Download Does the MET reduce cardiac arrest

Atrial fibrillation and DM
Stephen Byrne and Fiona Barton Cardiology CNS
Aims and objectives
 What is AF?
 How is AF diagnosed?
 Why do we care?
 Treatment options?
 Pharmacology of AF
 Case Studies
 Questions?
Definition of atrial fibrillation
 Atrial fibrillation is an atrial arrhythmia characterised
by predominantly uncoordinated atrial activation with
consequent deterioration of atrial function.
• NICE 2008
Atrial fibrillation
Sinus rhythm
Atrial fibrillation
Multiple foci causing
fibrillation waves
AV node slows conduction to ventricles
A Fib
Atrial flutter
SA node
A single irritable focus
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.
ECG
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
 Congestive heart failure (41%)
 COPD (11%)
 Hypertension (71%)
 Sleep apnoea
 Valvular heart disease (63%)
 Ageing
 Diabetes mellitus (20%)
 Thyroid dysfunction (10%)
 Coronary artery disease (36%)
 Renal disease (13%)
EORP-AF study Europace 2014;16(3):308-319
Blood clot in the LAA
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 AD
H ypertension
A2 ge >75
D iabetes
S2 troke
V ascular Disease
A ge >65
S ex category (F)
Sites of AF
Radio frequency ablation of AF
The Watchman device to close the left
atrial appendage.
Rate Control and
Pharmacotherpay Options
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 Drugs
Vaughan 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 depositsnight 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 VaughanWilliams 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 AD
H ypertension
A2 ge >75
D iabetes
S2 troke
V ascular Disease
A ge >65
S ex category (F)
Ischemic Stroke Risk - CHA2DS2-VASc
Lip et al Stroke 2010
Ischemic Stroke Risk
(Clinical Application)
ESC Guidelines 2011
Bleeding Risk
Bleeding Risk
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
RE-LY
ROCKET-AF
ARISTOTLE
Clinical trial
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
20mg od
5mg bd
>80yrs 110mg bd
Dosing and CrCl
150mg bd
15mg od
CrCl 30 – 49 ml/min CrCl 15 – 49 ml/min
110mg bd if high risk
of bleeding
2.5mg bd
CrCl 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
Questions??
Thank you