11/27/2017 DISCLOSURE CRYPTOGENIC STROKE CLINICAL PATHWAYS. No Relevant Financial Disclosures Sub-Investigator LEARNING OBJECTIVES

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1 CRYPTOGENIC STROKE CLINICAL PATHWAYS Michelle Lee Kearney, ACNP-BC NP, Stroke Program St Thomas Health Nashville, TN DISCLOSURE No Relevant Financial Disclosures Sub-Investigator Stroke-AF Trial (Medtronic) RESPECT-ESUS (Boehringer Ingelheim) LEARNING OBJECTIVES Define cryptogenic stroke Apply the current diagnostic testing to identify cryptogenic stroke Implement appropriate interventions for cryptogenic stroke Provide possible pathway guidance 1

2 THE STROKE WORK-UP THE ETIOLOGY? CT CTA/MRA TELEMETRY LAB WORK ECHOCARDIOGRAM PROLONGED ECG MONITORING Adams et al., 1993; Li et al., 2015 (Jauch et al., 2013) EMBOLIC STROKE OF UNKNOWN SOURCE (ESUS)=CRYPTOGENIC Not lacunar, no extra- or intracranial stenosis supplying infarct area, no obvious ES, not other known reason (cancer, etc.) 1/3 of strokes are cryptogenic 1/3 of those are due to AF Atrial Fibrillation-Policy and Facility Priorities More AF to come as the population ages AF = 5x more likely to have a stroke Largest strokes Most debilitating Occult AF=AF that eluded detection during the initial stroke evaluation ParoxysmaAF= AF that is difficult to detect Only detectable with moderate or long term continuous monitoring Knowing = Changing Treatment Antiplatelet Agents vs Anticoagulation Adams et al., 1993; Li et al.,

3 CASE STUDY 21 year old male Right sided weakness, right face paresthesia, headache When he tried to stand in AM, he fell Anything else that you want to know? Headaches frequent especially on awakening and without meals Plays college football-denies any recent trauma Local ED: MRI, H/N CTA negative per report What do you think it is? ESR, CBC wnl Then new right eye blurriness Symptoms improved on arrival to CSC No medications, PMH: Sickle Cell Trait On initial assessment by hospitalist: Neuro intact; FNF without ataxia Initial DX: Atypical Migraine, started on 81mg ASA, admitted for observation NIHSS 0 LP NEGATIVE WHAT ABOUT THOSE OSH SCANS? NO ACUTE STROKE LATE SUBACUTE/EARLY CHRONIC INFARCT RIGHT LATERAL ASPECT OF MEDULLA What testing do you expect now? TESTING AND SPENDING TIME Echo with left to right shunt via PFO in the baseline state Oh, by the way: 2 weeks prior, dehydrated at football practice Hospitalized with Acute renal insufficiency, treated with fluids Coach says I can t believe you found a stroke, we see him every day Brainstem stroke = tough to find/see 3

4 DEFINING CRYPTOGENIC STROKE-AHA GUIDELINES 2014 (STROKE, 2014) Occult Atrial Fibrillation 10% with stroke DX in hospital 10% may be found in 30 days with monitoring Recommendation: prolonged monitoring for AF within 30D of event (IIA, C) 30% incidence of occult AF over a year Paradoxical Aortic Arch Hypercoagulable Embolism-Patent Atheroma states New Evidence Foramen (NEJM 2017): Ovale(PFO) Age > 50 or multiple vascular risk factors Multiple recommendations: Consider closure, Use ILR for AF detection Antiplatelet therapy the only IA evidence TEE w/aortic PFO plaque closure did not eliminate stroke risk Antiplatelet: thickness 4 mm Level <50 years IA ~fourfold increased Closure may be beneficial Statin: Level IB risk of recurrent Anticoagulant: ischemic stroke. Level IIbC WHY WAS THE MONITORING SO IMPORTANT AGAIN? Infarct topography did not predict AF detection (Bernstein et al. CerebrovascDis. 2015;40:91-6 ) Age and prolonged PR interval had minimal predictive ability (Thijs et al. Neurology 2016,19: ) Persistent and Paroxysmal AF carry the same risk AF may be intermittent AF often asymptomatic AF duration less important in presence of a Stroke? Think about your CHADS2VASC score Short/paroxysmal AF may lead to CHF and/or stroke WHAT S A CRYPTOGENIC PATHWAY? POST ACUTE ECG MONITORING OPTIONS? 4

5 WHAT TYPE OF MONITORING? Inpatient or Outpatient? Bridge Monitoring? 5

6 THE GOAL IS TO FIND AF AND TO TREAT AF RECORD CHADS2VASC SCORES STROKE AUTOMATICALLY MAKES IT A 2 = OAC In patients with a history of ischemic stroke or TIA and atrial fibrillation(af) including paroxysmal AF, GRADE 1A Oral anticoagulation over no antithrombotic therapy GRADE 1B Aspirin or combination of aspirin and clopidogrel (Jauch et al., 2013) BACK TO THE CASE STUDY Hypercoagulable Labs still pending External 14-day patch continuous monitoring loop recorder Returns to the Stroke Bridge Clinic Nothing significant with the labs External monitoring negative for any arrhythmia Insistent on returning to the football field Second opinion/conferral with neurologist who works with football teams Referral to Cardiology to evaluate the PFO FE-FI-FO WHAT ABOUT THAT PFO? Historical Data -PFO is present in 15% to 25% of the adult population -PFO and risk for cryptogenic ischemic stroke higher in younger patients Long-term f/u studies indicate that the patient with stroke and PFO eventually had another reason for the stroke (Elmariah et al., JACC, 2014) -Stroke may be more likely with coexistent atrial septal aneurysm Stroke, PFO, VTE = OAC Stroke, PFO = antiplatelet IMAGE: Stroke, PFO, VTE maybe closure Carroll et al. NEJM, 2013; Elmariah et al., JACC, 2014; Kent & Thaler. American Scientist, 2015; Mas et al. NEJM, 2017; Saver et al. NEJM, 2017 Stroke, PFO no closure evidence Kernan et al., Stroke,

