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Hypothyroidism can have a significant impact on cardiac contractility, vascular resistance, blood pressure, and cardiac rhythm. Ventricular arrhythmias induced by hypothyroidism are infrequently reported, especially in pediatric cases. A 15-year-old girl with autoimmune hypothyroidism experienced pulseless ventricular arrhythmias on 2 separate occasions because of nonadherence to levothyroxine medication. Subsequent investigations revealed an SCN5A mutation associated with Brugada syndrome. A loop recorder captured polymorphic ventricular tachycardia (PMVT), specifically Torsades de Pointes during her second event. Both arrhythmias were addressed only after stabilizing her thyroid hormone levels with replacement therapy. Although rare, patients with uncontrolled hypothyroidism may present with ventricular arrhythmias, particularly PMVT. The cornerstone of treatment for hypothyroidism-induced ventricular arrhythmia is thyroid replacement therapy. The identification of an SCN5A mutation unmasked by overt hypothyroidism emphasizes the need for a comprehensive cardiac evaluation in patients with hypothyroidism being assessed for PMVT.
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BACKGROUND: Catecholaminergic polymorphic ventricular tachycardia (CPVT) may cause sudden cardiac death (SCD) despite medical therapy. Therefore, implantable cardioverter-defibrillators (ICDs) are commonly advised. However, there is limited data on the outcomes of ICD use in children. OBJECTIVE: The purpose of this study was to compare the risk of arrhythmic events in pediatric patients with CPVT with and without an ICD. METHODS: We compared the risk of SCD in patients with RYR2 (ryanodine receptor 2) variants and phenotype-positive symptomatic CPVT patients with and without an ICD who were younger than 19 years and had no history of sudden cardiac arrest at phenotype diagnosis. The primary outcome was SCD; secondary outcomes were composite end points of SCD, sudden cardiac arrest, or appropriate ICD shocks with or without arrhythmic syncope. RESULTS: The study included 235 patients, 73 with an ICD (31.1%) and 162 without an ICD (68.9%). Over a median follow-up of 8.0 years (interquartile range 4.3-13.4 years), SCD occurred in 7 patients (3.0%), of whom 4 (57.1%) were noncompliant with medications and none had an ICD. Patients with ICD had a higher risk of both secondary composite outcomes (without syncope: hazard ratio 5.85; 95% confidence interval 3.40-10.09; P < .0001; with syncope: hazard ratio 2.55; 95% confidence interval 1.50-4.34; P = .0005). Thirty-one patients with ICD (42.5%) experienced appropriate shocks, 18 (24.7%) inappropriate shocks, and 21 (28.8%) device-related complications. CONCLUSION: SCD events occurred only in patients without an ICD and mostly in those not on optimal medical therapy. Patients with an ICD had a high risk of appropriate and inappropriate shocks, which may be reduced with appropriate device programming. Severe ICD complications were common, and risks vs benefits of ICDs need to be considered.
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Disorders of the cardiac rhythm may occur in both the fetus and neonate. Because of the immature myocardium, the hemodynamic consequences of either bradyarrhythmias or tachyarrhythmias may be far more significant than in mature physiological states. Treatment options are limited in the fetus and neonate because of limited vascular access, patient size, and the significant risk/benefit ratio of any intervention. In addition, exposure of the fetus or neonate to either persistent arrhythmias or antiarrhythmic medications may have yet-to-be-determined long-term developmental consequences. This scientific statement discusses the mechanism of arrhythmias, pharmacological treatment options, and distinct aspects of pharmacokinetics for the fetus and neonate. From the available current data, subjects of apparent consistency/consensus are presented, as well as future directions for research in terms of aspects of care for which evidence has not been established.
