Increased Prevalence of the Electrocardiographic Early Repolarization Pattern in Young Patients With Vagally Mediated Syncope: A Case-Control Study.

Background: Electrocardiographic early repolarization (EER) is linked with idiopathic ventricular fibrillation in adults. It is frequently seen in children, with poorly understood significance. Some evidence suggests that it could be a vagally mediated phenomenon. A retrospective case-control study was undertaken to test the hypothesis that EER is more common among children with typical vasovagal syncope (VVS) than among their peers with nonvagal syncope (NVS) or with no syncope. Methods: Patients aged 4-18 years with syncope were identified by a single-centre database search followed by a review of history for features of VVS (n = 150) or NVS (n = 84). The first available electrocardiogram (ECG) for VVS or for NVS was retrieved. Age- and sex-matched children with no known syncope or heart disease were then identified (n = 216). ECGs were assessed separately for EER based on published criteria by 2 observers blinded to patients' clinical status. Results: Mean age was 12.3 ± 3.2 years, and heart rate was 74.2 ± 16.5 beats/min. EER was more prevalent in VVS (33.3%) than among patients with NVS (19.1%; odds ratio: 2.29; confidence interval: 1.32-5.50) or among those with no syncope (12.5%; odds ratio: 3.14; confidence interval: 1.81-5.46). Heart rates were significantly lower in VVS and NVS (heart rate: 70.1 ± 13.8 and 70.7 ± 12.4 beats/min, respectively) compared with children with no syncope (heart rate: 78.2 ± 18.0 beats/min), both P < 0.001. Conclusions: EER is more common in paediatric patients with VVS than those with NVS or without syncope, consistent with a possible vagal contribution to the ECG finding.

Contexte: La repolarisation précoce (RP) à l'électrocardiogramme (ECG) est liée à une fibrillation ventriculaire idiopathique chez les adultes. Fréquente chez les enfants, sa signification est toutefois nébuleuse. Certaines données laissent penser qu'il pourrait s'agir d'un phénomène d'origine vagale. Une étude rétrospective cas-témoins a donc été réalisée dans le but de vérifier l'hypothèse selon laquelle la RP à l'ECG est plus courante chez les enfants atteints de syncope vasovagale (SVV) typique que chez leurs pairs atteints de syncope non vagale (SNV) ou non atteints de syncope. Méthodologie: Des patients de 4 à 18 ans atteints de syncope ont été recensés au moyen d'une recherche dans la base de données d'un centre, suivie d'un examen des antécédents visant à retracer des manifestations de SVV (n = 150) ou de SNV (n = 84). Le premier ECG disponible traduisant une SVV ou une SNV a été récupéré. Un appariement selon l'âge et le sexe entre les sujets atteints et des enfants qui n'étaient pas atteints de syncope ni de maladie cardiaque (n = 216) a ensuite été effectué. Deux observateurs qui ne connaissaient pas l'état clinique des enfants ont évalué les ECG séparément, à la recherche d'une RP, en se basant sur les critères publiés. Résultats: L'âge moyen des sujets était de 12,3 ± 3,2 ans et la fréquence cardiaque moyenne, de 74,2 ± 16,5 battements/minute. La prévalence de la RP à l'ECG était plus élevée chez les patients atteints de SVV (33,3 %) que chez les patients atteints de SNV (19,1 %; rapport de cotes [RC] : 2,29; intervalle de confiance [IC] : 1,32-5,50) ou les enfants non atteints de syncope (12,5 %; RC : 3,14; IC : 1,81-5,46). La fréquence cardiaque (FC) était significativement plus faible chez les sujets atteints de SVV ou de SNV (FC : 70,1 ± 13,8 et 70,7 ± 12,4 battements/minute, respectivement), en comparaison des enfants non atteints de syncope (FC : 78,2 ± 18,0 battements/minute); p < 0,001 dans les deux cas. Conclusion: La repolarisation précoce à l'ECG est plus courante chez les enfants atteints de syncope vasovagale que chez les enfants atteints de syncope non vagale ou non atteints de syncope, ce qui concorde avec une possible composante vagale dans le tracé de l'ECG.

Transcatheter Closure of a Iatrogenic Gerbode Type Ventricular Septal Defect Post Surgical Septal Myectomy With Mitral and Aortic Valve Replacement.

