Patent Ductus Arteriosus Group Research Articles

Complex genotype–phenotype correlation of MYH11: new insights from monozygotic twins with highly variable expressivity and outcomes

BackgroundThoracic aortic aneurysm/dissection (TAAD) and patent ductus arteriosus (PDA) are serious autosomal-dominant diseases affecting the cardiovascular system. They are mainly caused by variants in the MYH11 gene, which encodes the heavy chain of myosin 11. The aim of this study was to evaluate the genotype–phenotype correlation of MYH11 from a distinctive perspective based on a pair of monozygotic twins.MethodsThe detailed phenotypic characteristics of the monozygotic twins from the early fetal stage to the infancy stage were traced and compared with each other and with those of previously documented cases. Whole-exome and Sanger sequencing techniques were used to identify and validate the candidate variants, facilitating the analysis of the genotype–phenotype correlation of MYH11.ResultsThe monozygotic twins were premature and presented with PDA, pulmonary hypoplasia, and pulmonary hypertension. The proband developed heart and brain abnormalities during the fetal stage and died at 18 days after birth, whereas his sibling was discharged after being cured and developed normally post follow-up. A novel variant c.766 A > G p. (Ile256Val) in MYH11 (NM_002474.2) was identified in the monozygotic twins and classified as a likely pathogenic variant according to the American College of Medical Genetics/Association for Molecular Pathology guidelines. Reviewing the reported cases (n = 102) showed that the penetrance of MYH11 was 82.35%, and the most common feature was TAAD (41.18%), followed by PDA (22.55%), compound TAAD and PDA (9.80%), and other vascular abnormalities (8.82%). The constituent ratios of null variants among the cases with TAAD (8.60%), PDA (43.8%), or compound TAAD and PDA (28.6%) were significantly different (P = 0.01). Further pairwise comparison of the ratios among these groups showed that there were significant differences between the TAAD and PDA groups (P = 0.006).ConclusionThis study expands the mutational spectrum of MYH11 and provides new insights into the genotype–phenotype correlation of MYH11 based on the monozygotic twins with variable clinical features and outcomes, indicating that cryptic modifiers and complex mechanisms beside the genetic variants may be involved in the condition.

Biventricular function in preterm infants with patent ductus arteriosus ligation: A three-dimensional echocardiographic study.

The detailed hemodynamics after patent ductus arteriosus (PDA) ligation in preterm infants remain unknown. We aimed to clarify the effect of surgical ligation on left ventricular (LV) and right ventricular (RV) volume and function. Echocardiography was performed in 41 preterm infants (median gestational age: 25 weeks) before and after PDA ligation. Global longitudinal strain was determined using three-dimensional speckle-tracking echocardiography. These values were compared with those in 36 preterm infants without PDA (non-PDA). Preoperatively, the PDA group had greater end-diastolic volume (EDV) and cardiac output (CO) in both ventricles, a higher LV ejection fraction (LVEF) (53% vs 44%) and LV global longitudinal strain, and a lower RVEF (47% vs 52%) than the non-PDA group. At 4-8 h postoperatively, the two groups had a similar LVEDV and RVEDV. However, the PDA group had a lower EF and CO in both ventricles than the non-PDA group. At 24-48 h postoperatively, the RVEF was increased, but the LVEF remained decreased, and LVCO was increased. PDA induces biventricular loading and functional abnormalities in preterm infants, and they dramatically change after surgery. Three-dimensional echocardiography may be beneficial to understand the status of both ventricles. Preterm infants are at high risk of hemodynamic compromise following a sudden change in loading conditions after PDA ligation. Three-dimensional echocardiography enables quantitative and serial evaluation of ventricular function and volume in preterm infants with PDA. PDA induces biventricular loading and functional abnormalities in preterm infants, and they dramatically change after surgery.

Lung ultrasound score in the decision of patent ductus arteriosus closure in neonates.

