Atrial Conduction Velocity Research Articles

Chronic myocardial infarction promotes atrial action potential alternans, afterdepolarizations, and fibrillation

AimsAtrial fibrillation (AF) is increased in patients with heart failure resulting from myocardial infarction (MI). We aimed to determine the effects of chronic ventricular MI in rabbits on the susceptibility to AF, and underlying atrial electrophysiological and Ca2+-handling mechanisms.Methods and resultsIn Langendorff-perfused rabbit hearts, under β-adrenergic stimulation with isoproterenol (ISO; 1 µM), 8 weeks MI decreased AF threshold, indicating increased AF susceptibility. This was associated with increased atrial action potential duration (APD)-alternans at 90% repolarization, by 147%, and no significant change in the mean APD or atrial global conduction velocity (CV; n = 6–13 non-MI hearts, 5–12 MI). In atrial isolated myocytes, also under β-stimulation, L-type Ca2+ current (ICaL) density and intracellular Ca2+-transient amplitude were decreased by MI, by 35 and 41%, respectively, and the frequency of spontaneous depolarizations (SDs) was substantially increased. MI increased atrial myocyte size and capacity, and markedly decreased transverse-tubule density. In non-MI hearts perfused with ISO, the ICaL-blocker nifedipine, at a concentration (0.02 µM) causing an equivalent ICaL reduction (35%) to that from the MI, did not affect AF susceptibility, and decreased APD.ConclusionChronic MI in rabbits remodels atrial structure, electrophysiology, and intracellular Ca2+ handling. Increased susceptibility to AF by MI, under β-adrenergic stimulation, may result from associated production of atrial APD alternans and SDs, since steady-state APD and global CV were unchanged under these conditions, and may be unrelated to the associated reduction in whole-cell ICaL. Future studies may clarify potential contributions of local conduction changes, and cellular and subcellular mechanisms of alternans, to the increased AF susceptibility.

Rate-Dependent Electrophysiologic Effects of the Class III Antiarrhythmic Drugs Nifekalant, Amiodarone, and Ibutilide on the Atrium in Patients With Persistent Atrial Fibrillation

Persistent atrial fibrillation (AF) is characterized by electrical remodeling, ie, marked decreases in the atrial effective refractory period (ERP), ERP rate adaptation, and atrial conduction velocity. Little information is available on the effects of class III antiarrhythmic drugs on the remodeled atrium. We studied the effects of the class III antiarrhythmic drugs nifekalant, ibutilide, and amiodarone on rate-dependent changes in atrial action potential duration in patients with persistent AF. Right atrial (RA) monophasic action potential duration (MAPD) and intra-atrial conduction time (IACT) were measured at pacing cycle lengths (CLs) of 800, 700, 600, 500, 400, 350, 300, and 250 ms before and after administration of nifekalant (0.4 mg/kg + 0.3 mg/kg/hr, iv), amiodarone (5 mg/kg, iv), or ibutilide (0.01 mg/kg, iv) in 31 patients after successful internal cardioversion of chronic AF of > 2 months duration. Nifekalant and ibutilide significantly increased RA MAPD and the ERP at each CL in a reverse rate-dependent manner. Amiodarone did not affect RA MAPD. Nifekalant did not affect IACT, whereas amiodarone increased IACT at each CL in a rate-dependent manner, and ibutilide increased IACT at CLs ≤ 350 ms. The atrial electrophysiologic effects of the class III antiarrhythmic drugs nifekalant, amiodarone, and ibutilide differ, depending on the degree of electrical and structural remodeling and the effects of the drugs on the depolarizing and repolarizing currents.

Electrophysiological Effects of an Anti-influenza Drug Oseltamivir on the Guinea-Pig Atrium: Comparison with Those of Pilsicainide

We assessed the effects of oseltamivir on the conduction velocity and effective refractory period in the guinea-pig atrium in comparison with those of a class Ic antiarrhythmic drug pilsicainide. The recording and stimulating electrodes were attached on the epicardium close to the sinus nodal region and on the left atrial appendage. Oseltamivir (10-100 µM) as well as pilsicainide (1-10 µM) decreased the atrial conduction velocity in a frequency-dependent manner. Both drugs also increased the effective refractory period in both atria; but the frequency-dependent property of oseltamivir was lacking in the left atrium, and it was less obvious in the right atrium compared with that of pilsicainide. These results suggest that oseltamivir can directly modify the electrophysiological functions in the guinea-pig atrium possibly via combination of Na(+) and K(+) channel-blocking actions.