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American Heart Association , Arritmias Cardíacas , Recém-Nascido , Estados Unidos , Criança , Humanos , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/tratamento farmacológico , Taquicardia , Feto , EletrofisiologiaRESUMO
Sinus node dysfunction with concomitant junctional rhythm (JR) is frequently observed among Fontan patients and has been recognized as a contributor to heart failure. The impact and management of JR is unclear. A survey was mailed to all members of the Pediatric and Congenital Electrophysiology society (PACES) and members were asked to forward the questionnaire to their non-electrophysiology colleagues. Responses were received from 154 physicians (88 electrophysiologists (EP's) and 66 non-EP's (46 pediatric cardiologists and 20 adult congenital cardiologists). There were few differences in the response between EP's and non-EP's. Overall, 57% recommended an annual ambulatory ECG (AECG). A significant majority (80%) opted to continue to follow patients with significant periods of JR on AECG as long as the patients were asymptomatic, and showed no echocardiographic signs of cardiac decompensation. However, 84% would place a pacemaker in a patient with JR who was having open chest surgery for other reasons. Finally, pacemaker placement would be performed by 91% if a patient with JR showed signs of heart failure. Most congenital cardiologists would not recommend pacemaker placement in asymptomatic Fontan patients with JR. Further studies are needed on the Fontan population to determine the impact of SND and JR on longer term outcomes and to determine the role and optimal timing of pacemaker placement in these patients.
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Cardiologia , Técnica de Fontan , Cardiopatias Congênitas , Insuficiência Cardíaca , Adulto , Criança , Humanos , Cardiopatias Congênitas/cirurgia , Cardiopatias Congênitas/complicações , Arritmias Cardíacas/terapia , Arritmias Cardíacas/complicações , Inquéritos e Questionários , Insuficiência Cardíaca/complicaçõesRESUMO
BACKGROUND: In severely affected patients with catecholaminergic polymorphic ventricular tachycardia, beta-blockers are often insufficiently protective. The purpose of this study was to evaluate whether flecainide is associated with a lower incidence of arrhythmic events (AEs) when added to beta-blockers in a large cohort of patients with catecholaminergic polymorphic ventricular tachycardia. METHODS: From 2 international registries, this multicenter case cross-over study included patients with a clinical or genetic diagnosis of catecholaminergic polymorphic ventricular tachycardia in whom flecainide was added to beta-blocker therapy. The study period was defined as the period in which background therapy (ie, beta-blocker type [beta1-selective or nonselective]), left cardiac sympathetic denervation, and implantable cardioverter defibrillator treatment status, remained unchanged within individual patients and was divided into pre-flecainide and on-flecainide periods. The primary end point was AEs, defined as sudden cardiac death, sudden cardiac arrest, appropriate implantable cardioverter defibrillator shock, and arrhythmic syncope. The association of flecainide with AE rates was assessed using a generalized linear mixed model assuming negative binomial distribution and random effects for patients. RESULTS: A total of 247 patients (123 [50%] females; median age at start of flecainide, 18 years [interquartile range, 14-29]; median flecainide dose, 2.2 mg/kg per day [interquartile range, 1.7-3.1]) were included. At baseline, all patients used a beta-blocker, 70 (28%) had an implantable cardioverter defibrillator, and 21 (9%) had a left cardiac sympathetic denervation. During a median pre-flecainide follow-up of 2.1 years (interquartile range, 0.4-7.2), 41 patients (17%) experienced 58 AEs (annual event rate, 5.6%). During a median on-flecainide follow-up of 2.9 years (interquartile range, 1.0-6.0), 23 patients (9%) experienced 38 AEs (annual event rate, 4.0%). There were significantly fewer AEs after initiation of flecainide (incidence rate ratio, 0.55 [95% CI, 0.38-0.83]; P=0.007). Among patients who were symptomatic before diagnosis or during the pre-flecainide period (n=167), flecainide was associated with significantly fewer AEs (incidence rate ratio, 0.49 [95% CI, 0.31-0.77]; P=0.002). Among patients with ≥1 AE on beta-blocker therapy (n=41), adding flecainide was also associated with significantly fewer AEs (incidence rate ratio, 0.25 [95% CI, 0.14-0.45]; P<0.001). CONCLUSIONS: For patients with catecholaminergic polymorphic ventricular tachycardia, adding flecainide to beta-blocker therapy was associated with a lower incidence of AEs in the overall cohort, in symptomatic patients, and particularly in patients with breakthrough AEs while on beta-blocker therapy.
