Fred Kusumoto Professor of Medicine

Fred Kusumoto Professor of Medicine Faculty photo will be placed here Kusumoto.Fred@mayo.edu 2015 MFMER 3543652-1

Atrial Fibrillation Presentation Subtitle Here Mayo School of Continuous Professional Development 2nd Annual Inpatient Medicine for NPs & Pas: Hospital Care from Admission to Discharge Wednesday-Saturday, October 19-22, 2016 Sawgrass Marriott Hotel Ponte Vedra Beach, Florida 2015 MFMER 3543652-2

Disclosures None 2016 MFMER 3543652-3

Case #1 56 year old lawyer comes to the hospital with a 3 month history of progressive dyspnea on exertion and fatigue, without chest pain. No prior medical problems Physical examination reveals an irregular fast heart rate but is otherwise normal 2016 MFMER 3543652-4

Kusumoto, ECG Interpretation: from Pathophysiology to Clinical Application 2009 2016 MFMER 3543652-5

Four kinds of tachycardia 2016 MFMER 3543652-6

Four kinds of tachycardia 2016 MFMER 3543652-7

Multifocal Atrial Tachycardia Kusumoto, ECG Interpretation: from Pathophysiology to Clinical Application 2009 2016 MFMER 3543652-8

Case #1 Kusumoto, ECG Interpretation: from Pathophysiology to Clinical Application 2009 2016 MFMER 3543652-9

Atrial Fibrillation Inpatient Management How s the patient right now? Rate or rhythm control? Decide on a Strategy (hospital and long-term) Is something going to get better? Rate or Rhythm Control? Stroke risk-during hospitalization and longterm? 2016 MFMER 3543652-10

Four kinds of tachycardia 2016 MFMER 3543652-11

Rate control for atrial fibrillation (Slow AV conduction) Calcium channel blockers Slows AV node conduction directly Diltazem Beta blockers Decrease sympathetic activation Metoprolol, esmolol Digoxin Increase parasympathetic activation Do not overdo (Amiodarone) 2016 MFMER 3543652-12

RACE II: 614 patients with permanent atrial fibrillation randomly assigned to a lenient rate-control strategy (resting HR < 110 bpm) or a strict ratecontrol strategy (resting heart rate < 80 bpm and exercise HR < 110 bpm). Van Gelder et al NEJM 2010 2016 MFMER 3543652-14

RACE II: Symptoms Van Gelder et al NEJM 2010 2016 MFMER 3543652-15

34 million people in the world have atrial fibrillation Chugh et al Circ 2013 2016 MFMER 3543652-16

Risk factor modification and AF: Goal-directed weight loss (LEGACY trial) 1,415 patients with AF 825 (%) had a BMI 27 kg/m 2 and 355 were offered weight management Without rhythm control Pathak et al JACC 2015 2016 MFMER 3543652-17

Risk factor modification and AF: Fitness and risk of AF 64,561 patients without AF underwent TMT and were followed for 5.4 years. Qureshi et al Circ 2015 2016 MFMER 3543652-18

AFFIRM Primary Endpoint: All-Cause Mortality Mortality (%) 30 25 20 15 10 5 P=.058* Rhythm Rate 0 0 1 2 3 4 5 Time (years) Rhythm N: 2033 1932 1807 1316 780 255 Rate N: 2027 1925 1825 1328 774 236 *After adjustment for confounders significant!

AFFIRM Time-Dependent Covariates associated with survival Covariate P-Value Hazard Ratio 99% CI Sinus rhythm <.0001 0.53 0.39-0.72 Warfarin use <.0001 0.50 0.37-0.69 Digoxin use.0007 1.42 1.09-1.86 AAD* use.0005 1.49 1.11-2.01 HR <1.00: decreased risk of death. HR >1.00: increased risk of death. *Antiarrhythmic drug. The AFFIRM Investigators. Circulation. 2004;109:1509-1513.