We aimed to investigate the role of lung ultrasound (LUS) score in the closure of hemodynamically insignificant patent ductus arteriosus (PDA) and the clinical findings of the patients before and after closure. The study groups (107 preterm neonates under 34 gestational weeks) were classified as hemodynamically significant PDA (group 1), hemodynamically insignificant PDA with closure therapy (group 2), hemodynamically insignificant PDA without closure therapy (group 3), and no PDA group (group 4) based on the echocardiography. 6- and 10-region LUS scores were compared for each group. There was a significant difference between groups 1 and 3 on first, third, and seventh days. In contrast, groups 1 and 2 had similar LUS scores on the first, third, and seventh days. There was a negative correlation between LUS scores on the first and third days and gestational age, birth weight, the first- and fifth-minute APGAR scores, and there was a positive correlation between aortic root to left atrium ratio, and PDA diameter/weight ratio. We observed that LUS scores in patients with hemodynamically insignificant PDA treated with closure therapy were similar to in patients with hemodynamically significant PDA. Thus, LUS score can have role in PDA closure in preterm neonates. However, more comprehensive studies are needed.

The investigation of thrombocytopenia after transcatheter occlusion of patent ductus arteriosus

ObjectiveTo investigate the risk factors for thrombocytopenia after transcatheter occlusion operation of patent ductus arteriosus (PDA).MethodRetrospective analyses were conducted using clinical data from 106 patients with PDA who underwent transcatheter closure operations at Henan Provincial Chest Hospital, Zhengzhou University, from January 2018 to June 2022. The study compared the changes in platelet counts before and after the operation, and investigated the risk factors for thrombocytopenia following PDA closure in different groups and layers.ResultsThe platelet count of patients with PDA significantly decreased after undergoing transcatheter PDA occlusion. Logistic regression analysis revealed that factors such as PDA diameter, occluder diameter, pressure difference on the two sides of the occluder, and residual shunt were associated with an increased risk of thrombocytopenia following PDA occlusion. Specifically, the size of the occluder and the pressure difference between the two sides of the occluder were found to have a negative correlation with the postoperative platelet count. Further subgroup analysis demonstrated that the incidence of total thrombocytopenia was significantly higher in the large PDA group compared to the small-medium PDA groups.ConclusionOur findings suggest that occluder diameter, the pressure difference between the two sides of the occluder, and the residual shunt are major risk factors correlated with the incidence of postoperative thrombocytopenia. However, a multicenter and long-term prospective study is required to further evaluate the prognosis of PDA patients with thrombocytopenia after transcatheter occlusion.

Impact of Neonatal Intervention on Left Ventricular Performance in Ebstein’s Anomaly and Tricuspid Valve Dysplasia

Severe neonatal Ebstein's anomaly (EA) and tricuspid valve dysplasia (TVD) are associated with high perinatal morbidity and mortality. The authors recently demonstrated left ventricular (LV) dysfunction and dyssynchrony to be prevalent in affected newborns and to contribute to poor outcomes. The aim of this study was to investigate the impact of patent ductus arteriosus (PDA) closure, spontaneous or surgical ligation, or right ventricular exclusion (Starnes procedure) on LV performance in neonatal EA and TVD. Neonates with EA or TVD encountered from 2004 to 2018 at three institutions were identified. Pre-and postoperative LV function was assessed using two-dimensional, Doppler-derived deformation (six-segment vector velocity imaging) and two measures of mechanical dyssynchrony (the SD of time to peak and global dyssynchrony index), and values were compared using paired t test analysis or the Wilcoxon rank sum test. Before the intervention, LV function was impaired in the PDA (n=18) and Starnes (n=6) groups and was similar between groups. After PDA closure, LV performance did not change. After the Starnes procedure, however, LV function, including synchrony, improved significantly: fractional area change from 45±5% to 58±8% (P=.003), global circumferential strain from -18.2±5.0% to -32.5±5.5% (P=.01), cardiac index from 1.9±0.3 to 3.9±1.5L/min/m2 (P=.05), and circumferential strain dyssynchrony (dyssynchrony index from 0.19±0.09 to 0.04±0.02 [P=.009] and SD of time to peak from 59.8±18.5 to 29.9±8.2 [P=.02]). The Starnes procedure results in early improvements in LV dysfunction and dyssynchrony, not observed after PDA closure in neonatal severe EA and TVD, which may benefit critically unwell neonates.

Hemoglobin/Red Cell Distribution width Ratio (HRR): A Novel and Promising Red Cell Parameter in Ductal Closure.

