Natural History and Risk Stratification in Andersen-Tawil Syndrome Type 1.

BACKGROUND: Andersen-Tawil Syndrome type 1 (ATS1) is a rare arrhythmogenic disorder, caused by loss-of-function mutations in the KCNJ2 gene. We present here the largest cohort of patients with ATS1 with outcome data reported. OBJECTIVES: This study sought to define the risk of life-threatening arrhythmic events (LAE), identify predictors of such events, and define the efficacy of antiarrhythmic therapy in patients with ATS1. METHODS: Clinical and genetic data from consecutive patients with ATS1 from 23 centers were entered in a database implemented at ICS Maugeri in Pavia, Italy, and pooled for analysis. RESULTS: We enrolled 118 patients with ATS1 from 57 families (age 23 ± 17 years at enrollment). Over a median follow-up of 6.2 years (interquartile range: 2.7 to 16.5 years), 17 patients experienced a first LAE, with a cumulative probability of 7.9% at 5 years. An increased risk of LAE was associated with a history of syncope (hazard ratio [HR]: 4.54; p = 0.02), with the documentation of sustained ventricular tachycardia (HR 9.34; p = 0.001) and with the administration of amiodarone (HR: 268; p < 0.001). The rate of LAE without therapy (1.24 per 100 person-years [py]) was not reduced by beta-blockers alone (1.37 per 100 py; p = 1.00), or in combination with Class Ic antiarrhythmic drugs (1.46 per 100 py, p = 1.00). CONCLUSIONS: Our data demonstrate that the clinical course of patients with ATS1 is characterized by a high rate of LAE. A history of unexplained syncope or of documented sustained ventricular tachycardia is associated with a higher risk of LAE. Amiodarone is proarrhythmic and should be avoided in patients with ATS1.

Long-term prognosis of patients with life-threatening ventricular arrhythmias induced by coronary artery spasm.

Aims: Coronary artery spasm (CAS) is associated with ventricular arrhythmias (VA). Much controversy remains regarding the best therapeutic interventions for this specific patient subset. We aimed to evaluate the clinical outcomes of patients with a history of life-threatening VA due to CAS with various medical interventions, as well as the need for ICD placement in the setting of optimal medical therapy. Methods and results: A multicentre European retrospective survey of patients with VA in the setting of CAS was aggregated and relevant clinical and demographic data was analysed. Forty-nine appropriate patients were identified: 43 (87.8%) presented with VF and 6 (12.2%) with rapid VT. ICD implantation was performed in 44 (89.8%). During follow-up [59 (17-117) months], appropriate ICD shocks were documented in 12. In 8/12 (66.6%) no more ICD therapies were recorded after optimizing calcium channel blocker (CCB) therapy. SCD occurred in one patient without ICD. Treatment with beta-blockers was predictive of appropriate device discharge. Conversely, non-dihydropyridine CCB therapy was significantly protective against VAs. Conclusion: Patients with life-threatening VAs secondary to CAS are at particularly high-risk for recurrence, especially when insufficient medical therapy is administered. Non-dihydropyridine CCBs are capable of suppressing episodes, whereas beta-blocker treatment is predictive of VAs. Ultimately, in spite of medical intervention, some patients exhibited arrhythmogenic events in the long-term, suggesting that ICD implantation may still be indicated for all.

Evaluación comparativa de cuatro puntuaciones de riesgo para predecir la mortalidad de pacientes con desfibrilador automático implantable en prevención primaria / Comparative evaluation of four risk scores for predicting mortality in patients with implantable cardioverter-defibrillator for primary prevention

