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FOR PEER REVIEW - CONFIDENTIAL

Pacing Through Complexity: Navigating a Catch-22 Situation in Congenital Heart Block.

Tracking no: 06-2024-MFCS-00122

Authors:
Prashanth Urs (Apollo Hospitals, Bannerghatta Road), Gagandeep Singh Nagi (Apollo Hospitals, Bannerghatta Road), Anup Itihas G B (Apollo Hospitals,
Bannerghatta Road), and Basila TV (Apollo Hospitals, Bannerghatta Road)

Abstract:
A secundigravida mother conceived spontaneously after 5 years of marriage and had an un-eventful pregnancy till the 20th week of gestation. On a
routine clinical follow-up, fetal bradycardia was noted, and worked up, leading to the diagnosis of fetal heart block secondary to Sjogren's syndrome. The
mother was started on immunosuppressant therapy, but the heart block continued to progress from second-degree to complete heart block. Soon after
birth, an ECG confirmed the diagnosis of a complete congenital heart block. The patient was managed with a multidisciplinary approach involving
pediatric cardiology, cardio-thoracic surgery, and neonatology teams. Treatment options including medication and pacing were considered, and the
decision to proceed with pacemaker implantation was made despite the challenges posed by comorbidities, which rendered the surgery high-risk. This
strategic choice aimed to effectively manage persistent bradycardia and ensure optimal cardiac function drawing a poignant parallel to the mythological
struggle of navigating through the treacherous waters of the Strait of Messina. Post-implantation, the patient showed significant improvement in
symptoms and cardiac function.

Author Cover Letter:

Dear Editor-in-Chief, I am writing to submit a case report titled "Pacing Through Complexity: Navigating a Catch-22 Situation in Neonatal Congenital
Complete Heart Block" for potential publication in NeoReviews. This report provides an in-depth examination of a challenging and rare case of congenital
complete heart block (CCHB) in a neonate, detailing the complexities and critical decision-making processes involved in the management of this
condition. The case highlights the therapeutic dilemma of balancing act between the urgency of early intervention and the risks associated with pacing in
such a delicate patient population. The report not only underscores the medical and technical aspects of managing CCHB but also delves into the ethical
considerations and multidisciplinary coordination required to optimize patient outcomes. Given the rarity of CCHB and the unique challenges it presents,
this case report offers valuable lessons and can contribute to the existing literature by guiding clinicians facing similar situations. On behalf of all the
contributors I will act as a guarantor and will correspond with the journal from this point onward. We hereby transfer, assign, or otherwise convey all
copyright ownership, including any and all rights incidental thereto, exclusively to the journal, in the event that such work is published by the journal. I have
enclosed the manuscript along with this cover letter. I look forward to the possibility of publishing our work in NeoReviews. Thank you for considering
our submission. Sincerely, Dr. Anup Itihas, Apollo Hospitals, Bangalore

Competing interests:

Funding:

Disclaimer: This is a confidential document and must not be discussed with others, forward in any form, or posted on websites without
the express written consent of AAP.
 Cover Letter

Dear Editor-in-Chief,

I am writing to submit a case report titled "Pacing Through Complexity: Navigating a Catch-22
Situation in Congenital Heart Block" for potential publication in NeoReviews. This report
provides an in-depth examination of a challenging and rare case of congenital complete heart
block (CCHB) in a neonate, detailing the complexities and critical decision-making processes
involved in the management of this condition.

The case highlights the therapeutic dilemma of balancing act between the urgency of early
intervention and the risks associated with pacing in such a delicate patient population.
The report not only underscores the medical and technical aspects of managing CCHB but also
delves into the ethical considerations and multidisciplinary coordination required to optimize
patient outcomes. Given the rarity of CCHB and the unique challenges it presents, this case
report offers valuable lessons and can contribute to the existing literature by guiding clinicians
facing similar situations.

