Nonsustained Atrial Fibrillation Research Articles

Distribution of Epoch Lengths in Non-Sustained Atrial Fibrillation is Consistent With Type-II Supertransient Behaviour, a Property of Spatiotemporal Chaos

Distribution of Epoch Lengths in Non-Sustained Atrial Fibrillation is Consistent With Type-II Supertransient Behaviour, a Property of Spatiotemporal Chaos

PO-01-037 RISK FACTORS FOR PRESENCE OF NON-PULMONARY VEIN TRIGGERS FOR ATRIAL FIBRILLATION

Targeting of non-pulmonary vein triggers (NPVTs) after pulmonary vein isolation (PVI) may reduce atrial fibrillation (AF) recurrence. Incrementally dosed isoproterenol infusion (up to 30mcg/min) and cardioversion of induced AF used to provoke NPVTs typically requires additional vasopressor support and increases procedure time. We aimed to identify risk factors for the presence of NPVTs in order to identify patient profiles in which NPVT provocation would have greatest yield. Using the Hospital of the University of Pennsylvania AF ablation registry, we compared patients in whom NPVTs were observed to patients in whom NPVTs were not observed using a standard provocation protocol. NPVTs were defined as a single or sequence of non-pulmonary vein atrial ectopic beats triggering non-sustained or sustained AF or focal atrial tachycardia. Continuous variables were compared using unpaired t-Test and categorical variables were compared using Fisher exact test. In a total of 1,306 AF ablation patients between January 2021 and August 2022, 87% underwent NPVT standard provocation testing and 10% of all patients had NPVTs observed. Compared to those without NPVTs, patients who had NPVTs were more likely to be female (41% vs 30%, OR 1.62 [1.12-2.35], p=0.01), and to have sinus node dysfunction (17% vs 7%, OR 2.83 [1.72-4.65], p=0.0002), prior AF ablation (68% vs 34%, OR 4.16 [2.82-6.19], p=<0.0001), and left atrial scar (>2cm2) (71% vs 36%, OR 4.28 [2.78-6.53], p=<0.0001) identified during voltage mapping (defined as peak to peak bipolar voltage <0.5mV of at least three abnormal contiguous electrograms outside pulmonary veins, Table 1). In this patient cohort, the absence of these four risk factors yielded NPVT provocation rate of 0.02%, while the presence of three or four risk factors led to NPVT provocation rate of 30-50% (Figure 1). Incremental presence of the NPVT associated risk factors allows prediction of the likelihood that provocation testing will lead to the induction of NPVTs and may influence decision making to undertake NPVT provocation testing during AF ablation.Tabled 1Table 1VariableOverall (N=1306)NPVT (N=130)No NPVT (N=1006)P ValueOdds Ratio (95% CI)Age (years)130665.89 ± 9.9965.00 ± 10.590.36BMI130629.16 ± 5.6229.95 ± 6.270.17LVEF (%)126656.42 ± 9.5755.28 ± 11.210.27LA volume index (mL/m2)62639.34 ± 17.8939.25 ± 17.180.97CHA2DS2VASc score13002.40 ± 1.452.41 ± 1.560.94Female40353 (41)350 (30)0.011.62 (1.12-2.35)Hx of CVA/TIA12314 (11)109 (9)0.53Diabetes20215 (12)187 (16)0.25Heart Failure / CM41738 (29)379 (32)0.55Hypertension1031105 (81)926 (79)0.65Obstructive Sleep Apnea42343 (33)380 (32)0.84Sinus Node Dysfunction10122 (17)79 (7)0.00022.83 (1.72-4.65)Non-Paroxysmal AF478/124151 (41)427 (38)0.63Had Previous AF Ablation48288 (68)394 (34)<0.00014.16 (2.82-6.19)Has LA scar (Any LVA)426/106978 (71)348 (36)<0.00014.28 (2.78-6.53)Values are reported as mean ± SD, or number (%). P value is comparing NPVT group vs No NPVT group. Continuous variables compared using unpaired t-Test, and categorical variables compared using Fisher exact test. BMI=body mass index; LVEF=left ventricular ejection fraction; LA=left atrium; CVA=cerebrovascular accident; TIA=transient ischemic attack, CM=cardiomyopathy; AF=atrial fibrillation; LVA=low voltage area; NPVT=non-pulmonary vein trigger Open table in a new tab

The therapeutic potential of relaxin for heart failure with preserved ejection fraction

