Long-term follow-up of atrioventricular valve function in Fontan patients: effect of atrioventricular valve surgery.

OBJECTIVES: The aim of this study was to evaluate the relationship between atrioventricular valve and ventricular function in Fontan survivors, including the effect of atrioventricular valve surgery. METHODS: Analysis focused on transplant-free survival and the need for atrioventricular valve surgery in single ventricle patients after Fontan completion. Longitudinal echocardiographic examination of long-term valve and ventricular function was performed. RESULTS: Fontan completion was performed in 113 patients, having a right univentricular morphology in 33.6%, a left ventricle morphology in 62.8% and ambiguous in 3.6%. Perioperative mortality was 2.7% (n = 3). Within a median follow-up of 16.3 years (interquartile range 10.6-23.6), transplant-free survival was 96.1 ± 1.9% and 90.4 ± 5.8% at 10-25 years. Twenty AV valve procedures were performed in 14 (12.4%) children, respectively, pre-Fontan (n = 10), per-Fontan (n = 8) and post-Fontan (n = 2), resulting in a cumulative incidence of AV valve surgery is 5.7 ± 2.2% and 12.3 ± 3.2% at 1-5 years. Atrio-ventricular valve function deteriorated over time [hazard ratio (HR) 1.112, 95% confidence interval (CI) 1.089-1.138, P < 0.001], without difference for valve morphology (P = 0.736) or ventricular dominance (P = 0.484). AV valve dysfunction was greater in patients requiring AV valve surgery (HR 20.383, 95% CI 6.223-36.762, P < 0.001) but showed a comparable evolution since repair to those without valve surgery (HR 1.070, 95% CI 0.987-1.160, P = 0.099). Progressive time-related ventricular dysfunction was observed (HR 1.141, 95% CI 1.097-1.182, P < 0.001), significantly less in left ventricle-dominance (HR 0.927, 95% CI 0.860-0.999, P = 0.047) but more after AV valve surgery (HR 1.103, 95% CI 1.014-1.167, P = 0.022). CONCLUSIONS: In a homogeneously treated Fontan population, 25-year transplant-free survival is encouraging. Atrio-ventricular valve surgery was necessary in 12.4%, resulting mostly in a durable valve function. However, a slow time-related decline of atrioventricular valve function as of ventricular function is worrisome, evoking a role for additional heart failure therapy.

Last year of life of adults with congenital heart diseases: causes of death and patterns of care.

AIMS: Although life expectancy in adults with congenital heart diseases (CHD) has increased dramatically over the past five decades, still a substantial number of patients dies prematurely. To gain understanding in the trajectories of dying in adults with CHD, the last year of life warrants further investigation. Therefore, our study aimed to (i) define the causes of death and (ii) describe the patterns of healthcare utilization in the last year of life of adults with CHD. METHODS AND RESULTS: This retrospective mortality follow-back study used healthcare claims and clinical data from BELCODAC, which includes patients with CHD from Belgium. Healthcare utilization comprises cardiovascular procedures, CHD physician contacts, general practitioner visits, hospitalizations, emergency department (ED) visits, intensive care unit (ICU) admissions, and specialist palliative care, and was identified using nomenclature codes. Of the 390 included patients, almost half of the study population (45%) died from a cardiovascular cause. In the last year of life, 87% of patients were hospitalized, 78% of patients had an ED visit, and 19% of patients had an ICU admission. Specialist palliative care was provided to 17% of patients, and to only 4% when looking at the patients with cardiovascular causes of death. CONCLUSIONS: There is a high use of intensive and potentially avoidable care at the end of life. This may imply that end-of-life care provision can be improved. Future studies should further examine end-of-life care provision in the light of patient's needs and preferences, and how the healthcare system can adequately respond.

Non-invasive assessment of liver abnormalities in pediatric Fontan patients.

