AimsDiseased atria are characterized by functional and structural heterogeneities, adding to abnormal impulse generation and propagation. These heterogeneities are thought to lie at the origin of... Show moreAimsDiseased atria are characterized by functional and structural heterogeneities, adding to abnormal impulse generation and propagation. These heterogeneities are thought to lie at the origin of fractionated electrograms recorded during sinus rhythm (SR) in atrial fibrillation (AF) patients and are assumed to be involved in the onset and perpetuation (e.g. by re-entry) of this disorder. The underlying mechanisms, however, remain incompletely understood. Here, we tested whether regions of dense fibrosis could create an electrically isolated conduction pathway (EICP) in which re-entry could be established via ectopy and local block to become ‘trapped’. We also investigated whether this could generate local fractionated electrograms and whether the re-entrant wave could ‘escape’ and cause a global tachyarrhythmia due to dynamic changes at a connecting isthmus.Methods and resultsTo precisely control and explore the geometrical properties of EICPs, we used light-gated depolarizing ion channels and patterned illumination for creating specific non-conducting regions in silico and in vitro. Insight from these studies was used for complementary investigations in virtual human atria with localized fibrosis. We demonstrated that a re-entrant tachyarrhythmia can exist locally within an EICP with SR prevailing in the surrounding tissue and identified conditions under which re-entry could escape from the EICP, thereby converting a local latent arrhythmic source into an active driver with global impact on the heart. In a realistic three-dimensional model of human atria, unipolar epicardial pseudo-electrograms showed fractionation at the site of ‘trapped re-entry’ in coexistence with regular SR electrograms elsewhere in the atria. Upon escape of the re-entrant wave, acute arrhythmia onset was observed.ConclusionsTrapped re-entry as a latent source of arrhythmogenesis can explain the sudden onset of focal arrhythmias, which are able to transgress into AF. Our study might help to improve the effectiveness of ablation of aberrant cardiac electrical signals in clinical practice. Show less
Background and aimsCancer provides challenges to the continuity of anticoagulant treatment in patients with atrial fibrillation (AF), e.g. through cancer-related surgery or complications. We aimed... Show moreBackground and aimsCancer provides challenges to the continuity of anticoagulant treatment in patients with atrial fibrillation (AF), e.g. through cancer-related surgery or complications. We aimed to provide data on the incidence and reasons for interrupting and discontinuing anticoagulant treatment in AF patients with cancer and to assess its contribution to the risk of thromboembolism (TE) and major bleeding (MB).MethodsThis retrospective study identified AF patients with cancer in two hospitals between 2012 and 2017. Data on anticoagulant treatment, TE and MB were collected during two-year follow-up. Incidence rates (IR) per 100 patient-years and adjusted hazard ratios (aHR) were obtained for TE and MB occurring during on- and off-anticoagulant treatment, during interruption and after resumption, and after permanent discontinuation.Results1213 AF patients with cancer were identified, of which 140 patients permanently discontinued anticoagulants and 426 patients experienced one or more interruptions. Anticoagulation was most often interrupted or discontinued due to cancer-related treatment (n = 441, 62 %), bleeding (n = 129, 18 %) or end of life (n = 36, 5 %). The risk of TE was highest off-anticoagulation and during interruptions, with IRs of 19 (14–25)) and 105 (64–13), and aHRs of 3.1 (1.9–5.0) and 4.6 (2.4–9.0), respectively. Major bleeding risk were not only increased during an interruption, but also in the first 30 days after resumption, with IRs of 33 (12–72) and 30 (17–48), and aHRs of 3.3 (1.1–9.8) and 2.4 (1.2–4.6), respectively.ConclusionsInterruption of anticoagulation therapy harbors high TE and MB risk in AF patients with cancer. The high incidence rates call for better (periprocedural) anticoagulant management strategies tailored to the cancer setting. Show less
