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Aims and objectives
What is AF?
How is AF diagnosed?
Why do we care?
Treatment options?
Pharmacology of AF
Case Studies
Questions?
Atrial fibrillation
Multiple foci causing fibrillation waves
AV node slows conduction to ventricles
Sinus rhythm
Atrial fibrillation
Diagnosing AF
Pulse checks
3 lead monitor, 12 lead ECG, 24/48 hour 7 day Holter monitor
If found
History Clinical examination
CXR ECHO
Labs electrolytes thyroid renal hepatic function FBC BNP is some.
Classification
Paroxysmal (23%) Self-terminating (<7 days)
Persistent (38%) Lasting longer than 7 days
Permanent (39%) Episodes > 1 year or unresponsive to reversal
Non valvular AF is AF in the absence of rheumatic mitral stenosis, a mechanical or bioprosthetic heart valve, or mitral valve repair
Epidemiology
Most common presenting arrhythmia in cardiology
Affects 2% of the population
Incidence of AF increasing (13% in last 20years)
Stewart et al Population, prevalence, incidence and predictors of atrial fibrillations. Heart 2001 86:516-521
Increasing Prevalence with age. Approx 1% of those <60 years whereas 12% of those in the 75 to 84 year age range.
AHA/ASC Guidelines for management of AF JACC 2014
Why do we care?
Impact of Atrial Fibrillation on the Risk of Death The Framingham Heart Study
Conclusions—In subjects from the original cohort of the Framingham Heart Study, AF was associated with a 1.5- to 1.9-fold mortality risk after adjustment for the preexisting cardiovascular conditions with which AF was related. The decreased survival seen with AF was present in men and women and across a wide range of ages.
Circulation 1998:946-952
Rotterdam Study - Ommoord
7983 participants over age 55 years
1990 – 1999
209 cases of AF noted on inception
167 developed new AF over course of study
Over all incidence 5.5%
Prevalence increasing with age 55 – 60yrs 0.7% 85yr and above 17.8%
Heeringa et al 2006 EHJ 27: 949 - 953
Etiology of AF
Atrial dilatation and micro fibrosis are the most important factors contributing to the occurrence and maintenance of AF
AF is associated with increase in connective tissue between cardiac cells
Leads to increase deposits of collagen and fibronectin causing fibrosis
Fibrosis within atrial tissues leads to the development of arrhythmias
The appearance of AF is often associated with exacerbation of underlying heart disease.
Decompensation
Loss of atrial contraction may markedly decrease cardiac output particularly if diastolic ventricular filling is impaired by mitral stenosis hypertension hypertrophic or restrictive cardiomyopathy.
Sympathetic activation and vagal withdrawal such as with exertion or illness accelerate the ventricular response.
Contributing factors
Obesity 15% increase in obesity
equates to a 7.5% increase in AF
Hypertension (71%)
Valvular heart disease (63%)
Diabetes mellitus (20%)
Coronary artery disease (36%)
Congestive heart failure (41%)
COPD (11%)
Sleep apnoea
Ageing
Thyroid dysfunction (10%)
Renal disease (13%)
EORP-AF study Europace 2014;16(3):308-319
Risk of Stroke.
Associated with a 5 fold increase risk of stroke and stroke risk increases with age.
AF related strokes are likely to be more severe then non AF strokes
AHA/ACC/HRS Guidelines JACC 2014
Observed absolute stroke rates for nonanticoagulated patients with single independent risk factors were in the range of 6 to 9% per year for prior stroke/TIA, 1.5 to 3% per year for history of hypertension, 1.5 to 3% per year for age >75, and 2.0 to 3.5% per year for diabetes.
Neurology August 7 2007 Vol 69 No 6 546-554
AF non a benign issue!
5 fold increase in Stroke
3 fold increase in Heart Failure
2 fold increase in Dementia
Patients with AF are hospitalized twice as often as patients without AF: Are three times more likely to have multiple admissions and 2.1% of patients with AF died in hospital compared to 0.1% without it.
Diabetes patients are at higher risk of AF
Diabetes Mellitus is a strong independent risk factor for atrial fibrillation atrial flutter.
Control 10.3% A Fib 2.5% A Flutter
DM 14.9% A Fib 4% A Flutter
International Journal of Cardiology Vol 105 Issue 3 P315-318 2005
Symptoms
Symptoms can range from non existent to severe.
Chronic fatigue
Breathlessness on exertion
Palpitations
Syncope/ pre syncope
Chest pain/ tightness on exertion
Tachycardia induced cardiomyopathy
Embolic stroke (5 fold risk of stroke)
Acute Management
Stable or unstable?