Liver abnormalities are well known among long-term survivors of Fontan palliation, which remains the definite surgery for complex congenital heart disease and single ventricle physiology. Pediatric data however are scarce. We assessed the prevalence and degree of liver abnormalities in pediatric Fontan patients through non-invasive investigations suitable for longitudinal follow-up. Thirty-five patients with a median age of 11.8 years (5.2-16.6) and median time since Fontan of 6 years (1.17-13.83) were studied. Each child underwent a blood test, liver Doppler ultrasound (US), and transient elastography (TE). Healthy children were used as controls for TE measurement. AST, ALT, γGT, and direct bilirubin were abnormal in respectively 12 (34%), 5 (14%), 24 (69%), and 7 (20%) patients, while platelet count was decreased in 7 (20%). Splenomegaly was present in 7 (20%) patients. Portal vein mean flow velocity was < 15 cm/s in 19 (54%) patients indicative of portal hypertension. Twenty-two patients (63%) showed inferior vena cava collapsibility index values below 17%, indicating venous congestion. Hepatic artery and superior mesenteric artery resistance index were inversely correlated with time post Fontan (p < 0.05). TE values in Fontan patients were significantly higher than controls, with a median of 12.6 versus 4.6 kPa (p < 0.001) and were already increased shortly after Fontan completion. Conclusion: Liver abnormalities are frequently observed in pediatric Fontan patients. The non-invasive investigations used were not able to confirm liver fibrosis or differentiate hepatic congestion from fibrosis. Based on our findings, we propose a prospective screening protocol with serial measurements of laboratory, (Doppler) US, and TE parameters. What is Known: • Hepatic dysfunction is a well-known consequence of the Fontan circulation. • The natural history of Fontan-associated liver disease in the pediatric age group remains unclear. What is New: • Liver abnormalities are frequently observed in pediatric Fontan patients; however, differentiating liver fibrosis and hepatic congestion with non-invasive investigations remains challenging. Sonographic Doppler measurements may improve our insight in both Fontan-associated liver disease development and the functioning of the Fontan circulation. • A prospective screening protocol is proposed to improve our ability to detect Fontan-associated liver disease early on and understand its natural history.

A Reassessment of Copy Number Variations in Congenital Heart Defects: Picturing the Whole Genome.

Copy number variations (CNVs) can modulate phenotypes by affecting protein-coding sequences directly or through interference of gene expression. Recent studies in cancer and limb defects pinpointed the relevance of non-coding gene regulatory elements such as long non-coding RNAs (lncRNAs) and topologically associated domain (TAD)-related gene-enhancer interactions. The contribution of such non-coding elements is largely unexplored in congenital heart defects (CHD). We performed a retrospective analysis of CNVs reported in a cohort of 270 CHD patients. We reviewed the diagnostic yield of pathogenic CNVs, and performed a comprehensive reassessment of 138 CNVs of unknown significance (CNV-US), evaluating protein-coding genes, lncRNA genes, and potential interferences with TAD-related gene-enhancer interactions. Fifty-two of the 138 CNV-US may relate to CHD, revealing three candidate CHD regions, 19 candidate CHD genes, 80 lncRNA genes of interest, and six potentially CHD-related TAD interferences. Our study thus indicates a potential relevance of non-coding gene regulatory elements in CNV-related CHD pathogenesis. Shortcomings in our current knowledge on genomic variation call for continuous reporting of CNV-US in international databases, careful patient counseling, and additional functional studies to confirm these preliminary findings.

Paediatric subaortic stenosis: long-term outcome and risk factors for reoperation.

OBJECTIVES: Surgical repair of subaortic stenosis (SAS) is associated with a substantial reoperation risk. We aimed to identify risk factors for reintervention in relation to discrete and tunnel-type SAS morphology. METHODS: Single-centre retrospective study of paediatric SAS diagnosed between 1992 and 2017. Multivariable Cox regression analysis was performed to identify reintervention risk factors. RESULTS: Eighty-five children [median age 2.5 (0.7-6.5) years at diagnosis] with a median follow-up of 10.1 (5.5-16.4) years were included. Surgery was executed in 83% (n = 71). Freedom from reoperation was 88 ± 5% at 5 years and 82 ± 6% at 10 years for discrete SAS, compared to, respectively, 33 ± 16% and 17 ± 14% for tunnel-type SAS (log-rank P < 0.001). Independent risk factors for reintervention were a postoperative gradient >20 mmHg [hazard ratio (HR) 6.56, 95% confidence interval (CI) 1.41-24.1; P = 0.005], tunnel-type SAS (HR 7.46, 95% CI 2.48-22.49; P < 0.001), aortic annulus z-score <-2 (HR 11.07, 95% CI 3.03-40.47; P < 0.001) and age at intervention <2 years (HR 3.24, 95% CI 1.09-9.86; P = 0.035). Addition of septal myectomy at initial intervention was not associated with lesser reintervention. Fourteen children with a lower left ventricular outflow tract (LVOT) gradient (P < 0.001) and older age at diagnosis (P = 0.024) were followed expectatively. CONCLUSIONS: Children with SAS remain at risk for reintervention, despite initially effective LVOT relief. Regardless of SAS morphology, age <2 years at first intervention, a postoperative gradient >20 mmHg and presence of a hypoplastic aortic annulus are independent risk factors for reintervention. More extensive LVOT surgery might be considered at an earlier stage in these children. SAS presenting in older children with a low LVOT gradient at diagnosis shows little progression, justifying an expectative approach.

Multidisciplinary Approach to the Child with Sex Chromosomal Mosaicism Including a Y-Containing Cell Line.

