Pneumonia, wheezing and asthma were more common in children after thymectomy due to open-heart surgery.

AIM: This nationwide study evaluated the clinical impact that an early thymectomy, during congenital heart defect (CHD) surgery, had on the health of children and adolescents. METHODS: The subjects were patients aged 1-15 years who had undergone CHD surgery at the University Children's Hospital, Helsinki, where all CHD surgery in Finland is carried out, from 2006 to 2018. The parents or the cases and population-based controls, matched for sex, age and hospital district, completed electronic questionnaires. We excluded those with low birth weights or a known immunodeficiency. Adjusted odds ratios (aOR) and 95% confidence intervals (CI) were calculated for prespecified outcomes. RESULTS: We received responses relating to 260/450 (58%) cases and 1403/4500 (31%) controls and excluded 73 cases with persistent cardiac or respiratory complaints after surgery. The CHD group reported more recurrent hospitalisations due to infections (aOR 6.3, 95% CI 3.0-13) than the controls and more pneumonia episodes (aOR 3.5, 95% CI 2.1-5.6), asthma (aOR 2.5, 95% CI 1.5-4.1) and wheezing (aOR 2.1, 95% CI 1.5-2.9). CONCLUSION: Hospitalisation due to infections, pneumonia, wheezing and asthma was more common in children after a thymectomy due to open-heart surgery than population-based controls, underlining the importance of immunological follow-ups.

Atrial septal defect patients have an elevated risk for infective endocarditis.

Background. It has been unclear whether simple atrial septal defect (ASD) is an independent risk factor for infective endocarditis (IE). This study aimed to untangle the risk of endocarditis in a large nationwide cohort. Methods. We acquired data from the Finnish hospital discharge register on all individuals with ASD diagnosis from 1969 to 2019. Patients with complex congenital cardiac abnormalities were ruled out. Five individualized controls from the general population were matched to the ASD patient's birth year, sex, and residence at the index date. All the patients with ICD-8, -9, or -10 diagnosis codes for IE were gathered from the hospital discharge registry. Results. Altogether, 8322 patients with ASD and 39,237 individualized controls were enrolled in the study. Median follow-up was 21.6 years (IQR 11.8-36.9) from the first hospital contact. In total, 24 (16 male) cases of infective endocarditis among ASD patients and 10 (8 male) cases among controls were diagnosed during the follow-up. The incidence of endocarditis was 0.11 per 1000 person-years in the patients with ASD and 0.011 per 1000 person-years in the controls. The adjusted risk ratio for endocarditis was 13.51 (95% CI: 6.20-29.46) in patients with ASD compared to the control cohort. Patients with ASD and endocarditis had higher long-term mortality than individualized control patients (MRR 2.25, 95% CI: 1.23-4.11). Conclusions. The incidence of IE in patients with ASD was higher than in the general population. Mortality associated with IE was higher in patients with ASD compared to controls.

Institutional transition from invasive to non-invasive imaging in children with univentricular heart defects: safety and cost savings.

OBJECTIVES: Patients with univentricular heart defects require lifelong imaging surveillance. Recent advances in non-invasive imaging have enabled replacing these patients' routine catheterisation. Our objective was to describe the safety and cost savings of transition of a tertiary care children's hospital from routine invasive to routine non-invasive imaging of low-risk patients with univentricular heart defects. METHODS: This single-centre cohort study consists of 1) a retrospective analysis of the transition from cardiac catheterisation (n = 21) to CT angiography (n = 20) before bidirectional Glenn operation and 2) a prospective study (n = 89) describing cardiac magnetic resonance before and after the total cavopulmonary connection in low-risk patients with univentricular heart defects. RESULTS: Pre-Glenn: The total length of CT angiography was markedly shorter compared to the catheterisation: 30 min (range: 20-60) and 125 min (range: 70-220), respectively (p < 0.001). Catheterisation used more iodine contrast agents than CT angiography, 19 ± 3.9 ml, and 10 ± 2.4 ml, respectively (p < 0.001). Controlled ventilation was used for all catheterised and 3 (15%) CT angiography patients (p < 0.001). No complications occurred during CT angiography, while they emerged in 19% (4/21) catheterisation cases (p < 0.001). CT angiography and catheterisation showed no significant difference in the radiation exposure. Pre-/post-total cavopulmonary connection: All cardiac magnetic resonance studies were successful, and no complications occurred. In 60% of the cardiac magnetic resonance (53/89), no sedation was performed, and peripheral venous pressure was measured in all cases. Cost analysis suggests that moving to non-invasive imaging yielded cost savings of at least €2500-4000 per patient. CONCLUSION: Transition from routine invasive to routine non-invasive pre-and post-operative imaging is safely achievable with cost savings.

