Atrial Fibrillation

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Atrial Fibrillation Treatment Update

• Judy R. Walling, RN, MSN, FNP-BC
• Nurse Practitioner
• MUSC Cardiology
• wallingj_at_musc.edu

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Disclosures

• I have no financial disclosures to reveal.

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Outline

• Review of atrial fibrillation (AF)
• New treatment guidelines of AF
• Anticoagulation and stroke prevention in AF
• Medical management of AF
• Procedural options of AF

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EKG
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Overview

• The American Heart
• Association estimates that
• 0.4 of the general
• populations have AF.
• AF is the most common
• clinically significant cardiac
• arrhythmia.
• The likelihood increases
• with age.

Fuster et al. ACC/AHA/ESC 2006 guidelines for
the management of patients with atrial
fibrillation. JACC 200648e149-e246.
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Overview (continued)

• 2.3 million Americans1
• 4 million by 20301,2
• 70 of pt with AF are 65-75 yo2
• Doubles mortality3
• 100,000 deaths/year associated with AF4
• 467,000 hospitalizations/year4
• 6-26 billion annual AF related health care costs

1. Nacarelli GV, et al. Am J Cardiol
   2009104(11)1534-1539. 4) Roger VL, et al.
   Circulation 2012125(1)e2-e220.
2. Go AS, et al. JAMA 2001285(18)2370-2375. 5)
   Kim MH, et al. Circ Cardiovasc Qual Outcomes
3. Miyasaka Y, et al. J Am Coll Cardiol
   200749(9)986-992. 20114(3)313-320.

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Overview (continued)

• Men are slightly more likely than women to
  develop AF but women diagnosed with it carry a
  longer-term risk of premature death.

Fuster et al. ACC/AHA/ESC 2006 guidelines for
the management of patients with atrial
fibrillation. JACC 200648e149-e246.
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So Why do Patients Develop AF

• There are a number of risk factors that
• predispose individuals to the development of
• AF. Some of them include.
• Age Hyperthyroidism
• Sleep apnea Obesity
• Drugs Ischemia
• Metastatic disease
• AND

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Associated Diseases

• Hypertension
• Congestive heart failure
• Diabetes
• Coronary artery disease
• Valvular disease
• BUT

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Truthfully
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Consequences of AF

• AF is not life-threatening in and of itself, but
  it can lead to other serious medical problems
  including
• Stroke Your chances
• of having a stroke are
• five times higher if you
• have AF.
• Additional heart rhythm
• problems
• Heart failure

Fuster et al. ACC/AHA/ESC 2006 guidelines for
the management of patients with atrial
fibrillation. JACC 200648e149-e246.
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Other Consequences of AF

• Decreased quality of life
• Increased hospital stays
• Increased mortality
• Substantial financial burden on health care
  system
• More AF

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OUR GREATEST CONCERN????
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Left atrial Thrombus
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Thrombus Formation

• 24 hours?
• 48 hours?
• Seconds?
• Minutes?

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ASSERT Trial

• Results of the Asymptomatic AF and Stroke
  Evaluation in Pacemaker Patients and the AF
  Reduction Atrial Pacing Trial (ASSERT) showed
  that, in this population of pacemaker patients
  with hypertension but no history of atrial
  fibrillation (AF), episodes of device-detected
  atrial tachycardia greater than six minutes were
  seen in approximately one-third of patients over
  almost three years of mean follow-up.
• Further, these arrhythmias were associated with a
  2.5-fold increase in the risk for ischemic stroke
  and systemic embolism. In a subgroup of patients
  with a CHADS2 score of 2 or higher,
  device-detected atrial tachyarrhythmias increased
  the absolute risk for stroke to 3.78 per year.

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2014 AHA/ACC/HRS AF Guidelines Guidelines Are
Just Guidelines

• "The guidelines attempt to define practices that
  meet the needs of most patients in most
  circumstances. The ultimate judgment about care
  of a particular patient must be made by the
  clinician and patient in light of all the
  circumstances presented by that patient."

