Pulmonary Valve Replacement in Tetralogy of Fallot: Procedural Volume and Durability of Bioprosthetic Pulmonary Valves.

BACKGROUND: Robust data on changes in pulmonary valve replacement (PVR) procedural volume and predictors of bioprosthetic pulmonary valve (BPV) durability in patients with tetralogy of Fallot (TOF) are scarce. OBJECTIVES: This study sought to assess temporal trends in PVR procedural volume and BPV durability in a nationwide, retrospective TOF cohort. METHODS: Data were obtained from patient records. Robust linear regression was used to assess temporal trends in PVR procedural volume. Piecewise exponential additive mixed models were used to estimate BPV durability, defined as the time from implantation to redo PVR with death as a competing risk, and to assess risk factors for reduced durability. RESULTS: In total, 546 PVR were performed in 384 patients from 1976 to 2021. The annual number of PVR increased from 0.4 to 6.0 per million population (P < 0.001). In the last decade, the transcatheter PVR volume increased by 20% annually (P < 0.001), whereas the surgical PVR volume did not change significantly. The median BPV durability was 17 years (Q1: 10-Q3: 10 years-not applicable). There was no significant difference in the durability of different BPV after adjustment for confounders. Age at PVR (HR: 0.78 per 10 years from <1 year; 95% CI: 0.63-0.96; P = 0.02) and true inner valve diameter (9-17 mm vs 18-22 mm HR: 0.40; 95% CI: 0.22-0.73; P = 0.003 and 18-22 mm vs 23-30 mm HR: 0.59; 95% CI: 0.25-1.39; P = 0.23) were associated with reduced BPV durability in multivariate models. CONCLUSIONS: The PVR procedural volume has increased over time, with a greater increment in transcatheter than surgical PVR during the last decade. Younger patient age at PVR and a smaller true inner valve diameter predicted reduced BPV durability.

Fatal Rupture of Occult Posttraumatic Left Ventricular Aneurysm in a Child.

Left ventricular aneurysm is a potentially serious but rare condition in children. This case describes delayed but fatal rupture of an occult posttraumatic left ventricular aneurysm in an 11-year-old boy with a history of blunt chest trauma from a high-impact automobile collision 7 months earlier. (Level of Difficulty: Intermediate.).

Changes in Kawasaki disease incidence and phenotype during the COVID-19 pandemic.

INTRODUCTION: The aetiology of Kawasaki disease (KD) remains unknown. Changes in infectious exposure during the COVID-19 pandemic owing to infection prevention measures may have affected the incidence of KD, supporting the pathogenic role of an infectious trigger. The purpose of this study was to evaluate the incidence, phenotype and outcome of KD before and during the COVID-19 pandemic in Denmark. METHODS: This was a retrospective cohort study based on patients diagnosed with KD at a Danish paediatric tertiary referral centre from 1 January 2008 to 1 September 2021. RESULTS: A total of 74 patients met the KD criteria of whom ten were observed during the COVID-19 pandemic in Denmark. All of these patients were negative for SARS-CoV-2 DNA and antibodies. A high KD incidence was observed during the first six months of the pandemic, but no patients were diagnosed during the following 12 months. Clinical KD criteria were equally met in both groups. The fraction of intravenous immunoglobulin (IVIG) non-responders was higher in the pandemic group (60%) than in the in the pre-pandemic group (28.3%), although the rate of timely administered IVIG treatment was the same in both groups (≥ 80%). Coronary artery dilation was observed in 21.9% in the pre-pandemic group compared with 0% in KD patients diagnosed during the pandemic. CONCLUSION: Changes in KD incidence and phenotype were seen during the COVID-19 pandemic. Patients diagnosed with KD during the pandemic had complete KD, higher liver transaminases and significant IVIG resistance but no coronary artery involvement. FUNDING: None. TRIAL REGISTRATION: The study was approved by the Danish Data Protection Agency (DK-634228).

Autosomal recessive Noonan-like syndrome caused by homozygosity for a previously unreported variant in SPRED2.

