Bicuspidisation of unicuspid stenotic pulmonary valve in a nine-year-old male.

We report the case of a 9-year-old male with severe congenital pulmonary valve stenosis referred to our centre for percutaneous valvotomy. On admission, trans-thoracic echocardiogram confirmed a unicuspid pulmonary valve with a peak/mean pulmonary valve gradient of 91/53 mmHg and a pulmonary annulus of 13.8 mm (-0.8 Z Score). It also showed an enlarged RV (RV/LV ratio 0,9). During cardiac catheterisation, an additional atrial septal defect (secundum) with significant left to right shunt (Qp/Qs > 2) was diagnosed, which was not amenable to percutaneous closure. The patient was referred for surgical repair.The atrial septal defect was closed by a direct running suture. The repair of the unicuspid valve consisted in bicuspidisation by a large commissurotomy to the left anterior wall of the pulmonary artery. The neo-commissure was created with two separate patches of autologous pericardium secured to the wall of the pulmonary root. The adjustment of the effective height of the pulmonary valve leaflets was done by trimming the patches and a triangular plication of the newly created posterior leaflet. Perioperative echocardiogram showed a peak gradient of 15 mm Hg and trivial pulmonary regurgitation. The total cross-clamp time was 92 min and the bypass time 123 min with a favourable evolution after the surgery.The particularity of the case is represented by the complexity of the bicuspidisation procedure. Using this technique, a tailored approach is needed for every patient.

Autologous vascularised pericardial flap tunneling technique in Scimitar syndrome repair with dextrocardia: lessons from the Senning procedure.

Scimitar syndrome is a rare variant (5%) of partial abnormal pulmonary venous return. Surgery is required when pulmonary overcirculation is present. Following repair, Scimitar vein stenosis occurs in approximately 20%. We applied a variant of the atrial switch technique using autologous pericardial flap in a patient with Scimitar syndrome and dextrocardia. This tunneling technique allowed tension-free anastomosis and minimal Scimitar vein rotation.

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.

Hypothermic continuous machine perfusion improves metabolic preservation and functional recovery in heart grafts.

The number of heart transplants is decreasing due to organ shortage, yet the donor pool could be enlarged by improving graft preservation. Hypothermic machine perfusion (MP) has been shown to improve kidney, liver, or lung graft preservation. Sixteen pig hearts were recovered following cardioplegia and randomized to two different groups of 4-hour preservation using either static cold storage (CS) or MP (Modified LifePort© System, Organ Recovery Systems, Itasca, Il). The grafts then underwent reperfusion on a Langendorff for 60 min. Energetic metabolism was quantified at baseline, postpreservation, and postreperfusion by measuring lactate and high-energy phosphates. The contractility index (CI) was assessed both in vivo prior to cardioplegia and during reperfusion. Following reperfusion, the hearts preserved using CS exhibited higher lactate levels (56.63 ± 23.57 vs. 11.25 ± 3.92 µmol/g; P < 0.001), increased adenosine monophosphate/adenosine triphosphate (AMP/ATP) ratio (0.4 ± 0.23 vs. 0.04 ± 0.04; P < 0.001), and lower phosphocreatine/creatine (PCr/Cr) ratio (33.5 ± 12.6 vs. 55.3 ± 5.8; P <0.001). Coronary flow was similar in both groups during reperfusion (107 ± 9 vs. 125 + /-9 ml/100 g/min heart; P = ns). CI decreased in the CS group, yet being well-preserved in the MP group. Compared with CS, MP resulted in improved preservation of the energy state and more successful functional recovery of heart graft.

Long-term outcome and anaesthetic management for non-cardiac surgery after Fontan palliation: a single-centre retrospective analysis.

