A Fib begets A fib An Ov - PowerPoint Presentation

Slide1

A Fib begets A fibAn Overview of AF and Treatment Strategies

Jad Skaf, MD11/12/15Slide2

Southern Regional AHEC adheres to ACCME Essential Areas and Policies regarding industry support of continuing medical education. All those in a position to control content have disclosed and there are no unresolved conflicts prior to this program.

The following

presenters and panelists (and their family members) have no relevant financial disclosures to make:

Jad Georges Skaf, MD

There will not be discussion of any off-label, experimental, or investigational use of drugs or devices in this presentation

This program is not being supported by any commercial funding.Slide3

BackgroundAtrial fibrillation is

the most prevalent cardiac arrhythmiaIt affects 1% to 2% of the general population with an important increase in incidence with age (10% after age 75)

AF has multiple adverse clinical implicationsThe loss of atrial systole and the irregular, fast heart rate contribute to symptoms such as palpitations and reduced

exercise tolerance and also predispose to the development of intracardiac thrombus and systemic thromboembolismSlide4

BackgroundAF can also cause tachycardia-mediated cardiomyopathy or worsening of preexisting heart

failureMoreover, AF is known to increase the mortality risk 1.5- to 2-fold and the risk for stroke 5-foldSlide5

CostSlide6

CLASSIFICATIONSlide7

SymptomsSlide8

~60% of patients with AF are asymptomatic initially.Slide9

MechanismsSlide10

ANTICOAGULATION

Class I

LOE C

In patients with AF, antithrombotic therapy should be individualized based on shared decision making after discussion of the absolute and relative risks of stroke and bleeding and the patient’s values and preferences

Class I

LOE B

In patients with

nonvalvular

AF, the CHA2DS2-VASc score is recommended for assessment of stroke riskSlide11

CHA2DS2-VAscSlide12

WARFARIN - ASA

Class

IIa

LOE B

For patients with

nonvalvular

AF with a

CHA2DS2-VASc score of 2

or greater and who have end-stage chronic kidney disease (CKD) (

creatinine

clearance < 15

mL

/min

) or are on

hemodialysis

, it is reasonable to prescribe

warfarin

(INR 2.0 to 3.0) for oral anticoagulation

Class I

LOE B

For patients with AF who have

mechanical heart valves

,

warfarin

is recommended, and the target international normalized ratio (INR) intensity (2.0 to 3.0 or 2.5 to 3.5) should be based on the type and location of the prosthesis

Class

IIb

LOE C

For patients with

nonvalvular

AF and a

CHA2DS2-VASc score of 1

, no antithrombotic therapy or treatment with an oral anticoagulant or aspirin may be considered. Slide13

MANAGEMENTRATE vs. RHYTHM

The decision to adopt a rhythm or rate control strategy is often dictated by the

presence of symptoms associated with atrial fibrillation and/or 

presence of diminutions in left ventricular systolic function thought secondary to the arrhythmia.Slide14

MANAGEMENTRATE vs. RHYTHM

What do we know?Slide15

Framingham study, 10 year follow-up

AF is BAD

Benjamin EJ, Wolf PA,

D'Agostino

RB, et al. Circulation 1998; 98:946.

5209 patientsSlide16

MANAGEMENTRATE vs. RHYTHM

Rate Control

Which Patients?Slide17

AFFIRM Trial

4060 patients

Age = 69.7

±

9.0 yrs

39% female

> 2 days of AF in 69%

CHF class

>

II in 9%

AFFIRM

Baseline Characteristics

Wyse DG, N

Engl

J Med. 2002;347(23):1825Slide18

AFFIRM Trial

Wyse DG, N

Engl J Med. 2002;347(23):1825Slide19

AFFIRM Trial

Wyse DG, N

Engl J Med. 2002;347(23):1825Slide20

AFFIRM Trial

Wyse DG, N

Engl J Med. 2002;347(23):1825Slide21

RACE Trial

Van

Gelder, I. et al. N Engl J Med 2002;347:1834-1840

Rate Control versus Electrical

Cardioversion

for Persistent Atrial Fibrillation (RACE) Trial

(n=522)Slide22

Are we done?

Is rate control the answer?Slide23

LIMITATIONS of Trials: AGE Guideline Statement

ACC/AHA/ESC Guidelines 2014

LIMITATIONS 1

-

The mean ages in AFFIRM and RACE were

70 and 68 years

, respectively.

