Johannes M.P.J. Breur

Dilated cardiomyopathy in isolated congenital complete atrioventricular block: early and long-term risk in children

OBJECTIVES We sought to identify the risk factors predicting the development of dilated cardiomyopathy (DCM) in patients with isolated congenital complete atrioventricular block (CCAVB). BACKGROUND Recently evidence has emerged that a subset of patients with CCAVB develop DCM. METHODS This was a retrospective study of 149 patients with CCAVB who had heart size and left ventricular (LV) function assessed by echocardiography and chest radiography over a follow-up period of 10 +/- 7 years. RESULTS Nine patients developed DCM at the age of 6.5 +/- 5 years. No definite cause could be identified. In these nine patients, CCAVB was diagnosed in eight at 23 +/- 2.3 weeks gestation and in one at birth. Maternal SSA/SSB antibodies were confirmed in seven of the nine patients. Pacemakers were implanted in eight patients in the first month and in one patient at five years of age. The initial left ventricular end-diastolic dimension (LVEDD) was in the 96th +/- 2.6 percentile and the cardiothoracic (CT) ratio was 64 +/- 3.8% in the nine patients who developed DCM, and differed significantly in patients with CCAVB (p < 0.005) who did not develop DCM. The LVEDD and CT ratio did not decrease in the patients with CCAVB and DCM, but decreased significantly in the patients with CCAVB without DCM (p < 0.001) once pacing was initiated. Two patients with DCM died within two months of diagnosis; one patient is neurologically compromised; two patients received a heart transplant; and four patients are listed for heart transplantation. CONCLUSIONS Isolated CCAVB is associated with a long-term risk for the development of DCM. Risk factors may be SSA/SSB antibodies, increased heart size at initial evaluation and the absence of pacemaker-associated improvement.

Adverse effects of propranolol when used in the treatment of hemangiomas: A case series of 28 infants

BACKGROUND Infantile hemangioma (IH) is a frequently encountered tumor with a potentially complicated course. Recently, propranolol was discovered to be an effective treatment option. OBJECTIVE To describe the effects and side effects of propranolol treatment in 28 children with (complicated) IH. METHODS A protocol for treatment of IH with propranolol was designed and implemented. Propranolol was administered to 28 children (21 girls and 7 boys, mean age at onset of treatment: 8.8 months). RESULTS All 28 patients had a good response. In two patients, systemic corticosteroid therapy was tapered successfully after propranolol was initiated. Propranolol was also an effective treatment for hemangiomas in 4 patients older than 1 year of age. Side effects that needed intervention and/or close monitoring were not dose dependent and included symptomatic hypoglycemia (n = 2; 1 patient also taking prednisone), hypotension (n = 16, of which 1 is symptomatic), and bronchial hyperreactivity (n = 3). Restless sleep (n = 8), constipation (n = 3) and cold extremities (n = 3) were observed. LIMITATIONS Clinical studies are necessary to evaluate the incidence of side effects of propranolol treatment of IH. CONCLUSIONS Propranolol appears to be an effective treatment option for IH even in the nonproliferative phase and after the first year of life. Potentially harmful adverse effects include hypoglycemia, bronchospasm, and hypotension.

Treatment of fetal heart block with maternal steroid therapy: case report and review of the literature

The presence of maternal autoantibodies to SS‐A/Ro and/or SS‐B/La is associated with the development of fetal heart block. There are data suggesting that maternal treatment with steroids might reverse heart block. We report on a pregnancy in a mother with secondary Sjögren syndrome and systemic lupus erythematosus with presence of autoantibodies to SS‐A/Ro and SS‐B/La, which was complicated by the development of incomplete fetal heart block. Oral dexamethasone treatment could not prevent progression to complete heart block and was associated with a number of complications.

Endocardial and epicardial steroid lead pacing in the neonatal and paediatric age group

Aim: To compare the performance of steroid eluting epicardial and endocardial leads in infants and children requiring permanent pacing. Methods: Evaluation of pacing and sensing characteristics, impedances, and longevity of 159 steroid eluting leads implanted in 95 children. Group A consisted of 24 children weighing less than 15 kg with 15 endocardial leads (five atrial, 10 ventricular) and 19 epicardial leads (five atrial, 14 ventricular). Group B consisted of 71 children weighing more than 15 kg with 106 endocardial leads (56 atrial, 58 ventricular) and 19 epicardial leads (nine atrial, 10 ventricular). Results: Group A: Stimulation thresholds were lower for ventricular endocardial leads at implant (mean (SD) 0.84 (0.54) v 1.59 (0.64) V, p < 0.014) and at two year follow up (ventricular 0.64 (0.24) v 1.65 (0.69) V, p < 0.003). Impedance and sensing thresholds did not differ significantly at implant and follow up. Group B: Stimulation thresholds were lower for ventricular endocardial leads at implant (0.72 (0.48) v 1.48 (0.58) V, p < 0.001) and at follow up (0.88 (0.46) v 1.55 (0.96) V, p < 0.009). Impedance did not differ. Sensing thresholds were also better for ventricular endocardial leads at follow up (9.1 (5.2) v 14.2 (6.4) mV, p < 0.02). Complications requiring intervention occurred in both groups (n = 7 for endocardial v n = 18 for epicardial leads). Conclusions: Endocardial and epicardial steroid eluting leads have comparable performance in the paediatric population.

