Atrial Fibrillation, Causes, Treatment and Whats New Louann Bailey, MSN, CRNP. FAANP Northeast Ohio Cardiovascular Specialist

Atrial Fibrillation, Causes, Treatment and What’s New

Louann Bailey, MSN, CRNP. FAANPNortheast Ohio Cardiovascular

Specialist

Objectives

• At the conclusion of the lectures the participant will:– Understand and apply current research and

guidelines for Atrial Fibrillation management– Be able to apply pharmacologic therapies to Atrial

arrhythmia management and treatment– Be able to verbalize non pharmacologic therapies

in treatment of Atrial arrhythmia

AANP 2012

Introduction

• Committee for documenting the evidence based medicine on Atrial Fibrillation – American College of Cardiology (ACC)– American Heart Association (AHA)– Heart Rhythm Society (HRS)– European Society Of Cardiology (ESC)– European Heart Rhythm Society (EHRS)

AANP 2012

Defining Atrial Fibrillation

• A supraventricular Tachyarrhythmia characterized by uncoordinated atrial activation with consequent deterioration of atrial mechanical function

• Depends on the properties of the AV node and conducting tissues

• Level of vagal and sympathetic tone• Presence or absence of accessory conduction

pathwaysJ AM Coll Cardiol, 2006: 48 149-246, ACC/AHA/ESC 2006 Guidelines for the Management of Patients with A-Fib

AANP 2012

Copyright ©2006 American College of Cardiology Foundation. Restrictions may apply.

Fuster, V. et al. J Am Coll Cardiol 2006;48:e149-e246

Electrocardiogram showing atrial fibrillation with a controlled rate of ventricular response

AANP 2012

Related Arrhythmias

• A flutter– Saw-tooth pattern of regular atrial activation called

flutter• Flutter waves most prominent in leads II, III, and aVF• Commonly 2:1 AV block• Regular or irregular• May display upright P waves in II, III, aVF, but downward in

V1

• Heart rate is somewhere between 120-160 bpm

• Atrial Tachycardia

AANP 2012



Electrocardiogram showing typical atrial flutter with variable atrioventricular conduction

AANP 2012

Classification of A Fib• Lone Atrial Fibrillation

– There is absence of cardiac or other conditions predisposing to A Fib

• Acute Atrial Fibrillation– AF that lasts < 48 hours

in duration

• Paroxysmal Afib– Recurrent, transient

episodes, reverting to sinus rhythm, spontaneously or with treatment

– usually < 7 days, often < 24 hours .

• Persistent Afib– AF that is persistent despite

treatment– > 7 days

”

AANP 2012

“Hht://askdrwiki.com/meiawiki/index.php?title=Classification_of_Atrial_Fibrillation



Patterns of atrial fibrillation (AF)

AANP 2012

Distinguishing features of Atrial arrhythmias

• Atrial Tachycardia– Atrial rate 100-240

• Atrial Tachycardia, multifocal– Atrial rate > 100

• Supraventricular tachycardia, paroxysmal– Rate > 100, P waves not

easily seen

• Aflutter– Saw tooth pattern, flutter

wave rate 240-300

• Atrial Fibrillation– P waves absent, atrial

activity totally irregular and represented by fibrillatory waves

– Ventricular rate 100-180

• The complete Guide to ECGs, 2nd ed.2002

AANP 2012

Epidemiology and Prognosis

• 2.2 million people in the US and 4.5 million people in Europe have Paroxysmal or persistent AF

• In the past 20 years, there has been a 66% increase in hospital admissions for AF

• Approximately 15.7 billion is spent annually in the U.S. alone

AANP 2012

Prevalence• AF is seen in 0.4%-1% of the general population• Increases with age• Incidence is higher in men• Median age is 75 years• Number of men and women are about equal• Approximately 60% of the patients > 75yo are

women• AA’s risk is about half of whites

AANP 2012



Estimated age-specific prevalence of atrial fibrillation (AF) based on 4 population-based surveys

AANP 2012

Incidence

• Less then 0.1% per year for those < 40

• To exceed 1.5% per year in women > 80

• To exceed 2% per year in men > 80

• The incidence of AF may be lower in HF patients treated with ACE I

AANP 2012

Prognosis

• AF is associated with an increased long term risk of stroke

• AF is associated with an increased risk for developing HF

• AF is associated with all cause mortality, especially in women

• AF patients have double the mortality rate as compared with those in sinus rhythm

AANP 2012



Relative risk of stroke and mortality in patients with atrial fibrillation (AF) compared with patients without AF

AANP 2012

Prognosis

• The rate of ischemic stroke among patients with nonvalvular AF avg 5% per year

• AF is a strong independent risk factor for mortality

• One in six strokes occurs in patients with AF• In HF studies, the annual risk due to AF was

