Fetal Cardiac Interventions

Fetal Cardiac Interventions
Dr Raghu Kishore Galla

Introduction
• With the steady development of medical imaging techniques, fetal cardiac
interventions (FCIs) have drawn considerable attention due to the
potential merits of prenatal diagnosis and successful management of fetal
CV anomalies, arrhythmias, and HF.
• FCIs are carried out to improve fetal cardiac function, promote fetal
intrauterine development and survival, and enhance postnatal survival.
• Rather than being a routine management for materno-fetal cardiac
disorders, FCIs are only applied in those fetal cardiac disorders that have
an increased risk of mortality and morbidity and warrant an interventional
therapy.

FETAL THERAPIES
• Fetal treatment (or fetal therapy) is
the “operative branch” of fetal
medicine
• It includes a series of interventions
performed on the “sick” fetus with
the aim of achieving fetal well being.
• These interventions include medical
(i.e. non-invasive) and surgical
procedures.

FETAL INTERVENTIONS

categorized into three types:
1) Pharmacological
2) Open FCIs
3) Closed FCIs
- indirect
- direct

PHARMACOLOGICAL FCI
FETAL TACHYARRYTHMIAS –VT/SVT/ATRIAL FLUTTER
Fetal SVT – AVRT / atrial flutter most common indication for pharmacological cardiac
intervention
Digoxin has been a mainstay of therapy
other agents used are
Sotalol
Amiodarone
Flecainide
Propranolol
Modes of administeration
1) Intravenous
2) Transplacental
3) Umblical vein
4) Maternal oral administeration
INDICATION FOR THERAPY
1.FETAL HYDROPS
2. SUSTAINED TACHYCARDIA
3.CARDIAC DYSFUNCTION

OTHER PHARMACOLOGICAL FCI INDICATION
• Fetal hydrops due to other structural cardiac anomalies
• Transplacental treatment with digoxin
– Ebstein’s anomaly
– Absent Pulmonary valve syndrome
– Right heart dysfunction from left heart disease
– Premature closure of the ductus arteriosus
– Cardiac tumor
– Cardiomyopathy
• Efficacy of digoxin not known

OPEN FETAL CARDIAC INTERVENTION
• “Open FCI” denotes any intervention in which the uterus is opened
surgically or accessed through a surgical trochar 3 mm in diameter, which
includes most fetoscopic techniques.
• The first reported open FCI procedure in a human fetus was pacemaker
placement for complete AV block.

CLOSED FETAL CARDIAC INTERVENTION
• Denotes mechanical interventions in which the uterus is not opened or
accessed with a port < 3 mm in diameter
• In practice, closed FCI consists primarily of percutaneous interventions in
which an 18- to 19-gauge needle is used to gain uterine and fetal access.
• The first reported case of closed FCI was a balloon aortic valvuloplasty
performed in 1989.

Principles of FCIs

• 5% of prenatally diagnosed CHDs including severe AS (1.6%), pulmonary
atresia with intact ventricular septum (PA/IVS) (1.9%) and severe PS
(1.5%) can be critical and therefore require intrauterine therapeutic
interventions.
• Early diagnosis of treatable CHDs may improve fetal intervention
outcomes, allowing ventricular growth and angiogenesis for fetus with
semilunar valve stenosis for successful adaptation to extrauterine life.
• Advanced imaging technology and equipment have made an accurate
diagnosis of most fetal CHDs possible.
• Echocardiography is a reliable means for prenatal diagnosis of a wide
spectrum of CHDs.
• At present, diagnosis of CHDs at midgestation (18-24-week gestation) has
become feasible in almost all situations

Criterias to select for FCI

Fetal Aortic Valvuloplasty
• The most common closed FCI procedure is aortic valvuloplasty.
• The primary indication for fetal aortic valvuloplasty is to alter the in utero
natural history of midgestation fetal AS with evolving HLHS.
• Severe AS is associated with LVOT obstruction and may lead to
irreversible LV dysfunction secondary to volume overload with right heart
failure and hydrops fetalis.
• Some patients with HLHS are diagnosed during the second trimester with
valvular AS and a normal-sized or dilated LV and evolve to HLHS over the
course of gestation.

