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Approaches towards decrypting ischemic strokes of unknown causes

(Cryptogenic ischemic strokes)

Deb Mojumder MD PhD

Neurology/Neurocritical care

3rd October 2017

Disclosures

None to disclose

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https://www.nbcnews.com/http://www.nbcnews.com/slideshow/cartoons-credit-crunch-31409267

Decoding

Objectives

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Ischemic Stroke

678,000/yr in the US1

1 Mozzafarian D, et al. Circulation. 2015;131:e29-e322.

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Case presentation

History:

40 Y-old rt-handed female

PMHx including smoking, Alcohol use, HTN, DLD

a/w Left face and arm weakness.

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Time course:

• 630 am : woke up went to feed her infant son-> feels weak-> falls down, unable to feed

• 9:30 am: loses manual dexterity lt UE, ex comes in, thinks she is drunk -> calls police-police does breathalyzer test=> negative, but does not activate EMS

• 10:00 pm her girlfriend comes in -> become increasingly concerned that pts deficits are not improving brings her to the hospital

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Initial CT head

DWI FLAIR

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http://www.timesfreepress.com/news/opinion/cartoons/story/2012/jul/22/probable-cause/83014/

Stroke WU = search for“probable cause”.

LEFT

RIGHT

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TTE: EF 55%, Enlarged right ventricle but with normal systolic function TEE: Non contributory LDL: 148 HbA1c: 4.9 Cardiac monitor: NSR documented so far EKG: Normal sinus rhythm. Possible Left atrial enlargement

Rest of Stroke WU

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?

Trial of ORG-10172 for Acute Stroke Treatment (TOAST) trial

Stroke of other determined etiology

?

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“Unknown” implies considering full workup:

• Neuroimaging: topographical features

• Imaging of large vessels,

• Cardiac rhythm monitoring

• Imaging of the heart,

• Serological studies

“Etiology” => Probabilistic Approach

Left Atrial Thrombus After Appendage Closure Using LARIAT Evaldas Giedrimas, Albert C. Lin and Bradley P. Knight Circulation: Arrhythmia and Electrophysiology. 2013;6:e52-e53, originally published August 20, 2013

Transesophageal image of the left atrial appendage: endocardial left atrial pedunculated thrombus

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“Etiology” => Probabilistic Approach..cont.

Variation in Risk Factors for Recent Small Subcortical Infarcts With Infarct Size, Shape, and Location Alessandra Del Bene, Stephen D.J. Makin, Fergus N. Doubal, Domenico Inzitari and Joanna M. Wardlaw Stroke. 2013;44:3000-3006, originally published October 21, 2013

“Etiology” => Probabilistic Approach..cont.

Cavitation After Acute Symptomatic Lacunar Stroke Depends on Time, Location, and MRI Sequence Francois Moreau, Shiel Patel, M. Louis Lauzon, Cheryl R. McCreary, Mayank Goyal, Richard Frayne, Andrew M. Demchuk, Shelagh B. Coutts and Eric E. Smith Stroke. 2012;43:1837-1842, originally published June 25, 2012

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“Etiology” => Probabilistic Approach..cont.

http://www.uwmedicine.org/health-library/Pages/large-artery-stroke.aspx

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Co-existance of more than one mechanism

“Etiology” => Probabilistic Approach..cont.

Epidemiology of cryptogenic stroke

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Geun Oh, Hyung & Rhee, Eun-Jung & Kim, Tae-Woong & Bok Lee, Kyung & Park, Jeong-Ho & Yang, Kwang & Jeong, Dushin & Park, Hyung-Kook. (2011). Higher Glycated Hemoglobin Level Is Associated with Increased Risk for Ischemic Stroke in Non-Diabetic Korean Male Adults. Diabetes & metabolism journal. 35. 551-7. 10.4093/dmj.2011.35.5.551.

