Integrating new approaches to atrial fibrillation management: the 6th AFNET/EHRA Consensus Conference
Integrating new approaches to atrial fibrillation management: the 6th AFNET/EHRA Consensus Conference
A. John 44 45 46 47
Gregory Y.H. Lip 44 45 46 47
Ulrich Schotten 44 45 46 47
Anders Ahlsson 44 45 46 47
David 44 45 46 47
Arnar 44 45 46 47
Angelo 44 45 46 47
Jeroen Bax 44 45 46 47
Stefano Benussi 44 45 46 47
Calkins 44 45 46 47
Manuel Castella? 44 45 46 47
Winnie 44 45 46 47
Harry Crijns 44 45 46 47
Dobromir Dobrev 44 45 46 47
Larissa Fabritz 44 45 46 47
Guasch 44 45 46 47
Haase 44 45 46 47
Stephane 44 45 46 47
Hatem 44 45 46 47
Karl Georg 44 45 46 47
Haeusler 44 45 46 47
Heidbuchel 44 45 46 47
A. Lane 44 45 46 47
Thorsten Lewalter 44 45 46 47
Panagiotis E. Vardas 44 45 46 47
0 University Heart Center Hamburg , Hamburg , Germany
1 Heart Center Leipzig, University of Leipzig , Leipzig , Germany
2 Ospedale dell'Angelo , Mestre-Venice , Italy
3 Heraklion University Hospital , Heraklion, Crete , Greece
4 Division of Cardiology, Southlake Regional Health Centre, University of Toronto , Toronto, Ontario , Canada
5 Ludwig-Maximilians-University , Munich , Germany
6 Stroke Research Group, Department of Brain Repair and Rehabilitation, UCL Institute of Neurology and The National Hospital for Neurology and Neurosurgery , London , UK
7 Roche Diagnostics International Ltd , Rotkreuz , Switzerland
8 Leiden University Medical Center , Leiden , The Netherlands
9 University Hospital Zurich , Zurich , Switzerland
10 Department of Cardiology, Institution of Medical Sciences, Uppsala University , Uppsala , Sweden
11 University of Mannheim , Mannheim , Germany
12 DIMES Department, University of Bologna , Bologna , Italy
13 Odense University Hospital , Odense , Denmark
14 The Johns Hopkins Hospital , Baltimore, MD , USA
15 Oxford University , Oxford , UK
16 Hospital Clinic, Universitat de Barcelona , Barcelona, Catalonia , Spain
17 University Hospital Maastricht , Maastricht , The Netherlands
18 Institute of Cardiovascular Sciences, University of Birmingham , B15 2TT Birmingham , UK
19 Department of Cardiovascular Medicine, University Hospital Mu ? nster , Mu ? nster , Germany
20 Atrial Fibrillation NETwork (AFNET) , Mu ? nster , Germany
21 St George's University of London , London , UK
22 School for Cardiovascular Diseases, Maastricht University , The Netherlands
23 Orebro University Hospital , Orebro , Sweden
24 The National University Hospital , Reykjavik , Iceland
25 Oslo University Hospital , Oslo , Norway
26 Fondazione Cardiocentro Ticino , Lugano , Switzerland
27 University Duisburg-Essen , Essen , Germany
28 University Hospital Mu ? nster , Mu ? nster , Germany
29 Boehringer Ingelheim Pharma GmbH & Co. KG , Germany
30 University of Sydney , Sydney , Australia
31 St Vincenz Krankenhaus , Paderborn , Germany
32 Pitie ?-Salpe?trie`re Hospital , Paris , France
33 Charite ?-Universita ?tsmedizin Berlin , Berlin , Germany
34 Antwerp University Hospital , Antwerp , Belgium
35 University of Adelaide , Adelaide , Australia
36 Ludwig- Maximilians University Clinic , Munich , Germany & DZHK (German Center for Cardiovascular Research), Partner Site Munich Heart Alliance , Munich , Germany
37 Bayer HealthCare AG , Berlin , Germany
38 HaeuslerCharite ?-Universita ?tsmedizin Berlin , Berlin , Germany
39 Hospital-Munich Thalkirchen , Munich , Germany
40 Aarhus University Hospital , Aarhus , Denmark
41 Sta ?dtisches Klinikum Brandenburg , Brandenburg , Germany
42 Department of Cardiology, Memorial Ankara Hospital , Ankara , Turkey
43 Maastricht University, Medical Center , Maastricht , The Netherlands
44 , Stefanie Kespohl
45 , Andreas Goette
46 , Axel Brandes
47 , Giuseppe Boriani
48 School of Medicine, University of Belgrade, Clinical Centre of Serbia , Belgrade , Serbia
49 University Heart Center Freiburg , Freiburg , Germany
50 Bristol-Myers Squibb , Rueil-Malmaison , France
51 University of Groningen, University Medical Center Groningen , Groningen , The Netherlands
Barbara Casadei Andrea Gerth Hunter
Oldgren , Ali Oto
, Tatjana Potpara
, Ursula Ravens
, Isabelle Richard-Lordereau
, Irina Savelieva , Renate Schnabel
, Moritz F. Sinner
, Sakis Themistoclakis
, Atul Verma
, Reza Wakili
, Evelyn Weber
, Andre? Ziegler
Atrial fibrillation Outcomes
There are major challenges ahead for clinicians treating patients with atrial fibrillation (AF). The population with AF
is expected to expand considerably and yet, apart from anticoagulation, therapies used in AF have not been shown
to consistently impact on mortality or reduce adverse cardiovascular events. New approaches to AF management,
including the use of novel technologies and structured, integrated care, have the potential to enhance clinical
phenotyping or result in better treatment selection and stratified therapy. Here, we report the outcomes of the 6th
Consensus Conference of the Atrial Fibrillation Network (AFNET) and the European Heart Rhythm Association
(EHRA), held at the European Society of Cardiology Heart House in Sophia Antipolis, France, 17?19 January 2017.
