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1.	Aburawi, Elhadi, et al. (author) A transthoracic Doppler echocardiography study of C-reactive protein and coronary microcirculation in children after open heart surgery. 2007 In: Cardiology in the Young. - 1467-1107. ; 17:5, s. 472-477 Journal article (peer-reviewed)abstract Background Systemic inflammation has been suggested to underlie in part the elevated risk of arrhythmias and myocardial dysfunction during the first weeks after cardiac surgery. Recent transthoracic Doppler studies from our centre indicated increased basal coronary arterial flow in children 5 days after cardiopulmonary bypass surgery. In these children, we investigated whether the inflammatory mediator, C-reactive protein, could influence this association. Methods The peak flow velocity, velocity time-integral in diastole and systole, and basal blood flow in the proximal part of the left anterior descending artery, were assessed by transthoracic Doppler echocardiography 1 day before, and 5 days after, cardiac surgery in 17 children with ventricular and atrioventricular septal defects whose mean age at surgery was 6 months. Levels of C-reactive protein in the plasma were measured at both time-points. Results Prior to surgery, all children had levels of C-reactive protein under the limit for detection, that is less than 0.8 milligrams per litre. The levels of the protein had increased significantly by the second day, when the median value was 25, and the range from 20 to 142 milligrams per litre. They remained elevated on the fifth day after surgery, when the median was 11, and the range from 3 to 20 milligrams per litre. On the fifth day, the percentage increase in velocity time integral corrected for left ventricular mass was significantly lower in those patients with C-reactive protein greater than or equal to 10 milligrams per litre than in the remaining patients. Also, both the velocity time integral and the velocity of diastolic peak flow correlated inversely with log C-reactive protein, r being equal to −0.54 and p less than 0.02 and r equal to −0.74 and p less than 0.01, respectively, particularly among those patients in whom clamping of the aorta lasted for more than 1 hour, r for this statistic being equal to −0.8. Conclusion The postsurgical increase in the velocity of coronary arterial flow in children is inversely associated with rising levels of C-reactive protein. The duration of the aortic cross-clamping during surgery strengthens the association between levels of C-reactive protein and the microcirculatory changes.
2.	Aburawi, Elhadi, et al. (author) Acute respiratory viral infections aggravate arterial endothelial dysfunction in children with type 1 diabetes. 2004 In: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 27:11, s. 2733-2735 Journal article (peer-reviewed)abstract Despite improvements in therapy for children with type 1 diabetes, the prevalence of cardiovascular morbidity in adulthood due to accelerated atherosclerosis remains significant (1). Similar to other cardiovascular risk factors, the diabetic state facilitates arterial endothelial injury, a primary event in the pathogenesis of atherosclerosis (2). Although several pediatric studies have reported an association of diabetes with arterial endothelial dysfunction (3,4), pathogenic animal studies have suggested that even though this disease predisposes to endothelial dysfunction and atherosclerosis, it might not be sufficient to cause them (5). Notably, type 1 diabetes increases the propensity for both chronic and acute infections in part by weakening the immune mechanisms (6). The risk is particularly increased for respiratory tract infections, but other infections have also been associated with diabetes (7). Furthermore, diabetic patients are at greater risk for infection-related mortality (8), and the excess risk appears to be linked to cardiovascular diseases (9). In the present study, we investigated whether viral respiratory tract infections in children with type 1 diabetes might impose an additional burden on the arterial endothelial function.
3.	Aburawi, Elhadi, et al. (author) Coronary Blood Flow by Transthoracic Echocardiography in Children with Endomyocardial Fibrosis. 2009 In: Pediatric Cardiology. - : Springer Science and Business Media LLC. - 0172-0643 .- 1432-1971. ; 30, s. 371-373 Journal article (peer-reviewed)abstract We report herein the coronary flow (CF) pattern determined by transthoracic Doppler echocardiography (TTDE) in two children with biventricular endomyocardial fibrosis (EMF). Endomyocardial biopsy showed various degrees of cardiac fibrosis in both patients as well as signs of chronic inflammation in one of the patients. TTDE showed a significant increase in CF in both the left anterior descending coronary artery and the posterior descending coronary artery compared with age-matched healthy controls. The diastolic flow in patients with EMF appeared to terminate earlier than in controls. The mechanisms and the potential significance of these novel findings are discussed.
4.	Aburawi, Elhadi, et al. (author) Early changes in myocardial repolarization and coronary perfusion after cardiopulmonary bypass surgery for ASD repair in children 2013 In: BMC Cardiovascular Disorders. - : Springer Science and Business Media LLC. - 1471-2261. ; 13 Journal article (peer-reviewed)abstract Background: In adults, impaired myocardial repolarization and increased risk of arrhythmia are known consequences of open heart surgery. Little is known, however, about post-operative consequences of cardiopulmonary bypass surgery in children. The aim of this study was to assess ventricular repolarization and coronary perfusion after bypass surgery for atrial septal defect (ASD) repair in children. Methods: Twelve patients with ASD were assessed one day before and 5-6 days after ASD repair. Myocardial repolarization (corrected QT interval, QTc, QT dispersion, QTd, and PQ interval) was determined on 12-lead electrocardiograms. Coronary flow in proximal left anterior descending artery (peak flow velocity in diastole, PFVd) was assessed by transthoracic Doppler echocardiography. Results: Ten of the 12 (83%) children had normal myocardial repolarization before and after surgery. After surgery, QTc increased 1-9% in 5 (42%) patients, decreased 2-11% in 5 (42%) patients and did not change in 2 (16%) patients. Post-op QTc positively correlated with bypass time (R=0.686, p=0.014) and changes in PFVd (R=0.741, p=0.006). After surgery, QTd increased 33-67% in 4 (33%) patients, decreased 25-50% in 6 patients (50%) and did not change in 2 (16%) patients. After surgery, PQ interval increased 5-30% in 4 (33%) patients, decreased 4-29% in 6 (50%) patients and did not change in 1 (8%) patient. Post-op PQ positively correlated with bypass time (R=0.636, p=0.027). As previously reported, PFVd significantly increased after surgery (p<0.001). Conclusions: Changes in QTc, PQ and PFVd are common in young children undergoing surgery for ASD repair. Post-op QTc significantly correlates with bypass time, suggesting prolonged cardiopulmonary bypass may impair ventricular repolarization. Post-op QTc significantly correlates with PFVd changes, suggesting increased coronary flow may also impair ventricular repolarization. The clinical significance and reversibility of these alternations require further investigations.
