Different Ventricular Fibrillation Types in Low-Dimensional Latent Spaces.

The causes of ventricular fibrillation (VF) are not yet elucidated, and it has been proposed that different mechanisms might exist. Moreover, conventional analysis methods do not seem to provide time or frequency domain features that allow for recognition of different VF patterns in electrode-recorded biopotentials. The present work aims to determine whether low-dimensional latent spaces could exhibit discriminative features for different mechanisms or conditions during VF episodes. For this purpose, manifold learning using autoencoder neural networks was analyzed based on surface ECG recordings. The recordings covered the onset of the VF episode as well as the next 6 min, and comprised an experimental database based on an animal model with five situations, including control, drug intervention (amiodarone, diltiazem, and flecainide), and autonomic nervous system blockade. The results show that latent spaces from unsupervised and supervised learning schemes yielded moderate though quite noticeable separability among the different types of VF according to their type or intervention. In particular, unsupervised schemes reached a multi-class classification accuracy of 66%, while supervised schemes improved the separability of the generated latent spaces, providing a classification accuracy of up to 74%. Thus, we conclude that manifold learning schemes can provide a valuable tool for studying different types of VF while working in low-dimensional latent spaces, as the machine-learning generated features exhibit separability among different VF types. This study confirms that latent variables are better VF descriptors than conventional time or domain features, making this technique useful in current VF research on elucidation of the underlying VF mechanisms.

Frecuentación y motivos de asistencia en el servicio de urgencias tras la ablación de fibrilación auricular con criobalón / Emergency department attendance and reasons for consultation after cryoballoon ablation for pulmonary vein isolation of atrial fibrillation

Introducción y objetivos Existe poca información sobre la frecuentación a urgencias en las semanas siguientes a un procedimiento de aislamiento de venas pulmonares con criobalón. El objetivo del estudio es cuantificar las visitas a urgencias en los primeros 3 meses tras el procedimiento, evaluando los motivos, el diagnóstico final y la actitud terapéutica. Métodos Estudio observacional retrospectivo sobre 330 pacientes sometidos a un primer procedimiento de crioablación de fibrilación auricular. Se realizó un seguimiento de 90 días tras el procedimiento durante el que se registraron las visitas a urgencias con los síntomas que motivaron la consulta, electrocardiograma, actitud terapéutica y diagnóstico final, clasificado como alteración del ritmo, complicación confirmada, complicación posible y sin relación con el procedimiento ni con el trastorno arrítmico. Resultados Un total de 112 pacientes (34%) consultaron en urgencias, 50 de ellos (44,6%) por palpitaciones. En 44 pacientes (39,3%) se documentó una arritmia auricular sostenida. De las 29 consultas (25,9%) por síntomas potencialmente relacionados con complicaciones del procedimiento, 5 fueron complicaciones confirmadas de la punción inguinal, 10 quedaron con diagnóstico no confirmado de posible complicación y 41 visitas no guardaron relación con el procedimiento. El 21,4% del total de consultas fueron por palpitaciones en las que no se tomó ninguna medida terapéutica. Conclusiones Un tercio de los pacientes consultaron en urgencias al menos 1 vez, y los síntomas arrítmicos fueron el motivo más frecuente. Las complicaciones diferidas del procedimiento son raras y, en general, benignas. La disponibilidad de un sistema de teleconsulta con transmisión del ECG a distancia podría evitar hasta un 20% de los desplazamientos a urgencias. (AU)

Introduction and objectives There are few data on emergency visits after cryoballoon-based pulmonary vein isolation. The aim of this study was to quantify emergency department visits during the first 3 months after the procedure and to identify the reasons for consultation, final diagnoses, and the therapeutic approach. Methods Observational, retrospective study of 330 consecutive patients undergoing a first cryoballoon-based ablation procedure. Patients were followed up for 90 days after the procedure. We recorded emergency visits, symptoms, electrocardiographic data, and the therapeutic approach. Final diagnoses were classified as rhythm disorder, confirmed complication, possible complication, and unrelated to the procedure or to the arrhythmic disorder. Results A total of 112 (34%) patients attended the emergency department, 50 (44.6%) for palpitations. Sustained atrial arrhythmias were documented in 44 (39.3%) patients. Among the 29 (25.9%) visits for complications potentially related to the procedure, 5 were confirmed inguinal puncture complications and 10 were classified as unconfirmed possible complications. Forty-one visits were unrelated to the procedure or to the arrhythmic disorder. A total of 21.4% of the visits were due to palpitations requiring no therapeutic action. Conclusions A third of the patients attended the emergency department at least once, with the most frequent reason being arrhythmia-related symptoms. Late complications were rare and generally mild. Up to 20% of emergency visits could potentially be avoided by the availability of a teleconsulting system with remote electrocardiogram transmission. (AU)

Catheter ablation of ventricular arrhythmias in left ventricular noncompaction cardiomyopathy.

