Back-pocket optimization of 2-aminopyrimidine-based macrocycles leads to potent dual EPHA2/GAK kinase inhibitors with antiviral activity.

Macrocyclization of acyclic compounds is a powerful strategy for improving inhibitor potency and selectivity. Here, we developed a 2-aminopyrimidine-based macrocyclic dual EPHA2/GAK kinase inhibitor as a chemical tool to study the role of these two kinases in viral entry and assembly. Starting with a promiscuous macrocyclic inhibitor, 6, we performed a structure-guided activity relationship and selectivity study using a panel of over 100 kinases. The crystal structure of EPHA2 in complex with the developed macrocycle 23 provided a basis for further optimization by specifically targeting the back pocket, resulting in compound 55 as a potent dual EPHA2/GAK inhibitor. Subsequent front-pocket derivatization resulted in an interesting in cellulo selectivity profile, favoring EPHA4 over the other ephrin receptor kinase family members. The dual EPHA2/GAK inhibitor 55 prevented dengue virus infection of Huh7 liver cells, mainly via its EPHA2 activity, and is therefore a promising candidate for further optimization of its activity against dengue virus.

Preoperative Venovenous ECMO in an Infant With Late Diagnosis of Hypoplastic Left Heart Syndrome.

Late diagnosis and late referral for the Norwood stage 1 procedure in patients with hypoplastic left heart syndrome is rare and associated with a higher mortality. We present a case of a cyanotic almost five-week-old infant with hypoplastic left heart syndrome, highly restrictive foramen ovale, and patent ductus arteriosus, who was bridged with venovenous extracorporeal membrane oxygenation to the Norwood stage 1 procedure.

Long-term outcome of preadolescents, adolescents, and adult patients undergoing total cavopulmonary connection.

OBJECTIVES: Patients with a single ventricle infrequently undergo total cavopulmonary connection as preadolescents, adolescents, or adults. The purpose of this study was to clarify the characteristics of this cohort and to analyze the factors influencing outcomes. METHODS: Between 1994 and 2015, 50 of 460 patients underwent total cavopulmonary connection as preadolescents, adolescents, or adults (group A). The patients' characteristics and operative results were compared with those of the remaining 410 patients aged less than 9 years who underwent total cavopulmonary connection (group B). Post-total cavopulmonary connection echocardiogram reports (n = 4862) were used to evaluate longitudinal ventricular function, and ejection fraction was characterized using nonlinear mixed-effects models and compared between groups. RESULTS: The median follow-up time was 10.3 (2.8-15.5) years. The differences between groups in 30-day mortality (P = .20), intensive care unit stay (P = .20), and incidence of prolonged effusion (P = .08) were not significant. The estimated survival at 15 years was lower in group A (86.5%) than in group B (94.0%, P = .04) patients. Long-term systemic ventricular ejection fraction, analyzed with linear mixed-effect models, was significantly reduced in group A than in group B patients (P < .001). At a median postoperative period of 8.4 (7.1-10.5) years, the peak oxygen uptake as measured by exercise capacity testing was lower in group A than in group B patients, respectively (22.3 ± 6.5 [n = 25] vs 30.6 ± 8.1 [n = 100] mL/kg/min, P < .001). CONCLUSIONS: The total cavopulmonary connection procedure was performed in preadolescent, adolescent, and adult patients with no significant difference in 30-day or hospital mortality compared with those in young children. However, long-term survival and ventricular performance were reduced in this older cohort.

Atrioventricular valve regurgitation in patients undergoing total cavopulmonary connection: Impact of valve morphology and underlying mechanisms on survival and reintervention.

