Evaluation of a nurse-led multi-component transition program for adolescents with congenital heart disease.

OBJECTIVE: To evaluate the effectiveness of the transition program for adolescents with congenital heart disease (CHD) 'Transition With a Heart' (TWAH) on disease-related knowledge, quality of life (QoL), transition experiences, and gaps in follow-up. METHODS: A study with pre-posttest and control group (post-test) using consecutive sampling, including adolescents with moderate to severely complex CHD, without intellectual disability, aged≥ 12 y, and parents. After weighting, t-tests were performed. A multivariable regression analysis explored the outcomes' determinants. RESULTS: In the intervention group, 28 adolescents and 25 parents were included, and 53 adolescents and 18 parents as controls. Adolescents' knowledge significantly increased after completing TWAH (from 59.8% to 75.7%;p < 0.01). Their knowledge was positively correlated with TWAH (ß = +13.3;p < 0.01). Adolescents' transition experiences were also positively related to TWAH (general experience: ß = +5.5;p < 0.01; transfer satisfaction: ß = +0.8; p < 0.01). Adolescents' QoL was mainly determined by CHD complexity and not by TWAH. No one showed gaps in follow-up. TWAH was not associated with parents' transition experiences. CONCLUSION: Implementing TWAH substantially improved adolescents' disease-related knowledge and transition experiences. PRACTICE IMPLICATIONS: The results regarding transition experiences need to be confirmed by further research. The TWAH design with the person-tailored educational program, skills training, and the transition coordinator can be used in settings with other chronic diseases.

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.

Multimodality 3D image fusion with live fluoroscopy reduces radiation dose during catheterization of congenital heart defects.

Introduction: Imaging fusion technology is promising as it is radiation and contrast sparing. Herein, we compare conventional biplane angiography to multimodality image fusion with live fluoroscopy using two-dimensional (2D)-three-dimensional (3D) registration (MMIF2D-3D) and assess MMIF2D-3D impact on radiation exposure and contrast volume during cardiac catheterization of patients with congenital heart disease (CHD). Methods: We matched institutional MMIF2D-3D procedures and controls according to patient characteristics (body mass index, age, and gender) and the seven procedure-type subgroups. Then, we matched the number of tests and controls per subgroup using chronological ordering or propensity score matching. Subsequently, we combined the matched subgroups into larger subgroups of similar procedure type, keeping subgroups with at least 10 test and 10 control cases. Air kerma (AK) and dose area product (DAP) were normalized by body weight (BW), product of body weight and fluoroscopy time (BW × FT), or product of body weight and number of frames (BW × FR), and stratified by acquisition plane and irradiation event type (fluoroscopy or acquisition). Three senior interventionists evaluated the relevance of MMIF2D-3D (5-point Likert scale). Results: The Overall group consisted of 54 MMIF2D-3D cases. The combined and matched subgroups were pulmonary artery stenting (StentPUL), aorta angioplasty (PlastyAO), pulmonary artery angioplasty (PlastyPUL), or a combination of the latter two (Plasty). The FT of the lateral plane reduced significantly by 69.6% for the Overall MMIF2D-3D population. AKBW and DAPBW decreased, respectively, by 43.9% and 39.3% (Overall group), 49.3% and 54.9% (PlastyAO), and 36.7% and 44.4% for the Plasty subgroup. All the aforementioned reductions were statistically significant except for DAPBW in the Overall and Plasty (sub)groups. The decrease of AKBW and DAPBW in the StentPUL and PlastyPUL subgroups was not statistically significant. The decrease in the median values of the weight-normalized contrast volume (CMCBW) in all five subgroups was not significant. Cardiologists considered MMIF2D-3D very useful with a median score of 4. Conclusion: In our institution, MMIF2D-3D overall enabled significant AKBW reduction during the catheterization of CHD patients and was mainly driven by reduced FT in the lateral plane. We observed significant AKBW reduction in the Plasty and PlastyAO subgroups and DAPBW reduction in the PlastyAO subgroup. However, the decrease in CMCBW was not significant.

