Progress in Pediatric Cardiology xxx (xxxx) xxx

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Progress in Pediatric Cardiology

journal homepage: www.elsevier.com/locate/ppedcard

Outcomes of total anomalous pulmonary venous drainage and predictors of

mortality—Tertiary center experience
Mohammad A. Ebrahim a, 1, *, Ameerah K. Alsaqobi b, 1, Aishah A. Alhajeri b, Mariam Al-Bahrani c,
Moustafa A. Elsayed d, Faisal M. Al-Saiedi d, Vadim G. Lyubomudrov d
a
Department of Pediatrics, Kuwait University Faculty of Medicine, Affiliated with Chest Diseases Hospital, Kuwait
b
Kuwait University Faculty of Medicine, Kuwait
c
Department of Medical Laboratory Sciences, Faculty of Allied Health Sciences, Kuwait University, Kuwait
d
Department of Pediatric Cardiac Surgery, Chest Diseases Hospital, Ministry of Health, Kuwait

A R T I C L E I N F O A B S T R A C T

Keywords: Total anomalous pulmonary venous drainage (TAPVD) is a rare congenital anomaly associated with a high
Total anomalous pulmonary venous drainage mortality rate, especially when associated with complex congenital heart disease (CHD). This is a retrospective
Surgical outcomes study, conducted between 2011 and 2020, aiming to document outcomes and identify predictors for mortality. A
Predictors of mortality
total of forty-three patients underwent repair. The mean follow-up time was 4.6 years (±2.3). Thirty-five patients
had isolated disease while 8 patients had complex TAPVD, 4 of which had single ventricle (SV) physiology. Pre-
and postoperative pulmonary venous obstruction (PVO) were documented at 28% and 21%, respectively. The
overall mortality rate was at 14% and highly associated with the SV group (p < 0.001). Multivariate analysis
revealed SV physiology, cardiopulmonary bypass time, intraoperative low rectal temperatures (ILRT), and open
chest (OC) as the only independent risk factors for early mortality. Conclusion: Outcomes were excellent in pa­
tients with the isolated type, but mortality remained high within the SV group. Death continues to be associated
with previously identified risk factors along with ILRT and an OC. PVO was not identified as a risk factor for
death, except in univariate analysis, with good outcomes following secondary repair to relieve the obstruction.
Overall survival beyond hospital discharge offers excellent outcome.

1. Introduction year of life [1,3,6,7].

Total anomalous pulmonary venous drainage (TAPVD) represents
1–3% of all patients with congenital heart disease (CHD) [1–8]. It results
from failure of the left atrium (LA) to unite with the pulmonary venous
plexus [6,9]. As a result, all pulmonary veins (PV) drain abnormally into
the systemic venous circulation. TAPVD is classified according to the site
of the pulmonary venous drainage into supracardiac (45%), cardiac
(25%), infracardiac (25%), and mixed (5%) [3,10].
The mortality following TAPVD repair remains relatively high,
despite the recent advances in diagnosis, management, and surgical
techniques [1,2,5,6,9,11]. In particular, outcomes for complex TAPVD
associated with single ventricle (SV) physiology and Heterotaxy syn­
drome remain grim [1,6]. Understandably without surgical repair,
TAPVD is invariably fatal with around 80% mortality during the first
The Chest Diseases Hospital (CDH) represents the only tertiary center
in Kuwait that manages all pediatric cardiac patients and is affiliated
with the Kuwait University, Faculty of Medicine. The aim of this study is
to present the most recent experience in managing TAPVD patients,
along with midterm outcomes. Risk factors for postoperative pulmonary
venous obstruction (PVO) and mortality were assessed. In addition,
outcomes for postoperative PVO repair are also described.
2. Methods
2.1. Study population
This is a retrospective study conducted from January 2011 to May
2020. This study included all patients with TAPVD that underwent

* Corresponding author at: Jabriya, Block 4, Street 102, 46300, Kuwait.

E-mail addresses: mohammad.ebrahim@ku.edu.kw (M.A. Ebrahim), Ameerah.saqobi@hsc.edu.kw (A.K. Alsaqobi), Aishah.hajeri@gmail.com (A.A. Alhajeri),
Mariam.albahrani@hsc.edu.kw (M. Al-Bahrani).
1
Contributed equally.

https://doi.org/10.1016/j.ppedcard.2021.101382
Received 19 August 2020; Received in revised form 15 March 2021; Accepted 6 April 2021
1058-9813/© 2021 Elsevier B.V. All rights reserved.

