Genetic etiology of truncus arteriosus excluding 22q11.2 deletion syndrome and identification of c.1617del, a prevalent variant in TMEM260, in the Japanese population.

Truncus Arteriosus (TA) is a congenital heart disease characterized by a single common blood vessel emerging from the right and left ventricles instead of the main pulmonary artery and aorta. TA accounts for 4% of all critical congenital heart diseases. The most common cause of TA is 22q11.2 deletion syndrome, accounting for 12-35% of all TA cases. However, no major causes of TA other than 22q11.2 deletion have been reported. We performed whole-genome sequencing of 11 Japanese patients having TA without 22q11.2 deletion. Among five patients, we identified pathogenic variants in TMEM260; the biallelic loss-of-function variants of which have recently been associated with structural heart defects and renal anomalies syndrome (SHDRA). In one patient, we identified a de novo pathogenic variant in GATA6, and in another patient, we identified a de novo probably pathogenic variant in NOTCH1. Notably, we identified a prevalent variant in TMEM260 (ENST00000261556.6), c.1617del (p.Trp539Cysfs*9), in 8/22 alleles among the 11 patients. The c.1617del variant was estimated to occur approximately 23 kiloyears ago. Based on the allele frequency of the c.1617del variant in the Japanese population (0.36%), approximately 26% of Japanese patients afflicted with TA could harbor homozygous c.1617del variants. This study highlights TMEM260, especially c.1617del, as a major genetic cause of TA in the Japanese population.

Survival After Single-Stage Repair of Truncus Arteriosus and Associated Defects.

BACKGROUND: The goal of this study was to describe in-hospital and long-term mortality after single-stage repair of truncus arteriosus communis (TAC) and explore factors associated with these outcomes. METHODS: This was a cohort study of consecutive patients undergoing single-stage TAC repair between 1982 and 2011 reported to the Pediatric Cardiac Care Consortium registry. In-hospital mortality was obtained for the entire cohort from registry records. Long-term mortality was obtained for patients with available identifiers by matching with the National Death Index through 2020. Kaplan-Meier survival estimates were created for up to 30 years after discharge. Cox regression models estimated hazard ratios for the associations with potential risk factors. RESULTS: A total of 647 patients (51% male) underwent single-stage TAC repair at a median age of 18 days; 53% had type I TAC, 13% had interrupted aortic arch, and 10% underwent concomitant truncal valve surgery. Of these, 486 (75%) patients survived to hospital discharge. After discharge, 215 patients had identifiers for tracking long-term outcomes; 30-year survival was 78%. Concomitant truncal valve surgery at the index procedure was associated with increased in-hospital and 30-year mortality. Concomitant interrupted aortic arch repair was not associated with increased in-hospital or 30-year mortality. CONCLUSIONS: Concomitant truncal valve surgery but not interrupted aortic arch was associated with higher in-hospital and long-term mortality. Careful consideration of the need and timing for truncal valve intervention may improve TAC outcomes.

Patent ductus arteriosus stenting as therapeutic bridge in a patient with type A3 truncus arteriosus variant with multiple comorbidities.

Type A3 truncus arteriosus describes pulmonary atresia with non-confluent mediastinal pulmonary arteries in which one pulmonary artery arises from a patent ductus arteriosus and the contralateral pulmonary artery from the aorta resulting in ductal dependent pulmonary blood flow. We describe a premature neonate with caudal regression syndrome and type A3 truncus arteriosus who was palliated with a ductal stent allowing completion of a prolonged neonatal ICU hospitalisation for multiple comorbidities.

Right Ventricular Outflow Tract Reconstruction in Truncus Arteriosus: A 30-Year Two-Center Comparison between Homografts and Bovine Jugular Vein.

INTRODUCTION: Homografts and bovine jugular vein are the most commonly used conduits for right ventricular outflow tract reconstruction at the time of primary repair of truncus arteriosus. METHODS: We reviewed all truncus patients from 1990 to 2020 in two mid-volume centers. Inclusion criteria were primary repair, age under one year, and implantation of either homograft or bovine jugular vein. Kaplan-Meier analysis was used to estimate survival, freedom from reoperation on right ventricular outflow tract, and freedom from right ventricular outflow tract reoperation or catheter intervention. RESULTS: Seventy-three patients met the inclusion criteria, homografts were implanted in 31, and bovine jugular vein in 42. There was no difference in preoperative characteristics between the two groups. There were 25/73 (34%) early postoperative deaths and no late deaths. Follow-up for survivals was 17.5 (interquartile range 13.5) years for homograft group, and 11.5 (interquartile range 8.5) years for bovine jugular vein group (P=0.002). Freedom from reoperation on right ventricular outflow tract at one, five, and 10 years in the homograft group were 100%, 83%, and 53%; and in bovine jugular vein group, it was 100%, 85%, and 50% (P=0.79). There was no difference in freedom from reoperation or catheter intervention (P=0.32). CONCLUSION: Bovine jugular vein was equivalent to homografts up to 10 years in terms of survival and freedom from right ventricular outflow tract reoperation or catheter intervention. The choice of either valved conduit did not influence the durability of the right ventricle-pulmonary artery conduit in truncus arteriosus.

