AF

DR K C NARZARY
MD, DNB_CARDIOLOGY, FSCAI (USA)
LIFE MEMBER, CARDIOLOGICAL SOCIETY OF INDIA
SENIOR INTERVENTIONAL CARDIOLOGIST
GNRC MEDICAL, NORTH GUWAHATI
Epidemiology
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

Cost and Consequences

• 750,000 hospitalizations/year.
• 130,000 deaths/year.
• Cost: $6 billion/year.
• AFib causes 15%–20% of ischemic strokes
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)
Mechanisms of AF
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
Evaluation and
Management
 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
Anticoagulation
 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

• Initial rapid and easy to use means of assessing stroke risk.

• 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

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
 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.
Rhythm 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)
Catheter ablation for AF
 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.
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