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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]

Background: The sinoatrial/sinus node (SAN) is the primary pacemaker of the heart. In humans, SAN is surrounded by the paranodal area (PNA). Although the PNA function remains debated, it is thought to act as a subsidiary atrial pacemaker (SAP) tissue and become the dominant pacemaker in the setting of sinus node disease (SND). Large animal models of SND allow characterization of SAP, which might be a target for novel treatment strategies for SAN diseases. Methods: A goat model of SND was developed (n = 10) by epicardially ablating the SAN and validated by mapping of emergent SAP locations through an ablation catheter and surface electrocardiogram (ECG). Structural characterization of the goat SAN and SAP was assessed by histology and immunofluorescence techniques. Results: When the SAN was ablated, SAPs featured a shortened atrioventricular conduction, consistent with the location in proximity of atrioventricular junction. SAP recovery time showed significant prolongation compared to the SAN recovery time, followed by a decrease over a follow-up of 4 weeks. Like the SAN tissue, the SAP expressed the main isoform of pacemaker hyperpolarization-activated cyclic nucleotide-gated channel 4 (HCN4) and Na+/Ca2+ exchanger 1 (NCX1) and no high conductance connexin 43 (Cx43). Structural characterization of the right atrium (RA) revealed that the SAN was located at the earliest activation [i.e., at the junction of the superior vena cava (SVC) with the RA] and was surrounded by the paranodal-like tissue, extending down to the inferior vena cava (IVC). Emerged SAPs were localized close to the IVC and within the thick band of the atrial muscle known as the crista terminalis (CT). Conclusions: SAN ablation resulted in the generation of chronic SAP activity in 60% of treated animals. SAP displayed development over time and was located within the previously discovered PNA in humans, suggesting its role as dominant pacemaker in SND. Therefore, SAP in goat constitutes a promising stable target for electrophysiological modification to construct a fully functioning pacemaker. [ABSTRACT FROM AUTHOR]

Background: Atrial fibrillation (AF) is the most common sustained arrhythmia in patients with acute heart failure (AHF). The presence of AF is associated with adverse prognosis in patients with chronic heart failure (CHF) but little is known about its impact in AHF. Methods: Data were collected between April 2007 and March 2013 across 185 (> 95%) hospitals in England and Wales from patients with a primary death or a discharge diagnosis of AHF. We investigated the association between the presence of AF and all-cause mortality during the index hospital admission, at 30 days and 1 year post-discharge. Results: Of 96,593 patients admitted with AHF, 44,642 (46%) were in sinus rhythm (SR) and 51,951 (54%) in AF. Patients with AF were older (mean age 79.8 (79.7–80) versus 74.7 (74.5–74.7) years; p < 0.001), than those in SR. In a multivariable analysis, AF was independently associated with mortality at all time points, in hospital (HR 1.15, 95% CI 1.09–1.21, p < 0.0001), 30 days (HR 1.13, 95% CI 1.08–1.19, p < 0.0001), and 1 year (HR 1.09, 95% CI 1.05–1.12, p < 0.0001). In subgroup analyses, AF was independently associated with worse 30-day outcome irrespective of sex, ventricular phenotype and in all age groups except in those aged between 55 and 74 years. Conclusion: AF is independently associated with adverse prognosis in AHF during admission and up to 1 year post-discharge. As the clinical burden of concomitant AF and AHF increases, further refinement in the detection, treatment and prevention of AF-related complications may have a role in improving patient outcomes. [ABSTRACT FROM AUTHOR]

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]

