Outcomes of heart transplants in children with heterotaxy syndrome.

OBJECTIVES: End-stage congenital heart disease (CHD) in children with heterotaxy syndrome might necessitate a heart transplant (HTx). An HTx in heterotaxy patients can be associated with several technical (e.g. redo, systemic/pulmonary-venous/situs anomalies, pulmonary artery reconstruction) and extra-cardiac (e.g. ciliary dyskinesia, infections, gastrointestinal) challenges. Our goal was to determine if heterotaxy syndrome is associated with increased early or late transplant risks. METHODS: The United Network for Organ Sharing transplant database was merged with the Paediatric Health Information System administrative database to identify children with heterotaxy who received an HTx. Characteristics and outcomes were compared between children with heterotaxy and contemporaneous non-heterotaxy congenital and non-congenital cardiomyopathy control groups. RESULTS: After we merged the databases, we divided our cohort of 1122 patients into 3 groups: the heterotaxy (n = 143), group the non-heterotaxy congenital (n = 428) group and the cardiomyopathy (n = 551) group. There were differences in the characteristics between the 3 groups, with the heterotaxy group being comparable to the non-heterotaxy congenital group. The waiting list duration was longer for the heterotaxy than for the non-heterotaxy congenital and cardiomyopathy groups (91 vs 63 vs 56 days, P < 0.001). Early post-transplant complications were similar for all groups except for operative mortality, which was 1% for the cardiomyopathy and 4% for the heterotaxy and non-heterotaxy congenital groups (P < 0.001). The post-transplant hospital stay was shorter for the cardiomyopathy (57 days) compared to the non-heterotaxy congenital (99 days) and heterotaxy (89 days) groups (P < 0.001). Whereas rejection prior to discharge was comparable between the heterotaxy and the CHD groups, it was higher at 1 year for the heterotaxy (22%) than for the non-heterotaxy congenital (19%) and cardiomyopathy (13%) groups (P < 0.001). Survival at 5 years was superior for the cardiomyopathy (87%) compared to the heterotaxy (69%) and non-heterotaxy congenital groups (78%) (P < 0.001). For the heterotaxy group, no risk factors affecting survival were identified on multivariable analysis. CONCLUSIONS: Regardless of the complexity, an HTx in selected children with heterotaxy is associated with good mid-term outcomes. Despite early results that are comparable to those of other patients with CHD, the increasing rejection rate at 1 year and the relatively accelerated attrition at mid-term warrant further follow-up. Due to database limitations in defining morphologic and surgical details, further work is warranted to delineate anatomical and surgical variables that could affect survival.

Interventions on residual lesions in patients with heterotaxy syndrome following orthotropic heart transplantation: A single-center experience.

BACKGROUND: Heterotaxy syndrome (HS) is a defect in lateralization which often results in complex intra and extracardiac abnormalities. Orthotropic heart transplantation (OHT) in HS involves intricate and individualized modifications to surgical technique. Post-OHT outcomes are worse in patients with HS, however, the impact of post-OHT residual lesions has not yet been characterized. METHODS: Patients with HS who underwent OHT at Ann & Robert H. Lurie Children's Hospital of Chicago between January 2012 and June 2023 were identified. Patients were excluded if follow-up data was not available due to follow up at a different institution of early mortality. Pre-OHT clinical data, surgical data, and post-OHT surgical and catheterization data were collected. RESULTS: Two early mortalities were excluded from analysis, leaving 15 patients in the study cohort. Median age at OHT was 3.7 years (range: 0.7-15.4). Nine out of 15 patients were diagnosed with residual lesions requiring intervention at a median of 188 days post transplantation. All interventions on residual lesions occurred via catheterization. Overall mortality rate was 27% (4/15) with all deaths occurring in patients with residual lesions (4/9 patients, 44%). 83% (10/12) of lesions were diagnosed via catheterization, and 83% (10/12) of lesions of occurred in the first year after transplant. CONCLUSIONS: Patients with HS are at high risk for residual lesions after OHT, which may contribute to increased mortality. Comprehensive invasive diagnostics were required to diagnose residual lesions, which were all addressed percutaneously.

Long-term outcomes of functional single ventricles associated with heterotaxy syndrome†.