BackgroundCancer is suggested to confer thromboembolic and bleeding risk in patients with atrial fibrillation (AF).ObjectivesWe aimed to describe current anticoagulant practice in patients with AF... Show moreBackgroundCancer is suggested to confer thromboembolic and bleeding risk in patients with atrial fibrillation (AF).ObjectivesWe aimed to describe current anticoagulant practice in patients with AF and active cancer, present incidences of thromboembolic and bleeding complications, and evaluate the association between cancer type or anticoagulant management strategy with AF-related complications.MethodsThis retrospective study identified patients with AF and active cancer in 2 hospitals between January 1, 2012, and December 31, 2017. Follow-up lasted for 2 years. Data on cancer and anticoagulant treatment were collected. The outcomes of interest included ischemic stroke or transient ischemic attack (TIA) and clinically relevant nonmajor bleeding (CRNMB/MB). Incidence rates (IRs) per 100 patient-years and subdistribution hazard ratios (SHRs) with corresponding 95% Cis were estimated.ResultsWe identified 878 patients with AF who developed cancer (cohort 1) and 335 patients with cancer who developed AF (cohort 2). IRs for ischemic stroke/TIA and MB/CRNMB were 3.9 (2.8-5.3) and 15.7 (13.3-18.5) for cohort 1 and 4.0 (2.2-6.7) and 16.7 (12.6-21.7) for cohort 2. 14.2% (cohort 1) and 19.1% (cohort 2) of patients with a CHA2DS2-VASc score of ≥2 did not receive anticoagulant treatment. Withholding anticoagulants was associated with thromboembolic complications (SHR: 5.1 [3.20-8.0]). In nonanticoagulated patients with a CHA2DS2-VASc score of <2, IRs for stroke/TIA were 4.5 (0.75-15.0; cohort 1) and 16.0 (5.1-38.7; cohort 2).ConclusionPatients with AF and active cancer experience high rates of thromboembolic and bleeding complications, underlying the complexity of anticoagulant management in these patients. Our data suggest that the presence of cancer is an important factor in determining the indication for anticoagulants in patients with a low CHA2DS2-VASc score. Show less
Kimura, Y.; Riva, M. de; Ebert, M.; Glashan, C.; Wijnmaalen, A.P.; Piers, S.R.; ... ; Zeppenfeld, K. 2023
Background: In dilated cardiomyopathy (DCM), outcome after catheter ablation of ventricular tachycardia (VT) is modest, compared with ischemic heart disease (IHD). Pleomorphic VT (PL-VT) has been... Show moreBackground: In dilated cardiomyopathy (DCM), outcome after catheter ablation of ventricular tachycardia (VT) is modest, compared with ischemic heart disease (IHD). Pleomorphic VT (PL-VT) has been associated with fibrotic remodeling and end-stage heart failure in IHD. The prognostic role of PL-VT in DCM is unknown. Methods: Consecutive IHD (2009-2016) or DCM (2008-2018) patients undergoing ablation for monomorphic VT were included. PL-VT was defined as >= 1 spontaneous change of the 12-lead VT-morphology during the same induced VT episode. Patients were followed for VT recurrence and mortality. Results: A total of 247 patients (86% men; 6313 years; IHD n=152; DCM n=95) underwent ablation for monomorphic VT. PL-VT was observed in 22 and 29 patients with IHD and DCM, respectively (14% versus 31%, P=0.003). In IHD, PL-VT was associated with lower LVEF (28 +/- 9% versus 34 +/- 12%, P=0.02) and only observed in those with LVEF<40%. In contrast, in DCM, PL-VT was not related to LVEF and induced in 27% of patients with LVEF>40%. During a median follow-up of 30 months, 79 (32%) patients died (IHD 48; DCM 31; P=0.88) and 120 (49%) had VT recurrence (IHD 59; DCM 61; P<0.001). PL-VT was associated with mortality in IHD but not in DCM. In IHD, VT recurrence was independently associated with LVEF, number of induced VTs, and procedural noncomplete success. Of note, in DCM, PL-VT (HR, 2.62 [95% CI, 1.47-4.69]), pathogenic mutation (HR, 2.13 [95% CI, 1.16-3.91]), and anteroseptal VT substrate (HR, 1.75 [95% CI, 1.00-3.07]) independently predicted VT recurrence. Conclusions: In IHD, PL-VT was associated with low LVEF and mortality. In DCM, PL-VT was not associated with mortality but a predictor of VT recurrence independent from LVEF. PL-VT in DCM may indicate a specific arrhythmic substrate difficult to control by current ablation techniques. Show less