7 PFO CLOSURE 2017 UPDATES NEJM, 2017, 377 All enrolled patients <60 years PFO closure did not eliminate stroke risk In older* (>50, OR multiple vascular risk factors) Consider closure AND use ILR In older*-more likely to find AF Benefit was there for the young person In younger *(age to 50 years) Closing these PFOs may be a good idea Carroll et al. NEJM, 2013;Elmariahet al., JACC, 2014; Kent & Thaler. American Scientist, 2015; Mas et al. NEJM, 2017; Saver et al. NEJM, 2017 CREATING A CRYPTOGENIC STROKE IN THE REAL WORLD ONE CENTER S EXPERIENCE (NOT PUBLISHED) OUR PRACTICE DESIGN 541 licensed bed Comprehensive Stroke Center 18,641 admissions per year 37,840 ER visits per year strokes per year (DRG based) Neurohospitalist model One NH 24/7 One NP 5 days per week 7

8 WRAPPING UP OUR CASE STUDY His PFO was closed Remains on ASA, Atorvastatin College Trainers have been in touch with NFL trainers for other players with Sickle Cell Trait NCAA Guidelines: He is on a medical redshirt until next fall and is preparing to play Intense teaching on hydration needs and symptoms to report TEE at 3 months shows no more PFO Follows with cardiology SUMMARY AND KEY LEARNING POINTS Complete work-up during the admission 30% of the time, no etiology PFO closure is for some patients External monitoring 7d-30d should catch % AF ILR should catch 9-30% (6 to 36 months) The investigation continues post-discharge PATHWAY ESSENTIALS Prolonged ECG monitoring to look for AF AF increases stroke risk by 5x! More debilitating strokes Discharged the patient without AF on Antiplatelet only Inpatient telemetry and ECG should catch % AF Create an alliance with EP/Cardiology to: Follow up on the external monitoring Communicate with the neurology team Create a way to receive ILR inpatient Help with the bridge monitoring Create a f/u cryptogenic stroke clinic THANK YOU! Michelle Kearney, ANCP-BC Michelle.kearney@ascension.org mkearney711@gmail.com

9 REFERENCES Carroll, J. D., Saver, J. L., Thaler, D. E., Smalling, R. W., Berry, S., MacDonald, L. A., Tirschwell, D. L. (2013). Closure of Patent Foramen Ovale versus Medical Therapy after Cryptogenic Stroke. New England Journal of Medicine, 368(12), Elmariah, S., Furlan, A. J., Reisman, M., Burke, D., Vardi, M., Wimmer, N. J., CLOSURE I Investigators. (2014). Predictors of recurrent events in patients with cryptogenic stroke and patent foramen ovale within the 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) trial. JACC. Cardiovascular Interventions, 7(8), Kent, D. M., & Thaler, D. E. (2015). When the Cause of Stroke Is Cryptic. American Scientist, 103(1), 54. Retrieved from Kernan, W. N., Ovbiagele, B., Black, H. R., Bravata, D. M., Chimowitz, M. I., Ezekowitz, M. D., Wilson, J. A. (2014). Guidelines for the Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke, 45(7), Li, L., Yiin, G. S., Geraghty, O. C., Schulz, U. G., Kuker, W., Mehta, Z., & Rothwell, P. M. (2015). Incidence, outcome, risk factors, and long-term prognosis of cryptogenic transient ischaemic attack and ischaemicstroke: a population-based study. The Lancet Neurology, 14(9), Li, J., Liu, J., Liu, M., Zhang, S., Hao, Z., Zhang, J., & Zhang, C. (2015). Closure versus medical therapy for preventing recurrent stroke in patients with patent foramen ovaleand a history of cryptogenic stroke or transient ischemic attack. The Cochrane Database of Systematic Reviews, (9), CD Mandrola, J. (2017, September 27). Positive Results for PFO Closure Come With Caveats. Retrieved November 13, 2017, from Mas, J.-L., Derumeaux, G., Guillon, B., Massardier, E., Hosseini, H., Mechtouff, L., Chatellier, G. (2017). Patent Foramen Ovale Closure or Anticoagulation vs. Antiplatelets after Stroke. New England Journal of Medicine, 377(11), Noble, S., Bonvini, R. F., Rigamonti, F., Sztajzel, R., Perren, F., Meyer, P., Roffi, M. (2017). Percutaneous PFO closure for cryptogenic stroke in the setting of a systematic cardiac and neurological screening and a standardised follow-up protocol. Open Heart, 4(1), e Saver, J. L., Carroll, J. D., Thaler, D. E., Smalling, R. W., MacDonald, L. A., Marks, D. S., & Tirschwell, D. L. (2017). Long-Term Outcomes of Patent Foramen Ovale Closure or Medical Therapy after Stroke. New England Journal of Medicine, 377(11), Thaler, D. E., & Kent, D. M. (2010). Patent foramen ovale: Rethinking trial strategies and treatment options. Current Opinion in Neurology, 23(1), Retrieved from 9