Aims: Atrial stunning, a loss of atrial mechanical contraction, can occur following a successful cardioversion. It is hypothesized that persistent atrial fibrillation-induced electrical remodeling (AFER) on atrial electrophysiology may be responsible for such impaired atrial mechanics. This simulation study aimed to investigate the effects of AFER on atrial electro-mechanics. Methods and Results: A 3D electromechanical model of the human atria was developed to investigate the effects of AFER on atrial electro-mechanics. Simulations were carried out in 3 conditions for 4 states: (i) the control condition, representing the normal tissue (state 1) and the tissue 2–3 months after cardioversion (state 2) when the atrial tissue recovers its electrophysiological properties after completion of reverse electrophysiological remodelling; (ii) AFER-SR condition for AF-remodeled tissue with normal sinus rhythm (SR) (state 3); and (iii) AFER-AF condition for AF-remodeled tissue with re-entrant excitation waves (state 4). Our results indicate that at the cellular level, AFER (states 3 & 4) abbreviated action potentials and reduced the Ca2+ content in the sarcoplasmic reticulum, resulting in a reduced amplitude of the intracellular Ca2+ transient leading to decreased cell active force and cell shortening as compared to the control condition (states 1 & 2). Consequently at the whole organ level, atrial contraction in AFER-SR condition (state 3) was dramatically reduced. In the AFER-AF condition (state 4) atrial contraction was almost abolished. Conclusions: This study provides novel insights into understanding atrial electro-mechanics illustrating that AFER impairs atrial contraction due to reduced intracellular Ca2+ transients. [ABSTRACT FROM AUTHOR]

Key points Previous studies have shown that atrial electrical properties are altered (remodelled) by atrial fibrillation (AF) and that the recurrence of AF is high following remodelling. However, demonstrating a causal link between atrial remodelling in experimental models and the increased risk of AF is a challenge., AF-induced electrical remodelling abbreviated atrial action potential duration (APD) non-uniformly across the atria; this resulted in relatively short APDs co-existing with marked regional differences in the APD at junctions of the crista terminalis/pectinate muscle, pulmonary veins/left atrium., It increases tissue vulnerability to re-entry initiation and maintenance at these tissue junctions., The AF-induced electrical remodelling also stabilized and accelerated re-entrant excitation waves, leading to rapid and sustained re-entry., This study provides novel insights towards understanding the mechanisms underlying the pro-arrhythmic effects of the AF-induced electrical remodelling in atrial tissue., Abstract Chronic atrial fibrillation (AF) is associated with structural and electrical remodelling in the atria, which are associated with a high recurrence of AF. Through biophysically detailed computer modelling, this study investigated mechanisms by which AF-induced electrical remodelling promotes and perpetuates AF. A family of Courtemanche-Ramirez-Nattel variant models of human atrial cell action potentials (APs), taking into account of intrinsic atrial electrophysiological properties, was modified to incorporate various experimental data sets on AF-induced changes of major ionic channel currents ( ICaL, IKur, Ito, IK1, IKs, INaCa) and on intracellular Ca2+ handling. The single cell models for control and AF-remodelled conditions were incorporated into multicellular three-dimensional (3D) atrial tissue models. Effects of the AF-induced electrical remodelling were quantified as the changes of AP profile, AP duration (APD) and its dispersion across the atria, and the vulnerability of atrial tissue to the initiation of re-entry. The dynamic behaviour of re-entrant excitation waves in the 3D models was characterised. In our simulations, AF-induced electrical remodelling abbreviated atrial APD non-uniformly across the atria; this resulted in relatively short APDs co-existing with marked regional differences in the APD at junctions of the crista terminalis/pectinate muscle, pulmonary veins/left atrium. As a result, the measured tissue vulnerability to re-entry initiation at these tissue junctions was increased. The AF-induced electrical remodelling also stabilized and accelerated re-entrant excitation waves, leading to rapid and sustained re-entry. Under the AF-remodelled condition, re-entrant scroll waves in the 3D model degenerated into persistent and erratic wavelets, leading to fibrillation. In conclusion, realistic 3D atrial tissue models indicate that AF-induced electrical remodelling produces regionally heterogeneous and shortened APD; these respectively facilitate initiation and maintenance of re-entrant excitation waves. [ABSTRACT FROM AUTHOR]

This is a commissioned review for ‘A Year in Cardiology 2012’, focusing on recent developments in the field of arrhythmias and pacing. [ABSTRACT FROM PUBLISHER]

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]

Cardioversion remains an important therapy in the management of atrial fibrillation. Here, we report a case where direct current cardioversion resulted in a sudden dramatic change of heart rate that was associated with multiple ventricular fibrillation arrests in a manner akin to that previously observed post-atrioventricular node ablation. (PACE 2012;35:e361-e364) [ABSTRACT FROM AUTHOR]