Abstract Background and significance Heart Failure (HF) is the leading cause of cardiovascular deaths and ∼50% of HF patients have HF with preserved ejection Fraction (HFpEF). HFpEF patients typically have co-morbidities such as atrial fibrillation (AF), diabetes, lung edema and hypertension. The latter is a predictor of mortality and is targeted to prolong survival given the lack of a direct therapy for HFpEF. To address this unmet public health problem, we investigate the therapeutic potential of the insulin-like hormone Relaxin (RLX) in a rat model of HFpEF that recapitulates most aspects of clinical HFpEF. Methods ZSF1 diabetic rats were placed on a high fat diet (HFD for 11-weeks) and echocardiograms were used to track HFpEF development. At week 20, osmotic mini-pumps were implanted to release vehicle (Na-acetate) or RLX (400μg/kg/day, 2-weeks). Hearts were then perfused with a voltage-sensitive dye (RH237) and a Ca2+ indicator (Rhod-2/AM) to optically map action potentials and Ca2+ transients and analyze arrhythmia phenotype. Left ventricular (LV) tissue sections were used for immune-fluorescence (IF) imaging for changes in fibrosis (collagen 1), connexin 43, Wnt1 and β-catenin in LV myocytes. Blood draws were taken to measure changes in serum NT-pro-ANP, ET-1 and RLX. Results ZSF1 rats on a HFD developed HFpEF with E/e' (an echo marker of diastolic dysfunction) decreasing to −24.4 from −17.9 MV (n=12) and was reversed to −18.6 MV by RLX (n=6, p&amp;lt;0.0001). In HFpEF rats that received the vehicle (n=6), a premature stimulus (S1-S2= 40 ms) elicited: a) no arrhythmia b) non-sustained AF or c) sustained AF, with (1/3 of rats in each group). RLX blocked sustained supraventricular (n=0/12) and n=4/12 had non-sustained AF. RLX improved conduction velocity (CV), at short cycle lengths (150 ms) from 0.74 to 0.9 m/s (n=4/group). IF indicated that RLX increased Cx43 (26.8±0.03%, p&amp;lt;0.0001, n=6), and β-catenin (52.8±0.05%, p&amp;lt;0.0001) at intercalated disks. RLX reduced collagen deposition in HFpEF rats (25±0.04%, p&amp;lt;0.04, back to normal) and caused a marked increase of cytosolic Wnt1 (47.3±0.06%, p&amp;lt;0.0001). IF data are given as mean ± SEM. Conclusions The ZSF1 diabetic rat on a high-fat diet recapitulates most of the phenotypes associated with human HFpEF, including atrial arrhythmias, fibrosis, and lung edema. RLX treatment post-development of HFpEF reversed the pro-arrhythmic phenotype, increased conduction velocity particularly at fast heart rates, reversed fibrosis, reduced NT-pro-ANP and ET-1 in male rats. Most intriguing, RLX treatment activated Wnt1 and β-catenin indicating that the beneficial actions of RLX occur via genomic remodeling of the heart. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Relaxera Pharmazeutische Gesellschaft mbH &amp; Co. KGStubenwald-Allee 8a, 64625 Bensheim, Germany &amp; Uhlandstraße 4-5, 10623 Berlin, Germany

Attenuation of Oxidative Injury With Targeted Expression of NADPH Oxidase 2 Short Hairpin RNA Prevents Onset and Maintenance of Electrical Remodeling in the Canine Atrium: A Novel Gene Therapy Approach to Atrial Fibrillation.

Atrial fibrillation (AF) is the most common heart rhythm disorder in adults and a major cause of stroke. Unfortunately, current treatments of AF are suboptimal because they are not targeted to the molecular mechanisms underlying AF. Using a highly novel gene therapy approach in a canine, rapid atrial pacing model of AF, we demonstrate that NADPH oxidase 2 (NOX2) generated oxidative injury causes upregulation of a constitutively active form of acetylcholine-dependent K+ current (IKACh), called IKH; this is an important mechanism underlying not only the genesis, but also the perpetuation of electric remodeling in the intact, fibrillating atrium. To understand the mechanism by which oxidative injury promotes the genesis and maintenance of AF, we performed targeted injection of NOX2 short hairpin RNA (followed by electroporation to facilitate gene delivery) in atria of healthy dogs followed by rapid atrial pacing. We used in vivo high-density electric mapping, isolation of atrial myocytes, whole-cell patch clamping, in vitro tachypacing of atrial myocytes, lucigenin chemiluminescence assay, immunoblotting, real-time polymerase chain reaction, immunohistochemistry, and Masson trichrome staining. First, we demonstrate that generation of oxidative injury in atrial myocytes is a frequency-dependent process, with rapid pacing in canine atrial myocytes inducing oxidative injury through the induction of NOX2 and the generation of mitochondrial reactive oxygen species. We show that oxidative injury likely contributes to electric remodeling in AF by upregulating IKACh by a mechanism involving frequency-dependent activation of PKCε (protein kinase C epsilon). The time to onset of nonsustained AF increased by >5-fold in NOX2 short hairpin RNA-treated dogs. Furthermore, animals treated with NOX2 short hairpin RNA did not develop sustained AF for up to 12 weeks. The electrophysiological mechanism underlying AF prevention was prolongation of atrial effective refractory periods, at least in part attributable to the attenuation of IKACh. Attenuated membrane translocation of PKCε appeared to be a likely molecular mechanism underlying this beneficial electrophysiological remodeling. NOX2 oxidative injury (1) underlies the onset, and the maintenance of electric remodeling in AF, as well, and (2) can be successfully prevented with a novel, gene-based approach. Future optimization of this approach may lead to a novel, mechanism-guided therapy for AF.

