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Division of Cardiovascular Surgery, Children's National Heart Institute, Children's National Hospital, The George Washington University School of Medicine and Health Sciences, Washington, DC
Division of Cardiovascular Surgery, Children's National Heart Institute, Children's National Hospital, The George Washington University School of Medicine and Health Sciences, Washington, DC
Division of Cardiovascular Surgery, Children's National Heart Institute, Children's National Hospital, The George Washington University School of Medicine and Health Sciences, Washington, DC
Division of Cardiovascular Surgery, Children's National Heart Institute, Children's National Hospital, The George Washington University School of Medicine and Health Sciences, Washington, DC
Division of Cardiovascular Surgery, Children's National Heart Institute, Children's National Hospital, The George Washington University School of Medicine and Health Sciences, Washington, DC
Division of Cardiovascular Surgery, Children's National Heart Institute, Children's National Hospital, The George Washington University School of Medicine and Health Sciences, Washington, DC
Division of Cardiovascular Surgery, Children's National Heart Institute, Children's National Hospital, The George Washington University School of Medicine and Health Sciences, Washington, DC
Address for reprints: Can Yerebakan, MD, Division of Cardiovascular Surgery, Children's National Hospital, The George Washington University School of Medicine and Health Sciences, 111 Michigan Ave NW, Washington, DC 20010.
Division of Cardiovascular Surgery, Children's National Heart Institute, Children's National Hospital, The George Washington University School of Medicine and Health Sciences, Washington, DC
The study objectives were to analyze the outcomes of pediatric patients with heterotaxy syndrome undergoing cardiovascular surgery and to determine the predictors of mortality.
Methods
A retrospective analysis of 82 patients diagnosed with heterotaxy syndrome who underwent cardiovascular surgery between January 2008 and December 2017 was performed. Univariate and multivariable Cox regression analyses to determine risk factors for mortality and Kaplan–Meier analysis for survival were performed.
Results
Patient mortality in the cohort was 34% (28/82), including 36% (20/55) for single ventricle palliation and 30% (8/27) for biventricular repair. At 5 years, the probability of survival did not differ between the groups by log-rank testing (P = .829). Multivariable analysis found extracorporeal membrane oxygenation support (hazard ratio, 10.4; 95% confidence interval, 4.3-25.4; P < .001), total anomalous pulmonary venous return (hazard ratio, 4.3; 95% confidence interval, 1.7-10.8; P = .002), and birth weight 2.5 kg or less (hazard ratio, 2.4; 95% confidence interval, 1.0-5.4; P = .041) to be independent risk factors for mortality in all-comers. Pulmonary vein stenosis was a univariate predictor of mortality among all patients with heterotaxy (hazard ratio, 3.0; 95% confidence interval, 1.4-6.4; P = .005) and in the subgroup of patients with single ventricles (hazard ratio, 4.0; 95% confidence interval, 1.7-9.7; P = .002). Overall survival was 66% (54/82) at a median follow-up time of 2.2 years (0.4-4.1) from the initial surgery.
Conclusions
Outcomes of children with heterotaxy syndrome, irrespective of the operative pathway, remain suboptimal in the current era. Risk factors for mortality in this population include birth weight 2.5 kg or less, extracorporeal membrane oxygenation, pulmonary vein stenosis, and total anomalous pulmonary venous return, which may help to further optimize surgical decision making. Multiorgan system involvment is frequently encountered in these patients.
In the current era, morbidity and mortality of patients with heterotaxy syndrome continue to be high for both univentricular and biventricular repair pathways.
Patients with heterotaxy syndrome continue to have poor outcomes in the current era despite advancements in perioperative care and refinements in operative techniques. Although low birth weight, anomalous pulmonary venous return, and ECMO support were predictors of mortality in our cohort, involvement of multiple organ systems may have contributed to unfavorable outcomes.
