The clinical and genetic spectrum of catecholaminergic polymorphic ventricular tachycardia: findings from an international multicentre registry.

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.

Key Role of Pacing Site as Determinant Factor of Exercise Testing Performance in Pediatric Patients with Chronic Ventricular Pacing.

Chronic right ventricular (RV) apical pacing has been associated with deterioration of functional capacity and chronotropic incompetence during exercise testing in children. The effects of alternative pacing site on exercise performance in pediatric population remain unknown. We evaluated the influence of ventricular pacing site on exercise capacity in pediatric patients with complete congenital atrioventricular block requiring permanent pacemaker therapy. Sixty-four children paced from RV apex (n = 26), RV midseptum (n = 15) and left ventricular (LV) apex (n = 23) were studied cross-sectionally. Treadmill exercise stress testing was performed according to modified Bruce protocol. LV apical pacing was associated with greater exercise capacity. In comparison with the other study groups, children with RV apical pacing showed significantly lower VO2peak (37 ± 4.11; p = 0.003), O2 pulse (8.78 ± 1.15; p = 0.006), metabolic equivalents (7 ± 0.15; p = 0.001) and exercise time (6 ± 3.28; p = 0.03). Worse values in terms of maximum heart rate (139 ± 8.83 bpm; p = 0.008) and chronotropic index (0.6 ± 0.08; p = 0.002) were detected in the RV apical pacing group although maximal effort (respiratory exchange ratio) did not differ among groups (p = 0.216). Pacing from RV apex (odds ratio 9.4; confidence interval 2.5-18.32; Wald 4.91; p = 0.0036) and low peak heart rate achieved (odds ratio 3.66; confidence interval 0.19-7.4; Wald 4.083; p = 0.015) predicted significantly decrease in exercise capacity. Duration of pacing, gender, VVIR mode, baseline heart rate and QRS duration had not significant impact on exercise capacity. The site of ventricular pacing has the major impact on exercise capacity in children requiring permanent pacing. Among the sites assessed, LV apex is related to the better exercise performance.

Electrocardiographic Markers of Appropriate Implantable Cardioverter-Defibrillator Therapy in Young People with Congenital Heart Diseases.

Implantable cardioverter-defibrillators (ICDs) are increasingly utilized in patients with congenital heart disease (CHD). Prediction of the occurrence of shocks is important if improved patient selection is desired. The electrocardiogram (ECG) has been the first-line tool predicting the risk of sudden death, but data in CHD patients are lacking. We aim to evaluate the predictive value of electrocardiographic markers of appropriate therapy of ICD in young people with CHD. We conducted a prospective, longitudinal study, in twenty-six CHD patients (mean age 24.7 ± 5.3 years) who underwent first ICD implantation. Forty-two age- and diagnosis-matched controls were recruited. Twelve-lead ECG and 24 h Holter analysis were performed during a mean follow-up of 38.9 months. Data included heart rate, heart rate variability, QRS duration (QRSd), QTc interval and its dispersion, Tpeak-Tend (Tp-Te) interval and its dispersion, presence of fragmented QRS (fQRS), T wave alternans, atrial arrhythmias, and non-sustained ventricular tachycardia. Implant indication was primary prevention in ten cases (38.5%) and secondary prevention in 16 (61.5%). Overall, 17 subjects (65.3%) received at least one appropriate and effective ICD discharge. fQRS was present in 64.7% of cases with ICD therapy compared with patients without events or controls (p < 0.0001). Tp-e and Tp-e dispersion were significantly prolonged in patients with recurrences (113.5 and 37.2 ms) versus patients without ICD discharge (89.6 and 24.1 ms) or controls (72.4 and 19.3 ms) (p < 0.0001 and p < 0.0001, respectively). On univariate Cox regression analysis QRSd (hazard ratio: 1.19 per ms, p = 0.003), QTc dispersion (hazard ratio: 1.57 per ms, p = 0.002), fQRS (hazard ratio: 3.58 p < 0.0001), Tp-e (hazard ratio: 2.27 per ms, p < 0.0001), and Tp-e dispersion (hazard ratio: 4.15 per ms, p < 0.0001), emerged as strong predictors of outcome. On multivariate Cox analysis fQRS, Tp-e and Tp-e dispersion remained in the model. The presence of fQRS, and both Tp-e and Tp-e dispersion are useful ECG tools in daily clinical practice to identify CHD patients at risk for appropriate ICD therapy.

