Heterotaxy Research Articles

Is combined MDCT and echocardiography needed to guarantee accuracy in diagnosis and surgical planning of DORV and associated anomalies?

BackgroundThe term of Double-outlet right ventricle (DORV) is used to describe a spectrum of complex congenital cardiac malformations where anomalies of the ventriculo-arterial alignment are noted where both great arteries (pulmonary artery and aorta) originate completely or predominantly from the right ventricle. The purpose of this study is to evaluate the diagnostic accuracy of electrocardiography (ECG) gated multidetector computed tomography (MDCT) in preoperative assessment of DORV and its associated malformations, providing key anatomic parameters that affect surgical planning.ResultsA total of 50 patients diagnosed by echocardiography with DORV referred from our institute between September 2018 and August 2020 were enrolled. The location of the ventricular septal defect (VSD) to the great vessels and the alignment of the great vessels to each other as well as other associated malformations that affect the surgical planning were assessed by MDCT. The patients were retrospectively classified into subgroups according to the relative positions of the great arteries, the relationship between the great arteries and the VSD, and the presence of associated malformations according to the classification of Society of Thoracic Surgeons database. The diagnostic value of MDCT and transthoracic echocardiography (TTE) in evaluation of associated cardiac malformations apart from double outlet right ventricle was compared in 20 patients, whom surgeries were performed and surgical results were obtained. Fallot type of DORV was the most common clinical type which represented 48% of the patients in which the VSD is committed to the aorta. The second most common clinical type was Taussig–Bing anomaly which represented 30% of the patients and the VSD was seen committed to the pulmonary artery. The atrio-ventricular septal defect (AVSD)/uni-ventricular type represented 16% of the patients in the current study, with pulmonary and systemic venous anomalies, heterotaxy syndrome and situs anomalies were commonly associated. A total of 53 malformations apart from DORV were found in 20 patients whom performed surgical interventions. MDCT detected different vascular and situs anomalies in those patients with 100% sensitivity and 100% positive predictive value compared to 71.4% and 94% respectively in TTE. On the other hand, in our study TTE was superior to MDCT for detection of intracardiac anomalies with 100% sensitivity and 100% accuracy compared to 87.5% and 95% respectively in MDCT.ConclusionsOur study suggested that ECG gated MDCT serves as a rapid, noninvasive imaging modality with good spatial resolution and provides excellent diagnostic image quality and has satisfactory diagnostic accuracy in the preoperative assessment of DORV. It is superior to echocardiography in providing a comprehensive mapping of the anatomy of complex anomalies especially that of extra-cardiac structures such as aorta, systemic veins, pulmonary veins, and pulmonary arteries. However, it can miss tiny intracardiac malformations. So combining the results of MDCT and echocardiography would be beneficial to guarantee the accuracy of diagnosis of DORV.

One-Stage Correction with Intra- and Extraatrial Rerouting of Anomalous Systemic and Pulmonary Venous Return and Intraventricular Repair of Double Outlet Right Ventricle in a Patient with Heterotaxy Syndrome

We report a very rare case of successful intracardiac correction in a patient with heterotaxy syndrome. The cardiac malformations included dextrocardia, double outlet right ventricle, pulmonary stenosis, interrupted inferior vena cava, hemiazygos continuation and total anomalous pulmonary venous return. One-stage correction was performed. The atrial procedure consisted of intra- and extraatrial rerouting of the anomalous systemic and pulmonary venous return. The hepatic veins were detached and diverted to the left atrium via an extracardiac conduit. The correction of the double outlet right ventricle was accomplished by intraventricular redirection of the blood flow from the left ventricle to the aorta. The right ventricular outflow was ultimately remodeled using a valved conduit. For better perception of the complex morphology, a three-dimensional model was designed, using CT scan images. This proved to be very useful for surgical planning, especially with regard to the intraatrial reconstruction of the systemic and pulmonary venous rerouting.

Situs ambiguous and Hepatic Vein Anomaly: A Case Report

Situs ambiguous is the placement of vessels and organs in the thoracoabdominal space that are anatomically located outside its normal position in a certain order. This condition is a broad definition that includes many variations. In this case report, we reported a patient with Situs ambiguus with an abnormal hepatic vein who was diagnosed incidentally during medical imaging (computed tomography, sonography and MRI study).