Children born with sex chromosomal mosaicism including material derived from the Y chromosome may present with a broad phenotypical spectrum. Both boys and girls can present with Turner features and functional health problems typically associated with Turner syndrome, but the presence of Y-chromosomal material can modify some aspects of the condition. We retrospectively analyzed the results of our cohort of 21 individuals (14 boys, 7 girls) with sex chromosomal mosaicism including Y-derived material followed at Ghent University Hospital according to our local multidisciplinary Turner surveillance protocol. Results were compared with literature data, focusing on similarities and differences between girls and boys with this condition. Age at diagnosis was lower in boys compared to girls but the difference was not significant. Short stature is a key feature of the condition both in girls and boys, but skeletal maturation may be different between groups. The effects of growth-hormone therapy remain unclear. Cardiac (33%), ear-nose- throat (ENT) (77.8%) and renal (28.6%) problems were as prevalent in boys as in girls from our cohort, and did not differ from literature data. In line with literature reports, a significant difference in the presence of premalignant germ cell tumors between males (0%) and females (42.9%) was found (p = 0.026). Taken together, this study demonstrates the similarities between girls with Turner syndrome and children with sex chromosomal mosaicism including Y-derived material, regardless of the child's gender. Nowadays, girls with Turner syndrome are offered a dedicated multidisciplinary follow-up in many centers. We advocate a similar follow-up program for all children who have sex chromosomal mosaicism that includes Y-derived material, with special attention to growth, cardiac and ear-nose-throat problems, gonadal function and malignancies.

Myocardial disease and ventricular arrhythmia in Marfan syndrome: a prospective study.

BACKGROUND: Aortic root dilatation and-dissection and mitral valve prolapse are established cardiovascular manifestations in Marfan syndrome (MFS). Heart failure and arrhythmic sudden cardiac death have emerged as additional causes of morbidity and mortality. METHODS: To characterize myocardial dysfunction and arrhythmia in MFS we conducted a prospective longitudinal case-control study including 86 patients with MFS (55.8% women, mean age 36.3 yr-range 13-70 yr-) and 40 age-and sex-matched healthy controls. Cardiac ultrasound, resting and ambulatory ECG (AECG) and NT-proBNP measurements were performed in all subjects at baseline. Additionally, patients with MFS underwent 2 extra evaluations during 30 ± 7 months follow-up. To study primary versus secondary myocardial involvement, patients with MFS were divided in 2 groups: without previous surgery and normal/mild valvular function (MFS-1; N = 55) and with previous surgery or valvular dysfunction (MFS-2; N = 31). RESULTS: Compared to controls, patients in MFS-1 showed mild myocardial disease reflected in a larger left ventricular end-diastolic diameter (LVEDD), lower TAPSE and higher amount of (supra) ventricular extrasystoles [(S)VES]. Patients in MFS-2 were more severely affected. Seven patients (five in MFS-2) presented decreased LV ejection fraction. Twenty patients (twelve in MFS-2) had non-sustained ventricular tachycardia (NSVT) in at least one AECG. Larger LVEDD and higher amount of VES were independently associated with NSVT. CONCLUSION: Our study shows mild but significant myocardial involvement in patients with MFS. Patients with previous surgery or valvular dysfunction are more severely affected. Evaluation of myocardial function with echocardiography and AECG should be considered in all patients with MFS, especially in those with valvular disease and a history of cardiac surgery.

Evaluation of cardiopulmonary exercise testing, heart function, and quality of life in children after allogenic hematopoietic stem cell transplantation.

BACKGROUND: Physical fitness is an important determinant of quality of life (QOL) after hematopoietic stem cell transplantation. Cardiac function can influence exercise performance. The aim of this study was to assess these factors and their interrelationship. PROCEDURE: Children underwent cardiopulmonary exercise testing (CPET) at least 1 year after hematopoietic stem cell transplantation (HSCT) and were compared with healthy controls. Systolic and diastolic heart function and left ventricle (LV) wall dimensions were measured. Health-related QOL (HR-QOL) was evaluated using PedsQL questionnaires. RESULTS: Forty-three patients performed CPET (26 boys, 13.6 ± 3.4 years, weight 45.5 ± 13.3 kg, length 152.9 ± 17.5 cm, body surface area 1.35 ± 0.28). HSCT patients had lower maximal oxygen consumption (VO2peak/kg, 34.7 ± 8.4 vs 46.3 ± 7.1 mL/kg/min, P < 0.001), shorter exercise duration (9.1 ± 2.5 vs 12.9 ± 2.6 min, P < 0.001), and lower maximal load (%Ppeak 70.8 ± 19.7 vs 102.4% ± 15.9%, P < 0.001). Echocardiography demonstrated decreased interventricular septal wall thickness (interventricular septum in diastole [IVSd] Z-value -0.64 ± 0.69, P < 0.001), and more systolic (11% of patients) and diastolic dysfunction (high E/E' Z-value 1.06 ± 1.13, P < 0.001). LV dilatation correlates with VO2max/kg (r = -0.364, P = 0.017). HR-QOL showed lower overall and emotional functioning scores (respectively, P = 0.016 and P = 0.001). Patients after anthracycline therapy have the lowest maximal exercise performance, but have no difference in QOL. Diminished exercise performance is not encountered as a QOL limitation. Total body irradiation influences the domain of psychosocial functioning. CONCLUSIONS: LV (systolic and diastolic) and right ventricle dysfunctions justify the need for thorough cardiac follow-up in children after HSCT. Lower physical fitness levels and lower HR-QOL emphasize the importance of CPET and fitness programs.