Sixty-two global specialists in AF and 13 industry partners met to develop innovative solutions based on new
approaches to screening and diagnosis, enhancing integration of AF care, developing clinical pathways for treating
complex patients, improving stroke prevention strategies, and better patient selection for heart rate and rhythm
control. Ultimately, these approaches can lead to better outcomes for patients with AF.
Quality of care Research
Bleeding Research priorities
Rhythm control Catheter Stroke Integrated care
The predicted rise in both incidence and prevalence of atrial
fibrillation (AF) presents an important health care challenge for
cardiovascular and general clinicians.1?4 However, it also offers an opportunity
to integrate novel approaches and new technologies to improve
patient outcomes. The diagnosis of AF encompasses a broad and
heterogeneous group of pathologies,5 and further classification of this
condition based on underlying cause or the extent of atrial disease is
likely to provide more personalized and effective treatments in the
future.1 The care of patients with AF can also be improved by
applying structured and patient-centred management that integrates the
expertise of different health care professionals.6 Beyond better
classification and quality of care, the most immediate advancement in AF
management is to incorporate practical ideas, tools, and technologies
into routine clinical practice. In particular, these approaches have the
potential to (i) provide cost-efficient methods of detection and
diagnosis, (ii) allow a platform for local integration of AF care, (iii) develop
streamlined clinical pathways for treating complex patients, (iv)
improve the benefit-to-risk ratio of stroke prevention strategies, (v)
apply more personalized control of heart rate to increase patient
well-being and function, and (vi) stratify the choice of rhythm control
therapy to enhance treatment success in AF patients.
These issues were raised and discussed during the 6th Consensus
Conference of the Atrial Fibrillation Network (AFNET) and the
European Heart Rhythm Association (EHRA) in Sophia Antipolis,
France (17?19 January 2017). Sixty-two specialists in AF attended
from 15 member countries of the European Society of Cardiology
(ESC), as well as from Australia, Canada, and the USA, in addition to
13 representatives from industry partners. The conference included
multidisciplinary workshops on the key themes of the conference,
with delegates obtaining consensus opinion within and across
workshops with plenary feedback sessions and wide-ranging discussion.
In this article, we report on the major outcomes of this conference
and present consensus statements on the integration of new
approaches to provide maximal benefit to AF patients and their
Diagnosis and screening
Atrial fibrillation detection in an era of digital evolution
In this workshop, delegates considered the question of what should
constitutes a diagnosis of AF, and whether AF detected by screening
has the same therapeutic implication as randomized controlled trials
where AF has presented clinically.
Electrocardiographic (ECG) demonstration of AF is a prerequisite
before treatment for AF is initiated.1 The easiest ECG methods to
diagnose AF are the 12-lead and ambulatory ECG, but different types
of medical technology to diagnose AF are now commonplace,
including event recorders, real-time telemetry, and implantable loop
recorders. The public also have a variety of options to measure heart
rate and identify arrhythmias, including sphygmomanometers,
handheld devices, smartphones, wearables, and health-related apps. As a
consequence of the lower detection threshold, it is of great
importance to evaluate the quality of rhythm monitors, their sensitivity,
specificity, and cost-effectiveness and to develop strategies to
interpret the findings. Furthermore, long-term monitoring of atrial rhythm
may identify patients with very rare episodes of AF who have a
different risk profile than patients who present with clinical AF, for whom
currently available treatments have been evaluated. We defined the
terminology of ?self-initiated rhythm monitoring? for those apparently
healthy individuals who decide (for whatever reason) to use
commercially available rhythm monitors, whereas ?AF detection,
diagnosis, or screening? is usually used in patients at risk of AF and its
Self-initiated heart rhythm monitoring
Medical practice is already transitioning from a profession that
remedies acute illnesses to one that prevents disease, often in patients
who do not feel acutely unwell. In AF, new technologies are now
available that direct populations to seek medical advice based on
detection from consumer electronics (Table 1). The hardware and
algorithms used in these devices are highly variable,17 validation may
be less than for medical devices, and reproducibility could be reduced
aMostly compared with 12-lead ECG interpretation by a cardiologist, based on published research studies in ideal situations. Note that some algorithms for AF detection are
not publicly available and some commercially available devices have modified the algorithms that were tested in these studies.
in the hands of the consumer. This raises the problem of false
positives, which may lead to anxiety for patients and costly additional
testing with ECG recorders and echocardiography. Conversely,
consumer devices can be helpful to highlight the possibility of paroxysmal
AF and the need for further investigation (Figure 1).
