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The lack of a scalable and robust source of well-differentiated human atrial myocytes constrains the development of in vitro models of atrial fibrillation (AF). Here we show that fully functional atrial myocytes can be generated and expanded one-quadrillion-fold via a conditional cell-immortalization method relying on lentiviral vectors and the doxycycline-controlled expression of a recombinant viral oncogene in human foetal atrial myocytes, and that the immortalized cells can be used to generate in vitro models of AF. The method generated 15 monoclonal cell lines with molecular, cellular and electrophysiological properties resembling those of primary atrial myocytes. Multicellular in vitro models of AF generated using the immortalized atrial myocytes displayed fibrillatory activity (with activation frequencies of 6-8 Hz, consistent with the clinical manifestation of AF), which could be terminated by the administration of clinically approved antiarrhythmic drugs. The conditional cell-immortalization method could be used to generate functional cell lines from other human parenchymal cells, for the development of in vitro models of human disease., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Atrial fibrillation (AF) is the most common arrhythmia, and its prevalence is increasing. Early diagnosis is important to reduce the risk of stroke. Mobile health (mHealth) devices, such as single-lead electrocardiogram (ECG) devices, have been introduced to the worldwide consumer market over the past decade. Recent studies have assessed the usability of these devices for detection of AF, but it remains unclear if the use of mHealth devices leads to a higher AF detection rate., Objective: The goal of the research was to conduct a systematic review of the diagnostic detection rate of AF by mHealth devices compared with traditional outpatient follow-up. Study participants were aged 16 years or older and had an increased risk for an arrhythmia and an indication for ECG follow-up-for instance, after catheter ablation or presentation to the emergency department with palpitations or (near) syncope. The intervention was the use of an mHealth device, defined as a novel device for the diagnosis of rhythm disturbances, either a handheld electronic device or a patch-like device worn on the patient's chest. Control was standard (traditional) outpatient care, defined as follow-up via general practitioner or regular outpatient clinic visits with a standard 12-lead ECG or Holter monitoring. The main outcome measures were the odds ratio (OR) of AF detection rates., Methods: Two reviewers screened the search results, extracted data, and performed a risk of bias assessment. A heterogeneity analysis was performed, forest plot made to summarize the results of the individual studies, and albatross plot made to allow the P values to be interpreted in the context of the study sample size., Results: A total of 3384 articles were identified after a database search, and 14 studies with a 4617 study participants were selected. All studies but one showed a higher AF detection rate in the mHealth group compared with the control group (OR 1.00-35.71), with all RCTs showing statistically significant increases of AF detection (OR 1.54-19.16). Statistical heterogeneity between studies was considerable, with a Q of 34.1 and an I 2 of 61.9, and therefore it was decided to not pool the results into a meta-analysis., Conclusions: Although the results of 13 of 14 studies support the effectiveness of mHealth interventions compared with standard care, study results could not be pooled due to considerable clinical and statistical heterogeneity. However, smartphone-connectable ECG devices provide patients with the ability to document a rhythm disturbance more easily than with standard care, which may increase empowerment and engagement with regard to their illness. Clinicians must beware of overdiagnosis of AF, as it is not yet clear when an mHealth-detected episode of AF must be deemed significant., (©Tom E Biersteker, Martin J Schalij, Roderick W Treskes. Originally published in JMIR mHealth and uHealth (https://mhealth.jmir.org), 28.04.2021.)

Introduction: Efficacy of cryoballoon ablation depends on balloon-tissue contact and ablation duration. Prolonged duration may increase extracardiac complications. The aim of this study is to determine the optimal additional ablation duration after acute pulmonary vein isolation (PVI)., Methods: Consecutive patients with paroxysmal AF were randomized to three groups according to additional ablation duration (90, 120, or 150 seconds) after acute PVI (time-to-isolation). Primary outcome was reconnection/dormant conduction (DC) after a 30 minutes waiting period. If present, additional 240 seconds ablations were performed. Ablations without time-to-isolation <90 seconds, esophageal temperature <18°C or decreased phrenic nerve capture were aborted. Patients were followed with 24-hour Holter monitoring at 3, 6, and 12 months., Results: Seventy-five study patients (60 ± 11 years, 48 male) were included. Reconnection/DC per vein significantly decreased (22%, 6% and 4%) while aborted ablations remained stable (respectively 4, 5, and 7%) among the 90, 120, and 150 seconds groups. A shorter cryo-application time, longer time-to-isolation, higher balloon temperature and unsuccessful ablations predicted reconnection/DC. Freedom of atrial fibrillation was, respectively, 52, 56, and 72% in 90, 120, and 150 seconds groups ( P = 0.27), while repeated procedures significantly decreased from 36% to 4% ( P = 0.041) in the longer duration group compared to shorter duration group (150 seconds vs 90 seconds group). In multivariate Cox-regression only reconnection/DC predicted recurrence., Conclusion: Prolonging ablation duration after time-to-isolation significantly decreased reconnection/DC and repeated procedures, while recurrences and complications rates were similar. In a time-to-isolation approach, an additional ablation of 150 seconds ablation is the most appropriate., (© 2019 The Authors. Journal of Cardiovascular Electrophysiology Published by Wiley Periodicals, Inc.)

Objectives: The purpose of this study was to randomly compare the incidence of asymptomatic cerebral embolism (ACE) between the second-generation pulmonary vein ablation catheter (PVAC Gold) and the irrigated Thermocool catheter., Background: Pulmonary vein isolation (PVI) with the PVAC is associated with ACE. The PVAC Gold was designed to avoid this complication., Methods: Patients with paroxysmal atrial fibrillation were randomized 1:1 to PVI with the PVAC Gold or Thermocool catheter. Cerebral magnetic resonance imaging was performed in the days before and after ablation and repeated after 3 months in case of a new lesion. Monitoring for microembolic signals (MES) was performed by using transcranial Doppler ultrasonography. Parameters of coagulation were determined before, during, and after ablation. Neuropsychological tests and questionnaires were applied 10 days before and 3 months after ablation., Results: Seventy patients were included in the study (mean age 61 ± 9 years; 43 male subjects; CHA 2 DS 2 -VASc [congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke/transient ischemic attack, vascular disease, age 65 to 74 years, sex category] score 1.6 ± 1.2; international normalized ratio 2.7 ± 0.5; activated clotting time 374 ± 24 s; p > 0.05 for all parameters). Procedural duration was shorter in the PVAC Gold group (140 ± 34 vs. 207 ± 44 min; p < 0.001). Eight (23%; 7 infarcts) patients in the PVAC Gold group exhibited a new ACE, compared with 2 (6%; no infarcts) patients in the Thermocool group (p = 0.042). Median number of MES was higher in the PVAC Gold group (1,111 [interquartile range, 715-2,234] vs. 787 [interquartile range, 532-1,053]; p < 0.001). There were no differences between groups regarding coagulation and neuropsychological outcomes., Conclusions: PVI with the new PVAC Gold was associated with a higher incidence of ACE/cerebral infarcts and number of MES. Both catheters induced a comparable procoagulant state. Because there were no measurable differences in neuropsychological status, the clinical significance of ACE remains unclear. (Cerebral Embolism [CE] in Catheter Ablation of Atrial Fibrillation [AF] [CE-AF]; NCT01361295)., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Because of suboptimal therapeutic strategies, restoration of sinus rhythm in symptomatic atrial fibrillation (AF) often requires in-hospital delivery of high-voltage shocks, thereby precluding ambulatory AF termination. Continuous, rapid restoration of sinus rhythm is desired given the recurring and progressive nature of AF. Here, we present an automated hybrid bioelectronic system for shock-free termination of AF that enables the heart to act as an electric current generator for autogenous restoration of sinus rhythm. We show that local, right atrial delivery of adenoassociated virus vectors encoding a light-gated depolarizing ion channel results in efficient and spatially confined transgene expression. Activation of an implanted intrathoracic light-emitting diode device allows for termination of AF by illuminating part of the atria. Combining this newly obtained antiarrhythmic effector function of the heart with the arrhythmia detector function of a machine-based cardiac rhythm monitor in the closed chest of adult rats allowed automated and rapid arrhythmia detection and termination in a safe, effective, repetitive, yet shock-free manner. These findings hold translational potential for the development of shock-free antiarrhythmic device therapy for ambulatory treatment of AF., (Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Background: The posterior wall of the left atrium (LA) is a well-known substrate for atrial fibrillation (AF) maintenance. Isolation of the posterior wall between the pulmonary veins (box lesion) may improve ablation success. Box lesion surface area size varies depending on the individual anatomy. This retrospective study evaluates the influence of box lesion surface area as a ratio of total LA surface area (box surface ratio) on arrhythmia recurrence., Methods: Seventy consecutive patients with persistent AF (63 ± 11 years, 53 men) undergoing computed tomography (CT) imaging and ablation procedure consisting of a first box lesion were included in this study. Box lesion surface area was measured on electroanatomical maps and total LA surface area was derived from CT. Patients were followed with 24-h electrocardiography and exercise tests at 3, 6, and 12 months after AF ablation. Arrhythmia recurrence was defined as any AF/atrial tachycardia (AT) beyond 3 months without antiarrhythmic drugs., Results: During a median follow-up of 13 (interquartile range = 10-17) months, 42 (60%) patients had AF/AT recurrence. Multivariate Cox proportional regression analysis showed that a larger box surface ratio protected against recurrence (hazard ratio [HR] = 0.81; 95% confidence interval [CI] = 0.690-0.955; P = 0.012). Left atrial volume index (HR = 1.01 [0.990-1.024, P = 0.427] and a history of mitral valve surgery (HR = 2.90; 95% CI = 0.970-8.693; P = 0.057) were not associated with AF recurrence in multivariate analysis., Conclusion: A larger box lesion surface area as a ratio of total LA surface area is protective for AF/AT recurrence after ablation for persistent AF., (© 2018 The Authors. Pacing and Clinical Electrophysiology published by Wiley Periodicals, Inc.)