5.	Aburawi, Elhadi, et al. (author) Effects of cardio-pulmonary bypass surgery on coronary flow in children assessed with transthoracic Doppler echocardiography. 2007 In: American Journal of Physiology: Heart and Circulatory Physiology. - : American Physiological Society. - 1522-1539 .- 0363-6135. ; 293:2, s. 1138-1143 Journal article (peer-reviewed)abstract Perturbation of coronary blood flow (CF) is an important contributor to myocardium-related complications. The study was primarily designed to assess the impact of cardiopulmonary bypass (CPB) surgery on CF by aid of transthoracic Doppler echocardiography. Changes in CF after off-pump coarctation surgery were also studied. All ultrasounds were performed before and 5 ± 1 days after surgery. Eighteen children underwent CPB surgery of ventricular left-to-right shunts at the mean age of 6 mo, while off-pump surgery (aortic coarctectomy) was undertaken at the mean age of 10 days in 12 children. After CPB surgery, both left anterior descending coronary artery mean diameter and basal CF increased from 1.7 ± 0.3 to 2.1 ± 0.4 mm (P = 0.001) and 27 ± 10 to 47 ± 15 ml/min (P = 0.0001), respectively. These two coronary variables decreased after off-pump coarctectomy: left anterior descending coronary artery mean diameter from 1.8 ± 0.1 to 1.7 ± 0.1 mm (P = 0.06), and CF from 44 ± 12 to 25 ± 8 ml/min (P = 0.001). The findings are in keeping with the hypothesis that the previously reported impairment of coronary flow reserve after CPB surgery could be due to increase in basal coronary flow after CPB. Off-pump coarctectomy seems to have little impact on CF, as the postsurgical decline in flow in these patients seems to relate to the reduction in cardiac pressure afterload.
6.	Aburawi, Elhadi H., et al. (author) Effects of N-3 Polyunsaturated Fatty Acids on Left Ventricular Function and Coronary Flow in Children with Type 1 Diabetes Mellitus 2011 In: Pediatric Research. - : Springer Science and Business Media LLC. - 1530-0447 .- 0031-3998. ; 70:227 Conference paper (peer-reviewed)abstract Purposes: Dietary supplementation with N-3 Polyunsaturated Fatty Acids (n-3 PUFAs) could have beneficial effects on cardiovascular system in patients with type 1 diabetes mellitus (DM1). Methods: In a double-blind placebo controlled crossover study, 33 children with DM1 duration of more than one year were randomly and equally assigned to either n-3 PUFAs (2 gm/day, Nycoplus® Omega-3, 1000 mg) or placebo treatment for 8 weeks. Following a 4-week period recovery, the groups were crossovered with above treatments for another 8 weeks. Transthoracic Doppler echocardiography (TTDE) study was done on pre and post treatment visits, and after one month's treatment free recovery for left ventricular function and flow in the left anterior descending coronary artery (LAD). Results: Of recruited children 28 (85%) completed the study. n-3 PUFAs treatment was associated with increase in mean cardiac index (CI; from 2.7±0.4 to 3.7±0.8 l/min/m2, p< 0.0001) and left ventricular fractional shortening (FS; from 31±2.5 to 39±3%, p< 0.0001). The treatment decreased both LAD peak flow velocity (PFVd) from 96±17 to 68±12 cm/s, p< 0.0001 and LAD CF from 105±31 to 66±15 ml/min, p< 0.0001). One month after stopping the treatment CI decreased from 3.7±0.8 to 2.6±0.5 l/min/m2, p< 0.0001 and mean FS from 39±3 to 32±2, p< 0.0001. Mean PFVd increased from 68±12 to 90±12 cm/s, p< 0.0001 and CF from 66±15 to 108±30 ml/min, p< 0.0001. Conclusions: In patients with DM1 n-3 PUFA therapy increased cardiac index and LV systolic function. The basal coronary flow decrease improving the circumstances for better coronary flow reserve.
7.	Aburawi, Elhadi, et al. (author) QTc and QTd Changes after Cardiopulmonary Bypass Surgery in Children 2014 In: European Journal of Cardiovascular Medicine. - : Healthcare Bulletin. - 2042-4884. ; 3:1 Journal article (peer-reviewed)abstract The aim of the study was to assess the impact of cardiopulmonary bypass surgery on corrected QT (QTc) and QT dispersion (QTd) intervals. The possible role of inflammation on these variables was investigated.
