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Atrial Fibrillation:Rate Control, Rhythm Control, Anticoagulation & Ablation. What Are My Options?

ROBERT T ROGERS MSN, ACNP-BC, AACC

NORTON HEART SPECIALISTS

HEART RHYTHM CENTER

Speaker Disclosure

None to report

How Atrial Fibrillation is like a bear?

What is Atrial Fibrillation?

Incidence of AF

Index Age, yrs Men Women

40 26.0% (24.0 – 27.0) 23.0% (21.0 – 24.0)

50 25.9% (23.9 – 27.0) 23.2% (21.3 – 24.3)

60 25.8% (23.7 – 26.9) 23.4% (21.4 – 24.4)

70 24.3% (22.1 – 25.5) 23.0% (20.9 – 24.1)

80 22.7% (20.1 – 24.1) 21.6% (19.3 – 22.7)

Lifetime Risk for AF at Selected Index Ages by Sex

Lloyd-Jones DM, et al. Circulation. 2004 Aug 31;110(9):1042-6. Pub Med PMID: 15313941.

1 in 4 Men & women>40 Yearswill develop AF

Lifetime risk if currently free of AF

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Incidence of AF Atrial fibrillation is the most prevalent cardiac arrhythmia

Untreated Atrial Fibrillation increases mortality

Cost

AFib Costs and Consequences

More than 750,000 hospitalizations occur each year because of AFib. The condition contributes to an estimated 130,000 deaths each year. The death rate from AFib as the primary or a contributing cause of death has been rising for more than two decades.3,4

AFib costs the United States about $6 billion each year. Medical costs for people who have AFib are about $8,705 higher per year than for people who do not have AFib.1,2

Causes of AF Hypertension (usually with LVH)

Ischemic heart disease

Dilated cardiomyopathy

Restrictive cardiomyopathies such as amyloidosis, constrictive

Pericarditis

Cardiac tumors

Severe pulmonary hypertension

Obesity and obstructive sleep

Excessive alcohol intake (holiday heart),

Open heart or thoracic surgery,

Myocarditis

Pulmonary embolism.

Hyperthyroidism

Pathophysiology

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How do you feel with AF?

Complications- Heart and Brain Diagnosis of AF

ECG

Holter monitor

Event monitor (ILR)

Echocardiogram

Stress test

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Management :Time to wrestle the bear…

Management- What do we do?

2 things must be done regardless of rate and rhythm control

1. Change their ways

Lifestyle changes

Weight control

Heart Healthy Diet

Exercise

Sleep hygiene

Stress reduction

Treat underlying Medical Conditions

Sleep apnea

High blood pressure

Diabetes control

Thyroid disease

2. Protect their brains!

How do we save the brain?

How to save the brain

Anticoagulation

Warfarin

NOACs/DOACs

Eliquis, Xarelto, Pradaxa and Savaysa

Mechanical Occlusion

Watchman device

How do we save the heart?

Rate Control

Controls symptoms in some people

Rhythm Control

Anti-arrhythmic medications

Daily vs “pill in the pocket”

Catheter ablation

Surgical ablation

Anticoagulant drugs

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Who should be anticoagulated?

Lip GY, Nieuwlaat R, Pisters R, Lane DA, Crijns HJ. Chest. 2010 Feb;137(2):263-72. Pub Med PMID: 19762550.

Bleeding Risk Scores in AF

ATRIA HAS-BLED HEMORR2HAGES

Anemia1 3 Hypertension4 1 Hepatic10 or Renal disease2

11

Severe renal disease2 3 Abnormal Renal5 or Liver function6

11 Ethanol abuse 1

Age ≥75 yrs 2 Stroke 1 Malignancy 1

Any prior hemorrhage 1 Bleeding 1 Older Age (>75 yrs) 1

Hypertension3 1 Labile INR8 1 Reduced platelet number or function11 1

Elderly (>65 yrs) 1 Rebleeding12 2

Drugs9 or Alcohol

11 Hypertension4 1

Anemia13 1

Genetic factors14 1

Excessive fall risk15 1

Stroke 1

Apostolakis S, Lane DA, Guo Y, Buller H, Lip GY. J Am Coll Cardiol 2012;60:000–000. 2012 Jul 24. [Epub ahead of print] Online Appendix. PMID: 22858389.

