-Prabhat Hebbar MD.

CDC Fact Sheet 2017

 2.7–6.1 million people in the United States have AFib.
 2% of people age < 65, 9% of people age > 65 years have AFib
 African Americans are less likely to have AFib.
 women generally live longer than men, more women than men
experience AFib.
Cost and Consequences
 750,000 hospitalizations/year.
 130,000 deaths/year.
 Cost: $6 billion/year.
 AFib causes 15%–20% of ischemic strokes
Overall and sex-specific trends in incidence
of AF between 1980 and 2000

-Miyasaka et al; Circulation 2006;114:119–125

Stroke risk related to various cardiac conditions
Framingham study

- Wolf et al. Stroke 1991;22:983–988.

Outcomes
 Mortality: doubled
 Stroke: increased 5 fold. More severe
 Hospitalization: more frequent
 Quality of life: wide variation, from no
change to marked reduction.
 Congestive heart failure: wide variation
from none to severe(tachymyopathy)
Electrophysiological mechanisms
Triggers for onset + Substrate for maintenance
Triggers
 mechanism: triggered activity and re-entry
 most common site: pulmonary veins

- shorter refractory periods

- abrupt changes in myocyte fiber orientation.
 paroxysmal AF: the junction between the PVs
and the left atrium.
 Triggers

Haïssaguerre M et al. N Engl J Med 1998;339:659-666.

 Substrate

Sustained atrial fibrillation triggers an inflammatory response leading to

activation of myofibroblasts and release of cytokines
- development of fibrosis
- myocyte apoptosis
- extracellular matrix generation and turnover
- electrical and structural remodeling provides substrate for maintenance of to atrial
fibrillation
Persistent Atrial Fibrillation
Natural History
 Detection
 An irregular pulse or irregular heart beat on
auscultation should raise suspicion
 ECG is necessary to diagnose AF.
 Any arrhythmia that has the ECG characteristics of
AF and lasts sufficiently long for a 12-lead ECG to
be recorded, or at least 30 s on a rhythm strip,
should be considered as AF.
 Holter (24-48 hrs)
 Event monitors (upto 1 month)
 Dual chamber pacemakers and defibrillators.
 Implantable loop recorder (upto 3 yrs)
 Evaluation and Management
 Acute management:
- relief of symptoms
- assessment of AF-associated risk.
 Clinical Evaluation:
Detailed history to assess
- CHADs-2VaSC score/Stroke risk.
- bleeding risk
- time of onset (48 hrs)
- conditions predisposing to AF
- complications of AF
Testing
 EKG, Holter and event monitors
 Labs: CBC, BMP, TSH, +/- LFTs
 Echo: valvular, ventricular, atrial and congenital heart
diseases, LA dimensions.
 Stress test: reasonable if signs/risk factors for CAD
 Management
Goals
 Reduce symptoms

- rate vs rhythm control

- cardioversion
 Preventing severe complications

- anticoagulation
- control of ventricular rate
- adequate therapy of concomitant cardiac diseases
Management Cascade
 Anticoagulation
 AF increases the risk of stroke by five-fold
 Stroke in atrial fibrillation more disabling.
 Anticoagulation reduces stroke risk by two-
thirds
 Anticoagulation only treatment shown to
reduce mortality in AF
 Antiplatelet therapy reduces stroke risk by
one-fifth
 CHADS2 Score
 Evolved from the AF investigators and SPAF investigators
criteria.
 Initial rapid and easy to use means of assessing stroke
risk.
 CHADS2 score of 0, an adjusted rate of 1.9 per 100 pt yrs
 Stroke rate increased by a factor of 1.5 for each 1-point
 Recommendations
low risk (score 0): No anticoagulation
moderate risk (score 1) Aspirin or oral anticoagulation
high risk (score >/= 2) Oral anticoagulation

- Gage et al, JAMA. 2001;285:2864 2870

 CHADS2 Score limitations
 Too many patients classified as moderate risk
 Even pt at mod risk (CHADs 2 =1) benefit from
anticoagulation over aspirin
 Did not include many stroke risk factors
CHA2DS2-VASc Score

Lip et al, Chest 2010;137:263–272

“And there’s an app for that too”
Recommendations
 CHA2DS2-VASc score of 0, reasonable to omit
antithrombotic therapy.
 CHA2DS2-VASc score of 1, no antithrombotic
therapy or treatment with an oral anticoagulant or
aspirin may be considered.
 CHA2DS2-VASc score of 2 or greater, oral
anticoagulants are recommended
 CHA2DS2-VASc score of 2 or greater and who
have end-stage CKD (CrCl <15 mL/min) or are on
hemodialysis, it is reasonable to prescribe warfarin
(INR 2.0 to 3.0) for oral anticoagulation.
Hart et al, Ann Intern Med. 2007;146:857-867
Adjusted dose warfarin vs placebo/control

