Chylothorax in newborns after cardiac surgery: a rare complication?

The aim of this study was to analyze patients diagnosed with chylothorax after congenital heart disease surgery among a cohort of neonatal patients, comparing the evolution, complications, and prognosis after surgery of patients who were and were not diagnosed with chylothorax, and to analyze possible risk factors that may predict the appearance of chylothorax in this population. Retrospective and observational study included all neonates (less than 30 days since birth) who underwent congenital heart disease surgery in a level III neonatal intensive care department. We included infants born between January 2014 and December 2019. We excluded those infants who were born before 34 weeks of gestational age or whose birth weight was less than 1800 g. We also excluded catheter lab procedures and patent ductus arteriosus closure surgeries. Included patients were divided into two groups depending on whether they were diagnosed with chylothorax or not after surgery, and both groups were compared in terms of perinatal-obstetrical information, surgical data, and NICU course after surgery. We included 149 neonates with congenital heart disease surgery. Thirty-one patients (20.8%) developed chylothorax, and in ten patients (32.3%), it was considered large volume chylothorax. Regarding the evolution of these patients, 22 infants responded to general dietetic measures, a catheter procedure was performed in 9, and 5 of them finally required pleurodesis. Cardiopulmonary bypass, median sternotomy, and delayed sternal closure were the surgical variables associated with higher risks of chylothorax. Patients with chylothorax had a longer duration of inotropic support and mechanical ventilation and took longer to reach full enteral feeds. As complications, they had higher rates of cholestasis, catheter-related sepsis, and venous thrombosis. Although there were no differences in neonatal mortality, patients with chylothorax had a higher rate of mortality after the neonatal period. In a multiple linear regression model, thrombosis and cardiopulmonary bypass multiplied by 10.0 and 5.1, respectively, the risk of chylothorax and have an umbilical vein catheter decreases risk. CONCLUSION: We have found a high incidence of chylothorax after neonatal cardiac surgery, which prolongs the average stay and causes significant morbidity and mortality. We suggested that chylothorax could be an underestimated complication of congenital heart disease surgery during the neonatal period. WHAT IS KNOWN: • Acquired chylothorax in the neonatal period usually appears as a complication of congenital heart disease surgery, being the incidence quite variable among the different patient series (2.5-16.8%). The appearance of chylothorax as a complication of a cardiac surgery increases both mortality and morbidity in these patients, which makes it a quality improvement target in the postsurgical management of this population. WHAT IS NEW: •Most of the published studies include pediatric patients of all ages, from newborns to teenagers, and there is a lack of studies focusing on neonatal populations. The main strength of our study is that it reports, to the best of our knowledge, one of the largest series of neonatal patients receiving surgery for congenital heart disease in the first 30 days after birth. We have found a high incidence of chylothorax after cardiac surgery during the neonatal period compared to other studies. We suggested that chylothorax could be an underestimated complication of congenital heart disease surgery during this period of life.

A Neonatal ABO non-compatible heart transplant from a circulatory-determined death donor using NRP/Cold storage.

BACKGROUND: Donation after Circulatory death is gaining worldwide acceptance. Most protocols regard their first cases to be performed with donor and recipient in the same institution. Few records of children or distant procurement have been published. METHODS: Our institution was offered a heart from a 3-day-old, 3.4-kg child, blood group A, suffering irreversible encephalopathy. Parents accepted withdrawal of life-sustaining therapy and agreed to donation. The donor hospital was located 340 km away. Concomitantly, a 2-month-old, 3.1 kg, blood group type B and with non-compaction ventricles was awaiting for the heart transplant in our unit. RESULTS: Thirty-seven minutes after withdrawal of life-sustaining therapy, the heart arrested. Five minutes afterwards, a sternotomy was performed. The supra-aortic vessels were clamped altogether. Aorta and right appendage were cannulated and connected to heart-lung machine. The innominate artery above the clamp was severed. The heart resumed spontaneous rhythm in less than 1 min. Ventilation was restored and extracorporeal circulation was maintained for 32 min. Upon cardiologic arrest, the graft was harvested as routinely. The heart was cold-stored and transported by plane to our Hospital. An orthotopic bicaval transplant was performed. Overall cold ischaemia was 245 min. Ten weeks later, the child was discharged home in good condition. CONCLUSION: Donation in circulatory death could increase the pool in neonates. Extracorporeal circulation proves successful for procurement in neonates. Distant procurement plus cold storage for donation in circulatory death is feasible. Donation in circulatory death and ABO non-compatible strategies are complementary to each other.