Jatrogenic communication between left ventricle and right atrium, known as Gerbode type ventricular septal defect (GVSD) may be observed after different surgical interventions. We present a case of iatrogenic GVSD following complex cardiac surgery including septal myectomy combined with mitral and aortic valve replacement, which was successfully closed percutanously by Occlutech septal occluder.

Postnatal recurrence and transesophageal inducibility of prenatally treated fetal supraventricular tachycardia.

BACKGROUND: Antiarrhythmic treatment of fetal supraventricular tachycardia (SVT) is used to prevent morbidity and mortality. The postnatal management of survivors is often arbitrary and varied. OBJECTIVE: The purpose of this study was to examine the utility of a risk-based postnatal management strategy. METHODS: Sixty-six prenatally treated newborns with fetal long or short ventriculoatrial tachycardia were reviewed. Postnatal diagnoses included atrioventricular reentrant tachycardia, atrial ectopic tachycardia, and permanent junctional reciprocating tachycardia. Unless SVT persisted to birth, early neonatal observation without treatment was recommended. For newborns without spontaneous arrhythmia after ≥2 days of observation, inducibility was tested by transesophageal pacing study (TEPS). Postnatal therapy was advised for spontaneous or inducible SVT. Characteristics associated with these outcomes were analyzed. RESULTS: Twenty-eight patients (42%) experienced SVT at or early after birth, which was associated with fetal long ventriculoatrial tachycardia (odds ratio [OR] 6.8; 95% confidence interval [CI] 1.88-24.57; P = .0029); delayed in utero cardioversion with treatment (median 11 days vs 5.5 days; P < .0001); prenatal treatment with multiple antiarrhythmics (OR 4.42; 95% CI 1.56-12.55; P = .0059); and postnatal atrial ectopic tachycardia/permanent junctional reciprocating (OR 18.0; 95% CI 2.11-153.9; P = .0013). Of the 38 neonates undergoing TEPS, 19 (50%) had inducible tachyarrhythmias. Recurrence of SVT during infancy or childhood was documented in 4 of 6 patients with SVT at birth (66%), 8 of 22 patients with early neonatal SVT (36%), 4 of 19 patients with inducible SVT (21%), and 0 of 19 untreated patients without inducible SVT (0%) (P = .0032). CONCLUSION: The postnatal risk of SVT is related to the arrhythmia mechanism and prenatal treatment response. In newborns without spontaneous SVT, TEPS may be useful to guide the need for postnatal treatment on the basis of SVT inducibility.

Rare haematogenous sarcoma metastasis to the heart in a child.

Haematogenous non-contiguous metastatic spread of remote solid tumours to the heart is rare. We describe a previously healthy 5-year-old girl who presented with extensive intracardiac involvement by metastatic pelvic sarcoma.

Occluded mammary graft post-coronary bypass surgery: do we need to look for the second one? A case report.

BACKGROUND: Anatomic variations of the left internal mammary artery (LIMA) can influence coronary artery bypass surgical technique as well as posing definite difficulties in the interpretation of angiographic findings. We present an unusual anatomic variant of two LIMAs originating from the left subclavian artery discovered post-coronary artery bypass grafting surgery. CASE SUMMARY: A 60-year-old man post-LIMA grafting of the left anterior descending (LAD) coronary artery underwent diagnostic cardiac catheterization. Selective angiography revealed occluded LIMA; therefore, it was decided to proceed with percutaneous coronary intervention (PCI) to the occluded native LAD. Once antegrade flow in the LAD was restored, retrograde filling of a vessel corresponding to the previously grafted LIMA was also detected. Additional contrast injection in the left subclavian artery (LSCA) showed a second patent LIMA originating from the distal segment of the LSCA. DISCUSSION: This patient has an unusual anatomic variant of two LIMAs originating from the LCSA. The proximal rudimentary LIMA was misinterpreted as an occluded arterial graft while the second, well-developed LIMA connected to the LAD had an unusually distal origin and had therefore been overlooked. This anatomical variant should be kept in mind when the internal mammary graft seems to be occluded.

Superior vena cava-right atrium junction flow-pattern post-transcatheter closure of patent foramen ovale.

