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In both developed and developing countries, the age-adjusted incidence and prevalence of AF are lower in women, while the risk of death in women with AF is similar to or higher than that in men with AF.
Women with diagnosed AF can be more symptomatic than men and are typically older with more comorbidities. Recommendations relating to gender.
AF, especially early-onset AF, has a strong heritable component that is independent of concomitant cardiovascular conditions.
These monogenic diseases also convey a risk for sudden death see Chapter 6. Up to one-third of AF patients carry common genetic variants that predispose to AF, albeit with a relatively low added risk.
At least 14 of these common variants, often single nucleotide polymorphisms, are known to increase the risk of prevalent AF in populations.
Genetic variants could, in the future, become useful for patient selection of rhythm or rate control. Activation of fibroblasts, enhanced connective tissue deposition, and fibrosis are the hallmarks of this process.
Pathophysiological alterations in atrial tissue associated with atrial fibrillation and clinical conditions that could contribute to such alterations.
Major mechanisms causing atrial fibrillation that can be considered when choosing therapy. These changes enhance both ectopy and conduction disturbances, increasing the propensity of the atria to develop or maintain AF.
At the same time, some of these alterations are involved in the occurrence of the hypercoagulable state associated with AF.
For example, hypocontractility reduces local endothelial shear stress, which increases PAI-1 expression, and ischaemia-induced inflammation enhances the expression of endothelial adhesion molecules or promotes shedding of endothelial cells, resulting in tissue factor exposure to the blood stream.
These changes contribute to the thrombogenic milieu in the atria of AF patients. AF in itself can aggravate many of the mechanisms shown, which may explain the progressive nature of the arrhythmia.
The functional and structural changes in atrial myocardium and stasis of blood, especially in the left atrial appendage LAA , generate a prothrombotic milieu.
Furthermore, even short episodes of AF lead to atrial myocardial damage and the expression of prothrombotic factors on the atrial endothelial surface, alongside activation of platelets and inflammatory cells, and contribute to a generalized prothrombotic state.
The seminal observation by Haissaguerre et al. The mechanism of focal activity might involve both triggered activity and localized reentry.
Moe and Abildskov proposed that AF can be perpetuated by continuous conduction of several independent wavelets propagating through the atrial musculature in a seemingly chaotic manner.
As long as the number of wavefronts does not decline below a critical level, they will be capable of sustaining the arrhythmia.
Numerous experimental and clinical observations can be reconciled with the multiple wavelet hypothesis. Absolutely irregular RR intervals and no discernible, distinct P waves.
ECG-documented AF was the entry criterion in trials forming the evidence for these guidelines. By accepted convention, an episode lasting at least 30 s is diagnostic.
Many AF patients have both symptomatic and asymptomatic episodes of AF. Silent, undetected AF is common, , with severe consequences such as stroke and death.
Ongoing studies will determine whether such early detection alters management e. Undiagnosed AF is common, especially in older populations and in patients with heart failure.
These findings encourage the further evaluation of systematic AF screening programmes in at-risk populations.
Paroxysmal AF is often missed. Implanted pacemakers or defibrillators with an atrial lead allow continuous monitoring of atrial rhythm.
Using this technology, patients with atrial high rate episodes AHRE can be identified. AF detection is not uncommon in unselected stroke patients 6.
Recommendations for screening for atrial fibrillation. Right atrial isthmus-dependent flutter has a typical ECG pattern and ventricular rate.
The ventricular rate can be variable usual ratio of atrial to ventricular contraction 4: Vagal stimulation or intravenous adenosine can therefore be helpful to unmask atrial flutter.
The management of atrial flutter is discussed in chapter Left or right atrial macro re-entrant tachycardia is mainly found in patients after catheter ablation for AF, AF surgery, or after open heart surgery.
In many patients, AF progresses from short, infrequent episodes to longer and more frequent attacks. Over time, many patients will develop sustained forms of AF.
Furthermore, asymptomatic recurrences of AF are common in patients with symptomatic AF. Based on the presentation, duration, and spontaneous termination of AF episodes, five types of AF are traditionally distinguished: If patients suffer from both paroxysmal and persistent AF episodes, the more common type should be used for classification.
Despite these inaccuracies, the distinction between paroxysmal and persistent AF has been used in many trials and therefore still forms the basis of some recommendations.
