M T Bink-Boelkens

University of Groningen, Groningen, Province of Groningen, Netherlands

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Publications (39)193.27 Total impact

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    ABSTRACT: To evaluate the presence of vascular damage in long-term childhood cancer survivors (CCS) and sibling controls, and to evaluate the association between vascular damage parameters and cancer treatment and influence of cardiovascular risk factors. Vascular assessment was performed in 277 adult CCSs (median age at diagnosis, 9 years; range, 0 to 20 years; median current age, 28 years; range, 18 to 48 years) treated with potentially cardiovascular toxic anticancer treatment (ie, anthracyclines, platinum, and/or radiotherapy [RT]). Measurements included carotid- and femoral-wall intima-media thickness (IMT), flow-mediated vasodilatation of the brachial artery by ultrasound, assessment of endothelial and inflammatory marker proteins (including tissue-type plasminogen activator [t-PA], plasminogen activator inhibitor type 1 [PAI-I]), and cardiovascular risk factors. CCS assessments were compared with those of 130 sibling controls (median age, 26 years; range, 18 to 51 years). At a median of 18 years (range, 5 to 31 years) after treatment, carotid and femoral IMTs in CCSs were not different from those of controls. However, CCSs who received RT as part of their treatment regimen had increased carotid and femoral IMTs and higher t-PA and PAI-I levels, indicating vascular damage and persistent endothelial activation. Patients treated with RT to the neck or chest also had greater femoral IMT. Greater IMT was associated with presence of cardiovascular risk factors (eg, hypertension and overweight). After potentially cardiovascular toxic anticancer treatment, CCSs who received RT showed signs of endothelial damage and an unfavorable cardiovascular risk profile compared with controls. CCSs treated with localized RT had increased IMT outside the primary irradiation field. These abnormalities are probably involved in the pathogenesis of cardiovascular morbidity in CCSs.
    Journal of Clinical Oncology 09/2013; · 18.04 Impact Factor
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    ABSTRACT: To assess systolic and diastolic function in adult childhood-cancer survivors (CCS) after treatment entailing potential cardiovascular toxicity. The study cohort consisted of 277 adult CCS (median age 28 [range 18-48]years), who had been treated with anthracyclines, platinum, and/or radiotherapy between 1976 and 1999, along with 130 healthy sibling controls. The assessments included echocardiography, baroreflex sensitivity measurement, and plasma N-terminal pro-brain natriuretic peptide (NT-proBNP). Echocardiography measurements were shortening fraction (SF) (abnormal<29%) for systolic function and tissue velocity imaging of early diastole (TVI Et) (abnormal<8.00)cm/sec for diastolic function; systolic function was also assessed by the wall motion score index (WMSI). At 18 (5-31)years post-treatment, the prevalence of both impaired SF and abnormal WMSI was increased in CCS compared to controls (p=0.003 and p<0.001, respectively). CCS also had an increased prevalence of diastolic dysfunction compared to the controls (12% versus 1%, p<0.001). Abnormal SF and/or abnormal diastolic function were found in 43% of CCS. NT-proBNP was higher in CCS and was associated to increased WMSI. Baroreflex sensitivity was lower in CCS and was associated with diastolic dysfunction. Systolic as well as diastolic dysfunction was associated with cumulative dose of anthracyclines and mediastinal irradiation. After treatment with potential cardiovascular toxic therapies, the risk of systolic and diastolic dysfunction in CCS is considerable. Since these abnormalities, in particular diastolic dysfunction, are age related, the observed effects might be considered a sign of precocious cardiac ageing.
