Transcranial Doppler is superior to TEE for detection of Patent Foramen Ovale

Joshua Tobe, Chrysi Bogiatzi, Claudio Munoz, Arturo Tamayo, J. David Spence

Stroke Prevention & Atherosclerosis Research Centre,

Robarts Research Institute, Western University,

London, Canada

dspence@robarts.ca http://www.robarts.ca/sparc

Disclosures

No relevant disclosures Grants from NIH, CIHR, HSF Canada Support for research from Pfizer Speaker’s fees from Merck, AstraZeneca, Boehringer-Ingelheim Consulting fees from Boehringer-Ingelheim, Novartis Contract research with Servier Canada, Pfizer, Bristol-Meyers Squibb, AGA and NMT Interest in Vascularis.com

Paradoxical embolism

Hankinson and Hutcheson 1978

4% of ischemic stroke

Patching sounds like a good idea, but…

PFO Closure: Statistical power issue • 25% of the population have a PFO • 4-5.5% of strokes are due to paradoxical

embolism1,2 • ~ 80% of PFO’s in stroke patients are incidental • ~ 50% incidental in cryptogenic stroke3

1. Hutchinson,EC and Acheson, EJ. Strokes: natural history, pathology and surgical treatment. (4). 1975. London, W.B. Saunders.

2. Ozdemir AO, et al. J Neurol Sci 2008; 275: 121–127 3. Kent D, Thaler D. Stroke 2010;

Complications of percutaneous closure

• Atrial fibrillation

• Embolization of the device

– Aortic valve occlusion

– Femoral artery occlusion

• Thrombus on the device

Courtesy of Dr. Bob Kiaii and Dr. Bryan Dias

Surgical removal of Cardioseal device with thrombus 6 years after closure

Stroke in 2000 age 54; closure 2003; 2008 thrombus on device 6 months intensive anticoagulation Device removed 2009

PFO closure in stroke patients: a definite maybe

1. Kitsios GD, et al. Stroke 2013; 44:2640-2643.

2.Ntaios G et al.. Int. J Cardiol 2013; 169:101-105.

So: We need to identify which PFO patients are more likely to have

paradoxical embolism

Clinical Clues to Paradoxical Embolism 5.5% of new TIA/stroke patients Suspect if: • Young patient without other cause • Dyspnoea*, tachycardia at onset • ↓ O2, ↓ pCO2 • Loud P2, Pulmonic regurge • Loss of consciousness at onset of carotid stroke • Long ride in a car, airplane or sitting at computer* • Swollen leg, previous DVT, varicose veins* • Pulmonary emboli in past* • Valsalva maneuver* • Waking up with stroke* • Sleep apnea* *p<0.05 Ozdemir AO, et al. J Neurol Sci 2008; 275: 121–127

PFO morphology and stroke risk

Small early studies suggested features of

“high-risk PFO”:

• Larger shunt, septal mobility1

• Atrial septal aneurysm2

1. De Castro S et al. Stroke 2000;31:2407-2413. 2. Mas J-L et al N Engl J Med 2001; 345:1740-6.

Recent large studies: septal aneurysm/mobility do not predict events

1. Wessler B et al. Circ. Cardiovasc. Imaging 2013 Nov 8. [Epub ahead of print]. 2. Di Tullio MR et al. J Am Coll Cardiol 2013; 62:35-41.

• ROPE study1

• combined analysis of 1294 cases from 12 observational databases

• Northern Manhattan Study2 • Population-based study of 1100

participants, 14.9% with PFO, followed for 11 years

Better tools needed

“Additional tools to describe PFOs may be useful in helping to determine whether an observed PFO is incidental or pathogenically related to (cryptogenic stroke).”1

1. Di Tullio MR et al. J Am Coll Cardiol 2013; 62:35-41.

TCD more sensitive than TEE1

• Inadequate Valsalva2

• ? Eustachian valve3

• One small study (n=59) suggested shunt grade predicted events4

1.Bogousslavsky J et al. Neurology 1996; 46:1301-1305. 2. Rodrigues AC et al. J Am Soc Echocardiogr. 2013; 26:1337-1343. 3. Anzola GP. Stroke 2004; 35:e137. 4. Anzola,GP et al. Eur J Neurol 2003; 10:129-135.

Our study

• Patients referred to the Urgent TIA Clinic between 2000 and 2013

• Cryptogenic stroke • Suspected of having paradoxical embolism • All had TCD saline studies (TCDSS)

Our study

• 340 patients with RLS confirmed on TCDSS • 61.5% female, age 53 + 14 years • Median followup 420 days, max 3240 days • 85 had a recurrent ischemic stroke or TIA • 280 cases had TEE available • Atrial septal aneurysm or mobile septum in

54 cases (19.3%) • Echo failed to show RLS in 43 (15.4%)

TCD shunt grades

• Grade 0: no microemboli detected • Grade I: 1-10 microemboli • Grade II: 11-30 microemboli • Grade III: 31-100 microemboli • Grade IV:101-300 microemboli • Grade V: > 300 microemboli

Spencer MP et al. J Neuroimaging 2004; 14:342-349.

Bubbles are not subtle; they are definite

Before injection Without Valsalva maneuver

With Valsalva maneuver Ozdemir AO, et al. J Neurol Sci 2008; 275: 121–127

Besides the visual output and bubble count, there is an audio signal that is unmistakeable – on video clip at end

TCD better than Echocardiogram Echo missed 15% of right-to-left shunts

TCD Shunt Grade

% of shunts Missed by Echo

1 45.5% 2 32.2% 3 13.3% 4 7.1% 5 4.7%

Echo misses even large shunts n = 54/280

25% Grade 3 or higher

Survival free of stroke/TIA by TCD shunt grade

Survival free of stroke/TIA by RLS on TEE

Survival free of stroke/TIA by septal aneurysm/mobility

Conclusions

• TCDSS better for diagnosis of PFO • TCDSS better for risk stratification in PFO • TEE still needed for diagnosis of other

cardioembolic sources such as: • Left atrial appendage thrombus • Left atrial myxoma • Ventricular aneurysm, dyskinesia • Valve problems

• TCD and TEE are complementary

Acknowledgements 3-D Ultrasound technology Genetics Drs. Aaron Fenster, Grace Parraga Dr. Rob Hegele Measurements Lab Manager 2-D : Maria DiCicco RVT Tisha Mabb 3-D: Craig Ainsworth, CAIN Anthony Landry, Chris Blake, Dr. J-C Tardif et al. Micaela Egger, Christiane Mallet, Silvia Riccio Dr. Rob Beanlands Bernard Chiu, Shayna McKay, Adam Krasinsky Dr. Myra Cocker Ulcers Dr. Vadim Beletsky, Jeremy Mason, Amin Madani

Plaque composition Jeremy Mason, Dr. Joseph Awad, Mariya Kuk TCD Studies Dr. Arturo Tamayo Stroke Subtypes MRI Dr. Claudio Munoz Chrysi Bogiatzi Dr. Brian Rutt Scanning Dr. Dan Hackam PET/CT/MRI Maria DiCicco RVT Dr. Frank Prato Janine Desroches RVT Dr. Ting Lee

http://www.imaging.robarts.ca/SPARC/ dspence@robarts.ca

Grade V shunt