• In other fetuses diagnosed with AS in midgestation, left heart growth and
function will remain sufficient for a biventricular outcome.
• Clinical observations also confirmed pre- and postnatal evolution of HLHS
were associated with not only prenatal critical AS, but also endocardial
fibroelastosis of the LV.
• By echocardiography, endocardial fibroelastosis is also implicated in post-
interventional outcomes and postnatal heart growth.

33 weeks24 weeks
Progression of Aortic stenosis To HLHS

Features are associated with progression to HLHS
 Retrograde flow in the transverse aortic arch
 Severe LV dysfunction
 Endocardial fibroelastosis
 Monophasic and short mitral valve inflow
 left-to-right flow across the foramen ovale
One can reliably predict which midgestation fetuses with AS
will evolve to HLHS

Fetal echocardiographic images prior to procedure.(a) Color Doppler image showing the stenotic aortic
valve. (b) 4C view revealing mitral regurgitation. (c) Foramen ovale shunting from left to right atrium.
(d) Endocardial fibroelastosis of the LV.

Criteria
• The entry criteria for prenatal intervention for critical AS have been
advocated as severe AS or atresia with severe LV dysfunction and the LV
length was not <2 SD below the mean for gestational age at diagnosis.
• The timing of intervention should be on an urgent basis because of the
potential for rapid progression into left ventricular growth failure in
fetuses

PROCEDURE
• Fetal aortic balloon valvuloplasty
is performed at 21–32 weeks
gestation under maternal LA and
sedation, by inserting a needle
through the mother’s abdominal
wall into the uterine cavity under
ultrasound guidance
• Fetal position is important for
procedure success

Fetal Aortic Valvuloplasty – Imp. Considerations
• Two patients – mother and the fetus
• Only fetus requires interventional treatment
• Procedure must be safe for both of them
• Preparation of the team is crucial
• The team has to be ready for both maternaland fetal
complications

Anesthesia of the mother
• General anesthesia
• intubation, drugs, long recovery time
• Local anesthesia
• anxiety, pain, reaction to all events in the theatre
• Sedation + analgesics + local anesthesia
• quick recovery, contact with the patient when necessary

Anesthesia of the fetus
• Intramuscular or Cordocentesis
• I.M.
• atracurium 0.2-0.4 mg/kg EFW
• fentanyl 10-50 mcg/kg EFW
• atropine 20 mcg/kg EFW
*EFW – Estimated Fetal Weight

Overview of a Fetal aortic valvuloplasty

Fetal sonographic images during the procedure.(a) Intramuscular injection of anesthetic agent
into the fetus.(b) Needle entry into the fetal thorax. (c) Needle alignment with the LVOT and
wire across the aortic valve.(d) Inflated balloon across the aortic valveFetal Cardiac Interventions

Fetal echocardiographic images 6 weeks following the procedure. (a) 4C view showing resolution
of endocardial fibroelastosis. (b) Color Doppler image revealing improved flow through the aortic
valve. (c) Four-chamber view in systole showing absence of mitral regurgitation. (d) Foramen
ovale shunting from right to left atrium

Fetal Aortic Regurgitation
Antegrade flow Aortic regurgitation

Fetal Aortic Regurgitation?
• Intentionally over-sizing balloon
• Resolves within weeks
• Well Tolerated
– Low systemic resistance – placenta
– High LV EDP
• Could there be beneficial effects?
– Volume loading LV

Allan, Sharland, Tynan, 1989
Balloon dilatation of the aortic valve in the fetus:
report of two cases.
a
Maxwell D, Allan, LD, Tynan M, Br Heart J. 1991 .May;65(5):256-8.