It is still unclear how effective hematological parameters are in the closure of patent ductus arteriosus (PDA). The primary aim of our study is to investigate the effect of hemoglobin (HB)-to-red cell distribution width (RDW) ratio (HRR) on the closure of PDA. Premature babies with very low birth weight (VLBW: <1500 g) and <32 gestational weeks were included in the study, and all data were recorded retrospectively. Demographic characteristics, clinical results, red cell parameters, and HRR and their ratios were compared between hemodynamically significant PDA (hsPDA) and non-hsPDA groups. All results were statically analyzed, and P<0.05 was considered statistically significant. A total of 677 premature babies, 269 in the hsPDA group and 408 in the non-hsPDA group, were included in the study. Hemoglobin (HB), hematocrit (HCT), mean cell volume (MCV), red blood cell (RBC), red cell distribution width (RDW), mean platelet volume (MPV), MCV/RBC ratio, HB/RBC ratio, RDW/RBC ratio, and RDW/MPV ratio were found to be similar between hsPDA and non-hsPDA groups, (p>0.05). HRR was found to be significantly lower in the hsPDA group [median (Quartile 1 (Q1) - Q3) (Q1 - Q3): 0.93 (0.8-1.0)] compared to non-hsPDA [median ( Q1 - Q3): 1.07 (1.0-1.2)] (p<0.001). The AUC for the diagnostic value of HRR in hsPDA was 0.816, and the cutoff value was ≤0.98 (p<0.001, 95% [CI]: 0.785-0.845, sensitivity: 90%, specificity: 92%). HRR value was found to be both an effective and powerful parameter in diagnosing hsPDA.

Subvalvular aortic stenosis and patent ductus arteriosus: a not so rare combination

Abstract Background The combination of subvalvular aortic stenosis and patent ductus arteriosus (PDA) has been described as rare. We present the largest case series of adult patients with this combination. Purpose To describe the prevalence and echocardiographic characteristics of subvalvular aortic stenosis in PDA adult patients in a 20-year period. Methods 7512 patients with PDA, 791 adults. We found 60 patients with subvalvular aortic stenosis and PDA and compare them with a 60 randomly selected PDA alone patients control group. Results The prevalence of subvalvular aortic stenosis in PDA patients was 7.5%. This combination was more frequent in women (71%), median age at diagnosis was 26 years. 45% had a third congenital heart condition (ventricular septal defect was the most frequent). 88% underwent PDA closure. Comprehensive echocardiography was performed in all patients, we found that patients with the combination of subvalvular aortic stenosis and PDA had larger left ventricle (LV) mass index (95 vs 79 g/m2, p 0.02), higher frequency of concentric LV hypertrophy (23 vs 10%, p 0.05) and higher LV ejection fraction (62 vs 58%, p&amp;lt;0.01) than PDA alone patients. Right ventricle (RV) enlargement (20 vs 11%, p 0.04) and a high echocardiographic probability of pulmonary hypertension (11 vs 2%, p 0.02) were more frequent in PDA alone patients. At long term post surgical correction follow-up, 73% of patients in the subvalvular aortic stenosis and PDA group developed a significant (at least moderate) valvular heart condition, specially aortic regurgitation (38 vs 10%, p&amp;lt;0.01). In a logistic regression model, subvalvular aortic stenosis was associated with developing at least moderate valvular heart disease at follow-up (OR 3.27 CI 1.44–7.39, p&amp;lt;0.01). Conclusion The combination of subvalvular aortic stenosis and PDA is not rare. This patients have larger LV mass, higher frequency of concentric LV hypertrophy and develop less pulmonary hypertension and RV enlargement than patients with PDA alone. The coexistence of subvalvular aortic stenosis is associated with long term post closure development of significant valvular heart disease in PDA patients. Funding Acknowledgement Type of funding sources: None.

