CHA2DS2-VASC vs Atrial Fibrosis for Predicting Stroke in the AF patient Nazem Akoum, MD, MS, FACC, FHRS Associate Professor of Medicine Director, Atrial Fibrillation Program University of Washington Seattle, WA @nazemakoum

Stroke and Atrial Fibrillation AF is associated with a 5-fold  in risk of stroke1 15-25 % of strokes in the US are attributable to AF1 Severity (and mortality) of stroke with AF is worse than without AF 3 Real number may be higher as some cryptogenic strokes are also suspected to be due to AF In 20-45% of those, AF is first diagnosed at the time of the stroke 1. Fuster V, et al. J Am Coll Cardiol. 2001;38:1232-1239. 2. Benjamin EJ, et al. Circulation. 1998;98:946-952. 3. Dulli A. et al. Neuroepidemiology. 2003;22:118-123. 4. Page RL et al. Circulation. 2003;107:1141-1145.

Embolic Stroke

Thrombo-embolism Risk Assessment Risk Category Risk Score AF Investigators NICE SPAF ACC/AHA/ESC ACCP CHADS2 CHA2DS2-VASc Content Slide Layout: TEXT Framingham CHADS2-revised

CHA2DS2-VASc CHF Hypertension Age Diabetes Stroke Vascular Disease 1 point for either clinical HF or LVEF <40% CHF 1 point Hypertension 1 point if 65-75 2 points if ≥75 Age Diabetes 2 points for prior stroke or TIA Stroke 1 point for coronary or peripheral vascular disease Vascular Disease 1 point if female Sex Category Total possible points = 9

Risk Assessment Tools Ease of Use Accuracy CHADS2 WA2S3DScR2 AFI CHA2DS2VASc AFI CHADS2 WA2S3DScR2

Stroke or Thrombo-embolism CHA2DS2-VASc

Receiver Operating Characteristic (ROC) curves

Comparison of Clinical Risk Stratification for Predicting Stroke and Thromboembolism in Atrial Fibrillation Fang et al, J Am Col Cardiol 2008 Aakre C et al Stroke2014

CHA2DS2-VASc scores for prediction of stroke Discrimination performance of CHADS2 and CHA2DS2-VASc scores for prediction of stroke or transient ischaemic attack (TIA). Receiver operator characteristic curves for the performance of CHADS2 (A) and CHA2DS2-VASc (B) scores in predicting incident stroke or TIA. L Brent Mitchell et al. Heart 2014;100:1524-1530

How to improve the predictive accuracy of CHA2DS2-VASc? Why does it perform poorly? Populations studied Specificity of component risk factors to AF related stroke Additional risk factors not included Mechanistic relationship to stroke, AF or both

Overall stroke rate in atrial fibrillation cohorts in order of descending stroke rate (events per 100 person-years). Overall stroke rate in atrial fibrillation cohorts in order of descending stroke rate (events per 100 person-years)‏ Gene R. Quinn et al. Circulation. 2017;135:208-219

CHA2DS2-VASc scores for prediction of stroke Discrimination performance of CHADS2 and CHA2DS2-VASc scores for prediction of stroke or transient ischaemic attack (TIA). Receiver operator characteristic curves for the performance of CHADS2 (A) and CHA2DS2-VASc (B) scores in predicting incident stroke or TIA. L Brent Mitchell et al. Heart 2014;100:1524-1530

Not Comprehensive Enough? Prior Stroke/TIA Age DM CHF Vascular disease Sex Kidney Disease Paroxysmal/Persistent Race/Ethnicity Family Hx/Genetics of Stroke Biomarkers

Goette, A Europace 2016

Biomarkers, AF and stroke Cushman, Stroke 2014

Troponin I NT-proBNP

Atrial Cardiomyopathy Goette, A Europace 2016

LGE-MRI of the left atrium

Image Processing: Segmentation and Quantification Quantification of left atrial fibrosis using LGE-MRI and image processing Oakes, Kholmovski, Marrouche et al. Circulation 2009 Apr 7;119(13):1758-67

LA LGE Correlates with Fibrosis in Human Tissue Samples 3D LGE-MRI image Masson’s trichome Myocytes (red) Collagen (blue) McGann, Wilson, Marrouche et al. Circ Arrhythm Electrophysiol 2014;7(1):23-30

LA Fibrosis and Ablation Success McGann et al. Circ Arrhythm Electrophysiol 2014;7:23-30

Left Atrial Sphericity Bisbal F, et al, JCE 2013

Atrial Fibrosis and Contractile Function Kuppahally S, Akoum N, et al Circ Cardiovasc Imag 2010

MRI fibrosis and history of stroke p<0.001 Stroke Prevalence (%) Quartile 1 (<8.5%) n=97 Quartile 2 (8.6-16%) n=97 Quartile 3 (16.1-21%) n=97 Quartile 4 (>21%) n=96 Daccarett et al J Am Coll Cardiol. 2011 Feb 15;57(7):831-8.

Trans-esophageal Echocardiography

Atrial Fibrosis and Thrombus Akoum et al, JCE 2013

LA Fibrosis and Risk of Stroke 1,223 patients King J et al. JACC 2017. 70 (11):1311-21

Predictive accuracy ROC analysis Model including CHADS2VASc, AF type, INR Model including CHADS2VASc, AF type, INR and Fibrosis Stage Akoum et al, JCE 2013

How to improve CHA2DS2-VASc? Better our understanding of thrombus formation and embolization Recognizing the role of atrial disease in this process is an important step forward We need more studies in large and inclusive populations to validate this approach

Thank you!

Stroke and Atrial fibrosis