Atrial fibrillation detection by the subcutaneous defibrillator: real-world clinical performances and implications from a multicentre study.

No data exist concerning the clinical performances of the subcutaneous implantable cardioverter-defibrillator (S-ICD) atrial fibrillation (AF) detection algorithm. We aimed to study the performances and implications of the latter in a 'real-world' setting. Between July 2017 and August 2019, 155 consecutive S-ICD recipients were included. Endpoint of the study was the incidence of de novo or recurrent AF using a combined on-site and remote-monitoring follow-up approach. After a mean follow-up of 13 ± 8 months, 2531 AF alerts were generated for 55 patients. A blinded analysis of the 1950 subcutaneous electrocardiograms available was performed. Among them 47% were true AF, 23% were premature atrial contractions or non-sustained AF, 29% were premature ventricular contractions or non-sustained ventricular tachycardia, and 1% were misdetection. Fourteen percent (21/155) patients had at least one correct diagnosis of AF by the S-ICD algorithm. One patient presented symptomatic paroxysmal AF not diagnosed by the S-ICD algorithm (false negative patient). Patient-based sensitivity, specificity, positive, and negative predictive values were respectively 95%, 74%, 38%, and 99%. Among patients with at least one correct diagnosis of AF, 38% (8/21) had subsequent clinical implications (anticoagulation initiation or rhythm control therapies). The S-ICD AF detection algorithm yields a high sensitivity for AF diagnosis. Low specificity and positive predictive value contribute to a high remote monitoring-notification workload and underline the necessity of a manual analysis. Atrial fibrillation diagnosis by the S-ICD AF detection algorithm might lead to significant therapeutic adjustments.

Burden of Premature Atrial Complexes and Risk of Recurrent Stroke and Death in Patients with Mild to Moderate Ischemic Stroke

BackgroundPremature atrial complexes (PACs) meet increased attention as a potential intermediary between sinus rhythm and atrial fibrillation (AF). Patients with even high numbers of PACs do not fulfill current guidelines for oral anticoagulation treatment though an associated stroke risk is suspected. Objective: We aimed to determine whether a high number of PACs or runs of AF less than 30 seconds in 2-day continuous electrocardiogram (ECG) recording was associated with risk of recurrent ischemic stroke/transient ischemic attack (TIA) or death in a large cohort of patients with acute ischemic stroke or TIA and no prior AF. MethodsWe performed 48 hours continuous ECG recording within 1 week after ischemic stroke/TIA. PACs were reported as mean number of PACs per hour. Patients were followed in Danish Stroke Registry, Danish Civil Registration System, and Danish National Patient Registry. Cox Regression analysis was used to calculate hazard ratios. ResultsWe included 1507 patients with TIA (40%) or ischemic stroke (60%), of which 98.7% had mild to moderate strokes. Mean age was 72.9 (7.8) years, 43.4% were females. Follow-up was 2.3 (1.3) years. Hazard ratio for recurrent stroke/TIA or death did not differ between quartiles of PAC burden, nor did any of the 2 components of this composite endpoint. Nonsustained AF less than 30 seconds was not associated with higher risk of recurrent stroke/TIA or death. ConclusionsIn a large cohort of patients with recent ischemic stroke or TIA, burden of PACs or nonsustained AF less than 30 seconds were not associated to higher risk of recurrent stroke/TIA or death.

ФЕНОТИПОВІ ОЗНАКИ І ПОЛІМОРФІЗМ RS10465885 ГЕНА КОНЕКСИНУ-40 ЯК ПРЕДИКТОРИ ВИНИКНЕННЯ РЕЦИДИВУ АРИТМІЇ У ПАЦІЄНТІВ З ФІБРИЛЯЦІЄЮ ПЕРЕДСЕРДЬ НЕКЛАПАННОГО ҐЕНЕЗУ ПІСЛЯ ВІДНОВЛЕННЯ СИНУСОВОГО РИТМУ ПРИ 1-РІЧНОМУ СПОСТЕРЕЖЕННІ: РЕЗУЛЬТАТИ НЕЙРОМЕРЕЖЕВОГО АНАЛІЗУ

