Atrial Fibrillation

     

    Introduction

    • Very common condition affectingn 2.2 million people in US.  Men > Women.
    • 10% common in people >80yo.
    • Blood stasis in LV can cause thrombus formation and leading cause of embolic stroke.
    • AFib = Increased risk of HF and all cause mortality.
    • Symptoms: palpitations, chest discomfort, weakness, fatigue, syncope.
      • Most patients asymptomatic esp if longstanding.
    • Types:
      • Paroxysmal - terminates on its own.
      • Persistent - sustains for ≥1 week.
      • Perminant - continued, cardioversion failed or too longstanding to attempt cardioversion.
    • Investigations:
      • Heart failure, hyperthyroidism, HTN, WPW, CV surgery, MI, myocarditis, pericarditis, acute pulmonary disease, MV disease.
      • If no structural heart disease <60yo = "Lone atrial fibrillation".
    • EKG - thyroid, renal, hepatic abnormalities (future antiarrhythmic/antocoagulant meds).
      • TTE: LV hypertrophy, valves, pulmn HTN.
    • If not planning DC cardioversion, no need to anticoagulate acutely with heparin.  (start oral).
    • Anticoagulation not mandatory if AFib <48hrs.
      • If unknown or >48hrs --> two strategies
        • 1. Medicate with warfarin for 3 weeks --> cardiovert
        • 2. TEE to r/o thrombus.
      • High risk of stroke post-cardioversion, should continue with warfarin ~1mo post-cardioversion.

    Management

    Anticoagulation

    • CHADS2 = 0 (1.9 strokes/100pt years) --> ASA or no therapy.8
    • CHADS2 = 1 --> ASA or Warfarin (risk stratify using CHADS-Vasc score)
    • CHADS2 > 2-6 --> Warfarin
    • NOTE: this is validated in non-valvular AF.  Pts in setting of valvular AF (i.e. rheumatic mitral stenosis) are high stroke risk (must anticoagulate 2-3 INR).
    • Mechanical valves:
      • INR 2.5-3.5 (additive risk of thromboembolism with mech valve, does not matter if aortic or mitral valve).
    • If cannot take warfarin, adding clopidogrel to ASA can reduce stroke risk more than ASA alone.  (definitely inferior to warfarin).
      • New classes for non-valvular AF:

     

    Agent Approved for    

    Dabigatran (BID)

    (Direct Thrombin Inhibitor)

    - Stroke prevention

      in non-valvular AF

     (ReLY Trial)

    - Superior to warfarin in preventing ischemic and

      hemorrhagic stroke with reduced risk of life-

      threatening bleeding, but higher risk of GI bleeds.

     

    - No reversal agent.

    - Benefits: Oral, no monitoring

     

    Rivaroxaban (OD)

    (Oral Factor Xa inhibitors)

    - Stroke prevention

      in non-valvular AF

    (ROCKET-AF trial)

     

    - VTE prophylaxis

     (MAGELLAN)

     

    - Secondary VTE

      prevention 

     (EINSTEIN trial)

    - Shown to be non-inferior of warfarin for stroke prevention

      with no difference in major bleeding.

      - Reduction of intracranial hemorrhagic risk.

    - Risk of thrombotic events is increased in 28d post-

      discontinuation, so highly recommended to bridge with 

      another agent.

     

    - Benefits: Oral, no monitoring, once daily.

    - Reversal agent pending. 

     
           

    (AF or afib) (ROCKET-AF), prevention of VTE in hospitalized medically ill patients (MAGELLAN), treatment and secondary prevention of VTE (EINSTEIN), and secondary prevention of major cardiovascular events in patients with acute coronary syndrome (ACS) (ATLAS ACS TIMI 51)

     

    • Post-ablation recommendation is Warfarin for 2-3 months, then treat as if ablation did not happen (prev. agent).
      • If a patient is unable take warfarin:
        • Aspirin and clopidogrel provide a greater stroke reduction than aspirin alone.
        • But this combination is less effective for stroke reduction than warfarin and carries a higher bleeding risk.
        • NOACs such as dabigatran and rivaroxaban may also be an option, but not yet studied post-ablation.

