Effects of Cardiac Stem Cell on Postinfarction Arrhythmogenic Substrate.

Clinical data suggest that cardiosphere-derived cells (CDCs) could modify post-infarction scar and ventricular remodeling and reduce the incidence of ventricular tachycardia (VT). This paper assesses the effect of CDCs on VT substrate in a pig model of postinfarction monomorphic VT. We studied the effect of CDCs on the electrophysiological properties and histological structure of dense scar and heterogeneous tissue (HT). Optical mapping and histological evaluation were performed 16 weeks after the induction of a myocardial infarction by transient occlusion of the left anterior descending (LAD) artery in 21 pigs. Four weeks after LAD occlusion, pigs were randomized to receive intracoronary plus trans-myocardial CDCs (IC+TM group, n: 10) or to a control group. Optical mapping (OM) showed an action potential duration (APD) gradient between HT and normal tissue in both groups. CDCs increased conduction velocity (53 ± 5 vs. 45 ± 6 cm/s, p < 0.01), prolonged APD (280 ± 30 ms vs. 220 ± 40 ms, p < 0.01) and decreased APD dispersion in the HT. During OM, a VT was induced in one and seven of the IC+TM and control hearts (p = 0.03), respectively; five of these VTs had their critical isthmus located in intra-scar HT found adjacent to the coronary arteries. Histological evaluation of HT revealed less fibrosis (p < 0.01), lower density of myofibroblasts (p = 0.001), and higher density of connexin-43 in the IC+TM group. Scar and left ventricular volumes did not show differences between groups. Allogeneic CDCs early after myocardial infarction can modify the structure and electrophysiology of post-infarction scar. These findings pave the way for novel therapeutic properties of CDCs.

Radiofrequency treatment for electrical storm: evolution and monitoring. / Tratamiento con radiofrecuencia de la tormenta eléctrica: evolución y seguimiento.

Introducción y objetivos: La tormenta eléctrica (TE) se caracteriza por episodios repetidos de taquicardia ventricular o fibrilación ventricular relacionados con mal pronóstico a corto y largo plazos. El objetivo fue evaluar la prevalencia, resultados y supervivencia de los pacientes sometidos a tratamiento intervencionista por TE en un centro de referencia. Métodos: Estudio unicéntrico, observacional y retrospectivo. Se revisaron los procedimientos de ablación por TE y se evaluaron las características basales de los pacientes, tipo de procedimiento, mortalidad total, recurrencia de arritmia, mortalidad cardiovascular y necesidad de trasplante. Resultados: Desde enero de 2009 hasta diciembre de 2016 se realizaron 67 procedimientos (38% de complejos: 19% de ablación endoepicárdica, 7.5% de crioablación epicárdica quirúrgica, 3% de simpatectomía, 3% de inyección coronaria con alcohol; 6% de apoyo con oxigenación con membrana extracorpórea) en 41 pacientes (61% de causa isquémica) por TE. La mortalidad intraprocedimiento fue del 1.5%. La mediana de seguimiento fue de 23.5 meses (RIQ, 14.2-52.7). Tras el primer ingreso por TE (uno o varios procedimientos), la mortalidad a un año fue de 9.8%. La incidencia acumulada de trasplante cardiaco por TE fue de 2.4%. En el análisis multivariado, el riesgo de recurrencias arrítmicas o muerte por cualquier causa fue significativamente mayor en pacientes con arritmias clínicas inducibles (HR, 9.03; p = 0.017). Conclusiones: El tratamiento de pacientes con TE, instituido en un centro de referencia y con experiencia, se relacionó con una tasa baja de recurrencia y supervivencia elevada, con una tasa de trasplante cardiaco por TE muy baja. Ante una recurrencia temprana es recomendable practicar un nuevo procedimiento durante el ingreso. Introduction and objective: Electrical storm (ES) is characterized by repeated episodes of ventricular tachycardia or ventricular fibrillation, with poor short and long term prognosis. Our objective was to evaluate the prevalence, results of interventional treatment and survival of patients undergoing interventional treatment for ES in our center. Methods: Retrospective, unicentric and observational study. ES ablation procedures were revised and data regarding baseline characteristics of the patients, type of procedure, total mortality, recurrence of arrhythmia, cardiovascular mortality and the need for transplantation were evaluated. Results: From January 2009 to December 2016, 67 procedures (38% complex procedures: 19% epicardial ablation, 7.5% surgical epicardial crioablation, 3% simpatectomy, 3% coronary alcohol injection, 6% extracorporeal membrane oxygenation support) were performed in 41 patients (61% Ischemic etiology) due to ES. Intraprocedural mortality was 1.5%. The median follow-up was 23.5 months (IQR [14.2-52.7]). After the first admission for ES (one or several procedures), 1-year mortality was 9.8%. The cumulative incidence of cardiac transplantation was 2.4%. The risk of arrhythmic recurrences or death was significantly higher in patients with inducible clinical arrhythmias after ablation (HR: 9.03, p = 0.017). Conclusions: The treatment of patients with ES, performed in a reference center, allows obtaining good rates of recurrence and survival, with very low rates of cardiac transplantation for ES. In the presence of an early recurrence, it is advisable to perform a new procedure during admission.