The incidence of recurrent laryngeal nerve injury resulting in vocal cord paralysis following interventional congenital catheterisation procedures.

BACKGROUND: Recurrent laryngeal nerve injury leading to vocal cord paralysis is a known complication of cardiothoracic surgery. Its occurrence during interventional catheterisation procedures has been documented in case reports, but there have been no studies to determine an incidence. OBJECTIVE: To establish the incidence of left recurrent laryngeal nerve injury leading to vocal cord paralysis after left pulmonary artery stenting, patent ductus arteriosus device closure and the combination of the procedures either consecutively or simultaneously. METHODS: Members of the Congenital Cardiovascular Interventional Study Consortium were asked to perform a retrospective analysis to identify cases of recurrent laryngeal nerve injury after the aforementioned procedures. Twelve institutions participated in the analysis. They also contributed the total number of each procedure performed at their respective institutions for statistical purposes. RESULTS: Of the 1337 patients who underwent left pulmonary artery stent placement, six patients (0.45%) had confirmed vocal cord paralysis. 4001 patients underwent patent ductus arteriosus device closure, and two patients (0.05%) developed left vocal cord paralysis. Patients who underwent both left pulmonary artery stent placement and patent ductus arteriosus device closure had the highest incidence of vocal cord paralysis which occurred in 4 of the 26 patients (15.4%). Overall, 92% of affected patients in our study population had resolution of symptoms. CONCLUSION: Recurrent laryngeal nerve injury is a rare complication of left pulmonary artery stent placement or patent ductus arteriosus device closure. However, the incidence is highest in patients undergoing both procedures either consecutively or simultaneously. Additional research is necessary to determine contributing factors that might reduce the risk of recurrent laryngeal nerve injury.

Perinatal and perioperative factors associated with mortality and an increased need for hospital care in infants with transposition of the great arteries: A nationwide 11-year population-based cohort.

INTRODUCTION: Newborn infants with transposition of the great arteries (d-TGA) need immediate care for an optimal outcome. This study comprised a nationwide 11-year population-based cohort of d-TGA infants, and assessed whether the implementation of a nationwide systematic fetal screening program, or other perinatal, or perioperative factors, are associated with mortality or an increased need for hospital care. MATERIAL AND METHODS: The national cohort consisted of all live-born infants with simple d-TGA (TGA ± small ventricular septal defect, n = 127) born in Finland during 2004-2014. Data were collected from six national registries. Prenatal diagnosis and perinatal and perioperative factors associated with mortality and length of hospitalization were evaluated. RESULTS: Preoperative mortality was 7.9%, and the total mortality was 8.7%. The prenatal detection rate increased after introducing systematic fetal anomaly screening from 5.0% to 37.7% during the study period (P < .0001), but the total mortality rate remained unchanged. All prenatally diagnosed infants (n = 27) survived. Lower gestational age (odds ratio 0.68, P = .012) and higher maternal age at birth (odds ratio 1.16, P = .036) were associated with increased mortality in multivariable analysis. Older infant age at time of operation (P = .002), longer aortic clamp time (P < .001), and higher maternal body mass index (P = .027) were associated with longer initial hospital stay. An extended need for hospital care during the first year of life was multi-factorial. CONCLUSIONS: In our cohort, none of the prenatally diagnosed d-TGA infants died. As a result of the limited prenatal detection rates, however, the sample size was insufficient to reach statistical significance. The d-TGA infants born with lower gestational age and to older mothers had increased mortality.