Technical modifications for transplant in the failing Fontan.

INTRODUCTION: Heart transplant after Fontan completion poses a unique surgical challenge. Twenty patients are presented, stressing the technical hints performed in the five anastomoses to match the graft in the recipient. METHODS: Data are collected from 20 Fontan patients between 2013 and 2019. Age (13 years), weight (37 kg.), and time interval between Fontan and transplant (7 years) are presented as median. Extracardiac conduit (size 18/20) was implanted in 15 patients, whereas atrio-pulmonary connection was performed in 4 and lateral tunnel in 1. Six patients developed protein-losing enteropathy. Seventeen stents had been previously deployed. RESULTS: The five anastomoses underwent some changes. Left atrium once, aorta 9 times, superior vena cava 7 times, pulmonary branches 15 times, and inferior vena cava 12 times. Follow-up was complete for a median of 42 months (range 6-84). Two patients died. ECMO was needed in six cases for pulmonary hypertension. Four patients had collateral vessels occluded in the cath lab, and stents were placed in superior vena cava (1) and aorta (1) post-transplant. Protein-losing enteropathy was resolved in five patients. Interestingly, one patient was on a systemic assist device before transplant (Levitronix) and right assistance (ECMO) afterwards. CONCLUSIONS: Transplant in Fontan patients is actually challenging. Hints in every of the five proposed anastomoses must be anticipated, including stents removal. Extra tissue from the donor (innominate vein, aortic arch, and pericardium) is strongly advisable. ECMO for right ventricular dysfunction was needed in nearly one-third of the cases. Overall results can match other transplant cohorts.

Late management of the aortic root after repair of tetralogy of Fallot: A European multicentre study.

OBJECTIVES: We sought to determine the indications, type, and outcomes of reoperations on the aortic root after repair of tetralogy of Fallot (TOF). METHODS: Eleven centers belonging to the European Congenital Heart Surgeons Association contributed to the data collection process. We included 36 patients who underwent surgical procedures on the aortic root, including surgery on the aortic valve and ascending aorta, between January 1975 and December 2017. Original diagnoses included TOF-pulmonary stenosis (n = 18) and TOF-pulmonary atresia (n = 18). The main indications for reoperation were aortic insufficiency (n = 19, 53%), aortic insufficiency and dilatation of the ascending aorta (n = 10, 28%), aortic root dilatation (n = 4, 11%), and ascending aorta dilatation (n = 3, 8%). RESULTS: The median age at reoperation was 30.4 years (interquartile range 20.3-45.3 years), and mechanical aortic valve replacement was the most common procedure performed. Five patients died early after reoperation (14%), and larger ascending aorta diameters were associated with early mortality (P = .04). The median age at the last follow-up was 41.4 years (interquartile range 24.5-51.6 years). Late death occurred in five patients (5/31, 16%). Most survivors (15/26, 58%) were asymptomatic at the last clinical examination (New York Heart Association, NYHA class I). The remaining patients were NYHA class II (n = 7) and III (n = 3). The most common symptoms were fatigue (n = 5), dyspnea (n = 4), and exercise intolerance (n = 3). CONCLUSIONS: Reoperations on the aortic root are infrequent but may become necessary late after TOF repair. The main indications for reoperation are aortic insufficiency, either isolated or associated with a dilatation of the ascending aorta. The surgical risk at reoperation was high and the presence of ascending aorta dilation is related to higher mortality.

"Double-barrel endocarditis".

We report a case of an 18-year-old woman who presented with infective endocarditis (IE), in two conduits percutaneously delivered in the right ventricle outflow tract ("double-barrel endocarditis"). The patient's clinical presentation, echocardiogram findings, infectious agent, clinical management, surgical approach, and follow-up assessment are described. Percutaneous pulmonary valve implantation has emerged as a viable therapy for conduit dysfunction in the right ventricular outflow tract. Although the percutaneous approach has several advantages, this strategy and the valves used are not complication-free. IE after transcatheter valve deployment has evoked the growing concern, as there is a higher incidence in these patients compared with patients with surgically repaired pulmonary valves. As a result, this type of surgical treatment is especially important.

Myocarditis, flail tricuspid valve, and normal rhythm: an exceptional form of neonatal cardiac lupus.

