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Childhood hypertrophic cardiomyopathy; Outcomes; Phenotype Miocardiopatía hipertrófica infantil; Resultados; Fenotipo Miocardiopatia hipertròfica infantil; Resultats; Fenotip Background Up to one-half of childhood sarcomeric hypertrophic cardiomyopathy (HCM) presents before the age of 12 years, but this patient group has not been systematically characterized. Objectives The aim of this study was to describe the clinical presentation and natural history of patients presenting with nonsyndromic HCM before the age of 12 years. Methods Data from the International Paediatric Hypertrophic Cardiomyopathy Consortium on 639 children diagnosed with HCM younger than 12 years were collected and compared with those from 568 children diagnosed between 12 and 16 years. Results At baseline, 339 patients (53.6%) had family histories of HCM, 132 (20.9%) had heart failure symptoms, and 250 (39.2%) were prescribed cardiac medications. The median maximal left ventricular wall thickness z-score was 8.7 (IQR: 5.3-14.4), and 145 patients (27.2%) had left ventricular outflow tract obstruction. Over a median follow-up period of 5.6 years (IQR: 2.3-10.0 years), 42 patients (6.6%) died, 21 (3.3%) underwent cardiac transplantation, and 69 (10.8%) had life-threatening arrhythmic events. Compared with those presenting after 12 years, a higher proportion of younger patients underwent myectomy (10.5% vs 7.2%; P = 0.045), but fewer received primary prevention implantable cardioverter-defibrillators (18.9% vs 30.1%; P = 0.041). The incidence of mortality or life-threatening arrhythmic events did not differ, but events occurred at a younger age. Conclusions Early-onset childhood HCM is associated with a comparable symptom burden and cardiac phenotype as in patients presenting later in childhood. Long-term outcomes including mortality did not differ by age of presentation, but patients presenting at younger than 12 years experienced adverse events at younger ages. This work was supported by the British Heart Foundation (grant FS/16/72/32270) to Drs Norrish and Kaski. This work is (partly) funded by the National Institute for Health Research Great Ormond Street Hospital Biomedical Research Centre. Dr Norrish is supported by Great Ormond Street Hospital Children’s Charity. Drs Field and Kaski are supported by Max’s Foundation and Great Ormond Street Hospital Children’s Charity. Dr Kaski is supported by a Medical Research Council–National Institute for Health Research Clinical Academic Research Partnership award. This work was financially supported by the Foundation for Paediatric Research of Finland (Dr Ojala). Dr Fernandez has received speaker fees from Sanofi-Genzyme. Dr Kubus is supported by MH CZ – DRO, Motol University Hospital (00064203). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

BackgroundA neurodevelopmental syndrome was recently reported in four patients withSOX4heterozygous missense variants in the high-mobility-group (HMG) DNA-binding domain. The present study aimed to consolidate clinical and genetic knowledge of this syndrome.MethodsWe newly identified 17 patients withSOX4variants, predicted variant pathogenicity using in silico tests and in vitro functional assays and analysed the patients’ phenotypes.ResultsAll variants were novel, distinct and heterozygous. Seven HMG-domain missense and five stop-gain variants were classified as pathogenic or likely pathogenic variant (L/PV) as they precluded SOX4 transcriptional activity in vitro. Five HMG-domain and non-HMG-domain missense variants were classified as of uncertain significance (VUS) due to negative results from functional tests. When known, inheritance was de novo or from a mosaic unaffected or non-mosaic affected parent for patients with L/PV, and from a non-mosaic asymptomatic or affected parent for patients with VUS. All patients had neurodevelopmental, neurological and dysmorphic features, and at least one cardiovascular, ophthalmological, musculoskeletal or other somatic anomaly. Patients with L/PV were overall more affected than patients with VUS. They resembled patients with other neurodevelopmental diseases, including theSOX11-related and Coffin-Siris (CSS) syndromes, but lacked the most specific features of CSS.ConclusionThese findings consolidate evidence of a fairly non-specific neurodevelopmental syndrome due toSOX4haploinsufficiency in neurogenesis and multiple other developmental processes.

Background: Maximal left ventricular wall thickness (MLVWT) is a risk factor for sudden cardiac death (SCD) in hypertrophic cardiomyopathy (HCM). In adults, the severity of left ventricular hypertrophy has a nonlinear relationship with SCD, but it is not known whether the same complex relationship is seen in childhood. The aim of this study was to describe the relationship between left ventricular hypertrophy and SCD risk in a large international pediatric HCM cohort. Methods: The study cohort comprised 1075 children (mean age, 10.2 years [±4.4]) diagnosed with HCM (1–16 years) from the International Paediatric Hypertrophic Cardiomyopathy Consortium. Anonymized, noninvasive clinical data were collected from baseline evaluation and follow-up, and 5-year estimated SCD risk was calculated (HCM Risk-Kids). Results: MLVWT Z score was Z scores were associated with heart failure symptoms, unexplained syncope, left ventricular outflow tract obstruction, left atrial dilatation, and nonsustained ventricular tachycardia. One hundred twenty-two patients (71.3%) with MLVWT Z score ≥20 had coexisting risk factors for SCD. Over a median follow-up of 4.9 years (interquartile range, 2.3–9.3), 115 (10.7%) had an SCD event. Freedom from SCD event at 5 years for those with MLVWT Z scores Z score, peaking at Z score +23. The presence of coexisting risk factors had a summative effect on risk. Conclusions: In children with HCM, an inverted U-shaped relationship exists between left ventricular hypertrophy and estimated SCD risk. The presence of additional risk factors has a summative effect on risk. While MLVWT is important for risk stratification, it should not be used either as a binary variable or in isolation to guide implantable cardioverter defibrillator implantation decisions in children with HCM.

Introduction Sudden cardiac death is the most common cause of mortality in childhood onset hypertrophic cardiomyopathy. Identifying individuals at highest risk is therefore an essential part of clinical care but remains challenging. The 12 lead electrocardiogram (ECG) has been proposed as a useful tool for risk stratification and an ECG risk score has been proposed. However, this has not been independently validated and the ECG phenotype of childhood HCM has not been previously described. The aim of this study was to describe the ECG phenotype of childhood HCM in a large, international, multi-centre cohort and investigate its role in risk prediction for arrhythmic events. Methods Participants with an available baseline resting 12-lead ECG were identified from a large, international, multi-centre, retrospective cohort of patients aged less than 16 years fulfilling the diagnostic criteria for HCM (n=1029). Resting baseline ECG was evaluated and ECG variables were extracted. In addition, the ECG risk score based on 8 parameters (deviation in QRS axis, pathological T-wave inversion in limb or precordial leads, ST-segment depression, dominant S-wave in V4, limb-lead amplitude sum, 12-lead amplitude duration product and QTc) was calculated as previously described. The primary study endpoint was a composite outcome of major cardiac events (MACE) defined as SCD, resuscitated cardiac arrest, appropriate implantable cardioverter defibrillator therapy, or sustained ventricular tachycardia (VT) with haemodynamic compromise. The discriminatory performance of using an ECG risk score >5 to identify patients at increased risk of MACE at 5 years was determined using Harrell’s C-index. Results Of 356 patients with childhood HCM (68.9% male, mean age at presentation 10.1 ± 4.5 years), 347 (97.5%) had baseline ECG abnormalities such as: repolarization abnormalities (n=277, 77.8%), left ventricular hypertrophy (n=240. 67.6%), abnormal QRS axis (n=126, 35.4%) or QT prolongation (n=131, 36.8%). Over a median follow up of 3.9 years (IQR 2.0-7.7), 25 (7%) had an arrhythmic event, with an overall annual event rate of 1.38 (95% CI 0.93-2.04). No ECG variables were associated with 5-year MACE on univariable or multivariable Cox regression analysis. Of the 164 participants with an ECG score >5, 153 (93.3%) did not have a MACE within 5 years. Harrell’s C-index (the probability of correctly distinguishing between high and low risk patients using an ECG risk score threshold of >5) was 0.60 (95% CI 0.484-0.715) at 5 years. The corresponding positive and negative predictive values were 6.7% (95% CI 4.7 – 9.4%) and 96.9% (95% CI 94.2 – 98.4%). Conclusions In a large, international, multi-centre cohort of children with HCM, ECG abnormalities are common. No ECG characteristic, either in isolation or combined in the ECG risk score, was associated with 5-year MACE risk. This suggests that the role of the baseline ECG phenotype in improving risk stratification in childhood HCM is limited. Conflict of Interest None

The original version of this Article contained an error in the spelling of the author Pleuntje J. van der Sluijs, which was incorrectly given as Eline (P. J.) van der Sluijs. This has now been corrected in both the PDF and HTML versions of the Article.