Surgical repair of atrioventricular septal defects: incidence and mode of failure of the left atrioventricular valve.

OBJECTIVES: Our goal was to investigate the outcome of the left atrioventricular valve (LAVV) after repair of atrioventricular septal defects (AVSDs) by analysing the mechanisms of LAVV failure. METHODS: A retrospective investigation of 202 children with AVSD, operated on between 1992 and 2016, was performed. Analysis focused on freedom from reoperation for LAVV dysfunction, with specific attention to the modes of failure. RESULTS: The population consisted of 129 (64%) patients with complete AVSD (cAVSD) and 73 (36%) patients with partial AVSD (pAVSD), corrected at a median age of 3.9 (interquartile range 3.4) months and 29.0 (interquartile range 90.4) months, respectively. Within a median follow-up period of 5.9 (interquartile range 12.6) years, 27 (13.4%) patients required reoperation for LAVV failure, respectively, in 17 (13.2%) patients with cAVSD and 10 (13.9%) patients with pAVSD. Freedom from reoperation for LAVV at 10 years was 87 ± 4% for cAVSD and 87 ± 5% for pAVSD (P = 0.789). The failure mode was predominantly technical in cAVSD (71% vs 20% in pAVSD), whereas residual anatomical anomalies entailed more frequently LAVV regurgitation (LAVVR) in pAVSD (80% vs 29% in cAVSD) (P = 0.018). Cleft suture dehiscence (n = 8) and incomplete cleft closure (n = 6) were considered technical failures, whereas remnant distortions of the subvalvular apparatus (n = 9), small asymmetric bridging leaflet (n = 2), double orifice (n = 1) and additional cleft (n = 1) were considered anatomical lesions. The incidence of repair at the 1st reoperation was 92.6%. Eight patients needed a 2nd and 2 patients a 3rd repeat LAVV operation. Five patients finally ended with a mechanical prosthesis. CONCLUSIONS: In the long term, patients with AVSD are still subject to LAVV failure. Despite systematic cleft closure, patients with cAVSD develop LAVV failure mainly because of a recurrent/residual deficit at the cleft, amenable to technical improvement. Patients with pAVSD need increased attention for additional anatomical features of the LAVV at the time of primary repair.

Small-sized conduits in the right ventricular outflow tract in young children: bicuspidalized homografts are a good alternative to standard conduits.

OBJECTIVES: Downsizing a homograft (HG) through bicuspidalization has been used for more than 2 decades to overcome the shortage of small-sized conduits for reconstruction of the right ventricular outflow tract (RVOT) in young children. Our goal was to investigate the durability of bicuspidalized HGs compared with other small HGs. METHODS: A retrospective analysis of 93 conduits ≤20 mm, implanted over 23 years, was performed. The end-points were survival, structural valve degeneration and conduit replacement. The conduits comprised 40 pulmonary HGs, 12 aortic HGs, 17 bicuspidalized HGs and 24 xenografts. RESULTS: The median age, mean conduit diameter and z-value at implantation were 1.4 (interquartile range 0.3-3) years, 16.5 ± 2.7 mm and 2.8 ± 1.3, respectively. Valve position was heterotopic in 59 patients and orthotopic in 34 patients. At a mean follow-up period of 7.6 ± 5.9 years, the hospital survival rate was 89%. Freedom from explant at 5 and 10 years was 83 ± 5% and 52 ± 6%, respectively. Freedom from structural valve degeneration was 79 ± 5% at 5 years and 47 ± 6% at 10 years [68 ± 8% for pulmonary HG, 42 ± 16% for bicuspidalized HG, 31 ± 15% for aortic HG and 20 ± 9% for xenografts (log rank P < 0.001)]. Multivariable analysis indicated an increased risk for structural valve degeneration with smaller conduit size (hazard ratio 0.79, 95% confidence interval 0.67-0.94; P < 0.008), extra-anatomic position (hazard ratio 2.71, 95% confidence interval 1.33-5.50; P = 0.006) and the use of xenografts compared with non-downsized pulmonary HGs (hazard ratio 4.90, 95% confidence interval 2.23-10.76; P < 0.001). CONCLUSIONS: Appropriately sized pulmonary HGs remain the most durable option for a right ventricular outflow tract conduit in young children. However, when a small pulmonary HG is unavailable, bicuspidalization offers a valid alternative, preferable to xenograft conduits, at mid-term follow-up.