Noonan syndrome is characterized by variable phenotypic expressivity with characteristic dysmorphic facial features, varying degrees of intellectual disability, developmental delay, short stature, and congenital heart defects in 50-80%. Other findings include a webbed neck, cryptorchidism, coagulation defects and eye abnormalities. Thus far, Noonan syndrome has mainly been attributed to heterozygous pathogenic variants in 10+ different genes, with the rare exception of cases due to biallelic pathogenic variants in LZTR1. Recently, homozygous loss-of-function variants in SPRED2 have been identified as a cause of a recessive Noonan syndrome-like phenotype. We present the phenotypes of two additional patients with homozygosity for a previously unreported loss-of-function variant in SPRED2, thereby adding relevant clinical information about the recently described Noonan syndrome-like SPRED2-related phenotype.

Temporal changes in the surgical management of patients with tetralogy of Fallot in Denmark: a nationwide cohort study.

OBJECTIVES: To assess temporal changes in the surgical management of patients with tetralogy of Fallot including the timing of interventions, surgical techniques, reinterventions and survival in a nationwide cohort. METHODS: Patients with tetralogy of Fallot in Denmark were divided into 3 eras based on their year of birth: early (1977-1991), intermediate (1992-2006) and late (2007-2021). RESULTS: The cohort consisted of 745 patients. Median follow-up was 21.2 years (13.7-30.5). There was a temporal trend towards less shunt palliation (-0.3% per year, 95% CI -0.05 to -0.1). Median age at intracardiac repair was 2.9 years (1.8-5.0), 0.8 years (0.5-1.3) and 0.5 years (0.4-0.7) (P < 0.001) in the early, intermediate and late era, respectively. There was a temporal trend towards less valve-sparing repair (-0.7% per year, 95% CI -0.5 to -1.0) and more repair with transannular patches (0.7% per year, 95% CI 0.5-1.0). Survival at 10 years was 79% (64-76), 90% (87-93) and 95% (92-98) (P < 0.001) and pulmonary valve replacement within the first 10 years after intracardiac repair was performed in 3% (1-6), 12% (8-16) and 21% (13-29) (P < 0.001) in the early, intermediate and late era, respectively. CONCLUSIONS: There was a temporal trend towards less shunt palliation and intracardiac repair at a younger age with more use of transannular patches. While survival throughout childhood and adolescence has improved, more patients undergo pulmonary valve replacement during the first 10 years after intracardiac repair.

Correlation between asparaginase enzyme activity levels and coagulation parameters during childhood acute lymphoblastic leukemia treatment.

Thromboembolism is a serious toxicity in the treatment of acute lymphoblastic leukemia (ALL), but little is known about the correlation between asparaginase enzyme activity (ASA) levels and coagulation parameters. We included 65 non-high risk ALL patients, aged 1-17 years. Coagulation parameters and corresponding ASA levels were measured during asparaginase treatment. We found ASA to be negatively correlated with antithrombin and fibrinogen up to ASA levels of 250 IU/L, after which these parameters reached a plateau and did not decrease further with further increase of ASA. Patients with silent inactivation of asparaginase had normal coagulation parameters.

Succesful MEK-inhibition of severe hypertrophic cardiomyopathy in RIT1-related Noonan Syndrome.

Infants with Noonan Syndrome and hypertrophic cardiomyopathy have a poor prognosis and a high mortality especially when diagnosed before six months of age. As for the majority of the RASopathies, no medical treatment has been approved for Noonan Syndrome. Meanwhile, several approved agents targeting the same RAS/MAPK signaling pathway are used in cancer treatment. In this case report we describe a child with Noonan Syndrome caused by a pathogenic RIT1 variant, who developed severe early-onset hypertrophic cardiomyopathy and pulmonary valve stenosis. She received off-label treatment with the MEK-inhibitor trametinib which resulted in complete remission of the cardiac hypertrophy and a significant improvement of the pulmonary valve stenosis. Our case emphasizes the potential of existing cancer agents targeting the RAS/MAPK signaling pathway as successful treatment for RASopathy manifestations.

Natural History of MYH7-Related Dilated Cardiomyopathy.