Background: Recently, a new ablation strategy for atrial fibrillation has emerged, which involves the identification of rotors (ie, local drivers) followed by the localized targeting of their core region by ablation. However, this concept has been subject to debate because the mode of arrhythmia termination remains poorly understood, as dedicated models and research tools are lacking. We took a unique optogenetic approach to induce and locally target a rotor in atrial monolayers., Methods and Results: Neonatal rat atrial cardiomyocyte monolayers expressing a depolarizing light-gated ion channel (Ca 2+ -translocating channelrhodopsin) were subjected to patterned illumination to induce single, stable, and centralized rotors by optical S1-S2 cross-field stimulation. Next, the core region of these rotors was specifically and precisely targeted by light to induce local conduction blocks of circular or linear shapes. Conduction blocks crossing the core region, but not reaching any unexcitable boundary, did not lead to termination. Instead, electric waves started to propagate along the circumference of block, thereby maintaining reentrant activity, although of lower frequency. If, however, core-spanning lines of block reached at least 1 unexcitable boundary, reentrant activity was consistently terminated by wave collision. Lines of block away from the core region resulted merely in rotor destabilization (ie, drifting)., Conclusions: Localized optogenetic targeting of rotors in atrial monolayers could lead to both stabilization and destabilization of reentrant activity. For termination, however, a line of block is required reaching from the core region to at least 1 unexcitable boundary. These findings may improve our understanding of the mechanisms involved in rotor-guided ablation., (© 2017 American Heart Association, Inc.)

Background: Recently published randomised clinical trials indicate that prolonged electrocardiom (ECG) monitoring might enhance the detection of paroxysmal atrial fibrillation (AF) in cryptogenic stroke or transient ischaemic attack (TIA) patients. A device that might be suitable for prolonged ECG monitoring is a smartphone-compatible ECG device (Kardia Mobile, Alivecor, San Francisco, CA, USA) that allows the patient to record a single-lead ECG without the presence of trained health care staff. The MOBILE-AF trial will investigate the effectiveness of the ECG device for AF detection in patients with cryptogenic stroke or TIA. In this paper, the rationale and design of the MOBILE-AF trial is presented., Methods: For this international, multicentre trial, 200 patients with cryptogenic stroke or TIA will be randomised. One hundred patients will receive the ECG device and will be asked to record their ECG twice daily during a period of 1 year. One hundred patients will receive a 7-day Holter monitor., Discussion: The primary outcome of this study is the percentage of patients in which AF is detected in the first year after the index ischaemic stroke or TIA. Secondary outcomes include markers for AF prediction, orally administered anticoagulation therapy changes, as well as the incidence of recurrent stroke and major bleeds. First results can be expected in mid-2019., Trial Registration: ClinicalTrials.gov, ID: NCT02507986 . Registered on 15 July 2015.

Background: The prevalence of atrial fibrillation (AF) in end-stage renal disease (ESRD) patients is relatively high. The present study evaluated the association between left atrial (LA) remodelling, including an increased size and myocardial fibrosis, and slow LA conduction and the occurrence of AF., Methods: In 171 ESRD patients enrolled in the Implantable Cardioverter Defibrillators in Dialysis patients (ICD2) trial, the LA dimensions, LA conduction delay [as reflected by the time difference between P-wave onset on surface electrocardiogram and A'-wave on tissue Doppler imaging (PA-TDI)] and LA function were compared between patients who exhibited AF versus patients without AF. Based on ICD remote monitoring or clinical records, the occurrence of AF was detected., Results: Of 171 patients, 47 (27%) patients experienced AF. Despite comparable left ventricular ejection fraction and prevalence of significant mitral regurgitation, patients with AF had significantly larger LA volume index (mean ± standard deviation) (29 ± 11 versus 23 ± 10 mL/m2, P = 0.001), longer PA-TDI duration (144 ± 30 versus 131 ± 27 ms, P = 0.010) and reduced late diastolic mitral annular velocity (A') (7.1 ± 2.8 versus 8.2 ± 2.4 cm/s, P = 0.012) compared with patients without AF. On multivariable analysis, larger LA volume index [odds ratio (OR) 1.04, 95% confidence interval (CI) 1.01-1.08, P = 0.017], longer PA-TDI duration (OR 1.02, 95% CI 1.00-1.03, P = 0.025) and reduced A' (OR 0.84, 95% CI 0.72-0.98, P = 0.025) were independently associated with AF after adjusting for age and left ventricle diastolic relaxation., Conclusion: ESRD patients with AF show more advanced changes in the LA substrate than ESRD patients without AF., (© The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Aims: Limited left atrial (LA) surgical ablation with bipolar radiofrequency is considered to be an effective procedure for treatment of atrial fibrillation (AF). We studied whether limited LA surgical ablation concomitant to cardiac surgery is able to maintain LA function., Methods and Results: Thirty-six consecutive patients (age 66 ± 12 years, 53% male, 78% persistent AF) scheduled for valve surgery and/or coronary revascularization and concomitant LA surgical ablation were included. Epicardial pulmonary vein isolation (PVI) and additional endo-epicardial lines were performed using bipolar radiofrequency. An age- and gender-matched control group (n = 36, age 66 ± 9 years, 69% male, 81% paroxysmal AF) was selected from patients undergoing concomitant epicardial PVI only. Left atrial dimensions and function were assessed on two-dimensional echocardiography preoperatively and at 3- and 12-month follow-up. Sinus rhythm (SR) maintenance was 67% for limited LA ablation and 81% for PVI at 1-year follow-up (P = 0.18). Left atrial volume decreased from 72 ± 21 to 50 ± 14 mL (31%, P < 0.01) after limited LA ablation and from 65 ± 23 to 56 ± 20 mL (14%, P < 0.01) after PVI. Atrial transport function was restored in 54% of patients in SR after limited LA ablation compared with 100% of patients in SR after PVI. Atrial strain and contraction parameters (LA ejection fraction, A-wave velocity, reservoir function, and strain rate) significantly decreased after limited LA ablation. After PVI, strain and contraction parameters remained unchanged., Conclusion: Even limited LA ablation decreased LA volume, contraction, transport function, and compliance, indicating both reverse remodelling combined with significant functional deterioration. In contrast, surgical PVI decreased LA volume while function remained unchanged., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.)

