Disclosures Major Research grant: R01 HL102090 (NIH / NHLBI) - - PDF document

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Asymptomatic Atrial Fibrillation: Detection and Management

18 December 2015 32nd Annual Advances in Heart Disease Palace Hotel, San Francisco Zian H. Tseng, M.D., M.A.S. Associate Professor of Medicine in Residence Murray Davis Endowed Professor Cardiac Electrophysiology Section University of California, San Francisco

Disclosures

◆ Major

◆ Research grant: R01 HL102090 (NIH / NHLBI) ◆ Research grant: R01 HL126555 (NIH / NHLBI) ◆ Research grant: DP14-1403 (CDC) ◆ Research grant: R24 A1067039 (NIH)

◆ Minor

◆ Honorarium: Biotronik

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■ Is it appropriate to screen for asx

AF?

■ What screening methods are

currently available for asx AF?

■ What populations might harbor

high rates of asx AF?

■ Should asx AF be treated with

OAC?

Outline

■ ~3M in U.S. ■ Sx: palpitations, dyspnea, fatigue ■ AF is a well-established RF for

thromboembolic events, especially CVA

■ Independently increases risk of

CVA 5x (Framingham)

Atrial Fibrillation

Go AS, et al. Circulation 2014;129:e28–292 Camm AJ et al. Europace 2010;12:1360–420 Wolf PA, et al. Stroke 1991;22:983–8

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■ ~1/3 of pts w/ AF are asx ■ Asx, subclinical AF is common

even in pts w/ documented sx AF

■ Only 20% of sx AF pts will have sx

temporally related AF

■ Therefore, prevalence of AF may be

much higher Asymptomatic Atrial Fibrillation

Hindricks G, et al. Circulation 2005;112:307–13 Quirino G et al. PACE 2009;32:91–8 Silberbauer J, et al. JICE 2009;26:31–40

■ Undiagnosed, asx AF:

◆ undetected indefinitely ◆ diagnosed incidentally ◆ eventually result in sx

■ Most concerning initial

presentation of asx AF is CVA

◆ first presentation of AF in 24%

(Framingham)

■ Asx AF detected in ~20% of pts

with acute CVA Asymptomatic Atrial Fibrillation

Rizos T, et al. Cerebrovasc Dis 2010;30:410–17 Seet RC, et al. Circulation 2011;124:477–86

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■ Paroxysmal = Permanent ■ OAC reduces the RR of CVA in AF

pts by 2/3

■ Does early OAC for asx AF confer

similar benefit? Atrial Fibrillation and CVA Risk

Wolf PA, et al. Stroke 1991;22:983–8 Camm AJ et al. Europace 2010;12:1360–420

■ Gold standard is 12-lead ECG ■ Systematic vs opportunistic ECG

screening (abnl pulse à ECG) of 14,000 1o care pts > 65 y equivalent and superior to routine practice

◆ AF detection per y: 1.6% vs 1%

(p=0.01)

Screening Methods for Asx AF

Camm, AJ, et al. Europace 2012;14:1385–413 Fitzmaurice DA, et al. BMJ 2007;335:383.

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■ 24-48 h Holter gold standard of

ambulatory ECG monitoring

◆ Many pts do not tolerate patches

for 48 h

◆ 48 h may be insufficient

Screening Methods for Asx AF

■ Zio Patch continuous 14 d

recording

◆ Superior to Holter for AF and

arrhythmia detection

■ BP monitors (Microlife BP A200

Plus, Omron M6)

■ Single-lead ECG (Omron

Heartscan)

■ iPhone apps (AliveCor)

Screening Methods for Asx AF

Barrett PM, et al. Am J Med 2014;127:95

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■ Implantable loop recorder (ILR)

◆ Reveal (MDT) ◆ Confirm (SJM)

■ Analyzes irregularity of R-R ■ Require minimum duration of AF ■ Ongoing studies of detection rates

• f asx AF in high-risk pts

Screening Methods for Asx AF

■ CIEDs (PPM, ICDs, and CRTs) ■ Sensitivity for AF detection ~98%

98% DC PPMs

■ Uncertain significance of device-

detected atrial high rate episodes (AHREs)

◆ Duration? ◆ Rate? ◆ Frequency?