Pulmonary artery banding as adjunct therapy for ventricular recovery after anomalous left coronary artery from the pulmonary artery repair: a case report.

Anomalous left coronary artery from the pulmonary artery is a rare congenital coronary anomaly commonly associated with severe but reversible left ventricular dysfunction. We present an anomalous left coronary artery from the pulmonary artery case of persisting left ventricular failure with inability to wean off the ventilator and inotropes after successful coronary reimplantation, in whom pulmonary artery banding enhanced myocardial recovery.

Exploring the Mutational Landscape of Isolated Congenital Heart Defects: An Exome Sequencing Study Using Cardiac DNA.

Congenital heart defects (CHD) are the most common congenital anomalies in liveborn children. In contrast to syndromic CHD (SCHD), the genetic basis of isolated CHD (ICHD) is complex, and the underlying pathogenic mechanisms appear intricate and are incompletely understood. Next to rare Mendelian conditions, somatic mosaicism or a complex multifactorial genetic architecture are assumed for most ICHD. We performed exome sequencing (ES) in 73 parent-offspring ICHD trios using proband DNA extracted from cardiac tissue. We identified six germline de novo variants and 625 germline rare inherited variants with 'damaging' in silico predictions in cardiac-relevant genes expressed in the developing human heart. There were no CHD-relevant somatic variants. Transmission disequilibrium testing (TDT) and association testing (AT) yielded no statistically significant results, except for the AT of missense variants in cilia genes. Somatic mutations are not a common cause of ICHD. Rare de novo and inherited protein-damaging variants may contribute to ICHD, possibly as part of an oligogenic or polygenic disease model. TDT and AT failed to provide informative results, likely due to the lack of power, but provided a framework for future studies in larger cohorts. Overall, the diagnostic value of ES on cardiac tissue is limited in individual ICHD cases.

Hypertension after coarctation repair-a systematic review.

Background: Coarctation of the Aorta (CoA) leads to increased morbidity and mortality later in life despite early surgical or percutaneous treatment. Many long-term complications are related to hypertension (HT) which is a common finding late after coarctation repair. Methods: A systematic Review was performed including articles published between February 2012 to December 2020. Systematic searches were conducted on PubMed and the Cochrane Controlled Trials Register to look for studies on HT after aortic CoA-repair. PRISMA guidelines were used. Results: In this systematic review on HT after CoA Repair the mean prevalence of HT was 47.3% (20-70%). A progressive character was of the HT was found, furthermore if only studies are included with 24 h blood pressure (BP) recording in addition to standard BP measurements, the incidence of HT rose to 57.8%. Discussion: Most clinical studies look at complications, mortality rate and residual pressure gradient rather than correlating hemodynamic indices with long-term outcome. Although HT is commonly based in measurement of peripheral BP, it has been shown that peripheral BP in CoA patients has a poor correlation with central aortic pressure. Central aortic hemodynamics are significantly altered in patients with repaired CoA, which can now adequately be investigated non-invasively. At the present time there are no studies linking long-term outcome with abnormal central hemodynamics.

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.

Ethical and practical dilemmas in cardiac transplantation in infants: a literature review.