BACKGROUND: There are limited data on ventricular arrhythmias (VAs) associated with left ventricular noncompaction (LVNC) cardiomyopathy. OBJECTIVES: This study aims to analyze the clinical and electrocardiographic characteristics of VAs in a group of patients with LVNC. METHODS: Forty-two nonrelated patients with LVNC and VAs were included that were evaluated at the Inherited Cardiac Disease Unit of the University Hospital Virgen Arrixaca (Murcia-Spain) (ERN Guard-Heart Centre, European Reference Network for Rare and Low Prevalence Complex Diseases of the Heart). RESULTS: Thirteen patients (30.9%) had isolated LVNC, 27 (64.3%) had LVNC associated with dilated cardiomyopathy, and 2 (4.8%) had LVNC associated with hypertrophic cardiomyopathy. Among isolated LVNC individuals, 9 (69.2%) had premature ventricular complexes (PVCs)/nonsustained ventricular tachycardias (VTs), and 4 (30.8%) VTs (1 VT degenerating in ventricular fibrillation). In the dilated cardiomyopathy group, 11 (40.7%) patients had PVCs, 14 (51.9%) VTs, and 2 (7.4%) ventricular fibrillation. In the hypertrophic cardiomyopathy group, one patient had PVCs and the other VTs. Endocardial mapping and ablation were performed in 19 patients (45.2%): 7 ventricular outflow tracts (4 right ventricular outflow tract, 1 left coronary cusp, and 2 right coronary cusp), 2 in the left ventricular summit, 5 related to Purkinje potentials at the mid inferoseptal area, and 5 associated with endocardial scar localized in the basal anterolateral and inferolateral segments. Epicardial ablation was performed in 3 cases. CONCLUSION: The substrate of VAs in LVNC cardiomyopathy is heterogeneous, with origin in ventricular outflow tracts, Purkinje system related, and resembling scar patterns in nonischemic cardiomyopathy.

Emergency department attendance and reasons for consultation after cryoballoon ablation for pulmonary vein isolation of atrial fibrillation.

INTRODUCTION AND OBJECTIVES: There are few data on emergency visits after cryoballoon-based pulmonary vein isolation. The aim of this study was to quantify emergency department visits during the first 3 months after the procedure and to identify the reasons for consultation, final diagnoses, and the therapeutic approach. METHODS: Observational, retrospective study of 330 consecutive patients undergoing a first cryoballoon-based ablation procedure. Patients were followed up for 90 days after the procedure. We recorded emergency visits, symptoms, electrocardiographic data, and the therapeutic approach. Final diagnoses were classified as rhythm disorder, confirmed complication, possible complication, and unrelated to the procedure or to the arrhythmic disorder. RESULTS: A total of 112 (34%) patients attended the emergency department, 50 (44.6%) for palpitations. Sustained atrial arrhythmias were documented in 44 (39.3%) patients. Among the 29 (25.9%) visits for complications potentially related to the procedure, 5 were confirmed inguinal puncture complications and 10 were classified as unconfirmed possible complications. Forty-one visits were unrelated to the procedure or to the arrhythmic disorder. A total of 21.4% of the visits were due to palpitations requiring no therapeutic action. CONCLUSIONS: A third of the patients attended the emergency department at least once, with the most frequent reason being arrhythmia-related symptoms. Late complications were rare and generally mild. Up to 20% of emergency visits could potentially be avoided by the availability of a teleconsulting system with remote electrocardiogram transmission.

Spectral Analysis and Mutual Information Estimation of Left and Right Intracardiac Electrograms during Ventricular Fibrillation.

Ventricular fibrillation (VF) signals are characterized by highly volatile and erratic electrical impulses, the analysis of which is difficult given the complex behavior of the heart rhythms in the left (LV) and right ventricles (RV), as sometimes shown in intracardiac recorded Electrograms (EGM). However, there are few studies that analyze VF in humans according to the simultaneous behavior of heart signals in the two ventricles. The objective of this work was to perform a spectral and a non-linear analysis of the recordings of 22 patients with Congestive Heart Failure (CHF) and clinical indication for a cardiac resynchronization device, simultaneously obtained in LV and RV during induced VF in patients with a Biventricular Implantable Cardioverter Defibrillator (BICD) Contak Renewal IVTM (Boston Sci.). The Fourier Transform was used to identify the spectral content of the first six seconds of signals recorded in the RV and LV simultaneously. In addition, measurements that were based on Information Theory were scrutinized, including Entropy and Mutual Information. The results showed that in most patients the spectral envelopes of the EGM sources of RV and LV were complex, different, and with several frequency peaks. In addition, the Dominant Frequency (DF) in the LV was higher than in the RV, while the Organization Index (OI) had the opposite trend. The entropy measurements were more regular in the RV than in the LV, thus supporting the spectral findings. We can conclude that basic stochastic processing techniques should be scrutinized with caution and from basic to elaborated techniques, but they can provide us with useful information on the biosignals from both ventricles during VF.

