Abbreviations:
TOF: Tetralogy of Fallot
NIS: National Inpatient Sample
HCUP: Healthcare Cost and Utilization Project
AHRQ: Agency for Healthcare Research and Quality
ICD-9: International Classification of Disease-Ninths edition
ICD-10: International Classification of Disease-Tenths edition
LOS: length of stay
IQR: Inter Quartile Range.
Abstract
Background: Surgical management of severely symptomatic neonates with
Tetralogy of Fallot (TOF) is controversial. Some centers perform primary
surgical repair (EPSR) in neonates with TOF, while others perform staged
palliation with initial palliative intervention (PI).
Aim: of the study: To compare outcomes between neonates with TOF who had
EPSR and those who had PI.
Materials and Methods: The study utilized the US National Inpatient
Sample dataset for the years 2000 to 2018. We identified patients who
had EPSR and those with PI (aortic to pulmonary shunt or cardiac
catheter palliative intervention).
Results: A total of 29,292 neonates with TOF were identified; of them
1726 neonates had EPSR, 4363 had PI. Hospital mortality was similar in
both groups (PI 7.4% vs EPSR 8.0%, p = 0.41). Patient in the PI group
had more comorbidities; chromosomal anomalies (PI 13.2% vs. ESPR
7.8%, p < 0.001), prematurity (PI 15.1% vs. EPSR
10.4%, p < 0.001), and low birth weight <
2500 grams (PI 15.4% vs. EPSR 10.3%, p < 0.001).
Median length of stay and median cost of hospitalization were
significantly higher in the EPSR (25 days vs. 19 days, and $312,405 vs.
$191,863, respectively, p < 0.001).
Conclusion: EPSR had similar mortality to PI but comes with a higher
resource utilization and complications. If we include the cumulative
morbidity and resource utilization associated with a two staged repair,
EPSR could be proven as a better strategy in symptomatic neonates with
TOF. A prospective superiority study on symptomatic neonates with TOF
randomized to either ESPR or PI is needed to further answer this
question.
Introduction:
The ideal surgical approach when managing neonates with Tetralogy of
Fallot (TOF) is still controversial (1). In 1945, subclavian artery to
pulmonary artery anastamosis was created as a palliation for patients
with TOF (2). A decade later, Lillehei and colleagues performed first
intracardiac repair for TOF with ventricular septal defect closure and
right ventricular outflow obstruction relief (3). The surgical and
perfusion techniques, as well as the postoperative care has advanced and
evolved since that time. Despite that evolution, the two concepts of
surgical interventions had remained the same. There is still much debate
on what is the ideal surgical approach to infants with TOF, an early
primary surgical repair versus a two-staged surgical approach with an
initial temporarily shunt for pulmonary blood flow. The aim of this
study was to determine if one strategy had lower mortality than the
other, and to assess the hospital length of stay and cost of charge in
both groups.
Methods:
The data were obtained from the National (Nationwide) Inpatient Sample,
part of the Healthcare Cost and Utilization Project (HCUP), sponsored by
the Agency for Healthcare Research and Quality. This is the largest
publicly available all-payer inpatient care database in the United
States, containing data from more than seven million hospital stays each
year (4). The National Inpatient Sample database randomly samples 20%
of the discharges from participating hospitals in 47 US states and the
District of Columbia. The sampling method provides a geographically
distributed sample that represents all inpatient admissions in the
nation. The use of data from approved public datasets is not considered
human subject research; the study was granted exempt status from the
Cleveland Clinic Institutional Review Board.
The study population was identified using the International
Classification of Diseases, Ninth and Tenth Revisions, Clinical
Modification (ICD-9&10-CM). Data were queried from the years 2010 –
2018. Neonates (age < 30 days) with diagnosis of TOF were
included in the study. These patients were further stratified into 3
groups: no intervention, complete surgical repair or palliative
intervention (systemic-to-pulmonary arterial shunt, cardiac catheter
intervention on the pulmonary valve or ductus arteriosus stent).
The primary outcome is the in-hospital mortality between the patients
who underwent repair in the neonatal period versus those who underwent
palliative intervention in the neonatal period. The secondary outcomes
include the length of hospital stay and the hospital cost of charge.
Continuous variables were described using median and interquartile range
(IQR). Categorical variables were described using frequencies and
percentages. Demographics, clinical characteristics, and outcomes were
compared using Mann-Whitney U test for continuous variables and
Chi-square or Fisher’s exact tests for categorical variables.