OBJECTIVES: The goal of this study was to determine the long-term surgical outcomes of patients with functional single ventricles associated with heterotaxy syndrome, risk factors for mortality and factors associated with Fontan stage completion. METHODS: Overall, 279 patients with a functional single ventricle associated with heterotaxy syndrome who underwent an initial surgical procedure at our institute between 1978 and 2021 were grouped into 4 "eras" based on the surgical year during which the initial procedure was performed: era 1 (1978-1989, n = 71), era 2 (1990-1999, n = 98), era 3 (2000-2009, n = 64) and era 4 (2010-2021, n = 46). Neonatal surgery was more frequent in eras 3 and 4 than in eras 1 and 2. RESULTS: Overall, 228 patients had right atrial isomerism; 120 patients (43.0%) had a total anomalous pulmonary venous connection; and 58 patients (20.8%) underwent an initial procedure as neonates. Overall survival rates at 10, 20 and 30 years after the initial procedure were 47.1%, 40.6% and 36.1%, respectively. Neonatal surgery (P < 0.001), total anomalous pulmonary venous connection repair at the initial procedure (P < 0.001) and early era (P < 0.001) were identified as risk factors for mortality, with the last 2 variables being negatively associated with Fontan stage completion (P < 0.001 for both). CONCLUSIONS: Although era had a favourable effect on survival, total anomalous pulmonary venous connection with intrinsic pulmonary vein obstruction was associated with both mortality and Fontan stage completion. CLINICAL REGISTRATION NUMBER: R19092.

Intracardiac total anomalous pulmonary venous return or septum primum malposition? Complete repair in left atrial isomerism.

Total anomalous pulmonary venous return due to septum primum malposition is a poorly understood condition despite being very common in left atrial isomerism or polysplenia syndrome. Due to the leftward displacement of the septum primum, either the two right pulmonary veins or all four pulmonary veins can drain abnormally into the right atrium, despite their correct position. In other words, the four pulmonary veins (or the two right pulmonary veins), looking from outside the heart, return at the back of the atrium in the normal position. Nevertheless, from the inside of the heart, two or all four pulmonary veins drain into the right atrium due to the leftward displacement of the septum primum. As an example, we report a 5-month-old patient with severe malposition of the septum primum and consequent total anomalous pulmonary venous drainage into the right atrium. The patient underwent surgical correction with resection of the malpositioned septum primum and reconstruction of a normal interatrial septation with a pericardial patch.

Outcomes After Ladd Procedures for Intestinal Malrotation in Newborns with Heterotaxy Syndrome.

PURPOSE: Intestinal malrotation may be asymptomatic in patients with heterotaxy syndrome (HS), and whether these newborns benefit from prophylactic Ladd procedures is unknown. This study sought to uncover nationwide outcomes of newborns with HS receiving Ladd procedures. METHODS: Newborns with malrotation were identified from the Nationwide Readmission Database (2010-2014) and stratified into those with and without HS utilizing ICD-9CM codes for situs inversus (759.3), asplenia or polysplenia (759.0), and/or dextrocardia (746.87). Outcomes were analyzed using standard statistical tests. RESULTS: 4797 newborns with malrotation were identified, of which 16% had HS. Ladd procedures were performed in 70% overall and more common in those without heterotaxy (73% vs. 56% HS). Ladd procedures in newborns with heterotaxy were associated with higher complications compared to those without HS including surgical site reopening (8% vs. 1%), sepsis (9% vs. 2%), infections (19% vs. 11%), venous thrombosis (9% vs. 1%), and prolonged mechanical ventilation (39% vs. 22%), all p < 0.001. HS newborns were less frequently readmitted with bowel obstructions (0% vs. 4% without HS, p < 0.001) with no readmissions for volvulus in either group. CONCLUSION: Ladd procedures in newborns with heterotaxy were associated with increased complications and cost without differences in rates of volvulus and bowel obstruction on readmission. TYPE OF STUDY: Retrospective Comparative. LEVEL OF EVIDENCE: III.

Novel Diabolo Configuration of a Large Covered Stent to Treat Cyanosis Related to Pulmonary Arteriovenous Malformations.