Purpose: Several studies have reported diagnostic yields up to 57% for rapid exome or genome sequencing (rES/GS) as a single test in neonatal intensive care unit (NICU) patients, but the additional yield of rES/GS compared with other available diagnostic options still remains unquantified in this population. Methods: We retrospectively evaluated all genetic NICU consultations in a 2-year period. Results: In 132 retrospectively evaluated NICU consultations 27 of 32 diagnoses (84.4%) were made using standard genetic workup. Most diagnoses (65.6%) were made within 16 days. Diagnostic ES yield was 5/29 (17.2%). Genetic diagnoses had a direct effect on clinical management in 90.6% (29/32) of patients. Conclusions: Our study shows that exome sequencing has a place in NICU diagnostics, but given the associated costs and the high yield of alternative diagnostic strategies, we recommend to first perform clinical genetic consultation.

OBJECTIVES We evaluated the outcomes of biventricular repair after initial hybrid palliation performed in small infants with various forms of left ventricle hypoplasia. METHODS Between September 2010 and January 2020, a total of 27 patients had biventricular repair after hybrid palliation at a median age of 11 days. Indications for the hybrid approach included growth promotion of the left ventricle outflow tract and/or the aortic valve in 14 patients and that of the left ventricle in 13 patients. Seven reinterventions and 7 reoperations were performed during the interstage period. Significant growth of left ventricle parameters was noted during the median interstage period of 62 days. Sixteen subjects had aortic arch repair, ventricular septal defect closure and relief of subaortic stenosis; 5 patients had the Ross–Konno procedure; 5 patients underwent the Yasui procedure; and 1 patient had unbalanced atrioventricular septal defect and aortic arch repair. RESULTS Twenty-three patients (85.2%) are alive at a median follow-up of 3.3 years. Two and 3 patients died early and late after achieving biventricular circulation, respectively. There were 22 reinterventions and 15 reoperations after biventricular repair. CONCLUSIONS Hybrid palliation can stimulate left heart growth in some patients with left ventricle hypoplasia. More patients may eventually achieve biventricular circulation than was initially thought. Additional interventions and operations are foreseeable. Despite ventricular rehabilitation, some patients with borderline left ventricles may develop restrictive physiology.

Aims The Leiden Convention coronary coding system structures the large variety of coronary anatomical patterns; isolated and in congenital heart disease. It is widely used by surgeons but not by cardiologists as the system uses a surgeons’ cranial view. Since thoracic surgeons and cardiologists work closely together, a coronary coding system practical for both disciplines is mandatory. To this purpose, the ‘surgical’ coronary coding system was adapted to an ‘imaging’ system, extending its applicability to different cardiac imaging techniques. Methods and results The physician takes place in the non-facing sinus of the aortic valve, oriented with the back towards the pulmonary valve, looking outward from the sinus. From this position, the right-hand sinus is sinus 1, and the left-hand sinus is sinus 2. Next, a clockwise rotation is adopted starting at sinus 1 and the encountered coronary branches described. Annotation of the normal anatomical pattern is 1R-2LCx, corresponding to the ‘surgical’ coding system. The ‘imaging’ coding system was made applicable for Computed Tomography (CT), Magnetic Resonance Imaging (MRI), echocardiography, and coronary angiography, thus facilitating interdisciplinary use. To assess applicability in daily clinical practice, images from different imaging modalities were annotated by cardiologists and cardiology residents and results scored. The average score upon evaluation was 87.5%, with the highest scores for CT and MRI images (average 90%). Conclusion The imaging Leiden Convention is a coronary coding system that unifies the annotation of coronary anatomy for thoracic surgeons, cardiologists, and radiologists. Validation of the coding system shows it can be easily and reliably applied in clinical practice.

Aims The 12-lead electrocardiogram (ECG) is routinely performed in children with hypertrophic cardiomyopathy (HCM). An ECG risk score has been suggested as a useful tool for risk stratification, but this has not been independently validated. This aim of this study was to describe the ECG phenotype of childhood HCM in a large, international, multi-centre cohort and investigate its role in risk prediction for arrhythmic events. Methods and results Data from 356 childhood HCM patients with a mean age of 10.1 years (±4.5) were collected from a retrospective, multi-centre international cohort. Three hundred and forty-seven (97.5%) patients had ECG abnormalities at baseline, most commonly repolarization abnormalities (n = 277, 77.8%); left ventricular hypertrophy (n = 240, 67.7%); abnormal QRS axis (n = 126, 35.4%); or QT prolongation (n = 131, 36.8%). Over a median follow-up of 3.9 years (interquartile range 2.0–7.7), 25 (7%) had an arrhythmic event, with an overall annual event rate of 1.38 (95% CI 0.93–2.04). No ECG variables were associated with 5-year arrhythmic event on univariable or multivariable analysis. The ECG risk score threshold of >5 had modest discriminatory ability [C-index 0.60 (95% CI 0.484–0.715)], with corresponding negative and positive predictive values of 96.7% and 6.7% Conclusion In a large, international, multi-centre cohort of childhood HCM, ECG abnormalities were common and varied. No ECG characteristic, either in isolation or combined in the previously described ECG risk score, was associated with 5-year sudden cardiac death risk. This suggests that the role of baseline ECG phenotype in improving risk stratification in childhood HCM is limited.

Background In a normal neonatal heart the ductus arteriosus forms the direct continuity of the pulmonary trunk to the descending aorta being the main channel for the prenatal blood flow. The pulmonary arteries originate separately from the pulmonary trunk. In congenital heart malformations with pulmonary stenosis to atresia there is often an abnormal lateral DA to left pulmonary artery connection combined with a localised narrowing (pulmonary ductal coarctation / PDC) or even interruption. We investigated embryonic remodelling and pathogenesis of this area Material and methods Normal development was studied in WntCre reporter mice (E10.0-12.5) for neural crest cells and Nkx2.5 immunostaining for second heart field cells. Data were compared to stage matched human embryos including histopathology of neonatal specimen, and a VEGF120/120 mutant mouse strain developing pulmonary atresia. Results Normal mouse and human embryos showed that, in the early embryo, the mid-pharyngeal endothelial plexus, partly covered by second heart field, connected side-ways to the 6 th pharyngeal arch artery (PAA). The ventral segment of this PAA effectively formed the proximal pulmonary artery. The origin of the cells encasing the endothelial tubes differed significantly. The dorsal 6 th PAA segment (future DA on the left side) was solely surrounded by neural crest cells. The ventral segment had a dual outer lining with neural crest cells laterally and second heart field cells medially, while the distal pulmonary artery was covered by neither of these cells. The asymmetric contribution of second heart field to the future pulmonary trunk on the left side of the aortic sac (so-called pulmonary push) was evident. During remodelling the ventral segment of the 6 th PAA became incorporated into the pulmonary trunk leading to a separate connection of the left and right pulmonary arteries to the latter. The VEGF120/120 embryos showed a severely stunted pulmonary push and later on a variety of vascular anomalies in the DA to pulmonary artery connections. Conclusion Side-way connection of the DA to the left pulmonary artery is a congenital anomaly. The primary problem is a stunted development of the second heart field-derived pulmonary push leading to pulmonary stenosis/atresia and a subsequent lack of proper incorporation of the ventral segment of the 6 th PAA into the aortic sac. Clinically, the aberrant smooth muscle tissue of the DA should be addressed to prohibit development of severe PDC or even interruption of the left pulmonary artery.

