Neonatal Outcomes of Critical Congenital Heart Defects: A Multicenter Epidemiological Study of Turkish Neonatal Society : Neonatal Outcomes of CCHD.

Critical congenital heart disease (CCHD) is one of the leading causes of neonatal and infant mortality. We aimed to elucidate the epidemiology, spectrum, and outcome of neonatal CCHD in Türkiye. This was a multicenter epidemiological study of neonates with CCHD conducted from October 2021 to November 2022 at national tertiary health centers. Data from 488 neonatal CCHD patients from nine centers were entered into the Trials-Network online registry system during the study period. Transposition of great arteria was the most common neonatal CHD, accounting for 19.5% of all cases. Sixty-three (12.9%) patients had extra-cardiac congenital anomalies. A total of 325 patients underwent cardiac surgery. Aortic arch repair (29.5%), arterial switch (25.5%), and modified Blalock-Taussig shunt (13.2%). Overall, in-hospital mortality was 20.1% with postoperative mortality of 19.6%. Multivariate analysis showed that the need of prostaglandin E1 before intervention, higher VIS (> 17.5), the presence of major postoperative complications, and the need for early postoperative extracorporeal membrane oxygenation were the main risk factors for mortality. The mortality rate of CCHD in our country remains high, although it varies by health center. Further research needs to be conducted to determine long-term outcomes for this vulnerable population.

A rare and fatal cause of hypertrophic cardiomyopathy: Danon disease.

Danon disease is a rare and fatal disease caused by a mutation in the lysosome-associated membrane protein 2 gene. Impaired intracellular autophagy causes lysosomal vacuoles to accumulate mainly in myocardial and skeletal muscle cells, leading to hypertrophic cardiomyopathy, skeletal myopathy, and varying degrees of intellectual disability. Two distinct childhood presentations of Danon disease are described in this report.

The Role of External Loop Recorders in Arrhythmia-Related Symptoms in Children: A Single Center Experience.

In this study, we report our experience with the use of external loop recorders (ELRs), in terms of diagnostic efficiency according to symptoms and symptom-rhythm correlation in pediatric patients. We evaluated ELRs applied to 178 patients between April 2017 and November 2020 at our center. The mean age of 172 patients included in the study was 13.6 ± 3.8 years, and 69.8% were female. ELR indications were palpitations in 98 (56.9%) cases, chest pain and palpitations in 43 (25%) cases, presyncope/syncope in 28 (16.2%) cases, and pacemaker/ implantable cardioverter-defibrillator (ICD) problems in 3 (0.2%) cases. ELR recording times were 14.2 ± 9.7 days on average, ranging from 2 to 67 days. While the symptom-rhythm correlation was 29.1% in total, when the indications were evaluated one by one, this correlation was found to be 30.2% in palpitations, 34.7% in chest pain and palpitations, and 10.7% in presyncope/syncope. The total diagnostic efficiency was 68.1%. In the follow-up of ELR cases, a total of 139 (80.8%) patients received clinical follow-up without medication, 15 (8.8%) patients received medical treatment, and 18 (10.4%) patients underwent EPS. The cardiac ELR system is useful in detecting underlying arrhythmias. Demonstrating sinus tachycardia at the time of the symptom may be seen as negative finding, but while experiencing symptoms, it is diagnostically valuable and may help avoid further investigation with costly and invasive diagnostic procedures. For diagnostic efficiency and cost effectiveness, the optimal recording time is 2 weeks, but it should be extended to 4 weeks in cases such as of presyncope/syncope that cannot be explained with a 2-week ELR use.

Congenital arteriovenous fistula between descending aorta and the left innominate vein.