Objective Following national guidance on management of sudden unexplained death (SUD) in the young, inherited cardiac conditions (ICC) clinics were established to identify and treat relatives thought to be at increased risk. Studies have examined diagnostic yield of these clinics but outcome of clinical management has not been reported. Design Observational outcome study of consecutively referred relatives of SUD victims. Setting Regional ICC clinic. Patients 193 individuals (108 families) referred to a regional ICC clinic following SUD/aborted cardiac arrest of a young relative (mean follow-up 16.5 months, range 0.1e61). Interventions All individuals underwent assessment by history, examination, ECG and echocardiography. Exercise electrocardiography, ajmaline provocation, further imaging techniques and genetic testing were performed in selected individuals. Implantable cardioverter-defibrillator (ICD) insertion based on national guidelines. Main outcome measures and results Forty-five patients (23%) from 38 families (35%) were diagnosed with an inheritable cause of sudden death. Eighteen had potentially prognostically important medication commenced and 4 had an ICD inserted on clinic recommendation (2 hypertrophic cardiomyopathy, 1 dilated cardiomyopathy, 1 arrhythmogenic right ventricular cardiomyopathy). Two other individuals had ICDs removed after negative testing for familial RYR2 mutations. No deaths have occurred during follow-up to date. Conclusion A diagnosis of an inheritable cause of sudden death was obtained in a significant minority of those with a family history of SUD/aborted cardiac arrest. The number of ICDs inserted as a result of specialist assessment was very small (2%). A major function of the clinic is reassurance of the clinically normal and cessation of treatment after exclusion of familial disease by genetic testing [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 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]

Whilst the decision regarding defibrillator implantation in a patient with a familial sudden cardiac death syndrome is likely to be most significant for any particular individual, the clinical decision-making process itself is complex and requires interpretation and extrapolation of information from a number of different sources. This document provides recommendations for adult patients with the congenital Long QT syndromes, Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia, hypertrophic cardiomyopathy, and arrhythmogenic right ventricular cardiomyopathy. Although these specific conditions differ in terms of clinical features and prognosis, it is possible and logical to take an approach to determining a threshold for implantable cardioveter-defibrillator implantation that is common to all of the familial sudden cardiac death syndromes based on estimates of absolute risk of sudden death. [ABSTRACT FROM AUTHOR]

Whilst the decision regarding defibrillator implantation in a patient with a familial sudden cardiac death syndrome is likely to be most significant for any particular individual, the clinical decision-making process itself is complex and requires interpretation and extrapolation of information from a number of different sources. This document provides recommendations for adult patients with the congenital Long QT syndromes, Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia, hypertrophic cardiomyopathy, and arrhythmogenic right ventricular cardiomyopathy. Although these specific conditions differ in terms of clinical features and prognosis, it is possible and logical to take an approach to determining a threshold for implantable cardioveter-defibrillator implantation that is common to all of the familial sudden cardiac death syndromes based on estimates of absolute risk of sudden death. [ABSTRACT FROM PUBLISHER]

Aims: The purpose of this study was to determine simple features of the standard 12-lead electrocardiogram (ECG) and incorporate them in a stepwise algorithm that would help confirm or exclude the presence of ventricular pre-excitation. [ABSTRACT FROM PUBLISHER]

Aims: Atrial fibrillation (AF) is the most common sustained arrhythmia in patients with chronic heart failure (CHF). Under-detection of asymptomatic paroxysmal AF (PAF) underestimates the true burden of AF in patients with CHF. We retrospectively studied the prevalence of asymptomatic PAF in 162 CHF patients through analysis of cardiac resynchronization therapy (CRT) device downloads to determine whether these episodes are associated with adverse outcomes. [ABSTRACT FROM PUBLISHER]

Aims: Atrial fibrillation (AF) is one of the commonest sustained arrhythmias in chronic heart failure (CHF), although the prognostic implications of the presence of AF in CHF remain controversial. We have therefore performed this meta-analysis to study the effects of the presence of AF on mortality in CHF patients. [ABSTRACT FROM PUBLISHER]

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.