Reference Study Design Sample Size Mean Age (years) Criteria for

Cryptogenic Stroke Frequency of Cryptogenic

Stroke

Besancon Stroke Registry (2000)63 Prospective registry 1776 71 Study-specific 18%

Athens Stroke Registry (2000)64 Prospective registry of first-ever strokes 885 70 Not specified 21%

German Stroke Data Bank (2001)65 Prospective registry 5017 66 Modified TOAST criteria 23%

WARSS (2001)66 Randomized trial 2206 63 TOAST criteria 26%

Erlangen Study (2001)67 Population-based 583 73 TOAST criteria 32%

Ankara (2002)68 Prospective registry 264 66 TOAST criteria 33%

Suwon (2003)69 Prospective registry 204 62 TOAST criteria 18%

TULIPS (Japan) (2004)70 Prospective registry 831 72 NINDS SDB 23%

Perugia (2006)71 Prospective stroke unit 358 NR TOAST criteria 17%

PRoFESS (2008)72 Randomized trial 20,332 66 TOAST criteria 16%

Bern (2008)73 Prospective registry 1288 NR TOAST criteria 39%

Buenos Aires (2010)74 Retrospective case series 155 67 TOAST criteria 27%

ASTRAL (2010)75 Prospective inpatient registry 1633 73 Modified TOAST

criteria 12%

North Dublin (2010)8 Population-based registry 381 NR Causative Classification System 26%

VITATOPS (2010)76 Randomized trial 8164 63 Study-specific 14%

PERFORM (2011)77 Randomized trial 19,100 67 Study-specific 22%

Mannheim Stroke Center (2012)78 Prospective case series 103 69 TOAST criteria 30%

Hebi, China (2012)79 Retrospective case series 425 65 TOAST criteria 16%

South Korea (2012)80 Prospective hospital-based registry 3278 64 TOAST criteria 21%

Miami/Mexico City (2012)81 Prospective registry of Hispanics 671 NR Modified TOAST criteria 17%

Santiago, Chile (2012)82 Prospective stroke unit 380 66 TOAST criteria 20%

Barcelona (2012)83 Prospective stroke unit 274 NR TOAST criteria 32%

Santiago de Compostela (2013)84 Prospective case series 1050 NR TOAST criteria 35% Bavaria (2013)85 Prospective stroke unit 393 62 TOAST criteria 17%

NR = not reported. TIA = transient ischemic attack. NINDS SDB = National Institute of Neurological Disorders and Stroke Data Bank

Frequency of Cryptogenic Ischemic Stroke Varies According to Study Design, Age, and Diagnostic Criteria for Cryptogenic Stroke Adapted from Hart RG, Diener H-C, Coutts SB, Easton JD, Granger CB, O’Donnell MJ, Sacco RL, Connolly SJ, for the Cryptogenic Stroke/ESUS International Working Group, with permission.

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Factors influencing prevalence

• Classification scheme:

– TOAST

– Causative Classification Scheme (CCS)

• supra-aortic large-vessel disease, cardioaortic embolism, small-vessel occlusion, other uncommon causes, or undetermined

• evident, probable, or possible

• Undetermined: unknown-cryptogenic embolism, unknown-other cryptogenic, unclassified, and incomplete evaluation

• lowest proportion classified as undetermined (26% versus 39% for TOAST in the North Dublin Stroke Study, n = 381

Factors influencing prevalence

• Population characteristics

– Age: younger cohorts

– Sex: ᴓ

– Race: AA and Hispanic

– Vascular risk factors: particularly hypertension: lower proportions (more than controls though)

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Factors influencing prevalence..cont.