If both persistent and paroxysmal episodes are present, the predominant pattern should guide the classification. There is some evidence suggesting that AF burden may influence stroke risk 44 , , and could modify the response to rhythm control therapy.
Therefore, AF burden should not be a major factor in deciding on the usefulness of an intervention that is deemed suitable for other reasons.
This suggests that stratifying AF patients by underlying drivers of AF could inform management, for example, considering cardiac and systemic comorbidity e.
It is recognized that these types of AF will overlap in clinical practice, and that their impact for management needs to be evaluated systematically.
Patients with AF have significantly poorer quality of life than healthy controls, experiencing a variety of symptoms including lethargy, palpitations, dyspnoea, chest tightness, sleeping difficulties, and psychosocial distress.
The identification of such conditions, their prevention and treatment is an important leverage to prevent AF and its disease burden. Knowledge of these factors and their management is hence important for optimal management of AF patients.
Heart failure and AF coincide in many patients. Prevention of adverse outcomes and maintenance of a good quality of life are the aims of management in all patients with AF and concomitant heart failure, regardless of LVEF.
Of note, the only therapy with proven prognostic value in these patients is anticoagulation, and appropriate OAC should be prescribed in all patients at risk of stroke see Chapter 9.
Rate control of AF is discussed in detail in Chapter In brief, only beta-blockers and digoxin are suitable in HFrEF because of the negative inotropic potential of verapamil and diltiazem.
Beta-blockers are usually the first-line option in patients with clinically stable HFrEF, although a meta-analysis using individual patient data from randomized controlled trials RCTs found no reduction in mortality from beta-blockers vs.
In a meta-analysis of observational studies, digoxin had a neutral effect on mortality in patients with AF and concomitant heart failure adjusted observational studies HR 0.
Patients with AF and HFrEF who present with severe symptoms may require rhythm control therapy in addition to rate control therapy.
For patients who develop HFrEF as a result of rapid AF tachycardiomyopathy , a rhythm control strategy is preferred, based on several relatively small patient cohorts and trials reporting improved LV function after restoration of sinus rhythm.
Initial management of patients presenting acutely with atrial fibrillation and heart failure. Adapted from Kotecha and Piccini. The diagnosis of heart failure with preserved ejection fraction HFpEF in patients with AF is problematic because of the difficulty in separating symptoms that are due to HF from those due to AF.
Although diagnostic differentiation can be achieved by cardioversion and clinical reassessment but should be reserved for symptomatic improvement as a specific therapy that improves prognosis in HFpEF is currently lacking.
Echocardiography can support the detection of HFpEF in patients with symptomatic AF by providing evidence of relevant structural heart disease [e.
Further study of this group is required before particular treatment strategies in AF patients with HFmrEF can be recommended. Hypertension is a stroke risk factor in AF; uncontrolled high blood pressure enhances the risk of stroke and bleeding events and may lead to recurrent AF.
Therefore, good blood pressure control should form an integral part of the management of AF patients. Valvular heart disease is independently associated with incident AF.
In fact, while AF implies an incremental risk for thrombo-embolism in patients with mitral valve stenosis, , , there is no clear evidence that other valvular diseases, including mitral regurgitation or aortic valve disease, need to be considered when choosing an anticoagulant or indeed to estimate stroke risk in AF.
Recommendations for patients with valvular heart disease and atrial fibrillation. Diabetes and AF frequently coexist because of associations with other risk factors.
Intensive weight reduction in addition to the management of other cardiovascular risk factors in the range of 10—15 kg weight loss achieved , led to fewer AF recurrences and symptoms compared with an approach based on general advice in obese patients with AF.
Obesity may increase the rate of AF recurrence after catheter ablation, — with obstructive sleep apnoea as an important potential confounder.
Obesity has also been linked to a higher radiation dose and complication rate during AF ablation. Recommendation for obese patients with atrial fibrillation.
AF has been associated with obstructive sleep apnoea. Risk factor reduction and continuous positive airway pressure ventilation can reduce AF recurrence.
Obstructive sleep apnoea treatment should be optimized to improve AF treatment results in appropriate patients. Patients with chronic obstructive pulmonary disease often suffer from atrial tachycardias, which need to be differentiated from AF by ECG.
Agents used to relieve bronchospasm, notably theophyllines and beta-adrenergic agonists, may precipitate AF and make control of the ventricular response rate difficult.