1. Hemoglobin <13 g/dl men; <12 g/dl women2. Estimated glomerular filtration rate <30 ml/min or dialysis-dependent3. Diagnosed hypertension4. Systolic blood pressure >160 mmHg5. Presence of chronic dialysis or renal transplantation or serum creatinine ≥200 mmol/L6. Chronic hepatic disease (eg cirrhosis) or biochemical evidence of significant hepatic derangement (eg bilirubin 2 x upper

limit of normal, in association with aspartate aminotransferase/alanine aminotransferase/alkaline phosphatase >3 x upper limit normal, etc.)

8. Unstable/high INRs or poor time in therapeutic range (eg <60%)9. Concomitant use of drugs, such as antiplatelet agents, non-steroidal anti-inflammatory drugs, or alcohol abuse etc. 10. Cirrhosis, two-fold or greater elevation of AST or APT, or albumin <3.6 g/dl11. Platelets <75,000, use of antiplatelet therapy (eg daily aspirin) or NSAID therapy; or blood dyscrasia12. Prior hospitalization for bleeding13. Most recent hematocrit <30 or hemoglobin <10 g/dl14. CYP2C9*2 and/or CYP2C9*315. Alzheimer's dementia, Parkinson's disease, schizophrenia, or any condition predisposing to repeated falls

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Anticoagulants

Vitamin K Antagonists

Coumarin

Warfarin

Factor Xa Inhibitors

Heparins

Low molecular heparins

Apixaban (DOAC)

Rivaroxaban (DOAC)

Edoxaban (DOAC)

Direct Thrombin Inhibitors

Argatroban

Ximelagatran

Lepirudin

Bivalirudin

Dabigatran (DOAC)

1930s

Heparin

1950s 1990s 20021970s

Warfarin LMWHs Factor Xa inhibitor

DTIs

ArgatrobanBivalirudinLepirudinIprivask

FondaparinuxEnoxaparinDalteparinTinzaparin

1980s 2010-current

DTI and Factor Xainhibitors

DabigatranRivaroxaban

ApixabanEdoxaban

Developmental History –Current FDA Approved Anticoagulants

Warfarin- the old standby

DOSING

Usual dose is 5 mg/day (1-20 mg) Lower doses require in

Elderly Pt on increased risk of bleeding eg. Pt on aspirin Heart failure Liver disease Renal impairment Malnutrition Thyrotoxicosis (Opposite in Myxedema) Asian patients: Explained by genetic variation in hepatic enzymes

(CYP3C9 & VKORC1 Polymorphism) High intake dietary Vit-K (green vegetables e.g. broccoli)

reduces the efficacy of Warfarin. Practically best time to give warfarin is ~ 6 PM.

Commencement of oral anticoagulant therapy

If the baseline INR≤1.3 the patient will receive 5mg of warfarin once daily on days 1 and 2. The INR is checked on day 3 and 4 and the warfarin dose is adjusted according to the schedule.

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Caution with VITAMIN K containing food

It is okay to eat food with different levels of vitamin K, but because vitamin K can interfere with blood-thinning effects of warfarin, it is important to eat the same amount from day to day. Do not eat a lot one day and none the next

Vitamin K foods

Factors that affect warfarin effectiveness Side effects of Warfarin

Bleeding

Skin necrosis

Purple toe syndrome

Teratogenicity

Osteoporosis

Others: Agranulocytosis, leukopenia, diarrhea,

nausea, anorexia.

It’s a Brave New World of Anticoagulation….NOAC/DOAC…

Whatever you call them they are new and better than we had before

NOAC vs Warfarin

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NOAC vs WarfarinNOAC vs Warfarin

NOACs approved or under evaluation for prevention of systemic embolism or stroke in patients with non-valvular AF

Dabigatran Apixaban Edoxaban Rivaroxaban

Action Direct thrombin inhibitor

Activated factor Xa(FXa) inhibitor

Activated factor Xa (FXa) inhibitor

Activated factor Xa(FXa) inhibitor

Dose150 mg BID

110 mg BID

5 mg BID

2.5 mg BID

60 mg QD

30 mg QD

15 mg QD

20 mg QD

15 mg QD

Phase III clinical trial RE-LY 1ARISTOTLE 2

AVERROES 3ENGAGE-AF 4 ROCKET-AF 5

1. Connolly et al, N Engl J Med 2009; 361:1139-51 4. Ruff et al, Am Heart J 2010; 160:635-412. Granger et al, N Engl J Med 2011; 365:981-92 5. Patel et al, N Engl J Med 2011;365:883-913. Connolly et al , N Engl J Med 2011; 364:806-17

