Deniz Kececioglu

Factor V Leiden, protein C, and lipoprotein (a) in catheter-related thrombosis in childhood: A prospective study

OBJECTIVE To determine the association between catheter-related thromboses and hereditary causes of thrombophilia, including the factor V Leiden mutation, deficiencies of protein C or protein S, or increased lipoprotein (a). STUDY DESIGN To evaluate the incidence of genetic risk factors for familial thrombophilia in catheter-related thrombosis, 163 consecutively admitted infants and children (cardiac disease and catheter placement [C] n = 140; Broviac catheter [B] n = 23) were prospectively investigated. In addition, an age-matched, healthy control group undergoing elective surgery (S: n = 155) was investigated. RESULTS Heterozygous factor V Leiden mutation was diagnosed in 20 of the 318 study subjects (C: n = 5; B: n = 4; S: n = 11), homozygous factor V Leiden mutation was found in two subjects (C: n = 1; S: n = 1), protein C deficiency type I was diagnosed in nine subjects (C: n = 4; B: n = 1; S: n = 4), and five subjects showed increased lipoprotein (a) (C: n = 3; S: n = 2). The frequency of thrombosis (C: n = 13; B: n = 5) in patients with familial thrombophilia was significantly higher (p < 0.0001; chi square: 27.79) in the catheter groups (15 of 17 subjects) than in control subjects after minor elective surgery (none of 18). Fifteen of the 18 infants with thrombosis had congenital thrombophilia; two children with congenital thrombophilia did not have documented thrombosis, and three infants with vascular occlusion had no inherited predisposition to thrombophilia. CONCLUSIONS Genetic risk factors for familial thrombophilia play an important role in the manifestation of catheter-related thromboembolism in children.

Is Torsion a Suitable Echocardiographic Parameter to Detect Acute Changes in Left Ventricular Afterload in Children

BACKGROUND Congenital heart defects such as coarctation or valvular aortic stenosis are followed by changes in left ventricular myocardial deformation mechanics induced by pressure overload. METHODS Echocardiography was performed in 37 patients (aged 0-27 years, 15 female) with coarctation (27) or valvular aortic stenosis (10) before and after interventional catheterization and compared with 37 body surface area/age-matched healthy children. Deformation was calculated by 2-dimensional strain speckle tracking. RESULTS Stress gradients under provocation with orciprenaline in coarctation decreased from 51.8 +/- 20.0 mm Hg to 6.0 +/- 12.0 mm Hg (P < .0001), and resting gradients in aortic stenoses decreased from 57.5 +/- 18.8 mm Hg to 25.5 +/- 14.0 mm Hg (P < .0001) after intervention. Patients had an increased maximal torsion (tor(max): 16.7 +/- 6.7 deg vs 11.0 +/- 4.7 deg (controls; P < .0001), which decreased significantly after therapy (11.8 +/- 4.9 deg, P < .0001). CONCLUSION Compensatory elevation of left ventricular tor(max) in children with moderate left ventricular pressure load changes rapidly after successful interventional treatment. tor(max) may be a valuable tool to assess cardiac unloading or indicate the need for interventional treatment.

Left ventricular volumetry in healthy children and adolescents: comparison of two different real-time three-dimensional matrix transducers with cardiovascular magnetic resonance

AIMS To assess the accuracy of different hardware and software settings for left ventricular (LV) volume quantification in children using real-time three-dimensional echocardiography (RT3DE). METHODS AND RESULTS The impact of different matrix transducers (IE 33, X3-1 and VIVID 7, V3) and quantification software settings [TOMTEC; contour-finding activity (tCFA) values ranging from 30 to 70 U] on the accuracy of LV indices was tested in 24 healthy children/adolescents (median = 12.6 years) and 25 paediatric patients with Tetralogy-of-Fallot (TOF) (median = 7.3 years) with abnormally shaped ventricles. RT3DE was compared with cardiovascular magnetic resonance (CMR) volumetry as reference. Best agreement (Bland-Altman analysis) was achieved using a tCFA value of 30 U. Applying the V3 device, end-diastolic volume (EDV) and end-systolic volume (ESV) were underestimated by 14.8 +/- 10.6% (mean +/- SD) and 11.2 +/- 16.3%, respectively (r = 9.42, P < 0.001 and r = 0.937, P = 0.003); with the X3-1 system 24.2 +/- 11.0 and 14.6 +/- 15.2%, respectively (r = 0.951, P < 0.001 and r = 0.912, P = 0.001). Negligible differences <1% (P = n.s.) between both transducers were detected applying a tCFA value of 70 U but with significant underestimation (EDV: approximately 35%, P < 0.001; ESV: approximately 26%, P < 0.001) compared with CMR. EDV and ESV of TOF patients were underestimated by 3.2 +/- 15.4 and 8.1 +/- 22.6%, respectively. Intra- and interobserver variability was <4%. CONCLUSION In contrast to recommendations of the manufacturer, data sets from both RT3DE transducers showed acceptable agreement to CMR for volumetric parameters only for low tCFA. Fine-tuning of software settings is mandatory to improve accuracy.