Suboptimal diet is a major modifiable risk factor in cardiovascular disease. Governments, individuals, educational institutes, healthcare facilities and the industry all share the responsibility to... Show moreSuboptimal diet is a major modifiable risk factor in cardiovascular disease. Governments, individuals, educational institutes, healthcare facilities and the industry all share the responsibility to improve dietary habits. Healthcare facilities in particular present a unique opportunity to convey the importance of healthy nutrition to patients, visitors and staff. Guidelines on cardiovascular disease do include policy suggestions for population-based approaches to diet in a broad list of settings. Regrettably, healthcare facilities are not explicitly included in this list. The authors propose to explicitly include healthcare facilities as a setting for policy suggestions in the current and future ESC Guidelines for cardiovascular disease prevention in clinical practice. (c) 2022 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). Show less
Endt, V.H.W. van der; Milders, J.; Vries, B.B.L.P. de; Trines, S.A.; Groenwold, R.H.H.; Dekkers, O.M.; ... ; Jong, Y. de 2022
Aims Multiple risk scores to predict ischaemic stroke (IS) in patients with atrial fibrillation (AF) have been developed. This study aims to systematically review these scores, their validations... Show moreAims Multiple risk scores to predict ischaemic stroke (IS) in patients with atrial fibrillation (AF) have been developed. This study aims to systematically review these scores, their validations and updates, assess their methodological quality, and calculate pooled estimates of the predictive performance.Methods and results We searched PubMed and Web of Science for studies developing, validating, or updating risk scores for IS in AF patients. Methodological quality was assessed using the Prediction model Risk Of Bias ASsessment Tool (PROBAST). To assess discrimination, pooled c-statistics were calculated using random-effects meta-analysis. We identified 19 scores, which were validated and updated once or more in 70 and 40 studies, respectively, including 329 validations and 76 updates-nearly all on the CHA(2)DS(2)-VASc and CHADS(2). Pooled c-statistics were calculated among 6 267 728 patients and 359 373 events of IS. For the CHA(2)DS(2)-VASc and CHADS(2), pooled c-statistics were 0.644 [95% confidence interval (CI) 0.635-0.653] and 0.658 (0.644-0.672), respectively. Better discriminatory abilities were found in the newer risk scores, with the modified-CHADS(2) demonstrating the best discrimination [c-statistic 0.715 (0.674-0.754)]. Updates were found for the CHA(2)DS(2)-VASc and CHADS(2) only, showing improved discrimination. Calibration was reasonable but available for only 17 studies. The PROBAST indicated a risk of methodological bias in all studies.Conclusion Nineteen risk scores and 76 updates are available to predict IS in patients with AF. The guideline-endorsed CHA(2)DS(2)-VASc shows inferior discriminative abilities compared with newer scores. Additional external validations and data on calibration are required before considering the newer scores in clinical practice. Show less
Harlaar, N.; Oudeman, M.A.; Trines, S.A.; Ruiter, G.S. de; Mertens, B.J.; Khan, M.; ... ; Brakel, T.J. van 2021
OBJECTIVES: Catheter ablation of long-standing persistent atrial fibrillation (LSPAF) remains challenging, with suboptimal success rates obtained following multiple procedures. Thoracoscopic... Show moreOBJECTIVES: Catheter ablation of long-standing persistent atrial fibrillation (LSPAF) remains challenging, with suboptimal success rates obtained following multiple procedures. Thoracoscopic ablation has shown effective at creating transmural lesions around the pulmonary veins and box; however, long-term rhythm follow-up data are lacking. This study aims, for the first time, to assess the long-term outcomes of thoracoscopic pulmonary vein and box ablation in LSPAF.METHODS: Rhythm follow-up consisted of continuous rhythm monitoring using implanted loop recorders or 24-h Holter recordings. Rhythm status and touch-up