Dual-Chamber Stimulation with Single-Lead VDD Pacing System in Mustard Surgery.

Sinus node disease is a problem encountered in patients after the Mustard surgery, requiring a pacemaker implantation. The knowledge of the complexity anatomy is crucial because of the possible challenges associated with this procedure. We report a case of a 24-year-old woman presented with symptomatic bradycardia, in which a bicameral stimulation using a single-lead VDD pacing system was successfully performed.

Catecholaminergic polymorphic ventricular tachycardia in children: analysis of therapeutic strategies and outcomes from an international multicenter registry.

BACKGROUND: Catecholaminergic polymorphic ventricular tachycardia is an uncommon, potentially lethal, ion channelopathy. Standard therapies have high failure rates and little is known about treatment in children. Newer options such as flecainide and left cardiac sympathetic denervation are not well validated. We sought to define treatment outcomes in children with catecholaminergic polymorphic ventricular tachycardia. METHODS AND RESULTS: This is a Pediatric and Congenital Electrophysiology Society multicenter, retrospective cohort study of catecholaminergic polymorphic ventricular tachycardia patients diagnosed before 19 years of age. The cohort included 226 patients, including 170 probands and 56 relatives. Symptomatic presentation was reported in 176 (78%). Symptom onset occurred at 10.8 (interquartile range, 6.8-13.2) years with a delay to diagnosis of 0.5 (0-2.6) years. Syncope (P<0.001), cardiac arrest (P<0.001), and treatment failure (P=0.008) occurred more often in probands. ß-Blockers were prescribed in 205 of 211 patients (97%) on medication, and 25% experienced at least 1 treatment failure event. Implantable cardioverter defibrillators were placed in 121 (54%) and was associated with electrical storm in 22 (18%). Flecainide was used in 24% and left cardiac sympathetic denervation in 8%. Six deaths (3%) occurred during a cumulative follow-up of 788 patient-years. CONCLUSIONS: This study demonstrates a malignant phenotype and lengthy delay to diagnosis in catecholaminergic polymorphic ventricular tachycardia. Probands were typically severely affected. ß-Blockers were almost universally initiated; however, treatment failure, noncompliance and subtherapeutic dosing were often reported. Implantable cardioverter defibrillators were common despite numerous device-related complications. Treatment failure was rare in the quarter of patients on flecainide. Left cardiac sympathetic denervation was not uncommon although the indication was variable.

Terapia de resincronización cardíaca: Índice del QRS como predictor de respuesta / Cardiac resynchronization therapy: QRS index as a response predictor

RESUMEN Introducción: La terapia de resincronización cardíaca (TRC) es indicación en la insuficiencia cardíaca con QRS ancho y disminución grave de la fracción de eyección del ventrículo izquierdo. Objetivos: Definir los predictores de respuesta favorable a la TRC. Método: Se realizó un estudio observacional, descriptivo, retrospectivo, para evaluar el índice del QRS (diferencia entre anchura del QRS antes y después del implante, dividido entre su valor antes del implante, multiplicado por 100) como predictor de respuesta favorable a la TRC. Se realizaron electrocardiogramas antes del procedimiento, a los 6 y a los 12 meses del implante. Las mediciones se hicieron por dos observadores independientes, la primera digital en el monitor del salón de operaciones y el resto manual. Resultados: Se incluyeron 91 pacientes (edad media 61,2 años, 76% hombres), QRS mayor de 120 ms y fracción de eyección menor de 35%. Se obtuvo respuesta favorable en un 59%. No hubo diferencias significativas pre-implante en la duración del QRS entre respondedores y no respondedores (151,3 ms vs 151,34 ms, p=0,98), pero sí post-implante (100 vs 115 ms, p<0,0001), así como en el porcentaje de disminución del QRS (33,2% vs 24,3%, p<0,0001). La curva ROC mostró que un valor de corte del índice de QRS del 30% fue sensible (62%) y específico (75%), para predecir respuesta favorable. Conclusiones: La disminución de la anchura del QRS luego del implante de la TRC se relaciona con una respuesta favorable a la misma.

