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Familial cardiomyopathy in pediatric stages is a poorly understood presentation of heart disease in children that is attributed to pathogenic mutations. Through exome sequencing, we report a homozygous variant in tropomodulin 1 (TMOD1; c.565C>T, p.R189W) in three individuals from two unrelated families with childhood-onset dilated and restrictive cardiomyopathy. To decipher the mechanism of pathogenicity of the R189W mutation in TMOD1, we utilized a wide array of methods, including protein analyses, biochemistry and cultured cardiomyocytes. Structural modeling revealed potential defects in the local folding of TMOD1 R189W and its affinity for actin. Cardiomyocytes expressing GFP-TMOD1 R189W demonstrated longer thin filaments than GFP-TMOD1 wt -expressing cells, resulting in compromised filament length regulation. Furthermore, TMOD1 R189W showed weakened activity in capping actin filament pointed ends, providing direct evidence for the variant's effect on actin filament length regulation. Our data indicate that the p.R189W variant in TMOD1 has altered biochemical properties and reveals a unique mechanism for childhood-onset cardiomyopathy., (© 2024. The Author(s).)

Background: Renal-hepatic-pancreatic dysplasia type 2 (RHPD2) is a rare condition that has been described in the literature disproportionately in perinatal losses. The main features of liver and kidney involvement are well described, with cardiac malformations and cardiomyopathy adding additional variation to the phenotype. Many patients reported are within larger cohorts of congenital anomalies of kidney and urinary tract (CAKUT) or liver failure, and with minimal phenotypic and clinical course data., Methods: An independent series of phenotypes and prognosis was aggregated from the literature. In this literature review, we describe an additional patient with RHPD2, provide a clinical update on the oldest known living patient, and report the cumulative phenotypes from the existing published patients., Results: With now examining the 17 known patients in the literature, 13 died within the perinatal period-pregnancy to one year of life. Of the four cases living past the first year of life, one case died at 5 years secondary to renal failure, the other at 30 months secondary to liver and kidney failure. Two are currently alive and well at one year and 13 years. Two cases have had transplantation with one resulting in long-term survival., Conclusions: These patients serve to expand the existing phenotype of RHPD2 as a perinatal lethal condition into a pediatric disorder with variable expressivity. Additionally, we introduce the consideration of transplantation and outcomes within this cohort and future patients., (© 2023 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)