Atrial fibrillation (AF) is a violation of the heart rhythm associated with 1 % (or even more) of the health budget expenditure in Europe. Despite the fact that there is a constant increase in the socio-economic burden of AF, and there has been significant progress in understanding the pathophysiology of this arrhythmia, the effectiveness of its treatment is still far from satisfactory. One of the reasons for the insufficient effectiveness of modern strategies for the prevention and treatment of AF is the existence of limitations in understanding the complex pathophysiology of this disturbance of the heart rhythm.The aim of the study – to leran the phenotypic and genotypic (rs10465885 polymorphism in connexin-40 [Cx40] gene) predictors of arrhythmia recurrence in patients with non-valvular atrial fibrillation (AF) after sinus rhythm restoring (SRR ) at 1-year follow-up (AF360), in particular by the use of artificial neural networks (ANN ) analysis.Materials and Methods. We enrolled 104 patients (pts) with non-sustained non-valvular AF (average age (53±10) years, 80 (76.9 %) men). The distribution of rs10465885 polymorphic variants in Cx40 gene (n=73) was as follows: TT – 17 (23.3 %) pts, CT – 33 (45.2 %), СС – 23 (31.5 %). We analyzed 122 cases of SR restoring: 32 (26.2 %) – pharmacological cardioversion (29 pts); 63 (51.6 %) – electrical cardioversion (53 pts); 27 (22.2 %) – radiofrequency catheter ablation (22 pts). AF360 occurred in 76 (65.5 %) of 116 cases. In order to identify AF360 predictors, we used logistic regression analysis, as well as ANN analysis (building the linear [LIN] and nonlinear [multilayer perceptron (MLP )] ANN`s).Results and Discussion. Genetic algorithm Input Selection revealed 16 parameters, associated with AF360, including SRR type, rs10465885 polymorphism, and certain clinical (in particular, CHA 2DS 2-VAS c score), lab and echo parameters. CHA 2DS 2-VAS c score was the only independent AF360 predictor, according to the results of multivariable logistic regression analysis. The area under curve (AU C) for MLP , included all 16 variables, revealed by the Genetic algorithm, was significantly higher than in linear LIN: 0.874 (95 % confidence interval [CI] 0.798–0.929) vs. 0.678 (CI 0.583–0.763), respectively (p&lt;0.001). In order to obtain the maximal reduction of predictors, we built the MLP , included the set of 5 variables (MLP 5): SRR type; rs10465885 polymorphism; the heart failure presence and its stage; AF type (recurrent or first diagnosed); and antero-posterior left atrial dimension. MLP 5 AU C (0.808 (95 % CI 0.723–0.876)) was significantly higher than those for LIN (р = 0.027).Conclusion. AF360 was non-linearly associated with SRR type, rs10465885 polymorphism in Cx40 gene, as well as certain phenotypic parameters. The further search of the most significant genetic and epigenetic predictors of AF recurrence at different terms after SRR is of crucial importance.

P1437Time course of electrogram organization of sustained versus non-sustained atrial fibrillation

P1437Time course of electrogram organization of sustained versus non-sustained atrial fibrillation

Abstract WP187: Subclinical Macro and Microvascular Disease in Stroke-free Subjects With Nonsustained Atrial Fibrillation

Introduction: Prevalence of nonsustained atrial fibrillation (NSAF), described as irregular atrial runs lasting shorter than 30-seconds, is higher in patients with ischemic stroke compared to stroke-free controls. Nonetheless, its role in causality of stroke and future cerebrovascular risk is still not established. Subclinical atherosclerotic burden and vascular stiffness are more prevalent, and have been shown to modify future risk of vascular events in patients with atrial fibrillation (AF). We aimed to determine the relationship between NSAF and subclinical atherosclerosis, vascular dysfunction and cerebral microvascular disease. Methods: Sonographic carotid distensibility metrics, carotid intima-media thickness (IMT), carotid plaque burden score (Ten Cate’s), middle cerebral artery (MCA) pulsatility index (PI) and cerebral white matter disease burden (Fazekas’ periventricular and subclinical scores) were studied in 263 stroke-free control subjects. 24-hour Holter monitoring documented NSAF in 27% of study population. Abnormality limits were set as mean±standard deviation. Results: Compared to those without NSAF (age 62±8 yr, 43% male), subjects with NSAF (age 67±9 yr, 31% male) had significantly higher total carotid plaque burden score (p=0.009) and significantly lower common carotid artery carotid distensibility (p=0.019). Maximum and averaged IMT, carotid stiffness and elastic modulus, and asymptomatic significant (≥50%) carotid artery stenosis were numerically higher. Patients with NSAF had significantly higher MCA PI (p=0.007) and numerically higher white matter disease scores. Regression analysis models showed that NSAF is one independent predictors of abnormal carotid distensibility (p=0.026) and presence of carotid plaque (p=0.023); but not for carotid plaque burden score (&gt;4), MCA PI (&gt;1.1) and IMT max (&gt;0.966). Conclusions: The presence of a significant relationship between NSAF and presence of carotid artery plaque and decreased cervical artery distensibility raises the possibility that NSAF might be a reflection of subclinical atherosclerotic burden. This crosstalk between surrogate markers might explain the higher prevalence of NSAF in ischemic stroke patients.