Factors Associated With Mortality and Adverse Outcomes After Truncus Arteriosus Repair.

BACKGROUND: Truncus arteriosus repair is associated with higher morbidity and mortality compared with many other congenital heart operations. We sought to determine factors associated with mortality and adverse outcomes in infants undergoing truncus arteriosus repair. METHODS: We used the Pediatric Health Information System Database to identify infants aged < 90 days who underwent truncus arteriosus repair from 2004 to 2019. The primary outcome was hospital mortality. Secondary outcomes were prolonged postoperative length of stay (>30 days) and hospital readmission within 90 days. Multivariable logistic regression models were used to identify associated factors for adverse outcomes. RESULTS: A total of 1645 subjects were included. Hospital mortality occurred in 164 (10%). Factors independently associated with mortality included birth weight < 3 kg, admit age < 48 hours, truncal valve surgery, cardiac arrest, extracorporeal membrane oxygenation, acute kidney injury, cardiac catheterization, tracheostomy, and earlier era. Prolonged postoperative length of stay occurred in 508 patients (31%). Factors independently associated with prolonged postoperative length of stay included prematurity, DiGeorge syndrome, admit age < 48 hours, later surgical era, acute kidney injury, infection, cardiac catheterization, vocal cord paralysis, tracheostomy, and gastrostomy. Readmission within 90 days occurred in 511 of 1481 surviving patients (34%). DiGeorge syndrome, cleft lip/palate, cardiac catheterization, and extracorporeal membrane oxygenation were factors independently associated with hospital readmission. CONCLUSIONS: We identified multiple factors associated with hospital mortality and adverse outcomes in infants undergoing truncus arteriosus repair. This information is useful for quality improvement initiatives, perioperative counseling, and discharge planning.

Outcomes in Primary Repair of Truncus Arteriosus with Significant Truncal Valve Insufficiency: A Systematic Review and Meta-analysis.

Data regarding the effect of significant TVI on outcomes after truncus arteriosus (TA) repair are limited. The aim of this meta-analysis was to summarize outcomes among patients aged ≤ 24 months undergoing TA repair with at least moderate TVI. A systematic literature search was conducted in PubMed, Scopus, and CINAHL Complete from database inception through June 1, 2022. Studies reporting outcomes of TA repair in patients with moderate or greater TVI were included. Studies reporting outcomes only for patients aged > 24 months were excluded. The primary outcome was overall mortality, and secondary outcomes included early mortality and truncal valve reoperation. Random-effects models were used to estimate pooled effects. Assessment for bias was performed using funnel plots and Egger's tests. Twenty-two single-center observational studies were included for analysis, representing 1,172 patients. Of these, 232 (19.8%) had moderate or greater TVI. Meta-analysis demonstrated a pooled overall mortality of 28.0% after TA repair among patients with significant TVI with a relative risk of 1.70 (95% CI [1.27-2.28], p < 0.001) compared to patients without TVI. Significant TVI was also significantly associated with an increased risk for early mortality (RR 2.04; 95% CI [1.36-3.06], p < 0.001) and truncal valve reoperation (RR 3.90; 95% CI [1.40-10.90], p = 0.010). Moderate or greater TVI before TA repair is associated with an increased risk for mortality and truncal valve reoperation. Management of TVI in patients remains a challenging clinical problem. Further investigation is needed to assess the risk of concomitant truncal valve surgery with TA repair in this population.

Outcomes of Gastrostomy and Tracheostomy in Infants Undergoing Truncus Arteriosus Repair: Database Study Using the Pediatric Health Information System.