As ECG-diagnosed AF is the preferred method to decide on
treatment1 (an enrolment criterion for all controlled trials of AF
interventions), patients with potential AF detected on devices that do not
provide an interpretable ECG rhythm strip should undergo further
assessment of cardiovascular and stroke risk, with additional rhythm
monitoring as clinically required. This can also apply to technology in
use by medical professionals, for example atrial high-rate episodes
(AHREs) detected on pacemakers.18 The physician should decide the
stringency of ECG-based rhythm diagnosis based on these factors.
Although there are no data available to assist this decision as yet, it
seems reasonable to only initiate further rhythm monitoring if the
finding of AF would alter management, such as preventing
thromboembolism or reducing the risk of other adverse outcomes.
Criteria for atrial fibrillation diagnosis and the impact of screening
Inclusion criteria regarding documentation of AF have varied in recent
clinical trials. Although most trials required two ECGs with
documentation of AF on separate days,19?22 one recent trial required a
history of AF of any duration recorded by any electrical tracing within
the last 12 months23 and another required symptomatic episodes with
resting, ambulatory or trans-telephonic ECG within the last 4 weeks.24
Such differences in the recording and documentation of AF may have an
influence on the composition and generalizability of patient cohorts.
The setting in which patients are selected for inclusion may also
determine characteristics, including age and the risk of stroke or adverse
cardiovascular events.25,26 The yield from screening for AF will also depend
on the underlying risk of incident AF27 and the type of AF. For example,
the probability that AF is detected by a short recording in patients with
paroxysmal AF depends on the underlying burden. Thus, a screening
programme that uses a single time point of detection will favour
identification of persistent AF, while intermittent short recordings will identify
additional patients with paroxysmal AF and a relatively high AF
burden.28,29 Conversely, devices capable of continuous atrial rhythm
monitoring will identify many more people with short-duration AF episodes
and low AF burden of relatively unknown clinical significance.
The impact of atrial fibrillation detection and stroke risk
A major question, as yet unanswered, is whether different modes
of detection of AF and the resulting AF pattern and burden
Heart rate detection
identified have an implication on stroke risk and the need for
anticoagulation. Screening programmes initiated within the health
care system will tend to target those patients who have previously
unidentified, mostly asymptomatic AF. On the contrary, AF
detected by consumer devices will more often identify
paroxysmal symptomatic AF which may, when detected or treated early
during the course of disease, have a different risk of stroke and
The risk of stroke in a screened population can be enriched by
requiring additional risk factors such as age and others, and the
decision to anticoagulate will require consideration of the net clinical
benefit of anticoagulation, taking into account the risk of stroke, major
bleeding, and residual cardiovascular risk. Subclinical AF detected on
implanted devices is also associated with elevated stroke risk.32,33 In
contrast, AHRE detected by implanted devices may not have the
same prognostic impact for stroke as AF detected by ECG
recordings, due to the low frequency, short duration of AHRE episodes, and
the uncertainty with respect to their nature (AF or other
arrhythmias). The stroke risk associated with AHREs is usually lower than
for clinically detected AF, and absolute stroke rates with AHRE are
often close to 1%, despite the presence of stroke risk factors.18,34,35
In summary, medical technologies provide exciting new options to
diagnose and screen for AF (from the patient, health care, and
societal perspectives). However, it is uncertain whether detection of
atrial arrhythmias using these methods has the same implication as
using conventional 12-lead ECG, or indeed those who present
clinically with AF, particularly with regard to stroke risk and prevention.
More studies are needed to investigate the potentially different AF
disease states that are uncovered by the use of more advanced and
continuous rhythm monitors.
Integrated care of atrial fibrillation patients
In this workshop, delegates were asked to consider how to develop
integrated care models in AF, the challenges limiting dissemination,
and how novel approaches could support further integration.