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Desfibriladores Implantáveis , Taquicardia Ventricular , Feminino , Humanos , Adolescente , Masculino , Flecainida/efeitos adversos , Incidência , Estudos Cross-Over , Taquicardia Ventricular/diagnóstico , Taquicardia Ventricular/tratamento farmacológico , Taquicardia Ventricular/epidemiologia , Antagonistas Adrenérgicos beta/efeitos adversos , Morte Súbita Cardíaca/epidemiologia , Morte Súbita Cardíaca/etiologia , Morte Súbita Cardíaca/prevenção & controleRESUMO
Hypertrophic cardiomyopathy (HCM), a common cardiomyopathy in children, is an important cause of morbidity and mortality. Early recognition and appropriate management are important. An electrocardiogram (ECG) is often used as a screening tool in children to detect heart disease. The ECG patterns in children with HCM are not well described.ECGs collected from an international cohort of children, and adolescents (≤ 21 years) with HCM were reviewed. 482 ECGs met inclusion criteria. Age ranged from 1 day to 21 years, median 13 years. Of the 482 ECGs, 57 (12%) were normal. The most common abnormalities noted were left ventricular hypertrophy (LVH) in 108/482 (22%) and biventricular hypertrophy (BVH) in 116/482 (24%) Of the patients with LVH/BVH (n = 224), 135 (60%) also had a strain pattern (LVH in 83, BVH in 52). Isolated strain pattern (in the absence of criteria for hypertrophy) was seen in 43/482 (9%). Isolated pathologic Q waves were seen in 71/482 (15%). Pediatric HCM, 88% have an abnormal ECG. The most common ECG abnormalities were LVH or BVH with or without strain. Strain pattern without hypertrophy and a pathologic Q wave were present in a significant proportion (24%) of patients. Thus, a significant number of children with HCM have ECG abnormalities that are not typical for "hypertrophy". The presence of the ECG abnormalities described above in a child should prompt further examination with an echocardiogram to rule out HCM.
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Ventricular premature beats originating from the right ventricular outflow tract can have myocardial extensions to the pulmonary valve and pulmonary artery. Treatment may consist of catheter ablation combined with the use of three-dimensional mapping to determine the exact location of ectopy. The location of ectopy relative to the pulmonary valve may be hard to ascertain. Intracardiac echocardiography (ICE) is a noninvasive approach by which one can determine the relationship of the pulmonary valve relative to the ablation catheter prior to ablation. ICE has achieved increasing popularity during the ablation of other arrhythmias such as tricuspid valve arrhythmias and has been shown to be helpful in guiding catheter placement prior to ablation. The additional information gained from deploying ICE may ensure more precise ablation, prevent theoretical damage to the pulmonary valve, and alleviate the need for a repeat procedure. Here, we present a case involving the use of ICE during a pediatric patient's second ablation procedure to precisely determine the location of ectopy of nonsustained ventricular tachycardia originating from the distal pulmonary valve.
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Brugada syndrome (BrS) is a hereditary condition that is characterized by ST elevation, ventricular tachycardia or fibrillation, and sudden cardiac death in otherwise healthy patients. Life-threatening arrhythmias generally occur, while at rest, with fever or during vagotonic states. Exercise is generally not considered a trigger for ventricular arrhythmias or syncope in patients with BrS. We describe a patient who presented with exercise-induced syncope, ventricular tachycardia during an exercise test, and was found to be both genotypically and phenotypically positive for BrS. This case highlights a potentially important role of exercise testing in diagnosing and risk stratifying certain patients with BrS.
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This article reviews important features for improving the diagnosis and management of fetal arrhythmias. The normal fetal heart rate ranges between 110 and 160 beats per minute. A fetal heart rate is considered abnormal if the heart rate is beyond the normal ranges or the rhythm is irregular. The rate, duration, and origin of the rhythm and degree of irregularity usually determine the potential for hemodynamic consequences. Most of the fetal rhythm disturbances are the result of premature atrial contractions (PACs) and are of little clinical significance. Other arrhythmias include tachyarrhythmias (heart rate in excess of 160 beats/min) such as atrioventricular (AV) reentry tachycardia, atrial flutter, and ventricular tachycardia, and bradyarrhythmias (heart rate <110 beats/min) such as sinus node dysfunction, complete heart block (CHB) and long QT syndrome (which is associated with sinus bradycardia and pseudo-heart block).