• Diagnostic testing:

– Large vessel: Intracranial and intracranial: MRA, CTA and catheter based angio better than US

– Small vessel: Imaging : MRI, Clinical stroke syndrome: clinician

– Cardio-embolic: TEE>TTE

Proposed etiologies

• Common risk factors shared by small vessel, large vessel, or cardiac cause: HTN, smoking, DLD, Obesity, DM

• Conceptual framework:

– Under-classified,

– under-measured

– true cryptogenic

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https://en.wikipedia.org/wiki/Carotid_artery_stenosis https://herbalcareproductstreatment.files.wordpress.com/2015/06/atrial-fibrillation.jpg

? Classification (Under-classified)

Measurement (Under measured)

True cryptogenic

Case presentation 1 (Under-Measured Cryptogenic)

• 62-year-old female

• H/o hypertension and obesity

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Rx ASA 325 + Atorvastatin 80

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3 months later : severe palpitations

CHADS-VASC2 score

4 points : Stroke risk was 4.8% /yr

Criteria Value Points

Age

<65 years old 0

65-74 years old +1

≥ 75 years old +2

Sex Male 0

Female +1

Congestive heart failure history

Y/N +1

Hypertension history Y/N +1

Stroke/TIA/thromboembolism history

Y/N +2

Vascular disease history Y/N +1

Diabetes mellitus history Y/N +1

Ntaios G, Lip GY, Makaritsis K, Papavasileiou V, Vemmou A, Koroboki E, Savvari P, Manios E, Milionis H, Vemmos K. CHADS₂, CHA₂S₂DS₂-VASc, and long-term stroke outcome in patients without atrial fibrillation. Neurology. 2013 Mar 12;80(11):1009-17. doi: 10.1212/WNL.0b013e318287281b. Epub 2013 Feb 13. PubMed PMID: 23408865.

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Rx

Summary

• Initial presentation supports an embolic etiology, with M2 clot.

• RF for Afib: hypertension + obesity+ enlarged left atrium

• Paroxysmal atrial fibrillation in retrospect the likely cause of her initial stroke

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“Detection of AF” most important in determining therapy

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Duration of monitoring affects Afib detection in patients with

cryptogenic stroke

Study Duration of

monitoring

(months)

Definition

of AF

Time to

Diagnosis

(days)

AF detection rate

(%)

Ritter1 10 >30 seconds 64 17

Etgen2 12 >6 minutes 152 27

Cotter3 8 2 minutes 48 25

SURPRISE4 19 >2 minutes 109 16

Rojo-Martinez5 9 2 minutes 102 33

Ziegler6 6 2 minutes 58 12

Poli7 12 > 2 minutes 105 33

Jorfida8 14.5 > 5 minutes 162 46

CRYSTAL AF9

(ICM arm)

6

12

36

>30

seconds

41

84

252

9

12

30

1Ritter et al, Stroke. 2013, 44:1449-52; 2Etgen et al, Stroke. 44:2007-2009; 3Cotter et al, Neurology. 2013, 80:1546-50; 4Christensen et al, Eur J Neurol. 2014, 21:884-89; 5Rojo-Martinez Rev Neurol

2013; 57 (6): 251-257; 6Ziegler et al, Cerebrovasc Dis. 2015, 40:175-81. 7Poli Eur J Neurol. 2015 Oct 16 Epub ahead of print ;8 Jorfida J Cardiovasc Med (Hagerstown). 2014 Nov 15. [Epub ahead

of print] 9Sanna T et al, NEJM. 2014;370:2478-2486;

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Detection of AF is most important in determining therapy, how long the heart is monitored is important: CRYSTAL-AF trial (2014)

CRYSTAL AF = CRYptogenic STroke and underlying. AtriaL Fibrillation

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http://www.medtronic.com/us-en/patients/treatments-therapies/fainting-heart-monitor/reveal-linq-icm.html

Reveal-Linq implantable cardiac monitor

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CRYSTAL AF1:

STUDY DESIGN AND END POINTS

• RCT 441 patients

• Continuous, long-term monitoring with

Reveal™ ICM vs. conventional follow-up

• Assessment at scheduled and unscheduled visits

• ECG monitoring performed at the discretion of the site

investigator

20%

15%

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

End Point

Primary Time to first detection of AF at 6 months of follow-up

Secondary Time to first detection of AF at 12 months

Recurrent stroke or TIA

Change in use of oral anticoagulant drugs

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CRYSTAL AF1:

