Atrial fibrillation

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QuotationMarkLeft.png "...have noticed, that after the heart proper, and even the right auricle were ceasing to beat and appeared on the point of death, an obscure movement, undulation/palpitation had clearly continued in the right auricular blood itself for as long as the blood was perceptibly imbued with warmth and spirit." QuotationMarkRight.pngWilliam Harvey Exercitatio anatomica de motu cordis et Sanguinis in animalibus 1628

Atrial fibrillation (AF), an ECG diagnosis, is an irregular heart rhythm due to chaotic electrical activity in the atria. AF predisposes to thrombus formation and embolic phenomena leading in some cases to the most important complication of stroke disease and other thromboembolic phenomena. It decreases cardiac output leading to cardiac symptoms.

LogoKeyPointsBox.pngAtrial fibrillation increases relative risk of:
  • Stroke 5 times
    • Anticoagulation reduces this risk by about two thirds and is usually simplistically traded off against the risk of major bleeding in an individual
  • Heart failure 3 times
  • Mortality twice

Contents

History

  • 1628 William Harvey in De motu cordis first describes atrial fibrillation
  • 1749 Jean Baptiste de Senac confirms Harvey in Traite de la Structure du Coeur de son action et de ses maladies and notes irregular heart beat in those with mitral valve disease at autopsy in Traite des Maladies du Coeur.[1]
  • 1906 Arthur Cushny and Charles Edmunds deshttp://www.doctors.net.uk/cribe auricular fibrillation in man in life[2].
  • 1906 Willem Einthoven describes ECG with pulsus inaequalis et irregularis[3]
  • 1909 Carl Rothberger, Heinrich Winterberg and Thomas Lewis realise atrial fibrillation common arrhythmia[2]
  • 1963 DC cardioversion of AF first described[4]
  • 1960s Increasing use of oral anticoaguloccurred within ation in complicated atrial fibrillation
  • 1970 First recognition of antiarrhythmic properties amiodarone and sotalol
  • 1972 First suggestion that atrial arrhythmias alone are the cause of systemic embolism[5][6]
  • 1989 First RCT of warfarin in non-rheumatic AF[7]

Aetiology

LogoKeyPointsBox.pngPrevalance of AF in some diseases (the big 3 causes accounting for over 70% of incidence in bold):

Seen with increasing age. Loss of normal atrial systole. Much PAF appears to have initial foci in the pulmonary veins, but in due course after repeated bouts of AF the atria themselves generate the arrhythmia. Thus atrial remodeling with fibrosis and dilation is associated but so are mitochondrial DNA mutations. Atria fibrillate at 400-500 bpm. Loss of any mechanical component to ventricular filling which then becomes entirely passive. Leads to stasis in atria and clot formation and increased incidence of thromboembolic disease. Anticoagulation should always be considered in those at risk.

Causes

Prevention

See also below. There are a number of commonly used drugs for other conditions that are associated with either reduced (statins) or increased risk of AF (corticosteroids)[8].

Post-operative

Intravenous magnesium[9] and amiodarone are well established to be effective after cardiac surgery. Ranolazine is in development for this indication[10].

Treatment

Management is generally aimed at getting the heart back into sinus rhythm, by rhythm control. “AF begets AF” is the aphorism. The longer a patient is in AF the more difficult it will be to return them to sinus rhythm. Repeated cardioversions may be needed.

In long-standing AF or where cardioversion is unlikely to produce sustained sinus rhythm, treatment is aimed at ameliorating the symptoms and complications. In patients with a fast ventricular response rate, rate control improves the efficiency of the heart. The potential thromboembolic complications are addressed with anti-coagulation, though the choice of drug must be tailored to the patient.

There is no mortality advantage in using either a rate control or rhythm control strategy in patients with or without left ventricular failure. Cardiac symptom control tends to be better with rate control but it is usually the most resource intensive option.

Rhythm control

Cardioversion

  • DC Cardioversion - Synchronised biphasic DC shock of 50-200 J given to a sedated patient. If a symptomatic patient cannot be treated, as would be best, within a day or so of the condition developing then they should be anticoagulated for 4-6 weeks before and 4 weeks after. Acute AF will spontaneously revert in about two thirds by 30 days[11].
  • Chemical Cardioversion

Maintenance sinus rhythm

Rate Control

An uncontrolled fast ventricular response rate can affect the efficiency of the heart and exacerbate pre-existing heart failure or ischaemic heart disease. However lenient rate-control (resting heart rate <110/min) is not inferior to stricter rate control (resting heart rate <80/min) and indeed larger trials are needed as the trend is towards better outcome with lenient rate control[12]

