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Cardiac electrical alternans (CEA), manifested as T-wave alternans in ECG, is a clinical biomarker for predicting cardiac arrhythmias and sudden death. However, the mechanism underlying the spontaneous transition from CEA to arrhythmias remains incompletely elucidated. In this study, multiscale rabbit ventricular models were used to study the transition and a potential role of INa in perpetuating such a transition. It was shown CEA evolved into either concordant or discordant action potential (AP) conduction alternans in a homogeneous one-dimensional tissue model, depending on tissue AP duration and conduction velocity (CV) restitution properties. Discordant alternans was able to cause conduction failure in the model, which was promoted by impaired sodium channel with either a reduced or increased channel current. In a two-dimensional homogeneous tissue model, a combined effect of rate- and curvature-dependent CV broke-up alternating wavefronts at localised points, facilitating a spontaneous transition from CEA to re-entry. Tissue inhomogeneity or anisotropy further promoted break-up of re-entry, leading to multiple wavelets. Similar observations have also been seen in human atrial cellular and tissue models. In conclusion, our results identify a mechanism by which CEA spontaneously evolves into re-entry without a requirement for premature ventricular complexes or pre-existing tissue heterogeneities, and demonstrated the important pro-arrhythmic role of impaired sodium channel activity. These findings are model-independent and have potential human relevance. [ABSTRACT FROM AUTHOR]

The incidence and prevalence of atrial fibrillation (AF) are projected to increase significantly worldwide, imposing a significant burden on healthcare resources. The disease itself is extremely heterogeneous in its epidemiology, pathophysiology, and treatment options based on individual patient characteristics. Whilst ageing is well recognised to be an independent risk factor for the development of AF, this condition also affects the young in whom the condition is frequently symptomatic and troublesome. Traditional thinking suggests that the causal factors and pathogenesis of the condition in the young with structurally normal atria but electrophysiological "triggers" in the form of pulmonary vein ectopics leading to lone AF are in stark contrast to that in the elderly who have AF primarily due to an abnormal substrate consisting of fibrosed and dilated atria acting in concert with the pulmonary vein triggers. However, there can be exceptions to this rule as there is increasing evidence of structural and electrophysiological abnormalities in the atrial substrate in young patients with "lone AF," as well as elderly patients who present with idiopathic AF. These reports seem to be blurring the distinction in the pathophysiology of so-called idiopathic lone AF in the young versus that in the elderly. Moreover with availability of improved and modern investigational and diagnostic techniques, novel causes of AF are being reported thereby seemingly consigning the diagnosis of "lone AF" to a rather mythical existence. We shall also elucidate in this paper the differences seen in the epidemiology, causes, pathogenesis, and clinical features of AF in the young versus that seen in the elderly, thereby requiring clearly defined management strategies to tackle this arrhythmia and its associated consequences. [ABSTRACT FROM AUTHOR]

Radiofrequency ablation of the cavotricuspid isthmus is the first-line treatment for typical atrial flutter. Despite the close proximity of the right coronary artery (RCA) to the cavotricuspid isthmus, only four cases of arterial injury have been reported during radiofrequency ablation, all detected postablation by inferior ST elevation. Here, we report atrioventricular (AV) conduction delay during coronary sinus pacing as a possible early sign of RCA involvement and review the previous literature on RCA damage and variations of AV nodal circulation. (PACE 2010; 33:e110-e113) [ABSTRACT FROM AUTHOR]

Atrial fibrillation (AF) is self-perpetuating, via mechanisms of acute electrical remodelling and ‘second factors’ acting over a longer time course. Renin—angiotensin system (RAS) blockade may inhibit AF self-perpetuation. We evaluated the effects of RAS blockade with candesartan in a burst-paced goat model of lone AF in which both mechanisms are known to operate. Bioactivity of oral candesartan was demonstrated in 10 goats by inhibition of the pressor effect of angiotensin II. The effects of candesartan on electrical remodelling were assessed in 12 placebo and 12 candesartan-treated goats in a 28-day burst pacing protocol. To assess the effects of candesartan on second factors (structural remodelling), 16 goats underwent further 28-day periods of burst pacing (two periods in 16 goats, three periods in eight goats) each separated by periods of sinus rhythm sufficient for electrical remodelling to reverse. There was a progressive rise in angiotensin levels in both groups. Candesartan (0.5 mg/kg/day) achieved a 76% blunting of the pressor effect of angiotensin II and had no effect on electrical remodelling; the half time for fall of atrial effective refractory period (AERP) was 22.3 ± 4.9 h (placebo) and 22.0 ± 3.2 h (candesartan) (p = ns). Candesartan had no effect on AF stability, which progressively increased over successive 28-day periods (ANOVA p < 0.05). Candesartan had no effect on atrial electrical remodelling or the operation of ‘second factors’ in a goat model of lone AF. These findings suggest that any benefits of RAS blockade in patients with AF are unlikely to be due to direct effects on atrial remodelling. [ABSTRACT FROM PUBLISHER]