64%

- Hart et al, Ann Intern Med. 2007;146:857-867

 Hart et al
Stroke reduction
 Warfarin: 64% (95% CI, 49% to 74%)
 absolute risk reduction: 2.7% per year

 Aspirin: Nonsignificant 19% (CI, -1% to 35%)

 absolute risk reduction: 0.8% per year

 Warfarin vs antiplatelet therapy: 37% (CI, 23% to 48%)

Major Bleeding
 warfarin vs aspirin: risk for intracranial hemorrhage doubled
 absolute risk increase small (0.2% per year)

Mortality
 warfarin versus control: all-cause mortality substantially reduced (26%
[CI, 3% to 43%])
NoACs vs Warfarin

Limited reversal agents

Dabigatran
 Direct Thrombin Inhibitor
 Alternative to warfarin for CHADS2VaSc of 2 or
greater in those with nonvalvular afib
 RE-LY Trial: 150 mg dose superior to warfarin in
preventing ischemic stoke with no difference in
bleeding
 Praxbind ® (idarucizumab) is a specific reversal
agent for Pradaxa
RELY
Rivaroxaban
 Oral factor Xa inhibitor
 Rocket AF: noninferior to warfarin for
stroke prevention
 no significant difference in risk of major
bleeding
 intracranial and fatal bleeding occurred
less frequently
 Antidote: FDA approves AndexXa
Rocket AF
Apixaban
 Oral factor Xa inhibitor
 Aristotle : superior to warfarin in preventing stroke
 caused less bleeding
 resulted in lower mortality
 Antidote: FDA approves AndexXa
 Dose Adjustment: Cr >1.5, Age > 80, Wt < 60 kgs
Aristotle
Edoxaban
Edoxaban: ENGAGE AF study
Oral factor Xa inhibitor
edoxaban 30 mg and 60 mg vs Warfarin
noninferior to warfarin with respect to the prevention
of stroke or systemic embolism
significantly lower rates of bleeding and death from
cardiovascular causes
 Rate vs Rhythm control trials

• Rhythm-control strategy offers no survival advantage over rate-control.

• Lower risk of adverse drug effects, with the rate-control strategy.
• Anticoagulation should be continued in this group of high-risk patients.
 Outcomes
 Mortality and hospitalization:
- No benefit of rhythm control
- Post-hoc analysis: maintenance of sinus rhythm

improves survival
 Quality of Life:
- No differences in quality if life .
- Post-hoc analyses: maintenance of sinus rhythm

may improve quality of life.

 Ideal patient for rate control: Elderly patient with

asymptomatic atrial fibrillation.
 Sinus Rhythm associated with decreased risk of death (HR 0.53).
 Warfarin use associated with decreased risk of death (HR 0.50)
 AADs associated with increased mortality only after adjustment for
the presence of SR(HR1.49).
 AADs are not associated with improved survival, which suggests that
any beneficial antiarrhythmic effects of AADs are offset by their
adverse effects.
 If an effective method for maintaining SR with fewer adverse effects
were available, it might be beneficial.
RACE II Trial
• 614 pts with permanent AF
• Lenient rate control: resting heart rate <110 bpm in AF
• Strict rate control: resting heart rate of <80 bpm and an adequate
increase in heart rate upon moderate exertion
• Lenient rate control is as effective as strict rate control and is easier
to achieve
• Symptoms, adverse events, and quality of life similar in both groups.
• Patients assigned to lenient rate control had fewer hospital visits.
Optimal rate control
Principles of antiarrhythmic drug(AAD) therapy
 Treatment is to reduce AF-related symptoms.
 Efficacy to maintain sinus rhythm is modest.
 If one AAD ‘fails’, a clinically acceptable response may be
achieved with another agent.
 Proarrhythmia or extra-cardiac side effects are frequent.
 Safety rather than efficacy considerations should guide the
choice of AAD.
 Young patients should be considered for rhythm control
 Make sure patient has had adequate anticoagulation prior to
initiation.
New algorithm for sinus rhythm maintenance in AF
Flecainide
 Drug of choice in pts with structurally normal hearts
 Start with 50 mg BID and then increase to 100 mg BID
 Start AV nodal blocking agent concomitantly
 Treadmill stress test 1 week after initiation
 Avoid if Cr Cl < 35
 Adverse effects:
- proarrhythmias
- conduction abnormalities
- acute rise in pacing threshold
- heart failure exacerbation
Propafenone
 similar to Flecainide
 only difference: liver metabolism, so
safe to use in renal failure patients
 150 mg TID, upto 300 mg TID
Dofetilide
 Pure Class III agent
 Dose 125 – 500 mg BID based on Cr Cl
 cannot use with Verapamil or HCTZ
 Proarrhythmia risk 3.3% highest in first 72 hrs
 Initiate in hospital
 can be used in CAD and CHF patients
Sotalol
 Class III + non specific beta blocker
 provides good rate control if Afib recurs
 renal excretion- dose adjustment in CRI
 80-160 mg BID
 preferred in pts with ICD
 preferred in pts with CAD
 Do not use in patients with CHF and EF<25%
 Proarrhythmia risk 2-3%
 initiate in hospital
 Dronedarone
 Amiodarone without the iodine moiety
 Class III agent, multichannel blocker + antiadrenergic
activity.
 ATHENA: Reduction in hospitalization compared to
placebo. reduction in cardiovascular deaths
 ANDROMEDA: stopped prematurely increased
mortality in pts with advanced heart failure.
 PALLAS: increased rates of heart failure, stroke, and
death from cardiovascular causes in permanent afib
pts who were at risk for major vascular events
 Dosage: 400 mg BID
Amiodarone
 Most effective of the AADs but also most toxic
 Multi channel blocker
 Loading: 400 mg PO BID/TID
 Maintenance: 200 mg daily
 EKG 1 week after initiation
 Adverse effects: Bradycardia, liver toxicity, QT prolongation
(<0.5%), Hypothyroidism(20%), Hyperthyroidism (3%), Lung
toxicity, Skin pigmentation
 Drug interaction: reduces hepatic metabolism of digoxin and
warfarin.
 Monitoring: LFTs, TFTs, CXR, PFTs( yearly)
Guidelines