Introducción y objetivos: Se han elaborado varias puntuaciones clínicas del riesgo para identificar a los pacientes con un riesgo de mortalidad por cualquier causa elevado a pesar del implante de un desfibrilador implantable. El objetivo de este trabajo es examinar y comparar la capacidad predictiva de 4 sistemas de puntuación sencillos (MADIT-II, FADES, PACE y SHOCKED) por lo que respecta a la predicción de la mortalidad tras implante de desfibrilador para la prevención primaria de la muerte súbita cardiaca en un país mediterráneo. Métodos: Se llevó a cabo un estudio multicéntrico retrospectivo en 15 hospitales españoles. Se incluyó a los pacientes consecutivos remitidos para implante de desfibrilador entre enero de 2010 y diciembre de 2011. Resultados: Se incluyó a 916 pacientes con cardiopatía isquémica o no isquémica (media de edad, 62 ± 11 años; el 81,4% varones). Durante un periodo de 33,4 ± 12,9 meses, fallecieron 113 pacientes (12,3%), el 9,4% (86 pacientes) por causa cardiovascular. A los 12, 24, 36 y 48 meses, la tasa de mortalidad fue del 4,5, el 7,6, el 10,8 y el 12,3% respectivamente. Todas las puntuaciones de riesgo mostraron un aumento escalonado del riesgo de muerte a lo largo de todo el sistema de puntuación de cada una de ellas y las 4 identificaron a los pacientes en mayor riesgo de mortalidad. Las puntuaciones tuvieron asociación significativa con la mortalidad por cualquier causa en todo el periodo de seguimiento. La puntuación PACE fue la que mostró un valor del índice c más bajo, tanto si la población tenía una cardiopatía de origen isquémico (estadístico c = 0,61) como si era de origen no isquémico (estadístico c = 0,61), mientras que la puntuación MADIT-II (estadístico c = 0,67 y 0,65 en la miocardiopatía isquémica y no isquémica respectivamente), las puntuaciones SHOCKED (estadístico c = 0,68 y 0,66 respectivamente) y FADES (estadístico c = 0,66 y 0,60) mostraron unos valores del estadístico c similares (p ≥ 0,09). Conclusiones: En esta cohorte de pacientes mediterráneos que no formaba parte de un ensayo clínico, las 4 puntuaciones de riesgo evaluadas mostraron un significativo aumento escalonado del riesgo de muerte. De entre las puntuaciones de riesgo existentes, MADIT-II, FADES y SHOCKED aportan un rendimiento ligeramente superior al de la puntuación PACE (AU)

Introduction and objectives: Several clinical risk scores have been developed to identify patients at high risk of all-cause mortality despite implantation of an implantable cardioverter-defibrillator. We aimed to examine and compare the predictive capacity of 4 simple scoring systems (MADIT-II, FADES, PACE and SHOCKED) for predicting mortality after defibrillator implantation for primary prevention of sudden cardiac death in a Mediterranean country. Methods: A multicenter retrospective study was performed in 15 Spanish hospitals. Consecutive patients referred for defibrillator implantation between January 2010 and December 2011 were included. Results: A total of 916 patients with ischemic and nonischemic heart disease were included (mean age, 62 ± 11 years, 81.4% male). Over 33.4 ± 12.9 months, 113 (12.3%) patients died (cardiovascular origin in 86 [9.4%] patients). At 12, 24, 36, and 48 months, mortality rates were 4.5%, 7.6%, 10.8%, and 12.3% respectively. All the risk scores showed a stepwise increase in the risk of death throughout the scoring system of each of the scores and all 4 scores identified patients at greater risk of mortality. The scores were significantly associated with all-cause mortality throughout the follow-up period. PACE displayed the lowest c-index value regardless of whether the population had heart disease of ischemic (c-statistic = 0.61) or nonischemic origin (c-statistic = 0.61), whereas MADIT-II (c-statistic = 0.67 and 0.65 in ischemic and nonischemic cardiomyopathy, respectively), SHOCKED (c-statistic = 0.68 and 0.66, respectively), and FADES (c-statistic = 0.66 and 0.60) provided similar c-statistic values (P ≥ .09). Conclusions: In this nontrial-based cohort of Mediterranean patients, the 4 evaluated risk scores showed a significant stepwise increase in the risk of death. Among the currently available risk scores, MADIT-II, FADES, and SHOCKED provide slightly better performance than PACE (AU)

Comparative Evaluation of Four Risk Scores for Predicting Mortality in Patients With Implantable Cardioverter-defibrillator for Primary Prevention.

