The Brain & Heart Connection

Ryna K. Then, MDDirector of Stroke ProgramAssistant Professor of Neurology Cooper Medical School of Rowan Medical School (CMSRU)Cooper Neurological Institute (CNI)Cooper University Health CareMT2020+ US Physician Liaison

Disclosures

• No relevant disclosures

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Learning Objectives

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• Determine how the heart and brain are connectedo Cardioembolic strokes

• Learn about relationship between cardiac markers and stroke• Discuss common stroke risk factors related to cardioembolism

(Afib/Atrial Cardiopathies)

Brain & Heart Relationship

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Background

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• 20-30% of ischemic strokes are caused by cardiac disease• Cardioembolic stroke generally carries a worse prognosis with respect to disability, mortality, and

both early and long-term recurrence of stroke compared to other etiologies• There is clinical and experimental evidence suggests a causal relationship between brain damage and

heart dysfunction• The Framingham study reported that stroke incidence more than doubled in the presence of

coronary heart disease, more than tripled with hypertension, increased 4-fold with cardiac failure, and increased 5-fold with atrial fibrillation

Ischaemic stroke in young adults: risk factors and long-term consequences. Maaijwee, N. A. M. M. et al. Nat. Rev. Neurol. 10, 315–325 (2014)

Zhili Chen, Poornima Venkat, Don Seyfried, Michael Chopp, Tao Yan, Jieli Chen. Brain–Heart Interaction. Cardiac Complications After Stroke. Circulation Research. 2017;121:451–468

Hayang Yang1,2, Martina Nassif1, Paul Khairy3, Joris R. de Groot, Yvo B.W.E.M. Roos4, Robbert J. de Winter1, Barbara J.M. Mulder1,2, and Berto J. Bouma1 . Cardiac diagnostic work-up of ischaemic stroke. European Heart Journal (2018) 39, 1851–1860

Overlap among stroke etiologies

5Hooman Kamel, Jeff S. Healey. Cardioembolic Stroke. Circ Res. 2017;120:514-526

How do you know a stroke is cardioembolic?

• Sudden onset of neurological deficits that are maximal at onset

• Cardiac embolism often lodges in distal arteries supplying the cerebral cortex

• Clinical characteristics pluso Neuroimagingo Cardiaco Vascular evaluation

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Oh Young Bang, MD, PhD, Bruce Ovbiagele, MD; Jong S. Kim, MD, PhD. Evaluation of Cryptogenic Stroke With Advanced Diagnostic Techniques. Stroke. 2014;45:1186-1194

Cardioembolic Stroke

7Hayang Yang, Martina Nassif, Paul Khairy, Joris R. de Groot, Yvo B.W.E.M. Roos, Robbert J. de Winter, Barbara J.M. Mulder, and Berto J. Bouma . Cardiac diagnostic work-up of ischaemic stroke. European Heart Journal (2018) 39, 1851–1860

Updated Model of Cardioembolic Stroke

8Hooman Kamel, MD; Peter M. Okin, MD; Mitchell S.V. Elkind, MD, MS; Costantino Iadecola, MD Atrial Fibrillation and Mechanisms of Stroke Time for a New Model. Stroke. 2016;47:895-900

The Brain & Heart Connection

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Zhili Chen, Poornima Venkat, Don Seyfried, Michael Chopp, Tao Yan, Jieli Chen. Brain–Heart Interaction. Cardiac Complications After Stroke. Circulation Research. 2017;121:451–468

The Brain & Heart Connection

10Zhili Chen, Poornima Venkat, Don Seyfried, Michael Chopp, Tao Yan, Jieli Chen. Brain–Heart Interaction. Cardiac Complications After Stroke. Circulation Research. 2017;121:451–468

• Cardiac dysfunction manifested during the acute phase after brain injury usually resolves over the following several weeks alongside improvement of neurological function

o Decreased LVEFo Ventricular wall motion abnormalitieso Elevated serum cardiac enzymes

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The Brain & Heart Connection

12Rongjun Zou, Wanting Shi, Jun Tao, Hongmu Li, Xifeng Lin, Songran Yang, and Ping Hua. Review Article. Neurocardiology: Cardiovascular Changes and Specific Brain Region Infarcts. BioMed Research International. Volume 2017, Article ID 5646348.

The Brain & Heart Connection

Clinical Case

• 72 years old Woman with history of CAD on ASA and Plavix, HTN, DM, HLD, bilateral pontine strokes presents with right arm and leg weakness

• Outside the window for IVT or MER• Initial labs were unrevealing except for mildly elevated

troponins• TTE was normal

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Clinical Case

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What are the clues?

15Oh Young Bang, MD, PhD, Bruce Ovbiagele, MD; Jong S. Kim, MD, PhD. Evaluation of Cryptogenic Stroke With Advanced Diagnostic Techniques. Stroke. 2014;45:1186-1194

Troponin Elevation

• What are the mechanisms and pathophysiology behind an elevated troponin in the setting of acute stroke?

• Does it affect prognosis and mortality?