Thoracic aortocaval fistulae are rare entities where a direct shunt between thoracic arteries and systemic veins is seen. They can be traumatic or congenital in origin. Congenital thoracic aortocaval fistulae usually involve descending aorta and azygos, hemiazygos systems. Presenting symptoms range from continuous murmur to signs of congestive heart failure. In this case report, imaging findings of a 3-year-old girl referred for continuous murmur over the left sternal border are presented. Computed tomography angiography revealed multiple tortuous vessels along the descending aorta with a course toward the left brachiocephalic vein, and was suspicious for an aorta-venous fistula. Subsequent digital subtraction angiography for treatment planning showed a fistula originating at the level of the left 6th intercostal artery, with direct drainage into the left brachiocephalic vein without involvement of the azygos/hemiazygos system.

Correction: Arterial tortuosity syndrome: 40 new families and literature review.

In the published version of this paper the author Neus Baena's name was incorrectly given as Neus Baena Diez. This has now been corrected in both the HTML and PDF versions of the paper.

The frequency of asymptomatic urinary system abnormalities in children detected with cineurography imaging during angiocardiography.

IntroductionDiagnostic and interventional catheter angiography of the heart is frequently used in paediatric cardiology. It is also possible to detect urinary system anomalies with cineurography images that may be obtained during angiocardiography. In this study, the aim was to determine the frequency, distribution, and properties of urinary system anomalies accompanying heart diseases, and to find out the effectiveness of cineurographic images in detecting the urinary system anomalies. METHODS: The cineurographic images of 2022 children who had undergone angiocardiography between 1995 and 2015 were retrospectively examined. RESULTS: Urinary system anomalies were detected in 261 of the 2022 cases (12.9%). Of these 261 cases, 148 were males (56.7%), whereas 113 were females (43.3%). Among the heart diseases, the group most accompanied by urinary system anomalies was the non-cyanotic left-to-right shunted heart diseases, which was detected in 120 (39.1%) patients. Pelvicalyceal ectasia was the most common urinary system anomaly encountered and was detected in 89 patients (34.1%). Of the urinary system anomalies cases, 94 detected by cineurography were determined to be clinically severe. When the effectiveness of the cineurography was evaluated using the ultrasonography records of the patients, it was found to have 63.8% accuracy. CONCLUSION: Many of the patients with CHDs concomitantly have urinary system anomalies. It is possible to determine asymptomatic urinary system anomalies using cineurographic imaging during angiocardiography. This may lead to earlier treatments and improved prognosis for the patients, thus making it possible to prevent potential future problems.

Arterial tortuosity syndrome: 40 new families and literature review.

PURPOSE: We delineate the clinical spectrum and describe the histology in arterial tortuosity syndrome (ATS), a rare connective tissue disorder characterized by tortuosity of the large and medium-sized arteries, caused by mutations in SLC2A10. METHODS: We retrospectively characterized 40 novel ATS families (50 patients) and reviewed the 52 previously reported patients. We performed histology and electron microscopy (EM) on skin and vascular biopsies and evaluated TGF-ß signaling with immunohistochemistry for pSMAD2 and CTGF. RESULTS: Stenoses, tortuosity, and aneurysm formation are widespread occurrences. Severe but rare vascular complications include early and aggressive aortic root aneurysms, neonatal intracranial bleeding, ischemic stroke, and gastric perforation. Thus far, no reports unequivocally document vascular dissections or ruptures. Of note, diaphragmatic hernia and infant respiratory distress syndrome (IRDS) are frequently observed. Skin and vascular biopsies show fragmented elastic fibers (EF) and increased collagen deposition. EM of skin EF shows a fragmented elastin core and a peripheral mantle of microfibrils of random directionality. Skin and end-stage diseased vascular tissue do not indicate increased TGF-ß signaling. CONCLUSION: Our findings warrant attention for IRDS and diaphragmatic hernia, close monitoring of the aortic root early in life, and extensive vascular imaging afterwards. EM on skin biopsies shows disease-specific abnormalities.

"Homozygous, and compound heterozygous mutation in 3 Turkish family with Jervell and Lange-Nielsen syndrome: case reports".