Fetal Intervention - 1990s

Fetal
patients
Intervention - 1990
• 4
• 5 attempts
• 2 balloon dilation successfully performed
• 1 intrauterine death
• 2 neonatal deaths
• 1 long term survivor
• Technical complication
in 2.
balloon fragments sheared off in the LV wall

Outcome of Fetal Interventions World-wide
Kohl et al
• 14 fetuses
• 8 had aortic stenosis
• 2 had aortic atresia
• 2 had pulmonary atresia & intact ventricular septum
• 2 had aortic stenosis & pulmonary atresia
There was only 1 long term survivor

Problems
• Poor outcome
• Ultrasound imaging of limited quality
• Fetal position critical
• Limitations of the available equipment
FCIs-1990S

Transuterine Technique – Fetal Aortic Valvuloplasty

n=69
Tworetzky 2010
Live Born
n=72
Fetal Demise
n=9 (1/9 TOP)
Fetal Loss due to procedure
8/84 (~10%)
Technically SuccessfulTechnically Unsuccessful
N=15 (17%)
9/37 (24) vs. 6/47 (12)
Still In Utero
n=3
Attempted fetal aortic valvoplasty
n=84

LH
n=21
BIVENTRICULAR
Tworetzky 2010 Median age at follow-up:
2.8 yrs (0.5, 8.3)
Median age 2.3 yrs
(all after BDG)
n=4
ACHIEVED
CIRCULATION
n=25
Converted to 2V
after BDG N=4
Rx HLHS from birth
n=48
Biventricular from birth
Comfort care, n=1
Died from sepsis, n=1
Died post-transplant, n=1
Live born
n=72
Attempted fetal aortic valvoplasty
n=84

Complications of fetal aortic ballooning
• Bradycardia requiring Rx (40%) - treatable
• Moderate-severe AR (40%) - resolves
• Hemopericardium requiring drainage n=3
• Balloon rupture n=2
• Peri-procedural fetal demise (10%)
Courtesy: Wayne TworetzkyFetal Cardiac Interventions

Gerald Tulzer
Linz, Austria
•
December 2001- January 2010
• 24 attempted fetal aortic valvoplasties in 23 fetuses
• Median GA: 26+4 weeks (21±4 to 32±1 weeks)
•
4 fetuses had advanced end-stage heart failure with
hydrops.

Results
Successful:
Technical failure:
15/23 fetuses (70%)
8/23 (33%)
5 HLHS, 2 IUD,
1 repeated successfully
3/23 (13%)Overall mortality:
Biventricular circulation 10/15 successful procedures (67%) 1 IUD
F/U: median 27 months (4 - 63 months):
Aortic balloon alone (no surgery): 3
Ross-Konno operation: 6 (+MVR: 1)
Coarct. repair: 1 severe AR, PHT - died @ 3 months
Gerald Tulzer, AustriaFetal Cardiac Interventions

Complications
pericardial effusion >3mm
bradycardia
thrombosis LV
balloon tear off
Aortic regurgitation
3/24
9/24
5/24
2/24
11/24
no drainage
intracardiac therapy
stop, repeat procedure
wait
resolved
IUD 3/24
Gerald Tulzer, AustriaFetal Cardiac Interventions

• Intrauterine aortic valvuloplasty for AS is technically feasible.
• Success depends on a series of predictive factors, including cardiac
structural changes (severe endocardial fibroelastosis), devices available
(angle of cannula entry, cannula designs and catheter and wire
configurations), fetal positioning, ultrasound imaging, maneuver
sophistications and post-interventional care, etc.
• In addition, quick maneuvers may minimize the progressive fetal
bradycardia.
• A successful procedure was anyway achieved in 81% at 21-26-week
gestation fetuses.
• However, fetal aortic valvuloplasty was not a definitive solution for fetal
AS.

Intrauterine pulmonary valvuloplasty
• PA/IVS is characterized by complete obstruction to RVOT with varying
degrees of right ventricular and tricuspid valve hypoplasia.
• Intrauterine pulmonary valvuloplasty in fetuses with PA/IVS allows
potential growth and functional improvement of the right heart thereby
increasing postnatal survival and biventricular repair.
• Prenatal treatment of the lesion may prevent development of non-
immune hydrops and intrauterine death, however, only limited cases have
been reported.
• Fetal cardiac intervention for PA/IVS is a challenging procedure because of
the anatomical features of the RVOT and the difficult access to the
pulmonary valve.
• With advancing gestation, a steady increase of the RV-to-PA gradient
could lead to a high rate of pregnancy termination (61%) and some
intrauterine death (5%) if left untreated.

