RESUMEN
Truncus arteriosus (TA) is a congenital heart defect where one main blood vessel emerges from the heart, instead of individual aorta and pulmonary artreries. Peripheral mononuclear cells (PBMCs) of a male infant with TA were reporogrammed using Sendai virus. The resultant iPSC line (NCHi015-A) displayed normal colony formation, expressed pluripotency markers, and differentiated into cells from three germ layers. NCHi015-A was matched to the patient's genetic profile, had normal karyotype, retained genetic variants in KMT2D and NOTCH1, and tested negative for reprogramming transgene. This iPSC line can be used for studying congenital heart defects associated with genetic variants in KMT2D and NOTCH1.
Asunto(s)
Células Madre Pluripotentes Inducidas , Receptor Notch1 , Humanos , Células Madre Pluripotentes Inducidas/metabolismo , Masculino , Receptor Notch1/genética , Receptor Notch1/metabolismo , Tronco Arterial , Proteínas de Unión al ADN/genética , Línea Celular , Heterocigoto , Diferenciación Celular , Proteínas de NeoplasiasRESUMEN
Integrated human genetics and molecular/developmental biology studies have revealed that truncus arteriosus is highly associated with 22q11.2 deletion syndrome. Other congenital malformation syndromes and variants in genes encoding TBX, GATA, and NKX transcription factors and some signaling proteins have also been reported as its etiology.
Asunto(s)
Tronco Arterial Persistente , Humanos , Tronco Arterial Persistente/genética , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Tronco Arterial/metabolismo , Síndrome de DiGeorge/genética , Proteínas de Dominio T Box/genética , Proteínas de Dominio T Box/metabolismo , Predisposición Genética a la Enfermedad/genéticaRESUMEN
In normal cardiovascular development in birds and mammals, the outflow tract of the heart is divided into two distinct channels to separate the oxygenated systemic blood flow from the deoxygenated pulmonary circulation. When the process of outflow tract septation fails, a single common outflow vessel persists resulting in a serious clinical condition known as persistent truncus arteriosus or common arterial trunk. In this chapter, we will review molecular pathways and the cells that are known to play a role in the formation and development of the outflow tract and how genetic manipulation of these pathways in animal models can result in common arterial trunk.
Asunto(s)
Modelos Animales de Enfermedad , Tronco Arterial Persistente , Animales , Humanos , Transducción de Señal , Tronco Arterial/metabolismo , Tronco Arterial/fisiopatología , Tronco Arterial/patología , Tronco Arterial Persistente/genética , Tronco Arterial Persistente/fisiopatología , Tronco Arterial Persistente/patologíaRESUMEN
Truncus arteriosus (TA, also known as common arterial trunk) consists of only one great artery ("the truncus") with a semilunar valve (truncus valve) arising from the heart and an additional ventricular septal defect and (Fig. 50.1). This great artery is positioned above the ventricular septal defect and gives rise to the coronary arteries, the pulmonary arteries, and the aortic arch. Historically, TA has been classified by Collet and Edwards in three types, where in type I there was a common pulmonary artery truncus, in type II the left and right PA arise separately but close to each other, in type III both PA arise independently; in addition, there was a type IV that was later characterized as pulmonary atresia with VSD and major aortopulmonary collateral arteries arising from the descending aorta.
Asunto(s)
Tronco Arterial Persistente , Humanos , Arteria Pulmonar/fisiopatología , Arteria Pulmonar/anomalías , Arteria Pulmonar/patología , Atresia Pulmonar/terapia , Atresia Pulmonar/diagnóstico por imagen , Atresia Pulmonar/cirugía , Atresia Pulmonar/fisiopatología , Tronco Arterial/diagnóstico por imagen , Tronco Arterial/cirugía , Tronco Arterial Persistente/cirugía , Tronco Arterial Persistente/terapia , Tronco Arterial Persistente/fisiopatología , Tronco Arterial Persistente/diagnósticoRESUMEN
Background: Truncus arteriosus is a rare congenital heart defect resulting from the failure of the truncus arteriosus to divide during fetal development. It leads to a single outflow tract from the heart and, if left untreated, can be fatal. Late presentation and repair can also increase the risk of pulmonary hypertensive crises, which can lead to morbidity and mortality after repair. Methods: We performed a retrospective study examining outcomes of late-presenting patients who were repaired for this anomaly at our institution. Results: We identified seven patients who underwent late repair of truncus arteriosus who were 3 to 11 years of age. There were six females and one male. Postoperatively, all patients showed improvement in symptoms and hemodynamic parameters, with no reported mortality. The median duration of stay in the intensive care unit was nine days and with a range from 3 to 18 days, while the median hospital stay was 29 days with a range from 21 to 60 days. Conclusion: These findings highlight the potential for successful outcomes even in cases of delayed diagnosis.
Asunto(s)
Tiempo de Internación , Tronco Arterial Persistente , Humanos , Femenino , Masculino , Estudios Retrospectivos , Preescolar , Niño , Tiempo de Internación/estadística & datos numéricos , Resultado del Tratamiento , Tronco Arterial Persistente/cirugía , Procedimientos Quirúrgicos Cardíacos/métodos , Factores de Tiempo , Tronco Arterial/cirugíaRESUMEN
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.
