Management of Atrial Fibrillation. Leon Ptaszek, MD, PhD, FACC, FHRS 25 March 2018

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1 Management of Atrial Fibrillation Leon Ptaszek, MD, PhD, FACC, FHRS 25 March 2018

2 Disclosures Speaker: St. Jude Medical, Biotronik Consultant: St. Jude Medical, World Care Clinical

3 Objectives Recognize the importance of atrial fibrillation treatment in stroke risk reduction Recognize the challenges associated with anticoagulation management of atrial fibrillation Recognize opportunities to identify patients with asymptomatic atrial fibrillation who are at risk for stroke Recognize treatment options for management of symptoms associated with AF

4 Goals of AF Management Pillar 1: Minimize risk of stroke associated with AF Pillar 2: OAC LAA occlusion devices Minimize symptoms associated with AF Rate versus rhythm control For rhythm control, AADs versus ablation

5 Stroke: Magnitude of the Problem Stroke is 5 th leading cause of death in US* 795,000 per annum, ~80% are first events 130,000 deaths per annum Acute treatment costs $4 billion per annum in US Long-term treatment costs $34 billion per annum** * D Mozaffarian et al, Circulation 2015;133:e38-e360 ** HCUP Statistical Brief #51, hcup-us.ahrq.gov, accessed 19 Apr 2016

6 Case 78-year-old woman with HTN is brought to the ED due to slurred speech, imbalance. Slight right facial droop on exam. Brain MR reveals multiple acute ischemic areas (same age) in both hemispheres. Head/neck angiogram reveals 60% stenosis in Right ICA. ECG reveals NSR, no arrhythmias on telemetry. How would you describe the etiology of the event? A. Cerebrovascular disease (Right ICA) B. Patent foramen ovale with paradoxical thrombus C. Cryptogenic D. Atrial fibrillation

7 Case 78-year-old woman with HTN is brought to the ED due to slurred speech, imbalance. Slight right facial droop on exam. Brain MR reveals multiple acute ischemic areas (same age) in both hemispheres. Head/neck angiogram reveals 60% stenosis in Right ICA. ECG reveals NSR, no arrhythmias on telemetry. How would you describe the etiology of the event? A. Cerebrovascular disease (Right ICA) B. Patent foramen ovale with paradoxical thrombus C. Cryptogenic D. Atrial fibrillation

8 Case Highly suspicious for AF-related cardioembolic event No proof of arrhythmia or other etiology* If AF were identified, the patient would qualify for anticoagulation therapy (CHADS2VASC = 6) * Amarenco et al, Stroke 2009;27:502-8

9 Who is at risk? Increased Age 90% of strokes occur after 50 Cardiovascular Risk Factors HTN Hyperlipidemia Smoking Atrial Fibrillation Increases risk of stroke 500% At least 15% of all strokes are associated with AF

10 Outcomes of AF-Related Strokes AF-related strokes are associated with higher acute morbidity and mortality* >50% increase in mortality as compared with strokes not due to AF (~20% to ~33%) 50% of patients with AF-related stroke experience permanent disability ~30% for patients with stroke not related to AF *Lamassa et al, Stroke 2001;32:392-8 Steger et al, Eur Heart J 2004;25:

11 Mechanism of AF-Related Strokes Superior RAO

12 Mechanism of AF-Related Strokes Superior RAO Sluggish blood flow in the atria, leading to thrombus formation

13 Outcomes of AF-Related Strokes: why are they worse? Cardioembolic events associated with: Multiple areas of the brain affected Hemorrhagic conversion increased Higher rate of recurrence

14 Preventing AF-Related Strokes As many as 70% of patients with AF die of a stroke (long-term) With appropriate anticoagulation therapy, up to 75% of AF-related strokes are preventable* *Wolf et al, Arch Intern Med 1987; 147:1561-4

15 Stroke Risk Calculation Congestive heart failure +1 HTN +1 Age Age Diabetes +1 Stroke/TIA/thromboembolism +2 Sex (female) +1 Vascular disease (peripheral or CAD) +1

16 Stroke Risk Calculation Congestive heart failure +1 HTN +1 Age Age Diabetes +1 Stroke/TIA/thromboembolism +2 Sex (female) +1 Vascular disease (peripheral or CAD) +1 Score 1: 0.6% CVA/year* (no, asa, or coumadin/noac) * Friberg et al, Eur Heart J 2012;33:1500

17 Stroke Risk Calculation Congestive heart failure +1 HTN +1 Age Age Diabetes +1 Stroke/TIA/thromboembolism +2 Sex (female) +1 Vascular disease (peripheral or CAD) +1 Score 1: 0.6% CVA/year* (no, asa, or coumadin/noac) Score 2: 2.2% CVA/year (coumadin/noac) * Friberg et al, Eur Heart J 2012;33:1500

