Urinary N-terminal Pro-Brain Natriuretic Peptide in Newborn Infants with Cardiac and Pulmonary Diseases

Objectives The aim of this study was to assess the feasibility of urinary N-terminal pro-brain natriuretic peptide (NT-proBNP) as noninvasive screening tool for congenital heart diseases in full-term neonates with respiratory distress. Study Design A prospective cohort study was conducted on 90 full-term infants. Newborn were assigned into three groups: pulmonary, cardiac, and control groups. Urinary NT-proBNP were measured in all studied groups at day 1 (NT-proBNP1) and day 5 (NT-proBNP5). Results Urinary NT-proBNP1 was higher in cardiac group compared with pulmonary and control groups (488 ± 91, 321 ± 80, and 218 ± 41 ng/L, respectively; p ≤ 0.001). NT-proBNP5 was lower in pulmonary and control group than cardiac group (245 ± 84, 137 ± 39, and 546 ± 284 ng/L, respectively, with p ≤ 0.001). Receiver operating characteristic (ROC) analysis was performed to assess predictive value of NT-proBNP1 in cardiac and pulmonary populations. ROC showed area under curve of 0.97 and cutoff point of ≥386.5 ng/L referring to a cardiac etiology with sensitivity of 93.3%, specificity of 86.7%, negative predictive value of 93%, and positive predictive value of 88%. Conclusion Urinary NT-proBNP is feasible to be a noninvasive screening tool to predict congenital heart diseases in full-term neonates. Further studies are needed to assess the correlation between plasma and urinary levels of NT-proBNP in congenital heart diseases in full-term and preterm infants.

Diagnostic value of virtual autopsy using pm-MRI at 3T on malformed second trimester fetuses vs classic autopsy

Objective To determine the diagnostic value of virtual autopsy using post mortem-MRI (pm-MRI) at 3Tesla (T) compared to classic autopsy for the confirmation of fetal structural anomalies and secondly to establish which cases of termination of pregnancy would benefit mostly from a virtual autopsy. Methods In each of 32 fetuses included in the study, 32 anatomical structures were assessed, after termination of pregnancy in the second trimester. All cases were evaluated by prenatal ultrasonography, virtual autopsy and classic autopsy, and then divided into four groups: Cerebral Group, Cardiac Group, Renal Group and Other Group (miscellaneous group). The concordance of virtual autopsy with classic autopsy was calculated overall and for each group and each structural item. Also, the concordance between the two methods was assessed using a diagnostic error score (DgE_score), calculated as the absolute value of the difference between the number of malformations detected by classic autopsy per case (CA score) and the number of malformations detected at virtual autopsy per case (VA score). Results Overall virtual autopsy demonstrated a diagnostic sensitivity (Se) compared to classic autopsy of 67.33% [95% CI 57.28–76.33], with a specificity (Sp) of 98.37% [95% CI 97.33–99.09], a positive predictive value (PPV) of 81.93% [95% CI 71.95–89.52], a negative predictive value (NPV) of 96.49% [95% CI 95.11–97.57] achieving a diagnostic accuracy of 95.31% [95% CI 93.83–96.52]. Overall, no statistic significant correlation was demonstrated between DgE_score and the gestational age of the fetuses or between DgE_score and the weight of the fetuses, but a significant correlation was revealed between the virtual autopsy and classic autopsy score. The diagnostic utility of virtual autopsy using pm-MRI at 3 T as compared to classic autopsy for each category of termination of pregnancy revealed in the Cerebral Group a Se of 80.00% [95% CI 28.36–99.49], with a 96.30% [95% CI 81.03–99.91], a PPV of 80.00% [95% CI 35.75–96.64] a NPV of 96.30% [95% CI 81.81–99.34], with a diagnostic accuracy of 93.75% [95% CI 79.19% to 99.23] and a Cohen’s Kappa coefficient of 0.76 [95% CI 0.4494–1.0765]; in the Renal Group a Se and Sp of 100%, but in the Cardiac Group the Se was only 60.00% [95% CI 26.24–87.84], Sp 75% [95% CI 34.91–96.81], the PPV 75.00% [95% CI 44.92–91.69], NPV 60% [95% CI 38.87–77.96], with a diagnostic accuracy of 66.67% [95% CI 40.99–86.66] and a Cohen’s Kappa coefficient of 0.32 [95% CI -0.07–0.76]. Conclusions The results support virtual autopsy using pm-MRI at 3T as a reliable alternative to classic autopsy for the non-forensic analysis of second trimester fetuses. Analyzing the diagnostic utility of virtual autopsy using pm-MRI at 3 T for the confirmation of prenatal ultrasound findings in second trimester fetuses as compared to classic autopsy, the best results were obtained in the Cerebral and Renal Group. Reserved results were found in the Cardiac Group. Therefore, for the pregnancies with termination of pregnancy for cerebral or renal abnormalities, virtual autopsy by pm-MRI at 3T can be taken into consideration as a first-line investigation to confirm the prenatal findings.