Asunto(s)
Síndrome de DiGeorge , Proteínas de la Membrana , Femenino , Humanos , Masculino , Alelos , Síndrome de DiGeorge/genética , Pueblos del Este de Asia/genética , Japón/epidemiología , Proteínas de la Membrana/genética , Receptor Notch1/genética , Tronco Arterial/patología , Secuenciación Completa del GenomaRESUMEN
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.
Asunto(s)
Conducto Arterioso Permeable , Conducto Arterial , Tronco Arterial Persistente , Recién Nacido , Humanos , Conducto Arterioso Permeable/complicaciones , Conducto Arterioso Permeable/cirugía , Tronco Arterial , Tronco Arterial Persistente/cirugía , Arteria Pulmonar/diagnóstico por imagen , Arteria Pulmonar/cirugía , StentsRESUMEN
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.
Asunto(s)
Coartación Aórtica , Tronco Arterial Persistente , Niño , Humanos , Masculino , Lactante , Recién Nacido , Femenino , Tronco Arterial Persistente/cirugía , Tronco Arterial/cirugía , Estudios de Cohortes , Estudios de Seguimiento , Válvulas Cardíacas/cirugía , Coartación Aórtica/cirugía , Reoperación , Resultado del TratamientoRESUMEN
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.
Asunto(s)
Ventrículos Cardíacos , Tronco Arterial , Humanos , Animales , Bovinos , Lactante , Ventrículos Cardíacos/cirugía , Tronco Arterial/cirugía , Venas Yugulares/trasplante , Resultado del Tratamiento , Estudios Retrospectivos , Aloinjertos , ReoperaciónRESUMEN
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.
Asunto(s)
Cardiopatías Congénitas , Tronco Arterial Persistente , Humanos , Lactante , Tronco Arterial/cirugía , Estudios de Seguimiento , Tronco Arterial Persistente/cirugía , Cardiopatías Congénitas/cirugía , ReoperaciónRESUMEN
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.
Asunto(s)
Lesión Renal Aguda , Procedimientos Quirúrgicos Cardíacos , Labio Leporino , Fisura del Paladar , Síndrome de DiGeorge , Cardiopatías Congénitas , Lactante , Humanos , Niño , Tronco ArterialRESUMEN
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.
Asunto(s)
Gastrostomía , Sistemas de Información en Salud , Humanos , Niño , Lactante , Recién Nacido , Gastrostomía/efectos adversos , Estudios Retrospectivos , Tronco Arterial , TraqueostomíaRESUMEN
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.
Asunto(s)
Estenosis de la Válvula Aórtica , Implantación de Prótesis de Válvulas Cardíacas , Prótesis Valvulares Cardíacas , Reemplazo de la Válvula Aórtica Transcatéter , Tronco Arterial Persistente , Humanos , Niño , Estenosis de la Válvula Aórtica/cirugía , Estenosis de la Válvula Aórtica/etiología , Tronco Arterial/cirugía , Resultado del Tratamiento , Válvula Aórtica/cirugía , Tronco Arterial Persistente/cirugía , Implantación de Prótesis de Válvulas Cardíacas/métodos , Factores de RiesgoRESUMEN
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.
Asunto(s)
Ablación por Catéter , Complejos Prematuros Ventriculares , Humanos , Complejos Prematuros Ventriculares/cirugía , Músculos Papilares/cirugía , Tronco Arterial/cirugía , Ventrículos Cardíacos/cirugía , Catéteres/efectos adversos , Ablación por Catéter/efectos adversos , Resultado del TratamientoRESUMEN
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.
Asunto(s)
Enfermedades de las Válvulas Cardíacas , Tronco Arterial Persistente , Humanos , Recién Nacido , Tronco Arterial/diagnóstico por imagen , Tronco Arterial/cirugía , Dilatación , Tronco Arterial Persistente/complicaciones , Tronco Arterial Persistente/diagnóstico por imagen , Tronco Arterial Persistente/cirugía , Enfermedades de las Válvulas Cardíacas/complicaciones , Enfermedades de las Válvulas Cardíacas/diagnóstico por imagen , Enfermedades de las Válvulas Cardíacas/cirugía , Dilatación PatológicaRESUMEN
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.
Asunto(s)
Cardiopatías Congénitas , Tronco Arterial Persistente , Humanos , Tronco Arterial Persistente/cirugía , Cardiopatías Congénitas/cirugía , Tronco Arterial , MorfogénesisAsunto(s)
Arteria Pulmonar , Tronco Arterial Persistente , Humanos , Arteria Pulmonar/diagnóstico por imagen , Arteria Pulmonar/cirugía , Tronco Arterial/diagnóstico por imagen , Tronco Arterial/cirugía , Ventrículos Cardíacos/diagnóstico por imagen , Ventrículos Cardíacos/cirugía , Tronco Arterial Persistente/cirugía , Resultado del TratamientoRESUMEN
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.