Drug-drug interactions and pharmacokinetics of NOACs

Absorption and metabolism of NOACs

Absorption and metabolism of NOAC

Dabigatran Apixaban Edoxaban Rivaroxaban

Bioavailability 3-7% 50% 62% 66% (w/o food) ~100% with food

Prodrug yes no no no

Clearance: non-renal/renal of adsorbed dose if normal renal function

20%/80% 73%/27% 50%/50% 65%/35%

Liver metabolism: CYP3A4 no yes (elimination; minor CYP3A4)

minimal (<4% of elimination)

yes (elimination)

Absorption with food no effect no effect 6-22% more +39%

Intake with food? no no no official recommendation yet

mandatory

Absorption with H2B/PPI plasma level -12 to -30% no effect no effect no effect

Asian ethnicity plasma level +25% no effect no effect no effect

GI tolerability dyspepsia 5-10% no problem no problem no problem

Elimination half-life 12-17h 12h 9-11h 5-9h (young)/11-13h (elderly)

Possible drug-drug interactions –Effect on NOAC plasma levels part 1

Dabigatran Apixaban Edoxaban Rivaroxaban

Atorvastatin P-gp/ CYP3A4 +18% no data yet no effect no effect

Digoxin P-gp no effect no data yet no effect no effect

Verapamil P-gp/ wk CYP3A4+12–180%

no data yet+ 53% (slow release)

minor effect

Diltiazem P-gp/ wk CYP3A4 no effect +40% No data minor effect

Quinidine P-gp +50% no data yet +80% +50%

Amiodarone P-gp +12–60% no data yet no effect minor effect

Dronedarone P-gp/CYP3A4 +70–100% no data yet +85% no data yet

Ketoconazole; itraconazole; voriconazole; posaconazole;

P-gp and BCRP/ CYP3A4 +140–150% +100% no data yet up to +160%

Red – contraindicated; orange – reduce dose; yellow – consider dose reduction if another yellow factor present; hatching – no data available; recommendation made from pharmacokinetic considerations

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Possible drug-drug interactions –Effect on NOAC plasma levels part 2

Interaction Dabigatran Apixaban Edoxaban Rivaroxaban

Fluconazole CYP3A4 no data no data no data +42%

Cyclosporin; tacrolimus

P-gp no data no data no data +50%

Clarithromycin; erythromycin

P-gp/ CYP3A4 +15–20% no data no data +30–54%

HIV protease inhibitors

P-gp and BCRP/ CYP3A4

no data strong increase no data up to +153%

Rifampicin; St John’s wort; carbamezepine; phenytoin; phenobarbital

P-gp and BCRP/ CYP3A4/CYP2J2

-66% -54% -35% up to -50%

Antacids GI absorption -12-30% no data no effect no effect

Red – contraindicated; orange – reduce dose; yellow – consider dose reduction if another yellow factor present;hatching – no data available; recommendation made from pharmacokinetic considerations

Switching between anticoagulant regimensVKA to NOAC INR <2.0: immediate

INR 2.0–2.5: immediate or next day INR >2.5: use INR and VKA half-life to estimate time to INR <2.5

Parenteral anticoagulant to NOAC:Intravenous unfractioned heparin(UFH)Low molecular weight heparin (LMWH)

Start once UFH discontinued (t½=2h). May be longer in patients with renal impairmentStart when next dose would have been given

NOAC to VKA Administer concomitantly until INR in appropriate rangeMeasure INR just before next intake of NOACRe-test 24h after last dose of NOACMonitor INR in first month until stable values (2.0–3.0) achieved

NOAC to parenteral anticoagulant Initiate when next dose of NOAC is due

NOAC to NOAC Initiate when next dose is due except where higher plasma concentrationsexpected (e.g. renal impairment)

Aspirin or clodiprogel to NOAC Switch immediately, unless combination therapy needed

Summary of the NOACThe Brain is now safe, how about the Heart?