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• Elevated troponin level after acute stroke is common

• Associated with ECG changes suggestive of myocardial ischemia

• Increases risk of death

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Troponin Elevation

• 5 to 10%• Troponin T more specific biomarker• Most recent reviews showed 1 in 5 patients

have elevated troponins • Some studies stated that troponin elevation is

an independent predictor of death

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Troponin Elevation

• Implantable cardiac monitor placed• Discharge to inpatient rehabilitation

• Afib found at 83 days post index event• Patient started on DOAC

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Back to our clinical case…

Atrial Fibrillation

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• 33 million people worldwide• Subclinical Afib leading mechanism of ESUS • Recent guidelines make a moderate recommendation for post

discharge heart-rhythm monitoring• It remains unclear whether anticoagulation is superior to

antiplatelet therapy for secondary prevention of stroke in patients with subclinical AF detected after ESUS

Mechanism of Stroke in Afib

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Atrial Fibrillation (Afib)

23Youcheng Wang, Yongsheng Qian, Daniel Smerin, Shujuan Zhang, Qingyan Zhao, Xiaoxing Xiong. Newly Detected Atrial Fibrillation after Acute Stroke: A Narrative Review of Causes and Implications. AF and Stroke: Review Article. Cardiology . DOI: 10.1159/000502971

Occult Atrial Fibrillation

• ¼ of all AIS ; > ½ of cardioembolic origin• 8% receives new diagnosis on first ECG• Loop recorder, 2-4 weeks cardiac telemetry, PPM and ICD with

ability to detect Afib• CRYSTAL AF 9% 6 months, 12% at 1 year, and 30% at 3 years

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Heart Monitoring

25Carlos Cantu´-Brito, MD, PhD, Gisele Sampaio Silva, MD, MPH, PhD,w and Sebastia´n F. Ameriso, MD Embolic Stroke of Undetermined Source in Latin America. A Review. The Neurologist Volume 22, Number 5, September 2017

Treatment of Atrial Fibrillation

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Reversal agents for non-vitamin K antagonist oral anticoagulants. NATURE REVIEWS | CARDIOLOGY. 2018

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Hooman Kamel, Jeff S. Healey. Cardioembolic Stroke. Circ Res. 2017;120:514-526.

Atrial Cardiopathy

• First introduced 1972 • 1997 associated Afib• 2017-Introduced as Atrial cardiomyopathy (EHRA,

A/PHRA, AHA, ACC)• “ Any complex of structural, architectural, contractile

or electrophysiological changes affecting the atria with potential to produce clinical relevant manifestations”

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• May cause cardiac thromboembolism• LA volume measurement (34 ml/m2)

o Volume adjusted for body surface area

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Atrial Cardiopathy

How do we measure atrial cardiopathy?

• P wave terminal force in lead V1 of EKG • Paroxysmal supraventricular tachycardia• Biomarkers

o NT-proBNP (Amino-terminal pro-B type natriuretic)

o HS cTNT (high sensitive troponins)

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Stroke Mechanism of Atrial Atriopathy

• Left atrial enlargemento Promotes stasis, endothelial dysfunction and

thrombus formation

• Cardiac fibrosis (HTN, CAD, aging)• Inflammation

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Atrial Cardiopathy

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Atrial Cardiopathy

ARCADIA

• ASA Vs Apixaban• ESUS and

markers of atrial cardiopathy

• Incidence of recurrent stroke

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Embolic Stroke of Undetermined Source (ESUS)

• 20-30%• Recent

studies have tried to prove benefit on AC

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Hooman Kamel, MD1,3; Alexander E. Merkler, MD1; Costantino Iadecola, MD1; et al Ajay Gupta, MD1,2; Babak B. Navi, MD1 . Tailoring the Approach to Embolic Stroke of Undetermined Source: A Review. JAMA Neurol. 2019;76(7):855-861

Common causes of ESUS

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Ntaios, G. J Am Coll Cardiol. 2020;75(3):333–40.

Sometimes things do not go as planned…

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Recent Clinical Trials

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Hooman Kamel, MD1,3; Alexander E. Merkler, MD1; Costantino Iadecola, MD1; et al Ajay Gupta, MD1,2; Babak B. Navi, MD1 . Tailoring the Approach to Embolic Stroke of Undetermined Source: A Review. JAMA Neurol. 2019;76(7):855-861

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ESUS TRIALS

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Ntaios 2020

Right to Left shunt: PFO

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• Normal connection between the right and left atria• The communication closes in the majority of people over a period of time

after birth• However, if the septum primum fails to fuse with the septum secundum,

the PFO remains patent allowing interatrial blood flow• 25% of the adult population; 70 % has atrial septum aneurysm• A Bayesian attributable risk analysis of pooled data from 12 studies

suggested that PFO is probably causally related to the stroke in approximately half of the cryptogenic patient

High Risk PFO

• Young age• Valsalva maneuver at the onset of stroke• Extended immobility• Concomitant venous thrombosis in the leg/pelvis• Coexisting venous hypercoagulable state• Coexisting atrial septal aneurysm• History of migraine with aura• Cortical location and multiplicity• Large size of cerebral infarcts

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Andrew Farb, M.D., Nicole G. Ibrahim, Ph.D., and Bram D. Zuckerman, M.D. Patent Foramen Ovale after Cryptogenic Stroke — Assessingthe Evidence for Closure. N Engl J Med. 2017 Sep 14;377(11):1006-1009

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Patent Foramen Ovale (PFO)

PFO Closure: Latest Evidence

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BaoshanQiu,M.D.,YingCai, M.D., DilongWang, M.D., JingLin,M.D.,and XuhuaFan, M.D. Closure versus Medical Therapy for Patent Foramen Ovale in Patients with Cryptogenic Stroke: An Updated Meta-Analysis of Randomized Controlled Trials. Journal of Stroke and Cerebrovascular Diseases, Vol.27,No.12(December),2018:pp3463 3472

Overview

45Hooman Kamel, MD1,3; Alexander E. Merkler, MD1; Costantino Iadecola, MD1; et al Ajay Gupta, MD1,2; Babak B. Navi, MD1 . Tailoring the Approach to Embolic Stroke of Undetermined Source: A Review. JAMA Neurol. 2019;76(7):855-861

Brain & Heart

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