Atrial Fibrillation by mikeholy


									Atrial Fibrillation

   Michael E. Lazarus, M.D,
   Hospital Medicine
   David Geffen School of Medicine at
            Atrial Fibrillation
 The most common sustained cardiac
 Affects 2.2 million Americans.
 Increases mortality 2 fold and stroke risk 5
 A great deal of new information has come
  to light recently related to management.
   Paroxysmal -episodes terminate
  spontaneously in under 7 days.
 Persistent -episodes do not
  spontaneously terminate but patients can
  be converted to NSR pharmacologically or
 Permanent –long lasting state of AF
  which cannot be permanently terminated.
              Risk factors
 Age
 Congestive heart failure\ EF<40%
 Diabetes
 Hypertension
 Increased LA size e.g. Rheumatic mitral
 Left Ventricular hypertrophy
 Familial Atrial Fibrillation
      Other associated factors
 Pericardial disease
 Post CABG
 Hyperthyroidism
 Hypoxic Pulmonary disease.
 Alcohol intoxication.
                  Clinical course
   Stroke risk
     15%   of all strokes in the USA.
     Risk increases with age
     Left atrial appendage clots embolize.

   Other cardiovascular outcomes
     Increasesoverall mortality.
     Tachycardia induced cardiomyopathy
         Clinical impact of A.Fib
   Rhythm anomalies
     Tachycardia
             Short term
                 Palpitations
                 Congestive heart failure
                 Ischemia
                 Syncope
             Long term
                 Increased mortality

   Loss of atrial contraction
     Hemodynamic          compromise esp. in the elderly
         Management Strategies
   Rate control vs. rhythm control

   Anticoagulation

   Maintenance therapy
Rate better than rhythm control?
   The evidence.
     PIAF -Pharmacological Intervention in Atrial
     STAF -Strategies of Treatment of Atrial
     RACE -Rate control vs, Electrical cardioversion
             for persistant Atrial fibrillation.
     AFFIRM –Atrial Fibrillation Follow-up
             Investigation of Rhythm Management
 252 patients with persistent symptomatic atrial
  fib all patients anticoagulated followed up at 1
 Mean age ~60
 Rate control group-Diltiazem for sympton control
 Rhythm control group-Amiodarone followed by
   Primary end point-symptom improvement
   Results:
      Rhythm control
            Overall symptom improvement 55%
            56% in NSR
            Improved QOL
            Improved exercise tolerance (6 min walk)
            Increased hospitalizations (69%)
            25% drop out rate due to SE’s
       Rate control
            Overall symptom improvement 61%
            10% in NSR
            Improved QOL
            Hospitalizations (24%)
            14% drop out rate
   200 patients with Atrial Fibrillation and one or
    more LA size >45mm, CHF >NYHA II ,
    LVEF<45% or one or more cardioversions with
    afib recurrence followed up at 1 year
   Mean age 65.5
   Rate control group-AC, digoxin, β-blocker, CaCh
    blocker or AV node ablation and pacemaker
   Rhythm control strategy-AC, electrical
    cardioversion, amiodarone, or a class 1
    antiarrythmic agent
   Primary end points: Composite of Death, CVA,
    systemic embolism and need for CPR.
   Results:
       Rate control
            9% composite end point
       Rhythm control
            10% composite end point
            More hospitalizations and longer lengths of stay for repeat
             cardioversions and antiarrythmic drug loading.
            At 3 years only 23% of patients who had undergone
             cardioversion were still in NSR