OBJECTIVE: The study objective was to determine the mechanisms of atrioventricular valve regurgitation in single-ventricle physiology and their influence on outcomes after total cavopulmonary connection. METHODS: Among 460 patients who underwent a total cavopulmonary connection, 101 (22%) had atrioventricular valve surgery before or coincident with total cavopulmonary connection. RESULTS: Atrioventricular valve morphology showed 2 separated in 33 patients, mitral in 11 patients, tricuspid in 41 patients, and common in 16 patients. Patients with a tricuspid and a common atrioventricular valve underwent atrioventricular valve surgery frequently, 27% and 36%, respectively. Atrioventricular valve regurgitation was due to 1 or more of the following mechanisms: dysplastic leaflet (62), prolapse (53), annular dilation (27), cleft (22), and chordal anomaly (14). Structural anomalies were observed in 89 patients (88%). The procedure was atrioventricular valve repair in 81 patients, atrioventricular valve closure in 16 patients, and atrioventricular valve replacement in 4 patients. Among 81 patients who underwent initial repair, repeat repair was required in 20 patients, atrioventricular valve replacement was required in 7 patients, and atrioventricular valve closure was required in 3 patients. Among patients undergoing atrioventricular valve surgery, overall survival after total cavopulmonary connection (88% vs 95% at 15 years, P = .01), freedom from atrioventricular valve reoperation after total cavopulmonary connection (75% vs 99% at 15 years, P < .01), and grade of atrioventricular valve regurgitation at a median follow-up of 6.6 years (P < .01) were worse than in those who did not require atrioventricular valve surgery. CONCLUSIONS: Atrioventricular valve regurgitation in univentricular heart is more frequently associated with a tricuspid or a common atrioventricular valve, and structural anomalies are the primary cause. Significant atrioventricular valve regurgitation requiring surgery influences survival after total cavopulmonary connection, especially when atrioventricular valve replacement was needed. Surgical management based on mechanisms of regurgitation is mandatory.

Early and late outcomes after surgical repair of congenital supravalvular aortic stenosis: a European Congenital Heart Surgeons Association multicentric study.

OBJECTIVES: Our goal was to evaluate the early and late results of the surgical management of congenital supravalvular aortic stenosis (SVAS). METHODS: We performed a retrospective, multicentre study using data from the European Congenital Heart Surgeons Association. Exclusion criteria were age >18 years, operation before 1990 and redo supravalvular aortic stenosis operations. Multivariate Cox regression analysis was performed to detect independent predictors of adverse events. RESULTS: Of a total of 301 patients (male/female = 194/107; median age 3.9 years, range 13 days-17.9 years), 17.6% had a prior surgical or interventional procedure. Pulmonary artery stenosis was present in 41.5% and coronary anomalies in 13.6%. The operation consisted of a single patch repair in 36.7%, a pantaloon-shaped patch in 36.7%, a 3-patch technique in 14.3% and other techniques in 11.7%. Postoperative complications occurred in 14.9%, and the early mortality rate was 5%. At a median follow-up of 13 years (interquartile range 3.5-7.8; follow-up completed 79.1%), there were 10 late deaths (4.2%). A surgical reoperation or an interventional cardiology procedure occurred in 12.6% and 7.2%, respectively. No significant differences in outcomes between the techniques were found. Age at repair <12 months and pulmonary artery stenosis were associated with an increased risk of early (P = 0.0001) and overall mortality (P = 0.025), respectively. Having an operation after 2005 and co-existing pulmonary artery stenosis were significant predictors of late reintervention (P = 0.0110 and P = 0.001, respectively). CONCLUSIONS: Surgical repair of congenital stenosis is an effective procedure with acceptable surgical risk and good late survival, but late morbidity is not negligible, especially in infants and when associated pulmonary artery stenosis is present.

Impact of early Fontan completion on postoperative outcomes in patients with a functional single ventricle.