Impact of Congenital Heart Disease on Growth of Down Syndrome Children (6-36 months)

Background Down syndrome (DS), the most common chromosomal abnormality is associated by congenital heart disease (CHD) in (44%) of cases. Children with DS might have different growth pattern compared to children without DS. Objective To assess the impact of congenital heart disease on the growth of Down syndrome children who attend the Genetic clinic, Children’s Hospital, Ain Shams University. Materials and Methods This case controlled study was conducted on 40 children with DS aged 6-36 months and compared to 40 age and sex matched healthy children. The DS children were divided in to two groups, the Cardiac Group: Included 20 DS children with CHD, Non Cardiac Group: 20 DS children without CHD. All children enrolled in the study were subjected to detailed history, thorough clinical examination including (anthropometric measurements (weight, height and HC) and cardiac examination. Results A statistically highly significant decrease was found in children with DS in comparison to normal children in all evaluated anthropometric measurements (P = 0.000) for weight, height, WT/length SDS, head circumference and Z-scores (weight, height and HC).A statistically highly significant decrease was found in DS children with congenital heart disease (cardiac group) in comparison with DS children without congenital heart disease (non-cardiac group) as regards weight (P = 0.002), Height (P = 0.000), head circumference (P = 0.000), Zscores (weight) (P = 0.001) and WT/length SDS (P = 0.001). Conclusion Children with trisomy 21 have well documented growth retardation. Congenital heart diseases have a negative influence on growth pattern in children with DS.

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<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.

The Influence of Oxidative Stress-Related Factors on Pregnancy and Neonatal Outcomes

Background: Pregnancy is a physiological process associated with an excessive oxidative stress for both the mother and the neonate. Oxidative stress was extensively studied and is still in focus as a factor of maternal pathologies during pregnancy, with consequences on the outcome of the neonate.Aim: The aim of our study was to determine whether oxidative stress-related factors can influence the outcome of pregnancy, delivery, and the neonate’s wellbeing.Material and methods: The study was conducted using a questionnaire among pregnant women with voluntary enrollment. Exclusion criteria were preeclampsia or other cardiovascular diseases, gestational diabetes, and hypothyroidism at admission. Patients were enrolled in a control group of 60 pregnant women without preexisting pathology and pregnancy with physiological course, a premature group of 21 pregnant women with premature delivery, and a cardiac group of 8 pregnant women with fetal heart disease known before birth. The study population was separated into subgroups based on dietary supplement use within the three main groups, and other subgroups for smoking/non-smoking mothers in the control group and one for smoking/non-smoking mothers in the premature and cardiac groups together.Results: The mean Apgar score at 1 minute was significantly higher in the control group compared to the cardiac group (p = 0.0023). The 1-minute Apgar score was significantly lower in infants that were born premature, from smoking mothers, compared to babies that were delivered at term (p = 0.0191). Although we did not obtain significant differences in birth weight corrected by gestational age between the control (mature) group and premature group, there was a good correlation in gestational age and birth weight of the preterm born infants (r = 0.8517, p <0.0001).Conclusions: Smoking can aggravate oxidative stress in pregnancy, which will contribute to a difficult postnatal adaptation of newborns from smoking mothers and will increase the risk of premature delivery.

Independent predictors of repeat emergency room presentations in patients with noncardiac chest pain: insights from a cohort of 1066 consecutive patients with 4770 repeat presentations

Introduction Repeat attendances with noncardiac chest pain (NCCP) to emergency room (ER) are frequent..Our aim was to analyse predictors of repeat presentations to ER in patients with NCCP. Methods We prospectively enrolled 1066 consecutive presentations with NCCP to a major urban hospital ER. Index of multiple deprivation (IMR) was computed. Charlson comorbidity (CCM) index was determined. Repeat presentation to ER to any national hospital was determined by a national linked database (pop. 53.5m). Results Median age was 43 (IQR 28, 59), 50.8% were male. 63% were current or previous smokers. 1 year incidence of adjudicated MI, coronary revascularisation and all-cause death was 0.6%, 2% and 5.3% respectively. There was a total of 4770 repeat ER presentations. After taking account of death independent predictors for repeat presentation were current smoking (OR 1.844, p=0.001) and CCM score ≥1 (OR 1.58, p=0.014) (table). Conclusions Smoking and patients with multiple comorbidities represent health policy targets for lessening hospital burden of NCCP. Funding Acknowledgement Type of funding source: Public hospital(s). Main funding source(s): Liverpool University Hospital NHS Trust; North-West Educational Cardiac Group

Assessment of Dental Status and Oral Health Status in Children with Congenital Heart Diseases