The muscular ductus arteriosus (DA) has many unique characteristics setting it apart from the adjoining elastic arteries. Preparation for neonatal closure takes place in utero with the development of intimal thickening. Ductus-specific gene and protein expression patterns were demonstrated during this process. We postulated that the closing process, with increased expression of progerin, might reflect aspects of premature ageing. Persistent patency of the DA, can be congenitally or immaturity based. During embryonic development the sixth pharyngeal arch arteries are the last to develop. In avian embryos this arch is divided into a proximal (part of the future pulmonary artery) and a distal part (on the left side the origin of the DA). The consequence is that the pulmonary arteries have a double vascular contribution being a proximal sixth arch artery component and a distal true pulmonary artery segment. We have conclusive evidence that this is not encountered in the human embryo. Both sixth arch arteries and the right and left pulmonary arteries connect separately and at distinct locations to the pulmonary trunk side of the aortic sac. The insertion of the wall of the DA between the proximal and distal part of the left pulmonary artery, referred to as pulmonary coarctation, constitutes a congenital malformation and not a remnant of what is encountered during normal development. This configuration is found almost exclusively in combination with pulmonary atresia leading to neonatal interruption of the proximal left pulmonary artery with consequences for surgical or intervention repair.

Objectives: Supravalvar aortic stenosis (SVAS) is a rare congenital anomaly. The “single-patch technique,” “‘two sinus augmentation with an inverted Y-patch” (both nonsymmetrical corrections), “three-patch technique,” and the “slide aortoplasty” (both symmetrical corrections) are the techniques implemented by the majority of surgeons for the correction of SVAS. In the few studies that compared these techniques, no technique was shown to be superior over another. The aim of the present study is to review the 52-year experience with the surgical correction of SVAS in two of four congenital cardiothoracic surgical centers in the Netherlands. Methods: We retrospectively reviewed all patient files of those who underwent an operation to correct their SVAS, between 1962 and 2014 in our centers. Patients were divided according to their operating technique. These groups were compared using the end points freedom from reoperation and mortality. Results: A total of 49 patients were included, 23 (46.9%) patients in the nonsymmetrical group and 26 (53.1%) patients in the symmetrical group. Survival after 20 years in the nonsymmetrical group was 80% (standard error [SE]: 0.091) and in the symmetrical group was 85% (SE: 0.085; P = .163). Freedom from reoperation after 20 years in the nonsymmetrical group was 88% (SE: 0.079) and in the symmetrical group was 71% (SE: 0.107; P = 0.313). Conclusion: In this patient group, there is no significant difference in survival and freedom from reoperation between the different surgical techniques for SVAS repair. Compared to the survival in the general population, the survival of SVAS patients is remarkably low. Apparently, SVAS is not a benign disease and probably patients should be followed more closely for the rest of their lives.

OBJECTIVES We analysed the outcomes of patients undergoing biventricular repair (BVR) after an initial hybrid Norwood approach as a salvage procedure in extremely sick infants; or as the initial palliation in patients with uncertain feasibility of single-stage BVR due to severe left ventricular outflow tract obstruction; or as part of a left ventricle (LV) recruitment strategy in patients with borderline LVs. METHODS Between September 2010 and July 2018, 26 patients underwent BVR after initial hybrid palliation at a median age of 13 days. The rationale for the hybrid approach was to promote the growth of the LV in 10 patients and that of the left ventricular outflow tract and/or aortic valve in 12 patients and to be a salvage procedure in 4 patients. Significant growth of the LV was noted during the interstage period, which had a median length of 65 days (P = 0.008). Fourteen patients underwent aortic arch repair, ventricular septal defect closure and relief of subaortic stenosis; 5 patients underwent the Yasui procedure; 4 patients had the Ross–Konno procedure; 2 patients had an arterial switch operation; and 1 patient had truncus arteriosus repair. RESULTS Twenty-two patients (84.6%) are alive at a median follow-up period of 1.8 (range 0.04–6.2) years. There were 2 early and 2 late deaths. Nineteen catheter-based reinterventions and 15 reoperations were performed after BVR. CONCLUSIONS The hybrid Norwood procedure permits stabilization of critical infants. It allows for growth of left ventricular structures in some patients with borderline left hearts and in those with severe left ventricular outflow tract obstruction. More patients may eventually have BVR than was thought during the newborn period.

The first human mutations in GATA6 were described in a cohort of patients with persistent truncus arteriosus, and the phenotypic spectrum has expanded since then. This study underscores the broad phenotypic spectrum by presenting two patients with de novo GATA6 mutations, both exhibiting complex cardiac defects, pancreatic, and other abnormalities. Furthermore, we provided a detailed overview of all published human genetic variation in/near GATA6 published to date and the associated phenotypes (n = 78). We conclude that the most common phenotypes associated with a mutation in GATA6 were structural cardiac and pancreatic abnormalities, with a penetrance of 87 and 60%, respectively. Other common malformations were gallbladder agenesis, congenital diaphragmatic hernia, and neurocognitive abnormalities, mostly developmental delay. Fifty‐eight percent of the mutations were de novo, and these patients more often had an anomaly of intracardiac connections, an anomaly of the great arteries, and hypothyroidism, compared with those with inherited mutations. Functional studies mostly support loss‐of‐function as the pathophysiological mechanism. In conclusion, GATA6 mutations give a wide range of phenotypic defects, most frequently malformations of the heart and pancreas. This highlights the importance of detailed clinical evaluation of identified carriers to evaluate their full phenotypic spectrum.

Objectives Bioprosthetic pulmonary valve conduits have been reported with an increased risk of endocarditis. Thrombus formation is considered as source of these serious and life-threatening infections. We reviewed a series of explanted valved pulmonary conduits for histological evidence for thrombus formation. Materials and methods Explanted bioprosthetic pulmonary valves were fixed in formalin and embedded in paraffin or in methylmethacrylate. Standard staining as well as immunohistochemical staining techniques were applied. Native pulmonary valves of German domestic pigs served as controls. Results 47 valved pulmonary conduits (Hancock n = 23, Homograft n = 7, Contegra n = 7, Melody n = 7, other n = 3) were analyzed histologically. Average time of implantation had been 63 months (6 to 342 months). Indications for explantation included significant obstruction (n = 45), regurgitation (n = 7), and/or endocarditis (n = 6). In 44/47 (93%) specimen, we found accumulation of thrombotic material at the basis of the semilunar valve sinus to a variable degree. 11 patients had been treated with antiplatelet agents, 2 had received anticoagulants at the time of explantation. There was no suspicion of thrombus formation clinically or echocardiographically prior to explantation in any of the patients. Control porcine pulmonary valves (n = 5) did not show any evidence of accumulation of thrombotic material. Conclusions In a large series of explanted valved pulmonary conduits, formation of subclinical, mostly non-infectious thrombotic material was an almost ubiquitous finding. We speculate that high incidence of endocarditis in bioprosthetic valves may in part be explained by thrombus apposition at the basis of conduit valve sinus.