Abstract 9976: Human Atrial Fibrillation Initiates by Formation of a Dominant Spiral Wave at the Site Where Triggers Cause Dynamic Conduction Slowing

Introduction Triggers may initiate human atrial fibrillation (AF), but by unclear mechanisms. We hypothesized that triggers would dynamically slow atrial conduction velocity, to enable the formation of a single localized spiral wave or repetitive focal beat that may drive the atria into AF. Methods We studied 13 patients at clinically-indicated AF ablation (5 persistent, age 63±11 years, LA size 43±6mm) in whom we placed 64-pole basket catheters (Boston Scientific, Natick, MA) in both atria. AF was initiated by accelerating pacing initially from 120 beats/min to AF onset. We constructed isochronal maps of both atria for beats leading to and including the first cycles of AF. We computed conduction time to each bi-atrial electrode at each rate, thus defining rate-dependence (restitution) of conduction throughout the atria. Results AF initiated in the left atrium in 13/13 patients. Notably, atrial conduction slowed dynamically with rate at the site of AF onset in 8 patients, either gradually (Figure A) or abruptly. In all patients, spatial mapping showed that triggers initiated AF at a site of dynamic conduction slowing (76%±60%) by the formation of a single spiral wave (n=7; figure B) or repetitive focal beat (n=1). Notably, these regions were not the slowest to activate at baseline. Figure A shows dynamic conduction velocity slowing only at faster rates (Fig A, steep curve) at a site in the septal posterior LA, which enabled block (Figure B, site marked *) and formation of a spiral wave (Fig B, curved arrow) that initiates AF. Conclusions Triggers initiate human AF by causing dynamic conduction slowing, enabling the formation of a single reentrant spiral wave (or repetitive focal beat) that drives the atria into AF. Of note, these sites did not exhibit conduction slowing at baseline, showing the central dynamic role of the trigger in AF initiation. Future studies should modulate conduction slowing from a trigger to prevent AF initiation.

Activation of Glibenclamide-Sensitive ATP-Sensitive K + Channels During β-Adrenergically Induced Metabolic Stress Produces a Substrate for Atrial Tachyarrhythmia

Cardiac ATP-sensitive K(+) channels have been suggested to contribute to the adaptive physiological response to metabolic challenge after β-adrenoceptor stimulation. However, an increased atrial K(+)-conductance might be expected to be proarrhythmic. We investigated the effect of ATP-sensitive K(+) channel blockade on the electrophysiological responses to β-adrenoceptor-induced metabolic challenge in intact atria. Atrial electrograms were recorded from the left atrial epicardial surface of Langendorff-perfused rat hearts using a 5×5 electrode array. Atrial effective refractory period and conduction velocity were measured using an S(1)-S(2) protocol. The proportion of hearts in which atrial tachyarrhythmia was produced by burst-pacing was used as an index of atrial tachyarrhythmia-inducibility. Atrial nucleotide concentrations were measured by high performance liquid chromatography. Perfusion with ≥10(-9) mol/L of the β-adrenoceptor agonist, isoproterenol (ISO), resulted in a concentration-dependent reduction of atrial effective refractory period and conduction velocity. The ISO-induced changes produced a proarrhythmic substrate such that atrial tachyarrhythmia could be induced by burst-pacing. Atrial [ATP] was significantly reduced by ISO (10(-6) mol/L). Perfusion with either of the ATP-sensitive K(+) channel blockers, glibenclamide (10(-5) mol/L) or tolbutamide (10(-3) mol/L), in the absence of ISO had no effect on basal atrial electrophysiology. On the other hand, the proarrhythmic substrate induced by 10(-6) mol/L ISO was abolished by either of the sulfonylureas, which prevented induction of atrial tachyarrhythmia. Atrial ATP-sensitive K(+) channels activate in response to β-adrenergic metabolic stress in Langendorff-perfused rat hearts, resulting in a proarrhythmic substrate.