STUDY POPULATION

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

447 patients were enrolled

6 were excluded 4 did not meet eligibility criteria

2 withdrew consent

441 underwent randomization

221 were assigned to ICM 208 had ICM inserted

13 did not have ICM inserted

220 were assigned to control 220 received standard of care

12 crossed over to control

12 exited the study 3 died

1 was lost to follow-up

5 withdrew

3 were withdrawn by investigator

6 crossed over to ICM

13 exited the study 2 died

1 was lost to follow-up

7 withdrew

3 were withdrawn by investigator

221 were included in intention-to-treat analysis 220 were included in intention-to-treat analysis

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CRYSTAL AF1:

ELIGIBILITY

• ≥ 40 years

• Stroke or TIA < 90 days

• Stroke was classified as cryptogenic

after extensive testing:

• 12-lead ECG

• ≥ 24 hours of ECG monitoring

• TEE

• Screening for thrombophilic states

(in patients < 55 years of age)

• Magnetic resonance angiography,

computerized tomography

angiography, or catheter angiography

of head and neck

• Ultrasonography of cervical arteries or

transcranial Doppler ultrasonography

of intracranial arteries allowed in place

of MRA or CTA for patients aged

≥ 55 years

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

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CRYSTAL AF1:

BALANCED BASELINE PATIENT CHARACTERISTICS

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

Characteristic ICM

(n = 221)

Control (n = 220)

P

Age (years) 61.6 ± 11.4 61.4 ± 11.3 0.84

Male 64.3% 62.7% 0.77

White 87.8% 86.8% 0.60

Patent foramen ovale 23.5% 20.9% 0.57

Index event 0.87

Stroke 90.5% 91.4%

TIA 9.5% 8.6%

50

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

Scheduled and unscheduled EKG monitoring

Duration of cardiac monitoring

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CRYSTAL AF:

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

12 months

97% of patients in whom AF was detected received oral anticoagulants

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CRYSTAL AF:

MEDIAN TIME TO DETECTION OF AF

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

84 Days in the ICM group (range 18 to 265 days)

53 Days in control group (range 17 to 212 days)

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CRYSTAL AF1:

SAFETY

•2.4% removed due to infection or pocket

erosion

•Most common adverse events:

•Infection (1.4%)

•Pain (1.4%)

•Irritation or inflammation (1.9%)

Note: Reveal™ XT used in this study.

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

• Under-Measured Cryptogenic: Paroxysmal atrial fibrillation

• Detection makes a difference in treatment

• New evidence on monitoring duration

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Case presentation 2 : under-classified

• 71-year-old man

• h/o MI and PVD

CT angiography of carotids reports 40% stenosis bilaterally. Cardiac monitoring and transthoracic echocardiogram are normal. Transesophageal echocardiogram reveals non-significant atherosclerosis of aortic arch (<4 mm)

Neglect

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Interpretation

• No large-vessel disease (per defination)

• Multi-bed atherosclerosis • Alternative etiologies (e.g., paroxysmal atrial

fibrillation) that may co-exist in patients with atherosclerosis should also be considered

Novel approaches to imaging acute thrombosis or unstable plaque in large vessels may clarify these types of cases in the future.

Complexity of plaques on 3D transoesophageal imaging of atheromas

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Amarengo , P., et al. (1992). "The Prevalence of Ulcerated Plaques in the Aortic Arch in Patients with Stroke." New England Journal of Medicine 326(4): 221-225.

Amarengo , P., et al. (1992). "The Prevalence of Ulcerated Plaques in the Aortic Arch in Patients with Stroke." New England Journal of Medicine 326(4): 221-225.

1992

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Aortic atheromas & acute ischemic stroke

Di Tullio, M. R., et al. (1996). "Aortic atheromas and acute ischemic stroke: a transesophageal echocardiographic study in an ethnically mixed population." Neurology 46(6): 1560-1566.