Which to choose? Trials of Rate vs Rhythm Control

ACC/AHA/ESC Guidelines 2006

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AFFIRMBaseline Characteristics

Age = 69.7 ± 9.0 yrs

39% female

> 2 days of AF in 69%

CHF class > II in 9%

Symptomatic AF in 88%

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Rate Control versus Electrical Cardioversion for Persistent Atrial Fibrillation (RACE) Trial (n=522)

Van Gelder, I. et al. N Engl J Med 2002;347:1834-1840

CV death, HF, thromboembolic complications, bleeding, pacemaker, and SAEs.

Based on the data, why try for rhythm control at all?

LIMITATIONS of Trials: AGEGuideline Statement

ACC/AHA/ESC Guidelines 2014

LIMITATIONS 1

- The mean ages in AFFIRM and RACE were 70 and 68 years, respectively. -The RACE and AFFIRM trials did not address AF in younger, symptomatic patients with little underlying heart disease, in whom restoration of sinus rhythm by cardioversion antiarrhythmic drugs or non-pharmacological interventions still must be considered a useful therapeutic approach.

One may conclude from these studies that rate control is a reasonable strategy in elderly patients with minimal symptoms related to AF.

LIMITATIONS 2

Approximately one-half of patients in AFFIRM who had a detailed history had symptomatic episodes of AF that occurred less often than once per month.

Such patients would be expected to derive little symptomatic benefit from rhythm control, and the results may not directly apply to patients with frequent episodes of symptomatic AF

LIMITATIONS of Trials: SYMPTOMS

LIMITATIONS 3

Both trials allowed for cessation of anticoagulant therapy four weeks after documentation of SR, leading to a higher rate of stroke.

It has been postulated that continued anticoagulation might have led to a lower mortality in the rhythm control group

LIMITATIONS of Trials: ANTICOAGULATION

LIMITATIONS 4

The use of antiarrhythmic drugs in AFFIRM was associated with a significant increase in mortality (HR 1.49), which was due to non-cardiovascular causes, while the presence of SR was associated with a significant reduction in mortality (HR 0.53).

A similar benefit from being in sinus rhythm (relative risk 0.44) was noted in the DIAMOND trial that compared dofetilide to placebo in patients with reduced left ventricular systolic function

LIMITATIONS of Trials: DRUGS

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LIMITATIONS

One interpretation of these data is that maintenance of SR might be beneficial if there were a safer and more effective approach than current antiarrhythmic drugs:

The AFFIRM and RACE data were largely gathered before catheter ablation was common. The potential impact of this procedure (versus chronic antiarrhythmic therapy) remains incompletely explored

LIMITATIONS of Trials: DRUGS Bottom Line: Rate versus Rhythm Control for AF

The AFFIRM, RACE and AF-CHF trials have shown no mortality benefit from a rhythm control strategy compared to a rate control strategy.

Therefore, a rate control strategy, without attempts at restoration or maintenance of sinus rhythm (SR), is reasonable in some patients with AF, especially those who are elderly and asymptomatic.

If rate control offers inadequate symptomatic relief, restoration of SR may become a long-term goal.

Restoration and maintenance of SR continues to be a reasonable treatment approach in many patients with AF.

68

Knight, et al, Practical Rate and Rhythm Management of Atrial Fibrillation, January 2010 ed.

Rate ControlVentricular Rate Control

Principles of a Rate Control Strategy: Adequate control of the ventricular response during AF can significantly improve

symptoms and is critical to avoid tachycardia-mediated cardiomyopathy. Most patients managed using a rhythm control strategy also require medications for

rate control. Rate control during atrial flutter tends to be more difficult than during AF.What is Adequate Rate Control? Control of the ventricular rate during AF is important both at rest and with exertion.

No standard method for assessment of heart rate control has been established.

Criteria for rate control vary with patient age but usually involve achieving ventricular rates between 60 and 80 bpm at rest and between 90 and 115 bpm during moderate exercise.

For the AFFIRM trial, adequate control was defined as an average HR up to 80 bpm at rest and either an average rate up to 100 bpm during Holter monitoring with no rate above 100% of the maximum age-adjusted predicted exercise HR, or a maximum HR of 110 bpm during a 6-min walk test.

