Juan José Sánchez Muñoz

A Probabilistic Model of Cardiac Electrical Activity Based on a Cellular Automata System

Introduction and objectives Mathematical models of cardiac electrical activity may help to elucidate the electrophysiological mechanisms involved in the genesis of arrhythmias. The most realistic simulations are based on reaction-diffusion models and involve a considerable computational burden. The aim of this study was to develop a computer model of cardiac electrical activity able to simulate complex electrophysiological phenomena but free of the large computational demands required by other commonly used models. Material and method A cellular automata system was used to model the cardiac tissue. Each individual unit had several discrete states that changed according to simple rules as a function of the previous state and the state of the neighboring cells. Activation was considered as a probabilistic process and was adjusted using restitution curves. In contrast, repolarization was modeled as a deterministic phenomenon. Cell currents in the model were calculated with a prototypical action potential that allowed virtual monopolar and bipolar electrograms to be simulated at any point in space. Results Reproducible flat activation fronts, propagation from a focal stimulus, and reentry processes that were stable and unstable in two dimensions (with their corresponding electrograms) were obtained. The model was particularly suitable for the simulation of the effects observed in curvilinear activation fronts. Fibrillatory conduction and stable rotors in two- and three-dimensional substrates were also obtained. Conclusions The probabilistic cellular automata model was simple to implement and was not associated with a high computational burden. It provided a realistic simulation of complex phenomena of interest in electrophysiology.

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 members 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.

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.

Desarrollo de un modelo probabilístico de la actividad eléctrica cardíaca basado en un autómata celular

Introduccion y objetivos La utilizacion de modelos matematicos de activacion y propagacion del impulso ha mejorado la comprension de diversos mecanismos electrofisiologicos involucrados en la genesis de las arritmias. Las simulaciones mas realistas se basan en los modelos de reaccion-difusion e implican una carga computacional muy elevada. El objetivo del estudio es desarrollar un modelo de activacion electrica cardiaca por ordenador que permita simular fenomenos electrofisiologicos complejos y que no requiera la carga computacional necesaria en otros modelos habitualmente empleados. Material y metodo Se ha modelado el tejido cardiaco como un automata celular, cada uno de cuyos elementos adopta estados discretos en funcion de su estado previo y del de las celulas vecinas siguiendo unas reglas sencillas. La activacion se contempla como un proceso probabilistico y se ajusta mediante el fenomeno de restitucion, mientras la repolarizacion se modela como un proceso determinista. Finalmente, las corrientes celulares se calculan utilizando un potencial de accion prototipo, lo que permite simular los electrogramas virtuales monopolares y bipolares en cualquier punto del espacio. Resultados Se ha conseguido reproducir frentes planos de activacion, propagacion de un estimulo focal y reentradas estables e inestables en 2 dimensiones, con sus electrogramas correspondientes. El modelo es particularmente adecuado para simular los fenomenos asociados a la curvatura de los frentes, y permite reproducir la conduccion fibrilatoria y los rotores estables en 2 y 3 dimensiones. Conclusiones Aunque el modelo de automata celular probabilistico desarrollado es sencillo y no requiere cargas computacionales elevadas, es capaz de simular de forma realista fenomenos complejos de gran interes en electrofisiologia.

Impacto de la angioplastia primaria en la indicaciÓn de desfibrilador implantable en pacientes con infarto de miocardio

