Medicines and management

1. ATRIAL FIBRILLATION
-Dr. Mahesh Pujari
Senior Resident

2. INTRODUCTION
• It is the most common sustained cardiac arrythmia
• Occurrance increases with increasing age
• The Framingham study estimated that lifetime risk for
development of AF after the age of 40 years is

3. TYPES OF ATRIAL FIBRILLATION
• TEMPORAL PATTERN:
• Paroxysmal atrial fibrillation
• Persistant atrial fibrillation
• Permanent atrial fibrillation

4. TYPES OF ATRIAL FIBRILLATION
• BASED ON ETIOLOGY:
• Secondary to structural heart disease
• Idipathic (lone AF) – accounts to 15%

5. PATHOPHYSIOLOGY
• In atrial fibrillation there is interaction
between:
 trigger – initiator/ driver
 abnormal atrial tissue substrate – to
maintain the atrial fibrillation

6. FOCAL INITIATERS OF ATRIAL FIBRILLATION:
• Ectopics – which are rapidly firing
• Present in the atrial sleeve around the
pulmonary veins(more common) or superior
venacava

7. ABNORMAL ATRIAL SUBSTRATES
• Important in maintaining persistent and permanent atrial
fibrillation
• Abnormal atrial substrates are formed because of atrial
ELECTRICAL and structural REMODELLING
• Because of atrial fibrillation per se or because of the
structural heart disease.

8. • Because of the fibrillatory activity in the atria
• No effective contraction of the atria(quivering of
the atria)
• No atrial kick
• Stasis of blood in the atria and defective diastolic
filling of the ventricle

9. CAUSES OR RISK FACTORS:
• Hypertension
• Congestive heart failure
• Valvular heart disease
• Ischemic heart disease
• Hypertrophic and dilayted cardiomyopathy
• Severe pulmonary hypertension
• Obesity
• OSA

11. CLINICAL FEATURES:
• Vary widely
• Approx. 25% are asymptomatic
• Palpitations , fatigue , dyspnoea , effort
intolerance and light headedness
• Polyuria
• Difficult to assess the frequency and duration
of the AF on the basis of symptoms

12. TEMPORARY OR REVERSIBLE CAUSES
• Excessive alcohol intake
• Cardiac or thoracic surgeries
• Myocardial infarction
• Pericarditis
• Myocarditis
• Pulmonary embolism
• Hyperthyroidism

13. DIAGNOSTIC EVALUATION:
• Electrocardiograph
• Holter monitoring
• Exercise stress test for IHD
• Echocardiogram for LA size ,thrombthrombosis ,
LV function
• LFT and RFT ,TFT
• Chest radiograph (if chest diseases is suspected)
• Livid profile

14. ECG:
• Varying RR interval
• Narrow QRS complex
• Absent p waves , presence of fibrillatory
waves

15. ATRIAL FLUTTER
• MAT:

16. HYPERTENSION and AF
• Is one of the most important modifiable risk factor in AF
• In the Framingham study , hypertension increases the risk
of AF by 40% in males and 30% in females
• Hypertension induces early and progressive changes in LA
anatomy and function which promote AF
• Hypertension induces hypertrophy , fibrosis and
inflammation of the left atrium
• Obesity in hypertensive patients enhances fibrosis and
structural changes

18. • RAAS SYSTEM – enhances fibrosis and
electrophysiological alteration in the atria
• Hence RAAS inhibitors seem to be benificial in
prevention of AF , yet to be concluded
• Hypertension is also a independent predictor of
increased thrombotic and hemorrhagic
complications
• The benificial effect of strict maintaining of blood
pressures to prevent AF is also yet to be concluded

19. CHF and AF
• These conditions frequently co-exist
• Each condition predisposes to the other
• The incedence of AF in CHF is 3%-15%
• The prevalence of AF was higher in patients
with HFpEF than in left ventricular dysfunction
• They share the most of the risk factors

20. CHF and AF
• Elevations in the left atrial and pulmonary pressures
increase the chance of AF because of myocyte stretch
• Atrial remodelling
• Neuroheumoral activation- increase in RAAS and
adrenergic system- increase in fibrosis
• Inceased risk of thromboembolism is seen in chf with AF
• The use of RAAS inhibitor and beta blocker in CHF has
shown to be benificial in preventing AF

21. TREATMENT APPROACH
• TO REDUCE STROKE RISK
• PREVENT TACHYCHARDIA INDUCED HEART
FAILURE(CARDIOMYOPATHY)
• TO REDUCE OR RELIEVE SYMPTOMS