INTRODUCTION AND OBJECTIVES: Several clinical risk scores have been developed to identify patients at high risk of all-cause mortality despite implantation of an implantable cardioverter-defibrillator. We aimed to examine and compare the predictive capacity of 4 simple scoring systems (MADIT-II, FADES, PACE and SHOCKED) for predicting mortality after defibrillator implantation for primary prevention of sudden cardiac death in a Mediterranean country. METHODS: A multicenter retrospective study was performed in 15 Spanish hospitals. Consecutive patients referred for defibrillator implantation between January 2010 and December 2011 were included. RESULTS: A total of 916 patients with ischemic and nonischemic heart disease were included (mean age, 62 ± 11 years, 81.4% male). Over 33.4 ± 12.9 months, 113 (12.3%) patients died (cardiovascular origin in 86 [9.4%] patients). At 12, 24, 36, and 48 months, mortality rates were 4.5%, 7.6%, 10.8%, and 12.3% respectively. All the risk scores showed a stepwise increase in the risk of death throughout the scoring system of each of the scores and all 4 scores identified patients at greater risk of mortality. The scores were significantly associated with all-cause mortality throughout the follow-up period. PACE displayed the lowest c-index value regardless of whether the population had heart disease of ischemic (c-statistic = 0.61) or nonischemic origin (c-statistic = 0.61), whereas MADIT-II (c-statistic = 0.67 and 0.65 in ischemic and nonischemic cardiomyopathy, respectively), SHOCKED (c-statistic = 0.68 and 0.66, respectively), and FADES (c-statistic = 0.66 and 0.60) provided similar c-statistic values (P ≥ .09). CONCLUSIONS: In this nontrial-based cohort of Mediterranean patients, the 4 evaluated risk scores showed a significant stepwise increase in the risk of death. Among the currently available risk scores, MADIT-II, FADES, and SHOCKED provide slightly better performance than PACE.

Prevención primaria de muerte súbita en pacientes con miocardiopatía valvular / Primary prevention of sudden death in patients with valvular cardiomyopathy

Introducción y objetivos: Existe escasa evidencia sobre la evolución de los pacientes con miocardiopatía valvular remitidos para implante de desfibrilador por prevención primaria. Se pretende describir la evolución de este subgrupo particular. Métodos: Estudio multicéntrico retrospectivo en 15 centros españoles que incluyó pacientes consecutivos remitidos para implante de desfibrilador en los años 2010 y 2011, y en tres centros desde el 1 enero de 2008. Resultados: De un total de 1.174 pacientes, 73 (6,2%) presentaron miocardiopatía valvular. Comparados con los pacientes con miocardiopatía isquémica (n = 659; 56,1%) o dilatada (n = 442; 37,6%), presentaron peor clase funcional, mayor anchura del QRS y antecedente de fibrilación auricular. Durante un seguimiento de 38,1 ± 21,3 meses, 197 (16,7%) pacientes fallecieron por cualquier causa, sin diferencias significativas entre grupos (19,2% en miocardiopatía valvular, 15,8% en isquémica y 17,9% en miocardiopatía dilatada; p = 0,2). De estos, 136 murieron por causa cardiovascular (11,6%), sin diferencias significativas (12,3%; 10,5% y 13,1%, respectivamente; p = 0,1). Tampoco hubo diferencias en la proporción de intervenciones apropiadas del desfibrilador (13,7%; 17,9% y 18,8%; p = 0,4), pero sí en el de inapropiadas (8,2%; 7,1% y 12,0%, respectivamente; p = 0,03). Conclusiones: Las tasas de mortalidad por cualquier causa y por causa cardiovascular en pacientes con miocardiopatía valvular fueron similares a las del resto de los pacientes remitidos para implante de desfibrilador. También presentaron similares tasas de intervenciones apropiadas. Estos datos parecen indicar que el implante de un desfibrilador en este grupo confiere un beneficio similar al que obtienen los pacientes con miocardiopatía isquémica y miocardiopatía dilatada (AU)

