Cryptogenic Stroke and AF - PowerPoint Presentation

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Cryptogenic Stroke and AF

Amit Kishore

Consultant and Honorary Senior Lecturer

in Stroke Medicine ,

SRFT

Amit.Kishore@srft.nhs.uk

January 2017Slide2

Cryptogenic strokes

‘

Brain infarction

that is not attributable to a source of definite cardioembolism, large artery atherosclerosis, or small artery disease despite a standard vascular, cardiac, and serologic evaluation’. Amount to 30% -35% of all stroke etiologies1

1. Adams HP et al. Stroke. 1993;24:35-41; 2. Causative Classification System for Ischemic Stroke (CCS). Available at: https://ccs.mgh.harvard.edu/ccs_intro.php; 3. Hart RG et al. Lancet Neurol. 2014;13:429-438; 4. Amarenco P et al. Cerebrovasc Dis. 2013;36:1-5

Classification

Diagnostic evaluation

TOAST criteria

1

Not specified

Causative Classification of Stroke (CCS)

2

Brain CT/MR, 12-lead ECG, precordial echocardiogram, extra/intravascular imaging

Embolic strokes of undetermined source

3

Brain CT/MR, 12-lead ECG, precordial echocardiogram, extra/intravascular imaging, cardiac monitoring for ≥24 hours

ASCO(D) phenotyping

4

Does not include a cryptogenic stroke categorySlide3

Cumulative probability of survival (A), stroke recurrence (B), and composite cardiovascular event (C) by stroke type.

George Ntaios et al. Stroke. 2015;46:2087-2093

Copyright © American Heart Association, Inc. All rights reserved.

ESUS 10%

20% recurrent stroke risk at 2 yearsSlide4

Potential aetiologies

Occult Paroxysmal Atrial Fibrillation

Patent Foramen Ovale (PFO)

Aortic Arch AtheromaOthersSlide5

PAF

Ischaemic

stroke is as common in PAF as in

permanent

AF 5,6 Earlier studies -The type of AF and the length of time the patient was in AF had no effect on the stroke rate 5,7

Difficult- >90% are asymptomatic, > 30% are intermittent

Change in management once AF diagnosedHow hard do we look to find PAF???5 Atrial fibrillation investigators. Risk factors for stroke and efficacy of antithrombotic therapy in atrial fibrillation. Analysis of pooled data from five randomized controlled trials. Arch Intern Med. 1994; 154: 1449-57 , 6 Friberg L, et al. Stroke prophylaxis in atrial fibrillation: who gets it and who does not? Report from the Stockholm Cohort-study on Atrial Fibrillation (SCAF-study). Eur Heart J. 2006; 27:1954-1964. 7 Hart RG,, et al. Stroke with intermittent atrial fibrillation: incidence and predictors during aspirin therapy. Stroke Prevention in Atrial Fibrillation Investigators. J Am Coll Cardiol. 2000; 35: 183–7 .Slide6
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I/P telemetry

(95% CI)

24h Holter

(95% CI)

>24h monitoring

(95% CI)

Pooled Proportion

(95% CI)

Unselected

5.5 (4.2-6.9)

5.0(2.0-9.0)

14.1(1.5-36.4)

6.2(4.4-8.3)

Selected

15.0(7.0-25.0)

10.7(3.4-21.5)

14.7(10.7-19.3)

13.4(9.0-18.4)Slide9

Incremental Yield of Prolonged ECG Monitoring

Gladstone DJ et al. N Engl J Med 2014;370:2467-2477Slide10

Time to First Detection of Atrial Fibrillation

30% new AF detection rates v 3%control at 3 yrs

Sanna T et al. N Engl J Med 2014;370:2478-2486Slide11

Cost effectiveness

Invasive monitoring: CS patients for three years using an ICM is cost-effective for the prevention of recurrent stroke, compared to SoC. An ICER of £17,175 per QALY gained was

<

£20,000 and £30,000 threshold considered as acceptable for government funding, according to the UK NICE 8Non-Invasive monitoring: With 7 days additional monitoring, the cost-utility ratio of outpatient cardiac monitoring would be $13,000 per quality-adjusted life-years gained based on 6% new AF detection rates

9Diamantopoulos A et al. Cost-effectiveness of an insertable cardiac monitor to detect atrial fibrillation in patients with cryptogenic stroke International Journal of Stroke 2016, Vol. 11(3) 302–312. Kamel H et al Stroke. 2010 Jul;41(7):1514-20Slide12

Standard AIS Work-Up

Brain Imaging

12-lead ECG

Lipid/Hba1cCarotid DopplersArrhythmia monitoring- 5-7 day cardiac monitoring+/-TTESlide13
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? 10 %Slide15

Stroke Patients

Stroke Burden

Number of patients with ischaemic stroke admitted in 2013/2014

3952

Percentage of strokes with undetermined cause (ESUS-Cryptogenic)

10%

 Number of ESUS- Cryptogenic Stroke Patients395 

AF detection and stroke risk reduction  Clinical OutcomesAF detection rate of Reveal at 3 years30%

AF detection rate of Standard of Care at 3 years

3%

Additional patients detected with AF with Reveal

107

Recurrence risk of stroke at 10 years

39%

Stroke risk reduction through treating AF with OAC

73%

Costs of Recurrent Stroke

Costs of stroke

NHS costs per stroke per patient over

5 years

£22,000

NHS costs per stroke per patient over

lifetime:

minor - major event

£28,000- £84,000

Total

costs per stroke over

10 years

£60,000

Results - Using Reveal in Secondary stroke prevention:

Without Reveal

With Reveal

Recurrent Strokes

Number of recurrent ischaemic strokes over lifetime

176

158

Clinical and economic outcomes

Estimated number of strokes avoided with Reveal

18

Quality adjusted life years gained with Reveal

47

Incremental Cost Effectiveness Ratio (DOACs)

£17,184Slide16

Conclusion

Diagnostic evaluation of IS important for targeted secondary prevention strategies

Occult AF is ‘tip of iceberg’ as cause of cryptogenic

strokesInitial cardiac monitoring strategies currently insufficient to pick up PAF: 9-fold increase in AF detection with ICMProlonged cardiac monitoring is cost-effectiveA cryptogenic stroke registry and ‘real-life’ data may be vital for QI.