Definition of integrated care
Based on the World Health Organization definition of integrated
care,36 we defined this approach in AF as ?a coordinated
patientcentred approach by interdisciplinary specialists to improve AF
outcomes?. Integrated care enables treatment of AF patients in all five
domains of management: acute stabilization, detection and
management of underlying cardiovascular co-morbidities and risk factors,
appropriate oral anticoagulation for stroke prevention, and treatment
with rate and/or rhythm control therapy.37,38 Electronic decision aids
can be helpful for both the patient and the care provider, guiding the
management team in clinical decision support, offering education, and
measuring the effectiveness of treatment. Figure 2 illustrates the
concept of integrated, patient-centred AF care. A core team, for example
an AF nurse and a cardiologist (or other physician who specializes in
AF care), is supported by appropriate technology, and this team
communicates with the patient and forms an intermediary with other
health care professionals to co-ordinate optimal AF management.
Eligible patients and entry/exit criteria for integrated care
Ideally patients with newly diagnosed AF should have at least one
appointment with the core team in an integrated care service, based
Back to routine care
di al Referring
(e.g. CATCHME/ESC AF app)
in either the primary or secondary care setting. This will include a
diagnostic assessment, discussion of treatment options, initiation of
appropriate therapy according to guidelines, and tailored education
and empowerment of the patient and caregiver.1 Thereafter, stable
and adequately managed patients can be followed up by supported
self-management in the community. Criteria for another visit with
the integrated AF team might include worsening of symptoms,
hospitalization, stroke or bleeding complications, unstable situations (e.g.
haemodynamic compromise or acute symptomatic arrhythmia
recurrence), or suboptimal management. Conversely, empowered and
educated patients who are clinically stable on fully established,
guideline-based treatment with appropriate general practice support
could take on their own management without further routine visits.
Integrated AF care will take different shapes in different health care
environments and will have to answer to challenges, including the
extra time for patient interaction, the availability of treatment options
to all patients, and the provision of technology support. Funding and
reimbursement of integrated care is also dependent on local factors
(particularly the provision of hospital and out-of-hospital specialist
care), although integrated AF care may be a cost-effective solution to
implement good AF management.39
Technology tools to ensure the success of integrated care
Although electronic health portals are now available in many
countries, the availability of tools that apply to AF specifically is limited.
Furthermore, electronic patient records are often owned by health
care providers (e.g. hospitals or general practices) and not by
patients. As part of the 2016 AF Guidelines, the ESC in collaboration
with the CATCH ME consortium have developed smartphone and
tablet apps for patients and health care professionals (freely available
from Google Play, Amazon, and Apple Appstores).40 The patient app
offers information and education about AF, encourages active
selfmanagement, and also allows transfer of information to health care
professionals. The health care professional app includes a patient
register, in which risk factors, co-morbidities, and treatments can be
prefilled by patients, and is designed as an interactive management
tool incorporating the new ESC AF Guidelines. Other apps and
websites are also available, for example educational aids available in
numerous languages by cardiovascular and AF-specific charities such
as the British Heart Foundation (https://www.bhf.org.uk/heart-health/
conditions/atrial-fibrillation), the Atrial Fibrillation Association (www.
heartrhythmalliance.org), and ?AFib Matters? by EHRA (http://www.
The Atrial Fibrillation Heart
Team for complex management decisions
In this workshop, delegates were asked to propose practical
measures and requirements for setting up local AF Heart Teams to
support advanced AF management.
The AF Heart Team is proposed as a means to improve the care of
selected and complex cases by providing specialist multidisciplinary
input.1 It is an adjunct to integrated AF care that provides a
comprehensive consideration of therapeutic options to patients who
would benefit from such an approach (Figure 2). It is important to
highlight that the AF Heart Team, while having an important role to
support complex decision-making processes for difficult to manage
patients with AF, is not required for the vast majority of AF
management decisions. Complex AF patients are characterized by failure of
first- and second-line therapies in the presence of severe AF-related
symptoms, a high event rate, and often several coexisting
co-morbidities. The two main areas where AF Heart Teams will be useful are:
) Complex rhythm control therapy, for example failure of catheter
ablation to control symptomatic AF, consideration of AF surgery,
or other situations that make rhythm control therapy difficult.
) Complex stroke prevention, for example patients with a relevant
contraindication to anticoagulation or the need for left atrial
appendage (LAA) exclusion, ligation, or clipping.
As different treatment modalities are evolving rapidly, the AF
Heart Team offers such patients expertise from several specialities,
with the ultimate goal of optimizing the use of available resources and
improving the quality of care.41
Set-up and process
The constitution of this team depends on the local infrastructure. An
interventional electrophysiologist would preferably be the leader of
such a team, which also includes a ?fixed core? consisting of a general
or referring cardiologist and a cardiac surgeon for a rhythm control
AF Heart Team, and anticoagulation and stroke specialists for a
stroke prevention AF Heart Team. Other specialists are invited as
needed, such as anaesthesiologists and experts in cardiac imaging,
among others (Figure 2). Once a patient has been discussed within
the AF Heart Team and a strategy has been proposed, one member
of the team should take responsibility for the proposed management
and interact with the patient and referring physician. An AF Heart
Team is preferably implemented by defining membership and
responsibilities in advance. The team should meet?at least initially?on a
regular basis, and close cooperation with other local heart teams will
be useful. It is important to critically review and optimize locally
available care pathways and design advanced treatment pathways, with
the AF Heart Team defining referral pathways for internal and
external caregivers (e.g. general practitioners and other local hospitals).
