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.

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.

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.

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.

A prospective pediatric clinical trial of digital music players: do they interfere with pacemakers?

BACKGROUND: There has been recent concern in the media about iPod interference with pacemakers. We systematically tested two types of digital music players (DMP) on pacemaker or ICD function in children. METHODS/RESULTS: Patients were monitored by a 6-lead ECG and programmer telemetry. The pacemaker was tested in bipolar and unipolar sensing at normal and maximal sensitivities. The order of DMP tested was randomized. Each DMP was placed on top of the pacemaker pocket, put into "play" mode three times (5 seconds each), with and without programmer wand placed one cm adjacent to DMP. Pacemaker interference was defined as: pacing inhibition, inappropriate pacing, oversensing, or detection of high-rate episodes associated with the use of DMP. Of the 67 patients (mean age 12 +/- 5 years), 62 had pacemakers and five had ICDs; 39 endocardial and 28 epicardial systems. Patients were tested with Sansa (67), iPod 30 GB (51), and other DMPs (43). There was no evidence of interference with pacemaker function by any DMP under any of the study conditions (each performed in triplicate). Reproducible programmer telemetry interference was shown in 11 cases (Medtronic 6/47, St. Jude Medical 5/18, Guidant 0/2) related to use of iPod (6), Sansa (1), or others (4). None of these were associated with any evidence of pacemaker malfunction. CONCLUSION: Interference with pacemaker function could not be shown with iPod or MP3 players. No additional precaution beyond standard is necessary for patients with pacemakers when they are using these players.

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.

Transcatheter cryoablation of tachyarrhythmias in children: initial experience from an international registry.

OBJECTIVES: We sought to describe the early pediatric experience of transcatheter cryoablation, and identify whether specific arrhythmia substrates and/or ablation locations were particularly suited to cryoablation. BACKGROUND: Radiofrequency (RF) ablation has become established therapy for pediatric tachyarrhythmias. However, challenges remain in terms of the safety and efficacy of RF ablation in specific locations; new methods may address these issues. METHODS: Prospective data were available for 64 patients age 13 +/- 4 (mean +/- SD) years undergoing cryoablation at 14 centers participating in the Cryocath International Patient Registry. Dysrhythmia duration was 5.0 +/- 4.2 years, with diagnoses of atrioventricular node re-entrant tachycardia (AVNRT) (n=30), anteroseptal (n=11), midseptal (n=5), or other (n=15) accessory pathway (AP) mediated AV re-entry, ventricular tachycardia (VT) (n = 3), and ectopic atrial tachycardia (EAT) (n=2). Two patients had more than one arrhythmia substrate. Transcatheter cryoablation was offered by cardiologist preference after written informed procedural consent of each patient and/or legal guardian. Cryomapping was performed at -30 degrees C and cryoablation was delivered with 4-min applications at -75 degrees C. RESULTS: Acute success was achieved in 45 of 65 (69%) cryoablation patients, with best success rates in AVNRT (83%) and right septal AP (75%), and lower success rates in other AP (43%), VT (66%), and EAT (0%). No device-related adverse events were reported. The success of radiofrequency (RF) ablation applied in 14 cryoablation failures was 4 of 4 for AVNRT patients, 1 of 1 for anteroseptal AP patients, 5 of 6 for other AP patients, 0 of 1 for VT patients, and 0 of 2 for EAT patients. CONCLUSIONS: Transcatheter cryoablation is a safe and well-tolerated alternative to RF ablation in pediatric patients on the basis of our initial experience. Success is highest in AVNRT and in substrates recognized as technically challenging or risky for RF ablation.

Natural history of postoperative heart block in congenital heart disease: implications for pacing intervention.

After half a century of major progress in congenital heart disease management, atrioventricular conduction block continues to complicate 1-3% of surgical procedures. Unless treated with an implanted pacemaker, permanent postoperative heart block is associated with 28-100% mortality. Postoperative heart block often proves to be transient, typically resolving within 10 days of onset. The duration of postoperative heart block is widely used as a key determinant for permanent pacemaker implantation. Current professional pacemaker implantation guidelines are largely based on this criterion. However, available natural history data suggest that other factors, such as residual conduction system injury, likely play a role in increasingly recognized cases of very late postoperative mortality and morbidity in patients who have experienced transient postoperative heart block. As growing numbers of congenital heart disease patients survive into adulthood, and artificial pacemaking capabilities continue to improve, it might be necessary to reconsider and refine currently accepted pacing indications for postoperative heart block.

Ventricular rate determines early bradycardic electrical remodeling.