Please cite this article as: Mohammad A. Ebrahim, Progress in Pediatric Cardiology, https://doi.org/10.1016/j.ppedcard.2021.101382
M.A. Ebrahim et al.
cardiac surgery in Kuwait. Such patients were identified using a surgical
database, created in 2008, which incorporated all pediatric cardiac
surgeries performed at CDH. Patients were divided into 2 groups, iso­
lated or complex. The complex group was further subdivided into
biventricular (BV) or SV group. Isolated TAPVD included all patients
without CHD other than atrial septal defect (ASD), hemodynamically
insignificant ventricular septal defect (VSD), or a patent ductus arte­
riosus. Complex TAPVD group included all patients with other forms of
CHD. This study was approved by the Ministry of Health Standing
Committee for Coordination of Health and Medical Research and by the
Health Science Center Ethics Committee, Kuwait University.
All cases underwent detailed echocardiographic examinations. For
some patients, computed tomography and/or cardiac catheterization
were done to better delineate the cardiac and the pulmonary venous
anatomy. Preoperative, intraoperative, and postoperative variables
were assessed. Follow-up data was performed by evaluation of clinical
and echocardiographic data obtained at routine outpatient visits.
2.2. Definitions
Hospital death was defined as mortality prior to hospital discharge.
Mixed-type TAPVD was defined as an anomalous pulmonary venous
connection either with more than one draining vertical vein (VV) or
without a single pulmonary venous confluence (PVC) [2]. Major adverse
events are events subsequent to the hospital discharge following the
initial TAPVD repair and include surgical or interventional reoperations,
postoperative PVO, and/or late death. Preoperative PVO was diagnosed
by echocardiography if there was a flow acceleration of more than 2 m/s
within the PVs, the PVC, and/or the VV draining into the systemic cir­
culation. Similarly, postoperative PVO was also diagnosed if there was a
flow acceleration of more than 2 m/s within the PVs, and/or the PVC.
Postoperative PVO was classified into ‘anastomotic’ when it involves
solely the anastomosis previously constructed between the PVC and the
LA or the pulmonary venous atrium (PVA), and ‘ostial’ when it involves
individual PVs and/or their ostia. Prolonged intubation was defined as
more than 2 days of endotracheal intubation postoperatively. With
regards to the low cardiac output, there was no stringent diagnostic
criteria, except for an accepted collection of hemodynamic and physi­
ologic aberrations (metabolic acidosis, decreased urine output,
decreased cardiac function, hypotension, sinus tachycardia, etc.) which
alerted the cardiac intensivist to its presence and was documented in the
patient file.
2.3. Primary surgical techniques
Supra- and infracardiac TAPVD surgeries were performed with large
‘side to side’ anastomosis between the LA or the PVA and the PVC.
Specifically, for supracardiac TAPVD, a ‘superior approach’ anastomosis
was created using the space between the superior vena cava and the
ascending aorta [9]. The draining VV was usually ligated at the
innominate or lower diaphragm level, unless for SV patients with con­
cerns for developing anastomosis obstruction at the discretion of the
surgeon. For infracardiac TAPVD, the VV is typically used as a flap to
increase the length of the anastomosis and the volume of the ‘neo-PVA’.
PVs draining into the coronary sinus (CS) were repaired with unroofing
of the CS with pericardial patch sutured around the CS and the ASD,
separating the PVs from the systemic atrium. Otherwise, three patients
underwent direct anastomosis of the left upper PV with the LA
appendage and another patient underwent Warden procedure with
bovine pericardium channel created as part of their mixed-type TAPVD
repair. The surgeons also aim to preserve the natural patent foramen
ovale valve mechanism to allow right to left shunting, should post­
operative PVO develops, create the largest anastomosis possible be­
tween the LA appendage and the interatrial septum along with the
confluence hilum to hilum, as well as to minimize handling of the PVs
and avoid trauma to the PVs ostia.
2
Progress in Pediatric Cardiology xxx (xxxx) xxx
Most patients were exposed to normothermic or mild hypothermia
cardiopulmonary bypass (CPB) during primary repair. Moderate hypo­
thermia with decreased flow or deep hypothermia with circulatory ar­
rest (DHCA) was only utilized in few cases with temperatures measured
throughout the repair.
2.4. Statistical analysis
Statistical analysis was performed with the IBM Statistical Product
and Service Solution 26 (SPSS - IBM Corporations, Armonk, NY, USA).
Continuous variables were expressed as mean ± standard deviation or
median ± range, as appropriate. Differences in categorical variables
were compared using chi-square or Fisher’s Exact test, and Mann-
Whitney U test, Kruskal-Wallis test, or ANOVA test were used to
compare continuous variables, as appropriate. Variables for primary
time-related outcomes (postoperative PVO and death) were evaluated
using log-rank test in univariate analysis and Cox regression analysis in
multivariate analysis. A p-value (<0.06) was used for variable inclusion
on multivariate analysis. Otherwise, p-value <0.05 was considered
significant.
3. Results
3.1. Patients’ characteristics
A total of 49 patients with TAPVD were identified, however only 43
patients underwent TAPVD repair, comprising 2.8% of all intracardiac
surgeries performed. The mean follow-up time was 4.6 years (±2.3).
Seven patients were lost to follow-up. Thirty-five patients had isolated
disease versus 8 with complex TAPVD. Main preoperative characteris­
tics, types of TAPVD, preoperative PVO, associated CHD and mortality
were summarized in Tables 1 and 2. The weight at surgery was lower for
the complex groups (p = 0.04). In addition, cardiac-type TAPVD was
more commonly associated with the complex BV group (p = 0.038).
Preoperative PVO was documented at 28%. There were 4 SV physiology
patients, representing 9% of the cohort and 50% of the complex group.
The only mortality in the isolated group was unrelated to the cardiac
disease itself, rather due to obstructive jaundice and liver failure from
presumed Alagille syndrome (Tables 1 and 4).
3.2. Surgical results
Surgical and intraoperative data are summarized in Table 3. Post­
operative data and outcomes are shown in Table 4. Immediate post­
operative complications such as low cardiac output syndrome, open
chest (OC), and hospital death were significantly associated with the
complex groups (p = 0.003, p = 0.090, and p < 0.001, respectively).
3.3. Outcomes
During follow-up, major adverse events occurred in nine patients
(21%). Fig. 1 summarizs the overall surgical outcomes of the cohort.
Postoperative PVO occurred in nine patients (21% of all TAPVD repairs),
without a statistical difference among groups (Table 4). Kaplan Meier
curve for postoperative PVO is shown in Fig. 3.
Seven patients underwent surgical repair to relieve the postoperative
PVO (Table 5). In general, for postoperative PVO, enlargement of the
previous anastomosis was carried out for the ‘anastomotic’ type PVO
using autopericardium (Table 5). Otherwise, in two patients, sutureless
marsupialization repair was performed. Additionally, one patient un­
derwent patch plasty of a long segment left PV to LA obstruction (ostial)
and another patient underwent replacement of a previously created
stenotic channel from SVC into the LA (Warden repair). The mean
postoperative PVO diagnosis was at 92 days (±90 days).
Most obstructions were ‘anastomotic’ type and required site revision.
However, one patient underwent emergent VV ligation release prior to
M.A. Ebrahim et al. Progress in Pediatric Cardiology xxx (xxxx) xxx