   Both groups: Same incidence of bleeding,
    syncope, CHF and same scores in QOL measures
   522 patients in Atrial fibrillation, on AC (Warfarin or
    ASA), all had 1-2 attempts at DC version in prior year.
   Mean age 68 yrs, mean follow up 2.3 yrs
   Rate control group: β-blockers, CaCh blockers or digitalis
    with a target HR of 100. Pts who had intolerable SE’s
    were cardioverted or ablated and paced
   Rhythm control group: DC version followed by p.o.
    Sotalol. If failed re-DC verted and given flecainide or
    propafenone. If 2nd failure DC version and p.o.
    amiodarone. 3rd failures either left in AF or ablated and
   Primary end points: Composite of cardiovascular death,
    heart failure, thromboembolic complications, bleeding,
    need for pacemaker, a severe adverse effect of therapy.
   Results:
       Rate control:
            10% in NSR
            17.2% reached primary end point
            0.8% experienced a drug side effect.
            Less thromboembolic events-probably due to being
             maintained on AC
       Rhythm control:
            39% in NSR
            22.6% reached a primary end point.
            4.5% experienced a drug side effect.
            More thromboembolic events
   4060 patients
   Mean age of 69.7 yrs and all patients were either over
    65 or had at least one risk factor for stroke or death (see
    slide 4)
   All candidates for Anticoagulation.
   Rate control group: β-blockers, CaCh blocker, Digoxin or
    combinations. Target HR 80 at rest and 110 with 6min
   Rhythm control group: According to current guidelines,
    included: amiodarone, dofetilide, disopyramide,
    flecainide, moricizicine, procan, propafenone, quinidine,
    sotalol and combinations of these.
 After pharmacologic trials of at least 2 drugs in
  either group, nonpharmacologic therapies were
  allowed-RFA, MAZE or pacemakers.
 All patients were anticoagulated to an INR of 2-
 End points were:
    Primary: All cause mortality
    Secondary: Composite of death, CVA, major
     bleed, and cardiac arrest.
 Mean follow up 3.5 years max was 6 years
   Results:
      Rate control group:
         35% in NSR
         15% cross over to Rhythm control group
         25.9% overall mortality
         Lower risk of death in patients with CAD, No CHF, or older
           than 65 yrs
      Rhythm control group:
         63% in NSR
         37.5% crossed over into the Rate control group
         26.7% overall mortality
         Subgroups with a trend towards improvement were those
           with CHF and pts <65 yrs
         Higher incidences of Torsade, PEA, bradycardia and more
 Rate control acceptable as primary
  approach or in cases where rhythm control
  is difficult
 Older patients >65 more benefits from
  rate control
 Rhythm control for younger patients and
  those who are persistently symptomatic
  with rate control alone
             How to restore NSR
   Electric Cardioversion
     If<48 hrs or after 3 weeks of AC and 4
      weeks post.
     90% immediate efficacy.
   Pharmacologic cardioversion
     54   randomized trials support the use of
      ibutilide, flecainide, dofetilide, propafenone
      and amioodarone.
     Amiodarone is administered orally and has
      lower rates of arrythmias.
          Rhythm Control Agents
  Medication      Indication                Dosing
Amiodarone     Conversion and         300 mg PO bid for 1-3
               maintenance in         weeks then 200 mg
               patients with normal   QD. Check Thyroid,
               and low LVEF           liver and PFT baseline.
                                      IV 150 mg over 10
                                      min then 1 mg / kg for
                                      6 hrs, then 0.5 mg
                                      /min for 18 hrs.
Flecainide     PAF, N LVEF and NO     50 mg PO bid
Propafenone    Structurally normal    600 mg PO once then
               hearts and no CAD      150-300 mg PO bid

Sotalol        Maintenance            80 mg PO bid, Follow
                                      QT interval for 3 days.
               only                   Renal dose.
 Assessment of Cardioversion Using TE

 ACUTE study looked at risk stratifying patients
  for thromboembolic events.
 Study group got TEE, if no evidence of
  microemboli-short term AC and version with 4
  weeks post AC vs. conventional therapy
 Results: No difference in CVA, TIA or peripheral
  embolism but more episodes of bleeding in the
  conventional therapy group. The TEE group
  shorter time to cardioversion and a higher initial
  success rate.
             Maintaining NSR
 35 randomized trials
 Strong evidence for the efficacy of amiodarone,
  disopyramide, propafenone, and sotalol
 True risks of arrythmias are not well elucidated
  in the literature but amiodarone and
  disopyramide had the lowest incidence of
  ventricular arrythmias
 The largest trial of amiodarone side effects 201
  patients, 4 with pulmonary toxicity, 1 with
  hyperthyroidism and 2 with hypothyroidism.
  (NEJM 2000;342:913-920)
 All patients with risk factors for
  thromboembolic disease should be
  evaluated for anticoagulation.
 Risk criteria defined and validated in SPAF
     High   Risk Criteria:
       Previous  CVA/TIA
       Systolic BP>160
       CHF/LV Fractional Shortening < 25% by Echo
       Women> 75
 Moderate     Risk
   Hypertension
   No   high risk criteria
 Low   Risk
   No Hypertension
   No high risk criteria
                              SPAF 1
   Are ASA and warfarin effective in reducing rates of
    stroke and systemic embolism in patients with
    nonrheumatic atrial fibrillation?
   Design
       Randomized, double blind, placebo-controlled (ASA) and open
        label to warfarin.
   Inclusion Criteria
       Chronic or paroxysmal AFib.
   Exclusion Criteria
       CHF, Prosthetic valves or rheumatic heart disease
   Intervention
       Warfarin to target INR of 2-4.5 and ASA vs. placebo.
       SPAF 1                SPAF 1 STUDY

