Management of Atrial Fibrillation Science:Myths & Fashion


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Management of Atrial Fibrillation Science:Myths & Fashion

  1. 1. Management of Atrial FibrillationScience, Myths and Fashion <br />What you need to know as a community practitioner<br />Dr Duncan Hogg<br />Consultant Cardiologist,<br /> Aberdeen Royal Infirmary.<br />
  2. 2. Atrial FibrillationScience, Myths and Fashion<br />By the end of this talk I hope you will: <br />Have increased understanding of the epidemiology & pathophysiology of atrial fibrillation (AF)<br />Recognise the clinical consequences of AF. <br />Understand the different treatment options in AF<br />Be aware of current & future developments.<br />
  3. 3. Atrial Fibrillation: Epidemiology<br />AF is the commonest cardiac dysrhythmia. <br />Estimated to affect 5% of the population over 60 years & increasing to 10% over 75 years old. <br />Likely to become more prevalent with an ageing population and their increased exposure to pre-disposing cardiovascular disease.<br />Wolf et al. Secular trends in the prevalence of atrial fibrillation: The Framingham Study. Am Heart J 1996;131:790-795.<br />
  4. 4. AF: Costs to the Health Care System<br />1985-1990, 35% of all arrhythmia hospitalizations had principal diagnosis of atrial fibrillation. <br /> Average hospital stay = 5 days.<br />Other AF-related provision include:<br />Outpatient reviews and day-case cardioversions<br />Anti-arrhythmic drugs & INR monitoring<br />AF-induced strokes.<br /> The significant cost to the healthcare system is clear. <br />Geraets DR. Clin Pharm. 1993;12:721-735.<br />
  5. 5. Cardiac risk factors for AF <br />Independent risk factors for AF include- <br />Male gender, hypertension, diabetes, LV systolic (& diastolic) dysfunction, any valvular disease.<br />Hypertension now more responsible than any other. <br />AF also associated with any structural abnormality e.g all forms cardiomyopathies, tumours (atrial myxoma), or acute insults e.g. pericarditis, post cardiac surgery, myocardial infarction. <br />Kannel et al. Prevalence, incidence, prognosis, and predisposing conditions for atrial fibrillation: population-based estimates. Am J Cardiol 1998;82:2N-9N.<br />
  6. 6. Non-cardiac risk factors for AF <br />Non-cardiac causes of AF include:<br />Pulmonary: Any acute or chronic lung disease e.g. COPD, pneumonia, pulmonary embolism<br />Metabolic: Hyperthyroidism, electrolyte disorder<br />Toxic: Alcohol, acute & chronic systemic illness. <br />“Lone AF”. Those AF patients with absence of identifiable cardiovascular, or acute systemic insult or disease:<br />
  7. 7. Electrophysiology of AF <br />AF is caused by multiple circulating wavelets of excitation around the cardiac atria. <br />
  8. 8. Electrophysiology of AF<br />Atrial fibrillation is triggered into existence. <br />Single initiator or the interaction of many e.g.<br />supraventricularectopy, myocardial ischaemia, left atrial stretch due to pressure or volume load.<br />Atrial myocardium electrically remodels increasing the stability of AF- ‘AF begets AF’.<br />Later pathological remodelling (left atrium fibrosis) permanently affects the atrias’ electrical conductivity.<br />
  9. 9. Electrophysiology of AF<br />2 broad overlapping electrophysiological groups<br />Patients with normal hearts generally have a ‘trigger-predominant’ initiation.<br />Patients with abnormal hearts generally have a ‘substrate-predominant’ initiation.<br />Therapeutic potentials may differ between these two, particularly with respect to potential for AF ablation. <br />
  10. 10. ‘3P’ classification of AF <br />AF first detected<br />Paroxysmal AF<br /> (Self-terminating)<br />Persistent AF<br /> (Non self-terminating)<br />Permanent AF <br />Gallagher & Camm. Classification of atrial fibrillation. PACE 1997;20:1603-1605.<br />
  11. 11. Clinical: Mortality of AF<br />Relative risk of stroke & mortality in patients with AF cf in SR <br />
  12. 12. Clinical: Mortality of AF<br />Excess mortality in patients with AF is linked with severity of underlying heart disease eg CHF.<br />AF can facilitate the induction of ventricular arrhythmias eg Wolf-Parkinson-White.<br />Iatrogenic- anti-arrhythmic drugs (AADs) used for AF can be pro-arrhythmic and anticoagulants can cause fatal haemorrhagic events.<br />
  13. 13. Clinical: Morbidity of AF <br />Two aspects of patient morbidity in AF<br />Thromboembolic risk and <br />Cardiovascular symptoms<br />
  14. 14. Thromboembolism in AF<br />Atrial fibrillation can be a prothrombotic state. <br />AF is associated with an increased risk of stroke or thromboembolism (TE) of 1-17% per annum, depending on co-existent risk factors e.g.<br />age >65yrs, hypertension, diabetes, left ventricular dysfunction (LVD) or mitral valve disease. <br />Exact causes of thrombus formation not clear. <br />
  15. 15. AF thrombus formation in LAA <br />