BACKGROUND: Variants in myosin heavy chain 7 (MYH7) are responsible for disease in 1% to 5% of patients with dilated cardiomyopathy (DCM); however, the clinical characteristics and natural history of MYH7-related DCM are poorly described. OBJECTIVES: We sought to determine the phenotype and prognosis of MYH7-related DCM. We also evaluated the influence of variant location on phenotypic expression. METHODS: We studied clinical data from 147 individuals with DCM-causing MYH7 variants (47.6% female; 35.6 ± 19.2 years) recruited from 29 international centers. RESULTS: At initial evaluation, 106 (72.1%) patients had DCM (left ventricular ejection fraction: 34.5% ± 11.7%). Median follow-up was 4.5 years (IQR: 1.7-8.0 years), and 23.7% of carriers who were initially phenotype-negative developed DCM. Phenotypic expression by 40 and 60 years was 46% and 88%, respectively, with 18 patients (16%) first diagnosed at <18 years of age. Thirty-six percent of patients with DCM met imaging criteria for LV noncompaction. During follow-up, 28% showed left ventricular reverse remodeling. Incidence of adverse cardiac events among patients with DCM at 5 years was 11.6%, with 5 (4.6%) deaths caused by end-stage heart failure (ESHF) and 5 patients (4.6%) requiring heart transplantation. The major ventricular arrhythmia rate was low (1.0% and 2.1% at 5 years in patients with DCM and in those with LVEF of ≤35%, respectively). ESHF and major ventricular arrhythmia were significantly lower compared with LMNA-related DCM and similar to DCM caused by TTN truncating variants. CONCLUSIONS: MYH7-related DCM is characterized by early age of onset, high phenotypic expression, low left ventricular reverse remodeling, and frequent progression to ESHF. Heart failure complications predominate over ventricular arrhythmias, which are rare.

Population-based Incidence of Myopericarditis After COVID-19 Vaccination in Danish Adolescents.

In this prospective nationwide multicenter study from Denmark, myopericarditis after Pfizer-BioNTech mRNA COVID-19 vaccination was identified in 13 males and 2 females between May 15 and September 15, 2021, among 133,477 vaccinated males and 127,857 vaccinated females 12-17 years of age, equaling 97 males and 16 females per million. In conclusion, the incidence of myopericarditis after COVID-19 vaccination among males appears higher than reports from the United States.

[Preoperative risk assessment of patients with congenital heart disease in non-cardiac surgery].

Over the last decades, remarkable advances in survival in patients with congenital heart disease (CHD) have been reported. Currently, 90% of infants born with CHD can expect to reach adulthood. Moderate and severe CHD is associated with increased perioperative mortality. To ensure optimal management of CHD patients undergoing non-cardiac surgery, preoperative risk assessment is pivotal, along with a multidisciplinary approach and collaboration across hospitals. The objective of this review is to provide a simple model to identify CHD patients at risk prior to non-cardiac surgery.

Radiofrequency catheter ablation in 246 children with supraventricular tachyarrhythmia.

INTRODUCTION: Radiofrequency catheter ablation (RFA) is the treatment of choice for a variety of cardiac arrhythmias in adults. RFA is considered effective and is associated with few complications. We aimed to review the characteristics and outcomes of invasive electrophysiological study (EPS) and RFA in children with supraventricular tachyarrhythmia. METHODS: Consecutive patients younger than 16 years of age undergoing EPS and possible RFA from January 2009 to September 2018 at Aarhus University Hospital (uptake three million people) were reviewed retrospectively. Procedural and outcome data were collected from patient charts and from the Danish Ablation Database. Numbers (%) or median (range) are reported. RESULTS: A total of 304 patients (148 girls) underwent EPS (352 procedures). RFA was performed in 246 patients (279 procedures), aged 13 (1-15) years and weighing 46 (6-99) kg. Treatment success was achieved in 195 (79%) of the initial procedures. Using more than one procedure, 227 (92%) patients were free from arrhythmia after 89 (26-143) months of follow-up. The procedure time was 60 (22-222) min. and ablation time 2 (1-23) min. Major complications occurred in two cases. One patient developed transient superior vena cava syndrome and one patient developed an atrioventricular block requiring pacemaker implantation. CONCLUSIONS: RFA may be performed in children with a high success rate and a low but not negligible risk of complications. FUNDING: none. TRIAL REGISTRATION: Approval was obtained from the Danish Data Protection Agency (1-16-02-430-13).