ObjectiveIn patients with bicuspid aortic valve (BAV), coronary anatomy is variable. High take-off coronary arteries have been described, but data are scarce, especially when associated with complex congenital heart disease (CHD). The purpose of this study was to describe coronary patterns in these patients.MethodsIn 84 postmortem heart specimens with BAV and associated CHD, position and height of the coronary ostia were studied and related to BAV morphology.ResultsHigh take-off right (RCA) and left coronary arteries (LCA) were observed in 23% and 37% of hearts, respectively, most frequently in hearts with hypoplastic left ventricle (HLV) and outflow tract anomalies. In HLV, high take-off was observed in 18/40 (45%) more frequently of LCA (n=14) than RCA (n=6). In hearts with aortic hypoplasia, 8/13 (62%) had high take-off LCA and 6/13 (46%) high take-off RCA. High take-off was seen 19 times in 22 specimens with perimembranous ventricular septal defect (RCA 8, LCA 11). High take-off was associated with type 1A BAV (raphe between right and left coronary leaflets), more outspoken for the RCA. Separate ostia of left anterior descending coronary artery and left circumflex coronary artery were seen in four hearts (5%), not related to specific BAV morphology.ConclusionHigh take-off coronary arteries, especially the LCA, occur more frequently in BAV with associated CHD than reported in normal hearts and isolated BAV. Outflow tract defects and HLV are associated with type 1A BAV and high take-off coronary arteries. Although it is unclear whether these findings in infants with detrimental outcome can be related to surviving adults, clinical awareness of variations in coronary anatomy is warranted.

Objectives Variations in coronary anatomy are common and may relate to the position of the coronary ostium relative to the aortic sinus, the angle of coronary take-off, or the course of the coronary arterial branches. Several classification systems have been proposed. However, they all lack a simple rationale that is applicable irrespective of the relative position of the great arteries, as well as in bicuspid aortic valves. We present a modification of a relatively simple system introduced in the early 1980s, designated the "Leiden Convention." Methods The first step of the Leiden Convention is that the clinician takes position in the nonfacing sinus of the aorta looking toward the pulmonary orifice. The right-hand facing sinus is sinus 1, and the left-hand facing sinus is sinus 2. The coronary branches arising from sinus 1 are annotated proceeding in a counterclockwise fashion toward sinus 2. "Usual" (normal) coronary anatomy would be 1R-2LCx. Given their clinical relevance, single sinus coronary arteries are discussed separately. Results This system was originally designed and highly applicable in hearts with an altered great artery relationship, such as in the variable and complicated patterns seen in transposition of the great arteries and double outlet right ventricle. The modified system also can be used in cases with normally related great arteries, cases with single sinus coronary arteries, and cases with bicuspid aortic valves. Conclusions The modified Leiden Convention is not a strict classification but a simple coronary coding system that is broadly applicable.

The aortic and pulmonary valve share a common developmental origin from the embryonic arterial trunk. Bicuspid aortic valve is the most common congenital anomaly and can occur isolated as well as in association with other congenital heart disease (CHD). Data on pulmonary valve morphology in these cases are scarce. In this study, we aimed to determine pulmonary valve morphology in hearts with BAV associated with CHD. In 83 post-mortem heart specimens with BAV and associated CHD, pulmonary valve morphology was studied and related to BAV morphology. In 14/83 (17%) hearts, the pulmonary valve was affected, bicuspid in 8/83 (10%), dome-shaped in 3/83 (4%) and atretic in 3/83 (4%). In specimens with a bicuspid pulmonary valve, 5/8 (63%) had a strictly bicuspid aortic valve (without raphe), 2/3 hearts (67%) with dome-shaped pulmonary valves and 2/3 hearts (67%) with atretic pulmonary valves had BAV without raphe. Six out of eight (75%) specimens with a bicuspid pulmonary valve had a perimembranous ventricular septal defect (VSD). 4/8 (50%) specimens with a bicuspid pulmonary valve were associated with chromosomal abnormalities: 3 (38%) had trisomy 18 and 1 (13%) had trisomy 13. In BAV with associated CHD, abnormal pulmonary valve morphology was observed in 17% of the hearts. The majority of hearts with abnormal pulmonary valve morphology had a Type B bicuspid aortic valve (without raphe). Bilateral semilunar valvular disease is associated with Type B BAVs and in many cases related to chromosomal abnormalities. As this study was performed in post-mortem specimens with high frequency of associated CHD, caution is warranted with application of these results to the general BAV population.

Background The aim of this study was to analyze long-term outcomes after the Ross procedure, focusing on autograft function and risk of reoperation in time. Methods Between February 1994 and February 2016, 154 patients underwent the Ross (n = 105) and Ross-Konno (n = 49) procedure at our institution and were included in this study. Data were collected retrospectively from patients' medical records or through telephone contact. Competing risks analyses were performed to determine incidences of death and reoperation. A multistate model was constructed to provide insights in the clinical trajectory after operation. Results Median age was 12 years, 74% were pediatric patients, and 66% had previous surgical procedures. There were 8 (5%) early deaths, 6 of whom underwent the Ross-Konno procedure, and 10 (7%) late deaths. Survival rates at 15 and 20 years were 86% in the total cohort and 91% in the isolated Ross subgroup. Linearized occurrence rates of endocarditis and valve thrombosis, thromboembolism, and bleeding events combined were 0.30% per patient-year and 0.15% per patient-year, respectively. Cumulative incidences of all-cause reoperation at 15 and 20 years were 35.2% and 45.3%, respectively. Twenty-six patients needed autograft reoperation, 20 due to dilatation. Cumulative incidences of autograft reoperation at 15 and 20 years were 20.1% and 31.1%, respectively. At latest echocardiogram, 4 patients had moderate aortic regurgitation and none had stenosis. Conclusions The Ross procedure can be performed safely in young patients with low number of valve-related events. Autograft function remains stable in the first decade after operation, but autograft dilatation in the second decade necessitates reintervention.

Background Mutations in the myosin heavy chain 7 (MYH7) gene commonly cause cardiomyopathy but are less frequently associated with congenital heart defects. Methods In this study, we describe a mutation in the MYH7 gene, c. 5754C > G; p. (Asn1918Lys), present in 15 probands and 65 family members. Results Of the 80 carriers (age range 0–88 years), 46 (57.5%) had cardiomyopathy (mainly dilated cardiomyopathy (DCM)) and seven (8.8%) had a congenital heart defect. Childhood onset of cardiomyopathy was present in almost 10% of carriers. However, in only a slight majority (53.7%) was the left ventricular ejection fraction reduced and almost no arrhythmias or conduction disorders were noted. Moreover, only one carrier required heart transplantation and nine (11.3%) an implantable cardioverter defibrillator. In addition, the standardised mortality ratio for MYH7 carriers was not significantly increased. Whole exome sequencing in several cases with paediatric onset of DCM and one with isolated congenital heart defects did not reveal additional known disease-causing variants. Haplotype analysis suggests that the MYH7 variant is a founder mutation, and is therefore the first Dutch founder mutation identified in the MYH7 gene. The mutation appears to have originated in the western region of the province of South Holland between 500 and 900 years ago. Conclusion Clinically, the p. (Asn1918Lys) mutation is associated with congenital heart defects and/or cardiomyopathy at young age but with a relatively benign course. Electronic supplementary material The online version of this article (10.1007/s12471-017-1037-5) contains supplementary material, which is available to authorized users.