  • Beta-blockers (usually first choice)
    • However if heart failure present at time of initiation they offer no mortality benefit and other rate control options are likely to be superior[13].
  • Class IV anti-arrhythmics (never in heart failure or with beta blocker)
  • Digoxin (Good in heart failure but major catch is that doses for good resting rate control may exceed the serum level of digoxin associated with optimal mortality outcome)

Acute rate control

For rapid rate control the intravenous possibilities include metoprolol, esmolol, propanolol, diltiazem, verapamil, amiodarone (not with pre-excitation but good with severe hear failure or hypertension) and if the patient has uncompensated heart failure digoxin. In Wolf-Parkinson-White syndrome associated AF, procainamide or flecanide are best, with the class III agent ibutilide also being effective.

Embolism prevention

Until 2011 there was no drug based strategy directed towards embolism reduction that definitely reduced total mortality although trends in some trials of warfarin anticoagulation were suggestive[14] although the trends in the RE-LY trial[15] suggest this may be possible with the newer anticoagulants being developed. Apixaban does show a mortality reduction relative to warfarin[16]. The aim however still remains to reduce significant morbidity which in AF is from systemic embolisation. There are likely to be rapid developments in this area as all present evidence suggests all other factors being equal there is a strong relationship between effectiveness of a therapy and bleeding risk. In other words any agent that reduces clotting (and enough platelet) function will work, but those with the lowest bleeding risk for the same level of anticoagulation will be superior.

Anticoagulation

Event comparison of the anticoagulants dabigatran etexilate, rivaroxaban and apixaban in the indication of non-rheumatic atrial fibrillation against warfarin
LogoKeyPointsBox.png
  • Anticoagulation produces a large reduction in stroke and emboli which otherwise occur commonly with AF.
  • The risk of stroke corrected for other risk factors appears very similar for the first year after the issue is considered in any form of AF (paroxysmal, persistent, permanent)[17]
  • A mini-mental state examination score of less than 26 requires careful evaluation of risk/benefit with warfarin

The purpose of anti-coagulation is to prevent embolic strokes and other systemic embolisations. Stroke is common in established AF in the elderly and also in paroxysmal AF in the elderly with benefit in otherwise well patients in non-rheumatic AF starting about 65 years. Absolute benefit to the patient of anticoagulation continues to increase with age. Stroke is not common in younger patients and so net benefit may not be seen. The moment when a younger patient should start anticoagulation requires individual consideration. There is hard evidence that patients with cognitive impairment whose anticoagulation with warfarin can not be supervised should not be offered coagulation if their MMSE score is less than 26. Doing so results in more bleeding (9.6% versus 7% per 100 patient-years, p=0.04) and loss the stroke reduction benefit (vascular events 6.7% versus 3.6% per 100 patient-years, P=0.002).[18]. It is known that bleeding risk from falls in properly monitored warfarin anticoagulation is over-estimated by many physicians. It is also known that the hard evidence for risk from clinical trials is essentially absent for those who are cognitively impaired (but see above), non compliant and substance dependent (eg alcoholics). Patients with a high risk of falling are at increased risk of serious adverse consequences from anticoagulation and this constitutes a reason to cease anticoagulation in some of them. The decision should be individual, but a combination of several risk factors such as dementia and falls together could suggest conservative management. For example the non adjusted risk of intracranial haemorrhage in fallers with AF on warfarin is about a third their stroke risk. It can be expected that the combination of moderate dementia and falling would however make the ratio approach unity. However little objective guidance is possible due to literature limitations. One study showed that the combination in the elderly of AF, dementia and/or falling in those on warfarin was associated with a 45% annual mortality rate compared to a 12% annual mortality rate for those with AF alone on warfarin[19]. The small size of that study and the observation that death rates in dementia alone or falls alone matched for age in the elderly population are much lower, only suggests the possibility that there might be an additive risk. Warfarin has long been the anticoagulant of choice but dabigatran etexilate is non inferior at the doses of 110mg or 150mg twice a day[15] and along with other new anticoagulants such as rivaroxaban[20] and apixaban[16] are likely to have an increasing place in therapy. Indeed the higher 150mg dose of dabigatran etexilate and apixaban appear to be superior to poorly controlled warfarin therapy.