Background: Up to one-half of childhood sarcomeric hypertrophic cardiomyopathy (HCM) presents before the age of 12 years, but this patient group has not been systematically characterized., Objectives: The aim of this study was to describe the clinical presentation and natural history of patients presenting with nonsyndromic HCM before the age of 12 years., Methods: Data from the International Paediatric Hypertrophic Cardiomyopathy Consortium on 639 children diagnosed with HCM younger than 12 years were collected and compared with those from 568 children diagnosed between 12 and 16 years., Results: At baseline, 339 patients (53.6%) had family histories of HCM, 132 (20.9%) had heart failure symptoms, and 250 (39.2%) were prescribed cardiac medications. The median maximal left ventricular wall thickness z-score was 8.7 (IQR: 5.3-14.4), and 145 patients (27.2%) had left ventricular outflow tract obstruction. Over a median follow-up period of 5.6 years (IQR: 2.3-10.0 years), 42 patients (6.6%) died, 21 (3.3%) underwent cardiac transplantation, and 69 (10.8%) had life-threatening arrhythmic events. Compared with those presenting after 12 years, a higher proportion of younger patients underwent myectomy (10.5% vs 7.2%; P = 0.045), but fewer received primary prevention implantable cardioverter-defibrillators (18.9% vs 30.1%; P = 0.041). The incidence of mortality or life-threatening arrhythmic events did not differ, but events occurred at a younger age., Conclusions: Early-onset childhood HCM is associated with a comparable symptom burden and cardiac phenotype as in patients presenting later in childhood. Long-term outcomes including mortality did not differ by age of presentation, but patients presenting at younger than 12 years experienced adverse events at younger ages., Competing Interests: Funding Support and Author Disclosures This work was supported by the British Heart Foundation (grant FS/16/72/32270) to Drs Norrish and Kaski. This work is (partly) funded by the National Institute for Health Research Great Ormond Street Hospital Biomedical Research Centre. Dr Norrish is supported by Great Ormond Street Hospital Children’s Charity. Drs Field and Kaski are supported by Max’s Foundation and Great Ormond Street Hospital Children’s Charity. Dr Kaski is supported by a Medical Research Council–National Institute for Health Research Clinical Academic Research Partnership award. This work was financially supported by the Foundation for Paediatric Research of Finland (Dr Ojala). Dr Fernandez has received speaker fees from Sanofi-Genzyme. Dr Kubus is supported by MH CZ – DRO, Motol University Hospital (00064203). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Maximal left ventricular wall thickness (MLVWT) is a risk factor for sudden cardiac death (SCD) in hypertrophic cardiomyopathy (HCM). In adults, the severity of left ventricular hypertrophy has a nonlinear relationship with SCD, but it is not known whether the same complex relationship is seen in childhood. The aim of this study was to describe the relationship between left ventricular hypertrophy and SCD risk in a large international pediatric HCM cohort., Methods: The study cohort comprised 1075 children (mean age, 10.2 years [±4.4]) diagnosed with HCM (1-16 years) from the International Paediatric Hypertrophic Cardiomyopathy Consortium. Anonymized, noninvasive clinical data were collected from baseline evaluation and follow-up, and 5-year estimated SCD risk was calculated (HCM Risk-Kids)., Results: MLVWT Z score was <10 in 598 (58.1%), ≥10 to <20 in 334 (31.1%), and ≥20 in 143 (13.3%). Higher MLVWT Z scores were associated with heart failure symptoms, unexplained syncope, left ventricular outflow tract obstruction, left atrial dilatation, and nonsustained ventricular tachycardia. One hundred twenty-two patients (71.3%) with MLVWT Z score ≥20 had coexisting risk factors for SCD. Over a median follow-up of 4.9 years (interquartile range, 2.3-9.3), 115 (10.7%) had an SCD event. Freedom from SCD event at 5 years for those with MLVWT Z scores <10, ≥10 to <20, and ≥20 was 95.6%, 87.4%, and 86.0, respectively. The estimated SCD risk at 5 years had a nonlinear, inverted U-shaped relationship with MLVWT Z score, peaking at Z score +23. The presence of coexisting risk factors had a summative effect on risk., Conclusions: In children with HCM, an inverted U-shaped relationship exists between left ventricular hypertrophy and estimated SCD risk. The presence of additional risk factors has a summative effect on risk. While MLVWT is important for risk stratification, it should not be used either as a binary variable or in isolation to guide implantable cardioverter defibrillator implantation decisions in children with HCM.

