Post on 06-Jan-2022
©2018 Gil Wernovsky
What I’ve Learned About the Brain As a Pediatric Cardiac Intensivist
Gil Wernovsky, MD, FAAP, FACC Senior Consultant in Pediatric Cardiology and Cardiac Critical Care
©2018 Gil Wernovsky
Disclosures
None pertaining to this presentation
©2018 Gil Wernovsky
Outline
• The “AHA!” Moment Which Changed My Career
• Understanding the Contribution of the Fetal and Transitional Circulations to the Neurodevelopmental Phenotype Seen in Children and Young Adults with CHD
• From a Pediatric Cardiologist’s Perspective:
• How is the physiology of the fetus with CHD different than that in the fetus with a structurally normal heart – particularly as it relates to cerebral blood flow, substrate and oxygen delivery?
• How does the transitional circulation affect the brain?
• How may those effects be different in different heart diseases?
• Future directions
©2018 Gil Wernovsky
Aha! Moment – Clinic Visit 2007
©2018 Gil Wernovsky
Clinic Visit 2007
Published 2005
©2018 Gil Wernovsky
In the “Conclusions”
©2018 Gil Wernovsky
©2018 Gil Wernovsky
2009 - NeuroCardiac Care Program
©2018 Gil Wernovsky
If It’s Not the Surgery What Is It?
How Can I Help in the CICU
©2018 Gil Wernovsky
Effects of CHD in the Fetus
Some Stuff Happens
Outpatient Findings
©2018 Gil Wernovsky
Effects of CHD in the Fetus
Transitional Circulation
Outpatient Findings
©gilwernovsky2018
Fetal circulation normally preferentially oxygenates the brain
©gilwernovsky2018
In single ventricle, complete mixing decreases cerebral oxygen delivery
©gilwernovsky2018
In TGA, unfavorable streaming decreases cerebral oxygen delivery
©gilwernovsky2018
Cerebral Resistance is Abnormal in Fetuses With Congenital Heart Disease
• Doppler studies of the middle cerebral artery (MCA) in 225 fetuses
– 122 normal
– 103 with complex CHD
• Right-sided lesions – (e.g. tetralogy of Fallot, pulmonary atresia)
• Left-sided lesions – (e.g. aortic stenosis)
• Hypoplastic left heart syndrome
• Ratio of MCA to umbilical artery velocity
Kaltman J et al.
Ultrasound Obstet Gynecol 2004
©gilwernovsky2018
-1.5 -1 -0.5 0 0.5 1 1.5
Right-Sided
Normal
Left-Sided
HLHS
Cerebral Vascular Resistance is Abnormal
in Fetuses With Congenital Heart Disease
Cerebral Vascular Resistance
Low High
©gilwernovsky2018
Middle Cerebral Artery Doppler in the Fetus
Hypoplastic Left
Heart Syndrome
Normal
Pulmonary Atresia
with Intact
Ventricular Septum
Kaltman J et al.
Ultrasound Obstet Gynecol 2004
LOW
High
©gilwernovsky2018
In “Right Sided” Lesions – Obstruction to the Pulmonary Artery: How Does Blood Get to the Placenta??
Placenta: Low
Resistance
CNS: High
Resistance
©gilwernovsky2018
In “Left Sided” Lesions – Obstruction to the Aorta: How Does Blood Get to the Brain??
Placenta: Low
Resistance
CNS: Lower
Resistance
©gilwernovsky2018
Hypoplastic Left Heart Syndrome in the Fetus
Low Cerebral Vascular Resistance
HLHS = LOW
cerebral resistance
in fetus
Placenta
Pulmonary Atresia in the Fetus
High Cerebral Vascular Resistance
Pulm Atr = HIGH
cerebral resistance
in fetus
Placenta
In Children with One Ventricle: “Competition” and “Balance” between the Brain and the Placenta for Ventricular Output
Cerebral Blood Flow and Resistance Is Different in Different CHD
©gilwernovsky2018
Congenital Brain Disease in HLHS
Small Ascending Aorta =
Small Head Circumference
• CNS is immature, less “complex”
• At term, brain has • ↓ myelination • ↓ cortical folding, • ↑ risk of PVL;
• Associated genetic abnormalities in ~¼
• Additional congenital anomalies in ~¼
Shillingford AJ, Ittenbach RF, Marino BS, Rychik J, Clancy RR, Spray TL, Gaynor JW, Wernovsky G. Aortic morphometry and microcephaly in hypoplastic left heart syndrome. Cardiol Young 2007;17:1-7.