Background: The value of left atrial (LA) diameter, volume, and strain to risk stratify hypertrophic cardiomyopathy patients for new-onset atrial fibrillation (AF) was explored., Methods and Results: A total of 242 hypertrophic cardiomyopathy patients without AF history were evaluated by (speckle-tracking) echocardiography. During mean follow-up of 4.8±3.7 years, 41 patients (17%) developed new-onset AF. Multivariable analysis showed LA volume (≥37 mL/m 2 ; hazard ratio, 2.68; 95% confidence interval, 1.30-5.54; P =0.008) and LA strain (≤23.4%; hazard ratio, 3.22; 95% confidence interval, 1.50-6.88; P =0.003), but not LA diameter (≥45 mm; hazard ratio, 1.67; 95% confidence interval, 0.84-3.32; P =0.145), as independent AF correlates. Importantly, 59% (n=24) of AF events occurred despite a baseline LA diameter <45 mm, observed in 185 patients. In this patient subset, LA strain (area under the curve 0.73) and LA volume (area under the curve 0.83) showed good predictive value for new-onset AF. Furthermore, patients with LA volume <37 versus ≥37 mL/m 2 and LA strain >23.4% versus ≤23.4% had superior 5-year AF-free survival of 93% versus 80% ( P =0.003) and 98% versus 74% ( P =0.002), respectively. Importantly, LA volume <37 mL/m 2 and strain >23.4% yielded high negative predictive value (93% and 98%, respectively) for new-onset AF. Likelihood ratio test indicated incremental value of LA volume assessment ( P =0.011) on top of LA diameter to predict new-onset AF in hypertrophic cardiomyopathy patients with LA diameter <45 mm, which tended to increase further by addition of LA strain ( P =0.126)., Conclusions: LA diameter, volume, and strain all relate to new-onset AF in hypertrophic cardiomyopathy patients. In patients with normal LA size, however, both LA volume and strain further refine risk stratification for new-onset AF., (© 2017 American Heart Association, Inc.)

Aims: Electrical reconnection after pulmonary vein (PV) isolation is associated with atrial fibrillation (AF) recurrence. Reconnection may already develop within a 30 min waiting period and may only occur as dormant conduction (DC) revealed by adenosine infusion. This study determines incidence and predictors of DC after cryoballoon ablation incorporating a 30 min waiting period and the effect of treating this 'late' DC on 1 year AF-recurrence., Methods and Results: Consecutive patients scheduled for a first ablation were prospectively included. Intravenous adenosine was administered 30 min after PV isolation to unmask DC (adenosine+). Additional applications were performed to abolish DC. Atrial fibrillation recurrence was evaluated after 3, 6, and 12 months with ECG and 24 h Holter recordings. Results were compared with a prior group of consecutive patients that underwent cryoablation without DC testing (adenosine-). The adenosine+ group consisted of 36 patients (78% male, 61 ± 10 years, paroxysmal AF 86%). ***Dormant conduction was found in 42% of patients (15/36) and 14% of PVs (20/143). Multivariate analysis showed that PV isolation during the first freeze independently reduced DC risk (OR = 0.064, P < 0.01). After 12 ± 1 months, 11 (83%) of adenosine+ patients had no AF-recurrences, compared with 37 (60%) of adenosine- patients (n = 62, 70% male, 59 ± 11 years, 90% paroxysmal AF, P = 0.02). Ablation with DC treatment independently reduced the risk of AF-recurrence (OR = 0.26, P = 0.02)., Conclusion: Incorporating a 30-min waiting period after cryoballoon ablation increases the incidence of DC compared with previous results. Absence of PV isolation during the first freeze is associated with an increased risk of late DC. Treatment of this DC seems to improve outcome., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.)

Aims: Atrial fibrillation (AF) is the most common cardiac arrhythmia and often involves reentrant electrical activation (e.g. spiral waves). Drug therapy for AF can have serious side effects including proarrhythmia, while electrical shock therapy is associated with discomfort and tissue damage. Hypothetically, forced expression and subsequent activation of light-gated cation channels in cardiomyocytes might deliver a depolarizing force sufficient for defibrillation, thereby circumventing the aforementioned drawbacks. We therefore investigated the feasibility of light-induced spiral wave termination through cardiac optogenetics., Methods and Results: Neonatal rat atrial cardiomyocyte monolayers were transduced with lentiviral vectors encoding light-activated Ca(2+)-translocating channelrhodopsin (CatCh; LV.CatCh∼eYFP↑) or eYFP (LV.eYFP↑) as control, and burst-paced to induce spiral waves rotating around functional cores. Effects of CatCh activation on reentry were investigated by optical and multi-electrode array (MEA) mapping. Western blot analyses and immunocytology confirmed transgene expression. Brief blue light pulses (10 ms/470 nm) triggered action potentials only in LV.CatCh∼eYFP↑-transduced cultures, confirming functional CatCh-mediated current. Prolonged light pulses (500 ms) resulted in reentry termination in 100% of LV.CatCh∼eYFP↑-transduced cultures (n = 31) vs. 0% of LV.eYFP↑-transduced cultures (n = 11). Here, CatCh activation caused uniform depolarization, thereby decreasing overall excitability (MEA peak-to-peak amplitude decreased 251.3 ± 217.1 vs. 9.2 ± 9.5 μV in controls). Consequently, functional coresize increased and phase singularities (PSs) drifted, leading to reentry termination by PS-PS or PS-boundary collisions., Conclusion: This study shows that spiral waves in atrial cardiomyocyte monolayers can be terminated effectively by a light-induced depolarizing current, produced by the arrhythmogenic substrate itself, upon optogenetic engineering. These results provide proof-of-concept for shockless defibrillation., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.)

Background: This study evaluates the influence of 3 therapeutic approaches on the incidence of pericarditis and atrial fibrillation (AF) after percutaneous epicardial mapping and ablation for ventricular tachycardia., Methods and Results: Eighty-five consecutive procedures (2006-2011) were retrospectively reviewed. After the first 17 procedures (20.0%), no steroids were administered. For the subsequent 30 procedures (35.3%), systemic steroids were administered intravenously or orally, whereas the last 38 procedures (44.7%) were followed by intrapericardial steroid injection. Compared with no steroids, the incidence of pericarditic chest pain was significantly reduced by intrapericardial steroids (58.8% versus 21.1%; P=0.006) but not by intravenous or oral steroids (58.8% versus 43.4%; P=0.31). There was no significant difference in the incidence of pericarditic ECG with steroids (36.8%, 30.0%, and 41.2% for intrapericardial, intravenous or oral, and none, respectively). There was a nonsignificant reduced incidence of chest pain with ECG changes with steroids (13.2%, 10.0%, and 29.4% for intrapericardial, intravenous or oral, and none, respectively). Radiofrequency applications (65.9% of procedures) did not affect the incidence of pericarditic ECG changes, pericarditic chest pain, or pericarditis (all P>0.05). In 7 (8.3%) patients with no prior history of AF, AF was documented a median 36 hours after procedure. Patients with pericarditic ECG tended to be at greater risk of AF (16.7 versus 3.6%; P=0.091)., Conclusions: There is a high incidence of pericarditic chest pain and ECG changes after epicardial ventricular tachycardia mapping and ablation. Pericarditic chest pain is significantly decreased by intrapericardial steroids. Procedure-related AF is relatively frequent and tends to occur more commonly with pericarditic ECG changes., (© 2014 American Heart Association, Inc.)

Aims: To assess the left atrial appendage (LAA) geometry with multidetector-row computed tomography (MDCT) and its implications for selection of closure devices., Methods and Results: One hundred and ninety-seven patients who underwent MDCT prior to catheter ablation for atrial fibrillation were evaluated. Feasibility for Watchman and Amplatzer Cardiac Plug (ACP) devices was assessed based on the maximal cross-sectional diameter and perimeter of the ostium and at 10 mm depth and on the LAA diameter on the MDCT plane resembling the transoesophageal echocardiography (TEE) view. Mean maximal diameters of the ostium and at 10 mm depth were 28.7±4.4 mm and 24.6±4.5 mm, respectively, resulting in feasibilities of 80.7%, 84.8% and 91.4% for the Watchman, the ACP and for either one of the two devices, respectively. Mean perimeters of the ostium and at 10 mm depth were 79.1±12.2 mm and 69.8±11.6 mm, resulting in feasibilities of 87.8%, 92.9% and 96.4% for the Watchman, the ACP and for either one of the two devices, respectively. Mean TEE-like MDCT LAA diameter was 22.0±3.3 mm, resulting in feasibilities of 93.9%, 97% and 99.0% for the Watchman, the ACP and for either one of the two devices, respectively., Conclusions: The feasibility of current devices is high, based on MDCT measurements of the LAA, with no difference for either one of the devices.

