Intracorporeal LVAD implantation in pediatric patients: A single-center 10 years' experience.

BACKGROUND: Mechanical cardiac support is currently an effective strategy to reduce morbidity and mortality in pediatric patients. However, solid evidence regarding the feasibility of intracorporeal devices in children still needs to be provided. We report our 10-year experience with intracorporeal left ventricular assist devices (LVAD) in children. MATERIALS AND METHODS: We included all patients undergoing intracorporeal, continuous-flow LVAD implantation between 2012 and 2022. Baseline and postoperative data were collected from the institutional database. RESULTS: Seven HeartWare and 4 HeartMate3 were implanted in 11 patients (median age 13.9 years, median body surface area - BSA - 1.42 m2, IQR 1.06-1.68). The most frequent indication to LVAD implant was dilated cardiomyopathy (72.7%). All candidates underwent a thorough preoperative advanced imaging. Three-dimensional reconstructions and implant fit simulation were performed when BSA was <1.2 m2, weight <30 kg, or internal transverse thoracic diameter <20 cm. There was no operative death. The most common postoperative complication was surgical re-exploration due to bleeding (27.3%). One patient died of severe neurological complications after about 3 months of hospitalization. No late deaths or unplanned re-hospitalizations occurred in the remaining 10, 6 of whom were discharged home. There were no major complications at the follow-up. All survivors underwent successful heart transplantation. CONCLUSIONS: Intracorporeal LVAD implantation proved to be a potentially feasible and safe option in young teenagers and children whose BSA was >1.0 m2. In borderline cases, the 3D reconstruction with implant fit simulation can effectively help to identify those patients who can safely undergo intrathoracic LVAD implantation.

Tricuspid Valve Repair Can Restore the Prognosis of Patients with Hypoplastic Left Heart Syndrome and Tricuspid Valve Regurgitation: A Meta-analysis.

To date, evidence supporting the efficacy of tricuspid valve (TV) repair in interrupting the progression of systemic right ventricular (RV) adverse remodeling in hypoplastic left heart syndrome (HLHS) is conflicting. We conducted a systematic review and meta-analysis of scientific literature to assess the impact of TV repair in effectively modifying the prognosis of patients with HLHS. We conducted a systematic review of PubMed, Web of Science, and Scopus databases. A random-effect meta-analysis was performed and transplant-free survival, freedom from TV regurgitation, and TV reoperation data were reconstructed using the published Kaplan-Meier curves. Nine studies were included, comprising 203 HLHS patients undergoing TV repair and 323 HLHS controls. The estimated transplant-free survival at 1, 5, and 10 years of follow-up was 75.5% [95% confidence interval (CI) = 67.6-84.3%], 63.6% [95% CI = 54.6-73.9%], and 61.9% [95% CI = 52.7-72.6%], respectively. Transplant-free survival was comparable to HLHS peers without TV regurgitation (p = 0.59). Five-year freedom from recurrence of TV regurgitation and freedom from TV reoperation was 57% [95% CI = 46.7-69.7%] and 63.6% [95% CI = 54.5-74.3%], respectively. Younger age and TV repair at the time of Norwood operation increased the risk of TV regurgitation recurrence and the need for TV reoperation. Our meta-analysis supports the efficacy of TV repair in favorably modifying the prognosis of patients with HLHS and TV regurgitation, reestablishing a medium-term transplant-free survival which is comparable to HLHS peers. However, durability of surgery and long-term fate of TV and RV performance are still unclear.

Decellularized cryopreserved human pericardium: a validation study towards tissue bank practice.

Pericardial patches are currently used as reconstructive material in cardiac surgery for surgical treatment of cardiac septal defects. Autologous pericardial patches, either treated with glutaraldehyde or not, can be used as an alternative to synthetic materials or xenograft in congenital septal defects repair. The availability of an allogenic decellularized pericardium could reduce complication during and after surgery and could be a valid alternative. Decellularization of allogenic tissues aims at reducing the immunogenic reaction that might trigger inflammation and tissue calcification over time. The ideal graft for congenital heart disease repair should be biocompatible, mechanically resistant, non-immunogenic, and should have the ability to growth with the patients. The aim of the present study is the evaluation of the efficacy of a new decellularization protocol of homologous pericardium, even after cryopreservation. The technique has proven to be suitable as a tissue bank procedure and highly successful in the removal of cells and nucleic acids content, but also in the preservation of collagen and biomechanical properties of the human pericardium.