©gilwernovsky2018
Microcephaly in HLHS
Patients with Microcephaly Have Smaller Ascending Aortas
Compared to Those with Normal Head Circumference
©gilwernovsky2018
Microcephaly in HLHS
Patients with Microcephaly Have Smaller Ascending Aortas
Compared to Those with Normal Head Circumference
To Placenta
TO CNS
Small
Aorta
©gilwernovsky2018
©gilwernovsky2018
Intracranial Cavity Volume (ICV)
Control > CHD
Total Brain Volume (TBV)
Control > CHD
Limperopoulos C et al
Brain MRI in Fetuses with CHD
Circulation 2010:121;26-33
©gilwernovsky2018
The normal rise
in NAA:Choline
in CHD fetuses
was significantly
attenuated
compared to
controls
Limperopoulos C et al
Brain MRI in Fetuses with CHD
Circulation 2010:121;26-33
©gilwernovsky2018
Cerebral Oxygen Delivery Can Now Be Studied in CHD
©gilwernovsky2018
Cerebral Oxygen Delivery Can Now Be Studied in CHD
Normal TGA HLHS
©gilwernovsky2018
• Failure of the normal fetal streaming due to CHD was associated with:
– Mean in ascending Ao saturation of 10%
– Mean 15% in cerebral O2 delivery
– Mean 32% cerebral VO2
– Associated with a 13% in fetal brain volume
• Fetal brain size correlated with ascending aortic oxygen saturation and cerebral VO2 (p = 0.004).
• Babies with Transposition of the Great Arteries Had the Lowest Oxygen Delivery of any CHD Studied
Cerebral Oxygen Delivery Can Now Be Studied in CHD
©2018 Gil Wernovsky
What Happens After Birth During the Transitional Circulation?
↓PVR -> ↑ Flow to Lungs
↑SVR -> ↓Flow to Body/Brain
©gilwernovsky2018 ©gilwernovsky2018
Pulmonary Veins
Pulmonary Artery
Pulmonary Veins
Right Atrium
Right Ventricle
Left Atrium
Left Ventricle
SVC IVC
Aorta
“Parallel Circulation” Transposition of the Great
Arteries
©gilwernovsky2018 ©gilwernovsky2018
Pulmonary Veins
Pulmonary Artery
Pulmonary Veins
Right Atrium
Right Ventricle
Left Atrium
Left Ventricle
Systemic Venous Return
Systemic Blood Flow
Pulmonary Venous Return
Pulmonary Blood Flow
SVC IVC
Aorta PGE1
©gilwernovsky2018 ©gilwernovsky2018
Single Ventricle Results in a
“Multi-Distribution Circulation”
Qp
+Qs
©gilwernovsky2018 ©gilwernovsky2018
Even if the PDA is open, in the first days of life, pulmonary vascular resistance
continues to fall Pulmonary blood flow increases at the
expense of systemic blood flow
If the PDA closes -> Death
SINGLE
RIGHT VENTRICLE
SVC
IVC
Qp
LUNGS (high PVR)
PA
Physiology of Hypoplastic Left Heart Fetal Flow
Right Atrium
atrial
septum
Left Atrium
LV
pv
O2 Sat < 65% Qs
PDA-Ao BODY/
Placenta (low SVR)
HIGH PVR Low SVR
Qs
Right Atrium
SINGLE
RIGHT VENTRICLE
SVC
IVC
atrial
septum
Qp