Anatomical dilatation of the superior vena cava associated with an arrhythmogenic response induced by SVC scan pacing after atrial fibrillation ablation

BackgroundThe relationship between pulmonary vein (PV) arrhythmogenicity and its anatomy has been reported. However, that of the superior vena cava (SVC) has not been well discussed. Arrhythmogenic response induced by pacing stimulation at SVC might help with identifying SVC arrhythmogenicity. The purpose of this study was to investigate the relationship between the anatomical dilatation of SVC and the arrhythmogenic response induced by pacing at SVC. MethodsForty-three patients who underwent atrial fibrillation (AF) ablation were enrolled in this study. After PV isolation, scan pacing (up to triple extra stimulation following intrinsic sinus beats) was performed at SVC. The arrhythmogenic response was defined as following: (1) repetitive atrial responses, (2) non-sustained, and (3) sustained AF/ atrial tachycardia. To assess the dilatation of SVC, we measured the cross-sectional area of the SVC (SVC-area) using multi-planar reconstruction CT imaging. ResultsArrhythmogenic responses were documented in 24 patients (Group 1). No arrhythmogenic responses were documented in the remaining 19 patients (Group 2). The SVC-area was significantly larger in Group 1 than Group 2 (3.1±0.9 vs. 2.2±0.8cm2, P=0.004). A multivariate analysis revealed only SVC-area was associated with arrhythmogenic responses (odds ratio=2.87, CI 1.05–7.82, P=0.04). Furthermore, AF recurrence rate was significantly higher in patients with SVC-area>2.56cm2 than those with SVC-area <2.56cm2 (9 [42.9%] of 21 vs. 3 [13.6%] of 22, P=0.026). ConclusionDilatation of SVC was associated with an arrhythmogenic response, and the AF recurrence rate was significantly higher in patients with large SVC-area. Adjunctive catheter intervention for the SVC might be indicated in patients with a dilated SVC and an arrhythmogenic response.

Abstract WP226: Short Lasting Runs (&lt;30 sec) of Atrial Fibrillation are More Commonly Observed in Ischemic Stroke Patients in Comparison to Controls

Background: The role of short-lasting (&lt;30 sec) runs of atrial fibrillation (AF) in ischemic stroke pathophysiology is currently unknown. Although these non-sustained attacks are considered as a risk factor for future development of longer lasting, classical AF episodes, prior research has highlighted that associated clinical stroke features are not entirely similar between these two types of arrhythmias. In this study we determined the prevalence of short-lasting AF in stroke-free controls and compared it to a consecutive series of ischemic stroke patients. Methods: A total 235 controls, without any prior history stroke or AF, were evaluated with ECG and 24-hour Holter monitoring for the presence of &lt;30-sec or ≥30-sec lasting AF episodes. The results were compared to a consecutive series of ischemic stroke patients without prior history of AF (n=456). Univariate and multivariate analyses were performed to determine demographic and cardiovascular factors related to &lt;30-sec lasting AF and its association with ischemic stroke. Results: Expectedly, the frequency of newly diagnosed ≥30-sec lasting AF, detected either on ECG or Holter monitoring, was significantly higher in patients with ischemic stroke (18% vs. 2%; p&lt;0.01). Non-sustained AF was positively related to old age (p&lt;0.01), female gender (p=0.01) and hypertension (p&lt;0.01) in univariate analyses. In multivariate analyses, after adjustment for demographic and cardiovascular risk factors, presence of non-sustained AF was significantly higher among both cryptogenic (OR 1.78; 95% CI 1.02-3.10) and non-cryptogenic (OR 1.84; 95% CI 1.15-2.94) stroke patients with respect to controls. Conclusion: Our study shows a higher prevalence of non-sustained AF episodes in ischemic stroke patients in comparison to controls. Whether this cross-sectional association translates into causality in terms of stroke pathophysiology will be the subject of future studies.

Ischemic stroke phenotype in patients with nonsustained atrial fibrillation.

The widespread use of ambulatory cardiac monitoring has not only increased the detection of high-risk arrhythmias like persistent and paroxysmal atrial fibrillation (AF), but also made it possible to identify other aberrations such as short-lasting (<30 seconds) irregular runs of supraventricular tachycardia. Ischemic stroke phenotype might be helpful in understanding whether these nonsustained episodes play a similar role in stroke pathophysiology like their persistent and paroxysmal counterparts. In a consecutive series of patients with ischemic stroke, we retrospectively determined clinical and imaging features associated with nonsustained AF (n=126), defined as <30-second-lasting supraventricular tachyarrhythmias with irregular RR interval on 24-hour Holter monitoring, and compared them to patients with persistent/paroxysmal AF (n=239) and no AF (n=246). Patients with persistent/paroxysmal AF significantly differed from patients with nonsustained AF by a higher prevalence of female sex (odds ratio [95% confidence interval], 1.8 [1.1-2.9]), coronary artery disease (1.9 [1.1-3.0]), and embolic imaging features (2.7 [1.1-6.5]), and lower frequency of smoking (0.4 [0.2-0.8]) and hyperlipidemia (0.5 [0.3-0.8]). In contrast, patients with no AF were younger (0.5 [0.4-0.6] per decade) and more likely to be male (1.7 [1.0-2.8]) in comparison with nonsustained AF population. The prevalence of nonsustained AF was similar among cryptogenic and noncryptogenic stroke patients (32% versus 29%). Voxel-wise comparison of lesion probability maps revealed no significant difference between cryptogenic stroke patients with and without nonsustained AF. Clinical features of patients with nonsustained AF exhibited an intermediary phenotype in between patients with persistent/paroxysmal AF and no AF. Furthermore, imaging features did not entirely resemble patterns observed in patients with longer durations of AF.

