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Many patients with atrial fibrillation (AF) experience stroke, cardiovascular death and other cardiovascular complications. Early rhythm control can prevent some of these events but is often withheld from elderly patients with multiple comorbidities. Catheter ablation is the most effective rhythm-controlling therapy but has mainly been tested in younger patients. The German Atrial Fibrillation Network (AFNET) initiated the EASThigh – AFNET 11 trial to investigate whether early catheter ablation can reduce outcomes in patients with AF and comorbidities. EASThigh – AFNET 11 enrolled the first patient on 14.10.2024.

Atrial fibrillation (AF) epidemic affects the health of a growing number of people worldwide. Patients with AF are at risk of stroke, heart failure, death and dementia. Many patients develop AF in old age, and older people with cardiovascular comorbidities are at highest risk of AF-related complications.

The EAST – AFNET 4 trial, successfully completed in 2020, and subsequent sub-analyses demonstrated that systematic rhythm control therapy, initiated early in all patients using antiarrhythmic drugs or AF ablation, can reduce AF-related complications compared to usual care (1). These findings and subsequent analyses by others shifted the AF treatment paradigm towards earlier and broader use of rhythm control therapy.

Prespecified secondary analyses of the EAST – AFNET 4 data suggest that patients with AF and a high comorbidity burden benefit most from early rhythm control (2). The outcome-reducing effect of early rhythm control is mediated by attaining sinus rhythm (3). AF ablation targeting the pulmonary veins is the most effective rhythm control therapy and is therefore an attractive rhythm control therapy in patients with a high comorbidity burden who need multiple other medications and are at high risk of recurrent AF. Therefore, the Early atrial fibrillation Ablation for STroke prevention in patients with high comorbidity burden (EASThigh – AFNET 11) trial evaluates early AF ablation targeting the pulmonary veins as a first-line rhythm control therapy in elderly patients with multiple comorbidities, defined by a CHA2DS2VASc score of 4 or more. All participants will be randomized 1:1 to either early AF ablation using established single-shot devices or usual care consisting of anticoagulation and guideline-compliant treatment of existing concomitant diseases. EASThigh – AFNET 11 plans to randomize approximately 2350 patients in 200 sites in Europe, Canada and Australia. The primary outcome is a composite of cardiovascular death, stroke and hospitalization due to heart failure. Safety outcomes include ablation-related complications and mortality.

Rhythm control therapy, and especially AF ablation, is still not often used in elderly patients with AF and comorbidities. The trial will determine the safety and effectiveness of early AF ablation in this understudied population. While AF ablation is a mature technology, there are few controlled trials evaluating the safety of AF ablation in elderly patients with AF and comorbidities. The EASThigh – AFNET 11 investigators intend to fill this evidence gap.

Prof. Paulus Kirchhof, University Medical Center Eppendorf (UKE), Hamburg, Germany, international chief investigator of EASThigh – AFNET 11 and chair of the AFNET board, clarifies the role of catheter ablation: “The outcome-reducing effect of early rhythm control in the EAST – AFNET 4 trial mainly relied on the safe use of established antiarrhythmic drugs. EASThigh – AFNET 11 evaluates a more effective rhythm control therapy, AF ablation. This is a logical and important next step to define the role of early AF ablation to help our patients with AF.” 

Prof. Andreas Goette, St. Vincenz Hospital Paderborn, Germany, member of the EASThigh – AFNET 11 steering committee and of the AFNET board, expresses the expectations of the study as follows: “The results will inform practice guidelines and routine patient care, helping to define the best treatment for patients with AF and a high comorbidity burden. The results of the EASThigh – AFNET 11 trial have great potential to contribute to healthier ageing in a large population at increased risk of premature death, stroke, and heart failure.”

Dr. Andreas Rillig, University Medical Center Eppendorf (UKE), Hamburg, Germany, and co-chief investigator of the EASThigh – AFNET 11 trial states: “To maximize safety and warrant highly consistent efficacy the steering committee decided that early AF ablation will be delivered using single-shot cryoballoon-based isolation of the pulmonary veins in the trial. EASThigh – AFNET 11 is a team effort, thanks to which we can enroll the first patient in the trial today.”

EASThigh – AFNET 11, like EAST – AFNET 4, is an investigator-initiated trial comparing two approved treatment strategies in patients with AF. Sponsor of the trial is AFNET. Following an endorsement by the Global Cardiovascular Research Funders Forum, the trial is currently funded by the Else Kröner-Fresenius-Stiftung (EKFS), other public funders, and by Medtronic. Steering committee members include Paulus Kirchhof AFNET and Hamburg, Germany, Andreas Rillig, Hamburg, Germany, Jason Andrade, Vancouver, Canada, Andreas Goette, AFNET and Paderborn, Germany, José Merino, Madrid, Spain, Andreas Metzner, Hamburg, Jens Cosedis Nielsen, Aarhus, Denmark, Andre Ng, Leicester, UK, Sam Riahi, Aalborg, Denmark, Prash Sanders, Adelaide, Australia, Ulrich Schotten, AFNET and Maastricht, Netherlands, Kevin Vernooy, Maastricht, Stephan Willems, AFNET and Hamburg, Germany, Antonia Zapf, AFNET and Hamburg, Germany and a patient representative who contributes the perspective of those affected.