HETEROTAXY SYNDROME IN COVID-19 PATIENT WITH PULMONARY EMBOLISM AND AORTIC ANEURYSM: A RARE ACCIDENTAL COMBINATION (RADIOLOGICAL ASSESSMENT).

With limited time for analysing computed tomography (CT) data in medical emergencies, radiologists and clinicians are not always aware of congenital pathologies, especially in asymptomatic cases. We present a case report of heterotaxy syndrome detected incidentally in a 62-year-old female with massive pulmonary embolism, local saccular aneurysm of the aortic arch and COVID-19. The presented case describes an unusual combination of life-threatening conditions and congenital anomalies. Using the CT angiography, we reported the preserved topography and morphology of the heart chambers. The superior and inferior venae cavae were located on the left, draining into a significantly dilated coronary sinus. Disordered abdominal organ arrangement included midline liver, right-sided stomach, the central location of the short pancreas, malrotation of the intestine, polysplenia, and atypical rise of visceral branches of the abdominal aorta. A comprehensive assessment of CT images promoted verification of undiagnosed congenital anomalies. Prompt recognition of heterotaxy syndrome in life-threatening conditions significantly impacts treatment tactics and should be the course of diagnostic and cautious interventions to reduce further complications.

Surgery for Functional Single Ventricle Associated with Heterotaxy Syndrome: Common Atrioventricular Valve Repair

Surgery for Functional Single Ventricle Associated with Heterotaxy Syndrome: Common Atrioventricular Valve Repair

Abstract 10569: Risk Factors for Adverse Outcome in Prenatally Diagnosed Heterotaxy Syndrome in the Current Era

Introduction: Fetuses with heterotaxy syndrome (HS) and congenital heart disease continue to have worse outcomes compared to other lesions. We sought to explore differences between asplenia and polysplenia subtypes and to identify risk factors for poor outcome in the current era. Methods: All cases of fetal HS seen at our center between 1/2005 and 3/2018 were included in this study. Prenatal echocardiographic parameters and clinical outcomes were recorded. Findings were compared between the asplenia and polysplenia subtypes via Chi-square or Fisher’s exact analysis. Univariate logistic regression was utilized to identify prenatal variables predictive of fetal demise. Postnatal survival was examined with Kaplan-Meier curves and univariate Cox proportional hazards models. Results: The cohort consisted of 155 subjects: 86 with asplenia and 69 with polysplenia. There were 36 with biventricular (2V) and 119 with univentricular (1V) physiology. Asplenia subjects were more likely to have 1V physiology, common atrioventricular canal (CAVC), conotruncal anomaly, and pulmonary venous obstruction (all p<0.001). Polysplenia subjects were more likely to have systemic venous anomalies (p<0.001), complete heart block (CHB, p<0.001), ventricular dysfunction (p=.005), and hydrops (p=0.03). There were 105 subjects born alive, 7 fetal demises, 40 terminations, and 3 lost to follow-up prior to birth. Postnatal follow-up data were available for 96/105 (91%) subjects with median follow-up of 5.5 years (IQR 1.2-10.5). Estimated 5-year survival was 72% (95% CI 62-80) for the entire cohort and there was no difference in overall postnatal survival between polysplenia and asplenia subtypes (p=0.24). CHB and ventricular dysfunction were significant risk factors for both fetal demise and postnatal death. Pulmonary venous obstruction and CAVC were additional risk factors for postnatal death. Conclusions: Fetuses with HS continue to have high rates of postnatal mortality, particularly if CHB, ventricular dysfunction, or pulmonary venous obstruction are identified. CHB and ventricular dysfunction are also significant risk factors for fetal demise. Further research is needed to improve management of CHB and pulmonary venous obstruction in this high-risk group.

