AF detection: What s new? Christopher B. Granger

Transcription

1 AF detection: What s new? Christopher B. Granger

2 Disclosures Research contracts: Apple, AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Daiichi Sankyo, Janssen, Novartis, GSK, Medtronic Foundation, Pfizer, The Medicines Company, FDA, NIH Consulting/Honoraria: Abbvie, AstraZeneca, Bayer, BMS, Boston Scientific, Gilead, GSK, Pfizer, Daiichi Sankyo, Novartis, Boehringer Ingelheim, Medtronic, Merck, Novo Nordisk, The Medicines Company, Rho, Roche Diagnostics, Sirtex, Verseon For full listing see

3 76 year old woman, diabetes, hypertension, prior TIA and carotid stent, HFpEF, creatinine 1.6 (creat clearance 30), who has had dyspnea on exertion and palpitations. In clinic, sinus rhythm. What would you do to screen for arrhythmias? 1. Nothing specific for screening 2. Holter monitor for 48 hours 3. Patch or surface monitor for 2 to 4 weeks 4. Apple Watch 5. AliveCor app 6. Implantable cardiac monitor 7. Echo and NTproBNP, put on anticoagulant if high risk

4 76 year old woman, diabetes, hypertension, prior TIA and carotid stent, HFpEF, creatinine 1.6 (creat clearance 30), who has had dyspnea on exertion and some palpitations. In clinic, sinus rhythm. What would your threshold be to treat with NOAC? 1. 2 min 2. 6 min 3. 6 hours hours hours

5 Clinical AF Is overt AF the real problem, or is it just the tip of the iceberg? Subclinical AF 1. There is a lot of subclinical, undiagnosed AF 2. Subclinical AF is associated with risk of stroke, in patients with risk factors 3. Whether and when treating subclinical AF with OAC reduces stroke is uncertain

6 How much subclinical AF exists in general populations?

7 1.4% of population 65 years have AF on screening There are 35 million people in US age 65 This translates into 490,000 Americans Thromb Haemost 2013; 110:

8 How much subclinical AF exists in high-risk populations

9 Design 2580 patients Enrolled after new pacemaker or ICD Age 65 years + history of hypertension Excluded if any history of AF or on VKA Prospective Cohort Design To determine if device-detected atrial tachyarrhythmias are associated with an increased risk of stroke or embolism? Enrolled 0-8 wks post implant Arrhythmia Detection Follow Up Period Primary Outcome: Ischemic Stroke or Systemic Embolism Visits Months 36% had 1 AHRE over 2.8 y Healey N Engl J Med 2012;366:120-9.

10 ASSERT-II (n=256): age 65; CHA2DS2-VASc 2, OSA, high BMI; elevated probnp and/or LAE Incidence of sub-clinical AF (SCAF) Rate per year (95% CI) 34.4% (27.7% 42.3%) 21.8% (16.7% 27.8%) 7.1% (4.5% 10.6%) 2.7% (1.2% 5.0%) Healey et al, Circulation 2017;136:

11 Who gets subclinial AF? SCAF 5 Minutes by Sub-Group Healey et al, Circulation 2017;136:

12 50 Results of REVEAL AF 394 Patients CHADS Incidence rate (%) % 6+ min episode of AF 95% confidence bounds 20.4% 27.1% 29.3% 33.6% Primary endpoint Months post-insertion (no.) 40.0% Median time to detection 123 (41-330) days AF may have gone undetected in over ¾ of pts had monitoring been limited to 30 days Similar rates among CHADS subgroups Reiffel: JAMA Cardiol, MFMER

13 % patients with AF detected At 3 years, 30% had AF detected Months N Engl J Med 2014;370:

14 What is the risk of stroke with subclinical AF?

15 Pattern of AF and Embolic Stroke 6563 ASA-treated patients from ACTIVE-A and AVERROES Permanent, persistent, paroxysmal Vanassche T. Eur Heart J 2014

16 ASSERT: 36% had 1 AHRE over 2.8 y > 6 minutes of AHRE in first 3 months AF by duration (reached anytime during study) Stroke and systemic embolism RR 2.49, p=0.007 Healey et al., N Engl J Med 2012 Van Gelder et al., Eur Heart J 2017

17 Meta-Analysis of SCAF Duration and Stroke Risk Long > 24h Medium 6 h to 24 h Short 6 m to 6 h Rahimi Eur Heart J 2017

18 Stroke Risk for SCAF is Lower than AF Annual stroke risk (%/yr) SCAF: no 1 SCAF: yes overt AF CHADS 1 CHADS 2 CHADS 3 1 Healey JS et al. N Engl J Med. 2012;366: Gage BF et al. JAMA. 2001;285:

19 Are strokes associated with SCAF modifiable with anticoagulation?

20 Are recurrent stokes in patients with ESUS modifiable with anticoagulation? ClinicalTrials.gov Identifier: NCT Hart R et al. N Engl J Med 2018;378:

21 NAVIGATE (n=7,312) 332 events Follow up 11 months RE-SPECT (n=5,390) 384 events Follow up 19 months Riva Aspirin Dabi Aspirin Age 66.9 years 64.2 years Prior stroke/tia 17% 18% Stroke to 37 days 44 days random. NOAC dose 15 mg/day Recurrent stroke/ SE (annual) 5.1% 4.8% 1.07 ( ) Major bleeding 1.8% 0.7% 2.72 ( ) 150/110 mg bd 4.1% 4.8% 0.85 ( ) 1.7% 1.4% 1.19 ( ) Hart R NEJM 2018 Deiner HC WSC 2018 All Rights Reserved, Duke Medicine 2007