Cardiovascular biomarkers in the evaluation of patent ductus arteriosus in very preterm neonates: A cohort study.

BACKGROUND: The evaluation of the patent ductus arteriosus (PDA) in the very premature neonate is a challenge. Echocardiography provides an interpretation of the hemodynamic condition. It is however, only a snapshot. Biomarkers may represent a physiological response to the hemodynamic alterations brought on by the PDA and may add to the identification of the clinical significant PDA. AIM: To investigate the association between mid regional proadrenomodulin (MR-proADM), N-terminal pro b-type natriuretic peptide (NT-proBNP), mid regional pro-atrial natriuretic peptide (MR-proANP), C-terminal pro endothelin-1 (CT-proET1) and copeptin and echocardiographic measures of PDA. STUDY DESIGN: Cohort study with echocardiography performed on day 3 and 6. Blood samples from day 3. SUBJECT: 139 consecutive neonates born at a gestational age <32 weeks. OUTCOME MEASURES: The main outcomes were presence of a PDA day 3 and 6, PDA diameter, left atrium to aorta ratio (LA:Ao-ratio), and descending aorta diastolic flow (DADF). RESULTS: Adjusted plasma levels of all investigated biomarkers, except CT-proET1, were found to be associated with both PDA diameter and LA:Ao-ratio, and also the presence of a large PDA. CT-proET1 and copeptin was found to be associated with abnormal DADF. Using pre-specified cut-off values NT-proBNP and MR-proANP day 3 seemed to be of value in identifying a large PDA day 3 and 6 in very preterm neonates. CONCLUSION: Among the investigated biomarkers NT-proBNP and MR-proANP performed best in relation to echocardiographic markers of PDA severity in very preterm neonates.

Attention-deficit/hyperactivity disorder symptoms in children with surgically corrected Ventricular Septal Defect, Transposition of the Great Arteries, and Tetralogy of Fallot.

BACKGROUND: Children with complex CHD are at risk for psychopathology such as severe attention-deficit/hyperactivity disorder symptoms after congenital heart surgery. OBJECTIVE: The aim of this study was to investigate if children with Ventricular Septal Defect, Transposition of Great Arteries, or Tetralogy of Fallot have an increased occurrence of attention-deficit/hyperactivity disorder symptoms compared with the background population and to investigate differences between the three CHDs in terms of occurrence and appearance of attention-deficit/hyperactivity disorder symptoms. METHOD: A national register-based survey was conducted, including children aged 10-16 years with surgically corrected CHDs without genetic abnormalities and syndromes. The Attention-Deficit/Hyperactivity Disorder-Rating Scale questionnaires were filled in by parents and school teachers. RESULTS: In total, 159 out of 283 questionnaires were completed among children with CHDs and compared with age- and sex-matched controls. Children with CHDs had significantly increased inattention scores (p = 0.009) and total attention-deficit/hyperactivity disorder scores (p = 0.008) compared with controls. Post hoc analyses revealed that children with Tetralogy of Fallot had significantly higher inattention scores compared with children both with Ventricular Septal Defect (p = 0.043) and controls (p = 0.004). CONCLUSION: Attention-deficit/hyperactivity disorder symptoms and inattention symptoms were significantly more frequent among children aged 10-16 years with CHDs, in particular in children with corrected Tetralogy of Fallot.

The accuracy of prenatal diagnosis of major congenital heart disease is increasing.