The diagnostic and therapeutic aspects of loss-of-function cardiac sodium channelopathies in children.

BACKGROUND Loss-of-function sodium channelopathies manifest as a spectrum of diseases including Brugada syndrome (BrS) and cardiac conduction disease. OBJECTIVE To analyze the diagnostic and therapeutic aspects of these disorders in children. METHODS Patients aged ≤ 16 years with genetically confirmed loss-of-function sodium channelopathies (SCN5A mutation), presenting with cardiac symptoms, positive family history, and/or abnormal electrocardiogram (ECG), were included. Abnormal ECG consisted of type 1 BrS ECG and/or prolonged conduction intervals (PR interval/QRS duration > 98th percentile for age). RESULTS Among the cohort (n = 33, age 6 ± 5 years, 58% male subjects, 30% probands), 14 (42%) patients were symptomatic, presenting with syncope (n = 5), palpitations (n = 1), supraventricular arrhythmias (n = 3), aborted cardiac arrest (n = 3), and sudden cardiac death (n = 2). Heart rate was 91 ± 26 beats/min, PR interval 168 ± 35 ms, QRS duration 112 ± 20 ms, and heart-rate corrected QT interval 409 ± 26 ms. Conduction intervals were prolonged in 28 (85%) patients; 6 of these patients also had spontaneous type 1 BrS ECG. Eight fever-associated events occurred in 6 patients; 2 of these were vaccination-related fever episodes. Treatment included aggressive antipyretics during fever in all patients; antiarrhythmic treatment included implantable cardioverter-defibrillator (n = 4), pacemaker (n = 2), and beta-blockers, either alone (n = 3) or in combination with device (n = 2). During follow-up (4 ± 4 years), 2 previously symptomatic patients had monomorphic ventricular tachycardia; there were no deaths. CONCLUSIONS Diagnosis of loss-of-function sodium channelopathies in children relies on cardiac symptoms, family history, and ECG. Fever and vaccination are potential arrhythmia triggers; conduction delay is the commonest finding on ECG. Beta-blockers have a role in preventing tachycardia-induced arrhythmias; implantable cardioverter-defibrillator should probably be reserved for severe cases.

Is cardiovascular evaluation necessary prior to and during beta-blocker therapy for infantile hemangiomas?: A cohort study.

BACKGROUND Although consensus guidelines for pretreatment evaluation and monitoring of propranolol therapy in patients with infantile hemangiomas (IH) have been formulated, little is known about the cardiovascular side effects. OBJECTIVES We sought to analyze cardiovascular evaluations in patients with IH at baseline and during treatment with an oral beta-blocker. METHODS Data from 109 patients with IH were retrospectively analyzed. Patient and family history, pretreatment electrocardiogram (ECG), heart rate, and blood pressure were evaluated before initiation of beta-blocker therapy. Blood pressure and standardized questionnaires addressing side effects were evaluated during treatment. RESULTS Questionnaire analyses (n = 83) identified 3 cases with a family history of cardiovascular disease in first-degree relatives. ECG findings were normal in each case and no serious complication of therapy occurred. ECG abnormalities were found in 6.5% of patients but there were no contraindications to beta-blocker therapy and no major complications. Hypotension in 9 patients did not require therapy adjustment. In all, 88 parents (81%) reported side effects during beta-blocker treatment. LIMITATIONS The relatively small patient cohort is a limitation. CONCLUSION Pretreatment ECG is of limited value for patients with an unremarkable cardiovascular history and a normal heart rate and blood pressure. Hypotension may occur during treatment.