Non-selective beta-blockers, sotalol, propafenone, and adenosine should be used with caution in patients with significant bronchospasm, while they can safely be used in patients with chronic obstructive pulmonary disease.
Beta-1 selective blockers e. Recommendations for patients with atrial fibrillation and respiratory diseases. CrCl in AF patients can deteriorate over time.
Recommendations for patients with kidney disease and atrial fibrillation. Most patients initially access the healthcare system through pharmacists, community health workers, or primary care physicians.
The initial assessment should be performed at the point of first contact with the healthcare system, and is feasible in most healthcare settings when an ECG is available.
Haemodynamic instability or limiting, severe symptoms;. Presence of precipitating factors e. Integrated care of all patients with newly diagnosed AF should help to overcome the current shortcomings of AF management, such as underuse of anticoagulation, access to rate and rhythm control therapy, and inconsistent approaches to cardiovascular risk reduction.
Clinical signs calling for urgent involvement of a specialized atrial fibrillation service a. Acute and chronic management of atrial fibrillation patients, desired cardiovascular outcomes, and patient benefits.
Several structured approaches to AF care have been developed. Some evidence underpins their use, while more research is needed into the best way of delivering integrated AF care.
Integrated AF management in an RCT increased the use of evidence-based care, and reduced by approximately one-third the composite outcome of cardiovascular hospitalization and cardiovascular death over a mean follow-up of 22 months Patients should have a central role in the care process.
As treatment of AF requires patients to change their lifestyles and adhere to chronic therapy, at times without an immediately tangible benefit, they need to understand their responsibilities in the care process.
Delegation of tasks from specialists to general physicians and from physicians to allied health professionals is a fundamental concept of integrated care models.
A multidisciplinary AF team approach includes an efficient mix of interpersonal and communication skills, education, and expertise in AF management, as well as the use of dedicated technology.
This approach underlines the importance of redesigning daily practice in a way that encourages non-specialists and allied professionals to have an important role in educating patients and co-ordinating care, while the specialist remains medically responsible.
Cultural and regional differences will determine the composition of AF teams. Some non-specialist health care professionals, e. Others may seek training to acquire such knowledge.
Other components of AF management e. Integrated AF care structures should support treatment initiation by non-specialists where appropriate, and provide ready access to specialist knowledge to optimize AF care.
Technology, such as decision support software, has the potential to enhance the implementation of evidence-based care and improve outcomes, when used to enhance expert advice.
With a view to support the wider use of such technology, this Task Force is providing digital decision tools, in the form of freely accessible smartphone apps, to AF healthcare professionals and to AF patients.
Recommendations for an integrated approach to care. AF is often found in patients with other, at times undiagnosed, cardiovascular conditions.
Thus, all AF patients will benefit from a comprehensive cardiovascular assessment. A complete medical history should be taken and all patients should undergo clinical evaluation that includes thorough assessment for concomitant conditions, establishing the AF pattern, estimation of stroke risk and AF-related symptoms, and assessment of arrhythmia-related complications such as thrombo-embolism or LV dysfunction.
A lead ECG is recommended to establish a suspected diagnosis of AF, to determine rate in AF, and to screen for conduction defects, ischaemia, and signs of structural heart disease.
Initial blood tests should evaluate thyroid and kidney function, as well as serum electrolytes and full blood count.
Transthoracic echocardiography is recommended in all AF patients to guide treatment decisions. Transthoracic echocardiography should be used to identify structural disease e.
Ambulatory ECG monitoring in AF patients can assess the adequacy of rate control, relate symptoms with AF recurrences, and detect focal induction of bouts of paroxysmal AF.
Transoesophageal echocardiography TOE is useful to further assess valvular heart disease and to exclude intracardiac thrombi, especially in the LAA, to facilitate early cardioversion or catheter ablation.
In patients with AF and signs of cerebral ischaemia or stroke, computed tomography CT or magnetic resonance imaging MRI of the brain is recommended to detect stroke and support decisions regarding acute management and long-term anticoagulation.
Delayed-enhancement MRI of the left atrium using gadolinium contrast, — T1 mapping using cardiac MRI, and intracardiac echo may help to guide treatment decisions in AF, but require external validation in multicentre studies.
Most AF patients need regular follow-up to ensure continued optimal management. Follow-up may be undertaken in primary care, by specially trained nurses, by cardiologists, or by AF specialists.