Effectiveness of Repair of Aortic Coarctation in Neonates: A Long-Term experience.

To evaluate early and long-term results of surgical treatment of aortic coarctation (CoAo) in neonates. This is a retrospective clinical review of neonates with CoAo, who underwent surgery between 1995 and 2019. Data were retrieved from our institutional database, to identify preoperative and postoperative characteristics. Statistical analysis was performed by means of relative risk ratio and Cox and logistic multivariate analysis. 218 consecutive neonates (M/F: 129/89, median age 11 days, IQR 7-17 days) were included; 202 (92.7%) had a left thoracotomy; 178 underwent extended end-to-end anastomosis (EEEA, 81.6%). Hypoplastic aortic arch (HAA) was present in 102 patients (46.8%); complex cardiac anomalies in 85 (39%). Significant postoperative complications occurred in 20 (9.2%). Thirty-day mortality was 2.3% (most in complex types). At a median follow-up of 10.4 years (IQR 5.6-15.0 years; FU completeness 95.9%), there were 8 late deaths (3.7%), all associated to complex CoAo. Among 196 survivors, 177 (93.2%) were in NYHA class I; re-interventions on aortic arch occurred in 9.2% (2.0% were surgical). Freedom from mortality and re-intervention on aorta at 10 years were 94.3% and 96.7%, respectively. Surgical repair of CoAo in newborns without CPB in our series was safe and low-risk, with excellent early and late outcomes.

Surgical strategies for the management of end-stage heart failure in infants and children: A 15-year experience with a patient-tailored approach.

End-stage heart failure (ESHF) in pediatric age is an ongoing challenge. Heart transplantation is the final option, but its long-term outcomes are still suboptimal in children. An alternative patient-tailored surgical protocol to manage ESHF in children is described. Retrospective, single-center analysis of pediatric patients admitted to our institution between April 2004 and February 2021 for ESHF. Our current protocol is as follows: (a) Patients <1 year with isolated left ventricular dysfunction due to dilated cardiomyopathy underwent pulmonary artery banding (PAB). (b) Patients <10 years and <20 kg, who did not meet previous criteria were managed with Berlin Heart EXCOR. (c) Patients >10 years or >20 kg, underwent placement of intracorporeal Heartware. Primary outcomes were survival, transplant incidence, and postoperative adverse events. A total of 24 patients (mean age 5.3 ± 5.9 years) underwent 26 procedures: PAB in 6 patients, Berlin Heart in 11, and Heartware in 7. Two patients shifted from PAB to Berlin Heart. Overall survival at 1-year follow-up and 5-year follow-up was 78.7% (95%CI = 62%-95.4%) and 74.1% (95%CI = 56.1%-92.1%), respectively. Berlin Heart was adopted in higher-risk settings showing inferior outcomes, whereas a PAB enabled 67% of patients to avoid transplantation, with no mortality. An integrated, patient-tailored surgical strategy, comprehensive of PAB and different types of ventricular assist devices, can provide satisfactory medium-term results for bridging to transplant or recovery. The early postoperative period is critical and requires strict clinical vigilance. Selected infants can benefit from PAB that has demonstrated to be a safe bridge to recovery.

End-of-life care for children with complex congenital heart disease: Parents' and medical care givers' perceptions.