OBJECTIVES: Our aim was to evaluate whether early timing of total cavopulmonary connection (TCPC) affects postoperative outcomes. METHODS: Of 460 consecutive TCPC patients, 51 (11.1%) underwent TCPC ≤ 18 months of age (group A), and 409 patients >18 months of age (group B). We compared the clinical outcomes and exercise capacity between groups. RESULTS: Median age at TCPC was 1.4 (interquartile ranges: 1.3-1.5) years in group A and 2.5 (1.9-4.5) years in group B. Duration of intensive care unit stay (6 vs 7 days), hospital stay (20 vs 20 days), and 30-day survival (100 vs 98%) was not significantly different between groups. Estimated survival (95.3 vs 92.1%), freedom from reoperation (93.7 vs 86.3%), freedom from catheter intervention (60.1 vs 77.0%), and freedom from protein losing enteropathy (97.6 vs 93.8%) at 10 years was not significantly different between groups. At last follow-up, no patient in group A but 13 patients in group B exhibited reduced ventricular function ( P = 0.035). Exercise-capacity testing showed that both peak oxygen uptake (36.4 vs 28.6 ml/kg/min; P = 0.026) and its percentage of predicted value (82.9 vs 70.0%; P = 0.004) were significantly higher in group A ( n = 6, mean postoperative period: 8.9 years) than in group B ( n = 119, mean postoperative period: 8.7 years). CONCLUSIONS: Fontan completion for TCPC can be performed at an early age with a low perioperative risk and good intermediate results. Earlier unloading of the systemic ventricle and earlier elimination of chronic cyanosis by staged cavopulmonary connection might be advantageous for preservation of long-term ventricular function.

Early postoperative extubation of unstable patients following total cavopulmonary connection: impact on circulation and outcome.

OBJECTIVES: We aimed to investigate whether early postoperative extubation following the Fontan operation is universally feasible and can be used as a management tool in unstable patients. METHODS: All patients undergoing the Fontan operation in our centre between 2004 and 2013 (n=253) were analysed. Until 2008, patients were extubated according to standard criteria and comprised group 1. Group 2 included all patients presenting after 2009, when early extubation was always aimed regardless of the haemodynamic status. Patients who exceeded the 75th percentiles for volume requirements and inotrope scores for the respective group were defined as unstable. Comparisons of outcomes between groups and subgroups and analysis of the changes in haemodynamic and treatment parameters with extubation in unstable patients after 2009 were performed. RESULTS: Compared with group 1, patients from group 2 were ventilated for shorter duration (p<0.001), had similar re-intubation rates (p=0.50), and needed less volume (p=0.01). In group 2, the unstable patients were not ventilated for longer durations (p=0.19), but had higher re-intubation rates (p=0.03) than the stable patients. Compared with the unstable patients from group 1, the unstable patients from group 2 were ventilated for shorter duration (p<0.001), had similar re-intubation rates (p=0.66), and needed less volume (p=0.006). There was a significant acute and sustained increase in mean arterial pressure with extubation and a parallel reduction in volume requirements and inotrope scores in the unstable patients from group 2. CONCLUSIONS: Timely extubation is universally applicable following the Fontan operation. Early postoperative extubation can be valuable for improving Fontan haemodynamics.

Long-Term Outcome of Patients With Complete Atrioventricular Septal Defect Combined With the Tetralogy of Fallot: Staged Repair Is Not Inferior to Primary Repair.

BACKGROUND: Primary repair is the preferred strategy for surgical treatment of complete atrioventricular septal defect combined with the tetralogy of Fallot. However, a staged approach may be preferable for very small or cyanotic infants. The long-term outcomes of infants undergoing staged vs primary repair were compared. METHODS: Data from 47 patients with complete atrioventricular septal defect combined with the tetralogy of Fallot who were operated on at our institution between 1974 and 2013 were reviewed. The study end points were all-cause death and reoperation. The patients were classified into two groups: staged repair (SR) and primary repair (PR). The indications for staged repair were cyanosis and young age. RESULTS: There were 22 SR and 25 PR patients. The SR patients were younger at the time of the initial operation (p = 0.001), and were more frequently cyanotic (21 SR vs 5 PR patients, p = 0.003). The 10-year survival after repair of the SR and PR patients was 78% ± 11% and 83% ± 8%, respectively (p = 0.8). No risk factors for death were identified. The 10-year freedom from reoperation for atrioventricular valve regurgitation of SR and PR patients after repair was 73% ± 12% and 71% ± 10%, respectively (p = 0.5). At least moderate atrioventricular valve regurgitation before repair was the only risk factor for reoperation (p = 0.01). CONCLUSIONS: Cyanotic and very young children with complete atrioventricular septal defect combined with the tetralogy of Fallot who require urgent treatment have long-term outcomes after staged repair similar to those of patients who undergo primary repair. Preoperative atrioventricular valve regurgitation is associated with increased risk for reoperation over the long-term.