Table 1
Main preoperative characteristics, types of TAPVD, preoperative PVO, associated CHD and mortality.
Total Isolated Complex, BVe Complex, SVf P-value
(n = 43) (n = 35) (n = 4) (n = 4)

Gender (male), na (%) n = 27 (65%) n = 21 (59%) n = 4 (100%) n = 2 (50%) 0.1251

Operation age (days) – median 17 days (0–8395) 18.5 days (0–8395) 15.5 days (1–60) 10 days (1− 20) 0.1832
Operation weight (kgb) – median 3.2 kg (1.8–50) 3.2 kg (1.8–50) 2.85 (2.1–3.4) 2.7 kg (2.6–2.8) 0.0402
GAc (weeks) – median 38 (32–42) 38 (32–42) 37 (37–39) 38 (38) 0.4552
TAPVDd type, n (%):
- Supracardiac 19 (44%) 16 (46%) 1 (25%) 2 (50%) 0.3551
- Infracardiac 13 (30) 11 (31%) 0 (0%) 2 (50%) 0.1431
- Cardiac 6 (14%) 4 (11%) 2 (25%) 0 (0%) 0.0381
- Mixed 5 (12%) 4 (11%) 1 (50%) 0 (0%) 0.3311
Obstructed TAPVD, n (%) 12 (28%) 8 (23%) 2 (50%) 2 (50%) 0.1131
Mortality, n (%) 6 (14%) 1 (3%) 1 (25%) 4 (100%) <0.0011
1
Fisher’s exact test.
2
Kruskal-Wallis test.
a
n: number.
b
kg: kilogram.
c
GA: Gestational age.
d
TAPVD: total anomalous pulmonary venous drainage.
e
BV: Biventricular.
f
SV: Single ventricle.