Effect of lifetime endurance training on left atrial mechanical function and on the risk of atrial fibrillation

BackgroundLeft atrium (LA) dilation and P-wave duration are linked to the amount of endurance training and are risk factors for atrial fibrillation (AF). The aim of this study was to evaluate the impact of LA anatomical and electrical remodeling on its conduit and pump function measured by two-dimensional speckle tracking echocardiography (STE). MethodAmateur male runners >30years were recruited. Study participants (n=95) were stratified in 3 groups according to lifetime training hours: low (<1500h, n=33), intermediate (1500 to 4500h, n=32) and high training group (>4500h, n=30). ResultsNo differences were found, between the groups, in terms of age, blood pressure, and diastolic function. LA maximal volume (30±5, 33±5 vs. 37±6ml/m2, p<0.001), and conduit volume index (9±3, 11±3 vs. 12±3ml/m2, p<0.001) increased significantly from the low to the high training group, unlike the STE parameters: pump strain −15.0±2.8, −14.7±2.7 vs. −14.9±2.6%, p=0.927; conduit strain 23.3±3.9, 22.1±5.3 vs. 23.7±5.7%, p=0.455. Independent predictors of LA strain conduit function were age, maximal early diastolic velocity of the mitral annulus, heart rate and peak early diastolic filling velocity. The signal-averaged P-wave (135±11, 139±10 vs. 148±14ms, p<0.001) increased from the low to the high training group. Four episodes of non-sustained AF were recorded in one runner of the high training group. ConclusionThe LA anatomical and electrical remodeling does not have a negative impact on atrial mechanical function. Hence, a possible link between these risk factors for AF and its actual, rare occurrence in this athlete population, could not be uncovered in the present study.

Effect of lifetime endurance training on left atrial mechanical function and on the risk of atrial fibrillation

Background: Left atrial (LA) dilation and prolongation of the signal-averaged P-wave duration (SAPWD) are linked to the amount and intensity of training. There is growing evidence that this atrial anatomical and electrical remodeling could be the substrate for the increased risk of atrial fibrillation (AF) observed in retrospective cohort studies of athletes. The aim of this study was to evaluate the impact of LA anatomical and electrical remodeling, in the context of lifetime exercise endurance training, on its passive (conduit) and active (pump) function measured by 2-D speckle tracking echocardiography (STE), and to find a link between LA functional adaptation and AF. Methods: Amateur male runners ≥30 years old were recruited (n=109) and, after exclusion of subjects having an office blood pressure >140/90mmHg or other cardiovascular risk factors, stratified in 3 groups according to lifetime training hours: low ( 4'500 h, n=30). Baseline examination consisted of an ECG with analysis of the SAPWD, Doppler echocardiography including STE, 24-hour ambulatory ECG and BP monitoring. Results: No differences were found, between the groups, in terms of age, BP, and diastolic function. LA maximal volume index (30±5, 33±5 vs. 37±6ml/m2, p<0.001), and conduit volume index (9±3, 11±3 vs. 12±3ml/m2, p<0.001) increased significantly from the low to the high training group, unlike the STE parameters which were comparable between the groups: strain pump -15.0±2.8, -14.7±2.7 vs. -14.9±2.6%, p=0.927; strain conduit 23.3±3.9, 22.1±5.3 vs. 23.7±5.7%, p=0.455. Independent predictors of LA strain conduit function were age, maximal early diastolic velocity of the mitral annulus, heart rate and peak early diastolic filling velocity. Left ventricular end diastolic volume index and stroke volume index both increased significantly with lifetime training hours. SAPWD (135±11, 139±10 vs. 148±14ms, p<0.001) and the number of premature atrial contractions (3 [1-7], 6 [2-12], 9 [3-26], p=0.008) increased from the low to the high training group. In one runner of the high training group 4 episodes of non-sustained AF were recorded. Conclusions: The LA anatomical and electrical remodeling does not have a negative impact on atrial mechanical function. LA enlargement may be an adaptation to volume overload, which permits a greater volume delivery to the simultaneously dilating left ventricle. A possible link between these risk factors for AF and its actual, rare occurrence in this athlete population, could not be uncovered in the present study.