Outcome after prenatal and postnatal diagnosis of complex congenital heart defects and the influence of genetic anomalies.

OBJECTIVE: Determine prenatal detection rate, mortality and association with genetic abnormalities in patients with severe CHD. METHOD: Single center retrospective study in patients with severe CHD diagnosed prenatally or postnatally (2006 to 2014). RESULTS: A total of 567 patients were included, 176 (31%) after prenatal diagnosis, with large differences in prenatal detection rate among CHD types. Coarctation (24%), tetralogy of Fallot (21%) and univentricular heart (19%) were the most prevalent CHD. Overall mortality rate was 30% with important contributions of prenatal mortality including termination of pregnancy (40%) and postnatal compassionate care (15%). In the group requiring surgery, mortality rate was 12%. Genetic testing was available in 70%. A genetic cause was present in 140/394 patients tested (36%; 25% in the total group). Mortality was higher in the group with abnormal genetic testing compared with those with normal or no genetic testing (57/141 vs 112/423; p = 0,002). CONCLUSION: Only one third of severe CHD are detected; overall mortality remains high (30%) with major contributions of termination of pregnancy and compassionate care. A genetic cause was found in 36% and was associated with a decreased survival. Counseling must include the possibility of associated genetic pathology and its impact on survival. © 2017 John Wiley & Sons, Ltd.

Current outcomes of the bi-directional cavopulmonary anastomosis in single ventricle patients: analysis of risk factors for morbidity and mortality, and suitability for Fontan completion.

OBJECTIVES: The bi-directional cavopulmonary anastomosis forms an essential staging procedure for univentricular hearts. This review aims to identify risk factors for morbidity, mortality, and suitability for Fontan completion. METHODS: A total of 114 patients undergoing cavopulmonary anastomosis between 1992 and 2012 were reviewed to assess primary - mortality and survival to Fontan completion - and secondary outcome endpoints - re-intubation, new drain, and ICU stay. Median age and weight were 8 months and 6.9 kg, respectively. In 83% of patients, 1-3 interventions had preceded. Norwood-type procedures became more prevalent over time. RESULTS: Extubation occurred after a median of 4 hours, median ICU stay was 2 days; 10 patients (8.8%) needed re-intubation and 18 received a new drain. Higher central venous pressure and transpulmonary gradient were risk factors for new drain insertion (p<0.01). Higher pre-operative pulmonary pressure correlated with increased inotropic support and prolonged intubation (p=0.01). Need for re-intubation was significantly affected by younger age at operation (p=0.01). Hospital and pre-Fontan mortality were 11.4 and 5.3%, respectively. Operative mortality was independently affected by younger age (p=0.013), lower weight (p=0.02), longer bypass time (p=0.04), and re-intubation (p=0.004). Interstage mortality was mainly influenced by moderate ventricular function (p=0.03); 82% of survivors underwent or are candidates for Fontan completion. CONCLUSION: The cavopulmonary anastomosis remains associated with adverse outcomes. Age at operation decreases with rising prevalence of complex univentricular hearts. Considering the important impact of re-intubation on hospital mortality, peri-operative management should focus on optimising cardio-respiratory status. Once this selection step is taken, successful Fontan completion can be expected, provided that ventricular function is maintained.

Disease-specific outcome analysis of palliation with the modified Blalock-Taussig shunt.

BACKGROUND: Albeit being a simple surgical procedure, adverse outcomes with the modified Blalock-Taussig shunt (MBTS) are commonly reported in generalizing terms, independent of the underlying heart disorder. METHODS: From August 1995 to December 2013, a total of 150 children underwent an MBTS for tetralogy of Fallot (TOF; n = 44, 29%), pulmonary atresia with ventricular septal defect (PA/VSD; n = 28, 19%), pulmonary atresia with intact ventricular septum (PA/IVS; n = 17, 11%), transposition of the great arteries with ventricular septal defect (TGA/VSD) with pulmonary stenosis (PS; n = 12, 8%), Ebstein malformation (n = 2, 1%), and complex univentricular anomalies (n = 47, 31%). Outcome analysis focused on operative mortality and survival until shunt takedown, adjusted to the underlying disease. RESULTS: In-hospital mortality was 8.7% (n = 13), and interstage mortality was 5.1% (n = 7), resulting in 86.1% survival to the next surgery. Hospital mortality was 14% in PA/VSD, 13% in univentricular heart, and 18% in PA/IVS, while no mortality was observed in TOF, TGA/VSD/PS, and Ebstein disease. A shunt-related complication was observed in 18% (n = 27) of the children, including acute thrombosis (n = 7, 5%), shunt stenosis (n = 3, 2%), overshunting (n = 7, 5%), and pulmonary artery stenosis (n = 10, 7%). Multivariate analysis of shunt-dependent time survival identified a shunt complication occurring in a univentricular circulation (hazard ratio [HR] 4.10, 95% confidence interval [CI] = 1.05-17.43, P = .01) and increased shunt size-to-weight ratio (HR 2.72, 95% CI = 0.80-9.18, P = .04) as risk factors. Shunt thrombosis was also a negative outcome predictor in PA/VSD, when requiring associated unifocalization (P = .05). CONCLUSION: This study shows that the outcome of palliation with the MBTS is importantly affected by the occurrence of a shunt-related complication, whose circulatory effect is even more dismal in single ventricle hearts. Since an increased shunt size-to-weight ratio additionally compromises the shunt-dependent survival, it emphasizes that the choice of the shunt with regard to size as well as surgical approach remains critical.