-

The RACE and AFFIRM trials

did not address AF in younger, symptomatic patients with little underlying heart disease

, in whom restoration of sinus rhythm by

cardioversion

antiarrhythmic

drugs or non-pharmacological interventions still must be considered a useful therapeutic approach.

One may conclude from these studies that rate control is a reasonable strategy in elderly patients with minimal symptoms related to AF. Slide24

Trials of Rate vs Rhythm Control

RATE

vs

RHYTHMSlide25

LIMITATIONS 2

Approximately

one-half

of patients in AFFIRM who had a detailed history had symptomatic episodes of AF that occurred less often than once per month.

Such patients would be expected to derive little symptomatic benefit from rhythm control, and the results may not directly apply to patients with frequent episodes of symptomatic AF

LIMITATIONS of Trials:

SYMPTOMS

Slide26

LIMITATIONS 3

Both trials allowed for cessation of anticoagulant therapy four weeks after documentation of SR, leading to a higher rate of stroke.

It has been postulated that continued anticoagulation might have led to a lower mortality in the rhythm control group

LIMITATIONS of Trials:

ANTICOAGULATION

Slide27

LIMITATIONS 4

The use of

antiarrhythmic

drugs in AFFIRM was associated with a significant increase in mortality (HR 1.49), which was due to non-cardiovascular causes, while the presence of SR was associated with a significant reduction in mortality (HR 0.53).

A similar benefit from being in sinus rhythm (relative risk 0.44) was noted in the

DIAMOND trial

that compared 

dofetilide

 to placebo in patients with reduced left ventricular systolic function

LIMITATIONS of Trials:

DRUGS

Slide28

LIMITATIONS

One interpretation of these data is that maintenance of SR might be beneficial if there were a safer and more effective approach than current

antiarrhythmic

drugs:

The AFFIRM and RACE data were largely gathered

before catheter ablation was common

. The potential impact of this procedure (versus chronic

antiarrhythmic

therapy) remains incompletely explored

LIMITATIONS of Trials:

DRUGS

Slide29

CABANA

The Catheter Ablation versus Antiarrhythmic Drug Therapy for Atrial Fibrillation trial is being done to compare drug therapy

with catheter ablation in patients with atrial fibrillation. This study will help to decide which

treatment approach is best and if under certain circumstances, one therapy is preferred over the other treatment. 

NEW TRIALSSlide30

CABANA

Estimated Enrollment: 2200 patientsStudy Start Date: August 2009Estimated Study Completion Date: June 2018Estimated Primary Completion Date: December 2017

(Final data collection date for primary outcome measure)https://clinicaltrials.gov/ct2/show/NCT00911508

NEW TRIALSSlide31

Anti-

ArrhythmicsSlide32

ABLATION

100

80

20

40

% Patients Free of Symptomatic AF

2

4

6

8

10

12

Months

60

Amiodarone*

Sotalol

**

Propafenone

**

Hx of Two Failed Drugs***

*

Roy et al NEJM, 2000

**

Antman

et.al., JACC 1990

***

Crijns

et. al., AJC 1991

Ablation…Slide33

ABLATION GuidelinesParoxysmal AF

Class I

LOE A

AF catheter ablation is useful for

symptomatic paroxysmal

AF refractory or intolerant

to at least 1 class I or III

antiarrhythmic

medication when a rhythm-control strategy is desired

Class

IIa

LOE B

In patients with recurrent s

ymptomatic paroxysmal AF, catheter ablation is a reasonable initial rhythm-control strategy

before therapeutic trials of

antiarrhythmic

drug therapy, after weighing the risks and outcomes of drug and ablation therapy

PAROXYSMAL REFRACTORY

PAROXYSMAL INITIAL

ACC/AHA/ESC Guidelines 2014Slide34

ABLATION GuidelinesPersistent AF

Class

IIb

LOE B

AF catheter ablation may be considered for symptomatic

long-standing (>12 months)

persistent AF refractory or intolerant

to at least 1 class I or III

antiarrhythmic

medication when a rhythm-control strategy is desired

Class

IIb

LOE C

AF catheter ablation may be considered

before initiation of

antiarrhythmic

drug therapy

with a class I or III

antiarrhythmic

medication for symptomatic persistent AF when a rhythm-control strategy is desired.