    European journal of cancer (Oxford, England: 1990) 06/2011; 47(16):2453-62. · 4.12 Impact Factor
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    Gertie C M Beaufort-Krol, Sebastiaan S P Dijkstra, Margreet Th E Bink-Boelkens
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    ABSTRACT: Premature ventricular contractions (PVCs) are thought to be innocent in children with normal hearts, especially if they disappear during exercise. The aim of our study was to study the natural history of PVCs in childhood and whether there is a difference between PVCs originating from the right [premature ventricular contraction with left bundle branch block (PVC-LBBB)] or the left ventricle [premature ventricular contraction with right bundle branch block (PVC-RBBB)]. We evaluated children with frequent PVCs and anatomically normal hearts (n= 59; 35M/24F) by 12-lead ECG, echocardiography, Holter recording, and an exercise test. Age at the first visit was 7.1 +/- 4.3 years (mean +/- SD), and follow-up was 3.1 +/- 3.1 years. We could evaluate each child for 2.5 +/- 1.5 times. Premature ventricular contraction with left bundle branch block was seen in 41% of the children; PVC-RBBB in 36%; and undetermined in 23%. Mean percentage PVCs in the Holter recording decreased (14.3 +/- 13.7% in the age group 1-3 years to 4.8 +/- 7.2% in the age group >OR=16 years; P= 0.08). Mean percentage PVC-LBBB did not change (12.3 +/- 21.4 vs. 11.7 +/- 5.5%), whereas PVC-RBBB decreased (16.3 +/- 4.2 to 0.6 +/- 1.4%; P < 0.02). We conclude that there is a difference in the natural history between PVC-LBBB and PVC-RBBB in children with an anatomically normal heart. Premature ventricular contraction with right bundle branch block disappears during childhood. Follow-up of these children seems not necessary. Premature ventricular contraction with left bundle branch block does not disappear and, therefore, it may be necessary to follow these children even during adulthood.
    Europace 05/2008; 10(8):998-1003. · 2.77 Impact Factor
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    ABSTRACT: Due to a low heart rate (HR) in children with congenital complete atrioventricular block (CCAVB), a larger stroke volume of the left ventricle (LV) may be expected. If so, end-diastolic (LVEDD) and end-systolic (LVESD) diameters may be enlarged and even dilated cardiomyopathy (DCM) may occur. The aim of this study was to answer the question if children with CCAVB develop LV dilatation. Furthermore, we investigated whether LV dilatation would decrease after pacing. We longitudinally evaluated echocardiographic data (LVEDD, LVESD, shortening fraction [SF]) in 36 children with CCAVB. Age at the first visit was 2.5 +/- 3.3 years (mean +/- SD); follow-up 10.6 +/- 7.3 years. Three children had DCM, already at 1st visit. LVEDD and LVESD Z scores in all children with CCAVB were larger than in normal controls (LVEDD Z score 1.38 +/- 1.80; LVESD Z score 0.64 +/- 1.35). Both Z scores were larger when HR was lower. Both Z scores increased over time in children who met criteria for pacing, but did not change in non-paced children. Physiologic pacing decreased both Z scores. SF of all children was normal and remained normal during follow-up (0.39 +/- 0.05 1st visit vs 0.39 +/- 0.06 last visit). We conclude that children with CCAVB have LV dilatation, which is progressive in children who met criteria for pacing. LV dilatation regressed by physiologic pacing. LV dilatation was larger when HR was lower. SF does not deteriorate over time. DCM occurs early in the disease and does not develop during childhood, not even in children with LV dilatation.
    Pacing and Clinical Electrophysiology 12/2007; 30(11):1339-43. · 1.75 Impact Factor
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    ABSTRACT: In children with cancer a well-known risk factor for cardiotoxicity is a high cumulative dose of anthracyclines, but little is known about cardiac function in low-dose anthracycline-treated survivors. Also, it is unclear if a safe anthracycline-dose exists at all. Cardiac function was assessed in 23 long-term ALL-survivors with a median follow-up of 22 years (range 19.5-24.5) post-treatment. Age at diagnosis and current age were 5.0 (2.0-14.0) and 29.0 (24.0-39.0) years. All 23 survivors were treated according to DCLSG protocol ALL-5, including 18-25 Gy cranial irradiation. Thirteen of them received 4 x 25 mg/m(2) daunorubicin by randomization. Cardiac evaluation included blood pressure measurement, echocardiography, and (24 h-) electrocardiogram. Results were compared with an earlier assessment at median 12 years post-treatment. None of the survivors had cardiac abnormalities. Cardiac status of daunorubicin-treated survivors showed no deterioration compared with the previous assessment in 1995. CONCLUSION AND IMPLICATION FOR CANCER SURVIVORS: After prolonged follow-up (more than 20 years post-treatment), ALL-survivors treated with low dose daunorubicin had no clinical relevant deterioration of cardiac function.