References

1. Kirchhof P, Camm AJ, Goette A, Brandes A, Eckardt L, Elvan A, Fetsch T, van Gelder IC, Haase D, Haegeli LM, Hamann F, Heidbüchel H, Hindricks G, Kautzner J, Kuck K-H, Mont L, Ng GA, Rekosz J, Schön N, Schotten U, Suling A, Taggeselle J, Themistoclakis S, Vettorazzi E, Vardas P, Wegscheider K, Willems S, Crijns HJGM, Breithardt G, for the EAST–AFNET 4 trial investigators. Early rhythm control therapy in patients with atrial fibrillation. N Engl J Med 2020; 383:1305-1316. DOI: 10.1056/NEJMoa2019422
2. Rillig A, Borof K, Breithardt G, Camm AJ, Crijns HJGM, Goette A, Kuck KH, Metzner A, Vardas P, Vettorazzi E, Wegscheider K, Zapf A, Kirchhof P. Early rhythm control in patients with atrial fibrillation and high comorbidity burden. Circulation. 2022 Sep 13;146(11):836-847. DOI: 10.1161/CIRCULATIONAHA.122.060274
3. Eckardt L et al. Attaining sinus rhythm mediates improved outcome with early rhythm control therapy of atrial fibrillation: the EAST – AFNET 4 trial. Eur Heart J, 2022 Oct 21;43(40):4127-4144. DOI: 10.1093/eurheartj/ehac471

Registration: NCT06324188.

About the EAST – AFNET 4 trial

EAST – AFNET 4 was completed in 2020. It was an investigator-initiated trial (IIT) that compared two different treatment strategies in atrial fibrillation (AF). The EAST – AFNET 4 trial tested whether an early, comprehensive rhythm control therapy can prevent adverse cardiovascular outcomes in patients with AF compared to usual care.

A total of 2789 patients with early AF (diagnosed less than a year ago) and at least two cardiovascular conditions (approximating a CHA₂DS₂-VASc score >=2) were enrolled by 135 sites in 11 countries during 2011 to 2016. Patients were randomized 1:1 to early rhythm control therapy or usual care, stratified by sites. Patients in both groups received guideline-recommended treatment for underlying cardiovascular conditions, anticoagulation, and rate control.

All patients in the early rhythm control group received antiarrhythmic drugs or catheter ablation after randomization (chosen by the local study teams). Rhythm control therapy was escalated with AF ablation and/or antiarrhythmic drugs when recurrent AF was documented clinically or by ECG, including monitoring with patient-operated ECG devices.

Patients in the usual care group were initially managed with rate control. Rhythm control therapy was only used to improve AF-related symptoms despite optimal rate control, following current guidelines.

Several publications reported the effects of early rhythm control therapy in different subpopulations and the interaction of early rhythm control therapy with genetic data and biomolecule concentrations in the EAST – AFNET 4 biomolecule study.