Abstract: Atrial fibrillation (AF) has been linked to increased inward rectifier potassium current, I K1, either due to AF-induced electrical remodelling, or from functional changes due to the Kir2.1 V93I mutation. The aim of this simulation study was to identify at cell and tissue levels'' mechanisms by which increased I K1 facilitates and perpetuates AF. The Courtemanche et al. human atrial cell action potential (AP) model was modified to incorporate reported changes in I K1 induced by the Kir2.1 V93I mutation in both heterozygous (Het) and homozygous (Hom) mutant forms. The modified models for wild type (WT), Het and Hom conditions were incorporated into homogeneous 1D, 2D and 3D tissue models. Restitution curves of AP duration (APD), effective refractory period (ERP) and conduction velocity (CV) were computed and both the temporal and the spatial vulnerability of atrial tissue to re-entry were measured. The lifespan and tip meandering pattern of re-entry were also characterised. For comparison, parallel simulations were performed by incorporating into the Courtmanche et al. model a linear increase in maximal I K1 conductance. It was found that the gain-in-function of V93I ‘mutant’I K1 led to abbreviated atrial APs and flattened APD, ERP and CV restitution curves. It also hyperpolarised atrial resting membrane potential and slowed down intra-atrial conduction. V93I ‘mutant’I K1 reduced the tissue''s temporal vulnerability but increased spatial vulnerability to initiate and sustain re-entry, resulting in an increased overall susceptibility of atrial tissue to arrhythmogenesis. In the 2D model, spiral waves self-terminated for WT (lifespan < 3.3 s) tissue, but persisted in Het and Hom tissues for the whole simulation period (lifespan > 10 s). The tip of the spiral wave meandered more in WT tissue than in Het and Hom tissues. Increased I K1 due to augmented maximal conductance produced similar results to those of Het and Hom Kir2.1 V93I mutant conditions. In the 3D model the dynamic behaviour of scroll waves was stabilized by increased I K1. In conclusion, increased I K1 current, either by the Kir2.1 V93I mutation or by augmented maximal conductance, increases atrial susceptibility to arrhythmia by increasing the lifespan of re-entrant spiral waves and the stability of scroll waves in 3D tissue, thereby facilitating initiation and maintenance of re-entrant circuits. [Copyright &y& Elsevier]

The article discusses the upstream management of atrial fibrillation (AF) which involves treating the abnormalities that are thought to predispose certain patient groups to this arrhythmia. It examines the predisposing clinical factors for AF. It also explains the underlying electrophysiological mechanisms of AF, AF development in animal models, and effects of therapies in animal models of AF in the setting of structural heart disease or inflammation.

FITCHET, A., et al. : Holter Monitoring vs Tilt Testing in the Investigation of Suspected Vasovagal Syncope. --> The aim of this study was to compare the diagnostic yield of 48‐hour Holter monitoring with head‐up tilt (HUT) test in patients presenting with blackouts suggestive of vasovagal syncope. One hundred and eighteen consecutive patients, 68 women, aged (mean [SD])50 ± 20  years(range 16–88 years), underwent 48‐hour Holter monitoring and 60° HUT test within 3 months. Endpoints were symptom‐ECG correlation during Holter monitoring and positive HUT test. Syncope occurred in 3 (3%) patients during Holter monitoring, the rhythm being sinus tachycardia in all. Presyncope was reported in 22 (19%), the rhythm being sinus tachycardia in 6, persistent atrial fibrillation in 2, and normal sinus rhythm in the remainder. Asymptomatic arrhythmias were recorded in 103 (87%) patients. Positive HUT tests occurred in 39 (33%), the pattern being mixed (VASIS type 1) in 14 (36%), cardioinhibitory (VASIS type 2) in 3 (8%), and vasodepressor (VASIS type 3) in 22 (56%). Change in patient management occurred in 3 (3%) patients following Holter monitoring and 39 (33%) patients following HUT test. Holter monitoring produces a low yield of clinically useful information in the investigation of suspected vasovagal syncope. An HUT test should be considered the primary investigation of choice in such patients. (PACE 2003; 26[Pt. I]:1523–1527) [ABSTRACT FROM AUTHOR]