1.5% in persons 50-59 and 23.5% in ages 80-89

AANP 2012

Pathophysiological Mechanisms

AANP 2012

• Atrial Pathology• Anatomical substrate• Electrical Remodeling• Counteracting Atrial Remodeling• Other factors

– Inflammation– Autonomic nervous system– Changes associated with aging

Anatomical and Electrophysiological substrates

Diseases Anatomical Cellular Electrophysiological

HTNA substrate

Atrial Dilatation Myolysis Conduction abnormalities

HFA substrate

PV dilatation Apoptosis, necrosis

ERP dispersion

CAD

A substrate

Fibrosis Channel Expression Change

Ectopic activity

Valvular diseaseA substrate

Focal AF

B substrate

Only with prolonged High rates

Only with prolonged High rates

Ectopic activity

A FlutterB substrate

Atrial dilatation Ca++ channel down regulation

Short ERP

AANP 2012

Mechanisms of Atrial Fibrillation

• Automatic Focus theory– May be automatic focus or micro entrant circuit,

rapid local activation in the LA cannot extend into the RA in an organized way

• Multiple Wavelet Hypothesis– A large atrial mass with short refractory time and

delayed conduction increases the number of wavelets, favoring sustained AF

AANP 2012



Posterior view of principal electrophysiological mechanisms of atrial fibrillation

AANP 2012

What Structural Changes Influences Atrial Fibrillation

• Atrial size

• Left Ventricular size

• Structural changes to the Pulmonary Veins

• Pre-disposition of pre-excitation syndrome

• Loss of synchronous atrial mechanical activity AANP 2012

Etiologies and Factors Predisposing to A Fib

• Electrophysiological abnormalities– Enhanced automaticity

(focal AF)– Conduction abnormality

(re-entry)

• Atrial pressure elevation– Mitral or tricuspid valve

disease– Myocardial disease (systolic

or diastolic disease)– Semi lunar Valvular

abnormalities (causing ventricular hypertrophy

– Systemic or pulmonary HTN (pulmonary Hypertrophy

– Intracardiac tumors or thrombi

AANP 2012


• Atrial Ischemia– CAD

• Drugs– Alcohol– Caffeine

• Endocrine– Hyperthyroidism– Pheochromocytoma

• Inflammatory or infiltrative disease– Pericarditis– Amyloidosis– Myocarditis– Age-induced atrial

fibrotic changes

AANP 2012


• Changes in autonomic tone– parasympathetic

activity– sympathetic activity

• Primary or metastatic diseases in or adjacent to the atrial wall

• Congenital heart disease

• Postoperative– Cardiac, pulmonary,

esophageal

• Neurogenic– SAH– Nonhemorrhagic, major

stroke

• Idiopathic (lone AF)• Familial AF

AANP 2012

Why is it a concern?

• There are myocardial and hemodynamic consequences of Atrial Fib

• The risk of Thromboembolism is very real• The risk of Stroke is very real• The risk of catastrophic debilitation is very real• The risk of increased morbidity and mortality

is very real

AANP 2012

Pathology of Thrombus Formation

• Thrombotic material associated with AF most frequently is due turbulent flow in LAA

• This is not seen using transthoracic echo• For AF that is > 48 hours long, risk increases• Virchow's triad of stasis applies

– Venous stasis– Endothelial dysfunction– Hypercoagulable state

AANP 2012

Other Interesting Facts• During conversion of AF to SR, decreased

velocities of flow are noted in LAA• This increases risk for thromboembolic events

due to stunning of the Atria• Atrial stunning occurs immediately after

Cardioversion and may last up till 3-4 days post Cardioversion

• 80% of thromboembolic strokes occur 3-10 days after Cardioversion

AANP 2012

Other Interesting Facts

• HF, either diastolic or systolic, increases risk for stroke

• Strong association of stroke with AF and HTN• Often see elevated C-reactive protein (CRP) in

these patients with increased risk for stroke• Pathophysiology of thromboembolism in

patients with AF is uncertain and poorly defined

AANP 2012

Other Associated Causes and Conditions that Influence AF

• Catecholamine surges• AF without associated HD

– 20-25% of AF in young adults who present

• Medical conditions associated with AF– Obesity and and LA dilatation

• AF with associated HD– Valvular (Mitral), HF, CAD, HTN, LVH

• Familial (Genetic) AF– Poorly understood, ongoing research

AANP 2012

Impact on Quality of Life

• Can be very life limiting• Worry when it will reoccur• Lifelong toxic meds• Bad consequences for non compliance• Potential bad consequences for compliance• No good substitutes for treatment• Best to prevent and treat underlying cause