Background: Atrial fibrillation is the most common cardiac arrhythmia. Ventricular proarrhythmia hinders pharmacological atrial fibrillation treatment. Modulation of atrium-specific Kir3.x channels, which generate a constitutively active current (I(K,ACh-c)) after atrial remodeling, might circumvent this problem. However, it is unknown whether and how I(K,ACh-c) contributes to atrial fibrillation induction, dynamics, and termination. Therefore, we investigated the effects of I(K,ACh-c) blockade and Kir3.x downregulation on atrial fibrillation., Methods and Results: Neonatal rat atrial cardiomyocyte cultures and intact atria were burst paced to induce reentry. To study the effects of Kir3.x on action potential characteristics and propagation patterns, cultures were treated with tertiapin or transduced with lentiviral vectors encoding Kcnj3- or Kcnj5-specific shRNAs. Kir3.1 and Kir3.4 were expressed in atrial but not in ventricular cardiomyocyte cultures. Tertiapin prolonged action potential duration (APD; 54.7±24.0 to 128.8±16.9 milliseconds; P<0.0001) in atrial cultures during reentry, indicating the presence of I(K,ACh-c). Furthermore, tertiapin decreased rotor frequency (14.4±7.4 to 6.6±2.0 Hz; P<0.05) and complexity (6.6±7.7 to 0.6±0.8 phase singularities; P<0.0001). Knockdown of Kcnj3 or Kcnj5 gave similar results. Blockade of I(K,ACh-c) prevented/terminated reentry by prolonging APD and changing APD and conduction velocity restitution slopes, thereby altering the probability of APD alternans and rotor destabilization. Whole-heart mapping experiments confirmed key findings (e.g., >50% reduction in atrial fibrillation inducibility after I(K,ACh-c) blockade)., Conclusions: Atrium-specific Kir3.x controls the induction, dynamics, and termination of fibrillation by modulating APD and APD/conduction velocity restitution slopes in atrial tissue with I(K,ACh-c). This study provides new molecular and mechanistic insights into atrial tachyarrhythmias and identifies Kir3.x as a promising atrium-specific target for antiarrhythmic strategies.

Aims: A novel duty-cycled bipolar/unipolar ablation catheter pulmonary vein ablation catheter (PVAC) has been developed to achieve pulmonary vein (PV) isolation in patients with atrial fibrillation (AF). Ablation with PVAC was recently found to induce PV narrowing at 3 months follow-up. The long-term effects of this catheter on PV dimensions are however unknown and were evaluated with this study., Methods and Results: Patients (n = 62, 71% male, age 60 ± 7 years) with drug-refractory AF scheduled for a first ablation procedure were evaluated. A multi-slice computed tomography (MSCT) scan was performed before and 1 year after the initial procedure. Pulmonary vein dimensions and left atrial (LA) volume were measured on MSCT. To correct for reverse remodelling of the LA, the ostial area/LA volume ratio before and after PVAC was calculated. As reverse remodelling may depend on procedural outcome, patients were divided in two groups depending on sinus rhythm (SR) maintenance or AF recurrence 1 year after ablation. Baseline characteristics were comparable between the SR group (n = 41) and the AF recurrence group (n = 21). At one year follow-up, ostial area of the PVs (n = 219) was significantly reduced from 236 ± 7.0 to 173 ± 7.4 mm(2) (27% narrowing, P < 0.01), independent of ablation outcome. Pulmonary vein narrowing was mild in 37% of PVs (25-50%), 9% was moderate (50-70%), and 3% severe (>70%). Left atrial volumes were found to be significantly reduced after ablation (14 and 5% for the SR group and AF recurrence group, respectively, P < 0.01). After adjustment for LA volume reduction, narrowing of PV ostial area remained significant in these patients (P < 0.01)., Conclusion: Ablation with PVAC results in a significant decrease in PV dimensions after long-term follow-up. In line with previous literature, PV narrowing was mild and patients did not develop any clinical symptoms.

Aims: Coronary atherosclerosis has been associated with the development of atrial fibrillation (AF). However, little is known about the impact of coronary atherosclerosis on the outcome treatment of AF. The aim of this study was to investigate the impact of coronary atherosclerosis on the efficacy of radiofrequency catheter ablation (RFCA) for AF using multi-detector row computed tomography (MDCT)., Methods: In 125 consecutive patients undergoing RFCA for AF, a pre-procedural MDCT examination (coronary angiography and/or coronary calcium score) was performed to evaluate the presence and severity of coronary atherosclerosis. Furthermore, all patients underwent a comprehensive echocardiographic evaluation to measure the left atrial size and to rule out structural heart disease. After RFCA all patients were regularly evaluated at the outpatient clinic., Results: After a mean follow-up of 12 ± 3 months, 78 patients (62%) had maintained stable sinus rhythm and 47 patients (38%) had recurrence of AF. Left atrial volume index was a significant predictor of AF recurrence after RFCA. The presence of coronary atherosclerosis on MDCT did not influence the efficacy of RFCA for AF., Conclusions: The presence of coronary atherosclerosis on MDCT is not associated with a higher risk for AF recurrence after RFCA.

Aim: Post-operative atrial tachyarrhythmias (AT) in patients with tetralogy of Fallot (ToF) are associated with congestive heart failure, stroke, and cardiac death. Effective treatment is therefore essential. The aim of the study is to evaluate long-term outcome of ablative therapy of AT in ToF patients and to study characteristics of AT recurrences., Methods and Results: Tetralogy of Fallot patients (N = 38, age 43 ± 12 years) referred for ablation of post-operative AT, appearing 26 ± 10 years after complete repair, were studied. Electro-anatomical/entrainment mapping was performed prior to ablation. Successful ablation was defined as (i) achievement of bi-directional conduction block for isthmus-dependent atrial flutter (IDAF), (ii) termination during ablation for intra-atrial reentrant tachycardia (IART) and focal atrial tachycardia (FAT). Fifty-two AT were ablated, including 37 IDAF [cycle length (CL) 294 ± 70 ms], 11 IART (CL 295 ± 46 ms), and 4 FAT (CL 371 ± 93 ms). Ablation was successful in 98%. Fifty-one of 52 AT involved the cavo-tricuspid isthmus and/or the area between scar tissue related to prior atriotomy incisions and the inferior caval vein. Multiple AT developed in 11 patients, with different mechanisms in 9. After 45 ± 24 months, 32 patients were in sinus rhythm; 5 used anti-arrhythmic drugs., Conclusion: Ablative therapy of AT in ToF patients is an effective curative treatment modality with a high procedural success rate. Sinus rhythm during long-term follow-up was obtained in the majority of patients. Fifty-one of 52 AT originated from sites related to surgical incisions created at complete repair, suggesting that extending the atriotomy incision towards the inferior caval vein during cardiac surgery combined with surgical ablation of the cavo-tricuspid isthmus will be effective in preventing development of AT.

Background: Left atrial (LA) dilatation is an important risk factor for recurrence of atrial fibrillation (AF) after radiofrequency catheter ablation (RFCA). However, the clinical applications to select patients eligible for RFCA according to LA size is limited. Additional pre-procedural assessment of LA fibrosis might improve patient selection for RFCA., Objective: To investigate the impact of LA size and LA fibrosis on the outcome of RFCA for AF., Methods: One hundred and seventy consecutive patients undergoing RFCA for AF were studied. LA size was assessed by measuring maximum LA volume index on echocardiography. LA wall ultrasound reflectivity was assessed by measuring echocardiography-derived calibrated integrated backscatter (IBS) as a surrogate of LA fibrosis., Results: After 12±3 months' follow-up, 103 patients (61%) had maintained sinus rhythm and 67 patients (39%) had recurrence of AF. Univariate Cox analyses identified LA wall ultrasound reflectivity, as well as LA size and type of AF, as predictors of AF recurrence after RFCA. Importantly, multivariate analyses showed that LA wall ultrasound reflectivity remained a strong predictor after correction for LA size and type of AF. Moreover, LA wall ultrasound reflectivity provided an incremental value in predicting outcome of RFCA over LA size and type of AF (increment in global χ(2)=61.6, p<0.001)., Conclusion: Assessment of LA fibrosis using two-dimensional echocardiography-derived calibrated IBS can be useful to predict AF recurrence after RFCA. Combined assessment of LA wall ultrasound reflectivity and LA size improves the identification of patients with a high likelihood for a successful ablation.