BACKGROUND: The patent foramen ovale (PFO) occluder is a bulky metallic device. Its impact on the normal blood flow at the superior vena cava-right atrial (SVC-RA) junction is not clear. METHODS: We examined SVC-RA junction flow-pattern using pulsed-wave (PW) ultrasound Doppler in 21 patients (4 male, aged 52.7 ± 9 years) who underwent PFO device closure 4-120 months previously, in comparison with 21 age- and sex-matched controls (4 male, aged 51 ± 8.5 years) with structurally normal hearts. RESULTS: Mean systolic flow velocity at the SVC-RA junction was 60 ± 11 cm/s in the PFO closure group and 64 ± 17 cm/s in the control group (P = 0.27). Mean diastolic blood flow velocity at the SVC-RA junction in those groups was 30 ± 8 and 35 ± 9 cm/s, respectively (P = 0.1).The mean systolic wave duration was 439 ± 52 ms in the PFO closure group and 422 ± 67 ms in the control group (P = 0.4). The mean diastolic wave duration was 320 ± 75 and 277 ± 88 ms, respectively (P = 0.12). CONCLUSION: The study results show that transcatheter PFO closure does not affect the normal blood flow at the SVC-RA junction.

Fetal overgrowth in pregnancies complicated by diabetes: development of a clinical prediction index.

PURPOSE: To develop an index to predict fetal overgrowth in pregnancies complicated by diabetes. METHODS: Data were derived from a cohort of 275 women with singleton gestations in a collaborative diabetes in pregnancy program. Regression analysis incorporated clinical factors available in the first 20-30 weeks of pregnancy that were assigned beta-coefficient-based weights, the sum of which yielded a fetal overgrowth index (composite score). RESULTS: Fifty-one (18.5%) pregnancies were complicated by fetal overgrowth. The derived index included five clinical factors: age ≤ 30, history of macrosomia, excessive gestational weight gain, enlarged fetal abdominal circumference, and fasting hyperglycemia. Area under the curve (AUC) for the index is 0.88 [95% confidence interval (CI) 0.82-0.92]. Cut-points were selected to identify "high-risk" and "low-risk" ranges (≥ 8 and ≤ 3) that have positive and negative predictive values of 84% (95% CI 70-98%) and 95% (95% CI 92-98%), respectively. The majority of women in our cohort (n = 182, 66%) had a "low-risk" index while 9% (n = 25) had a "high-risk" index. Sub-analyses of nulliparous women and women with gestational and pre-gestational diabetes revealed that the overgrowth index was equally or more predictive when applied separately to each of these groups. CONCLUSION: This fetal overgrowth index that incorporates five clinical factors provides a means of predicting fetal overgrowth and thereby serves as a tool for targeting the allocation of healthcare resources and treatment individualization.

Cardiac findings in children with juvenile Dermatomyositis at disease presentation.

BACKGROUND: Juvenile Dermatomyositis (JDM) is a pediatric vasculopathy characterized primarily by skin and muscle involvement. Cardiac findings have been reported in children with JDM but have rarely been investigated in detail. METHODS: We aimed to describe the relevant clinical and laboratory cardiac findings of a cohort of patients with JDM, followed at one centre, at disease diagnosis. RESULTS: We performed a retrospective review of 105 patients with JDM, followed from 1991 to 2007. Six of 70 patients (9%, 6% of the entire cohort) had abnormal electrocardiographic (ECG) findings, while 26 of 54 patients (48%, 25% of the entire cohort) had abnormal echocardiographic (echo) findings. Many of these findings were either mild or unlikely to be a result of JDM. CONCLUSIONS: Our findings suggest that cardiac abnormalities at JDM disease onset are frequently seen, but are rarely significant findings due to disease; however, JDM patients should be considered for screening for cardiac disease as late cardiac complications are well recognized.

Treatment Utility of Postpartum Antibiotics in Chorioamnionitis Study.