AANP 2012

Clinical Evaluation

• Diagnosis is based on History and clinical examination and confirmed ECG

• Determine cause• Defining associated cardiac and extracardiac

factors pertinent to the etiology, tolerability and history of prior management

• WU and therapy initiation can usually be done in one outpatient encounter

AANP 2012

Clinical Evaluation

• History and physical Exam– Presence and nature of symptoms associated with AF– Clinical type of AF– Onset of the first symptomatic attack or date of discovery– Frequency, duration, precipitating factors, modes to

terminate– Response to any pharmacological agents that have been

tried– Presence of any underlying heart disease or other

reversible conditions

AANP 2012

Clinical Evaluation• Electrocardiogram, to identify

– Rhythm– LV hypertrophy– P-wave duration and morphology or fibrilliatory waves– Pre-excitation– BBB– Prior MI– Other atrial arrhythmias– Measure R-R, QRS, QT intervals

AANP 2012

Clinical evaluation

• Transthoracic echocardiogram– LA and RA size– LV size and function– Peak RV pressure (pulmonary HTN)– LV hypertrophy– LA thrombus (low sensitivity)– Pericardial disease

AANP 2012

Clinical Evaluation

• Blood tests– Thyroid– Renal– Hepatic function– CBC– BNP if appropriate– CRP

AANP 2012

Clinical Evaluation• Six minute walk test

– Assess for rate response

• Exercise Testing– To reproduce exercise induced AF– Evaluate for ischemia

• Holter monitoring or event recording– If type of arrhythmia is in question

• Transesophageal echocardiography– To ID LA thrombosis, guide DCC

AANP 2012

Clinical Evaluation

• Electrophysiological study– To clarify the mechanism of wide QRS complex

tachycardia– To identify a predisposing arrhythmia such as

atrial flutter or paroxysmal supraventricular tachycardia

• CXR– Lung parenchyma, Pulmonary vasculature, cardiac

size

AANP 2012

Management

• Primary goals are to meet 3 objectives

– Rate control– Prevention of thromboembolism– Correction of the rhythm disturbance

AANP 2012

Management Considerations

• Type and duration of AF• Severity an type of symptoms• Associated CV disease• Patient age• Associated medical conditions• Short-term and long-term treatment goals• Pharmacological and nonpharmacological

therapeutic optionsAANP 2012

Pharmacological and Nonpharmacological Therapeutic Options

• Drugs and ablation are effective for both rate control and rhythm control

• Surgery, Maze Procedure may also be an option

• “ablate and pace” strategy may be an option

AANP 2012

Studies and Trials that support therapy

• Affirm Trial– Atrial Fibrillation Follow-Up Investigation of

Rhythm Management

• RACE– Rate Control Versus Electrical Cardioversion for

Persistent Atrial Fibrillation

• STAF– Strategies of Treatment of Atrial Fibrillation

AANP 2012

Studies that support therapy

• HOT CAFE’

– How to Treat Chronic Atrial Fibrillation

• PIAF– Pharmacological Intervention I Atrial Fibrillation

AANP 2012

Affirm Trial (2002)• Over 4000 patients• Mean age 69.7 yrs of age• F/U: 3.5 yrs• Inclusion criteria: PAF, Persistent AF, 65 yrs or

older, or risk of stroke or death• Primary endpoint: All- cause mortality• % Rate control: 25.9%• % Rhythm control 26.7%• P value: 0.8

AANP 2012

IV and PO Pharmacological Agents for Rate control

• Acute Setting– Beta blockers

• Esmolol, Metoprolol, Propanolol

– Nondihydropyridine Calcium channel blockers• Diltiazem, Verapamil

– Amiodarone (heart rate control with accessory pathway)

– Digoxin (heart rate control in pts with HF without accessory pathways)

AANP 2012

Non – Acute and Chronic MaintenanceDrug Class

/LOELoading Dose Onset Maintenance

DoseMajor SE

Metoprolol I/C Main Dose 4-6 hrs 25-100mg BID BP, HB, HR, asthma, HF

Propanolol I/C Main Dose 60-90 min

80-240mg divided

BP, HB, HR, asthma, HF

Diltiazem I/C Main Dose 2-4 hrs 120-360mg divided

BP, HB, HF

Verapamil I/C Main Dose 1-2 hrs 120-360mg divided

BP, HB, HF, digoxin interaction

Digoxin I/C 0.5mg 2 days 0.125-0.375mg daily

Digitalis toxicity, HB, HR

Amiodarone IIb/C 800mg daily for 1 wk then 600mg daily for 1 wk400mg daily for 4-6 wks

1-3 wks 200mg daily BP, HB, pulm, thyroid, lung toxicity, Corneal deposits, optic neuropathy, warfarin interaction, SB

AANP 2012

Preventing Thromboembolism Who is at Risk?

