Lukas Rammeloo

Pediatric Pulmonary Hypertension in the Netherlands Epidemiology and Characterization During the Period 1991 to 2005

Background— Incidence and prevalence rates for pediatric pulmonary hypertension (PH) and pulmonary arterial hypertension (PAH) are unknown. This study describes the nationwide epidemiological features of pediatric PH in the Netherlands during a 15-year period and the clinical course of pediatric PAH. Methods and Results— Two registries were used to retrospectively identify children (0–17 years) with PH. Overall, 3263 pediatric patients were identified with PH due to left heart disease (n=160; 5%), lung disease/hypoxemia (n=253; 8%), thromboembolic disease (n=5; <1%), and transient (n=2691; 82%) and progressive (n=154; 5%) PAH. Transient PAH included persistent PH of the newborn and children with congenital heart defects (CHD) and systemic-to-pulmonary shunt, in whom PAH resolved after successful shunt correction. Progressive PAH mainly included idiopathic PAH (n=36; iPAH) and PAH associated with CHD (n=111; PAH-CHD). Pulmonary arterial hypertension associated with CHD represented highly heterogeneous subgroups. Syndromes were frequently present, especially in progressive PAH (n=60; 39%). Survival for PAH-CHD varied depending on the subgroups, some showing better and others showing worse survival than for iPAH. Survival of children with Eisenmenger syndrome appeared worse than reported in adults. For iPAH and PAH-CHD, annual incidence and point prevalence averaged, respectively, 0.7 and 4.4 (iPAH) and 2.2 and 15.6 (PAH-CHD) cases per million children. Compared to studies in adults, iPAH occurred less whereas PAH-CHD occurred more frequently. Conclusions— Pediatric PH is characterized by various age-specific diagnoses, the majority of which comprise transient forms of PAH. Incidence of pediatric iPAH is lower whereas incidence of pediatric PAH-CHD is higher than reported in adults. Pediatric PAH-CHD represents a heterogeneous group with highly variable clinical courses. # Clinical Perspective {#article-title-25}Background— Incidence and prevalence rates for pediatric pulmonary hypertension (PH) and pulmonary arterial hypertension (PAH) are unknown. This study describes the nationwide epidemiological features of pediatric PH in the Netherlands during a 15-year period and the clinical course of pediatric PAH. Methods and Results— Two registries were used to retrospectively identify children (0–17 years) with PH. Overall, 3263 pediatric patients were identified with PH due to left heart disease (n=160; 5%), lung disease/hypoxemia (n=253; 8%), thromboembolic disease (n=5; <1%), and transient (n=2691; 82%) and progressive (n=154; 5%) PAH. Transient PAH included persistent PH of the newborn and children with congenital heart defects (CHD) and systemic-to-pulmonary shunt, in whom PAH resolved after successful shunt correction. Progressive PAH mainly included idiopathic PAH (n=36; iPAH) and PAH associated with CHD (n=111; PAH-CHD). Pulmonary arterial hypertension associated with CHD represented highly heterogeneous subgroups. Syndromes were frequently present, especially in progressive PAH (n=60; 39%). Survival for PAH-CHD varied depending on the subgroups, some showing better and others showing worse survival than for iPAH. Survival of children with Eisenmenger syndrome appeared worse than reported in adults. For iPAH and PAH-CHD, annual incidence and point prevalence averaged, respectively, 0.7 and 4.4 (iPAH) and 2.2 and 15.6 (PAH-CHD) cases per million children. Compared to studies in adults, iPAH occurred less whereas PAH-CHD occurred more frequently. Conclusions— Pediatric PH is characterized by various age-specific diagnoses, the majority of which comprise transient forms of PAH. Incidence of pediatric iPAH is lower whereas incidence of pediatric PAH-CHD is higher than reported in adults. Pediatric PAH-CHD represents a heterogeneous group with highly variable clinical courses.