Objective To determine if postpartum antibiotics are necessary for patients with chorioamnionitis after a cesarean delivery (CD). Study Design Multicenter randomized controlled trial. Laboring patients with singleton gestations and chorioamnionitis who underwent CD were eligible. Patients were treated with ampicillin and gentamicin per standard protocol, then given clindamycin prior to skin incision. Patients were randomized to either postpartum antibiotic prophylaxis or no treatment following delivery. The primary outcome was the rate of endometritis. Assuming a 30% risk of endometritis in patients with chorioamnionitis who undergo CD, 119 patients per arm would be required to detect a 50% decrease in endometritis. Results The trial was stopped for futility following a planned interim analysis after 80 patients were randomized. There was no difference in the rate of the primary outcome between the two groups (9.8 vs. 7.7%, relative risk [RR]: 1.27; 95% confidence interval [CI]: 0.30, 5.31). A meta-analysis comparing post-CD antibiotics versus no treatment did not find a statistically significant difference between the groups (16.7 vs. 12.0%, pooled RR: 1.43; 95% CI: 0.72, 2.84). Conclusion Additional postpartum antibiotics do not decrease the rate of endometritis in patients with chorioamnionitis who undergo CD. The current preoperative antibiotic regimen including clindamycin should remain the standard of care in these patients.

Integrin-linked kinase mediates force transduction in cardiomyocytes by modulating SERCA2a/PLN function.

Human dilated cardiomyopathy (DCM) manifests as a profound reduction in biventricular cardiac function that typically progresses to death or cardiac transplantation. There is no effective mechanism-based therapy currently available for DCM, in part because the transduction of mechanical load into dynamic changes in cardiac contractility (termed mechanotransduction) remains an incompletely understood process during both normal cardiac function and in disease states. Here we show that the mechanoreceptor protein integrin-linked kinase (ILK) mediates cardiomyocyte force transduction through regulation of the key calcium regulatory protein sarcoplasmic/endoplasmic reticulum Ca(2+)ATPase isoform 2a (SERCA-2a) and phosphorylation of phospholamban (PLN) in the human heart. A non-oncogenic ILK mutation with a synthetic point mutation in the pleckstrin homology-like domain (ILK(R211A)) is shown to enhance global cardiac function through SERCA-2a/PLN. Thus, ILK serves to link mechanoreception to the dynamic modulation of cardiac contractility through a previously undiscovered interaction with the functional SERCA-2a/PLN module that can be exploited to rescue impaired mechanotransduction in DCM.

Lone atrial fibrillation in the pediatric population.

BACKGROUND: There are few reports of pediatric studies of atrial fibrillation (AF). We sought to describe the clinical characteristics, management strategies, and recurrence rates and to identify predictors of AF recurrence in a contemporary pediatric population. METHODS: A retrospective review was performed of patients ≤ 18 years with lone AF who were seen at 4 pediatric institutions from 1996-2011. Patients with AF in the setting of thyroid disease, ventricular pre-excitation, coexisting congenital heart disease, or a history of cardiac surgery were excluded. Demographics, clinical presentation, investigations, treatment, and follow-up were analyzed. RESULTS: Forty-two patients were diagnosed with a first episode of lone AF, and 4 of these cases were later classified as persistent AF. Thirty-one (74%) were male patients, median age was 15.3 years, and median (interquartile range [IQR]) duration of AF episode was 12 (IQR, 7-24) hours. AF recurred in 39% (15 of 38) of patients. The Kaplan-Meier median time to estimated recurrence was 19 months. By univariate analysis, initial AF episode duration was associated with a higher risk of recurrence (hazard ratio [HR], 1.01; 95% confidence interval [CI], 1-1.02; P = 0.034). Sex, age, family history, size of the left atrium, and history of cardioversion were not associated with recurrence. Recurrence with another supraventricular tachyarrhythmia (SVT) was observed in 6 of 38 (16%) patients, and 12 patients underwent electrophysiology (EP) study, with 6 patients receiving ablation. CONCLUSIONS: Our reported rate of recurrence of 39% is important when counseling pediatric patients and their parents on the expected course and treatment goals.

Biowire: a platform for maturation of human pluripotent stem cell-derived cardiomyocytes.