Case-control study :106 ischemic stroke vs 114 stroke-free. • TEE. • Categories:

1. Thickness: small, large 2. Complexity (i.e., ulceration or mobility): complex, non-

complex • Measure: OR (outcome/exposure)

Large noncomplex aortic atheromas >0.5cm

Aortic atheromas and acute ischemic stroke..cont.

Di Tullio, M. R., et al. (1996). "Aortic atheromas and acute ischemic stroke: a transesophageal echocardiographic study in an ethnically mixed population." Neurology 46(6): 1560-1566.

Small noncomplex aortic atheromas: 0.2 to 0.4 cm

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Aortic atheromas and acute ischemic stroke..cont.

Di Tullio, M. R., et al. (1996). "Aortic atheromas and acute ischemic stroke: a transesophageal echocardiographic study in an ethnically mixed population." Neurology 46(6): 1560-1566.

Complex aortic atheromas : Ulceration

Complex aortic atheromas : mobile comp.

Results

large aortic atheromas ↔stroke, (adjusted for stroke risk factors) (OR 2.3, 95% CI 1.1 to 5.0).

(20.5 cm)

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Frequency of Ulcerated or mobile plaque in >60 yr olds with cryptogenic stroke vs controls

>60 years

? 22% 8%;

OR 3.4,

95% CI 1.1 to 11.21,

14%

Summary

• While considering aortic arch atheroma one must consider the size as well as the complexity as a risk factor for cryptogenic stroke

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Secondary prevention: Aortic Arch Plaques

Treatment With Warfarin or Aspirin:

RCT 0 to 85 years of age 516 patients TEE Aspirin in 325-mg tablets vs Warfarin :INR of 1.4 to 2.8 Vs identical placebo. FU 2 years Di Tullio MR, Russo C, Jin Z, Sacco RL, Mohr JP, Homma S. Aortic Arch Plaques and Risk of Recurrent Stroke and Death. Circulation. 2009;119(17):2376-2382. doi:10.1161/CIRCULATIONAHA.108.811935.

Primary end-points (2 yrs)

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• Two-year incidence of recurrent stroke/death was similar between the warfarin-treated (43 of 256, 16.4%) and aspirin-treated (41 of 260, 15.8%; P=0.43) groups.

• The incidence of major hemorrhagic events was low and similar between the warfarin and aspirin groups (0.88 versus 2.16 per 100 patient-years; P0.13).

• Minor hemorrhagic events were more frequent in the warfarin group (26.76 versus 10.0 per 100 patient-years; P0.001).

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Caveat: patient selection - procoag activity of atheromatous plaque

Morteza Naghavi, Peter Libby, Erling Falk, S. Ward Casscells, Silvio Litovsky, John Rumberger, Juan Jose Badimon, Christodoulos Stefanadis, Pedro Moreno, Gerard Pasterkamp, Zahi Fayad, Peter H. Stone, Sergio Waxman, Paolo Raggi, Mohammad Madjid, Alireza Zarrabi, Allen Burke, Chun Yuan, Peter J. Fitzgerald, David S. Siscovick, Chris L. de Korte, Masanori Aikawa, K.E. Juhani Airaksinen, Gerd Assmann, Christoph R. Becker, James H. Chesebro, Andrew Farb, Zorina S. Galis, Chris Jackson, Ik-Kyung Jang, Wolfgang Koenig, Robert A. Lodder, Keith March, Jasenka Demirovic, Mohamad Navab, Silvia G. Priori, Mark D. Rekhter, Raymond Bahr, Scott M. Grundy, Roxana Mehran, Antonio Colombo, Eric Boerwinkle, Christie Ballantyne, William Insull, Robert S. Schwartz, Robert Vogel, Patrick W. Serruys, Goran K. Hansson, David P. Faxon, Sanjay Kaul, Helmut Drexler, Philip Greenland, James E. Muller, Renu Virmani, Paul M Ridker, Douglas P. Zipes, Prediman K. Shah and James T. Willerson Circulation. 2003;108:1664-1672, originally published October 6, 2003

http://physrev.physiology.org/content/physrev/93/3/1247/F3.large.jpg

Caveat: patient selection - procoag activity of atheromatous plaque

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Aortic Plaques and Risk of Ischemic Stroke