Neonatal cardiac lupus is a rare, passively acquired autoimmune disease. We report a case of in utero myocarditis, confirmed postnatally, with papillary muscle rupture and severe tricuspid regurgitation after birth in the absence of conduction disturbances. Tricuspid repair was successfully performed with polytetrafluoroethylene neochordae. In this article, we discuss the pathophysiology, medical and surgical management, and implications at follow-up in this unique scenario.

End-stage ischemic heart failure and Williams-Beuren syndrome: A unique scenario for pediatric heart transplantation.

WBS is a rare disorder caused by mutations in the chromosomal sub-band 7q11.23 involving the elastin gene. The clinical features (craniofacial, developmental, and cardiovascular abnormalities) are variable. The association with cardiac anomalies is a well-recognized feature, and SVAS is the most common cardiac defect found. End-stage ischemic heart disease is unusual in this setting but when it occurs, OHT remains the final therapeutic option. This decision can be difficult to determine, and it must be tailored to the individual patient based on the clinical status and concomitant cardiovascular and multisystem lesions. To date, no cases of OHT in patients with WBS have been described. We present a 14-month-old patient with WBS who developed severe LV dysfunction secondary to ischemia following a complex staged surgery for SVAS repair. He underwent successful OHT with no post-operative complications, and at three-month follow-up, he remains asymptomatic on standard immunosuppressive therapy. This case constitutes the first demonstration that OHT may be indicated for extended survival in selected children with WBS and we discuss the basic principles for extending the indication for OHT to this scenario as well as the particularities for post-transplant care.

Batista Procedure for a Coronary Anomaly in an Infant: Long-Term Follow-Up.

A partial left ventriculectomy (Batista operation) is extremely unusual in infants. Follow-up data are unknown. We report the findings at long-term follow-up in an infant after the Batista procedure, following reimplantation of an anomalous coronary artery. The initial approach and options for management are discussed, along with late cardiac remodeling. doi: 10.1111/jocs.12775 (J Card Surg 2016;31:556-558).

Orthotopic Heart Transplantation in an Adult Patient with Heterotaxy Syndrome: Surgical Implications.

Modified techniques for orthotopic heart transplantation are mandatory when complex congenital anomalies are associated in adult patients. An unusual case of a heterotaxy syndrome and dilated cardiomyopathy following mitral ring annuloplasty is presented in a 62-year-old male. Orthotopic cardiac transplantation was performed by using a modified operative strategy: selective peripheral and central venous cannulation according to the thoraco-abdominal venous challenges, biatrial technique, and preservation of venous drainage via the native coronary sinus. We discuss the anatomical features of heterotaxy in adult patients and surgical approaches when heart transplantation is needed.

Modified Fontan Conversion: An Alternative Technique for Adult Patients.

A need persists for Fontan conversion that provides alternative approaches for the individual anatomical challenges occurring in these unusual and complex adult patients. The pulmonary arteries present unique variations and the surgical technique needs to be intraoperatively addressed. We describe a technique for Fontan conversion for performing the distal anastomosis of the extracardiac conduit, allowing adequate matching to the pulmonary arteries and preserving an optimal flow into the Fontan circuit.

Surgical Management of Vascular Stents in Pediatric Cardiac Surgery: Clues for a Staged Partnership.

Complex cases undergo step surgical and percutaneous procedures, including stent deployment. Concerns arise on stent removal at latest surgery. Our initial experience is presented. Forty-six stents in 35 patients were partially or totally removed at surgery. Univentricular heart was diagnosed in 20 patients. Stents were previously deployed in: ductus (6), right ventricle outflow tract (12), atrial septal defect (4), right pulmonary artery (4), left pulmonary artery (16), inferior vena cava (2), superior vena cava (1) and ascending aorta (1). Surgical procedures performed: 9 transplants, 6 Fontan, 4 Glenn, 1 comprehensive repair (Norwood + Glenn), 1 Glenn takedown, 8 conduit replacement, 2 Fallot, 2 Rastelli, 1 ventricular septal defect closure and 1 iatrogenic aortopulmonary window. Five ductal stents were clipped. Eleven stents in right ventricle, four ones in atrial septal defect, two in right pulmonary artery, seven in the left pulmonary artery and two in inferior vena cava were completely removed. Two stents in right pulmonary artery, one in superior vena cava, one in ascending aorta and nine in the left pulmonary artery were partially retrieved. Handling the stents in ductus, right ventricle and atrial septal defect was straightforward. On the contrary, stent removal in the ductus (comprehensive case), pulmonary branches, both vena cavae or aorta required short periods of deep hypothermia with circulatory arrest. Surgery over stents is increasing in complex, step procedures. Univentricular hearts are most prevalent. Congenital transplant surgery faces new challenges. Stent removal at the time of surgery may require deep hypothermic circulatory arrest.

