Thromboembolism During Sinus Rhythm in Patients with a History of Atrial Fibrillation

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1 48 th Annual New York Cardiovascular Symposium Thromboembolism During Sinus Rhythm in Patients with a History of Atrial Fibrillation Is Left Atrial Appendage Dysfunction Sufficient to Generate Clots? December 13, 2015 Jonathan L. Halperin, M.D. The Cardiovascular Institute Mount Sinai Medical Center

2 Disclosure Relationships with Industry Consultant to the following companies involved in developing anticoagulant drugs and device-based strategies for thromboembolism prevention: Bayer HealthCare Biotronik Boehringer Ingelheim Boston Scientific Bristol-Myers Squibb Daiichi Sankyo Janssen Ortho McNeil Johnson & Johnson Medtronic Pfizer

3 Munger TM, et al. J Biomed Res, 2014: 28; 1. Atrial Fibrillation in Context

4 Fibrotic Atrial Cardiomyopathy Characterization by Delayed-Enhancement MRI Marrouche NF, et al. JAMA 2014; 311: 498.

5 Recovery and Progression of Fibrosis after AF Ablation Relationship to Arrhythmia Recurrence Stable atrial lesions in a patient who remained arrhythmia-free after ablation Progressive atrial fibrosis in patient with recurrent AF after ablation Gal P, Marrouche NF. Eur Heart J 2015; (E-published September 25).

6 CV Event Rates in Patients with AF Related to CHADS 2 Score REACH Registry Goto S, et al. Am Heart J 2008; 156: 855.

7 CHA 2 DS 2 VASc Predicts Stroke in Patients with Heart Failure With or Without AF Melgaard L, et al. JAMA 2015; 314:1030.

8 Correlations of Cardiac Troponin I with Clinical and TEE Markers of Thromboembolic Risk in Patients with AF ROC Curves Providência R, et al. Int J Cardiol 2013; 167:877.

9 TEE Predictors of Thromboembolism In Relation to Inherent Risk S P A F TEE Frequency of TEE Finding (%) LAA abnormality* Complex aortic plaque LAA thrombus LAA flow velocity <20 cm/s * Dense SEC 0 Low risk Intermediate risk High risk Blackshear JL, et al. J Am Coll Cardiol 1998; 31:1622.

10 Relation of P-wave Dispersion to Appendage Function A Predictor of Recurrent AF after Conversion to NSR Dogan A, et al. Echocardiography 2004; 21: 523.

11 Association of Abnormal P-wave Morphology with Incident Stroke Multi-Ethnic Study of Atherosclerosis P-wave Terminal Force (Left Atrial Conduction Delay) in ECG Lead V1 Kamel H, et al. Stroke 2014; 45: 2786.

12 Stroke and Systemic Embolism in Relation to NT-proBNP Levels and CHA 2 DS 2 VASc Score ARISTOTLE Trial Hijazi Z, et al. J Am Coll Cardiol 2013; 61: 2274.

13 LAA Dysfunction and Embolic Stroke During NSR A Hypothesis in Need of Validation n = 9, Yaghi S, et al. Stroke 2015; 46: 3554.

14 S P A F III

15 Cardiac Rhythm Monitoring After Cryptogenic Ischemic Stroke CRYSTAL-AF Study Sanna T, et al. N Engl J Med 2014 ; 370: 2478.

16 Thromboembolism Related to the Burden of Subclinical Atrial Tachyarrhythmias TRENDS Study of Patients with Implanted Pacemakers Thromboembolism Rate (Events per 100 Patient-years) Zero AT Low AT (<5.5h) High AT (5.5 h) Glotzer TV, et al. Circ Arrhythm Electrophysiol 2009;2:474.

17 AF Burden and Stroke Risk in Patients with Implanted Monitoring Devices Odds Ratios for Ischemic Stroke AF burden 5.5 hours/day for Sequential 5-day Intervals n = 9, Turakhia MP, et al. Circ Arrhythm Electrophysiol 2015; 8: 1040.

18 Device-Detected Atrial Tachyarrhythmias and Clinical Thromboembolic Events Observations in 3 Studies Device-detected AT/AF (%) ASSERT TRENDS IMPACT 0 AT detected >30 d before TE Detection of AT/AF >30 Prior to TE Event (%) AT detected <30 d before TE Detection of AT/AF Within the 30 Days Prior to TE Event (%) AT detected at time of TE Detection of AT/AF At time of TE (%) AT detected after TE Detection of AT/AF After TE (%) Healey JS, et al. N Engl J Med 2012; 366: 120. Glotzer TV, et al. Circ Arrhythm Electrophysiol 2009; 2: 474. Martin DT, et a. Eur Heart J 2015; 38: 1660.

19 Temporal Relationship of AF & Thromboembolism IMPACT Trial AF Burden (0 to 100%, log scale) Months from TE Martin DT, et al. Eur Heart J 2015; (in press).

20 Contractile Discordance Between the LA and LAA In Patients with Paroxysmal AF Warraich HJ, et al. Stroke 2014; 45: 1481.

21 Thromboembolism During Sinus Rhythm in Patients with a History of Atrial Fibrillation Atrial Cardiomyopathy and Stroke During NSR Trials that defined the efficacy of anticoagulation predominantly enrolled patients with persistent and permanent AF, and the benefit for patients with low AF burdens has been less well explored. Current guidelines recommend continuing anticoagulation for patients with stroke risk factors and a history of AF, even when a rhythm control strategy is employed, based on the possibility of asymptomatic recurrent AF. Interrupting anticoagulation during antiarrhythmic drug therapy of AF has been associated with increased stroke risk, but whether this applies following AF ablation is less certain.

22 Thromboembolism During Sinus Rhythm in Patients with a History of Atrial Fibrillation Atrial Cardiomyopathy and Stroke During NSR Paroxysmal AF may lead to thrombus formation, but appendage morphology or flow patterns might delay the occurrence of embolism. Thrombus in the LAA and other mechanisms of embolic stroke may apply in patients without AF, and the risks associated with these mechanisms also correlate with increasing CHADS 2 and CHA 2 S 2 VASc scores. An inflammatory and/or hypercoagulable state present during AF might persist and predispose to thromboembolism during periods of sinus rhythm.

23 Device-detected Atrial Tachyarrhythmias Insights and Caveats: The AT Burden Device-detected AT are associated with stroke, but electrograms should be evaluated to exclude artifact and verify AT. The burden of AT associated with stroke varies across studies, but averages ~5 hours over a 30 day period. Consider the AT burden in the context of clinical risk factors.

24 Device-detected Atrial Tachyarrhythmias Insights and Caveats: Temporal Dissociation The temporal dissociation of AT from stroke in some studies raises the possibility that AF may not be the sole cause of stroke but a marker of stroke risk. Anticoagulation should be based on comprehensive assessment of risk and benefit rather than the onset or offset of device-detected AT.

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