Johannes M.P.J. Breur

Hypoglycemia as a Result of Propranolol During Treatment of Infantile Hemangioma: A Case Report

Abstract:u2002 Propranolol is a new and promising treatment for hemangiomas of infancy. We report of a patient in whom steroid maintenance therapy is successfully tapered after introduction of propranolol. This patient, however, developed symptomatic hypoglycemic events presumably because of a concurrent deficiency of epinephrine and cortisol as a direct result of both beta‐blockage by propranolol and adrenal insufficiency as a result of prednisone use. Extreme care should be taken in patients treated with both propranolol and prednisone as they are at increased risk of hypoglycemia.

Pacemaker therapy in isolated congenital complete atrioventricular block.

BREUR, J.M.P.J., et al.: Pacemaker Therapy in Isolated Congenital Complete Atrioventricular Block. The aim of this study was to evaluate the effect of pacemaker (PM) therapy in patients with isolated congenital complete atrioventricular block (CCAVB). Patients with CCAVB eventually qualify for PM implantation, however, timing remains controversial. Retrospective evaluation of left ventricular end‐diastolic diameter (LVEDD), shortening fraction (SF), and cardiothoracic ratio (CTR) in 149 CCAVB patients, before, at, and after PM implantation was carried out. LVEDD shows an average increase of 0.48%/month in non‐PM patients, and an average decrease of 0.88%/month in PM patients. SF shows an average increase of 0.10%/month in non‐PM, and an average decrease of 0.32%/month in PM patients. CTR shows an average increase of 0.02%/month in non‐PM, and an average decrease of 0.19%/month in PM patients. The difference between the non‐PM and PM groups is significant (P = 0.05) for all variables. Symptomatic patients show no significant change in LVEDD after PM therapy (from 66.5% before to 68.5% after PM therapy). Asymptomatic patients do show a significant (P < 0.001) decrease in LVEDD after PM therapy (from 78.4% before to 73.3% after PM therapy). CTR does not differ significantly between symptomatic and asymptomatic patients before PM therapy (58% and 57%, respectively). CTR does differ significantly (P < 0.001) between symptomatic and asymptomatic patients after PM therapy (52% and 48%, respectively). Heart size and SF are increased in most patients with isolated CCAVB. PM implantation is associated with a decrease in heart size and normalization of SF in most patients. Indications for PM therapy in children may require reevaluation in asymptomatic patients with increased cardiac size and decreased cardiac function.

Five years of Kawasaki disease in the Netherlands a national surveillance study

Background: The aim of this study was to evaluate the incidence, disease presentation, treatment and cardiac outcome of Kawasaki disease (KD) in The Netherlands. Methods: The national Dutch Pediatric Surveillance Unit was used to prospectively register new KD cases from 2008 through 2012. Questionnaires were sent to pediatricians to obtain clinical information. Results: Nationwide 341 cases were reported during the 5-year study period, of which 319 questionnaires (93.0%) were returned. The mean incidence of KD was estimated to be 5.8/100,000 children <5 years of age. The median age at disease onset was 2.4 years (range 0.1–14.6 years) and 79.2% of cases were <5 years of age. The male-to-female ratio was 1.5 to 1. Incomplete KD was diagnosed in 22.3% of cases and these cases were significantly younger than complete cases [median: 1.1 (0.1–13.7) vs. 2.8 (0.2–14.6) years, P < 0.001]. In total, 308 patients (96.6%) received intravenous immunoglobulins (IVIG). Retreatment with IVIG was given in 71 (23.1%) and additional steroid treatment in 17 patients (5.5%). During the acute phase, coronary artery aneurysms developed in 43 cases (13.5%). Multivariate logistic regression analysis showed that male gender, delay of treatment (>10 days) and IVIG retreatment were independent risk factors for coronary artery aneurysms development. Conclusions: This prospective study of KD in The Netherlands revealed a mean annual incidence of 5.8/100,000 children <5 years of age. Clinicians should consider the diagnosis of KD in young (male) children with persistent inexplicable fever to start IVIG treatment within 10 days to prevent development of coronary artery aneurysms.

Transient non-autoimmune fetal heart block.

Objectives: Fetal heart block is a rare and irreversible condition associated with structural heart defects or maternal autoantibodies (SS-A/Ro and SS-B/La) resulting in permanent damage of the atrioventricular (AV) node. This is the first report of 4 cases with a transient fetal heart block in structurally normal hearts without maternal autoantibodies. Methods: A report on 4 patients seen within a 14-year period at one center with fetal heart block without intracardiac abnormalities or maternal autoantibodies. Results: Three patients were referred to our center with a fetal bradycardia (heart rate 70–85 bpm), between 20 and 33 weeks’ gestational age, and 1 for a ‘triple’ test at 16 weeks’ gestational age. Echocardiography showed a complete heart block in 2 fetuses, and a second-degree AV block in the other 2. Heart block had completely resolved at all following visits. Postnatal ECG recordings showed normal sinus rhythm in all patients. Echocardiographic evaluation at presentation and follow-up showed normal cardiac anatomy, without signs of hydrops or cardiac decompensation in all patients. All mothers tested negative on SS-A/Ro and SS-B/La autoantibodies. Conclusions: Fetal heart block can occur in the absence of structural heart defects and maternal autoantibodies to SS-A/Ro and SS-B/La. The origin of such heart block is unknown, but its course seems benign: none of the patients ever showed ventricular heart rates <55 bpm, signs of congestive heart failure or fetal hydrops. Heart block resolved spontaneously in all patients.