  16. 16. AF thrombus formation in LAA<br /> Virchows’ triad<br />Loss of ordered atrial contraction produces turbulent blood flow within the cardiac atria. <br />Fibrillating atria can activate the endothelium. <br />The turbulent blood flow & endothelial activation of AF can produce platelet activation.<br />
  17. 17. Stroke prevention in AF <br />Aspirin & warfarin have been studied in AF thromboembolic prophylaxis.<br />Warfarin has strongest evidence for both primary & secondary prevention. <br />The SPAF (stroke prophylaxis in AF) investigators suggested prescription of warfarin to those at high thromboembolic risk. <br />
  18. 18. Stroke prevention in AF<br />From meta-analysis of thrombo-prophylaxis trials the overall benefit of treatment was- <br />Warfarin (INR 1.8-2.6) reduces risk of AF thrombo-embolic event by 66%.<br />Aspirin (75-300mg) reduces risk of AF thrombo-embolic events by 25%.<br /> (Clopidogrel alone, probably equivalent to aspirin)<br />
  19. 19. Thrombo-embolic risk stratification <br />CHADS2 score is a simple way to estimate stroke risk: <br />0: low risk <br /> 1-2: moderate risk<br /> >2 : high-risk<br />
  20. 20. Thrombo-embolic risk stratification <br />CHA2DS2 VASc score is a newer, still simple but more complete way to estimate risk: <br />
  21. 21. Thrombo-embolic risk stratification <br />Newly devised HAS-BLED score predictive tool for bleeding AF patients on warfarin<br />
  22. 22. Thrombo-embolic risk stratification <br />Balancing the risks and benefits of warfarin: <br />No warfarinif:<br />HAS-BLED > CHADS2 or<br />HAS-BLED >2 in CHADS2 0/1 <br />HAS-BLED >3 in CHADS2 2<br />Using this algorithm would reduce >10% of major bleeds<br />
  23. 23. AF cardiovascular morbidity <br />At least 40% of patients are asymptomatic at initial detection of AF. <br />Most patient symptoms are at the onset of AF and/ or related to exertion.<br />Symptoms are predominately caused by the elevated resting heart rate and rapid increase associated with exertion. <br />
  24. 24. Ventricular rate control in AF<br />AADs for ventricular rate (VR) control should aim to address VR at rest and on exertion. <br />ß-blockers, calcium channel blockers if no concern of left ventricular dysfunction (LVD). <br />If LVD, digoxin or amiodarone can be 1st line. <br /> NB. digoxin does not control VR on exertion. <br />Choice of rate or rhythm control management.<br />
  25. 25. Rhythm control of AF <br />Remains no evidence that restoration of SR is beneficial in reducing patient mortality or morbidity. <br />The PIAF study assessed rhythm or rate control effects on patient symptoms or QoL. <br />No difference in QoL assessment despite statistically better 5 min walking test in rhythm control group.<br />Rhythm or rate control in AF- Pharmacological Intervention in Atrial Fibrillation: a randomised trial. Lancet 2000;356:1789-94.<br />
  26. 26. Rhythm control of AF<br />The AFFIRM study found no benefit in overall mortality, thromboembolic events, 6-minute walk or QoL in rhythm control patients.<br />Decision on rhythm or rate control is guided by patient symptoms & clinic parameters for success in maintaining SR for example:<br /> Longevity of AF, LA size, LVD & MVD. <br />The AFFIRM investigators. NEJM 2002;347:1825-33.<br />
  27. 27. Rhythm control options for AF<br />Pharmacological conversion is most often effective for recent onset AF i.e. <48 hrs. <br />Many small studies for acute onset AF, but in a randomised comparison <br /> flecainide > propafenone > amiodarone (~90%) (~ 70%) (~ 60%)<br />Amiodarone best (10-15%) for persistent AF<br />
  28. 28. Rhythm control options in AF<br />
  29. 29. Electrical cardioversion (DC-CV)<br />DC-CV has a high initial success rate but high probability of future relapse to AF. <br />AADs differ in SR post DC-CV maintainenance<br />Van Gelder et al., Arch Intern Med 1996;156:2585–92.<br />
  30. 30. Maintaining SR post DC-CV<br />In CTAF study amiodarone > sotalol/propafenone<br />Debated whether sotalol has extra benefit over regular ß-blockers; potential pro-arrhythmic by QT prolongation.<br />Class I AAD (flecainide, propafenone) reduce relapse and often used in combination with ß-blockers. <br />Calcium channel blockers have modest benefit alone.<br />Canadian trial of atrial fibrillation (CTAF). NEJM 2000;342:913-20.<br />
  31. 31. Electrical cardioversion in AF<br />Without warfarin DC-CV associated with a significant risk of thrombo-embolic events, most in 2-10 days; significantly reduced risk with warfarin, but even with therapeutic INR about 1 in 200/250.<br />Elevation of thrombotic markers post DC-CV, probably due to ‘atrial stunning’. <br />phenomenon of atrialasystole in SR post DC-CV.<br />Optimal duration of warfarin post DC-CV still unclear. <br />