8.	Ahlström, Love, et al. (author) Preoperative Coronary Anatomy Assessment with Echocardiography and Morbidity After Arterial Switch Operation of Transposition of the Great Arteries 2018 In: Pediatric Cardiology. - : Springer Science and Business Media LLC. - 0172-0643 .- 1432-1971. ; 39:8, s. 1620-1626 Journal article (peer-reviewed)abstract In transposition of the great arteries (TGA), certain coronary patterns have been associated with major adverse events early after the arterial switch operation (ASO). We sought to determine the impact of preoperative echocardiographic (ECHO) diagnosis on the intra and postoperative morbidity. All patients with TGA born between June 2001 and June 2017 and who underwent ASO were reviewed. Data on presumed coronary anatomy (CA) preoperatively were obtained from the preoperative ECHO report. Intraoperative CA was categorized according to Yacoub classification. Major postoperative morbidity included at least one of the following: delayed sternal closure (DSC), prolonged (> 72 h) mechanical ventilation, reintubation, peritoneal dialysis (PD), ECMO, reoperation, and readmission within 30 days after surgery. 240 patients with median age of 5 days (range 1–614) and mean weight at surgery was 3.6 kg (1.8–8.4) were included. Preoperative ECHO assessment of CA was available in 228 patients. Intraoperatively, 181 patients (75%) were found to have type A, 25 patients had type B or C or intramural (B–C–IM; 10%), and 34 patients had type D or E (D–E; 14%). Patients with types B, C, and intramural coronary (B–C–IM) had increased risk for delayed sternum closure (9/25 vs. 20/181 in type A and 8/34 in type D–E; p = 0.04), peritoneal dialysis (4/25 vs. 8/181 and 1/34; p = 0.04), and ECMO (2/25 vs. 1/131 and 1/34; p = 0.02). Within the B–C–IM group, preoperative ECHO raised suspicion of type A in 13 patients (i.e., incorrect diagnosis, ID; 52%), whereas non-A CA was suspected in 12 patients (i.e., correct diagnosis, CD; 48%). With the exception of reoperation, which was seen only in the ID subgroup (4/12 vs. 0/10 in the CD subgroup; p = 0.04), the intraoperative (cardiopulmonary bypass time and cross-clamp time) and postoperative morbidity indices were comparable in both ID and CD subgroups (p > 0.1). Although there is a significant risk for early postoperative morbidity in TGA patients with single, interarterial, and intramural CA, there seems to be relatively limited influence of preoperative ECHO assessment of coronary anatomy on this morbidity burden.
9.	Ahlström, Love, et al. (author) Surgical Age and Morbidity After Arterial Switch for Transposition of the Great Arteries 2019 In: Annals of Thoracic Surgery. - : Elsevier BV. - 1552-6259 .- 0003-4975. ; 108:4, s. 1242-1247 Journal article (peer-reviewed)abstract Background: Transposition of the great arteries (TGA) is a complex congenital heart disease that requires early diagnosis as well as advanced surgical repair and postoperative support. We sought herein to study the impact of surgical timing on early postoperative morbidity.Methods: We reviewed all patients with TGA corrected at our institution via arterial switch operation (ASO) between June 2001 and June 2016. Major postoperative morbidity (MPM) and death within 30 days after ASO were documented. Patients with double outlet right ventricle, chromosome abnormalities and non-cardiac diseases were excluded. MPM was defined as presence of at least 1 of the following: delayed sternum closure, reoperation, prolonged mechanical ventilation, noninvasive ventilation after extubation, peritoneal dialysis, ECMO and readmission. Results: 241 patients were included, with medians for birth weight, gestational week and age at surgery of 3.5 kg, 39 weeks, and 5 days, respectively. MPM was encountered in 32.3% of patients. Prematurity (p=0.001) and need for aortic arch repair at the time of ASO (p=0.04) were associated with significant increase in MPM. Non-A coronary anatomy, associated ventricular septal defect requiring surgical closure and fetal diagnosis of TGA had no significant impact on MPM (p=0.35, 0.08 and 0.21, respectively). There was no significant difference in MPM between the surgical groups (p=0.49).Conclusions: Early complications after ASO do occur and are mostly associated with prematurity and need for aortic arch repair. Timing of surgical repair does not seem to influence the rate of these complications.
10.	Avdikos, Vasileios, et al. (author) Outcomes following surgical repair of absent pulmonary valve syndrome : 30 years of experience from a Swedish tertiary referral centre 2022 In: Interactive Cardiovascular and Thoracic Surgery. - : Oxford University Press (OUP). - 1569-9293 .- 1569-9285. ; 35:2 Journal article (peer-reviewed)abstract Surgical approach with reduction pulmonary artery plasty and valved conduit in patients with respiratory compromise prior to repair is associated with excellent long-term survival at the cost of a higher reintervention rate. OBJECTIVES: Absent pulmonary valve syndrome is a rare congenital heart defect with pulmonary artery dilatation and secondary airway compression. Although preoperative respiratory support and early surgical repair with pulmonary arterioplasty are often required in patients with airway compromise, the need for extensive plasty in these patients and for plasty in general in those with no or mild respiratory issues remains debatable. METHODS: We performed a retrospective survey of patients with this diagnosis and repair from 1988 to 2018. RESULTS: Twenty patients were identified. The median age and weight at repair were 0.8 (0.1-2.4) years and 7.0 (2.5-13.8) kg and included a valved conduit in 17 (85%) patients and a transannular patch in 3 patients. Five (29%) patients were ventilator-dependent prior to repair at the age of 0.3 (0.1-0.4) years. Pulmonary arterioplasty was performed in 7 patients (35%), including all 5 with ventilator dependency and 2 with respiratory symptoms due to recurrent infections. Two patients (10%) with preoperative ventilator dependency underwent extensive intrahilar arterioplasty. Preoperative ventilator dependency was associated with earlier repair and reinterventions (P < 0.05). There were 3 late deaths among cases with repair after 2000 (n = 14), none with preoperative ventilator dependency. CONCLUSIONS: The long-term outcomes of patients with this rare defect are good, comparable to those of other previous studies. Reduction pulmonary arterioplasty, which in this study was used only in patients with respiratory distress and ventilator dependency, is associated with excellent survival. Reinterventions are common in these patients.