Hematological indices in pediatric patients with acyanotic congenital heart disease: a cross-sectional study of 248 patients

BackgroundCongenital heart disease CHD is a significant cause of mortality and morbidity in children worldwide. Patients with congenital heart disease may develop hematological problems, including thrombocytopenia and neutropenia. In addition, several studies indicate the higher frailty of patients with CHDs to infections and malignancies. Nevertheless, the mechanisms of immune system changes in these patients have remained in the shadow of uncertainty. Moreover, very few studies have worked on cytopenia in CHD. This study has assessed the frequency of thrombocytopenia, neutropenia, lymphopenia, and anemia in pediatric patients with acyanotic congenital heart disease ACHD prior to open-heart surgery.MethodsThis cross-sectional study was handled in the Pediatric Cardiology Clinic, Tehran University of Medical Sciences, during pre-operation visits from 2014 till 2019. Two hundred forty-eight children and adolescents with acyanotic congenital heart disease before open-heart surgery met the criteria to enter the study.ResultsA total of 191 (76.7%) patients with Ventricular Septal Defects (VSD), 37 (14.85%) patients with Atrial Septal Defects (ASD), and 20 (8.11%) patients with Patent Ductus Arteriosus (PDA) were enrolled in this study. The median age was 23.87 months. Thrombocytopenia and neutropenia were found, respectively, in 3 (1.2) and 23 (9.2%) patients. Hemoglobin level and lymphocyte count were significantly lower in patients with neutropenia than patients with normal neutrophil count (P value = 0.024 and P value = 0.000). Significant positive correlations were found between neutropenia and anemia. There were no correlations between neutrophil count and Platelets. Also, anemia was found in 48 patients (19.3%). The study also found a statistically significant correlation between the co-existence of VSD and neutropenia in the patients (P value = 0.000).ConclusionAlthough most were mildly neutropenic, there was a significant correlation between neutropenia and Ventricular Septal Defect compared to PDA and ASD groups. Regarding the importance of neutropenia to affect the prognosis of congenital heart defects in infections, it is important to consider further studies on the status of immune system function in these patients.

Value of bedside echocardiography in predicting persistent patency of the ductus arteriosus during the early postnatal period in very low birth weight infants.

To study the value of bedside echocardiography in predicting persistent patency of the ductus arteriosus during the early postnatal period in very low birth weight (VLBW) infants. A retrospective analysis was performed for 51 VLBW infants who were admitted from March 2020 to June 2021, with an age of ≤3 days and a length of hospital stay of ≥14 days. According to the diameter of patent ductus arteriosus (PDA) on days 14 and 28 after birth, the infants were divided into three groups: large PDA group (PDA diameter ≥2 mm), small PDA group (PDA diameter <2 mm), and PDA closure group (PDA diameter =0 mm). The echocardiographic parameters measured at 72 hours after birth were compared among the three groups. The receiver operating characteristic (ROC) curve was used to evaluate the value of the echocardiographic parameters in predicting persistent patency of the ductus arteriosus (PDA≥2 mm) at the ages of 14 and 28 days. On day 14 after birth, there were 17 infants in the large PDA group, 11 in the small PDA group, and 23 in the PDA closure group. On day 28 after birth, there were 14 infants in the large PDA group, 9 in the small PDA group, and 26 in the PDA closure group. There were significant differences in gestational age, birth weight, rate of pulmonary surfactant use, and incidence rate of hypotension among the three groups (P<0.05). PDA diameter, end-diastolic velocity of the left pulmonary artery, left ventricular output, and left ventricular output/superior vena cava flow ratio measured at 72 hours after birth were associated with persistent patency of the ductus arteriosus at the ages of 14 and 28 days (P<0.05), and the ratio of the left atrium to aorta diameter was associated with persistent patency of the ductus arteriosus at the age of 28 days (P<0.05). The ROC curve analysis showed that the area under the curve that the PDA diameter measured at 72 hours after birth predicting the persistent patency of the ductus arteriosus at the ages of 14 and 28 days was the largest (0.841 and 0.927 respectively), followed by end-diastolic velocity of the left pulmonary artery, with the area under the curve of 0.793 and 0.833 respectively. The indicators obtained by beside echocardiography at 72 hours after birth, especially PDA diameter and end-diastolic velocity of the left pulmonary artery, can predict persistent patency of the ductus arteriosus at the ages of 14 and 28 days in VLBW infants, which provides a basis for the implementation of early targeted treatment strategy for PDA.