interventions were assessed up to 5 years.RESULTS: Seventy-seven patients with symptomatic LSPAF underwent thoracoscopic ablation in 2 centres. Freedom from atrial arrhythmias at 5 years was 50% following a single thoracoscopic procedure and 68% allowing endocardial touch-up procedures (performed in 21% of patients). The mean atrial fibrillation burden in patients with continuous monitoring was reduced from 100% preoperatively to 0.1% at the end of the blanking period and 8.0% during the second year. Antiarrhythmic drug use decreased from 49.4% preoperative to 12.1% and 14.3% at 2 and 5 years, respectively (P < 0.001). Continuous rhythm monitoring resulted in higher recurrence detection rates compared to 24-h Holter monitoring at 2-year follow-up (hazard ratio: 6.5, P= 0.003), with comparable recurrence rates at 5-year follow-up.CONCLUSIONS: Thoracoscopic pulmonary vein and box isolation are effective in long-term restoration of sinus rhythm in LSPAF, especially when complemented by endocardial touch-up procedures, as demonstrated by the 68% freedom rate at 5 years. Continuous rhythm monitoring revealed earlier, but not more numerous documentation of recurrences at 5-year follow-up. Show less
Riva, M. de; Naruse, Y.; Ebert, M.; Watanabe, M.; Scholte, A.J.; Wijnmaalen, A.P.; ... ; Zeppenfeld, K. 2021
Aims In patients with post-myocardial infarction (post-MI) ventricular tachycardia (VT), the presence of myocardial calcification (MC) may prevent heating of a subepicardial VT substrate... Show moreAims In patients with post-myocardial infarction (post-MI) ventricular tachycardia (VT), the presence of myocardial calcification (MC) may prevent heating of a subepicardial VT substrate contributing to endocardial ablation failure. The aims of this study were to assess the prevalence of MC in patients with post-MI VT and evaluate the impact of MC on outcome after endocardial ablation.Methods and results In 158 patients, the presence of MC was retrospectively assessed on fluoroscopy recordings in seven standard projections obtained during pre-procedural coronary angiograms. Myocardial calcification, defined as a distinct radiopaque area that moved synchronously with the cardiac contraction, was detected in 30 patients (19%). After endocardial ablation, only 6 patients (20%) with MC were rendered non-inducible compared with 56 (44%) without MC (P = 0.033) and of importance, 8 (27%) remained inducible for the clinical VT [compared with 9 (6%) patients without MC; P = 0.003] requiring therapy escalation. After a median follow-up of 31 months, 61 patients (39%) had VT recurrence and 47 (30%) died. Patients with MC had a lower survival free from the composite endpoint of VT recurrence or therapy escalation at 24-month follow-up (26% vs. 59%; P = 0.003). Presence of MC (HR 1.69; P = 0.046), a lower LV ejection fraction (HR 1.03 per 1% decrease; P = 0.017), and non-complete procedural success (HR 2.42; P = 0.002) were independently associated with a higher incidence of VT recurrence or therapy escalation.Conclusion Myocardial calcification was present in 19% of post-MI patients referred for VT ablation and was associated with a high incidence of endocardial ablation failure. Show less
Ebert, M.; Wijnmaalen, A.P.; Riva, M. de; Trines, S.A.; Androulakis, A.F.A.; Glashan, C.A.; ... ; Zeppenfeld, K. 2020
OBJECTIVES This study aimed to assess the frequency of (likely) pathogenic variants (LP/Pv) among dilated cardiomyopathy (DCM) ventricular tachycardia (VT) patients referred for CA and their impact... Show moreOBJECTIVES This study aimed to assess the frequency of (likely) pathogenic variants (LP/Pv) among dilated cardiomyopathy (DCM) ventricular tachycardia (VT) patients referred for CA and their impact on procedural outcome and long-term prognosis.BACKGROUND The prevalence of genetic variants associated with monomorphic VT among DCM is unknown.METHODS Ninety-eight consecutive patients (age 56 +/- 15 years; 84% men, left ventricular ejection fraction [LVEF] 39 12%) referred for DCM-VT ablation were included. Patients underwent electroanatomical mapping and testing of >= 55 cardiomyopathy-related genes. Mapping data were analyzed for low-voltage areas and abnormal potentials. LP/Pv-positive (LP/Pv+) patients