Cerebral Palsy and Heterotaxy Syndrome: A Case Report

Background: Cerebral palsy is not only a serious neurodevelopmental disease causing significant morbidity in children, but also a traumatic experience leading to psychosocial trauma to the parents/caregivers of the affected children. It is usually caused by prenatal or early post-natal insults to the newborn brain which may be associated with some congenital syndromes like congenital heart disease with transposition of the viscera but rarely a heterotaxy syndrome, a condition characterized with congenitally abnormal arrangement of the thoracic and abdominal viscera. Method: We present a case report of a 12-month-old boy with neurodevelopmental delay, recurrent episodes of non-mucoid and non-bloody diarhoea, occasional constipation, bilious vomiting, abdominal distension and fever with associated cough and difficulty in breathing. Results: We discuss an unusual presentation of cerebral palsy and heterotaxy syndrome diagnosed clinically with supporting evidence from both laboratory and radiological tests. Cerebral palsy was diagnosed from the history of birth asphyxia, delayed developmental milestone, limb spasticity and low values for all sub-scores of Bayley-III scale. Heterotaxy syndrome was diagnosed from the radiologic evidence of dextrocardia, left-sided stomach, centrally located liver and malrotation of gut with volvulus. We also provide a brief literature review of the incidence and prevalence, causes and risk factors, classification, clinical presentation and associated co-morbidities of heterotaxy syndrome. Conclusion: Diagnosis of heterotaxy syndrome in a child with background cerebral palsy is a great challenge to both physicians and radiologists. This is more so in developing countries due to poor availability of good diagnostic apparatus, therefore, a high index of suspicion is needed. A clear understanding of the clinical features, comprehensive history taking and thorough physical examination are important in making prompt diagnosis. Timely and appropriate imaging is necessary to prevent delays in diagnosis and treatment which lead to poor outcomes.

Predictors and outcomes of heart block during surgical stage I palliation of patients with a single ventricle: A report from the NPC-QIC.

Mortality in cohorts with a single ventricle remains high with multiple associated factors. The effect of heart block during stage I palliation remains unclear. The purpose of this study was to study patient and surgical risks of heart block and its effect on 12-month transplant-free survival in patients with a single ventricle. Patient, surgical, outcome data and heart block status (transient and permanent) were obtained from the National Pediatric Cardiology Quality Improvement Collaborative single ventricle database. Bivariate analysis was performed comparing patients with and without heart block, and multivariate modeling was used to identify variables associated with block. One-year outcomes were analyzed to identify variables associated with lower 12-month transplant-free survival. In total, 1423 patients were identified, of whom 28 (2%) developed heart block (second degree or complete) during their surgical admission. Associated risk factors for block included heterotaxy syndrome (odds ratio [OR] 6.4) and atrial flutter/fibrillation (OR 3.8). Patients with heart block had lower 12-month survival, though only in patients with complete heart block as opposed to second degree block. At 12 months of age, 43% (12/28) of patients with heart block died and were more likely to experience mortality at 12 months than patients without block (OR 4.9; 95% confidence interval 1.4-17.5; P = .01). Although rare, complete heart block after stage I palliation represents an additional risk of poor outcomes in this high-risk patient population. Heterotaxy syndrome was the most significant risk factor for the development of heart block after stage I palliation. The role of transient block in outcomes and potential rescue with long-term pacing remains unknown and requires additional study.

2021 PACES Expert Consensus Statement on the Indications and Management of Cardiovascular Implantable Electronic Devices in Pediatric Patients: Executive Summary.

2021 PACES Expert Consensus Statement on the Indications and Management of Cardiovascular Implantable Electronic Devices in Pediatric Patients: Executive Summary.

Rare Case of a Newborn with Heterotaxy Syndrome, Right Aortic Arch and an Isolated Left Brachiocephalic Artery Arising from a Left Ductus Arteriosus

Heterotaxy is an abnormal arrangement of viscera across the left-right axis of the body often associated with a variety of complex cardiac lesions. We present a case of left isomeric heterotaxy, a right aortic arch, and a left brachiocephalic artery arising from a left ductus arteriosus.