Mortality Following Congenital Heart Surgery in Adults Can Be Predicted Accurately by Combining Expert-Based and Evidence-Based Pediatric Risk Scores.

OBJECTIVES: Currently, there are few specific risk stratification models available to predict mortality following congenital heart surgery in adults. We sought to evaluate whether the predictive power of the common pediatric scores is applicable for adults. In addition, we evaluated a new grown-ups with congenital heart disease (GUCH) score specifically designed for adults undergoing congenital heart surgery. METHODS AND RESULTS: Data of all consecutive patients aged 18 years or more, who underwent surgery for congenital heart disease (CHD) between 2004 and 2013 at our institution, were collected. We evaluated the Aristotle Basic Complexity (ABC), the Aristotle Comprehensive Complexity (ACC), the Risk Adjustment in Congenital Heart Surgery (RACHS-1), and the Society of Thoracic Surgeons (STS)-European Association for Cardiothoracic Surgery (EACTS) scores. The proposed GUCH score consists of the STS-EACTS score, the procedure-dependent and -independent factors of the ACC score, and age. The discriminatory power of the scores was assessed using the area under the receiver-operating characteristics curve (c-index). A total of 830 operations were evaluated. Hospital mortality was 2.9%. C-indexes were 0.67, 0.80, 0.62, 0.78, and 0.84 for the ABC, ACC, RACHS-1, STS-EACTS, and GUCH mortality scores, respectively. CONCLUSION: The evidence-based EACTS-STS score outperforms the expert-based ABC score. The expert-based ACC score is superior to the evidence-based EACTS-STS score since comorbidities are considered. Our proposed GUCH score outperforms all other scores since it integrates the advantages of the evidence-based EACTS-STS score for procedures and the expert-based ACC score for comorbidities. Evidence-based scores for adults with CHD should include comorbidities and patient ages.

Exercise performance in Ebstein's anomaly in the course of time - Deterioration in native patients and preserved function after tricuspid valve surgery.

OBJECTIVE: The purpose of this study was to assess the longitudinal follow-up of exercise performance in patients with native Ebstein anomaly and patients who had received previous tricuspid valve surgery. PATIENTS AND METHODS: We identified 59 patients with Ebstein anomaly who had performed at least two cardiopulmonary exercise tests within a minimum of 6months. 22 patients (15 female, 29.0±13.4years) with native conditions, 37 patients (21 female, 32.1±15.3years) had undergone surgery of their tricuspid valve before baseline testing. RESULTS: In the non-operated group peak workload (2.58±0.7 to 2.38±0.7W/kg, p=.019) declined during a mean follow-up of 4.6±2.6years, whereas peak workload remained stable in the surgical group (2.02±0.6 to 2.06±0.7W/kg, p=.229) throughout the follow-up of 3.4±2.3years. In the 18 patients who had their surgery less than one year prior to the first CPET the exercise performance even increased during the follow-up. Peak blood pressure as a marker of cardiac adaption to exercise increased in the follow-up examination only in the surgical group (159±23 vs. 171±30mmHg, p=.007). In the non-operated group blood pressure remained unchanged at follow-up (161±26 vs. 166±29, p=.358). CONCLUSION: Exercise performance deteriorates in non-operated patients with Ebstein anomaly in contrast to patients after tricuspid valve surgery where exercise performance remains stable. These facts promote a surgical intervention latest at the time when exercise performance decreases.

