Sustained Atrial Fibrillation Research Articles

PO-04-123 TACHYARRHYTHMIA OUTCOMES IN CONGENITALLY CORRECTED TRANSPOSITION OF THE GREAT ARTERIES: DOES TREATMENT PATHWAY MATTER?

Patients with congenitally corrected transposition of the greater arteries (cc-TGA) are at risk for developing both atrial and ventricular tachyarrhythmia. However, data on the impact of treatment pathway (non-surgical management, anatomic repair, or physiologic repair) is limited. To describe arrhythmia types and freedom from early (≤30 days post-op) and late (>30 days post-op) sustained tachyarrhythmia requiring intervention (medication, cardioversion, or ablation) in patients with cc-TGA based on treatment pathway. We conducted a retrospective cohort study including all patients with cc-TGA who were followed at our institution between January 1995 and December 2021. Patients were stratified according to treatment pathway as follows: non-surgical, anatomic repair, and physiologic repair. Tachyarrhythmia types analyzed included sustained atrial fibrillation (AF), atrial flutter (AFL), atrial tachycardia and ventricular tachycardia. A total of 170 patients were included in the study, of whom 82 underwent anatomic repair (median age 1.5 yrs, median follow-up 11.5 yrs), 46 physiologic repair (median age 25.2 yrs, median follow-up 12.6 yrs), and 42 non-surgical (median age 35.7 yrs, median follow-up 11 yrs). Overall 50 patients (29%) had tachyarrhythmia: 12/82 (15%) anatomic repair, 15/46 (33%) physiologic repair, and 23/42 (55%) non-surgical. Prevalence of AFL was highest after anatomic repair compared to physiologic repair or non-surgical (32% vs. 22% vs 0%, p=0.024). Prevalence of AF was higher in physiologic repair and non-surgical compared to anatomic repair (52% vs. 65% vs. 0%, p<0.0001). Patients with physiologic repair had more late tachyarrhythmia versus anatomic repair (83% vs. 33%, p=0.002). Freedom from tachyarrhythmia was lowest in anatomic repair vs. physiologic repair and non-surgical (p=0.013), Figure 1A. Estimated freedom from tachyarrhythmia at 20 years in the anatomic, physiologic, and non-surgical groups were 80%, 88%, and 95%, respectively. Freedom from postsurgical tachyarrhythmia trended towards increase prevalence after physiologic repair compared to anatomic repair (p=0.065), Figure 1B. Arrhythmia type differed based on treatment pathway, with AFL more prevalent after anatomic repair and AF more prevalent in physiologic repair and non-surgical management. Freedom from tachyarrhythmia was lowest in the anatomic repair group. Continued follow-up after anatomic repair is needed to determine their long-term risk beyond the 2nd decade.

High-density and high coverage composite mapping of repetitive atrial activation patterns

BackgroundRepetitive atrial activation patterns (RAAPs) during atrial fibrillation (AF) may be associated with localized mechanisms that maintain AF. Current electro-anatomical mapping systems are unsuitable for analyzing RAAPs due to the trade-off between spatial coverage and electrode density in clinical catheters. This work proposes a technique to overcome this trade-off by constructing composite maps from spatially overlapping sequential recordings. MethodsHigh-density epicardial contact mapping was performed during open-chest surgery in goats (n=16, left and right atria) with 3 or 22 weeks of sustained AF (249-electrode array, electrode distance 2.4 mm). A dataset mimicking sequential recordings was generated by segmenting the grid into four spatially overlapping regions (each region 6.5 cm2, 48±10% overlap) without temporal overlap. RAAPs were detected in each region using recurrence plots of activation times. RAAPs in two different regions were joined in case of RAAP cross-recurrence between overlapping electrodes. We quantified the reconstruction success rate and quality of the composite maps. ResultsOf 1021 RAAPs found in the full mapping array (32±13 per recording), 328 spatiotemporally stable RAAPs were analyzed. 247 composite maps were generated (75% success) with a quality of 0.86±0.21 (Pearson correlation). Success was significantly affected by the RAAP area. Quality was weakly correlated with the number of repetitions of RAAPs (r=0.13, p<0.05) and not affected by the atrial side (left or right) or AF duration (3 or 22 weeks of AF). ConclusionsConstructing composite maps by combining spatially overlapping sequential recordings is feasible. Interpretation of these maps can play a central role in ablation planning.