    Acute

    • Patients with hypotension, angina, or acute heart failure should undergo emergent DC cardioversion.
      • Cardioversion synchronization should be turned ON, to avoid R-on-T shock (can cause VFib).
      • Following cardioversion, must receive 4 weeks of anticoagulation with warfarin (goal INR 2-3).
    • If hemodynamically stable, can initially rate control to 60-110bpm.

     

    Rate vs. Rhythm Control

    • AFFIRM/RACE1 trials: Rhythm control is no better than rate control (Rate control = less hospitalizations).
    • RACE2 trial: lenient heart rate control (<110) better over strict (<80) as long as LVEF >40%.
    • NO mortality or stroke reduction benefit in restoring sinus rhythm.
    • Goals:
      • Identify and treat underlying structural heart disease and other predisposing conditions
      • Relieve symptoms
      • Improve functional capacity/quality of life
      • Reduce morbidity/mortality associated with AF/AFL
      • Prevent tachycardia-induced cardiomyopathy
      • Reduce/prevent emergency room visits or hospitalizations secondary to AF/AFL
      • Prevent stroke or systemic thromboembolism 
    • How do you decide if you are going to pursue rate or rhythm control for a patient with AF

     

    • No right or wrong answer
    • Often, the two are simultaneous:
    • Rhythm control requires good rate control when patient goes back into AF

     

    • Bottom line:
      • Asymptomatic patients can be managed with rate control. (no benefit in rhythm control).
      • Resting HR <110bpm as long as LVEF > 40%.

     

    Rate Control

    • Acute Rate Control
      • Doc - Nov 1, 2015, 8-12 PM.jpg

        Source: "The Little ICU Book" by Marino 2009
    •  
    • CCS Guidelines Target < 100bpm (For permanent/persistent AF/AFL)
      • (Even though RACE2 trial had <110 target, though few patients were >100).
      • Guidelines: can target <110, but lower rate if pts symptomatic.
    • Typically metoprolol is first line (esp. if CAD or HF)
    • Agents:
      • Drug Dosing S/E
        Atenolol 50-150mg po daily Bradycardia, hypotension, fatigue, depression
        Bisoprolol 2.5-10mg po daily same
        Metoprolol 25-200mg po BID same
        Nadolol 20-160mg po daily - BID same
        Propranolol 80-240mg po TID same
        Non-Dihydropuridine CCB
        Verapamil

        120-480mg po daily

        120-240mg po BID

        Bradycardia, hypotension, constipation
        Diltiazem

        120-480mg po daily

        120-240mg po BID

        Bradycardia, hypotension, ankle swelling
        Other
        Digoxin 0.0625mg - 0.25mg po daily

        bradycardia, nausea, vomiting, visual disturbance

        (Used as a secondary agent for those with HF or LV dysfunction)

        (may take up to 6hrs to see peak effect).

      • Atenolol 50-150mg po daily (S/E: Bradycardia, hypotension, fatigue, depression)
      • Bisoprolol 2.5-10mg po daily (same as atenolol)
      • Metoprolol 25-200mg po BID (same as atenolol)
      • Digoxin (blocks Na/K+ atpase, increases Na/Ca atpase, inotropy, but increases vagal tone for AV blockade)
        • Load: 0.5 + 0.25 + 0.25 (each 2hrs apart given IV), digoxin takes a bit of time to reach plasma peak levels or slow load over days.
        • Maintenance: 0.25 (general) 0.125 (typical elderly), or 0.0625 (elderly, severe renal failure) 
    • If cannot rate control despite all attempts/optimal therapy ---> RF ablation + pacemaker.