January CT, et al. Circulation
2014129000-000. Doi 10.1161/CIR.000000000000004
1
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2014 AHA/ACC/HRS AF Guidelines Anticoagulation

• Shared decision process
• CHA2DS2-VASc (not CHADS2)
• If warfarin, then INR weekly till stable, then
  monthly
• If NOAC, then creatinine on initiation and then
  at least yearly
• Warfarin for mechanical valves
• Warfarin if CrCl lt15 ml/min or on HD

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Use of Anticoagulants in Renal Failure

• AHA/ACC/HRS Guidelines 2014
• Use warfarin if CrCl lt15 ml/min (IIa.B)
• IIa and Xa inhibitors not recommended in renal
  failure with hemodialysis (III-No benefit)
• But FDA approved
• Dabigatran 75 mg bid with CrCl 15-30 (modeling)
• Rivaroxaban 15 mg qd with CrCl 15-30 (modeling)
• Apixaban 5 mg bid with ESRD on HD and no other
  risk factors (age 80 or weight 60 kg)
  (modeling)

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Who do we anticoagulate?
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CHA2DS2 VASc

• The CHADS2 score is a clinical prediction rule
  for estimating the risk of stroke in patients
  with non-rheumatic atrial fibrillation (AF), a
  common and serious heart arrhythmia associated
  with thromboembolic stroke. It is used to
  determine whether or not treatment is required
  with anticoagulation therapy or antiplatelet
  therapy.

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CHA2DS2 VASc (continued)
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Annual Stroke Risk
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2014 AHA/ACC/HRS AF Guidelines Recommendations
for Anticoagulation
CHA2DS2-VASc Recommended Anticoagulation
0 No therapy
1 No therapy warfarin, dabigatran, rivaroxaban, apixaban
2 Warfarin, dabigatran, rivaroxaban, apixaban
Valvular Disease Warfarin with INR 2.0-3.5
CHA2DS2-VASc score for NVAF patients C CHF (1
pt) H hypertension (1 pt) A2 Age gt75 yo
(2 pts) D DM (1 pt) V Vascular disease (1
pt) A Age 65-75 yo (1 pt) S Female gender
(1 pt)
January CT, et al. Circulation
2014129000-000. Doi 10.1161/CIR.000000000000004
1
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Types of Anticoagulation

• Warfarin (Coumadin)
• Heparin
• Aspirin
• Clopidogrel (Plavix)
• Prasugrel (Effient)
• Ticagrelor (Brilinta)
• Dipyridamole (Persantine)
• Enoxaparin (Lovenox)
• Ardeparin (Normiflo)
• Dalteparin (Fragmin)

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Types of Anticoagulation (continued)

• Ticlopidine (Ticlid)
• Danaparoid (Orgaran)
• Tinzaparin (Innohep)
• Dabigatran etexilate (Pradaxa) 
• Rivaroxaban (Xarelto)
• Apixaban (Eliquis)

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Definition of Non-Valvular AF

• Nonvalvular AF is that which occurs in the
  absence of rheumatic mitral stenosis, a
  mechanical or bioprosthetic heart valve, or
  mitral-valve repair.

From Table 4 January CT, et al. Circulation
2014129000-000. Doi 10.1161/CIR.000000000000004
1
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Pradaxa

• Direct thrombin inhibitor
• Indications nonvalvular AF
• 150mg BID dosing with or without food
• - CrCl gt 30mL/min
• 75mg BID dosing with or without food
• - CrCl 15-30mL/min
• Converting from Coumadin to Pradaxa
• - INR lt 2.0
• Converting from Pradaxa to Coumadin
• Based on CrCl and see package insert

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Pradaxa (continued)

• Not available in generic AKA dabigatran
• When compared to Coumadin, 35 risk reduction in
  stroke in relatively health pts, mean CHADS2
  score of 2.2 statistically significant (RE-LY
  and RECOVER trials)
• SEs bleeding, dyspepsia, gastritis

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Xarelto

• Factor Xa inhibitor
• Indications nonvalvular AF
• 20mg once daily with evening meal
• - CrCl gt 50mL/min
• 15mg once daily with evening meal
• - CrCl 15 to 50mL/min
• Converting from Coumadin to Xarelto
• - INR lt 3.0
• Converting from Xarelto to Coumadin
• - No trial data available

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Xarelto (continued)

• Not available in generic AKA rivaroxaban
• When compared to Coumadin it showed a risk
  reduction for stroke that was not statistically
  significant but they looked at sicker patients
  with a mean CHADS2 score of 2.5 (ROCKET AF and
  ARISTOTLE trials)
• SEs bleeding, thrombocytopenia, elevated LFTs,
  pruritis

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Eliquis

• Factor Xa inhibitor
• Indications nonvalvular AF
• Dosing -5mg BID OR
• The recommended dose of ELIQUIS is 2.5 mg twice
  daily in patients with any 2 of the following
  characteristics
• age 80 years
• body weight 60 kg
• serum creatinine 1.5 mg/dL

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Eliquis (continued)

• Converting from Coumadin to Eliquis
• INR lt 2.0
• Converting from Eliquis to Coumadin
• ELIQUIS affects INR, so that initial INR
  measurements during the transition to warfarin
  may not be useful for determining the appropriate
  dose of warfarin. If continuous anticoagulation
  is necessary, discontinue ELIQUIS and begin both
  a parenteral anticoagulant and warfarin at the
  time the next dose of ELIQUIS would have been
  taken, discontinuing the parenteral anticoagulant
  when INR reaches an acceptable range.