Organization of atrial fibrillation using a pure sodium channel blocker: Implications of rotor ablation therapy.

Rotors are the source of atrial fibrillation (AF). However, the ablation of rotors for persistent AF is challenging. The purpose of this study was to identify the dominant rotor by accelerating the organization of AF using a sodium channel blocker and detecting the rotor's preferential area that governs AF. Overall, 30 consecutive patients with persistent AF who underwent pulmonary vein isolation and still sustained AF were enrolled. Pilsicainide 50 mg was administered. An online real-time phase mapping system (ExTRa Mapping™) was used to identify the meandering rotors and multiple wavelets in 11 left atrial segments. The time ratio of non-passive activation (%NP) was evaluated as the frequency of rotor activity in each segment. Conduction velocity became slower-from 0.46 ± 0.14 to 0.35 ± 0.14 mm/ms (p = .004)-and the rotational period of the rotor was significantly prolonged-156 ± 21 to 193 ± 28 ms/cycle (p < .001). AF cycle length was prolonged from 169 ± 19 to 223 ± 29 ms (p < .001). A decrease in %NP was observed in seven segments. Additionally, 14 patients had at least one complete passive activation area. Of them, the use of high %NP area ablation resulted in atrial tachycardia and sinus rhythm in two patients each. A sodium channel blocker organized persistent AF. In selective patients with a wide organized area, high %NP area ablation could convert AF into atrial tachycardia or terminate AF.

New atrial fibrillation model with endocardial approach by CRT bi-electrode atrial pacing in mini-pigs

Objective: To evaluate the model of atrial fibrillation (AF) in mini-pigs with endocardial approach implantation of CRT-P using bi-electrodes pacing through RV/LV connectors.Methods: All surgical interventions were minimally invasive and conducted under general anaesthesia. CRT-P was implanted endocardially, using X-ray. First electrode was fixed in the right atrial appendage. The second one — in the interatrial septum or the right atrial free wall. Both of them were connected with CRT-P through RV/LV. Bi-electrode atrial stimulation was realized during a week with a basic heart rate of 150 bpm and a delay between electrodes of 80 ms (mean 450 bpm), which corresponds to the heart rate (HR) of AF. Electrophysiological study was performed during the experiment to analyze the cardiac conduction system. AF inducibility was evaluated before and after stimulation.Results: A series of experiments demonstrated that there were no complications following the device and electrodes implantation. There was a non-sustained paroxysm of AF before permanent pacing in one of three pigs. After pacing we noted a tendency to increase the baseline HR (average frequency from 94 ± 4 to 98 ± 6 bpm). Non-sustained paroxysm of AF was induced in all cases. The sustained AF with 92 min burden was induced in one pig.Conclusion: Endocardial bi-electrode atrial pacing in mini-pigs has proven to be safe. This AF model improves AF inducibility and can be considered as an alternative to epicardial stimulation for experiments employing AF models. Received 4 December 2022. Revised 17 January 2023. Accepted 18 January 2023. Funding: The study was supported by Russian Science Foundation (project No. 22-25-00672). Conflict of interest: The authors declare no conflict of interest. Contribution of the authorsConception and study design: V.V. Beloborodov, D.V. Losik, E.V. FisherData collection and analysis: E.V. Fisher, V.V. Beloborodov, D.V. Losik, A.G. FilippenkoDrafting the article: D.V. Losik, E.V. Fisher, V.I. Murtazin, V.V. BeloborodovCritical revision of the article: A.B. Romanov, D.V. Losik, V.V. Shabanov, I.L. MikheenkoFinal approval of the version to be published: D.V. Losik, V.V. Beloborodov, E.V. Fisher, V.I. Murtazin, A.G. Filippenko, I.L. Mikheenko, V.V. Shabanov, A.B. Romanov

Prognosis evaluation of chronic inflammatory cardiomyopathy with ring-like late gadolinium enhancement.