Pro‐arrhythmogenic effects of the S140G KCNQ1 mutation in human atrial fibrillation – insights from modelling

Functional analysis has shown that the missense gain-in-function KCNQ1 S140G mutation associated with familial atrial fibrillation produces an increase of the slow delayed rectifier potassium current (I(Ks)). Through computer modelling, this study investigated mechanisms by which the KCNQ1 S140G mutation promotes and perpetuates atrial fibrillation. In simulations, Courtemanche et al.'s model of human atrial cell action potentials (APs) was modified to incorporate experimental data on changes of I(Ks) induced by the KCNQ1 S140G mutation. The cell models for wild type (WT) and mutant type (MT) I(Ks) were incorporated into homogeneous multicellular 2D and 3D tissue models. Effects of the mutation were quantified on AP profile, AP duration (APD) restitution, effective refractory period (ERP) restitution, and conduction velocity (CV) restitution.Temporal and spatial vulnerabilities of atrial tissue to genesis of re-entry were computed. Dynamic behaviours of re-entrant excitation waves (lifespan (LS), tip meandering patterns and dominant frequency) in 2D and 3D models were characterised. It was shown that the KCNQ1 S140G mutation abbreviated atrial APD and ERP and flattened APD and ERP restitution curves. It reduced atrial CV at low excitation rates, but increased it at high excitation rates that facilitated the conduction of high rate atrial excitation waves. Although it increased slightly tissue temporal vulnerability for initiating re-entry, it reduced markedly the minimal substrate size necessary for sustaining re-entry (increasing the tissue spatial vulnerability). In the 2D and 3D models, the mutation also stabilized and accelerated re-entrant excitation waves, leading to rapid and sustained re-entry. In the 3D model, scroll waves under the mutation condition MT conditions also degenerated into persistent and erratic wavelets, leading to fibrillation. In conclusion, increased I(Ks) due to the KCNQ1 S140G mutation increases atrial susceptibility to arrhythmia due to increased tissue vulnerability, shortened ERP and altered atrial conduction velocity, which, in combination, facilitate initiation and maintenance of re-entrant excitation waves.

Reconstruction of atrial excitation conduction velocities and implementation into the inverse problem of electrocardiography

Article Reconstruction of atrial excitation conduction velocities and implementation into the inverse problem of electrocardiography was published on August 30, 2012 in the journal Biomedical Engineering / Biomedizinische Technik (volume 57, issue SI-1-Track-F).

Is Pitx2 Growing Up?

In this issue of Circulation: Cardiovascular Genetics , Kirchhof et al1 present an interesting study on the expression of the developmental transcription factor Pitx2c in adult heart and its potential role in atrial fibrillation (AF). AF is the most common sustained cardiac arrhythmia, with a prevalence that increases with age and affects 1% to 2% of the general population.2 Despite recent advances in AF research, underlying pathophysiologic mechanisms are not fully understood. In general, initiation and perpetuation of AF needs a trigger for its onset and a vulnerable substrate for its maintenance.3 Focal ectopic activity can act as a trigger to initiate AF on the basis of a single- or multiple-circuit reentry.4 Especially, cardiomyocyte sleeves around the pulmonary veins have been shown as an origin of focal activity.5 Underlying mechanisms are early and delayed after depolarizations as a result of disturbances in depolarizing inward (Na+ or Ca2+) or repolarizing outward (K+) currents.6 Article see p 123 Once initiated, AF itself induces structural and electric remodeling, which stabilizes reentry and AF maintenance.6 Structural remodeling due to signaling through angiotensin, profibrotic cytokines like transforming growth factor-β, or microRNAs leads to upregulation of extracellular matrix proteins (eg, collagen) and downregulation of matrix-degrading enzymes (eg, matrix metalloproteinase), resulting in progressive atrial fibrosis. Electric remodeling is caused by expressional changes in ion channel subunits. AF induces calcium overload and increases activity of protein phosphatases, leading to downregulation of depolarizing L-type calcium channels and upregulation of repolarizing potassium channels. Measurable substrate of these changes in atrial electric properties is the shortening of action potential duration (APD), leading to shortening of refractory period and enabling reentry mechanisms. In most cases, therefore, AF is self-terminating (paroxysmal) in the beginning, developing to more sustained forms (persistent and permanent) over …

Anti-Arrhythmic Action of an ATP-Sensitive Potassium Channel Blocker Against Atrial Fibrillation Associated with Beta-Adrenergic Stress in Rat Hearts