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Eliquis (continued)

• Not available in generic AKA apixaban
• When compared to Coumadin with pts with PAF and
  persistent AF, it was superior in all categories
  bleeding, stroke risk reduction, systemic
  embolism, and lower mortality (ARISTOTLE and
  AVERROES trials)
• SEs bleeding, anemia, nausea

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Newest Guidelines on Anticoagulation
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On the Horizon

• Edoxaban
• Factor Xa inhibitor
• Once daily dosing
• Conclusions Both once-daily regimens of edoxaban
  were noninferior to warfarin with respect to the
  prevention of stroke or systemic embolism and
  were associated with significantly lower rates of
  bleeding and death from cardiovascular causes.
  (New England Journal of Medicine)

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Treatment options for AF

• ANTICOAGULATION!!!!!
• Rate control (AVN blocking drugs)
• Cardioversion
• Anti-arrhythmic medications (Class I III)
• Catheter ablation
• Surgical ablation
• Pacemakers (and AV node ablation)
• Watchman device
• Lariat

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Antiarrhythmic Medications

• Classification
• Class I Interfere with the sodium channel.
• Class II Antisympathetic nervous system agents.
  All agents in this class are beta blocker.
• Class III Affect potassium influx
• Class IV Affect the AV node.
• Class V Work by other or unknown mechanisms.

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Examples

• Ia quinidine, procainamide, dysopyramide
• Ib lidocaine, mexiletine, tocainide, phenytoin
• Ic encainide, flecainide, moricizine, and
  propafenone
• II esmolol, propranolol, metoprolol
• III amiodarone, azimilide, bretylium, clofilium,
  dofetilide, ibutilide, sematilide, dronedarone,
  sotalol
• IV verapamil diltiazem
• V adenosine digoxin

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Anti-arrhythmic Medications

• The good, the bad, and the ugly

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Tambacor and Rythmol

• Class IC
• Indications - AF, AFL, PSVT, ventricular
  arrhythmias
• Dosing and titrate to effect
• EKG after 6 doses
• Available in generic flecainide, propafenone, and
  propafenone SR
• Contraindicated in pts with CHF and CAD

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Tambacor and Rythmol (continued)

• Addition of Beta Blocker
• SEs from Tambacor nausea, dizziness, headache,
  blurred vision, dyspnea, fatigue
• SEs from Rythmol chest pain, edema,
  palpitation, constipation, nausea, altered sense
  of taste, vomiting, dizziness, anxiety, dyspnea,
  fatigue

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Betapace

• Class III
• Indications atrial arrhythmias and ventricular
  arrhythmias
• BB and AAD
• Dosing and titration 80mg BID to 160mg BID
• Available in generic sotalol
• Hospitalize for doses for initiation

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Betapace (continued)

• Studies show 80mg BID no better than placebo
• QTc prolongation
• Less drug interactions than Tikosyn
• SEs bradycardia, fatigue, chest pain,
  lightheadedness, palpitations, rash, nausea,
  headache, dyspnea.

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Pacerone

• Class III
• Indications ventricular arrhythmias and AF for
  pts with heart failure and HOCM.
• NOT front tier therapy, ie not FDA approved for
  AF pts otherwise.
• Should get pts to sign that they are aware
  because of risks associated with medication

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Pacerone (continued)

• Dosing and titration
• Available in generic amiodarone
• Baseline PFTs, LFTs, TFTs, and chest xray
• Yearly eye exams
• Q6 month LFTs, TFTs, and chest xray
• PFTs debatable
• BIG concern pulmonary fibrosis

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Pacerone (continued)

• SEs bradyarrhythmias, hypotension,
  photodermatitis, photosensitivity, thyroid
  dysfunction, constipation, loss of appetite,
  nausea, vomiting, increased liver enzymes,
  abnormal gait, movement disorders, corneal
  deposit, malaise and fatigue