Events per 1000 patient years in non-rheumatic AF[21]
Intervention Stroke Bleed Crude net benefit
None 51 0 0
Aspirin 35 6 10
Warfarin 24 11 16

In patients with AF the following risk factors increase stroke risk[22]:

  • Prior stroke/TIA (relative risk 2.5, 95% CI 1.8 - 3.5) - absolute stroke rates for nonanticoagulated patients 6 - 9%/annum
  • Age (relative risk 1.5 per decade, 95% CI 1.3 - 1.7) - absolute stroke rates for nonanticoagulated patients 1.5 - 3%/annum if older than 75
  • Hypertension (relative risk 2.0, 95% CI 1.6 - 2.5) - absolute stroke rates for nonanticoagulated patients 1.5 - 3%/annum
  • Diabetes mellitus (relative risk 1.7, 95% CI 1.4 - 2.0) absolute stroke rates for nonanticoagulated patients 2.0 - 3.5%/annum
  • warfarin
    • Adjusted dose warfarin. Relative Rate cf placebo - 0.35 (95% credible interval 0.24 to 0.52)
    • Low dose warfarin. Relative Rate cf placebo - 0.35 (95% credible interval 0.19 to 0.60)
  • aspirin
    • Relative Rate cf placebo - 0.64 (95% credible interval 0.44 to 0.88)[21]

Antiplatelet agents

Aspirin was ineffective in those over 75 in the SPAF-1 trial, while the 325mg aspirin dose did work for younger patients. These issues were much better understood following the ACTIVE A[14] and ACTIVE K[23] trials. ACTIVE K established that anticoagulation therapy is superior to clopidogrel plus aspirin for prevention of vascular events in patients with atrial fibrillation. ACTIVE A established that clopidogrel plus aspirin is superior to aspirin (at least in those aged between 65 and 75) for prevention of vascular events in patients with atrial fibrillation at high risk of stroke. The two trials suggest that there is a reasonable alternative in initiating therapy to anticoagulation if anticoagulation is contraindicated. However for those already taking oral anticoagulation therapy clopidogrel plus aspirin is definitely inferior to anticoagulation. The actual absolute rate of major vascular events in ACTIVE A was 7.6% per year on aspirin and 6.8% on aspirin and clopidogrel. The rate of major haemorrhage on aspirin and clopidogrel was 2.0% per year, an increase of 0.7% per year against the vascular event gain of 0.8% per year. Some might interpret this as needing to treat about 1000 in a year to get a gain over aspirin alone.

Triple therapy

ESC consensus guidelines on what to do in patients on prior antithrombotic therapy for atrial fibrillation, who present with acute coronary syndrome and/or undergo percutaneous coronary intervention/coronary stenting exist. [24] Essentially the antiplatelet agents are given as well as the anticoagulant for the period of highest thrombotic risk with some modification if the risk of haemorrhage is high.

Paroxysmal atrial fibrillation

Paroxysmal atrial fibrillation (PAF) treatment is usually by antiarrhythmic cardioversion or DC shock (especially in accessory pathway related PAF) and often the same agent is used for long term rhythm control. Flecainide tends to be used when there is no cardiac ischaemia, sotalol when there is ischaemic heart disease (note that 80mg bd is needed for antiarrhythmic properties in average adult) and amiodarone, but the later has distinct long term toxicity disadvantages. In the first year after a cardioverted episode of paroxysmal atrial fibrillation the incidence of stroke or any thrombo-embolism is higher than persistent AF. This is seen as a strong argument for anticoagulation in this group of patients, which many physicians have been reluctant to do[17]. There is even evidence accumulating in the context of implantable rhythm monitoring device technology that the proportion of ischaemic strokes die to PAF has been somewhat underestimated[25].

Ablation

Pulmonary vein ablation is a proven and useful therapy especially for paroxysmal atrial fibrillation

Surgery

NICE Key Recommendations

The NICE published guidance was last updated in 2014 in which the key recommendations edited for brevity are:

  • Identification and diagnosis
    • An electrocardiogram (ECG) should be performed in all patients in whom atrial fibrillation (AF) is suspected because an irregular pulse has been detected.
  • Treatment for persistent AF
    • The indications for either an initial rate-control or rhythm-control strategy should not be regarded as mutually exclusive and the potential advantages and disadvantages of each strategy should be explained to patients before agreeing which to adopt
    • Comorbidities that might indicate one approach rather than the other should be taken into account
    • Appropriate antithrombotic therapy should be used.
    • In patients with permanent AF, who need treatment for rate-control:
      • Beta-blockers or rate-limiting calcium antagonists should be the preferred initial monotherapy
      • Digoxin should only be considered as monotherapy in the predominantly sedentary.
    • In patients with newly diagnosed AF for whom antithrombotic therapy is indicated, treatment should be initiated with minimal delay after the appropriate management of comorbidities.
      • Aspirin has no effective role
    • The stroke risk stratification algorithm should be used.