OBJECTIVES: We sought to determine the prevalence of and factors associated with gastrostomy tube placement and tracheostomy in infants undergoing truncus arteriosus repair, and associations between these procedures and outcome. DESIGN: Retrospective cohort study. SETTING: Pediatric Health Information System database. PATIENTS: Infants less than 90 days old who underwent truncus arteriosus repair from 2004 to 2019. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Multivariable logistic regression models were used to identify factors associated with gastrostomy tube and tracheostomy placement and to identify associations between these procedures and hospital mortality and prolonged postoperative length of stay (LOS; > 30 d). Of 1,645 subjects, gastrostomy tube was performed in 196 (11.9%) and tracheostomy in 56 (3.4%). Factors independently associated with gastrostomy tube placement were DiGeorge syndrome, congenital airway anomaly, admission age less than or equal to 2 days, vocal cord paralysis, cardiac catheterization, infection, and failure to thrive. Factors independently associated with tracheostomy congenital airway anomaly, truncal valve surgery, and cardiac catheterization. Gastrostomy tube was independently associated with prolonged postoperative LOS (odds ratio [OR], 12.10; 95% CI, 7.37-19.86). Hospital mortality occurred in 17 of 56 patients (30.4%) who underwent tracheostomy versus 147 of 1,589 patients (9.3%) who did not ( p < 0.001), and median postoperative LOS was 148 days in patients who underwent tracheostomy versus 18 days in those who did not ( p < 0.001). Tracheostomy was independently associated with mortality (OR, 3.11; 95% CI, 1.43-6.77) and prolonged postoperative LOS (OR, 9.85; 95% CI, 2.16-44.80). CONCLUSIONS: In infants undergoing truncus arteriosus repair, tracheostomy is associated with greater odds of mortality; while gastrostomy and tracheostomy are strongly associated with greater odds of prolonged postoperative LOS.

Transapical Delivery of a Sapien Valve for Transcatheter Aortic Valve Replacement in an 11-Year-Old Patient with Truncus Arteriosus.

Complex congenital heart defects may necessitate repeated surgical interventions throughout a patient's lifetime. Each subsequent procedure exposes patients to a greater cumulative risk, thus adding to the potential morbidity and mortality of the surgery. Transcatheter interventions can help mitigate the surgical risk for many defects and can delay or mitigate the need for surgery. This case report describes the rare use of a transapically delivered transcatheter aortic valve replacement (TAVR) therapy in a high-risk pediatric patient to postpone the need for surgery and potentially reduce the number of lifelong surgical interventions. The case highlights how transcatheter aortic valve therapies can be considered for non-standard, higher risk pediatric patients to postpone the need for surgical valve replacement and may serve as a paradigm shift in the care of complex patients with aortic valve pathology.

Use of a QDOT MICRO catheter to identify a premature ventricular contraction origin in the right ventricular anterior papillary muscle in a repaired truncus arteriosus.

The ventricular papillary muscles (VPMs) can be a source of premature ventricular contractions (PVCs). Catheter ablation of VPM PVCs is challenging because of the anatomical complexity, such as the apical structures in proximity to the ventricular walls. The QDOT MICRO catheter (Biosense Webster, Diamond Bar, CA, USA) has microelectrodes embedded along the circumference of its distal tip and can provide information on which side of its tip myocardial activation is earlier. This repaired truncus arteriosus case demonstrates the usefulness of the microelectrode recording in identifying a PVC origin in a right VPM apex close to the right ventricular anterior wall.

Natural History of Truncal Root Dilatation and Truncal Valve Regurgitation in Truncus Arteriosus.

BACKGROUND: The natural history of the dilated truncal root in repaired truncus arteriosus (TA) is incompletely understood. METHODS: A single-center review of patients who underwent TA repair between January 1984 and December 2018 was performed. Echocardiographically determined root diameters and derived z scores were measured at the annulus, sinus of Valsalva (SoV), and sinutubular junction (STJ) immediately before TA repair and throughout follow-up. Linear mixed-effects models assessed trends in root dimensions over time. RESULTS: Of 193 patients who underwent TA repair at a median age of 12 days (interquartile range, 6-48 days) and survived to discharge, 34 (17.6%), 110 (57.0%), and 49 (25.4%) patients had bicuspid, tricuspid, and quadricuspid truncal valves, respectively. Median postoperative follow-up was 11.6 years (interquartile range, 4.4-22.0 years; range, 0.1-34.8 years). Truncal valve or root intervention was required in 38 patients (19.7%). The mean rates of annular, SoV, and STJ growth were 0.7 ± 0.3 mm/y, 0.8 ± 0.5 mm/y, and 0.9 ± 0.4 mm/y, respectively. Root z scores remained stable with time. At baseline, compared with patients with tricuspid leaflet anatomy, bicuspid patients had larger diameters at the SoV (P = .003) and STJ (P = .029), whereas quadricuspid patients had larger STJ diameters (P = .004). Over time, the bicuspid and quadricuspid cohorts demonstrated comparatively greater annular dilatation (both P < .05). Patients with ≥75th percentile root growth rates had a higher incidence of moderate-severe truncal regurgitation (P = .019) and truncal valve intervention (P = .002). CONCLUSIONS: Root dilatation in TA persisted for up to 30 years after primary repair. Patients with bicuspid and quadricuspid truncal valves demonstrated greater root dilatation over time and required more valve interventions. Continued longitudinal follow-up is warranted in this higher-risk cohort.