BACKGROUND: Jervell and Lange-Nielsen syndrome (JLNS) isa recessive model of long QT syndrome which might also be related to possible hearing loss. Although the syndrome has been demonstrated to be originated from homozygous or compound heterozygous mutations in either the KCNQ1 or KCNE1 genes, additional mutations in other genetic loci should be considered, particularly in malignant course patients. CASE PRESENTATIONS: Three patients were admitted into hospital due to recurrent seizures/syncope, intrauterine and postnatal bradycardia respectively; moreover all three patients had congenital sensorineural hearing-loss. Their electrocardiograms showed markedly prolonged QT interval. Implantable defibrillator was implanted and left cardiac sympathetic denervation was performed due to the progressive disease in case 1. She had countless ventricular fibrillation and appropriate shock while using an implantable defibrillator. The DNA sequencing analysis of the KCNQ1 gene disclosed a homozygous c.728G > A (p.Arg243His) missense mutation in case1. Further targeted next generation sequencing of cardiac panel comprising 68 gene revealed a heterozygous c.1346 T > G (p.Ile449Arg) variant in RYR2 gene and a heterozygous c.809G > A (p.Cys270Tyr) variant in NKX2-5 gene in the same patient. Additional gene alterations in RYR2 and NKX2-5 genes were thought to be responsible for progressive and malignant course of the disease. As a result of DNA sequencing analysis of KCNQ1 and KCNE1 genes, a compound heterozygosity for two mutations had been detected in KCNQ1 gene in case 2: a maternally derived c.477 + 1G > A splice site mutation and a paternally derived c.520C > T (p.Arg174Cys) missense mutation. Sanger sequencing of KCNQ1 and KCNE1 genes displayed a homozygous c.1097G > A (p.Arg366Gln) mutation in KCNQ1 gene in case 3. ß-blocker therapy was initiated to all the index subjects. CONCLUSIONS: Three families of JLNS who presented with long QT and deafness and who carry homozygous, or compound heterozygous mutation in KCNQ1 gene were presented in this report. It was emphasized that broad targeted cardiac panels may be useful to predict the outcome especially in patients with unexplained phenotype-genotype correlation. Clinical presentations and molecular findings will be discussed further to clarify the phenotype genotype associations.

Evaluation of electrocardiographic parameters for early diagnosis of autonomic dysfunction in children and adolescents with type-1 diabetes mellitus.

BACKGROUND: The aim of this study was to identify the sensitivity of electrocardiogram (ECG) in early diagnosis of cardiac autonomic function disorder in children with type 1 diabetes mellitus. METHODS: A total of 150 children and adolescents with type 1 diabetes mellitus were enrolled between June 2009 and June 2010, as well as 100 age- and sex-matched healthy control children. Twelve-lead ECG was done in all cases and heart rate, QT and QTc interval, dispersion of P wave (Pd), and of QT (QTd) and QTc interval (QTcd) were measured. The clinical and demographic features such as age, gender, duration of follow up and level of HbA1c and fasting glucose were obtained and the effects of these parameters on ECG measurements were investigated. RESULTS: The mean age of the patients and controls was 11.61 ± 3.72 years and 10.92 ± 3.2 years, respectively. QT and QTc interval and QTcd interval were significantly higher in diabetic children compared to healthy controls but these ECG findings were not associated with the duration of diabetes or glycemic state. Pd was significantly higher in the diabetic patients with HbA1c >7.5% compared to control, and this was also found in patients that were followed up >1 year. CONCLUSIONS: Cardiac autonomic function disorder, which is one of the most important causes of morbidity and mortality, may emerge in the course of type 1 diabetes mellitus. It can be diagnosed on ECG even when the patients are asymptomatic.

Congenital anomalies of coronary arteries in children: the evaluation of 22 patients.