Surgical outcomes of the treatment of congenital heart disease continue to improve. However, certain patient groups are still burdened with suboptimal outcomes despite extensive efforts to augment surgical strategies and perioperative management. Patients with heterotaxy syndrome are one group whose survival has been known to be inferior in comparison with those patients without this syndrome.
The goal of our study is to analyze the operative outcomes of patients with heterotaxy syndrome and to compare differences between those undergoing single ventricle (SV) palliation and those undergoing biventricular (BiV) repair in the last decade. We also sought to determine predictors of mortality to better understand and treat this unique patient population.
Materials and Methods
Patient Selection
The Institutional Review Board of Children's National Hospital approved this study with a waiver of individual consent (Institutional Review Board #10485, approved October 29, 2018).
All patients with heterotaxy syndrome who underwent cardiac surgery at our institution between January 2008 and December 2017 were identified. The Children's National echocardiogram database was queried for all cardiac features suggesting heterotaxy, including an unroofed coronary sinus, abnormal systemic venous connections, abnormal pulmonary venous connections, and dextrocardia. Patients were included if they met the definition of heterotaxy promulgated by Jacobs and colleagues,
specifically an abnormal arrangement of thoracoabdominal organs across the left-right axis of the body. Other inclusion criteria including abnormally symmetric lungs/bronchi, an abnormally symmetric liver, abnormally symmetric atrial appendages, abnormal mesenteric attachments/bowel locations, and abnormal spleen (asplenia, polysplenia, or single-right sided spleen) were looked for in the echocardiography results as proposed by Van Praagh and colleagues.
Patients with thoracoabdominal situs inversus totalis were excluded. All patients who underwent primary cardiovascular repair at outside institutions were excluded from the study.
Patients were then classified as SV or BiV according to their functional anatomy after final repair. SV patients were further divided according to the stage of repair: stage 1 (pulmonary artery banding, Blalock–Taussig shunt or Norwood procedure), stage 2 (bidirectional Glenn operation or Kawashima operation), or stage 3 (Fontan operation).
Outcome Data Collection
Detailed patient data were recorded from a review of electronic medical records including cardiac catheterization reports, cardiopulmonary bypass records, daily progress notes, discharge summaries, operative reports, and all cardiac imaging (echocardiographic reports, cardiac computed tomography angiogram results, and cardiac magnetic resonance imaging results). Demographics, detailed cardiac anatomy, extracorporeal membrane oxygenation (ECMO) support, hospital stay, length of mechanical ventilation, mortality, and surgical interventions were recorded for all patients. Every cardiac surgical intervention (including each stage in cases of staged repair/palliation) was detailed for each patient in the SV and BiV groups. However, surgical and catheter reinterventions were excluded. Prematurity has been defined as gestational age 37 weeks or less. Low birth weight has been defined as 2.5 kg or less. Pulmonary vein stenosis was defined as echocardiographic evidence of narrowing in combination with a measured mean gradient greater than or equal to 5 mm Hg. Operative mortality has been defined according to the Society of Thoracic Surgeons Congenital Heart Surgery Database as both (1) all deaths occurring during the hospitalization in which the operation was performed, even if after 30 days; and (2) those deaths occurring after discharge from the hospital, but within 30 days of the procedure.
Interstage mortality has been defined as all deaths occurring between 30 days postoperatively and the next stage of palliation. Last cardiology follow-up and mortality status were confirmed for all patients, including all international patients. Collaboration with physicians for outside institutions was attempted for all patients who were lost to follow-up but were unsuccessful.
Statistical Analysis
Categorical data are presented as frequencies and percentages, and continuous variables are presented as medians and interquartile ranges. Kaplan–Meier curves were constructed to estimate cumulative patient survival over time, as well as survival after each palliative stage of repair in the SV group. Numbers at risk are presented for Kaplan–Meier curves and 95% confidence limits around the curves were obtained using Greenwood's formula.