Atrial fibrillation (AF) is the most common disturbance of cardiac rhythm and results in a significantly increased risk of death. Although it is widely accepted that changes to the atrial muscle associated with heart disease make prolonged episodes of AF more likely to occur, the mechanisms underlying the origins of AF remain unclear. It is thought that sympathetic innervation plays an important role in the initiation of paroxysms of AF. ATP-sensitive K+ channels (KATP channels) have been suggested to contribute to myocardial responses to beta-adrenergic stress. To investigate the role of KATP channel opening in the genesis of AF associated with beta-adrenergic stress, we examined the susceptibility to AF of excised Langendorff-perfused hearts from adult male Wistar rats. Unipolar electrograms were recorded from the left atrial epicardial surface of perfused hearts using a multi-electrode array, allowing measurements of atrial effective refractory period (AERP) and conduction velocity (CV) through the construction of activation maps. Paroxysms of AF were induced by burst pacing and the incidence and duration of the arrhythmia noted. Beta-adrenergic stress was induced by perfusion of the hearts with isoprenaline (ISO). While it was not possible to induce paroxysms of AF in control conditions, perfusion of the hearts with ISO rendered the left atrium susceptible to pacing-induced AF; the incidence and duration of which increased in a concentration-dependent manner. The shortening of AERP and incidence of AF induced by 10−6 M ISO were completely blocked in the presence of the KATP channel blocker, glibenclamide (10−5 M). In the absence of ISO, glibenclamide had no effect on AERP or CV. Taken together, our results suggest that KATP channels can contribute to atrial arrhythmogenesis during beta-adrenergic stress.Supported by the BHF (PG/09/046).

PITX2c Is Expressed in the Adult Left Atrium, and Reducing Pitx2c Expression Promotes Atrial Fibrillation Inducibility and Complex Changes in Gene Expression

Intergenic variations on chromosome 4q25, close to the PITX2 transcription factor gene, are associated with atrial fibrillation (AF). We therefore tested whether adult hearts express PITX2 and whether variation in expression affects cardiac function. mRNA for PITX2 isoform c was expressed in left atria of human and mouse, with levels in right atrium and left and right ventricles being 100-fold lower. In mice heterozygous for Pitx2c (Pitx2c(+/-)), left atrial Pitx2c expression was 60% of wild-type and cardiac morphology and function were not altered, except for slightly elevated pulmonary flow velocity. Isolated Pitx2c(+/-) hearts were susceptible to AF during programmed stimulation. At short paced cycle lengths, atrial action potential durations were shorter in Pitx2c(+/-) than in wild-type. Perfusion with the β-receptor agonist orciprenaline abolished inducibility of AF and reduced the effect on action potential duration. Spontaneous heart rates, atrial conduction velocities, and activation patterns were not affected in Pitx2c(+/-) hearts, suggesting that action potential duration shortening caused wave length reduction and inducibility of AF. Expression array analyses comparing Pitx2c(+/-) with wild-type, for left atrial and right atrial tissue separately, identified genes related to calcium ion binding, gap and tight junctions, ion channels, and melanogenesis as being affected by the reduced expression of Pitx2c. These findings demonstrate a physiological role for PITX2 in the adult heart and support the hypothesis that dysregulation of PITX2 expression can be responsible for susceptibility to AF.

Facilitatory and inhibitory effects of SCN5A mutations on atrial fibrillation in Brugada syndrome

Brugada syndrome (BrS) is associated with increased risk for atrial fibrillation (AFib). However, the role of SCN5A mutations in the occurrence of AFib remains unclear. Cardiac sodium current reduction caused by SCN5A mutations may facilitate AFib by slowing intra-atrial conduction and inducing structural changes, but also prevent it by suppressing atrial ectopic activity. Here, we examined the relation between SCN5A mutations, atrial conduction velocity, atrial structural changes, and atrial ectopic activity in BrS. Data from 214 BrS patients [78 with an SCN5A mutation (patients with an SCN5A mutation, BrSSCN5A+) and 136 without an SCN5A mutation (patients without an SCN5A mutation, BrSSCN5A-)] were collected. Intra-atrial conduction velocity was assessed by measuring P-wave durations at baseline and during sodium channel provocation testing. Atrial structural changes were assessed by measuring atrial dimensions using cardiac magnetic resonance imaging. Atrial ectopic activity was assessed by determining the incidence of atrial ectopic beats using 24 h Holter recordings. Clinical characteristics (including AFib occurrence) did not differ between BrSSCN5A+ and BrSSCN5A-. Baseline P-wave durations were longer in BrSSCN5A+ than in BrSSCN5A-, but lengthened markedly in BrSSCN5A- during provocation testing. Atrial dimensions did not differ. Atrial ectopic beats occurred more often in BrSSCN5A-, and the proportion of patients experiencing one or more atrial ectopic beats was larger in BrSSCN5A- than in BrSSCN5A+. In BrS, the presence of an SCN5A mutation is associated with intra-atrial conduction slowing and suppressed atrial ectopic activity. Intra-atrial conduction slowing may provide a plausible substrate for AFib maintenance, while reduced atrial ectopic activity may constitute inhibition of the trigger for AFib initiation.