Tratamiento con radiofrecuencia de la tormenta eléctrica: evolución y seguimiento / Radiofrequency treatment for electrical storm: evolution and monitoring

Resumen Introducción y objetivos: La tormenta eléctrica (TE) se caracteriza por episodios repetidos de taquicardia ventricular o fibrilación ventricular relacionados con mal pronóstico a corto y largo plazos. El objetivo fue evaluar la prevalencia, resultados y supervivencia de los pacientes sometidos a tratamiento intervencionista por TE en un centro de referencia. Métodos: Estudio unicéntrico, observacional y retrospectivo. Se revisaron los procedimientos de ablación por TE y se evaluaron las características basales de los pacientes, tipo de procedimiento, mortalidad total, recurrencia de arritmia, mortalidad cardiovascular y necesidad de trasplante. Resultados: Desde enero de 2009 hasta diciembre de 2016 se realizaron 67 procedimientos (38% de complejos: 19% de ablación endoepicárdica, 7.5% de crioablación epicárdica quirúrgica, 3% de simpatectomía, 3% de inyección coronaria con alcohol; 6% de apoyo con oxigenación con membrana extracorpórea) en 41 pacientes (61% de causa isquémica) por TE. La mortalidad intraprocedimiento fue del 1.5%. La mediana de seguimiento fue de 23.5 meses (RIQ, 14.2-52.7). Tras el primer ingreso por TE (uno o varios procedimientos), la mortalidad a un año fue de 9.8%. La incidencia acumulada de trasplante cardiaco por TE fue de 2.4%. En el análisis multivariado, el riesgo de recurrencias arrítmicas o muerte por cualquier causa fue significativamente mayor en pacientes con arritmias clínicas inducibles (HR, 9.03; p = 0.017). Conclusiones: El tratamiento de pacientes con TE, instituido en un centro de referencia y con experiencia, se relacionó con una tasa baja de recurrencia y supervivencia elevada, con una tasa de trasplante cardiaco por TE muy baja. Ante una recurrencia temprana es recomendable practicar un nuevo procedimiento durante el ingreso.

Abstract Introduction and objective: Electrical storm (ES) is characterized by repeated episodes of ventricular tachycardia or ventricular fibrillation, with poor short and long term prognosis. Our objective was to evaluate the prevalence, results of interventional treatment and survival of patients undergoing interventional treatment for ES in our center. Methods: Retrospective, unicentric and observational study. ES ablation procedures were revised and data regarding baseline characteristics of the patients, type of procedure, total mortality, recurrence of arrhythmia, cardiovascular mortality and the need for transplantation were evaluated. Results: From January 2009 to December 2016, 67 procedures (38% complex procedures: 19% epicardial ablation, 7.5% surgical epicardial crioablation, 3% simpatectomy, 3% coronary alcohol injection, 6% extracorporeal membrane oxygenation support) were performed in 41 patients (61% Ischemic etiology) due to ES. Intraprocedural mortality was 1.5%. The median follow-up was 23.5 months (IQR [14.2-52.7]). After the first admission for ES (one or several procedures), 1-year mortality was 9.8%. The cumulative incidence of cardiac transplantation was 2.4%. The risk of arrhythmic recurrences or death was significantly higher in patients with inducible clinical arrhythmias after ablation (HR: 9.03, p = 0.017). Conclusions: The treatment of patients with ES, performed in a reference center, allows obtaining good rates of recurrence and survival, with very low rates of cardiac transplantation for ES. In the presence of an early recurrence, it is advisable to perform a new procedure during admission.