Azygos approach for pacemaker placement in an infant.

A pacemaker insertion through the azygos vein in a child is presented. When both the low weight of the child and mediastinitis precluded standard approaches, the azygos approach proved to be an alternative and a straightforward bailout solution.

Left axillary approach for pulmonary valve replacement.

A 14-year-old girl was scheduled for pulmonary valve replacement. A computed tomography scan showed an enlarged cardiac silhouette with an aneurysmal pulmonary artery. A less-invasive approach through the left axilla with peripheral cannulation was selected. The patient was draped in the decubitus position, with a roll under the left shoulder and the left arm over the head. The anatomical landmarks were the left nipple and the tip of the scapula. A 5-cm vertical incision in the mid-axillary line was performed, and the thorax was entered through the fourth intercostal space. Peripheral cannulation for cardiopulmonary bypass was achieved by a right groin dissection. Partial bypass was instituted and, on an unloaded heart, the ascending aorta plus the right appendage and the pulmonary artery were further cannulated. With the heart beating, the pulmonary artery was opened, and a 25-mm biological Carpentier Perimount-Magna valve was chosen. A second stitch was used to close the arteriotomy with large bites in a double row to reduce the perimeter of the trunk. Cardiopulmonary bypass was discontinued (after 64 minutes), and the cannulas were removed sequentially. Echocardiography showed a good result, with proper valve function and a reduced pulmonary artery. The patient was discharged on postoperative day 12 on antiplatelet therapy.

First-in-human therapy with Treg produced from thymic tissue (thyTreg) in a heart transplant infant.

Due to their suppressive capacity, regulatory T cells (Tregs) have attracted growing interest as an adoptive cellular therapy for the prevention of allograft rejection, but limited Treg recovery and lower quality of adult-derived Tregs could represent an obstacle to success. To address this challenge, we developed a new approach that provides large quantities of Tregs with high purity and excellent features, sourced from thymic tissue routinely removed during pediatric cardiac surgeries (thyTregs). We report on a 2-year follow-up of the first patient treated worldwide with thyTregs, included in a phase I/II clinical trial evaluating the administration of autologous thyTreg in infants undergoing heart transplantation. In addition to observing no adverse effects that could be attributed to thyTreg administration, we report that the Treg frequency in the periphery was preserved during the 2-year follow-up period. These initial results are consistent with the trial objective, which is to confirm safety of the autologous thyTreg administration and its capacity to restore the Treg pool.

Short- and long-term survival of children treated with ventricular assist devices in Spain, based on 15 years' experience.

OBJECTIVES: To describe the use of ventricular assist devices (VAD) in children in Spain and to identify variables related to survival. METHODS: This is an observational cohort study of all children younger than 18 years of age who underwent an initial implantation of a VAD at any of the 6 paediatric heart transplant centres from May 2006 to December 2020. Subjects were identified retrospectively from each hospital's database. RESULTS: Paracorporeal VADs were implanted in 118 children [pulsatile (63%), continuous (30.5%) or both types (5.9%)]. Small children (<0.7 m2 of body surface area) comprised the majority of this cohort (63.3%). Overall, 67% survived to VAD explantation, and 64.9% survived to hospital discharge. Non-central nervous system haemorrhage (39%) and stroke (38.1%) were the most common complications. Body weight <5 kg, congenital heart disease, pre-implantation bilirubin >34 µmol/l and bridge to decision strategy were associated with a higher mortality at hospital discharge and in the long-term. Interagency registry for mechanically assisted circulatory support (INTERMACS) status 1 and cardiac arrest prior to VAD implantation were related to long-term mortality, whereas pre-implantation renal replacement therapy and extracorporeal membrane oxygenation were not related to mortality. CONCLUSIONS: In Spain, 67% of the VAD-supported children have been bridged to heart transplantation or to recovery. Body weight lower than 5 kg, congenital heart disease diagnosis, cholestatic liver dysfunction, bridge to decision as VAD strategy, INTERMACS-1 status and cardiac arrest were pre-implantation variables related to mortality, whereas pre-implantation renal replacement therapy and extracorporeal membrane oxygenation were not.