FetuswithPulmonaryAtresiawithIVS
“HypoplasticRightHeartSyndrome”

Procedure
• Pulmonary valvuloplasty in fetal life is also technically feasible in mid
gestation.
• With optimal fetal positioning with the aid of adequate echo imaging, a
limited maternal laparotomy without uterine exteriorization or incision
could be attained.
• Performed at 21-32-week gestation under maternal local anesthesia and
sedation by inserting a needle through maternal abdominal wall into the
uterine cavity under ultrasound guidance.
• Fetal analgesic is then injected before advancing the needle through the
fetal chest wall into the RV infundibulum of the fetus.

Procedure
• A guidewire is inserted through the needle and across the pulmonary
valve.
• A balloon catheter is inserted and then inflated to dilate the stenotic
valve.
• Access to the RVOT is acchieved through direct puncture by using a 19-
gauge cannula via a subcostal approach on the fetal chest or an
intercostal space next to the sternum, the cannula tip is directed into the
RVOT and the atretic PV is dilated by inflating a coronary angioplasty
balloon.
• After the final balloon deflation, the wire, balloon and cannula are
removed. The catheter and needle are then withdrawn.

Fetal balloon pulmonary valvotomy
Sharland 2006

39
Determinants of Outcome in Fetal Pulmonary Valve
Stenosis or Atresia with Intact Ventricular Septum
K evin, F ouron, Masaki, S mallhorn, C haturvedi, J aeggi - Toronto
Am J C ardiol 2007;99:699-703
Prediction of a non - biventricular outcome:
/ Montreal
•
•
•
•
TV / MV ratio < 0.7
RV / LV length ratio < 0.6
TV inflow duration < 31.5%
Presence of sinusoids
Sensitivity: 100%
75%Specificity:If 3/4 were present:
Children’s Heart C entre Linz Fetal Cardiac Interventions

Pulmonary Atresia with Intact Ventricular Septum n=12
Pt# GA Result Outcome Current
1
2
3
4
5
6
7
8
9
10
11
12
26
26
23
23
22
24
27
24
26
26
28
26
-
-
-
+
+++
++
+++
+++
++
++
++
++
liveborn 1V
liveborn 1V
TOP
alive
s/p BDG
s/p BDG
s/p BDG
biventricularliveborn
liveborn
liveborn
liveborn
liveborn
liveborn
liveborn
liveborn
balloon only
balloon+shunt
RVOT+shunt
balloon+RVOT
biventricular
biventricular
biventricular
BTS coronary anomalies
RVOT + BTS
RVOT+BTS
RVOT+BTS
biventricular
biventricular?
?
Tworetzky Dec 2010Fetal Cardiac Interventions

42
London / Linz experience
Pulmonary atresia with intact septum / critical PS
2 26 - Liveborn 32w, Charge Syndr., died after shunt Linz
4+5 24 +++ Re-atresia, 2nd proc 31w +++, 1.5 ventricle London
7+8 31 + No succ, 2nd proc 32w, 1.5 ventricle Linz
Children’s Heart Centre , Linz
9 28 +++ Liveborn, balloon+shunt, expected biventricular Linz
10 29 +++ In utero Linz
6 29 - Placental bleeding, delivery – IVH – died London
3 29 +++ Liveborn 36w, cath+shunt, biventricular London
Proc GA Res ult Outcome
1 26 +++ Liveborn, biventricular, balloon+shunt Linz

• Gómez Montes et al. reported fetal intervention was performed for PA/IVS
in 4 fetuses with technical success in all of them and with some
improvement of the right heart growth and hemodynamics early after the
procedure, thereby increasing the chances for a biventricular repair.
• Galindo et al. reported successful valvuloplasty of the pulmonary valve
performed in a fetus with critical pulmonary valve stenosis and heart
failure at 25-week gestation.
• It is important to learn that midgestation fetal tricuspid valve z score>-3
and good tricuspid valve growth are the important factors leading to
postnatal biventricular repair in fetuses with PA/IVS.
• According to the Boston experience, a Z-score >-3 is associated with
biventricular outcome and a <-3 score with univentricular palliation.