Cox proportional hazards regression was implemented to determine risk factors of mortality, and variables with P less than .05 were included in the multivariable Cox model. Regression analyses were performed in all patients with heterotaxy (SV and BiV), as well as among SV patients only. Results from time-to-event models are presented as adjusted hazard ratios (HRs) with corresponding 95% confidence intervals (CIs). The assumption of proportionality of hazards was verified using Schoenfeld residuals.
Stata (version 16.0, Stata Corp LLC) was used for all statistical analyses.
The total sample size of 82 patients with an observed mortality rate of 34% provided 80% power for detecting an HR of 3 in Cox regression modeling, assuming a 2-tailed 5% alpha level. A sample size of 55 patients in the SV subgroup will provide 80% power to detect an HR of 3.5 in Cox regression analysis, assuming a 2-tailed 5% alpha and 36% observed mortality rate. Power and sample size calculations were performed using the “power cox” package in Stata (version 16.0, Stata Corp LLC).
Results
Characteristics of Patients With Heterotaxy Syndrome Undergoing Cardiac Surgery
Eighty-two patients with heterotaxy syndrome met the inclusion criteria described and underwent cardiac surgery. Of the cohort, 55 patients (67%) underwent SV palliation and 27 patients (33%) had a complete BiV repair. The operative course of each group and the number of patients at each operative stage are shown in Figure 1. The underlying cardiac diagnoses are elucidated in Figure 2.
Figure 1Flow diagram depicting the operative pathway of patients with heterotaxy syndrome who underwent cardiac surgery consisting of SV palliation or complete BiV repair. SV, Single ventricle; PA, pulmonary artery.
Figure 2Pie chart illustrating the primary cardiac diagnosis of patients with heterotaxy who underwent SV palliation versus those who were amenable for complete BiV repair. DORV, Double outlet right ventricle; HLHS, hypoplastic left heart syndrome; AV, atrioventricular; L-TGA, L-transposition of the great arteries; DILV, double inlet left ventricle; TOF, tetralogy of Fallot; VSD, ventricular septal defect; ASD, atrial septal defect; IAA, interrupted aortic arch.
Patient characteristics including demographics, anatomy, and the presence of preoperative risk factors are shown in Table 1. The median number of risk factors per patient was 3 in the SV group and 2 in the BiV group. Among patients with hypoplastic left heart syndrome or double outlet right ventricle, the prevalence of low birth weight was 29% (6/21) and 32% (7/22), respectively, and 36% (8/22) of patients with double outlet right ventricle were premature. The segmental analysis for the SV and BiV groups by the Van Praagh classification is summarized in Table E1. Preoperative ECMO was used in 2 patients (4%) undergoing SV palliation and none in the BiV group.
Table 1Preoperative characteristics of patients with heterotaxy undergoing cardiac surgery
SV(n = 55)
BiV(n = 27)
Demographics
Male/female
29/26
17/10
Prematurity
≤37 wk
12 (22%)
5 (19%)
Birth weight
≤2.5 kg
15/54 (28%)
5/26 (19%)
≤2.0 kg
3/54 (6%)
1/26 (4%)
Age
177 d (75-235)
Stage 1 6 d (4-13)
Stage 2 171 d (134-198)
Stage 3 2.1 y (1.7-2.4)
Birth weight, kg
5.6 (4.0-7.6)
Stage 1 3.0 (2.5-3.3)
Stage 2 5.8 (5.2-6.8)
Stage 3 11.2 (10.4-12.1)
Malrotation
Yes
16 (29%)
12 (44%)
No
11 (20%)
0 (0%)
No record
28 (51%)
15 (56%)
Spleen
Normal
14 (25%)
10 (37%)
Asplenia
22 (40%)
5 (19%)
Right-sided
8 (15%)
2 (7%)
Polysplenia
7 (13%)
8 (30%)
No record
4 (7%)
2 (7%)
Cardiac position
Dextrocardia
16 (29%)
9 (33%)
Levocardia
32 (58%)
17 (63%)
Mesocardia
7 (13%)
1 (4%)
Preoperative risk factors
Total anomalous pulmonary veins
15 (27%)
3 (11%)
Bilateral SVC
26 (47%)
6 (22%)
Complete AVC
18 (32%)
10 (37%)
Genetic anomaly
11 (20%)
8 (30%)
HLHS
21 (38%)
0 (0%)
Interrupted IVC
4 (7%)
9 (33%)
Low birth weight
15 (27%)
5 (19%)
Prematurity
12 (22%)
5 (19%)
Pulmonary vein stenosis
14 (25%)
3 (11%)
Values are presented as median (interquartile range) or n (%). SV, Single ventricle; BiV, biventricular; SVC, superior vena cava; AVC, atrioventricular canal; HLHS, hypoplastic left heart syndrome; IVC, inferior vena cava.
