◆ 12/18/15 Asymptomatic Atrial Fibrillation: Detection and Management 18 December 2015 32 nd 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 ◆ 1
◆ 12/18/15 Outline ■ 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? Atrial Fibrillation ■ ~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) 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 ◆ 2
◆ 12/18/15 Asymptomatic Atrial Fibrillation ■ ~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 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 Asymptomatic Atrial Fibrillation ■ 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 Rizos T, et al. Cerebrovasc Dis 2010;30 :410–17 Seet RC, et al. Circulation 2011;124 :477–86 ◆ 3
◆ 12/18/15 Atrial Fibrillation and CVA Risk ■ Paroxysmal = Permanent ■ OAC reduces the RR of CVA in AF pts by 2/3 ■ Does early OAC for asx AF confer similar benefit? Wolf PA, et al. Stroke 1991;22 :983–8 Camm AJ et al. Europace 2010;12 :1360–420 Screening Methods for Asx AF ■ Gold standard is 12-lead ECG ■ Systematic vs opportunistic ECG screening (abnl pulse à ECG) of 14,000 1 o care pts > 65 y equivalent and superior to routine practice ◆ AF detection per y: 1.6% vs 1% (p=0.01) Camm, AJ, et al. Europace 2012;14 :1385–413 Fitzmaurice DA, et al. BMJ 2007;335 :383. ◆ 4
◆ 12/18/15 Screening Methods for Asx AF ■ 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) Barrett PM, et al. Am J Med 2014;127 :95 ◆ 5
◆ 12/18/15 Screening Methods for Asx AF ■ Implantable loop recorder (ILR) ◆ Reveal (MDT) ◆ Confirm (SJM) ■ Analyzes irregularity of R-R ■ Require minimum duration of AF ■ Ongoing studies of detection rates of asx AF in high-risk pts Screening Methods for Occult 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? Rosero, et al. Prog CV Dis 2013;56 :143–52 ◆ 6
◆ 12/18/15 High Risk Subpopulations for Asymptomatic AF ■ Cryptogenic stroke ■ CIEDs ■ Elderly Cryptogenic Stroke ■ 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) Gladstone DJ, et al. NEJM 2014;370 :2467–77 Sanna T , et al. NEJM 2014;370 :2478–86 ◆ 7
◆ 12/18/15 Cryptogenic Stroke ■ 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 Gladstone DJ, et al. NEJM 2014;370 :2467–77 Sanna T , et al. NEJM 2014;370 :2478–86 Cryptogenic Stroke ■ 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 ◆ 8
◆ 12/18/15 Ongoing ILR Trials for Asx AF Keach, et al. Heart 2015;101:1097-1102 CIEDs ■ 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 Glotzer TV, et al. Circulation 2003;107 :1614–19 Glotzer TV, et al. Circ A&E 2009;2 :474–80. ◆ 9
◆ 12/18/15 CIEDs ■ 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 Elderly ■ AF in 1.6% of 1 o 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 Go AS, et al. Circulation 2014 ;129 :e28–292 Engdahl J, et al. Circulation 2013;127 :930–7 ◆ 10
◆ 12/18/15 Risk Models ■ 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) Alonso A, et al. JAHA 2013;2 :e000102 Brunner KJ, et al. Mayo CP 2014;89 :1498–505 Turakhia MP. Clin Cardiol 2015 Novel Markers for Asx/New-Onset AF ■ 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 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 ◆ 11
◆ 12/18/15 OAC and Asx AF ■ Will asx AF show same benefit from OAC as traditionally detected AF (paroxysmal, persistent or permanent)? Consider OAC based on CHADS2-VASC Keach, et al. Heart 2015;101:1097-1102 OAC and Asx AF ■ Will asx AF show same benefit from OAC as traditionally detected AF (paroxysmal, persistent or permanent)? Index CVA Consider OAC? Keach, et al. Heart 2015;101:1097-1102 ◆ 12
◆ 12/18/15 OAC and Asx AF ■ 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 Ongoing Trials of OAC for Asx AF Keach, et al. Heart 2015;101:1097-1102 ◆ 13
◆ 12/18/15 Ongoing Trials of OAC management for low burden AF Keach, et al. Heart 2015;101:1097-1102 OAC and Asx AF ■ 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 ◆ 14
◆ 12/18/15 Lessons Learned from HRT for Postmenopausal Women ■ 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 2 o prevention of CVA in women ■ WHI showed 29% increase in MI and 41% increase in CVA OAC and Asx AF ■ Will asx AF show same benefit from OAC as traditionally detected AF (paroxysmal, persistent or permanent)? Index CVA More risk w/ OAC Keach, et al. Heart 2015;101:1097-1102 ◆ 15
◆ 12/18/15 Conclusions ■ 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) 1 o 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 ◆ 16
◆ 12/18/15 Conclusions ■ 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 ◆ 17
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