared to low CF. In all other locations CF had no impact on lesion size and mural extension after 48 h as well as after 6 months. Additional parameters such as lesion size index and force time integral were also not related to lesion size. Coronary artery damage was present in two animals after 48 h and in one after 6 months and was not related to CF.CONCLUSION:In our experimental setting, lesion size in piglets was not related to catheter CF. Transmural extension of the RF lesions involving the layers of the coronary arteries was frequently noted irrespective of CF. Coronary artery narrowing was present in 3/24 animals and was not related to CF. In infants and toddlers, low CF (10-20 g) may be of adequate effect. Impact of CF monitoring during conventional RF ablation in children requires further investigation.

Objectives. Aim of this study was to evaluate the long-term course of patients with congenital heart disease (CHD) requiring repeat ablation procedures (RAP) of atrial tachycardias (AT). Background. Reports on RAP of AT in patients with CHD are sparse.Patients and Methods. All 144 patients with CHD who had undergone ablation of AT at our center between January 2003 and October 2018 were enrolled. Patients were classified according to complexity of CHD: complex CHD (cCHD), moderate CHD (mCHD) and simple CHD (sCHD). Results. A total of 101 RAP were performed in 64 patients. One RAP was performed in n=40, two in n=13, three in n=10 and 5 in n=1. Acute success rate was 82% (83/101) and was not associated with complexity of CHD (p=1.0). Mean number of procedures was lower in patients with sCHD than in patients with mCHD and cCHD (sCHD 1.3{plus minus}0.6, mCHD 1.8{plus minus}1.0 and cCHD 1.8{plus minus}1.1, p=0.04). RAP were most frequent in patients after Fontan palliation or atrial switch procedure (2.0{plus minus}1.1 (n=41) vs. 1.6{plus minus}0.9 all others, p=0.016) and in patients with multiple unstable AT´s (2.5{plus minus}1.1 (n=11) vs. 1.7{plus minus}1.0, p=0.008). Major complications occurred in 4/101 procedures. Complete follow-up was available in 125 patients. Since last RAP 73% of the patients were in sinus/atrial rhythm and 34/125 patients (27%) with AT recurrence did not require re-ablation with mean follow-up of 52{plus minus}40 months. Conclusions. Recurrences after ablation of AT in CHD patients were frequent. After RAP promising long-term results could be achieved. Data encourage repetitive ablation procedures in this patient population.

Background: PDA stenting is a technically feasible and effective palliation in congenital heart disease with duct-dependent pulmonary circulation. Serious complications can result from arterial access by the introduced sheath. Smaller sheath sizes could result in reduction of vessel injuries.

BACKGROUND:Children with catecholaminergic polymorphic ventricular tachycardia (CPVT) are at risk for sudden death, and a risk stratification tool does not exist. OBJECTIVE:The purpose of this study was to determine whether proband status, age at symptom onset, and/or sex are independent predictors of cardiac events. METHODS:A multicenter, ambispective, cohort of pediatric CPVT patients was categorized by sex, proband status, and age at symptom onset (D1: first decade of life [symptom onset <10 years] or D2: second decade of life [symptom onset 10-18 years, inclusive]). Demographics, therapy, genetics, and outcomes were compared between groups. RESULTS:A total of 133 patients were included and stratified into 58 D1 and 75 D2 patients (68 female and 65 male; 106 probands and 27 relatives). Localization of RYR2 variants to hotspots differed based on proband status and age at symptom onset. The cardiac event rate was 33% (n = 44/133), inclusive of a 3% (n = 4/133) mortality rate, over a median of 6 years (interquartile range 3-11) after time of symptom onset. Proband status, rather than age at of symptom onset or sex, was an independent predictor of time to first cardiac event (P = .008; hazard ratio = 4.4). The 5-, 10- and 15-year event-free survival rates for probands were 77%, 56%, and 46%, respectively, and for relatives were 96%, 91%, and 86%, respectively. Event risk after diagnosis was 48% (32/67) in patients on β-blocker or flecainide alone vs 10% (5/48) in patients on β-blocker plus flecainide and/or left cardiac sympathetic denervation (P <.001). CONCLUSION:Proband status, but not age at symptom onset or male sex, independently predicted an earlier onset of cardiac events. A larger sample size would enable a comprehensive investigation of other risk factors.

While Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT) is typically characterized by adrenergic-induced bidirectional or polymorphic ventricular tachycardia, atrial arrhythmias also occur. However, little is known about this manifestation.

Transseptal puncture (TSP) is a standard procedure to obtain access to the left heart. However, data on TSP in infants and children particularly with congenital heart defects (CHD) is sparse. Safety and efficacy of TSP in infants and children < 18 years with normal cardiac anatomy and with CHD were assessed. 327 TSP were performed in a total of 300 individuals < 18 years from 10/2002 to 09/2018 in our tertiary pediatric referral center. Median age at TSP was 11.9 years (IQR 7.8–15; range: first day of life to 17.9 years). 13 subjects were < 1 year. Median body weight was 43.8 kg (IQR 26.9–60; range: 1.8–121 kg). CHD was present in 28/327 (8.6%) procedures. TSP could be successfully performed in 323/327 (98.8%) procedures and was abandoned in 4 procedures due to imminent or incurred complications. Major complications occurred in 4 patients. 3 of these 4 subjects were ≤ 1 year of age and required TSP for enlargement of a restrictive atrial septal defect in complex CHD. Two of these babies deceased within 48 h after TSP attempt. The third baby needed urgent surgery in the cath lab. Pericardial effusion requiring drainage was noted in the forth patient (> 1 year) who was discharged well later. Minor complications emerged in 5 patients. The youngest of these individuals (0.3 years, 5.8 kg) developed small pericardial effusion after anterograde ballon valvuloplasty for critical aortic stenosis. The remaining 4/5 patients developed small pericardial effusion after ablation of a left-sided accessory atrioventricular pathway (6.1–12.2 years, 15.6–34.0 kg). TSP for access to the left heart was safe and effective in children and adolescents > 1 year of age. However, TSP was a high-risk procedure in small infants with a restrictive interatrial septum with need for enlargement of interatrial communication.

Primary prevention implantable cardioverter defibrillators (PP-ICD) are used in CPVT, but pediatric data supporting their use is lacking. To analyze PP-ICD outcomes in a cohort of pediatric CPVT patients. We compared the risk of arrhythmic events with and without PP-ICDs in symptomatic children without a history of cardiac arrest. The primary outcome was sudden cardiac death (SCD); secondary outcomes were a composite incidence of SCD, cardiac arrest, appropriate ICD shocks and syncope. Our cohort consisted of 56 patients. Sixteen (29%) had a PP-ICD with a mean age of implant of 11.7±3.1 years. ICDs were implanted for arrhythmogenic syncope (75%), ventricular arrhythmias on stress tests (44%), family history of CPVT death (19%) and family preference (13%). The 40 patients without ICDs served as controls. Mean age at symptom onset (PP-ICD: 8.5±3.4 years; controls: 9.2±4.5 years; p=0.50) and proband status (p=0.81) were not significantly different between groups, however ICDs were more likely in males (p=0.028). Over a median follow-up of 5 years, the primary outcome occurred in 2 (5%) controls and no PP-ICD recipients (p=0.2). The secondary outcome of SCD, SCA or appropriate ICD shocks occurred in 8 (50%) PP-ICD patients vs 4 (10%) controls (p=0.08). When syncope was added to the secondary composite outcome, 9 (56%) PP-ICD patients had events vs 14 (35%) controls (p=0.97). Eight (50%) PP-ICD patients experienced 32 appropriate shocks. Of these, 7 (44%) had >1 and 5 (31%) had >2 appropriate shocks. All 8 patients were on a beta-blocker, and 3 (17%) were also on flecainide at the time of 11 appropriate shocks. One patient had sympathectomy prior to 2 appropriate shocks. Device complications included 4 (25%) with inappropriate shocks, 4 (25%) with electrical storm and 7 (44%) with other device complications. PP-ICDs were not associated with a survival benefit in this cohort. PP-ICD patients received a high rate of appropriate shocks and experienced frequent complications. CPVT-specific device programming may diminish shock burden. Flecainide use was uncommon and further studies may be helpful to determine the role of optimal medical therapy in patient outcomes.