AIM: In complex congenital heart diseases (CHD), patients may remain affected by significant morbidity and mortality after surgery. We analysed the end-of-life (EoL) care in children with severe CHD who died in our institution and investigated perspectives of parents and health-care professionals (HCPs). METHODS: Medical records of all children (age < 18 years old) affected by a severe CHD who died in a tertiary cardiac care centre were reviewed. Subsequently, a cross-sectional questionnaire-based study of parents and HCPs of children involved in the study was designed. RESULTS: In total, 30 children died (median age: 45 days; range: 15 days to 3.4 years). Of them, 97% (31/32) died in an intensive care unit setting and were intubated and sedated at EoL. A total of 77% (23/30) died without parents being present at bedside. Eighteen families and 10 HCPs were interviewed. For 61% of the parents (11/18) and 70% of the clinicians (7/10), the goal of therapy at the EoL was 'to lessen your child's suffering as much as possible'. Overall, 44% of parents (8/18) and 50% of HCPs recognised that their child had no chance of survival 'a few days before the child died'. CONCLUSIONS: We believe that these data suggest an unconscious reluctance to change goals of care in EoL, shifting from intensive care to comfort and quality of life.

Vacuum-Assisted Closure Therapy for the Treatment of Poststernotomy Wound Dehiscence in Neonates and Infants.

We sought to analyze effectiveness and results of a vacuum-assisted closure system for the treatment of sternal wound dehiscence in newborns and children after cardiac surgery in our institution. Six patients with poststernotomy wound problems (large defects of epithelialization or mediastinitis) were treated with a vacuum-assisted closure (VAC) therapy. Median age was 5 months (range: 1-144); VAC therapy was started with negative pressure -75 mm Hg, continuously. All children achieved healing of the sternal wound and a subsequent closure after a median length of treatment of 8.3 days (range: 4-14). In conclusion, VAC therapy with high negative pressure is safe, effective, and is a well-tolerated therapy in pediatric patients with either early- or late poststernotomy wound dehiscence.

Arterial switch operation for transposition of the great arteries: A single-centre 32-year experience.

OBJECTIVE: Arterial switch operation (ASO) is nowadays the standard of care for neonates with D-transposition of the great arteries (D-TGA). We evaluated our early and late results with ASO for D-TGA. MATERIALS AND METHODS: We collected data on 267 patients with D-TGA, either with intact ventricular septum (D-TGA/IVS; n = 182, 68%) and with other associated congenital heart malformations (complex D-TGA; n = 85, 32%) that underwent ASO between January 1987 and July 2018. RESULTS: Median age at ASO was 8 days (interquartile range [IQR], 6-12 days). Fifteen patients (5.6%) died in hospital (6/182 with D-TGA/IVS, 3.3% and 9/85 with complex D-TGA, 11%; P = 0.02). Median follow-up time was 10.2 years (IQR, 3.7-18 years). There were 2 (0.8%) late sudden deaths. Overall survival at 10 and 20 years was 94% and 93%, respectively. Thirty-five patients (14%) required either reoperations or reinterventions, mainly for right ventricular outflow tract obstruction (n = 28, 11%). Freedom from reoperation/reintervention at 10 and 20 years was 87% and 78%, respectively. All patients were in NYHA I at latest clinical examination. Six over 173 patients (3.4%) who underwent a postoperative evaluation of their coronaries presented acquired anomalies. Forty-four patients (17%) who performed a cardiopulmonary exercise testing (CPET) have a predicted VO 2 comparable to normal peers. CONCLUSIONS: The results of ASO for D-TGA are excellent, with a fairly low mortality and reoperation/reintervention rate. Functional capacity evaluated with CPET is comparable to normal peers. Continuous follow-up for detecting asymptomatic acquired coronary artery disease is mandatory. A reassessment of competitive sport eligibility criteria for specific D-TGA patients should be considered.

Surgical repair of aortic coarctation in pediatric age: A single center two decades experience.