Comparison of Transplacental Treatment of Fetal Supraventricular Tachyarrhythmias With Digoxin, Flecainide, and Sotalol Results of a Nonrandomized Multicenter Study

Background— Fetal tachyarrhythmia may result in low cardiac output and death. Consequently, antiarrhythmic treatment is offered in most affected pregnancies. We compared 3 drugs commonly used to control supraventricular tachycardia (SVT) and atrial flutter (AF). Methods and Results— We reviewed 159 consecutive referrals with fetal SVT (n=114) and AF (n=45). Of these, 75 fetuses with SVT and 36 with AF were treated nonrandomly with transplacental flecainide (n=35), sotalol (n=52), or digoxin (n=24) as a first-line agent. Prenatal treatment failure was associated with an incessant versus intermittent arrhythmia pattern (n=85; hazard ratio [HR]=3.1; P<0.001) and, for SVT, with fetal hydrops (n=28; HR=1.8; P=0.04). Atrial flutter had a lower rate of conversion to sinus rhythm before delivery than SVT (HR=2.0; P=0.005). Cardioversion at 5 and 10 days occurred in 50% and 63% of treated SVT cases, respectively, but in only 25% and 41% of treated AF cases. Sotalol was associated with higher rates of prenatal AF termination than digoxin (HR=5.4; P=0.05) or flecainide (HR=7.4; P=0.03). If incessant AF/SVT persisted to day 5 (n=45), median ventricular rates declined more with flecainide (−22%) and digoxin (−13%) than with sotalol (−5%; P<0.001). Flecainide (HR=2.1; P=0.02) and digoxin (HR=2.9; P=0.01) were also associated with a higher rate of conversion of fetal SVT to a normal rhythm over time. No serious drug-related adverse events were observed, but arrhythmia-related mortality was 5%. Conclusion— Flecainide and digoxin were superior to sotalol in converting SVT to a normal rhythm and in slowing both AF and SVT to better-tolerated ventricular rates and therefore might be considered first to treat significant fetal tachyarrhythmia.

Fever-Induced Life-Threatening Arrhythmias in Children Harboring an SCN5A Mutation

Cardiac channelopathies caused by SCN5A mutation are well tolerated by most patients. However, the dramatic presentation of a previously healthy 4-month-old girl with life-threatening arrhythmias and the subsequent findings in the child and her family provide evidence that loss-of-function sodium channel mutations can present very early in life. An SCN5A mutation was detected in the infant, her brother, and their father. Both the siblings manifested recurrent serious arrhythmias during febrile episodes, which followed immunization, as well as fever of nonspecific origin. Management consisted of prompt antipyretic measures, hospitalization with vigorous monitoring during immunization and febrile episodes, and prevention of tachycardia-induced conduction disturbance with β-blockers.

Surgical Repair of Aortopulmonary Window: Thirty-Seven Years of Experience

An aortopulmonary window (APW) is a communication between the ascending aorta and the pulmonary trunk in the presence of two separate semilunar valves. In order to increase our understanding about the surgical management of this rare lesion and its long-term results, we describe our experience over a 37-year period. Between 1968 and 2005, 18 patients were diagnosed with APW. Seventeen underwent surgical correction. Age at operation ranged from 22 days to 22 years (median, 0.20 years). Follow-up ranged from 2 weeks to 28.6 years (median, 11.0 years). Surgical closure was achieved using a single patch in 7 patients (41.2%) double patch in 4 (23.5%), primary closure in 3 (17.6%), clip in 2 (11.8%), and ligation in 1 (5.9%). Complex APW was present in 8 patients (44.4%). One patient was treated nonsurgically. There were no early or late deaths after surgery. Both primary closure and patch closure gave excellent long-term results. Sporadic postoperative complications were only associated with complex lesions. One patient who was treated conservatively died (of pulmonary hypertension) 21 years after diagnosis. Repair of APW is ideally performed in the first months of life, before irreversible PHT has developed. Various surgical repair techniques in this series of patients gave excellent short-term and long-term results, without significant hemodynamic sequelae.