Postoperative data and ECMO use are shown in Table 2 according to functional cardiac anatomy after repair. Mortality after cardiac surgery in the entire cohort of patients with heterotaxy syndrome was 34% (28/82) including 36% (20/55; 95% CI, 24-50) who underwent SV palliation and 30% (8/27; 95% CI, 14-50) in those who were routed toward a BiV repair. One patient on preoperative ECMO died multiorgan failure after stage 1, and 1 patient recovered, underwent staged palliation, and is surviving post-Fontan.
Table 2Operative data of patients with heterotaxy undergoing cardiac surgery
SV (n = 55)
BiV (n = 27)
Length of intubation, d
Stage 1 9 (3-20)
Stage 2 1 (0-3)
Stage 3 1 (0-4)
3 (1-15)
Length of CICU stay, d
Stage 1 21 (11-31)
Stage 2 4 (2-13)
Stage 3 5 (3-11)
7 (3-20)
Length of hospital stay, d
Stage 1 33 (13-61)
Stage 2 7 (6-25)
Stage 3 13 (8-25)
9 (7-23)
Last follow-up, y
2.2 (0.5-4.8)
2.2 (0.1-3.7)
Use of ECMO therapy
Total number of patients
17 (31%)
5 (19%)
Preoperative ECMO
2 (4%)
0 (0%)
Postoperative ECMO
16 (29%)
5 (19%)
Stage 1
12 (75%)
Stage 2
3 (19%)
Stage 3
1 (6%)
Length of ECMO, d
7 (4-11)
14 (8-21)
Values are presented as median (interquartile range) and n (%). SV, Single ventricle; BiV, biventricular; CICU, cardiac intensive care unit; ECMO, extracorporeal membrane oxygenation.
In-hospital death occurred in 85% of SV patients (17/20) and 88% of BiV patients (7/8). The death occurred in the emergency department postdischarge for 2 SV patients (10%) and 1 BiV patient (13%). One SV patient died in an acute care center (5%). Overall, mortality occurred during the first hospital admission for 64% of all patients who died (18/28): 13 of 20 SV, and 5 of 8 BiV. Operative mortality was 27% in the SV group (15/55); 10 of 20 deaths (50%) occurred 30 days or less postoperatively. Operative mortality was 30% in the BiV group (8/27); 6 of 8 deaths (75%) occurred 30 days or less postoperatively. Three patients who underwent BiV repair had an SV palliation initially, 2 in the form of pulmonary artery bands (1 with a concomitant interrupted arch repair). Both patients died, the first in the interstage period and the second after the BiV repair. The third patient had an initial systemic-pulmonary artery shunt and then a Glenn before a successful BiV repair.
The Kaplan–Meier survival curve for the whole cohort of patients with heterotaxy syndrome is depicted in Figures 3 and 4, A. A comparison throughout 5 years of follow-up showed that the probability of survival did not differ between the SV and BiV groups by the log-rank test (P = .829). Kaplan–Meier survival curves after each stage of SV palliation are depicted in Figure 4, B-D. Among SV patients, mortality after each stage of repair was as follows: 29% after stage 1 (12/46; 95% CI, 14-50), 17% after stage 2 (7/42; 95% CI, 7-31), and 4% after stage 3 (1/23; 95% CI, 0.1-22).
