Transcatheter Aortic Valve Replacement - Keystoneheart.com

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Brain Emboli Clinical Consequences and Brain
Injury
Kevin Abrams, MD. Chief of Radiology Medical
Director of Neuroradiology Baptist Hospital and
Neuroscience Center, Miami, FL Clinical Associate
Professor of Radiology FIU School of Medicine
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Why are We Discussing Brain Lesions in Cardiology?
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Clinical Stroke After TAVR at 30 Days

• VARC defined 1.5-6 in recent RCTs
• Confer 3- to 9-fold increased risk of mortality

• AHA/ASA defined Symptoms (ask the neurologist)
  Brain MRI
• Stroke range is 15-28

30-day stroke rates in recent RCTs
Are we under-reporting stroke?
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New Ischemic Lesions are Present in a
Substantial Number of Patients Undergoing
Cardiovascular Interventions with Diffusion
weighted (DWI) MRI
TAVI 58-100
CAS 20-70
AVR 48
Cardiac Cath 3-18
CABG 18-42
AF Ablation 7-42
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Calcific Aortic Valve Stenosis

• Primary source of embolic material following TAVI

Large irregular masses of dystrophic
calcification prevent normal valve opening
Sizeable calcific deposits prevent normal valve
function
Calcified stenotic aortic valve
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Most of the Stroke Events Take Place
Periprocedural

• PARTNER (Cohort A)

TAVI (32 Stroke Pts)
AVR (15 Stroke Pts)
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47
59
53
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TAVI Potential Paths of Cerebral Emboli
Three aortic arch take-offs typically lead to the
four arteries feeding the brain
Right Carotid Right Vertebral
Left Carotid Left Vertebral
Layton KF et al. Bovine Aortic Arch Variant in
Humans. AJNR 2006.
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Distribution of Embolic LesionsFollowing TAVI as
Assessed by DWI

• Equally distributed in all major cerebral
  vascular territories except ACA

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Cerebellum/Brainstem
Middle cerebral
Vascular Territories
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Anterior Cerebral
Posterior Cerebral
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Arnold 2010, Wityk 2001.
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Clinical Embolic Stroke Syndromes
Right Carotid
Middle Cerebral Territory

• Left hemiparesis, face and arm more than leg
• Left neglect

Vertebral, Basilar and Posterior Cerebral Artery
Territories
Right Vertebral

• Vertigo, falling to left
• Diplopia (blurred vision)
• Dysarthria (slurred speech)
• Hemiparesis or quadriparesis
• Hemisensory loss
• Hemianopia or cortical blindness

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Clinical Embolic Stroke Syndromes
Left Carotid
Middle Cerebral Territory

• Right hemiparesis, face and arm more than leg
• Aphasia, loss of expressive as well as receptive
  language

Vertebral, Basilar and Posterior Cerebral Artery
Territories
Left Vertebral

• Vertigo, falling to left
• Diplopia, dysarthria
• Hemiparesis or quadriparesis
• Hemisensory loss
• Hemianopia or cortical blindness

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DWI Lesions, Reversal and Brain Damage

• Acute DWI lesion is generally a reliable
  signature of infarct core and represent mostly
  permanent brain damage - sustained reversal is
  infrequent (Campbell et al. J of Cerebral Blood
  Flow metabolism 20123250-56).
• Transient or permanent resolution of initial DWI
  lesion depends on the duration of ischemia - 10
  vs 30 min. Transient resolution of DWI lesion is
  associated with widespread neuronal necrosis
  moreover, permanent resolution of DWI lesions
  even after 10 min of ischemia does not indicate
  complete salvage of brain tissue from ischemic
  injury. (Li et al. Stroke. 200031946-954.)
• Based on histology and experimental studies on
  cerebral ischemia
• normalization of DWI does not imply that the
  tissue is normal - neurons already exhibit
  evidence of structural damage and stress.
• Other non-neuronal cell populations may partially
  compensate for altered fluid balances at the time
  of DWI reversal despite the presence of neuronal
  injury probably caused by delayed neuronal cell
  death by apoptosis (Ringer et al. Stroke.
  2001322362-2369.)

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Each New DWI Lesion Matters10 MAY 2013 VOL 340
SCIENCE

• Each 1-mm3 voxel of Brain Tissue contains
• at least 80,000 neurons
• Each neuron may be connected to up to 10,000
  other neurons
• 4.5 million synapses

At 294.7 mm3 on median lesion volume (the median
volume of new DWI lesions post TAVR in US, Lansky
et al London Valve 2015)
Each patient lost on average during his
unprotected TAVR procedure Over 20 Million
Neurons Over 1 Billion synapses
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Measuring Cognition

• Attention / Processing Speed
• Visuospatial Abilities
• Perception (match shapes)
• Construction (arrange blocks to form complex
  pattern)
• Memory
• Implicit
• Procedural (riding a bike)
• Explicit
• Episodic (I went to the store this morning)
• Semantic (who was the first president?)
• Language
• Naming
• Vocabulary
• Fluency (name as many words as you can in 60
  seconds)
• Executive Functioning