Congenital aortic stenosis: treatment outcomes in a nationwide survey.

OBJECTIVE: To evaluate treatment outcomes of pediatric valvar aortic stenosis (AS) in a nationwide follow-up. DESIGN: Balloon aortic valvuloplasty (BAV) has been the preferred treatment for congenital AS in Finland since the year 2000. All children treated due to isolated AS during 2000-2014 were included in this retrospective study. Treatment outcomes were categorized into Optimal: residual gradient ≤35 mmHg and trivial or no aortic regurgitation (AR), Adequate: gradient ≤35 mmHg with mild AR, or Inadequate: gradient >35 mmHg and/or moderate to severe AR. RESULTS: Sixty-one patients underwent either BAV (n = 54) or surgical valvuloplasty (n = 7) for valvar AS at a median age of 29 days (range 6 hours to 16.9 years). The proportion of patients not requiring reintervention at 1, 5, and 10 years was 61%, 50%, and 29% in neonates and 83%, 73%, and 44% in older patients, respectively (p = .02); without difference between treatment groups. Larger proportion of patients remained free from valve surgery after optimal BAV result than after adequate or inadequate result (p = .01). The reason for the first reintervention was AS in 50%, AR in 36%, and combined aortic valve disease in 16% of cases. Early mortality (before hospital discharge) was 4.9%, and associated with critical AS in neonates. There was no late mortality during the follow-up. CONCLUSIONS: Although majority of congenital AS patients require more than one intervention during childhood, an optimal BAV result improves long-term outcome by increasing the proportion of patients remaining free from valve surgery. High long-term freedom from reintervention is attainable also in the neonatal population.

Right ventricular systolic function in hypoplastic left heart syndrome: A comparison of manual and automated software to measure fractional area change.

BACKGROUND: Quantitative echocardiographic assessment of right ventricular function is important in children with hypoplastic left heart syndrome (HLHS). The aim of this study was to examine the repeatability of different echocardiographic techniques, both manual and automated, to measure fractional area change (FAC) in patients with HLHS and to correlate these measurements with magnetic resonance imaging (MRI)-derived ejection fraction (EF). METHODS: Fifty-one children with HLHS underwent transthoracic echocardiography and cardiac MRI under the same general anesthetic as part of routine inter-stage assessment. FAC was measured from the apical four-chamber view using three different techniques: velocity vector imaging (VVI) (Syngo USWP 3.0; Siemens Healthineers), QLAB (Q-lab R 10.0; Philips Healthcare), and manual endocardial contour tracing (Xcelera, Philips Healthcare). Intra- and inter-observer variability was calculated using intra-class correlation coefficient (ICC). FAC was correlated with MRI EF calculated using a single standard method. RESULTS: Fractional area change had a good correlation with MRI-derived EF with an R value for VVI, QLAB, and manual methods of .7, .6, and .4, respectively. Intra- and inter-observer variability for FAC was good for automated echocardiographic methods (ICC>.85) but worse for manual method particularly inter-observer variability of FAC and end-systolic area. Both automated techniques tended to produce higher FAC values compared with manual measurements (P<.001). CONCLUSION: Automation improves the repeatability of FAC in HLHS. There are some differences between automated software in terms of correlation with MRI-derived EF. Measurement bias and wide limits of agreement mean that the same echocardiographic technique should be used during the follow-up of individual patients.

Fate of fenestration in children treated with fontan operation.