OBJECTIVES: The improved management of Fontan patients has resulted in good outcome. As such, these patients may necessitate care for non-cardiac surgery. We sought to determine the long-term outcome of our Fontan series palliated with the most recent surgical techniques. Our second objective was to report the incidence and the perioperative course after non-cardiac procedures. We reviewed the records of all patients with either a lateral tunnel or an extracardiac conduit Fontan between 1996 and 2008. Follow-up was recorded until June, 2013, including records regarding non-cardiac interventions. RESULTS: Overall, 58 patients were included. Of them, one patient underwent a takedown of his Fontan, and five patients died in the immediate postoperative course. The cumulative survival of the remaining 52 patients was 81%. There was no significant difference in survival between right and left ventricle morphologies (p=0.56), nor between both types of Fontan (p=0.9). Chronic arrhythmias (25%), fatigue/dyspnoea (40%), thrombotic complications (19%), and embolic events (10%) were among the most recurrent comorbidities. In total, 45 non-cardiac interventions were performed on 26 patients, with three bleeding complications and one death. CONCLUSIONS: This study shows excellent long-term survival after both lateral tunnel and extracardiac conduit Fontan. The incidence of cardiovascular morbidity remains high, however. We also report a high number of non-cardiac interventions. Thorough understanding of the Fontan physiology is mandatory when non-cardiac anaesthesiologists are in charge of these patients.

Pediatric vascular ring outcomes for surgically repaired vs. unoperated children: a single-center experience.

Background: Vascular rings represent 1% of congenital cardiovascular abnormalities. Phenotypic expression varies from asymptomatic to severe forms related to either oesophageal or tracheal compression. While refinement in prenatal screening led to an increase in fetal diagnosis, optimal management in asymptomatic neonates and infants is currently a matter of debate. We report our center experience of vascular ring management over three decades. Methods: In this single-center retrospective study, data were extracted from patient medical records. To obtain information on symptoms/medication at follow-up, clinical records from pediatric clinics were reviewed. For patients followed in other institutions, a web-based questionnaire was sent to referring pediatricians. Results: Out of 82 patients, 69 were symptomatic (84%). Common symptoms included recurrent respiratory tract infections (43%), stridor (32%), gastro-esophageal reflux (33%), and dysphagia (26%). Diagnosis relied on cardiac ultrasound, barium swallow studies, and chest computerized tomography scan. Surgical repair (thoracotomy 91%) was performed in 79 patients (96%). Median age at repair was 13 [interquartile range (IQR), 4.4-48] months. There was no mortality. Minor complications occurred in 14 patients (18%). Median hospital length of stay was 7 (IQR, 6-9) days. In total, 24% of patients remained symptomatic (median follow-up 54 months). Half of those were asthma-related, with nearly 90% freedom from ring-related symptoms. Conclusions: Most patients were symptomatic at the time of diagnosis. Vascular rings such as pulmonary slings or tracheal compression syndromes require prompt management. Despite surgery, 24% of patients were not symptom-free at follow-up. Finally, surgery in asymptomatic patients resulted in low morbidity supporting the current recommendation of early surgical repair. Level of Evidence: III.

Neutrophil:lymphocyte ratio and intraoperative use of ketorolac or diclofenac are prognostic factors in different cohorts of patients undergoing breast, lung, and kidney cancer surgery.

BACKGROUND: Inflammation is associated with a worse outcome in cancer and neutrophil:lymphocyte ratio (NLR) is a strong prognostic value. In cancer, nonsteroidal anti-inflammatory drugs (NSAIDs) could be of interest. We investigated the prognostic significance of NLR and the impact of intraoperative NSAIDs in cancer surgeries. METHODS: We performed an observational study in early breast, kidney, and lung cancers (357, 227, and 255 patients) with uni- and multivariate analyses (Cox model). RESULTS: In breast cancer (Centre 1), NLR ≥ 4 is associated with a higher risk of relapse (hazards ratio (HR) = 2.41; 95 % confidence interval (CI) 1.01-5.76; P = 0.048). In breast cancer (Centre 2), NLR ≥ 3 is associated with a higher risk of relapse (HR = 4.6; 95 % CI 1.09-19.1; P = 0.04) and higher mortality (HR = 4.0; 95 % CI 1.12-14.3; P = 0.03). In kidney cancer, NLR ≥ 5 is associated with a higher risk of relapse (HR = 1.63; 95 % CI 1.00-2.66; P = 0.05) and higher mortality (HR = 1.67; 95 % CI 1.0-2.81; P = 0.05). In lung cancer, NLR ≥ 5 is associated with higher mortality (HR = 1.45; 95 % CI 1.02-2.06; P = 0.04). The intraoperative use of NSAIDs in breast cancer patients (Centre 1) is associated with a reduced recurrence rate (HR = 0.17; 95 % CI 0.04-0.43; P = 0.0002) and a lower mortality (HR = 0.25; 95 % CI 1.08-0.75; P = 0.01). NSAIDs use at the beginning of the surgery is independently associated with a lower metastases risk after lung cancer surgery (HR = 0.16; 95 % CI 0.04-0.63; P = 0.009). Ketorolac use is independently associated with longer survival (HR = 0.55; 95 % CI 0.31-0.95; P = 0.03). CONCLUSIONS: In these cohorts, these analyses show that NLR is a strong perioperative prognosis factor for breast, lung, and kidney cancers. In this context, intraoperative NSAIDs administration could be associated with a better outcome.