Ring-like late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) imaging is a special LGE pattern in patients with chronic inflammatory cardiomyopathy (infl-CMP), which is associated with cardiac dysfunction and ventricular remodelling and attributed to viral infection followed by bacterial and parasitic infections. Data on the combination of CMR imaging and clinical parameters that can add long-term prognostic value in patients with infl-CMP are still rare. We aimed to evaluate the prognostic value of CMR in risk stratification in this kind of patients. A total of 319 consecutive patients with clinically suspected myocarditis were retrospectively identified. Forty-seven patients with ring-like LGE on CMR who diagnosed as infl-CMP, and 72 patients with other LGE pattern were eligible for standardized follow-up. The left ventricle (LV) and right ventricle function and mass were analyses by CMR. Myocardial strain of the ventricles was evaluated by feature tracking. Major (cardiac death, resuscitated cardiac arrest, ventricular assist device, transplantation, and appropriate implantable cardioverter-defibrillator shock) and minor (rehospitalization due to heart failure and sustained atrial fibrillation) adverse cardiovascular events were assessed during follow-up since the date of nCMR examination. Cox proportional hazards model was used to investigate which of the prognostic factors identified by univariable analysis were significantly associated with cardiac events. In the ring-like LGE group, adverse cardiac events occurred in 14 (31.11%) patients, including 7 deaths (15.56%), 6 (13.33%) heart-failure hospitalizations, and 1 (2.22%) case of sustained atrial fibrillation during the mean follow-up period of 70.15±45.68months (interquartile range: 32.83-103.71months). No major or minor adverse cardiac event occurred in the other LGE pattern group, except rehospitalization in one patient due to arrhythmia. Further analyses of ring-like LGE group by univariable and Multivariable Cox proportional hazard regression analysis showed that body mass index (BMI) (hazard ratio [HR]: 0.54, 95% confidence interval [CI]: 0.40-0.73, P=0.000), right ventricle cardiac index (RVCI) (HR: 0.31, 95% CI: 0.14-0.71, P=0.002), LV basal peak circumferential strain (LV-PCSbasal ) (HR: 1.26, 95% CI: 1.11-1.43, P=0.000) were independently associated with the long-term outcome. Receiver operator characteristic curve indicated that the cut-off of LV-PCSBasal was -7.95%, and it has added prognostic value to BMI and RVCI. For infl-CMP patients with ring-like LGE on CMR, low BMI and RVCI were associated with a poor prognosis. LV-PCSBasal with a cut-off of -7.95% can add prognostic value for patients with infl-CMP who have ring-like LGE.

Contribution of atrial myofiber architecture to atrial fibrillation.

The role of fiber orientation on a global chamber level in sustaining atrial fibrillation (AF) is unknown. The goal of this study was to correlate the fiber direction derived from Diffusion Tensor Imaging (DTI) with AF inducibility. Transgenic goats with cardiac-specific overexpression of constitutively active TGF-β1 (n = 14) underwent AF inducibility testing by rapid pacing in the left atrium. We chose a minimum of 10 minutes of sustained AF as a cut-off for AF inducibility. Explanted hearts underwent DTI to determine the fiber direction. Using tractography data, we clustered, visualized, and quantified the fiber helix angles in 8 different regions of the left atrial wall using two reference vectors defined based on anatomical landmarks. Sustained AF was induced in 7 out of 14 goats. The mean helix fiber angles in 7 out of 8 selected regions were statistically different (P-Value < 0.05) in the AF inducible group. The average fractional anisotropy (FA) and the mean diffusivity (MD) were similar in the two groups with FA of 0.32±0.08 and MD of 8.54±1.72 mm2/s in the non-inducible group and FA of 0.31±0.05 (P-value = 0.90) and MD of 8.68±1.60 mm2/s (P-value = 0.88) in the inducible group. DTI based fiber direction shows significant variability across subjects with a significant difference between animals that are AF inducible versus animals that are not inducible. Fiber direction might be contributing to the initiation and sustaining of AF, and its role needs to be investigated further.

Electrophysiological guided accessory-pathway ablation strategy in children with asymptomatic WPW: it may not be enough to prevent sudden cardiac death.