EAST – AFNET 4 sub-analyses

• Rillig A et al. Early rhythm control therapy in patients with heart failure. Circulation 2021;144(11):845-858. DOI: 10.1161/CIRCULATIONAHA.121.056323
• Metzner A et al. Anticoagulation, therapy of concomitant conditions, and early rhythm control therapy: a detailed analysis of treatment patterns in the EAST - AFNET 4 trial. Europace 2022; 24:552–564. DOI: 10.1093/europace/euab200
• Willems S et al. Systematic, early rhythm control therapy equally improves outcomes in asymptomatic and symptomatic patients with atrial fibrillation: the EAST-AFNET 4 Trial. Eur Heart J. 2022; 43:1219-1230. DOI: 10.1093/eurheartj/ehab593
• Goette A et al. Presenting Pattern of Atrial Fibrillation and Outcomes of Early Rhythm Control Therapy. J Am Coll Cardiol. 2022; 80:283-95. DOI: 10.1016/j.jacc.2022.04.058
• Rillig A et al. Early rhythm control in patients with atrial fibrillation and high comorbidity burden. Circulation. 2022 Sep 13;146(11):836-847. DOI: 10.1161/CIRCULATIONAHA.122.060274
• Eckardt L et al. Attaining sinus rhythm mediates improved outcome with early rhythm control therapy of atrial fibrillation: the EAST – AFNET 4 trial. Eur Heart J, 2022 Oct 21;43(40):4127-4144. DOI: 10.1093/eurheartj/ehac471
• Jensen M et al. Early rhythm-control therapy for atrial fibrillation in patients with a history of stroke: a subgroup analysis of the EAST- AFNET 4 trial. Lancet Neurol 2023; 22: 45–54. DOI: 10.1016/PIIS1474-4422(22)00436-7 
• Van Gelder IC et al; EAST-AFNET 4 Trial Investigators. Sex Differences in Early Rhythm Control of Atrial Fibrillation in the EAST-AFNET 4 Trial. J Am Coll Cardiol. 2023 Feb 28;81(8):845-847. DOI: 10.1016/j.jacc.2022.12.011
• Gottschalk S et al. Cost- effectiveness of early rhythm-control versus usual care in atrial fibrillation care: an analysis based on the German subsample of the EAST-AFNET 4 trial. Europace 2023 May 19;25(5). DOI: 10.1093/europace/euad051
• Kany S et al. Association of genetic risk and outcomes in patients with early rhythm control therapy in atrial fibrillation: results from the EAST-AFNET4 study. Cardiovasc Res 2023 Aug 7;119(9):1799-1810. DOI: 10.1093/cvr/cvad027
• Fabritz L et al. Blood-based cardiometabolic phenotypes in atrial fibrillation and their associated risk: EAST-AFNET 4 biomolecule study. Cardiovasc Res 2024. DOI: 10.1093/cvr/cvae067     
• Rillig A et al. Safety and efficacy of long-term sodium channel blocker therapy for early rhythm control: the EAST-AFNET 4 trial. Europace 2024 Jun 3;26(6). DOI: 10.1093/europace/euae121
• Fabritz L et al. Biomarker-based prediction of sinus rhythm in atrial fibrillation patients: the EAST-AFNET 4 biomolecule study. Eur Heart J. 2024, published online 2 Sep 2024, doi: 10.1093/eurheartj/ehae611

About the Atrial Fibrillation NETwork (AFNET)

The Atrial Fibrillation NETwork is an interdisciplinary research network comprising scientists and physicians from hospitals and practices dedicated to improving the management of atrial fibrillation through coordinated research in Germany, Europe, and worldwide. Its main objective is to conduct high quality investigator-initiated clinical trials and registries on a national and international level as well as translational research projects. The AFNET continues the long-term activities of the network which has been funded by the German Federal Ministry of Research and Education over a decade. Since January 2015, specific projects and infrastructures of the AFNET are funded by the German Centre for Cardiovascular Research (DZHK), and some projects by EU research grants. AFNET has long expertise in the management of atrial fibrillation, but also provides support for work in other fields informing cardiovascular care. The results of 20 years of clinical and translational research improved the lives of patients with cardiovascular diseases and influenced treatment guidelines.

www.af-net.eu

Press Contact

Angelika Leute, PhD

Phone: +49 202 2623395

a.leute@t-online.de

Press release

A combined subgroup analysis of the similar trials NOAH – AFNET 6 (1) and ARTESiA (2) revealed: Patients with device-detected atrial fibrillation and concomitant vascular disease are at higher risk of stroke and cardiovascular events and may derive a greater benefit from oral anticoagulation than those without vascular disease. The finding was presented by AFNET Steering Committee member Prof. Renate Schnabel, University Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany, at the annual congress of the European Society of Cardiology (ESC) in London on 02.09.2024 and published in the European Heart Journal (3).

Device-detected atrial fibrillation (DDAF) are short and typically rare episodes of atrial fibrillation (AF) detected by pacemakers, defibrillators, or implanted loop recorders. Device-detected atrial fibrillation is found in every fifth patient with a cardiac implanted electronic device (4). Device-detected atrial fibrillation can lead to stroke, but the stroke risk in patients with device-detected atrial fibrillation appears lower than the stroke risk in patients with ECG-documented atrial fibrillation (1%/year).

Two recent trials, NOAH – AFNET 6 and ARTESiA, assessed the benefit of anticoagulation in patients with DDAF and stroke risk factors, but without ECG-documented AF. In both trials, patients were randomized either to anticoagulation (edoxaban in NOAH – AFNET 6 and apixaban in ARTESiA) or no anticoagulation in order to compare efficacy and safety outcomes in both groups.

NOAH – AFNET 6 (Non vitamin K antagonist Oral anticoagulants in patients with Atrial High-rate episodes), an investigator-initiated trial conducted by the AFNET, was terminated early due to an expected increase in bleeding events in patients with device-detected atrial fibrillation while the stroke preventing effect was smaller than expected (1). The weak effects of anticoagulation are also found in several subgroups including patients with long episodes of device-detected AF (5), patients with a high comorbidity burden (6), and patients with prior stroke (7).

