1. Gianluca Botto, FESC Presidente AIAC Associazione Italiana Aritmologia e Cardiostimolazione FA Sintomatica e Asintomatica Epidemiologia e Rischio Clinico

2. Presenter Disclosure Information Research support: Boston Scientific, Medtronic; St. Jude Medical, Bayer Healthcare, Gilead, Sanofi Advisory Board: Biotronik, Medtronic; St. Jude Medical, MSD, Bayer Healthcare, Boehringer, Sanofi Speaker Fees: Boston Scientific, Medtronic, St. Jude Medical, Sorin Group, Bayer Healthcare, Boehringer, BMS, Meda, MSD, Pfizer, Sanofi

3. Paroxysmal Atrial Fibrillation Symptomatic vs Asymptomatic a b c b = asymptomatic PAF a = symptomatic PAF c = sinus rhythm AF can be silent Courtesy of John Camm

4. Stroke as a First Devastating Sign of Atrial Fibrillation

5. Comprehensive Management Of AF Should Address The Multiple Impacts Of The Condition  In addition to stroke prevention and reduction of AF burden, successful management of AF should aim to reduce hospitalisations and CV morbidity and mortality Camm AJ, Eur Heart J 2012;33:2719-2747 Reduction in CV mortality Reduction in CV mortality Reduction in the risk of CV- events and hospitalisations Prevention of stroke Reduction of AF burden*  QoL  Symptoms Reduction of AF burden*  QoL  Symptoms 5

6. Relation B/ween Symptoms and ECG Transmission in AF Vesamreddy et al. J Cardiovasc Electrophysiol 2006; 17: 134-139

7. Lowres et al. Thrombosis & Haemostasis 2014 Cost-Effectiveness of Stroke Prevention Through Screening for AF Using iPhone ECG The Search-AF Study

8. 52 patients with PAF with 24 hour Holter Wolk R. Int J: Cardiol 1996; 54: 207-211 74%26% 73% 27% 53%47% 78% 22% No symptoms Symptomatic No PAF on Holter PAF on Holter AF duration at baseline (s) AF duration on treatment (s) 2215 +/- 384316 +/- 10 HR at baseline (bpm) HR on treatment (bpm) 126 +/- 2782 +/- 8 Before After Conversion From Symptomatic to Silent AF During AAD Rx

9. Atrial Fibrillation The More You Look, The More You Find More intensive monitoring results in more AF detection Gladstone DJ. For the EMBRACE Invests. N Engl J Med 2014; 370: 2467-77 Incremental Yield of Prolonged ECG Monitoring for the Detection of AF in Pts with Cryptogenic Stroke or TIA.

10. AF Monitoring Options Yes No Yes Continuous Implanted Under skin 3 on skin On wrist or 2-3 on skin On skin 3 on skin 10 on skin Electrodes DiscontinuousMinutes/ dayTranstelephonic ECG monitoring ImplantedContinuousInsertable loop recorder Implanted, PM/ICD pt.ContinuousPacemaker, ICD 7 – 28 daysExternal loop recorder CommentsStorageTechnology Direct transmissionContinuous, (<28 days)‏ Mobile cardiac outpatient monitoring (MCOT) Only symptomatic events7 – 28 daysEvent recorder 24 – 48 hours Holter < 1 minuteECG

11. AF Detection 24-h Holter: Something Like a Disaster ■425 Holter ECGs after cerebral ischemic event ■18.2% of all Holters in the hospital AF diagnosis OAC start Number of patients9 (2.1%)5 (1.2%) Holters needed4785 Costs per case$9,400$17,000 Schaer B. Stroke 2004; 35: e68-70

12. Opportunistic Screening of AF Pulse vs Microlife Tech Hobbs 2592 Morgan 1099 Wiesel 405 Stergiou 73 Kearly 999 Botto GL, Russo G. 2015

13. Lowres et al. Thrombosis & Haemostasis 2014 Cost-Effectiveness of Stroke Prevention Through Screening for AF Using iPhone ECG The Search-AF Study

14. Lowres et al. Thrombosis & Haemostasis 2014 Cost-Effectiveness of Stroke Prevention Through Screening for AF Using iPhone ECG The Search-AF Study If ECG screening was extended to general comunity the incremental cost-effectiveness would be: ■USD 4.066 per QALY ■USD 20.695 per prevention of one stroke

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16. Acqusition of single or multiple signals Internet of things ECG and pulse wave detecting driving wheel from Toyota Courtesy of P. Guzik

17. Improvement of Device Technology Allows Greater Quantification of AF Burden Botto GL. JCE. 2009;20:241-248

18. Cardiac Monitoring Set Mobile Alerts Streamlined Reports Improved CareLink ® User Interface Patient Assistant MyCareLink™ Patient Monitor Simplified Implant Procedure Reveal LINQ™ ICM Wireless Cellular All patient and clinical data are fictitious and for demonstration purposes only

19. ANTIARRHYTHMIC STARTED HERE 20-Oct-2010 26-Jul-2011

20. AF Detected By Dual-Chamber Devices And Risk For Stroke Camm J, Corbucci G, Padeletti L. Am J Cardiol 2012; 110: 270-276

21. ASSERT Trial: Primary Outcome 2582 pts with SSS; HTx and no prior AF (76±7 years, CHADS 2 score 2.41) goal AF > 6 min, > 190 bpm in 36% of pts; F-U 2.8 years Healey JS. New Engl J Med 2012; 366: 120-9 (modif.) 6 min

22. CHADS 2 Score, AF Duration and Stroke Risk 568 Pts with MDT AT500 IPG Continuously Monitored for 1 Year No AF at FU (AT/AF < 5 min in 1 day)‏ 5 min < AT/AF Episodes < 24 h AT/AF Episodes > 24 h CHADS 2 score 012 33 1.7%25%0% 1.8%0%1.3%2.4% 0% 4.4% 33%4.4% (3 out of 351 Pts) 0.8 % vs 5 % (11 out of 217 Pts)‏ P = 0.035 Botto GL. J Cardiovasc Electrophys 2009; 20: 241-248

24. Incremental Cost Burden of Undiagnosed AF By Prevalence of Undiagnosed AF Turakhia MP. AJC 2015, 116: 733-739

25. Atrial Fibrillation and Stroke Bread for the Brain Asymptomatic device-detected AHRE are of clinical importance The impact of device-detected atrial high-rate episodes and arrhythmia burden on thrombogenesis and clinical thromboembolism is attracting much interest Thromboembolic risk is not only related to AT/AF episodes, but likely involves a complex interplay of - atrial arrhythmias - atrial myopathy - endotelial dysfunction related to comorbidity - abnormal hemostasis The need for anticoagulation Rx is mostly depending on stroke risk factors once a low threshold of AT/AF burden is exceed rather than merely the presence/absence of AF Cost-effectiveness of future approaches needs to be determined