OBJECTIVE: To review the operative history and clinical and catheterization data on patients treated with total cavopulmonary connection (TCPC) with baffle fenestration and to study whether it is possible to predict the fate of fenestration. BACKGROUND: A baffle fenestration may improve postoperative outcomes after Fontan operation but is later associated with cyanosis and thromboembolic risk. Fenestration may close spontaneously or it can be closed percutaneously in patients with favorable hemodynamics. METHODS: Patients were divided into three groups: those with spontaneous closure of fenestration (group S, n = 34) and those with patent fenestration and favorable (group F, n = 36) or unfavorable (group U, n = 20) response to fenestration test occlusion. Clinical records were reviewed for demographic and anatomical characteristics, previous surgeries, and catheterizations. RESULTS: Predominant ventricular morphology was right ventricle (RV)/left ventricle (LV)/undeterminate in 19/14/1 patients in group S, 14/22/0 in group F, and 14/6/0 in group U. No differences were detected between groups in pre-TCPC catheterization data. Type of baffle fenestration was window/tube in 20/14 in group S, 28/8 in group F, and 20/0 in group U. All tube fenestrations either closed spontaneously or could be closed percutaneously. Twenty-nine percent of patients with window-type fenestrations failed the test occlusion. CONCLUSIONS: Spontaneous closure and favorable result in test occlusion are more common in tube than in window fenestrations. Since most preoperative anatomic and hemodynamic factors were similar in all patient groups, we find it difficult to predict the fate of a window-type fenestration and the result of test occlusion. © 2015 Wiley Periodicals, Inc.

LMNA Mutation c.917T>G (p.L306R) Leads to Deleterious Hyper-Assembly of Lamin A/C and Associates with Severe Right Ventricular Cardiomyopathy and Premature Aging.

Mutations in the LMNA gene coding for the nuclear lamina proteins lamin A and its smaller splice form lamin C associate with a heterogeneous group of diseases collectively called laminopathies. Here, we describe a 2-year-old patient with a previously undescribed phenotype including right ventricular cardiomyopathy, progeroid features, and premature death. Sequencing of LMNA revealed a novel heterozygous de novo mutation p.L306R located in the α-helical rod domain of A-type lamins. Fibroblasts from the patient showed reduced proliferation and early premature replicative senescence, as characterized by progressive hyperlobulation of the nuclei, abnormally clustered centromeres, loss of lamin B1, and reorganization of promyelocytic leukemia nuclear bodies. Furthermore, the patient cells were more sensitive to double-strand DNA breaks. Similar structural and phenotypic defects were observed in normal fibroblasts transfected with FLAG-tagged p.L306R lamin A. Correspondingly, in vitro assembly studies revealed that the p.L306R generates a "hyper-assembly" mutant of lamin A that forms extensive fiber arrays under physiological conditions where wild-type lamin A is still largely soluble. In summary, we report a novel LMNA p.L306R mutation that leads to previously undescribed hyper-assembly of lamin A, heavy distortion of nuclear shape and that manifests as right ventricular cardiomyopathy and premature aging.

[Screening of congenital heart defects in the newborn--time to unify the practices of oxygen saturation screening in Finland]. / Vastasyntyneiden sydänvikojen seulonta--aika yhtenäistää happisaturaatioseulonnan käytännöt.

Saturation screening of congenital heart defects in the newborn takes place in Finnish maternity hospitals. Saturation screening has been shown to be a cost-effective way to screen critical heart defects in the newborn. Screening aims to reveal the heart defect before potential circulatory collapse. Early diagnosis is important, as invasive therapeutic measures for congenital heart defects have been concentrated to one center. There are differences in the implementation of saturation screening. We therefore recommend unifying the screening system to conform with the recently published Nordic recommendation. Screening should be conducted during the first day of life by measuring the saturation values of both the right upper limb and one of the lower limbs.

Thrombin formation and effect of unfractionated heparin during pediatric cardiac catheterization.