Introduction and objectives: Few data exist on the outcomes of valvular cardiomyopathy patients referred for defibrillator implantation for primary prevention. The aim of the present study was to describe the outcomes of this cardiomyopathy subgroup. Methods: This multicenter retrospective study included consecutive patients referred for defibrillator implantation to 15 Spanish centers in 2010 and 2011, and to 3 centers after 1 January 2008. Results: Of 1174 patients, 73 (6.2%) had valvular cardiomyopathy. These patients had worse functional class, wider QRS, and a history of atrial fibrillation vs patients with ischemic (n = 659; 56.1%) or dilated (n = 442; 37.6%) cardiomyopathy. During a follow-up of 38.1 ± 21.3 months, 197 patients (16.7%) died, without significant differences among the groups (19.2% in the valvular cardiomyopathy group, 15.8% in the ischemic cardiomyopathy group, and 17.9% in the dilated cardiomyopathy group; P = .2); 136 died of cardiovascular causes (11.6%), without significant differences among the groups (12.3%, 10.5%, and 13.1%, respectively; P = .1). Although there were no differences in the proportion of appropriate defibrillator interventions (13.7%, 17.9%, and 18.8%; P = .4), there was a difference in inappropriate interventions (8.2%, 7.1%, and 12.0%, respectively; P = .03). Conclusions: All-cause and cardiovascular mortality in patients with valvular cardiomyopathy were similar to those in other patients referred for defibrillator implantation. They also had similar rates of appropriate interventions. These data suggest that defibrillator implantation in this patient group confers a similar benefit to that obtained by patients with ischemic or dilated cardiomyopathy (AU)

La hiponatremia como marcador de riesgo en pacientes sometidos a implante de desfibrilador en prevención primaria / Prognostic impact of hyponatremia in patients receiving implantable cardioverter in primary prevention

Introducción y objetivos: La hiponatremia es un factor de mal pronóstico en pacientes con insuficiencia cardiaca. Nuestro objetivo fue valorar el impacto de la hiponatremia en la evolución de los pacientes sometidos a implante de desfibrilador en prevención primaria. Método: Se trata de un estudio observacional retrospectivo multicéntrico en el que se valoró la natremia periimplante y los eventos adversos (la mortalidad de cualquier causa y la cardiovascular, el primer ingreso por insuficiencia cardiaca, la primera terapia apropiada e inapropiada del desfibrilador), en una cohorte española sometida a implante de desfibrilador en la prevención primaria. Se comparó la hiponatremia ligera (Na ≤ 135 mEq/l) y la moderada-severa (Na ≤ 131 mEq/l) respecto a la ausencia de la hiponatremia. Resultados: Un total de 725 pacientes, con un valor medio de sodio en la sangre periimplante de 139 ± 3,6 mEq/l y un tiempo medio de seguimiento de 34,1 ± 18,5 meses. En los pacientes con Na ≤ 135 mEq/l (n = 105) se observó una mayor incidencia de primer ingreso por insuficiencia cardiaca (odds ratio: 1,701; p = 0,031). En los pacientes con hiponatremia moderada-severa (n = 18) se observó mayor mortalidad total (hazard ratio; 3,552; p = 0,002) y mayor mortalidad cardiovascular (hazard ratio: 4,24; p = 0,003). Ninguno de los grados de la hiponatremia estudiados se asoció con mayor incidencia de terapias apropiadas o inapropiadas. Conclusiones: La hiponatremia ligera en el momento del implante de un desfibrilador se asocia a una mayor incidencia de ingreso por insuficiencia cardiaca en el seguimiento, mientras que en el caso de una hiponatremia moderada-severa, se asocia a un riesgo de muerte 4 veces mayor.

Introduction and objectives: Hyponatremia is a prognostic factor in patients with heart failure. Our objective was to assess the impact of hyponatremia in the evolution of patients undergoing cardioverter implantation in primary prevention. Method: This is a multicenter retrospective observational study in which serum sodium periimplant and adverse events (all-cause and cardiovascular mortality, first admission for heart failure, first appropriate and inappropriate therapy) were assessed in a Spanish cohort receiving cardioverter in primary prevention. Patients with mild hyponatremia (Na ≤ 135 mEq/L) and those with moderate to severe hyponatremia (Na ≤ 131 mEq/L) were compared to those without hyponatremia. Results: 725 patients, with a mean value of sodium in blood peri-implant of 139 ± 3.6 mEq/L and a mean follow-up was 34.1 ± 18.5 months. In patients with Na ≤ 135 mEq/L (n = 105), an increased incidence of first admission for heart failure was observed (Odds Ratio: 1.701; P = .031). In patients with moderate to severe hyponatremia (n = 18), higher total mortality (Hazard Ratio: 3.552; P = .002) and increased cardiovascular mortality (Hazard Ratio: 4.24; P = .003) were observed. None of those values of hyponatremia were associated with increased incidence of appropriate or inappropriate therapies Conclusions: Mild hyponatremia at the time of cardioverter implantation is related with a higher incidence of hospitalization for heart failure during follow-up, while moderate to severe hyponatremia increases the risk of death during follow-up.