Artificial intelligence model comparison for risk factor analysis of patent ductus arteriosus in nationwide very low birth weight infants cohort

Despite the many comorbidities and high mortality rate in preterm infants with patent ductus arteriosus (PDA), therapeutic strategies vary depending on the clinical setting, and most studies of the related risk factors are based on small sample populations. We aimed to compare the performance of artificial intelligence (AI) analysis with that of conventional analysis to identify risk factors associated with symptomatic PDA (sPDA) in very low birth weight infants. This nationwide cohort study included 8369 very low birth weight (VLBW) infants. The participants were divided into an sPDA group and an asymptomatic PDA or spontaneously close PDA (nPDA) group. The sPDA group was further divided into treated and untreated subgroups. A total of 47 perinatal risk factors were collected and analyzed. Multiple logistic regression was used as a standard analytic tool, and five AI algorithms were used to identify the factors associated with sPDA. Combining a large database of risk factors from nationwide registries and AI techniques achieved higher accuracy and better performance of the PDA prediction tasks, and the ensemble methods showed the best performances.

Change and clinical significance of serum cortisol, BNP, and PGE-2 levels in premature infants with patent ductus arteriosus.

BackgroundTo analyze the change and clinical significance of cortisol, B-type brain natriuretic peptide (BNP), and prostacyclin-2 (PGE-2) levels in premature infants with patent ductus arteriosus (PDA).MethodsA total of 67 cases of premature infants admitted to our hospital from January 2018 to April 2020 were included, all of whom developed PDA (PDA group). According to the presence or absence of symptoms, they were divided into the symptomatic group (28 cases) and the asymptomatic group (39 cases). In addition, 62 premature infants without PDA who were born in our hospital during the same period were selected as the control group. The expression levels of cortisol, BNP, and PGE-2 in infants in different groups and between infants with symptoms and without symptoms were analyzed, along with the risk factors leading to PDA in preterm infants. The value of cortisol, BNP, and PGE-2 in the diagnosis of PDA in premature infants was also analyzed.ResultsCompared with the control group, cortisol in the PDA group was significantly decreased (P<0.05), while the levels of BNP and PGE-2 were significantly increased (P<0.05). The cortisol level in the asymptomatic group was significantly higher than that in the symptomatic group, while the levels of BNP and PGE-2 were opposite, and the differences were statistically significant (P<0.05). Logistic regression analysis showed that birth weight <1,200 g, decreased cortisol, increased BNP, and increased PGE-2 were independent risk factors leading to PDA in preterm infants, and the differences were statistically significant (P<0.05). Receiver operating characteristic (ROC) curve showed that the sensitivity and specificity of cortisol+BNP+PGE-2 in the diagnosis of PDA in premature infants were 75.60% and 73.10%, respectively. The area under the curve (AUC) value was 0.759 (95% CI: 0.611–0.859), which was significantly higher than the AUC values of the 3 tests alone (P<0.05).ConclusionsThe expression of cortisol decreased in premature infants with PDA, while the levels of BNP and PGE-2 significantly increased. Dynamic detection of the changes in these levels can provide an important reference for the early diagnosis of PDA and for the assessment of disease progression.

Plasma Amino Acid Concentrations at Birth and Patent Ductus Arteriosus in Very and Extremely Preterm Infants

Background: Amino acids are increasingly recognized as bioactive molecules in numerous physiological and pathophysiological pathways. The non-essential amino acid glutamate is vasoactive in the rat ductus arteriosus (DA) and a decrease in its levels within the 1st days of life has been associated with the presence of patent DA (PDA) in extremely preterm infants. However, these findings have not been confirmed in other studies.Objective: To investigate the possible association between amino acid concentrations in the 1st day of life and the presence of PDA in a cohort of 121 newborns with gestational age (GA) below 30 weeks and birth weight (BW) below 1,500 g.Methods: Plasma samples were collected 6–12 h after birth and amino acid concentrations were determined by tandem mass spectrometry. Besides PDA, we analyzed the potential association of amino acid concentrations with infant sex, small for GA (SGA, defined as BW < third percentile), antenatal corticosteroids, chorioamnionitis, and preeclampsia. Group differences were analyzed by ANOVA adjusted for GA and BW. A Bonferroni significance threshold of P < 0.0024 was used to correct for multiple testing.Results: PDA was found in 48 of the 121 infants examined. We observed higher mean levels of glutamate in infants with PDA (147.0 μmol/L, SD 84.0) as compared with those without (106.7 μmol/L, SD 49.1, P = 0.0006). None of the other amino acid concentrations in the PDA group reached the level of statistical significance that was pre-set to correct for multiple comparisons. Glutamate levels were not significantly affected by infant sex, being SGA, or by exposure to antenatal corticosteroids, clinical chorioamnionitis, or preeclampsia.Conclusion: Our study not only does not confirm the previous findings of low glutamate levels in preterm infants with PDA, but we have even found elevated glutamate concentrations associated with PDA. Nevertheless, despite the high statistical significance, the difference in glutamate levels may lack clinical significance or may be an epiphenomenon associated with the particular clinical condition of infants with PDA.