Main pulmonary artery area limits exercise capacity in patients long-term after arterial switch operation

OBJECTIVESnDespite excellent survival in patients after the arterial switch operation, reintervention is frequently required and exercise capacity is decreased in a substantial number of patients. This study relates right-sided imaging features in patients long-term after the arterial switch operation to exercise capacity and ventilatory efficiency to investigate which lesions are functionally important.nnnMETHODSnPatients operated in the UMC Utrecht, the Netherlands (1976-2001) and healthy controls underwent cardiac magnetic resonance imaging and cardiopulmonary exercise testing within 1 week. We measured main, left, and right pulmonary artery cross-sectional areas, pulmonary blood flow distribution, peak oxygen uptake, and minute ventilation relative to carbon dioxide elimination.nnnRESULTSnA total of 71 patients (median age, 20 [12-35] years, 73% were male) and 21 healthy controls (median age, 26 [21-35] years, 48% were male) were included. Main, left, and right pulmonary artery areas were decreased compared with controls (190 vs 269 mm(2)/m(2), 59 vs 157 mm(2)/m(2), 98 vs 139 mm(2)/m(2), respectively, all P < .001); however, pulmonary blood flow distribution was comparable (P = .722). Peak oxygen uptake and minute ventilation relative to carbon dioxide elimination were 88% ± 20% and 23.7 ± 3.8, respectively, with 42% and 1% of patients demonstrating abnormal results (≤ 84% and ≥ 34, respectively). The main pulmonary artery area significantly correlated with peak oxygen uptake (r = 0.401, P = .001) and pulmonary blood flow distribution with minute ventilation relative to carbon dioxide elimination (r = -0.329, P = .008). Subanalysis (<18, 18-25, >25 years) showed that the main pulmonary artery area was smaller in older age groups. In multivariable analysis, the main pulmonary artery area was independently associated with peak oxygen uptake (P = .032).nnnCONCLUSIONSnIn adult patients after the arterial switch operation, narrowing of the main pulmonary artery is a common finding and is the main determinant of limitation in functional capacity, rather than pulmonary branch stenosis.

Long-term outcome of transvenous pacemaker implantation in infants: A retrospective cohort study

AimnEvaluation of long-term outcome of transvenous pacemaker (PM) implantation in infants.nnnMethods and ResultsnA retrospective analysis of all transvenous PM implantations in infants <10 kg between September 1997 and October 2001 was made. Indications for PM implantation, age at implantation, and determinants of long-term outcome including cardiac function, PM function, and PM (system) complications were noted. Seven patients underwent transvenous VVI(R) PM implantation. Median age at implantation was 3 days (range: 1 day to 14 months), median weight 3.5 kg (range: 2.3-8.7 kg), and median follow-up 14 years (range: 12.3-16.3 years). Pacemaker indications were congenital complete atrioventricular block (n = 4), long QT syndrome with heart block (n = 2), and post-operative complete atrioventricular block with sinus node dysfunction (n = 1). No procedural complications were noted. Today all patients are alive and symptom free with good PM and cardiac function. Two patients underwent PM generator relocation for imminent skin necrosis and skin traction. Two patients suffered from asymptomatic left subclavian vein occlusion and developed thrombosis on the PM electrode. Three patients were converted to an epicardial PM system, due to atrial perforation after upgrading procedure (n = 1), syncope with need for implantable cardioverter defibrillator implantation (n = 1), and systolic dysfunction with development of dilated cardiomyopathy, which normalized under cardiac resynchronization therapy pacing (n = 1). Two patients needed atrioventricular (AV) valve repair for severe insufficiency. Two patients underwent repositioning of dysfunctional PM leads. In five patients, transvenous leads were removed. Indications were elective lead replacement (n = 1), atrial perforation (n = 1), and switch to an epicardial system (n = 3).nnnConclusionnTransvenous PM implantation in infants (<10 kg) is associated with a high incidence of vascular occlusion, thrombosis, and severe atrioventricular valve regurgitation during long-term follow-up. We advocate an epicardial approach for PM implantation in small children.