Regular audit of results of prenatal screening for congenital heart disease (CHD) is crucial to ensure reliable prenatal diagnosis. We aimed to assess the accuracy of prenatal diagnosis of major CHD between 1996 and 2013. During the study period, prenatal detection of major CHD improved from 4.5% to 71.0% (p<.001). Prenatal diagnoses on 628 live born children and terminated pregnancies were compared with postnatal findings or autopsy reports. The proportion of correct diagnoses increased throughout the study period from 42.9% in 1996 and reached 88.2% in 2013 (p<.001). A total of 32 foetuses with suspected major CHD were terminated though no major CHD was found at autopsy. In these pregnancies, termination was mainly performed due to other anomalies in the foetus.Along with improved detection of major CHD, the validity of a prenatal diagnosis is increasing. No cases of misinterpreted major CHD resulted in the termination of a healthy foetus in this study.Impact statementWhat is already known on this subject? Prenatal diagnosis of isolated congenital heart disease (CHD) correlates well with lesions found during autopsy performed in terminated foetuses. Few studies have assessed the accuracy of prenatal diagnosis of major CHD in live born children, cases with associated anomalies and the time trend in validity.What the results of this study add? This study illustrates that the validity of prenatal diagnosis of major CHD is increasing. Prenatal diagnoses in terminated pregnancies as well as in live born children is high except for coarctation of the aorta and atrioventricular septal defects. Chromosomal anomalies are associated with lower accuracy of prenatal diagnosis.What the implications are of these findings for clinical practice and/or further research? Prenatal diagnosis is an accurate tool for detecting major CHD. Misinterpretation has not led to the termination of a healthy foetus; however, this study illustrates that vigilant care should be placed on the cardiac evaluation when termination is considered due to the cardiac defect.

Impact of congenital heart surgery on quality of life in children and adolescents with surgically corrected Ventricular Septal Defect, Tetralogy of Fallot, and Transposition of the Great Arteries.

OBJECTIVE: To describe the impact of CHD surgery in early childhood on quality of life in children aged 10-16 years with surgically corrected Ventricular Septal Defect, Transposition of the Great Arteries, and Tetralogy of Fallot. METHOD: A cross-sectional survey study of quality of life survey on 161 children and adolescents aged 10-16 years with surgically corrected Ventricular Septal Defect, Transposition of the Great Arteries, and Tetralogy of Fallot. The international Paediatric Quality of Life 4.0 quality of life questionnaires were applied and collected for assessment from patients and parents. The endpoints were total, physical, emotional, social, and school quality of life scores. RESULTS: The quality of life total and school scores was significantly lower in children with CHD than their healthy peers. There was no significant difference in quality of life between the three CHD groups. All three CHD groups had a significantly lower total (7.7-13.2%, p<0.001) and school scores (21.1-31.6%, p<0.001) than the control group. The tetralogy of Fallot group was the only group that had significantly lower scores in the physical subscale (p<0.001) than the controls. CONCLUSION: Children and adolescents with surgically corrected CHD show losses in quality of life in total and school scores compared to healthy controls. The tetralogy of Fallot group was the only CHD group that had significantly lower physical score than the controls.

Mortality and morbidity of major congenital heart disease related to general prenatal screening for malformations.

BACKGROUND: Major congenital heart diseases (CHD) often demand intervention in the neonatal period. Prenatal diagnosis may improve mortality by eliminating the diagnostic delay; however, there is controversy concerning its true effect. We aimed to evaluate the effect of general prenatal screening on prognosis by comparing a period without general prenatal screening to a period with general prenatal screening. METHODS: We conducted a nationwide retrospective study including live born children and terminated fetuses diagnosed with major CHD. Prenatal screening was recommended only in high risk pregnancies between 1996 and 2004, whereas general prenatal screening was recommended between 2005 and 2013. We assessed the influence of general prenatal screening on all-cause mortality, cardiac death, preoperative and postoperative 30-day mortality and complication rate. RESULTS: 1-year mortality decreased over both periods, but the decrease was greater in the screening period (Odds ratio 0.92 (CI 0.83-1.00), p = 0.047). Prenatal detection of major CHD was associated with cardiac death in the period without general screening (Hazard Ratio 2.40 (CI 1.72-3.33), p < 0.001), whereas there was no significant association once general screening was implemented. Similarly, the association between prenatal diagnosis and pre- and postoperative mortality found in the period without general screening was insignificant after the implementation of general screening. CONCLUSION: Mortality in major CHD decreased throughout the study, especially in the period with general prenatal screening. However, comparing a prenatally diagnosed group with a postnatally diagnosed group is vulnerable to selection bias and proper interpretation is difficult.

Live-Born Major Congenital Heart Disease in Denmark: Incidence, Detection Rate, and Termination of Pregnancy Rate From 1996 to 2013.