Application of block matching method-based Echocardiography combined with serum NT-PROBNP level detection in the early prediction of PDA in premature infants.

Objectives:The paper uses block matching method combined with echocardiography to explore the value of N-terminal pro-brain natriuretic peptide (NT-proBNP) in predicting symptomatic patent ductus arteriosus (PDA) in preterm infants.Methods:We selected premature infants born between February 2019 and March 2020, gestational age ≤32 weeks, and echocardiography within 48 hours to determine the presence of arterial ducts as the research object, monitor their clinical manifestations, and detect serum at three and five days after birth The level of NT-proBNP was checked with echocardiography, and the children were divided into PDA group and asymptomatic patent ductus arteriosus (aPDA) group according to the clinical manifestations and echocardiographic.Results:The area under the ROC curve of PDA predicted by serum NT-proBNP level at 3 days after birth was 0.949, the cut-off value was 27035pg/mL, the sensitivity was 92.3%, and the specificity was 94.6%; serum NT-proBNP level at 5 days after birth predicted the ROC curve of PDA The lower area is 0.924, the critical value is 6411 pg/mL, the sensitivity is 92.3%, and the specificity is 92.9%.Conclusion:NT-proBNP may be a quantitative indicator of arterial duct shunt; the detection of serum NT-proBNP levels at 3 and 5 days after birth is helpful for early prediction of PDA.

Exploring the NT-proBNP expression in Premature Infants with Patent Ductus Arteriosus (PDA) by Echocardiography.

Objectives:To investigate the correlation between echocardiographic indicators and the expression level of N-terminal pro-brain natriuretic peptide (NT-proBNP) in premature infants (PIs) with patent ductus arteriosus (PDA) and the value of NT-proBNP in diagnosing symptomatic PDA (sPDA) in PIs whose gestational age (GA) was less than 32 weeks.Methods:Ninty premature infants were selected as the research objects, including 52 in the non-PDA group and 38 in the PDA group (26 sPDA cases and 12 cases with asymptomatic PDA (asPDA)) from February 2019 to March 2020. The general information of these infants was recorded, including gender, delivery method, maternal infection, and serum NT-proBNP level on the 3rd day after birth. They were screened by echocardiographic indicators under an artificial intelligence convolutional neural network (AI-CNN). The Receiver Operating Characteristic (ROC) curves were illustrated to decide serum NT-proBNP expression levels, thereby determining specificity and sensitivity of sPDA and the correlation between serum sPDA NT-proBNP expression and echocardiographic indicators.Results:The expression level of serum NT-proBNP in the sPDA group was greater than that in the asPDA group and the non-PDA group (P<0.001). The serum NT-proBNP expression level was positively correlated with the diameter of the ductus arteriosus in the sPDA group (r=0.462, P<0.001); it was also positively correlated with the ratio of left atrium/aorta (LA/AO) (r=0.573, P<0.001), but was not correlated with left ventricular ejection fraction (LVEF) (r=-0.015, P=0.747).Conclusion:The combination of serum NT-proBNP expression and echocardiography had clinical values in early diagnosis of PDA.

High prevalence of a linear valve-like structure on CT at the pulmonary artery terminus of patent ductus arteriosus in adult patients, mimicking endarteritis.