Heterotaxy syndrome with accompanying azygos continuation of the inferior vena cava, patent ductus arteriosus and replaced common hepatic artery

Abnormal anatomical organization of thoraco-abdominal visceral organs and vascular structures is called “Heterotaxy Syndrome.” Heterotaxy is generally classified under two main headings as polysplenia and asplenia syndromes. Complex cardiac anomalies are closely associated with poor prognosis in the patient group with asplenia syndrome. On the other hand, cardiac anomalies are less common in polysplenic syndrome. It is particularly important to define the findings accurately in the planning of surgical and interventional treatment. We present the findings of a patent ductus arteriosus (PDA) patient with co-existent heterotaxy syndrome associated with abdominal anomalies, such as polysplenia, azygos continuation of interrupted inferior vena cava, liver with midline localization, short pancreas, preduodenal portal vein, replaced common hepatic artery (HA) originating from the superior mesenteric artery (SMA) and left sided superior mesenteric vein to the SMA. To the best of our knowledge, there is no previous report of HA originating from the SMA found together with PDA and heterotaxy syndrome.

Novel MYO1D Missense Variant Identified Through Whole Exome Sequencing and Computational Biology Analysis Expands the Spectrum of Causal Genes of Laterality Defects.

Laterality defects (LDs) or asymmetrically positioned organs are a group of rare developmental disorders caused by environmental and/or genetic factors. However, the exact molecular pathophysiology of LD is not yet fully characterised. In this context, studying Arab population presents an ideal opportunity to discover the novel molecular basis of diseases owing to the high rate of consanguinity and genetic disorders. Therefore, in the present study, we studied the molecular basis of LD in Arab patients, using next-generation sequencing method. We discovered an extremely rare novel missense variant in MYO1D gene (Pro765Ser) presenting with visceral heterotaxy and left isomerism with polysplenia syndrome. The proband in this index family has inherited this homozygous variant from her heterozygous parents following the autosomal recessive pattern. This is the first report to show MYO1D genetic variant causing left–right axis defects in humans, besides previous known evidence from zebrafish, frog and Drosophila models. Moreover, our multilevel bioinformatics-based structural (protein variant structural modelling, divergence, and stability) analysis has suggested that Ser765 causes minor structural drifts and stability changes, potentially affecting the biophysical and functional properties of MYO1D protein like calmodulin binding and microfilament motor activities. Functional bioinformatics analysis has shown that MYO1D is ubiquitously expressed across several human tissues and is reported to induce severe phenotypes in knockout mouse models. In conclusion, our findings show the expanded genetic spectrum of LD, which could potentially pave way for the novel drug target identification and development of personalised medicine for high-risk families.

Impact of gastrointestinal comorbidities in patients with right and left atrial isomerism.

Heterotaxy syndrome, being right atrial isomerism (RAI) or left atrial isomerism (LAI), often presents with Congenital Heart Disease (CHD). Intestinal abnormalities, including malrotation are common. We assessed the spectrum of gut abnormalities and their impact on medium-term outcome in a cohort of patients with fetal and postnatal diagnoses of heterotaxy syndrome. We reviewed the cardiology records of heterotaxy syndrome patients from two centres, regarding the presence of CHD, time for cardiac intervention, presence of gastrointestinal abnormalities, and type/time of surgery. A questionnaire about gastrointestinal status was sent to patients <18 years old. Kaplan-Meier curves were derived for survival data and freedom from intervention. Data were included for 182 patients (49 RAI and 133 LAI) of 247 identified. Questionnaires were sent to 77 families and 47 replied. CHD was present in all RAI and 61.7% of LAI cases. Thirty-eight patients had abdominal surgery (20.9%), similar for RAI and LAI (20.4% versus 21%, p> 0.99): Ladd procedure in 17 (44.7%), non-Ladd in 12 (31.5%), and both procedures in 9 (23.7%). Ten-year freedom from Ladd procedure for all was 86% for the whole cohort (RAI = 87%; LAI = 85%, p = 0.98). Freedom from any gastrointestinal surgery at 10 years was 79% for the whole cohort (RAI = 77%; LAI = 80%, p = 0.54). Ten-year freedom from cardiac surgery was 31% for the whole cohort (RAI = 6%; LAI = 43%, p < 0.0001). In our cohort, one in five patients required abdominal surgery, mostly in their first year of life, similar for RAI and LAI. Between 1 and 10 years of follow-up, the impact of gastrointestinal abnormalities on outcome was minimal. Medium term survival was related to CHD.