Table 2 Table 3
Detailed description of associated CHD in the complex group. Initial TAPVD surgical and intraoperative data.
CHDa, n (%) Total (n = 43) Complex (n = 8) Total (n Isolated Complex, Complex, P-value
= 43) TAPVDa BVj SVk
Single ventricle repair: 4 (9%) 4 (50%)
(n = 35) TAPVD (n TAPVD (n
- HLHSb 1 (2%) 1 (12.5%)
= 4) = 4)
- Heterotaxy/RAIc/AVSDd/PAe 2 (5%) 2 (25%)
- unbg AVSD/small RV 1 (2%) 1 (12.5%) Associated 7 (16%) 0 3 (75%) 4 (100%) <0.0011
Biventricular repair: 4 (12%) 4 (50%) procedures,
- LAIi/hypoplastic TVl/VSDm 1 (2%) 1 (12.5%) nb (%):
- TOFn 1 (2%) 1 (12.5%) - BT shuntc 3 0 1 2 0.0031
- CoAo 1 (2%) 1 (12.5%) - Norwood/ 1 0 0 1 0.0931
- VSD + CoA 1 (2%) 1 (12.5%) Sano shunt
a - PABd 1 0 0 1 0.0931
CHD: congenital heart disease. - VSDe repair 1 0 1 0 0.0931
b
HLHS: hypoplastic left heart syndrome. (patch)
c
RAI: right atrial isomerism. - CoAf repair 1 0 1 0 0.0931
d
AVSD: atrioventricular septal defect. CPBg time 59 59 78 73.5 0.4502
e (minh) – (28–180) (28–180) (35–177) (36–177)
PA: pulmonary atresia.
g
unb: unbalanced. median
i
LAI: left atrial isomerism. ACCi time 26 26 (14–67) 23 23 0.2802
l (min) – (14–69) (21–69) (21–47)
TV: tricuspid valve.
m median
VSD: ventricular septal defect.
n 1
TOF: tetralogy of fallot. Fisher’s exact test.
o 2
CoA: coarctation of the aorta. Kruskal-Wallis test.
a
TAPVD: total anomalous pulmonary venous drainage.
b
n: number.
the ultimate revision and another patient developed ‘ostial’ obstruction c
BT shunt: Blalock-Taussig shunt.
subsequent to an initial ‘anastomotic’ stenosis, with persistent residual d
PAB: pulmonary artery banding.
obstruction and death while being on ECMO due to myocardial e
VSD: ventricular septal defect.
dysfunction. f
CoA: coarctation of the aorta.
g
CPB: cardiopulmonary bypass.
h
3.4. Deaths Min: minutes.
i
ACC: aortic cross clamp.
j
Six patients died following TAPVD repair (Table 6). Five of which BV: biventricular.
k
SV: single ventricle.
were within the complex groups (4 SV) and three patients had preop­
erative PVO. One patient died following repair of postoperative PVO and
another patient died due to Alagille syndrome associated liver failure Additionally, other variables significantly associated with death
(isolated-type) after discharge. Otherwise, all mortality were in-hospital included age at surgery (p = 0.03), complex TAPVD (p < 0.001), SV
deaths. Kaplan Meier curve for survival is shown in Fig. 4. physiology (p < 0.001), CPB time (p = 0.0185), and OC (p < 0.001) with
intraoperative low rectal temperatures (ILRT) approaching near statis­
tical significance (p = 0.052). Multivariate analysis revealed SV physi­
3.5. Risk factors for postoperative PVO and deaths
ology, CBP time, ILRT, and OC as the only independent risk factors for
early mortality. No independent risk factors were found for post­
Univariable analysis identified weight at operation as the only var­
operative PVO however, weight at operation approached statistical
iable significantly associated with postoperative PVO (p = 0.017)
significance (p = 0.066).
(Table 7). Similarly, univariable analysis identified weight at operation
as a risk factor significantly associated with mortality (p = 0.008).

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M.A. Ebrahim et al. Progress in Pediatric Cardiology xxx (xxxx) xxx

Table 4
Initial post-operative and follow up data.
Initial repair Total (n = 43) Isolated TAPVD (n = 35) Complex, BVh Complex, SVi (n = 4) P-value
(n = 4)