Although congenital coronary artery anomalies are seen in 0.6-1 % of adult patients undergoing coronary angiography, the data for the pediatric population are few. This study of 22 children with coronary artery anomalies evaluated them in terms of demographic and clinical features and analyzed their angiographic findings and surgical results. Databases in the Department of Pediatric Cardiology at the University of Uludag were searched for all the patients with a diagnosis of congenital coronary artery anomaly who underwent coronary angiography between 1993 and 2013. Patients with coexistent congenital heart disease were excluded from the study. The study noted 22 patients (0.9 %; 10 boys and 11 girls) with coronary artery anomalies. The mean age of these patients was 58.77 ± 52.04 months (range, 1 month-16 years). Coronary arteriovenous fistula (50 %) and anomalous left coronary artery from the pulmonary artery (ALCAPA) (36 %) were the most common anomalies. In addition, the study included one patient with diffuse coronary artery hypoplasia, one patient with muscular bridge, and one patient with left main coronary artery originating from the right aortic sinus valsalva. Of the 11 patients who had coronary atrioventricular fistula, 7 were asymptomatic, whereas 75 % of the patients with ALCAPA syndrome were admitted because of heart failure. Although 13 patients had an exact diagnosis by echocardiography, 50 % of the patients with ALCAPA syndrome had their diagnosis determined by catheter angiography performed because of severe mitral regurgitation or dilated cardiomyopathy. The mortality rate for all the patients was found to be 18.1 %. Eight patients with coronary arteriovenous fistula have been followed up without surgery to the present. In contrast, seven patients with ALCAPA syndrome have undergone surgery, and three have died. Two of these patients died during the postoperative period, and the remaining patient died suddenly during the preoperative period at home. Isolated congenital coronary artery anomalies are very rare in the pediatric population. Although most congenital coronary artery anomalies are clinically silent, they may be associated with severe symptoms in children. Recognition of potentially serious anomalies such as ALCAPA syndrome is mandatory so that early surgical treatment can be prescribed.

Effect of Magnesium on Ventricular Extrasystoles in Children.

Magnesium (Mg) is a crucial element for cardiovascular system and its deficiency results in a variety of cardiac arrhythmias. The aim of this study is to determine the effect of oral Mg supplementation on the frequency of ventricular extrasystoles (VES) in children. Magnesium supplementation was given to 42 children who had VES without structural heart disease. Clinical, electrocardiographic, and Holter monitoring studies were reviewed. The mean baseline 24 h VES burden on Holter monitoring was 10.26% ± 4.13% and it was decreased to 6.62% ± 3.88% after. There was no significant difference between the pre-treatment serum Mg levels and the decrease in the frequency of VES. In conclusion, oral Mg therapy was found to be effective at suppressing VES in children regardless of serum Mg levels. Large and randomized studies are needed to demonstrate the effect of magnesium on VES suppression.

Evaluation of subvalvular aortic stenosis in children: a 16-year single-center experience.

Subvalvular aortic stenosis accounts for 1-2 % of all congenital heart disease and for 8-20 % of cases of left-ventricular outflow tract (LVOT) obstruction in children. Recurrence of subaortic stenosis (SAS) is not uncommon after surgical management. This study was performed to investigate the clinical and surgical outcomes and to estimate the predictability of recurrences of SAS. Seventy-nine patients age 3-21 years with SAS between 1994 and 2010 were reviewed. Fifty-one patients had discrete SAS, whereas the remaining 15 patients had fibromuscular ridge-type SAS. Mean follow-up time without surgery was 22 months (range of 1-94). Forty-one patients with a diagnosis of SAS underwent surgery. Recurrence rates were 22.7 % (15 patients), and these patients developed SAS at a mean of 4.7 years follow-up. We performed second surgical membrane resection in only 1 patient. The risk of recurrence of SAS was only linked to higher preoperative LVOT gradient. Twenty-three patients had no aortic regurgitation (AR) at preoperative echocardiography. Of these, 39.1 % had trivial, 8.7 % had mild, and 8.7 % had moderate AR after surgery; there was no significant AR. We conclude that surgical intervention was required most of the time in patients with SAS, and surgical outcomes was excellent even if there were associated cardiac defects. The risk of recurrences was higher, especially in patients with higher initial LVOT gradients, although a second surgery was rarely necessary in these patients.