Risk Factors Relative Risk

Previous Stroke or TIA 2.5

DM 1.7

H/O HTN 1.6

HF 1.4

Advanced Age 1.4

AANP 2012



Stroke rates in relation to age among patients in untreated control groups of randomized trials of antithrombotic therapy

AANP 2012

Using the CHADS 2 Index

CHADS2 Risk Criteria Score

Prior Stroke or TIA 2

Age > 75y 1

HTN 1

DM all types 1

HF 1

AANP 2012

Tools Available for Predicting Bleeding Risks

• Two tools available for predicting bleeding risk HEMORR2HAGES HAS-BLED

• Pros/Cons Factors identified from registries or research data Yet based on warfarin only

• Recommendations Use info to identify those at high risk w/warfarin Stay tuned for newer predictive tools

AANP 2012

Factors Associated w/Bleeding Risks

HEMORR2HAGES Prior bleed (greatest risk) Liver or kidney disease Stroke Older age (> 75 years) Uncontrolled HTN Ethanol abuse Malignancy Reduced plt count/function Anemia Genetic factors Excessive fall risk

HAS-BLED score Bleeding hx or predisposition Abnormal kidney/liver function Stroke Elderly (> 65 yrs) Hypertension Drugs/alcohol concomitantly Labile INR

*Identified from registries/surveys using warfarin. AANP 2012

Antithrombotic Therapy for Patients with AF

Risk Category Recommended Therapy

No Risk factors Aspirin 81 mg to 325 mg daily

One moderate risk factor ASA 81 mg to 325 mg or warfarin (INR 2.0-3.0)

Any High Risk or more than 1 moderate-risk factor

Warfarin (INR 2.0-3.0)

AANP 2012

The CHADS2 Score: Stroke Risk In Atrial Fibrillation

Condition Points

C Congestive heart failure 1

H Hypertension (or treated HTN) 1

A Age > 75 years 1

D Diabetes 1

S Prior Stroke or TIA 2

Score Stroke Risk Therapy

0-1 Low (< 3 %/ year) ASA

1-2 Moderate (≈ 3-4%/yr)

VKA or alternatives

3-5 High (≈ 6-12%/yr) VKA or alternatives

6 Very High (≈ 18%/yr)

VKA or alternatives

AANP 2012

See slide 60 for alternatives to VKA

Antithrombotic Therapy for Patients with AF

Less validated or weaker Risk Factors

Moderate Risk Factors High Risk Factors

Female gender Age > to 75 Previous stroke, TIA, or embolism

Age 65-74 HTN Mitral Stenosis

CAD HF Prosthetic Heart Valve

Thyrotoxicosis LV EF 35% or lessDM

AANP 2012

Risk Based Approach to Antithrombotic Therapy

Patient Features Antithrombotic Therapy Class of Recommendation

Age < 60 , no HD (lone AF) ASA 81-325 mg or no therapy I

Age < 60 , HD but no risk factors

ASA 81 -325mg I

Age 60-74, no risk factors ASA 81-325 mg I

Age 65-74, with DM or CAD OAC INR 2-3 I

Age 75 or >, Women OAC INR 2-3 I

Age 75 or > Men, no risk factors

OAC INR 2-3 or ASA 81-325mg I

Age 65 or > with HF OAC INR 2-3 I

LV EF < 35% + HTN OAC INR 2-3 I

RHD (MS) OAC INR 2-3 I

Prior Thromboembolism OAC INR 2-3 or higher I

Prosthetic Heart Valve OAC INR 2-3 or higher I

Persistent Atrial Thrombus on TEE

OAC INR 2-3 of higher IIa

AANP 2012



Adjusted odds ratios for ischemic stroke and intracranial bleeding in relation to intensity of anticoagulation

AANP 2012



Effects on all stroke (ischemic and hemorrhagic) of therapies for patients with atrial fibrillation: warfarin compared with aspirin and aspirin compared with placebo

AANP 2012

ACTIVE A ASA +/- Clopidogrel + vs. in Atrial Fibrillation (AF)

AANP 2012

AF Patient Description Treatment OptionsModerate high risk for stroke +No contraindication to VKA

VKA e.g. warfarin (target INR 2-3) unless contraindicated*(demonstrates max stroke prevention with an acceptable major bleed risk: esp. if CHADS2 > 2, > 85 yr of age no bleed hx, or an ischemic stroke hx1)

Moderate high risk for stroke + cannot/will not tolerate VKA OR high-quality anticoag not achieved with VKA OR low risk for stroke

ASA monotherapy 75mg daily + ASA 75-100mg daily

OrClopidogrel 75mg daily + ASA 75-100mg daily

Choice depends on overall bleed risk & cost considerations:•ASA + clopidogrel is similar to that with warfarin; therefore those who are not suitable for warfarin due to bleed risk, may also not be suitable for ASA + clopidogrel.•Thus ASA + clopidogrel option really only suitable for patients who are not candidates for warfarin due to factors other than high risk of bleeding e.g. purple toe syndrome, lack of access to lab for required INR tests, likely not to be adherent to therapy/INR testing requirements, etc.