A linear valve-like structure at the pulmonary artery terminus is identified on CT in some patients with patent ductus arteriosus (PDA) and can potentially be mistaken for endarteritis. The purpose of this study was to evaluate the differences in CT features between adult patients with PDA and a linear structure and those without. We retrospectively evaluated ECG-gated cardiac CT of 38 patients with PDA dividing them into two groups [patients with linear symmetrical valve-like structure (group1, n = 16), and those without (group 2, n = 22)]. We analyzed CT findings of the PDA including length, minimal and maximal diameter, presence of calcification, and PDA type, comparing the two subgroups. The authors also investigated the prevalence of endarteritis. There was no difference in CT findings between the two groups in the prevalence of calcification and length, and minimal and maximal diameter of PDA. Notably the linear valve-like structure was only identified in type 1 PDA (cone-shaped PDA) (p = 0.04), while there were variable types of PDA in group 2. There was only one case of endarteritis as a complication of PDA in group 1. In contrast to a linear valve-like structure, asymmetrical nodular thickening was noted in the patient with endarteritis on CT overlying the pre-existing linear valve-like structure at the pulmonary end of PDA. A linear valve-like structure is frequently identified at the pulmonary end in type 1 PDA. This CT finding should not be mistaken for endarteritis in the absence of other clinical evidence.

Evaluating the severity of aortic coarctation in infants using anatomic features measured on CTA.

A machine learning model was developed to evaluate the severity of aortic coarctation (CoA) in infants based on anatomical features measured on CTA. In total, 239 infant patients undergoing both thorax CTA and echocardiography were retrospectively reviewed. The patients were assigned to either mild or severe CoA group based on their pressure gradient on echocardiography. They were further divided into patent ductus arteriosus (PDA) and non-PDA groups. The anatomical features were measured on double-oblique multiplanar reconstructed CTA images. Then, the optimal features were identified by using the Boruta algorithm. Subsequently, the coarctation severity was classified using linear discriminant analysis (LDA). We further investigated the relationship between the anatomical features and re-coarctation using Cox regression. Four anatomical features showed significant differences between the mild and severe CoA groups, including the smallest aortic cross-sectional area indexed to body surface area (p < 0.001), the narrowest aortic diameter (CoA diameter) indexed to height (p < 0.001), the diameter of the descending aorta at the diaphragmatic level (p < 0.001) and weight (p = 0.005). With these features, accuracy of 88.6% and 90.2%, sensitivity of 65.0% and 72.1%, and specificity of 92.9% and 100% were obtained for classifying the CoA severity in the non-PDA and PDA groups, respectively. Moreover, CoA diameter indexed to weight was associated with the risk of re-coarctation. CoA severity can be evaluated by using LDA with anatomical features. When quantifying the severity of CoA and risk of re-coarctation, both anatomical alternations at the CoA site and the growth of the patients need to be considered. • CTA is routinely ordered for infants with coarctation of the aorta; however, whether anatomical variations observed with CTA could be used to assess the severity of CoA remains unknown. • Using the diameter and area of the coarctation site adjusted to body growth as features, the LDA model achieved an accuracy of 88.6% and 90.2% in differentiating between the mild and severe CoA patients in the non-PDA group and PDA group, respectively. • The narrowest aortic diameter (CoA diameter) indexed to weight has a hazard ratio of 10.29 for re-coarctation.

Platelets and platelet derived growth factor and ductus arteriosus in preterm neonates

BackgroundPlatelets and platelet derived growth factor (PDGF) play an important role in persistence and closure of ductus arteriosus (DA) in preterm neonates. AimTo study the effect of Platelets count and PDGF on DA patency in preterm neonates. MethodsIn a prospective study, performed in the neonatal intensive care unit (NICU) of Fayoum University Hospital, 75 preterm neonates with gestational age >33 weeks were assessed by Doppler echocardiography after 72 h of birth and classified into two groups (group 1: patent ductus arteriosus (PDA) group which included 40 preterm neonates and group 2: non-PDA group which included 35 preterm neonates). For all of them, complete blood count (CBC), C reactive protein (CRP) and serum PDGF were assessed. ResultsTwenty six preterm neonates of group1 had hemodynamically significant PDA and received medical treatment in the form of an oral course of ibuprofen. Platelets count was significantly lower among PDA group, platelet distribution width (PDW) was significantly higher among PDA group, and platelets mass index (PMI) was significantly lower among PDA group. PDGF was significantly lower among PDA group on day 2 in comparison to non-PDA group and increased significantly from day 2 to day 5 in cases of PDA with spontaneous closure. ConclusionsLow platelets count and PMI and high PDW are associated with persistence of PDA and poor response to medical treatment, while up trending of PDGF level is associated with spontaneous PDA closure and good response to medical treatment in preterm neonates.