ABSTRACT Introduction: Cardiac resynchronization therapy (CRT) is an indication in heart failure with wide QRS and severely reduced left ventricular ejection fraction. Objectives: To define the response predictors favorable to CRT. Method: An observational, descriptive, retrospective study was conducted to evaluate the QRS index (difference between the QRS width before and after implantation, divided by its value before implantation, multiplied by 100) as a predictor of favorable response to CRT. Electrocardiograms were performed before the procedure, at 6 and 12 months after implantation. The measurements were made by two independent observers, the first digital on the operating room monitor and the rest manual. Results: A total of 91 patients (mean age 61.2 years, 76% men) were included, with QRS wider than 120 ms and ejection fraction less than 35%. A favorable response was obtained in 59%. There were no significant pre-implant differences in the QRS duration between responders and non-responders (151.3 ms vs. 151.34 ms, p=0.98), but there were differences post-implant (100 vs. 115 ms, p<0.0001), as well as in the QRS percentage of decrease (33.2% vs. 24.3%, p<0.0001). The ROC curve showed that a cut-off value of the QRS index of 30% was sensitive (62%) and specific (75%) in order to predict a favorable response. Conclusions: The decrease in the QRS width after the CRT implant is related to a favorable response to it.

Left ventricular synchrony and function in pediatric patients with definitive pacemakers.

BACKGROUND: Chronic right ventricular pacing (RVP) induces a dyssynchronous contraction pattern,producing interventricular and intraventricular asynchrony. Many studies have shown the relationship of RVP with impaired left ventricular (LV) form and function. OBJECTIVE: The aim of this study was to evaluate LV synchrony and function in pediatric patients receiving RVP in comparison with those receiving LV pacing (LVP). METHODS: LV systolic and diastolic function and synchrony were evaluated in 80 pediatric patients with either nonsurgical or postsurgical complete atrioventricular block, with pacing from either the RV endocardium (n = 40) or the LV epicardium (n = 40). Echocardiographic data obtained before pacemaker implantation, immediately after it, and at the end of a mean follow-up of 6.8 years were analyzed. RESULTS: LV diastolic function did not change in any patient during follow-up. LV systolic function was preserved in patients with LVP. However, in children with RVP the shortening fraction and ejection fraction decreased from medians of 41% ± 2.6% and 70% ± 6.9% before implantation to 32% ± 4.2% and 64% ± 2.5% (p < 0.0001 and p < 0.0001), respectively, at final follow-up. Interventricular mechanical delay was significantly larger with RVP (66 ± 13 ms) than with LVP (20 ± 8 ms). Similarly, the following parameters were significantly different in the two groups: LV mechanical delay (RVP: 69 ± 6 ms, LVP: 30 ± 11 ms, p < 0.0001); septal to lateral wall motion delay (RVP: 75 ± 19 ms, LVP: 42 ± 10 ms, p < 0.0001); and, septal to posterior wall motion delay (RVP: 127 ± 33 ms, LVP: 58 ± 17 ms, p < 0.0001). CONCLUSION: Compared with RV endocardium, LV epicardium is an optimal site for pacing to preserve cardiac synchrony and function.

Efecto electromecánico de los antiarrítmicos clase Ic durante el tratamiento de arritmias auriculares en cardiopatías congénitas / Electromechanical effect of Ic class antiarrhythmic drugs during the treatment of atrial arrhythmias in congenital heart diseases

Introducción: los fármacos antiarrítmicos son la primera línea de tratamiento para el control de las taquiarritmias en el paciente pediátrico. La terapéutica con drogas clase Ic en los pacientes con cardiopatías congénitas ha sido limitada, por los reportes que demostraron incremento de la mortalidad en los sujetos con cardiopatías estructurales. Objetivo: valorar el efecto de los antiarrítmicos clase Ic sobre los fenómenos electro-mecánicos cardiacos en los niños con cardiopatías congénitas con arritmias auriculares. Métodos: se realizó un estudio analítico, observacional, longitudinal y prospectivo en los pacientes con cardiopatías congénitas que desarrollaron arritmias auriculares, tratados con antiarrítmicos clase Ic en el Cardiocentro Pediátrico William Soler . Se analizaron variables electrocardiográficas, así como estimación de la función sistodiastólica mediante el ecocardiograma. Resultados: fueron evaluados 46 pacientes, 25 tratados con flecainida (grupo I) y 21 con propafenona (grupo II) durante 4,57±0,86 años. La taquicardia por reentrada intraatrial fue la arritmia de mayor incidencia (58,69 por ciento), mientras que, la tetralogía de Fallot, el defecto cardiaco más común (36,9 por ciento). Las variables electrocardiográficas no sufrieron variaciones nítidas durante el seguimiento. El análisis comparativo intragrupal demostró la preservación de la función sistólica en la totalidad de los sujetos (I, p= 0,275; II, p= 0,262). Comportamiento análogo exhibió la función diastólica, expresada en el índice de Tei (I, p= 0,244; II, p= 0,286). Conclusiones: la utilización de antiarrítmicos clase Ic en los pacientes pediátricos con cardiopatías congénitas no se asocia a largo plazo con alteraciones electrocardiográficas significativas ni compromiso de la función sistodiastólica, por lo que se recomienda su uso en esta población(AU)