High risk of bleed &low moderate stroke risk

ASA (75-100mg daily)

1 singer De Chang Y, Fang MC, et al. The net clinical benefit of warfarin anticoagulation in atrial fibrillation . Ann Intern Med 2009: 151: 297-305

(VKA), Vitamin K antagonist

Research Trials• Active A

– In patients with atrial fibrillation at low-moderate risk for stroke who are not suitable for warfarin therapy, the combination of ASA+ clopidogrel is associated with a decrease in vascular event risk that is equal to the increase in risk of major bleeding

– Drug cost per patient per year: ASA + clopidogrel = $1,260; ASA = $95– Assess risk of bleed vs. any potential benefit for individual patient– If patient is on clopidogrel + a PPI, reassess need for clopidogrel &/or

need for a PPI

• Active W– Warfarin is superior to clopidogrel + ASA for prevention of vascular

events in patient with AF and at least 1 stroke risk factors especially in those already taking VKA therapy

AANP 2012

• RE-LY– Dabigatran 75-150 mg cap bid an alternative to

warfarin. At the lower dose, is was as effective as warfarin with less bleeding; at the higher dose it was more effective than warfarin but with similar bleeding rates. Alter dose for GFR

• ROCKET AF– Rivaroxaban 15-20 mg daily, Direct Factor Xa

inhibitor: evaluated and approved once a day dosing

AANP 2012

Research TrialsTreatment Non-Valvular Afib

A new Era in the management of Atrial Fibrillation: An update on OAC, 2011, Heart.Org


• AVERROES• ARISTOTLE

– Apixaban 5 mg twice daily or 2.5 mg twice daily (age > 80, wt < 60kg, Cr >1.5 mg/dl)

• Primary outcome: Stroke or systemic embolism• Stopped early• After one year Apixaban reduced stroke by half as

compared to ASA• Decrease in ischemic and hemorrhagic stroke• Reduction in myocardial infarction and hospitalization• Reduction in death• Was an increase bleeding but not significant

AANP 2012A new Era in the management of Atrial Fibrillation: An update on OAC, 2011, Heart.Org


• Engage• AF-TIMI 48

– Looking at using Edoxaban• Twice a day dosing was associated with increase in

bleeding vs. Warfarin• Once daily dosing was associated with similar or lower

rates of bleeding of warfarin

AANP 2012A new Era in the management of Atrial Fibrillation: An update on OAC, 2011, Heart.Org

New Anticoagulants

• Direct Thrombin Inhibitors– Dabigatran

• Factor Xa Inhibitors– Rivaroxaban– Apixaban– Edoxaban

AANP 2012


Comparison of features of New Anticoagulants with those of Warfarin

Features Warfarin New Agents

Onset Slow Rapid

Dosing Variable Fixed

Food Effect Yes No

Monitoring Yes No

Half-life Long Short

Antidote Yes No

AANP 2012


New Oral Anticoagulants

Advantage Clinical Implications

Rapid Onset No need for bridging

Predictable No need for routine monitoring

Specific Coagulation enzyme target Low risk for off target adverse effects

Low Potential for food interaction No dietary precautions

Low potential for drug interactions Few drug interactions

AANP 2012


Disadvantages vs. Warfarin

Features Warfarin New Agents

Frequency Once Daily Twice daily

Monitoring INR Uncertain

Clearance Non-renal Renal 25%-80%

Antidote Vitamin K, FFP, PCC Nil

Familiarity Extensive Minimal

AANP 2012


Indirect Comparisons vs WarfarinFeature Dabigatran

(110 mg)Dabigatran(150 mg)

Rivaroxaban

Efficacy Non-inferior Superior Non-inferior

Ischemic Stroke Similar Reduced Similar

Intracranial hemorrhage

Reduces Reduced Reduced

Major bleeding Reduced Similar Similar

MI Increased Increased Similar

Dyspepsia Yes Yes No

Dosing Twice Daily Twice Daily Once daily

Time in therapeutic range

67% (median) 67% (median) 58%(Median)

AANP 2012


Interrupting Therapies• For Surgical or diagnostic procedures

– Elective, off therapy for 5-7 days– For Prosthetic valves, bridge with LMWH or unfractionated

heparin

• Dental extractions– May not have to stop

• GI bleeds– Till cleared by GI, look at alternative

• Intra cranial bleeds– Stop indefinitely

AANP 2012

Non Pharmacological Approaches to Prevention of Thromboembolism

• Obliteration of the LAA

– Surgical removal

– Intravascular catheters

– Transpericaridal approaches

AANP 2012

PROTECT AF Clinical Trial Design• Prospective, randomized study of WATCHMAN LAA Device vs. Long-term

Warfarin Therapy• 2:1 allocation ratio device to control• 800 Patients enrolled from Feb 2005 to Jun 2008

– Device Group (463)– Control Group (244)– Roll-in Group (93)

• 59 Enrolling Centers (U.S. & Europe)• Follow-up Requirements

– TEE follow-up at 45 days, 6 months and 1 year– Clinical follow-up biannually up to 5 years– Regular INR monitoring while taking warfarin

• Enrollment continues in Continued Access Registry

AANP 2012

Watchman LAA Closure Technology

The WATCHMAN LAA Closure Technology is The WATCHMAN LAA Closure Technology is designed to prevent embolization of thrombi that designed to prevent embolization of thrombi that may form in the LAA. may form in the LAA.

