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

Multiple foci causing fibrillation waves

AV node slows conduction to ventricles

Sinus rhythm

Atrial fibrillation

A Fib

Atrial flutter

A single irritable focusSA node

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

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

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 ADH ypertensionA2 ge >75D iabetesS2 trokeV ascular DiseaseA ge >65S 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 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)

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

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

Questions??

Thank you