Statistical significance was set at P < 0.05. The analysis
was performed by SPSS software, version 25 (SPSS Inc., Chicago, IL) was
used for statistical analysis.
Results:
We identified 29,292 neonates with TOF, neonates who needed intervention
during first 30 days of life were found to be 6089 (20.78%). Of those,
1726 (28.35%) had early primary surgical repair (EPSR) and 4363
(71.65%) had palliative intervention (PI). Table 1 shows basic
characteristics of the study groups. The majority of these patients were
males, PI male (55.0%) and EPSR male (57.3%). Neonates with PI had
higher frequency of diagnoses chromosomal abnormalities (PI 13.2% vs
EPSR 7.8%, p < 0.001). Other non-cardiac anomalies were
present at higher frequency in EPSR group (EPSR 21.9% vs. PI 19.2% p =
0.015). Patients who had PI had higher rate of prematurity (<
37 weeks-gestation: PI 15.1% vs EPSR 10.4%, p< 0.001) and
higher frequency of low birth weight (birth weight < 2500
grams: PI 15.4% vs EPSR 10.3%, p < 0.001). Outcomes are
presented in table 2. Hospital mortality was similar in both groups (PI
7.4% vs EPSR 8.0%, p = 0.41). Mechanical ventilation was used more
frequently in the patients with EPSR (EPSR 50.4% vs PI 47.2%, p=
0.027). The length of hospital stay was longer in the EPSR (EPSR 25 days
vs PI 19 days, P < 0.001). The cost of charge was
significantly higher in the EPSR (EPSR $ 312,405 vs PI $191,863, p
< 0.001). Extracorporeal membrane oxygenation utilization was
similar in both groups (EPSR 4.6% vs PI 3.5%, p=0.053).
Discussion:
There is still much debate about management of symptomatic neonates with
TOF, a two staged repair (initial stage of securing source of pulmonary
blood flow followed by later stage of a full repair) versus an early
(neonatal) primary surgical repair. This study goal was to compare the
outcomes of these two approaches, we evaluated 6089 neonates with TOF
who either had an early primary surgical repair (1726, 28.3%) versus
4363 neonates (71.65%) who had a palliative intervention
(aortopulmonary shunt, or cardiac catheter intervention on pulmonary
valve or ductus arteriosus stenting). The major findings of this study
are as follows: in hospital mortality is similar between the two groups
(EPSR vs PI) but EPSR approach comes with higher resource utilization
(prolonged hospital stay, higher frequency of mechanical ventilation and
higher cost of charge). It is important to mention that the resource
utilization includes only the index hospitalization, however a two
staged approach requires another hospitalization for full repair,
therefore the cumulative morbidity and mortality of PI could be higher,
but this was not the focus of this study. There are advantages and
disadvantages to each approach, an early primary surgical repair would
restore normal cardiovascular anatomy and physiology, resolve chronic
cyanosis and promote neurodevelopment during critical period of brain
growth in early infancy. Early primary surgical repair would also relief
the right ventricular afterload and allow for early myocardial
remodeling. Early repair may also restore the normal development of
pulmonary vasculature and alveologenesis in patients with diminished
pulmonary perfusion (5). The advantages of a two staged repair are
mainly avoiding potential organ damage with neonatal open-heart surgery
and allow for time to attain somatic growth and organ maturity prior to
the utilization of CPB in the second stage. The risks associated with
systemic to pulmonary shunts are well described and they include shunt
thrombosis, pulmonary artery distortion, excess of volume load on the
pulmonary vasculature and the left ventricle with potential pulmonary
vasculature disease and congestive heart failure. (6-9) In this study we
are comparing approaches in symptomatic neonates with TOF who needed an
intervention during the 30 days of life, we are not comparing early
primary surgical repair versus late surgical repair, previous studies
had shown that primary surgical repair at later age in infancy in
asymptomatic TOF patients carries less morbidity and mortality than
neonatal surgical repair (10,11).
We used data from a large multicenter national database that randomly
samples 20% of the discharges from hospitals across the United States
with both a large number of patients and a wide range of practice
variations, this allowed us to evaluate the surgical management in
neonates with TOF. An important finding on the current surgical practice
of TOF is that only 28.3% of neonates had an early complete surgical
repair, which eludes that majority of centers prefer palliative
intervention rather than early surgical repair in neonates with TOF. We
also noted a patient selection bias in this retrospective study, we find
that hospitals in the United States are inclined to use a palliative
intervention in patients with significant comorbidities as low birth
weight, prematurity and chromosomal anomalies. The only comorbidity that
was present at higher frequency in the EPSR was the presence of other
non-cardiac anomalies.