On behalf of all the contributors I will act as a guarantor and will correspond with the journal
from this point onward.
We hereby transfer, assign, or otherwise convey all copyright ownership, including any and all
rights incidental thereto, exclusively to the journal, in the event that such work is published by
the journal.

I have enclosed the manuscript along with this cover letter. I look forward to the possibility of
publishing our work in NeoReviews. Thank you for considering our submission.

Sincerely,
Dr. Anup Itihas,
Apollo Hospitals, Bangalore
Title:
Pacing Through Complexity: Navigating a Catch-22 Situation in Congenital Heart Block.

Running title:
Prashanth, et al.: Congenital atrioventricular block

Author(s):
Prashanth Urs, DCH, DNB, Fellowship in Neonatology (Australia)*,
Brig Gagandeep Singh Nagi MS, Mch (CTVS)#,
Anup Itihas, MD, FNNF †,
Basila Rahman, MD, DNB ‡

Affiliations:

*Head of Department-Neonatology, Apollo Hospitals, Bannerghatta Road, Bengaluru.

#Consultant Cardio-thoracic and vascular surgeon, Apollo Hospitals, Bannerghatta Road,
Bengaluru.
† Clinical Fellow, Department of Neonatology, Apollo Hospitals, Bannerghatta Road,
Bengaluru.
‡Clinical Fellow, Department of Neonatology, Apollo Hospitals, Bannerghatta Road,
Bengaluru.

Address correspondence to: Dr. Anup Itihas, Clinical Fellow-Department of Neonatology

Apollo Hospitals, Bannerghatta Road,
Bengaluru-560076

Email id- anupitihas12@gmail.com

Mobile no.- +919844406447
ORCID- 0000-0002-0250-3248

Funding Source: No funding was secured for this study.

Financial Disclosure: The authors have no financial relationships relevant to this article to
disclose.

Conflict of Interest: The authors have nonconflicts of interest to disclose.

Abbreviations:
Congenital atrioventricular block (CAVB)
Congenital heart block (CHB)
Cardiothoracic and Vascular Surgery (CTVS)
Implantable Electronic Devices (IEDs)
Neonatal intensive care unit (NICU)
Permanent pacemaker (PPM)
Case presentation:
A 37-year-old mother with no known comorbidities G2P1A1 conceived spontaneously after 5
years of marriage. The pregnancy was booked and registered. 1st-trimester USG was normal
with normal fetal cardiac activity with HR of 164 bpm. The Anomaly scan done on the 18th
week was also normal. But two weeks later on a follow-up visit, a low fetal heart rate was noted,
and a repeat ultrasound was advised, which was suggestive of fetal bradycardia with FHR of
57bpm with pericardial effusion and mild cardiomegaly. A fetal echocardiogram was conducted
to validate and reaffirm the identified findings. There were no associated antenatal comorbidities
known at that time.