OBJECTIVES: To assess the strength of thrombin formation and determine the effects of unfractionated heparin (UFH) in children during cardiac catheterization. BACKGROUND: UFH reduces the thrombotic risk related to catheterization but the effects of UFH on the coagulation system in children, and proper monitoring of UFH remain unclear. METHODS: We studied 42 patients aged 3-12 years undergoing catheterization. Twenty-seven received UFH (group A) and 15 patients did not (group B). Anticoagulation was assessed by measurements of plasma prothrombin fragment F1 + 2, thrombin-antithrombin (TAT) complexes, D-dimer, activated partial thromboplastin time (APTT), anti-FXa, and prothrombinase-induced clotting time (PiCT). RESULTS: Markers of thrombin generation remained low during catheterization in group A. In group B, both F1 + 2 and TAT had increased significantly (P < 0.05) by the end of the procedure versus baseline and versus respective levels in group A. In group A, 15 min after heparinization, APTT was over 180 sec (in all patients), anti-FXa 1.4 U/ml (1.1-2.4 U/ml) and PiCT 1.5 U/ml (1.3-2.4 U/ml). Anti-FXa and PiCT were correlated (R = 0.84, P < 0.0001). CONCLUSIONS: Thrombin generation was enhanced in patients who did not receive UFH, which may increase the risk of thrombotic complications. In group A, routine heparinization seemed excessive by all monitoring methods. UFH prevented an increase in prothrombin to thrombin conversion, resulting in unaltered fibrin formation. The current UFH protocol seemed to have no effect on postprocedural activation of coagulation. Further studies are needed to clarify adequate heparin dosing for children during cardiac catheterization to prevent thrombotic complications without predisposing the patient to bleeding complications.

Outcome of pediatric heart transplantation recipients treated with ventricular assist device.

This study was conducted to evaluate the long-term prognosis of pediatric HTx patients treated with VAD before transplantation. The clinical data of six patients bridged to HTx with Berlin Heart EXCOR pediatric device were analyzed retrospectively. Information about graft function, CA results, and EMB findings as well as appearance DSA was collected. Also, information about growth and cognitive function was analyzed. These findings were compared with age-, gender-, and diagnosis-matched HTx patients. During the median follow-up time of four and half yr after HTx, the prognosis including graft function, number of rejection episodes, and incidence of coronary artery vasculopathy, growth and cognitive development did not differ between VAD-bridged HTx patients compared with control patients. In both groups, one patient developed positive DSA titer after HTx. Our single-center experience suggests that the prognosis of pediatric HTx patients treated with VAD before transplantation is not inferior to that of other HTx patients.

Cardiac troponin I in congenital heart defects with pressure or volume overload.

OBJECTIVE: To evaluate the prevalence of cardiac troponin I (cTnI) and autoantibodies to cTn in children with congenital heart defects with volume or pressure overload fulfilling the criteria for treatment, and in healthy children. DESIGN: The study groups comprised 78 children with volume overload caused by an atrial septal defect or a patent ductus arteriosus, and 60 children with pressure overload caused by coarctation of the aorta or stenosis of the aortic or the pulmonary valve, and 74 healthy controls. Serum levels of natriuretic peptides, cTnI, and autoantibodies to cTn were analyzed at baseline, prior to treatment and in 64 patients 6 months after treatment. RESULTS: At baseline, one child with volume overload, 12 children with pressure overload, and one healthy control had positive cTnI. Further analysis of the pressure overload subgroup revealed that the children with positive cTnI were younger than those with negative cTnI, and had higher levels of natriuretic peptides. The pressure gradient at the coarctation site or stenotic valve was higher in those with positive TnI. Six months after treatment, 63 of 64 children examined were cTnI negative. CONCLUSIONS: The cTnI release is more frequently associated with pressure than volume overload which resolves after treatment in most children.

[Percutaneous treatment of pulmonary artery stenoses]. / Keuhkovaltimoahtaumien perkutaaninen hoito.

Pulmonary artery stenoses are a common problem in pediatric cardiology. They may interfere with the growth and development of the lung and cause pressure overload on the right heart and by increasing pulmonary arterial valvular insufficiency, also volume overload on the right ventricle. This may predispose the patient to cardiac failure, limitation of exercise tolerance and arrhythmias. Percutaneous treatment of pulmonary artery stenoses has undergone significant development over the last 20 years. Above all, the development of high pressure balloon catheters and stents has made treatment results better.