We used a new grid-style multi-electrode mapping catheter (Advisor™ HD Grid, Abbott) and investigated its use for high density mapping of atrial tachycardias in adult patients with congenital heart disease. All patients with congenital heart disease who had mapping of atrial tachycardias using the new grid-style catheter between March 2018 and April 2019 were included. A total of 24 adult patients had high density mapping of atrial tachycardias using the grid-style multi-electrode catheter. Mean procedure duration was 207 ± 72 min., mean fluoroscopy time was 7.1 ± 7.9 min. In patients with right atrial substrates, fluoroscopy time was shorter compared to biatrial or left atrial substrates (0.9 ± 2.2 min for right atrial substrates, n = 19 vs. 6.3 ± 8.3 min for left atrial substrates, n = 2 and 7.5 ± 4.3 min for biatrial substrates, n = 3, p = 0.01). A mean number of 14.814 ± 10.140 endocardial points were collected and 2.319 ± 1244 points were finally used to characterize the tachycardia. Procedural success was achieved in 21/24 (88%) subjects and partial success in 2/24 (8%) patients. Recurrence rate was low (12.5%). In one patient, radiofrequency ablation within the cavotricuspid isthmus resulted in occlusion of a branch of the right coronary artery. No complications related to the use of the mapping catheter itself occurred. High density mapping of AT using the grid-style catheter showed promising results with respect to procedural and midterm outcome and fluoroscopy time. Using the grid-style catheter might offer advantages compared to other multi-electrode catheters used for high density mapping of AT in patients with CHD.

Background Pacemaker used in small children typically consist of an abdominally placed generator and epicardially affixed leads, making such a system prone to lead dysfunction during growth. Aim of this study was to investigate the feasibility of epicardial pacing with a leadless pacemaker in a lamb model. Animals and methods Seventeen lambs underwent epicardial implantation of a Micra transcatheter pacing system (TPS) (Medtronic, Minneapolis, MN, USA) via left-lateral thoracotomy to the left ventricle (LV) surface (n = 11/17) and to the left atrial appendage (n = 6). Ventricular devices were fixated with the tines within the pericardium, whereas the tines of the atrial devices penetrated the myocardium of the left atrial appendage. After 31 weeks, animals were sacrificed and hearts were explanted for histological analysis. Results Following implantation, median P/R amplitude was 4.25/5.5 mV while median pacing threshold was 1.1/1.9 V at 0.24 ms. After 31 weeks, median P/R amplitude was 3.3/4.2 mV. Median atrial pacing threshold was 0.5/0.24 ms. Eight of 10 ventricular pacemakers had lost capture at standard impulse width even at maximum impulse amplitude. On explantation, firm adhesion of the device to the thoracic wall and dislodgement of the electrode tip was found in those ventricular devices. Conclusions Firm fixation of the Micra electrode to the epicardial surface as applied to the atrial devices resulted in excellent electrical properties during midterm follow up. Pericardial fixation as in the ventricular devices was associated with loss of capture. Therefore, it is important to embed the tines in the myocardium and to choose an alternative implantation site allowing for safe fixation of the Micra TPS in a position perpendicular to ventricular epimyocardium.

Objectives: Current pacemaker therapy in newborns and small toddlers requires epicardial lead fixation with the pulse generator, most commonly implanted abdominally. During growth, lead fracture can occur due to tension or mechanical strain. The aim of this study was to investigate the feasibility of epicardial pacing with a commercially available leadless pacemaker in an animal model.