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.

Management of children with dilated cardiomyopathy in The Netherlands: Implications of a low early transplantation rate

BACKGROUND The policy for listing and transplant for children with dilated cardiomyopathy (DCM) in The Netherlands has been conservative because of low donor availability. The effects of this policy on outcome are reported. METHODS This was a multicenter, nationwide study performed in 148 children with DCM. The primary outcome was death or heart transplant. RESULTS Overall, 43 patients (29%) died or were transplanted. Within 1 year of diagnosis, 21 patients died, and only 4 underwent transplantation (3 on mechanical circulatory support). The 1-year survival was 85% (95% confidence interval [CI] = 79-91), and 5-year survival was 84% (95% CI = 78-90). Transplantation-free survival at 1 year was 82% (95% CI = 75-88) and at 5 years was 72% (95% CI = 64-80). Within 1 year of diagnosis, with death as the main end-point (21 of 25, 84%), intensive care unit admission (hazard ratio = 2.6, p = 0.05) and mechanical circulatory support (hazard ratio = 3.2, p = 0.03) were risk factors (multivariable Cox analysis); inotropic support was longer in patients reaching an end-point. At >1 year after diagnosis, with transplantation as the main end-point (15 of 18, 83%), age >6 years (hazard ratio = 6.1, p = 0.02) was a risk factor. There were 56 (38%) children who recovered, 50% within 1 year of diagnosis. Recovery was associated with younger age; was similar in patients with myocarditis (43%) and idiopathic disease (41%); and was similar in patients initially admitted to the intensive care unit, admitted to the ward, or treated as outpatients. CONCLUSIONS The transplantation rate in our cohort in the first year was low, with 1-year and 5-year survival rates similar to other cohorts. Our results suggest that a conservative approach to list children for transplantation early after presentation may be justifiable except for patients with prolonged intensive care unit or mechanical circulatory support.

Rapid and full recovery after life-threatening complete atrioventricular block: an isolated feature of myocarditis?

Complete atrioventricular block in children is rare and usually congenital or acquired after cardiac surgery. Non-surgical acquired complete atrioventricular block is even less frequently encountered and the initial presentation can be syncope. A 9-year-old girl was referred to our hospital because of syncope with bradycardia, preceded by a period of fever and vomiting. She had no history of cardiac disease. On physical examination, the girl was pale and had a persistent bradycardia of 30–35 beats per minute (bpm), a temperature of 36.9 C, a blood pressure of 90/45 mmHg and weak peripheral pulses. No heart murmur was audible. Laboratory studies revealed: Creactive protein 57 mg/l (normal <10 mg/l), troponin T 5.3 lg/ml (normal <0.1 lg/ml), creatine kinase 1844 U/l (normal <170 U/l), aspartate aminotransferase 5215 U/l (normal <40 U/l) and alanine aminotransferase 3344 U/l (normal <45 U/l). Electrocardiography revealed complete atrioventricular block (CAVB) with a low ventricular rate of 35 bpm (Fig. 1). Echocardiography showed a normal left and right ventricular size with borderline shortening fraction of 30%. Due to persistent haemodynamic instability, a temporary transvenous pacemaker was inserted in the right ventricle. Within 2 days, the CAVB recovered spontaneously and completely and 4 days after admission, the pacemaker could be removed. Laboratory values normalised within a few weeks. Despite the clinical course and elevated heart enzymes suggestive of acute myocarditis, diagnostic studies failed to detect any responsible micro-organism. Six months later, she remains in continuous good health with regular sinus rhythm and good cardiac function. Since the first report in 1947 by Gore and Saphir [3] who described CAVB as a rare complication of myocarditis, several cases have been published with various micro-organisms [2], held responsible for the myocarditis. However, microbiological studies often yield negative results [6]. CAVB with a slow ventricular rate can cause various symptoms including syncope, signs of congestive heart failure, and electrical instability leading to ventricular tachycardia and ventricular fibrillation. When occurring in the course of myocarditis, these symptoms may be accompanied by chest pain, dyspnoea and systemic symptoms of the aetiological agent such as fever, malaise and myalgias. There is no evidence that treatment of the supposed underlying viral infection will favourably affect the natural course of myocarditis [4]. In the case of CAVB with a slow ventricular rate and haemodynamic instability, a temporary transvenous pacemaker should be inserted as soon as possible. When the CAVB has not resolved within 10–14 days, a permanent pacemaker is inserted [5]. Prognostic data on children with CAVB and myocarditis are scarce. Of 40 patients with myocarditis and CAVB recently reviewed [1], 2 patients (5%) died, 11 (28%) needed permanent pacemakers, and 27 (67%) returned to normal sinus rhythm within 7 days. Since dilated cardiomyopathy can develop months to years after the acute phase, long-term follow-up is warranted. An acquired transient CAVB can cause syncope in children. It can be the only isolated manifestation of a myocarditis. A temporary transvenous pacemaker should be inserted as soon as possible if haemodynamic instability exists. Although life-threatening in the acute phase, CAVB can recover early and completely. K. M. J. Heitink-Pollé (&) Department of Paediatrics, VU Medical Centre, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands E-mail: kmj.heitink@vumc.nl Tel.: +31-20-4444444 Fax: +31-20-4442422