Jervell and Lange-Nielsen syndrome: homozygous missense mutation of KCNQ1 in a Turkish family.

Long QT syndrome is one of the most common cardiac ion channel diseases, but its morbidity and mortality rate can be lessened with an early diagnosis and proper treatment. This cardiac ventricular repolarization abnormality is characterized by a prolonged QT interval and a propensity for ventricular tachycardia (VT) of the torsades de pointes type. The long QT syndrome represents a high risk for presyncope, syncope, cardiac arrest, and sudden death. Jervell and Lange-Nielsen syndrome (JLNS) is a recessively inherited form of long QT syndrome characterized by profound sensorineural deafness and prolongation of the QT interval. Findings have shown that JLNS occurs due to homozygous and compound heterozygous pathogenic variants in KCNQ1 or KCNE1. A 3.5-year-old girl presented to the hospital with recurrent syncope, seizures, and congenital sensorineural deafness. Her electrocardiogram showed a markedly prolonged QT interval, and she had a diagnosis of JLNS. The sequence analysis of the proband showed the presence of a pathogenic homozygous missense variant (c.728G>A, p.Arg243His). Heterozygous mutations of KCNQ1 were identified in her mother, father, and sister, demonstrating true homozygosity. Even with high-dose beta-blocker therapy, the patient had two VT attacks, so an implantable cardioverter defibrillator was fitted. The authors suggest early genetic diagnosis for proper management of the disease in the proband and genetic counseling for both the proband and the girl's extended family.

Ventricular Extrasystole in Children: Single-Center Experience.

OBJECTIVE: Ventricular extrasystole is one of the most common rhythm disorders in children, and almost all of them are characterized by normal cardiac functions without structural cardiac abnormalities. The aim of this study was to assess the clinical course of ventricular extrasystole in children who did not have cardiac structural abnormalities. MATERIALS AND METHODS: This retrospective study analyzed 24-hour rhythm Holter recordings performed in our clinic in children. Patients diagnosed with isolated ventricular extrasystole in Holter records and without structural heart disease on echocardiography were included in the evaluation. RESULTS: A total of 20 160 Holter results were evaluated in the study, and 226 patients (male; 66%) met the criteria. The mean follow-up time was 8.7 ± 3.2 years. While 81.8% of the patients were asymptomatic, the most common symptom was palpitation and 5 patients had syncope. Of the patients, 72 (31.8%) received medical therapy. Beta-blockers were the most often pre- scribed medication. Cardiomyopathy did not develop in any of the patients during the follow- up period. A partial reduction in the frequency of ventricular extrasystole was observed in 42% of the patients, while complete recovery was observed in 22%. CONCLUSION: Ventricular extrasystole in children generally has a good prognosis; most of them are asymptomatic, and the rates of spontaneous regression over time are quite high, regard- less of the origin.

Early left ventricular diastolic dysfunction in premature infants born to preeclamptic mothers.

AIM: To evaluate the cardiac function in premature infants born to preeclamptic mothers and its clinical consequences. METHODS: This was a prospective observational cohort study performed in a tertiary neonatal intensive care unit. Fifty-three premature infants born to preeclamptic mothers comprising the study group were evaluated and compared with 42 premature infants born to normotensive mothers (control group). Relationship between echocardiographic measures and neonatal morbidity were assessed as the main outcome measures. RESULTS: Left ventricle end-diastolic dimension (LVEDD), peak flow velocities during early diastole (peak E wave), peak flow velocities during atrial contraction (peak A wave), and peak E/A ratio were significantly lower in the study group. Within the study group, these parameters were also significantly lower in infants with respiratory problems. LVEDD was significantly smaller in preeclamptic infants with intrauterine growth retardation (IUGR). CONCLUSION: Left ventricle diastolic dysfunction (LVDD) was detected in premature infants born to preeclamptic mothers in the first week after delivery. LVDD was associated with higher incidence of respiratory problems, transient tachypnea of the newborn, longer duration of oxygen requirement, and IUGR.