Comparison of Quality-of-Life scores: Age matched normals vs. study group Normal Atrial fibrillation SF-36 category Goldberg 2000, Ware 1970

Relative contributions of different risk factors to the CHADS 2 score 73,558 patients with AF not treated with OAC (Denmark) Olesen et al BMJ 2011;342:d124 2016 MFMER 3543652-24

Relationship Between the CHA 2 DS 2 -VASc Score and the Risk of Stroke Annual Risk of Stroke (%) 20 15 10 5 ACC 0 ESC 0 1 2 3 4 > 4 0% 1.3% 2.2% 3.2% 4% Does it matter? Anticoagulate Anticoagulate 0 1 2 3 4 5 6 7 8 9 CHA 2 DS 2 -VASc Score CHA 2 DS 2 -VASc: Weights age, adds vascular disease and gender Greater granularity at low and moderate risk Lip et al Circ 2012 2016 MFMER 3543652-25

Large randomized trials of NOACs Dabigatran (ReLy) Rivaroxaban (Rocket-AF) Apixaban (Aristotle) Edoxaban (Engage AF) N Age (y) CHADS F/U (y) 18,113 72 2.1 2 14,264 73 3.5 1.9 18,201 70 2.0 1.8 21,105 72 2.8 2.8 71,683 patients Connolly et al NEJM 2009, Patel et al 2011, Granger et al NEJM 2011, Giugliano NEJM 2013 2016 MFMER 3543652-26

Summary of the NOAC Trials: Annual Risk of Stroke and Systemic Embolism 2.5 Annual Rate of Stroke and Systemic Embolism (%) 2 1.5 1 0.5 0 dab riv apix edox War Rx CHADS 2 2.1 3.5 2.0 2.8 Connolly et al NEJM 2009, Patel et al 2011, Granger et al NEJM 2011, Giugliano NEJM 2013 2016 MFMER 3543652-27

Summary of the NOAC Trials: Annual Risk of Major bleeding Annual Rate of major bleeding (%) 5 4.5 4 3.5 3 2.5 2 1.5 1 0.5 0 dab riv apix edox War Rx CHADS 2 2.1 3.5 2.0 2.8 Connolly et al NEJM 2009, Patel et al 2011, Granger et al NEJM 2011, Giugliano NEJM 2013 2016 MFMER 3543652-28

Case #1 Started on metoprolol 50 mg twice daily Stroke risk: CHA 2 DS 2 -Vasc: 0 Education Follow-up/Continuity Oral anticoagulation (NOAC) Rate control in moderation 2016 MFMER 3543652-29

Case #2 74 year old admitted with 3 hours of chest pain Undergoes CABG POD #2 develops atrial fibrillation (average HR 120-130 bpm) 2016 MFMER 3543652-30

Prevalence of Postoperative Atrial Fibrillation 100 80 % 60 40 Min Max 20 0 CABG Valve C+V Tx Creswell 1993, Andrews 1991, Aranki 1996, Pavri 1995, Crosby 1995, Zaman 2000 2016 MFMER 3543652-31

Postoperative atrial fibrillation Temporal development over time Mathew et al JAMA 2004 2016 MFMER 3543652-32

Postoperative atrial fibrillation may predict future increased mortality (PREVENT-IV) Al-Khatib et al AHJ 2009 2016 MFMER 3543652-33

Postoperative AF Rhythm vs. rate control Postoperative AF in 695 (33%) of 2,109 patients enrolled randomized to rate control or rhythm control (amiodarone ± CV) strategies. D/C 30 d 60 d Rate Control 10.1% 5% 3.4% Rhythm Control 6.5% 2% 0.4% Gillinov et al NEJM 2016 2016 MFMER 3543652-34

Conversion and pause No indication for permanent pacemaker Education Follow-up/Continuity No specific Rx Oral anticoagulation (NOAC)? Kalman, Sinus node dysfunction. In Cardiac Pacing for the Clinician Kusumoto and Goldschlager 2006, Springer 2016 MFMER 3543652-35

Case #3 72 year old man is admitted for chest pain Past medical Hx: Hypertension Diabetes PAF Medications: Rivaroxaban 20 mg daily Lisinopril 20 mg daily 2016 MFMER 3543652-36

Case #3 2016 MFMER 3543652-37

Case #3 2016 MFMER 3543652-38

Case #3 2016 MFMER 3543652-39

Case #3: Drug eluting stent paced Recommendations for anticoagulation? Drug(s) Aspirin Other platelet inhibitor Warfarin NOAC Duration 2016 MFMER 3543652-40