Cardiac Mechanical and Electrical Relevance Facilitating the Evolution of PAF to PRAF

Atrial Fibrillation (AF) is the commonest sustained arrhythmia. The absence of a reliable, cure for AF has fuelled research on its pathophysiology. This presentation will discuss electrical and mechanical abnormalities that initiate and perpetuate AF. AF has been known to require triggers, a suitable substrate and modifying factors. It is easy to understand that while the role of trigger is more important in paroxysmal AF, substrate abnormality is necessary for more permanent forms. The electrical triggers identified have been rapidly firing atrial focus, primarily from the pulmonary veins, atrial flutter and less commonly, supraventricular tachycardia. The substrate involves, first, an adequate mass capable of encompassing the number of wavelets required to maintain AF. Furthermore, in the presence of cardiac disease, heterogeneous electrophysiologic properties act to provide the milieu for sustained arrhythmia. Dilatation of the atria, fibrosis and loss of atrial muscle, can all lead to the necessary electrophysiologic substrate. Recent studies have pointed to more cellular and genetic abnormalities, including abnormalities of atrial angiotensin receptors in the, repolarisation alternans, enhanced and delayed atrial action potential repolarisation, cellular hyperexcitability, and conduction velocity hetrogenicity. Conventional compartmentalization of atrial fibrillation, into paroxysmal, persistent and permanent, has proven to be useful. However, pathophysiologically, they form a continuum, as demonstrated by presence of substrate abnormality in paroxysmal lone atrial fibrillation, and reverse remodeling of atria after treatment of mitral valve disease.

Connexin Gene Transfer Preserves Conduction Velocity and Prevents Atrial Fibrillation

Introduction: Fibrosis, cellular dysfunction and gap junction protein alterations occur in AF and cause conduction delay. We performed this study to test the hypothesis that gap junction protein overexpression would improve conduction and prevent AF. Methods and Results: Thirty Yorkshire swine were randomized into sinus rhythm (SR) and AF groups (n=15 per group). Each group included 3 subgroups: sham-operated control, gene therapy with adenovirus expressing connexin (Cx) 40 and Cx43, with 5 animals in each subgroup. All animals had epicardial gene painting; the AF group had burst atrial pacing. All animals underwent terminal study 7 days after gene transfer. SR animals had strong transgene expression but no atrial conduction changes. In AF animals, controls had reduced and lateralized Cx43 expression, and Cx43 gene transfer restored the expression of total and phosphorylated Cx43 to SR control levels. Immunohistochemical analysis revealed connexin localization to the intercalated disk after gene transfer. In the AF group, both Cx40 and Cx43 gene transfer improved conduction and reduced AF relative to controls. Conclusions: Atrial-specific gene therapy with gap junction protein preserved atrial conduction velocity and prevented AF.

Chromosome 4q25 Variants Have Less Co-Morbid Risk Factors and High Left Atrial Conduction Velocity in Korean Patients Who Underwent Radiofrequency Catheter Ablation of Atrial Fibrillation