Screening Methods for Occult AF

Rosero, et al. Prog CV Dis 2013;56:143–52

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High Risk Subpopulations for Asymptomatic AF

■ ¼ of all CVAs ■ Asx AF may be underlying cause of

many

■ Cryptogenic Stroke and Underlying

AF (CRYSTAL-AF)

■ Event Monitor Belt for Recording

Atrial Fibrillation after a Cerebral Ischemic Event (EMBRACE)

Cryptogenic Stroke

Gladstone DJ, et al. NEJM 2014;370:2467–77 Sanna T, et al. NEJM 2014;370:2478–86

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■ CRYSTAL-AF ILR for AF >30 s

◆ AF in 8.9% vs. 1.4% at 6 m and

12.4% vs. 2% at 12 m

■ EMBRACE electrode belt for AF

>30 s

◆ AF in 16.1% vs. 3.2% at 30 d

Cryptogenic Stroke

Gladstone DJ, et al. NEJM 2014;370:2467–77 Sanna T, et al. NEJM 2014;370:2478–86

■ Asx AF seems likely culprit for CVA, but: ■ 30 s of AF is arbitrary

◆ Does single 30 s AF have same stroke

risk as longer AF?

◆ Does it warrant OAC?

■ Neurogenic AF

◆ May be effect not cause of CVA

■ CRYSTAL-AF initiated monitoring 90 d,

EMBRACE 6 m from index CVA

■ No clear consensus on when, how long,

and method for monitoring

Cryptogenic Stroke

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Ongoing ILR Trials for Asx AF

Keach, et al. Heart 2015;101:1097-1102

■ AHREs: AF/AT A rate >175–190 bpm ■ ~1/2 CIEDs ■ Mode Selection Trial (2003)

◆ > 1 5 min AHRE >220 bpm ◆ 2.8 x risk CVA or death, 9x risk of

permanent AF

■ TRENDS trial (2009)

◆ AHRE > 5.5 h/d: 2.4x risk of

thromboembolism

■ HF pts with CRT (2012):

◆ AHRE > 3.8 h/d: 9x risk of

thromboembolism

CIEDs

Glotzer TV, et al. Circulation 2003;107:1614–19 Glotzer TV, et al. Circ A&E 2009;2:474–80.

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■ Clear association between CIED-

detected AHREs and CVA/death/ thromboembolism

■ Association ≠ Causation ■ Weak temporal association between

AHREs and CVA

■ AHREs may be a risk marker of pts

more prone to CVA

■ Variable AHRE definition ■ No clear evidence that OAC will reduce

CVA risk in this population

CIEDs

■ AF in 1.6% of 1o care pts > 65y w/

screening ECG (2007)

■ AF in 7.4% pts 75 y, CHADS 2 ≥2,

no prior AF w/ twice daily ECGs x 2 w (2013)

■ Prevalence of ~25% in > 80 y ■ Current guidelines: pulse palpation

in pts > 65 y, screening ECG if pulse abnormal

Elderly

Go AS, et al. Circulation 2014;129:e28–292 Engdahl J, et al. Circulation 2013;127:930–7

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■ Cohorts for Heart and Aging

Research in Genomic Epidemiology (CHARGE, 2013) C-statistic, 0.765 (95% CI 0.748 to 0.781)

■ Brunner et al (2014) AUC 0.812

(95% CI 0.805 to 0.820)

■ Screening Study for Undiagnosed

Atrial Fibrillation (STUDY-AF, 2015)