The WATCHMANThe WATCHMAN® ® Left Atrial Appendage Closure Left Atrial Appendage Closure Technology is intended as an alternative to warfarin Technology is intended as an alternative to warfarin therapy for patients with non-valvular atrial therapy for patients with non-valvular atrial fibrillation. fibrillation.

AANP 2012

Left Atrial Appendage Device

Watchman Device Placed in LAA

AANP 2012

WATCHMAN LAA Closure Device in situ

AANP 2012

PROTEC AFConclusion

The WATCHMAN LAA Technology offers a safe and effective alternative to warfarin in patients with non-valvular atrial fibrillation at risk for stroke and who are eligible for warfarin therapy

AANP 2012

Cardioversion of AF

• Performed electively or urgently

• By means of drug or electrical shock

• Pharmacological Cardioversion – Most effective if AF has been less than 7 days– First time documented

• Often will spontaneously convert within 24-48 hrs

AANP 2012

Drugs used for DCC within7 days of discovery

Agents with proven Efficacy

Drug Route Class LOE

Dofetilide oral I A

Flecainide oral/IV I A

Ibutilide IV I A

Propafenone Oral/IV I A

Amiodarone Oral/IV IIa A

Agents Less Effective/Less studiedDrug Route Class LOE

Disopyramide IV IIb B

Procainamide IV IIb B

Quinidine oral IIb B

AANP 2012

Drugs used > 7 days

Agents with proven efficacy

Drug Route Class LOE

Dofetilide oral I A

Amiodarone Oral/IV IIa A

Ibutilide IV IIa A

Agents less effective/less studiedDrug Route Class LOE

Diopyramide IV IIb B

Flecanide oral IIb B

Procainamide Oral/IV IIb C

Propafenone Oral/IV IIb B

Quinidine oral IIb B

AANP 2012

Proven Drugs for Pharmacological CardioversionDrug Route Dosage Potential adverse

effects

Amiodarone Oral

IV/oral

Inpatient: 1.2 to 1.8 g per day in divided doses until 10 g, then 200-400mg per day or 30mg/kg as single dose

5-7 mg/kg over 30-60 min then 1.2-1.8 g per day continuous IV or in divided doses until 10 g, then 200-400mg daily

HypotensionBradycardiaQT prolongationTorsadesGI upsetConstipation

Dofetlide oral Creat Clear > 60ml/min 500mcq bid40-60ml/min 250mcq bid20-40ml/min 125mcq bid< 20ml/min contraindicated

QT prolongationTorsadesAdjust dose for RF, body size and age

Flecainide OralIV

200-300 mg1.5 to 3.0 mg/kg over 10-20 min

HypotensionA flutter w RVR

Ibutilide IV 1mg over 10 min may repeat QT prolongationTorsades

Propafenone oral 600mg HypotensionA flutter

AANP 2012



Pharmacological management of patients with newly discovered atrial fibrillation (AF

AANP 2012



Pharmacological management of patients with recurrent paroxysmal atrial fibrillation (AF)

AANP 2012



Pharmacological management of patients with recurrent persistent or permanent atrial fibrillation (AF)

AANP 2012

Vaughan Williams Classification of Antiarrhythmic Drugs

• Type IA– Dispyramide– Procainamide– Quinidine

• Type IB– Lidocaine– Mexiletine

• Type IC– Flecainide– Propanfenone

• Type II– Beta blockers

• Type III– Amiodarone– Bretylium– Dofetilide– Ibutilide– Sotalol

• Type IV– Nondihydropyridine

calcium antagonistsAANP 2012

Other Antiarrhythmic without Iodine SE

• Dronedarone• Dose 400 mg twice daily, PO• Cost $9.00/day, $4.50/pill• Achieve steady state in 4-8 days• Elimination ½ life is 13-19 hours• Metabolized via CYP 3A• Several studies looking at reduced M&M• ATHENA, EUROIDIS/ADONIS, ANDROMEDA