Screening for atrial fibrillation

Despite the morbidity and mortality associated with atrial fibrillation, screening and treatment of cases detected thereby would probably do more harm than good. This article explains this clearly.[26]

Other guidance and reviews

Risk calculators

References

  1. McMichael J. History of atrial fibrillation 1628-1819 Harvey - de Senac - Laënnec. British heart journal. 1982 Sep; 48(3):193-7.
  2. a b Fye WB. Tracing atrial fibrillation--100 years. The New England journal of medicine. 2006;355:1412-4. (Direct link – subscription may be required.)
  3. Einthoven W. Le télécardiogramme. Arch Int Physiol 1906;4:132-164
  4. MATHIVAT A, CLEMENT D, MARIE LOUISE J. A NEW TREATMENT OF CONTINUOUS ARRHYTHMIA DUE TO AURICULAR FIBRILLATION: EXTERNAL ELECTRIC SHOCKS BY THE CONTINUOUS CURRENT DC-103 DEFIBRILLATOR. (PRELIMINARY NOTE APROPOS OF 31 CASES). La Presse médicale. 1963 Dec 14; 71:2557-60.
  5. Runenstein JJ, Schulman CL, Yurchak PM et al. Clinical spectrum of the sick sinus syndrome. Circulation 1972;46:5-13
  6. Fairfax AJ, Lambert CD, Leatham A. Systemic embolism in chronic sinoatrial disorder. The New England journal of medicine. 1976 Jul 22; 295(4):190-2.(Link to article – subscription may be required.)
  7. Petersen P, Boysen G, Godtfredsen J, Andersen ED, Andersen B. Placebo-controlled, randomised trial of warfarin and aspirin for prevention of thromboembolic complications in chronic atrial fibrillation. The Copenhagen AFASAK study. Lancet. 1989 Jan 28; 1(8631):175-9.
  8. Hodgkinson JA, Taylor CJ, Hobbs FD. Predictors of incident atrial fibrillation and influence of medications: a retrospective case-control study. The British journal of general practice : the journal of the Royal College of General Practitioners. 2011 Jun; 61(587):e353-61.(Link to article – subscription may be required.)
  9. Shepherd J, Jones J, Frampton GK, Tanajewski L, Turner D, Price A. Intravenous magnesium sulphate and sotalol for prevention of atrial fibrillation after coronary artery bypass surgery: a systematic review and economic evaluation. Health technology assessment (Winchester, England). 2008 Jun; 12(28):iii-iv, ix-95.
  10. Burashnikov A, Antzelevitch C. Ranolazine versus amiodarone for prevention of postoperative atrial fibrillation. Future cardiology. 2011 Nov; 7(6):733-7.(Link to article – subscription may be required.)
  11. Doyle B, Reeves M. "Wait and see" approach to the emergency department cardioversion of acute atrial fibrillation. Emergency medicine international. 2011; 2011:545023.(Link to article – subscription may be required.)
  12. Van Gelder IC, Groenveld HF, Crijns HJ, Tuininga YS, Tijssen JG, Alings AM, Hillege HL, Bergsma-Kadijk JA, Cornel JH, Kamp O, Tukkie R, Bosker HA, Van Veldhuisen DJ, Van den Berg MP. Lenient versus strict rate control in patients with atrial fibrillation. The New England journal of medicine. 2010 Apr 15; 362(15):1363-73.(Link to article – subscription may be required.)
  13. Kotecha D, Holmes J, Krum H, Altman DG, Manzano L, Cleland JG, Lip GY, Coats AJ, Andersson B, Kirchhof P, von Lueder TG, Wedel H, Rosano G, Shibata MC, Rigby A, Flather MD. Efficacy of β blockers in patients with heart failure plus atrial fibrillation: an individual-patient data meta-analysis. Lancet. 2014 Dec 20; 384(9961):2235-43.(Link to article – subscription may be required.)
  14. a b Effect of Clopidogrel Added to Aspirin in Patients with Atrial Fibrillation. The New England journal of medicine. 2009 Mar 31.(Epub ahead of print) (Link to article – subscription may be required.)
  15. a b Connolly SJ, Ezekowitz MD, Yusuf S, Eikelboom J, Oldgren J, Parekh A, Pogue J, Reilly PA, Themeles E, Varrone J, Wang S, Alings M, Xavier D, Zhu J, Diaz R, Lewis BS, Darius H, Diener HC, Joyner CD, Wallentin L. Dabigatran versus warfarin in patients with atrial fibrillation. The New England journal of medicine. 2009 Sep 17; 361(12):1139-51.(Link to article – subscription may be required.)