Aims: Total atrial activation time has been identified as an independent predictor of new-onset atrial fibrillation (AF). Echocardiographic assessment of PA-TDI duration provides an estimation of total atrial conduction time. The aim of this study was to investigate the prognostic value of total atrial conduction time to predict AF recurrence after radiofrequency catheter ablation (RFCA)., Methods and Results: In 213 patients undergoing RFCA for symptomatic drug-refractory paroxysmal AF, the total atrial conduction time was estimated by measuring the time delay between the onset of the P-wave in lead II of the surface electrocardiogram and the peak A'-wave on the tissue Doppler tracing of the left atrial (LA) lateral wall (PA-TDI duration). After RFCA, all patients were evaluated on a systematic basis at the outpatient clinic. After a mean follow-up of 13 ± 3 months, 74 patients (35%) had recurrent AF whereas 139 patients (65%) maintained sinus rhythm. Left atrial maximum volume index and PA-TDI duration were identified as independent predictors of AF recurrence after RFCA. However, receiver operator characteristics curve analyses demonstrated that PA-TDI duration had a superior accuracy to predict AF recurrence compared with LA maximum volume index (area under the curve 0.765 vs. 0.561, respectively)., Conclusion: Assessment of total atrial conduction time using tissue Doppler imaging can be used to predict AF recurrence after RFCA.

Atrial fibrillation (AF) has been linked to the presence of underlying coronary artery disease (CAD). However, whether the higher burden of CAD observed in AF patients translates into higher burden of myocardial ischemia is unknown. In 87 patients (71% male, mean age 61 ± 10 years) with paroxysmal or persistent AF and without history of CAD, MSCT coronary angiography and stress testing (exercise ECG test or myocardial perfusion imaging) were performed. CAD was classified as obstructive (≥50% luminal narrowing) or not. Stress tests were classified as normal or abnormal. A population of 122 patients without history of AF, similar to the AF group as to age, gender, symptomatic status and pre-test likelihood, served as a control group. Based on MSCT, 17% of AF patients were classified as having no CAD, whereas 43% showed non-obstructive CAD and the remaining 40% had obstructive CAD. A positive stress test was observed in 49% of AF patients with obstructive CAD. Among non-AF patients, 34% were classified as having no CAD, while 41% showed non-obstructive CAD and 25% had obstructive CAD (P = 0.013 compared to AF patients). A positive stress test was observed in 48% of non-AF patients with obstructive CAD. In conclusion, the higher burden of CAD observed in AF patients is not associated to higher burden of myocardial ischemia.

Objectives: The purpose of this study was to assess left atrial (LA) strain during long-term follow-up after catheter ablation for atrial fibrillation and to find predictors for LA reverse remodeling., Background: The association between LA reverse remodeling and improvement in LA strain after catheter ablation has not been investigated thus far., Methods: In 148 patients undergoing catheter ablation for atrial fibrillation, LA volumes and LA strain were assessed with echocardiography at baseline and after a mean of 13.2 ± 6.7 months of follow-up. The study population was divided according to LA reverse remodeling at follow-up: responders were defined as patients who exhibited 15% or more reduction in maximum LA volume at long-term follow-up. Left atrial systolic (LAs) strain was assessed with tissue Doppler imaging., Results: At follow-up, 93 patients (63%) were classified as responders, whereas 55 patients (37%) were nonresponders. At baseline, LAs strain was significantly higher in the responders as compared with the nonresponders (19 ± 8% vs. 14 ± 6%; p = 0.001). Among the responders, a significant increase in LAs strain was noted from baseline to follow-up (from 19 ± 8% to 22 ± 9%; p < 0.05), whereas no change was noted among the nonresponders. LAs strain at baseline was an independent predictor of LA reverse remodeling (odds ratio: 1.813; 95% confidence interval: 1.102 to 2.982; p = 0.019)., Conclusions: In the present study, 63% of the patients exhibited LA reverse remodeling after catheter ablation for atrial fibrillation, with a concomitant improvement in LA strain. LA strain at baseline was an independent predictor of LA reverse remodeling., (Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Multislice computed tomography (MSCT) is commonly acquired before radiofrequency catheter ablation (RFCA) for atrial fibrillation (AF) to plan and guide the procedure. MSCT allows accurate measurement of the left atrial (LA) and pulmonary vein (PV) dimensions and classification of the PV anatomy. The aim of the present study was to investigate the effect of LA dimensions, PV dimensions, and PV anatomy on the outcome of circumferential RFCA for AF. A total of 100 consecutive patients undergoing RFCA for AF (paroxysmal 72%, persistent 28%) were studied. The LA dimensions, PV dimensions, and PV anatomy were evaluated three dimensionally using MSCT. The PV anatomy was classified as normal or atypical according to the absence/presence of a common trunk or additional veins. After a mean follow-up of 11.6 ± 2.8 months, 65 patients (65%) maintained sinus rhythm. The enlargement of the left atrium in the anteroposterior direction on MSCT was related to a greater risk of AF recurrence. No relation was found between the PV dimensions and the outcome of RFCA. In addition, normal right-sided PV anatomy was related to a greater risk of AF recurrence compared to atypical right-sided PV anatomy. Multivariate analysis showed that an anteroposterior LA diameter on MSCT (odds ratio 1.083, p = 0.027) and normal right-sided PV anatomy (odds ratio 6.711, p = 0.006) were independent predictors of AF recurrence after RFCA. In conclusion, enlargement of the anteroposterior LA diameter and the presence of normal anatomy of the right PVs are independent risk factors for AF recurrence. No relation was found between the PV dimensions and outcome of RFCA., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: the presence of atrial fibrillation (AF) is related to increased levels of natriuretic peptides. In addition, increased natriuretic peptide levels are predictive of the development of AF. However, the role of natriuretic peptides to predict recurrence of AF after radiofrequency catheter ablation (RFCA) is controversial., Objective: the study aimed to investigate the role of natriuretic peptides in the prediction of AF recurrence after RFCA for AF., Methods: pre-procedural amino-terminal pro-atrial natriuretic peptide (NT-proANP) and amino-terminal-pro-B-type natriuretic peptide (NT-proBNP) plasma levels were determined in 87 patients undergoing RFCA for symptomatic drug-refractory AF. In addition, a comprehensive clinical and echocardiographic evaluation was performed at baseline. Left atrial volumes, left ventricular volumes, and function (systolic and diastolic) were assessed. During a 6-month follow-up period, AF recurrence was monitored and defined as any registration of AF on electrocardiogram or an episode of AF longer than 30 seconds on 24-hour Holter monitoring. The role of natriuretic peptide plasma levels to predict AF recurrence after RFCA was studied., Results: During follow-up, 66 patients (76%) maintained sinus rhythm, whereas 21 patients (24%) had AF recurrence. Patients with AF recurrence had higher baseline natriuretic peptide levels than patients who maintained sinus rhythm (NT-proANP 3.19 nmol/L [2.55-4.28] vs 2.52 nmol/L [1.69-3.55], P = .030; NT-proBNP 156.4 pg/mL [64.1-345.3] vs 84.6 pg/mL [43.3-142.7], P = .036). However, NT-proBNP was an independent predictor of AF recurrence, whereas NT-proANP was not. Moreover, NT-proBNP had an incremental value over echocardiographic characteristics to predict AF recurrence after RFCA., Conclusion: baseline NT-proBNP plasma level is an independent predictor of AF recurrence after RFCA.