11.	Bhat, Misha, et al. (author) Fetal iGRASP cine CMR assisting in prenatal diagnosis of complicated cardiac malformation with impact on delivery planning 2019 In: Clinical Physiology and Functional Imaging. - : Wiley. - 1475-0961 .- 1475-097X. ; 39:4, s. 231-235 Journal article (peer-reviewed)abstract Limited visualisation of the fetal heart and vessels by fetal ultrasound due to suboptimal fetal position, patient habitus and skeletal calcification may lead to missed diagnosis, overdiagnosis and parental uncertainty. Counseling and delivery planning may in those cases also be tentative. The recent fetal cardiac magnetic resonance (CMR) reconstruction method utilising tiny golden angle iGRASP (iterative Golden-angle RAdial Sparse Parallel MRI) allows for cine imaging of the fetal heart for use in clinical practice. This case describes an unbalanced common atrioventricular canal where limited ultrasound image quality and visibility of the aortic arch precluded confirming or ruling out presence of a ventricular septal defect. Need of prostaglandins or neonatal intervention was thus uncertain. Cardiovascular magnetic resonance imaging confirmed ultrasound findings and added value by ruling out a significant ventricular septal defect and diagnosing arch hypoplasia. This confirmed the need of patient relocation for delivery at a paediatric cardiothoracic surgery centre and prostaglandins could be initiated before the standard postnatal ultrasound. The applied CMR method can thus improve diagnosis of complicated fetal cardiac malformation and has direct clinical impact. This article is protected by copyright. All rights reserved.
12.	Bhat, Misha, et al. (author) Longitudinal ECG changes in tetralogy of Fallot and association with surgical repair 2024 In: Frontiers in Cardiovascular Medicine. - 2297-055X. ; 11 Journal article (peer-reviewed)abstract Background: ECG abnormalities have been linked to adverse changes in right ventricular (RV) morphology and poor clinical outcomes in repaired Tetralogy of Fallot (rTOF). Our aim was to describe how ECG changes progress in early and intermediate follow-up and whether types of surgical strategy at the time of primary repair affected these changes. Methods: We studied patients with rTOF born 2000–2018 operated at our institution. Seven time points in relation to primary repair, follow-up, and pulmonary valve replacement (PVR) were identified. Patients correct with valve sparing repair (VSR), trans-annular patch (TAP) including with a monocusp valve (TAP + M) and with at least 3 ECGs were included. PQ interval, QRS duration, dispersion, and fragmentation, QTc duration and dispersion, JTc as well as presence of a right bundle branch block (RBBB) were analyzed. Medical records were reviewed for demographic and surgical data. Results: Two hundred nineteen patients with 882 ECGs were analyzed with a median follow-up time of 12.3 years (8.4, 17) with 41 (19%) needing PVR during the study period. QRS duration increased at time of primary repair to discharge from 66 msec (IQR 12) to 129 msec (IQR 27) (p < 0.0001) and at 1- and 6- year follow-up but showed only a modest and temporary decrease after PVR. QTc increased at the time of primary repair as well as prior to PVR. PQ interval showed a small increase at the time of primary repair, was at its highest prior to PVR and decreased with PVR. Type of surgical repair affected mainly QTc and JTc and was consistently longer in the TAP + M group until PVR. In VSR, QTc and JTc were prolonged initially compared to TAP but were similar after 1 year. After PVR, there were no differences in adverse ECG changes between surgical groups. Conclusions: PQ interval and QRS duration best correspond to the assumed volume load whereas the relationship with QTc and JTc is more complex, suggesting that these represent more complex remodeling of the myocardium. Before PVR, QTc and JTc are longer in the TAP + M group which may be due to a longer surgical incision.
13.	Birck, Malene M., et al. (author) Infection-induced coronary dysfunction and systemic inflammation in piglets are dampened in hypercholesterolemic milieu 2011 In: American Journal of Physiology: Heart and Circulatory Physiology. - : American Physiological Society. - 1522-1539 .- 0363-6135. ; 300:5, s. 1595-1601 Journal article (peer-reviewed)abstract Birck MM, Pesonen E, Odermarsky M, Hansen AK, Persson K, Frikke-Schmidt H, Heegaard PM, Liuba P. Infection-induced coronary dysfunction and systemic inflammation in piglets are dampened in hypercholesterolemic milieu. Am J Physiol Heart Circ Physiol 300: H1595-H1601, 2011. First published February 25, 2011; doi:10.1152/ajpheart.01253.2010.-The synergism of infection with conventional cardiovascular risk factors in atherosclerosis is much debated. We hypothesized that coronary arterial injury correlates with infection recurrence and pathogen burden and is further aggravated by hypercholesterolemia. Forty-two Gottingen minipigs were assigned to repeated intratracheal inoculation of PBS, Chlamydia pneumoniae (Cpn), or both Cpn and influenza virus at 8, 11, and 14 wk of age. Animals were fed either standard or 2% cholesterol diet (chol-diet.). At 19 wk of age coronary vasomotor responses to acetylcholine (ACh) and adenosine were assessed in vivo and blood and tissue samples were collected. Nonparametric tests were used to compare the groups. In cholesterol-fed animals, total cholesterol/HDL was significantly increased in infected animals compared with noninfected animals [3.13 (2.17-3.38) vs. 2.03 (1.53-2.41), respectively; P = 0.01]. C-reactive protein (CRP) rose in infected animals [10.60 (4.96-18.00) vs. 2.47 (1.44-3.01) mu g/ml in noninfected; P < 0.01] without significant difference between the mono- and coinfected groups. Among coinfected animals, both CRP and haptoglobin were lower in those fed chol-diet than in those fed standard diet (P < 0.05). The vasoconstricting response to ACh was most prominent in coinfected animals (769.3 (594-1,129) cm; P = 0.03 vs. noninfected [342 (309-455) cm] and P = 0.07 vs. monoinfected [415 (252.5-9711.8) cm]}. Among monoinfected animals, similar to CRP, a trend for less vasoconstriction was observed in those fed chol-diet (P = 0.08). Coinfection of piglets appears to be associated with more pronounced coronary muscarinic vasomotor dysfunction. In monoinfected animals, use of chol-diet seems to dampen both coronary dysfunction and systemic inflammation induced by infection.