22. TREATMENT OF UNDERLYING
CONDITION
• Earlier recognition and management of underlying conditions may
prevent the development of AF. More than 70% patients with AF have
structural heart disease like congestive heart failure, ischemic heart
disease, myocarditis, pericarditis, cardiomyopathy, and hypertensive
heart disease.
• Extrinsic determinants like hyperthyroidism, diabetes mellitus, sleep
apnea, and obesity are important and may be overlooked.
• Autonomic signaling may provide new drug therapy targets.Vagal
enhancement may be a key mediator of the AF-promoting effects of
intense endurance exercise; lifestyle modification may help in
managing the arrhythmia.
• AF shares risk factors with other cardiovascular diseases like
atherosclerosis, and epidemiological studies suggest that more than
half of AF cases can be explained on the basis of risk factors like
hypertension, diabetes mellitus, obesity, and cigarette smoking. Thus,
effective primary prevention by RISK factor modification may be real.

24. RHYTHM CONTROL
1. CARDIOVERSION-SYNCHRONISED DC CARDIOVERSION
• PHARMACOLOGICAL AGENTS(CLASS 1C AND 3
ANTIARRYTHMICS) Dofetilide
• Flecainide
• Propafenone
• Amiodarone
• Sotalol
SURGERY(MAZE PROCEDURE,ABLATION)
DEVICE IMPLANTATION-PACEMAKER

25. RATE CONTROL
PREFERRED IN
1. AGE>65 YR
2. LESS SYMPTOMATIC
3. HYPERTENSION
4. RECURRENT ATRIAL FIBRILLATION
5. PREVIOUS ANTIARRYTHMIC DRUG FAILURE
6. UNLIKELY TO MAINTAIN SINUS
RHYTHM(ENLARGED LA)

26. MEDICATION FOR RATE CONTROL
• BETA BLOCKER-
METOPROLOL,ESMOLOL,BISOPROLOL
• NDH CALCIUM CHANNEL BLOCKER-
DILTIAZEM,VERAMAPIL
• DIGOXIN-PATIENTS WITH HYPOTENSION
• AMIODARONE-ALSO FOR RHYTHM CONTROL

28. ACUTE MANAGEMENT
• If AF < 7 days -
dofetilide,flecainide,ibutilide,propaferone or
amiodarone
If AF > 7 day – dofetilide or amiodarone
IV vernakalant has demonstrated superior
efficacy to amiodarone for acute conversion of
recent-onset AF
Oral vernakalant appears to be effective in
preventing AF recurrence post-cardioversion

29. ANTICOAGULATION
• Thrombotic material in atrial fibrillation (AF) usually develops in the left atrial
appendage as a result of decreased flow and stasis, possible endothelial dysfunction
and a hypercoagulable state as indicated by increased fibrinogen, D-dimer,
thromboglobulin and platelet factor 4 levels
• In the Framingham Heart Study, the percentage of strokes attributable to AF increases
steeply from 1.5 % in patients aged 50–59 years to 23.5 % in those aged 80–89 years.
• In patients with a history of hypertension but no prior diagnosis of clinical AF,
subclinical AF predisposes them to embolic events. Undiagnosed silent AF is a probable
cause of cryptogenic strokes, and subclinical episodes of AF are associated with silent
cerebral infarcts, particularly in patients with diabetes.
• The frequency of AF-related incident ischaemic strokes in patients aged ≥80 years have
increased threefold over the last 25 years, despite the introduction of anticoagulants,
and are projected to futher increase threefold by 2050.
• Among patients with AF who are at moderate-to-high risk of stroke and are receiving
anticoagulation, those with persistent AF have a higher risk of thromboembolic events
and worse survival rates compared with those with paroxysmal AF. The risk of stroke is
similar in patients with and without valvular disease.

30. ANTICOAGULATION
• Adjusted-dose warfarin and antiplatelet agents reduce the risk of stroke by
approximately 60 % and 20 %, respectively, in patients with AF2
• In general, oral anticoagulation is preferred in patients with CHA2DS2-VASc
score ≥2, and no anticoagulation in patients with a score of 0
• In patients with CHA2DS2-VASc score of 1, anticoagulation should be
individualised as the risk of stroke is low.
• However, patients aged >65 years, especially women, are at high risk of
ischaemic stroke,and in these individuals anticoagulation reduces the rate of
mortality.
• The risk of bleeding is assessed by schemes such as the HAS-BLED, ATRIA and
HEMORR2HAGES scoring systems.
• A HAS-BLED score ≥3 indicates ‘high risk’. New oral anticoagulants are now
recommended for nonvalvular AF as a potential alternative to warfarin.
• Nonsteroidal anti-inflammatory drugs increase the risk of both serious
bleeding and thromboembolism in anticoagulated patients with AF.
•

