Biallelic TMEM260 variants cause truncus arteriosus, with or without renal defects.

Only two families have been reported with biallelic TMEM260 variants segregating with structural heart defects and renal anomalies syndrome (SHDRA). With a combination of genome, exome sequencing and RNA studies, we identified eight individuals from five families with biallelic TMEM260 variants. Variants included one multi-exon deletion, four nonsense/frameshifts, two splicing changes and one missense change. Together with the published cases, analysis of clinical data revealed ventricular septal defects (12/12), mostly secondary to truncus arteriosus (10/12), elevated creatinine levels (6/12), horse-shoe kidneys (1/12) and renal cysts (1/12) in patients. Three pregnancies were terminated on detection of severe congenital anomalies. Six patients died between the ages of 6 weeks and 5 years. Using a range of stringencies, carrier frequency for SHDRA was estimated at 0.0007-0.007 across ancestries. In conclusion, this study confirms the genetic basis of SHDRA, expands its known mutational spectrum and clarifies its clinical features. We demonstrate that SHDRA is a severe condition associated with substantial mortality in early childhood and characterised by congenital cardiac malformations with a variable renal phenotype.

Extracorporeal Membrane Oxygenation in Infants Undergoing Truncus Arteriosus Repair.

BACKGROUND: Infants undergoing truncus arteriosus (TA) repair suffer one of the highest mortality rates of all congenital heart defects. Extracorporeal membrane oxygenation (ECMO) can support patients undergoing TA repair, but little is known about factors contributing to mortality in this cohort. The objective of this study was to identify risk factors for mortality in infants with TA requiring perioperative ECMO. METHODS: Data from the Extracorporeal Life Support Organization from 2002 to 2017 for infants less than 60 days old undergoing TA repair were analyzed. Demographics, clinical characteristics, and ECMO characteristics and complications were compared between survivors and nonsurvivors. Multivariable logistic regression was used to evaluate independent risk factors for mortality. RESULTS: Of 245 patients analyzed, 92 (37.6%) survived to discharge. Nonsurvivors had a lower weight and a longer ECMO duration. A higher proportion of nonsurvivors suffered complications on ECMO, including mechanical complications, circuit thrombus, bleeding, and need for renal replacement therapy. In multivariable analysis lower weight (odds ratio [OR], 0.56; 95% confidence interval [CI], 0.33-0.95), duration of ECMO (OR, 1.1; 95% CI, 1.02-1.18), need for renal replacement therapy (OR, 3.23; 95% CI, 1.68-6.2), cardiopulmonary resuscitation on ECMO (OR, 11.52; 95% CI, 1.3-102.33), and infection on ECMO (OR, 4.47; 95% CI, 1.2-16.64) were independently associated with mortality. CONCLUSIONS: Many factors associated with mortality for infants requiring perioperative ECMO with TA repair are related to complications suffered on ECMO. Thoughtful patient selection and meticulous ECMO management to prevent complications are essential in improving outcomes for these infants.

Rare Association of an Intramural Coronary Artery and Truncus Arteriosus.

The association of truncus arteriosus (TA) and an intramural coronary artery is rare. Seven (7) patients had TA and an intramural coronary artery at the Royal Children's Hospital, Melbourne between 1996 and 2018. Four (4) patients underwent concomitant unroofing of their intramural coronary artery. One (1) patient who did not undergo concomitant unroofing had a cardiac arrest on postoperative day 1 and subsequently underwent reoperation for coronary unroofing. Given the potential for serious complications, patients with TA and an intramural coronary artery may benefit from coronary unroofing with creation of a generous neo-ostium.

Truncus Arteriosus With Double Aortic Arch.

Truncus arteriosus (TA) or common arterial trunk is a congenital cardiac anomaly having high association with arch anomalies such as right aortic arch or aortic arch interruption. However, TA with double aortic arch (DAA) is a rare occurrence. We report a case of TA with DAA where the diagnosis of DAA was missed initially.

Gata4 regulates hedgehog signaling and Gata6 expression for outflow tract development.