In the RACE trial, rate control was defined as less than 100 bpm at rest.

Only about 5%of patients from these trials required AV ablation to achieve HR control.

70Knight, et al, Practical Rate and Rhythm Management of Atrial Fibrillation, January 2010 ed.

Ventricular Rate Control:Drugs to Control the Ventricular Response

Beta blockers are the most effective drug class for rate control.

Calcium channel antagonists (non-dihydropyridine) are good choices for patients with asthma or COPD requiring beta agonist inhaler therapy.

Digoxin provides relatively poor rate control during exertion and should be reserved for patients with systolic HF.

Digoxin does not convert AF to SR and may perpetuate AF.

Digoxin is marginally effective as a sole agent, but may prove useful in combination with beta blocker or calcium channel antagonists, particularly in hypotensive patients.

71

Knight, et al, Practical Rate and Rhythm Management of Atrial Fibrillation, January 2010 ed. with modifications.

How controlled is controlled?

No strict definition of rate control

Rest – 60-80/min

Holter – Mean 80 - 100/min

Moderate exercise – 90-115/min

Peak exercise – 20-30% reduction of age predicted heart rate

Treatment to achieve strict heart rate control (<80 at rest or <110 during 6 minute walk) IS NOT BENEFICIAL compared with treating a resting heart rate <110 in patients with normal LV function

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Ventricular Rate Control:Drugs to Control the Ventricular Response

A combination of a beta blocker and either a calcium channel antagonist or digoxin may be needed to control the HR.

The choice of medication should be individualized and the dose modulated to avoid bradycardia.

Beta blockers and calcium channel antagonists should be used cautiously in patients with HF.

AV nodal blocking drugs at doses required to control the ventricular response can cause symptomatic bradycardia that requires pacemaker therapy.

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Knight, et al, Practical Rate and Rhythm Management of Atrial Fibrillation, January 2010 ed.

Ventricular Rate Control:Drugs to Control the Ventricular Response

Some antiarrhythmic drugs that are used to maintain sinus rhythm, such as sotalol, dronedarone (multaq), and amiodarone, also provide some control of the ventricular response when patients are in AF.

Amiodarone should rarely be used for rate control because of its potential for toxicity.

IV digoxin or non-dihydropyridine calcium channel antagonists given to patients with AF and WPW may accelerate the ventricular response and are not recommended.

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Knight, et al, Practical Rate and Rhythm Management of Atrial Fibrillation, January 2010 ed.

Ventricular Rate Control:AV Nodal Ablation

Ablation of the AV conduction system and permanent pacing (the “ablate and pace” strategy) is an option for patients who have rapid ventricular rates despite maximum medical therapy and often yields remarkable symptomatic relief.

There is growing concern about the negative effects of long-term RV pacing.

Biventricular pacing, on the other hand, may overcome many of the adverse hemodynamic effects associated with RV pacing and is preferred when systolic dysfunction is present.

Catheter ablation of the AV node should not be attempted without a prior trial of medication to control the rate.

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Knight, et al, Practical Rate and Rhythm Management of Atrial Fibrillation, January 2010 ed. with modifications.

Rate Control AgentsRate Control Agents

Calcium Channel blockers-non-dihydropyridine agents

IV diltiazem-initial dose 10 mg IV over 2 minutes

Can increase dose to 20mg IV if needed

Maintenance diltiazem 30mg PO q6hrs (short acting) or can transition to total long acting diltiazem

Can also use 10mg IVP q6 hrs prn

Start PO dose at same time as IV dosing, so PO can kick in by time IV dosing wears off

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Rate Control Agents

Beta blockers Metoprolol- Initial dose: 5mg IVP q5 minutes x3 doses and q6hrs

prn Maintenance Dose: 25 mg PO BID, can uptitrate to 100mg

PO BID max Start PO at same time as IV medication

Esmolol –Initial dose: 500mcg/kg IV over 1 min, can repeat in 5 minutes

Maintenance drip: 50-300 mcg/kg per min IV continuous infusion

Used only in ICU: Advantage: short duration of action, easy to titrate to

heart rate goal

Rate Control Agents

Digoxin can be used in acute setting but rarely as monotherapy Initial loading dose: 0.5mg IVthen 0.25mg IV in 6

hrs0.25 mg IV 6 hours afterMaintenance dose: 0.125mg daily POCaution in elderly patients and those with renal

failure TREAT-AF study-increased risk in mortality in elderly patients by >20% on digoxin