Follow-up should ensure implementation of the management plan, continued engagement of the patient, and therapy adaptation where needed.
Recommendations for diagnostic workup of atrial fibrillation patients. Therapies with prognostic benefit need careful explanation to patients when their benefits are not directly felt.
Rhythm control therapy can be successful if symptoms are controlled, even when AF recurs. Explaining the expected benefits to each patient at the start of AF management will prevent unfounded expectations and has the potential to optimize quality of life.
OAC therapy can prevent the majority of ischaemic strokes in AF patients and can prolong life. Despite this evidence, underuse or premature termination of OAC therapy is still common.
Simple, clinically applicable stroke risk-stratification schemes in AF patients were developed in the late s in small cohort studies, and have later been refined and validated in larger populations.
Since its first incorporation in the ESC guidelines in , it has been widely used. Other, less established risk factors for stroke include unstable international normalized ratio INR and low time in therapeutic range TTR in patients treated with VKAs; previous bleed or anaemia; alcohol excess and other markers for decreased therapy adherence; CKD; elevated high-sensitivity troponin; and elevated N-terminal pro-B-type natriuretic peptide.
Controlled trials studying OAC in AF patients have been enriched for patients at high risk of stroke, 38 , 39 , 42 , , , , , and hence there is strong evidence that patients with a CHA 2 DS 2 -VASc risk score of 2 or more in men, and 3 or more in women, benefit from OAC.
Fortunately, we now have a growing evidence base regarding stroke risk in patients with one clinical risk factor i. In many of these patients, anticoagulation seems to provide a clinical benefit.
Importantly, age 65 years and older conveys a relatively high and continuously increasing stroke risk that also potentiates other risk factors such as heart failure and sex.
Hence, an individualized weighing of risk, as well as patient preferences, should inform the decision to anticoagulate patients with only one CHA 2 DS 2 -VASc risk factor, apart from female sex.
Measurement of cardiac troponin high-sensitivity troponin T or I and N-terminal pro-B-type natriuretic peptide may provide additional prognostic information in selected AF patients.
Several bleeding risk scores have been developed, mainly in patients on VKAs. For example, older age is one of the most important predictors of both ischaemic stroke and bleeding in AF patients.
Rather, bleeding risk factors should be identified and treatable factors corrected see chapter 8. Modifiable and non-modifiable risk factors for bleeding in anticoagulated patients based on bleeding risk scores.
VKA therapy reduces the risk of stroke by two-thirds and mortality by one-quarter compared with control aspirin or no therapy. The use of VKAs is limited by the narrow therapeutic interval, necessitating frequent monitoring and dose adjustments, but VKAs, when delivered with adequate time in therapeutic range TTR , are effective for stroke prevention in AF patients.
Patients who fare well on this score, when treated with a VKA, have on average a higher TTR than patients who do not fare well on the score.
Their use in clinical practice is increasing rapidly. Rates of haemorrhagic stroke and intracranial haemorrhage, but not of ischaemic stroke, were lower on apixaban.
Rates of gastrointestinal bleeding were similar between the two treatment arms. Both dabigatran doses significantly reduced haemorrhagic stroke and intracranial haemorrhage.
There was a non-significant numerical increase in the rate of myocardial infarction with both dabigatran doses, , which has not been replicated in large post-authorization analyses.
Cardiovascular death was reduced in patients randomized to edoxaban 60 mg once daily or edoxaban 30 mg once daily compared with warfarin. Only the higher dose regimen has been approved for stroke prevention in AF.
Rivaroxaban did not reduce the rates of mortality, ischaemic stroke, or major bleeding events compared to VKA.
There was an increase in gastrointestinal bleeding events, but a significant reduction in haemorrhagic stroke and intracranial haemorrhage with rivaroxaban compared with warfarin.
Comparable event rates have been reported in post-authorization analyses, which are part of the post-approval risk management process.
A meta-analysis 39 based on the high-dose treatment groups of the pivotal studies of warfarin vs. Notably, the substantial reduction in intracranial haemorrhage by NOACs compared with warfarin seems unrelated to the quality of INR control.
CKD is associated with stroke and bleeding in large data sets. Approximately one in eight dialysis patients suffer from AF, with an incidence rate of 2.
There are no randomized trials assessing OAC in patients after kidney transplantation. Potential pharmacokinetic interactions of OAC with immunosuppressive agents should be considered.