Complications, na (%): 38 (88%) 30 (86%) 4 (100%) 4 (100%) 0.5001

- Low cardiac output syndrome 4 (9%) 1 (3%) 0 (0%) 3 (75%) 0.0011
- Open Open 11 (26%) 7 (20%) 1 (25%) 3 (75%) 0.0451
- Hypoxia 2 (5%) 1 (3%) 1 (25%) 0 (0%) 0.1711
- Postoperative acidosis 4 (9%) 3 (9%) 0 (0%) 1 (25%) 0.2881
- Acute kidney injury 3 (7%) 2 (6%) 1 (25%) 0 (0%) 0.2351
- Mechanical ventilatory support (>72 h) 6 (14%) 4 (9%) 1 (25%) 1 (25%) 0.1541
- SVTb 6 (14%) 6 (17%) 0 (0%) 0 (0%) 0.5001
- Sepsis 10 (23%) 7 (20%) 2 (50%) 1 (25%) 0.2071
- NECc 2 (5%) 2 (6%) 0 (0%) 0 (0%) 0.5001
- Wound infection 2 (5%) 2 (6%) 0 (0%) 0 (0%) 0.5001
- Pleural effusion 4 (9%) 2 (6%) 1 (25%) 1 (25%) 0.1511
- Pericardial effusion 2 (5%) 2 (6%) 0 (0%) 0 (0%) 0.5001
- Diaphragmatic palsy 4 (9%) 4 (11%) 0 (0%) 0 (0%) 0.5001
- Hypoglycemia 2 (5%) 1 (3%) 0 (0%) 1 (25%) 0.1711
- Bleeding 6 (14%) 4 (11%) 1 (25%) 1 (25%) 0.1541
- Hyperbilirubinemia 3 (7%) 3 (9%) 0 (0%) 0 (0%) 0.5001
- Hypertension 3 (7%) 2 (6%) 1 (25%) 0 (0%) 0.2351
- IVHd 2 (5%) 1 (3%) 1 (25%) 0 (0%) 0.1711
- Ventricular septal infarction 1 (2%) 1 (3%) 0 (0%) 0 (0%) 0.5001
- ECMOe 1 (2%) 0 (0%) 0 (0%) 1 (25%) 0.0931
- Intraoperative death 1 (2%) 0 (0%) 0 (0%) 1 (25%) 0.0931
- Hospital death 4 (9%) 0 (0%) 1 (25%) 3 (75%) <0.0011

Follow up data
FUf length (years) - mean (±SD) 4.6 (±2.3) 4.5 (±2.3) 3.3 (±2.4) 0.3 (±0.5) 0.3782
Number of patients with major adverse events, n (%) 9 (21%) 7 (20%) 1 (25%) 1 (25%) 0.5001
Major adverse event, n (%): 18 (42%) 15 (43%) 1 (25%) 2 (50%) 0.4321
- Reintervention rate 10 (23%) 7 (20%) 1 (25%) 2 (50%) 0.2071
- PVOg 9 (21%) 7 (20%) 1 (25%) 1 (25%) 0.5001
- Late death 1 (2.3%) 1 (3%) 0 (0%) 0 (0%) 0.5001
1
Fisher’s Exact test.
2
ANOVA.
a
n: number.
b
SVT: supraventricular tachycardia.
c
NEC: necrotizing enterocolitis.
d
IVH: intraventricular hemorrhage.
e
ECMO: extracorporeal membrane oxygenation.
f
FU: follow up.
g
PVO: pulmonary venous obstruction.
h
BV: biventricular.
i
SV: single ventricle.

4. Discussion
The incidence for TAPVD in the country was similar to previous
publications with reported incidence between 1 and 3% [1–8,10,12].
Herein, we describe a single-center’s most recent experience, aiming to
review the surgical results, midterm outcomes and assess risk factors for
postoperative PVO and death in TAPVD patients.
A couple of observations were noted within the cohort. Of note, this
cohort likely represented high-risk patients, due to the high frequency of
preoperative PVO, and Heterotaxy with SV physiology patients [1]
along with the complexity of the associated surgeries. Such a high-risk
group may explain some of the findings within this report.
The preoperative PVO rate had been ranging between 15 and 57%
[1–4,6–10,12,13], similar to this cohort. Preoperative PVO was not
found to affect mortality in this report, however, it did approach sta­
tistical significance. This is in contrast with other reports where a pre­
operative PVO had been shown to affect mortality especially for the SV
group [2,7,9,11,12]. A larger number of patients may have been
required to identify such an association. Our data support the known
association between the infracardiac-type TAPVD and the preoperative
PVO, with approximately half of which had a documented preoperative
PVO [1,5,7,8,13]. Patients with infracardiac TAPVD are more likely to
have a longer connection and portal system communication predispos­
ing to obstruction [6].
All the mixed-type TAPVD patients had done well without mortality,
similar to one report [8], but contrary to other studies [1,2,6,8,9,13,14].
All patients with mixed-type TAPVD in this study had isolated disease
except for one with Tetralogy of Fallot. All but one, had all veins
draining into CS except for the left upper PV and none had preoperative
PVO. Perhaps such factors may explain the excellent prognosis in such
subset of the cohort. Similarly, and in contrast to other reports [8],
cardiac-type TAPVD had not been associated with mortality.
Our surgical results and the techniques adopted were associated with
excellent survival rates, especially in the isolated group. The overall
mortality for TAPVD repair has been reported in the range of 8–34%,
depending on the complexity of the cohort, whether SV and Heterotaxy
syndrome were included, as well as the follow-up duration
[1,3,6,9,13,15]. There was only one mortality among the isolated group,
due to a non-cardiac etiology, compared to other reports between 5 and
27% [1,4,5,7,8,15]. In general, mortality rates had improved over the
most recent studies [1,3,4,6–9,12,13], and this is likely related to the
improved imaging, pre- and postoperative care along with better sur­
gical techniques [1,3,4,6,7,9]. Recently, sutureless technique had been
reported to be potentially superior to other forms of repairs, at least in
terms of rate of postoperative PVO, however, we only had a limited
number of patients with sutureless repair to draw any conclusions
[6–8,10,13]. Large multicenter randomized control studies need to be
conducted to determine the most appropriate surgical approach for such