Fetal Echocardiographic Variables Associated with Pre-Surgical Mortality in Truncus Arteriosus: A Pilot Study.

Truncus arteriosus (TA) is a rare congenital heart defect that can be prenatally detected by fetal echocardiography. However, prognostication and prenatal counseling focus primarily on surgical outcomes due to limited fetal and neonatal pre-surgical mortality data. We aimed to describe the incidence and identify predictors of pre-surgical mortality in prenatally detected TA. This two-center, retrospective cohort study included fetuses diagnosed with TA between 01/2010 and 04/2020. The primary outcome was pre-surgical mortality, defined by fetal or neonatal pre-surgical death or primary listing for transplantation prior to discharge. Univariable regression modeling, Chi-square tests, and t tests assessed for associations between prenatal clinical, demographic, and fetal echocardiographic (fetal-echo) variables and pre-surgical mortality. Of 23 pregnancies with prenatal diagnosis of TA, 4 (17%) were terminated. Of the remaining 19, pre-surgical mortality occurred in 4 (26%), including 2 (11%) fetal deaths and 2 (11%) neonatal pre-surgical deaths. No transplantation listings. Of liveborn fetuses (n = 17), 15 (88%) underwent a neonatal surgery, and 1 (6%) required ECMO. As compared to the survivors, the pre-surgical mortality group had a higher likelihood of having left ventricular dysfunction (0% vs. 40%; p = 0.01), right ventricular dysfunction (0% vs. 60%; p = 0.002), cardiovascular profile score < 7 (0% vs. 40%; p = 0.01), skin edema (0% vs. 40%; p = 0.01), and abnormal umbilical venous (UV) Doppler (0% vs. 60%; p = 0.002). The presence of truncal valve regurgitation or stenosis neared significance. In this cohort with prenatally diagnosed TA, there is significant pre-surgical mortality, including fetal death and neonatal pre-surgical death. Termination rate is also high. Fetal-echo variables associated with pre-surgical mortality in this cohort include ventricular dysfunction, low CVP, skin edema, and abnormal UV Doppler. Knowledge about prenatal risk factors for pre-surgical mortality may guide parental counseling and postnatal planning in prenatally diagnosed TA.

Surgical Repair of a Rare Variant of Common Arterial Trunk, With Considerations of its Significance for Morphogenesis.

We present a successful surgical repair of a rare variant of the common arterial trunk with unusual arrangement of the pulmonary arteries. The variant was not readily classified using either of the popular classifications for the common arterial trunk. It is appropriately described as a common arterial trunk showing aortic dominance, but with extrapericardial origin of the pulmonary arteries from the underside of the truncal arch. We also provide an account of cardiac development, which we suggest offers an accurate explanation for its morphogenesis.

Congenital Aortic Valve Repair When the Options aren't Good: Truncus Arteriosus and Transposition of the Great Arteries.

Patients with truncus arteriosus and transposition of great arteries are prone to neo-aortic valve insufficiency. Although presenting at opposite ends of the age spectrum, both conditions tend to be commonly associated with neo aortic root dilatation. In patients with truncus arteriosus there is an additional complexity of quadricuspid valve morphology, which make up the majority of valves requiring repair. A unified approach to all these patients would include reduction and stabilization of the annulus and sinotubular junction, as well as achieving equal and symmetrical coaptation of the valve leaflets. By systematically employing these techniques, valve replacement should be avoidable in most children.

Association Between Birth Weight Z-Scores and Early Outcomes Following Truncus Arteriosus Repair.