Balloon dilation of pulmonary valve in fetus
• It is feasible
• RV can be decompressed
• TR may improve and there may be growth of TV, RV and pulmonary
valve
• However valve may restenose or become atretic
• Complications eg placental bleeding, pericardial effusion,
bradycardia may occur
• Technically challenging
• Still need to learn a lot more patient selection

Prenatal intervention on the atrial septum
• 10-12% of HLHS patients have a restrictive IAS
• In HLHS , the existence of an interatrial communication is important for
oxygenated blood to be distributed to the body and to prevent pulmonary
congestion.
• Prenatal intervention on the IAS is indicated for an intact or highly
restrictive atrial septum, which promotes profound cyanosis and
pulmonary edema after birth, leading to little effective pulmonary blood
flow and resulting in chronic pulmonary venous hypertension and
lymphatic dilation.
• This can in turn result in increased perioperative morbidity and mortality
with stage I Norwood procedure.

• Postnatal atrial septotomy, albeit rapid and effective, may not reverse
pulmonary vasculature pathologies and further mortality in the first few
weeks or months of life.
• Therefore, midgestation intervention on atrial septum is imperative for
preventing pulmonary vasculature changes, reducing the need for
additional or urgent procedures and improving the infant’s surgical
outcome

• Thick septum
• Prone to re-stenosis
• Cannot perform a “septostomy”
• 19G cannula and a 3 mm balloon
Stent placement
• Larger cannula 18G
• Larger balloon 4 mm
• Access via left atrium
Problems with INTACT ATRIAL SEPTUM in HLHS

HLHS Intact Atrial Septum
Fetal Stent Placement
Tworetzky, 2010Fetal Cardiac Interventions

HLHS with restrictive or intact atrial septum
Marshall ,BostonFetal Cardiac Interventions

HLHS with IAS
BAS
Current survival 11/19 >50%
Tworetzky, 2010
Stage1 Survival to d/c = 14/19
Late deaths n=3
Fetal Demise n=2
In Utero n=0
Tech. Unsuccess. N=3
Stage1 Surv =1
Stage1 Died =1
Stage1 Died =1
(stent no flow)
Tech Success n=21
(stent x 2)
Liveborn n=19
After tech success
No Cath 9/19
Liveborn
Stage1 n=19
Procedures n=24

1990 – 2002 Children’s Hospital Boston
n=33 (10% of all HLHS)
Died Prior to Stage I
n = 7 (21%) Stage I
n = 26
Died < 30 days
10/26 (38%)
Overall survival was 48% at 30 days
(Vlahos et. al. Circulation

• By Marshall et al. Of 21 fetuses at 24- 34-week gestation who received this
procedure, there were 19 technical successes and two fetal deaths. An
ASD of at least 3 mm was confirmed to allow postnatal benefit. However,
postnatal outcomes were disappointing with a mortality of 58%.
• Chaturvedi et al. performed percutaneous USG-guided stenting of the IAS
in 10 fetuses. Two fetuses developed stent stenosis and died postnatally
from pulmonary hypertension and sepsis, respectively.
• Kalish et al. reported nine fetuses at 24-31- week gestation with HLHS/IAS
received fetal atrial septal stent placement, with technical success in five
and failure in four cases. Stent deployment may decompress the left
atrium. Additionally, there were no maternal complications.

Fetal cardiac pacing
• CHB can be life-threatening in fetuses. The etiologies were considered to
be inflammation and fibrosis at the AV node associated with the
production of antibodies.
• Heart block can progress during pregnancy and may result in hydrops
fetalis and eventual fetal demise.
• There are few effective treatment options for fetal heart block, as side
effects of fluorinated steroids (betamethasone or dexamethasone) have
been concerned.
• Poor response of congenital fetal heart block to IV maternal isoproterenol
can be an indication for permanent pacemaker implant before birth.
• In general, a permanent pacemaker is required in about 66% of the cases.