[Psychological adjustment in patients with an implantable cardioverter defibrillator: primary prevention and secondary prevention. A comparative study.] / Ajuste psicológico en pacientes portadores de un desfibrilador automático implantado: prevención primaria frente a prevención secundaria. Un estudio comparativo.

OBJECTIVE: The implantation of the Implantable Cardioverter Defibrillator (ICD) influences the psychological adjustment and the degree of subjective discomfort. The objective of this work was to analyze differences in psychological adjustment, fear of shocks and the degree of subjective discomfort derived from the illness depending on the reasons for implantation (primary vs secondary). METHODS: A sample of 82 patients with an ICD, for primary (58.5%) or secondary (41.5%) prevention indications was studied. A sociodemographic and clinical questionnaire and List of Brief Symptoms (LBS-50) was used. Descriptive univariate and bivariate analysis, t-tests on mean differences for independent samples and z-tests on proportion differences were performed. RESULTS: Regarding psychological adjustment, 43.9% of the patients reported to have sleeping disorder, regardless the type of prevention. A greater percentage of patients of primary prevention had scored higher in clinical scales. The 29.4% of patients with secondary prevention reported to be afraid of experiencing some shock. The 25% of patients whose type of prevention was primary showed severe or moderate level of subjective discomfort derived from the illness compared with the 14.7% of the secondary prevention patients (p=0.7). CONCLUSIONS: The patients with an ICD show symptoms clinically significant in Psychoactivity, Obsession-Compulsion, Anxiety, Somatization, Sleeping disorders and Psychopathology Risk Index. Both groups, regardless the type of prevention showed a similar psychological adjustment. Regarding the fear of shocks and the degree of subjective discomfort derived from the illness, no statistically significant differences between the groups were found.

OBJETIVO: La implantación del Desfibrilador Automático Implantado (DAI) influye en el ajuste psicológico y en el grado de malestar de los pacientes. El objetivo de este trabajo fue analizar las diferencias en el ajuste psicológico, el miedo a las descargas y el grado de malestar subjetivo derivado de la enfermedad en función del motivo de implantación (primaria frente a secundaria). METODOS: La muestra fue de 82 pacientes portadores de un DAI, tanto por prevención primaria (58,5%) como secundaria (41,5%). Se utilizó un cuestionario sociodemográfico y clínico, así como el Listado de Síntomas Breves (LSB­50). Se realizaron análisis descriptivos univariados y bivariados, pruebas t de diferencias entre medias y pruebas z de diferencias entre proporciones. RESULTADOS: Respecto al ajuste psicológico, el 43,9% de los pacientes refirió tener alteraciones del sueño, independientemente del tipo de prevención. Un mayor porcentaje de pacientes de prevención primaria mostraron puntuaciones altas en escalas clínicas. El 29,4% de los pacientes de prevención secundaria mostró miedo a sufrir alguna descarga. El 25% de los pacientes cuyo motivo de implantación fue primario indicó un nivel moderado o intenso en cuanto al malestar subjetivo derivado de la enfermedad, comparado con el 14,7% de los pacientes de prevención secundaria (p=0,7). CONCLUSIONES: Los pacientes con DAI presentan síntomas clínicamente relevantes en Psicoreactividad, Obsesión-compulsión, Ansiedad, Somatización, Alteraciones del sueño y el Índice de riesgo psicopatológico. Independientemente del tipo de prevención ambos grupos muestran un ajuste psicológico similar. No se encuentran diferencias entre los grupos ni en el miedo a las descargas ni en el grado de malestar subjetivo.