Aims: Sudden cardiac death (SCD) is the most common mode of death in childhood hypertrophic cardiomyopathy (HCM). The newly developed HCM Risk-Kids model provides clinicians with individualized estimates of risk. The aim of this study was to externally validate the model in a large independent, multi-centre patient cohort., Methods and Results: A retrospective, longitudinal cohort of 421 patients diagnosed with HCM aged 1-16 years independent of the HCM Risk-Kids development and internal validation cohort was studied. Data on HCM Risk-Kids predictor variables (unexplained syncope, non-sustained ventricular tachycardia, maximal left ventricular wall thickness, left atrial diameter, and left ventricular outflow tract gradient) were collected from the time of baseline clinical evaluation. The performance of the HCM Risk-Kids model in predicting risk at 5 years was assessed. Twenty-three patients (5.4%) met the SCD end-point within 5 years, with an overall incidence rate of 2.03 per 100 patient-years [95% confidence interval (CI) 1.48-2.78]. Model validation showed a Harrell's C-index of 0.745 (95% CI 0.52-0.97) and Uno's C-index 0.714 (95% 0.58-0.85) with a calibration slope of 1.15 (95% 0.51-1.80). A 5-year predicted risk threshold of ≥6% identified 17 (73.9%) SCD events with a corresponding C-statistic of 0.702 (95% CI 0.60-0.81)., Conclusions: This study reports the first external validation of the HCM Risk-Kids model in a large and geographically diverse patient population. A 5-year predicted risk of ≥6% identified over 70% of events, confirming that HCM Risk-Kids provides a method for individualized risk predictions and shared decision-making in children with HCM., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Familial dilated cardiomyopathy (DCM) is typically a monogenic disorder with dominant inheritance. Although over 40 genes have been linked to DCM, more than half of the patients undergoing comprehensive genetic testing are left without molecular diagnosis. Recently, biallelic protein-truncating variants (PTVs) in the nebulin-related anchoring protein gene (NRAP) were identified in a few patients with sporadic DCM., Methods and Results: We determined the frequency of rare NRAP variants in a cohort of DCM patients and control patients to further evaluate role of this gene in cardiomyopathies. A retrospective analysis of our internal variant database consisting of 31,639 individuals who underwent genetic testing (either panel or direct exome sequencing) was performed. The DCM group included 577 patients with either a confirmed or suspected DCM diagnosis. A control cohort of 31,062 individuals, including 25,912 individuals with non-cardiac (control group) and 5,150 with non-DCM cardiac indications (Non-DCM cardiac group). Biallelic (n = 6) or two (n = 5) NRAP variants (two PTVs or PTV+missense) were identified in 11 unrelated probands with DCM (1.9%) but none of the controls. None of the 11 probands had an alternative molecular diagnosis. Family member testing supports co-segregation. Biallelic or potentially biallelic NRAP variants were enriched in DCM vs. controls (OR 1052, p<0.0001). Based on the frequency of NRAP PTVs in the gnomAD reference population, and predicting full penetrance, biallelic NRAP variants could explain 0.25%-2.46% of all DCM cases., Conclusion: Loss-of-function in NRAP is a cause for autosomal recessive dilated cardiomyopathy, supporting its inclusion in comprehensive genetic testing., Competing Interests: Drs. Koskenvuo, Saarinen, Ahonen, Tommiska, Seppälä, Tuupanen, Kangas-Kontio, Schleit, Hathaway, Kytölä, Muona, Sistonen, Salmenperä, Gentile, Paananen, Myllykangas, Alastalo are full-time employees of Blueprint Genetics, a Quest Diagnostics Company, which offers genetic diagnostics for cardiomyopathies. The funder provided support in the form of salaries for authors [JWK, IS, SA, JT, ST, TKK, JS, JH, VK, MM, JS, PS, MG, JP, SM, TPA], but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Objectives: Both excessive and restricted fetal growth are associated with changes in cardiac geometry and function at birth. There are significant issues when indexing cardiac parameters for body size in the neonatal period. The aims of this study were to determine to what extent cardiac geometry is dependent on body size in term and preterm neonates with restricted or excessive fetal growth and how this is affected by adiposity., Methods: This was a cross-sectional study of neonates born between 31 and 42 weeks of gestation, divided into three groups: (1) small-for-gestational age (SGA, birth weight > 2 SD below the mean); (2) large-for-gestational age (LGA, birth weight > 2 SD above the mean); and (3) appropriate-for-gestational-age controls (AGA, birth weight ≤ 2 SD from the mean). Cardiac geometry and function were compared between the study groups, adjusting for body size. The potential impact of infant adiposity and maternal disease was assessed., Results: In total, 174 neonates were included, of which 39 were SGA, 45 were LGA and 90 were AGA. Body size was reflected in cardiac dimensions, with differences in cardiac dimensions disappearing between the SGA and AGA groups when indexed for body surface area (BSA) or thoracic circumference. The same was true for the differences in atrial and ventricular areas between the LGA and AGA groups. However, left ventricular inflow and outflow tract dimensions did not follow this trend as, when indexed for BSA, they were associated negatively with adiposity, resulting in diminished dimensions in LGA compared with AGA and SGA neonates. Adiposity was associated positively with left ventricular mass, right ventricular length and area and right atrial area. The SGA group showed increased right ventricular fractional area change, possibly reflecting differences in the systolic function of the right ventricle. We found evidence of altered diastolic function between the groups, with the mitral valve inflow E- to lateral E'-wave peak velocity ratio being increased in the LGA group and decreased in the SGA group., Conclusions: Cardiac geometry is explained by body size in both term and preterm AGA and SGA infants. However, the nature of the relationship between body size and cardiac dimensions may be influenced by adiposity in LGA infants, leading to underestimation of left ventricular inflow and outflow tract dimensions when adjusted for BSA. Adjustments for thoracic circumference provide similar results to those for BSA. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.)