Background: Implantation and testing of implantable defibrillators (ICDs) using local anesthetic and conscious sedation is widely practiced; however, some centers still use general anesthesia. We assessed safety and patient acceptability for implantation of defibrillators using local anesthetic and conscious sedation. Methods: The records of 500 consecutive device implants from two UK cardiac centers implanted under local anesthetic and conscious sedation from January 1996 to December 2004 were reviewed. Procedure time, left ventricular ejection fraction (LVEF) sedative dosage (midazolam), analgesic dosage (fentanyl or diamorphine), requirement for drug reversal, and respiratory support were recorded. Patient acceptability of the procedure was also assessed. Results: Of 500 implants examined, 387 were ICDs, 88 were biventricular ICDs, and 25 were generator changes. Patients with biventricular-ICDs had significantly longer (mean ± SD) procedure times 129.7 ± 7.6 minutes versus 63.3 ± 32.3 minutes; P < 0.0001 and lower LVEF 24.4 ± 8.4% versus 35.7 ± 15.4%; P < 0.0001. There were no differences in the doses (mean ± SD) of midazolam 8.9 ± 3.5 mg versus 8.0 ± 3.1 mg; P = NS, diamorphine 4.3 ± 2.0 mg versus 3.8 ± 1.7 mg; P = NS or fentanyl 94.4 ± 53.7 mcg versus 92.2 ± 48.6 mcg; P = NS, between the two groups. There were no deaths or tracheal intubations in either group. Acceptability was available for 373 of 500 (75%) patients, 41 of 373 (11%) described “discomfort,” but from these 41 patients only 14 of 373 (3.8%) declined a second procedure under the same conditions. Conclusions: Implantation of defibrillators under local anesthetic and sedation is safe and acceptable to patients. General anesthesia is no longer routinely required for implantation of defibrillators. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: Although previous studies in dogs have indicated a minimal role for changes in I K1 in the shortening of action potential duration (APD) associated with atrial fibrillation (AF), in humans, there is evidence for significant AF-induced up-regulation of this current. In this computer model study, we investigated the relative contributions of the remodeling of I K1, L-type calcium current, and other remodeled ionic channel currents to AF-induced APD reduction in human atrium. Methods: Two computer models of electrical activity of human atrial cell were modified by incorporating experimental data of AF-induced changes in human atrial ionic channel conductance and kinetics reported by Bosch et al. (I CaL, I to, I K1, and I Na) (AF-1) and Workman et al. (I CaL, I to, and I K1) (AF-2). The roles and relative importance of individually remodeled ion channels in the APD reduction in human atrium were evaluated by the removal and exclusive methods, in which remodeling of specific currents was omitted, or considered in isolation, in the two models. Results: When tested together, previously reported AF-induced changes in sarcolemmal ion currents result in marked shortening of atrial APD90. With the AF-1 remodeled parameters, there is a 62% reduction in APD90 for the Nygren et al. model, and a 68% reduction for the Courtemanche et al. model, which are comparable to experimental results of 60% reduction seen in humans. When tested individually, AF-1-induced changes in I CaL, I K1, or I to alone result in APD90 reduction of 20%, 64%, and −10%, respectively, for the Nygren et al. model, and 27%, 40%, and 11.6%, respectively, for the Courtemanche et al. model. With the AF-2 remodeled parameters, there is a 47% reduction in APD90 for the Nygren et al. model and a 49% reduction for the Courtemanche et al. model, which are also comparable to experimental results of 45% reduction. When tested individually, AF-2-induced changes in I CaL or I K1 alone result in APD90 reduction of 20% and 40%, respectively, for the Nygren et al. model, and 14% and 21%, respectively, for the Courtemanche et al. model. Conclusion: Previously reported changes in L-type Ca2+ current are insufficient to account for the observed reduction in atrial APD associated with persistent AF. Up-regulation of I K1 has a greater influence on atrial APD in the human model. [Copyright &y& Elsevier]

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]

