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Investigator-initiated trials led by the German Atrial Fibrillation NETwork (AFNET) provide evidence for several recommendations in the 2023 guideline for the diagnosis and management of atrial fibrillation (AF) developed by the American College of Cardiology (ACC) and the American Heart Association (AHA) in collaboration with the Heart Rhythm Society (HRS). The updated guideline has recently been published in Circulation (1).

During the past 20 years, AFNET delivered a set of investigator-initiated trials in the field of atrial fibrillation. The results of these trials now provide evidence for several recommendations in the 2023 American guideline for the diagnosis and management of AF.

The 10 take home messages emphasize the importance of early and continued management of patients with AF that should focus on maintaining sinus rhythm and minimizing AF burden. This new recommendation is based on the results of the EAST – AFNET 4 trial (2). The up-to-date guidance contains the following new recommendation: “In patients with a recent diagnosis of AF (<1 year), rhythm control can be useful to reduce hospitalizations, stroke, and mortality.” (Section 8.1 on rhythm control therapy). This means that early rhythm control therapy should be considered in all patients fulfilling the enrolment criteria of EAST – AFNET 4. Several sub-studies of EAST – AFNET 4 have influenced the recommendations on rhythm control in patients with atrial fibrillation and heart failure, in asymptomatic patients, and in other subgroups.

In patients with device-detected atrial fibrillation the risk of stroke appears low (1% per year) compared to patients with ECG-detected atrial fibrillation, even in patients with long episodes. Anticoagulation can slightly reduce stroke risk, but also increase major bleeding. This is the main finding of a sub-analysis of the NOAH – AFNET 6 trial presented by Dr Nina Becher, University Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany, in the late-breaking clinical trials session at the annual congress of the American Heart Association (AHA) in Philadelphia, USA, and published on 12th November, 2023, in the European Heart Journal (1).

On 12 and 13 September international experts in atrial fibrillation come together in Münster, Germany, to take part in the 9th AFNET/EHRA consensus conference. “Longer and better lives for patients with atrial fibrillation” is the pronounced intention of the two-day expert meeting which is jointly organized by the German Atrial Fibrillation Network (AFNET) and the European Heart Rhythm Association (EHRA) every two years.

Atrial fibrillation (AF) is the most common heart arrhythmia and a growing health problem in an aging society. It affects several million people in Europe and worldwide.

Prof. Paulus Kirchhof, Hamburg, Germany, one of the four chairpersons of the conference and board member of AFNET, explains the background of the expert meeting: “Despite improved treatment options AF patients still suffer strokes, heart failure, and premature death. There are various approaches to optimize care for AF patients. We set out to bring these approaches together. The AFNET/EHRA consensus conference provides a high-level expert forum to discuss recent advances in AF diagnosis and therapy.”

The clinical trial NOAH – AFNET 6 conducted by the German Atrial Fibrillation Network (AFNET), Münster, Germany, revealed: In patients with atrial high rate episodes (AHRE), but without ECG-documented atrial fibrillation (AF), oral anticoagulation increases bleeding without reducing strokes. Stroke rate was low in patients with AHRE with and without oral anticoagulation. The results were presented today at the annual congress of the European Society of Cardiology (ESC) in Amsterdam and published in the New England Journal of Medicine (1).

Atrial high-rate episodes are short and rare atrial arrhythmias that resemble atrial fibrillation detected by implanted pacemakers, defibrillators, and loop recorders that enable long-term monitoring of heart rhythm. AHRE are found in 10-30% of patients with implanted devices (2). AHRE episodes resemble atrial fibrillation. Therefore, patients with AHRE are often offered treatment with blood thinners (oral anticoagulation) without ECG-documented atrial fibrillation. So far, the efficacy and safety of oral anticoagulation has never been tested in patients with AHRE (2,3).