Clinical review: Thyroid hormone replacement in children after cardiac surgery – is it worth a try?

Cardiac surgery using cardiopulmonary bypass produces a generalized systemic inflammatory response, resulting in increased postoperative morbidity and mortality. Under these circumstances, a typical pattern of thyroid abnormalities is seen in the absence of primary disease, defined as sick euthyroid syndrome (SES). The presence of postoperative SES mainly in small children and neonates exposed to long bypass times and the pharmacological profile of thyroid hormones and their effects on the cardiovascular physiology make supplementation therapy an attractive treatment option to improve postoperative morbidity and mortality. Many studies have been performed with conflicting results. In this article, we review the important literature on the development of SES in paediatric postoperative cardiac patients, analyse the existing information on thyroid hormone replacement therapy in this patient group and try to summarize the findings for a recommendation.

Neonatal mechanical bridging to total orthotopic heart transplantation

BACKGROUND Until recently, newborns with medically intractable cardiac failure caused by congenital malformations were mostly doomed to death because of the severity of the disease, which precludes a palliative operation, or because of fatal deterioration before availability of a suitable donor heart. METHODS The recently developed paracorporeal pneumatically driven Medos HIA ventricular assist device offers a therapeutic option for these small infants because it is manufactured in various sizes and is even suitable for cardiac assistance in neonates with a body surface area less than 0.3 m2. RESULTS We report our initial experience with this device, which we used for univentricular bridging to total orthotopic cardiac transplantation in 3 infants. The device was inserted to support the left ventricle in two instances and to support the right heart in one. Successful bridging to transplantation was achieved in 2 infants for periods of 2 and 7 weeks. CONCLUSIONS Our experience demonstrates the feasibility of univentricular mechanical support followed by successful cardiac transplantation in infants and newborns.

Interaction of Fibrinolysis and Prothrombotic Risk Factors in Neonates, Infants and Children With and Without Thromboembolism and Underlying Cardiac Disease-A Prospective Study

UNLABELLED To evaluate the role of plasminogen activator inhibitor-1 (PAI-1) and tissue-type plasminogen activator (t-PA) in children with an estimated risk of vascular occlusion reported to range from 7% to 16%, we conducted a prospective study in infants and children with underlying cardiac disease. One hundred and twenty-five children (neonate - 16 years) were investigated. In 9 infants out of the 125 children vascular occlusion occurred, closely related to cardiac catheterisation and arterial or venous lines during major cardiac surgery. Six of the nine neonates and infants with (n=6) and without (n=3) prothrombotic risk factors showed evidence of a basically impaired fibrinolytic system. Five of the nine infants showed increased PAI-1 clearly correlated to the 4G/4G genotype of the plasminogen activator-1 promoter polymorphism along with elevated t-PA concentration before the first diagnostic cardiac catheterisation was performed. One infant presented with increased t-PA concentration only. Five of the six children with reduced fibrinolytic capacity had further prothrombotic risk factors. CONCLUSION Data of this study indicate that neonates and infants with underlying cardiac disease and basically increased PAI-1 due to the 4G/4G variant of the PAI-1 promoter polymorphism along with elevated t-PA levels in combination with further prothrombotic risk factors are at high risk of developing early thromboembolism during cardiac catheterisation.