Fetal heterotaxy: Should we still categorize?

Heterotaxy (HTX) is usually stratified in right (RI) and left isomerism (LI). We analyzed 61 fetal specimens with HTX divided in 5 groups: classic LI [CLI: bronchopulmonary LI, bilaterally absent pectinate muscles (PM), polysplenia, n = 22], non-classic LI (NCLI: one discordant feature, n = 13), classic RI (CRI: bronchopulmonary RI, bilateral extent of PM to the crux, asplenia, n = 12), non-classic RI (NCRI: one discordant feature, n = 6, totally discordant features, n = 8). Non-classic patterns were found in 44% (33% RI, 37% LI). Among those, the status of the spleen was highly variable (NCLI with asplenia 38%, NCRI with single spleen 66%), while the bronchial status was almost always concordant. Intestinal malrotation was present in 83% CRI, 64% CLI, 50% NCLI, 50% NCRI. Extent of PM was highly variable in NCLI (bilaterally left 46%, normal 46%, bilaterally right 8%), and bilaterally right in 83% of NCRI only. Interrupted inferior caval vein was seen in LI only; total extracardiac anomalous pulmonary venous connection (APVC) was seen only in RI, ipsilateral APVC only in LI. A common atrioventricular (AV) junction was constant in RI vs. 66% in LI, with a complete AV canal in 100% RI, 75% LI. Functionally univentricular hearts were found in 67% RI, 46% LI, right in 62.5%. Ventriculo-arterial (VA) connections were abnormal in 100% RI, 59% LI, double outlet right ventricle (DORV) being the most frequent type in all categories. Pulmonary atresia and stenosis were frequent in RI (77%), rare in LI. Aortic arch hypoplasia and coarctation were found almost exclusively in LI (57%). Right-sided aortic arch was found in 67% RI, 6% LI. HTX and isomerism are not synonymous. Extent of PM is not always symmetrical (15%) and cannot therefore be considered the hallmark of HTX. Because HTX includes both abnormal symmetry and random organization of organs, each anatomic feature should be analysed individually rather than trying to categorize.

A Novel Method to Safely De-Air a HeartWare System in a Single-Ventricle Patient by Utilizing ECMO and a Minimized CPB Circuit

The survival of congenital heart disease (CHD) patients with single-ventricle (SV) physiology has markedly increased as a result of advances in operative techniques and postsurgical management. Nonetheless, these patients remain highly susceptible to end-stage heart failure requiring cardiac replacement therapies at early ages. Given a worldwide shortage of transplantable organs, mechanical circulatory support (MCS) represents an alternative treatment option. The significant heterogeneity of the SV population presents unique indications for MCS that have begun to be evaluated. This case study describes a 12-year-old female with heterotaxy syndrome and an SV condition, previously palliated with a Fontan operation at another institution. The patient was placed on veno-arterial (VA) extracorporeal membrane oxygenation (ECMO) during prolonged cardiopulmonary resuscitation, and later underwent HeartWare ventricular assist device (HVAD) implantation as a bridge to transplantation (BTT). A novel method was chosen to optimize careful de-airing of the heart through a minimized cardiopulmonary bypass (CPB) setup, during full ECMO support and surgical insertion of the HeartWare. The ascending aorta was vented proximal to the HVAD outflow graft anastomosis through a minimized CPB circuit at &lt;10% of the ECMO flow rate. This circuit adaption allowed for euvolemic resuscitation via connection from the minimized CPB circuit to the venous limb of the ECMO circuit. The transition from VA-ECMO to the HeartWare was well tolerated despite a challenging sternotomy and cardiac anomaly. A minimized bypass circuit proved efficacious for the benefit of volume resuscitation and safe de-airing of the HVAD while on ECMO support. The literature is limited concerning safe practices for implantation of durable VADs in complex SV patients coupled with those transitioning from varying modalities of MCS. As SV survivability regresses to heart failure, it is essential that we share techniques that aim to improve the long-term outcomes for successful BTT or bridge to decision (BTD).