ARTESiA (Apixaban for the Reduction of Thrombo-Embolism in Patients with Device-Detected Sub-Clinical Atrial Fibrillation) confirmed the low rate of stroke in patients with DDAF and demonstrated a small stroke-reducing effect of anticoagulation (2). A meta-analysis of NOAH – AFNET 6 and ARTESiA confirmed an increase in bleeding and detected a small reduction in ischemic strokes with anticoagulation (8).

Prof. Schnabel, leading investigator of the combined NOAH – AFNET 6 / ARTESiA sub-analysis presented now at the ESC congress, explained the background of this research: “About half of patients with device-detected atrial fibrillation have concomitant vascular disease, i.e. prior stroke or transient ischemic attack (TIA), coronary or peripheral vascular disease. The main goal of our pre-specified subgroup analysis was to assess whether vascular disease affects the efficacy and safety of oral anticoagulation therapy in patients with DDAF. The NOAH – AFNET 6 results were validated in a pre-specified secondary analysis of ARTESiA and meta-analysed.”  

About half of the study population of NOAH – AFNET 6 and ARTESiA (56% in NOAH – AFNET 6; 46% in ARTESiA) had concomitant vascular disease with an established indication for acetylsalicylic acid therapy. In these patients, stroke, myocardial infarction, systemic or pulmonary embolism, or cardiovascular death occurred less often with than without anticoagulation (3.9% versus 5.0% per patient-year in NOAH – AFNET 6 and 3.2% versus 4.4% per patient-year in ARTESiA). Without vascular disease, outcomes were equal with and without anticoagulation (2.7% per patient-year in NOAH – AFNET 6 and 2.3% per patient-year in ARTESiA in both groups). Meta-analysis found consistent results across both trials.

Anticoagulation increased major bleeding in a comparable fashion in patients with vascular disease (edoxaban 2.1% per patient-year; no anticoagulation 1.3% per patient-year; apixaban 1.7% per patient-year; no anticoagulation 1.1% per patient-year) and without vascular disease (edoxaban 2.2% per patient-year; no anticoagulation 0.6% per patient-year; apixaban 1.4% per patient-year; no anticoagulation 1.1% per patient-year).

AFNET board chair Prof. Paulus Kirchhof, UKE, principal investigator of the NOAH – AFNET 6 trial, concluded: “This combined NOAH – AFNET 6 and ARTESiA sub-analysis suggests different effects of anticoagulation in DDAF patients with and without concomitant vascular disease. In the high-risk subgroup of patient with DDAF and vascular disease, anticoagulation therapy appears to reduce thromboembolic events with a greater magnitude than in patients without vascular disease. These data can guide shared clinical decision making on anticoagulation therapy in patients with DDAF.”

References

(1) Kirchhof P, Toennis T, Goette A, et al. Anticoagulation with Edoxaban in Patients with Atrial High-Rate Episodes. N Engl J Med 2023; 389:1167-1179. DOI: 10.1056/NEJMoa2303062.

(2) Healey JS, Lopes RD, Granger CB et al. Apixaban for Stroke Prevention in Subclinical Atrial Fibrillation. N Engl J Med 2024; 390:107-117. DOI: 10.1056/NEJMoa2310234.

(3) Schnabel R et al. Anticoagulation in patients with device-detected atrial fibrillation with and without concomitant vascular disease – A combined secondary analysis of the NOAH-AFNET 6 and ARTESiA trials. Eur Heart J, accepted. DOI: 10.1093/eurheartj/ehae596

(4) Toennis T, Bertaglia E, Brandes A, et al. The influence of Atrial High Rate Episodes on Stroke and Cardiovascular Death - An update. Europace. 2023 Jul 4;25(7). DOI: 10.1093/europace/euad166.

(5) Becher N, Toennis T, Bertaglia E, et al. Anticoagulation with edoxaban in patients with long Atrial High-Rate Episodes ≥24 hours. Eur Heart J. 2024 Mar 7;45(10):837-849. DOI: 10.1093/eurheartj/ehad771

(6) Lip YH, Nikorowitsch J, Sehner S et al. Oral anticoagulation in device-detected atrial fibrillation: effects of age, sex, cardiovascular comorbidities, and kidney function on outcomes in the NOAH-AFNET 6 trial. Eur Heart J. 2024 April 9. DOI: 10.1093/eurheartj/ehae225

(7) Diener HC, Becher N, Sehner S, Toennis T et al. Anticoagulation in patients with device-detected atrial fibrillation with and without a prior stroke or transient ischemic attack. The NOAH-AFNET 6 trial. JAHA, in press.