Introduction: antiarrhythmic drugs are the first line of treatment for the control of tachyarrhythmias in pediatric patients. Therapy with Ic class drugs in patients with congenital heart disease has been limited, mainly due to reports that showed an increase in mortality in patients with structural heart disease. Objective: to assess the effect of Ic class antiarrhythmic drugs on cardiac electro-mechanical phenomena in children with congenital heart disease with atrial arrhythmias. Methods: an analytical, observational, longitudinal and prospective study was performed in patients with congenital heart diseases who developed atrial arrhythmias treated with Ic class antiarrhythmic drugs in William Soler Pediatric Cardiocenter. Electrocardiographic variables were analyzed, as well as the estimation of systo-diastolic function by echocardiography. Results: 46 patients were evaluated, 25 treated with flecainide (group I) and 21 with propafenone (group II) during 4.57 ± 0.86 years. The intra-atrial reentrant tachycardia was the arrhythmia with the highest incidence (58.69 percent); while tetralogy of Fallot was the most common cardiac defect (36.9 percent). The electrocardiographic variables did not undergo sharp variations during the follow-up. The intergroup comparative analysis showed the preservation of systolic function in all subjects (I, p= 0.275; II, p= 0.262). Analogous behavior showed diastolic function, that was expressed in the Tei index (I, p= 0.244; II, p= 0.286). Conclusions: the use of Ic class antiarrhythmic drugs in pediatric patients with congenital heart disease is not associated in the long term with significant electrocardiographic alterations or compromise of systo-diastolic function, so its use is recommended in this population(AU)

Sincronia e função ventricular esquerda em pacientes pediátricos portadores de marca-passo definitivo / Left ventricular synchrony and function in pediatric patients with definitive pacemakers

FUNDAMENTO: A estimulação crônica do ventrículo direito (EVD) induz um padrão de contração dessincronizado, produzindo assincronia interventricular e intraventricular. Muitos estudos têm mostrado a relação entre EVD e a forma e função ventricular esquerda (VE) comprometida. OBJETIVO: O objetivo deste estudo foi avaliar a sincronia e a função do VE em pacientes pediátricos que receberam EVD em comparação com aqueles que receberam estimulação do VE (EVE). MÉTODOS: As funções sistólica e diastólica e a sincronia do VE foram avaliadas em 80 pacientes pediátricos com bloqueio atrioventricular total não cirúrgico ou pós-cirúrgico, com estimulação a partir do endocárdio do ventrículo direito (VD) (n = 40) ou do epicárdio do VE (n = 40). Foram analisados dados ecocardiográficos obtidos antes da implantação do marca-passo, imediatamente após a implantação, e no final de um acompanhamento médio de 6,8 anos. RESULTADOS: A função diastólica do VE não se alterou em nenhum dos pacientes durante o acompanhamento. A função sistólica ventricular esquerda foi preservada nos pacientes que receberam EVE. No entanto, a fração de encurtamento e a fração de ejeção diminuíram de medianas de 41% ± 2,6% e 70% ± 6,9% antes da implantação para 32% ± 4,2% e 64% ± 2,5% (p < 0,0001 e p < 0,0001), respectivamente, no acompanhamento final. O atraso mecânico interventricular foi significativamente maior com a EVD (66 ± 13 ms) do que com a EVE (20 ± 8 ms). Da mesma forma, nos dois grupos houve uma diferença significativa entre os seguintes parâmetros: atraso mecânico do VE (EVD: 69 ± 6 ms, EVE: 30 ± 11 ms, p < 0,0001); atraso septo-lateral (RVP: 75 ± 19 ms, LVP: 42 ± 10 ms, p < 0,0001) e atraso septo-posterior (EVD: 127 ± 33 ms, EVE: 58 ± 17 ms, p < 0,0001). CONCLUSÃO: Quando comparado ao endocárdio do VD, o epicárdio do VE é um local ideal para a estimulação para preservar a sincronia e a função cardíaca.