Ajuste psicológico en pacientes portadores de un desfibrilador automático implantado: prevención primaria frente a prevención secundaria. Un estudio comparativo / Psychological adjustment in patients with an implantable cardioverter defibrillator: primary prevention and secondary prevention. A comparative study

OBJETIVO: La implantación del Desfibrilador Automático Implantado (DAI) influye en el ajuste psicológico y en el grado de malestar de los pacientes. El objetivo de este trabajo fue analizar las diferencias en el ajuste psicológico, el miedo a las descargas y el grado de malestar subjetivo derivado de la enfermedad en función del motivo de implantación (primaria frente a secundaria). MÉTODOS: La muestra fue de 82 pacientes portadores de un DAI, tanto por prevención primaria (58,5%) como secundaria (41,5%). Se utilizó un cuestionario sociodemográfico y clínico, así como el Listado de Síntomas Breves (LSB-50). Se realizaron análisis descriptivos univariados y bivariados, pruebas t de diferencias entre medias y pruebas z de diferencias entre proporciones. RESULTADOS: Respecto al ajuste psicológico, el 43,9% de los pacientes refirió tener alteraciones del sueño, independientemente del tipo de prevención. Un mayor porcentaje de pacientes de prevención primaria mostraron puntuaciones altas en escalas clínicas. El 29,4% de los pacientes de prevención secundaria mostró miedo a sufrir alguna descarga. El 25% de los pacientes cuyo motivo de implantación fue primario indicó un nivel moderado o intenso en cuanto al malestar subjetivo derivado de la enfermedad, comparado con el 14,7% de los pacientes de prevención secundaria (p = 0,7). CONCLUSIONES: Los pacientes con DAI presentan síntomas clínicamente relevantes en Psicoreactividad, Obsesión-compulsión, Ansiedad, Somatización, Alteraciones del sueño y el Índice de riesgo psicopatológico. Independientemente del tipo de prevención ambos grupos muestran un ajuste psicológico similar. No se encuentran diferencias entre los grupos ni en el miedo a las descargas ni en el grado de malestar subjetivo

OBJECTIVE: The implantation of the Implantable Cardioverter Defibrillator (ICD) influences the psychological adjustment and the degree of subjective discomfort. The objective of this work was to analyze differences in psychological adjustment, fear of shocks and the degree of subjective discomfort derived from the illness depending on the reasons for implantation (primary vs secondary). METHODS: A sample of 82 patients with an ICD, for primary (58.5%) or secondary (41.5%) prevention indications was studied. A sociodemographic and clinical questionnaire and List of Brief Symptoms (LBS-50) was used. Descriptive univariate and bivariate analysis, t-tests on mean differences for independent samples and z-tests on proportion differences were performed. RESULTS: Regarding psychological adjustment, 43.9% of the patients reported to have sleeping disorder, regardless the type of prevention. A greater percentage of patients of primary prevention had scored higher in clinical scales. The 29.4% of patients with secondary prevention reported to be afraid of experiencing some shock. The 25% of patients whose type of prevention was primary showed severe or moderate level of subjective discomfort derived from the illness compared with the 14.7% of the secondary prevention patients (p = 0.7). CONCLUSIONS: The patients with an ICD show symptoms clinically significant in Psychoactivity, Obsession-Compulsion, Anxiety, Somatization, Sleeping disorders and Psychopathology Risk Index. Both groups, regardless the type of prevention showed a similar psychological adjustment. Regarding the fear of shocks and the degree of subjective discomfort derived from the illness, no statistically significant differences between the groups were found

Medium- and long-term outcome after a single second-generation cryoballoon ablation in patients with paroxysmal and persistent atrial fibrillation.

INTRODUCTION AND OBJECTIVES: To report medium- and long-term results following a single second-generation cryoballoon (CB2)-based ablation procedure in patients with paroxysmal (PAF) and persistent (PeAF) atrial fibrillation. METHODS: A retrospective study was performed of consecutive patients undergoing a first CB2-based ablation procedure in a tertiary center. Cryoenergy was applied for 3 min if a time to effect <60 s was documented or 4 min otherwise, with a bonus application in cases of late isolation or suboptimal temperature. Follow-up was obtained from the regional health electronic records system and by telephone or personal interviews. Recurrence was defined as any atrial arrhythmia >30 s beyond a three-month blanking period. The clinical impact of recurrences was classified using a severity score. RESULTS: A total of 172 patients (134 PAF and 38 PeAF) were included, of whom 25 (14.5%) had structural heart disease and 120 (69.7%) had a normal or mildly dilated left atrium. Acute success was achieved in 167 (97.1%). After a median follow-up of 27 (14-41) months, 100 patients (58.1%) remained free of atrial arrhythmias (64.2% for PAF and 36.8% for PeAF, p=0.006). Left atrial size (p=0.05) and clinical presentation as PeAF (p=0.006) were predictors of recurrence. Of patients with recurrences, 11.1% did not require further therapies and an additional 16.7% had good control with antiarrhythmic drugs. CONCLUSIONS: A single CB2 procedure resulted in 58.1% of patients remaining free of atrial arrhythmias at 27-month follow-up. Conservative management was useful in 27.8% of patients with recurrences.

Force Trends and Pulsatility for Catheter Contact Identification in Intracardiac Electrograms during Arrhythmia Ablation.