Amiodarone and AF. Introduction: Amiodarone is effective in preventing the recurrence of atrial fibrillation (AF) after cardioversion (CV). Dispersion of atrial refractoriness may be relevant to the generation of AF. We designed a study to determine the electrophysiologic effects of amiodarone in patients with previous early recurrence of AF after CV. Methods and Results: Fifteen patients with previous AF recurrence (without antiarrhythmic drugs) after CV (CV1) were selected for amiodarone therapy and repeat CV (CV[sub amio]). Prior to CV1, mean AF cycle length (AFCL) had been recorded at four atrial sites (right atrial appendage [RAA], distal coronary sinus [DCS], right atrial lateral wall [LAT], and interatrial septum [IAS]) and dispersion of AFCL had been calculated. These patients were treated with amiodarone and, prior to CV[sub amio], AFCL was recorded at the four atrial sites as for CV1. Between CV1 and CV[sub amio], AFCL increased at all atrial sites: 153 ± 13 msec to 179 ± 14 msec at RAA, 144 ± 12 msec to 174 ± 18 msec at DCS, 158 ± 13 msec to 182 ± 16 msec at LAT, and 161 ± 18 msec to 181 ± 17 msec at IAS. Dispersion of AFCL decreased from 24 ± 10 msec at CV1 to 15 ± 11 msec at CV[sub amio] (P = 0.01) . The median time in sinus rhythm increased from 3.12 hours post CV1 to 28 days post CV[sub amio] (P < 0.02) . Conclusion: Amiodarone causes a reduction in the dispersion of AFCL. This action may be relevant to the beneficial effects of amiodarone in patients with AF.(J Cardiovasc Electrophysiol, Vol. 14, pp. 485-491, May 2003). [ABSTRACT FROM AUTHOR]

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]

Introduction: Recent reports have highlighted the importance of focal atrial arrhythmias as a curable cause for a group of patients with frequently recurrent paroxysmal atrial fibrillation (AF). The importance of this arrhythmia mechanism in the general population of patients with persistent AF is unknown. Methods and Results: After successful internal cardioversion of 50 consecutive patients with persistent AF (mean age 60 years, mean duration of AF 26 months), endocardial activity in the immediate postcardioversion period was analyzed for the presence of focal atrial activity. Postcardioversion atrial arrhythmias were considered to be local if there was evidence of a localized source of repetitive early atrial activation, either in the form of (1) self-terminating monomorphic atrial tachycardia (at least five beats) or (2) recurrences of AF with an initial atrial activation sequence (first five beats) that was both monomorphic and reproducible with repeated recurrences. Evidence for a focal atrial arrhythmia was present in 20 of the total group of 50 patients (40%). Multivariate analysis of clinical characteristics revealed the diagnosis of lone AF as the only independent predictor of a focal source of AF (P = 0.028). Thirty-nine patients were discharged from hospital in sinus rhythm. At 1-month follow-up, 25 (64%) of these 39 patients had suffered AF recurrence. The only significant predictor of AF recurrence was evidence of a focal source of atrial arrhythmia immediately after cardioversion, with a relative risk of 1.73 (range 1.1 to 2.7; P = 0.015). Conclusion: Focal atrial arrhythmias are common in patients presenting with "idiopathic" persistent AF, suggesting a possible causative role in the generation of this common arrhythmia. [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]

Repetitive Atrial Electrical Remodeling. Introduction: Episodes of atrial fibrillation (AF) are known to cause both a rapid reduction in atrial refractoriness (atrial electrical remodeling) and a more delayed increase in AF stability in the chronic goat model. The aims of this study were to examine (1) the hypothesis that an AF-induced increase in AF stability might be due to a mechanism with a longer onset and offset than that of changes in refractoriness and (2) the possibility that repeated paroxysms of maintained AF might cause a cumulative increase in AF stability independent of changes in atrial refractoriness. Methods and Results: AF was maintained by rapid atrial pacing in seven goats for three consecutive 5-day periods, each separated from each other by 48 hours of sinus rhythm. Assessments of atrial refractory periods, conduction velocity, AF inducibility, and duration of individual episodes of AF were attempted at intervals throughout the protocol. Forty-eight hours of sinus rhythm was just sufficient for refractoriness changes to fully reverse in all goats, with no evidence of any "residual" increase in AF inducibility. There was no significant difference among any of the three periods of pacing-maintained AF with regard to time to develop episodes of AF of 60-second duration (22.1 ± 13, 23.8 ± 16, and 30.3 ± 29 hours), 1-hour duration (56.6 ± 28, 61.3 ± 31, and 60.1 ± 32 hours), or 24-hour duration (84.0 ± 31, 87.0 ± 33, and 83.5 ± 32 hours). Conclusion: There is no evidence for a cumulative effect of AF paroxysms on AF inducibility or stability independent of changes in refractoriness. These findings highlight the importance of atrial refractoriness as a potential target for antiarrhythmic strategies aimed at inhibiting the self-perpetuation of AF. [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]