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BACKGROUND: The long-term benefits of Melody valve implant for right ventricular outflow tract conduit obstruction or insufficiency on exercise capacity are undefined. METHODS: As part of the Melody valve clinical trial, 136 patients with congenital heart disease underwent serial cardiopulmonary exercise testing prior to, 6 months after, and annually for up to 5 years postimplant. RESULTS: Mean age at Melody valve implantation was 22.4 ± 0.9 years (range 7-53 years). The 95 patients who completed the study protocol provide the basis of this report. An initial improvement in % predicted workload was present at 6 months postimplant; however, at the final (5 year) follow-up, sustained or further improvements in workload were not demonstrated for the entire cohort compared to baseline. By subgroup analysis, age <17 years at implant and pulmonary regurgitation as the primary lesion were variables associated with sustained improvement in exercise performance. There were sustained improvements in the ventilatory equivalents for O2 (minute ventilation/O2 intake, P = .01) and CO2 (minute ventilation/CO2 output, P < .01) at the ventilatory anaerobic threshold at the study conclusion. Improvements in forced vital capacity were also observed during the study but not sustained at the final follow-up. CONCLUSIONS: A cautious appraisal of the cardiovascular benefits of Melody valve implant on sustained improvements in exercise performance appears warranted. Although the observed changes in pulmonary function suggest improved restrictive lung physiology and more efficient gas exchange, after an initial increase in % predicted performance, neither sustained nor further improvements in exercise performance were observed, except in specific patient subgroups.
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Cateterismo Cardíaco/métodos , Tolerância ao Exercício/fisiologia , Cardiopatias Congênitas/complicações , Próteses Valvulares Cardíacas , Insuficiência da Valva Pulmonar/cirurgia , Valva Pulmonar/cirurgia , Função Ventricular Esquerda/fisiologia , Ecocardiografia , Teste de Esforço , Seguimentos , Cardiopatias Congênitas/fisiopatologia , Cardiopatias Congênitas/cirurgia , Imagem Cinética por Ressonância Magnética , Estudos Prospectivos , Desenho de Prótese , Valva Pulmonar/diagnóstico por imagem , Insuficiência da Valva Pulmonar/etiologia , Insuficiência da Valva Pulmonar/fisiopatologia , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is often a life-threatening arrhythmia disorder with variable penetrance and expressivity. Little is known about the incidence or outcomes of CPVT patients with ≥2 variants. METHODS: The phenotypes, genotypes and outcomes of patients in the Pediatric and Congenital Electrophysiology Society CPVT Registry with ≥2 variants in genes linked to CPVT were ascertained. The American College of Medical Genetics & Genomics (ACMG) criteria and structural mapping were used to predict the pathogenicity of variants (3D model of pig RyR2 in open-state). RESULTS: Among 237 CPVT subjects, 193 (81%) had genetic testing. Fifteen patients (8%) with a median age of 9 years (IQR 5-12) had ≥2 variants. Sudden cardiac arrest occurred in 11 children (73%), although none died during a median follow-up of 4.3 years (IQR 2.5-6.1). Thirteen patients (80%) had at least two RYR2 variants, while the remaining two patients had RYR2 variants plus variants in other CPVT-linked genes. Among all variants identified, re-classification of the commercial laboratory interpretation using ACMG criteria led to the upgrade from variant of unknown significance (VUS) to pathogenic/likely pathogenic (P/LP) for 5 variants, and downgrade from P/LP to VUS for 6 variants. For RYR2 variants, 3D mapping using the RyR2 model suggested that 2 VUS by ACMG criteria were P/LP, while 2 variants were downgraded to likely benign. CONCLUSIONS: This severely affected cohort demonstrates that a minority of CPVT cases are related to ≥2 variants, which may have implications on family-based genetic counselling. While multi-variant CPVT patients were at high-risk for sudden cardiac arrest, there are insufficient data to conclude that this genetic phenomenon has prognostic implications at present. Further research is needed to determine the significance and generalizability of this observation. This study also shows that a rigorous approach to variant re-classification using the ACMG criteria and 3D mapping is important in reaching an accurate diagnosis, especially in the multi-variant population.