PERSISTENT REFRACTORY

PERSISTENT INITIAL

ACC/AHA/ESC Guidelines 2014Slide35

Does not work in AFSlide36

285 cows

18 months

7 cows2.5 %

Zentralbl Veterinaries A.

1993 Apr;40(3):233-9.

Department of Veterinary Pathology, Tokyo University of Agriculture and Technology, Japan.

PAF:

postpartum (2), after ceasing lactation (2)

CAF:

postpartum (3)

Sympathetic

Vagal

Keep The Milk Flow and AF will GrowSlide37
Slide38

HypothesisAtrial fibrillation itself causes progressive electrophysiological and/or

structural changes to the atria, which promote the initiation or perpetuation of atrial fibrillationElectrical RemodelingMechanical RemodelingSlide39

Diagram showing the localization of the 27 chronically implanted electrodes on the atria.

Wijffels M C et al. Circulation. 1995;92:1954-1968

Copyright © American Heart Association, Inc. All rights reserved.Slide40

Prolongation of the duration of episodes of electrically induced atrial fibrillation (AF) after maintaining AF for respectively 24 hours and 2 weeks.

Wijffels

M C et al. Circulation. 1995;92:1954-1968

Copyright © American Heart Association, Inc. All rights reserved.Slide41

Prolongation of the duration of episodes of electrically induced atrial fibrillation (AF) after maintaining AF for respectively 24 hours and 2 weeks.

Wijffels

M C et al. Circulation. 1995;92:1954-1968

Copyright © American Heart Association, Inc. All rights reserved.Slide42

AF

Begets

AF

AF causes changes in atrial

electrophysiology

that

promote

AF maintenance

Wijffels

Circulation 1995; 92: 1954-68Slide43

Clinical implicationsShortening of the atrial refractory

might explain the diminished success rate of chemical and electrical cardioversion in patients with long-lasting atrial fibrillationStudy implicates that the best prevention of atrial fibrillation is to terminate the arrhythmia as soon

as possible, thus interrupting the electrophysiological sequelae which will lead to chronic atrial fibrillationSlide44

MechanismsInterplay of Trigger and

SubstrateInduction of AF requires an initiating trigger (usually the pulmonary veins ~80% of times)Perpetuation occurs

because triggering activity is sustained or because of the presence of a susceptible atrial substratePremature atrial ectopy

has been shown to be the most frequent trigger for AFSlide45

PrecipitantsObservations in patients with dual chamber pacemakers

revealed that 48% of AF episodes were triggered by premature atrial beats, 33% were preceded by bradycardia, and 17% were sudden in onsetAlso, continuous cardiac monitoring in postoperative

patients demonstrated that supraventricular premature beats induced AF in 72% to 100% of casesSlide46

AF SustenanceSlide47
Slide48
Slide49
Slide50

TRIGGERS

Development of AF requires trigger + susceptible substrate

(may also interrupt

innervation from autonomic ganglia)

Goal of ablation:

Eliminate triggers

and/or

alter substrate

PV Isolation

APDSlide51

ABLATION

RadioFrequency Ablation – RFA

Vs.

CryoablationSlide52

RFA

RadioFrequency Ablation – RFA

Vs.

CryoablationSlide53

TRIGGERS

PV Origin for Triggers for

Initiating

Atrial Fibrillation ~ 80 –90% of Triggers

Focal Ablation

PV Isolation

myocardial

sleeves

Preferential inputs or

“breakthroughs”

enable non-circumferential

disconnectionSlide54

TRIGGERS

MRA of LA

Multiple Foci from Multiple Veins

Success ~ 70-80% paroxysmal

~ 50-70% persistentSlide55

PVISlide56

CRYOSlide57

CRYOSlide58

CRYO

Contrast injected to verify pulmonary vein

ostium

occlusion and full contactSlide59

CRYOSlide60

Complications of RF ablation:Systemic embolism/CVA (1-2%)

PV stenosis < 1-3%Pericardial effusion/cardiac tamponade (1%) Proarrhythmia (intra-atrial reentry tachycardia/left atrial flutter)

Atrial-esophageal fistula (very rare)Need for multiple procedures (10 to 30%) to achieve clinical efficacySlide61

Complications of Cryo-ablation

Systemic embolism/CVA (1-2%)PV stenosis < 1-3%

Pericardial effusion/cardiac tamponade (1%) PN palsy 1-3%Atrial-esophageal fistula (very rare)Need for multiple procedures (10 to > 30%) to achieve clinical efficacySlide62

end

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