14.	Björk Werner, Josefin, et al. (author) Factors Influencing Need for Late ASD Closure after Neonatal Repair of Severe Pulmonary Valve Obstruction and Intact Ventricular Septum 2018 In: Cardiology in the Young. - 1467-1107. ; 28:S1, s. 151-151 Conference paper (peer-reviewed)abstract Background: In neonates with critical pulmonary stenosis (CPS) or pulmonary atresia with intact ventricular septum (PAIVS), a nonrestrictive atrial septal defect (ASD) has been speculated to improve the initial clinical course after pulmonary valvotomy (PV) but some concerns exist in terms of its potentially longterm adverse effect on the right ventricle`s (RV) growth and persistent desaturation due to right-to-left (R-L) shunt. Objective: to assess the relationship between the size of ASD and the need for post-valvotomy reinterventions. Method: Patients with PAIVS and CPS treated at our center during 2001- 2015 were reviewed. Exclusion criteria were associated cardiac malformations and hypoplastic RV deemed unsuitable for biventricular circulation. Clinical and echocardiographic data were retrieved from the hospital ́s databases. Results: In total, 48 patients (18 with PAIVS and 30 CPS) were included. The median follow-up was 5 and 8 years, respectively. One patient with PAIVS died on day 3 after surgical valvotomy and Blalock- Taussig shunt (BTs). The majority (89%) of patients with PAIVS had surgical valvotomy whereas transcatheter valvotomy was used in the majority (87%) of patients with CPS. Palliation with BTs or PDA stenting was used in 13 (72%) patients with PAIVS and in 4 (13%) patients with CPS. Reintervention within 1 month after initial repair was needed in 4 (22%) patients with PAIVS and in 4 (13%) patients with CPS. Later reinterventions were performed in in 11(61%) patients with PAIVS and in 10(33%) patients with CPS. Of these, 7 (39%) patients with PAIVS and 5 (17%) with CPS underwent ASD closure due to persistent resting desaturation. The latter did not correlate with ASD size after valvotomy (p>0.1). Initial palliation with BTs was the only variable associated with ASD device closure (p=0.04). No patient required univentricular conversion. Conclusion: Neonatal biventricular repair for severe pulmonary valve obstruction has low mortality but significant need for late reinterventions, mostly consisting of ASD closure due to clinically significant desaturation secondary to R-L shunt. The use of aorto-pulmonary shunt, probably illustrating a more severe form of RV hypoplasia, but not the size of the ASD, predicts the need for later ASD closure due to desaturation.
15.	Bonamy, Anna-Karin Edstedt, et al. (author) Blood Pressure in 6-Year-Old Children Born Extremely Preterm 2017 In: Journal of the American Heart Association. - : WILEY. - 2047-9980. ; 6:8 Journal article (peer-reviewed)abstract Background-Advances in perinatal medicine have increased infant survival after very preterm birth. Although this progress is welcome, there is increasing concern that preterm birth is an emerging risk factor for hypertension at young age, with implications for the lifetime risk of cardiovascular disease. Methods and Results-We measured casual blood pressures (BPs) in a population-based cohort of 6-year-old survivors of extremely preterm birth (< 27 gestational weeks; n=171) and in age-and sex-matched controls born at term (n=172). Measured BP did not differ, but sex, age-, and height-adjusted median z scores were 0.14 SD higher (P=0.02) for systolic BP and 0.10 SD higher (P=0.01) for diastolic BP in children born extremely preterm than in controls. Among children born extremely preterm, shorter gestation, higher body mass index, and higher heart rate at follow-up were all independently associated with higher BP at 6 years of age, whereas preeclampsia, smoking in pregnancy, neonatal morbidity, and perinatal corticosteroid therapy were not. In multivariate regression analyses, systolic BP decreased by 0.10 SD (P=0.08) and diastolic BP by 0.09 SD (P=0.02) for each week-longer gestation. Conclusions-Six-year-old children born extremely preterm have normal but slightly higher BP than their peers born at term. Although this finding is reassuring for children born preterm and their families, follow-up at older age is warranted.
16.	Broberg, Olof, et al. (author) Ceramides : a potential cardiovascular biomarker in young adult childhood cancer survivors? 2024 In: European Heart Journal Open. - 2752-4191. ; 4:2 Journal article (peer-reviewed)abstract Aims The aim of this study was to investigate circulating ceramides involved in cardiovascular disease (CVD) in young adult childhood cancer survivors (CCS) and their correlations to previously reported adverse cardiovascular changes in this cohort. Methods Fifty-seven CCS and 53 healthy controls (age 20-30 years) were studied. Plasma long-chain ceramides, known to be cardi- and results otoxic (C16:0, C18:0, C24:0, and C24:1), were analysed by mass spectrometry. The coronary event risk test 2 (CERT2) score was calculated from the ceramide data. Cardiac and carotid artery ultrasound data and lipid data available from previous studies of this cohort were used to study partial correlations with ceramide and CERT2 score data. All four analysed ceramides were elevated in CCS compared with controls (P ≤ 0.012). The greatest difference was noted for C18:0, which was 33% higher in CCS compared with controls adjusted for sex, age, and body mass index (BMI) (P < 0.001). The CERT2 score was higher in CCS compared with controls (P < 0.001). In the CCS group, 35% had a high to very high CERT2 score (7-12) when compared with 9% in the control group (P < 0.001). The CCS subgroup with a CERT2 score ≥ 7 had higher heart rate, systolic blood pressure, and higher levels of apolipoprotein B compared with CCS with a CERT2 score < 6 (P ≤ 0.011). When adjusted for age, sex, and BMI, CERT2 score was significantly correlated with arterial stiffness, growth hormone, and cranial radiotherapy (P < 0.044). Conclusion Ceramides could be important biomarkers in understanding the pathophysiology of CVD and in predicting CVD disease risk in young adult CCS.