The AF Heart Team should be an important driver of improving the
quality and efficiency of care, including review of care pathways, and
collation and reporting of data on local outcome and complications
In this workshop, delegates were asked to consider the remaining
barriers to stroke prevention, including the use of biomarkers to
improve patient selection for anticoagulation, the available evidence
for the safety of discontinuing anticoagulation after transient AF or
AF ablation, how clinicians should manage anticoagulation after
serious bleeding, and the role of LAA occluders in current clinical
Biomarkers to refine risk scores
Current clinical risk scores have only a modest predictive ability to
define stroke and bleeding risk in individual patients and do not
differentiate the severity of component risk factors. This leads to
uncertainties of the benefit of stroke prevention treatment, most obvious
when considering initiation of oral anticoagulation in patients at the
lower end of the risk spectrum by clinical risk scores or in patients
with bleeding complications on oral anticoagulation.1 The digital era
facilitates the calculation of risk based on continuous variables and
more complex risk calculators on smartphones, computers, or with
integration into electronic health records. Several biomarkers are
linked with underlying pathophysiology and clinical outcomes,
including markers of myocardial injury (troponins), cardiac stress and
dysfunction [natriuretic peptides, growth differentiation factor (GDF)
15], myocardial fibrosis (galectin-3 and fibroblast growth factors),
renal dysfunction (creatinine and cystatin C), inflammation
(C-reactive protein and cytokines), and coagulation activity (D-dimer).42 Risk
scores combining clinical characteristics and biomarkers have
recently been developed, validated (generally in anticoagulated
populations), and compared with established clinical risk scores (such as
CHA2DS2-VASc43). These biomarker risk scores include, among
others, the ATRIA stroke risk score [The AnTicoagulation and Risk
factors In Atrial Fibrillation; includes glomerular filtration rate
(GFR)]44,45 and the ABC stroke score (Age, Biomarkers, Clinical
history; includes troponin and NT-proBNP).46,47 Biomarker-based risk
scores for prediction of major bleeding in AF include ORBIT-AF
(Outcomes Registry for Better Informed Treatment of Atrial
Fibrillation; GFR < 60 mL/min and categorical cut-offs for
haemoglobin or haematocrit)48 and the ABC bleeding score (Age, Biomarkers,
Clinical history; haemoglobin, troponin, and GDF-15 or GFR).49 Two
recent scores also include the estimation of composite outcomes
using a multi-biomarker approach,50,51 allowing clinicians to refine
their assessment of balance between stroke and bleeding risk and
thus potentially the net clinical benefit of stroke prevention therapies.
This approach can avoid the overestimation of bleeding risk that can
lead to inappropriate withholding of anticoagulation from suitable
patients but is limited by the delay and practical difficulty of relying on
biomarkers. The major evidence gaps for this approach at present
are the cost-effectiveness and incremental precision of such scores,
and the lack of prospective randomized trials to evaluate the use of
risk scores on cardiovascular outcomes in AF patients. Properly
validated and well-calibrated risk scores delivered by technology
solutions may in the future prove useful to support more personalized
approaches to anticoagulant therapy.
Safety of discontinuing anticoagulation in specific patient groups
Atrial fibrillation ablation is increasingly being used to treat
symptomatic AF patients, with 1 year success rates of around 60?80% for
paroxysmal AF and 50?70% for persistent AF.52?55 Despite these
reductions in recurrent AF, it is unclear whether ablation reduces the
associated risk of stroke. Between 2% and 5% of patients per year
will experience late recurrences of AF, and this seems to continue up
to 5 years post-ablation and beyond.54,56 The minimum amount of
AF required to increase the risk of stroke is unknown, and the risk
stratification schemes such as CHA2DS2-VASc do not take account
of AF burden, implying that even one episode of AF may carry the
same stroke risk as recurrent or persistent AF. In the TRENDS study
(Temporal Relationship of Atrial Tachyarrhythmias, Cerebrovascular
Events, and Systemic Emboli Based on Stored Device Data), the risk
of stroke increased two-fold in those patients with an atrial
tachycardia/AF burden of >5.5 h in any 30 days window.57 In the ASSERT trial
(ASymptomatic atrial fibrillation and Stroke Evaluation in pacemaker
patients and the atrial fibrillation Reduction atrial pacing Trial), atrial
arrhythmias detected within 90 days of pacemaker implant increased
the risk of stroke, although the increase was smaller than for
conventionally detected AF.34 Further analysis of ASSERT showed that
subclinical AF with a duration >24 h (but not less) was associated with
increased risk of subsequent stroke or embolism (hazard ratio 3.24,
95% confidence interval 1.51?6.95).32
However, the absolute risk of stroke may still fall below the
perceived threshold for anticoagulant treatment. In the ASSERT trial, the
annualized risk of stroke reported for patients with brief occurrences
of AF were only 0.28%, 0.70%, and 0.97% for patients with CHADS2
scores of 1, 2 and >2, respectively.38 Observational cohort studies