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M.A. Ebrahim et al. Progress in Pediatric Cardiology xxx (xxxx) xxx

TAPVD1 repair
n = 43

Mortality Survivors
n=6 n = 37

Demise aer inial PVO2 Reoperaons No PVO

repair n = 7 (8 surgeries) reoperaons
n=5 n = 30

Demise aer
Alive Alive
reoperaon
n=7 n = 30
n=1

Dead Dead
n=0 n=0

Fig. 1. Summary of outcomes of the patients within this study.

1
TAPVD: total anomalous pulmonary venous drainage.
2
PVO: pulmonary venous obstruction.

Table 5
Postoperative PVO interventions and outcomes.
Patient TAPVD type Anatomy Pre-op Pathology Intervention Latest echo
PVOa

1 Supracardiac Isolated No Anastomosis None Borderline PVO - mean 5 mmHgb

2 Supracardiac Isolated No Channel obstruction Gore-Tex replacement No PVO
(Warden)
3 Supracardiac Isolated No Anastomosis 1- VVc ligation release No PVO
2- Revise anastomosis
4 Supracardiac Isolated No Anastomosis None Post-op PVO - mean 14 mmHg
5 Infracardiac Isolated No Anastomosis Revise anastomosis No PVO
6 Infracardiac Isolated No Ostial Sutureless repair No PVO
7 Cardiac Isolated Yes Anastomosis Revise anastomosis No PVO
8 Cardiac Complex – LAId/hypoplastic TVe/ Yes Anastomosis Revise anastomosis No PVO
VSDf
9×2 Infracardiac Complex – unbalanced AVSDg/ Yes 1- Anastomosis 2- Ostial 1- Sutureless repair Died on ECMOi after latest
small RV 2- Patch-plasty PV-LA intervention
junctionh
a
PVO: pulmonary venous obstruction.
b
mmHg: millimetre of mercury.
c
VV: vertical vein.
d
LAI: left atrial isomerism.
e
TV: tricuspid valve.
f
VSD: ventricular septal defect.
g
AVSD: atrioventricular septal defect.
h
PV-LV junction: pulmonary vein-left atrial junction.
i
ECMO: extracorporeal membrane oxygenation.

patients.
Nevertheless, mortality rates for the complex TAPVD patients remain
high, especially for the SV patients and Heterotaxy syndrome [1]. The
specific mortality for the complex group approached 50%, with reports
up to 74% in other series [1,2,9,11], and 100% in SV with Heterotaxy
syndrome [1]. Specifically, for the 10 patients with SV physiology in this
study, 6 patients had died. Unfortunately, all 4 patients with repaired
TAPVD and associated SV had died (Fig. 2). In contrast, only 2 patients
among the unrepaired TAPVD/SV group had died, both with Hypo­
plastic left heart syndrome. Of note, 2 patients with Heterotaxy/SV
patients that underwent concomitant TAPVD repair did not survive. In
contrast, all 3 Heterotaxy/SV patients that underwent surgical palliation
without TAPVD repair had survived, two of which had completed the
Fontan operation, and one was scheduled for the Fontan palliation at the
time of the manuscript submission (Fig. 2). While comparing TAPVD/SV
repaired group outcomes with SV palliation results, in general, is beyond

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M.A. Ebrahim et al. Progress in Pediatric Cardiology xxx (xxxx) xxx

Table 6
Mortality of TAPVD-repaired patients.
Patient Group Diagnosis Operations Mortality Cause of death