     


    Rhythm Control

    • Recommended in patients in who remain symptomatic with rate control therapy or in whom rate control therapy is unlikely to control symptoms.
    • Two Types:
      • Continuous.
      • Intermittent ("pill in pocket")
        • CCS Guideline: We recommend intermittent antiarrhythmic drug therapy ("pill in pocket") in symptomatic patients with infrequent, longer-lasting episodes of AF/AFL as an alternative to daily antiarrhythmic therapy. (Strong Recommendation, Moderate Quality)

        • Single dose flecainide (200-300 mg) or propafenone (450-600 mg) as an oral dose
        • Often prescribed with a short-acting beta-blocker at the same time (metoprolol 50-100 mg) to take 30min before antiarrhythmic or be on background rate control
          • ...due to concern of post-conversion pause. 
          • First time antiarrhythmic conversion should be monitored to ensure no post-conversion pause.
        • (As long as no sinus/AV dysfunction, no bundle block, no long QT)
    • ​Agents: (From Skanes et al 2012, Can. J. Cardiol.)
      • Drug/Dose Efficacy Toxicity Comments

        Flecainide

        50-150mg BID

        30-50%

        - Ventricular tachycardia

        - Bradycardia

        - Rapid vetricular response to

          AF/Flutter (1:1 conduction)

        - CONTRAINDICATED IN:

                 CAD and LV dysfunction

        - Should combine with AV

          nodal blocking agent.

        Propafenone

        150-300mg TID

        30-50%

        - Ventricular tachycardia

           or bradycardia

        - Rapid ventricular response

          to AF/Flutter (1:1 conduction)

        - Abnormal taste

         

        - CONTRAINDICATED IN:

                 CAD and LV dysfunction

        - Should combine with AV

          nodal blocking agent.

        Amiodarone

        100-200mg OD

        (After 10g loading)

        60-70%

        - Photosensitivity

        - Bradycardia

        - GI upset

        - Thyroid dysfunction

        - Hepatic toxicity

        - Neuropathy

        - Tremor

        - Pulmonary Toxicity (fibrosis)

        - Torsades de Pointes (rare)

        - Low risk of pro-arrhythmia

        - Limited by side effects.

        - Side Effects are dose and duration

          dependent.

        NEW!! (limited 

        experience)

         

        Dronedarone

        400mg BID

        40%

        - GI upset

        - Bradycardia

        - Hepatic Toxicity

        - CONTRAINDICATED IN:

           CHF and LVEF < 40%

        - Caution when added to digoxin

        - Liver enzyme monitoring required

         

        Sotalol

        80-160mg BID

        30-50%

        - Torsades de pointes

        - Bradycardia

        - B-blocker side effects

        - AVOID in pts with high risk of Torsades

          (esp Female, >65, on diuretics, with renal

          disease)

        - Monitor QT interval 1w after starting

        - Caution when EF < 40%

     