Unstable
transfer to hospital
Stable
Rate control
Consider Anticoagulation
Refer for Cardiology opinion.
Initial aims of treatment
Reduce symptoms Rate control
Beta blockade/ calcium channel blockade
Determine LV function - Echocardiogram Antiarrhythmic selection
DC Cardioversion Performed under G.A. (propofol)
Synchronised electrical shock AP position of pads
Success rate >95%
Risks 1-2% cardiac arrest (VF/VT) – beware digoxin/ over use of rate control Stroke Skin burns Aspiration
Awake within 5-10min, If fails – proceed to chemical then immediate DC cardioversion
Post Discharge
Anticoagulation monitoring for further 6 - 8 weeks If CHADS2VA2Sc score < 2 aspirin 75mg od If > 2 warfarin, dabigatran or rivaroxaban life-long
Antiarrhythmic continues (long term)
Advice for patients Avoid alcohol (specifically spirits) Avoid caffeine Avoid eating large meals
If palpitations reoccur – get to hospital immediately
C oronary ADH ypertensionA2 ge >75D iabetesS2 trokeV ascular DiseaseA ge >65S ex category (F)
The management cascade for patients with AF
ACEI = angiotensin-converting enzyme inhibitor; AF = atrial fibrillation; ARB = angiotensin receptor blocker;PUFA = polyunsaturated fatty acid; TE = thrombo-embolism.
Available DrugsVaughan Williams Classification
Class I-Sodium channel blockers quinidine, disopyramide, lignocaine flecainide, propafenone
Class II-Beta blockers propranolol, atenolol, metoprolol, bisoprolol, nebivolol
Class III- Potassium channel blockers sotalol, amiodarone, ibutilide
Class IV-Calcium channel blockers verapamil, diltiazem
Others-Digoxin, Adenosine
Class 1 drugs-Sodium channel blockers
1a-Disopyramide-anticholinergic side effects, occasionally torsades des pointes-dose is 250mg SR bd
Quinidine-not used anymore as high chance of torsades des pointes. Procainamide-lupus like syndrome without renal involvement, torsades.
1b-Lignocaine-toxicity usually in elderly patients with
heart failure manifest by confusion and convulsions
Class 2. Beta blockers
Class 3.-Potassium channel blockers
Amiodarone, Sotalol, Ibutilide, Bretylium
• Nausea, hypothyroidism, less commonly hyperthyroidism, skin discolouration-blue-gray, photosensitive rash-use sunblock, corneal deposits-night driving, hepatitis-cumulative with oral preparation, allergic with intravenous preparation, pulmonary fibrosis, torsades (unusual)
Use minimum dose, usually 200mg/d
Check TFTs and LFTs and CxR at intervals
Class 4-Calcium channel blockers
Verapamil-constipation, hypotension, ankle and finger oedema, facial flushing, headache
Diltiazem-as above but less likely to cause side-effects
Digoxin, and adenosine are not classified in Vaughan-Williams classification
Types of rhythm correction
DC cardioversion (20%)
Chemical cardioversion (36%) Ibutilide Vernakalant Amiodarone
Radiofrequency ablation (7%)
EORP-AF study Europace 2014;16(3):308-319
Depends on Whether paroxysmal, persistent or
chronic Presence or absence of other heart
disease Presence of diabetes, hypertension, CVA,
age > 75 years Severity of symptoms Reversible precipitant Response to medication
Treatment Journey (Onset > 48hrs)
Anticoagulation with warfarin*/ sinthrome*/ rivaroxaban/ dabigatran/ apixaban for at least 4 weeks (*INR 2.0 – 3.0)
Commence antiarrhythmic drugs prior to cardioversion (need echocardiogram)
DC cardioversion (day case or in-pt)
Anticoagulation for at least 6 weeks post procedure
OPD follow-up appointment
C oronary ADH ypertensionA2 ge >75D iabetesS2 trokeV ascular DiseaseA ge >65S ex category (F)
Diagnostic Evaluation
Time of onset
Patients in AF with signs of HF require immediate rate control, cardioversion and echocardiogram
Assess for stroke risk – CHADS2VA2Sc
TFT’s, FBC, U&E, BP, ECG, fasting glucose, LFT’s
AMADEUS Trial
Chronic kidney disease is associated with hypo and hypercoagulability
Impact of renal function on outcomes of anticoagulated AF patients
4576 patients
Mean age 70 years
Apostolakis et al Eur Heart J. 2013;34 (46):3572-3579
AMADEUS conclusion
Mild renal impairment (CrCl 60mL/min) doubles the risk of stroke and increased the risk of bleeding by almost 60% in anticoagulated patients with AF.