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Predisposição Genética para Doença , Sistema de Registros , Taquicardia Ventricular/genética , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Recém-Nascido , Masculino , Miocárdio/patologia , Domínios Proteicos , Canal de Liberação de Cálcio do Receptor de Rianodina/química , Canal de Liberação de Cálcio do Receptor de Rianodina/genética , Taquicardia Ventricular/terapia , Resultado do TratamentoRESUMO
Aims: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an ion channelopathy characterized by ventricular arrhythmia during exertion or stress. Mutations in RYR2-coded Ryanodine Receptor-2 (RyR2) and CASQ2-coded Calsequestrin-2 (CASQ2) genes underlie CPVT1 and CPVT2, respectively. However, prognostic markers are scarce. We sought to better characterize the phenotypic and genotypic spectrum of CPVT, and utilize molecular modelling to help account for clinical phenotypes. Methods and results: This is a Pediatric and Congenital Electrophysiology Society multicentre, retrospective cohort study of CPVT patients diagnosed at <19 years of age and their first-degree relatives. Genetic testing was undertaken in 194 of 236 subjects (82%) during 3.5 (1.4-5.3) years of follow-up. The majority (60%) had RyR2-associated CPVT1. Variant locations were predicted based on a 3D structural model of RyR2. Specific residues appear to have key structural importance, supported by an association between cardiac arrest and mutations in the intersubunit interface of the N-terminus, and the S4-S5 linker and helices S5 and S6 of the RyR2 C-terminus. In approximately one quarter of symptomatic patients, cardiac events were precipitated by only normal wakeful activities. Conclusion: This large, multicentre study identifies contemporary challenges related to the diagnosis and prognostication of CPVT patients. Structural modelling of RyR2 can improve our understanding severe CPVT phenotypes. Wakeful rest, rather than exertion, often precipitated life-threatening cardiac events.
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Calsequestrina/genética , Mutação , Canal de Liberação de Cálcio do Receptor de Rianodina/genética , Taquicardia Ventricular/genética , Adolescente , Criança , Análise Mutacional de DNA , Morte Súbita Cardíaca/epidemiologia , Feminino , Marcadores Genéticos , Predisposição Genética para Doença , Hereditariedade , Humanos , Masculino , Modelos Moleculares , Linhagem , Fenótipo , Prognóstico , Conformação Proteica , Sistema de Registros , Estudos Retrospectivos , Fatores de Risco , Canal de Liberação de Cálcio do Receptor de Rianodina/química , Canal de Liberação de Cálcio do Receptor de Rianodina/metabolismo , Relação Estrutura-Atividade , Taquicardia Ventricular/diagnóstico , Taquicardia Ventricular/mortalidade , Taquicardia Ventricular/fisiopatologiaRESUMO
Importance: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a potentially lethal genetic arrhythmia syndrome characterized by polymorphic ventricular tachycardia with physical or emotional stress, for which current therapy with ß-blockers is incompletely effective. Flecainide acetate directly suppresses sarcoplasmic reticulum calcium release-the cellular mechanism responsible for triggering ventricular arrhythmias in CPVT-but has never been assessed prospectively. Objective: To determine whether flecainide dosed to therapeutic levels and added to ß-blocker therapy is superior to ß-blocker therapy alone for the prevention of exercise-induced arrhythmias in CPVT. Design, Setting, and Participants: This investigator-initiated, multicenter, single-blind, placebo-controlled crossover clinical trial was conducted from December 19, 2011, through December 29, 2015, with a midtrial protocol change at 10 US sites. Patients with a clinical diagnosis of CPVT and an implantable cardioverter-defibrillator underwent a baseline exercise test while receiving maximally tolerated ß-blocker therapy that was continued throughout the trial. Patients were then randomized to treatment A (flecainide or placebo) for 3 months, followed by exercise testing. After a 1-week washout period, patients crossed over to treatment B (placebo or flecainide) for 3 months, followed by exercise testing. Interventions: Patients received oral flecainide or placebo twice daily, with the dosage guided by trough serum levels. Main Outcomes and Measures: The primary end point of ventricular arrhythmias during exercise was compared between the flecainide and placebo arms. Exercise tests were scored on an ordinal scale of worst ventricular arrhythmia observed (0 indicates no ectopy; 1, isolated premature ventricular beats; 2, bigeminy; 3, couplets; and 4, nonsustained ventricular tachycardia). Results: Of 14 patients (7 males and 7 females; median age, 16 years [interquartile range, 15.0-22.5 years]) randomized, 13 completed the study. The median baseline exercise test score was 3.0 (range, 0-4), with no difference noted between the baseline and placebo (median, 2.5; range, 0-4) exercise scores. The median ventricular arrhythmia score during exercise was significantly reduced by flecainide (0 [range, 0-2] vs 2.5 [range, 0-4] for placebo; P < .01), with complete suppression observed in 11 of 13 patients (85%). Overall and serious adverse events did not differ between the flecainide and placebo arms. Conclusions and Relevance: In this randomized clinical trial of patients with CPVT, flecainide plus ß-blocker significantly reduced ventricular ectopy during exercise compared with placebo plus ß-blocker and ß-blocker alone. Trial Registration: clinicaltrials.gov Identifier: NCT01117454.