18 Issues with Anticoagulation Underutilization of anticoagulants Concerns regarding risks Variability in adoption of published guidelines Identification of all patients with atrial fibrillation Asymptomatic patients

19 Issues with Anticoagulation Underutilization of anticoagulants Concerns regarding risks Incomplete education Identification of all patients with atrial fibrillation Asymptomatic patients Large population: ~2.2M with AF in US --- Wolf et al, Arch Intern Med 1987; 147:1561-4

20 Pts. anticoagulated Anticoagulants are Underutilized Only ~60% of patients who qualify for anticoagulation are prescribed an anticoagulant Anticoagulant use goes down with increase in CHADS2 score* 70% 60% 50% 40% 30% 20% 10% 0% CHADS2 score *Piccini et al, Heart Rhythm 2012;9:1403-8

21 Anticoagulation for AF With increasing CHADS2VASC score, likelihood of anticoagulation prescription reduces As many as 75% of high-risk patients are not anticoagulated (no prescription or poor INR control)* Decreased likelihood of anticoagulation prescription in older patients Likely driven by increase in bleed risk in patients >80 yrs** * Chan et al, Heart Rhythm 2016; epub ahead of print 28 Mar 2016 ** Hylek et al, Circulation 2007;115:

22 HAS-BLED Score HTN (+1) Abnormal liver fxn (+1) Abnormal renal fxn (+1) Stroke/TIA (+1) Bleeding predisposition (+1) Elderly: Age 65 (+1) Drugs (anti-platelet) (+1) Drugs (alcohol) (+1)

23 HAS-BLED Score HTN (+1) Abnormal liver fxn (+1) Abnormal renal fxn (+1) Stroke/TIA (+1) Bleeding predisposition (+1) Elderly: Age 65 (+1) Drugs (anti-platelet) (+1) Drugs (alcohol) (+1) Score 1: 1% bleed/yr Score 2: 1.9% bleed/yr Score 3: 3.7% bleed/yr Score 4: 8.7% bleed/yr Score 5: >10% bleed/yr

24 Anticoagulation for AF Improved clinical decision support SPARCTOOL ( Increase clinician awareness of the guidelines AHA Get with the guidelines program

25 Anticoagulation for AF CHADS2VASC HASBLED Congestive heart failure (+1) HTN (+1) Age 65 (+1) Age 75 (+1) Diabetes (+1) Stroke/TIA (+2) Sex (female) (+1) Vascular disease (+1) HTN (+1) Abnormal liver funct (+1) Abnormal renal funct (+1) Stroke/TIA (+1) Bleeding predisposition (+1) Elderly: Age 65 (+1) Drugs (anti-platelet) (+1) Drugs (alcohol) (+1)

26 Anticoagulation for AF CHADS2VASC HASBLED Congestive heart failure (+1) HTN (+1) Age 65 (+1) Age 75 (+1) Diabetes (+1) Stroke/TIA (+2) Sex (female) (+1) Vascular disease (+1) HTN (+1) Abnormal liver funct (+1) Abnormal renal funct (+1) Stroke/TIA (+1) Bleeding predisposition (+1) Elderly: Age 65 (+1) Drugs (anti-platelet) (+1) Drugs (alcohol) (+1)

27 Anticoagulation for AF CHADS2VASC HASBLED Congestive heart failure (+1) HTN (+1) Age 65 (+1) Age 75 (+1) Diabetes (+1) Stroke/TIA (+2) Sex (female) (+1) Vascular disease (+1) HTN (+1) Abnormal liver funct (+1) Abnormal renal funct (+1) Stroke/TIA (+1) Bleeding predisposition (+1) Elderly: Age 65 (+1) Drugs (anti-platelet) (+1) Drugs (alcohol) (+1)

28 Anticoagulation for AF CHADS2VASC HASBLED Congestive heart failure (+1) HTN (+1) Age 65 (+1) Age 75 (+1) Diabetes (+1) Stroke/TIA (+2) Sex (female) (+1) Vascular disease (+1) HTN (+1) Abnormal liver funct (+1) Abnormal renal funct (+1) Stroke/TIA (+1) Bleeding predisposition (+1) Elderly: Age 65 (+1) Drugs (anti-platelet) (+1) Drugs (alcohol) (+1)

29 Anticoagulation for AF CHADS2VASC HASBLED Congestive heart failure (+1) HTN (+1) Age 65 (+1) Age 75 (+1) Diabetes (+1) Stroke/TIA (+2) Sex (female) (+1) Vascular disease (+1) HTN (+1) Abnormal liver funct (+1) Abnormal renal funct (+1) Stroke/TIA (+1) Bleeding predisposition (+1) Elderly: Age 65 (+1) Drugs (anti-platelet) (+1) Drugs (alcohol) (+1) walking the tightrope