Indicated in patients with LVEF<30% (inotropic agent)

Rate Control Agents

Amiodarone- both a rate control and rhythm control agent Initial loading dose: 150 mg IV over 10 minutes,

then 1 mg/min x 6 hrs, then 0.5mg/min x18 hrsMaintenance dose: can change to oral 100mg-

200mg dailyCan promote cardioversion-so need to be on

anticoagulationPreferred agent in WPW to prevent AF impulses

down accessory pathway leading to promotion of VF

Rhythm Control

With AF Rhythm Control, timing is everything… AF Begets AF

AF causes changes in atrial electrophysiology that promote AF maintenance

AF causes changes in atrial electrophysiology that promote AF maintenance

Wijffels Circulation 1995; 92: 1954-68Wijffels Circulation 1995; 92: 1954-68

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Spontaneous Conversion of Patients with AF Scheduled for Electrical CardioversionAn ACUTE Trial Ancillary Study

Tejan-Sie J Am Coll Cardiol 2007;42:1638-1643

Conversion According to Duration of Pre-existing AF

Daily Conversion According to Strategy

Cardioversion: Forcing the issue.

Direct Current Cardioversion

Chemical Cardioversion

Some things to consider with DCCV

Anticoagulation and Cardioversion

• Afib < 48 hours:

– Cardioversion (CV)

– No anticoagulation indicated

• Afib > 48 hours:

– Anticoagulate for 3-4 weeks before CV

– OR get TEE

– Anticoagulate for 1 month after CV

DCCV

Atrial Fibrillation: DC Cardioversion

• Advantage- Highly effective

Disadvantage-

Risk of Thromboembolism (1-7%)

Requires conscious sedation

Arrhythmia (Sinus Arrest , Bradycardia - VF, VT)

Recurrence

• Complete shock failure and immediate recurrence – 25%

• Subacute recurrence in 2 wk – 25%

• 70% in NSR at 24 hour after cardioversion

• High chance of recurrences- old age, long duration of AF

DCCV

Atrial Fibrillation: DC Cardioversion

Method –

Synchronized DC shock- External

Biphasic preferred ( high success- 79-84%)

Monophasic- 100 J- 14% success

200 J- 39% success

360 J- 95% success

Initial 200 J is recommended with monophasic

100 J with biphasic [ Jogler et al, AJC 2000, 86: 348]

[ Mittal et al, Circ 2000, 101:1282]

[ Page et al , JACC 2002,39:1956]

Chemical Cardioversion

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Cardioversion with Amiodarone

AMIODARONE [ IIa] • Efficacy - 18-80%

• 150 mg IV bolus, 1mg/min for 6 hours then .5mg/min for 18 hours

• Tab Amiodarone 200 mg TDS x 1 wk 200 mg BD x 3 wk

• Efficacy–48.5%at 30 days vs placebo 0% - 82% if LA size < 45 mm

- 76 % if AF duration < 1 month[ Kochiadakis et al AJC 1999, 83: 58]

Cardioversion with Amiodarone

Ibutilide and Dofetilide

IBUTILIDE [CORVERT] Class III agent Efficacy-45-60% If f/b DC Cardioversion – 100% Only IV 1 mg bolus [ 0.01 mg/kg] Risk-TDP[1.7-4%] DOFETILIDE [TIKOSYN] Class III • Efficacy-30%

• Only oral 500 microgram BD • Risk-TDP

Flecainide

FLECAINIDE [ TAMBOCOR] – Class 1C

• Efficacy- 75-91% for recent onset AF

• Should be avoided in patients with underlying organic heart disease with LV dysfunction

• Dose – 200-300 mg PO-maintenance 50mg– 150mg BID

• Side effects- TDP, Reduce LV contractility, exacerbation of sinus node dysfunction

Propafenone

PROPAFENONE [ RYTHMOL] Class 1C Useful for recent onset AF Efficacy- 56-83% Dose- 600 mg PO - 1.5 – 2 mg/kg over 10-20 min Should be used cautiously or not at all in patients

with HF or severe COPD. Side effects- Atrial Flutter, VT, Hypotesion,

Bradycardia, Intraventricular conduction defects.