Successful management with bisphosphonate treatment in a child with tuberculosis-associated hypercalcemia.

Hypercalcemia is a common metabolic abnormality in children and generally occurs due to hyperparathyroidism, vitamin D toxicity, some genetic disorders and malignant diseases. Granulomatous diseases are a rare cause of hypercalcemia in children, which are usually mild and asymptomatic. Severe hypercalcemia in granulomatous diseases has also been reported in the literature. Here, we report a child presenting with severe hypercalcemia secondary to miliary tuberculosis with successful management with bisphosphonate treatment. Increased 1,25(OH)2D3 synthesis by activated macrophages in the granuloma tissue is the major mechanism of hypercalcemia in tuberculosis.

Suspicion, diagnosis, and successful surgical treatment of anomalous origin of the anterior descending coronary artery from the pulmonary trunk.

Anomalous origin of the anterior descending coronary artery from the pulmonary trunk is very rare. We suspected such anomalous origin in a boy aged 2.5 years owing to the echocardiographic demonstration of mitral regurgitation and abnormal diastolic flow in the ventricular septum. The diagnosis was confirmed by angiography. The anomalous artery was successfully reimplanted into the aorta.

Carvedilol therapy in pediatric patients with dilated cardiomyopathy.

Carvedilol reduces mortality and hospitalization in adults with congestive heart failure. Limited information is available about its use in children. The objective of this study was to determine the dosing, efficacy and side effects of carvedilol for the management of dilated cardiomyopathy in children. Sixteen children with idiopathic dilated cardiomyopathy, aged 7 months to 138 months and with an ejection fraction less than 40%, were treated with carvedilol. The average initial dose was 0.1 mg/kg/day and it was uptitrated to 0.4 mg/kg/day. After six months on carvedilol, there were improvements in clinical scoring system from an average of 2.94 to 2.50 (p<0.05), in mean fractional shortening from 17.2 +/- 6.1% to 22.7 +/- 5.1% (p<0.05), and in ejection fraction from 35.2 +/- 6.8% to 43.1 +/- 11.2% (p<0.05). No side effect was observed during the study period. Two patients died due to serious infection. Carvedilol in addition to standard therapy for dilated cardiomyopathy in children improves cardiac function and symptoms. It is well tolerated, with minimal adverse effects, but close monitoring is necessary.

Horseshoe lung associated with scimitar syndrome.

Horseshoe lung is a rare congenital anomaly and mostly accompanied by scimitar syndrome. Most aspects of this complex anomaly can be demonstrated via multidetector CT (MDCT). We present two baby girls who had horseshoe lung associated with right lung hypoplasia and scimitar vein. The chest roentgenograms showed displacement of the heart and mediastinum to the right with smaller right lung. Echocardiography revealed dextroposition, secundum atrial septal defect and bilateral slight peripheral pulmonary stenosis in the first case and dextroposition, severe pulmonary hypertension, secundum atrial septal defect and tricuspid regurgitation in the other one. On thoracic MDCT, the right lung and pulmonary artery were hypoplastic with cardiomediastinal shift to the right. There was an abnormal right pulmonary vein draining into the inferior vena cava on the lower zone of the right lung (scimitar vein). The posterobasal portions of the both lungs were fused through a midline isthmus behind the heart.

Treatment of infective endocarditis with recombinant tissue plasminogen activator.

Infective endocarditis (IE) caused by microbial infection is virtually always fatal if untreated. High-dose and long-term antibiotic treatment is required to eradicate microorganisms. If increased risk of embolic events, persistent infection, and progressive cardiac failure are present, surgery is indicated. However, surgery can carry an increased risk of mortality and morbidity in critically ill children of whom other treatment options such as administering, a thrombolytic agent; recombinant tissue plasminogen activator (r-tPA) could be an alternative choice. Here, we report a 14-year-old male with Down syndrome and acute myeloblastic leukemia, diagnosed with IE characterized by two large vegetations on aortic and mitral valves, who was successfully treated with r-tPA.