Case Presentations (Table 1):
Patient A was initially evaluated by pediatric cardiology at 20 1/7
weeks gestational age (wga) for fetal bradycardia noted that same day on
20-wga anatomy scan, with persistent heart rates of 72-78 beats per
minute (bpm). The fetal heart rate was 163 bpm on a 12 wga ultrasound.
Fetal echocardiogram (echo) demonstrated regular atrial rates of 146-152
bpm and ventricular rates of 75-80 bpm in a pattern consistent with 2:1
2° AVB. The echo was otherwise normal. Due to concerns for
immune-mediated heart block, we initiated dexamethasone but discontinued
this therapy when maternal anti-Ro/SSA and anti-La/SSB antibodies were
negative; of note, this treatment strategy was used for all the cases
reported in this series. Follow-up ultrasound at 21 6/7 wga demonstrated
a normal heart rate and rhythm of 163 bpm. Weekly ultrasounds until 25
wga and then every few weeks through the remainder of pregnancy
confirmed normal rate and rhythm. A female infant was delivered at 39
2/7 wga via emergency c-section for prolonged heart rate deceleration
and maternal chorioamnionitis; Apgar scores were 2, 4, 8. Postnatal EKG
demonstrated sinus rhythm with a normal QTc interval; telemetry
monitoring demonstrated intact AV conduction. Postnatal echo confirmed a
structurally normal heart.
Patient B was initially seen at 19 1/7 wga for bradycardia noted on
routine obstetrical evaluation at 19 wga. Fetal echo confirmed a
structurally normal heart and 2:1 2° AVB with atrial rates of 145-162
bpm and ventricular rates of 72-75 bpm. The pregnancy was also notable
for selective reduction of a twin with trisomy 21. Follow-up echo at 21
1/7 wga demonstrated atrial and ventricular rates of 146-155 bpm with a
normal mechanical PR interval. Weekly obstetrical fetal heart rate
assessments were normal through 25 4/7 wga, at which time a follow-up
echo also confirmed normal rate and rhythm. The mother was returned to
routine obstetrical monitoring. A female infant was delivered at term
(37 5/7wga) at another hospital; a postnatal EKG was recommended.
Patient C (Figure 2) was diagnosed with multiple fetal
anomalies (open neural tube defect with hydrocephalus, horseshoe kidney,
echogenic bowel, anorectal malformation, 2-vessel umbilical cord) at 25
1/7 wga and referred to pediatric cardiology for right >
left ventricular size discrepancy and ventricular septal defect. The
initial fetal echo demonstrated a left superior vena cava to coronary
sinus and suspected coarctation of the aorta; the fetal heart rate was
138 bpm with a normal mechanical PR interval. However, during an
ultrasound in the Maternal Fetal Medicine Center 2 hours later, fetal
AVB was suspected. An urgent, repeat fetal echo confirmed 2° AVB with
atrial rates of 130-140 bpm and ventricular rates of 65-70 bpm. There
was also a brief period of sinus bradycardia (92 bpm) with first-degree
AVB (mechanical PR interval 160-180 msec). A follow-up fetal heart
rate/rhythm check the next day was normal (137 bpm). A repeat echo at 25
4/7 wga confirmed atrial and ventricular rates of 129-141 bpm with a
normal mechanical PR interval. Weekly fetal heart rate checks for 4-6
weeks and follow-up echos at 31 1/7 wga and 35 1/7 wga demonstrated
normal rate and rhythm. A male infant was born at 37 wga via c-section
for spontaneous rupture of membranes with an open neural tube defect; he
was confirmed to have a large lumbar meningomyelocele and CHARGE
syndrome. Postnatal echo confirmed bilateral superior vena cavae,
bicuspid aortic valve, and long-segment coarctation of the aorta, for
which he underwent aortic arch augmentation at 1 month of age. Although
his post-operative course was complicated by an accelerated junctional
rhythm, his EKGs and telemetry monitoring otherwise demonstrated sinus
rhythm and normal QTc intervals.
Patient D was found to have bradycardia on obstetrical anatomy
ultrasound at 18 6/7 wga. Fetal echo the following day (19 wga)
confirmed 2° AVB with atrial rates of 150-158 bpm and ventricular rates
of 73-77 bpm. Follow-up obstetrical ultrasound at 21 wga demonstrated
atrial and ventricular rates of 144 bpm; fetal rate and rhythm remained
normal for the duration of pregnancy. A female infant was born at term
(40 1/7wga) via an uncomplicated vaginal delivery. Postnatal EKGs
demonstrated sinus rhythm with normal QTc intervals.
Discussion :
Fetal immune-mediated AVB is well understood and is known to be
associated with maternal anti-Ro/SSA antibodies that can irreversibly
damage the developing AV node and injure the
myocardium[1-4].
However, AVB is often diagnosed in women who do not know they have
anti-Ro/SSA
antibodies[12].