Closed loop control of rate adaptive pacing has theoretical advantages over current rate responsive pacemakers. The first available system (which senses the ventricular depolarization gradient) has been evaluated in ten patients. The pacing response to a variety of exercise and nonexercise stimuli was assessed. Response to isotonic exercise was prompt and proportional to the exertion involved while isometric exercise and mental stress produced obvious but more gradual increases in pacing rate. In seven patients, comparison between the intrinsic P wave and pacing rate showed a high correlation during exercise (r = 0.91) and mental activity (r = 0.87). Postural changes induced a paradoxical response. Closed loop rate responsive pacing based upon analysis of the ventricular depolarization gradient produces a fast and appropriate rate response to most physiological stimuli. [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]

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.

A three phase relation has been demonstrated between increasing heart rate and cardiac output at rest. Phase I with cardiac output increasing with increasing heart rate, phase II a plateau, and phase III decreasing cardiac output with any further increase in heart rate. The "optimal rate" can be defined as the heart rate at the onset of phase II. Twenty patients were studied, 13 male, mean age 60 years (range 31-71 years). All had chronic complete heart block and established DDD pacing. A maximal exercise test was performed to determine peak sinus rate. Exercise hemodynamics were measured using an ambulatory monitor (Capintec Vest), which permits measurement of relative cardiac output and relative ejection fraction. The patients were programmed to VVI pacing at a rate of 60 beats/min and performed three exercise tests at different workloads. The order of workloads was randomized and selected from a range (0, 25, 50, or 75 W) depending on fitness. After 3-minute stabilization, the VVI pacing rate was increased at 1-minute intervals until higher than peak sinus rate giving a total exercise time of 12 minutes. The "optimal rate band" was determined at each workload. The mean of this "optimal rate band" for each workload varied in a nonlinear manner. There was no correlation between "mean optimal rate" and age or the peak rate predicted by the Astrand formula. Current definitions of chronotropic incompetence are inaccurate. Are some of these people at their "optimal rate" already? The arbitrary selection of rate response curves on age related criteria may lead to an impaired hemodynamic response. [ABSTRACT FROM AUTHOR]

Most signal averaging processes used for cardiac signals align successive waveforms using a template matching process. In addition to achieving accurate temporal alignment of the signals, this operation must also ensure that the signal average comprises signals of the same morphology. For P wave signal averaging, systems designed for QRS complex averaging are often used, with the template acquisition window shifted to include the P wave. Theoretically, with this technique, variations in P wave morphology could reduce the high frequency content of the signal. We tested this hypothesis by comparing the performance of a selective P wave averaging system with a conventional system, based on template matching by cross-correlation over a fixed acquisition window, on identical P wave recordings from 15 subjects. The selective system identifies variations in P wave morphology and generates up to five candidate templates for averaging. Subsequently, the most frequently matched template over a 100-beat sample is used for averaging. Only P waves with the same morphology as this template are averaged. Selective averaging mainly increased the measured high frequency P wave energy, without affecting P wave duration after high pass filtering at 40 Hz, (Duration: 157(4)ms selective vs 155(4) nonselective. Energy 80–150 Hz: 1.77(0.28)µV².s selective vs 1.61(0.3)µV².s non selective, P < 0.01). These observations confirm that nonselective P wave averaging can reduce apparent P wave energy, especially at high frequency. Before meaningful studies of the value of frequency domain analysis of the P wave can be performed, it is important that signal averaging systems of sufficient fidelity are utilized. [ABSTRACT FROM AUTHOR]

Presents a correspondence on several medical issues in Great Britain. Update on shortages in nursing manpower in several districts; Approaches to improve the funding of National Health Service; Efforts for immunization due to increase incidence on Hepatitis B.