30 Anticoagulant Study Drug Discontinuation Rate Major Bleeding (rate/year) Rivaroxaban* 24% 3.6% Apixaban # 25% 2.1% Dabigatran $ (150 mg) (60 mg / 30 mg) 21% 3.3% 33 % / 34% 2.8% / 1.6% Warfarin 17 28% % * ROCKET AF trial # ARISTOTLE trial $ RELY ENGAGE TIMI 48

31 Preventing AF-Related Strokes: Identifying Asymptomatic Patients Large population: ~2.2 million people in the US are diagnosed with AF* It is thought 1/3 of people with AF are not diagnosed Anticoagulation therapy is not reaching these patients How do you screen for patients with asymptomatic AF? *Wolf et al, Arch Intern Med 1987; 147:1561-4

32 Case 78-year-old woman is brought to the ED due to slurred speech, imbalance. Slight right facial droop on exam. Brain MR reveals multiple acute ischemic areas (same age) on the left and right. Head/neck angiogram reveals 60% stenosis in Right ICA. What is the best method for AF screening? A. 12-lead ECG B. Holter monitor C. Event monitor (30-day) D. Implantable loop recorder E. Pacemaker/defibrillator

33 Screening for Asymptomatic AF Duration of snapshot is proportional to likelihood of capturing intermittent events ECG (10 sec) Holter (24, 48 hrs) Loop monitor (30 days) Implantable loop monitor (2 years) Pacemaker/Defibrillator (indefinite)

34 Screening for Asymptomatic AF Duration of snapshot is proportional to likelihood of capturing intermittent events ECG Holter Loop monitor Implantable loop monitor Pacemaker/Defibrillator SENSITIVITY

35 Screening for Asymptomatic AF Duration of snapshot is proportional to likelihood of capturing intermittent events ECG Holter Loop monitor Implantable loop monitor Pacemaker/Defibrillator SENSITIVITY INVASIVENESS

36 EGMs Provided by PPM

37 EGMs Provided by PPM

38

39 Screening for AF after Stroke Inpatient monitoring 6%* Serial 12-lead ECG Ambulatory monitor (24-72 hours) 7%, $ 10% & 2-12% # * Rizos et al, Stroke 2012;43: $ Kamel et al, J Stroke Cerebrovasc Dis;18:453-7; & Douen et al, Stroke 2008;39:480-2 # Seet et al, Circulation 2011;124:477-86

40

41 CRYSTAL-AF Guidelines call for ambulatory arrhythmia monitoring after cryptogenic stroke CRYSTAL-AF: Multicenter RCT comparing ILR non-invasive ambulatory monitoring Recruited patients after cryptogenic stroke Primary end point: time to AF detect within 6m Intention-to-treat analysis

42 CRYSTAL-AF Patient characteristics: 447 patients, 55 centers in US, Canada, Europe Recruited CCVA patients 40 yrs (mean 65) 1:1 randomized assignment to ICM or ambulatory

43 CRYSTAL-AF AF detection at 6 months (primary endpoint): ICM: 8.9% Control: 1.4% AF detection at 12 months (secondary endpoint): ICM: 12.9% Control: 2.0% Anticoagulation use greater in ICM group ~10% for ICM group, ~4% for control group Decreased subsequent stroke rate in ICM (not powered)

44 CRYSTAL-AF Conclusions: ICM implant is superior to ambulatory monitoring for detection of AF after cryptogenic stroke Months after event # ICM implants required to detect one AF event

45 Implantable Monitors

46 Cardiac Electrograms 1 st clinical experience in Australia (30 patients) showed R-wave amplitudes of up to 1.7 mv after insertion and also at 1-month follow-up) BioMonitor 2 Pilot Study, Version 1.0, 10 August 2015, BIOTRONIK SE & Co. KG

47 Arrhythmia Detection AF Bradycardia High Ventricular Rate

48 Web-Based Alert Management Immediate detection of clinical events (<24 h) Customize by group or individual patient Alert triage and on call management available

49 Conclusions AF is a major risk factor for stroke

50 Conclusions AF is a major risk factor for stroke Anticoagulation can reduce risk of AF-related stroke

51 Conclusions AF is a major risk factor for stroke Anticoagulation can reduce risk of AF-related stroke The decision to anticoagulate is challenging Bleeding risk Unidentified atrial fibrillation

52 Conclusions AF is a major risk factor for stroke Anticoagulation can reduce risk of AF-related stroke The decision to anticoagulate is challenging Bleeding risk Unidentified atrial fibrillation Monitoring can identify AF in asymptomatic patients and drive therapy* * Sanna et al, NEJM 2014;370: Alonso and Norby, Circ J 2016; epub ahead of print 24 Mar 2016

53 Thank you

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