Risk Models

Alonso A, et al. JAHA 2013;2:e000102 Brunner KJ, et al. Mayo CP 2014;89:1498–505 Turakhia MP. Clin Cardiol 2015

■ B-type natriuretic peptide ■ Cardiac troponin after CVA/TIA ■ P-wave duration on standard ECG ■ Atrial ectopy after ETT in pts w/

LVH

■ LAE and LA dysfunction on echo

Novel Markers for Asx/New-Onset AF

Shibazaki K, et al. Am J Cardiol 2012;109:1303–7 Magnani JW, et al. Am J Cardiol 2011;107:917–21 Wong JM et al. Am J Cardiol 2014;113:1679–84

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■ Will asx AF show same benefit

from OAC as traditionally detected AF (paroxysmal, persistent or permanent)? OAC and Asx AF

Keach, et al. Heart 2015;101:1097-1102

Consider OAC based

• n CHADS2-VASC

■ Will asx AF show same benefit

from OAC as traditionally detected AF (paroxysmal, persistent or permanent)? OAC and Asx AF

Keach, et al. Heart 2015;101:1097-1102

Consider OAC? Index CVA

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■ Current guidelines recommend Rx

based on clinical RFs (CHADS2- VASC), not by type or duration of AF

◆ Consider OAC based on RFs for asx

permanent AF (on PPM or index CVA)

◆ No guidelines for asx paroxysmal

AF

◆ Conflicting data on CVA risk and

duration of AF

OAC and Asx AF Ongoing Trials of OAC for Asx AF

Keach, et al. Heart 2015;101:1097-1102

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Ongoing Trials of OAC management for low burden AF

Keach, et al. Heart 2015;101:1097-1102

■ Anticoagulation Guided by Remote

Rhythm Monitoring in ICDs and CRT-Ds (IMPACT, 2009)

■ Prematurely terminated due to no

difference between earlier OAC for AHREs on remote monitoring vs control (3 d vs 54 d)

■ AF ~ RFs ~ CVA

◆ Those at highest risk for AF related

CVA are also at high risk for non- AF related CVA

OAC and Asx AF

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■ HRT was widely prescribed based on

convincing epidemiologic evidence

◆ lower rates of MI and CVA in women ◆ HRT decreased MI and CVA by half in

postmenopausal women

■ HERS trial showed no benefit of HRT in

women with established heart disease

■ WEST showed no benefit of estrogen for

2o prevention of CVA in women

■ WHI showed 29% increase in MI and

41% increase in CVA

Lessons Learned from HRT for Postmenopausal Women

■ Will asx AF show same benefit

from OAC as traditionally detected AF (paroxysmal, persistent or permanent)? OAC and Asx AF

Keach, et al. Heart 2015;101:1097-1102

More risk w/ OAC Index CVA

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■ Should we screen for asx AF?

◆ Overall benefit, cost-effectiveness yet

to be demonstrated: STROKESTOP

■ How should we screen for asx AF?

◆ Opportunistic ECGs, event monitors,

single-lead ECGs, BP monitors, iPhone apps

◆ ILR for high-risk groups ◆ Trials needed to compare screening

methods

Conclusions

■ Whom should we screen for asx AF?

◆ Opportunistic ECGs in elderly (>65 y) 1o

care population

◆ ILR for cryptogenic stroke

◆ Other high-risk subgroups TBD: REVEAL

AF and ASSERT-II

■ Does asx AF directly cause CVA?

◆ Trials in the CIED population suggest

AHREs increase CVA risk

◆ Weak temporal relationship between asx

AF and CVA

◆ REACT COM and TACTIC-AF

Conclusions

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■ Should asx AF be treated with

OAC?

◆ Yes, for asx permanent AF ◆ Burden of asx paroxysmal AF needed

to increase risk of CVA and risk- benefit ratio of OAC is unknown

◆ ARTESiA

■ Will screening for occult AF reduce

CVA?

◆ STROKESTOP

Conclusions