    Journal of Cancer Survivorship 12/2007; 1(4):255-60. · 3.57 Impact Factor
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    ABSTRACT: Catecholaminergic polymorphic ventricular tachycardia is a disease characterized by ventricular arrhythmias elicited exclusively under adrenergic stress. Additional features include baseline bradycardia and, in some patients, right ventricular fatty displacement. The clinical spectrum is expanded by the 2 families described here. Sixteen members from 2 separate families have been clinically evaluated and followed over the last 15 years. In addition to exercise-related ventricular arrhythmias, they showed abnormalities in sinoatrial node function, as well as atrioventricular nodal function, atrial fibrillation, and atrial standstill. Left ventricular dysfunction and dilatation was present in several affected individuals. Linkage analysis mapped the disease phenotype to a 4-cM region on chromosome 1q42-q43. Conventional polymerase chain reaction-based screening did not reveal a mutation in either the Ryanodine receptor 2 gene (RYR2) or ACTN2, the most plausible candidate genes in the region of interest. Multiplex ligation-dependent probe amplification and long-range polymerase chain reaction identified a genomic deletion that involved RYR2 exon-3, segregated in all the affected family members (n=16) in these 2 unlinked families. Further investigation revealed that the genomic deletion occurred in both families as a result of Alu repeat-mediated polymerase slippage. This is the first report on a large genomic deletion in RYR2, which leads to extended clinical phenotypes (eg, sinoatrial node and atrioventricular node dysfunction, atrial fibrillation, atrial standstill, and dilated cardiomyopathy). These features have not previously been linked to RYR2.
    Circulation 11/2007; 116(14):1569-76. · 15.20 Impact Factor
  • Gertie C M Beaufort-Krol, Ymkje Stienstra, Margreet Th E Bink-Boelkens
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    ABSTRACT: Children with congenital complete atrioventricular block (CCAVB) often need pacemaker therapy. In these children, it may be preferable to use single-lead VDD pacing, but for VDD pacing a normal sinus node function is required. Our aim was to study sinus node function in children with CCAVB. We longitudinally evaluated sinus rate in 36 children with CCAVB and normal anatomy of the heart. The rate of sinus rhythm on a 12-lead ECG, in Holter recordings, and exercise tests were evaluated at regular intervals. Age at the first visit of the children was 2.5+/-3.3 years (mean+/-SD). Follow-up was 10.6+/-7.3 years. The rate of sinus rhythm on a 12-lead ECG was at every age within the normal values for age (e.g. 0-1 year: 153+/-24 bpm, and 17-18 years: 76+/-4 bpm). Lowest and highest sinus rates in the Holter recordings were normal. During exercise, mean sinus rate in the total group of children increased from 92+/-8 at rest to 171+/-9 bpm at maximal exercise. We conclude that sinus node function is normal in children with CCAVB. Because of the normal increase in sinus rate during exercise, a single-lead VDD pacemaker can be safely implanted in these children.
    Europace 10/2007; 9(9):844-7. · 2.77 Impact Factor
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    ABSTRACT: Longitudinal studies of cardiac function in long-term childhood cancer survivors are scarce and frequently concern a median follow-up shorter than 13 years. Cardiac assessment was performed in 22 doxorubicin-treated long-term survivors of a malignant bone tumour at median 22 years (range 15-27.5) post-treatment. Age at follow-up was 39 years (range 27-59) and cumulative dose of doxorubicin was 360 mg/m(2) (range 225-550). Cardiac function was assessed by echocardiography and (24-h) ECG. The results were compared with those of earlier assessments at 9 years (1992) and 14 years (1997) post-treatment. Systolic dysfunction was found in 27% (9% in 1997; P = 0.02) and diastolic dysfunction in 45% (18% in 1997; P = 0.02). Heart rate variability showed further deterioration compared with earlier results. Twenty-two years after doxorubicin-treatment, bone tumour survivors showed progressive cardiac dysfunction.