BACKGROUND: To evaluate early and long-term results of surgical treatment of aortic coarctation (CoAo) in infants and children. METHODS: A retrospective clinical review of patients less than 18 years with CoAo, undergoing surgery between 1995 and 2015. Data were retrieved from our institutional database, to identify preoperative and postoperative characteristics. Statistical analysis was performed by bivariate, Cox's, and logistic regression analysis. RESULTS: Three hundred forty-one consecutive patients (male/female: 192/149; the median age at surgery of 25 days; interquartile range [IQR], 10-143 days) were included; 187 patients were less than 1 month (54.9%); 276 underwent extended end-to-end anastomosis (EEEA) (80.9%). Hypoplastic aortic arch (HAA) occurred in 34.6% and bicuspid aortic valve in 21.1%. The isolated type was present in 249 (73.0%). Significant postoperative complications occurred in 5.6%. Thirty-day mortality was 1.4%. At a median follow-up of 10.2 years (IQR, 6-15 years; FU completeness, 91.2%), there were eight late deaths (2.6%), most in the complex type. Among 298 survivors, 284 (95.3%) were in NYHA class I; 10 (3.0%) were on antihypertensive treatment. Reinterventions on aortic arch occurred only in 4.5%, being HAA a significant risk factor for reoperation ( P = 0.00173). Freedom from mortality and reintervention on aorta at 21 years were 93.5% and 93.6%, respectively. CONCLUSIONS: Surgical repair of CoAo by EEEA without CPBP is a safe and low-risk procedure, concerning either early or late outcomes, despite the presence of HAA and neonatal age can influence recoarctation. Most patients are clinically well in the long-term, and only a few require antihypertensive therapy.

Repair Techniques for Mitral Valve Insufficiency in Children.

Congenital mitral valve (MV) dysplasia is a relatively rare and highly complex cardiac disease. We sought to provide a comprehensive analysis of the current surgical techniques for treating mitral valve insufficiency and the results of mitral valve repair at our institution. Between 1972 and 2017, 104 consecutive patients underwent surgical repair of congenital MV dysplasia-insufficiency at our institution. Among these, 59 patients presented with MV insufficiency (or prevalent MV insufficiency) and were part of the study. There was 1 early (1.7%) and 1 late death (1.7%). Survival at 5, 10 and 20 years was 98%, 98% and 94%, respectively. Eight patients (14%) required MV replacement for residual significant MV insufficiency. Freedom from re-intervention for MV dysfunction at 5, 10 and 20 years were 89%, 84% and 79%, respectively. Surgical techniques for treating mitral valve insufficiency must be tailored for each patient with the main goal of achieving a proper valve function, rather than a "normal" anatomy. The mechanism underlying valve dysfunction in congenital mitral valve insufficiency is multifactorial and requires the application of a variety of surgical techniques in each case.

Long-term outcomes following transatrial versus transventricular repair on right ventricular function in tetralogy of Fallot.

BACKGROUND AND AIM OF THE STUDY: Outcomes after repair of tetralogy of Fallot (TOF) are good with either a transventricular (TV) or transatrial (TA) approach. We sought to determine if there is a relationship between the TV or TA approach and right ventricular (RV) function, and the role of residual pulmonary regurgitation (PR) on the long-term outcomes. METHODS: This was a retrospective cohort multicentric study on survivors after surgical repair of TOF (TA versus TV approach, ±transannular patch) between 1990 and 2004. All patients underwent magnetic resonance imaging to assess RV volume, function, and PR. Patients were matched for length of follow-up and age. Clinical adverse events were retrieved from institutional databases. RESULTS: Seventy-nine patients (TA/TV = 37/42, median age 0.3 and 1.0 yrs, respectively) were included. At a median follow-up of 16.6 years (12.5-20.3), there were no differences in freedom from reintervention (either catheter or surgical), RV volumes, function, and PR between the TA and TV groups. Pulmonary valve (PV) replacement was significantly less frequent in the TA subgroup (P = 0.033) and patients with a preserved PV showed significantly lower RV volumes and less adverse events at follow-up. CONCLUSIONS: There is no significant difference in RV volumes and function between the TA and TV. However, the TA approach seems to be protective against PV replacement in the long-term. When PV is not preserved at repair, residual pulmonary regurgitation is a significant cause of late RV dysfunction and dilation, and is associated with a higher rate of late adverse events.

Combined Surgical and Interventional Approaches for Treating Patients with Congenital Heart Disease.