Dominant mutations of Gata4, an essential cardiogenic transcription factor (TF), were known to cause outflow tract (OFT) defects in both human and mouse, but the underlying molecular mechanism was not clear. In this study, Gata4 haploinsufficiency in mice was found to result in OFT defects including double outlet right ventricle (DORV) and ventricular septum defects (VSDs). Gata4 was shown to be required for Hedgehog (Hh)-receiving progenitors within the second heart field (SHF) for normal OFT alignment. Restored cell proliferation in the SHF by knocking-down Pten failed to rescue OFT defects, suggesting that additional cell events under Gata4 regulation is important. SHF Hh-receiving cells failed to migrate properly into the proximal OFT cushion, which is associated with abnormal EMT and cell proliferation in Gata4 haploinsufficiency. The genetic interaction of Hh signaling and Gata4 is further demonstrated to be important for OFT development. Gata4 and Smo double heterozygotes displayed more severe OFT abnormalities including persistent truncus arteriosus (PTA). Restoration of Hedgehog signaling renormalized SHF cell proliferation and migration, and rescued OFT defects in Gata4 haploinsufficiency. In addition, there was enhanced Gata6 expression in the SHF of the Gata4 heterozygotes. The Gata4-responsive repressive sites were identified within 1kbp upstream of the transcription start site of Gata6 by both ChIP-qPCR and luciferase reporter assay. These results suggested a SHF regulatory network comprising of Gata4, Gata6 and Hh-signaling for OFT development.

Successful Truncal Valve Replacement With a Mechanical Valve After Bilateral Pulmonary Artery Banding.

Surgical management of truncus arteriosus, or common arterial trunk, has expanded over the past three decades to include earlier surgical intervention, initially during infancy and now chiefly in the neonatal period. Many studies have shown that preoperative truncal valve insufficiency is an independent risk factor for mortality. We herein present the case of a five-month-old boy with severe truncal valve insufficiency who underwent repair of common arterial trunk and prosthetic replacement of the truncal valve with associated annular enlargement after initial stabilization in the newborn period via palliative bilateral pulmonary artery banding. We believe that initial bilateral pulmonary artery banding represents a viable option for some cases of common arterial trunk involving truncal valve insufficiency.

Prenatal diagnosis of the fetal common arterial trunk. A case series.

Fetal common arterial trunk is an anomaly represented by a unique arterial trunk that arouses from the base of the heart, and gives birth to systemic branches, both pulmonary and coronary, frequently associated with a ventricular septal defect (VSD) and has a poor prognosis. We present a series of 17 cases diagnosed in our tertiary center with different types of fetal common arterial trunk, its associated disorders, the evolution of the pregnancies, and of the neonates. We concluded that our cases support the fact that a complete intrauterine evaluation of each case of the common arterial trunk is impossible. The postnatal prognosis of the cases from our center was fatal, similar to most reports of the literature.

Intramural Left Coronary Artery in Truncus Arteriosus.

An intramural coronary artery in the setting of truncus arteriosus (common arterial trunk) is an uncommon association. Following an uneventful surgical repair, a neonate developed a low cardiac output state deteriorating into cardiac arrest shortly after arrival into the intensive care unit, requiring extracorporeal membrane oxygenation support. Echocardiography and angiography showed occlusion of the left coronary artery, prompting emergency surgical reexploration. A "slit-like" orifice with an intramural left coronary artery was successfully unroofed, allowing full recovery. Full definition of the proximal coronary anatomy beyond the orifices should be investigated preoperatively in truncus arteriosus, as a missed intramural segment could lead to significant morbidity or mortality.

Common Arterial Trunk Repair by Means of a Handmade Bovine Pericardial-Valved Woven Dacron Conduit.

BACKGROUND: Surgical repair of common arterial trunk (CAT) by means of a homograft conduit has become a standard practice. We report our experience in the correction of this heart disease with a handmade bovine pericardial-valved woven Dacron conduit as an alternative procedure to homografts, with a focus on early, mid-term, and long-term results. METHODS: We designed a retrospective study that included 15 patients with a mean age of 1.5 years (range: three months to eight years), who underwent primary repair of simple CAT. Right ventricular outflow tract was reconstructed in all the cases with this handmade graft that was explanted at the time of its biological stenotic degeneration. A peeling procedure was performed at this time, in order to reconstruct the right ventricle-to-pulmonary artery continuity. RESULTS: Overall mortality was 13.3% (one death at the early postoperative primary repair and the other at the mid-term postoperative peeling reoperation). Actuarial survival rate was 93.3%, 86.7%, and 86.7% at 5, 10, and 15 years, respectively. All of the 14 survivors developed stenosis of the handmade conduit at the mid-term period (8 ± 3 years), but after the peeling procedure, 13 survivors remain asymptomatic to date. CONCLUSIONS: Primary repair of common arterial trunk using a handmade conduit can be performed with very low perioperative mortality and satisfactory mid-term and long-term results, which can be favorably compared with those reported with the use of homografts. When graft obstruction develops, peeling procedure is a good option because it does not affect the overall survival, although long-term outcomes warrant further follow-up.