(8) McIntyre WF, Benz AP, Becher N, et al. Direct Oral Anticoagulants for Stroke Prevention in Patients with Device-Detected Atrial Fibrillation: A Study-Level Meta-Analysis of the NOAH-AFNET 6 and ARTESiA Trials. Circulation. 2023. DOI: 10.1161/CIRCULATIONAHA.123.067512

Press Contact

Angelika Leute, PhD

Phone: +49 202 2623395

a.leute@t-online.de

Funding of the NOAH trial: AFNET, DZHK, Daiichi Sankyo

NOAH registration: NCT 02618577, ISRCTN 17309850

About the Atrial Fibrillation NETwork (AFNET)

The Atrial Fibrillation NETwork is an interdisciplinary research network comprising scientists and physicians from hospitals and practices dedicated to improving the management of atrial fibrillation through coordinated research in Germany, Europe, and worldwide. Its main objective is to conduct high quality investigator-initiated clinical trials and registries on a national and international level as well as translational research projects. The AFNET continues the long-term activities of the network which has been funded by the German Federal Ministry of Research and Education over a decade. Since January 2015, specific projects and infrastructures of the AFNET are funded by the German Centre for Cardiovascular Research (DZHK), and some projects by EU research grants. AFNET has long expertise in the management of atrial fibrillation, but also provides support for work in other fields informing cardiovascular care. The results of 20 years of clinical and translational research improved the lives of patients with cardiovascular diseases and influenced treatment guidelines.

www.af-net.eu

Press release

Low concentrations of three selected biomarkers in the blood of patients with atrial fibrillation identify patients with a high chance of attaining sinus rhythm. This is the main result of this analysis of the EAST – AFNET 4 biomolecule study. Today the findings have been presented by AFNET Steering Committee member Prof. Larissa Fabritz, University Medical Center Hamburg Eppendorf (UKE), Hamburg, Germany, at the annual congress of the European Society of Cardiology (ESC) in London and published in the European Heart Journal (1).

Atrial Fibrillation (AF) is the most common arrhythmia in senior people. AF often occurs in patients with cardiovascular comorbidities. Recurrent AF is determined by interactions between cardiovascular disease processes and rhythm-control therapy. Predictors of attaining sinus rhythm at follow-up are not well known.

The EAST – AFNET 4 (Early Treatment of Atrial Fibrillation for Stroke Prevention) trial demonstrated that early rhythm control – with antiarrhythmic drugs or atrial fibrillation ablation – delivered within one year after AF diagnosis improves outcomes in 2789 patients with early AF and cardiovascular risk factors compared to usual care (UC) over a 5-year follow-up time (2). A series of sub-analyses of the EAST – AFNET 4 data set verified the results for different sub-groups. (3-12). A biomolecule study embedded into the EAST – AFNET 4 trial found that biomolecule concentrations in the blood of AF patients can be used to identify patients at high and low cardiovascular risk (13).

Prof. Paulus Kirchhof, UKE, principal investigator of EAST – AFNET 4 and AFNET board chair, explained: “Predicting the chance of attaining sinus rhythm could help to identify patients requiring intensive rhythm control. The cardiovascular complication-reducing effect of early rhythm control therapy shown in the EAST – AFNET 4 study is mainly mediated by sinus rhythm at 12-month follow-up. In this new analysis, we wanted to assess which biomarkers can be used to predict sinus rhythm at 12 months in patients with atrial fibrillation with and without early rhythm control therapy.”

14 biomarkers reflecting AF-related cardiovascular disease processes were quantified in the blood of 1586 participants of the EAST – AFNET 4 biomolecule study. Three of these biomarkers – ANGPT2, BMP10, and NT-proBNP – proved to be linked to future sinus rhythm. Higher baseline concentrations of these biomarkers were independently associated with a lower chance of sinus rhythm at 12-months, and low concentrations of ANGPT2, BMP10 and NT-proBNP predicted sinus rhythm during follow-up. The predictive effect of NT-proBNP was reduced in patients receiving early rhythm control therapy (Pinteraction=0.033). Analysis of heart rhythm at 24 months and external validation confirmed the results.

Prof. Fabritz concluded: “Our findings suggest that the three biomarkers NT-proBNP, ANGPT2 and BMP10 identify patients with AF at high risk of not attaining sinus rhythm in the future. The disease processes related to the novel biomarkers ANGPT2 and BMP10 likely also contribute to future sinus rhythm with and without rhythm control therapy. NT-proBNP elevations interact with early rhythm control, potentially suggesting repeat assessment of NT-proBNP to monitor the effectiveness of rhythm control.”

The EAST – AFNET 4 biomolecule substudy was performed on an international level in cooperation with the European research consortia CATCH ME and MAESTRIA.