The intracardiac electrical activation maps are commonly used as a guide in the ablation of cardiac arrhythmias. The use of catheters with force sensors has been proposed in order to know if the electrode is in contact with the tissue during the registration of intracardiac electrograms (EGM). Although threshold criteria on force signals are often used to determine the catheter contact, this may be a limited criterion due to the complexity of the heart dynamics and cardiac vorticity. The present paper is devoted to determining the criteria and force signal profiles that guarantee the contact of the electrode with the tissue. In this study, we analyzed 1391 force signals and their associated EGM recorded during 2 and 8 s, respectively, in 17 patients (82 ± 60 points per patient). We aimed to establish a contact pattern by first visually examining and classifying the signals, according to their likely-contact joint profile and following the suggestions from experts in the doubtful cases. First, we used Principal Component Analysis to scrutinize the force signal dynamics by analyzing the main eigen-directions, first globally and then grouped according to the certainty of their tissue-catheter contact. Second, we used two different linear classifiers (Fisher discriminant and support vector machines) to identify the most relevant components of the previous signal models. We obtained three main types of eigenvectors, namely, pulsatile relevant, non-pulsatile relevant, and irrelevant components. The classifiers reached a moderate to sufficient discrimination capacity (areas under the curve between 0.84 and 0.95 depending on the contact certainty and on the classifier), which allowed us to analyze the relevant properties in the force signals. We conclude that the catheter-tissue contact profiles in force recordings are complex and do not depend only on the signal intensity being above a threshold at a single time instant, but also on time pulsatility and trends. These findings pave the way towards a subsystem which can be included in current intracardiac navigation systems assisted by force contact sensors, and it can provide the clinician with an estimate of the reliability on the tissue-catheter contact in the point-by-point EGM acquisition procedure.

Valor del «test de bipedestación» en el diagnóstico y la evaluación de la respuesta al tratamiento con bloqueadores beta en el síndrome de QT largo / Value of the 'standing test' in the diagnosis and evaluation of beta-blocker therapy response in long QT syndrome

Introducción y objetivos: Los pacientes con síndrome de QT largo (SQTL) tienen una adaptación anormal del QT a los cambios bruscos de la frecuencia cardiaca producidos con la bipedestación. Este trabajo estudia la utilidad del test de bipedestación en una cohorte de pacientes con SQTL y evalúa si el fenómeno de «mala adaptación» del QT se normaliza con el tratamiento con bloqueadores beta. Métodos: Se realizó un electrocardiograma basal y otro inmediatamente tras la bipedestación a 36 pacientes con SQTL (6 [17%] con QTL1, 20 [56%] con QTL2, 3 [8%] con QTL7 y 7 [19%] con genotipo no identificado) y 41 controles. Se midió el intervalo QT corregido (QTc) basal (QTcdecúbito) y tras la bipedestación (QTcbipedestación) y el incremento del QTc (ΔQTc = QTcbipedestación - QTcdecúbito). Se repitió el test en 26 de los pacientes bajo tratamiento con bloqueadores beta. Resultados: El QTcbipedestación y el ΔQTc fueron mayores en el grupo de SQTL que en el grupo control (QTcbipedestación, 528 ± 46 frente a 420 ± 15 ms; p < 0,0001; ΔQTc, 78 ± 40 frente a 8 ± 13 ms; p < 0,0001). No hubo diferencias significativas entre los pacientes con QTL1 y QTL2. Los pacientes con SQTL presentaron patrones típicos del segmento ST-onda T tras la bipedestación. Las curvas receiver operating characteristic del QTcbipedestación y ΔQTc mostraron un incremento significativo del valor diagnóstico comparadas con la del QTcdecúbito(área bajo la curva de ambos, 0,99 frente a 0,85; p < 0,001). El tratamiento con bloqueadores beta atenuó la respuesta a la bipedestación de los pacientes con SQTL (en tratamiento, QTcbipedestación, 440 ± 32 ms [p < 0,0001] y ΔQTc, 14 ± 16 ms [p < 0,0001]). Conclusiones: La evaluación del intervalo QTc tras la bipedestación proporciona un alto rendimiento diagnóstico y podría ser de gran utilidad en la monitorización del tratamiento con bloqueadores beta en los pacientes con SQTL (AU)