The waiting time in infants for a cardiac transplant remains high, due to the scarcity of donors. Consequently, waiting list morbidity and mortality are higher than those in other age groups. Therefore, the decision to list a small infant for cardiac transplantation is seen as an ethical dilemma by most physicians. This review aims to describe outcomes, limitations, and ethical considerations in infant heart transplantation. We used Medline and Embase as data sources. We searched for publications on infant (< 1 year) heart transplantation, bridge-to-transplant and long-term outcomes, and waiting list characteristics from January 2009 to March 2021. Outcome after cardiac transplant in infants is better than that in older children (1-year survival 88%), and complications are less frequent (25% CAV, 10% PTLD). The bridge-to-transplant period in infants is associated with increased mortality (32%) and decreased transplantation rate (43%). This is mainly due to MCS complications or the limited MCS options (with 51% mortality in infancy). Outcomes are worse for infants with CHD or in need of ECMO-support.Conclusion: Infants listed for cardiac transplantation have a high morbidity and mortality, especially in the period between diagnosis and transplantation. For those who receive cardiac transplant, the outlook is encouraging. Unfortunately, despite growing experience in VAD, mortality in children < 10 kg and children with CHD remains high. After transplantation, patients carry a psychological burden and there is a probability of re-transplantation later in life, with decreased outcomes compared to primary transplantation. These considerations are seen as an important ethical dilemma in many centers, when considering cardiac transplantation in infants (< 1 year). What is Known: • For infants, waitlist mortality remains high. In the pediatric population, MCS reduces the waiting list mortality. What is New: • Outcomes after infant cardiac transplantation are better than other age groups; however, MCS options remain limited, with persistently high waiting list mortality. • Future developments in MCS and alternative options to reduce waiting list mortality such as ABO-incompatible transplantation and pulmonary artery banding are encouraging and will improve ethical decision-making when an infant is in need of a cardiac transplant.

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.

Determinants of Physical Fitness in Children with Repaired Congenital Heart Disease.

The aim of this study was to determine factors associated with physical fitness (PF) in children who underwent surgery for congenital heart disease (CHD). Sixty-six children (7-14 years) who underwent surgery for ventricular septal defect (n = 19), transposition of great arteries (n = 22), coarctation of aorta (n = 10), and tetralogy of Fallot (n = 15) were included. All children performed PF tests: cardiorespiratory fitness, upper- and lower-limb muscle strength, speed, balance, and flexibility. Cardiac evaluation was done via echocardiography and cardiopulmonary exercise test. Factors related to child's characteristics, child's lifestyle, physical activity motivators/barriers, and parental factors were assessed. Linear regression analyses were conducted. The results showed no significant differences in physical activity (PA) level by CHD type. Boys had better cardiorespiratory fitness (difference = 1.86 ml/kg/min [0.51;3.22]) and were more physically active (difference = 19.40 min/day [8.14;30.66]), while girls had better flexibility (difference = - 3.60 cm [- 7.07;- 0.14]). Physical activity motivators showed an association with four out of six PF components: cardiorespiratory fitness, coefficient = 0.063 [0.01;0.11]; upper-limb muscle strength, coefficient = 0.076 [0.01;0.14]; lower-limb muscle strength, coefficient = 0.598 [0.07;1.13]; and speed, coefficient = 0.03 [0.01;0.05]. Age, sex, and motivators together reached a maximum adjusted R2 = 0.707 for upper-limb strength. Adding other possible determinants did not significantly increase the explained variance. Apart from age and sex as non-modifiable determinants, the main target which might improve fitness would be the introduction of an intervention which increases the motivation to be active.

Analysis of the recovery phase after maximal exercise in children with repaired tetralogy of Fallot and the relationship with ventricular function.

BACKGROUND: Few studies demonstrate delayed recovery after exercise in children and adults with heart disease. We assess the recovery patterns of gas exchange parameters and heart rate (HR) in children with repaired Tetralogy of Fallot (rToF) compared to healthy peers and investigate the correlation with ventricular function and QRS duration. METHODS: 45 children after rToF and 45 controls performed a maximal incremental cardiopulmonary exercise test. In the subsequent recovery period, patterns of VO2, VCO2 and HR were analysed. Half-life time (T1/2) of the exponential decay and drop per minute (Recmin) were compared between groups. In the rToF group, correlations were examined between the recovery parameters and QRS-duration and ventricular function, described by fractional shortening (FS) and tricuspid annular plane systolic excursion (TAPSE) measured at baseline prior to exercise. RESULTS: Recovery of VO2 and VCO2 was delayed in rToF patients, half-life time values were higher compared to controls (T1/2VO2 52.51 ±11.29 s vs. 44.31 ± 10.47 s; p = 0.001 and T1/2VCO2 68.28 ± 13.84 s vs. 59.41 ± 12.06 s; p = 0.002) and percentage drop from maximal value was slower at each minute of recovery (p<0.05). Correlations were found with FS (T1/2VO2: r = -0.517; p<0.001; Rec1minVO2: r = -0.636, p<0.001; Rec1minVCO2: r = -0.373, p = 0.012) and TAPSE (T1/2VO2: r = -0.505; p<0.001; Rec1minVO2: r = -0.566, p<0.001; T1/2VCO2: r = -0.466; p = 0.001; Rec1minVCO2: r = -0.507, p<0.001), not with QRS-duration. No difference was found in HR recovery between patients and controls. CONCLUSIONS: Children after rToF show a delayed gas exchange recovery after exercise. This delay correlates to ventricular function, demonstrating its importance in recovery after physical activity.