Sudden cardiac death (SCD) may rarely occur among asymptomatic patients with Wolff-Parkinson-White (WPW) pattern. Risk stratification is based on electrophysiological study (EPS). We aimed to evaluate long-term efficacy of such a strategy in preventing SCD. Retrospective analysis of asymptomatic children with WPW who underwent EPS using isoproterenol. Patients considered at risk had inducible sustained atrial fibrillation or atrioventricular reentry tachycardia (AVRT) associated with the following: (1) accessory pathway (AP) effective refractory period or (2) 1:1 shortest cycle length along the AP or (3) shortest pre-excited R-R interval during AF ≤ 250ms. Fifty-one consecutive cases (7-18years, 12 ± 3) were identified, 40 (78%) with right and 11 (22%) with left AP. Twenty-eight (55%) were classified as high risk (HI) and 23 (45%) as low risk (LO), with no significant differences in demographic characteristics and AP locations. Ablation was performed in 20/28 HI and 11/23 LO patients (p 0.08), with no significant differences in acute success (20/20 versus 10/11, p 0.17) or recurrence (1/20 versus 2/10, p 0.15). Follow-up (46 ± 27months): ablated patients remained asymptomatic; among the 23 non-ablated, 18 (78%) remained asymptomatic, 5 (22%) were successfully ablated, and 5 (22%) presented events (4 AVRT, 1 SCD). Arrhythmic events did not differ significantly between non-ablated HR and LR (2/8 versus 3/15, p 0.29) and the SCD was in the LO group. More than 50% asymptomatic WPW children present high-risk AP properties. EPS-based risk stratification using isoproterenol was not able to identify increased risk of future events or SCD.

The influence of atrial fibrillation on the prognostic value of brain natriuretic peptide (BNP) in risk assesment of paroxysmal ventricular tachycardia

Introduction. Brain natriuretic peptide (BNP) as marker of higher left ventricular myocardial mechanical stress has a strong prognostic value in patients with heart failure (HF). Elevated BNP levels are associated with the of malignant ventricular arrhythmias. Atrial fibrillation (AF) is known to futher elevate BNP levels and this can influence on BNP prognostic value. The aim of the study was to assess the predictive value of BNP in risk assessment of paroxysmal ventricular tachycardia (PVT) in patients with HF and AF. Materials and methods. Totally, 92 patients with sustained or persistent AF, HF with left ventricular ejection fraction &lt; 50 %. All patients underwent transthoratic echocardiography; 24-hour ECG monitoring to assess the ventricular arrhythmia burden. BNP determination by enzyme immunoassay in venous blood serum. Results. Patients with HF, AF and PVTcompared with patients with HF and AF without PVT have higher levels of BNP (298,8 [149; 500,6] pg/ml versus 152 [145,7; 335,4] pg/ml, р = 0,02). There is a significant positive correlation between the level of BNP and the amount of PVT per 24 hours (r = 0,26; р &lt; 0,05). Increased BNP levels are associated with an increased risk of VPT, OR = 3,71 [95 % CI 1,2 to 13,1]. Discussion. BNP is a novel biomarker to improve risk stratification of sudden cardiac death not only for patients in sinus rhythm but for patients with AF. Conclusions. BNP has a predictive value in risk assessment of PVT in patients with HF and AF.

Assessing the impact of blocking distal coronary sinus-left atrial muscular connection on inducible rate of atrial fibrillation and follow-up recurrence in persistent atrial fibrillation patients with different fibrotic degrees of left atrial: A retrospective study.

BackgroundThe musculature of the coronary sinus (CS), especially its distal connection with the post wall of the left atrial (LA), has been associated with the genesis and maintenance of atrial flutter (AFL) and atrial fibrillation (AF). However, the relative contributions of the distal coronary sinus (CSD)-LA connection to PersAF with various degrees of atrial fibrosis remain unknown.ObjectiveThis study aimed to explore the different roles of blocking the CSD-LA connection in the induction of acute AF and middle-term follow-up of recurrence among PersAF patients with various degrees of LA fibrosis.Methods and resultsA retrospective cohort of 71 patients with drug-refractory and symptomatic PersAF underwent ablation for the first time were studied. The population was divided into two groups according to disconnection of the CSD-LA or not. All patients enrolled accepted the unified ablation procedure (circumferential pulmonary vein isolation, non-pulmonary vein trigger ablation and ablation of the CSD-LA connection). Group A (n = 47) successfully blocked the CSD-LA electrical connection and Group B (n = 24) failed. Twenty-five patients could be induced into sustained AF in the Group A compared to 20 in the Group B (53.2 vs. 83.3%, p = 0.013). After a mean follow-up of 185 ± 8 days, 24 (33.8%) patients experienced atrial arrhythmia recurrences. The Group A had significantly fewer recurrences (25.5%) compared to Group B (50%). Meanwhile, in Group A, the ROC curve analysis suggested that in the case of blocking CSD-LA, low voltage area (LVA) of LA can act as a predictive factor for acute AF induction (AUC = 0.943, Cut-off = 0.190, P < 0.001) with sensitivity and specificity of 92.3 and 90.5%, and middle-term recurrence (AUC = 0.889, Cut-off = 0.196, P < 0.001) with sensitivity and specificity of 100 and 65.7%.ConclusionDisconnection of CSD-LA could reduce the inducible rate of acute AF and the recurrences of atrial arrhythmia during middle-term follow-up. The PersAF patients with CSD-LA muscular connection blocked, experienced a higher acute AF inducible rate with larger proportion of LVA of LA (≥19%) and a higher recurrent rate of atrial arrhythmias with a larger proportion of LA fibrosis (≥19.6%).