Duration of significant patent ductus arteriosus and bronchopulmonary dysplasia in extremely preterm infants.

To demonstrate the association between the duration of significant patent ductus arteriosus (PDA) and bronchopulmonary dysplasia (BPD) in extremely preterm infants. All extremely preterm infants (<29 weeks) treated in our Neonatal Intensive Care Unit from January 2013 to March 2016 were included if their PDA status was confirmed at <7 days of life. Infants with genetic syndromes, complex congenital anomalies and insignificant PDAs were excluded. Total duration of significant PDA was estimated by reviewing serial echocardiograms. Significant PDA was diagnosed using our scoring system that was based upon echocardiographic parameters and clinical status of the infants. Study cohort was divided into four groups based on the duration of significant PDA. Group A-No PDA, Group B-PDA <1-week, Group C- PDA 1-2 weeks, and Group D-PDA >2 weeks. ANOVA and multivariate analysis were performed to compare the groups. There were 147 infants with no PDA (Group A), 50, 35, and 41 infants were enrolled in Groups B, C, and D, respectively. There were no differences in maternal and neonatal variables among groups except for the following: maternal smoking, chorioamnionitis, antenatal indomethacin, gestation, birth weight, mode of delivery and incidence of death or BPD. Logistic regression analysis showed that longer duration of significant PDA was associated with higher risk for death or BPD (adjusted OR 1.37, 95% CI 1.03-1.82). Longer duration of significant PDA is associated with the higher risk for BPD/death in extremely preterm infants.

Patent ductus arteriosus ligation on neurodevelopmental outcomes at corrected 2\u2009years

BackgroundOur aim in this study was to evaluate whether very low birth weight infants (VLBWI) ligated for patent ductus arteriosus (PDA) were associated with worse neurodevelopmental outcomes at corrected 2 years. The ligated group was subdivided into ≤2 weeks of life (early) and ligated > 2 weeks of life (late) groups and compared the in-hospital morbidities and long term outcomes.MethodsBetween Dec 2013 and Dec 2015, VLBWI diagnosed with hs PDA were evaluated.ResultsOf the 191 VLBW infants with hs PDA, 28 (14.7%) infants had surgical ligation for PDA; 11 (39%) infants had EL and 17 (61%) infants had LL. Surgical ligation of hs PDA group had higher morbidities and mortality. Among the142 (83.0%) infants of 171 VLBWI with PDA survived, infants who were ligated had significantly lower scores of Bayley Scales of Infant and Toddler Development III at corrected age of 18 months. However, among the ligated group, there was little evidence of differences between the EL and LL groups. In a multivariable logistic regression analysis, only longer exposure of hs PDA and mechanical ventilation were consistently associated with worse neurodevelopmental outcomes.ConclusionOur results suggest that surgical ligation for hs PDA may not increase risk for poor neurodevelopmental outcomes at corrected 2 years of age. The early surgical ligation may not be a risk factor.

Hemodynamics of infants with strong fluctuations of internal cerebral vein.

There is a high incidence of intraventricular hemorrhage in extremely low-birthweight (ELBW) infants of low gestational age with high-grade fluctuations in the perfusion waveform of the internal cerebral vein. This study investigated changes in the hemodynamic status of ELBW infants during initial strong fluctuations in the perfusion waveform of the internal cerebral vein. We evaluated the perfusion waveform of the internal cerebral vein in 192 ELBW infants from birth, every 8h for a total of 120h. Sixty-seven infants had high-grade fluctuations. On the basis of the presence of patent ductus arteriosus (PDA), patients were subdivided into PDA(-) (n=32) and PDA(+) (n=35) groups. During the first high-grade fluctuation, the PDA(-) group had significant increases in systolic, diastolic, and mean blood pressure (P<0.001 for all). The PDA(+) group did not have significant changes in blood pressure but did have significant increases in the number of interruptions or regurgitations of diastolic renal arterial blood flow (P=0.04) and end-diastolic left pulmonary arterial flow velocity (P<0.001), indicating increased left-to-right shunt. Blood pressure elevation may underlie fluctuations in the perfusion waveform of the internal cerebral vein and lead to the first high-grade increases during acute management of ELBW infants. When no elevation in blood pressure occurred, hemodynamically significant PDA was considered a potential underlying factor.