Importance: Sudden cardiac death (SCD) is the most common mode of death in childhood hypertrophic cardiomyopathy (HCM), but there is no validated algorithm to identify those at highest risk.Objective: To develop and validate an SCD risk prediction model that provides individualized risk estimates.Design, Setting, and Participants: A prognostic model was developed from a retrospective, multicenter, longitudinal cohort study of 1024 consecutively evaluated patients aged 16 years or younger with HCM. The study was conducted from January 1, 1970, to December 31, 2017.Exposures: The model was developed using preselected predictor variables (unexplained syncope, maximal left-ventricular wall thickness, left atrial diameter, left-ventricular outflow tract gradient, and nonsustained ventricular tachycardia) identified from the literature and internally validated using bootstrapping.Main Outcomes and Measures: A composite outcome of SCD or an equivalent event (aborted cardiac arrest, appropriate implantable cardioverter defibrillator therapy, or sustained ventricular tachycardia associated with hemodynamic compromise).Results: Of the 1024 patients included in the study, 699 were boys (68.3%); mean (interquartile range [IQR]) age was 11 (7-14) years. Over a median follow-up of 5.3 years (IQR, 2.6-8.3; total patient years, 5984), 89 patients (8.7%) died suddenly or had an equivalent event (annual event rate, 1.49; 95% CI, 1.15-1.92). The pediatric model was developed using preselected variables to predict the risk of SCD. The model's ability to predict risk at 5 years was validated; the C statistic was 0.69 (95% CI, 0.66-0.72), and the calibration slope was 0.98 (95%, CI 0.59-1.38). For every 10 implantable cardioverter defibrillators implanted in patients with 6% or more of a 5-year SCD risk, 1 patient may potentially be saved from SCD at 5 years.Conclusions and Relevance: This new, validated risk stratification model for SCD in childhood HCM may provide individualized estimates of risk at 5 years using readily obtained clinical risk factors. External validation studies are required to demonstrate the accuracy of this model's predictions in diverse patient populations.

Objectives The Ross-Konno procedure is a last resort for patients with complex multilevel left ventricular outflow tract obstruction (LVOTO) often having other cardiovascular anomalies. It is typically preceded by multiple surgeries. Literature is scarce on long-term follow-up series. Therefore, we have reviewed our 20-year experience with this procedure in order to provide insights in patients' outcomes and to optimize patient selection. Methods Between January 1995 and December 2014, 48 patients underwent the Ross-Konno procedure. The median age at operation was 12.8 months (range, 11 days to 31 years). Twenty-two (46%) patients were under 1 year of age. Forty-four (92%) patients had undergone a total of 82 previous procedures. Eleven (23%) patients had concomitant surgery, predominantly mitral valve (n = 5) and aortic arch surgery (n = 5). Results The median follow-up time was 4.3 years (range, 0-20 years). There were 6 (12.5%) early deaths and 4 (8.3%) late deaths. Estimated overall survival at 5, 10 and 15 years was 83, 79 and 70%, respectively. Poor LV function was a risk factor for early mortality (odds ratio = 9.5; 95% confidence interval = 1.4-63.7; P = 0.020). Twelve patients required a total of 29 procedures in 17 reoperations. Five patients required reoperation for autograft failure at a median of 14 years (range, 5-15 years) postoperatively. Estimated freedom from all causes of reoperation at 5, 10 and 15 years was 82, 55 and 30%, respectively. All patients had complete and durable relief of LVOTO. At latest follow-up, 5 patients had a sinus of Valsalva Z-score of 5 or greater. One patient had Grade II autograft insufficiency. Conclusions The Ross-Konno procedure is a durable solution for multilevel LVOTO in a highly complex patient population with high incidence of previous procedures. High early mortality rates in patients with impaired left ventricular function emphasize the importance of patient selection. Freedom from reoperation shows a continuous attrition rate. Reoperation for autograft failure may occur late after the Ross-Konno procedure.

OBJECTIVES Right ventricular outflow tract obstruction (RVOTO) is one of the reasons for late reinterventions after repair of transposition of the great arteries (TGA) with aortic arch obstruction (AAO). The aim of the present study was to identify predictors of reoperation for RVOTO in patients who underwent arterial switch operation (ASO) and arch repair for TGA or Taussig-Bing anomaly with AAO. METHODS Between 1977 and 2015, 45 patients [TGA/intact ventricular septum (IVS) 5, TGA/ventricular septal defect (VSD) 13, Taussig-Bing 27] with coarctation (21), arch hypoplasia (5), coarctation and hypoplasia (12) and aortic arch interruption (7) underwent ASO and arch repair. The median age at the ASO was 19 days (range, 1 day to 12.7 years). AAO was repaired concomitantly with ASO in 36 patients. Operation reports and 2D-echocardiographic data were retrospectively reviewed to determine the following parameters: position of the great arteries, coronary artery anatomy, and diameters of RVOT, aortic annulus, aortic sinotubular-junction, pulmonary annulus and transverse aortic arch previous to ASO. The median follow-up time was 6 years (range, 0-30 years). Four patients were lost to follow-up; reliable echo data were available in 24 subjects. Cox proportional hazard models were performed to examine predictors of reoperation for RVOTO. RESULTS Thirty-day mortality rate after ASO was 13% (n = 6), and late mortality rate 9% (n = 4). Ten patients (TGA/VSD 2, Taussig-Bing 8) had 14 reoperations for RVOTO. One patient died after reoperation. Taussig-Bing anomaly was a significant predictor of reoperation for RVOTO [hazard ratio (HR) = 5.5, 95% confidence interval (CI) = 1.15-26.38, P = 0.033]. Higher preoperative aortic annulus Z-score significantly decreased the reoperation risk (HR = 0.6, 95% CI = 0.42-0.93, P = 0.020). In reoperated patients, the mean gradient across the RVOT reduced from 84 ± 12.2 mmHg prior to reoperation to 15.29 ± 13.70 mmHg at latest follow-up. CONCLUSIONS Taussig-Bing anomaly and smaller preoperative aortic annulus diameter (Z-score) were significant predictors of reoperation for RVOTO in patients after ASO for TGA or Taussig-Bing anomaly with AAO. In Taussig-Bing hearts, the more complex anatomy often necessitates modifications of the operation technique, sometimes precluding RVOT relief at primary ASO. During follow-up, the possibility of recurrent RVOTO should always be considered in this specific patient population. Yet, in case of a reoperation for RVOTO, the surgical relief is in general effective.

The ductus arteriosus (DA) is a fetal vessel bypassing the still nonfunctional lungs. Closure of the DA at birth is essential for the transition from a fetal to a neonatal circulation. This closing process begins with a physiological contraction followed by definitive anatomical closure. The latter process starts already before birth by development of intimal thickening followed after birth by degeneration of the inner media, including cytolytic necrosis and apoptosis. The DA will remain patent when there is insufficient maturation in prematurely born babies or when there is a structural abnormality as seen in persistent DA (PDA). The histological changes during normal DA closure resemble the features seen in the premature ageing vessels in children with the Hutchinson progeria syndrome. The latter syndrome is caused by a mutation in the lamin A/C gene resulting in accumulation of the progerin splice variant. We studied human DA biopsies from the fetal to the neonatal period to investigate whether lamin A/C and progerin might be involved in the DA closure process. The results show an increase in the intima and inner media of progerin in the normal neonatal DA, while expression of lamin A/C is diminished. In the non-closing aorta, the fetal DA and the PDA, no or hardly any progerin expression was found. We postulate that the lamin A/C to progerin balance is important during normal anatomical closure of the DA presenting a unique case of physiological premature vascular ageing.