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

Novel spatiotemporal processing tools for body-surface potential map signals for the prediction of catheter ablation outcome in persistent atrial fibrillation.

Background: Signal processing tools are required to efficiently analyze data collected in body-surface-potential map (BSPM) recordings. A limited number of such tools exist for studying persistent atrial fibrillation (persAF). We propose two novel, spatiotemporal indices for processing BSPM data and test their clinical applicability through a comparison with the recently proposed non-dipolar component index (NDI) for prediction of single-procedure catheter ablation (CA) success rate in persAF patients. Methods: BSPM recordings were obtained with a 252-lead vest in 13 persAF patients (8 men, 63 ± 8 years, 11 ± 13 months sustained AF duration) before undergoing CA. Each recording was divided into seven 1-min segments of high signal quality. Spatiotemporal ventricular activity (VA) cancellation was applied to each segment to isolate atrial activity (AA). The two novel indices, called error-ratio, normalized root-mean-square error (ERNRMSE) and error-ratio, mean-absolute error (ERABSE), were calculated. These indices quantify the capacity of a subset of BSPM vest electrodes to accurately represent the AA, and AA dominant frequency (DF), respectively, on all BSPM electrodes over time, compared to the optimal principal component analysis (PCA) representation. The NDI, quantifying the fraction of energy retained after removal of the three largest PCs, was also calculated. The two novel indices and the NDI were statistically compared between patient groups based on single-procedure clinical CA outcome. Finally, their predictive power for univariate CA outcome classification was assessed using receiver operating characteristic (ROC) analysis with cross-validation for a logistic regression classifier. Results: Patient clinical outcomes were recorded 6 months following procedures, and those who had an arrhythmia recurrence at least 2 months post-CA were defined as having a negative outcome. Clinical outcome information was available for 11 patients, 6 with arrhythmia recurrence. Therefore, a total of 77 1-min AA-BSPM segments were available for analysis. Significant differences were found in the values of the novel indices and NDI between patients with arrhythmia recurrence post-ablation and those without. ROC analysis showed the best CA outcome predictive performance for ERNRMSE (AUC = 0.77 ± 0.08, sensitivity = 76.2%, specificity = 84.8%). Conclusion: Significant association was found between the novel indices and CA success or failure. The novel index ERNRMSE additionally shows good predictive power for single-procedure CA outcome.

In-silico drug trials for precision medicine in atrial fibrillation: From ionic mechanisms to electrocardiogram-based predictions in structurally-healthy human atria.

Atrial fibrillation (AF) inducibility, sustainability and response to pharmacological treatment of individual patients are expected to be determined by their ionic current properties, especially in structurally-healthy atria. Mechanisms underlying AF and optimal cardioversion are however still unclear. In this study, in-silico drug trials were conducted using a population of human structurally-healthy atria models to 1) identify key ionic current properties determining AF inducibility, maintenance and pharmacological cardioversion, and 2) compare the prognostic value for predicting individual AF cardioversion of ionic current properties and electrocardiogram (ECG) metrics. In the population of structurally-healthy atria, 477 AF episodes were induced in ionic current profiles with both steep action potential duration (APD) restitution (eliciting APD alternans), and high excitability (enabling propagation at fast rates that transformed alternans into discordant). High excitability also favored 211 sustained AF episodes, so its decrease, through prolonged refractoriness, explained pharmacological cardioversion. In-silico trials over 200 AF episodes, 100 ionic profiles and 10 antiarrhythmic compounds were consistent with previous clinical trials, and identified optimal treatments for individual electrophysiological properties of the atria. Algorithms trained on 211 simulated AF episodes exhibited >70% accuracy in predictions of cardioversion for individual treatments using either ionic current profiles or ECG metrics. In structurally-healthy atria, AF inducibility and sustainability are enabled by discordant alternans, under high excitability and steep restitution conditions. Successful pharmacological cardioversion is predicted with 70% accuracy from either ionic or ECG properties, and it is optimal for treatments maximizing refractoriness (thus reducing excitability) for the given ionic current profile of the atria.