have suggested a reduced risk of stroke after catheter ablation58,59;
however, propensity matching cannot entirely account for patient
selection bias.60 Current guidelines recommend that even patients
with ?successful? ablation should be treated with OAC according to
underlying stroke risk.1 These recommendations reflect the fact that
recurrence is common post-AF ablation, recurrent AF is often
asymptomatic, and patients accumulate stroke risk factors as they
age. Further trials, such as OCEAN (Optimal Anticoagulation for
Higher Risk Patients Post-Catheter Ablation for Atrial Fibrillation
Trial; NCT02168829) need to report their outcomes before this
?safety-first? practice can change. Similarly, the role of new digital
technologies that can obtain frequent (or even continuous) rhythm
monitoring needs to be studied in the context of stroke rates, also
considering the low risk of major complications from contemporary
Another important area where anticoagulation is often
discontinued is ?reversible? or ?transient? AF, terms used to describe bouts of
AF related to the postoperative state or an acute illness (e.g. sepsis
or metabolic disturbances).61,62 Although some patients may have
truly self-limiting AF, many are at longer-term risk of AF recurrence
(and therefore stroke).63,64 This uncertainty has led to major
variation in practice, with some advocating short-term anticoagulation
(e.g. 3?6 months), followed by careful monitoring for recurrent AF
and others recommending long-term anticoagulation for those with
an elevated CHA2DS2-VASc score. Importantly, such patients were
not specifically evaluated in the pivotal anticoagulation trials, and so
further research is vital to address this major gap in evidence.
Anticoagulation after serious bleeding
Anticoagulants increase the risk of bleeding, and after minor bleeding
events with a clear precipitating cause, oral anticoagulation should
often be reinitiated once bleeding has been controlled.1 More severe
or life-threatening bleeding [e.g. intracranial haemorrhage (ICH)]
requires cessation or even therapeutic ?reversal? of anticoagulation,
with careful consideration about the risks and benefits of resumption.
There is wide variation in clinical practice for whether or not to
restart anticoagulation after ICH,65 and patients who are reinitiated
on anticoagulation seem to have better outcomes than those who
are not.66,67 Patients at highest risk of recurrent bleeding are often
those at highest risk of thrombo-embolic stroke.1 The risk of
recurrent ICH can be stratified by ICH location (deep vs. lobar) and
markers of small vessel disease. Cerebral amyloid angiopathy is
associated with a high annual bleeding risk of around 10%.68 Advances in
cerebral imaging,69 biomarkers and technology for AF screening all
have the potential to clarify stroke and bleeding risk in individual
Left atrial appendage occlusion
Exclusion of the LAA is now possible with percutaneous devices,
although scientific evidence is mainly based on observational studies
and registries, with just two randomized controlled trials of a single
device compared with warfarin therapy.70?72 The Watchman VR device
has been approved by the Food and Drug Administration (FDA) for
patients with AF not related to heart valve disease, at an increased
risk of stroke and suitable for warfarin but with an appropriate reason
to seek a warfarin alternative. In a composite analysis, the device was
associated with less haemorrhagic strokes and
cardiovascular/unexplained death than warfarin, but there were more ischaemic strokes
in the device group.73 Unfortunately, there are no direct comparisons
of occluder therapy and non-vitamin K antagonist oral anticoagulants,
and no comparisons of occluders in patients deemed ineligible for
anticoagulation. Left atrial appendage occluders are often used in AF
patients who cannot be anticoagulated, a group with no other
realistic treatments. Further information is needed about long-term
efficacy, adverse events, and comparison with other stroke prevention
strategies, such as thoracoscopic LAA exclusion. It is also unclear
whether the results from one device can be extrapolated to the
many others in development or what the minimal duration of
antithrombotic therapy after LAA exclusion should be. Adequately
powered controlled trials are urgently needed to inform the best use of
these devices, and several such studies are under way.
Rate control therapy
In this workshop, delegates were asked to consider novel approaches
to heart rate control, to define the gaps in current evidence, and
consider the impact of new technologies on rate control in routine
When and how to use rate control therapy
Rate control is usually the first-line treatment strategy for patients
with symptomatic AF1 but has a relatively poor evidence-base.74
There are also two major groups of patients in whom rate control is
used even when a rhythm control strategy is attempted.75 First, rate
control should be background therapy for nearly all AF patients,
because well-controlled heart rates are important during relapses of
AF. Secondly, rate control is the therapy of choice to contain
symptoms in patients for whom the risks of restoring sinus rhythm
outweigh the benefits, or in those in whom advanced rhythm control
The choice of rate-controlling drugs, alone or in combination,
depends on symptoms, co-morbidities and potential side effects.