Figure 3A total of 82 patients with heterotaxy syndrome underwent cardiac surgery (55 SV, 27 BiV) with comparable survival regardless of operative pathway. Low birth weight, ECMO use, and anomalous pulmonary veins were predictive of mortality, and multiple systems were implicated. SV, Single ventricle; BiV, biventricular; ECMO, extracorporeal membrane oxygenation; TAPVR, total anomalous pulmonary venous return.
Figure 4Kaplan–Meier estimated survival of all patients with heterotaxy syndrome from the time of their first cardiac surgery (A). For patients who underwent SV palliation (n = 55), Kaplan–Meier survival curves are shown for patients undergoing each stage of palliation, including stage 1 (B), stage 2 (C), and stage 3 (Fontan) (D). This figure has the number at risk at each time point and has 95% confidence limits shown by the shaded region. Overall mortality in the SV group was 36% (20/55) (95% CI, 24-50), and the overall mortality in the BiV group was 30% (8/27) (95% CI, 14-50). Overall mortality for stage 1, stage II, and stage III in the SV group was 26% (12/46) (95% CI, 14-41). 17% (7/42) (95% CI, 7-31), and 4% (1/23) (95% CI, 0.1-22), respectively. SV, Single ventricle; BiV, Biventricular.
Univariate analysis of the cohort revealed preoperative or postoperative ECMO, pulmonary vein stenosis, total anomalous pulmonary venous return (TAPVR), and birth weight 2.5 kg or less as predictors of mortality among all patients with heterotaxy (Table 3). Multivariable analysis showed all of these factors to be predictors of mortality, except for pulmonary vein stenosis (Table 3). Subanalysis of SV patients identified ECMO (HR, 11.0; 95% CI, 3.6-34.2; P < .001) and TAPVR (HR, 7.0; 95% CI, 2.3-21.7; P = .001) to be risk factors for mortality (Table 4). Pulmonary vein stenosis was a univariate predictor of mortality among all patients with heterotaxy (HR, 3.0; 95% CI, 1.4-6.4; P = .005) and in the subgroup of SV patients (HR, 4.0; 95% CI, 1.7-9.7; P = .002) (Table 3). In the BiV group, low birth weight was a significant risk factor for mortality (P = .018) (Table 5). Overall survival of all patients with heterotaxy was 66% (54/82) at a median follow-up time of 2.2 years (0.4-4.1) from the time of the first operation.
Table 3Univariate and multivariable Cox regression analysis of overall mortality among all patients with heterotaxy undergoing cardiac surgery
and bold indicates the statistically significant values.
Shunt circulation
None
Reference
.
BT
0.82 (0.32-2.14)
.689
Norwood-Sano
1.1 (0.29-4.15)
.889
Diagnosis of HLHS
0.46 (0.17-1.28)
.139
Presence of complete AVC
1.43 (0.58-3.5)
.435
Birth weight ≤2.5 kg
1.48 (0.59-3.7)
.408
Variables with P < .05 on univariate analysis were included in the multivariable Cox model. SV, Single ventricle; CI, confidence interval; HR, hazard ratio; ECMO, extracorporeal membrane oxygenation; TAPVR, total anomalous pulmonary venous return; BT, Blalock–Taussig; HLHS, hypoplastic left heart syndrome; AVC, atrioventricular canal.
∗ and bold indicates the statistically significant values.
Figure 5 shows the organ system failure immediately preceding death. For example, one of the patients who underwent systemic to pulmonary artery shunt developed bowel ischemia (possibly both due to low Qs and/or malrotation could have been a contributing factor) and then died of a cardiac arrest after bowel resection; we counted as 2 organ system failures preceding and contributing to mortality and placed that number at the intersection of “cardiac” and “gastrointestinal.” Of the 28 patients who died, 12 (43%) had cardiovascular system involvement as the sole cause of death, and 10 (35.7%) had multiple systems involved or failure of other noncardiac systems. There were 7 patients (25%) in whom the cardiovascular system was not attributed to the cause of death.