Microvascular pulmonary arteriovenous malformations (pAVMs) can lead to profound hypoxemia. "Hepatic factor" is postulated to play a role in their development. Certain patients with congenital heart disease are at particular risk to develop pAVMs, including those with heterotaxy syndromes and complex Fontan palliation. Ideally, an underlying cause is identified and corrected, although pAVMs may persist despite those interventions. We report a patient with heterotaxy syndrome s/p Fontan who had pAVMs that persisted despite Fontan revision with equal hepatic flow to both lungs. We employed a novel method to produce a diabolo configuration of a large covered stent to restrict lung flow while maintaining the potential for future dilation.

A Prospective Management Strategy for Heterotaxy Syndrome with Intestinal Rotation Abnormalities: Imaging Does Not Predict Need for Surgery.

PURPOSE: Heterotaxy syndrome (HS) affects right-left anatomical development in 3% of children with congenital heart disease. Commonly, these patients have intestinal rotation abnormalities (IRA) that differ from typical malrotation. In this prospective study, we examine the development of a management pathway, imaging findings, and clinical course of patients with HS and IRA. METHODS: After literature review, a multispecialty focus group designed a pathway for HS. Participants from a single institution were prospectively enrolled from 2016 to 2019. They underwent an abdominal ultrasound and UGI, however timing was variable based on symptoms. Symptomatic IRA was defined as feeding intolerance, bilious or non-bilious vomiting, bloating, severe reflux, and intermittent pain or abdominal distention. Screening for symptoms occurred every three months for the first two years and then annually. RESULTS: 18 participants were followed for a median of 5.0 years. Three clinical categories were identified: 1) asymptomatic, not requiring intestinal surgery, 72.2%, 2) symptomatic with feeding intolerance or failure to thrive requiring gastrostomy placement and diagnostic laparoscopy with Ladd procedure, 16.7%, and 3) symptomatic requiring urgent exploration for suspicion of volvulus, 11.1%. Need for surgery did not necessarily correlate with US and/or UGI findings. CONCLUSIONS: In children with HS and IRA, postnatal imaging did not inform the need for intestinal surgery. Although rare, volvulus or other forms of proximal obstruction can be anticipated, and symptomatic patients should be offered surgical intervention. A multidisciplinary care pathway for patients with HS and IRA can coordinate care and help counsel families on the likelihood of needing intestinal surgery for IRA. LEVEL OF EVIDENCE: Level II. TYPE OF STUDY: Prospective Cohort Study.

Long-Term Surgical Outcomes of Patients With Isomeric Right and Left Atrial Appendages.

Objectives: To compare the long-term outcomes of biventricular, univentricular, and so-called one-and-one-half ventricular repairs in patients with left and right isomerism. Methods: Surgical correction was undertaken, between 2000 and 2021, in 198 patients with right, and 233 with left isomerism. Results: The median age at operation was 24 days (interquartile range [IQR]: 18-45) and 60 days (IQR: 29-360) for those with right and left isomerism, respectively. Multidetector computed-tomographic angiocardiography demonstrated more than half of those with right isomerism had superior caval venous abnormalities, and one-third had a functionally univentricular heart. Almost four-fifths of those with left isomerism had an interrupted inferior caval vein, and one-third had complete atrioventricular septal defect. Biventricular repair was achieved in two-thirds of those with left isomerism, but under one-quarter with right isomerism (P < .001). Hazard regression for mortality revealed odds for prematurity at 5.5, pulmonary atresia at 2.81, atrioventricular septal defect with a common valvar orifice at 2.28, parachute mitral valve at 3.73, interrupted inferior caval vein at 0.53, and functionally univentricular heart with a totally anomalous pulmonary venous connection at 3.77. At a median follow-up of 124 months, the probability of survival was 87% for those with left, and 77% for those with right isomerism (P = .006). Conclusions: Multimodality imaging characterizes and delineates the relevant anatomical details, facilitating surgical management of individuals with isomeric atrial appendages. Continuing higher mortality despite surgical intervention in those with right isomerism points to the need for the reassessment of strategies for management.

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

OBJECTIVE: 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. STUDY DESIGN: 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). RESULTS: 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. CONCLUSION: 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. KEY POINTS: · 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..

A puzzling CHD: a late diagnosis of left atrial isomerism.

We present a case of a 41-year-old patient with an unknown complex cardiac anatomy, who was previously submitted to two cardiac surgeries. Using multimodality imaging, a retrospective diagnosis was established, revealing a heterotaxy syndrome (left isomerism).

Outcomes of Biventricular and Single Ventricle Heterotaxy Patients: A Single Center Five-Decade Experience.