Disease onset mostly commonly occurs between 16 and 26 wga; diagnosis
after 28 wga is
rare[1]. The
transition between sinus rhythm and complete AVB may be as short as 12
hours[13]. Children
with third-degree AVB require lifelong cardiac pacing; there is also
risk for developing cardiomyopathy with need for heart
transplantation[1-4].
However, anti-Ro/SSA-mediated 2° AVB treated rapidly with dexamethasone
and intravenous immunoglobulin (IVIG) has been shown to be
reversible[13].
Differentiating transient, non-immune mediated AVB from
anti-Ro/SSA-mediated AVB is critical, as the therapeutic window for
anti-Ro/SSA-mediated 2° AVB is
short[13]. The
differential diagnosis also includes AVB from LQTS, myocarditis, ccTGA
or LAI and blocked atrial
bigeminy[14-20].
Transient, fetal non-immune mediated AVB has rarely been described in
the setting of normal intracardiac anatomy and appears to be benign.
There have been a few prior case reports of fetal AV
block[8-11] that
self-resolved in a similar time frame to our reported cases. In our
cases, there were no structural cardiac abnormalities that led to
malformation of the fetal conduction system.
The mechanism of transient, non-immune fetal AVB remains poorly
understood; some suggest it may be a vagally-mediated phenomenon in the
immature conduction system, which has a preponderance of parasympathetic
tone[8]. All
reported cases demonstrate complete and permanent resolution within a
couple of
weeks[8-11]. In the
absence of maternal anti-Ro/SSA antibodies, it is reasonable to monitor
fetuses who are otherwise well without intervention. A management
approach is detailed below (Figure 3 ).
Careful analysis with fetal echo includes rhythm evaluation and
screening for structural heart disease. Simultaneous pulse Doppler
assessment of the mitral inflow and aortic outflow, the superior vena
cava and aorta, or the pulmonary artery and pulmonary vein can be used
to determine the atrial and ventricular relationship and to measure the
mechanical PR interval; M-mode and color M-mode can supplement this
assessment[14].
Hepatic vein Doppler can be used to determine if there is a regular or
irregular atrial rate and to confirm that the rhythm does not represent
blocked atrial bigeminy, characterized by a “short-long-short-long”
atrial interval and a variable atrial
rate[20,
21]. Second-degree AVB is
characterized by a regular atrial interval and
rate[20].
Structural analysis should exclude ccTGA or
LAI[5,
6] and evaluate for other echo signs
that may suggest anti-Ro/SSA-mediated disease or
myocarditis[12,
22-25]. It is also important to
measure the isovolumic relaxation time (IVRT), which is prolonged in
LQTS[15], and
surveil for other LQTS arrhythmias, including ventricular tachycardia,
torsade de pointes, and persistent sinus bradycardia, defined by fetal
heart rate below the third percentile for gestational
age[17-19].
Upon initial diagnosis of fetal AVB, maternal screening for autoimmune
disease includes testing for maternal anti-Ro/SSA antibodies and careful
clinical evaluation for signs/symptoms of autoimmune disease, which is
often unrecognized prior to detection of fetal
AVB[12].
Dexamethasone should also be considered pending anti-Ro/SSA results
given the risks of rapid progression of anti-Ro/SSA-mediated 2° AVB.
This can be discontinued if anti-Ro/SSA antibodies are negative.
Maternal thyroid studies can also be obtained, as maternal thyroid
disease may also impair fetal cardiac
conduction[26].
Parental EKGs, as well as inquiries into a family history of long QT
syndrome, seizures, syncope, cardiac arrest, or sudden unexplained death
encompass a complete screening for LQTS or other inherited
channelopathies[17].
Maternal avoidance of QT prolonging medications should also be
considered until the fetal diagnosis is
made[17].
Once a diagnosis of fetal AVB is made, home fetal heart rate monitoring
can be an empowering tool for ongoing fetal
assessment[27,
28]. At least weekly fetal heart rate
assessment, by the obstetrician or the cardiologist, is recommended
until AVB resolves and should be considered for at least four subsequent
weeks to exclude recurrence, which is not typical for transient, benign
AVB[11]. A
follow-up fetal echo in 2-4 weeks can be used to confirm resolution of
AVB, with additional fetal echos during the remainder of pregnancy as
needed to support obstetrical assessment. In our patients, we chose to
repeat a fetal echo at ~35-36 wga to confirm normal
fetal heart rate and rhythm prior to delivery. Fetal magnetocardiography
can be considered for more precise determination of fetal cardiac
conduction and evaluation for channelopathies; but this currently has
limited
availability[14-16].
A postnatal EKG completes the assessment.
Conclusion :
Transient, benign 2° AVB is a rare phenomenon that occurs in the second
trimester of pregnancy and is a diagnosis of exclusion. Key management
approaches include careful screening for anti-Ro/SSA mediated AVB and
LQTS, evaluation for structural heart disease, close in utero monitoring
for self-resolution, and postnatal EKG.
Table 1 . Summary of Cases of Transient Second-Degree
Atrioventricular Block