Case Progression:
Since the mother’s clinical examination was normal, a subclinical autoimmune disorder was
suspected and was worked up. She tested positive for anti-RO-52, anti-RO/SSA, and anti-
SSB/La antibodies. The mother was started on dexamethasone, IV Immunoglobulin, and
Hydroxychloroquine, and a fetal echo was performed every two weeks. On further follow-ups, a
2:1 second-degree CHB was noted on a 22-week fetal echo, which progressed to a complete AV
conduction block by 28 weeks of gestation.
Delivery and Maternal outcome:
The baby was delivered via an uncomplicated cesarean section at 38 weeks term gestation due to
concerns about fetal heart rate abnormalities noted on antenatal monitoring. The postpartum
course was normal.
Neonatal Outcome:
A male neonate was born with Apgar scores 8 and 9 at 1 and 5 minutes, respectively. The baby
exhibited no immediate signs of distress and weighed 2.24 kg at birth. On physical examination,
the neonate appeared well-nourished with a Heart rate of 76bpm, respiratory rate of 40 breaths
per minute, and oxygen saturation of 98% in room air. No signs of respiratory distress, cyanosis,
or heart murmurs were noted. Due to the high risk of complications associated with CHB, the
baby was transferred to the neonatal intensive care unit (NICU) for close monitoring.
At 30 minutes of life, the baby developed apnea and hence was intubated and put on respiratory
support. UVC was secured and Isoprenaline was started at 5 mic/kg/min and maintenance fluids.
The baby required minimal ventilatory support. An electrocardiogram (ECG) taken shortly after
birth revealed a complete heart block with a ventricular rate of 60 bpm and an atrial rate of 150
bpm (Fig 1a). These findings were consistent with a diagnosis of complete congenital heart
block. The patient's echocardiogram showed a large Ostium Secundum Atrial septal defect and a
large Patent ductus arteriosus with bradycardia and normal cardiac functions.
On Day 2 of life, first-line antibiotics were started as per the unit policy i/v/o positive sepsis
screen. Chest x-ray was s/o collapse-consolidation of the left upper lobe. Follow-up 2D echo on
day 3 of life revealed functional closure of PDA, with persistent OS-ASD, moderate pulmonary
hypertension, and bradycardia. Antibiotics were continued as CRP was in an increasing trend.
The baby continued to require ventilatory support and profound hypoxemia was found on blood-
gas analysis. Repeat 2D echo revealed severe pulmonary hypertension in addition to previous
anatomical findings. IV sildenafil was started and given for 4 days but pulmonary hypertension
was persistent. Multiple attempts to stop isoprenaline infusion failed as the baby developed
severe bradycardia with HR less than 50 bpm on tapering the chronotrope. On day 11, the baby
had tension pneumothorax which was promptly managed with needle decompression and chest
tube insertion. As a result of the progressively falling cardiac output possibly due to the loss of
synchrony between the atria and ventricles, the baby developed cardiogenic shock, which was
managed with fluid blouses and inotropes. Consequently, the decision was made to schedule a
permanent pacemaker implantation; however, the surgery was deferred due to the presence of
pneumothorax, lung collapse, hypotension, and potential sepsis. The Neonatology, Pediatric
Anesthesia, and Cardiothoracic and Vascular Surgery (CTVS) teams convened to collaboratively
assess the risk-benefit ratio for the surgery. These findings were then communicated to the
parents, and consent for the high-risk surgery was obtained. On day 17, epicardial pacemaker
(ATSR01-Medtronic) insertion was done by a Cardiothoracic surgeon with a set heart rate of 120
bpm (Fig 2). The baby tolerated the procedure well, and a normal ECG was documented (Fig
1b). Over a week, the respiratory support was gradually weaned, and the baby was successfully
transitioned to non-invasive ventilation. The baby was discharged from the NICU after 31 days
and continued to receive close follow-up care in the outpatient setting.
Discussion

Congenital atrioventricular block (CAVB) is a condition occurring in the fetal/neonatal period

characterized by the abnormal conduction of electrical impulses from the atria to the ventricles.
It is relatively rare, estimated to occur in approximately 1 in 15,000-20,000 live births (1).
However, the true incidence could be much higher as CAVB causes significant fetal loss (2). The
most common cause of congenital heart block (CHB) is maternal autoimmune disorders, which
account for approx. two-thirds of all cases. Anti-Ro/SSA and/or anti-La/SSB antibodies are
commonly associated. These antibodies cause fibrosis of the AV nodes and cause interruption of
electrical impulses, leading to a block at the AV level (3). Structural heart diseases and
Idiopathic familial CHB are responsible for the rest of the cases (4).