AIMS: During the last decade the cooperation between surgeons and cardiologists has further expanded by combining surgical and interventional techniques (CCBSI) performed in the operating room, without the use of fluoroscopy. We sought to evaluate the results of our experience with CCBSI. METHODS: All children with congenital heart disease (CHD) who underwent a CCBSI in the operating room between June 2007 and January 2014 were enrolled. RESULTS: Sixty-eight patients were included. Median age at CCBSI was five months (range 1-48 months). The three main diagnoses leading to surgery included: (1) tetralogy of Fallot (TOF) (n = 40), (2) muscular ventricular septal defects (VSD) (n = 12), (3) single ventricle with pulmonary artery branch stenosis (n = 4). There were 72 catheter-based procedures associated with surgical maneuvres, including: (1) transatrial balloon dilation (BD) of the pulmonary valve (n = 45), (2) transinfundibular BD of the main pulmonary artery trunk (n = 12), (3) perventricular VSD closure with septal occluder (n = 8), (4) BD of pulmonary artery branches (n = 5), and other less common procedures (n = 2). There were no procedure-related complications and no hospital deaths. Median follow-up time was four years (range 0.95-7.9 years). There was one late death for respiratory distress after transapical balloon dilation of the aortic valve. One patient required BD and stenting of the left pulmonary artery branch 3.6 years after intraoperative BD for residual stenosis. CONCLUSIONS: The CCBSI represents a safe and effective treatment for selected patients with complex CHD. It will be helpful in minimizing patients' surgical trauma and in shortening or avoiding the use of cardiopulmonary bypass.

HeartWare ventricular assist device as bridge to transplant in children and adolescents.

Limited options do exist for mechanical circulatory support as a bridge to transplantation in the pediatric population. This is especially true when it comes to intracorporeal technologies. We describe our successful experience with the use of HeartWare ventricular assist devices (HeartWare, Inc., Framingham, MA, USA) in three patients <16 years of age, as a successful and feasible bridge to transplant in patients weighing greater than 20 kg.

Surgical outcomes of total anomalous pulmonary venous connection repair: a 22-year experience.

BACKGROUND: Total anomalous pulmonary venous connection (TAPVC) is a rare congenital heart disease (CHD), whose surgical repair is associated with high mortality and reoperation rates. We sought to identify predictors of early and late outcomes. METHODS: Data from medical records of patients who underwent surgical repair for TAPVC from 1989 to 2012 were included. The patients were divided in two groups, according to absence or presence of associated major CHDs. RESULTS: Forty-six patients were included (M/F: 26/20, median age 26 days, interquartile range 15 to 59, median weight 3.350 kg, interquartile range 1800 to 4470). Anatomic types of TAPVC were: supracardiac in 48%, intracardiac in 20%, infracardiac in 20%, and mixed in 12%; TAPVC was obstructive in 33%; TAPVC was isolated in 63%, complex in 37%. Single ventricle physiology was present in 11 patients, heterotaxy in eight patients. Overall operative mortality was 19.6% (9/46): 6.9% in isolated TAPVC, 41.2% in complex type (p-value: 0.002). It was associated with low weight at intervention (<3 kg, p = 0.027), single ventricle physiology (p = 0.047), and aortic cross-clamp time >60 minutes (p = 0.097). At a median follow-up of 2.97 years (range 43 days to 22 years, 91% complete), there were nine late deaths (24.3%); 15 patients (40.5%) had major events (including late death). Multivariate analysis of event-free survival showed worse outcome in the complex group (p = 0.001). CONCLUSION: Surgical mortality and morbidity remain consistent in patients with TAPVC and associated major CHD, while the isolated type shows excellent outcomes. Pulmonary vein obstruction is a rare but highly lethal complication. doi: 10.1111/jocs.12399 (J Card Surg 2014;29:678-685).

Medical and surgical management of primary cardiac tumours in infants and children.