Durability of bioprostheses for the tricuspid valve in patients with congenital heart disease.

OBJECTIVES: Only little data exist on the durability of bioprostheses in the tricuspid position in patients with congenital heart disease (CHD). The aim of the study was to determine the reoperation rate and the valve function after primary implantation. METHODS: Between 1990 and 2013, 51 patients with CHD underwent tricuspid valve (TV) replacement with a bioprosthesis. The median age at operation was 32 years (range: 8-69). The underlying morphology was Ebstein's anomaly in 62% of the patients. Implanted valves included 38 pericardial and 13 porcine valves. All available echocardiographic examinations (n = 714) and clinical data were retrospectively reviewed. Dysfunction was defined as an at least moderate regurgitation or a mean diastolic gradient ≥9 mmHg. Freedom from death, reoperation and prosthetic valve dysfunction was estimated using the Kaplan-Meier method. RESULTS: The 30-day mortality rate was 9%. The estimated survival rate was 86% at one and 80% at ten years. The freedom from reoperation at 1, 5 and 10 years was 100, 86 and 81%, and that from prosthesis dysfunction detected by echocardiography at 1, 5 and 10 years was 89, 66 and 58%, respectively. The main reason for dysfunction was insufficiency (89%). Valve implantation at an age below 16 years was associated with earlier reoperation and dysfunction (the 5-year freedom rate from reoperation/dysfunction was 70%/30% compared with 89%/78% in the rest of the patients, P = 0.016/0.0009). CONCLUSIONS: Serial echocardiography shows a high rate of dysfunction of TV bioprosthesis in patients with CHD, which already occurred a few years after implantation. In patients below 16 years of age, most prostheses are dysfunctional within 5 years.

Clinical outcome following total cavopulmonary connection: a 20-year single-centre experience.

OBJECTIVES: This study aims to evaluate the clinical outcome following total cavopulmonary connection (TCPC) and to identify factors affecting early and late outcome. METHODS: Between May 1994 and March 2015, 434 patients underwent TCPC with 50 lateral tunnels and 374 extracardiac conduits. The clinical outcome, exercise capacity and liver examination results were retrospectively reviewed. RESULTS: Thirty-day survival was 98.2%, and the estimated survival rate at 15 years was 92.3%. Freedom from tachyarrhythmia at 15 years was 91.0%. Other late morbidities included bradyarrhythmia in 17, protein-losing enteropathy (PLE) in 15, thromboembolism in 3 and plastic bronchitis in 3 patients. At last follow-up, normal systemic ventricular function (ejection fraction >50%) was observed in 88.2%. Atrioventricular valve (AVV) regurgitation was mild or less in 90% of patients with systemic left ventricle, in 63% of those with systemic right ventricle and 58% of the patients with unbalanced atrioventricular septal defect or common inlet ventricles. Cardiopulmonary exercise capacity showed impaired peak oxygen uptake (71% of normal) in a sub-group of 120 patients at a mean of 9 years postoperatively. Biochemistry of 338 patients at last follow-up revealed a gamma-glutamyl transferase value beyond normal in 90 patients (26%), with a positive correlation between the level and the time after the initial operation (P < 0.01). Pre-TCPC high transpulmonary gradient emerged as a predictor for delayed hospital recovery (P = 0.002), late mortality (P = 0.016) and reoperation (P = 0.015) in multivariable analysis. CONCLUSIONS: Contemporary TCPC can be performed with low risk and provides excellent survival in the long-term. Classic morbidities of the original Fontan procedure, such as Fontan pathway revision, tachyarrhythmia and thromboembolism seem mitigated. However, exercise limitations, PLE and liver dysfunction remain an issue. AVV insufficiency and ventricular dysfunction are still a concern.