References

(1) Fabritz L, Al-Taie C, Borof K, Breithardt G, Camm J, Crijns HJGM, Cardoso VR, Chua W, van Elferen S, Eckardt L, Gkoutos G, Goette A, Guasch E, Hatem S, Metzner A, Mont L, Murukutla AV, Obergassel J, Rillig A, Sinner MF, Schnabel RB, Schotten U, Sommerfeld LC, Wienhues-Thelen U-H, Zapf A, Zeller T, Kirchhof P. Biomarker-based prediction of sinus rhythm in atrial fibrillation patients: the EAST-AFNET4 biomolecule study. Eur Heart J. accepted. DOI: 10.1093/eurheartj/ehae611

(2) Kirchhof P, Camm AJ, Goette A, Brandes A, Eckardt L, Elvan A, Fetsch T, van Gelder IC, Haase D, Haegeli LM, Hamann F, Heidbüchel H, Hindricks G, Kautzner J, Kuck K-H, Mont L, Ng GA, Rekosz J, Schön N, Schotten U, Suling A, Taggeselle J, Themistoclakis S, Vettorazzi E, Vardas P, Wegscheider K, Willems S, Crijns HJGM, Breithardt G, for the EAST–AFNET 4 trial investigators. Early rhythm control therapy in patients with atrial fibrillation. N Engl J Med 2020; 383:1305-1316. DOI: 10.1056/NEJMoa2019422

(3) Metzner A, Suling A, Brandes A, Breithardt G, Camm AJ, Crijns HJGM, Eckardt L, Elvan A, Goette A, Haegeli LM, Heidbuchel H, Kautzner J, Kuck KH, Mont L, Ng GA, Szumowski L, Themistoclakis S, van Gelder IC, Vardas P, Wegscheider K, Willems S, Kirchhof P. Anticoagulation, therapy of concomitant conditions, and early rhythm control therapy: a detailed analysis of treatment patterns in the EAST - AFNET 4 trial. EP Europace 2022; 24:552–564. DOI: 10.1093/europace/euab200

(4) Rillig A, Magnussen C, Ozga, Suling A, Brandes A, Breithardt G, Camm AJ, Crijns HJGM, Eckardt L, Elvan A, Goette A, Gulizia M, Haegeli LM, Heidbuchel H, Kuck KH, Ng GA, Szumowski L, van Gelder IC, Wegscheider K, Kirchhof P. Early rhythm control therapy in patients with heart failure. Circulation 2021;144(11):845-858. DOI: 10.1161/CIRCULATIONAHA.121.056323

(5) Willems S, Borof K, Brandes A, Breithardt G, Camm AJ, Crijns HJGM, Eckardt L, Gessler N, Goette A, Haegeli LM, Heidbuchel H, Kautzner J, Ng GA, Schnabel R, Suling A, Szumowski L, Themistoclakis S, Vardas P, van Gelder IC, Wegscheider K, Kirchhof P. Systematic, early rhythm control therapy equally improves outcomes in asymptomatic and symptomatic patients with atrial fibrillation: the EAST-AFNET 4 Trial. Eur Heart J. 2022; 43:1219-1230. DOI: 10.1093/eurheartj/ehab593.

(6) Goette a, Borof K, Breithardt G, Camm AJ, Crijns H, Kuck KH, Wegscheider K, Kirchhof P, MD. Presenting Pattern of Atrial Fibrillation and Outcomes of Early Rhythm Control Therapy. J Am Coll Cardiol. 2022; 80:283-95. DOI: 10.1016/j.jacc.2022.04.058

(7) Rillig A, Borof K, Breithardt G, Camm AJ, Crijns HJGM, Goette A, Kuck KH, Metzner A, Vardas P, Vettorazzi E, Wegscheider K, Zapf A, Kirchhof P. Early rhythm control in patients with atrial fibrillation and high comorbidity burden. Circulation. 2022 Sep 13;146(11):836-847. DOI: 10.1161/CIRCULATIONAHA.122.060274

(8) Jensen M, Suling A, Metzner A, Schnabel R, Borof K, Goette A, Haeusler KG, Zapf A, Wegscheider K, Fabritz L, Diener H-C, Thomalla G, Kirchhof P. Early rhythm-control therapy for atrial fibrillation in patients with a history of stroke: a subgroup analysis of the EAST- AFNET 4 trial. Lancet Neurol 2023; 22: 45–54. DOI: 10.1016/PIIS1474-4422(22)00436-7 

(9) Eckardt L, Sehner S, Suling A, Borof K, Breithardt G, Crijns HJGM, Goette A, Wegscheider K, Zapf A, Camm AJ, Metzner A, Kirchhof P. Attaining sinus rhythm mediates improved outcome with early rhythm control therapy of atrial fibrillation: the EAST – AFNET 4 trial. Eur Heart J, 2022 Oct 21;43(40):4127-4144. DOI: 10.1093/eurheartj/ehac471

(10) Van Gelder IC, Ekrami NK, Borof K, Fetsch T, Magnussen C, Mulder BA, Schnabel R, Wegscheider K, Rienstra M, Kirchhof P; EAST-AFNET 4 Trial Investigators. Sex Differences in Early Rhythm Control of Atrial Fibrillation in the EAST-AFNET 4 Trial. J Am Coll Cardiol. 2023 Feb 28;81(8):845-847. DOI: 10.1016/j.jacc.2022.12.011.