Figure 5Venn diagram showing the cause(s) of death in patients with heterotaxy syndrome, with the size of the circle roughly correlating with n and the patients with multiple systems in the overlapping region.
Outcomes of surgical correction or palliation of congenital heart disease have improved considerably, whereas some entities continue to have high surgical mortality and morbidity. Heterotaxy syndrome is an abnormal positioning of the thoracoabdominal viscera along the left-right axis. It is one such domain with a higher risk of early mortality, poor long-term survival, and increased morbidity even in the current era.
A propensity-matched analysis from our institution, which compared outcomes of cardiac surgery of patients with heterotaxy with nonheterotaxy controls, showed higher postoperative death, higher use of ECMO support, duration of mechanical ventilation, hospital stay, and tracheostomy.
In the current study, we sought to expound on the outcomes of this special subset of patients with a focus on evaluating survival in the BiV versus univentricular pathways and to determine predictors of mortality in both groups.
The results of BiV repair in patients with heterotaxy vary widely in the literature. Lim and colleagues
have shown excellent 10-year survival of 93.4% with BiV patients, whereas others have suggested that BiV repair may be a significant risk factor for long-term survival with a reported 10-year survival of 43.2% (HR, 3.0, P = .02).
In our study, the early mortality after a BiV repair was high. However, they did better after the early postoperative period and with a 5-year survival of 70.4%. The higher mortality could be explained by the high prevalence of risk factors (mean 3 risk factors/patient), multisystem involvement before death, low birth weight (24.3%), and rate of prematurity (20.7%) (Table E2).
Contrary to the varied outcomes of patients with heterotaxy syndrome after BiV repair, the univentricular pathway continues to show inferior results by different investigators. Alsoufi and colleagues
have shown higher mortality and a lower percentage of patients surviving to the second stage of palliation in patients with heterotaxy compared with nonheterotaxy controls. Vodiskar and colleagues
have shown decreased pulmonary blood flow and more than mild aortic valve regurgitation as significant risk factors for poor survival in infants with single ventrilce and heterotaxy syndrome. Our study revealed that patients undergoing SV palliation have high mortality after the stage 1 palliation. However, the mortality at or after subsequent surgical stages was lower (eg, 4% mortality after Fontan completion). This corroborates with recent studies, which have demonstrated a higher stage 1 mortality but outcomes of Fontan palliation that were favorable and comparable to patients without heterotaxy.
In our cohort, overall survival for univentricular and BiV palliation was comparable. We infer that although BiV repair should be considered in all patients whenever feasible, the survival is affected by the prevalence of other risk factors such as low birth weight.
A multitude of studies have demonstrated TAPVR to be a risk factor for mortality in patients with heterotaxy.
We also found anomalous pulmonary venous return to be a risk factor (HR, 4.26, P = .02) with an observed mortality of 61% for the entire cohort. Previous research has reported that patients fare even worse when the repair of TAPVR is required at the initial operation, with early mortality as high as 40% to 45% at 1 year.
Of note, most patients in the TAPVR and pulmonary vein stenosis group, the confluence was unobstructed at the time of repair and the stenoses appeared after repair (Table E3, Table E5, Table E5). Also of note, most patients who died had a concomitant stage 1 palliation procedure as part of SV palliation (Table E4). Pulmonary vein stenosis was present in 50% of patients with anomalous pulmonary veins (8/9 died). Although sutureless repair of pulmonary veins in heterotaxy has been reported, more widespread use of this technique for patients with heterotaxy remains to be elucidated.
Several researchers are trying to study the complex problem of pulmonary vein stenosis. A dedicated pulmonary vein team undertaking close follow-up and early intervention has been proposed by several center. Our pulmonary venous disease team comprises cardiac surgeons, pediatric cardiologists with special interest in pulmonary venous disease and pulmonary arterial hypertension, cardiac imaging specialists, and interventional cardiologists. Newer approaches targeting inhibition of myofibroblasts, transforming growth factor-β1, and mammalian target of rapamycin pathways are being investigated.