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Antiarrítmicos/uso terapêutico , Exercício Físico , Flecainida/uso terapêutico , Taquicardia Ventricular/tratamento farmacológico , Adolescente , Antagonistas Adrenérgicos beta/uso terapêutico , Estudos Cross-Over , Morte Súbita Cardíaca/prevenção & controle , Desfibriladores Implantáveis , Quimioterapia Combinada , Teste de Esforço , Feminino , Humanos , Masculino , Dose Máxima Tolerável , Método Simples-Cego , Taquicardia Ventricular/fisiopatologia , Adulto JovemRESUMO
Implantable cardioverter-defibrillators effectively reduce the rate of sudden cardiac death in children. Significant efforts have been made to better characterise the indications for their placement, and over the past two decades there has been a shift in their use from secondary to primary prevention. Primary prevention includes placement in patients thought to be at high risk of sudden cardiac death before the patient experiences any event. Secondary prevention includes placement after a high-risk event including sustained ventricular tachycardia or resuscitated cardiac arrest. Although liberal device implantation may be appealing even in patients having marginal indications, studies have shown high rates of adverse effects including inappropriate device discharges and the need for re-intervention because of hardware malfunction. The indications for placement of an implantable cardioverter-defibrillator, whether for primary or secondary prevention of sudden cardiac death, vary based on cardiac pathology. This review will assist the provider in understanding the risks and benefits of device implantation in order to enhance the shared decision-making capacity of patients, families, and providers.
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Morte Súbita Cardíaca/prevenção & controle , Desfibriladores Implantáveis , Prevenção Primária , Prevenção Secundária , Cardiomiopatia Hipertrófica/complicações , Morte Súbita Cardíaca/etiologia , Falha de Equipamento , Humanos , Medição de Risco , Fatores de Risco , Taquicardia Ventricular/complicaçõesRESUMO
Introduction The spatial peaks QRS-T angle accurately distinguishes children with hypertrophic cardiomyopathy from their healthy counterparts. The spatial peaks QRS-T angle is also useful in risk stratification for ventricular arrhythmias. We hypothesised that the spatial peaks QRS-T angle would be useful for the prediction of ventricular arrhythmias in hypertrophic cardiomyopathy patients under 23 years of age. METHODS: Corrected QT interval and spatial peaks QRS-T angles were retrospectively assessed in 133 paediatric hypertrophic cardiomyopathy patients (12.4±6.6 years) with versus without ventricular arrhythmias of 30 seconds or longer. Significance, positive/negative predictive values, and odds ratios were calculated based on receiver operating characteristic curve cut-off values. RESULTS: In total, 10 patients with ventricular arrhythmias were identified. Although the corrected QT interval did not differentiate those with versus without ventricular arrhythmias, the spatial peaks QRS-T angle did (151.4±19.0 versus 116.8±42.6 degrees, respectively, p<0.001). At an optimal cut-off value (124.1 degrees), the positive and negative predictive values of the spatial peaks QRS-T angle were 15.4 and 100.0%, respectively, with an odds ratio of 25.9 (95% CI 1.5-452.2). CONCLUSION: In children with hypertrophic cardiomyopathy, the spatial peaks QRS-T angle is associated with ventricular arrhythmia burden with high negative predictive value and odds ratio.