Shunt and pace: a novel experimental model of atrial fibrillation with a volume-loaded left atrium.

Atrial fibrillation (AF) is frequently seen in patients with a volume-loaded left atrium (LA) such as mitral valve regurgitation (MR). Previous animal models have incomplete relevance to human AF associated with MR. A novel experimental model with a combination of volume loading of LA by creating a shunt from the subclavian artery to pulmonary artery and electrical remodeling induced by continuous rapid LA pacing was designed and the electrophysiological effects were examined in 10 canines. Five weeks after the shunt surgery, the entire atrial epicardium was mapped during sustained AF with form-fitted electrode patches with 246 bipolar electrodes and a three-dimensional dynamic mapping system to characterize the induced AF. Three animals died of severe heart failure and pacing failure occurred in one. Remaining six animals were subjected to the analysis. The LA diameter increased progressively after the shunt surgery. Sustained AF was induced after 3 weeks of continuous rapid LA pacing in all animals. The activation maps revealed repetitive focal activations arising from the pulmonary veins, right or left atrial regions, and reentrant activations in the RA, which patterns of atrial activations are the same as those seen in human AF. The animal model with a combination of LA volume load and electrical remodeling was relevant to human AF associated with LA volume load. Studies using the present model may provide further knowledges of AF and may be useful in examining the effects of pharmacological and non-pharmacological therapies.

Sinus rhythm restoration and improved outcomes in patients with acute ischemic stroke and in-hospital paroxysmal atrial fibrillation.

It is unclear whether early cardiac rhythm control is beneficial in patients with acute ischemic stroke and paroxysmal atrial fibrillation (PAF). We sought to investigate whether PAF self-termination and in-hospital sinus rhythm (SR) restoration is associated with improved outcome in ischemic stroke patients with PAF, compared to those with sustained atrial fibrillation (AF). Consecutive patients with first-ever acute stroke and confirmed PAF during hospitalization were followed for up to 10 years after the index stroke or until death. We investigated the association of in-hospital self-terminated PAF and PAF conversion to SR compared to sustained AF with 10-year all-cause mortality, stroke recurrence, and major adverse cardiovascular events (MACE). Cox regression analysis was performed to identify independent predictors of each outcome. Among 297 ischemic stroke patients with in-hospital PAF detection, PAF was self-terminated in 87 (29.3%) patients, while 143 (48.1%) patients received antiarrhythmic medication in order to achieve PAF conversion to SR. During a median (Interquartile range, IQR) period of 28 (4-68) months, among patients with self-terminated PAF there were 13.5 deaths, 3.6 stroke recurrences, and 5.3 MACE per 100 patient-year while in patients who underwent medical PAF conversion there were 11.7 deaths, 4.6 stroke recurrences, and 5.8 MACE per 100 patient-year. Patients with sustained AF experienced 23.8 deaths, 8.7 stroke recurrences, and 13.9 MACE per 100 patient-years. In multivariable analysis, compared to patients with sustained AF, PAF self-termination was associated with significantly lower 10 years-risk of death (adjusted hazards ratio (adjHR): HR: 0.63, 95% Confidence interval: 0.40-0.96), stroke recurrence (adjHR: HR: 0.41, 95% CI: 0.19-0.91), and MACE (adjHR: 0.43, 95% CI: 0.23-0.81), while PAF medical conversion to SR was associated with lower 10 years-risk of death (adjHR: 0.65, 95% CI: 0.44-0.97) and MACE (adjHR: 0.56, 95% CI: 0.33-0.95). This study showed that in-hospital PAF self-termination was associated with lower risk of 10-year mortality, stroke recurrence, and MACE, potentially attributed to the lower burden of AF, whereas in-hospital PAF conversion to SR was associated with lower risk of 10-year mortality and MACE. Early restoration of sinus rhythm is associated with improved survival and MACE in patients with acute ischemic stroke and PAF.