Because heterotaxy involves multiple organ systems, postoperative morbidity and mortality are also compounded by the involvement of multiple organ systems. Shao and colleagues
noted a high incidence of nosocomial infections in patients with heterotaxy syndrome. Patients with heterotaxy are also at a particularly higher risk of respiratory complications. Abnormal ciliary clearance has been implicated as one of the mechanisms for increased respiratory morbidity.
Cardiovascular magnetic resonance parameters associated with early transplant-free survival in children with small left hearts following conversion from a univentricular to biventricular circulation.
A detailed analysis of the cause of death revealed an exclusive involvement of the cardiovascular system in 43% of patients and involvement of multiple organ systems in 35.7% of our patients. Multidisciplinary management seems to be of paramount importance for this subgroup in order to achieve better outcomes.
An analysis from our institution in a propensity-matched comparison showed high ECMO use in patients with heterotaxy syndrome compared with nonheterotaxy controls (odds ratio, 3.0, P = .015).
The present analysis supports our previous findings with 26.8% of patients requiring ECMO support. Of note, ECMO support was required postoperatively in 12 of 46 patients (26.08%) after first-stage palliation in the SV pathway and 9 died (75%). ECMO was a significant risk factor for mortality for the entire heterotaxy cohort, as well as for SV patients (P < .001). There were 3 clinical situations in which ECMO was used: (1) Two patients needed preoperative ECMO; (2) 2 patients required ECMO in the operating room, 1 for failure to come off cardiopulmonary bypass due to pulmonary hypertension and RV dysfunction and 1 due to hypotension and arrest after chest closure; (3) a vast majority of patients underwent ECMO for clinical deterioration due to unknown and possibly reversible causes such as infection/respiratory failure or as a consequence of low cardiac output. The high mortality in this group should urge us to carefully weigh the risks versus benefit in this patient population. It should be considered nonetheless is a reversible cause is a differential for the clinical deterioration. Because a common indication of ECMO is postoperative low cardiac output syndrome, we conclude that surgical planning to reduce myocardial ischemia and cardiopulmonary bypass times, or using alternative treatment strategies, such as off-pump/hybrid palliation to avoid postoperative low cardiac output syndrome, seems prudent (Video Abstract: American Association for Thoracic Surgery 2021 presentation with discussion with Dr Joseph Dearani following).
Study Limitations
This study is a single institution, retrospective analysis with limited sample size and lack of a control group. Despite its obvious limitations, the current analysis sheds light on a more comprehensive understanding of significant patient factors that may help in decision making and prognostication for the surgical and medical treatment of patients with heterotaxy. It is important to consider that ECMO as a risk factor is prone to a cause-effect bias because patients at high risk of mortality would need ECMO as an attempt to salvage them.
Conclusions
Outcomes of children with heterotaxy syndrome remain suboptimal in the current era, irrespective of the operative pathway. Risk factors for mortality in this population were found to be low birth weight, ECMO, and TAPVR, with the first being a risk factor for BiV and the latter 2 being risk factors for SV patients. Because of the multisystem involvement typically found in this disease, management pathways involving multidisciplinary experts are warranted to improve outcomes.
The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest.
American Association for Thoracic Surgery presentation and subsequent discussion/commentary with Dr Joseph Dearani. Video available at: https://www.jtcvs.org/article/PII/fulltext.