Significance of HLA-matching and anti-HLA antibodies in heart transplant patients receiving induction therapy?

OBJECTIVES: Though Human Leukocyte Antigen (HLA) matching benefits are demonstrated in renal transplantation, evidence in heart transplantation is lacking, and its clinical feasibility is uncertain. Post-transplantation anti-HLA antibodies are being increasingly studied in organ transplantation, with diverging conclusions between transplantated organs. METHODS: We analyzed retrospectively the influence of HLA matching and anti-HLA antibodies on overall survival, acute rejection and chronic allograft vasculopathy in 309 patients receiving induction therapy and triple-drug immunosuppression. RESULTS: The average number of HLA-A/B/DR mismatches between donor and recipient was 4.9 ± 1. The majority of mismatches was for Class I HLA-A/B with an average of 3.3, then for Class I HLA-DR with an average of 1.6. Overall, the HLA-A/-B/-DR mismatches had no influence on the cardiac allograft survival (p = 0.28). However, HLA-DR mismatches were negatively correlated to severe cellular and/or humoral allograft rejection (p = 0.04). Our analysis found anti-HLA antibodies in 27% of recipients, de novo anti-HLA antibodies in 16% of recipients, and donor-specific anti-HLA (DSA) antibodies in 8% of recipients. Furthermore, de novo DSA had no influence on the 5-year survival (78% with DSA vs. 92% without DSA; p = 0.49), which may be masked by the limited number of recipients in analysis By univariable analysis, anti-HLA antibodies (preexisting or de novo) unrelated or related to the donor had no influence on severe cellular and/or humoral rejection or on chronic allograft vasculopathy. CONCLUSIONS: HLA-DR mismatch was negatively correlated to severe cellular and/or humoral allograft rejection but had no influence on cardiac allograft survival. In this study, anti-HLA antibodies (preexisting or de novo) unrelated or related to the donor had no influence on cellular and/or humoral rejection or on chronic allograft vasculopathy. The results of this study add to the controversy on the impact of allo-antibodies in heart transplant recipients receiving induction therapy and contemporary immunosuppression.

Long-term outcomes of atrioventricular septal defect and single ventricle: A multicenter study.

OBJECTIVE: The study objective was to analyze survival and incidence of Fontan completion of patients with single-ventricle and concomitant unbalanced atrioventricular septal defect. METHODS: Data from 4 Dutch and 3 Belgian institutional databases were retrospectively collected. A total of 151 patients with single-ventricle atrioventricular septal defect were selected; 36 patients underwent an atrioventricular valve procedure (valve surgery group). End points were survival, incidence of Fontan completion, and freedom from atrioventricular valve reoperation. RESULTS: Median follow-up was 13.4 years. Cumulative survival was 71.2%, 70%, and 68.5% at 10, 15, and 20 years, respectively. An atrioventricular valve procedure was not a risk factor for mortality. Patients with moderate-severe or severe atrioventricular valve regurgitation at echocardiographic follow-up had a significantly worse 15-year survival (58.3%) compared with patients with no or mild regurgitation (89.2%) and patients with moderate regurgitation (88.6%) (P = .033). Cumulative incidence of Fontan completion was 56.5%, 71%, and 77.6% at 5, 10, and 15 years, respectively. An atrioventricular valve procedure was not associated with the incidence of Fontan completion. In the valve surgery group, freedom from atrioventricular valve reoperation was 85.7% at 1 year and 52.6% at 5 years. CONCLUSIONS: The long-term survival and incidence of Fontan completion in our study were better than previously described for patients with single-ventricle atrioventricular septal defect. A concomitant atrioventricular valve procedure did not increase the mortality rate or decrease the incidence of Fontan completion, whereas patients with moderate-severe or severe valve regurgitation at follow-up had a worse survival. Therefore, in patients with single-ventricle atrioventricular septal defect when atrioventricular valve regurgitation exceeds a moderate degree, the atrioventricular valve should be repaired.

