A modified approach for programmed electrical stimulation in mice: Inducibility of ventricular arrhythmias.

BACKGROUND: Electrophysiological studies in mice, the prevailing model organism in the field of basic cardiovascular research, are impeded by the low yield of programmed electrical stimulation (PES). OBJECTIVE: To investigate a modified approach for ventricular arrhythmia (VA) induction and a novel scoring system in mice. METHOD: A systematic review of literature on current methods for PES in mice searching the PubMed database revealed that VA inducibility was low and ranged widely (4.6 ± 10.7%). Based on this literature review, a modified PES protocol with 3 to 10 extrastimuli was developed and tested in comparison to the conventional PES protocol using up to 3 extrastimuli in anesthetized wildtype mice (C57BL/6J, n = 12). Induced VA, classified according to the Lambeth Convention, were assessed by established arrhythmia scores as well as a novel arrhythmia score based on VA duration. RESULTS: PES with the modified approach raised both the occurrence and the duration of VA compared to conventional PES (0% vs 50%; novel VA score p = 0.0002). Particularly, coupling of >6 extrastimuli raised the induction of VA. Predominantly, premature ventricular complexes (n = 6) and ventricular tachycardia <1s (n = 4) were observed. Repeated PES after adrenergic stimulation using isoprenaline resulted in enhanced induction of ventricular tachycardia <1s in both protocols. CONCLUSION: Our findings suggest that the presented approach of modified PES enables effective induction and quantification of VA in wildtype mice and may well be suited to document and evaluate detailed VA characteristics in mice.

Progression of late postoperative atrial fibrillation in patients with tetralogy of Fallot.

INTRODUCTION: ToF patients are at risk for ventricular deterioration at a relatively young age, which can be aggravated by AF development. Therefore, knowledge on AF development and its timespan of progression is essential to guide treatment strategies for AF. OBJECTIVE: We examined late postoperative AF onset and progression in ToF patients during long-term follow-up after ToF correction. In addition, coexistence of AF with regular supraventricular tachyarrhythmias (SVT) and ventricular tachyarrhythmias (VTA) was analyzed. METHODS AND RESULTS: ToF patients (N  =  29) with AF after ToF correction referred to the electrophysiology department between 2000 and 2015 were included. All available rhythm registrations were reviewed for AF, regular SVT, and VTA. AF progression was defined as transition from paroxysmal AF to (longstanding) persistent/permanent AF or from (longstanding) persistent AF to permanent AF. At the age of 44 ± 12 years, ToF patients presented with paroxysmal (N  =  14, 48%), persistent (N  =  13, 45%) or permanent AF (N  =  2, 7%). Age of AF development was similar among patients who either underwent initial shunt creation (N  =  15, 45 ± 11 [25-57] years) or primary total ToF correction (N  =  14, 43 ± 13 [26-66] years) (P  =  0.785). AF coexisted with regular SVT (N  =  18, 62%) and VTA (N  =  13, 45%). Progression of AF occurred in 11 patients (38%) within 5 ± 5 years after AF onset despite antiarrhythmic drug class II (AAD, P  =  0.052) or III (P  =  0.587) usage. CONCLUSIONS: AF in our ToF population developed at a young age and showed rapid progression. Rhythm control by pharmacological therapy was ineffective in preventing AF progression.

Management of ventricular arrhythmias in structural heart disease.

Ventricular arrhythmias (VA) are a source of significant morbidity and mortality in patients with structural heart disease (SHD). The advent of the implantable cardiac defibrillator (ICD) has had a positive effect on mortality, but the associated morbidity remains a significant problem. Modern treatment of VA has advanced far beyond medical therapy and includes strategies as simple as intelligent ICD programming and as complex as catheter ablation (CA). In these pages, the spectrum of management strategies will be discussed; from anti-arrhythmic drugs and ICD implantation and programming to CA and autonomic modulation. The focus of this review will be on strategies for secondary prevention of VA in patients with SHD, supported by clinical evidence for their utilization.

Influence of the mode of management of acute myocardial infarction on the inducibility of ventricular tachyarrhythmias with programmed ventricular stimulation after myocardial infarction.