(11) Gottschalk S, Kany S, König H-H, Crijns HJGM, Vardas P, Camm AJ, Wegscheider K, Metzner A, Rillig A, Kirchhof P, Dams J. Cost- effectiveness of early rhythm-control versus usual care in atrial fibrillation care: an analysis based on the German subsample of the EAST-AFNET 4 trial. EP Europace 2023 May 19;25(5). DOI: 10.1093/europace/euad051

(12) Kany S, Al-Taie C, Roselli C, Pirruccello JP, Borof K, Reinbold C, Suling A, Krause L, Reissmann B, Schnabel R, Zeller T, Zapf A, Wegscheider K, Fabritz L, Ellinor PT, Kirchhof P. Association of genetic risk and outcomes in patients with early rhythm control therapy in atrial fibrillation: results from the EAST-AFNET4 study. Cardiovasc Res 2023 Aug 7;119(9):1799-1810. DOI: 10.1093/cvr/cvad027

(13) Fabritz L, Chua W, Cardoso VR, Al-Taie C, Borof K, Suling A, Krause L, Kany S, Magnussen C, Wegscheider K, Breithardt G, Crijns HJGM, Camm AJ, Gkoutos G, Ellinor PT, Goette A, Schotten U, Wienhues-Thelen U-H, Zeller T, Schnabel RB, Zapf A, Kirchhof P. Blood-based cardiometabolic phenotypes in atrial fibrillation and their associated risk: EAST-AFNET 4 biomolecule study. Cardiovasc Res 2024. DOI: 10.1093/cvr/cvae067

Press Contact

Angelika Leute, PhD

Phone: +49 202 2623395

a.leute@t-online.de

Follow us on X @afnet_ev and hashtag #EASTtrial.

Funding: AFNET, BMBF, DZHK, EHRA, Deutsche Herzstiftung, Abbott, Sanofi

About the EAST – AFNET 4 trial

EAST – AFNET 4 is an investigator-initiated trial (IIT) that compared two different treatment strategies in atrial fibrillation. The EAST – AFNET 4 trial tested whether an early, comprehensive rhythm control therapy can prevent adverse cardiovascular outcomes in patients with atrial fibrillation (AF) compared to usual care.

A total of 2789 patients with early AF (diagnosed less than a year ago) and at least two cardiovascular conditions (approximating a CHA₂DS₂-VASc score >=2) were enrolled by 135 sites in 11 countries during 2011 to 2016. Patients were randomized 1:1 to early rhythm control therapy or usual care, stratified by sites. Patients in both groups received guideline-recommended treatment for underlying cardiovascular conditions, anticoagulation, and rate control.

All patients in the early rhythm control group received antiarrhythmic drugs or catheter ablation after randomization (chosen by the local study teams). Rhythm control therapy was escalated with AF ablation and/or antiarrhythmic drugs when recurrent AF was documented clinically or by ECG, including monitoring with patient-operated ECG devices.

Patients in the usual care group were initially managed with rate control. Rhythm control therapy was only used to improve atrial fibrillation-related symptoms despite optimal rate control, following current guidelines.

About the Atrial Fibrillation NETwork (AFNET)

The Atrial Fibrillation NETwork is an interdisciplinary research network comprising scientists and physicians from hospitals and practices dedicated to improving the management of atrial fibrillation through coordinated research in Germany, Europe, and worldwide. Its main objective is to conduct high quality investigator-initiated clinical trials and registries on a national and international level as well as translational research projects. The AFNET continues the long-term activities of the network which has been funded by the German Federal Ministry of Research and Education over a decade. Since January 2015, specific projects and infrastructures of the AFNET are funded by the German Centre for Cardiovascular Research (DZHK), and some projects by EU research grants. AFNET has long expertise in the management of atrial fibrillation, but also provides support for work in other fields informing cardiovascular care. The results of 20 years of clinical and translational research improved the lives of patients with cardiovascular diseases and influenced treatment guidelines.

www.af-net.eu

Press release

An international cardiology working group has published a consensus report on atrial cardiomyopathy (1). 21 scientists from the rhythmological societies of Europe (European Heart Rhythm Association (EHRA)), North America (Heart Rhythm Society (HRS)), South America (Latin American Heart Rhythm Society (LAHRS)) and the Asia-Pacific region (Asia Pacific Heart Rhythm Society APHRS) were involved. The expert group was led by AFNET board member Prof. Andreas Goette, Paderborn, Germany. He presented the results on August 31, 2024 at the annual congress of the European Society of Cardiology (ESC) in London.