Primary Prevention of Sudden Death in Patients With Valvular Cardiomyopathy.

INTRODUCTION AND OBJECTIVES: Few data exist on the outcomes of valvular cardiomyopathy patients referred for defibrillator implantation for primary prevention. The aim of the present study was to describe the outcomes of this cardiomyopathy subgroup. METHODS: This multicenter retrospective study included consecutive patients referred for defibrillator implantation to 15 Spanish centers in 2010 and 2011, and to 3 centers after 1 January 2008. RESULTS: Of 1174 patients, 73 (6.2%) had valvular cardiomyopathy. These patients had worse functional class, wider QRS, and a history of atrial fibrillation vs patients with ischemic (n=659; 56.1%) or dilated (n=442; 37.6%) cardiomyopathy. During a follow-up of 38.1 ± 21.3 months, 197 patients (16.7%) died, without significant differences among the groups (19.2% in the valvular cardiomyopathy group, 15.8% in the ischemic cardiomyopathy group, and 17.9% in the dilated cardiomyopathy group; P=.2); 136 died of cardiovascular causes (11.6%), without significant differences among the groups (12.3%, 10.5%, and 13.1%, respectively; P=.1). Although there were no differences in the proportion of appropriate defibrillator interventions (13.7%, 17.9%, and 18.8%; P=.4), there was a difference in inappropriate interventions (8.2%, 7.1%, and 12.0%, respectively; P=.03). CONCLUSIONS: All-cause and cardiovascular mortality in patients with valvular cardiomyopathy were similar to those in other patients referred for defibrillator implantation. They also had similar rates of appropriate interventions. These data suggest that defibrillator implantation in this patient group confers a similar benefit to that obtained by patients with ischemic or dilated cardiomyopathy.

[Electrical storm in patients with prophylactic defibrillator implantation]. / Evolución de los pacientes portadores de desfibrilador como prevención primaria tras un episodio de tormenta arrítmica.

INTRODUCTION: Little is known about the prevalence of electrical storm, baseline characteristics and mortality implications of patients with implantable cardioverter defibrillator in primary prevention versus those patients without electrical storm. We sought to assess the prevalence, baseline risk profile and survival significance of electrical storm in patients with implantable defibrillator for primary prevention. METHODS: Retrospective multicenter study performed in 15 Spanish hospitals. Consecutives patients referred for desfibrillator implantation, with or without left ventricular lead (at least those performed in 2010 and 2011), were included. RESULTS: Over all 1,174 patients, 34 (2,9%) presented an electrical storm, mainly due to ventricular tachycardia (82.4%). There were no significant baseline differences between groups, with similar punctuation in the mortality risk scores (SHOCKED, MADIT and FADES). A clear trigger was identified in 47% of the events. During the study period (38±21 months), long-term total mortality (58.8% versus 14.4%, p<0.001) and cardiac mortality (52.9% versus 8.6%, p<0.001) were both increased among electrical storm patients. Rate of inappropriate desfibrillator intervention was also higher (14.7 versus 8.6%, p<0.001). CONCLUSIONS: In the present study of patients with desfibrillator implantation for primary prevention, prevalence of electrical storm was 2.9%. There were no baseline differences in the cardiovascular risk profile versus those without electrical storm. However, all cause mortality and cardiovascular mortality was increased in these patients versus control desfibrillator patients without electrical storm, as was the rate of inappropriate desfibrillator intervention.

[Management of syncope in the emergency department without hospital admission: usefulness of an arrhythmia unit coordinated protocol]. / Manejo del síncope en el servicio de urgencias sin ingreso hospitalario: utilidad de un protocolo coordinado con la unidad de arritmias.