Patients with a CHA2DS2VASc 1-2 with CrCl 60mL/min Associated with an 8 fold higher stroke risk
New Oral Anticoagulants (NOACs)
Emerged as alternative to VKAs (warfarin) for thrombo-embolic prevention in non-valvular AF
Predicable effect without need for monitoring
Fewer drug interactions
Shorter plasma half life
Improved efficacy/ safety ratio
New anticoagulants
Dabigatran Rivaroxaban Apixaban
Action Direct thrombin inhibitor Xa inhibitor Xa inhibitor
Dose 150mg bd 20mg od 5mg bd
110mg bd 15mg od 2.5mg bd
Clinical trial
RE-LY ROCKET-AF ARISTOTLE
NOAC plasma levels
Dabigatran Rivaroxaban Apixaban
Plasma peak level
2hrs after ingestion
2-4 hrs after ingestion
1-4 hrs after ingestion
Plasma trough 12-24hr after ingestion
16-24hrs after ingestion
12-24 hrs after ingestion
PT Cannot be used Prolonged Cannot be used
INR Cannot be used Cannot be used Cannot be used
Dosing
Dabigatran Rivaroxaban Apixaban
Fraction renally excreted
80% 35% 27%
Normal dosing 150mg bd
>80yrs 110mg bd
20mg od 5mg bd
Dosing and CrCl 150mg bdCrCl 30 – 49 ml/min110mg bd if high risk of bleeding
15mg odCrCl 15 – 49 ml/min
2.5mg bdCrCl 15 – 49 ml/min
Not recommended
CrCl <30ml/min CrCl <15ml/min CrCl <15ml/min
Drug – Drug interactions
These are new agents so thee jury is still out on drug – drug interactions, some are listed in the respective SPC
E.g. Dabigatran – diclofenac risk of haemorrhage
E.g. Rivaroxaban – enzyme inducers, phenytoin and carbamazepine
All side effects and suspected Drug-drug interactions should be reported to the IMB
Management of bleeding in patients on dabigatran or rivaroxaban
There is currently no reversal agent or antidote for these medications.
Vitamin K is not effective.
In an acute overdose (<1hr) activated charcoal may be helpful.
Supportive care and control of bleeding site are the mainstays of managing bleeding.
Possible options Red cell concentrate Platelet transfusions if the patient has also received anti-platelet agents. Haemodialysis may be effective in removing dabigatran but not
rivaroxaban. Coagulation factors
Management of bleeding in patients on dabigatran or rivaroxaban
There is currently no reversal agent or antidote for these medications.
Vitamin K is not effective.
In an acute overdose (<1hr) activated charcoal may be helpful.
Supportive care and control of bleeding site are the mainstays of managing bleeding.
Possible options Red cell concentrate Platelet transfusions if the patient has also received anti-platelet agents. Haemodialysis may be effective in removing dabigatran but not
rivaroxaban. Coagulation factors
Swallowing Difficulties
Pradaxa (Dabigatran) should be swallowed as a whole with water, with or without food.(1)
Patients should be instructed not to open the capsule as this may increase the risk of bleeding.(1)
The oral bioavailability may be increased by 75 % compared to the reference capsule formulation when the pellets are taken without the Hydroxypropylmethylcellulose (HPMC) capsule shell..
Common Side effects (other than bleeding)
Dabigatran Abdominal pain Diarrhoea Nausea Dyspepsia
Rivaroxaban GI side effects - Abdominal pain,
diarrhoea, nausea, dyspepsia,constipation
Pruritus, rash (allergy uncommon) Fever Peripheral oedema Fatigue Headache, dizziness, syncope Tachycardia, hypotension
Switching to/ from warfarin
Warfarin to Dabigatran: Stop warfarin and start dabigatran when INR less than 2.
Warfarin to Rivaroxaban: Stop warfarin and start rivaroxaban when INR less than 3 (n.b.
rivaroxaban can cause false high INR)
Dabigatran to Warfarin: If CrCl >50ml/min – start warfarin 3 days before stopping dabigatran If CrCl 30-50ml/min – start warfarin 2 days before stopping dabigatran
Rivaroxaban to Warfarin Give both agents concurrently until INR is 2 or greater Test INR prior to next dose of rivaroxaban during this period
Missed Doses
Dabigatran Take dose if up to 6 hours late. Omit dose if over 6 hours late Do not double up next dose.
Rivaroxaban Take the tablet when you remember Do not take more than 1 tablet in 1 day
Predictors for long term SR
Short duration of AF
Antiarrhythmic therapy
Left atrial size
Avoidance of triggers
Upstream therapy
Upstream therapy to prevent fibrosis
ACE inhibitors
Statins
Angiotension receptor blockers (ARBs)
??Omega 3
Recommended