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Tikosyn

• Class III
• Indications AF and AFL
• Dosing
• Hospitalization for 5 doses to start medication
  and titration
• Not available in generic AKA dofetilide
• Cr q6 mos and EKG q3 mos

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Tikosyn (continued)

• Potassium and Magnesium
• SEs chest pain, dizziness, headache, QTc
  prolongation, torsades de pointes, ventricular
  arrhythmias
• Only approved physicians can prescribe

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Multaq

• Class III
• Indications AF, PAF and persistent
• Amiodarone derivative
• Chemical difference took out 2 iodines making
  drug less toxic and added one side chain making
  drug more soluble
• Effect Amios half life is 45 days and Multaqs
  half life is 12 hours

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Multaq (continued)

• Dosing
• Not available in generic AKA dronedarone
• Can be used with pts with compensated heart
  failure but not uncompensated
• Spacing of dosing
• Take with meals
• Liver Tx 2 out of 600,000
• PALLAS study

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Multaq (continued)

• SEs abdominal pain, diarrhea, indigestion,
  nausea, vomiting, asthenia, serum creatinine
  raised, heart failure, prolonged QTc, liver
  failure, CVA

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Risks-Benefits Analysis for AADs in Permanent AF

• Benefits
• Sinus rhythm
• Better rate
• control
• Pleotropic
• effects ?

• Risks
• Proarrhythmia
• Negative inotropy
• Bradyarrhythmia
• Drug interactions
• Non-cardiac
• toxicity

Benefits
Risks
Implications 1) AADs should not be used in
permanent AF and 2) Patients on AADs for
paroxysmal or persistent AF should be followed
regularly for development of persistent AF and
AAD stopped if re-establishment of sinus rhythm
not planned.
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Procedural Treatment for AF

• Cardioversion
• Pacemakers and AV node ablation
• Catheter ablation
• Surgical ablation
• Watchman device
• Lariat

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Pace and Ablate

• Do pacemakers treat AF?
• How are pacemakers used for AF patients?
• AV Node Ablation is a procedure by which the
  heart's AV node (Atrioventricular node, the
  electrical pathway that connects the top chambers
  to the bottom chambers of the heart) is modified
  to restore normal heart rhythms. The procedure
  involves cauterizing or freezing the AV node to
  block or alter electrical conduction through this
  region of the heart. During a typical AV node
  ablation, a permanent pacemaker is implanted in
  the chest to mechanically regulate the pulse rate
  in the lower chambers of the heart (ventricles)
  to match the natural pulse rate in the upper
  chambers of the heart (atria).

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2014 AHA/ACC/HRS GuidelinesCatheter Ablation is
Now Front-Line Therapy
January CT, et al. Circulation
2014129000-000. Doi 10.1161/CIR.000000000000004
1
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Ablation Technology
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LEFT ATRIAL APPENDAGE CLOSURE
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Patient Selection

• Patient with non-valvular AF
• CHADS2 score of 2 or higher
• Absolute or relative contraindication to long
  term oral anticoagulation therapy (OAT)
• Intolerance to OAT
• Recurrent GI Bleed
• Hemorrhagic CVA
• Embolic CVA on therapeutic OAT

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Left atrial appendage closure

• Amplatzer Plug (Watchman)
• Must be able to take Coumadin for 6 weeks post
  procedure
• Placement of flexible braided
  nitinol mesh
• Catheter-based delivery
• Lifetime/permanent

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Left atrial appendage closure

• LARIAT
• Suture closure, catheter-based
• CTA Heart pre-procedure to assess LAA anatomy
• Specifically looking at size, shape, positioning
• Assess for LAA thrombus
• If LAA is gt40 mm, tucked behind PA, or oddly
  shaped cannot/difficult to place.
• Cannot place if LAA thrombus is present
• Can attempt to dissolve with OAT

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Left atrial appendage closure

• LARIAT
• Does not require pre or post procedure OAT
• No prior sternotomy
• Advancing epicardial sheath difficult due to
  adhesions
• No prior pericarditis

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LARIAT
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Summary

• AF is the most common clinically significant
  cardiac arrhythmia.
• Stroke prevention is the primary concern in
  treatment of AF.
• There are increasing options for oral
  anticoagulation however, the new guidelines
  clearly recognize that the choice should be a
  shared decision process.
• Ablation is now considered front line treatment
  in some patients with AF.
• Left atrial appendage closure devices are an
  excellent option for patients who cannot tolerate
  oral anticoagulation.

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QUESTIONS