AANP 2012

Dronedarone

• Indications for use– Antiarrhythmic drug indicated to reduce the risk

of CV hospitalization in patients with paroxysmal or persistent atrial fibrillation (AF) or atrial flutter (AFL), with a recent episode of AF/AFL and associated CV risk factors (i.e., age > 70, HTN, DM, prior CVA, LAA diameter > 50mm or LVEF < 40%, who are in sinus rhythm or will be cardioverted)

AANP 2012

Dronedarone• Contraindications

– In patients with NYHA Class IV failure– In patients with recent decompensated NYHA

Class II-III HF, requiring hospitalization or referral to a specialist for HF or HF clinic

– Second and third degree heart block or SSS (exception is if they have PPM)

– Concomitant use of Strong CYP3A inhibitor

AANP 2012

Dronedarone

• Contraindications continued– Concomitant use of drugs or herbals that may

prolong QT interval– QTc Bazett interval > 500 ms– Severe hepatic impairment– Pregnancy– Nursing mothers

AANP 2012

Dronedarone

• Warnings and Precautions– If HF develops or worsens, drug should be

suspended– Maintain normal range levels of potassium and

magnesium– Stop drug if QTc is > 500 ms– Check renal function within 1 week of starting– Teratogen: advise women of childbearing age to

use contraception while on drug

AANP 2012

Dronedarone in Permanent Afib

• Recent findings found to affect Hepatic function

www.fda.gov/Drugs/drugssafety/ucm240011.htm

• Increased risk of first Coprimary outcomes (stroke, MI, Systemic Embolism, or death from CV Causes)

• Increased risk of second Coprimary Outcomes (Unplanned Hospitalizations for CV causes or Death)

AANP 2012

NEJM10.1056.Nov 14, 2011

http://www.fda.gov/Drugs/drugssafety/ucm240011.htm

Risk of First Copriamry Outcome

AANP 2012

NEJM10.1056.Nov 14, 2011

Risk of Second Coprimary Outcome

AANP 2012

NEJM10.1056.Nov 14, 2011

Typical Doses of Drugs used to Maintain Sinus Rhythm

Drug Daily dosage Potential Adverse Effects

Amiodarone 100 – 400 mg Photosensitivity, Pulm Toxicity, polyneuropathy, GI upset, bradycardia, Torsades de pointes (rare), Hepatic toxicity, thyroid dysfunction, eye complications

Disopyramide 400 – 750 mg Torsades de pointes, HF, glaucoma, urinary retention, dry mouth

Dofetilide 500 – 1000 mcq Torsades de pointes

Flecainide 200 – 300 mg VT, HF conversion to AFL with RVR

Profafenone 450 – 900 mg VT, HF conversion to AFL with RVR

Sotalol 160 – 320 mg Torsades de pointes, HF, bradycardia, exacerbation of COPD or bronchospastic lung disease

AANP 2012

Types of Proarrhythmia During Treatment

• Ventricular proarrhythmia– Torsades de pointes (VW IA and III drugs)– Sustained monomorphic VT (VW type IC)– Sustained polymorphic VT/VF without long QT (VW types

IA, IC)• Atrial proarrhythmia

– Provocation of Recurrence (Type IA, IC, and III)– Conversion of AF to flutter (Type IC)– Increase of defibrillation threshold (Type IC)

AANP 2012

Types of Proarrhythmia During Treatment

• Abnormalities of conduction or impulse formation– Acceleration of ventricular rate during AF (Type IA

and IC)– Accelerated conduction over accessory pathway

(digoxin, IV Verapamil, or Diltiazem)– Sinus node Dysfunction, AV blk (almost all drugs)

AANP 2012

Factors predisposing to Drug Induced Ventricular Proarrhythmia• VW types IA and III agents

– Long QT interval (QTc > than or = to 460ms– Long QT interval syndrome– Structural HD, substantial LVH– Hypokalemia/Hypomagnesemia– Female gender– Bradycardia

• Maybe drug induced, sinus node disease, etc• Go www.torsades.org

AANP 2012

Factors predisposing to Drug Induced Ventricular Proarrhythmia• VW type IC agents

– Wide QRS duration > 120 ms– Concomitant VT– Structural HD– Depressed LV function– RVR

• During exercise• During rapid AV conduction• Rapid dose increase• High dose accumulation• Adding Negative Inotropic drugs• Excessive QRS widening (more than 150%)

AANP 2012

Drugs that help with DCC

Efficacy Enhance DCC and Prevent IRAF

Class LOE Suppress SRAF

Known Amiodarone IIA B All drugs in Class I except ibutilide plus Beta blockers

Flecanide

Ibutilide

Propafenone

Quinidine

Sotalol

AANP 2012

Drugs uncertain if help with Cardioversion

Efficacy Enhance Conversion by DCC and prevent IRAF

Class LOE Suppress SRAF and Maintenance therapy

Uncertain/unknown

Beta blockers IIb C Diltiazem

Diltiazem Dofetilide

Disopyramide Verapamil

Dofetilide

Procainamide

Verapamil

AANP 2012

Recommendations for Thromboembolism Prevention

• AF less then 48 hrs not needed, assess risk, underlying cause

• AF 48 hrs or longer, non emergent, OAC with INR 2-3 for at least 3 wks or alternate OAC