A review article written by the NOAH – AFNET 6 investigators led by Tobias Tönnis from UKE Hamburg summarizes recent evidence on the impact of atrial high rate episodes on stroke and cardiovascular death (1). The new evidence suggests that blood thinners may not be as effective in preventing strokes as previously thought.

Implantable devices and wearables like smart-watches enable continuous or near-continuous monitoring of cardiac rhythm. This leads to detection of short arrhythmias in many people, especially elderly persons with cardiovascular conditions. These arrhythmias, called atrial high rate episodes (AHRE), look like atrial fibrillation (AF). It is well established that blood thinners (anticoagulants) provide effective stroke prevention in patients with AF. Therefore, patients with AHRE are often treated with blood thinners as well.

Dr. Tobias Toennis, University Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany, explained: “Implanted pacemakers, defibrillators, or cardiac monitors can continuously capture and quantify atrial arrhythmias. Patients with such devices are a suitable population to study the role of infrequent atrial arrhythmias for outcomes in elderly people. AHRE occur in 10-30 % of elderly patients without atrial fibrillation. We reviewed a number of previous AHRE studies and summarized the current knowledge on stroke risk.”

A sub-study analysis of the EAST – AFNET 4 trial revealed how genetic risk for atrial fibrillation (AF) and stroke interacts with early rhythm control therapy: Early rhythm control reduces cardiovascular events in patients with AF across the spectrum of genetic AF and stroke risks. Today the findings were published in the journal Cardiovascular Research [1].

The EAST – AFNET 4 (Early Treatment of Atrial Fibrillation for Stroke Prevention) trial demonstrated that rhythm control therapy – with antiarrhythmic drugs or atrial fibrillation ablation – delivered within one year after AF diagnosis improves outcomes in patients with AF and comorbidities [2]. Early rhythm control (ERC) with antiarrhythmic drugs and/or AF ablation reduced the primary outcome, a composite of cardiovascular death, stroke, and hospitalization for worsening heart failure or acute coronary syndrome, in 2789 patients with early AF and cardiovascular risk factors compared to usual care (UC) over a 5-year follow-up time.

The causes for atrial fibrillation and stroke are manifold and also comprise a heritable component. The genetic risk can be quantified by polygenic risk scores (PRS) using data from large genome-wide association studies. In a collaboration with the Broad Institute of MIT and Harvard in Cambridge, USA, these PRS were tested in the EAST – AFNET 4 study.
Dr. Shinwan Kany, University Medical Center Hamburg Eppendorf, Hamburg, Germany, explained: “Prior studies suggest that patients with a genetic predisposition to AF may suffer more recurrent AF on rhythm control therapy. Additionally, studies using PRS for stroke identified AF patients with an increase in stroke risk when otherwise classified as low risk by CHA2DS2-VASc. This information suggests that early rhythm control therapy could be less effective or less safe in patients with an elevated genomic risk for AF. To assess this, we analyzed the association between genetic AF and stroke risk and cardiovascular events in the EAST – AFNET 4 bio-sample study.”

Patients with atrial fibrillation (AF) and a history of stroke are at high risk of recurrent stroke and cardiovascular complications. Early rhythm control therapy is safe and appears particularly effective in this vulnerable patient group. This was shown by a subgroup analysis of the EAST – AFNET 4 trial. The results were published in The Lancet Neurology [1].

The EAST – AFNET 4 (Early Treatment of Atrial Fibrillation for Stroke Prevention) trial investigated whether rhythm control therapy – using antiarrhythmic drugs or atrial fibrillation ablation – delivered within one year after AF diagnosis improves outcomes. The main study result, published in 2020 [2], demonstrated that early rhythm control therapy reduced cardiovascular events by 21% in patients with AF and comorbidities: Early rhythm control (ERC) with antiarrhythmic drugs and/or AF ablation reduced the primary outcome, a composite of cardiovascular death, stroke, and hospitalization for worsening heart failure or acute coronary syndrome, in 2789 patients with early AF and cardiovascular risk factors compared to usual care (UC) over a 5-year follow-up time.