OBJECTIVES: The purpose of this study was to isolate chronic ventricular rate as the primary determinant of early bradycardic ventricular electrical remodeling. BACKGROUND: Ventricular repolarization delay predisposing to potentially lethal tachydysrhythmias occurs during chronic bradycardia. Prolonged QT intervals and torsades de pointes are associated with down-regulated ventricular myocyte delayed rectifier potassium (K(+)) currents. METHODS: Transcatheter AV node ablation in rabbits was followed by chronic right ventricular pacing at either 140 bpm (n = 16) or the near-physiologic rate of 280 bpm (n = 9). ECG QT intervals were assessed in vivo at days 0 and 8 of paced AV block. Repolarizing currents in isolated left and right ventricular myocytes were assessed using whole-cell patch clamp technique. RESULTS: Bradycardic rabbits had increased steady-state QT intervals (230 +/- 6 ms vs 206 +/- 7 ms [mean +/- SE], day 8 vs day 0; P < .001). Biventricular myocyte expression of the delayed rectifier K(+) currents I(Kr) and I(Ks) was down-regulated in bradycardic rabbits, with no change in the transient outward current I(to) or inwardly rectifying current I(K1). None of these changes were observed in rabbits paced at 280 bpm. Pause-dependent torsades de pointes was documented in one bradycardic animal on day 8. No heart failure or ventricular hypertrophy was apparent. CONCLUSIONS: Bradycardic ventricular electrical remodeling proceeds independently of structural remodeling, heart failure, or AV synchrony and is prevented by maintenance of near-physiologic ventricular rate.

Use of an implantable loop recorder in the evaluation of children with congenital heart disease.

BACKGROUND: A recently developed implantable loop recorder (ILR) has been used in adult patients whose syncope remains unexplained in spite of extensive investigations. Syncope in the patient with congenital heart disease presents a diagnostic challenge. We applied this technology to a cohort of pediatric patients. METHODS: We reviewed our experience with an ILR in patients with congenital heart disease with syncope or palpitations after conventional investigations failed to identify a cause for the symptoms. RESULTS: ILRs were implanted in 4 patients with congenital heart disease at 2 centers for investigation of syncope (n = 2), near-syncope (n = 1), and palpitations (n = 1). Implantations were performed at a mean age of 5.9 +/- 0.9 years (4.2 to 7.6 years) and a mean weight of 26.7 +/- 6.6 kg (15.7 to 42.5 kg) with patients under general anesthesia, with no complications. All patients experienced typical symptoms and activated the device appropriately at a median of 86 days (46 to 102) after implantation. Each patient had good-quality data that allowed interpretation of the rhythm. In 2 of 4 cases, a likely cause for the symptoms was identified, with exclusion of more malignant arrhythmic diagnoses in all patients. Escalation of therapy was avoidable in all patients on the basis of the data recorded by the ILR. CONCLUSIONS: Recently developed loop recorder technology can be implanted in the young child without difficulty. The ILR proved to be very useful for excluding malignant arrhythmias as a cause of symptoms in these patients at high risk.

Presentation, natural history, and outcome in children and adolescents with double orifice mitral valve.

Forty-six children, aged 2 days to 16 years (median 2.4 years) with double orifice mitral valve (DOMV), were studied. Partial atrioventricular septal defect was the most commonly associated cardiac lesion. Symptoms were related to the degree of mitral insufficiency and/or stenosis when present. Surgical intervention directed at DOMV was required in the minority of patients who underwent repair of associated cardiac lesions. The long-term morbidity attributable to DOMV was low.

A novel rabbit model of variably compensated complete heart block.

Complete heart block (CHB) provides a useful substrate for study of bradycardia-dependent ventricular arrhythmias and cardiac function. Existing CHB animal models are limited by surgical recovery time and reliance on intrinsic escape rhythms. We describe a novel closed-chest rabbit model of CHB involving transcatheter radiofrequency (RF) atrioventricular (AV) node ablation and ventricular rate control with chronic transvenous pacing. Permanent CHB was achieved in 34 of 38 attempts overall. Procedural mortality due to cardiac tamponade (n = 2), airway complications (n = 2), and unknown causes (n = 5) occurred in nine animals. Survivors with CHB (n = 28) were maintained for < or = 22 days, during which there were three late deaths related to infection (n = 1) or respiratory distress (n = 2). None of the survivors with CHB showed recovery of AV conduction or pacemaker capture loss during chronic ventricular pacing at about one-half normal sinus rates, and 25 animals surviving to death showed no overt signs of hemodynamic compromise such as lethargy, poor feeding, or respiratory distress. This approach provides a reproducible nonsurgical CHB model with adjustable ventricular rate control.

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.

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.

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.

Diagnostic usefulness of graded exercise testing in pediatric supraventricular tachycardia.

BACKGROUND: Episodic symptoms, often reported during exertion, complicate the assessment of suspected supraventricular tachycardia (SVT). OBJECTIVE: To examine the diagnostic sensitivity of graded exercise testing in young patients with documented SVT or ventricular preexcitation. METHODS: A single-centre retrospective review identified 53 patients (5.1 to 17.5 years of age) with structurally normal hearts who had undergone 65 graded treadmill exercise tests in the setting of either documented SVT with normal resting electrocardiograms (n=30) or ventricular preexcitation (n=23). Twenty-five patients (13 pre-excited and 12 nonpreexcited) had exercise-related symptoms. SVT induction during exercise testing was assessed in relation to pre-excitation and the patient's history of exercise-induced symptoms. RESULTS: SVT was induced during six of the 65 exercise tests performed in three of 53 patients (overall sensitivity 5.7%). All three patients had a history of exercise- induced symptoms, and two had ventricular preexcitation. SVT was induced in 12% of patients with exercise- related symptoms. No other rhythm disturbances occurred during exercise testing. CONCLUSION: The diagnostic yield of graded exercise testing in patients with suspected SVT is limited, even among those with exercise related symptoms.