17.	Broberg, Olof, et al. (author) Characterization of Cardiac, Vascular, and Metabolic Changes in Young Childhood Cancer Survivors 2021 In: Frontiers in Pediatrics. - : Frontiers Media SA. - 2296-2360. ; 9 Journal article (peer-reviewed)abstract Background: Childhood cancer survivors (CCS) are at an increased risk for cardiovascular diseases (CVD). It was the primary aim of this study to determine different measures of cardiac, carotid, lipid, and apolipoprotein status in young adult CCS and in healthy controls. Methods: Cardiac and common carotid artery (CCA) structure and function were measured by ultrasonography. Lipids and apolipoproteins were measured in the blood. Peripheral arterial endothelial vasomotor function was assessed by measuring digital reactive hyperemia index (PAT-RHI) using the Endo-PAT 2000. Results: Fifty-three CCS (20-30 years, 35 men) and 53 sex-matched controls were studied. The CCS cohort was divided by the median dose of anthracyclines into a low anthracycline dose (LAD) group (50-197 mg/m2, n = 26) and a high anthracycline dose (HAD) group (200-486 mg/m2, n = 27). Carotid distensibility index (DI) and endothelial function determined by PAT-RHI were both lower in the CCS groups compared with controls (p < 0.05 and p = 0.02). There was no difference in carotid intima media thickness. Atherogenic apolipoprotein-B (Apo-B) and the ratio between Apo-B and Apoliprotein-A1 (Apo-A1) were higher in the HAD group compared with controls (p < 0.01). Apo-B/Apo-A1-ratio was over reference limit in 29.6% of the HAD group, in 15.4% of LAD group, and in 7.5% of controls (p = 0.03). Measured lipid markers (low density lipoprotein and total cholesterol and triglycerides) were higher in both CCS groups compared with controls (p < 0.05). Systolic and diastolic function were measurably decreased in the HAD group, as evidenced by lower EF (p < 0.001) and lower é-wave (p < 0.005) compared with controls. CCA DI correlated with Apo-B/Apo-A1-ratio and Apo-A1. Follow-up time after treatment correlated with decreased left ventricular ejection fraction (p = 0.001). Conclusion: Young asymptomatic CCS exhibit cardiac, vascular, lipid, and apolipoprotein changes that could account for increased risk for CVD later in life. These findings emphasize the importance of cardiometabolic monitoring even in young CCS.
18.	Broberg, Olof, et al. (author) Childhood Cancer Survivors Have Impaired Strain-Derived Myocardial Contractile Reserve by Dobutamine Stress Echocardiography 2023 In: Journal of Clinical Medicine. - 2077-0383. ; 12:8, s. 1-14 Journal article (peer-reviewed)abstract Abnormal left ventricular contractile reserve (LVCR) is associated with adverse cardiac outcomes in different patient cohorts and might be useful in the detection of cardiomyopathy in childhood cancer survivors (CCS) after cardiotoxic treatment. The aim of this study was to evaluate LVCR by dobutamine stress echocardiography (DSE) combined with measures of myocardial strain in CCS previously treated with anthracyclines (AC). Fifty-three CCS (age 25.34 ± 2.44 years, 35 male) and 53 healthy controls (age 24.40 ± 2.40 years, 32 male) were included. Subjects were examined with echocardiography at rest, at low-dose (5 micrograms/kg/min), and at high-dose (40 micrograms/kg/min) dobutamine infusion. Left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS), strain rate (GSR), and early diastolic strain rate (GEDSR) at different DSE phases were used as measures of LVCR. The mean follow-up time among CCS was 15.8 ± 5.8 years. GLS, GSR, and LVEF were lower at rest in CCS compared to controls (p ≤ 0.03). LVEF was within the normal range in CCS. ΔGLS, ΔGSR, and ΔGEDSR but not ΔLVEF were lower in CCS compared to controls after both low- (p ≤ 0.048) and high-dose dobutamine infusion (p ≤ 0.023). We conclude that strain measures during low-dose DSE detect impaired myocardial contractile reserve in young CCS treated with AC at 15-year follow-up. Thus, DSE may help identify asymptomatic CCS at risk for heart failure and allows for tailored follow-up accordingly.
19.	Broberg, Olof, et al. (author) Circulating leptin is associated with adverse vascular changes in young adult survivors of childhood cancer 2024 In: Cardiology in the Young. - 1047-9511 .- 1467-1107. Journal article (peer-reviewed)abstract INTRODUCTION: Proteomics may help discover novel biomarkers and underlying mechanisms for cardiovascular disease. This could be useful for childhood cancer survivors as they show an increased risk of cardiovascular disease. The aim of this study was to investigate circulating cardiovascular proteins in young adult survivors of childhood cancer and their relationship to previously reported subclinical cardiovascular disease.METHODS: Ninety-two cardiovascular proteins were measured in 57 childhood cancer survivors and in 52 controls. For proteins that were significantly different between childhood cancer survivors and controls, we performed correlations between protein levels and measures of peripheral arterial stiffness (carotid distensibility and stiffness index, and augmentation index) and endothelial dysfunction (reactive hyperemia index).RESULTS: Leptin was significantly higher in childhood cancer survivors compared to controls (normalized protein expression units: childhood cancer survivors 6.4 (1.5) versus 5.1 (1.7), p < 0.0000001) after taking multiple tests into account. Kidney injury molecule-1, MER proto-oncogene tyrosine kinase, selectin P ligand, decorin, alpha-1-microglobulin/bikunin precursor protein, and pentraxin 3 showed a trend towards group differences (p < 0.05). Among childhood cancer survivors, leptin was associated with anthracycline treatment after adjustment for age, sex, and body mass index (p < 0.0001). Higher leptin correlated with lower carotid distensibility after adjustment for age, sex, body mass index, and treatments with radiotherapy and anthracyclines (p = 0.005).CONCLUSION: This proteomics approach identified that leptin is higher in young asymptomatic adult survivors of childhood cancer than in healthy controls and is associated with adverse vascular changes. This could indicate a role for leptin in driving the cardiovascular disease burden in this population.