Main pulmonary artery swing back for univentricular heart

Left pulmonary artery (LPA) surgical arterioplasty done for juxtaductal pulmonary artery coarctation is a challenging technique that has often produced unsatisfactory outcomes because of poor outcome later and incomplete understanding of the evolution of structural changes in these vessels. We report a unique technique for LPA plasty involving main pulmonary artery (MPA) swing back, in a toddler who presented with history of increased work of breathing, cyanosis and failure to thrive since birth, where the MPA was detached and was swung back cranially to be anastomosed to LPA. This technique can be done, especially in univentricular heart (future Fontan candidate), since MPA needs to be interrupted. The patient had heterotaxy syndrome, left atrial isomerism, hypoplastic pulmonary valve with severe sub-valvar stenosis, duct dependent pulmonary circulation, good sized confluent branch pulmonary arteries with LPA narrowing at ductal insertion site, interrupted IVC with hemiazygous continuation and left SVC draining into coronary sinus. Initially underwent right modified Blalock taussig (BT) shunt, atrial septectomy, LPA plasty and PDA ligation at 6 months of age. Upon follow up after a year, diagnostic angiogram confirmed good flow in BT shunt and LPA re-stenosis with malpositioned great arteries. Redo sternotomy and Kawashima procedure was performed. BT shunt and MPA stump were divided. To conclude, the detached MPA segment was swung cranially and anstomosed to LPA (end to end) inferiorly and left SVC-LPA anstomosed superiorly onto this by end to side fashion. The early outcome was satisfactory, however long-term outcome needs to be followed up

Novel Pathogenic DNAH5 Variants in Primary Ciliary Dyskinesia: Association with Visceral Heterotaxia and Neonatal Cholestasis.

The dynein axonemal heavy chain 5 gene codes for a subunit of axonemal dynein necessary for ciliary motor function. Though research has elucidated the consequences of some variants in this gene, it is still unclear whether many variants in the DNAH5 locus are benign or pathogenic due to the rarity of primary ciliary dyskinesia (PCD, of which Kartagener's syndrome is a subset). Here, we introduce the case of an infant boy presenting with the classical findings of PCD along with visceral heterotaxia and neonatal cholestasis. Genetic testing indicated that the patient is a compound heterozygote with a pathogenic c.8498G > A (known as pathogenic) on the maternally derived allele and two variants of uncertain significance, c.1206T > A and c.7800T > G, on the paternally derived allele. As PCD is autosomal recessive, we conclude that one, or both, of these paternally derived variants are pathogenic. To our knowledge, this is the first time that the clinical implications of c.1206T > A (p.Asn402Lys) and c.7800T > G (p.Ile2600Met) are documented. Furthermore, we use this case as an example to recommend clinicians to assess for PCD and laterality defects when presented with severe infantile cholestasis. While the association of cholestasis with PCD is relatively uncommon, PCD is a risk factor for increased prevalence of biliary atresia and infections, both of which are known causes of cholestasis in early infancy.

Familial recurrence patterns in congenitally corrected transposition of the great arteries: An international study

Congenitally corrected transposition of the great arteries (ccTGA) is a rare disease of unknown aetiology. We aimed to better understand familial recurrence pattern. An international, multicentre, retrospective cohort study was conducted in 29 tertiary hospitals in 6 countries between 1990 and 2018, leading to investigate 1043 unrelated ccTGA probands. Atrioventricular block at diagnosis and laterality defects were observed in 35.4% and 29.9%, respectively. ccTGA associated with primary ciliary dyskinesia in 10 patients. Parental consanguinity was noted in 3.4% cases. A congenital heart defect was diagnosed in 81 relatives from 69 families, 58% of them being first-degree relatives, including 28 siblings. The most prevalent defects in relatives were dextro-transposition of the great arteries (d-TGA: 28.4%), laterality defects (13.6%) and ccTGA (11.1%); 36 new familial clusters were described, including 8 pedigrees with concordant familial aggregation of ccTGA, 19 pedigrees with familial co-segregation of ccTGA and d-TGA and 9 familial co-segregation of ccTGA and laterality defects. In one family there was co-segregation of ccTGA, d-TGA and heterotaxy syndrome in 3 distinct relatives. ccTGA is not always a sporadic congenital heart defect. Familial clusters as well as evidence of an association between ccTGA, d-TGA, laterality defects and in some cases primary ciliary dyskinesia strongly suggest a common pathogenetic pathway involving laterality genes in the pathophysiology of ccTGA.

