John M. Costello, MD, MPHProfessor of Pediatrics

Northwestern University Feinberg School of Medicine

Director, Inpatient Cardiology

Medical Director, Regenstein Cardiac Care Unit

Ann & Robert H. Lurie Children’s Hospital of Chicago

PCICS 12th Annual International Meeting

December 9, 2016

HLHS Foundations of Care From Fetus to Fontan:

Fetal Considerations & Delivery

Stage 1

Bidirectional Glenn

Fontan

Transplant?

HLHS Journey

HLHS Journey:Reality for some patients

Interstage mortality

Fontan takedown

Unplanned

reinterventions

Preoperative death

CNS injury

IUFD

NEC

PLE

Plastic

Bronchitis

Arrhythmia

HLHS Fetal Considerations & Delivery Outline:

• In-utero physiology:

• New data- enhance understanding

• Impact on end-organs

• Modifiable ?

• Prenatal dx- impact postnatal outcomes

• Timing & location of delivery

HLHS:Prenatal Diagnosis Rates

Multicenter Study Rate Population

Morris SA. Circ 2014

39%Texas Birth Defects

Registry

ATZ AM. JTCVS 2010

75% SVR trial

Van Velzen CL. BJOG 2016

97%Netherlands:

national screening

HLHS: Potential Benefits of Prenatal Dx

• Counseling

– Screening for non-cardiac anomalies

– TOP:

• 12-48% after seen in quaternary cardiac center

• Actual TOP rate for prenatal dx <24 weeks in community likely higher

• Planning for delivery

• Fetal therapies

Beruokhim RB Ultra Obst Gyn 2015; Rychik J Ultra Obst Gyn 2010; Kipps AK AJC 2011

Fetal PhysiologyNormal

Sun L. Circulation 2015

HLHS

Hypothesis: abnormalities related to ↓O2

and/or substrate deliveryLimperopoulos C. Circulation 2010

N-acetylaspartate / choline ratioTotal brain volume

Sun L. Circulation 2015

umbilical vein SaO2combined vent. output

• ↓ placental weight

• ↓ fetal blood vessel density

• ↑ fibrin deposits

• ↑syncytial nuclear aggregates

• ↑leptin

Jones HN & Hinton RB. Placenta 2015

Sun L. Circulation 2015

↓ cerebral VO2

↓ cerebral VO2

assoc. with

↓brain weight

3 factors:• Abn. flow

• ↓ UV SaO2

• ↓CVO

Can maternal therapies improve outcomes in fetuses with HLHS?

Lara DA, Morris SA. US Ob Gyn 2016

ACUTE maternal

hyperoxygenation

CHRONIC maternal

hyperoxygenation

Trial of Maternal O2 Thpy in Fetal “Left Heart Hypoplasia”

• PI: Shane Morris (Baylor)

• RCT: 4L O2 vs. room air

• Primary outcomes: fetal MV & AoV growth

• Secondary outcomes:

– Brain maturation score & CNS injury (postnatal MRI)

– Neurodevelopmental outcomes

– Fetal neurosonogram & brain MRI indices

ClinicalTrails.gov NCT02965638

Fetal Echo at 24 weeks Fetal Echo at 36 weeks

Evolution to HLHS

L. Freud / W. Twortezky

HLHS: Fetal Aortic Valvuloplasty

Tworetzky et al, Circ 2004

L. Freud / W. Twortezky

Circulation 2014

Moon-Grady AJ. JACC 2015

HLHS:Highly Restrictive or Intact Atrial Septum

• ~ 5% of HLHS

Frommelt MA. Clin Perinatal 2014

Atz AM AJC 1999

Vlahos AP. Circulation 2004

Vida VL . ATS 2007

• 21 attempts

• 19 technically successful

– 2 in-utero demise

• 12/19 required urgent postnatal intervention

– 58% stage 1 survival Prenat Diagn 2008

• 9 attempts:

– 4 successful stent placements

– 1 in-utero demise

– 4 of 8 live births died as neonates

Cath Cardiovasc Int 2014

Moon-Grady AJ. JACC 2015

Does prenatal diagnosis improve postnatal outcomes in

fetuses with HLHS?

Thakur V. Prenatal Diagnosis 2016

Pre-op

vasoactive

meds

Pre-op RV

dysfunction ≥

moderate

Thakur V. Prenatal Diagnosis 2016

Pre-op

mortality

Post-op

mortality

• 1999 – 2007: Texas Birth Defects Registry

• 463 births with isolated HLHS

• Prenatal diagnosis: 39%

• Driving time from delivery hospital to cardiac center varied based on prenatal diagnosis:

– Yes: median 3 min. (IQR 1-10)

– No: median 29 min. (IQR, 10-136)Circulation 2014

• Of 463 neonates, 123 (27%) died in first month of life

– 36% of deaths occurred prior to surgery

Circulation 2014

• Independent risk factors for mortality:

– Pre-transport: • Greater driving time to cardiac surgical center

• Low birth weight

• Earlier birth year

– Pre-stage 1:• Greater driving time to cardiac surgical center

• Low HLHS volume cardiac surgical center (trend)

– Surgical:• Low HLHS volume cardiac surgical center

• Earlier birth year

• To improve outcomes:

– Better fetal detection rates (only 39% in this study)

– Delivery near high HLHS volume center

Morris Circulation 2014

Fetus with HLHS:Timing of Delivery?

Fetal

Outcomes:↓ IUFD

Neonatal

Outcomes:↓early delivery

↓LBW

• IUFD 74/1,584 (4.6%)

• Independent risk factors:– Cardiomegaly

– Hydrops

– Pericardial effusion

– Extracardiac anomalies

– IUGRPediatr Cardiol 2014

HLHS: IUFD Rates

3 / 176 (1.7%)J Ultrasound Med 2005

US Obstet Gynecol 2010 3 / 240 (1.2%)

All IUFDs had

risk factors!

Fetus with HLHS:Timing of Delivery?

Fetal

Outcomes:↓ IUFD

Neonatal

Outcomes:↓early delivery

↓LBW

HLHS: Prematurity• PHN- Infant Single Ventricle Trial:

– 16% single ventricles premature vs. 12% normals

Williams RV et al. CHD 2010;596-103

Prematurity:Traditional Definition

PREMATURE

(PRETERM)TERM

POST

TERM

24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44

Weeks Gestational Age at Birth

Data???

Circulation 2014

• Early term birth assoc. with greater:

– Executive dysfunction

– ADHD

– Psychiatric problems

2016

Prenatal Dx HLHS = Earlier DeliveryNPC-QIC

Brown DW. Pediatr Cardiol 2015

Donofrio MT Circulation 2014

“…. elective induction of fetuses with CHD before39 weeks is not recommended unless there arepatient-specific obstetric or logistical issues orfetus-specific concerns about well being.”

“The … management for other conditionsassociated with the evolution of fetal heart failureand sudden demise … has not, to date, been fullyevaluated”

Inferences

• Abnormal HLHS fetal physiology associated with delayed CNS maturation & development

– Likely contributes to ND outcomes

• Benefits of fetal therapies remain unproven

• Prenatal diagnosis a valuable tool

– Responsibility used for counseling & planning of delivery

Inferences

• Fetuses with HLHS at ↑ risk for early delivery

• Births <39 weeks gestation associated with– ↑ neonatal morbidity & mortality

– Adverse ND outcomes

• Fetal cohort studies:– Isolated HLHS may safely progress to 39 weeks

– Those with NCA, genetic anomalies, and/or severe AVVR: ↑ risk for IUFD; optimal monitoring & mgmt. unknown

Thank You