Effect of aortic stiffness versus stenosis on ventriculo-arterial interaction in an experimental model of coarctation repair.

OBJECTIVES: The aim of this study was to investigate the effect of short- versus long-segment aortic stiffness and stenosis on ventriculo-arterial interaction in a porcine model of coarctation repair. METHODS: Short-long aortic stiffness was created by transection/suture [coarctation (CoA) suture, n = 6] and stenting (stent, n = 5) of the proximal descending aorta. Short-long aortic stenosis was achieved by wrapping a prosthetic graft around the aorta to 1/3-circumference reduction, over a segment length of 1 cm (CoA suture stenosis, n = 5) and 4.5 cm (stent stenosis, n = 6). After 3 months, aortic pressure-flow haemodynamics, aortic distensibility by intravascular ultrasound and left ventricular performance by pressure-volume loops were compared to a Sham group (n = 5) at baseline and during dobutamine administration. RESULTS: The aortic impedance increased with 30.3 (12.6%) and 41.3 (20.9%) (P < 0.001) in CoA stenosis and stent stenosis during inotropic response. Impaired haemodynamic aortic compliance was associated with lower aortic distensibility by intravascular ultrasound, specifically in long-segment stenosis. The ventriculo-arterial coupling was disturbed in both groups with stenosis, with blunted contractile response [Sham 140.3 (19.8%), CoA suture 101.3 (14.5%), CoA suture stenosis 75.0 (8.4%), stent 115.5 (12.7%), stent stenosis 55.1 (14.6%), P < 0.001] and increased myocardial stiffness during dobutamine in the long-segment aortic stenosis group [Sham -26.0 (12.9%), CoA suture -27.5 (15.9%), CoA stenosis -9.5 (8.6%), stent -23.4 (4.8%), stent stenosis 19.9 (23.1%), P < 0.001]. CONCLUSIONS: This animal study on the sequelae of coarctation repair demonstrated that aortic stiffness had little effect on aortic pressure-flow characteristics in the absence of stenosis. However, the negative chronic effect of stenosis on aortic haemodynamics-especially a longer segment-leads to the rapid impairment of ventriculo-arterial interaction, which is accentuated by inotropy. Therefore, therapeutical management needs to focus on improving aortic remodelling after coarctation repair, preferably by minimizing residual stenosis, even at the cost of inducing aortic stiffness.

Echocardiography during submaximal isometric exercise in children with repaired coarctation of the aorta compared with controls.

Objective: Patients with repaired coarctation (RCoA) remain at higher risk of cardiac dysfunction, initially often only detected during exercise. In this study, haemodynamics of isometric handgrip (HG) and bicycle ergometry (BE) were compared in patients with RCoA and matched controls (MCs). Methods: Case-control study of 19 children with RCoA (mean age 12.9±2.3 years; mean age of repair 7 months) compared with 20 MC. HG with echocardiography followed by BE was performed in both groups. Results: During HG (blood pressure) BP increased from 114±11/64±4 mm Hg to 132±14/79±7 mm Hg, without significant differences. During HG as well as BE, HR increased less in patients with RCoA. There were no significant differences in (left ventricle) LV dimensions or LV mass.The RCoA group had diastolic dysfunction: both at rest and during HG they had significantly higher transmitral E and A velocities and lower tissue Doppler E' and A' velocities. E/E' was higher, reaching statistical significance during HG (p<0001).Conventional parameters of systolic function (FS and EF) were similar at rest and HG. More sensitive tissue Doppler S' was significantly lower at rest in CoA subjects (5.1±1.5 cm/s vs 6.5±1±1 cm/s; p<0.01), decreasing further during HG by 5% in the CoA group (NS) while unchanged in controls. Conclusions: We provide first evidence that HG with echocardiography is feasible, easy and patient-friendly. A decreased systolic (tissue Doppler) and impaired diastolic LV function was measured in the RCoA group, a difference that tended to increase during HG.