Improved heart transplant survival for children with congenital heart disease and heterotaxy syndrome in the current era: An analysis from the pediatric heart transplant society

Challenges exist with heterotaxy due to the complexity of heart disease, abnormal venous connections, and infection risks. This study aims to understand heart transplant outcomes for children with heterotaxy. All children with congenital heart disease listed for transplant from 1993 to 2018 were included. Those with and without heterotaxy were compared. Waitlist outcomes and survival post-listing and transplant were analyzed. Post-transplant risk factors were identified using multiphase parametric hazard modeling. There were 4814 children listed, of whom 196 (4%) had heterotaxy. Heterotaxy candidates were older (5.8 ± 5.7 vs 4.2 ± 5.5 years, p < 0.01), listed at a lower urgency status (29.8% vs 18.4%, p < 0.01), more commonly single ventricle physiology (71.3% vs 59.2%, p < 0.01), and less often supported by mechanical ventilation (22% vs 29.1%, p < 0.05) or extracorporeal membrane oxygenation (3.6% vs 7.5%, p < 0.05). There were no differences in waitlist outcomes of transplant, death, or removal. Overall, post-transplant survival was worse for children with heterotaxy: one-year survival 77.2% vs 85.1%, with and without heterotaxy, respectively. Heterotaxy was an independent predictor for early mortality in the earliest era (1993-2004), HR 2.09, CI 1.16-3.75, p=0.014. When stratified by era, survival improved with time. Heterotaxy patients had a lower freedom from infection and from severe rejection, but no difference in vasculopathy or malignancy. Mortality risk associated with heterotaxy is mitigated in the recent transplant era. Early referral may improve waitlist outcomes for heterotaxy patients who otherwise have a lower status at listing. Lower freedom from both infection and severe rejection after transplant in heterotaxy highlights the challenges of balancing immune suppression.

Predicting Cardiac Anatomy, Physiology, and Surgical Management Based on Fetal Echocardiography in Heterotaxy Syndrome.

Heterotaxy syndrome (HS) is often associated with complex congenital heart disease (CHD). While fetal echocardiography (FE) permits accurate prenatal identification of most CHD, the high level of disease complexity in HS may pose challenges in predicting postnatal findings and outcomes. This study aimed to define the accuracy of FE in predicting postnatal anatomy, physiology, and surgical management of CHD in the setting of HS. Retrospective single-center cohort study including all patients with a prenatal diagnosis of HS from 2003 to 2018. Anatomic diagnoses from FE reports were compared with postnatal echocardiogram, catheterization, and operative reports. Prenatal predictions were compared with postnatal outcomes with a focus on ductal dependence, time to first intervention (immediate, neonatal period, 1-6 months, or older than 6 months), and surgical approach (single or biventricular). There were 102 pregnancies with fetal HS resulting in 21 terminations, 5 fetal losses, and 76 live births. Of the live births, 55 had significant CHD and available postnatal data for review. Among this group, survival to 1 year was 62% and was no different comparing single versus biventricular surgical approach. FE diagnostic accuracy varied by anatomic feature and was the lowest for diagnosis of venous anatomy. Determination of postnatal care was most accurate for predicting single versus biventricular surgical approach (91%), followed by ductal dependence (75%). Accuracy for predicting time to first intervention was the lowest at 69%. The most common reason for an incorrect prediction was difficulty in assessing the severity of pulmonary stenosis. FE permits accurate predictions regarding surgical approach. Characterizing systemic and pulmonary veins is challenging, as is predicting ductal dependence and time to first intervention. These data suggest that despite the high diagnostic accuracy of CHD in HS, a circumspect approach may be reasonable with regard to predicting some anatomic details and postnatal management decisions. · In HS, FE was most accurate for intracardiac anatomy.. · Diagnostic accuracy of venous anatomy was less reliable.. · Predicting surgical approach (single ventricle vs. biventricular) was highly accurate.. · Predicting ductal dependence and time-to-intervention were more challenging in some instances..