Introduction and objectives: Patients with congenital long QT syndrome (LQTS) have an abnormal QT adaptation to sudden changes in heart rate provoked by standing. The present study sought to evaluate the standing test in a cohort of LQTS patients and to assess if this QT maladaptation phenomenon is ameliorated by beta-blocker therapy. Methods: Electrographic assessments were performed at baseline and immediately after standing in 36 LQTS patients (6 LQT1 [17%], 20 LQT2 [56%], 3 LQT7 [8%], 7 unidentified-genotype patients [19%]) and 41 controls. The corrected QT interval (QTc) was measured at baseline (QTcsupine) and immediately after standing (QTcstanding); the QTc change from baseline (ΔQTc) was calculated as QTcstanding - QTcsupine. The test was repeated in 26 patients receiving beta-blocker therapy. Results: Both QTcstanding and ΔQTc were significantly higher in the LQTS group than in controls (QTcstanding, 528 ± 46 ms vs 420 ± 15 ms, P < .0001; ΔQTc, 78 ± 40 ms vs 8 ± 13 ms, P < .0001). No significant differences were noted between LQT1 and LQT2 patients. Typical ST-T wave patterns appeared after standing in LQTS patients. Receiver operating characteristic curves of QTcstanding and ΔQTc showed a significant increase in diagnostic value compared with the QTcsupine (area under the curve for both, 0.99 vs 0.85; P < .001). Beta-blockers attenuated the response to standing in LQTS patients (QTcstanding, 440 ± 32 ms, P < .0001; ΔQTc, 14 ± 16 ms, P < .0001). Conclusions: Evaluation of the QTc after the simple maneuver of standing shows a high diagnostic performance and could be important for monitoring the effects of beta-blocker therapy in LQTS patients (AU)

Value of the "Standing Test" in the Diagnosis and Evaluation of Beta-blocker Therapy Response in Long QT Syndrome.

INTRODUCTION AND OBJECTIVES: Patients with congenital long QT syndrome (LQTS) have an abnormal QT adaptation to sudden changes in heart rate provoked by standing. The present study sought to evaluate the standing test in a cohort of LQTS patients and to assess if this QT maladaptation phenomenon is ameliorated by beta-blocker therapy. METHODS: Electrographic assessments were performed at baseline and immediately after standing in 36 LQTS patients (6 LQT1 [17%], 20 LQT2 [56%], 3 LQT7 [8%], 7 unidentified-genotype patients [19%]) and 41 controls. The corrected QT interval (QTc) was measured at baseline (QTcsupine) and immediately after standing (QTcstanding); the QTc change from baseline (ΔQTc) was calculated as QTcstanding - QTcsupine. The test was repeated in 26 patients receiving beta-blocker therapy. RESULTS: Both QTcstanding and ΔQTc were significantly higher in the LQTS group than in controls (QTcstanding, 528 ± 46ms vs 420 ± 15ms, P < .0001; ΔQTc, 78 ± 40ms vs 8 ± 13ms, P < .0001). No significant differences were noted between LQT1 and LQT2 patients. Typical ST-T wave patterns appeared after standing in LQTS patients. Receiver operating characteristic curves of QTcstanding and ΔQTc showed a significant increase in diagnostic value compared with the QTcsupine (area under the curve for both, 0.99 vs 0.85; P < .001). Beta-blockers attenuated the response to standing in LQTS patients (QTcstanding, 440 ± 32ms, P < .0001; ΔQTc, 14 ± 16ms, P < .0001). CONCLUSIONS: Evaluation of the QTc after the simple maneuver of standing shows a high diagnostic performance and could be important for monitoring the effects of beta-blocker therapy in LQTS patients.

Fenotipo heterogéneo del síndrome de QT largo causado por la mutación KCNH2-H562R: importancia del estudio genético familiar / Heterogeneous phenotype of long QT Syndrome caused by the KCNH2-H562R Mutation: Importance of familial genetic testing

Introducción y objetivos: El síndrome de QT largo es una canalopatía hereditaria que se asocia a síncope y muerte súbita. La heterogeneidad fenotípica de esta enfermedad hace que el estudio genético sea fundamental para detectar a los sujetos con síndrome de QT largo oculto. En este trabajo se exponen las características de una familia con 13 portadores de la mutación missense KCNH2-H562R que afecta a la región del poro del canal HERG. Métodos: Se describió la mutación KCNH2-H562R en un varón de 65 años con intervalo QTc prolongado que presentó un episodio de torsade de pointes. Posteriormente, se identificaron 13 portadores de la mutación en la familia. Se realizó evaluación clínica, electrocardiograma y ecocardiograma a los portadores (edad, 48 ± 26 años; el 46% varones). Resultados: El QTc medio en los portadores fue de 493 ± 42 ms (3 [23%] mostraron QTc normal); 6 (46%) tuvieron síntomas (4, síncope; 1, muerte súbita; 1, muerte súbita resucitada [probando]). Durante el tratamiento con bloqueadores beta, 11 (92%) de los 12 portadores permanecieron asintomáticos a los 5 años de seguimiento (1 paciente requirió simpatectomía cardiaca izquierda). El acortamiento del QTc con bloqueadores beta fue de 50 ± 37 ms. Hubo 1 muerte súbita en un paciente que rechazó tratamiento con bloqueadores beta. Conclusiones: El estudio familiar es fundamental en la interpretación de los resultados de los tests genéticos en la actualidad. Este artículo describe el fenotipo variable y heterogéneo de una amplia familia portadora de la mutación KCNH2-H562R y destaca el papel del estudio genético en la identificación de los individuos en riesgo que se beneficiarían del tratamiento con bloqueadores beta (AU)