Caveat: patient selection - procoag activity of atheromatous plaque (APRIS

trial)

Di Tullio MR, Homma S, Jin Z, Sacco RL. Aortic Atherosclerosis, Hypercoagulability and Stroke: the Aortic Plaque and Risk of Ischemic Stroke (APRIS) Study. Journal of the American College of Cardiology. 2008;52(10):855-861. doi:10.1016/j.jacc.2008.04.062.

Transesophageal echocardiography in 255 patients with first acute ischemic stroke Vs 209 control subjects matched by age, sex and race-ethnicity. The association between arch plaques and hypercoagulability, and its effect on the stroke risk, was assessed with a case-control design

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Di Tullio MR, Homma S, Jin Z, Sacco RL. Aortic Atherosclerosis, Hypercoagulability and Stroke: the Aortic Plaque and Risk of Ischemic Stroke (APRIS) Study. Journal of the American College of Cardiology. 2008;52(10):855-861. doi:10.1016/j.jacc.2008.04.062.

Caveat: patient selection - procoag activity of atheromatous plaque (APRIS trial)

3x more strokes

Statin (matched-paired analysis for stroke RF)

relative risk reduction for AIS 59 %

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• Under-classified Cryptogenic: Aortic arch atheroma

• ASA~Warfarin in general

• Untested potential for Warfarin in hypercoagulable states

• Statins highly effective in risk reduction

Case presentation 3: True cryptogenic

• 38-year-old woman

• ᴓ PMHx

• ᴓ traditional risk factors for ischemic stroke,

• ᴓ medical co-morbidities,

• ᴓ systemic illness

• ᴓ FH of premature stroke.

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Eyes and stroke: the visual aspects of cerebrovascular disease John H Pula, Carlen A Yuen Stroke and Vascular Neurology Jul 2017, svn-2017-000079; DOI: 10.1136/svn-2017-000079

R R

L

LED: -ve

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• Five-day Holter monitor: WNL

• CT angio H&N: WNL

• MRV: WNL

• Thrombophilic screen: WNL

Notes on true cryptogenic stroke

http://www.mayoclinic.org/diseases-conditions/patent-foramen-ovale/symptoms-causes/dxc-20345732 https://www.slideshare.net/Rajeswaran1990/cardio-vascular-diseases

?

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Notes on true cryptogenic stroke..cont.

multiple hit theory Langevin C, Lamarche C, Bell RZ, Vallée M. Presumed paradoxical embolus in a patient with diabetic ketoacidosis. International Journal of General Medicine. 2015;8:297-301. doi:10.2147/IJGM.S87521. http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/hematology-oncology/hypercoagulable-states/ Kopp, J. B. and R. Schiffmann (2003). "Fabry's Disease." New England Journal of Medicine 349(21): e20.

↓α-galactosidase A

Overell JR, Bone I, Lees KR. Interatrial septal abnormalities and stroke: a meta-analysis of case-control studies. Neurology. 2000 Oct 24;55(8):1172-9. PubMed PMID: 11071496.

Strong association of PFO and Cryptogenic Stroke (retrospective)

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Association of PFO and Stroke Meta-analysis of case control studies 2014 stroke patients to 2020 non-stroke controls

OR 1.8 (95%CI: 1.3-2.7) overall

OR 3.1 (95% CI: 2.3-4.2) <55 years old

.

Overell JR, Bone I, Lees KR. Interatrial septal abnormalities and stroke: a meta-analysis of case-control studies. Neurology. 2000 Oct 24;55(8):1172-9. PubMed PMID: 11071496.