Objective: Biventricular repair of hearts with left atrial isomerism often necessitates complex atrial and ventricular baffle procedures. We analysed our experience with an accent on baffle techniques. Methods: From 1997 until 2008, 12 patients (four male) with left atrial isomerism received biventricular repair. Their median age at surgery was 9 (range: 1-24) months. Four patients had dextrocardia. Nine patients presented with left superior vena cava, three with absent right superior vena cava, five with unroofed coronary sinus and nine others with inferior vena cava interruption with (hemi)azygos continuation. Anomalous pulmonary venous drainage was present in three patients. Eight had a monoatrium. Atrioventricular septal defect (AVSD) occurred in six (complete AVSD in two), One patient with complete AVSD had right pulmonary agenesia with tong segment tracheal stenosis. Multiple VSDs presented in one whereas three patients had double-outlet right ventricle (DORV) (one with borderline LV hypoplasia). Two had previous pulmonary artery banding. Complex intra-atrial baffle constructions were performed in seven patients. Complete AVSDs were corrected using two patches and all other AVSDs had one patch repair. Multiple VSDs were closed directly. DORV patients had intraventricular tunnel repair. Results: No early mortality occurred. Median follow-up was 54 (range: 2-134) months. One patient with complete AVSD and pulmonary agenesia died late after tracheal repair. Four patients needed five re-operations (closure of residual ASD (one), relief of left (two) or right (two) ventricular outflow obstruction, pulmonary artery branch plasty (one)). There was no atrial baffle stenosis. Four received a pacemaker. All survivors are in NYHA class I. Conclusions: Survival and functional status of left isomerism patients after biventricular repair is good. Complex repairs with atrial or ventricular baffles are frequent. Arrhythmias were common and pose a concern late after repair. (C) 2010 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

The unique differentiation program of the ductus arteriosus (DA) is essential for its specific task during fetal life and for the adapting circulation after birth. Phenotypic changes occur in the DA during the normal maturation and definitive closure. Morphological abnormalities of the vessel wall characterize the persistent DA (PDA) in older children. Here, we give an overview of the animal models of DA regulation and remodeling. Genetic research has identified the cause of syndromic forms of PDA, such as the TFAP2B mutations in Char syndrome. Genes that interfere with the remodeling of vascular smooth muscle cells (VSMCs) of the ductal media are affected in virtually all of these anomalies. Therefore, the pivotal regulatory role of VSMCs is emphasized. A better understanding of the genetic background of this developmental process may help develop new strategies to manipulate the DA in premature infants, neonates with duct-dependent anomalies, and patients with syndromic and non-syndromic PDA.

BACKGROUND: Percutaneous pulmonary valve implantation (PPVI) has been introduced as therapy for right ventricular (RV) to pulmonary artery conduit dysfunction in patients with congenital heart disease. It has been shown that RV systolic function improved early after PPVI. The effects of PPVI on RV diastolic function and RV hypertrophy have not yet been studied. PURPOSE: The objective of this study is to assess early and late changes in systolic and diastolic RV function and RV mass after PPVI. MATERIALS AND METHODS: Fourteen patients underwent PPVI (7 male, median age 15 years). Cardiac magnetic resonance imaging was performed before and at 2 time points after PPVI (at 1 and 16 months). Right ventricular volume and systolic and diastolic function as well as RV mass were assessed. RESULTS: At 1 and 16 months after PPVI, the RV mass decreased from 28.6 +/- 2.1 to 25.6 +/- 2.2 g/m(2) (P = .03) and to 22.3 +/- 2.1 g/m(2) (P = .002). E/A volume ratio increased from 1.91 +/- 0.4 to 2.6 +/- 0.4 (not significant [NS]) and to 3.3 +/- 0.4 (P = .01). E/A peak flow ratio increased from 1.34 +/- 0.14 to 1.48 +/- 0.16 (NS) and to 1.73 +/- 0.14 (P = .04). E-wave deceleration time increased from 142 +/- 25 to 160 +/- 27 milliseconds (NS) and to 211 +/- 26 milliseconds (P = .007). At 1 month, RV end-diastolic volume decreased from 124 +/- 8 to 113 +/- 8 mL (P = .01) and RV ejection fraction increased from 36% +/- 2% to 46% +/- 2% (P = .001) without further improvement at 16 months. CONCLUSION: After PPVI, in contrast to rapid improvement of RV systolic function, the improvement of RV diastolic function is delayed. The reduction of RV mass appears to be the underlying mechanism for improvement of RV diastolic function. Long follow-up for patients with PPVI is recommended

Background: Advances in diagnostic testing and surgical techniques have resulted in reduced mortality in neonates with congenital heart disease (CHD) and a major concern for neurological morbidity in the presence of preoperative neurological injury. Objectives: To determine the incidence and nature of preoperative cerebral ultrasound abnormalities in neonates with major CHD and to examine the relationship between cerebral abnormalities and the type of CHD. Methods: Retrospective study; inclusion criteria: (1) neonates with major CHD admitted to the NICU over a 3-y period, (2) gestational age > 35 wk, (3) documented preoperative cranial ultrasound available; exclusion criteria: (1) small for gestational age, (2) other congenital anomalies and/or chromosomal abnormalities, (3) a 5-min Apgar score < 7, (4) congenital infection. Cranial ultrasounds (CUS) were reviewed without knowledge of the cardiac defect. CHDs were categorized. Results: Fifty of 108 neonates with CHD met the inclusion criteria. Twenty-one patients (42%) had abnormalities on CUS. Thirteen of these (26%) had widened ventricular and/or subarachnoid spaces, three (6%) lenticulostriate vasculopathy, one (2%) calcification in the basal nuclei, and four (8%) had acute ischaemic changes. Cerebral abnormalities occurred more frequendy in patients with coarctation or hypoplastic left heart syndrome (HLHS) than transposition of the great arteries (TGA) (63% vs 14%; n.s.). Conclusion: There is a high incidence of preoperative cerebral ultrasound abnormalities in this group of neonates with major CHD.

Objective. To determine the incidence of congenital heart disease (CHD) and right ventricular outflow tract obstruction (RVOTO) in twin-to-twin transfusion syndrome (TTTS) treated with fetoscopic laser surgery and evaluate the role of increased afterload by determining the difference in blood pressure and endothelin-1 at birth between donor and recipient twins. Design. Prospective study. Setting. Tertiary medical center, serving as the national referral center for fetoscopic laser surgery for TTTS in The Netherlands. Patients. All consecutive cases of monochorionic twins with TTTS treated with laser (n = 46 twin pairs) and monochorionic twins without TTTS (n = 55 twin pairs) delivered at our center between June 2002 and June 2005 were included in the study. Interventions. Echocardiography was performed within 1 week after delivery. At birth, blood pressure was measured in all survivors and endothelin-1 was determined in umbilical cord blood. Data on RVOTO in TTTS treated with laser surgery at our center but delivered elsewhere were reviewed retrospectively from medical records. Results. The incidence of CHD in the TTTS group and non-TTTS group was 5.4% (4/74) and 2.3% (2/87) (P = .42), respectively. RVOTO was diagnosed in 1 recipient twin delivered at our center and 2 recipient twins delivered elsewhere. The incidence of RVOTO in recipients was 4% (3/75). Mean systolic blood pressure at birth was similar in donor and recipient twins, respectively, 53 mm Hg vs. 56 mm Hg (P = .42). Mean endothelin-1 level at birth was also similar between donors and recipients, respectively, 14.3 ng/L and 13.2 ng/L (P = .64). Conclusion. The incidence of CHD in TTTS treated with fetoscopic laser surgery is higher than in the general population (5.4% vs. 0.5%). We found no difference in afterload parameters between donors and recipients after laser treatment.