20.	Christierson, Lea, et al. (author) Multi-Modal in Vitro Experiments Mimicking the Flow Through a Mitral Heart Valve Phantom In: Cardiovascular Engineering and Technology. - 1869-408X. Journal article (peer-reviewed)abstract Purpose: Fluid-structure interaction (FSI) models are more commonly applied in medical research as computational power is increasing. However, understanding the accuracy of FSI models is crucial, especially in the context of heart valve disease in patient-specific models. Therefore, this study aimed to create a multi-modal benchmarking data set for cardiac-inspired FSI models, based on clinically important parameters, such as the pressure, velocity, and valve opening, with an in vitro phantom setup. Method: An in vitro setup was developed with a 3D-printed phantom mimicking the left heart, including a deforming mitral valve. A range of pulsatile flows were created with a computer-controlled motor-and-pump setup. Catheter pressure measurements, magnetic resonance imaging (MRI), and echocardiography (Echo) imaging were used to measure pressure and velocity in the domain. Furthermore, the valve opening was quantified based on cine MRI and Echo images. Result: The experimental setup, with 0.5% cycle-to-cycle variation, was successfully built and six different flow cases were investigated. Higher velocity through the mitral valve was observed for increased cardiac output. The pressure difference across the valve also followed this trend. The flow in the phantom was qualitatively assessed by the velocity profile in the ventricle and by streamlines obtained from 4D phase-contrast MRI. Conclusion: A multi-modal set of data for validation of FSI models has been created, based on parameters relevant for diagnosis of heart valve disease. All data is publicly available for future development of computational heart valve models.
21.	Clausen, Henning, et al. (author) Evaluation of Circulating Cardiovascular Biomarker Levels for Early Detection of Congenital Heart Disease in Newborns in Sweden 2020 In: JAMA Network Open. - : American Medical Association (AMA). - 2574-3805. ; 3:12 Journal article (peer-reviewed)abstract Importance: Congenital heart disease (CHD) is the most common congenital malformation in humans worldwide. Circulating cardiovascular biomarkers could potentially improve the early detection of CHD, even in asymptomatic newborns. Objectives: To assess the performance of a dried blood spot (DBS) test to measure the cardiovascular biomarker amino terminal fragment of the prohormone brain-type natriuretic peptide (NT-proBNP) levels in newborns and to compare DBS with standard EDTA analysis in control newborns during the first week of life. Design, Setting, and Participants: This diagnostic study was conducted in a single regional pediatric service in southern Sweden. Healthy, term neonates born between July 1, 2018, and May 31, 2019, were prospectively enrolled and compared against retrospectively identified newborns with CHD born between September 1, 2003, and September 30, 2019. Neonates who required inpatient treatment beyond the standard postnatal care were excluded. Exposure: New DBS test for NT-proBNP quantification in newborns that used 3 μL of blood vs the current screening standard. Main Outcomes and Measures: Performance of the new test and when combined with pulse oximetry screening was measured by receiver operating characteristic curve analysis. Performance of the new test and EDTA screening was compared using Pearson linear correlation analysis. Results: The DBS samples of 115 neonates (81 control newborns and 34 newborns with CHD, of whom 63 were boys [55%] and the mean [SD] gestational age was 39.6 [1.4] weeks) were analyzed. The new NT-proBNP test alone identified 71% (n = 24 of 34) of all CHD cases and 68% (n = 13 of 19) of critical CHD cases as soon as 2 days after birth. Detection of any CHD type improved to 82% (n = 28 of 34 newborns) and detection of critical CHD improved to 89% (n = 17 of 19 newborns) when combined pulse oximetry screening and NT-proBNP test results were used. Performance of the NT-proBNP test was excellent when control newborns were matched to newborns with CHD born between July 1, 2018, and May 31, 2019 (area under the curve, 0.96; SE, 0.027; 95% CI, 0.908-1.0; asymptotic P < .05). Conclusions and Relevance: This study found that NT-proBNP assay using minimal DBS samples appears to be timely and accurate in detecting CHD in newborns and to discriminate well between healthy newborns and newborns with various types of CHD. This finding warrants further studies in larger cohorts and highlights the potential of NT-proBNP to improve neonatal CHD screening.