Transaortic Fallot repair in a grown-up patient: advantages in a situs inversus setting.

We present the case studies of two adult patients with tetralogy of Fallot who were scheduled for surgery. After addressing the right ventricular outflow tract obstruction, the aorta was opened and the ventricular septal defect was approached in a straightforward manner as it was located just under the overriding aortic valve. The second patient presented with was a situs inversus, dextroapex Fallot. In this setting, the aortic approach simplified the repair expeditiously. After 2 years, both patients are in New York Heart Association class I, with no residual ventricular septal defect, no aortic regurgitation, and complete relief of right ventricular outflow tract obstruction.

Intrapericardial pacemaker in a 2-kilogram newborn.

A 2-kilogram child had a pacemaker implanted by a subxyphoid approach with the generator located under the rectus sheath. Days later, the battery eroded the abdominal wall and the peritoneum. The whole system was removed and a new one was implanted inside the pericardium on an emergent basis.

A Novel GMP Protocol to Produce High-Quality Treg Cells From the Pediatric Thymic Tissue to Be Employed as Cellular Therapy.

Due to their suppressive capacity, the adoptive transfer of regulatory T cells (Treg) has acquired a growing interest in controlling exacerbated inflammatory responses. Limited Treg recovery and reduced quality remain the main obstacles in most current protocols where differentiated Treg are obtained from adult peripheral blood. An alternate Treg source is umbilical cord blood, a promising source of Treg cells due to the higher frequency of naïve Treg and lower frequency of memory T cells present in the fetus' blood. However, the Treg number isolated from cord blood remains limiting. Human thymuses routinely discarded during pediatric cardiac surgeries to access the retrosternal operative field has been recently proposed as a novel source of Treg for cellular therapy. This strategy overcomes the main limitations of current Treg sources, allowing the obtention of very high numbers of undifferentiated Treg. We have developed a novel good manufacturing practice (GMP) protocol to obtain large Treg amounts, with very high purity and suppressive capacity, from the pediatric thymus (named hereafter thyTreg). The total amount of thyTreg obtained at the end of the procedure, after a short-term culture of 7 days, reach an average of 1,757 x106 (range 50 x 106 - 13,649 x 106) cells from a single thymus. The thyTreg product obtained with our protocol shows very high viability (mean 93.25%; range 83.35% - 97.97%), very high purity (mean 92.89%; range 70.10% - 98.41% of CD25+FOXP3+ cells), stability under proinflammatory conditions and a very high suppressive capacity (inhibiting in more than 75% the proliferation of activated CD4+ and CD8+ T cells in vitro at a thyTreg:responder cells ratio of 1:1). Our thyTreg product has been approved by the Spanish Drug Agency (AEMPS) to be administered as cell therapy. We are recruiting patients in the first-in-human phase I/II clinical trial worldwide that evaluates the safety, feasibility, and efficacy of autologous thyTreg administration in children undergoing heart transplantation (NCT04924491). The high quality and amount of thyTreg and the differential features of the final product obtained with our protocol allow preparing hundreds of doses from a single thymus with improved therapeutic properties, which can be cryopreserved and could open the possibility of an "off-the-shelf" allogeneic use in another individual.

Basiliximab impairs regulatory T cell (TREG) function and could affect the short-term graft acceptance in children with heart transplantation.

CD25, the alpha chain of the IL-2 receptor, is expressed on activated effector T cells that mediate immune graft damage. Induction immunosuppression is commonly used in solid organ transplantation and can include antibodies blocking CD25. However, regulatory T cells (Tregs) also rely on CD25 for their proliferation, survival, and regulatory function. Therefore, CD25-blockade may compromise Treg protective role against rejection. We analysed in vitro the effect of basiliximab (BXM) on the viability, phenotype, proliferation and cytokine production of Treg cells. We also evaluated in vivo the effect of BXM on Treg in thymectomized heart transplant children receiving BXM in comparison to patients not receiving induction therapy. Our results show that BXM reduces Treg counts and function in vitro by affecting their proliferation, Foxp3 expression, and IL-10 secretion capacity. In pediatric heart-transplant patients, we observed decreased Treg counts and a diminished Treg/Teff ratio in BXM-treated patients up to 6-month after treatment, recovering baseline values at the end of the 12-month follow up period. These results reveal that the use of BXM could produce detrimental effects on Tregs, and support the evidence suggesting that BXM induction could impair the protective role of Tregs in the period of highest incidence of acute graft rejection.