Predictors of pacemaker dependency in patients implanted with a pacemaker after Transaortic valve replacement.

INTRODUCTION AND OBJECTIVES: The development of complete AV block and the need for pacemaker implantation (PM) is the most frequent complication after Transaortic valve replacement (TAVR). In other PM clinical contexts, a higher percentage of ventricular stimulation has been associated with worse prognosis. The objective was to study the existence of predictors of PM dependence. METHODS: We identified 96 consecutive patients who had received a PM post-TAVR (all Core-Valve). We retrospectively analyzed this cohort with the aim of identifying predictors of a high and very high percentage of ventricular pacing (VP), PM dependency and survival. RESULTS: The mean age was 82.3 years, with a mean logistic EuroSCORE of 17.1, 53% were women and 12% of patients had LVEF < 50%. The indication was complete AV block in 40.5%, and LBBB in 59.5%. Mean survival was 62.7 months, IQR [54.4-71]. The only independent predictor of mortality was the pre-TAVR logistic Euro-SCORE (RR = 1,026, p = 0.033), but not LVEF < 50%, VP > 50%, VP > 85% or PM dependence. In 73 patients PM rhythm was documented at the end of follow-up. Of these, 14 (19.2%) were considered dependent, and 37 (50.7%) presented VP > 50%. The post-TAVR complete AV block recovery rate was 67.8%. In multivariate analysis, female sex (HR = 5.6, p = 0.005), and indication of complete AV block vs. LBBB (HR = 15.7, p = 0.017) were independently associated with PM dependency. CONCLUSIONS: Female sex and indication due to complete AV block were independent predictors of PM dependency during follow up. In our series of patients with mostly normal LVEF, a high percentage of stimulation does not influence prognosis.

Sensibilidad y valor predictivo negativo de la ergometría para el diagnóstico de la taquicardia ventricular polimórfica catecolaminérgica / Sensitivity and negative predictive value of treadmill exercise stress testing for the diagnosis of catecholaminergic polymorphic ventricular tachycardia

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Clinical and molecular characterization of a cardiac ryanodine receptor founder mutation causing catecholaminergic polymorphic ventricular tachycardia.

BACKGROUND: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a difficult-to-diagnose cause of sudden cardiac death (SCD). We identified a family of 1400 individuals with multiple cases of CPVT, including 36 SCDs during youth. OBJECTIVES: We sought to identify the genetic cause of CPVT in this family, to preventively treat and clinically characterize the mutation-positive individuals, and to functionally characterize the pathogenic mechanisms of the mutation. METHODS: Genetic testing was performed for 1404 relatives. Mutation-positive individuals were preventively treated with ß-blockers and clinically characterized with a serial exercise treadmill test (ETT) and Holter monitoring. In vitro functional studies included caffeine sensitivity and store overload-induced calcium release activity of the mutant channel in HEK293 cells. RESULTS: We identified the p.G357S_RyR2 mutation, in the cardiac ryanodine receptor, in 179 family members and in 6 SCD cases. No SCD was observed among treated mutation-positive individuals over a median follow-up of 37 months; however, 3 relatives who had refused genetic testing (confirmed mutation-positive individuals) experienced SCD. Holter monitoring did not provide relevant information for CPVT diagnosis. One single ETT was unable to detect complex cardiac arrhythmias in 72% of mutation-positive individuals, though the serial ETT improved the accuracy. Functional studies showed that the G357S mutation increased caffeine sensitivity and store overload-induced calcium release activity under conditions that mimic catecholaminergic stress. CONCLUSION: Our study supports the use of genetic testing to identify individuals at risk of SCD to undertake prophylactic interventions. We also show that the pathogenic mechanisms of p.G357S_RyR2 appear to depend on ß-adrenergic stimulation.