Appendix 1
Table E1Segmental analysis of cardiac anatomy for single ventricle and biventricular patients with heterotaxy syndrome according to the Van Praagh classification
SV (n = 55)
BiV (n = 27)
A, D, D
14 (25)
1 (4)
A, D, S
2 (4)
9 (33)
A, D, X
5 (9)
-
A, D, L
2 (4)
-
A, L, I
1 (2)
1 (4)
A, L, L
4 (7)
1 (4)
A, X, L
1 (2)
-
A, X, X
1 (2)
-
I, D, D
5 (9)
-
I, L, I
-
2 (7)
I, L, L
4 (7)
1 (4)
S, D, D
9 (16)
1 (4)
S, D, L
1 (2)
-
S, D, S
2 (4)
10 (37)
S, L, L
3 (5)
1 (4)
S, L, A
1 (2)
-
Values are displayed as n (%). SV, Single ventricle; BiV, biventricular.
Table E2Details of patients in the biventricular group who died
Diagnosis
Cardiacposition
InterruptedIVC
Details
Ventricularimbalance
ECMO
Causeof death
pAVC
L
Y
Repair of pAVC (cleft closure of MV)
No
No
MODS Sepsis
CAVC
L
Y
Placement of epicardial pacemaker Single patch for CAVC, Mustard procedure, and pulmonary valvotomy
No
No
Renal failure
DORV/PA/L-TGA
D
N
Rastelli procedure Placement of epicardial pacemaker
No
Yes (intraoperative/RVD)
Renal failure
Coarctation of aorta
D
Y
Removal of PDA device, Ligation and division of PDA, aortopexy, LPA plasty
No
No
Sepsis
Interrupted aortic arch
L
N
CoA repair, atrial reseptation
Yes (hypoplastic left ventricle)
Yes
MODS
Tetralogy of Fallot
L
N
Hybrid balloon mitral valvuloplasty, trans atrial axes to the mitral valve Repair of interrupted aortic arch Tightening of pulmonary artery band VSD closure
Table E4Patients with total anomalous pulmonary venous return or pulmonary vein stenosis
Type
Obstruction
Type of repair
Stage (in case of SV)
Preoperative pulmonary vein stenosis
Outcome L live M mortality
Supracardiac
No
1) Placement of bilateral branch pulmonary artery bands 2) Comprehensive stage II repair 3) Sutureless repair
2
Yes
M
Infracardiac
No
Direct anastomosis and shunt
1
None
M
Supracardiac
Yes
Direct anastomosis and shunt
1
None
M
Mixed
Yes
Repair of mixed obstructed total anomalous pulmonary venous connection, application of pulmonary artery band, later bilateral bidirectional Glenn shunts
1
None
M
Mixed
Yes
Direct anastomosis
1
None
M
Infracardiac
Yes
Direct anastomosis and shunt
1
None
M
Infracardiac
Yes
Direct anastomosis
1
None
M
Supracardiac
Yes
Direct anastomosis of right ventricle to pulmonary artery shunt
1
None
M
Mixed
No
Baffle redirection of anomalous pulmonary veins to left atrium including atrial septectomy
Table E5Patients with total anomalous pulmonary venous return
Type
Obstruction
Type of repair
Stage (in case of SV palliation)
Outcome
Infracardiac
Obstructed
Norwood stage 1 + direct anastomosis
1
M
Supracardiac
Unobstructed
Shunt Later direct anastomosis of the pulmonary venous confluence to the left atrium and bidirectional Glenn
2
L
Infracardiac
Unobstructed
Direct anastomosis, ligation and division of bilateral ducti, anastomosis of right pulmonary artery to left pulmonary artery, modified 3.5-mm right Blalock shunt
1
M
Supracardiac
Mild
Coarct repair and PA band Direct anastomosis of the pulmonary venous confluence to the left atrium and Bidirectional Glenn
2
M
Mixed
Unobstructed
Glenn followed by Fontan
Unrepaired
L
Cardiac
Unobstructed
Bilateral Glenn anastomosis with cessation of antegrade pulmonary blood flow, pulmonary valvectomy, division of ligamentum arteriosum or small collateral from the RPA to the aorta
Cardiovascular magnetic resonance parameters associated with early transplant-free survival in children with small left hearts following conversion from a univentricular to biventricular circulation.
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