INTRODUCTION AND OBJECTIVES: The main aim of this study was to demonstrate that a protocol for managing syncope in the emergency department that is based on the early detection of heart disease enables patients to be diagnosed quickly and with few admissions, without there being a negative impact on prognosis. METHODS: The study was performed prospectively in 199 consecutive patients (54% male; mean age, 67 [17] years) who presented with syncope at the emergency department of our hospital during a 17-month period. A two-step diagnostic algorithm was developed in which patients initially underwent clinical and electro-cardiographic assessment, and thereafter were submitted to a diagnostic protocol that involved carrying out a sequence of diagnostic tests in the emergency room to avoid hospital admission. RESULTS: A presumptive diagnosis was established in 120 (60%) patients during the initial assessment. After completion of the diagnostic protocol, 78% of patients were given a clear diagnosis within a mean stay of 19 [15] h in the emergency department. Some 10% of patients were admitted. Three patients died during a mean follow-up period of 237 days. CONCLUSIONS: Implementation of a protocol for managing syncope in the emergency department that was based on screening patients according to the presence of heart disease enabled a large percentage to receive a diagnosis. Moreover, the majority of patients could be discharged rapidly from the emergency department without there being any negative impact on medium-term prognosis.

Manejo del síncope en el servicio de urgencias sin ingreso hospitalario: utilidad de un protocolo coordinado con la unidad de arritmias / Management of syncope in the emergency department without hospital admission: usefulness of an arrhythmia unit coordinated protocol

Introducción y objetivos. El principal objetivo de este estudio es demostrar que un protocolo para el manejo del síncope en el servicio de urgencias basado en la detección precoz de cardiopatía permite diagnosticar a los pacientes de forma rápida y con una baja proporción de ingresos, sin que ello repercuta de forma negativa en su pronóstico. Métodos. El estudio se realizó de forma prospectiva en 199 pacientes consecutivos (54% varones; media de edad, 67 ± 17 años) que acudieron por síncope al servicio de urgencias de nuestro hospital en un período de 17 meses. Se desarrolló un algoritmo diagnóstico en dos pasos en el que los pacientes eran sometidos a una primera evaluación clínica y electrocardiográfica y posteriormente a un protocolo diagnóstico basado en la realización secuencial de pruebas diagnósticas en el servicio de urgencias, con lo que se evitó su ingreso hospitalario. Resultados. Tras la valoración inicial, se diagnosticó a 120 (60%) pacientes. Después de completado el protocolo, se obtuvo clasificación diagnóstica del 78% de los pacientes, con una estancia media en el servicio de urgencias de 19 ± 15 h; se ingresó al 10% de los pacientes. Con un seguimiento medio de 237 días, fallecieron 3 pacientes. Conclusiones. El manejo protocolizado del síncope en el servicio de urgencias basado en una estratificación de los pacientes según tengan o no cardiopatías permite el diagnóstico de una elevado porcentaje de pacientes y dar de alta a la mayoría de forma rápida desde el mismo servicio de urgencias, sin que ello repercuta de forma negativa en su pronóstico a medio plazo (AU)

Introduction and objectives. The main aim of this study was to demonstrate that a protocol for managing syncope in the emergency department that is based on the early detection of heart disease enables patients to be diagnosed quickly and with few admissions, without there being a negative impact on prognosis. Methods. The study was performed prospectively in 199 consecutive patients (54% male; mean age, 67 [17] years) who presented with syncope at the emergency department of our hospital during a 17-month period. A two-step diagnostic algorithm was developed in which patients initially underwent clinical and electro-cardiographic assessment, and thereafter were submitted to a diagnostic protocol that involved carrying out a sequence of diagnostic tests in the emergency room to avoid hospital admission. Results. A presumptive diagnosis was established in 120 (60%) patients during the initial assessment. After completion of the diagnostic protocol, 78% of patients were given a clear diagnosis within a mean stay of 19 [15] h in the emergency department. Some 10% of patients were admitted. Three patients died during a mean follow-up period of 237 days. Conclusions. Implementation of a protocol for managing syncope in the emergency department that was based on screening patients according to the presence of heart disease enabled a large percentage to receive a diagnosis. Moreover, the majority of patients could be discharged rapidly from the emergency department without there being any negative impact on medium-term prognosis (AU)