The effect of sildenafil on pleural and peritoneal effusions after the TCPC operation

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.Peer reviewe

External validation of the HCM Risk-Kids model for predicting sudden cardiac death in childhood hypertrophic cardiomyopathy

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.Peer reviewe

Prenatal Diagnosis Improves the Postnatal Cardiac Function in a Population-Based Cohort of Infants with Hypoplastic Left Heart Syndrome

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 damagemeasurements 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 &plusmn; 7.4% vs 21.1 &plusmn; 6.3%, P = .0004; strain rate, 1.1 &plusmn; 0.6/1.3 &plusmn; 1.0 vs 0.7 &plusmn; 0.2/0.7 &plusmn; 0.3 1/sec, P = .004/.003; myocardial velocity, 1.6 &plusmn; 0.6/2.0 &plusmn; 1.1 vs 1.3 &plusmn; 0.4/1.4 &plusmn; 0.4 cm/sec, P = .0035/.0009). Mechanical dyssynchrony was similar in both groups (P &gt; .30). Infants diagnosed prenatally had less acidosis (pH = 7.30 vs 7.25, P = .005) and end-organ dysfunction (alanine aminotransferase, 33 &plusmn; 38 vs 139 &plusmn; 174 U/L, P = .0001;creatinine, 78 &plusmn; 18 vs 81 &plusmn; 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. (J Am Soc Echocardiogr 2013;26:1073-9.)Keywords: Hypoplastic left heart syndrome, Prenatal diagnosis, Cardiac function, Velocity Vector Imaging<br /

Anticancer compound ABT-263 accelerates apoptosis in virus-infected cells and imbalances cytokine production and lowers survival rates of infected mice

Peer reviewe

Clinical Features and Natural History of Preadolescent Nonsyndromic Hypertrophic Cardiomyopathy

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. (C) 2022 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation.Peer reviewe

Relationship Between Maximal Left Ventricular Wall Thickness and Sudden Cardiac Death in Childhood Onset Hypertrophic Cardiomyopathy

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 to = 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 to = 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.Peer reviewe

Renal-hepatic-pancreatic dysplasia type 2 : Perinatal lethal condition or a multisystemic disorder with variable expressivity

BackgroundRenal-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. MethodsAn 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. ResultsWith 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. ConclusionsThese 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.Peer reviewe

Hybrid carbon materials:synthesis, characterization, and application in the removal of pharmaceuticals from water

Abstract Hydrothermal carbonization was used to develop novel carbon-based hybrids for the removal of diclofenac and amoxicillin from water. These non-crystalline and partly graphitic materials can be regenerated by photocatalysis. The synthesized materials have beneficial oxygen containing surface functional groups, of which C=O were observed only for tungsten-containing hybrid. An interaction between W, C and TiO₂ was observed, which could influence the photocatalytic performance. The best performance was observed for W-containing hybrid (HC butox W) at pH 3 (diclofenac photocatalytic degradation of 80% and removal of 93% after 60 min). Significant part of the removal appeared due to precipitation of diclofenac on the hybrid material surface. Removal efficiency was fully recovered after regeneration at pH 7 under uv-B irradiation. With the same hybrid, 10% removal of amoxicillin after 30 min with 42% photocatalytic degradation at non-adjusted pH was reached. In general, tungsten improved the photocatalytic activity of material, while specific surface area played only a minor role

Biallelic loss-of-function in NRAP is a cause of recessive dilated cardiomyopathy

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 Conclusion Loss-of-function in NRAP is a cause for autosomal recessive dilated cardiomyopathy, supporting its inclusion in comprehensive genetic testing.Peer reviewe