Background: Recent studies have demonstrated the association of 4q25 gene single nucleotide polymorphism (SNP) with atrial fibrillation (AF). We evaluated potential relationships of 4 SNPs on chromosome 4q25 with clinical and electrophysiological characteristics in patients undergoing catheter ablation for AF.Methods: A total of 295 consecutive patients (56±11 years, 78% male) with paroxysmal (68.7%) or persistent (31.3%) AF were included. Genotyping for 4 SNPs in close proximity to PITX2 gene on chromosome 4q25 (rs2200733, rs10033464, rs17042171, and rs6843082) were performed and compared with clinical, electrophysiological, and imaging database.Results: There were no significant differences in clinical and electrophysiological parameters between major and minor allele group of rs10033464, rs17042171, and rs6843082. In contrast, rs2200733 variant was associated with lower CHADS score (0.73±0.95 vs. 1.17±1.10, p=0.021), lower prevalence of heart failure (2.5 vs. 11.5%, p=0.023), hypertension (42.3 vs. 68.9%, p=0.006), and patients with age>75 (1.2 vs 6.9%, p=0.030). In electrophysiological study, conduction velocity of left atrium was significantly higher (0.67±0.35 m/s vs. 0.55±0.22 m/s, p=0.042) in patients with variant allele of rs2200733.Conclusions: In Korean population, rs2200733 at 4q25 was the only significant SNPs associated with clinical and electrophysiological trait. It may increase the risk of AF without traditional risk factors and significant electroanatomical remodeling.

Combined effects of up- and downstream therapies on atrial fibrillation in a canine rapid stimulation model

BackgroundRecent reports suggest angiotensin receptor blockers (ARBs) and some antiarrhythmic agents affect atrial remodeling in atrial fibrillation (AF). We evaluated the effect of combination therapy with olmesartan (Olm) and bepridil (Bep) in a canine model of AF. Methods and resultsAn atrial stimulation device was implanted in 10 dogs undergoing 6-week pacing at 400bpm. They were divided into Olm (2mg/kg/day) (n=5) and Olm+Bep (Olm, 2mg/kg/day; Bep, 10mg/kg/day) groups (n=5). Atrial effective refractory period (AERP), conduction velocity (CV), and AF inducibility were evaluated weekly, and hemodynamics, atrial histology, and mRNA expression and protein expression of ion-channel and gap junction-related molecules at 6weeks. Data were compared between groups and with non-pacing control and pacing-control groups from our previous report.The pacing-control group exhibited shortened AERP, decreased CV, increased AF inducibility and tissue fibrosis, and down-regulated L-type Ca2+ channel (LCC), SCN5A, Kv4.3 and connexin43 (Cx43). By comparison, the Olm group exhibited suppression of the decrease in CV and of the increase in AF inducibility, but no change in AERP shortening. The Olm+Bep group exhibited suppression of AERP shortening as well as the greatest decrease in AF inducibility. Histologically, tissue fibrosis was suppressed in Olm and Olm+Bep groups. Down-regulation of Cx43 was partly suppressed in the Olm group while that of LCC, SCN5A, and Cx43 was suppressed in the Olm+Bep group. ConclusionOlm and Bep in combination suppressed AF inducibility more strongly than Olm alone, and may be more useful in the suppression of AF.

Acute Atrial Dilatation Slows Conduction and Increases AF Vulnerability in the Human Atrium

The mechanisms by which atrial stretch favors the development of a substrate for atrial fibrillation (AF) are not fully understood. In this study, the role of stretch-induced conduction changes in the creation of a proarrhythmic substrate has been investigated by quantifying the spatial distribution of local conduction velocities (CVs) in the human atrium during acute atrial dilatation. Electroanatomic mapping of right atrial activation was performed in 10 patients during coronary sinus pacing under control condition and during acute atrial dilatation. Atrial stretch was obtained by simultaneous atrioventricular (AV) pacing at a cycle length of 450-500 ms. Local CVs were accurately estimated by applying the principle of triangulation and spatially mapped over the whole right atrial endocardial surface. Simultaneous AV pacing significantly increased right atrial volume from 72.0 ± 29.0 to 86.3 ± 31.3 mL (P < 0.001). The 23% increase in atrial volume resulted in an overall decrease in atrial CV from 65.8 ± 5.9 to 55.2 ± 7.2 cm/s (P < 0.001) and an increased incidence of slow conduction sites or local conduction blocks from 10.3 ± 4.2% to 15.9 ± 7.7% (P < 0.01). Acute atrial dilatation concurrently increased AF vulnerability, with 6 of 10 patients developing AF episodes under stretch condition. Quantification of stretch-induced conduction changes in the human atrium is feasible by combining simultaneous AV pacing and CV map construction. Acute atrial dilatation results in conduction slowing and significant increase in AF vulnerability, suggesting the role of stretch-induced conduction disturbances in the creation of a substrate for AF.

Can Etiology Predict Atrial Conduction Velocities in Congestive Heart Failure Patients?