Directed differentiation protocols enable derivation of cardiomyocytes from human pluripotent stem cells (hPSCs) and permit engineering of human myocardium in vitro. However, hPSC-derived cardiomyocytes are reflective of very early human development, limiting their utility in the generation of in vitro models of mature myocardium. Here we describe a platform that combines three-dimensional cell cultivation with electrical stimulation to mature hPSC-derived cardiac tissues. We used quantitative structural, molecular and electrophysiological analyses to explain the responses of immature human myocardium to electrical stimulation and pacing. We demonstrated that the engineered platform allows for the generation of three-dimensional, aligned cardiac tissues (biowires) with frequent striations. Biowires submitted to electrical stimulation had markedly increased myofibril ultrastructural organization, elevated conduction velocity and improved both electrophysiological and Ca(2+) handling properties compared to nonstimulated controls. These changes were in agreement with cardiomyocyte maturation and were dependent on the stimulation rate.

Mutation location effect on severity of phenotype during exercise testing in type 1 long-QT syndrome: impact of transmembrane and C-loop location.

BACKGROUND: Targeted mutation site-specific differences have correlated C-loop missense mutations with worse outcomes and increased benefit of beta-blockers in LQT1. This observation has implicated the C-loop region as being mechanistically important in the altered response to sympathetic stimulation known to put patients with LQT1 at risk of syncope and sudden cardiac death. OBJECTIVE: The objective of this study was to determine if there is mutation site-specific response to sympathetic stimulation and beta-blockers using exercise testing. METHODS: This study is a retrospective review of LQT1 patients undergoing exercise testing at 3 academic referral centers. RESULTS: A total of 123 patients (age 28 ± 17 years, 59 male) were studied including 34 patients (28%) with C-loop mutations. There were no significant differences in supine, standing, peak exercise and 1-minute recovery QTc duration between patients with C-loop mutations and patients with alternate mutation sites. In 37 patients that underwent testing on and off beta-blockers, beta-blocker use was associated with a significant reduction in supine, standing and peak exercise QTc. This difference was not seen in the small group of patients (7/37) with C-loop mutations. There was no difference in QTc at 1 and 4 minutes into recovery. CONCLUSIONS: Genetically confirmed LQT1 patients in this study cohort with C-loop mutations did not demonstrate the expected increase in QTc in response to exercise, or resultant response to beta-blocker. The apparent increased risk of cardiac events associated with C-loop mutation sites and the marked benefit received from beta-blocker therapy are not reflected by exercise-mediated effects on QTc in this study population.

The effect of NavX on fluoroscopy times in pediatric catheter ablation.

PURPOSE: Catheter ablation is the established curative therapy for pediatric tachyarrhythmias. However, exposure to ionizing radiation from fluoroscopy during the procedure is of concern to both patients and caregivers. We sought to assess the impact of an impedance-based three-dimensional navigation system (NavX(TM), Endocardial Solutions, Inc., St. Paul, MN) on pediatric catheter ablation procedures. METHODS: We retrospectively analyzed procedural data during a 7-year period (2002-2008), which spanned the transition between standard fluoroscopic mapping and adoption of NavX(TM) mapping for catheter ablation of atrioventricular nodal reentrant tachycardia (AVNRT) and right/left-sided accessory pathways (RAP/LAP). Comparisons of total procedure time, total fluoroscopy time, and ablation fluoroscopy time (from insertion of ablation catheter until completion of procedure) between NavX(TM) and conventional mapping were made. RESULTS: Three hundred eighty-eight patients (aged 1-18 years, M/F 236:183) underwent ablation of AVNRT (n = 101), LAP (n = 130), or RAP (n = 157) using either conventional (n = 70) or NavX(TM) (n = 318) mapping. Overall success rates were similar between the two mapping approaches (95.7% for conventional versus 95.9% for NavX(TM)). NavX(TM) mapping significantly reduced ablation fluoroscopy time (15.9 ± 14.3 versus 11.0 ± 8.9 min for NavX(TM), p < 0.01) with a trend towards a decrease in total fluoroscopy time (26.4 ± 15.6 versus 23.8 ± 11.1 min for NavX(TM), p = 0.095). Total procedure time was not significantly different between the two methods (210.1 ± 66 versus 222.8 ± 61 min for NavX(TM), p = 0.13). When analyzed by arrhythmia substrate, there were significant reductions in ablation fluoroscopy time for both LAP and RAP. CONCLUSIONS: NavX(TM) mapping reduced ablation fluoroscopy times for accessory pathways during pediatric catheter ablation.

Long QT, syndactyly, joint contractures, stroke and novel CACNA1C mutation: expanding the spectrum of Timothy syndrome.