Analysis of the aortic root in patients with tetralogy of Fallot undergoing early repair: form follows function.

OBJECTIVE: Aortic root dilatation remains of concern late after repair for tetralogy of Fallot (ToF). We have previously demonstrated that the aortic root size decreases progressively after early correction. To test whether the aortic wall changes are intrinsic or acquired, a histologic study was performed of infants at early repair. METHODS: From 24 of 31 infants undergoing ToF repair (mean age, 5.9±4.9 months), ascending aortic biopsies were obtained. After conventional staining, the specimens were given a histologic score (0-3) for medionecrosis, ground substance accumulation, fibrosis, smooth muscle cell disarray, and apoptosis. The aortic root diameters were monitored using echocardiography for ≤2 years postoperatively. RESULTS: Nearly one half of the specimens showed signs of fibrosis (45%), with increased mucoid accumulation in 15% and elastin fragmentation in 5%. The aortic root was dilated in all infants at operation (mean indexed diameter-annulus, 38.1±5.8; sinus, 47.8±6; sinotubular junction, 38.7±5.4 mm/m2) and had regressed significantly within 2 years (mean indexed diameter-annulus, 27.9±4.7; sinus, 36.4±5.1; sinotubular junction, 30.4±6 mm/m2; P<.0001). The total histology score showed no correlation with indexed diameter regression at 2 years. CONCLUSIONS: Infants with ToF undergoing repair around 6 months old already had limited features of aortic wall degradation at surgery. Echocardiographic follow-up, however, demonstrated significant reductions in the indexed aortic diameters. We presume that early repair of ToF will prevent a disproportionate aortic diameter increase by halting progression of the limited histologic changes potentially predisposing to late aortic dilatation.

Functional analysis of the anatomical right ventricular components: should assessment of right ventricular function after repair of tetralogy of Fallot be refined?

OBJECTIVE: Follow-up after tetralogy of Fallot (ToF) repair is directed to detect timely right ventricular (RV) dysfunction by following pulmonary regurgitation and global RV size, with little attention for the effective contribution of regional RV dysfunction. This study investigates the contribution of regional RV dysfunction on exercise capacity after ToF repair. METHODS: Forty-two patients were investigated with cardiac magnetic resonance imaging for regional RV dysfunction in relation to global RV function by functional quantification of the sinus and outflow part of the RV. The impact of regional and global RV dysfunction on clinical status was studied by exercise testing. RESULTS: Global RV function was lower than sinus function (ejection fraction (EF) 52±12% vs 58±10%, P<0.001), attributable to the adverse influence of right ventricular outflow tract (RVOT) dysfunction (EF 34±17%). Percent predicted peak VO2 correlated better with the RV sinus ejection fraction compared with the global RV ejection fraction (r=0.51, P=0.001 vs r=0.44, P=0.004). Multivariate analysis revealed the EF of RV sinus (ß=0.34, 95% CI 0.07-0.61, P=0.013) and the extent of RVOT akinesia (ß=-0.28, 95% CI -0.50; -0.06, P=0.015) as significant determinants of exercise capacity. Impaired exercise performance occurred in 43% of the patients, and was independently determined by the type of repair (transventricular vs transatrial: OR 6.0, 95% CI 1.31-17.3, P=0.02) by associating greater sinus and RVOT dysfunction. CONCLUSION: Functional analysis of the RV components shows that exercise capacity after repair of ToF is better predicted by systolic function of the RV sinus as the extent of RVOT dysfunction commonly leads to underestimation of global RV function. This method of differential quantification of regional RV function might be more appropriate than assessment of global RV function during the long-term follow-up of repaired ToF patients.

Univentricular heart and Fontan staging: analysis of factors impacting on body growth.