Introduction and objectives: Long QT syndrome is an inherited ion channelopathy that leads to syncope and sudden death. Because of the heterogeneous phenotype of this disease, genetic testing is fundamental to detect individuals with concealed long QT syndrome. In this study, we determined the features of a family with 13 carriers of the KCNH2-H562R missense mutation, which affects the pore region of the HERG channel. Methods: We identified the KCNH2-H562R mutation in a 65-year-old man with a prolonged QTc interval who had experienced an episode of torsade de pointes. Subsequently, a total of 13 mutation carriers were identified in the family. Carriers (age 48 [26] years; 46% males) underwent clinical evaluation, electrocardiography and echocardiography. Results: The mean (standard deviation) QTc in carriers was 493 (42) ms (3 [23%] showed normal QTc); 6 (46%) had symptoms (4, syncope; 1, sudden death; 1, aborted sudden death [proband]). While under treatment with beta-blockers, 11 of 12 carriers (92%) remained asymptomatic at 5 years of follow-up (1 patient required left cardiac sympathectomy). The QTc shortening with beta-blockers was 50 (37) ms. There was 1 sudden death in a patient who refused treatment. Conclusions: Family study is essential in the interpretation of a genetic testing result. This article describes the heterogeneous and variable phenotype of a large family with the KCNH2-H562R mutation and highlights the role of genetic study for the appropriate identification of at-risk individuals who would benefit from treatment (AU)

Diagnostic Approach to Unexplained Cardiac Arrest (from the FIVI-Gen Study).

Unexplained cardiac arrest (UCA) can be caused by low-penetrance genetic disorders. The aim of this cross-sectional study is to assess the usefulness of a new diagnostic protocol: Thirty-five patients were recruited from 9 Spanish centers. Electrocardiogram, echocardiogram, and coronary catheterization were used to rule out electrical or structural heart disease in all subjects. Patients underwent pharmacologic tests with epinephrine and flecainide, followed by assessment of family members using electrocardiogram and echocardiogram, and next-generation genetic sequencing to analyze 126 genes if all the other test results were negative. A firm diagnosis of channelopathy required phenotypic proof of the condition in unmasking tests, the presence of a pathogenic variant consistent with the phenotype observed, and/or co-segregation of the mutation found in a family member's phenotype. A firm diagnosis was made in 18 cases. The diagnoses were 7 Brugada syndrome, 5 catecholaminergic polymorphic ventricular tachycardia, 3 long QT syndrome, 2 early repolarization syndrome, and 1 short QT syndrome. Pharmacologic testing was the most frequent method of diagnosis. In 5 cases, the diagnosis was made based on positive genetic testing without phenotypic alterations. In conclusion, this sequential diagnostic protocol allows diagnoses to be made in approximately half of the UCA cases. These diagnoses are low clinical penetrance channelopathies. If interpreted carefully, genetic tests can be a useful tool for diagnosing UCA without a phenotype.

Heterogeneous Phenotype of Long QT Syndrome Caused by the KCNH2-H562R Mutation: Importance of Familial Genetic Testing.

INTRODUCTION AND OBJECTIVES: Long QT syndrome is an inherited ion channelopathy that leads to syncope and sudden death. Because of the heterogeneous phenotype of this disease, genetic testing is fundamental to detect individuals with concealed long QT syndrome. In this study, we determined the features of a family with 13 carriers of the KCNH2-H562R missense mutation, which affects the pore region of the HERG channel. METHODS: We identified the KCNH2-H562R mutation in a 65-year-old man with a prolonged QTc interval who had experienced an episode of torsade de pointes. Subsequently, a total of 13 mutation carriers were identified in the family. Carriers (age 48 [26] years; 46% males) underwent clinical evaluation, electrocardiography and echocardiography. RESULTS: The mean (standard deviation) QTc in carriers was 493 (42) ms (3 [23%] showed normal QTc); 6 (46%) had symptoms (4, syncope; 1, sudden death; 1, aborted sudden death [proband]). While under treatment with beta-blockers, 11 of 12 carriers (92%) remained asymptomatic at 5 years of follow-up (1 patient required left cardiac sympathectomy). The QTc shortening with beta-blockers was 50 (37) ms. There was 1 sudden death in a patient who refused treatment. CONCLUSIONS: Family study is essential in the interpretation of a genetic testing result. This article describes the heterogeneous and variable phenotype of a large family with the KCNH2-H562R mutation and highlights the role of genetic study for the appropriate identification of at-risk individuals who would benefit from treatment.