Background: During persistent atrial fibrillation (AF), waves with a focal spread of activation are frequently observed. The origin of these waves and their relevance for the persistence of AF are unknown., Methods and Results: In 24 patients with longstanding persistent AF and structural heart disease, high-density mapping of the right and left atria was performed during cardiac surgery. In a reference group of 25 patients, AF was induced by rapid pacing. For data analysis, a mapping algorithm was developed that separated the fibrillatory process into its individual wavelets and identified waves with a focal origin. During persistent AF, the incidence of focal fibrillation waves in the right atrium was almost 4-fold higher than during acute AF (median, 0.46 versus 0.12 per cycle per 1 cm² (25th to 75th percentile, 0.40 to 0.77 and 0.01 to 0.27; P<0.0001). They were widely distributed over both atria and were recorded at 46 ± 18 of all electrodes. A large majority (90.5) occurred as single events. Repetitive focal activity (>3) happened in only 0.8. The coupling interval was not more than 11 ms shorter than the average AF cycle length (P=0.04), and they were not preceded by a long interval. Unipolar electrograms at the site of origin showed small but clear R waves. These data favor epicardial breakthrough rather than a cellular focal mechanism as the underlying mechanism. Often, conduction from a site of epicardial breakthrough was blocked in 1 or more directions. This generated separate multiple wave fronts propagating in different directions over the epicardium., Conclusions: Focal fibrillation waves are due to epicardial breakthrough of waves propagating in deeper layers of the atrial wall. In patients with longstanding AF, the frequency of epicardial breakthroughs was 4 times higher than during acute AF. Because they provide a constant source of independent fibrillation waves originating over the entire epicardial surface, they offer an adequate explanation for the high persistence of AF in patients with structural heart disease.

Aims: Heart failure and atrial fibrillation (AF) frequently coexist and AF worsens heart failure prognosis. Device-based diagnostics derived from implantable cardioverter-defibrillator (ICD) interrogation provide an accurate method for detecting AF episodes. This study sought to determine clinical and echocardiographic predictors of AF occurrence, including an index of total atrial conduction time derived by tissue Doppler imaging (PA-TDI duration), in patients with heart failure. Moreover, the role of PA-TDI duration on the prediction of AF occurrence in subgroups of patients with and without history of AF was explored., Methods and Results: A cohort of 495 heart failure patients who underwent ICD implantation was studied. Baseline echocardiographic parameters of systolic and diastolic function were evaluated together with clinical parameters. Furthermore, PA-TDI duration was measured. All patients were prospectively followed up after ICD implantation for AF occurrence detected by ICD interrogation. A total of 142 (29%) patients experienced AF over a follow-up period of 16.4 ± 11.2 months. PA-TDI duration was longer in patients with AF occurrence when compared with patients without AF occurrence (154 ± 27 vs. 135 ± 24 ms, P < 0.001). On Cox-multivariable analysis, female gender [hazard ratio = 1.60; 95% confidence intervals (CI) = 1.09-2.35; P = 0.017], history of AF (hazard ratio = 2.22; 95% CI, 1.51-3.27; P < 0.001), and PA-TDI duration (hazard ratio = 1.27; 95% CI, 1.13-1.42; P < 0.001) were independent predictors of AF occurrence. In the subgroups of patients with and without history of AF, PA-TDI duration remained an independent predictor of AF occurrence., Conclusion: PA-TDI duration may be useful to risk-stratify for AF occurrence in heart failure patients with and without a history of AF.

Patients who develop new-onset atrial fibrillation (AF) after acute myocardial infarction (AMI) show an increased risk for adverse events and mortality during follow-up. Recently, a novel noninvasive echocardiographic method has been validated for the estimation of total atrial activation time using tissue Doppler imaging of the atria (PA-TDI duration). PA-TDI duration has shown to be independently predictive of new-onset AF. However, whether PA-TDI duration provides predictive value for new-onset AF in patients after AMI has not been evaluated. Consecutive patients admitted with AMIs and treated with primary percutaneous coronary intervention underwent echocardiography <48 hours after admission. All patients were followed at the outpatient clinic for > or =1 year. During follow-up, 12-lead electrocardiography and Holter monitoring were performed regularly, and the development of new-onset AF was noted. Baseline echocardiography was performed to assess left ventricular and left atrial (LA) function. LA performance was quantified with LA volumes, function, and PA-TDI duration. A total of 613 patients were evaluated. LA maximal volume (hazard ratio 1.07, 95% confidence interval 1.04 to 1.11), the total LA ejection fraction (hazard ratio 0.96, 95% confidence interval 0.93 to 0.99) and PA-TDI duration (hazard ratio 1.05, 95% confidence interval 1.04 to 1.06) were univariate predictors of new-onset AF. After multivariate analysis, LA maximal volume and PA-TDI duration independently predicted new-onset AF. Furthermore, PA-TDI duration provided incremental prognostic value to traditional clinical and echocardiographic parameters for the prediction of new-onset AF. In conclusion, PA-TDI duration is a simple measurement that provides important value for the prediction of new-onset AF in patients after AMI., (Copyright (c) 2010 Elsevier Inc. All rights reserved.)

Objectives: This study aimed to assess the prevalence of different types of atrial fibrillation (AF) and their prognostic importance in implantable cardioverter-defibrillator (ICD) patients., Background: The prevalence of AF has taken epidemic proportions in the population with cardiovascular disease. The prognostic importance of different types of AF in ICD patients remains unclear., Methods: Data on 913 consecutive patients (79% men, mean age 62 + or - 13 years) receiving an ICD at the Leiden University Medical Center were prospectively collected. Among other characteristics, the existence and type of AF (paroxysmal, persistent, or permanent) were assessed at implantation. During follow-up, the occurrence of appropriate or inappropriate device therapy as well as mortality was noted., Results: At implantation, 73% of patients had no history of AF, 9% had a history of paroxysmal AF, 7% had a history of persistent AF, and 11% had permanent AF. During 833 + or - 394 days of follow-up, 117 (13%) patients died, 228 (25%) patients experienced appropriate device discharge, and 139 (15%) patients received inappropriate shocks. Patients with permanent AF exhibited more than double the risk of mortality, ventricular arrhythmias triggering device discharge, and inappropriate device therapy. Patients with paroxysmal or persistent AF did not show a significant increased risk of mortality or appropriate device therapy but demonstrated almost 3 times the risk of inappropriate device therapy., Conclusions: In the population currently receiving ICD treatment outside the setting of clinical trials, a large portion has either a history of AF or permanent AF. Both types of AF have prognostic implications for mortality and appropriate as well as inappropriate device discharge., (Copyright 2010 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Atrial fibrillation (AF) is the most common cardiac arrhythmia, and is associated with an increased risk of cardiac morbidity and mortality. In this review, the role of multimodality imaging in the evaluation and treatment of AF is discussed in two main parts. First, an overview of the initial assessment of an AF patient is provided, including the role of different imaging techniques. Conditions that are associated with AF (coronary artery disease, heart failure, valvular heart disease, and left ventricular hypertrophy), and the assessment with various imaging modalities, will be reviewed. Furthermore, left atrial size assessment and the screening for thrombus formation are addressed. Secondly, the role of imaging in the invasive treatment of AF with catheter ablation is reviewed. Issues that should be considered before the procedure including contra-indications and pulmonary vein and left atrial anatomy will be discussed. Furthermore, the integration of different imaging modalities during catheter ablation is explored. Finally, an overview of the role of imaging in the follow-up of patients treated with catheter ablation will be provided.

Background: The effect of successful catheter ablation on left ventricular (LV) strain in patients with preserved LV systolic function is unknown. The aim of the present study was to assess the long-term effects of catheter ablation for atrial fibrillation (AF) on LV strain and strain rate in patients with preserved LV ejection fraction., Methods and Results: In 78 patients undergoing catheter ablation for AF, speckle tracking strain imaging was performed to assess LV strain in 3 directions (radial, circumferential, and longitudinal) at baseline and after 12-month follow-up. The study population was divided into 2 groups, according to the maintenance of sinus rhythm (SR) during follow-up. After 13.8+/-4.7 months of follow-up, 54 patients (69%) were in SR (SR group), whereas 24 patients (31%) had recurrence of AF (AF group). No significant changes in LV ejection fraction from baseline to follow-up were noted (60+/-7% versus 59+/-7%, P=NS). Circumferential strain improved significantly in the SR group (-18.3+/-3.2% versus -20.4+/-3.8%, P<0.001), whereas it remained unchanged in the AF group (-18.9+/-3.5% versus -17.9+/-3.1%, P=NS). In the SR group, significant improvements in LV longitudinal strain and strain rate were noted, whereas in the AF group, LV longitudinal strain and strain rate deteriorated significantly at long-term follow-up., Conclusions: After successful catheter ablation, LV circumferential and longitudinal strain and strain rate improve significantly in patients who maintain SR. In contrast, a decrease in LV longitudinal strain and strain rate is observed in patients with recurrence of AF.