• The first trial of fetal cardiac pacing with a pacemaker implant for CHB was
reported in 1986.
• Initial attempts of intrauterine percutaneous pacing through a
transthoracic approach or an IVC route resulted in fetal demise shortly
after the procedure.
• The initially proposed approach was an epicardial pacing lead on the fetal
heart with an extra-uterine PG implanted in the mother.
• However, a lack of myocardial fixation and dislodgment of the
percutaneous lead due to fetal movement were the major limitations of
the percutaneous approach.
• To resolve this problem, an entire single chamber pacing system without
exteriorized leads without risk of dislodgement of the pacing system was
developed.

• Assad et al. designed two modified pacing electrodes: a screw-in lead (1½
turns) and a stitch-on lead, which were tested in experimental models of
fetal heart block induced by cryosurgical ablation of the AV node.
• Assad et al. also designed a novel prototype T-shaped lead for secure
fixation onto the fetal myocardium and prevention from electrode
dislodgement, which could be introduced via an 18-G needle and
therefore an open surgery was not needed.
• Boudjemline et al. developed an implantable fetal pacing lead, which was
made of a flexible quadrifilar coil with outer silicone insulation and a fixed
screw on its distal tip.
• They found that the screw-in electrode was better for fetal pacing.

FCIs-Outcomes

Complications
• Isolated maternal anesthetic risks - however small, depend on the mode
of anesthetic used include maternal CV compromise with respiratory
distress and pulmonary edema.
• Placental abruption - and resultant maternal hemodynamic compromise
because of uterine manipulation to achieve optimal fetal positioning.
• Preterm labor (10%), after the procedure with a possible need for
maternal hospital admission and monitoring for implications of tocolysis.
• PROM (2% risk) may lead to a uterine infection, for which maternal
antibiotic therapy is required.
• Transient bradycardia (10-40%) due to needle puncture of the fetal heart
and needle manipulation during the procedure.

Complications
• Severe sustained fetal bradycardia and dysfunction have been noted,
requiring intracardiac or IM resuscitative medications.
• Hemopericardium, occasionally, pericardiocentesis is necessary for
impacting cardiac output.
• Intracardiac thrombus formation and loss of catheter tip have also been
reported.
• Higher incidence of fetal loss (10%) after the procedure than for
pregnancies continuing without invasive intervention.
• Generally, there is no change in the mode of delivery after cardiac surgery
in utero, and delivery plans are made on the basis of the usual obstetric
indications.

Contraindications
• Significant preexisting maternal disease or obstetric comorbidity
that would place the fetus or mother at higher risk, including:
 anesthesia and the invasive procedure itself
 a BMI exceeding 35 (relative contraindication)
 maternal communicable diseases such as HIV infection
 uncontrolled or pregestational diabetes (relative)
 history of cervical incompetence (relative)
 hematologic disorders that affect coagulation
 Significant extracardiac pathology in the fetus (significant
chromosomal abnormality and structural abnormalities other than
the cardiac lesion),
 Multiple gestation (relative)
 Inability of the mother to provide informed consent

FCIs-Recommendations

Limitations or failures of FCIs
• Although it is evident that technical success is possible for fetal aortic
and pulmonary valvuloplasty and atrial septoplasty, universal adoption
of in-utero treatment for all fetuses is not appropriate.
• The level of care both in the obstetric environment and for NICU may
not be available at all institutions.
• Currently, the practice of FCI is confined to a few institutions that have
invested a great deal of time and effort in research, development, and
refinement of technical expertise in this area.

Limitations or failures of FCIs
• Technical issues related to fetal positioning, stabilization,
and the need for continuous imaging by specially trained
personnel with experience in US guidance of invasive
procedures.
• Equipment-related limitations, including imaging artifacts
caused by the materials used to manufacture the needles,
wires, and catheters, exacerbated by the diminutive sizes of
the cardiac structures being imaged.

Future directions
• Given the relative rarity of these fetal CHDs, more collaborative effort is
necessary in order to improve the procedural techniques and to achieve
an acceptable safety level for both the mother and fetus.
• It is also essential to continue efforts to improve equipment technology
for diagnostic imaging and in the procedure room.
• One potentially important advance may come in the form of sophisticated
robot-guided FCI.
• Fetal therapy for congenital heart conditions is an area that holds great
promise in the management of complex cardiac disease.

Thank you

Fetal Cardiac Interventions

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