Importance: The occurrence of major congenital heart disease (CHD) is affected by several variables. Determining the development of the true incidence is critical to the establishment of proper treatment of these patients. Objective: To evaluate time trends in incidence, detection rate, and termination of pregnancy (TOP) rate of major CHD in fetuses in Denmark and assess the influence of the introduction of general prenatal screening in 2004. Design, Setting, and Participants: Nationwide, population-based, retrospective observational study in Denmark from 1996 to 2013 that included a consecutive sample of 14 688 live-born children and terminated fetuses diagnosed as having CHD. Patient records on TOP and children with major CHD were reviewed to validate the diagnoses. Major CHD included univentricular heart, transposition of the great arteries, congenitally corrected transposition of the great arteries, truncus arteriosus, interrupted aortic arch, atrioventricular septal defects, double outlet right ventricle, coarctatio of the aorta, Ebstein anomaly, pulmonary atresia with ventricular septal defect, pulmonary atresia with intact ventricular septum, and tetralogy of Fallot. Data were analyzed between January 2017 and March 2018. Main Outcomes and Measures: Temporal changes in incidence, detection rate, and TOP of major CHD. Results: Of 14 688 children and fetuses diagnosed with CHD, 2695 (18.4%; 95% CI, 17.8-19.1) had major CHD. A total of 7131 boys (1304 with major CHD) and 6926 girls (920 with major CHD) were included, with a median age of 11 years (interquartile range, 6-15 years). During the study period, the live-birth incidence of CHD was constant at 1.22% (95% CI, 1.18-1.26), whereas it decreased for major CHD. When including TOP, the incidence of major CHD did not change over time. The detection rate of major CHD increased from 4.5% (95% CI, 1.2-7.8) to 71.0% (95% CI, 63.3-78.7) (P < .001). At the end of the study, all cases of double outlet right ventricle, Ebstein anomaly, congenitally corrected transposition of the great arteries, and pulmonary atresia with ventricular septal defect were detected prenatally, whereas coarctation of the aorta had the lowest detection rate (21.7%; 95% CI, 3.5-40.0). The TOP rate increased from 0.6% (95% CI, -0.6 to 1.9) to 39.1% (95% CI, 30.9-47.4) (P < .001) among all major CHD. For prenatally diagnosed major CHD, 57.8% of cases were terminated and the proportion did not change significantly throughout the study. Diagnoses leading to TOP included all major CHD diagnoses. Conclusions and Relevance: Detection rates of major CHD improved during the study. This has led to increased TOP rates, with a subsequent 39% decrease in the live-birth incidence of major CHD.

HUS-induced cardiac and circulatory failure is reversible using cardiopulmonary bypass as rescue.

BACKGROUND: Extra-renal involvement in hemolytic uremic syndrome (HUS) includes gastrointestinal, pancreatic, hepatic, neurological and cardiac manifestations. The current 3-5% mortality rate in HUS patients is primarily attributed to complications related to the central nervous system and the heart. In this brief report, we illustrate that severe cardiac involvement in a patient with HUS is potentially reversible using cardiopulmonary bypass as rescue. CASE-DIAGNOSIS/TREATMENT: A 12-year-old boy was diagnosed with enterohemorrhagic Escherichia coli-induced HUS related to E. coli serotypes O55:H7 and O121:H19. The patient developed anuria and hypertension of 150/105 mmHg and had neurological symptoms, with lethargy, confusion and later a tonic-clonic seizure successfully treated with midazolam. Laboratory tests on blood samples revealed acute renal failure, with a creatinine level of 3.98 mg/dL, thrombocytopenia of 47 × 109/L, lactate dehydrogenase level of 3620 IU/L, low haptoglobin (<20 mg/dL), anemia (10.0 g/dL) and schistocytes on blood smears. Peritoneal dialysis was initiated without complications. Serum potassium level was normal. At day 3, the patient suffered cardiac arrest on two separate occasions. Troponin-T, creatine kinase and creatine kinase-MB levels were significantly increased. The second episode of cardiac arrest could not be reversed with advanced cardiopulmonary resuscitation, and a cardiopulmonary bypass circuit was established. Declining cardiac pump function to a near non-contractile state with an ejection fraction of <10% was observed on echocardiography. This persisted during the following days. After the patient had been on the cardiopulmonary bypass (CPB) circuit for 7 days, the myocardium slowly recovered function. Three days later, the CPB was successfully discontinued; the echocardiography showed near-normal ejection fraction, and electrocardiography (ECG) showed sinus rhythm. CONCLUSIONS: Fatal outcome in patients with HUS may be the result of severe cardiac involvement. The present case illustrates the need for intensive supportive care, including the use of CPB, as the cardiac symptoms in HUS patients may be reversible. We suggest the monitoring of cardiac-specific enzymes, ECG and echocardiography in high-risk patients.