Myhre syndrome: A first familial recurrence and broadening of the phenotypic spectrum.

Myhre syndrome is a rare multisystem connective tissue disorder, characterized by short stature, facial dysmorphology, variable intellectual disability, skeletal abnormalities, arthropathy, cardiopathy, laryngotracheal anomalies, and stiff skin. So far, all molecularly confirmed cases harbored a de novo heterozygous gain-of-function mutation in SMAD4, encoding the SMAD4 transducer protein required for both transforming growth factor-beta and bone morphogenic proteins signaling. We report on four novel patients (one female proband and her two affected children, and one male proband) with Myhre syndrome harboring the recurrent c.1486C>T (p.Arg496Cys) mutation in SMAD4. The female proband presented with a congenital heart defect, vertebral anomalies, and facial dysmorphic features. She developed severe tracheal stenosis requiring a total laryngectomy. With assisted reproductive treatment, she gave birth to two affected children. The second proband presented with visual impairment following lensectomy in childhood, short stature, brachydactyly, stiff skin, and decreased peripheral sensitivity. Transmission electron microscopy (TEM) of the dermis shows irregular elastin cores with globular deposits and almost absent surrounding microfibrils and suggests age-related increased collagen deposition. We report on the first familial case of Myhre syndrome and illustrate the variable clinical spectrum of the disorder. Despite the primarily fibrotic nature of the disease, TEM analysis mainly indicates elastic fiber anomalies.

Local DRLs and automated risk estimation in paediatric interventional cardiology.

INTRODUCTION: Cardiac catheterization procedures result in high radiation doses and often multiple procedures are necessary for congenital heart disease patients. However, diagnostic reference levels (DRL) remain scarce. Our first goal was finding the optimal DRL parameter and determining appropriate DRLs. The second goal was to calculate organ doses (OD), effective doses (ED) and lifetime attributable risks (LAR) per procedure and to provide conversion factors based on dose area product (DAP). MATERIALS AND METHODS: DRLs are calculated for each procedure type, as the 75th percentile of the cumulative value per procedure from the corresponding parameter. All irradiation events in the DICOM Structured Reports were automatically processed and simulated using PCXMC, resulting in OD, ED and LAR. Using a Kruskal Wallis H test and subsequent pairwise comparisons, differences in median values of the DRL parameter between procedure types were assessed. RESULTS: Linear regression showed a strong correlation and narrow confidence interval between DAP and product of body weight and fluoroscopy time (BWxFT), even when all procedures (diagnostic and interventional) are combined. Only 15% of the pairwise comparisons were statistically significant for DAP normalized to BWxFT (DAPBWxFT). The latter pairs contained less frequent procedure types with significant outliers. For DAP normalized to BW (DAPBW), 38% of the pairwise comparisons showed statistically significant differences. Conversion factors from DAPBW to OD and ED were reported for various weight groups, due to the higher correlation between DAPBW and both OD and ED than between DAP and both OD and ED. CONCLUSIONS: The P75 of DAPBWxFT for all procedures combined serves as an appropriate DRL value. This facilitates local DRL determination in smaller paediatric centres, which often have insufficient data to produce appropriate DRLs for different procedure types. Conversion factors are more reliable starting from DAPBW instead of DAP and should be used according to the appropriate BW group.