Desmoid Tumor After a Minimally Invasive Atrial Septal Defect Closure in an Adolescent.

The surgical closure of secundum atrial septal defect (ASD) is frequently performed. The minimally invasive approach, currently adopted by many centers as a way to preserve aesthetic appearance, particularly in female patients, seems to be safe. We describe the case of an adolescent who developed a desmoid tumor soon after a minimally invasive operation for surgical closure of a secundum ASD.

More than valve repair: Effect of cone reconstruction on right ventricular geometry and function in patients with Ebstein anomaly.

BACKGROUND: Cone reconstruction is a novel surgical procedure for tricuspid valve repair in Ebstein anomaly. This study examined the effect of cone reconstruction on right ventricle (RV) geometry, function, and synchronization. METHODS: Twenty-one patients (4-49 year-old) underwent cone reconstruction were enrolled, and matched with healthy individuals. Pre-operative and follow-up echocardiography was performed along with cardiac magnetic resonance (CMR) imaging in 18 patients. A new parameter, tricuspid annular movement synchronicity index (TAMSI), was used to describe global synchronization of RV in the annular plane. TAMSI was defined as standard deviation of the systolic excursion of the hinge points of the three leaflets divided by their average value. RESULTS: After 9.1 (range 1-12) months follow-up, there were no deaths; tricuspid regurgitation was reduced from moderate/severe to mild or less in 95.2% of patients. In 18 patients with both pre and post CMR data, functional RV volume decreased after repair (134.3 ± 58.3 ml/m(2) to 96.6 ± 29.6 ml/m(2); P=0.001), while ejection fraction was not significantly altered (38.2 ± 9.2% to 36.5 ± 8.5%; P=0.357). TAMSI was significantly reduced after surgery, from 0.613 ± 0.220 to 0.169 ± 0.088 (P<0.001). A value similar to the normal control (0.181 ± 0.081) indicated more synchronized RV movement pattern. CONCLUSIONS: Cone reconstruction yielded good short-term survival in Ebstein anomaly. It reduced functional RV volume, improved RV global synchronization, and restored RV geometry. As such, it may improve RV performance and long-term prognosis. In addition, our described TAMSI proved to be a useful adjunct to postoperative assessments.

Improved Exercise Performance in Patients With Tricuspid Atresia After the Fontan-Björk Modification With Pulsatile Systolic Pulmonary Flow.

BACKGROUND: After the Fontan-Björk modification for tricuspid atresia, some patients show pulsatile systolic pulmonary flow. We compared the hemodynamic findings and the clinical presentation of patients with and without pulsatile systolic flow after atrioventricular connection. METHODS: According to the pulmonary flow pattern by pulsed-wave Doppler assessment of transthoracic echocardiography, 41 patients after atrioventricular connection were divided into two groups: patients who showed dominant pulsatile systolic pulmonary flow (group P, n = 11), and patients who did not (group N, n = 30). RESULTS: Mean follow-up time was 27.8 ± 4.7 years in group P and 25.3 ± 3.8 years in group N (p = 0.1). Patients in group P had significantly less frequently catheter ablation procedures for tachyarrhythmia (9% versus 50%, p = 0.03). No patient in group P had had cardiac decompensation, whereas 7 patients (23%) in group N had had an episode of cardiac decompensation (p = 0.08). Cardiopulmonary exercise testing revealed that patients in group P showed higher oxygen uptake compared with patients in group N (25.0 ± 7.3 versus 19.6 ± 6.0 mL · kg(-1) · min(-1), p = 0.03). Patients in group P showed higher systolic pulmonary artery pressure (21.3 ± 8.4 versus 16.8 ± 4.5 mm Hg, p = 0.05), higher right ventricular end-diastolic volume index (88.6 ± 30.2 versus 50.3 ± 28.5 mL · L(-1) · m(-2), p = 0.03), and higher right ventricle to left ventricle ratio of end-diastolic volume index (1.4 ± 0.6 to 0.7 ± 0.3, p = 0.01). CONCLUSIONS: Patients with pulsatile systolic flow in the pulmonary artery had better hemodynamic and better exercise performance compared with patients without pulsatile systolic flow after atrioventricular connection. A sufficient volume and function of the right ventricle is a prerequisite to create pulsatile systolic flow.