The evidence supporting antiplatelet monotherapy for stroke prevention in AF is very limited. Recommendations for stroke prevention in patients with atrial fibrillation.
Interventional LAA occlusion, — and limited experience with percutaneous LAA ligation, has mainly been reported in observational studies and registries.
Surgical LAA occlusion or exclusion concomitant to cardiac surgery has been performed for many decades and with various techniques.
One randomized trial evaluating the role of concomitant AF surgery and LAA occlusion reported in , without a clear benefit of LAA exclusion for stroke prevention in the subgroup undergoing AF surgery.
The most important risk factors for stroke in patients with AF are advanced age and previous cardioembolic stroke or TIA, emphasizing the need for OAC in these patients.
The highest risk of recurrent stroke is in the early phase after a first stroke or TIA. Thrombectomy can be performed in anticoagulated patients with distal occlusion of the internal carotid artery or middle cerebral artery in a 6 h window.
Data on the optimal use of anticoagulants heparin, low-molecular-weight heparin, heparinoid, VKA, NOAC in the first days after a stroke are scarce.
Parenteral anticoagulants seem to be associated with a non-significant reduction in recurrent ischaemic stroke when administered 7—14 days after the acute stroke [odds ratio OR 0.
NOACs seem to convey slightly better outcomes, mainly driven by fewer intracranial haemorrhages and haemorrhagic strokes OR 0.
Initiation or continuation of anticoagulation in atrial fibrillation patients after a stroke or transient ischaemic attack. This approach is based on consensus rather than prospective data.
No prospective studies have investigated the benefit or risk of the initiation of OAC after intracranial haemorrhage, and patients with a history of intracranial bleeding were excluded from the randomized trials comparing NOACs with VKAs.
The available evidence indicates that anticoagulation in patients with AF can be reinitiated after 4—8 weeks, especially when the cause of bleeding or the relevant risk factor e.
Recommendations for secondary stroke prevention. Initiation or resumption of anticoagulation in atrial fibrillation patients after an intracranial bleed.
This approach is based on consensus opinion and retrospective data. In a meta-analysis of 47 studies, the overall incidence of major bleeding with VKAs was 2.
Uncontrolled hypertension increases the risk of bleeding on OAC. Treatment according to current guidelines is recommended in patients with known hypertension.
History of bleeding events and the presence of anaemia are important parts of the assessment of all patients receiving OAC. The majority of bleeding events are gastrointestinal.
Compared with warfarin, the risk of gastrointestinal bleeds was increased for dabigatran mg twice daily, , rivaroxaban 20 mg once daily, and edoxaban 60 mg once daily.
This also appears true for patients who have had an intracranial haemorrhage, once modifiable bleeding risk factors e. Patient information and empowerment, best delivered through integrated AF management, seem paramount to achieve this goal.
Alcohol excess is a risk factor for bleeding in anticoagulated patients, mediated by poor adherence, liver disease, variceal bleeding, and risk of major trauma.
Severe alcohol abuse and binge drinking habits should be corrected in patients eligible for OAC. Falls and dementia are associated with increased mortality in AF patients, without evidence that these conditions markedly increase the risk of intracranial haemorrhage.
In addition to food and drug interactions, multiple genetic variations affect the metabolism of VKAs. Most cardiovascular interventions e.
When interruption of OAC is required, bridging does not seem to be beneficial, except in patients with mechanical heart valves: In a randomized trial of patients with AF, interruption of anticoagulation was non-inferior to heparin bridging for the outcome of arterial thrombo-embolism incidence of 0.
General assessment of an anticoagulated patient with AF experiencing a bleeding event should include the assessment of bleeding site, onset, and severity of the bleeding, the time-point of last intake of OAC and other antithrombotic drugs, and other factors influencing bleeding risk such as CKD, alcohol abuse, and concurrent medications.
Laboratory tests should include haemoglobin, haematocrit, platelet count, renal function, and, for VKA patients, prothrombin time, activated partial thromboplastin time, and INR.
Coagulation tests do not provide much information in patients on NOACs, except for activated partial thromboplastin time in the case of dabigatran.
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Oxford University Press is a department of the University of Oxford. Sign In or Create an Account. Volume 40 Issue 5 01 February Year in Cardiology The Year in Cardiology series summarises key topics in cardiology from the past 12 months.
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