Oral Vanoxerine Prevents Reinduction of Atrial Tachyarrhythmias: Preliminary Results

Vanoxerine is a promising, new, investigational antiarrhythmic drug. The purpose of this study was to test the hypothesis that oral dosing of vanoxerine would first terminate induced atrial flutter (AFL) and atrial fibrillation (AF), and then prevent their reinduction. In 5 dogs with sterile pericarditis, on the fourth day after creating the pericarditis, we performed electrophysiologic (EP) studies at baseline, measuring atrial excitability, refractoriness (AERP), and conduction time (CT) when pacing from the right atrial appendage, Bachmann's bundle (BB), and the posteroinferior left atrium at cycle lengths (CLs) of 400, 300, and 200 ms. Then, after induction of AFL or AF, all dogs received hourly oral doses of vanoxerine: 90 mg, followed by 180 mg and 270 mg. Blood was obtained to determine plasma vanoxerine concentrations at baseline, every 30 minutes, when neither AFL nor AF were inducible, and, finally, 1 hour after the 270 mg dose. Then we repeated the baseline EP studies. Four dogs had inducible, sustained AFL, and 1 dog only had induced, nonsustained AF. In 4 AFL episodes, oral vanoxerine terminated the AFL and then rendered it noninducible after an average of 111 minutes (range 75-180 minutes) after the first dose was administered. The mean vanoxerine plasma level at the point of noninducibility was 84 ng/mL, with a narrow range of 76-99 ng/mL. In the dog with induced, nonsustained AF, it was no longer inducible at a drug level of 75 ng/mL. Vanoxerine did not significantly (1) prolong the AERP except at BB, and then only at the faster pacing CLs; (2) change atrial excitability thresholds; (3) prolong atrial conduction time, the PR interval, the QRS complex or the QT interval. Orally administered vanoxerine effectively terminated AFL and rendered it noninducible. It also suppressed inducibility of nonsustained AF. These effects occurred at consistent plasma drug levels. Vanoxerine's insignificant or minimal effects on measured electrophysiologic parameters are consistent with little proarrhythmic risk.

A Case Showing Close Relationship between the Pulse Instability and the Respiratory Instability Using Polysomnography Analysis

A 68-year-old man with paroxysmal atrial fibrillation (AF) was admitted due to sleep disordered breathing (SDB). Transthoracic echocardiography revealed left ventricular diastolic dysfunction (the ratio of early transmitral velocity to early diastolic velocity of the mitral annulus: E/E′=10.0) but well-preserved systolic function (left ventricular ejection fraction=64%). Overnight polysomnography (PSG) analysis was undergone for diagnosing SDB. Overnight PSG analysis revealed that this patient experienced severe SDB with an apnea-hypopnea index score of 47.3 events/h. Immediately after patient’s sleep, repetitive non-sustained AF was observed following sustained hypopnea events. Repetitive hypoxemia, autonomic nervous system imbalance and fluctuations in intrathoracic pressure may serve as a trigger for AF. Sustained AF was observed after non-sustained AF, indicating that AF begets AF. After sustained AF occurred, various kinds of repetitive SDB events were shown. These results suggest that AF causes respiratory instability. In summary, AF episodes of this patient could be induced by the respiratory instability and AF could induce respiratory instability. Sustained AF could cause circulation delay such as heart failure, resulting in the occurrence of various kinds of SDB. Therefore, both AF itself and respiratory instability could be a therapeutic target for improving patient’s morbidity. We report on a patient, showing the causative relationship between the pulse instability and the respiratory instability.

Comparison of Characteristics and Significance of Immediate Versus Early Versus No Recurrence of Atrial Fibrillation After Catheter Ablation

Atrial fibrillation (AF) recurrences after catheter ablation are common within the first month after AF ablation, and inflammatory processes may be related to AF genesis. This study aimed to clarify the relation between inflammatory processes and recurrence of AF after ablation and to characterize AF recurring within 3 days after ablation (immediate AF recurrence).The study included 186 patients with drug-refractory paroxysmal AF who underwent extensive pulmonary vein isolation. Body temperature and C-reactive protein level were measured before and consecutively on the first 3 days after ablation. Signs of pericarditis or atrial arrhythmias within 3 days after ablation were also monitored. Forty-five patients (24%) had immediate AF recurrence (immediate-AF-recurrence group), 27 (14%) had early recurrence 4 to 30 days after ablation (early-AF-recurrence group), and the remaining 114 (61%) had no AF recurrence within 1 month after ablation (no-AF-recurrence group). Increases in body temperature and C-reactive protein level from baseline in the immediate-AF-recurrence group were the highest among the 3 groups, and signs of pericarditis were observed in 15 of the 45 patients (33%) in the immediate-AF-recurrence group. Atrial premature contractions and nonsustained AF occurred most frequently in the early-AF-recurrence group. After 6-month follow-up, the AF-free rate was greater in the immediate-AF-recurrence group (76%) than in the early-AF-recurrence group (30%). In conclusion, immediate AF recurrence has an apparently different mechanism and impact on midterm outcomes than does early AF recurrence. Acute inflammatory changes after ablation may be responsible for immediate AF recurrence.