were compared with LP/Pv-negative (LP/Pv-) patients and followed for VT recurrence and mortality.RESULTS In 37 (38%) patients, LP/Pv were identified, most frequently LMNA (n = 11 of 37, [30%]), 17N (n = 6 of 37, [16%]), PLN (n = 6 of 37, [16%]), SCN5A (n = 3 of 37, [8%]), RBM20 (n = 2 of 37, [5%]) and DSP (n = 2 of 37, [5%]). LP/Pv+ carriers had tower LVEF (35 + 13% vs. LP/Pv-: 42 11%; p 0.005) and were less often men (n 27 [73%] vs. n 55 [90%] p 0.03). After a median follow-up of 2.4 years (interquartile range: 0.9 to 4.4 years), 63 (64%) patients had VT recurrence (LP/Pv+: 30 of 37 [81%] vs. LP/Pv-: 33 of 61 [54%]; p = 0.007). Twenty-eight patients (29%) died (LP/Pv +: 19 of 37 [51%] vs. LP/Pv-: 9 of 61 [15%]; p < 0.001). The cumulative 2-year VT-free survival was 41% in the total cohort (LP/Pv+: 16% vs. LP/Pv-: 54%; p 0.001). The presence of LP/Pv (hazard ratio: 1.9; 95% confidence interval: 1.1 to 3.4; p = 0.02) and unipolar low-voltage area size/cm(2) increase (hazard ratio: 2.5; 95% confidence interval: 1.6 to 4.0; p < 0.001) were associated with a decreased 2-year VT-free survival.CONCLUSIONS In patients with DCM-VT, a genetic cause is frequently identified. LP/Pv+ patients have a tower LVEF and more extensive VT substrates, which, in combination with disease progression, may contribute to the poor prognosis. Genetic testing in patients with DCM-VT should therefore be recommended. (C) 2020 by the American College of Cardiology Foundation. Show less
Chu, G.; Seelig, J.; Trinks-Roerdink, E.M.; Alem, A.P. van; Alings, M.; Bemt, B. van den; ... ; Huisman, M.V. 2020
Introduction Anticoagulation therapy is pivotal in the management of stroke prevention in atrial fibrillation (AF). Prospective registries, containing longitudinal data are lacking with detailed... Show moreIntroduction Anticoagulation therapy is pivotal in the management of stroke prevention in atrial fibrillation (AF). Prospective registries, containing longitudinal data are lacking with detailed information on anticoagulant therapy, treatment adherence and AF-related adverse events in practice-based patient cohorts, in particular for non-vitamin K oral anticoagulants (NOAC). With the creation of DUTCH-AF, a nationwide longitudinal AF registry, we aim to provide clinical data and answer questions on the (anticoagulant) management over time and of the clinical course of patients with newly diagnosed AF in routine clinical care. Within DUTCH-AF, our current aim is to assess the effect of non-adherence and non-persistence of anticoagulation therapy on clinical adverse events (eg, bleeding and stroke), to determine predictors for such inadequate anticoagulant treatment, and to validate and refine bleeding prediction models. With DUTCH-AF, we provide the basis for a continuing nationwide AF registry, which will facilitate subsequent research, including future registry-based clinical trials.Methods and analysis The DUTCH-AF registry is a nationwide, prospective registry of patients with newly diagnosed 'non-valvular' AF. Patients will be enrolled from primary, secondary and tertiary care practices across the Netherlands. A target of 6000 patients for this initial cohort will be followed for at least 2 years. Data on thromboembolic and bleeding events, changes in antithrombotic therapy and hospital admissions will be registered. Pharmacy-dispensing data will be obtained to calculate parameters of adherence and persistence to anticoagulant treatment, which will be linked to AF-related outcomes such as ischaemic stroke and major bleeding. In a subset of patients, anticoagulation adherence and beliefs about drugs will be assessed by questionnaire.Ethics and dissemination This study protocol was approved as exempt for formal review according to Dutch law by the Medical Ethics Committee of the Leiden University Medical Centre, Leiden, the Netherlands. Results will be disseminated by publications in peer-reviewed journals and presentations at scientific congresses. Show less
Harlaar, N.; Verberkmoes, N.J.; Voort, P.H. van der; Trines, S.A.; Verstraeten, S.E.; Mertens, B.J.A.; ... ; Brakel, T.J. van 2020