    Annals of Oncology 11/2006; 17(10):1586-91. · 7.38 Impact Factor
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    ABSTRACT: To evaluate the indications, underlying cardiac disorders, efficacy and complications involved with implantable cardioverter-defibrillators (ICDs) in paediatric patients in The Netherlands, the records of all patients aged 18 years or younger who underwent ICD placement were reviewed retrospectively. Between January 1995 and September 2002, 23 patients (11 males, 12 females; median age 12 years, range 6 months to 16 years) underwent ICD implantation. The ICD was implanted for aborted sudden cardiac death ( n = 14), syncope ( n = 5) or for primary prevention of sudden cardiac death ( n = 4). Underlying cardiac disorders were electrical diseases ( n = 16), hypertrophic or dilated cardiomyopathy ( n = 4) and congenital cardiac malformations ( n = 3). Five patients had an epicardially placed ICD, while 18 underwent a transvenous approach. The generator was placed in an abdominal position in eight patients, whereas it was placed in the subpectoral region in 15. There was no early mortality. Median hospital stay was 5 days (range 2-30 days). Median follow-up time was 29 months (range 1 month to 7 years). Seven patients experienced an inappropriate shock after a median period of 7 months; five patients an appropriate shock after a median period of 3 months. The reasons for inappropriate shock were supraventricular tachycardia ( n = 1), sinus tachycardia ( n = 4) or T-wave sensing (n = 2). One patient with malignant long QT syndrome died of intractable arrhythmias and irreversible cardiomyopathy. Generator replacement was necessary in four patients after 28, 44, 51 and 54 months respectively. CONCLUSION: Implantable cardioverter-defibrillator implantation in paediatric patients is a safe procedure with a good medium-term outcome. The most serious problem is the occurrence of a significant number of inappropriate shocks.
    European Journal of Pediatrics 08/2005; 164(7):436-41. · 1.98 Impact Factor
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    ABSTRACT: The aim was to investigate at what age electrocardiographic characteristics of long QT syndrome type 3 (LQT3) and Brugada syndrome (BS), based on a single SNC5A mutation, appear. The QT interval (QT) in LQT3 is prolonged during bradycardia. It is not clear yet if this is obvious in young children with a relative fast heart rate (HR). Thirty-six children with an SNC5A gene mutation (1795insD) and 46 non-carrier siblings were investigated. In different age groups, HR, QT, QTc, and ST-segment elevation on a 12-lead electrocardiogram (ECG), and HR, QT, QTc, and DeltaQT after the longest pause in a Holter (recording) were evaluated. In all age groups, HR at rest tended to be lower in carriers than in non-carriers, and QT was longer in carriers than in non-carriers. The Brugada phenotype was found >5 years. Gender specific differences were not identified. The QT at lower HR and DeltaQT were longer in carriers than in non-carriers. A QTc of > or =0.44 s at the lowest HR (sensitivity 100%; specificity 88.4%) and DeltaQT > or =60 ms (sensitivity 100%; specificity 82.6%) were good predictors for having LQT3. We conclude that electrocardiographic characteristics of LQT3 and BS show age-dependent penetrance. A QT prolongation and conduction disease were present from birth onwards, whereas ST-segment elevation only developed >5 years. Good tools for clinical diagnosis of LQT3 in this family are QTc at the lowest HR and DeltaQT after a pause in a Holter, even at very young age.
    Journal of the American College of Cardiology 07/2005; 46(2):331-7. · 14.09 Impact Factor
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    ABSTRACT: The goal of this research was to identify predictors for sudden death (SD) in patients with transposition of the great arteries (TGA) who have undergone atrial inflow repair. Sudden death is the most common cause of late death after atrial inflow repair of TGA. Little is known about the predictors of SD. This was a retrospective, multicenter, case-controlled study. We identified 47 patients after Mustard's or Senning's operation who experienced an SD event (34 SD, 13 near-miss SD). Each patient was matched with two controls with the same operation, but without an SD event. Information on numerous variables before the event was obtained and compared with controls at the same time frame. Presence of symptoms of arrhythmia or heart failure at most recent follow-up and history of documented arrhythmia (atrial flutter [AFL]/atrial fibrillation [AF]) were found to increase the risk of SD. Electrocardiogram (ECG), chest X-ray, and Holter ECG findings were not predictive of SD. Neither medication nor pacing was found to be protective. Most SD events (81%) occurred during exercise. Ventricular tachycardia/ventricular fibrillation were the recorded rhythm during SD in 21 of 47 patients. Presence of symptoms and documented AFL/AF are the best predictors of SD in TGA patients. Patients with these findings should be further evaluated for risk of SD.