Background: Patients with high-risk neuroblastoma (HR NBL) treated with myeloablative regimens are reported to be at risk for cardiovascular morbidity, and this risk may be increased by impaired renal function., Procedure: Long-term renal function was assessed in a national cohort of 18 (age 22.4 ± 4.9 years) HR NBL survivors by plasma creatinine (P-Cr), urea, and cystatin C (P-Cys C) concentrations, urine albumin/creatinine ratio (ACR), and estimated glomerular filtration rate (eGFR). Ambulatory blood pressure was monitored, and common carotid intima-media thickness (CIMT) and left ventricular mass index (LVMI) were evaluated., Results: No significant difference in P-Cr, P-Cys C, or eGFR was found between the NBL survivors and the age- and sex-matched 20 controls. P-Cys C-based eGFR (eGFRcysc) was significantly lower than the P-Cr-based eGFRcr (97 ± 17 mL/min/1.73 m 2 vs 111 ± 19 mL/min/1.73 m 2 , P < 0.001) among the NBL survivors. The eGFRcysc was below normal in 28%, and ACR was above normal in 22% of the NBL survivors. Abnormal blood pressure was found in 56% of the survivors, and an additional 17% were normotensive at daytime but had significant nocturnal hypertension. Both ACR and P-Cys C were associated with nighttime diastolic hypertension., Conclusions: Long-term survivors of childhood HR NBL showed signs of only mild renal dysfunction associated with diastolic hypertension. Elevated ACR and P-Cys C were the most sensitive indicators of glomerular renal dysfunction and hypertension in this patient cohort., (© 2020 Wiley Periodicals, Inc.)

Background: We evaluated whether the administration of sildenafil in children undergoing the TCPC operation shortened the interval from the operation to the removal of the pleural and peritoneal drains., Methods: We retrospectively reviewed the data of 122 patients who had undergone the TCPC operation between 2004 and 2014. Patients were divided into two groups on the basis of their treatments. Sildenafil was orally administered pre-operatively in the morning of the procedure or within 24 hours after the TCPC operation to the sildenafil group (n = 48), which was compared to a control group (n = 60). Fourteen patients were excluded from the study., Results: The primary outcome measure was the time from the operation to the removal of the drains. The study groups had similar demographics. The median [interquartile range] time for the removal of drains (sildenafil group 11 [8-19] vs control group 11 [7-16] d, P = .532) was comparable between the groups. The median [interquartile range] fluid balance on the first post-operative day was significantly higher (P = .001) in the sildenafil group compared with controls (47 [12-103] vs 7 [-6-67] mL kg -1 ). The first post-operative day fluid balance was a significant predictor for a prolonged need for drains in the multivariate analysis., Conclusions: Sildenafil administration, pre-operatively or within 24 hours after the TCPC operation, did not reduce the required time for pleural and peritoneal drains but was associated with a significantly higher positive fluid balance., (© 2019 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Background: Childhood cardiomyopathies are progressive and often lethal disorders, forming the most common cause of heart failure in children. Despite severe outcomes, their genetic background is still poorly characterized., Objectives: The purpose of this study was to characterize the genetics of severe childhood cardiomyopathies in a countrywide cohort., Methods: The authors collected a countrywide cohort, KidCMP, of 66 severe childhood cardiomyopathies from the sole center in Finland performing cardiac transplantation. For genetic diagnosis, next-generation sequencing and subsequent validation using genetic, cell biology, and computational approaches were used., Results: The KidCMP cohort presents remarkable early-onset and severe disorders: the median age of diagnosis was 0.33 years, and 17 patients underwent cardiac transplantation. The authors identified the pathogenic variants in 39% of patients: 46% de novo, 34% recessive, and 20% dominantly-inherited. The authors report NRAP underlying childhood dilated cardiomyopathy, as well as novel phenotypes for known heart disease genes. Some genetic diagnoses have immediate implications for treatment: CALM1 with life-threatening arrhythmias, and TAZ with good cardiac prognosis. The disease genes converge on metabolic causes (PRKAG2, MRPL44, AARS2, HADHB, DNAJC19, PPA2, TAZ, BAG3), MAPK pathways (HRAS, PTPN11, RAF1, TAB2), development (NEK8 and TBX20), calcium signaling (JPH2, CALM1, CACNA1C), and the sarcomeric contraction cycle (TNNC1, TNNI3, ACTC1, MYH7, NRAP)., Conclusions: Childhood cardiomyopathies are typically caused by rare, family-specific mutations, most commonly de novo, indicating that next-generation sequencing of trios is the approach of choice in their diagnosis. Genetic diagnoses may suggest intervention strategies and predict prognosis, offering valuable tools for prioritization of patients for transplantation versus conservative treatment., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