Cerebral oxygenation and echocardiographic parameters in preterm neonates with a patent ductus arteriosus: an observational study

Background A haemodynamically significant patent ductus arteriosus (hsPDA) is clinically suspected and confirmed by echocardiographic examination. A hsPDA decreases cerebral blood flow and oxygen saturation by the ductal steal phenomenon. Aim To determine the relationship between echocardiographic parameters, cerebral oxygenation and a hsPDA in preterm infants. Methods 380 preterm infants (<32 weeks gestational age) born between 2008 and 2010 were included. Blinded echocardiographic examination was performed on the second, fourth and sixth day after birth. Examinations were deblinded when hsPDA was clinically suspected. Regional cerebral oxygen saturation (rScO2) was continuously monitored by near-infrared spectroscopy during 72 h after birth, and afterwards for at least 1 h before echocardiography. Echocardiographic parameters included ductal diameter, end-diastolic flow in the left pulmonary artery, left atrium/aorta ratio and ductal flow pattern. Results rScO2 was significantly related only to ductal diameter over time. Mixed modelling analysed the course of rScO2 over time, where infants were divided into four groups: a closed duct, an open haemodynamically insignificant duct (non-sPDA), a hsPDA, which was successfully closed during study period (SC hsPDA) or a hsPDA, which was unsuccessfully closed during study period (UC hsPDA). SC hsPDA infants showed the highest rScO2 on day 6, while UC hsPDA infants had the lowest rScO2 values. Conclusions Ductal diameter is the only echocardiographic parameter significantly related to cerebral oxygenation over time. Cerebral oxygenation takes a different course over time depending on the status of the duct. Low cerebral oxygenation may be suggestive of a hsPDA.

Persistent Fetal Sinus Bradycardia Associated with Maternal Anti-SSA/Ro and Anti-SSB/La Antibodies

Objective. To study the clinical course and outcome of fetal sinus bradycardia (SB) due to maternal antibody-induced sinus node dysfunction. Methods. We reviewed the maternal, prenatal, and postnatal findings of fetuses with SB associated with elevated maternal anti-SSA/Ro and anti-SSB/La antibodies. Results. Of the 6 cases diagnosed prenatally, 3 had isolated SB persisting after birth and had a good prognosis. Three fetuses with SB and severe myocardial involvement (congenital complete heart block and/or endocardial fibroelastosis) succumbed in utero in spite of treatment. Postmortem histopathology in 1 fetus showed inflammatory destruction of the sinus and atrioventricular nodes. SB was detected incidentally in a 7-year-old girl. She had intermittent heart block with progressive sinus arrest requiring permanent pacemaker. Conclusion. Fetal SB associated with maternal autoantibodies may persist in childhood, with a good prognosis in the absence of widespread cardiac involvement.

Effective radiation dosage of three-dimensional rotational angiography in children

AIMS Three-dimensional rotational angiography (3DRA) is a relatively new but promising imaging technique in the paediatric catheterization laboratory. However, data on effective dose (ED) of this technique in children are lacking. The purpose of this study is to provide ED of 3DRA and to correlate this with parameters readily available in daily practice. Furthermore, the effect of dose-reducing techniques is evaluated. METHODS AND RESULTS Effective doses were calculated with Monte Carlo PCXMC 2.0 in 14 patients who underwent a total of 17 3DRAs at our paediatric catheterization laboratory. Median age was 5.7 years (range 1 day-16.6 years). Median ED was 1.6 milliSievert (mSv) (range 0.7-4.9). Effective dose did not correlate with age and body surface area but did correlate with dose area product (DAP) and milliGray (mGy) with r(2) of 0.75 and 0.83, respectively. Reduction of the total amount of frames from 248 to 133 per rotation resulted in further dose reduction of over 50% with preserved image quality. CONCLUSION The median ED of 3DRA in children is 1.6 mSv and correlates with DAP and mGy. This dose can be halved by applying frame reduction. A significant further dose reduction can be achieved by obtaining additional knowledge of the equipment used.

Neurological Outcome in Isolated Congenital Heart Block and Hydrops Fetalis

Objective: Isolated fetal heart block (HB), a condition associated with fetal hydrops, carries a high mortality rate and may result in neurodevelopmental sequelae. To the best of our knowledge, no data exist regarding the long-term outcome of such hydropic fetuses. We reviewed our experience with this condition to determine the neurodevelopmental outcome of prenatally diagnosed cases with isolated HB complicated by hydrops fetalis. Methods: Neurodevelopmental assessment of 5 children presented prenatally with isolated HB associated with hydrops fetalis. Results: During the last 18 years, 10 cases were detected prenatally with isolated HB and hydrops fetalis. 3 of the 10 fetuses died in utero, and 2 died postnatally, due to a dilated cardiomyopathy, at the age of 9 months and 4 years, respectively. Neurodevelopmental studies done on the 5 remaining children were normal. Conclusion: Long-term neurodevelopmental assessments of 5 surviving cases presented prenatally with isolated HB and hydrops fetalis are reassuring.