Background: Although atrial fibrillation (AF) has been linked to underlying coronary artery disease (CAD), data supporting this association have been based on ECG and clinical history for the definition of CAD rather than direct visualization of atherosclerosis., Methods and Results: The prevalence of CAD among patients with paroxysmal or persistent AF and without history of CAD was evaluated using multislice computed tomography. Multislice computed tomography was performed in 150 patients with AF (61+/-11 years, 67% males, 58% asymptomatic) with predominantly low (59%) or intermediate (25%) pretest likelihood of CAD. CAD was classified as obstructive (> or =50% luminal narrowing) or not. A population of 148 patients without history of AF, similar to the AF group as to age, gender, symptomatic status, and pretest likelihood, served as a control group. Logistic regression analysis was applied to evaluate the relationship between demographic and clinical data and the presence of obstructive CAD. On the basis of multislice computed tomography, 18% of patients with AF were classified as having no CAD, whereas 41% showed nonobstructive CAD and the remaining 41% had obstructive CAD. Among patients without AF, 32% were classified as having no CAD, whereas 41% showed nonobstructive CAD and 27% had obstructive CAD (P=0.010 compared with patients with AF). At logistic regression analysis, age, male gender, and the presence of AF were significantly related to obstructive CAD., Conclusions: A higher prevalence of obstructive CAD was observed among patients with AF, confirming the hypothesis that AF could be a marker of advanced coronary atherosclerosis.

Background: Data on the occurrence and implications of new-onset atrial fibrillation (AF) following cardiac resynchronization therapy (CRT) are scarce. We studied the incidence of new onset AF in CRT-defibrillator (CRT-D) recipients. The influence of new-onset AF on echocardiographic response to CRT and the rate of adverse events also were evaluated., Objective: The purpose of this study was to assess the incidence and implications of new-onset AF following CRT., Methods: The study population consisted of 223 consecutive patients with no history of AF. New-onset AF was defined as atrial high-rate episodes >180 bpm for more than 10 minutes/day as detected by the device. Echocardiography was performed at baseline and after 6 months of biventricular pacing. Long-term events included implantable cardioverter-defibrillator therapy for ventricular arrhythmias, hospitalization for heart failure, and all-cause mortality., Results: Fifty-five (25%) patients developed new-onset AF during mean follow-up of 32 +/- 16 months. When compared to the patients who maintained sinus rhythm during follow-up, patients who developed AF showed less left ventricular (LV) reverse remodeling (DeltaLV end-systolic volume 37 +/- 53 vs >19 +/- 37 mL, P <.05) and less improvement in LV function (DeltaLV ejection fraction 6.7% +/- 8.9% vs 3.5% +/- 10.3%, P <.05). Importantly, patients who developed AF experienced more appropriate ICD shocks for ventricular arrhythmias, more inappropriate shocks, and more hospitalizations for heart failure., Conclusion: Recipients of CRT-D who develop new-onset AF show less echocardiographic response to CRT and more cardiac adverse events during long-term follow-up.

Over the past few years, integration of different imaging modalities to guide catheter ablation procedures for atrial fibrillation has become possible. Various strategies are nowadays available that allow integration of the anatomical information provided by fluoroscopy, computed tomography, magnetic resonance imaging, or intracardiac echocardiography with the information provided by electroanatomic mapping. This review discusses the different image integration techniques, and an overview of the clinical experience with these systems will be provided. In addition, factors that may affect the accuracy of the image integration process will be addressed. Finally, the effect of image integration on procedural characteristics and outcome will be reviewed.

Background: Multislice computed tomography (MSCT) integration is commonly used to guide radiofrequency catheter ablation (RFCA) for atrial fibrillation (AF). MSCT provides detailed anatomical information but lacks the ability to provide real-time anatomy during RFCA. Intracardiac echocardiography (ICE) allows real-time visualization of cardiac structures., Objective: The purpose of this study was to investigate the feasibility of three-dimensional (3D) anatomical mapping of the left atrium (LA) with ICE and integrating the 3D map with MSCT to facilitate RFCA for AF., Methods: In 17 patients undergoing RFCA for AF, 3D mapping of the LA was performed with ICE using a new mapping system that allows tracking of a new ICE probe. On each ICE image, endocardial contours were traced and used to generate a 3D map of the LA and pulmonary veins (PVs). A preprocedurally acquired MSCT image of the LA was then integrated with the 3D map. Additionally, PV assessment with ICE was compared with MSCT., Results: Accurate 3D mapping could be performed in all patients with a mean number of 31.1 +/- 8.5 contours. Integration with MSCT resulted in a mean distance between the MSCT and ICE contours of 2.2 +/- 0.3 mm for the LA and PVs together and of 1.7 +/- 0.2 mm around the PV ostia specifically. Agreement in the assessment of PV anatomy and diameters between ICE and MSCT was excellent., Conclusion: Three-dimensional ICE mapping of the LA is feasible. The 3D map created with ICE can be merged with MSCT to facilitate RFCA for AF.

Real-time 3-dimensional echocardiography (RT3DE) can provide a unique combination of accurate left atrial (LA) volume quantification and rapid, automatic assessment of LA function. The aim of the study was to evaluate the changes in LA volumes and function in patients with atrial fibrillation (AF) undergoing radiofrequency catheter ablation (RFCA) using RT3DE; 57 consecutive patients referred for RFCA were studied. Paroxysmal AF was present in 43 patients (75%) and persistent AF in 14 (25%). After a mean follow-up of 7.9 +/- 2.7 months, patients were divided into 2 groups: successful RFCA (SR group) and recurrence of AF (AF group). RT3DE was performed before, within 3 days, and 3 months after RFCA to assess LA volumes (maximum, minimum, and preA) and LA functions (passive, active, and reservoir). A total of 38 patients (67%) had successful RFCA (SR group). Immediately after RFCA, no significant changes in LA volumes and function were observed. After 3 months, a significant reduction in LA volumes (maximum: 26 +/- 8 to 23 +/- 7 ml/m(2), p <0.01) was noted only in the SR group, with a significant improvement in LA active (22 +/- 8% to 33 +/- 9%, p <0.01) and reservoir functions (116 +/- 45% to 152 +/- 54%, p <0.01). Conversely, the AF group showed a trend towards a deterioration of LA volumes and function. In conclusion, in patients who maintain sinus rhythm after RFCA, a significant reverse remodeling and functional improvement of the left atrium is observed using RT3DE.

The left atrium (LA) anterior-posterior diameter was one of the first standardised echocardiographic parameters. However, the clinical importance of LA size assessment has been neglected for some time. Recent population-based studies have demonstrated the prognostic value of LA size for long-term outcome. Furthermore, with new dedicated techniques such as tissue Doppler imaging, it has become feasible to assess (regional) LA function. In addition, the introduction of catheter ablation procedures has changed the treatment of patients with drug-refractory atrial fibrillation (AF) dramatically. New image integration systems have become available for these catheter ablation procedures. With the use of image integration systems, a real anatomical "roadmap" of the LA is provided for catheter ablation procedures. All these factors may explain the renewed interest in LA anatomy. In this article, the importance of assessment of LA size and LA anatomy is discussed. Furthermore, the various imaging modalities that are available for the non-invasive visualisation of the LA will be reviewed. In addition, the role of these imaging techniques in catheter ablation procedures for AF will be discussed.

Objectives: Speckle-tracking strain analysis was used to assess the effects of permanent right ventricular (RV) pacing on the heterogeneity in timing of regional wall strain and left ventricular (LV) dyssynchrony., Background: Recent studies have shown detrimental effects of RV pacing, possibly related to the induction of LV dyssynchrony., Methods: Fifty-eight patients treated with His bundle ablation and pacemaker implantation were studied. To assess the effect of RV pacing on time-to-peak radial strain of different LV segments, we applied speckle-tracking analysis to standard LV short-axis images. In addition, New York Heart Association (NYHA) functional class, LV volumes, and systolic function were assessed at baseline and after long-term RV pacing., Results: At baseline, similar time-to-peak strain for the 6 segments was observed (mean 371 +/- 114 ms). In contrast, after a mean of 3.8 +/- 2.0 years of RV pacing, there was a marked heterogeneity in time-to-peak strain of the 6 segments. In 33 patients (57%), LV dyssynchrony, represented by a time difference > or =130 ms between the time-to-peak strain of the (antero)septal and the posterolateral segments, was present. In these patients, a deterioration of LV systolic function and NYHA functional class was observed. In 11 patients, an "upgrade" of the conventional pacemaker to a biventricular pacemaker resulted in partial reversal of the detrimental effects of RV pacing., Conclusions: Speckle-tracking analysis revealed that permanent RV pacing induced heterogeneity in time-to-peak strain, resulting in LV dyssynchrony in 57% of patients, associated with deterioration of LV systolic function and NYHA functional class. Biventricular pacing may reverse these adverse effects of RV pacing.