Primary cardiac tumours in infants and children are extremely rare, with an estimated incidence of 0.2% according to echocardiographic studies. Owing to their rarity, there is very little literature available, and most knowledge is based on collections of case reports. Therefore, we reviewed retrospectively our 27 years of clinical experience on the overall management of cardiac tumours among children in order to improve not only our knowledge but also to provide others with information about the incidence, clinical presentation, management, and long-term outcome of this rare disease. Between April, 1982 and April, 2009, 52 children were diagnosed with cardiac tumours at our Institution. Medical records and follow-up echocardiographic evaluations were studied. The diagnosis was prenatal in 35% of the patients. The most frequent tumour types were rhabdomyomas (61.5%), fibromas (15.4%), and myxomas (5.8%). There were no cases of primary malignant tumours. All diagnoses were achieved using two-dimensional echocardiography, and for 12 patients a pathological analysis was carried out. A total of 41 patients (79%) were managed medically, whereas 11 (21%) patients underwent surgical treatment. At a mean follow-up of 7.2 ± 5.4 years, two patients died of complications related to cardiac transplantation; all the remaining patients are in excellent clinical condition. In conclusion, cardiac tumours in paediatric practice are usually clinically and histologically benign. Only a few cases need surgery. Up to one-third of the cardiac masses are detectable prenatally. Rhabdomyoma is the most common histotype, followed by fibroma and myxoma. The long-term prognosis is generally good.

Successful Implantation of HeartMate3 in a Small Child After Multimodality Imaging Pathway to Assess Feasibility.

The current use of intracorporeal left ventricular assist devices in children is still limited by small body dimensions. Many children weighing of less than 30 kg requiring durable mechanical circulatory support are implanted with the Berlin Heart EXCOR, a paracorporeal device. We present the case of a girl aged 10 years with a body surface area of 1.01 m 2 undergoing a safe and effective HeartMate3 implantation despite extremely small thoracic dimensions. Using computed tomography-derived three-dimensional (3D) reconstruction, it was possible to simulate several device positions finding the best HeartMate3 lodging. Simulation-guided pump placement was then obtained in the operating room. Normal HeartMate3 functioning was registered until heart transplant. Our experience shows that preoperative planning and virtual fitting simulation can be effective to assess safety of HeartMate3 implantation even in small children. The 3D reconstruction and simulation may help to increase the pool of children candidates for this device, even though a larger experience is needed to assess the risk profile of the HeartMate3 in such small patients.

Surgery for primary cardiac tumors in children: early and late results in a multicenter European Congenital Heart Surgeons Association study.

BACKGROUND: To evaluate indications and results of surgery for primary cardiac tumors in children. METHODS AND RESULTS: Eighty-nine patients aged ≤18 years undergoing surgery for cardiac tumor between 1990 and 2005 from 16 centers were included retrospectively (M/F=41/48; median age 4.3 months, range 1 day to 18 years). Sixty-three patients (68.5%) presented with symptoms. Surgery consisted of complete resection in 62 (69.7%) patients, partial resection in 21 (23.6%), and cardiac transplant in 4 (4.5%). Most frequent histotypes (93.2%) were benign (rhabdomyoma, myxoma, teratoma, fibroma, and hemangioma). Postoperative complications occurred in 29.9%. Early and late mortality were 4.5% each (mean follow-up, 6.3±4.4 years); major adverse events occurred in 28.2% of the patients; 90.7% of patients are in New York Heart Association class I. There were no statistically significant differences in survival, postoperative complications, or adverse events after complete and partial resection in benign tumors other than myxomas. Cardiac transplant was associated significantly with higher mortality rate (P=0.006). Overall mortality was associated to malignancy (P=0.0008), and adverse events during follow-up (P=0.005). CONCLUSIONS: Surgery for primary cardiac tumors in children has good early and long-term outcomes, with low recurrence rate. Rhabdomyomas are the most frequent surgical histotypes. Malignant tumors negatively affect early and late survival. Heart transplant is indicated when conservative surgery is not feasible. Lack of recurrence after partial resection of benign cardiac tumors indicates that a less risky tumor debulking is effective for a subset of histotypes such as rhabdomyomas and fibromas.

Pulmonary valve-sparing technique in patient with tetralogy of Fallot and anomalous coronary artery crossing the infundibulum.