31. ASPIRIN
• The protective value of acetylsalicylic acid (aspirin) as
monotherapy has come under question, and there are
concerns that it may even increase risk of stroke in
elderly patients (aged >75 years).
• Warfarin is superior to aspirin in patients aged >75
years, offering a 52 % reduction in yearly risk of a
combined end-point of stroke, intracranial
haemorrhage and peripheral embolism
• Thus, the use of aspirin for stroke prevention in
patients with AF should be limited to those who refuse
any form of oral anticoagulation, or, perhaps, to those
with a CHA2DS2-VASc score of 1

32. ASPIRIN AND CLOPIDOGREL
• The combination of aspirin and clopidogrel offers
increased protection compared with aspirin alone, BUT
at an increased risk of major bleeding, and is preferred
when warfarin is contraindicated.
• However, aspirin and clopidogrel together offer less
protection than warfarin alone
• In patients who sustain an ischaemic stroke despite
international normalised ratio (INR) of 2.0–3.0, targeting
a higher INR should be considered (3.0–3.5) rather than
adding an antiplatelet agent, as major bleeding risk starts
at INR >3.5.

33. WARFARIN
• Warfarin is a racemic mixture of isomers that inhibits the synthesis of vitamin
K-dependent coagulation factors. The effective dose of warfarin varies
significantly among individuals, as a result of genetic variations in its receptor,
metabolism via the cytochrome P450 (CYP) system and interactions with other
drugs, vitamins and green vegetables.
• The risk of AF increases with INR >3.5–4.0. Recommended INR values for AF
are 2–3. Pharmacogenetic testing for guiding doses, by means of genotyping
for the variants CYP2C9 and VKORG1, which are associated with reduced
clearance and thus a decrease in warfarin requirement, is not clinically useful.
• Patients initiating warfarin may be at an increased risk of stroke during the
first 30 days of treatment, probably owing to rapid deactivation of proteins S
and C, two endogenous anticoagulants.
• In high-risk cases, warfarin should be started with concomitant low molecular
weight heparin administration for the initial 3–5 days of treatment. Increased
levels of coronary calcification have been recently reported in patients on
long-term therapy with vitamin K antagonists.

34. NON VITAMIN K ORAL
ANTICOAGULANTS

35. DABIGATRIN
• Dabigatran is preferred to warfarin for nonvalvular AF as recommended by the
European Society of Cardiology and the Canadian Cardiovascular Society.
• The European Medicines Agency (EMA) has approved both the 110 mg twice-daily
and 150 mg twice-daily doses for nonvalvular AF. Elective cardioversion may be
performed in patients taking dabigatran for at least 3 weeks.
• Dabigatran is excreted through the kidneys and no dosing recommendation is
given for clearance <15 ml/min. In elderly patients a reduced dose is reasonable
(75 mg twice daily), especially for those aged >80 years. It can be used safely
together with aspirin.
• A higher risk of major and gastrointestinal haemorrhage compared with warfarin
has been seen in African Americans and patients with chronic kidney disease, but
the risk of inrtracranial haemorrhage remains lower.3
• Main side-effects of dabigatran are dyspepsia and stomach pain (11 %), and
transaminase elevations 0.9–2.0 %, although with a frequency similar to that
caused by warfarin. There is no evidence of liver toxicity as observed with
ximelagatran.

36. APIXABAN
• Apixaban, an oral factor Xa inhibitor, is approved in Europe and Canada, and
by the FDA for nonvalvular AF, and may be the most cost-effective NOAC.
• Apixaban has demonstrated reduced risk of stroke or systemic embolism
without significantly increasing the risk of major bleeding or intracranial
haemorrhage in patients with nonvalvular AF for whom vitamin K antagonist
therapy was unsuitable (apixaban versus aspirin; AVERROES trial).
• In the Apixaban for the Prevention of Stroke in Subjects With Atrial Fibrillation
(ARISTOTLE) trial, apixaban was found superior to warfarin in preventing
embolic or haemorrhagic stroke, and resulted in less bleeding and lower
mortality rates (11 % reduction; p=0.047).
• Benefits of apixaban have been seen in both paroxysmal and
persistent/permanent AF. Rates of intracranial bleeding have been
demonstrated to be significantly lower in patients treated with apixaban than
with warfarin, regardless of renal function.Benefits of apixaban are
irrespective of concomitant aspirin use or of patients’ age.