Longitudinal Strain as Risk Factor for Outcome in Pediatric Dilated Cardiomyopathy.

In adults with dilated cardiomyopathy (DCM), it has been demonstrated that global longitudinal and circumferential strain have value in addition to left ventricular ejection fraction (LVEF) in predicting the risk of mortality, heart transplantation, and hospitalization for worsening heart failure [(

Left Pulmonary Artery Thrombosis in a Neonate with Left Lung Hypoplasia

Thrombotic events in neonates may origin from fetal life. A 4-day-old newborn infant with a family history of heterozygous type 1 protein C deficiency was diagnosed with left lung hypoplasia and left pulmonary artery thrombosis. Its source was prenatally closed ductus arteriosus. Surgical removal of the thrombus was performed.

Accuracy of Pulse Oximetry Screening for Critical Congenital Heart Defects after Home Birth and Early Postnatal Discharge

Objective To assess the accuracy of pulse oximetry screening for critical congenital heart defects (CCHDs) in a setting with home births and early discharge after hospital deliveries, by using an adapted protocol fitting the work patterns of community midwives. Study design Pre‐ and postductal oxygen saturations (SpO2) were measured ≥1 hour after birth and on day 2 or 3. Screenings were positive if the SpO2 measurement was <90% or if 2 independent measures of pre‐ and postductal SpO2 were <95% and/or the pre‐/postductal difference was >3%. Positive screenings were referred for pediatric assessment. Primary outcomes were sensitivity, specificity, and false‐positive rate of pulse oximetry screening for CCHD. Secondary outcome was detection of noncardiac illnesses. Results The prenatal detection rate of CCHDs was 73%. After we excluded these cases and symptomatic CCHDs presenting immediately after birth, 23 959 newborns were screened. Pulse oximetry screening sensitivity in the remaining cohort was 50.0% (95% CI 23.7‐76.3) and specificity was 99.1% (95% CI 99.0‐99.2). Pulse oximetry screening was false positive for CCHDs in 221 infants, of whom 61% (134) had noncardiac illnesses, including infections (31) and respiratory pathology (88). Pulse oximetry screening did not detect left‐heart obstructive CCHDs. Including cases with prenatally detected CCHDs increased the sensitivity to 70.2% (95% CI 56.0‐81.4). Conclusion Pulse oximetry screening adapted for perinatal care in home births and early postdelivery hospital discharge assisted the diagnosis of CCHDs before signs of cardiovascular collapse. High prenatal detection led to a moderate sensitivity of pulse oximetry screening. The screening also detected noncardiac illnesses in 0.6% of all infants, including infections and respiratory morbidity, which led to early recognition and referral for treatment.