  32. 32. Current & near future new options in AF management<br />Holy grail of ‘cleaner amiodarone’ is now very close to reality with Dronedarone, after many false starts. <br />An oral direct thrombin inhibitor (DTIs) ie ‘warfarin without monitoring’ is (again) almost ready for use having been assessed versus warfarin. <br />Percutaneous occlusion of the left atrial appendage. <br />Electrophysiological cure increasingly possible in a selected number of AF patients.<br />
  33. 33. ‘Cleaner amiodarone’, the holy grail?!<br />Dronedarone (Multaq, Sanofi-Aventis) appears to lack many of the extra-cardiac side-affects of amiodarone. <br />It seems effective in reducing paroxysms of AF and maintaining SR post cardioversion c.f. placebo. <br />Concerns remain in significant heart failure and/or LVD of ventricular pro-arrhythmias (prolongs QT interval). <br />Many potential drug interactions (CYP3A4 drugs) with potential for induction of torsades de pointes. <br />Cost.............<br />
  34. 34. No more INRs in AF patients?<br />First oral DTI Ximelagatran (Exanta,AstraZeneca), which was non-inferior to dose-adjusted warfarin in prevention of all strokes and systemic embolic events in non-valvular AF patients.<br />The combined rate of major and minor bleedings was significantly lower for ximelagatran c.f warfarin. <br />Concerns of transient LFT derangement lead to it not reaching the market for its AF indication. <br />
  35. 35. No more INRs in AF patients?<br />Dagibatran (Pradaxa, Boehringer Ingelheim), has received FDA approval for AF thrombo-prophylaxis <br />RE-LY study was randomised, open-label study non-inferiority study assessing two doses 110mg & 150mg. <br />110mg had similar rate of stroke cf warfarin with significantly reduced major bleeding. <br />150mg had reduced risk of stroke cf warfarin with similar risk of major bleeding. <br />Less ICH c.f. warfarin. No liver toxicity; GI upset main s-a. <br />
  36. 36. No more INRs in AF patients?<br />Dagibatran currently costs .........<br />Other oral DTIs in various stages of development: apixaban (Bristol-Myers Squibb/Pfizer), rivaroxaban (Xarelto, Bayer/Johnson & Johnson); doxaban (Daiichi-Sankyo); and, betrixaban (Portola Pharmaceuticals/Merck). <br />This congested field may well bring the cost down. <br />
  37. 37. High stroke risk but high bleeding risk - stop thrombus forming in appendage<br />Sievert et al Circulation 2002;105:1887-1889<br />
  38. 38. Percutaneous closure of appendage<br />Left atrial angiogram: <br />after trans-septal puncture and LAA cannulation, contrast injection outlines LAA from which an ostial diameter can be measured; <br />contrast injection via a lumen through the implant reveals hang up of dye behind the sealing surface, indicating proper position and occlusion; <br />after device release, contrast injection in the LA establishes complete seal.<br />
  39. 39. Ablation: a cure for AF? <br />Haissaguerre al. Spontaneous initiation of AF by ectopic beats originating in the pulmonary veins. N Engl J Med 1998; 339: 659-666<br />
  40. 40. Ablation: a cure for AF? <br />
  41. 41. Ablation: a cure for AF? <br />CS, coronary sinus; LUPV, left upper pulmonary vein; RUPV, right upper pulmonary vein; RA isthmus line, right atrial isthmus line.<br />CT angiogram of the posterior aspect of the left atrium. Red lines indicate lines of electrical conduction block . <br />
  42. 42.
  43. 43. Ablation: a cure for AF? <br />Substrate evolution leads to a change in ablation technique <br />AF type: Paroxysmal Persistent Permanent <br />Role of pulmonary veins:<br />Role of muscle & scar:<br />Ablation: PVI Substrate & hybrid<br />
  44. 44. Summary of AF management<br />Prevalence, hospitalisation and healthcare costs for AF are increasing.<br />Thrombo-embolic risk stratification by CHADS2 score for all patients: not everybody needs warfarin. <br />Rate control can be achieved with many drugs: but aim to control resting and exertional heart rate. <br />Sinus is worth pursuing in many patients with AF, those that are symptomatic and likely to maintain SR.<br />
  45. 45. Summary of AF management<br />AADs are essential to reduce the risk of relapse to AF post DC-CV: ß-blockers & amiodarone.<br />Dronedarone is a possible replacement for amiodarone<br />Oral thrombin inhibitors “warfarin without the monitoring” are on the verge of replacing warfarin, but at what cost is not currently certain.<br />AF catheter ablation can cure selected AF patients particularly paroxsymal, accepting procedural risks.<br />
  46. 46. Atrial FibrillationScience, Myths and Fashion<br />Hopefully now you will: <br />Have increased understanding of the epidemiology & pathophysiology of atrial fibrillation (AF)<br />Recognise the clinical consequences of AF. <br />Understand the different treatment options in AF.<br />Be aware of future developments including ablation.<br />
  47. 47. Management of Atrial FibrillationScience, Myths and Fashion <br />What you need to know as a community practitioner<br />Dr Duncan Hogg<br />Consultant Cardiologist,<br /> Aberdeen Royal Infirmary.<br />