Persistent ductus arteriosus (PDA) is a common cardiovascular anomaly in children caused by the pathologic persistence of the left sixth pharyngeal arch artery. The inbred Brown-Norway (BN) rat presents with increased vascular fragility due to an aortic elastin deficit resulting from decreased elastin synthesis. The strikingly high prevalence of PDA in BN rats in a pilot study led us to investigate this vascular anomaly in 12 adolescent BN rats. In all BN rats, a PDA was observed macroscopically, whereas a ligamentum arteriosum was found in adult controls. The macroscopic appearance of the PDA was tubular (n = 2), stenotic (n = 8), or diverticular (n = 2). The PDA had the structure of a muscular artery with intimal thickening. In the normal closing ductus of the neonatal controls, the media consisted of layers of smooth muscle cells (SMCs) intermingled with layers of elastin. The intima was thin and poor in elastin. By contrast, the media of PDA in BN rats elastin lamellae were absent and the intima contained many elastic fibers. The abnormal distribution of elastin in the PDA of BN rats suggests that impaired elastin metabolism is related to the persistence of the ductus and implicates a genetically determined factor that may link the PDA with aortic fragility.

Item does not contain fulltext AIMS: Stenting has become an established interventional cardiology procedure for congenital heart disease. Although most stent procedures are completed successfully, complications may occur. This multicentre study evaluated early complications after stenting in patients with congenital heart disease, including potential risk factors. METHODS AND RESULTS: In this combined Dutch-Belgian retrospective study, 309 consecutive patients had undergone 366 catheterizations and received 464 stents in 13 different anatomical positions (418 sites). Seventy-two stenting-related complications (19%) occurred, of which 24 (5.7%) were major. Seven procedure-related deaths were documented (2.3%). Stent malpositioning and embolization were most common (7.7%). The use of non-premounted stents tended to be associated with higher complication rates. Centre inexperience with stenting and stenting of native vs. post-surgical stenosis tended to be associated with increased major complication rates. CONCLUSION: After stenting, complications are common for congenital heart disease. The vast diversity of stenotic sites combined with relatively small patient populations makes these procedures sensitive to complications. Combining operator experience may reduce the risks of stenting in congenital heart disease. The availability of premounted stents for greater vessel diameters will likely reduce incidences of stent migration and embolization.

A premature neonate with hydrops was born at 32 weeks of gestation after successful direct fetal amiodarone therapy via cordocentesis for incessant supraventricular tachycardia. After birth the tachycardia could not be controlled despite high doses of amiodarone and flecainide and the patient developed severe respiratory and circulatory failure. After 3 weeks, weighing 2 kg, he underwent successful and uncomplicated catheter ablation of a left free-wall accessory pathway using low-energy radiofrequency. Conclusion:radiofrequency catheter ablation is rarely used in neonates, but when used with caution may provide the optimal treatment.

Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is a rare, but important cause for sudden death in adolescents and young adults. Part of the patients affected show the pattern of autosomal-dominant inheritance. Two pediatric patients with ARVD/C are presented who may reflect the spectrum of clinical presentation of ARVD/C in childhood resulting in difficulties or even delay to establish the correct diagnosis. One patient with a sporadic form of ARVD/C presented with a syncope and spontaneous as well as inducible ventricular tachycardia. On the ECG, an epsilon wave could be identified. An automatic cardioverter defibrillator was implanted. The second patient had a familiar form of ARVD/C with no symptoms. There was a history of frequent sudden deaths in this family. Biopsies of the right ventricular myocardium showed fibrosis with deposition of fatty tissue. There was clear evidence of ARVD/C in the necropsy of the patient's aunt. Therapy with propanolol was started in this patient.

Contains fulltext : 137806.pdf (Publisher’s version ) (Open Access) Closure of the ductus arteriosus (DA) is a crucial step in the transition from fetal to postnatal life. Patent DA is one of the most common cardiovascular anomalies in children with significant clinical consequences especially in premature infants. We aimed to identify genes that specify the DA in the fetus and differentiate it from the aorta. Comparative microarray analysis of laser-captured microdissected endothelial (ECs) and vascular smooth muscle cells (SMCs) from the DA and aorta of fetal rats (embryonic day 18 and 21) identified vessel-specific transcriptional profiles. We found a strong age-dependency of gene expression. Among the genes that were upregulated in the DA the regulator of the G-protein coupled receptor 5 (Rgs5) and the transcription factor distal-less homeobox 1 (Dlx1) exhibited the highest and most significant level of differential expression. The aorta showed a significant preferential expression of the Purkinje cell protein 4 (Pcp4) gene. The results of the microarray analysis were validated by real-time quantitative PCR and immunohistochemistry. Our study confirms vessel-specific transcriptional profiles in ECs and SMCs of rat DA and aorta. Rgs5 and Dlx1 represent novel molecular targets for the regulation of DA maturation and closure.

Atrioventricular nodal reentrant tachycardia was proven during electrophysiologic study in 41 children, aged from 3.7 to 16 years, who were referred for catheter ablation of symptomatic supraventricular tachycardia. Using an abbreviated combined anatomical and electrogram-guided approach for selective ablation of the slow pathway, a steerable ablation catheter was placed at the inferior region of the vestibule of the tricuspid valve close to the orifice of the coronary sinus, with the intention of recording a multicomponent local atrial electrogramm during sinus rhythm. If application of radiofrequency current of 500 kHz at 70°C at this site did not result in a slowly accelerated junctional rhythm, at a rate of less than 120 beats per minute, the catheter was stepwise advanced up to a position midway towards the apex of the triangle of Koch for additional applications of energy. Ablation was achieved in 35 of the patients. In 6 patients, the slow pathway was modulated such that the tachycardia could no longer be induced. The number of applications of energy ranged from 1 to 19, with a median of 6 applications. The mean period of fluoroscopy was reduced to 15.6 (4.3 to 39.8) minutes, while the overall duration of the catheterization procedures ranged from 88 to 280 (mean 173.2) minutes. In none of the patients did we observe permanent high grade atrioventricular block. During follow-up over a mean of 4.1 years, two patients had recurrence of tachycardia, corresponding to a 95% rate of success in the midterm. We conclude that selective radiofrequency ablation of the slow pathway using the abbreviated anatomical and electrophysiological approach is a safe and curative therapeutic approach in children with atrioventricular nodal reentrant tachycardia. Periods required for fluoroscopy can be significantly reduced, and mid-term results are excellent.

