1. 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

2. 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: Benjamin EJ, et al. Circulation. 1998;98: Dulli A. et al. Neuroepidemiology. 2003;22: Page RL et al. Circulation. 2003;107:

3. Embolic Stroke

4. 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

5. 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

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

7. Stroke or Thrombo-embolism
CHA2DS2-VASc

8. Receiver Operating Characteristic (ROC) curves

9. 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

10. 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:

11. 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

12. 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:

13. 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:

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

15. Goette, A Europace 2016

16. Biomarkers, AF and stroke
Cushman, Stroke 2014

17. Troponin I
NT-proBNP

18. Atrial Cardiomyopathy
Goette, A Europace 2016

19. LGE-MRI of the left atrium

20. 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):

21. 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

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

23. Left Atrial Sphericity
Bisbal F, et al, JCE 2013

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

25. 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
( %)
n=97
Quartile 4
(>21%)
n=96
Daccarett et al J Am Coll Cardiol Feb 15;57(7):831-8.

26. Trans-esophageal Echocardiography

27. Atrial Fibrosis and Thrombus
Akoum et al, JCE 2013

28. LA Fibrosis and Risk of Stroke
1,223 patients
King J et al. JACC (11):

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

30. 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

31. Thank you!

32. Stroke and Atrial fibrosis