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A study published in the journal Diabetes, Obesity & Metabolism examined the impact of hybrid closed-loop (HCL) insulin delivery on cardiac rhythm in older adults with type 1 diabetes (T1D). The study found that HCL devices improved glucose control and reduced the risk of low blood sugar, but did not have a significant impact on cardiac rhythm. The study suggests that HCL systems can be beneficial for managing T1D in older adults without negatively affecting cardiac rhythm. However, more research is needed to understand the relationship between glucose control and cardiac rhythm in individuals with T1D. [Extracted from the article]

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]

Atrial fibrillation (AF) is the world's most common cardiac arrhythmia. Due to the complexity of the heart and highly irregular electrical activity during AF it is a grand challenge to underpin the mechanisms underlying the initiation and maintenance of AF. Complimentary to experimental physiology, biophysically detailed models of the heart provide a powerful platform for investigating the substrates that prompt and perpetuate AF. In the last decade, there has been significant progress in the development of atrial models at the cellular, tissue and whole organ levels. This article presents a review of recent advances in modelling of the human atria and their application to understanding AF. [ABSTRACT FROM AUTHOR]

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.

Introduction: The clinical value of cardio-version (CV) of persistent atrial fibrillation (AF) is limited by the high rate of early AF recurrence, which may be related to the persistence of atrial electrical remodeling. We examined the hypothesis that the likelihood of maintaining sinus rhythm after CV of persistent AF is significantly enhanced by a policy of early repeated CV. Methods and Results: Fifty-nine patients with persistent AF underwent internal CV (CV 1). Those patients cardioverted were monitored with daily transtelephonic ECG. In the event of AF recurrence, these patients were admitted rapidly for repeat CV (CV 2) and, if further recurrence occurred, a third CV (CV 3) was performed. Daily ECG monitoring was continued until 1 month of sinus rhythm was maintained or a total of three CVs were performed. Of the 59 patients undergoing CV 1, 43 were discharged in sinus rhythm and 29 subsequently had AF recurrence during monitoring. Twenty-three of these underwent CV 2 and 11 of these underwent CV 3. Of those having repeated CVs, only 4 patients maintained sinus rhythm for 1 month (3 after CV 2 and 1 after CV 3). The remaining patients had repeated AF recurrence during the monitoring period. Mean time from AF recurrence to CV 2 was 20 ± 13 hours and from AF recurrence to CV 3 was 13 ± 7.2 hours. Atrial effective refractory periods increased from 189 ± 16 msec at CV 1 to 215 ± 18 msec at CV 3 (P < 0.05), indicating reversal of atrial electrical remodeling during this period. Conclusion: A policy of early repeated CVs for AF recurrence has very limited clinical value despite evidence of reversal of atrial electrical remodeling. The time between AF recurrence and repeat CV may need to be reduced further if such a policy is to succeed. [ABSTRACT FROM AUTHOR]

Introduction: The mechanisms by which Class IC drugs slow the rate of functional reentrant arrhythmias are not completely understood. We hypothesized that flecainide widens the excitable gap beyond the pivot point of premature turning wavefronts. Methods and Results: In eight perfused subepicardial layers of rahbit left ventricle, a linear lesion was made by radiofrequency (RF) ablation parallel to the fiber orientation. One end of the RF lesion was extended by a short incision. Pacing next to the lesion induced a wavefront propagating with a sharp U-turn around the end of the lesion in either the clockwise or counterclockwise direction. A high-density mapping electrode (240 electrodes, 350-μm resolution) was used to record unipolar electrograms at the pivot point During control, the shortest V1-V2 interval proximal to the pivot point was 162 ± 12 msec compared with 173 ± 13 msec distal to the pivot point difference 11 ± 8 msec; P < 0.01). After infusion of flecainide 2 mg/L, the shortest V1-V2 interval proximal and distal to the pivot point were 217 ± 29 msec and 244 ± 36 msec (difference 27 ± 16 msec; P < 0.01). Due to the increase in V1-V2 interval at the pivot point, flecainide widened the temporal excitable gap in the returning limb of the turning wavefront from 30 ± 11 msec to 55 ± 22 msec (P < 0.01). High-density mapping at the pivot point revealed that this widening of the excitable gap was due to both macroscopic discoutinuous conduction and functional conduction block at the pivot point. Conclusion: Flecainide widens the excitable gap in the returning limb of premature U-turning wavefronts by causing macroscopic discontinuous conduction and functional conduction block at the pivot point. [ABSTRACT FROM AUTHOR]