    Journal of the American College of Cardiology 10/2004; 44(5):1095-102. · 14.09 Impact Factor
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    ABSTRACT: This case report describes ventricular fibrillation without overt cardiomyopathy as the presenting symptom of primary carnitine deficiency due to organic cation transporter 2 (OCTN2)-deficiency in a 15-year-old girl. Normally this disease presents early in life with hypoketotic hypoglycemia, muscle weakness, and/or cardiomyopathy. The patient fully recovered after carnitine supplementation. Recognition of this disease is important because its treatment is easy and effective.
    Pacing and Clinical Electrophysiology 06/2004; 27(5):675-6. · 1.75 Impact Factor
  • Journal of The American College of Cardiology - J AMER COLL CARDIOL. 01/2004; 43(5).
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    ABSTRACT: Our objective was to assess the efficacy of pharmacological treatment in reducing the incidence of permanent junctional reciprocating tachycardia in young children, or to bring the mean heart rate over 24 h to a normal level. We included 21 children with a median age of 0.05 year seen with permanent junctional reciprocating tachycardia over the period 1990 through 2001. Of these children, two had abnormal left ventricular function. Follow-up visits were made at least every 6 months. We registered the presence of the tachycardia over 24 h, the mean heart rate over 24 h, and cardiac function. Treatment was started with propafenone alone, or in combination with digoxin as the first choice. Treatment was effective in 14 cases (67%), with either complete disappearance of the tachycardia after discontinuation of medication, or continuation in sinus rhythm with medication; partially effective in 4 cases (20%) when the mean heart rate over 24 h on the last Holter recording was less than 1 standard deviation above the normal for age; but was not effective in the remaining 3 cases (14%). In 3 patients treated with propafenone, or 13 given propafenone and digoxin, treatment was effective in 12 (75%), partially effective in 2 (13%), and ineffective in the other 2 (13%). All 21 children had a normal left ventricular function at the end of follow-up. The median duration of follow-up was 2.4 years. Permanent junctional reciprocating tachycardia had disappeared spontaneously in one-third of the children, 5 being less than 1 year old. Adverse effects, seen in 5 cases, were mild or asymptomatic. No signs of proarrhythmia were registered. Pharmacological treatment, either with propafenone alone, or in combination with digoxin, is safe and effective in young children with permanent junctional reciprocating tachycardia. The mean heart rate is normalized, and cardiac function is restored and preserved. Radiofrequency ablation may be delayed to a safer age, with the arrhythmia disappearing spontaneously in one-third.
    Cardiology in the Young 11/2003; 13(5):408-12. · 0.95 Impact Factor
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    ABSTRACT: Longitudinal assessment of cardiac toxicity in anthracycline-treated long-term bone tumor survivors. Cardiac status was assessed in 29 patients 14.1 (range 7-18.7) years after treatment with doxorubicin (DOXO) 360 mg/m(2) (median 225-550). The median age of the patients at the time of the study was 32.5 years (range 19.7-52). The evaluation consisted of an electrocardiogram (ECG), 24-hr ambulatory ECG with analysis of heart rate variability (HRV) and echocardiography. The results were compared to those of a study of the same patients that was performed 5 years earlier 8.9 years (range 2.3-14.1) after treatment. [Postma et al.: Med Pediatr Oncol 26:230-237, 1996] We found no progression of ECG abnormalities, arrhythmias, or echocardiographic abnormalities. Females were at risk for reduced contractility (P = 0.006). HRV was significantly reduced compared to age- and sex-matched controls and compared to the previous results. Anthracycline-related late echocardiographic abnormalities and arrhythmias detected 8.9 years after treatment, showed no further deterioration with ongoing follow-up. However, there was a significant reduction of HRV. This suggests that HRV might be a sensitive test for detection of anthracycline-induced cardiac toxicity.