Hintergrund: AV-Knoten-Reentry-Tachykardien stellen die zweithaufigste Form supraventrikularer Tachykardien im Kindesalter dar.¶ Patienten und Methoden: Bei 41 jungen Patienten mit einem mittleren Alter von 9,6 (3,7–16) Jahren wurde aufgrund medikamentos refraktarer AV-Knoten-Reentry-Tachykardien (n=38) bzw. rezidivierender Synkopen (n=3) eine elektrophysiologische Untersuchung durchgefuhrt. Hier konnte bei allen Patienten durch programmierte Vorhofstimulation eine duale AV-Knoten-Physiologie nachgewiesen und die typische Tachykardie (slow-fast-Typ, Kammerfrequenz im Mittel 220/min) induziert werden. Ein steuerbarer 7 F Ablationskatheter wurde zunachst in der inferoparaseptalen Region nahe am Ostium des Koronarvenensinus am Trikuspidalklappenanulus plaziert. Ziel war die Registrierung eines spaten und fraktionierten lokalen atrialen Elektrogramms wahrend Sinusrhythmus. Von dieser Stelle ausgehend wurde Hochfrequenzstrom (500 kHz) mit der Zieltemperatur von 70°C zur Ablation des langsam leitenden Schenkels appliziert. Sofern wahrend der Energieabgabe ein langsam beschleunigter junktionaler Rhythmus (

Radiofrequency Current Lesions in Young Pigs. Introduction: Radiofrequency current is widely used in children to ablate accessory AV pathways. Previous data in a pig model demonstrated coronary artery obstruction adjacent to radiofrequency current lesions 48 hours and 6 months after energy delivery. In the present study, the long-term effects (>6 months) of radiofrequency current application on coronary artery vessels in young pigs are assessed. Methods and Results: Radiofrequency current (500 kHz) was delivered over 30 seconds in ten piglets (mean body weight 12.8 kg) using a steerahle 6-French catheter with a 4-mm thermistor tip electrode (target temperature 75°C), Lesions were created under fluoroscopic and electrocardiographic guidance at the lateral right atrial (RA) wall above the tricuspid valve orifice, and at the lateral left atrial and left ventricular wall adjacent to the mitral valve orifice. Selective coronary angiography and intravascular ultrasound (IVUS) studies were performed 3, 6, 9, and 12 months after energy application. After 12 months, the lesions were studied pathohistologically. All lesions consisted of compact fibrous tissue, RA lesions extended to the adjacent right coronary artery and led to coronary artery involvement with increased fibrous tissue in the adventitia and media and intimal thickening in three animals. Coronary arterial narrowing was documented by IVUS during follow-up in all three cases 9 months after energy application. Angiography failed to demonstrate coronary pathology in any of the three animals. Conclusion: The risk of late coronary artery lesions must be considered when catheter ablation at the RA wail is planned in children with free-wall accessory AV pathways.

Supraventricular tachycardia is the most frequent form of symptomatic tachydysrhythmia in children. Neonates and infants with paroxysmal supraventricular tachycardias generally present with signs of acute congestive heart failure. In school-aged children and adolescents, palpitations are the leading symptom. Chronic-permanent tachycardia results in a secondary form of dilated cardiomyopathy. Therapy for episodes of tachycardia depends on the individual situation. In severe haemodynamic compromise, or if ventricular tachycardia is suspected, tachycardia should immediately be terminated by external cardioversion during deep sedation. Vagal manoeuvres are effective in patients with atrioventricular reentrant tachycardias. Adenosine is the drug of first choice in any age group for tachycardias involving the atrioventricular node; its advantages include short half-life and minimal or absent negative inotropic effects. Adenosine may also be used in patients with wide QRS complex tachycardia. Intravenous verapamil is contraindicated in neonates and infants because of the high risk of electromechanical dissociation. In older children (>5 years) and adolescents, verapamil may be administered with the same restrictions as in adult patients (wide QRS complex tachycardia, significant haemodynamic compromise). Spontaneous cessation of tachycardia can be expected in most neonates and infants during the first year of life. Prophylactic pharmacological treatment in this age group is advisable because recognition of tachycardia is often delayed until the occurrence of symptoms. Withdrawal of drug treatment should be attempted around the end of the first year. However, in older children, spontaneous cessation of tachycardia is rare. Prophylactic drug therapy is performed on an empirical basis. Digoxin may be administered in all forms of supraventricular tachycardia in which the atrioventricular node is involved, except in patients with pre-excitation syndrome aged >1 year. In patients with atrioventricular reentrant tachycardia, class IC drugs such as flecainide and propafenone are effective. Sotalol is also effective in atrioventricular reentrant tachycardia, as well as in primary atrial tachycardia. Although amiodarone has the highest antiarrhythmic potential, it should be used with caution because of its high rate of adverse effects. In school-aged children and adolescents, radiofrequency catheter ablation of the anatomical substrate is an attractive alternative to drug therapy, with a rate of permanent cessation of the tachycardia of up to 90%. Despite the clear advantages of this procedure, it should be performed only with unquestionable indication; the long term morphological and electrophysiological sequelae on the growing atrial and ventricular myocardium are still unknown.

Zehn junge Patienten im Alter von 10,5 (Median; Streubreite 6–31) Jahren wurden wegen permanenter junktionaler Reentry-Tachykardien (PJRT, n=7) und atrialer ektoper Tachykardien (AET, n=3) katheterinterventionell mit Hochfrequenzstromablation behandelt. Indikation zur interventionellen Therapie war das Nichtansprechen auf eine medikamentose Therapie mit Antiarrhythmika, im Median 3, bei allen Patienten. Ein Patient hatte eine Synkope erlitten, bei 4 Patienten war die linksventrikulare Verkurzungsfraktion eingeschrankt (PJRT n=3, AET n=1). Die Katheterablation war bei allen Patienten primar erfolgreich. Der Median der Durchleuchtungszeit betrug 17 (10–17) min. Im Median wurden 3 (1–14) Hochfrequenzstromimpulse (500 kHz) bei einer Zieltemperatur von 70°C bzw. mit 30 W fur 30 s appliziert. Bei einem Patienten mit PJRT wurde nach einenm Rezidiv der Tachykardie eine zweite Ablation erfolgreich durchgefuhrt. Wahrend der Nachbeobachtungszeit von im Median 14 (2–61) Monaten bestand bei allen Patienten ein normaler Sinusrhythmus, bei keinem Patienten war eine medikamentose Therapie erforderlich. Die initial eingeschrankte, linksventrikulare Verkurzungsfraktion hatte sich bei allen Patienten mit einer Nachbeobachtungszeit >6 Monaten zwischenzeitlich normalisiert. Die Hochfrequenzstromablation war ein sicheres und effektives Behandlungsverfahren fur junge Patienten mit medikamentos nicht beherrschbaren Formen chronisch-permanenter supraventrikularer Tachykardie wie der junktionalen Reentry-Tachykardie und der atrialen ektopen Tachykardie.

A newborn girl with progressive respiratory distress and cyanosis was found to have severely obstructed supracardiac total pulmonary venous return (TAPVR). Stenting of the stenosis provided immediate and effective relief of the obstruction until corrective surgery was performed. Catheter intervention should be considered in high-risk infants with obstructed supracardiac TAPVR as part of the strategy for preoperative cardiovascular stabilization.

Radiofrequency current (500 kHz) was delivered by temperature guidance (75° C) over a 30-second period in 10 young piglets with a steerable 6F electrode catheter equipped with a thermistor at the 4 mm tip electrode. Lesions were created at the right atrial aspect of the tricuspid valve anulus, at the left ventricular myocardium under the lateral mitral valve anulus, and at the left ventricular apex. After 48 hours, five animals were randomly sacrificed. Lesions in the five animals appeared as transmural gray-white coagulation necrosis. Lymphocytic infiltration around the right atrial lesions extended into the layers of the right coronary artery in four of five animals. After 6 months, lesions consisted of compact fibrous tissue in the remaining five animals. Right atrial lesions extended to the layers of the right coronary artery in four of five pigs. In two animals the lumen of the right coronary artery was narrowed because of intimal thickening by 25% and 40%, respectively. No increase in the lesion size was observed with the growth of the animals. Effects on the right coronary artery as a late sequela after radiofrequency current application may also be possible in human beings and should be considered when radiofrequency current ablation procedures are proposed in infants and young children. (Am Heart J 1997;133:436-40.)