The aim of this study was to analyze the prevalence of frailty and physical health limitations among long-term survivors of high-risk neuroblastoma (HR NBL) and to investigate whether frail health is associated with variables of cardiovascular function, markers of inflammation and telomere length. A national study cohort of 19 (median age 22, range 16-30 years) long-term (>10 years) HR NBL survivors was studied and the findings were compared with 20 age- and sex-matched controls. Frailty was defined as ⩾3 of the following conditions: low muscle mass, low energy expenditure, slow running and weakness. The prevalence of frailty was significantly higher among the HR NBL survivors 9/19 (47%) than among the controls (0%). Thirteen (68%) of the survivors reported significant physical health limitations in vigorous activities, as opposed to none of the controls. The HR NBL survivors had significantly shorter telomere length and higher serum levels of high sensitivity C-reactive protein than did the controls. Frail health and poor physical functioning are prevalent among HR NBL survivors and suggest premature aging. Survivors with gonadal damage, very low fat mass percentage, low glycosylated hemoglobin A1c and increased common carotid artery intima-media thickness may be more prone to early aging after high dose therapy.

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., (© 2017, Wiley Periodicals, Inc.)

Background: Restriction in fetal growth is associated with cardiovascular disease in adulthood. It is unclear whether abnormal intrauterine growth influences arterial morphology during the fetal or neonatal stage. The objective was to study the regional arterial morphology with respect to gestational age and abnormal fetal body size., Methods and Results: We studied body anthropometrics and arterial morphology and physiology in 174 neonates born between 31 and 42 weeks of gestation, including neonates with birth weights appropriate, small, and large for age, with very high resolution vascular ultrasound (35-55 MHz). In simple linear regressions, parameters of body size (body weight, body surface area, and organ circumference) and gestational age were statistically significantly associated with common carotid, brachial, femoral arterial parameters (lumen diameter [LD], wall layer thickness [intima-media thickness and intima-media-adventitia thickness], and carotid artery wall stress [CAWS]). Male sex was statistically significantly associated with LD and CAWS. In multiple linear regression models, body size, gestational age, and sex explained a large proportion of the arterial variance (R( 2) range, 0.37-0.47 for LD; 0.09-0.35 for intima-media thickness; 0.21-0.41 for intima-media-adventitia thickness; and 0.23 for CAWS; all models P<0.001). Arterial wall layer thickness, LDs, and CAWS were independently and strongly predicted by body size, and no effect of maternal disease was observed when added to the models. Gestational age and male sex were also independently but more weakly associated with arterial LDs and CAWS (P<0.01), but not with arterial wall layers., Conclusions: These results indicate that the intrauterine growth of fetal arterial LD and wall layer thickness are primarily attributed to body growth overall. LD and CAWS show weaker association with gestational age and sex., (© 2016 American Heart Association, Inc.)

Background: The aim of the study was to evaluate arterial morphology and function in a national cohort of long-term survivors of high-risk neuroblastoma (NBL) treated with high-dose chemotherapy and autologous hematopoietic stem cell transplantation with or without total body irradiation (TBI)., Methods and Results: Common carotid, femoral, brachial, and radial artery morphology were assessed with very-high-resolution vascular ultrasound (25-55 MHz), and carotid artery stiffness and brachial artery flow-mediated dilatation measured with conventional vascular ultrasound in 19 adult or pubertal (age 22.7 ± 4.9 years, range 16-30) NBL survivors transplanted during 1984-1999 at the mean age of 2.5 ± 1.0 years. Results were compared with 20 age- and sex-matched healthy controls. The cardiovascular risk assessment included history, body mass index, fasting plasma lipids, glucose, and 24-h ambulatory blood pressure (BP). The survivors had consistently smaller arterial lumens, increased carotid intima-media thickness (IMT), plaque formation (N = 3), and stiffness, as well as increased radial artery intima thickness (N = 5) compared with the control group. Survivors displayed higher plasma triglyceride and cholesterol levels, and increased heart rate, as well as increased systolic and diastolic BPs. TBI (N = 10) and a low body surface area were independent predictors for decreased arterial lumen size and increased IMT. Three out of five survivors with subclinical intima thickening had arterial plaques. Plaques occurred only among TBI-treated survivors., Conclusions: Long-term childhood cancer survivors treated with TBI during early childhood display significant signs of premature arterial aging during young adulthood., (© 2015 Wiley Periodicals, Inc.)