Introduccion y objetivos El desfibrilador implantable mejora la supervivencia en pacientes postinfarto de miocardio con a) fraccion de eyeccion ≤ 0,30 y b) fraccion de eyeccion ≤ 0,40, taquicardias ventriculares no sostenidas y arritmias ventriculares inducibles. Estos criterios no han sido evaluados en el contexto de la angioplastia primaria. El objetivo del estudio es evaluar el impacto de ambos criterios en las indicaciones de desfibrilador en pacientes con infarto revascularizados con angioplastia primaria. Pacientes y metodo Se estudio a 102 pacientes postinfarto (80 varones; edad, 63,6 ± 11,5 anos) incluidos en un programa regional de angioplastia primaria. Se realizo un registro Holter de 24 h entre las semanas 2 y 6 postinfarto, al mes, y se estimo la fraccion de eyeccion por ecocardiografia practicando estimulacion ventricular programada en el grupo con fraccion de eyeccion ≤ 0,40 y taquicardia ventricular no sostenida. Resultados Un total de 22 pacientes (21,6%; intervalo de confianza [IC] del 95%, 13,6-29,6) presentaron taquicardia ventricular no sostenida en el Holter. Seis de ellos tuvieron fraccion de eyeccion ≤ 0,40, siendo inducibles 2 de 5 en el estudio electrofisiologico. La fraccion de eyeccion fue ≤ 0,30 en 3 pacientes, ninguno de los cuales presento taquicardia ventricular no sostenida. En total, 5 pacientes (4,9%) tuvieron indicacion de desfibrilador aplicando alguno de los 2 criterios. Conclusiones La prevalencia de taquicardia ventricular no sostenida en pacientes con infarto tratados con angioplastia primaria es elevada. Sin embargo, la mayoria tiene una funcion ventricular conservada, por lo que la prevencion primaria con desfibrilador estaria indicada en un 5% aproximadamente utilizando los criterios evaluados en este estudio.

Extrasistolia ventricular desencadenante de la fibrilación ventricular

Introduccion y objetivos. Los mecanismos de inicio de la fibrilacion ventricular (FV) son poco conocidos. El objetivo de este estudio es analizar el inicio de la FV en los electrogramas almacenados en los desfibriladores automaticos implantables (DAI). Metodos. Hemos analizado los electrogramas de pacientes con DAI y al menos un episodio de FV. Resultados. De una poblacion de 250 pacientes portadores de DAI, 13 tuvieron al menos un episodio de FV, 10 varones y 3 mujeres (edad, 49 ± 22 anos), diagnosticados de sindrome de Brugada (n = 4), cardiopatia isquemica (n = 3), miocardiopatia dilatada (n = 2), miocardiopatia hipertrofica (n = 1), torsades de pointes por extrasistole ventricular (EV) con acoplamiento corto (n = 1), fibroelastosis cardiaca (n = 1) y FV idiopatica (n = 1). En 7 pacientes la FV fue el motivo del implante. Se registraron 31 episodios de FV (3 tormentas arritmicas). En cada paciente, todos los episodios comenzaron con una EV de la misma morfologia y similar intervalo de acoplamiento en los 7 pacientes con mas de un episodio (minutos-3 anos). Se objetivo ciclo corto-largo-corto en 2 pacientes. En 21 episodios, se registraron EV en ritmo sinusal que no desencadenaron FV. La morfologia, el intervalo de acoplamiento (409 ± 121 frente a 411 ± 123 ms) y el ciclo del latido sinusal precedente (801 ± 233 frente a 793 ± 230 ms) no presentaron diferencias significativas al compararlas con las EV inductoras de FV. Conclusiones. La FV espontanea se desencadena por EV en las tormentas arritmicas y en episodios aislados. En ocasiones las EV preceden a la FV sin desencadenarla

Early Heart Rate Increase Does Not Predict the Result of the Head-Up Tilt Test Potentiated With Nitroglycerin

INTRODUCTION AND OBJECTIVES The magnitude of the change in heart rate during the first few minutes of the head-up tilt test has been used to predict the tests result. The aim of this study was to investigate whether the heart rate increase during the head-up tilt test potentiated with nitroglycerin is related to the development of syncope. PATIENTS AND METHOD The study included 158 consecutive patients with syncope, with stable sinus rhythm, and without structural cardiac disease who were undergoing a head-up tilt test with nitroglycerin. The heart rate increment induced by the tilt maneuver and by nitroglycerin administration was calculated, and its relationship to clinical variables and to the tests results was analyzed. RESULTS The head-up tilt test gave positive results in 117 patients (74%). The heart rate was 68.7 (11.3) bpm in the decubitus position and 85.1 (15.4) bpm during the first 6 min of tilting. There was strong inverse correlation between the heart rate increase induced by tilting and age (r=--0.63; P<.001), but the increase (16.8 [9.3] bpm in patients with syncope versus 14.9 [11.3] bpm in those without; P=.3) did not predict the result of the test. The heart rate increase induced by nitroglycerin was also similar for patients with and without syncope during the pharmacologic phase of the test (27.3 [12.6] bpm and 26.7 (13.4) bpm, respectively; P=.8). CONCLUSIONS The magnitude of the heart rate increase during the first few minutes of tilt-testing and after nitroglycerin administration is inversely related to age but does not predict the result of the head-up tilt test with nitroglycerin.