BACKGROUND: Chronic right ventricular pacing (RVP) induces a dyssynchronous contraction pattern,producing interventricular and intraventricular asynchrony. Many studies have shown the relationship of RVP with impaired left ventricular (LV) form and function. OBJECTIVE: The aim of this study was to evaluate LV synchrony and function in pediatric patients receiving RVP in comparison with those receiving LV pacing (LVP). METHODS:LV systolic and diastolic function and synchrony were evaluated in 80 pediatric patients with either nonsurgical or postsurgical complete atrioventricular block, with pacing from either the RV endocardium (n = 40) or the LV epicardium (n = 40). Echocardiographic data obtained before pacemaker implantation, immediately after it, and at the end of a mean follow-up of 6.8 years were analyzed. RESULTS: LV diastolic function did not change in any patient during follow-up. LV systolic function was preserved in patients with LVP. However, in children with RVP the shortening fraction and ejection fraction decreased from medians of 41% ± 2.6% and 70% ± 6.9% before implantation to 32% ± 4.2% and 64% ± 2.5% (p < 0.0001 and p < 0.0001), respectively, at final follow-up. Interventricular mechanical delay was significantly larger with RVP (66 ± 13 ms) than with LVP (20 ± 8 ms). Similarly, the following parameters were significantly different in the two groups: LV mechanical delay (RVP: 69 ± 6 ms, LVP: 30 ± 11 ms, p < 0.0001); septal to lateral wall motion delay (RVP: 75 ± 19 ms, LVP: 42 ± 10 ms, p < 0.0001); and, septal to posterior wall motion delay (RVP: 127 ± 33 ms, LVP: 58 ± 17 ms, p < 0.0001). CONCLUSION: Compared with RV endocardium, LV epicardium is an optimal site for pacing to preserve cardiac synchrony and function.

Síndrome del QT largo / Syndrome of long Q-T interval

El síndrome del QT largo congénito de tipo Romano-Ward es una canalopatía arritmogénica poco frecuente, caracterizada por una grave alteración en la repolarización ventricular y traducida en el electrocardiograma por un alargamiento del intervalo QTc. Se documenta el caso de una paciente con síndrome del QT largo congénito de tipo 1, asintomßtica, con antecedentes familiares de muerte súbita y síndrome del QT largo, a quien se le realizó estudio ecocardiográfico, prueba ergométrica, detección de potenciales tardíos y dispersión del QT como complementos diagnósticos y estratificadores de riesgo. Se prescribió tratamiento farmacológico y semanas después se valoró su efectividad

The syndrome of congenital long Q-T interval (Q-T-i) of Romano-Ward type is an uncommon arrthymic channel disease, characterized by a severe alteration in ventricular repolarization and translated in the electrocardiogram by a lengthening of QTc interval. This is the case of a female patient presenting with type 1 congenital long Q-T, asymptomatic, with family history of sudden death and syndrome of long Q-T; an echocardiography study, ergometer test, late potentials detection and Q-T dispersion as diagnostic complements and risk stratification. Drug therapy was prescribed and several weeks later its effectiveness was assessed

Canalopatías arritmogénicas como causa de muerte súbita en pediatría / Arrhythmic canal diseases causing sudden death in children

La muerte súbita cardíaca de niños con corazón estructuralmente sano está estrechamente relacionada con las canalopatías arritmogénicas. Se presenta una revisión actualizada sobre las canalopatías y la relación de éstas con la muerte súbita. Se analiza especialmente la aplicación del método clínico y la importancia del trazado electrocardiográfico como herramientas indispensables para el certero diagnóstico de estas entidades.

Cardiac sudden death in children with a heart structurally healthy is closely related to arrhythmic canal diseases. An update review on canal diseases and its relation to the sudden death is presented. The application of clinical method is analyzed, as well as the significance of electrocardiographic recordings like essential tools for an accuracy diagnosis of these entities.