Timothy syndrome (TS) is an autosomal dominant condition with the constellation of features including prolonged QT interval, hand and foot abnormalities, and mental retardation or autism. Splawski et al. [2004] previously described two phenotypes associated with TS distinguished by two unique and different mutations within the CACNA1C gene. We report on a newborn who presented with prolonged QT interval and associated polymorphic ventricular tachycardia, dysmorphic facial features, syndactyly of the hands and feet, and joint contractures, suggestive of TS. He developed a stroke, subsequent intractable seizures, and was found to have cortical blindness and later profound developmental delay. Initial targeted mutation analysis did not identify either of the previously described TS associated mutations; however, full gene sequencing detected a novel CACNA1C gene mutation (p.Ala1473Gly). The clinical and genetic findings in our case expand both the clinical and molecular knowledge of TS.

A combined gene and cell therapy approach for restoration of conduction.

BACKGROUND: Abnormal conduction underlies both bradyarrhythmias and re-entrant tachyarrhythmias. However, no practical way exists for restoring or improving conduction in areas of conduction slowing or block. OBJECTIVE: This study sought to test the feasibility of a novel strategy for conduction repair using genetically engineered cells designed to form biological "conducting cables." METHODS: An in vitro model of conduction block was established using spatially separated, spontaneously contracting, nonsynchronized human embryonic stem cell-derived cardiomyocytes clusters. Immunostaining, dye transfer, intracellular recordings, and multielectrode array (MEA) studies were performed to evaluate the ability of genetically engineered HEK293 cells, expressing the SCN5A-encoded Na(+) channel, to couple with cultured cardiomyocytes and to synchronize their electrical activity. RESULTS: Connexin-43 immunostaining and calcein dye-transfer experiments confirmed the formation of functional gap junctions between the engineered cells and neighboring cardiomyocytes. MEA and intracellular recordings were performed to assess the ability of the engineered cells to restore conduction in the co-cultures. Synchronization was defined by establishment of fixed local activation time differences between the cardiomyocytes clusters and convergence of their activation cycle lengths. Nontransfected control cells were able to induce synchronization between cardiomyocytes clusters separated by distances up to 300 µm (n = 21). In contrast, the Na(+) channel-expressing cells synchronized contractions between clusters separated by up to 1,050 µm, the longest distance studied (n = 23). Finally, engineered cells expressing the voltage-sensitive K(v)1.3 potassium channel prevented synchronization at any distance. CONCLUSION: Genetically engineered cells, transfected to express Na(+) channels, can form biological conducting cables bridging and coupling spatially separated cardiomyocytes. This novel cell therapy approach might be useful for the development of therapeutic strategies for both bradyarrhythmias and tachyarrhythmias.

Diagnosis-specific characteristics of ventricular tachycardia in children with structurally normal hearts.

BACKGROUND: Improved mechanistic insights and clinical tools provide increasing diagnostic refinement for ventricular tachycardia in young patients with structurally normal hearts, yielding potentially important prognostic and management implications. OBJECTIVE: The purpose of this study was to survey the clinical characteristics and outcomes of otherwise healthy children with ventricular tachycardia (VT) who were classified according to contemporary diagnostic criteria. METHODS: A single-center retrospective review of patients younger than 18 years of age with VT diagnosed between January 1980 and December 2005 was undertaken. Patients with significant systemic illness or with underlying structural or functional heart disease were excluded. RESULTS: A total of 77 patients met inclusion criteria and were grouped as follows: accelerated idioventricular rhythm (AIVR; n = 19), right ventricular tachycardia (RVT; n = 30), left ventricular tachycardia (LVT; n = 23), and catecholamine sensitive polymorphic VT (CPVT; n = 5). AIVR patients were youngest at diagnosis and had the most benign natural history, while the opposite was true of CPVT patients. Ablation was attempted in 2/30 RVT (50% success) and 10/23 LVT (80% success) patients. Severe cardiac events occurred in 3/23 LVT (no deaths) and 2/5 CPVT (one death) patients. CONCLUSION: The natural history and appropriate management of VT in young patients with structurally normal hearts are highly dependent on the specific diagnosis. LVT and CPVT are associated with significantly greater morbidity and mortality than AIVR and RVT.