    Medical and Pediatric Oncology 09/2002; 39(2):86-92.
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    ABSTRACT: Cardiac conduction disorders slow the heart rhythm and cause disability in millions of people worldwide. Inherited mutations in SCN5A, the gene encoding the human cardiac sodium (Na+) channel, have been associated with rapid heart rhythms that occur suddenly and are life-threatening; however, a chief function of the Na+ channel is to initiate cardiac impulse conduction. Here we provide the first functional characterization of an SCN5A mutation that causes a sustained, isolated conduction defect with pathological slowing of the cardiac rhythm. By analysing the SCN5A coding region, we have identified a single mutation in five affected family members; this mutation results in the substitution of cysteine 514 for glycine (G514C) in the channel protein. Biophysical characterization of the mutant channel shows that there are abnormalities in voltage-dependent 'gating' behaviour that can be partially corrected by dexamethasone, consistent with the salutary effects of glucocorticoids on the clinical phenotype. Computational analysis predicts that the gating defects of G514C selectively slow myocardial conduction, but do not provoke the rapid cardiac arrhythmias associated previously with SCN5A mutations.
    Nature 03/2001; 409(6823):1043-7. · 38.60 Impact Factor
  • Biophysical Journal - BIOPHYS J. 01/2001; 80(1).
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    ABSTRACT: Three affected members of one family, each with a different clinical presentation of isolated biotin-resistant 3-methylcrotonyl-CoA carboxylase (MCC) deficiency are described. The index patient presented at 7 weeks of age with feeding difficulties, sweating and tachypnoea. Echocardiography showed a severely dilated left ventricle with minimal contractility. MCC deficiency was suspected on the basis of elevated urinary excretion of 3-hydroxyisovalerate and 3-methylcrotonylglycine. Deficiency of MCC activity was found in lymphocytes and fibroblasts (ca. 2% of mean normal). Serum carnitine was low (free 10 micromol/l). Some other possible causes of cardiomyopathy were excluded. Cardiomyopathy was not improved by carnitine therapy. The healthy father and a developmentally delayed brother also had MCC deficiency. Both also had decreased serum carnitine concentrations, but without cardiac involvement. Dilatative cardiomyopathy as predominant symptom in isolated MCC deficiency has not been described before, although severe carnitine deficiency is a common finding in MCC deficiency. It is not clear whether this is a coincidental association. CONCLUSION: In order to understand the phenotypic spectrum of this rare disorder, cardiac evaluation should be made in patients with 3-methylcrotonyl-CoA carboxylase deficiency. Biochemical and clinical investigations have also to be performed in their parents and siblings. In addition, 3-methylcrotonyl-CoA carboxylase deficiency should be included in the differential diagnosis of dilatative cardiomyopathy.
    European Journal of Pediatrics 01/2001; 159(12):901-4. · 1.98 Impact Factor
  • Journal of Applied Physics - J APPL PHYS. 01/2001; 409:1043-1047.
  • M T Bink-Boelkens
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    ABSTRACT: The role of antiarrhythmic drugs in the management of children with arrhythmias has changed due to the rapid development of radiofrequency ablation. Moreover, the release of new drugs and a better insight into the electrophysiologic mechanisms of arrhythmias have changed former patterns of drug management. However, because of lack of controlled trials, arrhythmia management in pediatrics is still mainly based on clinical studies and individual experience. Within these limitations, I attempt to give practical recommendations for the management of the different arrhythmias seen in children based on the latest developments in this area.
    Pediatric Cardiology 10/2000; 21(6):508-15. · 1.20 Impact Factor

Publication Stats

971 Citations
193.27 Total Impact Points


  • 1993–2008
    • University of Groningen
      • • Department of Cardiology
      • • Department of Pediatrics
      Groningen, Province of Groningen, Netherlands
  • 2005
    • Erasmus MC
      Rotterdam, South Holland, Netherlands
  • 1994–2002
    • Universitair Medisch Centrum Groningen
      • Department of Pediatrics
      Groningen, Groningen, Netherlands
  • 2001
    • University of Amsterdam
      • Faculty of Medicine AMC
      Amsterdam, North Holland, Netherlands