Indicated in patients with

Symptomatic paroxysmal AF refractory or intolerant
to at least 1 antiarrhythmic medication when a
rhythm-control strategy is desired (1A)
Symptomatic persistent AF refractory or intolerant to
at least 1 antiarrhythmic medication. (2A)
Recurrent symptomatic paroxysmal AF, catheter
ablation is a reasonable initial rhythm-control
strategy. (2A)
 Catheter ablation of AF
Radiofrequency Cryoablation
• Primary endpoint ( Death + CVA + Bleeding + Cardiac arrest)
• Ablation therapy not superior to drugs for CV outcomes at 5 years
• Significant reductions in death and CV hospitalizations with ablation
• On treatment analysis ablation demonstrated superior efficacy
• As this was a single blinded trial there was a high crossover rate.
• Time to first AF recurrence was greater
Restoration of sinus rhythm by catheter ablation in pts with CHF led to significant
improvements in
-LVEF (21%)
-Symptoms
-Exercise capacity
-Quality of life.
Catheter ablation as compared to amiodarone in pts with
CHF
-More successful in maintaining sinus rhythm
-Reduction in hospitalizations
-Reduction in mortality.
AV node ablation
 AV node ablation
Guidelines
AV nodal ablation with permanent ventricular
pacing is reasonable to control heart rate
when pharmacological therapy is inadequate
and rhythm control is not achievable. (IIA)
 AV node ablation
 provides highly effective control of ventricular rate
 patients in whom pharmacological rate control has
failed and rhythm control with drugs and/or LA ablation
has failed.
 improves quality of life
 reduces mortality
 patients with reduced LV function may require
biventricular pacing after atrioventricular node ablation.
 Left atrial appendage occlusion
 Watchman device only FDA
approved percutaneous LAA closure
device
 semi-spherical nitinol frame with a
polyethylene terephthalate
membrane coating
 deployed transseptally using a
dedicated 14 Fr sheath usually under
transesophageal echocardiography
and fluoroscopic guidance.
 707 pts with NV Afib randomized to Watchman vs
continued warfarin.
 Primary efficacy endpoint stroke, systemic embolism
and CV death 3.0% vs 4.3% WATCHMAN vs Warfarin
(noninferior)
 Primary safety events 5.5% vs 3.6% (more safety events
in the Watchman arm)
Recommendations
FDA approved for patients
 at increased risk of stroke and systemic
embolism based upon CHADS2 or
CHA2DS2-VASc scores
deemed by their physicians to be suitable
for warfarin therapy
have an appropriate rationale to seek a
nonpharmacological alternative to warfarin
Conclusions
 Epidemic of atrial fibrillation.
 Assess stroke risk and anticoagulate
appropriate patients.
 Rate vs rhythm control strategy.
 Ablation is effective and safe in selected
patients.
 AV node ablation and pacemaker.
 NOACs are effective and safe.
 Consider Watchman in patients not
suitable for long term anticoagulation.
Thank you