Recurrent Mild Acute Rejections and Donor-specific Antibodies as Risk Factors for Cardiac Allograft Vasculopathy in a National Pediatric Heart Transplant Cohort.

Background: Immune-mediated factors such as acute cellular rejections and donor-specific antibodies (DSAs) are risk factors for cardiac allograft vasculopathy (CAV). We studied a national cohort with a unified setting and thorough protocol endomyocardial biopsy (EMB) data for an association between cellular rejections, especially when mild and recurrent, and DSAs with CAV in pediatric heart transplant (HTx) patients. Methods: This is a retrospective, national cohort study of 94 pediatric HTxs performed between 1991 and 2019 and followed until December 31, 2020. Diagnosis of CAV was based on reevaluation of angiographies. Protocol and indication EMB findings with other patient data were collected from medical records. Associations between nonimmune and immune-mediated factors and CAV were analyzed with univariable and multivariable Cox regression analyses. Results: Angiographies performed on 76 patients revealed CAV in 23 patients (30%). Altogether 1138 EMBs (92% protocol biopsies) were performed on 78 patients (83%). During the first posttransplant year, grade 1 rejection (G1R) appeared in 45 patients (58%), and recurrent (≥2) G1R findings in 14 patients (18%). Pretransplant DSAs occurred in 13 patients (17%) and posttransplant DSAs in 37 patients (39%). In univariable analysis, pretransplant DSAs, appearance and recurrence of G1R findings, and total rejection score during the first posttransplant year, as well as recurrent G1R during follow-up, were all associated with CAV. In multivariable analysis, pretransplant DSAs and recurrent G1R during the first posttransplant year were found to be associated with CAV. Conclusions: Our results indicate that pretransplant DSA and recurrent G1R findings, especially during the first posttransplant year, are associated with CAV after pediatric HTx.

Transcatheter Intervention for Coarctation of the Aorta: A Nordic Population-Based Registry With Long-Term Follow-Up.

BACKGROUND: Coarctation of the aorta (CoA), a congenital narrowing of the proximal descending thoracic aorta, is a relatively common form of congenital heart disease. Untreated significant CoA has a major impact on morbidity and mortality. In the past 3 decades, transcatheter intervention (TCI) for CoA has evolved as an alternative to surgery. OBJECTIVES: The authors report on all TCIs for CoA performed from 2000 to 2016 in 4 countries covering 25 million inhabitants, with a mean follow-up duration of 6.9 years. METHODS: During the study period, 683 interventions were performed on 542 patients. RESULTS: The procedural success rate was 88%, with 9% considered partly successful. Complications at the intervention site occurred in 3.5% of interventions and at the access site in 3.5%. There was no in-hospital mortality. During follow-up, TCI for CoA reduced the presence of hypertension significantly from 73% to 34%, but despite this, many patients remained hypertensive and in need of continuous antihypertensive treatment. Moreover, 8% to 9% of patients needed aortic and/or aortic valve surgery during follow-up. CONCLUSIONS: TCI for CoA can be performed with a low risk for complications. Lifetime follow-up after TCI for CoA seems warranted.

Predictors of blood pressure and hypertension long-term after treatment of isolated coarctation of the aorta in children-a population-based study.