Congenital-CHB is a unique fetal-specific disease because it has never been recorded in the
maternal heart despite the presence of similar antibodies in the mother. The occurrence of fetal
bradycardia as a manifestation of CHB was first observed in 1921 and is often the earliest
indicator of the condition (5). Although congenital heart block is permanent, there are a few
sporadic cases in which AV nodal rhythm spontaneously converts to sinus rhythm. Buyon et al.
studied 107 babies with mothers positive for anti-SSA/SSB antibodies and needed pacemaker
implantation. Around two-thirds (63 babies) needed pacemaker therapy, 35 underwent
pacemaker implantation in the neonatal period, 15 in infancy, and 17 babies after one year (6).
Another study by Jaggi et al found that regardless of the time of onset of heart block, only 11%
of neonatal cases did not require pacemaker implantation at 20 years of age (7). Low fetal heart
rate may cause non-immune hydrops or neonatal low-output cardiac failure, while some
newborns can compensate with low heart rate, but most need pacemaker implantation (8)(9).

Our approach was consistent with the 2021 PACES Expert Consensus Statement on the
use of cardiovascular Implantable Electronic Devices (IEDs) in Pediatric Patients (8). Permanent
pacemaker (PPM) placement is a definitive treatment for CHB in the presence of symptomatic
bradycardia and a resting heart rate <50 beats/min without a structural cardiac defect, or <70
beats/min with a defect. Early pacing of high-risk newborns with CHB may mitigate the negative
effects of profound bradycardia and asystole shortly after birth, a period with high metabolic
demands. The prognosis after pacemaker implantation is often quite good (9). But even with
pacemaker insitu around 5 to 11 percent of patients experience long-term cardiac failure, most of
whom had abnormal echocardiograms before pacemaker implantation, and is linked to
underlying myocardial fibrosis caused by CHB (10).

Almost half of the mothers who have SLE autoantibodies are unaware of their disease
until their infants are born with CHB. It is only through the birth of an affected child that these
mothers are identified as having this autoimmune disorder, as they are asymptomatic at delivery
(11). When a fetus has isolated CHB, especially in the latter half of the second trimester,
autoantibodies against the intracellular SSA/Ro-SSB/La ribonucleoproteins are predicted to be
present in the mother with as much as 85% certainty (12). Consequently, additional testing of the
mother's anti-SSA/Ro and anti-SSB/La antibodies should be recommended upon incidental
discovery of fetal bradycardia/heart block on prenatal ultrasound.

Conclusion

Balancing the decision to wait for the lung to settle, risking potential deterioration, versus opting
for a high-risk surgery is a critical consideration. In navigating the decision between waiting for
comorbidities to settle (Scylla) and the need for improved cardiac condition (Charybdis), we find
ourselves in a situation akin to the mythological dilemma of sailing between Scylla and
Charybdis, through the Strait of Messina (From the Homer’s Odyssey). Much like the sailors
attempting to avoid the perils of both monsters, we must carefully steer a course between
delaying surgery and risking the child's deteriorating health, recognizing the potential pitfalls on
either side of the decision. Further studies with larger cohorts and longer follow-up periods are
warranted to better understand the optimal management strategies and long-term outcomes of
patients with CAVB.

Lessons learnt

 In cases of fetal bradycardia where there are no associated antenatal comorbidities and
normal mother's clinical examination, a subclinical autoimmune disorder must be
suspected.
 Permanent pacemaker placement is the definitive treatment for complete heart block
when symptomatic bradycardia is present.
 In making this decision, we must carefully weigh the pros and cons of high risk surgery.
In our case, the strategic choice to undergo high risk surgery successfully mitigated
persistent bradycardia and ensured optimal cardiac function.
References

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Fig 1a. ECG shows atrial (P waves) and ventricular (QRS complexes) activity that are
independent of each other, and an atrial rate faster than the ventricular rate, s/o Complete heart
block.
Fig 1b. Immediate Post-OP ECG showed normal cardiac activity, with similar atrial and
ventricular rates.
Fig 2. Epicardial Pacemaker ATSR01-Medtronic in situ.
Figure 1
Figure 1
 Figure 2

Fig 2. Epicardial Pacemaker ATSR01-Medtronic in-situ.