22.	Clausen, Henning, et al. (author) Newborn Screening for High-Risk Congenital Heart Disease by Dried Blood Spot Biomarker Analysis. 2024 In: JAMA Network Open. - 2574-3805. ; 7:6 Journal article (peer-reviewed)abstract Importance Congenital heart disease (CHD) is the most common human organ malformation, affecting approximately 1 of 125 newborns globally.Objectives Assessing the performance of 2 diagnostic tests using minimal amounts of dried blood spots (DBS) to identify high-risk CHD compared with controls in a Swedish cohort of neonates.Design, Setting, and Participants This diagnostic study took place in Sweden between 2019 and 2023 and enrolled full-term babies born between 2005 and 2023. All cases were identified through centralized pediatric cardiothoracic surgical services in Lund and Gothenburg, Sweden. Controls were followed up for 1 year to ensure no late presentations of high-risk CHD occurred. Cases were verified through surgical records and echocardiography.Exposure High-risk CHD, defined as cases requiring cardiac surgical management during infancy due to evolving signs of heart failure or types in which the postnatal circulation depends on patency of the arterial duct. Using 3-μL DBS samples, automated quantitative tests for NT-proBNP and interleukin 1 receptor-like 1 (IL-1 RL1; formerly known as soluble ST2) were compared against established CHD screening methods.Main Outcomes and Measures Performance of DBS tests to detect high-risk CHD using receiver operating characteristic curves; Bland-Altman and Pearson correlation analyses to compare IL-1 RL1 DBS with plasma blood levels.Results A total of 313 newborns were included (mean [SD] gestational age, 39.4 [1.3] weeks; 181 [57.8%] male). Mean (SD) birthweight was 3495 (483) grams. Analyzed DBS samples included 217 CHD cases and 96 controls. Among the CHD cases, 188 participants (89.3%) were high-risk types, of which 73 (38.8%) were suspected prenatally. Of the 188 high-risk cases, 94 (50.0%) passed pulse oximetry screening and 36 (19.1%) were initially discharged after birth without diagnoses. Combining NT-proBNP and IL-1 RL1 tests performed well in comparison with existing screening methods and enabled additional identification of asymptomatic babies with receiver operating characteristic area under the curve 0.95 (95% CI, 0.93-0.98).Conclusions and relevance In this diagnostic study, NT-proBNP and IL-1 RL1 DBS assays identified high-risk CHD in a timely manner, including in asymptomatic newborns, and improved overall screening performance in this cohort from Sweden. Prospective evaluation of this novel approach is warranted.
23.	Clausen, Henning, et al. (author) Single-centre experience of balloon valvuloplasty for severe aortic stenosis in childhood: could horizontal aortic root angulation predict outcomes? 2022 In: Cardiology in the Young. - 1467-1107. ; 32:S2, s. 197-198 Conference paper (peer-reviewed)
24.	Dalén, Magnus, et al. (author) Long‐Term Survival After Single‐Ventricle Palliation : A Swedish Nationwide Cohort Study 2024 In: Journal of the American Heart Association. - 2047-9980. ; 13:6 Journal article (peer-reviewed)abstract BackgroundLong‐term survival after single‐ventricle palliation and the effect of dominant ventricle morphology in large, unselected series of patients are scarcely reported.Methods and ResultsThis nationwide cohort study included all children undergoing operation with single‐ventricle palliation during their first year of life in Sweden between January 1994 and December 2019. Data were obtained from institutional records and assessment of underlying cardiac anomaly and dominant ventricular morphology was based on complete review of medical records, surgical reports, and echocardiographic examinations. Data on vital status and date of death were retrieved from the Swedish Cause of Death Register, allowing for complete data on survival. Among 766 included patients, 333 patients (43.5%) were classified as having left or biventricular dominance, and 432 patients (56.4%) as having right ventricular (RV) dominance (of whom 231 patients had hypoplastic left heart syndrome). Follow‐up was 98.7% complete (10 patients emigrated). Mean follow‐up was 11.3 years (maximum, 26.7 years). Long‐term survival was significantly higher in patients with left ventricular compared with RV dominance (10‐year survival: 91.0% [95% CI, 87.3%–93.6%] versus 71.1% [95% CI, 66.4%–75.2%]). RV dominance had a significant impact on outcomes after first‐stage palliation but was also associated with impaired survival after completed total cavopulmonary connection. In total, 34 (4.4%) patients underwent heart transplantation. Of these 34 patients, 25 (73.5%) had predominant RV morphology.ConclusionsThis study provides clinically relevant knowledge about the long‐term prognosis in patients with different underlying cardiac anomalies undergoing single‐ventricle palliation. RV dominance had a significant impact on outcomes after initial surgical treatment but was also associated with impaired survival after completed Fontan circulation.RegistrationURL: https://www.clinicaltrials.gov; Unique identifier: NCT03356574.
25.	Englund, Emma, et al. (author) Adverse Lipid and Inflammatory Changes in Young Nondiabetic First-Degree Relatives of Type 1-Diabetic Patients 2018 In: Cardiology in the Young. - 1467-1107. ; 28:S1, s. 43-44 Conference paper (peer-reviewed)abstract Background: Previous studies from our and other centers on young patients with type 1 diabetes (T1D) have indicated pro-atherosclerotic changes in the carotid arteries and in the lipid and systemic inflammatory profiles without a clear relationship between these changes and the hyperglycemic control. We have also earlier found in these patients a certain HLA-related genetic susceptibility to adverse vascular changes.Objective: To assess whether pro-atherosclerotic changes are present in apparently healthy first- degree relatives of patients with T1D.Methods: Plasma lipids, C-peptide (index of insulin secretion), C-reactive protein (CRP), and the carotid artery intima-media thickness (CA-IMT), compliance (CAC) and stiffness index (SI) were assessed in up to 116 non-diabetic first-degree relatives (FDR; mean age: 12.6 years; 56 female) of patients with T1D and in up to 43 age-matched control individuals (mean age: 13.3 years; 23 female) without heredity for cardiovascular risk factors. The number and type of clinically manifest acute infections during the past year were obtained via a questionnaire validated in our previous studies.Results: There was no difference in age, gender, body mass index, arterial blood pressure and C- peptide levels between the FDR and control groups (p>0.2). Also, there was no significant difference in SI (p=0.2), CAC (p=0.1) and CA-IMT (p=0.9) between the groups. In the FDR group, plasma CRP and LDL- cholesterol (LDL-C) were increased (p<0.05 for both) and HDL-C was decreased (p<0.0001) as compared to the control group. The changes in LDL-C and HDL-C were most marked in FDR individuals with ≥ 4 acute respiratory infections during the past year (Figure).Conclusion: Adverse lipidemic and inflammatory changes are present in healthy non-diabetic first- degree relatives of T1D patients, probably related to their genetic susceptibility to this disease. Further analyses of additional indices of peripheral arterial function in these groups are under way.

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