22 Consumer-Based Devices for Heart Rhythm Detection ECG-Based Pulse-Based Wearable Accessory Carriable Patch Mechanical Photoplethys -mography Apple Watch 4 Kardia Band Zenicor Kardia Omron Heart- Scan MyDiagnostick Zio Zephyr VitalConnect MC10 BodyGuardian Palpation Mechanocardiography Microlife WatchBP Fitbit Versa Apple Watch Striiv Smartphones

23 $99 at amazon.com

24 Apple Heart Study: Assessment of Wristwatch-Based Photoplethysmography to Identify Cardiac Arrhythmias ClinicalTrials.gov Identifier: NCT

25 ECG-Based Patch

26 Older patients without an AF diagnosis 359,161 Aetna members meeting eligibility criteria 2,655 consented & confirmed eligible R 5,310 observational controls matched for age, sex and CHADS-VASc score 1,364 randomized to immediate monitoring 1,291 randomized to delayed monitoring 456 never wore a patch 457 never wore a patch 908 actively monitored Primary Endpoint New Diagnosis of AF after 4 months 834 actively monitored 1,738 actively monitored participants with 12 months follow-up New Diagnosis of AF 12 months 3,476 matched observational controls with 12 months follow-up JAMA. 2018;320(2):

27 ECG-Based Patch At 4 months, 3.9% vs 0.9% AF diagnosis. At 1 year, AF was newly diagnosed in 109 monitored (6.7 per 100 person-years) and 81 unmonitored (2.6 per 100 person-years; difference, 4.1 [95%CI, ]) individuals. Steinhuble S et al. JAMA. 2018;320:

28 An example of a screening programme All residents born 1936/1937 n=28,768 Control group n=14, and 76 yo 54% Invited to screening n=13,331 12% had AF Attends screening clinic n=7,173 Not participating Twice daily and with palpitation Known AF without OAC n=149 (2.1%) New AF n=218 (3 %) 0.5% on 1 st ECG Candidate OAC initiation n=367 (5.1%) 5.1% untreated AF: 3.7% initiated on OAC Svennberg E, et al. Circulation 2015;131:

29 ESC guidelines 2016: Screening Recommendations Class Level Opportunistic screening for AF is recommended by pulse taking or ECG rhythm strip in patients >65 years of age I B Systematic ECG screening may be considered to detect AF in patients aged >75 years, or those at high stroke risk II B Adapted from Kirchhof P, et al Kirchhof P, et al. Eur J Cardiothorac Surg 2016:50:e1 e88.

30 U.S. Preventive Services Task Force Draft Recommendation Statement Atrial Fibrillation Screening with Electrocardiography 2017 Draft: Recommendation Summary Adults age 65 The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for atrial fibrillation with electrocardiography (ECG)

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32 OAC is very effective at preventing stroke for overt AF

33 Estimated 71% RRR in Stroke, NOAC vs Control Warfarin compared to control or placebo Relative Risk Reduction (95% CI) NOAC compared to warfarin Relative Risk Reduction (95% CI) Trial Trial AFASAK I (1990) SPAF I (1991) BAATAF (1990) CAFA (1991) SPINAF (1992) EAFT (1993) RE-LY (2009) ROCKET AF (2011) ARISTOTLE (2011) ENGAGE AF-TIMI 48 (2013) Combined Combined 100% 50% 0 50% 100% Favors warfarin Favors placebo or control Warfarin vs. Placebo or Control (6 trials, total n=2,900) Hart R, et al. Ann Intern Med. 2007;146: % 0 50% Favors NOAC RRR 64% RRR 19% Favors warfarin NOAC vs. Warfarin (4 trials, total n=71,683) Ruff C, et al. Lancet. 2014;383:

34 Ongoing studies

35 ARTESiA Study Design Patients with: - SCAF 6 min to 24 hrs - Risk factors for stroke (age 75, previous stroke/ TIA/ SE or multiple risk factors) - No clinical AF/not on OAC, no contraindication Double-blind, double-dummy design RANDOMIZE 4000 patients from 190+ hospitals in Canada, USA and Europe Apixaban: 5mg or 2.5mg bid Aspirin: 81 mg OD 1 Efficacy Outcomes: 1 Safety Outcome: Stroke (including TIA with imaging), Systemic Embolism Major Bleed Lopes RD et al. Am Heart J. 2017;189:

36 The LOOP study Design Randomized open-label, controlled study Age > 70 years and at least one of the following diseases: Diabetes, HTN, HF, or prior stroke Question: Can stroke events be reduced? Numbers 6,000 patients will be included - ILR group: patients - Control group: patients THE HEART CENTER, RIGSHOSPITALET Action When AF is detected and fulfil duration criteria (6 min) patients will start anticoagulation therapy ClinicalTrials.gov Identifier: NCT

37 76 year old woman, diabetes, hypertension, prior TIA and carotid stent, HFpEF, creatinine 1.6 (creat clearance 30), who has had dyspnea on exertion and palpitations. In clinic, sinus rhythm. What would you do to screen for arrhythmias? 1. Nothing specific for screening 2. Holter monitor for 48 hours 3. Patch or surface monitor for 2 to 4 weeks 4. Apple Watch 5. AliveCor app 6. Implantable cardiac monitor 7. Echo and NTproBNP, put on anticoagulant if high risk