OBJECTIVES: The aim of this study was to assess predictors of BP and hypertension and relations between BP and LV mass in a population-based retrospective study of repaired isolated coarctation of aorta. METHODS: We collected follow-up data until 2018 of 284/304 (93%) patients with coarctation treated by surgery (n = 235) or balloon angioplasty/stent (n = 37/12) in our unit 2000-2012. Systolic hypertension was defined as systolic BP (SBP) z-score ≥+2 standard deviation (SD) or regular use of BP medication. LV hypertrophy was defined as LV mass z-score ≥+2 SD or LV mass index g/m2.7 ≥95th percentile. RESULTS: The median (25-75th percentiles) follow-up time and age at follow-up were 9.7 years (6.9-13.2) and 11.8 years (7.9-16.0), respectively. Age at first procedure (P = 0.011) and systolic arm-leg-gradient (P = 0.007) were positively and transverse arch (P = 0.007) and isthmus diameter (P = 0.001) z-scores at follow-up were negatively associated with SBP z-score adjusted for age at follow-up and need for reintervention for coarctation. Systolic hypertension was present in 53/284 (18.7%) and related with increasing age at first procedure (median 33.2 vs 0.6 months; P < 0.001) and arm-leg-gradient at follow-up (mean ± SD, -0.3 ± 14.6 vs -6.4 ± 11.6 mmHg; P = 0.047) adjusted for reintervention for coarctation and age at follow-up. LV hypertrophy was present in 20/227 (9.3%) and related with SBP z-score. CONCLUSIONS: Higher SBP and hypertension in repaired coarctation of aorta are related with increasing age at first procedure and arm-leg-gradient at follow-up. Transverse arch and isthmus diameters at follow-up are inversely related with SBP.

Heart Transplantation for Early-Onset Anthracycline-Induced Cardiomyopathy Within 5 Months of Chemotherapy Completion.

A 9-year-old boy developed progressive anthracycline-induced cardiomyopathy three months after completion of chemotherapy for osteosarcoma. Five months after completion of chemotherapy, at the age of 10 years, heart transplantation was performed. At 29 months since transplantation, the patient remains free of rejection and recurrence of osteosarcoma. (Level of Difficulty: Intermediate.).

A Reductive Metabolic Switch Protects Infants with Transposition of Great Arteries Undergoing Atrial Septostomy against Oxidative Stress.

Transposition of the great arteries (TGA) is one of the most common cyanotic congenital heart diseases requiring neonatal surgical intervention. Parallel circulations that result in impaired cerebral oxygen delivery already in utero may lead to brain damage and long-term neurodevelopmental delay. Balloon atrial septostomy (BAS) is often employed to mix deoxygenated and oxygenated blood at the atrial level. However, BAS causes a sudden increase in arterial blood oxygenation and oxidative stress. We studied changes in oxygen saturation as well as metabolic profiles of plasma samples from nine newborn infants suffering from TGA before and until 48 h after undergoing BAS. The plasma metabolome clearly changed over time and alterations of four metabolic pathways, including the pentose phosphate pathway, were linked to changes in the cerebral tissue oxygen extraction. In contrast, no changes in levels of lipid peroxidation biomarkers over time were observed. These observations suggest that metabolic adaptations buffer the free radical burst triggered by re-oxygenation, thereby avoiding structural damage at the macromolecular level. This study enhances our understanding of the complex response of infants with TGA to changes in oxygenation induced by BAS.

Rare Variants in Genes Associated With Cardiomyopathy Are Not Common in Hypoplastic Left Heart Syndrome Patients With Myocardial Dysfunction.

Myocardial dysfunction is a known risk factor for morbidity and mortality in hypoplastic left heart syndrome (HLHS). Variants in some transcription factor and contractility genes, which are known to cause cardiomyopathy, have previously been associated with impaired right ventricular function in some HLHS patients. The care of HLHS patients is resource demanding. Identifying genetic variants associated with myocardial dysfunction would be helpful in tailoring the follow-up and therapeutic strategies. We tested whether a commercial cardiomyopathy gene panel could serve as a diagnostic tool in a Finnish cohort of HLHS patients with impaired right ventricular function to identify potentially pathogenic variants associated with poor prognosis. None of the patients had pathogenic or likely pathogenic variants in the studied cardiomyopathy-associated genes. Thus, our approach of performing a cardiomyopathy gene panel to identify pathogenic variants as directly causal or as modifiers for worse outcomes in hypoplastic left heart syndrome is not useful in clinical practice at the moment.