Triple Therapy in Patients on Oral Anticoagulation After Drug Eluting Stent Implantation ISAR Triple 614 patients on warfarin for 12 months who received a DES for stable CAD or ACS randomized to 6 weeks or 6 months of triple Rx (warfarin (lowest recommended INR), Aspirin Bleeding Ischemia (75-200 mg), clopidogrel 75 mg daily) 6 weeks 6 months 6 weeks 6 months Fiedler et al JACC 2015 2016 MFMER 3543652-41

Antiplatelet therapy and anticoagulation after acute coronary syndrome 2016 Focused Update on DAPT duration Assess ischemic and bleeding risks using validated risk predictors (e.g., CHA 2 DS 2 -VASc, HAS-BLED) Keep triple therapy duration as short as possible; dual therapy only (oral anticoagulant and clopidogrel) may be considered in selected patients Consider a target INR of 2-2.5 when warfarin is used Clopidogrel is the P2Y 12 inhibitor of choice Use low-dose ( 100 mg daily) aspirin PPIs should be used in patients with a history of gastrointestinal bleeding and are reasonable to use in patients with increased risk of gastrointestinal bleeding Levine et al JACC 2016 2016 MFMER 3543652-42

Case #3 Consider: CHA2DS2VAsc: 3 (Age, HTN, DM) Technical issues with the PCI? Bleeding Risk (HAS-BLED) Triple Rx? Event monitor? PPI Follow-up and education 2016 MFMER 3543652-43

Case #4 An 82 year old woman with a long history of atrial fibrillation complains of increasing tiredness. She developed atrial fibrillation three years ago and was treated with digoxin Thought to be a fall risk so has been on aspirin 325 mg daily for stroke risk reduction 2016 MFMER 3543652-44

1. Cardioversion to sinus rhythm 2. Stop her digoxin 3. Add amiodarone 4. Add atenolol Kusumoto, ECG Interpretation: From Pathophysiology to Clinical Application 2009 2016 MFMER 3543652-45

Digoxin stopped 2016 MFMER 3543652-46

Atrial Fibrillation Inpatient Management How s the patient right now? Rate or rhythm Stop control? the digoxin Decide on a Strategy Continue (hospital a rate and control long-term) strategy Is something going to get better? Rate or Rhythm Control? Stroke risk-during hospitalization and longterm? CHA 2 DS 2 Vasc : 3 (3%/yr risk of stroke) CHADS 2 : 1 (2%/yr risk of stroke) 2016 MFMER 3543652-47

AVERROES: Apixaban vs. Acetylsalicylic Acid to Prevent Stroke in Atrial Fibrillation Patients Who have Failed or are Unsuitable for Vitamin K Antagonist Treatment 5,599 warfarin ineligible patients with AF randomized to Asa (81 mg daily) or apixaban (5 mg BID) Primary endpoint: Stroke, noncns embolism Age 70 yo Persistent AF 70% CHADS 2 Reason for warfarin ineligibility: CHADS 1 and VKA NR Poor INR Pt Refusal Adverse bleeding 21% 90% 38% 6% Connolly SJ NEJM 2011 2016 MFMER 3543652-48

Edoxaban vs. warfarin in patients at risk for falling ENGAGE AF TIMI-48 21,105 patients, 900 patients (4,3%) thought to be at risk for falling 2016 MFMER 3543652-49

Case #4 29 year old complains of palpitations and comes to the emergency room with lightheadedness No other medical problems 2016 MFMER 3543652-50

Wide, irregular, and very very fast Kusumoto, ECG Interpretation: from Pathophysiology to Clinical Application 2009 2016 MFMER 3543652-51

Wide, irregular, and very very fast Kusumoto, ECG Interpretation: from Pathophysiology to Clinical Application 2009 2016 MFMER 3543652-52

AF with preexcitation Cardioversion? Drug Rx: Procainamide 1 gm IV over 20 minutes Amiodarone 150 mg IV 2016 MFMER 3543652-53

WPW Pathophysiology and risk of SCD Think roads between two cities Education No drug Rx Follow-up: Catheter ablation (outpatient) 2016 MFMER 3543652-54