Assessment of local atrial repolarization in a porcine acetylcholine model of atrial flutter and fibrillation

Objectives — Progressive electrical alternans followed by conduction block and fibrillatory conduction have been suggested to precede disorganization of atrial flutter (Afl) to atrial fibrillation (AF). The purpose of the present study was to investigate patterns of local repolarization in the high and low right atrium to determine the site with pronounced propensity to action potential disorganization during Afl and AF.Methods — Combination pacing/recording contact monophasic action potential (MAP) catheters were utilized to evaluate repolarization from the upper and low atrial endocardium in 16 pigs.To induce sustained atrial flutter (Afl) or fibrillation (AF), programmed atrial stimulation was carried out prior to and during intravenous acetylcholine (ACh) infusion at a dosage rate of 2.7 mg/min. Atrial repolarization was measured at 30, 50, and 90% of total MAP duration.Results — Two main types of atrial MAPs were distinguished: MAPs originated from high atrial regions showing a prominent notch and longer duration and MAPs recorded from the lower atrium displaying a much slower slope of phase 1 repolarization and shorter duration. Control stimulation did not elicit any significant atrial tachyarrhythmias. After ACh all animals developed reproducibly induced sustained and non-sustained whole Afl or AF during programmed stimulation. A total of 40 sustained arrhythmia episodes were selected for evaluation: fourteen episodes of primary AF and 26 episodes of Afl.Whole Afl and AF in all animals were associated with MAPs of almost regular morphology in lower parts of atrium and disorganized activation in higher atrial regions. ACh significantly reduced (P < 0.001) both high and low atrial effective refractory periods as well as MAP duration determined at 30, 50, and 90% repolarization.Conclusions — ACh facilitated the induction of Afl more than AF in this experimental model. MAPs recorded from high atrial regions revealed discordant repolarization during Afl or AF, whereas low atrial MAPs maintained their baseline regular morphology.These findings may help expand knowledge about mechanisms underlying instability and perpetuation of these arrhythmias

Evaluation of atrial fibrillation induced during anesthesia with fentanyl and pentobarbital in German Shepherd Dogs with inherited arrhythmias

To determine the type of atrial fibrillation induced by use of 2 pacing protocols during fentanyl and pentobarbital anesthesia before and after administration of atropine and to determine the organization of electrical activity in the left and right atria during atrial fibrillation in German Shepherd Dogs. 7 German Shepherd Dogs. Extrastimulus and pacedown protocols were performed before and after atropine administration. Monophasic action potential spectral entropy and mean dominant frequency were calculated during atrial fibrillation. Atrial fibrillation occurred spontaneously in 6 of 7 dogs. All 7 dogs had atrial fibrillation induced. Sustained atrial fibrillation occurred in 13 of 25 (52%) episodes induced by the extrastimulus protocol and in 2 of 12 episodes of atrial fibrillation induced by pacedown. After atropine administration, sustained atrial fibrillation did not occur, and the duration of the nonsustained atrial fibrillation (6 episodes in 2 dogs of 1 to 26 seconds) was significantly shorter than before atropine administration (25 episodes in 7 dogs of 1 to 474 seconds). The left atrium (3.67 +/- 0.08) had lower spectral entropy than the right atrium (3.81 +/- 0.03), indicating more electrical organization in the left atrium. The mean dominant frequency was higher in the left atrium in 3 dogs. Atrial fibrillation developed spontaneously and was induced in German Shepherd Dogs under fentanyl and pentobarbital anesthesia. Electrical activity was more organized in the left atrium than in the right atrium as judged by use of spectral entropy.

Propagation velocity kinetics and repolarization alternans in a free-behaving sheep model of pacing-induced atrial fibrillation

Experimental models have reported conflicting results regarding the role of dispersion of repolarization in promoting atrial fibrillation (AF). Repolarization alternans, a beat-to-beat alternation in action potential duration, enhances dispersion of repolarization when propagation velocity is involved. In this work, original electrophysiological parameters were analysed to study AF susceptibility in a chronic sheep model of pacing-induced AF. Two pacemakers were implanted, each with a single right atrial lead. Right atrial depolarization and repolarization waves were documented at 2-week intervals. A significant and gradual decrease in the propagation velocity at all pacing rates and in the right atrial effective refractory period (ERP) was observed during the weeks of burst pacing before sustained AF developed when compared with baseline conditions. Right atrial repolarization alternans was observed, but because of the development of 2/1 atrioventricular block with far-field ventricular interference, its threshold could not be precisely measured. Non-sustained AF was not observed at baseline, but appeared during the electrical remodelling in association with a decrease in both ERP and propagation velocity. We report here on the feasibility of measuring ERP, atrial repolarization alternans, and propagation velocity kinetics and their potential in predicting susceptibility to AF in a free-behaving model of pacing-induced AF using the standard pacemaker technology.