Long-term Outcomes after Truncus Arteriosus Repair: A Single-center Experience for More than 40 Years.

OBJECTIVES: This study aimed to analyze long-term survival and functional outcomes after truncus arteriosus repair in a single institution with more than 40 years of follow-up. METHODS: Medical records were analyzed retrospectively in 52 patients who underwent the Rastelli procedure for truncus arteriosus repair between 1974 and 2002. Thirty-five patients survived the initial repair. The median age at the initial operation was 2.8 months (range, 0.1-123 months) and the body weight was 3.9 kg (range, 1.6 to 15.0 kg). RESULTS: The median age at follow-up was 23.6 years (range, 12.4 to 44.5 years). The median follow-up duration was 23.4 years (range, 12.3 to 40.7 years). The actuarial survival rate was 97% at 10 years and 93% at both 20 years and 40 years after the initial operation. At follow-up, most patients were in New York Heart Association (NYHA) functional classes I (73%) and II (24%). Thirty-six percent of patients had full-time jobs, 40% were students, and 21% were unemployed. Most patients (97%) had undergone conduit reoperations. Freedom from reoperation for right ventricular (RV) outflow and pulmonary artery (PA) stenosis was 59% at 5 years, 28% at 10 years, and 3% at 20 years after the initial operation. Freedom from catheter interventions for RV outflow and PA stenosis was 59% at 5 years, 47% at 10 years, and 38% at 20 years after the initial operation. Freedom from truncal valve replacement was 88% at 5 years, 85% at 10 years, and 70% at 20 years after the initial operation. CONCLUSIONS: In this single-center retrospective study, with long-term follow-up after repair of truncus arteriosus, long-term survival and functional outcomes were acceptable, despite the requirement for reoperation and multiple catheter interventions for RV outflow and PA stenosis in almost all patients, and the frequent requirement for late truncal valve operations.

Outcomes of Truncus Arteriosus Repair in Children: 35 Years of Experience From a Single Institution.

We evaluated the long-term outcomes following repair of truncus arteriosus (TA) from a single institution. We conducted a retrospective review of children (n = 171) who underwent TA repair between 1979 and 2014. Early mortality rate was 11.7% (20/171). There were 19 late deaths. Most deaths (74%, 29/39) occurred within the first year following surgery. The 1-year mortality rate in 1979-2004 was 18% (25/136) and decreased to 11% (4/35) in 2005-2014. The overall survival rate was 73.6% at 30 years. Multivariate analysis identified postoperative extracorporeal membrane oxygenation (P = 0.003), operative weight <2.5kg (P = 0.012), prior surgical intervention (P = 0.018), and coronary artery anomaly (P = 0.037) as risk factors for early mortality. A Cox regression model identified DiGeorge syndrome (P = 0.008) as a risk factor for late mortality. Freedom from right ventricular outflow tract reoperation was 4.6% at 20 years. Concomitant truncal valve (TV) repair or replacement was undertaken in 20 patients. Additionally, 14 patients underwent late TV repair or replacement. The overall survival rate in patients who underwent TV operation was 76.9% at 20 years. A total of 19 patients had concomitant interrupted aortic arch with a survival rate of 89.5% at 20 years. Median follow-up was 19 years (mean = 17 years, range: 1-34 years). All patients were in New York Heart Association Class I/II at last follow-up. Following repair of TA, patients had good long-term functional status but had high reoperation rates. Repair of interrupted aortic arch and TV were not risk factors for mortality. Postoperative extracorporeal membrane oxygenation, operative weight <2.5kg, prior surgical intervention, and coronary artery anomaly were risk factors for early death. DiGeorge syndrome was associated with late death, most commonly from infection.

Palliation of Truncus Arteriosus Associated With Complete Atrioventricular Canal--Results of Single Ventricle Palliation.