LUNGS (falling PVR)
PA
Left Atrium
LV
pv
O2 Sat=80%
PDA-Ao BODY
( high SVR)
Physiology of Hypoplastic Left Heart Postnatal Flow
↓ PVR ↑SVR
Qs
Right Atrium
SINGLE
RIGHT VENTRICLE
SVC
IVC
atrial
septum
Qp
LUNGS (falling PVR)
PA
Left Atrium
LV
pv
O2 Sat=87%
PDA-Ao BODY
( high SVR)
Physiology of Hypoplastic Left Heart Postnatal Flow – Further Fall in PVR
↓ PVR ↑SVR
Baby is “Pinker” -but-
Cerebral Blood Flow Falls
SINGLE
RIGHT VENTRICLE
SVC
IVC
Qp
LUNGS (high PVR)
PA
Physiology of Hypoplastic Left Heart Fetal Flow
Right Atrium
atrial
septum
Left Atrium
LV
pv
O2 Sat < 65% Qs
PDA-Ao BODY/
Placenta (low SVR)
HIGH PVR Low SVR
Qs
Right Atrium
SINGLE
RIGHT VENTRICLE
SVC
IVC
atrial
septum
Qp
LUNGS (falling PVR)
PA
Left Atrium
LV
pv
O2 Sat=80%
PDA-Ao BODY
( high SVR)
Physiology of Hypoplastic Left Heart Postnatal Flow
↓ PVR ↑SVR
Qs
Right Atrium
SINGLE
RIGHT VENTRICLE
SVC
IVC
atrial
septum
Qp
LUNGS (falling PVR)
PA
Left Atrium
LV
pv
O2 Sat=87%
PDA-Ao BODY
( high SVR)
Physiology of Hypoplastic Left Heart Postnatal Flow – Further Fall in PVR
↓ PVR ↑SVR
Closing PDA Shock
Qs
Right Atrium
SINGLE
RIGHT VENTRICLE
SVC
IVC
atrial
septum
Qp
LUNGS (falling PVR) ↓↓PVR
Left Atrium
LV
pv
O2 Sat=92%
Physiology of Hypoplastic Left Heart Closing Ductus Arteriosus
Low Cardiac Output
Acidosis
↑ ↑ SVR
Baby is “Pinker” -but-
In Shock
SINGLE
Left VENTRICLE
SVC
IVC
Qp
LUNGS (high PVR)
PDA → PA
Physiology of Pulmonary Atresia Fetal Flow
Left Atrium Left Atrium
pv
O2 Sat < 65% Qs
Aorta BODY/
Placenta (low SVR)
HIGH PVR Low SVR
Qs
Left Atrium
SINGLE
LEFT VENTRICLE
SVC
IVC
Qp
LUNGS (falling PVR) PDA → PA
Left Atrium
pv
O2 Sat=80%
Aorta BODY
( high SVR)
Physiology of Pulmonary Atresia Postnatal Flow
↓ PVR ↑SVR
atrial
septum
Qs
Left Atrium
SINGLE
LEFT VENTRICLE
SVC
IVC
Qp
LUNGS (falling PVR)
Left Atrium
pv
O2 Sat=87%
Aorta BODY
( high SVR)
Physiology of Pulmonary Atresia Postnatal Flow – Further Fall in PVR
↓ PVR ↑SVR
PDA → PA
atrial
septum
Qs
Left Atrium
SINGLE
LEFT VENTRICLE
SVC
IVC
Qp
LUNGS (falling PVR)
Left Atrium
O2 Sat=40%
Aorta BODY
( high SVR)
Physiology of Pulmonary Atresia Postnatal Flow – Closure of PDA
↓ PVR ↑SVR
PDA → PA
atrial
septum
Profound Hypoxemia
©2018GilWernovsky
In a Baby with a PDA, Cerebral Blood Flow Falls
There is a “ductal steal” in diastole ↑ time
Rychik J, Bush DM, Spray TL,
Gaynor JW, Wernovsky G.
J Thorac Cardiovasc Surg 2000;120:81-7.
↑ ↑ ↑ over time
Kluckow M, Evans N, Osborn D
NeoReviews 2004;5:e98-e108
↓ ↓ cerebral blood flow
↑ Risk NEC ↑ Risk renal dysfunction
©2018GilWernovsky
What Are The Effects of a Delay in Cardiac Surgery
on the Brain?