Atrial cardiomyopathy (AtCM) refers to pathological changes in the heart's atria, including the atrial muscle cells. They contribute to the development of atrial fibrillation, can cause blood clots and strokes and are therefore of fundamental clinical importance.

The consensus document developed by the international group of experts within two years summarizes the current knowledge on atrial cardiomyopathy – from basic pathophysiological research to innovative imaging and diagnostic procedures to recommendations for therapy. It is already the second global consensus paper on atrial cardiomyopathy. In 2016, an international group of experts met for the first time on this topic and proposed a standardized definition and classification scheme for atrial cardiomyopathies (2).

Prof. Goette, who also headed the working group at that time, explained the background of the expert consensus: “Our aim is to further improve the prevention and treatment of atrial fibrillation. Atrial fibrillation has many different causes. It is therefore important to describe the underlying pathology and develop tailored therapies for atrial fibrillation based on the actual causes. The classification enables individualized therapy that offers patients the best possible treatment success.” 

Since the first global consensus document eight years ago, research in the field of atrial cardiomyopathy has made considerable progress. Prof. Goette summarizes the key findings of the current consensus document, to which AFNET board member Prof. Ulrich Schotten, Maastricht, NL, also made a significant contribution: “There is a scientific update to the previous document from 2016. For the first time, we have introduced a clinically applicable grading of atrial cardiomyopathy with three stages (stage 1, 2 and 3) as a consensus. Imaging has also been presented in great detail in order to detect atrial pathologies non-invasively.”

However, there are still numerous knowledge gaps that need to be filled in the future. The experts therefore also made recommendations for future studies in the consensus paper.

The international consensus document was drawn up in collaboration with the European research consortium MAESTRIA. Prof. Dobromir Dobrev, Essen, Germany, Prof. Stéphane Hatem and Dr. Laurie Soulat-Dafour, both Paris, France, from the MAESTRIA consortium were involved.

References

(1) Goette A, Corradi D, Dobrev D, Aguinaga L, Cabrera JA, Chugh SS, de Groot JR, Soulat-Dufour L, Fenelon G, Hatem SN, Jalife J, Lin YJ, Lip GYH, Marcus GM, Murray KT, Pak HN, Schotten U, Takahashi N, Yamaguchi T, Zoghbi WA, Nattel S. Atrial Cardiomyopathy Revisited - Evolution of a Concept. A Clinical Consensus Statement of the 1 European Heart Rhythm Association (EHRA) of the ESC, the Heart Rhythm Society (HRS), the Asian 2 Pacific Heart Rhythm Association (APHRS), and the Latin American Heart Rhythm Society (LAHRS). Europace. 2024 Jul 30. DOI: 10.1093/europace/euae204

(2) Goette A, Kalman JM, Aguinaga L, Akar J, Cabrera JA, Chen SA, et al. EHRA/HRS/APHRS/SOLAECE expert consensus on atrial cardiomyopathies: definition, characterization, and clinical implication. Europace. 2016;18(10):1455-90. DOI: 10.1093/europace/euw161

About the Atrial Fibrillation NETwork (AFNET)

The Atrial Fibrillation NETwork is an interdisciplinary research network comprising scientists and physicians from hospitals and practices dedicated to improving the management of atrial fibrillation through coordinated research in Germany, Europe, and worldwide. Its main objective is to conduct high quality investigator-initiated clinical trials and registries on a national and international level as well as translational research projects. The AFNET continues the long-term activities of the network which has been funded by the German Federal Ministry of Research and Education over a decade. Since January 2015, specific projects and infrastructures of the AFNET are funded by the German Centre for Cardiovascular Research (DZHK), and some projects by EU research grants. AFNET has long expertise in the management of atrial fibrillation, but also provides support for work in other fields informing cardiovascular care. The results of 20 years of clinical and translational research improved the lives of patients with cardiovascular diseases and influenced treatment guidelines.

www.af-net.eu

Press Contact

Angelika Leute, PhD

Phone: +49 202 2623395

a.leute@t-online.de

AFNET associated events:

30th of August 2024, 10:27 am (CEST/German time) / 9:27 am (BST/British time): "Prague", Adjunct pharmacology in PCI: beyond antiplatelet therapy, the next chapter - discussion (Renate Schnabel)

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31st of August 2024, 10:09 am (CEST/German time) / 9:09 am (BST British time): “Digital Health Stage”, Artificial intelligence-based management of arrhythmias (Renate Schnabel)

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31st of August 2024, 5:15 pm (CEST/German time) / 4:15 pm (BST/British time): "Cairo", Update on atrial cardiomyopathy (Andreas Götte)

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https://esc365.escardio.org/ESC-Congress/sessions/12325

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