Results of Coarctation Repair by Thoracotomy in Pediatric Patients: A Single Institution Experience.

BACKGROUND: Aortic coarctation is among the most common cardiovascular congenital abnormalities requiring repair after birth. Besides mortality, morbidity remains an important aspect. Accordingly, we reviewed our 20-year experience of aortic coarctation repair by thoracotomy, with emphasis on both short- and long-term outcomes. METHODS: From 1995 through 2014, 214 patients underwent coarctation repair via left thoracotomy. Associated arch lesions were distal arch hypoplasia (n = 117) or type A interrupted aortic arch (n = 6). Eighty-four patients had isolated coarctation (group 1), 66 associated ventricular septal defect (group 2), and 64 associated complex cardiac lesions (group 3). Median follow-up was 8.4 years. RESULTS: There was one (0.5%) procedure-related death. Nine (4.2%) patients died during index admission. In-hospital mortality was 0.7% in group 1 and 2 and 12.5% in group 3 (P < .001). No patient had paraplegia. Actuarial five-year survival was 97.5% in group 1, 94% group 2 and 66% in group 3. Recurrent coarctation developed in 29 patients, all but four (1.8%) successfully treated by balloon dilatation. Freedom from reintervention (dilatation or surgery) at five years was 86%. At hospital discharge, 28 (13.5%) patients were hypertensive. At follow-up, hypertension was present in 11 (5.3%) patients. CONCLUSIONS: Long-term results of aortic coarctation repair by thoracotomy are excellent, with percutaneous angioplasty being the procedure of choice for recurrences. Patient prognosis is dependent on associated cardiac malformations. In this study, the prevalence of late arterial hypertension was lower than previously reported.

Thoracic duct-azygos vein anastomosis in an infant with superior vena cava syndrome and recurrent chylothorax.

In this study, we describe an intrathoracic microsurgical lymphatico-venous anastomosis as an alternative surgical technique for the treatment of refractory chylothorax in an infant. This procedure allowed us to restore enteral nutrition within days of surgery. At 3-year follow-up, there was no recurrence of pleural effusion.

Cellular xenotransplantation.

PURPOSE OF REVIEW: Expectations are high on cellular therapy. Being fundamental to elucidate organogenesis, it is unlikely that embryonic stem cells will be used for clinical purposes. Postembryonic stage, developing cells are, therefore, the front-runner for regenerative medicine. In addition to autologous cells, both allogeneic and xenogeneic cells are hypothetical candidates to treat specific diseases. This review summarizes the current knowledge on immunological and functional aspects of xeno(allo)-cellular transplantation for cardiomyopathy, diabetes, liver failure, neural diseases, and bone regeneration. RECENT FINDINGS: Xenocellular transplantation is promising for tissue repair in immunologically privileged sites such as the central nervous system or nonvascularized tissues in which no or moderate immunosuppression is required. In vascularized organs, major immune responses are present when cells are transplanted without additional conditioning. Positive results from encapsulation methods that protect cells from the immune system should further stimulate preclinical research. Also, conditioning immunosuppression could be used to circumvent the initial immune response. Transgenic pigs cells are probably the best xenogeneic substitute for human application, although basic research on innate and noninnate immunity toward pig cells is still required. SUMMARY: In several fields of medicine, cellular xenotransplantation is slowly emerging as a potential therapeutic tool.

Intra-tumoral vascular or perineural invasion as prognostic factors for long-term survival in early stage non-small cell lung carcinoma.