Background: Non-invasive transcutaneous very-high resolution ultrasound (VHRU, 25-55 MHz) has recently been developed to quantify superficial vascular structures in humans. The performance of the method has yet not been evaluated in vivo in neonates. The aim of the study was to compare VHRU with conventional high-resolution ultrasound (HRU, 7-12 MHz), and to assess the feasibility and precision of VHRU in this population., Methods: 150 images from central elastic (common carotid, CCA) and peripheral muscular (brachial, BA; femoral, FA) arteries were obtained in 25 neonates of different gestational ages (range 33 + 0 to 41 + 5 gestational weeks) and weights (range 1570-4950 g) with VHRU, and the use of HRU for comparison assessed in five., Results: Images were captured from CCAs with 35 MHz, FAs using 35 and 55 MHz, and BAs using 55 MHz. 12 MHz was unable to assess FAs and BAs, and the CCA IMT was grossly overestimated compared with 35-55 MHz. IMTs of the smallest BAs and FAs were beyond the axial resolution of VHRU (<0.05 mm), thus immeasurable. For VHRU, the intra-, inter- and test-retest coefficients of variation (CV) were for LDs (range 1.44-2.62 mm, CVs between 1.6 and 4.8%), IMATs (range 0.141-0.161 mm, CVs between 8.8 and 19.9%), and IMTs (range 0.062-0.165 mm, CVs between 12.8 and 24.8%) for the different arteries., Conclusion: VHRU is feasible, accurate and precise in the assessment of superficial proximal conduit arteries but unable to assess the abdominal aorta in human neonates HRU-derived neonatal conduit arterial wall layer thicknesses are below the ultrasound axial resolution., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

The majority of congenital heart defects occur without identifiable risk factors. Detection rates are therefore highly dependent on the experience and expertise of the obstetrical screening operator. In the first trimester, the risk of congenital heart defects increases with increasing nuchal thickness (≥2.5 mm detects 44% of major congenital heart defects), but because of the number of false positives, the positive predictive value is only a few percent. The anatomy of major congenital heart defects may be delineated in less than half of the fetuses during early second trimester. The reported yield of congenital heart defects detection during the mid-gestational routine obstetrical screening has improved over time and detection rates up to 85% of major congenital heart defects have been reported when outflow tract and three-vessel views are included in conjunction with the four-chamber view. Improved detection rates have been achieved following screening operator training interventions combined with a low referral threshold to obtain a detailed fetal echocardiographic study., (© 2014 Nordic Federation of Societies of Obstetrics and Gynecology.)

Background: Prenatal diagnosis of hypoplastic left heart syndrome (HLHS) enables planning of perinatal care and is known to be associated with more stable preoperative hemodynamics. The impact on postnatal myocardial function is poorly known. The aim of this study was to determine the impact of prenatal diagnosis of HLHS on postnatal myocardial function., Methods: A consecutively encountered cohort of 66 infants with HLHS born between 2003 and 2010 in Finland was retrospectively reviewed. Twenty-five infants had prenatal diagnoses. Postnatal global and segmental right ventricular fractional area change, strain rate, and myocardial velocity were analyzed from the apical four-chamber view using Velocity Vector Imaging. Preoperative hemodynamic status and end-organ damage measurements were the lowest arterial pH, highest lactate, alanine aminotransferase, and creatinine. Early mortality was studied until 30 days after Norwood procedure., Results: Prenatally diagnosed infants had better cardiac function (fractional area change, 27.9 ± 7.4% vs 21.1 ± 6.3%, P = .0004; strain rate, 1.1 ± 0.6/1.3 ± 1.0 vs 0.7 ± 0.2/0.7 ± 0.3 1/sec, P = .004/.003; myocardial velocity, 1.6 ± 0.6/2.0 ± 1.1 vs 1.3 ± 0.4/1.4 ± 0.4 cm/sec, P = .0035/.0009). Mechanical dyssynchrony was similar in both groups (P > .30). Infants diagnosed prenatally had less acidosis (pH = 7.30 vs 7.25, P = .005) and end-organ dysfunction (alanine aminotransferase, 33 ± 38 vs 139 ± 174 U/L, P = .0001; creatinine, 78 ± 18 vs 81 ± 44 mmol/L, P = .05). No deaths occurred among the prenatally diagnosed infants, but four deaths were recorded among postnatally diagnosed infants (P = .15)., Conclusions: A prenatal diagnosis of HLHS is associated with improved postnatal right ventricular function, reduced metabolic acidosis, and end-organ dysfunction., (Copyright © 2013 American Society of Echocardiography. Published by Mosby, Inc. All rights reserved.)