Differences in cerebral and muscle oxygenation patterns during exercise in children with univentricular heart after Fontan operation compared to healthy peers.

BACKGROUND: We assess whether the lower exercise tolerance in children with univentricular heart (UVH) after Fontan operation is associated with altered peripheral muscular and cerebral tissue oxygenation. METHODS: 18 children with UVH and 20 healthy subjects performed an incremental ramp exercise test. Changes in the cerebral and muscular pattern of oxygenated (O2Hb) and deoxygenated hemoglobin (HHb) and local tissue oxygenation (TOI) were analyzed by means of Near Infrared Spectroscopy (NIRS). Correlations between arterial saturation during exercise and tissue oxygenation were evaluated. RESULTS: In UVH, maximal oxygen consumption (VO2peak/kg, 28.9 ±â€¯7.9 vs. 46.3 ±â€¯11.9 ml/min/kg, P < 0.001), heart rate (HRpeak, 168 ±â€¯13 vs. 193 ±â€¯12 bpm, P < 0.001) and load (Ppeak, 73 ±â€¯19 vs. 133 ±â€¯68 W, P < 0.001) were lower, VE/VCO2 slope was higher (34.5 ±â€¯5.9 vs. 27.1 ±â€¯3.9, P < 0.001). A faster and steeper course up to the same level of HHb and absent increase in O2Hb was seen at cerebral level in UVH; tissue oxygenation index (TOI) demonstrated a steady decrease from the start of exercise. At the muscular level, HHb curve has a similar pattern compared to controls, with an early cessation. O2Hb has a similar pattern, but with early discontinuation at a higher O2Hb-level. Muscular TOI has the same course throughout exercise, starting from a lower level. Lower arterial saturation and higher age correlated with lower VO2peak; higher amplitude of muscular TOI and lower amplitude cerebral TOI correlated with higher VO2peak. CONCLUSION: Children after Fontan procedure have different oxygenation mechanisms at muscular and cerebral level. This reflects a different balance between O2 supply to O2 demand which might contribute to the reduced exercise tolerance in this patient population.

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.

Different Patterns of Cerebral and Muscular Tissue Oxygenation 10 Years After Coarctation Repair.

The purpose of this study was to assess whether the lower exercise tolerance in children after coarctation repair is associated with alterations in peripheral tissue oxygenation during exercise. A total of 16 children after coarctation repair and 20 healthy control subjects performed an incremental ramp exercise test to exhaustion. Cerebral and locomotor muscle oxygenation were measured by means of near infrared spectroscopy. The responses of cerebral and muscle tissue oxygenation index (cTOI, mTOI), oxygenated (O2Hb), and deoxygenated hemoglobin (HHb) as a function of work rate were compared. Correlations between residual continuous wave Doppler gradients at rest, arm-leg blood pressure difference and local oxygenation responses were evaluated. Age, length, and weight was similar in both groups. Patients with aortic coarctation had lower peak power output (Ppeak) (72.3 ± 20.2% vs. 106 ± 18.7%, P < 0.001), VO2peak/kg (37.3 ± 9.1 vs. 44.2 ± 7.6 ml/kg, P = 0.019) and %VO2peak/kg (85.7 ± 21.9% vs. 112.1 ± 15.5%, P < 0.001). Cerebral O2Hb and HHb had a lower increase in patients vs. controls during exercise, with significant differences from 60 to 90% Ppeak (O2Hb) and 70% to 100% Ppeak (HHb). Muscle TOI was significantly lower in patients from 10 to 70% Ppeak and muscle HHb was significantly higher in patients vs. controls from 20 to 80% Ppeak. Muscle O2Hb was not different between both groups. There was a significant correlation between residual resting blood pressure gradient and Δmuscle HHb/ΔP at 10-20W and 20-30W (r = 0.40, P = 0.039 and r = 0.43, P = 0.034). Children after coarctation repair have different oxygenation responses at muscular and cerebral level. This reflects a different balance between O2 supply to O2 demand which might contribute to the reduced exercise tolerance in this patient population.