Electrical

More effective (90%)

Quick

One procedure with TEE

Cardioversion itself safe

Pharmacological

Works well for recent onset, for atrial flutter

Avoid sedation

Less expensive

Early maintenance enhanced by some drugs

Electrical vs Chemical

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Pill in the pocket approach

“PILL IN THE POCKET APPROACH” • A single oral bolus dose of propafenone or flecainide

(‘pill-in-the-pocket’) –terminate persistent AF outside the hospital if treatment was safe in hospital previously.

For selected patients without Sinus or AV node dysfunction, Bundle-branch block, QT interval prolongation, the Brugada syndrome, or

structural heart disease. Before antiarrhythmic medication is initiated, • A beta blocker or ccb should be given to prevent

rapid AV conduction in the event atrial flutter occurs.

Maintenance AAD’s

Maintenance of Sinus Rhythm in Specific Patient Populations

99

Maintenance of Sinus Rhythm

No (or minimal) Heart Disease

HypertensionCoronary Artery

DiseaseHeart Failure

FlecainidePropafenone

SotalolDronedarone

DofetilideSotalol

Dronedarone

AmiodaroneDofetilide

Substantial LVH

No Yes

Amiodarone

Dofetilide CatheterAblation

CatheterAblation

Amiodarone

CatheterAblation

AmiodaroneDronedarone

CatheterAblation

Amiodarone

Dofetilide

FlecainidePropafenone

SotalolDronedarone

Catheter

Ablation

Abbreviation: LVH, left ventricular hypertrophy. Modified from Fuster, V. et al. J. Am. Coll. Cardiol. 48, e149–e246 (2006).

Antiarrhythmic drugs

Antiarrhythmic Drugs to Maintain Sinus Rhythm

Recommendations COR LOEBefore initiating antiarrhythmic drug therapy, treatment of precipitating or reversible causes of AF is recommended.

I C

The following antiarrhythmic drugs are recommended in patients with AF to maintain sinus rhythm, depending on underlying heart disease and comorbidities:

a. Amiodaroneb. Dofetilidec. Dronedaroned. Flecainidee. Propafenonef. Sotalol

I A

The risks of the antiarrhythmic drug, including proarrhythmia, should be considered before initiating therapy with each drug.

I C

Antiarrhythmic Drugs to Maintain Sinus Rhythm (cont’d)

Recommendations COR LOEBecause of its potential toxicities, amiodarone should only be used after consideration of risks and when other agents have failed or are contraindicated.

I C

A rhythm-control strategy with pharmacological therapy can be useful in patients with AF for the treatment of tachycardia-induced cardiomyopathy.

IIa C

It may be reasonable to continue current antiarrhythmic drug therapy in the setting of infrequent, well-tolerated recurrences of AF when the drug has reduced the frequency or symptoms of AF.

IIb C

Antiarrhythmic drugs for rhythm control should not be continued when AF becomes permanent,… III:

Harm

C

…including dronedarone.B

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Antiarrhythmic Drugs to Maintain Sinus Rhythm (cont’d)

Recommendations COR LOEDronedarone should not be used for treatment of AF in patients with New York Heart Association class III and IV HF or patients who have had an episode of decompensated HF in the past 4 weeks.

III: Harm B

Enough suppression, lets get rid of this thing: Catheter Ablation

It must be symptomatic Atrial Fibrillation

Paroxysmal Atrial fibrillation

Early Persistent Atrial fibrillation

Ablation compared with Medication

100

80

20

40

% P

atie

nts

Fre

e o

f Sy

mp

tom

atic

AF

2 4 6 8 10 12

Months

60 Amiodarone*

Sotalol**Propafenone**

Hx of Two Failed Drugs***

* Roy et al NEJM, 2000**Antman et.al., JACC 1990***Crijns et. al., AJC 1991

Ablation…

Ablation SitesMRA of LA

Multiple Foci from Multiple

Veins

Success ~ 70-80% paroxysmal~ 50-70% persistent

Radiofrequency - Fire

RadioFrequency Ablation – RFA

Vs.