Background: Objective information on specific fetal heart rate (FHR) parameters would be advantageous when assessing fetal responses to hypoxia. Small, visually undetectable changes in FHR variability can be quantified by power spectral analysis of FHR variability., Aims: To investigate the effect of intrapartum hypoxia and acidemia on spectral powers of FHR variability., Study Design: This is a retrospective observational clinical study with data from an EU multicenter project., Subjects: We had 462 fetuses with a normal pH-value (pH>7.20; controls) in fetal scalp blood sample (FBS) and 81 fetuses with a low scalp pH-value (≤ 7.20; low-FBS pH-fetuses). The low-FBS pH-fetuses were further divided into two subgroups according to the degree of acidemia: fetuses with FBS pH7.11-7.20 (n = 58) and fetuses with FBS pH ≤7.10 (n = 23)., Outcome Measures: Spectral powers of FHR variability in relation to the concomitant FBS pH-value., Results: Fetuses with FBS pH ≤7.20 had increased spectral powers of FHR variability compared with controls (2.49 AU vs. 2.23 AU; p = 0.038). However, the subgroup of most affected fetuses (those with FBS pH ≤7.10) had significantly lower FHR variability spectral powers when compared to fetuses with FBS pH7.11-7.20., Conclusions: This study shows that spectral powers of FHR variability change as a fetus becomes hypoxic, and that spectral powers decrease with deepening fetal acidemia., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Clinical fetal heart failure occurs in conditions associated with increasing left and right atrial filling and/or central venous pressures and manifests as right heart failure with the development of pericardial and pleural effusions, ascites and peripheral and placental edema. Fetal heart failure may occur in primary myocardial disease, in presence of the extracardiac pathology impacting the loading conditions of the fetal heart and in conditions associated with secondary myocardial dysfunction including structural heart defects, bradycardia or tachycardia. This review summarizes recent literature of the understanding of the normal fetal circulation and the pathogenic mechanisms responsible for the evolution of fetal heart failure, strategies for fetal and perinatal management of fetal heart failure, and future directions that may lead to novel strategies to treat affected pregnancies and.

Objective: To assess whether intrapartum acidosis affects specific components of fetal heart rate variability., Design: Prospective clinical study., Setting: Twelve Nordic delivery units., Subjects: Fetal heart rate variability was studied in 334 fetuses divided into two groups according to cord pH value: the acidotic group (cord arterial pH < 7.05 at birth, n= 15) and the control group (cord arterial pH > or =7.05 at birth, n= 319)., Methods: In spectral analysis of fetal heart rate variability, frequencies were integrated over the total frequency band (0.04-1.0 Hz), low-frequency band (0.04-0.15 Hz) and high-frequency band (0.15-1.0 Hz). We also calculated the low-to-high frequency ratio., Main Outcome Measures: The spectral bands of fetal heart rate variability were compared between the acidotic and control fetuses., Results: We found that during the last hour of monitoring, baseline fetal heart rate gradually decreased, whereas total, low-frequency and high-frequency fetal heart rate variability initially increased but then, near the delivery, decreased in the acidotic fetuses when compared with the controls. Low-to-high frequency ratio was greater in the acidotic group during the whole study period (P= 0.002). Cord artery pH was inversely associated with total fetal heart rate variability (P < 0.001), low-frequency fetal heart rate variability (P < 0.001) and low-to-high frequency ratio (P= 0.004)., Conclusions: Marked fetal acidosis was associated with frequency-specific changes in fetal heart rate variability as reflecting the compensation ability of autonomic nervous activation during the last hour of labour.