OBJECTIVE: In recent studies focusing on the prognostic significance of histologic features of NSCLC tumors, vessel invasion was correlated to survival across all surgical stages. We similarly analyzed whether intra-tumoral permeation could affect survival in subgroups of stage I and II NSCLC. METHODS: A retrospective single institution analysis of a prospectively computed database. Specimens were analyzed for intra-tumoral vascular, lymphatic and nervous permeation. Overall mortality was determined and for each stage, a Cox regression analysis of selected variables was performed. Detailed histologic information was available in all patients. Follow-up was 100% complete (median=69 months). RESULTS: From 1989 to 2004, out of 346 patients with stage I and II NSCLC, 253 patients with p stage I (75.7%) and 81 patients with p stage II (24.3%) underwent surgery with complete resection, for a completeness resection rate of 97% (334/346). We performed 70 pneumonectomies, 255 lobectomies and 9 lesser resections (respectively, 21%, 76.3% and 2.7%). In-hospital mortality was 2.1%. The incidence of intra-tumoral permeation was 14.4% (48/334). Permeation correlated both with T status (p=0.04), grade of differentiation (p=0.03) and stage (p=0.02). Median survival and overall 5-year survival for patients with and without permeation were 42.3 months (95% CI [20-64.6]) and 72.1 months (95% CI [56.9-87.2]), respectively; and 44% and 54%, respectively (p=NS). However, intra-tumoral permeation was not a significant predictor for overall death (HR=1.1 [95% CI=0.74-1.66). CONCLUSION: In this large institutional study of early stage NSCLC, the presence of intra-tumoral permeation was correlated both to T, grade of differentiation, as well as to stage. However, in contrast to recent reports, we did not find that intra-tumoral permeation adversely affects long-term survival.

Prognostic value of FDG uptake in early stage non-small cell lung cancer.

BACKGROUND: Non-small cell lung cancer (NSCLC) has a poor prognosis even for early stages of the disease (stage I and II). We studied the prognostic value of PET FDG in patients with completely resected stage I and II NSCLC. METHODS: Retrospective study of 96 patients with NSCLC whose staging included 18F-FDG PET (fluoro deoxy glucose positron emission tomography). Histopathological stage was either stage I (75) or stage II (n=21). FDG uptake was measured as maximal standardized uptake value for body weight (SUVmax). Mean follow-up was 45+/-30 months (1-142 months). Overall and cancer-free survival rates were recorded. RESULTS: SUVmax were higher for stage II than for stage I (10.5+/-4.5 vs 8.5+/-5, p=0.04). Mean tumor volumes were equivalent for both stages (33 cm3, p=0.18), excluding a partial volume effect. The median SUVmax in the whole study population was 7.8. The median survival was significantly longer in patients with a lower (SUVmax7.8 (p=0.001). For stage II tumors (n=21), no statistical difference was observed: 72 months vs 40 months for SUVmax7.8, respectively (p=0.11), although there was a clear trend towards reduced survival for highly metabolic tumors. Disease-free survival was also significantly better for lower metabolic tumors: 96.1 months vs 87.7 months (p=0.01). CONCLUSION: High FDG uptake is associated with reduced overall survival and disease-free survival of patients with completely resected stage I-II NSCLC. Whether patients with highly metabolic tumors should undergo a closer postoperative surveillance or adjuvant chemotherapy has to be addressed in a properly designed prospective trial.

Allosensitization in bridge to transplant Novacor left ventricular assist device patients: analysis of long-term outcomes with regard to acute rejection and chronic allograft vasculopathy.