Following the RACE II trial (RAte Control Efficacy in permanent atrial
Technology Advantages Limitations Applicability to type of AF
Inaccurate (pulse deficit)
Standard 12-lead resting ECG (10 s) Gold standard for AF diagnosis No correlation to symptoms Persistent and permanent
Exercise test Heart rate dynamics No validation for moderate exercise Persistent and permanent
Ambulatory Holter ECG
Day and night heart rate dynamics
Accurate correlation to symptoms
All types of AF
Correlation with symptoms needs patient education
External event recorder
Day and night heart rate dynamics
Not widely available
All types of AF
?telemonitoring Correlation with symptoms
Wearable heart rate monitors
Correlation to symptoms
Patient education essential
All types of AF
(smartphones, watches, and
Self-management and empowerment Potential anxiety for patient
bands) Increased workload for physician
Wearable heart rate monitors
Potential for wide use
Pulse wave only
All types of AF
Diagnostic functions available in
Day and night heart rate dynamics
Cost of remote monitoring or
All types of AF in patients with
implanted cardiac devices
Correlation to symptoms
makers, implanted monitors, and
fibrillation II),76 AF guidelines have adopted a lenient rate control
strategy as the first-choice approach, with stricter control reserved
for patients with persistent symptoms or deterioration in cardiac
function.1 Even in heart failure and reduced ejection fraction, control
of heart rate with beta-blockers was not associated with mortality
benefit in the subgroup of patients with AF,77 in contrast to a marked
benefit in women and men with sinus rhythm of all ages.78 In the case
of cardiac resynchronization therapy that necessitates continuous
biventricular pacing, effective slowing of intrinsic AF is required to
prevent adverse outcomes.79
New approaches to monitoring heart rate control
Table 2 lists the major approaches to assessing rate control, including
novel methods such as wearable monitors and smartphone
applications. Key differences are concerned with cost (to the patient and
health care systems), the ability to correlate heart rate with
symptoms and patient activity, and the capacity to measure AF burden.
There are also multifaceted and contradictory patient effects; the
ability to record and transmit an ECG will reassure many and
underpin independent patients who ?own? their disease management but
can also increase anxiety, generate a focus on numerical heart rate,
and potentially lead to incorrect self-management. Each approach has
specific limitations due to the type of technology (as discussed in the
screening section), which need to be taken into account when
clinicians appraise the results.
Gaps in knowledge for rate control
Unfortunately, there are many evidence gaps in rate control that
of further study:
? Optimal heart rate (rest and exercise) with respect to symptoms
and outcomes and taking into account other comorbidities such
as heart failure.80
? Selection of drugs and drug combinations in general, but also in
specific patient groups, for example heart failure with preserved81
or reduced systolic function82 and pulmonary disease.83
? Parameters to assess the success of rate control and their
association with prognosis (heart rate, symptoms, B-type natriuretic
peptide, and others).
? Measurement of patient benefit, including AF-specific quality of life.84
? The role of irregularity (RR interval) vs. absolute heart rate and
their correlation with symptoms and the effects of specific drugs
on outcomes such as cardiac function.85
? Potential role for ?pill-in-the-pocket? approaches to rate control,
similar to that used for flecainide and propafenone in rhythm
Approaches for rhythm control
In this workshop, delegates were asked to consider new paradigms
for improving the success of rhythm control strategies, moving
beyond the conventional time-based concept of AF classification.
Context and success of rhythm control
Rhythm control therapy is very effective in some patients, whereas
others experience early, frustrating therapy failures despite
concerted efforts to restore and maintain sinus rhythm.1,86?89 Technical
failure can contribute to recurrent AF (e.g. due to reconnection of
isolated pulmonary veins90) or deterioration of associated conditions
and should be reduced by structured and high-quality care.6
treatment options (antiarrhythmic drugs, catheter ablation and AF
affect clinical management of AF. We identified the key areas in need
Combining therapy modalities, making use of all rhythm control
surgery1,91) and involving patients in the care process37,92 can help to
manage expectations and maintain patient satisfaction. In the future,
personalized implementation of different rhythm control therapy
modalities may improve this situation.5,93
In addition, there is a growing realization that rhythm control
interventions only target part of the relevant disease processes
driving recurrent AF.94 A variety of clinical conditions such as obesity,
lack of exercise, hypertension, heart failure, and sleep apnoea have
been associated with recurrent AF as well as with newly diagnosed
AF.95?99 Atrial damage caused by such factors can promote recurrent
AF (Table 3). Atrial myocardium is affected by several cardiac
and non-cardiac diseases or abnormalities.100 Of note, atrial cells
(cardiomyocytes, fibroblasts, endothelial cells, and neurons) react
extensively to pathological stimuli,100 and therefore atrial
cardiomyopathies can contribute to arrhythmia occurrence.101,102 These
markers for atrial damage can be found by careful analysis of
electrical atrial function103,104 and/or by assessment of atrial structure and
function.105,106 Integrated AF care tackling these underlying
conditions may have an important role in successful rhythm control
Role of imaging to support rhythm control
AF development and the recurrence of AF following rhythm control
are significantly related to left atrial (LA) substrate, including the
extent of dilatation and fibrosis and the severity of dysfunction. These
three parameters can be assessed and quantified using non-invasive
imaging techniques, in addition to defining the pulmonary vein
anatomy to support successful AF ablation (Figure 3). LA size is preferably
measured as a volume using 3D imaging techniques, including 3D
echocardiography, computed tomography (CT), or cardiac magnetic
resonance (CMR) imaging. Due to differences between these imaging
techniques and changes during the cardiac cycle, systematic use of
the same technique and care with timing of volume assessment are
required during follow-up.