©2018GilWernovsky
Cerebral Blood Flow is Diminished
48-72 hour Old Neonates on Prostaglandin
Licht DJ et al
J Thorac Cardiovasc Surg 2004
~50 ml/min/gram of brain
~25 ml/min/gram of brain
Daniel Licht, MD
©2018GilWernovsky
Cerebral Oxygen Delivery Falls DAILY
©2018GilWernovsky
By Electively Delaying Cardiac Surgery
↑ Risk of:
• White Matter Injury
• Medical Error
• ? Mortality
©2018GilWernovsky
By Electively Delaying Cardiac Surgery ↑ Risk of:
• White Matter Injury
• Medical Error
• ? Mortality
• Increases In:
• Cost
• Length of Stay
©2018 Gil Wernovsky
An Open PDA in Congenital Heart Disease is a Double Edged Sword
Life Saving – Provides Systemic and/or Pulmonary Blood Flow, aids
in ”Mixing”
Increased Pulmonary Blood Flow During the Transitional Circulation “Steals” Blood from the Systemic
Circulation
©2018 Gil Wernovsky
For Researchers: The Open PDA in the Transitional Circulation is Not an “On/Off” or “Yes/No” phenomenon
The Amount of “Cerebral Steal” due to the open PDA depends upon the size of the PDA and the
degree of ↓ ↓ pulmonary vascular resistance
©2018 Gil Wernovsky
Time
©2018 Gil Wernovsky
Take Home Points • In Complex CHD, Brain injury starts in the fetus
• The abnormalities are different with each type of CHD
• Brain injury continues – quite rapidly - during the transitional circulation • The abnormalities are different with each type of CHD • The ductus arteriosus is initially life saving, then contributes to the problem
• This negative contribution worsens daily
• The broad term “CHD” is too non-specific • “Clancy Classification”
• Type 1: Two Ventricles, Normal Arch • Type 2: Two Ventricles, Abnormal Arch • Type 3: One Ventricle, Normal Arch • Type 4: One Ventricle, Abnormal Arch
©2018 Gil Wernovsky
2018: Things I Know Are True
• In the Fetus with Congenital Heart Disease, Abnormalities of Blood Flow to the Fetal Brain are a Major Contributor to Long-term Neurodevelopmental Challenges
• In the Fetus with Congenital Heart Disease, Abnormalities of Blood Flow to the Fetal Brain May Be Modified
• In the Term Neonate with Critical CHD, Operate as Early As Possible
• Minimize Pain and Other Stressors in the ICU
• Cardiac Intensivists are Good Pediatric Neurologists
• Changing Practices in the ICU will Improve Outcomes
©2018 Gil Wernovsky
Cardiac Critical Care and Inpatient Neurodevelopmental Program
Part of the NeuroCardiac Critical Care Service
©2018 Gil Wernovsky
Effects of CHD in the Fetus
Some Stuff Happens
Outpatient Findings
©2018 Gil Wernovsky
Adré J. du Plessis, M.B.Ch.B., M.P.H. Catherine Limperopoulos, PhD
Institute for the Developing Brain
©2018 Gil Wernovsky
Nobuyuki Ishibashi, MD Director of Cardiac Surgery Research Laboratory
Center for Neuroscience Research
Richard Jonas, MD Director of Cardiothoracic Surgery
Co-Director Children’s National Heart Institute
©2018 Gil Wernovsky
Mary Donofrio, MD Jacqueline Sanz, PhD
Jessica Carpenter, MD Dana Harrar, MD Michael Mintz, PsyD
©2018 Gil Wernovsky
CICU Inpatient CANDO Team Melissa Jones, RN, MSN, CPNP-AC
©2018MelissaJones
©2018 Gil Wernovsky
Inpatient CANDO Program
Coordinators
Psychology
Medical Team
OT
PT
SLP
Social Work Family
Case Manager
Nutrition
Pharmacy
Nursing
Child Life
©2018MelissaJones
©2018 Gil Wernovsky
Our Mission
To eliminate brain injury in the CICU
©2018MelissaJones
©2018 Gil Wernovsky
NeuroCardiac Critical Care Changing the Care Paradigm During The Early “4th Trimester”
1. Protecting Brain Function, Structure and Development During the Perioperative Period in Neonates with Complex Congenital Heart Disease
2. Evaluating and Treating Maternal (Familial) Postpartum Depression, Stress, and Anxiety in the Perioperative Period
©2018 Gil Wernovsky
Low Cerebral Oxygen Delivery
Risk of Paradoxical
Embolus
Effects on the Brain
From Anesthesia
and CPB
Borderline Hemodynamics
Prolonged or Too Much
Mechanical Ventilation
Sedation
Analgesia
(& Subsequent “Wean”)
Bland Environment
Lack of Social Stimulation
Noxious Stimuli
↑Noise
Poor Oral Motor
Coordination
Decreased Feeding
Increased Parental Stress & Anxiety
Impacting Outcome
Wernovsky G and Licht D. Peds Crit Care Med 2016;17(Aug):S232-S242
©2018 Gil Wernovsky
www.cardiacneuro.org