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Measuring Cognition
Executive functioning

• Organization
• Strategy Development
• Mental flexibility
• Abstract Thought
• Working Memory
• Inhibition
• Complex Sequencing

RED
BLUE
YELLOW
GREEN
RED
GREEN
BLUE
YELLOW
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Cerebral Reserve

• The brains ability to compensate in the face of
  an insult (e.g. clinically overt stroke, trauma)
  or multiple insults (new clinically silent
  lesions) over time and refers to the amount of
  brain damage the brain can sustain before overt
  clinical symptoms are manifest (Staff,
  Neuroimaging Clinics of North America 2012)
• Any periprocedural stroke in all patient
  populations will add to the ischemic burden of
  the brain now and in the future thus decreasing
  the cerebral reserve (K Abrams 2013)

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Cerebral Reserve

• Infarcts are associated with brain volume
  reduction, but, importantly, also with detectably
  lower cognition (Blum et al, Neurology, Nov
  2012)
• Cognitive decline relates directly to loss of
  brain substance with progression of lesion burden
  (Schmidt et al, Annals of Neurology 2005)
• therefore brain infarcts will ultimately affect
  cognition

It All Adds Up
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Neurocognitive Decline

• Most studies with complete neurocognitive battery
  examining the association between

DEMENTIA
BRAIN INFARCTS
NEUROCOGNITIVE DECLINE
show a consistent link between the three
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New DWI Lesions and NeuroCognitive (NC) Function
First Author (ref) n of patients with NC decline of patients with new DWI lesions Procedure/diagnosis Comments
Restrepo et al (2002) 13 77 31 CABG Extensive NC testing Patients with new DWI lesions had larger NC decline
Choi et al (2000) 25 10 new mental change 15 without new event 100 70 20 Vascular Dementia Extensive NC testing New lesions correlated with new mental change
Lund et al (2005) 33 trans radial 9 trans femoral 16.7 15 TR 0 TF Left Heart Catheterization Extensive NC testing Patients with new DWI lesions had larger NC decline
Zhoue et al (2009) 68 CAS 100 CEA 2.9 2 46.3 12 Carotid stenting Carotid endarterectomy With embolic protect protection NC examination not defined
Schwartz et al (2011) 30 Cath 39 CABG 33 controls Not reported 3.3 17.9 Coronary catheterization CABG Extensive NC testing of DWI lesions correlated with NC decline
Sweet et al (2008) 42 PCI 43 CABG 6 7 Not done Coronary stenting CABG Extensive NC testing 1 year fu
Blum et al (2012) 658 97 26.4 Elderly non-dementia patients Extensive NC testing Brain infracts are associated with memory loss
Tatemichi et al (1995) 3697 27 dementia Healthy elderly patients Extensive NC testing, 3.6 years fu Presence of silent infracts more than doubled the risk of dementia and was associated with worse NC decline
Omran et al (2003) 101 3 22 Retrograde aortic valve cath NIHHS level of stroke assessment
Zhou et al (2012) 51 16 CAS 35 CEA 41 69 Carotid stenting Carotid endarterectomy Extensive NC testing DWI lesions only significant predictor of NC decline
Knipp et al (2004) 39 56 ac 23 3 mo 31 3 years 51 CABG Extensive NC testing 56 decline acutely and 31 decline at 3 years
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Long Term Clinical Consequences of Silent MRI
Lesions and Brain Pathology

• Large population-based studies demonstrate
  associations between MRI lesions and cognitive
  decline, clinical stroke, and mortality (Vermeer
  et al Lancet Neurol 20076611-9)
• There is increasing evidence that cumulative
  burden of ischemic brain injury causes
  neuropsychological deficits or aggravates
  vascular dementia (Bendszus Lancet Neurol
  20065364-72)
• Dementia is a cumulative effect of multiple
  hits and brain infarcts more than 50 of those
  with dementia have multiple pathologies on
  autopsy, whereas among those without dementia
  over 80 have single or no pathology (Tatemichi
  Stroke 1994251915-9)
• The presence of silent brain infarcts at base
  line more than doubled the risk of dementia, are
  associated with worse performance on
  neuropsychological tests and a steeper decline in
  global cognitive function.
• Silent thalamic infarcts are associated with a
  decline in memory performance, and nonthalamic
  infarcts with a decline in psychomotor speed.
  (Vermeer et al 20033481215-1222)
• In addition, patients with Atrial Fibrillation
  have an increased risk of dementia, excess
  mortality and neurocognitive impairment due to
  many factors including pre-existing microinfarcts
  and reduced brain volume (Kwok et al Neurology
  201176914-922, Santangeli et al Heart Rhythm
  201291761-1768)

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Conclusion

• A silent infarct is still an infarct whether
  random or iatrogenic
• Until someone proves these DWI lesions are
  somehow beneficial to the patient, we need to
  take steps to prevent them from occurring

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Is Cerebral Protection Necessary?
Absolutely!