In infants undergoing truncus arteriosus (TA) repair, we sought to determine associations between fetal growth restrictions as measured by birth weight Z-score and early outcomes. We utilized the Pediatric Health Information System (PHIS) database to identify infants < 90 days old who underwent TA repair from 2004 to 2019. The primary exposure variable was birth weight Z-score, calculated based on gestational age at birth, gender, and birth weight. The primary outcome was postoperative hospital mortality. Secondary outcomes included major complications, prolonged postoperative length of hospital stay (LOS; > 30 days), and hospital readmission within 1 year. Generalized estimating equation (GEE) models were used to identify adjusted associations between birth weight Z-score, small for gestational age (SGA) status, and mortality and included were 1039 subjects. Median birth weight was 2960 g, gestational age at birth was 38 weeks, and birth weight Z-score was - 0.47. SGA was present in 21% of subjects. Hospital mortality occurred in 104 patients (10%). By multivariable analysis, lower birth weight Z-score was associated with higher hospital mortality [for each unit decrease in birth weight Z-score below - 1.0, adjusted OR 1.71 (95% CI 1.10-4.25)]. SGA status was associated with increased hospital mortality (adjusted OR 2.17; 95% CI 1.39-3.40). Birth weight Z-scores and SGA status were not significantly associated with occurrence of cardiac arrest, ECMO use, gastrostomy tube placement, tracheostomy, seizures, infection, prolonged postoperative LOS, or hospital readmission. In infants undergoing TA repair, lower birth weight Z-scores and SGA status were strongly associated with increased hospital mortality.

Laparoscopic radical resection for rectal cancer in a patient with uncorrected truncus arteriosus type IV: A case report.

Persistent truncus arteriosus is a rare congenital heart malformation which if not corrected, results in the death of about 50% of the patients, while fewer than 20% of the patients survive the first year of life. Here, we report the successful anesthetic management of an adult patient with uncorrected truncus arteriosus who presented for the laparoscopic radical resection of rectal cancer.

Non-Conduit Repair of Truncus Arteriosus.

INTRODUCTION: The procedure of choice for treatment of truncus arteriosus is one-stage repair within the first few months of life. Establishing right ventricle-pulmonary artery direct continuity without conduit can be a good alternative in the absence of valved conduits in developing centers. METHODS: Between January 2021 and June 2021, a total of five patients (three males, two females) underwent definitive repair of truncus arteriosus without an extracardiac conduit. We used the Barbero-Marcial technique to allow age-related growth, eliminate the risk of conduit-related complications, and to avoid forcing a conduit to place in a very small mediastinal space. RESULTS: The patients' mean age was 31.2 days (11-54 days). Their mean bodyweight was 3.2 kg (2.7-3.8kg). Mean postoperative intensive care unit stay was 39.6 days (7-99 days). There were two mortalities in the intensive care unit on postoperative days 12 and 61 due to lung-related problems. The remaining three cases' mean ventilation time was 15.6 days (8-22 days). CONCLUSION: Having access to a valved conduit is still challenging for some centers, and the non-conduit repair technique defined by Barbero-Marcial can be a successful, life-saving alternative easy for young surgeons to perform in newly based centers.

Contemporary Multicenter Outcomes for Truncus Arteriosus With Interrupted Aortic Arch.

BACKGROUND: Truncus arteriosus with interrupted aortic arch (TA-IAA) is a rare congenital heart defect with historically poor outcomes. Contemporary multicenter data are limited. METHODS: A retrospective cohort study of children who underwent repair of TA-IAA between 2009 and 2016 at 12 tertiary care referral centers within the United States was performed. Major adverse cardiac events (MACE) were defined as postoperative extracorporeal membrane oxygenation, cardiopulmonary resuscitation, or operative mortality. TA-IAA patients were compared with TA patients who underwent repair during the study period from the same institutions. RESULTS: We reviewed 35 patients with TA-IAA. MACE occurred in 12 patients (34%). Improvement over time was observed during the study period with 11 events (92%) occurring in the first half of the study period (P = .03). Factors associated with MACE included moderate or severe truncal valve insufficiency (P < .01), concomitant truncal valve repair (P = .04), and longer cardiopulmonary bypass duration (P = .02). In comparison with 216 patients who underwent TA repair, patients with TA-IAA had a higher rate of MACE, but this finding was not statistically significant (34% vs 20%, respectively; P = .07). Additionally no differences between TA-IAA and TA groups were observed for unplanned reoperations (14% vs 22%, respectively; P = .3), hospital length of stay (24 vs 23 days, P = .65), or late deaths (7% vs 7%, P = 1.00). CONCLUSIONS: In this contemporary, multicenter cohort the rate of MACE after repair of TA-IAA was high but improved during the study period. Early childhood outcomes of patients with TA-IAA were similar to those with TA.