Objective: To compare clinical outcomes of clamping devices and linear nonclamping devices for isolation of the posterior left atrium (box) in thoracoscopic ablation of long-standing persistent... Show moreObjective: To compare clinical outcomes of clamping devices and linear nonclamping devices for isolation of the posterior left atrium (box) in thoracoscopic ablation of long-standing persistent atrial fibrillation.Methods: Eighty patients who underwent thoracoscopic pulmonary vein and box isolation using a bipolar clamping device (42 patients) or bipolar nonclamping device (38 patients) to create the roof/inferior lesions for box isolation were included from 2 centers. Follow-up consisted of 24-hour Holter at regular intervals. Freedom from AF during 1-year follow-up and catheter repeat interventions were compared between groups.Results: Acute intraoperative electrical isolation of the box compartment was significantly higher in the clamping group than in the nonclamping group (100% and 79%, respectively, P <.01). At 1-year follow-up, 91% of the clamping group and 79% of the nonclamping group were in sinus rhythm. During 1-year follow-up, recurrence rates did not significantly differ between the 2 groups (P = .08). Repeat catheter interventions were required in 10% of the clamping group and 21% of the nonclamping group (P = .15).Conduction gaps in the roof or inferior lesions were found in 1 patient (2%) in the clamping group versus 4 patients (11%) in the nonclamping group (P = .13). Conclusions: Thoracoscopic pulmonary vein and box isolation are highly effective in restoring sinus rhythm in long-standing persistent atrial fibrillation on short-term follow-up. Comparison of clamping and nonclamping devices revealed lower rates of intraoperative exit block of the box in the nonclamping group. However, this did not translate into a significant difference in atrial fibrillation freedom at short-term (1-year) follow-up. Show less
Background: Atrial fibrillation (AF), sternal wound infection, and cardiac decompensation are complications that can occur after cardiac surgery. Early detection of these complications is... Show moreBackground: Atrial fibrillation (AF), sternal wound infection, and cardiac decompensation are complications that can occur after cardiac surgery. Early detection of these complications is clinically relevant, as early treatment is associated with better clinical outcomes. Remote monitoring with the use of a smartphone (mobile health [mHealth]) might improve the early detection of complications after cardiac surgery.Objective: The primary aim of this study is to compare the detection rate of AF diagnosed with an mHealth solution to the detection rate of AF diagnosed with standard care. Secondary objectives include detection of sternal wound infection and cardiac decompensation, as well as assessment of quality of life, patient satisfaction, and cost-effectiveness.Methods: The Box 2.0 is a study with a prospective intervention group and a historical control group for comparison. Patients undergoing cardiac surgery at Leiden University Medical Center are eligible for enrollment. In this study, 365 historical patients will be used as controls and 365 other participants will be asked to receive either The Box 2.0 intervention consisting of seven home measurement devices along with a video consultation 2 weeks after discharge or standard cardiac care for 3 months. Patient information will be analyzed according to the intention-to-treat principle. The Box 2.0 devices include a blood pressure monitor, thermometer, weight scale, step count watch, single-lead electrocardiogram (ECG) device, 12-lead ECG device, and pulse oximeter.Results: The study started in November 2018. The primary outcome of this study is the detection rate of AF in both groups. Quality of life is measured with the five-level EuroQol five-dimension (EQ-5D-5L) questionnaire. Cost-effectiveness is calculated from a society perspective using prices from Dutch costing guidelines and quality of life data from the study. In the historical cohort, 93.9% (336/358) completed the EQ-5D-5L and patient satisfaction questionnaires 3 months after cardiac surgery.Conclusions: The rationale and design of a study to investigate mHealth devices in postoperative cardiac surgery patients are presented. The first results are expected in September 2020. Show less