BACKGROUND: The true relevance of allosensitization in patients benefiting from left ventricular assist device (LVAD) as bridge to transplant (BTT) is still debated. Available registry data referred to numerous devices precluding LVAD-specific analysis. Therefore, we studied all patients with Novacor LVAD prior to transplantation. METHODS: From 1985 to 2006, 37 Novacor LVADs were implanted as BTT, with 30 patients surviving to transplantation (81%). Post-LVAD sensitization was determined for anti-HLA-class I and class II IgGs. Study endpoints were overall survival and/or graft loss, > or =3A cellular rejection and chronic allograft vasculopathy (CAV). The results from LVAD patients were compared to non-LVAD primary heart transplant recipients (n=318). RESULTS: After LVAD insertion, 5 out of 27 patients available for analysis developed anti-HLA antibodies (18.5%). The mean anti-HLA titer after Novacor LVAD implantation was 14% [SD 31]. Actuarial 5- and 10-year patient/graft survival for LVAD and non-LVAD transplant recipients were 73% and 55%, and 70% and 55%, respectively (p=NS). Overall prevalence of rejection > or =3A was 23.3 % (LVAD group) and 18.9% (non-LVAD group) (p=NS). At follow-up, the respective incidence of CAV was 8% (LVAD group) and 32.4% (non-LVAD group) (p<0.01). However, mean follow-up was significantly different for LVAD and non-LVAD patients, 46 vs 90 months (p<0.001). CONCLUSION: In this study, allosensitization occurred infrequently after Novacor LVAD implantation. Secondly, analysis of outcome variables shows that Novacor-LVAD BTT patients can anticipate similar survival to non-LVAD patients, thus minimizing the impact of allosensitization after LVAD implantation.

Distal Aortic Arch Hypoplasia and Coarctation Repair: A Tailored Enlargement Technique.

BACKGROUND: Several techniques have been described to correct coarctation associated with distal arch hypoplasia. However, in neonates, residual gradients are frequently encountered and influence long-term outcome. We reviewed our experience with an alternative technique of repair combining carotid-subclavian angioplasty and extended end-to-end anastomosis. METHODS: From 1998 through 2014, 109 neonates (median age, 9 days) with coarctation and distal arch hypoplasia (n = 106) or type A interrupted aortic arch (n = 3) underwent repair using this technique. Thirty patients had isolated lesions (group 1), 44 associated ventricular septal defect (group 2), and 35 associated complex cardiac lesions (group 3). Median follow-up was 98 months. RESULTS: Repair was performed via left thoracotomy in 97%. There was one procedural-related death (0.9%) and overall five patients died during index admission (4.6%). Ten deaths were recorded at follow-up. Actuarial five-year survival was 86% (100% in group 1, 91% group 2, and 66% in group 3). Recurrent coarctation (clinical or invasive gradient >20 mm Hg) developed in 15 patients, all but 2 successfully treated by balloon dilatation. Freedom from any reintervention (dilatation or surgery) at five years was 86%. Only two patients were on antihypertensive drugs at last follow-up. CONCLUSIONS: This combined technique to correct distal arch hypoplasia and isthmic coarctation results in low mortality and acceptable recurrence rate. It preserves the left subclavian artery and allows enlargement of the distal arch diameter. Late outcome is excellent with very low prevalence of late arterial hypertension.

Although pig allogeneic mesenchymal stem cells are not immunogenic in vitro, intracardiac injection elicits an immune response in vivo.

BACKGROUND: In vitro, mesenchymal stem cells (MSCs) have demonstrated a low immunogenic profile. In this study, we tested the immune response to allogeneic MSCs in immunocompetent swines both in vitro and in vivo. METHODS: Major histocompatibility complex-controlled swine leukocyte antigen (SLA) and SLA were used as donor and recipient, respectively. In vitro, proliferative responses were tested by mixed lymphocyte reaction (MLR) or cocultures and cytokine profiling by enzyme-linked immunosorbent assay. In vivo, allogeneic MSCs were injected in cardiac infarcted area (n=3) and compared with subcutaneous injections of either MSCs (n=2) or peripheral blood mononuclear cells (PBMCs; n=2). Two additional animals received a skin graft as controls. No immunosuppression was used. Specific antidonor humoral responses were tested by flow cytometry and complement-dependent cytotoxicity assay. RESULTS: In vitro, either unstimulated MSCs or interferon (IFN)-gamma stimulated MSC failed to elicit a proliferative response (stimulation index: 1.23 vs. 1.12 vs. 36.9 for controls, P<.001). Concomitantly to the absence of proliferation to MSCs, low production of IFN-gamma and interleukin-2 was evidenced in supernatants while the production of Th2 cytokines was comparable to controls. In vivo, all animals receiving skin grafts, subcutaneous PBMCs and intracardiac MSCs injections developed donor-specific cellular and humoral responses (immunoglobulins M and G) with antibody-complement-mediated cytotoxicity. Subcutaneous MSCs injection needed a rechallenge to similarly develop a cytotoxic humoral response. CONCLUSIONS: Intracardiac allogeneic porcine mesenchymal stem cells elicit an immune response despite their low immunogenic profile in vitro. This result suggests that in vivo characteristics of allogeneic MSCs might differ and emphasizes the importance of pursuing research both in vitro and in vivo.