  16. a b Granger CB, Alexander JH, McMurray JJ, Lopes RD, Hylek EM, Hanna M, Al-Khalidi HR, Ansell J, Atar D, Avezum A, Bahit MC, Diaz R, Easton JD, Ezekowitz JA, Flaker G, Garcia D, Geraldes M, Gersh BJ, Golitsyn S, Goto S, Hermosillo AG, Hohnloser SH, Horowitz J, Mohan P, Jansky P, Lewis BS, Lopez-Sendon JL, Pais P, Parkhomenko A, Verheugt FW, Zhu J, Wallentin L. Apixaban versus warfarin in patients with atrial fibrillation. The New England journal of medicine. 2011 Sep 15; 365(11):981-92.(Link to article – subscription may be required.)
  17. a b Nieuwlaat R, Dinh T, Olsson SB, Camm AJ, Capucci A, Tieleman RG, Lip GY, Crijns HJ. Should we abandon the common practice of withholding oral anticoagulation in paroxysmal atrial fibrillation? European heart journal. 2008 Mar 10.(Epub ahead of print) (Link to article – subscription may be required.)
  18. Flaker GC, Pogue J, Yusuf S, Pfeffer MA, Goldhaber SZ, Granger CB, Anand IS, Hart R, Connolly SJ. Cognitive function and anticoagulation control in patients with atrial fibrillation. Circulation. Cardiovascular quality and outcomes. 2010 May; 3(3):277-83.(Link to article – subscription may be required.)
  19. Jacobs LG, Billett HH, Freeman K, Dinglas C, Jumaquio L. Anticoagulation for stroke prevention in elderly patients with atrial fibrillation, including those with falls and/or early-stage dementia: a single-center, retrospective, observational study. The American journal of geriatric pharmacotherapy. 2009 Jun; 7(3):159-66.(Link to article – subscription may be required.)
  20. Patel MR, Mahaffey KW, Garg J, Pan G, Singer DE, Hacke W, Breithardt G, Halperin JL, Hankey GJ, Piccini JP, Becker RC, Nessel CC, Paolini JF, Berkowitz SD, Fox KA, Califf RM. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. The New England journal of medicine. 2011 Sep 8; 365(10):883-91.(Link to article – subscription may be required.)
  21. a b Cooper NJ, Sutton AJ, Lu G, Khunti K. Mixed Comparison of Stroke Prevention Treatments in Individuals With Nonrheumatic Atrial Fibrillation. Arch Intern Med. 2006;166:1269-1275 - Note Cochrane review update based on this due shortly
  22. Independent predictors of stroke in patients with atrial fibrillation: a systematic review. Neurology. 2007 Aug 7; 69(6):546-54.(Link to article – subscription may be required.)
  23. Connolly S, Pogue J, Hart R, Pfeffer M, Hohnloser S, Chrolavicius S, Pfeffer M, Hohnloser S, Yusuf S. Clopidogrel plus aspirin versus oral anticoagulation for atrial fibrillation in the Atrial fibrillation Clopidogrel Trial with Irbesartan for prevention of Vascular Events (ACTIVE W): a randomised controlled trial. Lancet. 2006 Jun 10; 367(9526):1903-12.(Link to article – subscription may be required.)
  24. Lip GY, Huber K, Andreotti F, Arnesen H, Airaksinen KJ, Cuisset T, Kirchhof P, Marín F. Management of antithrombotic therapy in atrial fibrillation patients presenting with acute coronary syndrome and/or undergoing percutaneous coronary intervention/ stenting. Thrombosis and haemostasis. 2010 Jan; 103(1):13-28.(Link to article – subscription may be required.)
  25. Rizos T, Wagner A, Jenetzky E, Ringleb PA, Becker R, Hacke W, Veltkamp R. Paroxysmal Atrial Fibrillation Is More Prevalent than Persistent Atrial Fibrillation in Acute Stroke and Transient Ischemic Attack Patients. Cerebrovascular diseases (Basel, Switzerland). 2011 Aug 31; 32(3):276-282.(Epub ahead of print) (Link to article – subscription may be required.)
  26. Mandrola J, Foy A, Naccarelli G. Screening for atrial fibrillation comes with many snags. JAMA internal medicine 2018, DOI: 10.1001/jamainternmed.2018.4038 (https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2696617
  27. Lafuente-Lafuente C, Mahé I, Extramiana F. Management of atrial fibrillation. BMJ (Clinical research ed.). 2009; 339:b5216.(Epub)