37. • A substudy of the ARISTOTLE trial has also shown that
cardioversion of AF can be safely performed in apixaban-
treated patients. The drug is metabolised in the liver via
P450-dependent and -independent mechanisms and 25
% is excreted renally. It is not recommended for use in
patients with severe hepatic impairment. Apixaban is
also not recommended in patients receiving concomitant
treatment with strong inhibitors of both CYP3A4 and P-
glycoprotein, such as azole antimycotics and HIV
protease inhibitors, and should be used with caution in
patients taking rifampicin, phenytoin, carbamazepine and
phenobarbital.

38. RIVAROXABAN
• Rivaroxaban is an oral factor Xa inhibitor that has been approved
by the FDA and EMA for nonvalvular AF. In the ROCKET-AF trial
(Efficacy and Safety Study of Rivaroxaban With Warfarin for the
Prevention of Stroke and Non-Central Nervous System Systemic
Embolism in Patients With Non-Valvular Atrial Fibrillation),
rivaroxaban was not found to be inferior to warfarin (INR 2–3) in
patients with nonvalvular AF for the prevention of stroke or
systemic embolism, and offered a lower rate of intracranial
bleeding, but a higher rate of gastrointestinal bleeding. In a
substudy of this trial, rivaroxaban demonstrated equal safety
and efficacy with warfarin in patients aged >75 years.
• The half-life of rivaroxaban is 7–11 hours, but factor Xa is
inhibited for up to 24 hours, allowing once-daily dosage.

39. EDOXABAN
• Edoxaban has been demonstrated as
noninferior to warfarin with respect to
prevention of stroke or systemic embolism
and shown to be associated with significantly
lower rates of bleeding and death from
cardiovascular causes (ENGAGE AF-TIMI 48
trial) and is approved by FDA

40. BETRIXABAN
• HAVE BEEN FOUND TO BE EQYIVALENT TO
WARFARIN

41. SURGICAL PROCEDURES
• Pulmonary Vein Ablation: Pulmonary vein
ablation (also called pulmonary vein antrum
isolation or PVAI) may be an option for people
who cannot tolerate medications or when
medications are not effective in treating atrial
fibrillations.
• Because atrial fibrillation usually begins in the
pulmonary veins or at their attachment to the left
atrium, energy is applied around the connections
of the pulmonary veins to the left atrium during
the pulmonary vein ablation procedure.

42. ABLATION OF AV NODE
During this type of ablation, catheters are inserted through the
veins (usually in the groin) and guided to the heart.
• Radiofrequency energy is delivered through the catheter to
sever or injure the AV node. This prevents the electrical
signals of the atrium from reaching the ventricle.
• This result is permanent, and therefore, the patient needs a
permanent pacemaker to maintain an adequate heart rate.
Although this procedure can reduce atrial fibrillation
symptoms, it does not cure the condition.
• Because the patient will continue to have atrial fibrillation, an
anticoagulant medication is prescribed to reduce the risk of
stroke.

43. LEFT ATRIAL APPENDAGE CLOSURE
• The left atrial appendage (LAA) is a small, ear-
shaped sac in the muscle wall of the left atrium
(top left chamber of the heart).
• If you are at risk of developing clots in the left
atrium a procedure to seal off your LAA. This
can reduce your risk of stroke and eliminate the
need to take blood-thinning medication.There
are several options and devices available for
closure of the LAA, such as the WATCHMAN
device.

45. ABLATION

46. PACEMAKER INSERTION
• There are a number of applications for pacemaker
therapy in the management of Atrial Fibrillation (AF).
• The most frequent indication for pacing in AF is to
prevent bradycardia in patients with rapid ventricular
response and sinus node dysfunction.
• For elderly patients or patients with significant medical
comorbidities who have highly symptomatic, drug-
refractory AF, pacemaker implantation and
atrioventricular (AV) junction ablation can be an effective
alternative therapy.
• Pacing may also decrease symptoms during atrial
fibrillation by regularizing the ventricular rate

47. MAZE PROCEDURE
• During this procedure, a series of precise incisions or lesions are
made in the right and left atria to confine the electrical impulses to
defined pathways to reach the AV node.
• These incisions prevent the abnormal impulses from affecting the
atria and causing atrial fibrillation.
• The surgical Maze procedure can be performed traditionally with a
technique in which precise surgical scars are created in the atria. It
may also be performed using newer technologies designed to
create lines of conduction block with radiofrequency, microwave,
laser, ultrasound or cryothermy (freezing).
• With these techniques, lesions and ultimately scar tissue is created
to block the abnormal electrical impulses from being conducted
through the heart and to promote the normal conduction of
impulses through the proper pathway.

50. Thank You