Nationwide experience of catecholaminergic polymorphic ventricular tachycardia caused by RyR2 mutations.

OBJECTIVE: The aim of this study was to characterise disease penetrance, course of disease and use of antiarrhythmic medication and implantable cardioverter-defibrillator (ICD) therapy in a Danish nationwide cohort of patients with catecholaminergic polymorphic ventricular tachycardia (CPVT) due to mutations in the ryanodine receptor-2 (RyR2) gene. METHODS: The study population was identified through the national hereditary heart disease database (Progeny). The study population was divided into three groups: probands, symptomatic and asymptomatic relatives. RESULTS: We identified 23 symptomatic probands, 18 symptomatic and 10 asymptomatic relatives with a RyR2 mutation. Twenty (87%) probands and 10 (36%) relatives had severe presenting symptoms (sudden cardiac death (SCD), aborted SCD (ASCD) or syncope).As compared with symptomatic relatives, probands had lower age at onset of symptoms (16 years (IQR, 10-33) vs 43 years (IQR, 25-54), p<0.0001) and were more prone to fatal or near-fatal events (ASCD, SCD) (16vs5, p<0.0001). Twenty-eight patients had an ICD implanted, and eight experienced appropriate ICD therapy during follow-up (65 months (IQR, 43-175)). Electrical storm was seen in two of the 28 ICD treated patients (7%). No patients receiving treatment died during follow-up (57 months (IQR, 32-139)). Multifocal atrial tachycardia was the predominant symptom in five patients. CONCLUSIONS: In a national cohort of RyR2 mutation-positive CPVT patients, SCD, ASCD and syncope were presenting events in the majority of probands and also occurred in 36% of relatives identified through family screening. Probands were younger at disease onset and more prone to fatal or near-fatal events than relatives.

Urinary Neutrophil Gelatinase-associated Lipocalin in the evaluation of Patent Ductus Arteriosus and AKI in Very Preterm Neonates: a cohort study.

BACKGROUND: A patent ductus arteriosus (PDA) is frequently found in very preterm neonates and is associated with increased risk of morbidity and mortality. A shunt across a PDA can result in an unfavorable distribution of the cardiac output and may in turn result in poor renal perfusion. Urinary Neutrophil Gelatinase-associated Lipocalin (U-NGAL) is a marker of renal ischemia and may add to the evaluation of PDA. Our primary aim was to investigate if U-NGAL is associated with PDA in very preterm neonates. Secondary, to investigate whether U-NGAL and PDA are associated with AKI and renal dysfunction evaluated by fractional excretion of sodium (FENa) and urine albumin in a cohort of very preterm neonates. METHODS: A cohort of 146 neonates born at a gestational age less than 32 weeks were consecutively examined with echocardiography for PDA and serum sodium, and urine albumin and sodium were measured on postnatal day 3 and U-NGAL and serum creatinine day 3 and 6. AKI was defined according to modified neonatal Acute Kidney Injury Network (AKIN) criteria. The association between U-NGAL and PDA was investigated. And secondly we investigated if PDA and U-NGAL was associated with AKI and renal dysfunction. RESULTS: U-NGAL was not associated with a PDA day 3 when adjusted for gestational age and gender. A PDA day 3 was not associated with AKI when adjusted for gestational age and gender; however, it was associated with urine albumin. U-NGAL was not associated with AKI, but was found to be associated with urine albumin and FENa. CONCLUSIONS: Based on our study U-NGAL is not considered useful as a diagnostic marker to identify very preterm neonates with a PDA causing hemodynamic changes resulting in early renal morbidity. The interpretation of NGAL in preterm neonates remains to be fully elucidated.