OBJECTIVES: The optimal timing of the Fontan staging for a univentricular heart and its impact on growth remains debateable. In a Fontan cohort, the influence of staged interventions and patient factors on somatic development was explored. METHODS: We reviewed 64 total cavopulmonary connection (TCPC) patients treated since 1992. Serial anthropometric parameters recorded from birth to the latest follow-up (mean 12.5 ± 6.1 years) and at each intervention [neonatal surgery, bidirectional cavopulmonary anastomosis (BCPA), TCPC, catheter treatment] were converted to z-scores. The influence of saturation, heart failure treatment and surgery intervals on growth was determined. RESULTS: The mean z-scores for weight and height changed significantly at each surgery up to the TCPC (-0.3 ± 1.2 and 0 ± 1 at birth, -1.3 ± 1.9 and -0.9 ± 1.7 at neonatal surgery, -2.1 ± 1.2 and -1.6 ± 1.3 at the BCPA, -1.2 ± 1.3 and -0.7 ± 1.4 at the TCPC for weight and height, respectively; P < 0.05 for each interval), with the largest decline before the BCPA, and the most marked improvement before the TCPC. Z-scores did not change significantly after the TCPC. Younger age at the BCPA had a positive influence on the weight z-score at the TCPC (P < 0.05); somatic growth at the latest follow-up (FU) was negatively influenced by heart failure treatment (P < 0.05). CONCLUSIONS: Body growth is severely impaired in Fontan patients. A close interstage follow-up between the first surgery and the BCPA must be targeted at optimizing nutritional support to counter the important growth retardation occurring before the BCPA. The better catch-up growth at the TCPC when the BCPA is performed earlier in life supports the current trend to perform the BCPA at a younger age. Heart failure treatment after a Fontan completion is independently associated with decreased late somatic development.

Assessment of a right-ventricular infundibulum-sparing approach in transatrial-transpulmonary repair of tetralogy of Fallot.

OBJECTIVE: The study aimed to evaluate the outcome of transatrial-transpulmonary repair of tetralogy of Fallot in relation to a right-ventricular outflow tract (RVOT)-sparing surgery. METHODS: Based on the surgical management of right-ventricular outflow tract obstruction (RVOTO) at repair of tetralogy of Fallot, 140 children were retrospectively divided into three groups: (1) pulmonary valve (PV)-sparing, (2) infundibulum-sparing and (3) extended trans-annular patch (TAP). Clinical and echocardiographic outcome was assessed with regards to three equally divided study time eras between January 1994 and June 2010. RESULTS: Over a 15-year study period, median age decreased from 11 (2-101) to 5 (1-11) months (p<0.001), whereas type of RVOT repair changed significantly between the first and the last era (group 1: 18-40%, group 2: 25-40% vs group 3: 57-20% (p=0.002)). Mortality was 0%. Complications were mainly related to clinical restrictive RV physiology (27%) and arrhythmia (10%). This cardiac morbidity remained constant over the eras and was associated with younger age (p=0.04), increased postoperative right ventricle/left ventricle (RV/LV) pressure ratio (p=0.01) and type of RVOT repair at the cost of TAP (p=0.03). Median follow-up of 8 years (1-16 years) showed an overall freedom from RVOT re-operation of 84% and 73%, respectively at 5 and 10 years. Most re-operations were for residual/recurrent RVOTO (12%) occurring more frequently in the latter era: 16% versus 7% in era 1 (p=0.08). Late echocardiographic evaluation revealed a strong correlation between severity of pulmonary regurgitation and increased RV/LV size ratio, which was mainly determined by increased TAP length (p<0.001) and duration of follow-up (p=0.06). CONCLUSION: In a 15-year's experience with transatrial-transpulmonary correction of tetralogy of Fallot, a valve- and infundibulum-sparing approach has been advanced by lowering the age for elective repair. This change has been performed without compromising immediate clinical outcome, despite an increased early re-operation rate for residual obstruction. However, longer follow-up will disclose whether this approach is protective against progressive and late RV dysfunction.

The fate of the aortic root after early repair of tetralogy of Fallot.

OBJECTIVE: Late aortic root dilatation is a growing concern in patients operated on for tetralogy of Fallot (ToF). This longitudinal follow-up study sought to evaluate the changes in the aortic root dimensions in relation to body growth, assuming that early repair of tetralogy of Fallot might prevent late aortic dilatation. METHODS: A retrospective analysis of the aortic root dimensions was performed in 88 patients repaired early for tetralogy of Fallot by echocardiographic measurement of aortic annulus, sinus of Valsalva and sinotubular junction, adjusted for body surface area and expressed as z-scores. Mean age at repair was 9.7 + or - 7.4 months. Median age was 7.3 months (range 45 days-29 months). RESULTS: At the time of repair, all root dimensions were enlarged: z-score of the annulus 3.32 + or - 1.66; sinus 3.54 + or - 1.49; sinotubular junction 2.74 + or - 1.19. Within a mean follow-up of 6.9 + or - 4.4 years, the mean z-scores of both annulus and sinotubular junction significantly decreased to normal size at 7 years postoperatively: z-score of annulus 0.95 + or - 0.7 (p=0.006), z-score of sinotubular junction 0.99 + or - 1.47 (p=0.006). The z-score of the aortic sinuses appeared to regress slower to 2.78 + or - 1.26 (p=0.262). The indexed sinus diameter however regressed significantly from a mean of 51.4 + or - 13.4 mmm(-2) at correction to 28.9 + or - 7.2 mmm(-2) (p=0.0001) at latest follow-up. Evolution of aortic root size after repair was independent of aortic arch side, sex, age at repair or previous shunt palliation. CONCLUSIONS: The initially dilated aortic root in tetralogy of Fallot normalises in size at the level of the annulus and sinotubular junction within 7 years after early repair. This process seems delayed at the level of the aortic sinuses, although the indexed root diameter shows significant regression over time. These results suggest that early repair of ToF abrogates the enlargement of the aortic root, validating one aspect of the need for tetralogy correction at a young age.