Thromboembolism and resistance to activated protein C in children with underlying cardiac disease

OBJECTIVES In the majority of cases, resistance to activated protein C is caused by the point mutation Arg506 to Gln in the factor V gene and has emerged as the most important hereditary cause of thromboembolism. METHODS To determine to what extent resistance to activated protein C was present in children with thromboembolism and underlying cardiac disease, its occurrence was retrospectively investigated. By using a method based on activated partial thromboplastin time, with DNA technique derived from the polymerase chain reaction, we investigated nine children with underlying cardiac disease in whom thromboembolism had previously occurred. RESULTS Heterozygous Arg506-to-Gln mutation in the factor V gene was diagnosed in five of the nine children investigated. In addition, protein C type I deficiency w as found in three patients, and two of the nine children showed increased lipoprotein (a) plasma values. Risk factors were present in all children with symptoms. CONCLUSIONS These data indicate that deficiencies in the protein C anticoagulant pathway are likely to play an important role in the early manifestation of thromboembolism in children with underlying cardiac disease.

ECMO for cardiac rescue in a neonate with accidental amiodarone overdose

Intravenous (IV) amiodarone hydrochloride has proven to be a very effective antiarrhythmic treatment option for a variety of ventricular and supraventricular arrhythmias in adults and paediatric patients. Amiodarone is known to have significant side effects and these especially include profound hypotension in animals and adults, vasodilatation, negative inotropic effects, and significant bradycardia especially when administered intravenously. Special caution is warranted in patients with decreased contractility and end-stage heart failure. We present a case of accidental amiodarone overdose in a newborn treated for atrial flutter resulting in cardiovascular collapse. The patient could be rescued by rapid initiation of VA-ECMO treatment. The patient survived without neurological damage.

REGULAR ARTICLEInteraction of Fibrinolysis and Prothrombotic Risk Factors in Neonates, Infants and Children With and Without Thromboembolism and Underlying Cardiac Disease: A Prospective Study

UNLABELLED To evaluate the role of plasminogen activator inhibitor-1 (PAI-1) and tissue-type plasminogen activator (t-PA) in children with an estimated risk of vascular occlusion reported to range from 7% to 16%, we conducted a prospective study in infants and children with underlying cardiac disease. One hundred and twenty-five children (neonate - 16 years) were investigated. In 9 infants out of the 125 children vascular occlusion occurred, closely related to cardiac catheterisation and arterial or venous lines during major cardiac surgery. Six of the nine neonates and infants with (n=6) and without (n=3) prothrombotic risk factors showed evidence of a basically impaired fibrinolytic system. Five of the nine infants showed increased PAI-1 clearly correlated to the 4G/4G genotype of the plasminogen activator-1 promoter polymorphism along with elevated t-PA concentration before the first diagnostic cardiac catheterisation was performed. One infant presented with increased t-PA concentration only. Five of the six children with reduced fibrinolytic capacity had further prothrombotic risk factors. CONCLUSION Data of this study indicate that neonates and infants with underlying cardiac disease and basically increased PAI-1 due to the 4G/4G variant of the PAI-1 promoter polymorphism along with elevated t-PA levels in combination with further prothrombotic risk factors are at high risk of developing early thromboembolism during cardiac catheterisation.

Flush heparin during cardiac catheterisation prevents long-term coagulation activation in children without APC-resistance-preliminary results

This study was designed to prospectively evaluate haemostatic activation in 75 children undergoing cardiac catheterisation with intermittent flush heparin (10 IU/ml saline) and to relate these data to clinical findings and inherited risk factors for thrombophilia. In addition to flush heparin in infants < 6 months of age in whom additional arterial catheterisation was performed (n = 5) or patients with thrombophilia, heparin (300-400 IU/kg/d) was administered for a further 24 h. APTT was prolonged and anti Xa activity was significantly increased at the end of catheterisation and returned to normal 24 hours later. Whereas thrombin generation (F1 + 2) showed a significant coagulation activation at the end of catheterisation, no concomitant fibrinolytic activation (D-Dimer) was observed. Four children showed resistance to APC: one of them in whom stroke had occurred before and one additional child heterozygous for APCR received further prophylactic heparin. Two neonates with APCR and flush heparin only suffered from thrombosis after catheterisation. No further thrombotic events occurred. This study indicates that low-dose flush heparin during catheterisation may prevent long-term haemostatic activation in children without thrombophilia. Whether further heparin after cardiac catheterisation in children with APCR prevents vascular insults requires a more intensive study.