Potential Additional Indicators for Pacemaker Requirement in Isolated Congenital Atrioventricular Block

Low heart rate is the predominantly used indication for pacemaker intervention in patients with isolated congenital atrioventricular block (CAVB). The aim of this study was to compare the difference in heart rates recorded with ECG and Holter monitoring between paced (PM) and nonpaced (NPM) patients with isolated CAVB before pacemaker implantation to identify additional predictors for future PM need. Retrospective evaluation of atrial and ventricular rates (electrocardiography) and minimal and maximal (Holter) heart rates in 129 CAVB patients prior to PM implantation (n = 93) was performed, and results are expressed in V adjusted for age and sex. The average V score for the atrial rate was 0.51 (n = 50) in the PM group and 0.60 (n = 22) in the NPM group (not-significant). The average z score for the ventricular (average) rate was −0.91 (n = 83) in the PM group and −0.93 (n = 33) in the NPM group (not-significant). Minimal heart rate was −0.94 (n = 61) in the PM group and −0.86 (n = 25) in the NPM group (not significant). Maximal heart rate was −0.96 (n = 61) in the PM group and −0.95 (n = 26) in the NPM group (not significant). Initial recordings of the average heart rate and the minimal and maximal heart rate recorded during Holter monitoring do not seem to predict future pacemaker need in patients with CAVB. Studies with exercise stress tests are needed to confirm these findings.

Question 1: How safe are ACE inhibitors for heart failure in children?

A boy aged 1 year, recently diagnosed with dilated cardiomyopathy, has to be treated with enalapril according to the heart failure protocol. The physician wants to know which adverse events she can expect.nnWhat are the potential adverse events related to administration of an ACExa0inhibitor to children with heart failure? What is the prevalence and what are the possible risk factors?nnSecondary sources—nilnnElectronic databases (PubMed/Medline and Embase) and reference lists of relevant articles were searched with the following strategy: ‘angiotensin-converting enzyme inhibitors’ and ‘heart failure’ and ‘children’. The search yielded 415 individual articles, of which 14 were identified as relevant.nnHeart failure is an important cause of morbidity and mortality in children.1 nnIt is commonly treated with ACExa0inhibitors (ACE-i) despite the lack of evidence on its efficacy.2 This treatment is based on the assumption that blocking of the renin-angiotensin-aldosterone system has a positive effect on morbidity and mortality, as it does in adults with heart failure.3–6 In adults, the most prevalent adverse events (AEs) related to the use of ACER-i are renal failure,7 8 hypotension,9 10 hyperkalemia,9 11 cough12 and angioedema.13 It is assumed that the safety profile of ACE-i differs for children and differs from that for adults, and for children of different ages, as growth and development contribute to variation in the disposition and effect of most drugs administered …

Regression and Complications of z-score-Based Giant Aneurysms in a Dutch Cohort of Kawasaki Disease Patients

Kawasaki disease (KD) is a pediatric vasculitis. Its main complication is the development of coronary artery aneurysms (CAA), with giant CAA at the end of the spectrum. We evaluated regression and event-free rates in a non-Asian cohort of patients with giant CAA using the current z-scores adjusted for body surface area instead of absolute diameters. KD patients with giant CAA (z-scoreu2009≥10) visiting our outpatient clinic between January 1999 and September 2015 were included. Patient characteristics and clinical details were extracted from medical records. Regression was defined as all coronary arteries having a z-score of ≤3. A major adverse event was defined as cardiac death, myocardial infarction, cardiogenic shock, or any coronary intervention. Regression-free and event-free rates were calculated using the Kaplan–Meier method. We included 52 patients with giant CAA of which 45 had been monitored since the acute phase. The 1-, 2-, and 5-year regression-free rates were 0.86, 0.78, and 0.65, respectively. The 5-year, 10-year, and 15-year event-free rates were 0.79, 0.75, and 0.65, respectively. Four children, whose CAA would not have been classified as ‘giant’ based on absolute diameters instead of z-scores, had experienced an event during follow-up. Conclusion: We found a high percentage of children in whom the lumen of giant CAA completely normalized. Four children not classified as ‘giant’ based on absolute diameters with z-scores of ≥10 experienced a cardiac event. Hence, the use of z-scores seems to be justified.

Response from the authors of ‘Treatment of infantile haemangiomas with atenolol: Comparison with a historical propranolol group’

With great interest we have read the comments of Ashvin Raju and Roba Khundkar. We are pleased that the authors acknowledge atenolol as a possible alternative to propranolol. In respect to age adjustment, we included age as a categorical variable (1e6 months, 6e12 months and >12 months) in our model, so linearity between age and efficacy was not assumed. We agree that propranolol was shown to be the more efficacious option with regard to the percentage of patients with clinical involution, but this was not statistically significant (p Z 0.09). When confronted with two patients on propranolol that developed side effects, we initiated atenolol treatment. We hypothesized that the use of a hydrophilic, selective beta-1-blocker could be effective and prevent side effects of propranolol. Good results made atenolol our primary drug of choice. Patients #4 and #9 were excluded for analysis because of previous unsuccessful propranolol treatment and patient #11 because of its non-cutaneous location of IH and inability to assess quantitative outcome. They all responded well to atenolol. Patient #1 with a periorbital IH revealed minor improvement on atenolol and partial surgical debulking was performed. Patient #2 showed minor improvement on atenolol and because of severe pain due to ulceration, surgical excision was performed. For both patients no propranolol therapy was commenced. Patient #3 did not respond to propranolol after two weeks of atenolol treatment. Subsequently an excision was performed. Ever since, no atenolol failures were seen.