BACKGROUND: Truncus arteriosus associated with complete atrioventricular canal defect is rare and continues to be a surgical challenge with high morbidity and mortality. In the absence of extension of the ventricular septal defect to the outlet septum, biventricular repair is precluded, and single ventricle palliation remains the only option. We present our experience with five patients with truncus arteriosus and complete atrioventricular canal defect who underwent single ventricular palliation. METHODS: Five patients with truncus arteriosus and complete atrioventricular canal defect managed along the single ventricle palliation pathway were retrospectively reviewed. Demographic, echocardiographic, cardiac catheterization, and perioperative data were analyzed. RESULTS: All patients underwent neonatal palliation tailored to their anatomy (excision of pulmonary arteries from the common trunk and systemic to pulmonary artery shunt in two patients, excision of pulmonary artery and right ventricle to pulmonary artery conduit in two patients, and bilateral branch pulmonary artery bands in one patient). There were two early deaths after neonatal palliation. At a median follow-up of 210 days (interquartile range 1,210 days), all three survivors have undergone second-stage palliation. Of these patients, one is interstage II to III, and two patients have completed their Fontan procedure and are doing well. CONCLUSION: Truncus arteriosus with complete atrioventricular canal defect is a rare combination of defects. Single ventricle palliation pathway with a tailored neonatal approach may be employed for patients with uncommitted ventricular septal defects.

Reoperative double ventricular outflow tract reconstruction in grown-up congenital heart disease patients with conotruncal anomalies.

OBJECTIVE: Surgical experiences of the reoperative double ventricular outflow tract reconstruction long after the successful repair of conotruncal anomalies were reviewed. METHODS: Ten adult patients with conotruncal anomalies (6 females, 22.9 ± 5.5 years old) underwent the reoperative double ventricular outflow tract reconstruction. Primary diagnosis was pulmonary atresia with ventricular septal defect in 6 patients, truncus arteriosus in 3, and double-outlet right ventricle in 1. The indication for the left ventricular outflow tract reconstruction was the left ventricular dilatation and dysfunction derived from moderate or greater systemic semilunar valve insufficiency. The indication for the right ventricular outflow tract reconstruction was severe pulmonary insufficiency in all patients, and concomitant right ventricular outflow tract obstruction in 7. RESULTS: The systemic semilunar valve replacement was performed in all patients. The right ventricular outflow tract patching was performed in 4 patients, and the revision of extra-cardiac conduit in 6. Within a mean follow-up of 9.0 ± 7.0 years, there was no mortality. The left ventricular end-diastolic volume index improved from 147 ± 37 to 108 ± 19 ml/m(2) (p = 0.005), and the peak pressure gradient across right ventricular outflow tract improved from 43 ± 17 mmHg to 9 ± 2 at 1 year after (p = 0.02). The plasma brain natriuretic peptide level improved from 83 ± 57 to 34 ± 32 pg/ml (p = 0.03). CONCLUSIONS: Reoperative double ventricular outflow tract reconstruction long after the repair of conotruncal anomalies was safely performed, and provided the ventricular reverse remodeling and improvement of serum BNP level.

Intramural Ventricular Septal Defect Is a Distinct Clinical Entity Associated With Postoperative Morbidity in Children After Repair of Conotruncal Anomalies.

BACKGROUND: Intramural ventricular septal defects (VSDs) are interventricular communications through right ventricular free wall trabeculations that can occur after repair of conotruncal anomalies. We assessed the prevalence of residual intramural VSDs and their effect on postoperative course. METHODS AND RESULTS: Children who underwent biventricular repair of a conotruncal anomaly from January 1, 2006, to June 30, 2013, and had a postoperative transthoracic echocardiogram were included. Images were reviewed for residual intramural or nonintramural VSDs. The primary outcome was a composite of mortality, extracorporeal membrane oxygenation use, and need for subsequent catheter or surgical VSD closure. The secondary outcome was postoperative hospital length of stay. A residual VSD was present in 256 of the 442 subjects (58%), of which 231 (90%) were <2 mm in size. Forty-nine patients (11%) had intramural VSDs, and 207 (47%) had nonintramural VSDs. Patients with intramural VSDs were more likely to reach the primary composite outcome compared with those with nonintramural VSDs or no residual VSD (14 of 49 [29%] versus 15 of 207 [7%] versus 6 of 186 [3%]; P<0.0001). In addition, those with intramural VSDs had longer postoperative hospital length of stay compared with those with nonintramural VSDs or no residual VSD (20 days [interquartile range, 11-42 days] versus 7 days [interquartile range, 5-14 days] versus 6 days [interquartile range, 4-11 days]; P=0.0001). These associations remained significant after adjustment for known risk factors for poor outcomes, including residual VSD size and operative complexity. CONCLUSIONS: Among residual VSDs after repair of conotruncal anomalies, intramural VSDs are uniquely associated with postoperative morbidity, mortality, and longer postoperative hospital length of stay. It is important to recognize intramural VSDs in the postoperative period.