SYNERGISTIC EFFECT OF HIGH HOMOCYSTEINE AND LOW VITAMIN B12 LEVELS ON THE PREVALENCE OF ATRIAL FIBRILLATION IN HYPERTENSIVE PATIENTS

Objective: Atrial fibrillation (AF) is common arrhythmia in hypertensive patients. Besides hypertension, several other conditions are deemed to be associated with AF. High blood homocysteine levels (hyperhomocysteinemia) is a known risk factor for cardiovascular disease and are associated with vitamin B12 deficiency that possibly increase cardiovascular risk, as well. The present study assessed the possible effect of high homocysteine and low B12 levels on AF prevalence in hypertensive patients. Design and method: This retrospective study comprised all hypertensives referred to our institutions and had a blood sample measurement of homocysteine and B12 (n = 32800). The presence of sustained AF (SAF; Long-standing/Persistent or Permanent AF) was recorded with a resting electrocardiogram (ECG). Paroxysms of AF (PAF) were confirmed with previous relevant ECGs provided by the patient. The population was divided in quartiles according to homocysteine levels (groups 1, 2, 3 and 4 for increasing levels) and B12 levels (groups 1, 2, 3 and 4 for decreasing levels). The prevalence of AF (SAF and PAF) was calculated for each homocysteine and B12 quartile group as well as for each of the 16 homocysteine/B12 combination quartile subgroups. Results: The mean values for homocysteine were 13.3 ± 7.2 ?mol/l and for B12 525 ± 196 pg/ml. The prevalence of SAF, PAF and all-type AF (SAF and PAF) was 5.0%, 6.1% and 11.1%, respectively. For homocysteine quartiles 1, 2, 3, 4, SAF prevalence was 2.9%, 5.3%, 11.7%, 24.3% (pfor trend 0.049), PAF prevalence was 0.6%, 0.9%, 4.6%, 14.0% (pfor trend 0.090) and all-type AF prevalence was 3.2%, 5.4%, 11.5%, 22.2% (pfor trend 0.051), respectively. For B12 quartiles 1, 2, 3, 4, SAF prevalence was 2.9%, 6.4%, 11.0%, 20.2% (pfor trend 0.030), PAF prevalence was 2.5%, 5.1%, 7.7%, 9.0% (pfor trend 0.009) and all type-AF prevalence was 2.4%, 7.1%, 16.8% 21.0% (pfor trend 0.019), respectively. The synergistic effect of increasing homocysteine and decreasing B12 values on SAF, PAF and all-type AF prevalence is presented in Figure. Conclusions: High homocysteine levels and low vitamin B12 levels are individually and synergistically associated with the prevalence of AF in hypertensive individuals. Underlying mechanisms merit further examination.

Amplitude of fibrillatory wave correlates with long-term maintenance of sinus rhythm after ablation in persistent atrial fibrillation

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Commission for Technology and Innovation (CTI), Switzerland Background Amplitude of fibrillatory wave (fWA) on surface ECG is regarded as a predictor of ablation outcome for atrial fibrillation (AF). Purpose We sought to investigate whether fWA and its changes during ablation predicts long-term maintenance of sinus rhythm (SR) after wide circumferential isolation of pulmonary veins (WPVI) in persistent AF (peAF). Methods 41 patients (63±10 y, sustained AF 11±7 months) underwent a de-novo WPVI. A second WPVI was performed in patients with recurrent AF in order to provide complete PV disconnection. We defined "success" as patients who remained in SR after one or two procedures, and "failure" otherwise. 60-sec ECG signals devoid of QRST waves were recorded during the index ablation at baseline and at the end of ablation (end_WPVI, before cardioversion or conversion of AF into SR). fWA was computed on leads V1 and V6b (placed on the pts’ back) as the average difference between the upper and lower envelope of atrial ECG signals. Results Over a mean follow-up of 33±9 months, 30 patients remained free from AF (success group), while 11 patients had AF recurrence after 2 WPVIs (failure group). The clinical characteristics (e.g. age, body mass index, left atrial volume or duration in sustained AF) were similar between groups (p &amp;gt; 0.05). The success group displayed significantly higher fWA values at baseline and end_WPVI than that of the failure group (p&amp;lt;0.05, Panel A and B). No significant difference was found between baseline fWA values and those measured at end_WPVI (p &amp;gt; 0.05). Conclusion As fWA is independent of PVs contribution, it is a marker of atrial body remodelling. Low fWA values identify patients with peAF unresponsive to WPVI.