Utilidad de un catéter de ablación con sensor de fuerza en la evaluación de las áreas de cicatriz miocárdicas de pacientes con taquicardia ventricular / Usefulness of the contact force sensing catheter to assess the areas of myocardial scar in patients with ventricular tachycardia

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Genetics of myocarditis in arrhythmogenic right ventricular dysplasia.

BACKGROUND: Myocarditis occasionally is related to arrhythmogenic right ventricular dysplasia (ARVD) and sometimes overlaps during the early stages, which may lead to misdiagnosis. Acute myocarditis may reflect an active phase of ARVD. OBJECTIVE: The purpose of this study was to evaluate the genetic basis of myocarditis in ARVD and to investigate the association with a poorer prognosis and a higher risk of ventricular arrhythmias. METHODS: Two groups were analyzed: group A, which consisted of 131 affected patients-84 with ARVD (62% male, age 45 years [range 33-55 years]) and 47 with left-sided forms (arrhythmogenic left ventricular dysplasia [ALVD]) (47% male, age 45 years [range 25-61 years]); and group B, which consisted of 64 nonaffected mutation-carrying relatives (36% male, age 42 years [range 22-56 years]; 23 from classic ARVD families and 41 from ALVD families). RESULTS: Seven patients (3.5%) presented with a clinical diagnosis of acute myocarditis over median follow-up of 34 months. Myocarditis was the first clinical presentation in 6 of 7 cases. In 2 patients, acute myocarditis preceded worsening of left ventricular systolic function. In 1 case, myocarditis was associated with an increased gadolinium pattern in cardiac magnetic resonance. Two patients presented with ECG changes weeks after myocarditis resolution. Myocarditis preceded the development of ventricular tachycardia in 2 other patients. Myocarditis clustered in families bearing DSP Q447* and LDB3 c.1051A>G. CONCLUSION: Acute myocarditis reflects an active phase of ARVD that leads to changes in phenotype and abrupt progression of the disease. An active phase should be suspected in a patient with myocarditis associated with a family history of ARVD. Certain mutations may increase the susceptibility to superimposed myocarditis in ARVD.

Desmoplakin truncations and arrhythmogenic left ventricular cardiomyopathy: characterizing a phenotype.

AIMS: Risk stratification for sudden death in arrhythmogenic right ventricular cardiomyopathy (ARVC) is challenging in clinical practice. We lack recommendations for the risk stratification of exclusive left-sided phenotypes. The aim of this study was to investigate genotype-phenotype correlations in patients carrying a novel DSP c.1339C>T, and to review the literature on the clinical expression and the outcomes in patients with DSP truncating mutations. METHODS AND RESULTS: Genetic screening of the DSP gene was performed in 47 consecutive patients with a phenotype of either an ARVC (n = 24) or an idiopathic dilated cardiomyopathy (DCM), who presented with ventricular arrhythmias or a family history of sudden death (n = 23) (aged 40 ± 19 years, 62% males). Three unrelated probands with DCM were found to be carriers of a novel mutation (c.1339C>T). Cascade family screening led to the identification of 15 relatives who are carriers. Penetrance in c.1339C>T carriers was 83%. Sustained ventricular tachycardia was the first clinical manifestation in six patients and nine patients were diagnosed with left ventricular impairment (two had overt severe disease and seven had a mild dysfunction). Cardiac magnetic resonance revealed left ventricular involvement in nine cases and biventricular disease in three patients. Extensive fibrotic patterns in six and non-compaction phenotype in five patients were the hallmark in imaging. CONCLUSION: DSP c.1339C>T is associated with an aggressive clinical phenotype of left-dominant arrhythmogenic cardiomyopathy and left ventricular non-compaction. Truncating mutations in desmoplakin are consistently associated with aggressive phenotypes and must be considered as a risk factor of sudden death. Since ventricular tachycardia occurs even in the absence of severe systolic dysfunction, an implantable cardioverter-defibrillator should be indicated promptly.

Multiple interatrial electrical connection after heart transplantation.

A 62-year-old woman who underwent heart transplantation 6 years later presented a regular atrial tachycardia. Electrophysiologic evaluation showed an atrial arrhythmia in the recipient atrium with 2:1 conduction to the donor atrium, with a confusing electroanatomical map. With the suspect of alternant conduction through two different breakthroughs, the map was split in two concordant maps, corresponding to two connections that were successfully ablated. Later on, a third connection was detected and therefore ablated.