BACKGROUND: Programmed ventricular stimulation (PVS) is a technique for screening patients at risk for ventricular tachycardia (VT) after myocardial infarction (MI), but the results might be difficult to interpret. OBJECTIVES: To investigate the results of PVS after MI, according to date of completion. METHODS: PVS results were interpreted according to the mode of MI management in 801 asymptomatic patients: 301 (group I) during the period 1982-1989, 315 (group II) during 1990-1999, and 185 (group III) during 2000-2010. The periods were chosen based on changes in MI management. Angiotensin-converting enzyme (ACE) inhibitors had been given since 1990; primary angioplasty was performed routinely since 2000. The PVS protocol was the same throughout the whole study period. RESULTS: Group III was older (61 +/- 11 years) than groups I (56 +/- 11) and II (58 +/- 11) (P < 0.002). Left ventricular ejection fraction (LVEF) was lower in group III (36.5 +/- 11%) than in groups I (44 +/- 15) and II (41 +/- 12) (P < 0.000). Monomorphic VT < 270 beats/min was induced as frequently in group III (28%) as in group II (22.5%) but more frequently than in group I (20%) (P < 0.03). Ventricular fibrillation and flutter (VF) was induced less frequently in group III (14%) than in groups I (28%) (P < 0.0004) and II (30%) (P < 0.0000). Low left ventricular ejection fraction (LVEF) and date of inclusion (before/after 2000) were predictors of VT or VF induction on multivariate analysis. CONCLUSIONS: Induction of non-specific arrhythmias (ventricular flutter and fibrillation) was less frequent than before 2000, despite the indication of PVS in patients with lower LVEF. This decrease could be due to the increased use of systematic primary angioplasty for MI since 2000.

[Histiocytoid cardiomyopathy in an infant].

We present a description of a clinical observation of a histiocytoid cardiomyopathy in a female patient aged 4 months. This pathology is rare in pediatric cardiology. Its etiology is linked with mutation of the gene encoding mitochondrial cytochrome B (mitochondrial transport of electrons). This mutation leads to a specific morphological and functional abnormalities of cardiomyocytes. Purkinje cells and cells of conduction system at microscopy appear as histiocytolike foam cells cytoplasm of which contain large amount of lipids and glycogen. Girls prevail among those affected. The case reflects clinical picture characteristic for this nosology: malignant arrhythmia and cardiomegaly with fatal outcome.

Ventricular flutter triggered by fever in a patient with Brugada syndrome.

Brugada syndrome is a clinical-electrocardiographic entity predisposing to malignant ventricular arrhythmias. The typical arrhythmia is polymorphic ventricular tachycardia, which can potentially degenerate to ventricular fibrillation. Monomorphic ventricular tachycardia is uncommon. Our group is reporting the case of a 39-year-old man with known Brugada syndrome who developed ventricular flutter while febrile. Fever has previously been shown to unmask Brugada changes and to induce ventricular arrhythmias. The appearance of monomorphic ventricular tachycardia potentially attributable to sodium-channel dysfunction further confounds the mechanism of arrhythmogenesis in Brugada syndrome. This curious occurrence further underlines the likely complex nature of arrhythmogenesis in Brugada syndrome.

The natural history of asymptomatic ventricular pre-excitation a long-term prospective follow-up study of 184 asymptomatic children.

OBJECTIVES: The aim of this study was to describe the natural history of asymptomatic ventricular pre-excitation in children and to determine predictors of potentially life-threatening arrhythmic events. BACKGROUND: Sudden death can be the first clinical manifestation in asymptomatic children with ventricular pre-excitation, but reduction of its incidence by prophylactic ablation requires the identification of subjects at high risk. METHODS: Between 1995 and 2005 we prospectively collected clinical and electrophysiologic data from 184 children (66% male; median age 10 years; range 8 to 12 years) with asymptomatic ventricular pre-excitation on the electrocardiogram. After electrophysiologic testing, subjects were followed as outpatients taking no medications. The primary end point of the study was the occurrence of arrhythmic events. Predictors of potentially life-threatening arrhythmias were analyzed. RESULTS: Over a median follow-up of 57 months (min/max 32/90 months) after electrophysiologic testing, 133 children (mean age 10 years; range 8 to 12 years) did not experience arrhythmic events, remaining totally asymptomatic, while 51 children had within 20 months (min/max 8/60 months) a first arrhythmic event, which was potentially life-threatening in 19 of them (mean age 10 years; range 10 to 14 years). Life-threatening tachyarrhythmias resulted in cardiac arrest (3 patients), syncope (3 patients), atypical symptoms (8 patients), or minimal symptoms (5 patients). Univariate analysis identified tachyarrhythmia inducibility (p < 0.001), anterograde refractory period of accessory pathways (APERP)