Introduction: Verapamil and digoxin have been shown to modulate tachycardia-induced atrial electrical remodeling. The goal of the present study was to determine the direct effects of verapamil and digoxin on atrial fibrillation (AF), before and after electrical remodeling. Methods and Results: In six goats we measured the AF cycle length (AFCL) and duration of AF (DurAF) of 50 consecutive induced paroxysms, before (t = 0) and after 24 hours (t = 24) of electrical remodeling. During AF, conduction velocity (CVAF), refractory period (RPAF). and type of AF (I, II, III) were determined. Verapamil was administered at a Loading dose of 0.1 mg/kg, followed by a continuous (2-hour) infusion of 5 μg/kg/min. Digoxin was given intravenously as a single 0.02 mg/kg bolus. At t = 0 and t = 24, digoxin and verapamil caused a significant slowing of the ventricuLar rate of >40%. Digoxin had no effect on DurAF, AFCL, CVAF or RPAF. Infusion of verapamil had a direct proarrhythmic effect. Both at t = 0 and t = 24, AFCL and RPAF were shortened by about 15%. During acute AF, verapamil prolonged the average duration of AF paroxysms from 7 to 16 seconds. Alter 24 hours of AF, the proarrhythmic effect was much stronger. Shortly after starting infusion (6 ± 2 mm), verapamil converted paroxysmal AF into sustained AF. As Long as verapamil infusion was maintained, AF no longer terminated in any of the goats. This effect was associated with an increase in AF fragmentation from type I to type II-III. Conclusion: Verapamil shortens AFCL and RPAI in the presence and absence of electrical remodeling. After 24 hours, It exerted a marked proarrhythmic effect and converted paroxysmal (type I) into sustained (type III) AF. In contrast, digoxin had no effect on the rate or stability of AF. [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]

Focuses on the substrate for atrioventricular nodal reentrant tachycardia. Evolution of the clinical concept of multiple AV nodal pathways; Evidence for the reentrant mechanism of AVNRT.

Presents a letter to the editor commenting on an article on physical signs in the diagnosis of wide complex tachycardia published in the "Pace" periodical in 1996.

Abstract: Computational models of human atrial cells, tissues and atria have been developed. Cell models, for atrial wall, crista terminalis, appendage, Bachmann’s bundle and pectinate myocytes are characterised by action potentials, ionic currents and action potential duration (APD) restitution. The principal effect of the ion channel remodelling of persistent atrial fibrillation (AF), and a mutation producing familial AF, was APD shortening at all rates. Electrical alternans was abolished by the modelled action of Dronedarone. AF induced gap junctional remodelling slows propagation velocity at all rates. Re-entrant spiral waves in 2-D models are characterised by their frequency, wavelength, meander and stability. For homogenous models of normal tissue, spiral waves self-terminate, due to meander to inexcitable boundaries, and by dissipation of excitation. AF electrical remodelling in these homogenous models led to persistence of spiral waves, and AF fibrotic remodelling to their breakdown into fibrillatory activity. An anatomical model of the atria was partially validated by the activation times of normal sinus rhythm. The use of tissue geometry from clinical MRI, and tissue anisotropy from ex vivo diffusion tensor magnetic resonance imaging is outlined. In the homogenous model of normal atria, a single scroll breaks down onto spatio-temporal irregularity (electrical fibrillation) that is self-terminating; while in the AF remodelled atria the fibrillatory activity is persistent. The persistence of electrical AF can be dissected in the model in terms of ion channel and intercellular coupling processes, that can be modified pharmacologically; the effects of anatomy, that can be modified by ablation; and the permanent effects of fibrosis, that need to be prevented. [Copyright &y& Elsevier]