1 Isolated TAPVD (infracardiac - unobstructed) TAPVD repair Late death Obstructive jaundice with liver failure
TAPVDa (Alagille syndrome)
b
2 Complex HLHS , TAPVD (supracardiac - obstructed) Norwood, TAPVD Intraoperative Acute hypotension ➔ cardiac arrest
TAPVD repair death
3 Complex Unbalanced AVSDc, TAPVD (infracardiac - obstructed). S/pd Left PVe stenosis Hospital death Clot in ECMOf circuit
TAPVD TAPVD repair × 2 & Glenn
4 Complex Heterom, RAIg, AVSD, PAh, TAPVD (supracardiac – RBTSi, TAPVD Hospital death Desaturations ➔ bradycardia arrest
TAPVD unobstructed) repair
5 Complex Hetero, RAI, AVSD, PA, TAPVD (infracardiac - RBTS, TAPVD Hospital death Low cardiac output
TAPVD unobstructed) repair
6 Complex VSDj, CoAk, TAPVD (supracardiac – obstructed) CoA repair, TAPVD Hospital death Sepsis, ICHl, low cardiac output
TAPVD repair
a
TAPVD: total anomalous pulmonary venous drainage.
b
HLHS: hypoplastic left heart syndrome.
c
AVSD: atrioventricular septal defect.
d
S/p: status post.
e
PV: pulmonary vein.
f
ECMO: extracorporeal membrane oxygenation.
g
RAI: right atrial isomerism.
h
PA: pulmonary atresia.
i
RBTS shunt: right Blalock-Taussig shunt.
j
VSD: ventricular septal defect.
k
CoA: coarctation of the Aorta.
l
ICH: intracerebral hemorrhage.
m
Hetero: heterotaxy.

increased PVR following augmentation of Qp subsequent to surgical

Table 7
palliation, especially with tendency of intimal hyperplasia with such
Predictors of postoperative PVO and early death.
abnormal pulmonary vasculature [9,11,16]. Additionally, there is evi­
Outcomes Variable Univariate Cox multivariable analysis dence of genetic reprogramming of PV endothelium in the face of
P-value
Hazard 95% CIa P-value downstream obstruction leading to collagen production and fibrotic scar
ratio formation [9].
Postoperative Operation 0.0171 0.066 Moreover, patients with complex TAPVD had evidence of growth
PVOb weight retardation given lower weight at surgery despite similar GA compared
Early death Operation 0.031 0.159 to the isolated group, analogous to other patients with complex CHD
age
[17]. The lower weight at surgery is potentially, in part, contributing to
Operation 0.0081 0.732
weight the higher complication and reintervention rates, along with mortality
Complex 0.000 2
0.452 among this group [5,6,8,10,13]. In addition, the greater tendency for
TAPVDc reintervention rate among the complex group in part, due to patients
SVd 0.0002 75.73 8.135–705.1 <0.001
undergoing staged repair and/or palliation procedures.
physiology
CPBe time 0.01851 1.052 1.009–1.096 0.018
Most TAPVD repair cases have been done under normal or mild
Open chest 0.0002 24.46 2.704–221.2 0.004 hypothermia given neurodevelopmental concerns, the associated coa­
Rectal 0.0521 0.835 0.704–0.990 0.038 gulopathy and renal dysfunction; similar to other rare reports [4]. Over
tempf the past decade, we realized that even with substantial blood flow from
1
Mann-Whitney U test. the pulmonary venous return, it is still possible to visualize structures
2
Log-rant test. and perform wide anastomosis. Normally, the PVC is large enough to
a
CI: confidence interval. accommodate a suction tip until anastomosis completion.
b
PVO: pulmonary venous obstruction. Complex TAPVD, univentricular physiology, CPB time, ILRT, post­
c
TAPVD: total anomalous pulmonary venous return. operative OC, younger age, and less weight during surgery were all
d
SV: single ventricle. associated with mortality in the univariate analysis, which is a finding
e
CPB: cardiopulmonary bypass.
f similar to other reports [1,2,4–8,14]. Independent risk factors on
Temp: temperature.
multivariate analysis were SV physiology, CBP time, ILRT, and OC
(Table 7) [1,5,6,9]. To the best of our knowledge, ILRT and OC had not
the scope of this paper, it is reasonable to hypothesize that the added been previously known as risk factors for mortality in TAPVD patients.
complexity of the associated TAPVD repair to the SV palliation explains All of those factors are usually surrogate for more complex disease and
the poor outcomes in such subgroup of the cohort, especially that all poor postoperative recovery. Pre- and postoperative PVO was not
TAPVD repair in this setting had been during the initial stage of palli­ associated with mortality, especially for biventricular patients, unlike
ation where patients are mostly unwell, surgery was performed in an other reports [6,7,9,14]. This could be partly related to the excellent
urgent manner, and with usually lower weight during surgery. More­ outcomes of preoperative PVO in terms of relief of obstruction and the
over, most SV patients in this cohort had RV dominance, with higher timely surgery once patient is diagnosed with obstruction to avoid
mortality rates compared to LV dominant patients [11]. prolonged obstruction and its consequences to PVs.
Other reasons for high mortality rates amidst SV patients include Postoperative PVO occurred in 21% of the cohort, with prior reports
predisposition to high pulmonary vasculature resistance (PVR), with suggestive of a rate of 5–32% [1–8,10,11,13,14,16,18]. Similar to other
frequently some degree of obstruction masked by the decreased pul­ studies, early presentation of obstruction following repair was the most
monary blood flow (Qp), due to the abnormal anomalous veins [1,9,11], common presentation [16]. Weight at operation was significantly