Durability of down-sized homografts for the reconstruction of the right ventricular outflow tract.

OBJECTIVES: Small-sized homografts are rare but may be required for the reconstruction of the right ventricular outflow tract (RVOT). Down-sizing adult-sized homografts can be an option to overcome the shortage of availability. METHODS: Since 1994, we have been down-sizing adult-sized homografts by excising one cusp. The aim of the study was to analyse the durability of down-sized homografts and compare it with small-sized homografts in a paediatric population. All patients below a body weight of 14 kg were included in the study. The end-point of the study was homograft failure. RESULTS: A total of 152 patients met the inclusion criteria of the study, of which 82 patients (54%) received a down-sized homograft. The median age was 17.1 (0.3-64.8) months and the mean weight 8.4 ± 3.4 kg. Fifty-eight patients (38%) were under 1 year and 10 (6.5%) under 1 month of age at the time of homograft implantation. The mean homograft size of the whole study population was 14.7 ± 2.5 mm and the mean z-score was 1.6 ± 0.9. The median follow-up time was 10 (0.03-19.7) years. Early mortality after homograft implantation was 5% (n = 8), 4 of these patients had received a down-sized homograft. The study population comprised early survivors, that is, 144 patients. During follow-up, a total of 46 homografts failed, 23 in each group, after a mean time of 5.7 ± 4.2 years. Freedom from homograft failure was 94.6 ± 2.6, 87.2 ± 4 and 68.6 ± 6.6% for down-sized homografts and 95.2 ± 2.7, 78.7 ± 5.5 and 61 ± 7% for small-sized homografts at 1, 5 and 10 years, respectively (P = 0.3). Risk factors for homograft failure in the multivariable analysis were a homograft z-score of <1 and age below 1 year at the time of implantation (P = 0.02). CONCLUSION: Down-sized homografts demonstrated a durability similar to that of small-sized homografts. Therefore, down-sizing adult-sized homografts by creating a bicuspid valve to fit into the corresponding RVOT in children with congenital heart defects is an excellent method to overcome the shortage of small-sized homografts.

Geometric ring annuloplasty as an adjunct to aortic valve repair: clinical investigation of the HAART 300 device.

OBJECTIVES: This study assessed the safety and efficacy of an internal geometric annuloplasty ring in a regulatory trial of aortic valve reconstruction (ClinicalTrials.gov Identifier: NCT01400841). METHODS: Sixty-five patients with predominant moderate-to-severe trileaflet aortic insufficiency (AI) underwent aortic valve repair with an average age of 63 ± 13 years (mean ± SD). All had initial implantation of an internal aortic annuloplasty ring to correct annular dilatation and facilitate leaflet reconstruction. Leaflet plication was performed for prolapse in 80% of patients, and more complex leaflet procedures, usually employing autologous pericardium, were required in 22%. Ascending aortic and/or root aneurysms were replaced in 62%. RESULTS: Follow-up was for a maximum of 3 years and a mean of 2 years. No in-hospital operative mortalities, major complications or early or late valve-related events occurred. The annular diameter before repair was 26.5 ± 2.3 mm, and the average ring diameter used was 21.5 ± 1.6 mm. The preoperative AI grade (0-4) was 2.9 ± 0.8 and improved after repair to 0.6 ± 0.7 (P < 0.0001), as did the NYHA class. The mean valve gradient was 8.6 ± 4.3 mmHg, and at 3 years, the Kaplan-Meier survival rate was 95%, with no valve-related mortality. Over the 3 years, aortic valve replacement was required in 7 patients (10.8%) for reasons usually related to surgical technique. Most repair failures occurred early, and results stabilized after 6 months. No structural complications of the rings were observed. CONCLUSIONS: Geometric ring annuloplasty was a safe and effective adjunct to aortic valve repair. Initial correction of annular dilatation seemed to facilitate overall reconstruction. Because most early repair failures were technical, increasing experience with geometric ring annuloplasty for aortic valve reconstruction has the potential to standardize and improve outcomes.