Aortic valve repair in the paediatric population: insights from a 38-year single-centre experience.

OBJECTIVES: To analyse our institutional results in the setting of paediatric aortic valve (AV) repair. Primary end-points were overall survival, freedom from AV reoperation and freedom from AV replacement. METHODS: A retrospective analysis of all patients under 18 years of age operated on from 1977 to 2015 in a single tertiary care level institution. Patients were included if they benefited from any type of AV repair procedure, including commissurotomy, leaflet shaving or plication, or leaflet augmentation. All data were gathered from patients' medical records, operative reports and referring paediatric cardiologists. The median follow-up was 50 months (IQR [13-140]). RESULTS: Sixty-six patients were included. Indications for surgery were aortic stenosis, aortic regurgitation and mixed disease in 13 (19%), 36 (55%) and 17 (26%) patients, respectively. According to El Khoury's functional classification, among the 55 patients with some degree of regurgitation there were 5 type Ib regurgitation, 23 type II and 27 type III. During AV repair, additional procedures were performed in 36 patients, VSD closure, subaortic membrane resection and mitral valve repair being the most frequent (18, 8 and 7 patients). RACHS score was predominantly 2 (98.5% of patients). The in-hospital mortality rate was 1.5% (1/66). Major morbidity included 10 pericardial effusions (1 pericardocentesis), 1 low cardiac output syndrome and 1 stroke. There were three late deaths (at 104, 140 and 179 months after repair). All were cardiac related. Overall 5- and 10-year survival rates were 100 and 95.7%. The rates of freedom from AV reoperation and AV replacement at 5 and 10 years were 90.6, 72.1 and 92.5, 82.7%, respectively. During follow-up, there was no occurrence of valve-related complication (endocarditis, thromboembolism and bleeding). CONCLUSIONS: In our experience, AV repair in the paediatric population provides excellent results in terms of both overall survival and valve-related reoperation. It obviates the need for chronic anticoagulation and in most cases delays the time at which more complex surgery such as the Ross procedure should be undertaken.

Hypothermic continuous machine perfusion enables preservation of energy charge and functional recovery of heart grafts in an ex vivo model of donation following circulatory death.

OBJECTIVES: Cardiac transplantation using hearts from donors after circulatory death (DCD) is critically limited by the unavoidable warm ischaemia and its related unpredictable graft function. Inasmuch as hypothermic machine perfusion (MP) has been shown to improve heart preservation, we hypothesized that MP could enable the use of DCD hearts for transplantation. METHODS: We recovered 16 pig hearts following anoxia-induced cardiac arrest and cardioplegia. Grafts were randomly assigned to two different groups of 4-h preservation using either static cold storage (CS) or MP (Modified LifePort© System, Organ Recovery Systems©, Itasca, Il). After preservation, the grafts were reperfused ex vivo using the Langendorff method for 60 min. Energetic charge was quantified at baseline, post-preservation and post-reperfusion by measuring lactate and high-energy phosphate levels. Left ventricular contractility parameters were assessed both in vivo prior to ischaemia and ex vivo during reperfusion. RESULTS: Following preservation, the hearts that were preserved using CS exhibited higher lactate levels (57.1 ± 23.7 vs 21.4 ± 12.2 µmol/g; P < 0.001), increased adenosine monophosphate/adenosine triphosphate ratio (0.53 ± 0.25 vs 0.11 ± 0.11; P < 0.001) and lower phosphocreatine/creatine ratio (9.7 ± 5.3 vs 25.2 ± 11; P < 0.001) in comparison with the MP hearts. Coronary flow was similar in both groups during reperfusion (107 ± 9 vs 125 ± 9 ml/100 g/min heart; P = ns). Contractility decreased in the CS group, yet remained well preserved in the MP group. CONCLUSION: MP preservation of DCD hearts results in improved preservation of the energy and improved functional recovery of heart grafts compared with CS.