6
M.A. Ebrahim et al. Progress in Pediatric Cardiology xxx (xxxx) xxx

SV1 Paents
10

Unobstructed Unobstructed Obstructed

Unobstructed (cardiac- (supra+infracardiac-type) (supra+infracardiac-type)
(supracardiac-type)
type) unrepaired unrepaired repaired repaired
4 2 2 2

Fontan-stage Died
2:Hetero2/RAI3/PA4/AVSD5
Died Died
Hetero/RAI/AVSD/PA → 1:Unb AVSD --> PAB12 → BDG13
1:Hetero/RAI/DORV6/unb7 HLHS → Hybrid BTS 1: HLHS → Norwood/BTS
AVSD/PS8
3
1 2 2

Died Lost to f/u10

HLHS9 → Norwood/Sano unb AVSD/PA → BTS11
1 1

Fig. 2. Single ventricle patients’ outcomes.

1
SV: single ventricle.
2
Hetero: heterotaxy.
3
RAI: right atrial isomerism.
4
PA: pulmonary atresia.
5
AVSD: atrioventricular septal defect.
6
DORV: double outlet right ventricle.
7
Unb: unbalanced.
8
PS: pulmonary stenosis.
9
HLHS: hypoplastic left heart syndrome.
10
F/u: follow-up.
11
BTS: Blalock-Taussig Shunt.
12
PAB: pulmonary artery band.
13
BDG: bidirectional Glenn.

Fig. 3. Kaplan Meier curve for survival. Fig. 4. Kaplan Meier curve for postoperative pulmonary venous stenosis.

associated with postoperative risk for PVO, and lower age at surgery had
the tendency for postoperative PVO as well, resembling other studies
[5,6,10,19] (Table 7). In one patient, PVO began at the anastomotic site
but later progressed into the PV ostia, likely related to obstruction from
downstream anastomosis narrowing [6,16]. Less commonly, narrowing
of PVs occur in isolation, which may carry a higher morbidity and
mortality [9,13,16]. Anastomotic-type obstruction is the most common
[16], possibly related to the constriction of the contractile elements
within the PVC, resulting in inadequate postoperative growth [6,10] or
that PVO is enhanced by the mere difference in wall thickness at the
anastomosis site between PVC and PVA [10], or simply related to the
initial surgical manipulation predisposing into progressive obstruction
[6]. There was only one death among patients with postoperative PVO,
unlike other studies [1,6,7,11,14]. This is partly explained by the lack of
intimal hyperplasia of individual PVs observed which carry a worse
prognosis [16] and perhaps the aggressive re-repair to avoid such
complication.
We encountered an interesting adult patient with initial complaints
of shortness of breath and later diagnosed with unobstructed, supra­
cardiac TAPVD. This is extremely rare with only few patients surviving
into adulthood without repair [1,6,7,20]. Luckily, this patient had iso­
lated disease with large ASD which most likely contributed to her long
survival.

7
M.A. Ebrahim et al.
5. Conclusion
TAPVD repair results were excellent in the isolated type but mor­
tality remained high within the complex groups. However, the survival
for a subset of patients with unobstructed, cardiac-type TAPVD associ­
ated with Heterotaxy and SV physiology was excellent. Mortality con­
tinues to be associated with previously identified risk factors such as SV
physiology, and CBP time on multivariate analysis. In addition, ILRT and
OC were also shown to be independent risk factors for mortality. No
independent risk factors were associated with postoperative PVO, except
for weight at surgery on univariate analysis. Prognosis following post­
operative PVO repair was excellent. Overall, survival beyond hospital
discharge offers excellent outcome. There was no specific TAPVD-type
that was associated with worst outcomes.
6. Limitations
This study is subject to the usual limitations of retrospective studies.
Those patients with TAPVD that died prior to surgery or never had
surgery altogether were not captured in the database.
Funding
There is no funding source.
Ethical approval
This article does not contain any studies with human participants or
animals performed by any of the authors.
CRediT authorship contribution statement
MAE – Conceptualization, methodology, ethics paperwork, article
drafting, revision, concept, and design; 2) AKA – ethics paperwork,
methodology, literature search, data collection, article drafting; 3) AAA
– data collection; 4) MAB – statistical analysis; 5) MAE – critical revision
of article, performed surgeries; 6) FMA – critical revision of article,
performed surgeries; 7) VGL – critical revision of article, performed
surgeries.
Declaration of competing interest
The authors declare that they have no conflict of interest.
Progress in Pediatric Cardiology xxx (xxxx) xxx
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