BACKGROUND: Surgical palliation of patients with heterotaxy syndrome has proven challenging. Long-term outcomes have historically been poor. Factors contributing to these outcomes are not completely understood. METHODS: The institutional databases were queried for patients with heterotaxy syndrome from 1973 to 2021. Comparisons were made between patients managed with single ventricle physiology and biventricular physiology. RESULTS: Heterotaxy syndrome was identified in 230 patients (polysplenia, 47%; asplenia, 53%). In all, 199 patients had single ventricle physiology; 180 (78%) had undergone Fontan palliation. Thirty-one patients had biventricular physiology, including 20 (9%) with surgical intervention and 11 (5%) without surgical intervention. Median age at Fontan was 7.5 years (interquartile range, 8.8). Median follow-up was 20 years (interquartile range, 21). Kaplan-Meier analysis showed decreased survival with single ventricle physiology (53% ± 4%, vs biventricular 93% ± 5% at 30 years; P = .001), as well as asplenia compared with polysplenia (49% ± 5% vs 68% ± 5% at 30 years; P < .001). Polysplenia patients with biventricular physiology demonstrated the best survival (100% alive, vs 53% ± 25% of asplenia biventricular at 30 years; P < .001). Overall, 8 patients (3.5%) underwent cardiac transplantation at a median age of 17 years. On multivariable analysis, risk factors associated with mortality included single ventricle physiology (odds ratio [OR] 7.2; 95% CI, 2.4-21.7), no prior Glenn (OR 3.6; 95% CI, 1.9-6.7), need for permanent pacemaker (OR 2.3; 95% CI, 1.2-4.6), and asplenia (OR 2.7; 95% CI, 1.5-5.0). CONCLUSIONS: Overall, patients with asplenia demonstrated decreased survival compared with patients with polysplenia; and single ventricle physiology had decreased survival compared with biventricular. Patients with biventricular physiology and polysplenia had the best survival.

Successful biventricular repair in a 14-year-old patient of asplenia with congenital heart disease syndrome.

Heterotaxy syndrome is a rare disease, and asplenia with congenital heart disease syndrome, also known as Ivemark syndrome, is a special form of heterotaxy syndrome. These patients usually have severe cardiovascular malformations and a poor prognosis. Their surgical outcomes are rarely satisfactory. We report the case of a 14-year-old patient who underwent successful corrective surgery treatment.

Clinical implications of airway anomalies and stenosis in patients with heterotaxy syndrome.

In heterotaxy syndrome, bronchopulmonary situs usually reflects atrial situs, resulting in either right (RAI) or left atrial isomerism (LAI). This study determines airway anomalies and its implications in patients with heterotaxy. This retrospective study included 223 patients with heterotaxy syndrome who received an integrated cardiac computed tomography evaluation. Patient database from 1995 to 2020 was reviewed. The patients were examined by a congenital heart disease team comprising pediatric cardiologists, radiologists, pulmonologists, and cardiovascular surgeons. Among the 223 patients, 189 (84.8%, M/F = 1.66) had RAI and 29 had LAI (13.0%, M/F = 0.71). Five patients had indeterminate isomerism (2.2%, M/F = 1.5). Discordant bronchopulmonary and atrial situs occurred in 4% patients, while discordant bronchopulmonary, atrial, and splenic situs occurred in 23.2% patients. Lower airway stenosis was observed in 61 patients (27.4%), including 27.5%, 20.7%, and 60% RAI, LAI, and indeterminate isomerism patients, respectively (p = 0.189). One patient had an intrinsic long segment lower tracheal stenosis and received slide tracheoplasty. Initial cardiac operation was performed in 213 patients. Higher surgical mortality occurred in patients with RAI (19.5% vs. none for LAI and indeterminate isomerism, p = 0.038). In patients with RAI, lower airway anomaly/stenosis increased the duration of ventilator usage (p = 0.030) but did not affect surgical mortality. Total anomalous pulmonary venous return to systemic veins and pulmonary venous stenosis were major surgical risk factors. Bronchopulmonary isomerism shares a similar isomeric pattern to cardiac atrial appendage. Lower airway anomalies/stenosis was common in patients with heterotaxy, resulting in prolonged ventilator therapy in patients with RAI.

Diffuse hepatocellular carcinoma secondary to cardiac cirrhosis in heterotaxy syndrome.