Non-volumetric echocardiographic indices and qualitative assessment of right ventricular systolic function in Ebstein's anomaly: comparison with CMR-derived ejection fraction in 49 patients.

AIMS: Ebstein's anomaly (EA) is often associated with right ventricular (RV) dysfunction. Data on echocardiographic quantification of RV function are, however, rare. The aim of this study was to determine how non-volumetric echocardiographic indices and qualitative assessment of global systolic RV function correlate with cardiovascular magnetic resonance (CMR)-derived RV ejection fraction (EF). METHODS AND RESULTS: We compared six echocardiographic indices and qualitative assessment of RV function with the gold standard CMR. A total of 49 unoperated patients with EA and a mean age of 32 ± 18 years were examined. Tricuspid annular plane systolic excursion, tissue Doppler myocardial velocities (peak S and IVA) and 2D strain and strain rate measures for the RV were compared with CMR-derived EF. Only 2D global longitudinal strain (2D-GLS), out of the six parameters investigated, showed a weak, although statistically significant correlation with CMR-derived RVEF (R = -0.4, P = 0.01). Using a cut-off value of -20.15, 2D-GLS sensitivity (77%) and specificity (46%) in detecting patients with a CMR-derived EF of <50% were comparable with qualitative assessment (sensitivity 77%, specificity 45%). CONCLUSION: Overall echocardiographic parameters of RV function correlate poorly with CMR-derived EF in patients with EA. Only 2D global longitudinal RV strain correlated weakly with CMR-derived RVEF. However, the sensitivity and specificity for detecting RV dysfunction using 2D strain imaging were comparable with qualitative RV functional assessment.

Higher programmatic volume in paediatric heart surgery is associated with better early outcomes.

OBJECTIVE: Previous analyses have suggested an association between centre volume and in-hospital mortality, post-operative complications, and mortality in those patients who suffer from a complication. We sought to determine the nature of this association using a multicentre cohort. METHODS: All the patients, aged 18 years or younger, undergoing heart surgery at centres participating in the European Congenital Heart Surgeons Database (2003-2013) were included. Programmes were grouped as follows: small 350. Multivariable logistic regression was used to identify the differences between groups with the adjusted in-hospital mortality, onset of any and/or major complication, and in-hospital mortality in those patients with any and/or major complication. The outcomes were adjusted for patient specific risk factors and surgical risk factors. RESULTS: The data set consisted of 119,345 procedures performed in 99 centres. Overall, in-hospital mortality was 4.63%; complications occurred in 23.4% of the patients. In-hospital mortality in patients with complications was 13.82%. Multivariable logistic regression showed that the risk of in-hospital death was higher in low- and medium-volume centres (p<0.001). The rate of the occurrence of any post-operative complication in small, medium, and large programmes was lower compared with very large centres (p<0.001). Low- and medium-volume centres were associated with significantly higher mortality in patients with any complication (p<0.001). CONCLUSIONS: Our analysis showed that the risk of in-hospital mortality was lower in higher-volume centres. Although the risk of complications is higher in high-volume centres, the mortality associated with complications that occurred in these centres was lower.

Complete Aortic Valve Cusp Replacement in the Pediatric Population Using Tissue-Engineered Bovine Pericardium.

Three clinical cases of severe pediatric aortic valve defects undergoing complete aortic valve cusp replacement using tissue-engineered bovine pericardium are reported. All patients achieved excellent early results, and are being followed without complications.