Pleural effusions, water balance mediators and the influence of lisinopril after completion Fontan procedures.

OBJECTIVE: To investigate whether the duration of pleural drainage after Fontan completion operations can be influenced by postoperative lisinopril administration or can be related to water balance hormone levels. METHODS: In a prospective trial 21 patients scheduled for total cavopulmonary connection were randomized into two groups, with group I receiving lisinopril postoperatively, and group II receiving no angiotensin converting enzyme inhibitor. Plasma levels of antidiuretic hormone, renin and aldosteron were analyzed preoperatively and at four-time points postoperatively. Groups were comparable for age, preoperative saturation and pulmonary pressure, cardiopulmonary bypass time, cross-clamp time and preoperative hormone levels. RESULTS: Mean duration of pleural drainage was comparable for both groups (group I: 9.6+/-8 days vs group II: 10+/-7 days; p=0.78). The hormone profiles in each group changed significantly at 1 and 24h postoperatively compared to preoperative values (p<0.05), with no significant differences between the treatment groups. The duration of pleural drainage correlated significantly with hormone levels at 24h postoperatively, and with longer bypass times. At multivariate analysis only aldosteron and antidiuretic hormone level at 24h came out as factors reaching significance for prolonged pleural drainage. CONCLUSIONS: The Fontan completion induces significant changes in the levels of antidiuretic hormone, aldosteron and renin. Prolonged drainage correlates significantly with elevated levels of aldosteron, renin and antidiuretic hormone postoperatively, and with longer bypass time, but is not influenced by lisinopril. The eventual adjunct therapy with aldosteron antagonists warrants further study.

Midterm assessment of the reconstructed arteries after the arterial switch operation.

BACKGROUND: The arterial switch operation is the preferred treatment for transposition of the great arteries (TGA), but there are concerns on the fate of the neoarterial trunks. METHODS: Ninety-three children were reviewed for functional and morphologic assessment of both reconstructed arteries after the arterial switch operation. Longitudinal analysis focused on neoaortic valve function, neoaortic obstruction, and neopulmonary stenosis as well as on the time-related size changes of both roots, with its clinical implications. RESULTS: Within a mean follow-up of 4.8 +/- 3.9 years, aortic regurgitation of 2 or greater developed in 10% in TGA with intact ventricular septum (IVS) versus 23% in TGA with ventricular septal defect (VSD). A VSD and major pulmonary to aortic annulus size discrepancy were main precursors of early neoaortic valve dysfunction, whereas development of aortic regurgitation of 2 or greater was additionally promoted by the duration of follow-up. Presence of a VSD enhanced neoaortic root enlargement, resulting in a mean root z-score of 3.25 in TGA/VSD versus 1.96 in TGA/IVS. Root dilation was more severe in case of aortic regurgitation of 2 or greater (z = 3.38). Neoaortic obstruction occurred in 8%, mostly at the neosinotubular anastomosis, and correlated with prior pulmonary to aortic ratio greater than 1.5. Concerning the neopulmonary tract, increased flow velocity was observed in 24%, primarily at the supravalvular level. Two patients with pulmonary annulus hypoplasia (z < -2) required early reintervention. Regarding clinical outcome, freedom from reintervention at 1, 5, and 10 years was, respectively, 98%, 96%, and 96% for TGA/IVS, versus 65%, 63%, and 63% for TGA/VSD. A VSD and aortic arch obstruction were significant predictors for reintervention. CONCLUSIONS: After arterial switch operation, the neoaortic root is usually enlarged, but with a growth pattern comparable to that of a normal population. The association of a VSD and major arterial root size discrepancy predisposes to both neoaortic valve dysfunction and root enlargement. Severe root dilation appears to be closely related to significant neoaortic valve regurgitation, mainly as a result of a time-depending and reciprocal process. Neopulmonary stenosis is a frequent finding, but rarely has clinical consequences. Because the factor "time" is the principal determinant of late neoaortic valve dysfunction and root dilation, strict serial surveillance after arterial switch operation is mandatory.