Age-dependent risk for thromboembolism in atrial fibrillation: The Fushimi AF registry.

BackgroundThe risk for thromboembolism depending on the different age subgroups in patients with atrial fibrillation (AF) has not been fully elucidated.MethodsThe Fushimi AF Registry is a community-based prospective survey of patients with AF in Fushimi-ku, Kyoto. Follow-up data were available for 4,466 patients by the end of 2019. Clinical determinants and the description of variables which interact and lead to the incidence of thromboembolism (the composite of ischemic stroke and systemic embolism [SE]) were identified in overall population and in age subgroups (≤64, 65–74, and ≥ 75 years).ResultsA total of 314 patients developed thromboembolism during the median follow-up of 1,610 days (1.56 per 100 person-years). The independent determinants were age advance (per 10 years, hazard ratio [HR]: 1.51, 95% confidence interval [CI]: 1.22–1.86, P < 0.001), low body weight (HR: 1.91, 95% CI: 1.35–2.70, P < 0.001), history of stroke or SE (HR: 2.06, 95% CI: 1.54–2.76, P < 0.001), chronic kidney disease (HR: 1.34, 95% CI: 1.01–1.78, P = 0.043), and left atrial enlargement (HR: 1.57, 95% CI: 1.18–2.10, P = 0.0021). With regard to the age subgroup analysis, diabetes mellitus (P = 0.043), vascular disease (P = 0.005), male sex (P = 0.022), and sustained AF (P = 0.014) indicated significantly relevant interactions between the age subgroups and thromboembolism.ConclusionThe risk and the impact of baseline characteristics on thromboembolism in patients with AF varied depending on the age subgroups.

Inflammasome activation in end-stage heart failure-associated atrial fibrillation.

AimsInflammatory pathways are increasingly recognized as an important factor in the pathophysiology of both heart failure (HF) and atrial fibrillation (AF). However, there is no data about inflammation‐related histological and molecular alterations in HF‐associated AF. The objective of our study was to investigate inflammatory pathways and fibrosis in end‐stage HF‐associated AF.Methods and resultsLeft atrial samples of 24 male patients with end stage ischemic HF undergoing heart transplantation were analysed. Twelve patients suffered from sustained AF while the others had no documented AF. The expression of inflammasome sensors and their downstream signalling were investigated by Western blot. No differences were observed in the expression of inflammasome sensors between the two groups, while cleaved caspase‐1 increased tendentiously in the AF group (P = 0.051). Cleaved caspase‐1 also showed significant correlation with the expression of interleukin‐1β and its cleaved form in the total population and in the AF group (P < 0.05). The presence of myocardial and epicardial macrophages were assessed by ionized calcium‐binding adaptor molecule 1 (Iba1) immunostaining. Number of macrophages showed a tendency towards elevation in the left atrial myocardium and epicardium of AF compared with SR group. The amount of total and interstitial fibrosis was determined on Masson's trichrome‐stained sections. Histological assessment revealed no difference between AF and SR groups in the amount of either total or interstitial fibrosis.ConclusionsThis is the first study on inflammation‐related differences between HF with SR or AF showing elevated inflammasome activity and enhanced macrophage infiltration in left atrial samples of patients with AF.

This Month in Anesthesiology

This Month in Anesthesiology

PO-641-06 ROLE OF INTERATRIAL CONDUCTION IN ATRIAL FIBRILLATION. MECHANISTIC INSIGHTS FROM RENEWAL THEORY-BASED FIBRILLATORY DYNAMIC ANALYSIS

Inter-atrial conduction has been postulated to play an important role in atrial fibrillation (AF). The pathways involved in inter-atrial conduction during AF remain incompletely defined. A potential barrier in delineating the role of interatrial conduction in AF perpetuation has been that it has been challenging to physiologically probe these connections during sustained AF due to theturbulent nature of the fibrillatory process.