Objectives: This study was designed to assess the effects of long-term right ventricular (RV) pacing on left ventricular (LV) dyssynchrony, LV function, and heart failure symptoms., Background: Atrioventricular (AV) node ablation and subsequent long-term RV pacing is a well-established treatment option in patients with atrial fibrillation (AF)., Methods: In 55 patients with drug-refractory AF, AV node ablation and implantation of a pacemaker was performed. At baseline and after a mean of 3.8 +/- 1.7 years, LV dyssynchrony (by M-mode echocardiography and tissue Doppler imaging), LV function, and volumes and functional status were assessed., Results: After long-term RV pacing, 27 patients (49%) had developed LV dyssynchrony. Concomitantly, these patients worsened in heart failure symptoms (New York Heart Association functional class increased from 1.8 +/- 0.6 to 2.2 +/- 0.7, p < 0.05), with a decrease in LV ejection fraction (from 48 +/- 7% to 43 +/- 7%, p < 0.05) and an increase in LV end-diastolic volume (from 116 +/- 39 ml to 130 +/- 52 ml, p < 0.05). Conversely, patients without LV dyssynchrony did not deteriorate in heart failure symptoms, LV function, or LV volumes., Conclusions: Long-term RV pacing can induce LV dyssynchrony in almost 50% of patients treated with AV node ablation for chronic AF. The development of LV dyssynchrony was associated with deterioration in heart failure symptoms, systolic LV function, and LV dilatation.

Left atrial (LA) remodeling is associated with atrial fibrillation (AF). Radiofrequency catheter ablation offers a good treatment option for AF, with reasonable long-term results. The purpose of the present study was to assess whether LA reverse remodeling occurs after successful catheter ablation. Fifty-seven consecutive patients (45 men; age 53 +/- 8 years) with symptomatic drug-refractory AF were treated with radiofrequency catheter ablation. The patients were divided into 2 groups on the basis of AF recurrence as determined by Holter monitoring and 12-lead electrocardiographic findings at 6 weeks and 3 months of follow-up (sinus rhythm [SR] group, no recurrence; AF group, AF recurrence). At baseline and 3 months of follow-up, 2-dimensional echocardiography was performed to assess LA size and dimensions. Furthermore, LA volumes were measured at end-systole and end-diastole. After 3 months, 39 of 57 patients (68%) maintained SR. At 3 months of follow-up, the LA anteroposterior diameter showed a significant reduction in the SR group (4.5+/- 0.3 vs 4.2 +/- 0.2 cm, p <0.01), and an additional increase was observed in the AF group (4.5+/- 0.3 vs 4.8 +/- 0.3 cm, p <0.05). Furthermore, the LA end-systolic and end-diastolic volumes decreased significantly in the SR group from baseline to follow-up (59 +/- 12 vs 50 +/- 11 ml, p <0.01, and 37 +/- 9 vs 31 +/- 7 ml, p <0.01, respectively). However, a tendency toward an increase in LA volumes was observed in the AF group. In conclusion, the results of this study have demonstrated that LA reverse remodeling occurs after successful radiofrequency catheter ablation for AF.

Background: The outcome of catheter ablation procedures of cardiac arrhythmias depends on the ability to evaluate the underlying mechanism and to depict target sites for ablation. Fusion of different imaging modalities within one system may improve electroanatomic modeling and facilitate ablation procedures., Objectives: The purpose of this study was to study the feasibility of fusion of multislice computed tomography (MSCT) with electroanatomic mapping to guide radiofrequency catheter ablation of atrial arrhythmias., Methods: Sixteen patients (15 men, age 54 +/- 7 years) with drug-refractory atrial fibrillation (AF) underwent 64-slice MSCT within 2 days before radiofrequency catheter ablation. MSCT data were imported to the Carto electroanatomic mapping system. Using the new CartoMerge Image Integration Module, the MSCT images and the electroanatomic map were aligned. A statistical algorithm provided information about the accuracy of the fusion process., Results: In all patients, MSCT images could be fused with the electroanatomic map. Mean distance between the mapping points and the MSCT surface ranged from 1.7 +/- 1.2 mm to 2.8 +/- 1.8 mm. This resulted in an average of 2.1 +/- 0.2 mm for the patient group as a whole., Conclusion: MSCT images can be fused with the three-dimensional electroanatomic mapping system in an accurate manner. Anatomy-based catheter ablation procedures for atrial arrhythmias may be facilitated by integration of different imaging modalities.

Purpose: To evaluate multi-detector row computed tomographic (CT) depiction of pulmonary veins to provide a road map for radiofrequency catheter ablation., Materials and Methods: For patients, institutional review board (IRB) approval was not required, and consent was obtained for treatment. Control subjects were part of an IRB-approved research protocol at the institution, in which they had consented to participate. Multi-detector row CT was performed in 23 patients (17 men, six women; mean age, 48 years +/- 11 [standard deviation]) with atrial fibrillation who were admitted for isolation of pulmonary veins by means of radiofrequency catheter ablation. Pulmonary vein anatomy was evaluated, and diameters of pulmonary vein ostia were measured. To determine the shape of ostia, a venous ostium index was calculated for all veins by dividing anterior-posterior measurements by superior-inferior measurements. Results were compared with those in a control group of 11 patients (eight men, three women; mean age, 56 years +/- 11) without atrial fibrillation. Images were evaluated by two observers in consensus., Results: Pulmonary veins additional to the four main veins were found in seven (30%) of 23 patients. Common ostia of left and right pulmonary veins were detected in 19 (83%) and nine (39%) patients, respectively. Early branching occurred more often with right than with left veins (19 [83%] vs three [13%] cases, P <.05) in both patients and control subjects. Anterior-posterior diameter of ostia was 12.8 mm +/- 3.3 for left veins, 16.2 mm +/- 3.8 for right veins, and 18.8 mm +/- 7.7 and 28.7 mm +/- 5.1 for left and right common ostia, respectively. Ostia of right pulmonary veins were more round than were ostia of left pulmonary veins (venous ostium index in patients, 0.91 +/- 0.21 vs 0.75 +/- 0.17, P <.05; in control subjects, 0.93 +/- 0.12 vs 0.82 +/- 0.17, P <.05). The CT data were used to determine ablation strategy and guide catheters during radiofrequency ablation., Conclusion: Multi-detector row CT provides a valuable road map for pulmonary vein anatomy prior to radiofrequency catheter ablation. Variations in number and insertion of pulmonary veins were observed in a considerable number of patients and control subjects.

Cardiac resynchronization therapy (CRT) is a new therapeutic option for patients who have drug-refractory end-stage heart failure. Much information has been obtained from patients who have sinus rhythm, but the use of CRT in patients who have chronic atrial fibrillation (AF) has not been studied extensively. Accordingly, we evaluated the clinical response and long-term survival rate of CRT in patients who had heart failure and chronic AF, and the results were compared with those in patients who had sinus rhythm and who underwent CRT. Sixty patients who had end-stage heart failure (30 had sinus rhythm and 30 had chronic AF), New York Heart Association classes III to IV, left ventricular ejection fraction <35%, QRS interval >120 ms, and a left bundle branch block received a biventricular pacemaker. New York Heart Association class, Minnesota Quality of Life score, and 6-minute walking distance were evaluated at baseline and after 6 months of CRT. Long-term follow-up was

Intracardiac echocardiography was used to explore pulmonary venous (PV) anatomy and to monitor PV stenosis in 31 patients referred for radiofrequency catheter ablation at PV ostia. Interindividual variations in PV anatomy and insertion in the left atrium were observed. Narrowing of PV ostia after radiofrequency catheter ablation did not produce significant hemodynamic changes.