• Case-control study including 1072 subjects who underwent TEE, including 519 randomly selected controls from population - Adjusted for age, sex, and vascular risk factors - Blinded echo interpretation • No association of stroke with PFO - Stroke of known cause OR 0.95 (95%CI: 0.6-1.6) -Cryptogenic stroke OR 1.3 (95%CI: 0.8-2.1) • No impact of size or detection of PFO at rest

Petty GW, et al. Mayo Clinic Proc 2006

Debate: No association between PFO and Stroke

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PFO in Cryptogenic Stroke Study (PICSS)

PFO in (recurrent) Cryptogenic Stroke (PICSS): secondary prevention

• 42-center study that evaluated transesophageal echocardiographic findings in patients randomly assigned to warfarin or aspirin

• 630 stroke patients

– 312 (49.5%) warfarin

– 318 (50.5%) aspirin.

• Of these, 265 patients experienced cryptogenic stroke and 365 experienced known stroke subtypes

Homma S, Sacco RL, Di Tullio MR, Sciacca RR, Mohr JP; PFO in Cryptogenic Stroke Study (PICSS) Investigators. Effect of medical treatment in stroke patients with patent foramen ovale: patent foramen ovale in Cryptogenic Stroke Study. Circulation. 2002 Jun 4;105(22):2625-31. PubMed PMID: 12045168.

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Primary end-points (2 yrs)

efficacy of warfarin ~ aspirin

Medical management:

=

https://acphospitalist.org/archives/2008/02/expert.htm

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Pathophysiology of Paradoxical embolism in PFO

L

Detection of R->L Shunt : TCD

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High-intensity transient signals (HITS)

http://circ.ahajournals.org/content/circulationaha/126/10/1245/F1.large.jpg?width=800&height=600&carousel=1

Detection of RLS :TCD likely superior to TEE

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TCD detects effects of RLS “of any cause” in the cerebral vasculature

Noble, Stephane, Fabienne Perren, and Marco Roffi. "Cryptogenic stroke with right-to-left shunt and no patent foramen ovale." Archives of cardiovascular diseases 107.6 (2014): 418-419.

Surgical closure

• The first large, randomized trial of patent foramen ovale closure using a device, CLOSURE I (Evaluation of the STARFlex Septal Closure System in Patients with a Stroke and/or Transient Ischemic Attack due to Presumed Paradoxical Embolism through a Patent Foramen Ovale),

showed that the STARFlex device wasn’t superior to medical therapy

for preventing recurrent ischemic stroke

http://slideplayer.com/6041161/20/images/24/Atrial+Septal+Defect+Closure.jpg

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RESPECT TRIAL: Randomized Evaluation of Recurrent Stroke

Comparing PFO Closure to Established Current Standard of Care Treatment

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Acute management:

– Thrombolysis (tPA)

– Stroke unit care (organized inpatient care)

https://www.intechopen.com/books/fibrinolysis-and-thrombolysis/an-insight-into-the-abnormal-fibrin-clots-its-pathophysiological-roles

Organised stroke unit care is a form of care provided in hospital by nurses, doctors and

therapists who specialize in looking after stroke patients and work as a co-ordinated team

Acute management:….cont.

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• 28 trials, 5855 participants: – more likely to survive their stroke,

– return home

– become independent in looking after themselves.

• A variety of different types of stroke units.

Best results : dedicated ward.

Management implications…cont

• Secondary prevention:

– Lifestyle modifications

– Anti-HTN treatment

– Statin

– Anti-thrombotic (debate)

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Summary

https://en.wikipedia.org/wiki/Carotid_artery_stenosis https://herbalcareproductstreatment.files.wordpress.com/2015/06/atrial-fibrillation.jpg

? Under-classified

Under measured

True cryptogenic

Summary

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CRYSTAL AF

Summary

Neglect

Di Tullio, M. R., et al. (2009)

Summary

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efficacy of warfarin = aspirin Summary

Secondary prevention

Summary

Acute management

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Thank you

Questions?