• AF 48 hrs or longer, urgent/emergent, heparin should be given unless contraindicated, PTT should be 1.5-2 times normal

• AF less than 48 hrs associated with hemodynamic instability; DCC immediately

AANP 2012

Recommendations for Thromboembolism Prevention

• Alternative to anticoagulation prior to DCC, perform TEE to evaluate for LAA thrombus, then give unfractionated heparin

• For those with positive TEE for LAA thrombus, OAC with therapeutic INR for 3-4 wks prior to DCC and 3-4 wks after

AANP 2012

Maintenance of Sinus Rhythm• Look for underlying cause• Pharmacological therapy can be useful to

maintain SR and prevent Tachycardia induced CM

• Infrequent, well tolerated recurrence of AF is reasonable as a successful outcome of drug therapy

• Patients without structural HD can have meds started as an outpatient

AANP 2012

Maintenance of Sinus Rhythm

• Catheter ablation may be an alternative for patients with little or no LAE

• This is a procedure that requires a skilled electrophysiologist and staff

• Currently this is done via, percutaneously and/or also using Robotics

AANP 2012

Robotic Ablation with Niobe Stereo taxis

AANP 2012

ICE: LA Appendage

LAA

LA

IAS

AANP 2012

LIPV

LSPV

LA

AANP 2012

Transseptal

TSP NeedleRA

LA

AANP 2012

Transseptal: Needle advancement

AANP 2012

PV Angio: Identification of ostium

AANP 2012

ICE Imaging of the Esophagus

AANP 2012

“Char” formation

Pericardial Effusion

Cardiac Tamponade

AANP 2012

PV Antrum Isolation: Catheter AblationICE+Circular Mapping Catheter

AANP 2012

RECURRENTPAROXYSMAL

AF

RECURRENTPAROXYSMAL

AF

Minimal or no symptomsMinimal or no symptoms

Anticoagulation and rate control as needed


No drug for prevention of AF

No drug for prevention of AF

Disabling symptoms in AFDisabling symptoms in AF



Antiarrhythmic drug therapy


AF ablation if Antiarrythmic drug

treatment fails

AF ablation if Antiarrythmic drug

treatment fails

Treatment Algorithms for AFTreatment Algorithms for AF

AANP 2012

Fuster Vet et al. JACC. 2006, 48:e 149-246

Consider ablation for severelysymptomatic recurrent AF after failure of greater than or equal to 1 antiarrhythmic

drug plus rate control

Consider ablation for severelysymptomatic recurrent AF after failure of greater than or equal to 1 antiarrhythmic

drug plus rate control

Minimal or no

symptoms

Minimal or no

symptoms

Anticoagulation and rate control as neededAnticoagulation and

rate control as needed

Disabling symptoms in AF

Disabling symptoms in AF

Anticoagulation and rate control

Anticoagulation and rate control



Electricalcardioversion as

needed

Electricalcardioversion as

needed

Continue anticoagulationas needed and therapy to

maintain sinus rhythm

Continue anticoagulationas needed and therapy to

maintain sinus rhythm

RECURRENTPERSISTENT AF

RECURRENTPERSISTENT AF

Treatment Algorithms for AF (cont)Treatment Algorithms for AF (cont)

AANP 2012


PERMANENT AFPERMANENT AF

Anticoagulation and rate control as neededAnticoagulation and

rate control as needed

Treatment Algorithms for AF (cont)Treatment Algorithms for AF (cont)

AANP 2012


MAINTENANCE OF SINUS RHYTHMMAINTENANCE OF SINUS RHYTHM

No (or minimal) heart disease

FlecainidePropafenone

Sotalol


Sotalol

AmiodaroneDofetilide


Catheter ablationCatheter ablation

Hypertension

Substantial LVHSubstantial LVH

NoNo YesYes


Sotalol


Sotalol

AmiodaroneAmiodarone



CatheterablationCatheterablation


Coronary artery disease

DofetilideSotalol

DofetilideSotalol

AmiodaroneAmiodarone CatheterablationCatheterablation




Heart failure

Antiarrhythmic drug therapy to maintain sinus rhythm in patients with recurrent paroxysmal or persistent atrial fibrillation

Antiarrhythmic drug therapy to maintain sinus rhythm in patients with recurrent paroxysmal or persistent atrial fibrillation

AANP 2012


Documents

Atrial Fibrillation, Causes, Treatment and Whats New Louann Bailey, MSN, CRNP. FAANP Northeast Ohio Cardiovascular Specialist