Objective: The aim was to assess the effects of therapeutic doses of intravenous adenosine on human atrial and ventricular repolarisation. Methods: The effects of 6 mg and 12 mg bolus doses of adenosine on the atrial and ventricular monophasic action potentials were studied using the contact catheter technique in 19 patients undergoing routine diagnostic electrophysiology studies. The effect on atrial repolarisation was studied before and after β blockade in a subgroup of patients. Results: The duration of the monophasic action potential to 90% repolarisation (MAPD90) was measured in all cases. After 6 mg of adenosine the atrial MAPD90 shortened from 227(SD 29) ms to 188(25) ms (p<0.005); after 12 mg it shortened from 221(31) ms to 168(32) ms (p<0.001). The maximum shortening was unaltered by propranolol 0.15 mg·kg−1. The ventricular MAPD90 showed no significant change after 12 mg, at 240(32) ms v 234(33) ms. Conclusions: Therapeutic doses of adenosine shorten the atrial but not the ventricular monophasic action potential duration. The effect is dose dependent and not abolished by β blockade.Cardiovascular Research 1992;26:939–943 [ABSTRACT FROM PUBLISHER]

S-ICD in Danon Disease Danon disease is a rare X-linked lysosomal disease causing severe hypertrophic cardiomyopathy ( LAMP2 cardiomyopathy) and an extremely poor prognosis in males, with several reported cases of sudden cardiac death despite the use of transvenous implantable cardioverter defibrillators (TV-ICD). We describe a case in which a TV-ICD was unable to defibrillate induced ventricular fibrillation (VF), but a wholly subcutaneous system (S-ICD) was successful in terminating induced VF and spontaneous ventricular tachycardia. These findings have relevance to the selection of device therapy in the management of these individuals and a wider group of young patients with severe hypertrophic cardiomyopathy. [ABSTRACT FROM AUTHOR]

The article offers information on the 2015 British Cardiovascular Society (BCS) Annual Conference to be held from June 8-10, 2015 in Manchester, England, in which BCS president Dr. Iain Simpson will open the conference whose theme is "Hearts and Genes".

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.

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.

Focuses on the treatment of supraventricular tachycardia. Use of adenosine as a therapeutic agent; Action of adenosine in the body; Dosage of the drug.

Introduction: The inferior nodal extension (INE), compact node (CN) and penetrating/His bundle (PB/HB) form the atrioventricular (AV) conduction axis and are responsible for conduction and delay of the action potential from the atria to the ventricles. With ageing, dysfunction of the AV conduction axis results in prolongation of the PR interval and AV block.Methods: We have compared the INE, CN and PB/HB from male rats 3 months old (n 9) and 2 years old (n 8). From survival curves, 3 month old rat correspond to 20 yearr old human, whereas 2 year old rat correspond to 70 year old human. Morphological characteristics of these tissues were studied using Masson's trichrome (MT) and picrosirius red (PR) on serial histological sections. Protein expression was studied using immunofluorescence and confocal microscopy. Qualitative signal intensity of proteins investigated was measured using Volocity software.Results: MT staining showed that the cells of INE, CN and PB were more loosely packed and irregularly arranged thus showing myocardial disarray in old rats. PR staining showed that total collagen content was greater in CN and PB with ageing. There was an age dependent cellular hypertrophy in all regions of the AV conduction axis. Immunohistochemistry revealed that Cx43 (the major gap junction in the heart) down regulates in PB (P<0.05), but Cx40 (important gap junction in the atria and AV conduction axis) up regulates in INE and CN (P<0.05) in old rats. With ageing, there was a down regulation of Nav1.5 (major cardiac Na+channel) in CN and PB (P<0.05), up regulation of Cav1.3 (L-type Ca2+ channel) in PB (P<0.05) and in terms of Ca2+ handling proteins, downregulation of RyR2 in CN, PB (P<0.05) and up regulation of SERCA2a in PB (P<0.05). There was also trend to downregulation of HCN4 in PB/HB bundle (P=0.051)Conclusion: Ageing is associated with structural changes to the tissues in the AV conduction axis, which include myocardial disarray, fibrosis and hypertrophy. Ageing is also associated with changes in the expression of ion channels, gap junction proteins and Ca2+ handling proteins. These changes may explain the age dependent dysfunction of AV conduction axis. [ABSTRACT FROM PUBLISHER]

A letter to the editor is presented in response to the article on atrial fibrillation in chronic heart failure.