           Anticoagulation                       Non-anticoagulation
                eligible                               eligible,
             Randomly                                Randomly
               assigned                               assigned
               N=627                                   N=703

WARFARIN      ASPIRIN        PLACEBO        ASPIRIN              PLACEBO
 N=210         N=206          N=211          N=346                N=357
         The Results of SPAF 1
   Warfarin with ASA or placebo reduced
  stroke or embolism (2.3% vs. 7.4%) as
  did ASA with or without warfarin (3.6%
  vs. 6.3%)
 Bleeding risk negligible, warfarin-1.5%
  and ASA 1.4%
                         SPAF II

                              SPAF II

         AGE<75                                  AGE>75
     Randomly assigned                       Randomly assigned
          N=715                                   N=385

WARFARIN            ASPIRIN             WARFARIN            ASPIRIN
 N=358               N=357               N=197               N=188
                      SPAF III
 Is Warfarin alone (adj. dose) or ASA +
  Warfarin (fixed dose) superior for the
  prevention of stroke in patients with Afib.
  With risk factors for CVA?
 Randomized non-blinded trial.
 Inclusion criteria
     CHF,   Female>75, Prior CVA and SBP>160.
   Exclusion criteria
     Prosthetic   valves, MS, recent PE, or NSAID
                            SPAF III
                       SPAF III STUDY

                       1.   Women> 75 y                        One or
                       2.   Systolic Hypertension
                       3.   Impaired LV function               more
                       4.   Previous embolism

                                                           High risk
                                                       Randomly assigned
Low or moderate risk

                                                    WARFARIN        Combination
                                                     INR 2-3          1-3 mg
 Aspirin 325 mg/d                                    N=523            Warfarin
      N=892                                                           + Aspirin
 Combined events of ischemic stroke and
  embolism were decreased in the adjusted
  dose warfarin group (1.9% vs. 7.9%) as
  were disabling and fatal stroke (1.7% vs.
 Major bleeding events were comparable
  for adjusted-dose warfarin and ASA\fixed-
  dose warfarin (2.1% vs. 2.4%)
         Stroke Risk Assessment
   CHADS 2-risk Stratification Score
     C-congestive  heart failure           1
     H-hypertension                        1
     A-age>75                              1
     D-diabetes                            1
     S-stroke or TIA history               2
                                    Total   6
           CHADS 2
Score       Adjusted stroke rate
0       1.9 per 100 patient years
6       18.2 per 100 patient years
    Guidelines for Anticoagulation
Patient Characteristics       Treatment
Age<60, without heart disease ASA 325mg/d or
Age<60, with HD but no CHF or ASA 325 mg/d
Age>60, no CHF or HTN         ASA 325 mg/d
Age>60 with DM or CAD           Coumadin (2-3)
Age>75                          Coumadin (~2)
Rheumatic Heart Disease         Coumadin(2.5-3.5)
•146 patients with medically refractory, chronic atrial fibrillation
were randomly assigned to undergo circumferential
pulmonary-vein ablation vs. short-term medical therapy with
•Clinically significant structural heart disease was present in 8
percent of patients.
•All patients had received at least two ineffective
antiarrhythmic drugs and had undergone at least one
•At 12-months, 74% of patients who had undergone ablation
were in sinus rhythm without antiarrhythmic-drug therapy, as
compared with only 4% of control patients.
                         RFA study
•Demonstrates that catheter ablation alone can lead to sustained sinus
rhythm in specific patients with chronic atrial fibrillation.
•The nonpharmacologic maintenance of sinus rhythm is an important
clinical goal.
•Although recent trials have demonstrated no advantage to
pharmacologic rhythm control, as compared with rate control, for most
clinical outcomes, there is genuine concern that the benefits of sinus
rhythm are negated by the deleterious effects of antiarrhythmic drugs.
• Maintenance of sinus rhythm has been associated with a survival
advantage that may be offset by the use of antiarrhythmic drugs.
•The ability to maintain sinus rhythm without drugs may shift the current
balance between rate- and rhythm-control strategies and require a
complete reassessment of their relative benefits
            Limitations of RFA
 Catheter ablation is not yet a proven therapeutic
  option for the general population with chronic
  atrial fibrillation
 The greater population of patients with chronic
  atrial fibrillation are generally elderly and have
  structural heart disease and coexisting
 The electrical substrate for atrial fibrillation in
  these patients may be less responsive to
         RFA The final word
 Younger patients who are refractory to
  medical treatment and who have limited
  or no structural heart disease may be most
  likely to benefit from this procedure.
 Stroke and fatal complications are known
  risks of left atrial ablation, and major
  complications have been reported to occur
  in 1 to 5 percent of patients who undergo
  this procedure

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