Preferential Depression of Conduction at Pivot Points. Introduction: During reentrant arrhythmias, the circulating wavefront often makes a sharp turn around a functional or anatomic harrier. We tested the hypothesis that lowering the safety factor for conduction by high K+ or flecainide preferentially depresses conduction of sharply turning wavefronts. [ABSTRACT FROM AUTHOR]

We compared the electrophysiological effects of intravenous propafenone and flecainide on accessory pathway conduction by a randomized crossover study in 16 patients with Wolff-Parkinson-White syndrome. The antegrade refractory period of the pathway increased from 256 ± 18 msec at baseline to 288 ± 13 msec on propafenone (P < 0.05) and to 296 ± 27 msec on flecainide (P = 0.075). The minimum preexcited RR interval during atrial fibrillation or incremental atrial pacing was prolonged from 225 ± 37 msec to 262 ± 22 msec by propafenone (P < 0.05) and to 301 ± 31 msec by flecainide (P < 0.005). The prolongation was significantly greater with flecainide than propafenane (P < 0.05). Both drugs increased tachycardia cycle length (TCL) from 310 ± 35 msec to 354 ± 37 msec (propafenone P < 0.005) and to 352 ± 37 msec (flecainide P < 0.01). Both propafenone and flecainide blocked antegrade conduction in the pathway in five patients, Both drugs rendered atrial fibrillation noninducible in seven patients and orthodromic tachycardia noninducible in five patients. Conclusions: (1) Flecainide causes a greater prolongation of minimum preexcited RR interval than propafenone; (2) There is no significant difference between propafenone and flecainide on the inducibility of arrhythmias, TCL, or incidence of antegrade conduction block. [ABSTRACT FROM AUTHOR]

Introduction: QTc dispersion has traditionally been calculated from all 12 leads of a standard electrocardiogram (ECG). It is possible that alternative, quicker methods using fewer than 12 leads could be used to provide the same information. Methods and Results: We have previously shown a difference in QTc dispersion from ECGs recorded at least 1 month after myocardial infarction between patients who subsequently died and long-term survivors. In the current study, we recalculated QTc dispersion in these ECGs using different methods to determine if the observed difference in QTc dispersion measurements between the two groups, as calculated from 12-lead ECGs, persisted when using smaller sets of leads. QTc dispersion was recalculated by four methods: (1) with the two extreme QTc intervals excluded; (2) from the six precordial leads; (3) from the three leads most likely to contribute to QTc dispersion (aVF, V1, V4); and (4) from the three quasi-orthogonal leads (aVF, I, V2). For each of the 270 12-lead ECGs examined, a mean of 9.9 leads (SD 1.5 leads) had a QT interval analyzed; the QT interval could not be accurately measured in the remaining leads. Using the standard 12-lead measurement of QTc dispersion, there was a difference in the fall in QTc dispersion from early to late ECG between the groups: 9.1 (SD 60.8) msec for deaths versus 34.4 (55.2) msec for survivors (P = 0.016). This difference in QTc dispersion between early and late ECGs was maintained using either three-lead method (quasi-orthogonal leads: -2.6 [56.2] msec for deaths vs 26.9 [54.3] msec for survivors [P = 0.003]; "likeliest" leads: 8.6 [64.9] msec vs 29.5 [54.2] msec [P = 0.05]), but not when using the other two methods (precordial leads: 19.1 [55.5] msec vs 22 [50.8] msec [P = 0.76]; extreme leads removed: 9.2 [50.1] msec vs 21.8 [42] msec [P = 0.13]). Conclusion: QTc dispersion calculated from three leads may be as useful a measurement as QTc dispersion calculated from all leads of a standard ECG. Its advantages over the standard measurement are its simplicity and the lack of problems with lead adjustment. [ABSTRACT FROM AUTHOR]

The article focuses on a study related to the relevance of atrioventricular (AV) nodal physiology in patients with medically refractory atrial fibrillation (AF). Electrophysiologists developed more targeted techniques to suppress the rapid transmission of AF to the ventricles without producing complete heart block. An AV nodal modification procedure would be more successful in patients with an electrophysiologically well-defined "slow pathway." The presence of AV nodal duality indicates a substantial difference in electrophysiologic properties of the anterior and posterior atrionodal inputs in patients with AF and that, similar to patients with AV nodal reentrant tachycardia.