    • NOTE: Rhythm control DOES NOT replace anticoagulation. (no evidence reduces risk of thromboembolism)
      • Should still receive anticoagulation for thromboembolic prophylaxis (CCS guidelines)
    • Amiodarone (Class III antiarrhythmic)
    • Dronedarone (Class III antiarrhythmic)
      • Newer agent to amiodarone (approved for paroxysmal afib).
      • Less end-orgen side-effects of amiodarone
        • (i.e. less thyroid, liver, and pulmonary function)
      • CCS Guidelines 2014:
        • Dronedarone is a good choice for RHYTHM control in selected AF pts with nonpermanent (predonimantly paroxysmal AF) with minimal structural heart disease.
        • Consider monitoring for LFTs within 6mo of initiating therapy.
      • NOTE: Raises creatinine (partial inhibition of tubular transport of creatinine --> elevated serum levels), but does not affect GFR (regard new creat as a new baseline - i.e. CrCl drops, GFR unchanged)
        • Metabolized by liver, does not need renal dosing.
      • DO NOT USE in:
        • Severe heart failure
          • Recent hospitalization for HF shown to have 2-fold increase in mortality with dronedarone.
        • Permanent atrial fibrillation (higher rates of hospitalization for HF, stroke, death from CV causes)
        • CCS Guidelines: (based on ANDROMEDA Trial)
          • DO NOT use in LVEF < 40%
          • DO NOT use for only rate control
          • CAUTION when taking digoxin
    • Electrical Cardioversion:
      • If unstable (see ACLS flow charts)
      • If rhythm control strategy chosen, and patient flips back after non-pre-treated electrical cardioversion, then pre-treat with antiarrhythmics prior to doing a cardioversion.
      • 150-200J biphasic waveform recommended as initial energy setting.
    • RF Ablation
      • 9 RCTs / 3 systematic reviews in 1274 patients who have failed ≥ 1 drug
      • uniformly demonstrate large differences in recurrence of AF
        • (OR 9.74 95% CI, 3.98 to 23.87) in favourof ablation vsAAD 
      • Quite low risk, largest risk:
        • Tamponade 1.31% rate (worldwide study)
        • TIA 0.71% rate
        • Femoral pseudoaneurism 0.93% rate
        • AV Fistula 0.54
        • TOTAL Risk of complications: 4.54%.
      • CCS Guideline:
        • We recommend catheter ablation of AF in patients who remain symptomatic

          following adequate trials of anti-arrhythmic drug therapy and in whom a rhythm

          control strategy remains desired. 

    • We recommend curative catheter ablation for symptomatic patients with typical atrial flutter as first line therapy or as a reasonable alternative to pharmacologic rhythm or  rate control therapy. 

    Ablation

    • Typically if symptomatic and treated at least with one antiarrhythmic agent unsuccessfully.
    • Pulmonary veins ablation
      • Entails electrical isolation of pulmonary veins, so premature complexes that originate in pulmonary veins cannot initiate fibrillation.
        • In the past: complication of pulmonary vein stenosis, but now can perform without this risk (do not enter ostia of pulmonary veins).
      • Must stay on warfarin for 2-3mo post-ablation, then anticoagulation is based on CHADS2 score.
      • Success rate 84% AFib free at 1 year, often needs to be repeated.
      • Complications (4.5% of patients)
        • Stroke
        • Atrial-esophageal fistula
        • Pulmonary veins tenosis
        • Cardiac tamponade
        • Death.
    • 2nd Line: AV node ablation
      • Pacemaker inserted at time of ablation to control ventricular rate.
      • Small risk of polymorphic VT. (reduce by increase paced heart rate by 2mo after procedure).
    • MAZE Surgery
      • Several incisions or ablations in R or L atria which interrupt re-entrant pathways required for afib maintenance.
      • Not studied head-to-head with pulmonary vein isolation, but success rate long-term is similar.

    Bridging Anticoagulation

    • Stopping warfarin for a procedure, often a difficult call whether the patient needs bridging UFH or LMWH.
    • CCS Guidelines:
      • CHADS2 ≤2 and no additional RF's --> No bridging (risk too low)
      • CHADS2 ≥3 --> Yes bridging  
      • Other risk factors requiring bridging:
        • Known LA thrombus
        • Stroke/TIA
        • (significant LV dysfunction)
        • Mechanical heart valves
          • (Except if bi-leaflet mechanical aortic valve, don't have to bridge - low risk in short term).
            • They have optimal hemodynamic profile (higher flow rates in aortic), so less stasis along surface of valve, so can be safely managed w/o warfarin for several days.
            • Mitral valves: higher rate of thrombosis due to lower pressure between LA and LV.
    • Guidelines:
      • Discontinue warfarin 48-72hrs (3 days) before surgery, restart on the evening after surgery (in 24hrs post-procedure). (if no bridging required)
    • Post-Cardioversion
      • Must maintain anticoagulation 4 weeks post-cardioversion (bridge if needed).
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