In general, despite these limitations, LA dilatation has been
associated with the development of AF and recurrence of AF after catheter
ablation.108 The extent of LA fibrosis is related to LA size, although
small atria can still exhibit fibrosis and larger atria may not.109 In a
multicentre observational study, extensive LA fibrosis on CMR was
associated with an AF recurrence rate of 51% almost 1 year after first
catheter ablation compared to 15% in patients with the least
fibrosis.110 Echocardiography can also indirectly assess LA fibrosis,
including integrated backscatter techniques and the time interval
between the onset of the P-wave and atrial contraction measured
with tissue Doppler imaging (TDI); both techniques are predictive of
The atria provide an important contribution to the performance
of the heart101,113 and serve as a volume reservoir to regulate
ventricular filling and a booster pump in late diastole. Left atrial function
is typically assessed by echocardiography using transmitral and
pulmonary vein Doppler, TDI (active LA contraction reflected by the
atrial velocity, a0) and volume-based measures.114 Much of the
information on LA function can also be derived from CMR and CT, but
for practical reasons, echocardiography is mostly used in the clinical
setting. Active deformation of the LA during the cardiac cycle can be
assessed with strain imaging from 2D speckle-tracking
echocardiography, with LA global strain identified as another important predictor
of AF recurrence after catheter ablation.115
A recent expert consensus described the concept of an atrial
cardiomyopathy as ?any complex of structural, architectural, contractile or
electrophysiological changes affecting the atria with the potential to
produce clinically-relevant manifestations?.105 Histopathological
alterations reflecting such atrial cardiomyopathies are often not specific to
the damaging factor and may also vary substantially over time.116,117
Importantly, atrial cardiomyopathies with pathological or mechanical
atrial alterations may exist in the absence of atrial arrhythmia or AF.
Thus, these alterations may contribute to a ?pre-AF state? (Figure 4),
which could include electrical irritability, structural changes and
neurohormonal activation. Characterization of atrial pathology and
imaging techniques, in particular, are of utmost importance, consistent
with the observation that recurrent AF after catheter ablation seems
to be higher in patients with signs of atrial cardiomyopathy.118 Blood
biomarkers (natriuretic peptides, galectin-3, and others6) or imaging
of subtle cardiac dysfunction (e.g. cardiac strain) may be able to
PA-TDI: 160 ms
Left atrial size:
Mitral valve disease:
P wave duration / AF cycle length
Systolic and/or diastolic dysfunction
Cardiovascular risk factor management
Rate control therapy
Thoracoscopy and AF surgery
Likelihood of interventional success
detect drivers or markers of atrial cardiomyopathic damage.
The ultimate goal of these markers is to define different types of AF
that are characterized by a specific pathophysiology which may
warrant early aggressive intervention or will respond favourably to
stratified therapy. This group feels that assessing and reversing the major
factors damaging the atria in clinical practice would be an important
step to underpin a more systematic approach to rhythm control
therapy in AF patients. Providing this new approach is shown to be
clinically effective, it would support the development of personalized
rhythm control therapy and afford a pathway for improvement in
clinical outcomes and patient well-being.
The 6th Consensus Conference of AFNET and the EHRA outlined a
vision for future management that incorporates new approaches and
novel technologies to improve outcomes for patients with AF. With
large increases in the burden of AF expected in coming decades,
better diagnosis, integration of care, patient involvement and
stratification of treatment selection by a multidisciplinary AF team could help
to offset the impact of AF on health care services.
Supplementary material is available at Europace online.
We wish to thank all participants of the 6th AFNET/EHRA consensus
conference and especially the staff of AFNET, the EHRA, and the
ESC for excellent organization of the conference.
Conflict of interest: a detailed list of disclosures of financial
relations is provided in the Supplementary material online, Appendix.
The 6th AFNET/EHRA consensus conference was co-financed by
AFNET and EHRA, and received additional financial support from the
CATCH ME consortium (EU Horizon 2020 grant number 633196).
Industry participants paid an attendance fee for the conference and
provided an industry perspective during the discussions at the meeting but
had no involvement in the writing process.
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