Limitations: there are several limitations to this study, we were not
able to assess long-term outcomes, and specifically, which group will
have better neurological outcome and which group will have better right
ventricular function. We used an administrative database, and the study
relied on the ICD-9 and ICD-10 diagnosis and procedure codes for
identifying the study population and the associated comorbidities. The
benefits of using this database is the large sample size, some
limitations are inherent to all retrospective studies using
administrative databases. Incorrect or missing data may exist and the
lack of validation of the data collected by chart review is a source of
potential bias for errors. However, in a large study such as ours, the
patients’ volume likely offset these inaccuracies. Another limitation of
our study is the restriction to the hospitalization period, and this
prevented us from evaluating long term outcomes.
Conclusion: Early primary surgical repair of neonates with TOF had
similar in hospital mortality to neonates with TOF who received
palliative intervention as neonates. The resource utilization was much
higher in the EPSR but this included only the index hospitalization,
however a two staged approach requires another hospitalization for full
repair, therefore the cumulative morbidity and mortality of PI could be
higher. A future prospective randomized study with long-term follow up
is needed to further answer if early neonatal surgical repair is the
ideal approach for symptomatic neonates with TOF.
References:
- Kanter, K. R., Kogon, B. E., Kirshbom, P. M., & Carlock, P. R.
(2010). Symptomatic Neonatal Tetralogy of Fallot: Repair or Shunt?Annals of Thoracic Surgery , 89 (3), 858–863.
https://doi.org/10.1016/j.athoracsur.2009.12.060
- Blalock
A, Taussig HB: The surgical treatment of malformations of the heart in
which there is pulmonary stenosis pulmonary atresia. JAMA
1945;128:189-202.
- Lillehei, C. Walton Ph.D., M.D.; Varco, Richard L. Ph.D., M.D.; Cohen,
Morley Ph.D., M.D.; Warden, Herbert E. M.D.; Gott, Vincent L. M.D.;
Dewall, Richard A. M.D.; Patton, Cecelia R.N.; Moller, James H.
M.D. The First Open Heart Corrections Of Tetralogy Of Fallot, Annals
Of Surgery: October 1986 - Volume 204 - Issue 4 - P 49
- Agency for Healthcare Research and Quality. Overview of the National
(Nationwide) Inpatient Sample (NIS). Available at
https://www.hcupus.ahrq.gov/nisoverview.jsp
Accessed 23 Sep 2020
- Johnson RJ, Haworth SG. Pulmonary vascular and alveolar development in
tetralogy of Fallot: a recommendation for early
correction. Thorax . 1982;37(12):893-901.
doi:10.1136/thx.37.12.893
- Stanley PH, Chartrand C, Davignon A, et al. Palliative surgery in
tetralogy of Fallot. Can. J. Surg. J. canadien de chirurgie.
1981;24:475–479.
- Yuan SM, Shinfeld A, Raanani E. The Blalock-Taussig shunt. J. Cardiac.
Surg. 2009;24:101–108.
- Fermanis GG, Ekangaki AK, Salmon AP, et al. Twelve year experience
with the modified Blalock-Taussig shunt in neo- nates. Eur J
Cardiothorac Surg 1992;6:586–9.
- Gladman G, McCrindle BW, Williams WG, Freedom RM, Benson LN. The
modified Blalock-Taussig shunt: clinical impact and morbidity in
Fallot’s tetralogy in the current era. J Thorac Cardiovasc Surg
1997;114:25–30
- Loomba, R. S., Buelow, M. W., & Woods, R. K. (2017, June 1). Complete
Repair of Tetralogy of Fallot in the Neonatal Versus Non-neonatal
Period: A Meta-analysis. Pediatric Cardiology , Vol. 38,
pp. 893–901. https://doi.org/10.1007/s00246-017-1579-8
- Ghimire, L. V., Chou, F. S., Devoe, C., & Moon-Grady, A. (2020).
Comparison of In-Hospital Outcomes When Repair of Tetralogy of Fallot
Is in the Neonatal Period Versus in the Post-Neonatal Period.American Journal of Cardiology , 125 (1), 140–145.
https://doi.org/10.1016/j.amjcard.2019.09.025
Table 1. Basic Characteristics of Tetralogy of Fallot in
neonates.