Purpose: This study aims to identify the dental caries, decayed, missing, and filled teeth index (dmft/DMFT) scores amongst children with cyanotic, and acyanotic congenital heart diseases (CHD), compare with healthy controls and identify the risk factors for poor dental health. Methods: Between January 2016 and June 2017, 236 children aged 2 to 15 years (mean±SD=7.61±3.88 yrs, median 7 yrs) with CHD and 951 healthy children aged 2 to 15 years (mean±SD=8.83±7.34 yrs, median 9 yrs) were evaluated. Results: Children with CHD had more caries in their primary and permanent dentition (mean dmft: 2.42±3.82, cardiac group vs. 2.32±6.68, control group; p<0·05; mean DMFT: 2.15±3.38, cardiac group vs. 1.27±1.89, control group; p=0.002). The DMFT scores for children with CHD were higher in the rural areas. Children frequently consuming biscuits, confectionary and sugared milk had higher dmft±SD scores. The possibility of caries in permanent dentition was more in children with cyanotic CHD compared to acyanotic. Caries in primary dentition showed positive correlation with age. Conclusions: CHD is associated with poorer dental health in children. Close cooperation between pediatric cardiologists and pediatric dentists is warranted to raise awareness, prevent and institute early treatment for dental ailments.

Cardiac troponin I in cats with compromised renal function

ObjectivesCardiac troponins are sensitive and specific markers of myocardial injury. However, their reliability in renal disease has been questioned owing to possible renal involvement in troponin elimination. The primary objective of the present study was to examine whether serum cardiac troponin I is elevated in cats with compromised renal function and no clinically relevant structural cardiac disease. A secondary objective was to examine whether cardiac troponin I is measurable in the urine of cats with normal and compromised renal function.MethodsThis prospective case-control study included 52 cats (19 with compromised renal function, 19 with primary cardiac disease and 14 healthy controls). For all cats, clinical examination, echocardiography, electrocardiography, blood pressure, complete blood count, biochemistry, serum thyroxine and urinalysis were performed. Cardiac troponin I was measured in the serum and urine of each cat.ResultsMedian (range) serum cardiac troponin I concentrations were 0.052 ng/ml (0.015–0.78 ng/ml) for the renal group, 0.083 ng/ml (0.003–3.27 ng/ml) for the cardiac group and 0.012 ng/ml (0.003–0.14 ng/ml) for the control group. The renal and cardiac groups both had significantly higher serum cardiac troponin I concentrations than the control group, whereas no difference could be detected between the renal and cardiac groups. In the renal group 7/19 cats had measurable urine cardiac troponin I, whereas cardiac troponin I was measurable in the urine of one cat in the cardiac group and two healthy controls. There was no significant correlation between serum and urine cardiac troponin I.Conclusions and relevanceElevated serum cardiac troponin I in cats with compromised renal function may occur without evidence of clinically relevant structural cardiac disease. Moreover, detecting cardiac troponin I in urine is most likely in cats with compromised renal function.

Abstract 144: Differing Pattern of ECG Changes During Resuscitation From Pulseless Electrical Activity Depending on Etiology

Introduction: Pulseless electrical activity (PEA) is a frequent initial rhythm in in-hospital cardiac arrest. ECG changes during cardiopulmonary resuscitation (CPR) have been linked to prognosis; QRS complex narrowing and increase in QRS-rate/heart rate was observed before return of spontaneous circulation (ROSC). Our hypothesis was that ECG changes during CPR of patients with cardiac arrest with initial PEA could also be different depending on etiology of arrest. Methods: Patients with cardiac arrest with initial PEA at St. Olav University Hospital (Trondheim, Norway) between January 2009 and January 2012 were prospectively included. QRS duration and heart rate were measured at all pauses in chest compressions. Etiologies were categorized as ‘Cardiac’ or ‘Other’. Trends in the material were inspected using additive mixed effects models for the last 18 minutes before ROSC or end of CPR and development of QRS width was analyzed using linear mixed effects models based on these trends. Results: A total of 63 patients for whom a reliable cause of arrest could be identified retrospectively were included. 1844 combined measurements of QRS width and heart rate were made. According to the additive mixed effects model the development in heart rate was similar in both etiology groups. The change in QRS width differed in patients who obtained ROSC, with the Cardiac group narrowing more than the other group, and both groups ending at essentially the same QRS widths at ROSC (figure). By the linear mixed effects model this difference in change was statistically significant (p=0.04). In patients who did not have ROSC, the cardiac group had significantly (p=0.001, linear mixed effects model) wider QRS complexes, but the change towards ROSC was the same in both groups. Conclusion: During the last 18 minutes before ROSC ECG characteristics differed depending on etiology, with cardiac etiologies having wider QRS complexes in the no-ROSC groups and narrowing more towards ROSC in the ROSC groups.