Cryoablation

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Complications of RF ablation:

Systemic embolism/CVA (1-2%)

PV stenosis < 1-3%

Pericardial effusion/cardiac tamponade (1%)

Proarrhythmia (intra-atrial reentry tachycardia/left atrial flutter)

Atrial-esophageal fistula (very rare)

Need for multiple procedures (10 to 30%) to achieve clinical efficacy

CRYO- Ice

Complications of Cryo-ablation

Systemic embolism/CVA (1-2%) PV stenosis < 1-3% Pericardial effusion/cardiac tamponade

(1%) PN palsy 1-3% Atrial-esophageal fistula (very rare) Need for multiple procedures (10 to > 30%)

to achieve clinical efficacy

Surgical Ablation

Coronary Artery Disease

Valvular Heart Disease

Structural Heart Disease

More persistent AF

Atrial Fibrillation Ablation Outcomes

Paroyxsmal– 70-80% success at freedom from atrial fibrillation at one year off

anti-arrhythmic therapy.– 30% of patients required 2 procedures to achieve this result.– Most utilized pure-pulmonary vein isolation approach

Persistent– Similar success rates in persistent patients with similar end-point and

need for repeat procedure– More commonly requires substrate modification (targeting of CFAE)

and linear ablation Long-Standing Persistent

– Utilizing stepwise approach (PV isolation Linear ablation CFAE), some studies have demonstrated 70-80% freedom from atrial fibrillation at one year off anti-arrhythmic therapy

Calkins et al. HeartRhythm 2007; HRS/EHRA/ECAS Expert Consensus Statement on Catheter and Surgical Ablation of Atrial Fibrillation; 4: 1-46

Atrial Fibrillation Ablation Outcomes Randomized Trials:

– Paroxysmal Atrial Fibrillation (Flecainide or Sotalol vs Ablation)

One year freedom from atrial fibrillation (AF)

37% freedom from AF in anti-arrhythmic arm

87% freedom from AF in ablation arm

– Persistent Atrial Fibrillation (Ablation vs. Cardioversion)

One year freedom from AF or atrial flutter

74% freedom from AF in ablation arm

58% freedom from AF in cardioversion arm

Calkins et al. HeartRhythm 2007; HRS/EHRA/ECAS Expert Consensus Statement on Catheter and Surgical Ablation of Atrial Fibrillation; 4: 1-46

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Atrial Fibrillation Ablation Outcomes

Randomized Trials:– Paroxysmal or Persistent Atrial Fibrillation

One year freedom from AF (ablation vs. anti-arrhythmic (AA) drug)

9% freedom from AF in the AA arm

56% freedom from AF in the ablation arm– Paroxysmal Atrial Fibrillation

One year freedom from AF (ablation vs anti-arrhythmic (AA) drug)

22% freedom from AF in AA arm

86% freedom from AF in ablation arm

Stabile et al. European Heart Journal 2006; 27: 216-221

Atrial Fibrillation Ablation Outcomes

Paroxysmal Atrial Fibrillation

– One year freedom from AF (ablation vs anti-arrhythmic (AA) drug)

– 22% freedom from AF in AA arm

– 86% freedom from AF in ablation arm

Paroxysmal and Persistent Atrial Fibrillation

– One year freedom from AF (ablation vs. anti-arrhythmic (AA) drug)

– 7% freedom from AF in AA arm

– 75% freedom from AF in ablation arm

– 63% of AA treated patients crossed over

Stabile et al. European Heart Journal 2006; 27: 216-221

Final Summary for AF Ablation Identifying appropriate ablation candidates

Failing medical therapy Refusing medical therapy Need for symptoms Young patients

Differences in approach for paroxysmal and persistent patients Lesion set Utility of isuprel post ablation Likelihood of recurrence / need for additional procedures (see Cappato,

Circulation, AF registry outcomes paper) Definition of success / likelihood of success Managing atypical flutter / need for confirmation of block across lines

Surgical based ablation Relative efficacy vs. catheter based Rationale / benefit of appendage ligation / resection Cox III – the “gold standard” Efficacy of other lesion sets, modalities (bipolar RF, cryo, HIFU) vs. Cox

Bottom Line

Surgical Reduction in Stroke

Left Atrial Appendage Occlusion

High Stroke risk and high bleed risk

Watchman Device

Atri-Clip

Usually with other surgery, but not always

Surgical procedure vs catheter based procedure

Longer recovery

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Questions?