Atrial fibrillation (AF) is the most common cardiac arrhythmia in clinical practice with a large socioeconomic impact due to its associated morbidity, mortality, reduction in quality of life and... Show moreAtrial fibrillation (AF) is the most common cardiac arrhythmia in clinical practice with a large socioeconomic impact due to its associated morbidity, mortality, reduction in quality of life and health care costs. Currently, antiarrhythmic drug therapy is the first line of treatment for most symptomatic AF patients, despite its limited efficacy, the risk of inducing potentially life-threating ventricular tachyarrhythmias as well as other side effects. Alternative, in-hospital treatment modalities consisting of electrical cardioversion and invasive catheter ablation improve patients' symptoms, but often have to be repeated and are still associated with serious complications and only suitable for specific subgroups of AF patients. The development and progression of AF generally results from the interplay of multiple disease pathways and is accompanied by structural and functional (e.g., electrical) tissue remodeling. Rational development of novel treatment modalities for AF, with its many different etiologies, requires a comprehensive insight into the complex pathophysiological mechanisms. Monolayers of atrial cells represent a simplified surrogate of atrial tissue well-suited to investigate atrial arrhythmia mechanisms, since they can easily be used in a standardized, systematic and controllable manner to study the role of specific pathways and processes in the genesis, perpetuation and termination of atrial arrhythmias. In this review, we provide an overview of the currently available two- and three-dimensional multicellular in vitro systems for investigating the initiation, maintenance and termination of atrial arrhythmias and AF. This encompasses cultures of primary (animal-derived) atrial cardiomyocytes (CMs), pluripotent stem cell-derived atrial-like CMs and (conditionally) immortalized atrial CMs. The strengths and weaknesses of each of these model systems for studying atrial arrhythmias will be discussed as well as their implications for future studies. Show less
Background The influence of risk factors on atrial fibrillation (AF) ablation recurrence is increasingly recognized. We present a sub-analysis of the European Society of Cardiology-European Heart... Show moreBackground The influence of risk factors on atrial fibrillation (AF) ablation recurrence is increasingly recognized. We present a sub-analysis of the European Society of Cardiology-European Heart Rhythm Association-European Society of Cardiology AF ablation long-term registry on the effect of traditional risk factors for AF on postablation recurrence, reablation, and complications using real-world data. Methods Risk factors for AF were defined as body mass index >= 27 kg/m(2), hypertension, chronic obstructive pulmonary disease, diabetes, alcohol >= 2 units/day, sleep apnea, smoking, no/occasional sports activity, moderate/severe mitral or aortic valve disease, any cardiomyopathy, peripheral vascular disease, chronic kidney disease, heart failure, coronary artery disease/infarction, and previous pacemaker/defibrillator implant. Patients were divided in two groups with >= 1 or without risk factors. Primary outcomes were arrhythmia recurrence after blanking period, reablation, and adverse events or death. Differences between the groups and the influence of individual risk factors were analyzed using multivariate Cox regression. Results Three thousand sixty nine patients were included; 217 patients were without risk factors. Risk factor patients were older (58.4 vs 54.1 years), more often female (32% vs 19.8%) and had more often persistent AF (27.2% vs 23.5%). In a multivariate analysis, patients without risk factors had a hazard ratio of 0.70 (95% CI 0.49-0.99) for recurrence compared to risk factor patients. The multivariate hazard ratios for reablation or adverse events/death were not different between the two groups. Hypertension and body mass index were univariate predictors of recurrence. Conclusions Patients with >= 1 risk factor had a 30% higher risk for arrhythmia recurrence after ablation, but no differences in risk for repeat ablations and adverse events or death. Show less