A 15-month-old girl who presented at birth with tetralogy of Fallot and was followed after an echocardiographic diagnosis of an anomalous origin of the right coronary artery from the left anterior descending coronary artery, crossing the right ventricular infundibulum very close to the pulmonary valve annulus, was scheduled for repair. At surgery, after routine trans-atrial/trans-pulmonary repair, the pulmonary valve (PV) was balloon-dilated through the right ventricular outflow tract (RVOT) up to a 'normal size' PV annulus, based on the patient's body surface area. Two-dimensional echocardiography at discharge revealed an adequate relief of the RVOT obstruction, with a normal-sized PV annulus and a competent PV. In this subset of patients, this technique can be considered an additional surgical strategy to avoid the use of conduits.

Pulmonary artery branch stenosis in patients with congenital heart disease.

OBJECTIVE: We sought to evaluate our recent experience with surgical treatment of branch pulmonary artery (PA) stenosis both for native and acquired lesions. MATERIALS AND METHODS: The postoperative course of patients who underwent surgical PA plasty augmentation between January 2004 and January 2012 were reviewed. Primary outcomes included the need for further surgical procedures or interventional maneuvers on the branch PAs for residual stenosis. RESULTS: Thirty-four patients were included. Median age at PA plasty was eight months (range 8 days to 3.4 years). There were 12 native and 22 acquired PA stenoses, which were mainly located at the PA branch origin (n = 25, 73%). The PA plasty was defined as simple (n = 16, 47%) and as complex (n = 18, 53%), which included multiple maneuvers on the PA branches. Median follow-up time after surgical treatment was 4.7 years (range 0.9 to 8.7 years). One patient died 3 days after complex PA plasty for low output syndrome and another died 22 months later for congestive heart failure. Twenty-one (63.6%) underwent 40 catheter intervention procedures on the PA branches for residual stenosis. The majority of them (n = 10, 57.1%) were operated before the age of six months and the majority had an acquired PA stenosis (14, 66.7%). Three patients underwent additional surgical maneuvers on the PA branches. CONCLUSIONS: PA branch stenosis represents a life-threatening condition often necessitating further surgical or interventional treatment. A combined collaborative surgical followed by transcatheter approach is important, particularly in cases with an acquired PA stenosis who require complex surgical repair.

Correlations between the alpha-Gal antigen, antibody response and calcification of cardiac valve bioprostheses: experimental evidence obtained using an alpha-Gal knockout mouse animal model.

Introduction: Preformed antibodies against αGal in the human and the presence of αGal antigens on the tissue constituting the commercial bioprosthetic heart valves (BHVs, mainly bovine or porcine pericardium), lead to opsonization of the implanted BHV, leading to deterioration and calcification. Murine subcutaneous implantation of BHVs leaflets has been widely used for testing the efficacy of anti-calcification treatments. Unfortunately, commercial BHVs leaflets implanted into a murine model will not be able to elicit an αGal immune response because such antigen is expressed in the recipient and therefore immunologically tolerated. Methods: This study evaluates the calcium deposition on commercial BHV using a new humanized murine αGal knockout (KO) animal model. Furtherly, the anti-calcification efficacy of a polyphenol-based treatment was deeply investigated. By using CRISPR/Cas9 approach an αGal KO mouse was created and adopted for the evaluation of the calcific propensity of original and polyphenols treated BHV by subcutaneous implantation. The calcium quantification was carried out by plasma analysis; the immune response evaluation was performed by histology and immunological assays. Anti-αGal antibodies level in KO mice increases at least double after 2 months of implantation of original commercial BHV compared to WT mice, conversely, the polyphenols-based treatment seems to effectively mask the antigen to the KO mice's immune system. Results: Commercial leaflets explanted after 1 month from KO mice showed a four-time increased calcium deposition than what was observed on that explanted from WT. Polyphenol treatment prevents calcium deposition by over 99% in both KO and WT animals. The implantation of commercial BHV leaflets significantly stimulates the KO mouse immune system resulting in massive production of anti-Gal antibodies and the exacerbation of the αGal-related calcific effect if compared with the WT mouse. Discussion: The polyphenol-based treatment applied in this investigation showed an unexpected ability to inhibit the recognition of BHV xenoantigens by circulating antibodies almost completely preventing calcific depositions compared to the untreated counterpart.