Premature Ventricular Complexes as a Trigger for Ventricular Fibrillation

INTRODUCTION AND OBJECTIVES The mechanisms that trigger ventricular fibrillation (VF) are poorly understood. The aim of this study was to analyze the initiation of VF in electrograms stored in implantable cardioverter-defibrillators (ICDs). METHODS We analyzed ICD electrograms from patients who had suffered at least one episode of VF. RESULTS Of 250 patients with ICDs, 13 (10 male and 3 female, age 49+/-22 years) had at least one episode of VF. The diagnoses were Brugada syndrome (n=4), ischemic heart disease (n=3), dilated cardiomyopathy (n=2), hypertrophic cardiomyopathy (n=1), short-coupled variant of torsades de pointes (n=1), endocardial fibroelastosis (n=1) and idiopathic VF (n=1). In 7 patients, VF was the reason for ICD implantation. Overall, 31 episodes of VF were recorded, including three episodes of arrhythmic storm. In the 7 patients who had more than one episode of VF (within minutes or up to 3 years apart), all episodes started with premature ventricular complexes (PVCs) that had the same morphology and similar coupling intervals. A short-long-short cycle was observed in 2 patients. In 21 episodes, PVCs that did not trigger VF were observed during sinus rhythm. There was no significant difference between them and PVCs that did trigger VF in terms of morphology, coupling interval (409+/-121 ms vs. 411+/-123 ms) or the preceding sinus rhythm RR interval (801+/-233 ms vs. 793+/-230 ms). CONCLUSIONS Spontaneous VF in the form of an arrhythmic storm or an isolated episode were triggered by PVCs. On occasions, PVCs preceded VF without triggering it.

Spectral analysis of sustained and non-sustained ventricular fibrillation in patients with an implantable cardioverter-defibrillator.

The mechanisms responsible for the maintenance and termination of ventricular fibrillation (VF) are poorly understood. The aim of this study was to compare the spectral characteristics of the electrical signal during sustained and non-sustained VF in patients with an implantable cardioverter-defibrillator. The study included 51 patients who had had at least one episode of sustained VF (i.e., duration >5 s and requiring shock administration) and non-sustained VF (i.e., duration >3 s and spontaneously terminated) that were recorded by the device set in a unipolar configuration. Spectral analysis of the first 3 s of each episode was performed. The dominant frequency was higher in sustained VF (4.6+/-0.7 Hz) than in non-sustained VF (4.3+/-0.6 Hz; P=.01), while the other parameters were similar. Although the spectral characteristics of sustained and non-sustained VF were similar, differences were observed during the first 3 s that could be used in algorithms for the early detection of non-sustained VF.

Prognosis of Presyncope in Patients With Structural Heart Disease

Introduction and objectives Few data are available on the prognosis of presyncope in patients with structural heart disease. The aim of this study was to compare the clinical characteristics and long-term prognosis of patients with structural heart disease admitted for presyncope or syncope in the cardiology department of a tertiary hospital. Methods We reviewed the medical records of 449 patients (65% men, mean age 66.8 [13.1] years) with structural heart disease admitted because of syncope (n = 272) or presyncope (n = 177) during the period from 1992 to 1998. Clinical and demographic variables were analyzed and the final diagnosis was classified according to European Society of Cardiology criteria. The follow-up (available in 97.1% of patients) consisted of a personal interview with the patient or a review of the medical records and an interview with the relatives of the patients who had died. Results Both groups had similar demographic and clinical characteristics, except for the presence of atrial fibrillation on admission, which was more common in the presyncope group. Previous syncopal episodes were more frequent in patients admitted for syncope. The mechanism of the episode was considered arrhythmic in 25.7% of the patients with syncope and 22.0% of those in the presyncope group ( P = .37). After a mean follow-up of 57.4 [30.5 months the survival curves were similar for both groups and no significant differences were found regarding the causes of death or the rate of sudden death. Conclusions The clinical characteristics and the long-term prognosis in patients with structural heart disease admitted to a cardiology department for presyncope are similar to those of patients admitted for syncope. This suggests that the approach to diagnosis and risk stratification should be similar in both groups of patients.