Introduction: It has been suggested that differences in sensed and paced conduction velocity in the heart failure patient population may be responsible for increased atrial fibrillation. These differences may be due to both structural as well as electrophysiologic changes in conduction velocity. Our analysis evaluated the role of disease etiology in these differences in conduction. Methods: We evaluated implant data from patients undergoing CRTD implants between 2007 and 2008 (N = 155). 102 Male, 53 women, mean QRS duration of 151 ms (+ /− 35) with a mean EF 23% (+ /− 0.7).

Alterations of atrial electrophysiology induced by electrolyte variations: combined computational and P-wave analysis

Haemodialysis (HD) therapy represents a unique model to test in vivo, in humans, the effects of changes in plasma ionic concentrations. Episodes of paroxysmal atrial fibrillation (AF) often occur during the treatment. We investigated the effects of HD-induced electrolyte variations on atrial electrophysiology by analysing ECG P-wave duration (PWd), which reflects atrial conduction velocity (CV), and simulated atrial action potential (AP). In 20 end-stage renal disease patients PWd (signal-averaged ECG), heart rate (HR), blood pressure, Na(+), K(+), Ca(2+), and Mg(2+) plasma concentrations were measured before and after HD session. The Courtemanche computational model of human atrial myocyte was used to simulate the atrial AP. AP upstroke duration (AP(ud)), AP duration and atrial cell effective refractory period (ERP) were computed. Extracellular electrolyte concentrations and HR were imposed to the average values measured in vivo. HD decreased K(+) (from 4.9 +/- 0.5 to 3.9 +/- 0.4 mmol/L, P < 0.001) and Mg(2+) (0.92 +/- 0.08 to 0.86 +/- 0.05 mmol/L, P < 0.05), and increased Na(+) (139.8 +/- 3.4 to 141.6 +/- 3.1 mmol/L, P < 0.05) and Ca(2+) (1.18 +/- 0.09 to 1.30 +/- 0.07 mmol/L, P < 0.001) plasma concentrations. PWd systematically increased in all the patients after HD (131 +/- 11 to 140 +/- 12 ms, P < 0.001), indicating an intra-atrial conduction slowing. PWd increments were inversely correlated with K(+) variations (R = 0.73, P < 0.01). Model-based analysis indicated an AP(ud) increase (from 2.58 to 2.94 ms) after HD, coherent with experimental observations on PWd, and a reduction of ERP by 12 ms. Changes of plasma ionic concentrations may lead to modifications of atrial electrophysiology that can favour AF onset, namely a decrease of atrial CV and a decrease of atrial ERP.

Fractionated atrial electrograms during sinus rhythm: Relationship to age, voltage, and conduction velocity

Fractionated atrial electrograms (CFAEs) have been implicated in the mechanism of atrial fibrillation (AF). The prevalence and distribution of CFAEs in normal populations have not been clearly defined. This study sought to determine the influence of age on CFAEs and investigate the relationship between CFAEs and the underlying atrial substrate. Twenty-one patients without structural heart disease underwent electroanatomic mapping of their right atrium (RA). Patients were categorized into 3 groups according to age: group A, patients <30 years (25.1 +/- 3.1 years, n = 7); group B, patients between 31 and 59 years (51.7 +/- 10.3 years, n = 6); group C, patients >60 years (66.9 +/- 7.7 years, n = 8). The proportion of points with CFAEs was analyzed for the high and low septal RA, high and low lateral RA, and high and low posterior RA. The mean atrial voltage and conduction velocity were assessed in each of these regions. The percentage of CFAEs was greater in group C (14.6% +/- 7.7%) than in group A (2.7% +/- 2.1%; P = 0.001). The percentage of CFAEs in group B (8.5% +/- 3.5%) was not significantly different from that in group A (P = 0.21) and group C (P = 0.14). The CFAEs were predominantly located in the posterior RA and high septal RA. There were significant correlations between the proportion of CFAEs and age (R = 0.72; P < 0.01), atrial voltage (R = -0.57; P < 0.01), and conduction velocity (R = -0.73; P < 0.001). CFAEs increase with age and occur in regions of low atrial voltage and slowed conduction. The distribution of CFAE is predominantly along the posterior and high septal RA, regions where there are marked changes in myocardial fiber orientation. This suggests that the underlying myocardial architecture is the main influence on electrogram morphology.

Regional Left Atrial Conduction Velocity and Its Relationship to CFAE

Regional Left Atrial Conduction Velocity and Its Relationship to CFAE