Heterotaxy syndrome is a rare congenital defect of left-right laterality of major visceral organs, often categorised by the presence of symmetric left or right atrial heart chambers with a single effective ventricle. Known as left or right atrial isomerism, these conditions may present with a distinct pattern of extracardiac anomalies. Heterotaxy is often palliated with the Fontan procedure and is suggested to be subject to similar long-term sequelae of congestive hepatopathy and ischaemia, increasing the risk for hepatocellular carcinoma. Few works document primary, localised hepatocellular carcinoma in patients with heterotaxy syndrome. We present a case of diffuse, multifocal metastatic hepatocellular carcinoma in a young patient with left atrial isomerism and dextrocardia. We also review suggested guidelines of surveillance for liver disease and hepatocellular carcinoma in this patient population.

Surgical management of hearts with isomeric atrial appendages.

BACKGROUND AND AIM: On the basis of previously published accounts, coupled with our own experience, we have assessed the surgical approaches to patients with isomeric atrial appendages. METHODS: We reviewed pertinent published studies on surgical treatment of individuals with isomeric atrial appendages, with the pertinent surgical details provided by most of the manuscripts. RESULTS: Half of patients with right isomerism, and two-thirds of those with left isomerism have bilateral superior caval veins. Azygos extension of the inferior caval vein is reported in three-quarters of those with left isomerism. The coronary sinus is universally absent in right isomerism, along with totally anomalous pulmonary venous connection, and is absent in two-fifths of those with left isomerism. Univentricular atrioventricular connections are expected in up to three-quarters of those with right isomerism. Atrioventricular septal defect is reported in up to four-fifths, more frequently in right isomerism, with such patients typically having discordant ventriculoatrial connections or double outlet right ventricle. Reported mortalities extend to 85% for those with right, and 50% for those with left isomerism. In right isomerism, mortality is up to 54% for systemic-to-pulmonary arterial shunting, up to 75% for univentricular repair, and up to 95% for repair of totally anomalous pulmonary venous connection itself. No more than one-quarter had undergone Fontan completion, with reported mortalities of 21%. CONCLUSION: Early surgical results are satisfactory in patients with left isomerism, but disappointing for those with right. Recent advances in cardiac and liver transplantation may offer improved survival.

Risk factors for mortality after cardiovascular surgery in patients with functional single ventricle and right isomerism.

OBJECTIVES: Cardiac malformations are a major component of heterotaxy syndrome that results in significant mortality and morbidity, especially in patients with a single ventricle and right isomerism (RI). The goal of this study was to evaluate the mortality after cardiovascular surgery in patients with a functional single ventricle and RI over a long follow-up period (∼40 years) and to determine the predicted risk factors for mortality. METHODS: We performed a retrospective review of the medical records of 129 consecutive patients with functional single ventricle and RI who underwent pulmonary flow control operations at Mt. Fuji Shizuoka Children's Hospital between 1979 and 2020. To evaluate mortality rates, the patients were divided into 2 groups (era 1: 1979-1999 and era 2: 2000-2020) based on the date of the first-stage palliation. RESULTS: The estimated survival rate at 10 years was 36.4% in era 1 and 57.8% in era 2. The estimated survival rate improved significantly (P = 0.0268) between the 2 eras. The rate of Fontan procedure completion was also significantly better in the current era (P = 0.0392; 22/59 in era 1 and 38/66 in era 2). In the multivariable analysis, the date of the first-stage palliation was the only predictor of mortality. CONCLUSIONS: The mortality rate after cardiovascular surgery in patients with a functional single ventricle and RI has improved over the past 20 years; however, it still remains high. This improvement may be attributed to our current surgical strategy and clinical management; however, further investigations are needed to prove this observation.

Commentary: Extracardiac conduit-total cavopulmonary connection for heterotaxy-Is going the "extra" mile worth it.

Extracardiac conduit-total cavopulmonary connection (EC-TCPC) represents the latest evolution in Fontan palliation for single ventricle physiology. Here, we review a manuscript by Pan et al. in the Journal of Cardiac Surgery detailing a retrospective, single-center cohort study of patients with and without heterotaxy syndrome undergoing EC-TCPC. Although lacking a comparison to other techniques for single ventricle palliation, this approach appears to offer excellent outcomes for this complex patient cohort.