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... Show moreIntroduction 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 degrees 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. Show less
Aims Pulmonary vein isolation (PVI), the standard for atrial fibrillation (AF) ablation, is most commonly applied with radiofrequency (RF) energy, although cryoballoon technology (CRYO) has gained... Show moreAims Pulmonary vein isolation (PVI), the standard for atrial fibrillation (AF) ablation, is most commonly applied with radiofrequency (RF) energy, although cryoballoon technology (CRYO) has gained widespread use. The aim was to compare the second-generation cryoballoon and the irrigated RF energy regarding outcomes and safety.Methods and results Of 4657 patients undergoing their first AF ablation, 982 with CRYO and 3675 with RF energy were included from the Swedish catheter ablation registry and the Atrial Fibrillation Ablation Long-Term registry of the European Heart Rhythm Association of the European Society of Cardiology. The primary endpoint was repeat AF ablation. The major secondary endpoints included procedural duration, tachyarrhythmia recurrence, and complication rate. The re-ablation rate after 12 months was significantly lower in the CRYO vs. the RF group, 7.8% vs. 11%, P=0.005, while freedom from arrhythmia recurrence (30 s duration) did not differ between the groups, 70.2 % vs. 68.2%, P=0.44. The result was not influenced by AF type and lesion sets applied. In the Cox regression analysis, paroxysmal AF had significantly lower risk for re-ablation with CRYO, hazard ratio 0.56 (P=0.041). Procedural duration was significantly shorter with CRYO than RF, (meanSD) 133.6 +/- 45.2 min vs. 174.6 +/- 58.2 min, P<0.001. Complication rates were similar; 53/982 (5.4%) vs. 191/3675 (5.2%), CRYO vs. RF, P=0.806.Conclusion The lower re-ablation rates and shorter procedure times observed with the cryoballoon as compared to RF ablation may have important clinical implications when choosing AF ablation technique despite recognized limitations with registries. Show less
Background Atrial fibrillation (AF) promotes atrial remodeling that in turn promotes AF perpetuation. The aim of our study is to investigate the impact of AF history length on 1-year outcome of AF... Show moreBackground Atrial fibrillation (AF) promotes atrial remodeling that in turn promotes AF perpetuation. The aim of our study is to investigate the impact of AF history length on 1-year outcome of AF catheter ablation in a cohort of patients enrolled in the Atrial Fibrillation Ablation Registry. Methods We described the real-life clinical epidemiology, therapeutic strategies, and the short- and mid-term outcomes of 1948 patients (71.9% with paroxysmal AF) undergoing AF ablation procedures, stratified according to AF history duration (<2 years or >= 2 years). Results The mean AF history duration was 46.2 +/- 57.4 months, 592 patients had an AF history duration <2 years (mean 10.2 +/- 5.9 months), and 1356 patients >= 2 years (mean 75.5 +/- 63.5 months) (P < 0.001). Patients with AF history duration <2 years were younger; had a lower incidence of hypertension, coronary artery disease, and hypertrophic cardiomyopathy; and had a lower CHA(2)DS(2)-VaSc Score. At 1 year, the logrank test showed a lower incidence of AF recurrence in patients with AF history duration <2 years (28.9%) than in patients with AF history duration >= 2 years (34.0%) (P = 0.037). AF history duration >= 2 years, overall ablation procedure duration, hypertension, and chronic kidney disease were all predictors of recurrences after the blanking period. Conclusions In this multicenter registry, performing catheter ablation in patients with an AF history >= 2 years was associated with higher rates of AF recurrences at 1 year. Since cumulative time in AF in not necessarily equivalent to AF history, its role remains to be clarified. Show less
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... Show moreOBJECTIVES 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) (C) 2019 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation. Show less
