Pablo Marantz

Intravenous Amiodarone for Incessant Tachyarrhythmias in Children A Randomized, Double-Blind, Antiarrhythmic Drug Trial

Background— Intravenous (IV) amiodarone has proven efficacy in adults. However, its use in children is based on limited retrospective data. Methods and Results— A double-blind, randomized, multicenter, dose-response study of the safety and efficacy of IV amiodarone was conducted in 61 children (30 days to 14.9 years; median, 1.6 years). Children with incessant tachyarrhythmias (supraventricular arrhythmias [n=26], junctional ectopic tachycardia [JET, n=31], or ventricular arrhythmias [n=4]) were randomized to 1 of 3 dosing regimens (low, medium, or high: load plus 47-hour maintenance) with up to 5 open-label rescue doses. The primary efficacy end point was time to success. Of 229 patients screened, 61 were enrolled during 13 months by 27 of 48 centers in 7 countries. Median time to success was significantly related to dose (28.2, 2.6, and 2.1 hours for the low-, medium-, and high-dose groups, respectively; P=0.028). There was no significant association with dose for any arrhythmia subgroup, including JET, but the subgroups were too small for an accurate assessment. Adverse events (AEs) were common (87%), leading to withdrawal of 10 patients. There were 5 deaths in the 30-day follow-up period (2 possibly related to the study drug). Dose-related AEs included hypotension (36%), vomiting (20%), bradycardia (20%), atrioventricular block (15%) and nausea (10%). Conclusions— In children, the overall efficacy of IV amiodarone, as measured by time to success, was dose related but not significantly for any arrhythmia subgroup. AEs were common and appeared to be dose related. Although efficacious for critically ill patients, the dose-related risks of IV amiodarone should be taken into account when treating children with incessant arrhythmias. Prospective, placebo-controlled trials would be helpful in assessing antiarrhythmic drug efficacy in children, because their results may differ from retrospective series and adult studies.

Fetal Doppler mechanical PR interval: correlation with fetal heart rate, gestational age and fetal sex

To establish normal fetal values for the mechanical PR interval by pulsed‐wave Doppler at 16–36 weeks of gestation, and to evaluate the influence of fetal heart rate (FHR), gestational age (GA) and fetal sex.

Foetal aortic valvuloplasty: experience of five cases

OBJECTIVES Foetal aortic valvuloplasty has been proposed as a strategy to improve left heart growth and function in foetuses with severe aortic stenosis at risk of progression to hypoplastic left heart syndrome. We report our experience with this intervention. METHODS AND RESULTS Between 2005 and 2010, five foetuses with aortic stenosis and at risk of progression to hypoplastic left heart syndrome underwent ultrasound-guided percutaneous foetal aortic valvuloplasty. There were no associated maternal complications or foetal demise. In one case, the pregnancy was terminated a couple of weeks after the intervention, one foetus evolved to hypoplastic left heart syndrome, and three did not. CONCLUSIONS Foetal aortic valvuloplasty seems to be a safe and feasible procedure. It has been reported that it has the potential to prevent progression to hypoplastic left heart syndrome in selected foetuses with severe aortic stenosis. Further investigation regarding physiological and clinical aspects of this disease both prenatally and postnatally will probably allow to improve therapeutic strategies and clinical outcome.

Fetal intervention for critical aortic stenosis: advances, research and postnatal follow-up.

Purpose of review Fetal aortic valvuloplasty is intended to alter the natural history of aortic stenosis evolving to hypoplastic left heart syndrome. The most recently reported data and advances on this procedure were reviewed. Recent findings The highlights of the latest experience are the advances in further understanding of the prenatal and postnatal natural history of this disease, and the way in which fetal aortic valvuloplasty impacts on it, the identification of new predictors of biventricular outcome, and the report of postnatal survival of intervened patients. Recently reported short-term and middle-term results are encouraging. Experimental research on procedural aspects is ongoing, with no definite results. Multicenter studies are also ongoing. Summary In recent years, there have been advances in the understanding of the prenatal and postnatal process of aortic stenosis evolving to hypoplastic left heart syndrome and the effects of fetal aortic valvuloplasty, as well as the need of adequate postnatal therapeutic strategies for these patients. Procedural aspects are being studied with animal models, but still need far more experience before human application. Long-term results are still to be discovered, and multicenter studies may provide a new perspective. Continuing research is mandatory so that ultimately fetal heart intervention finds its place among the therapeutic resources for congenital heart disease.

Prenatal diagnosis of congenital heart disease: improving survival

We read with interest the article, ‘Prenatal diagnosis of critical congenital heart disease reduces risk of death from cardiovascular compromise prior to planned neonatal cardiac surgery: a meta-analysis’, by Holland et al.1, in which the authors noted that prenatal diagnosis was associated with a reduction in the risk of death prior to planned cardiac surgery relative to the risk in patients with comparable postnatal diagnosis. However, the intention-to-treat analysis did not show a significant decrease in the prenatal diagnosis group because of the death of a patient who did not receive optimal newborn care. As the authors state, failure to follow the optimal postnatal pathway, even with prenatal diagnosis, is an important practical consideration in fetal medicine. In our country, as in many others, prenatal diagnosis of congenital heart disease (CHD) is usually made in the third trimester (in our series the mean gestational age was 29.9 ± 5 weeks at initial assessment)2 and it is not possible to refer all patients to a tertiary healthcare center because of scarce resources2. In this context, we have developed a prediction model based on prenatal ultrasonographic findings to estimate the probability of the need for neonatal cardiac invasive therapy, defined as heart surgery or catheter-based therapy performed during the first month of postnatal life for clinical stabilization or for life-saving purposes2. In the limited-resource scenario of lowand mid-income countries2,3, this score may be a tool to aid non-specialist physicians in fetal medicine or fetal cardiology in their decision regarding referral. However, we agree with Gardiner, in her Opinion article in the same issue3, on the importance of the development of networks between maternity units and the specialist cardiac center. Moreover, we have reported a reduction in economic costs when comparing cases with prenatal and those with postnatal diagnosis of CHD4. We therefore believe that the importance of three points should be emphasized: first, improving the prenatal detection rate of CHD because it reduces the risk of death1; second, timely in-utero referral, if needed, in order to follow the optimal postnatal pathway – hand in hand with this, efforts should be made to achieve diagnosis earlier in pregnancy; third, even with early prenatal diagnosis, focusing on proper allocation of resources, not referring those patients who do not need referral and directing efforts towards those patients who would benefit from this policy.

Fetal Valvuloplasty for Critical Aortic Stenosis

Fetal aortic valvuloplasty (FAV) aims at modifying the progression of aortic stenosis evolving to hypoplastic left heart syndrome (Donofrio et al. Circulation 129(21):2183–2242, 2014). In the last decades, the observation of mid-term outcome of the patients that have been intervened prenatally has allowed further understanding of the disease and the effects of FAV, as well as of postnatal treatment of these patients. FAV is also being studied with animal models, but still with limited results. Given the small number of cases, multicenter studies are ongoing. We present a review of the most recently reported data and central aspects of our experience in the procedure.

OP01.02: Right ventricle dilatation: an alert sign in the fetal heart

Objectives: The purpose of this study was to determine the diagnostic accuracy of fetal Echocardiography in evaluating anatomic details of the functional single ventricle heart and the outcome of fetuses diagnosed with this anomaly. Methods: This is a retrospective study of 128 fetuses with single ventricle of our database (from January 2004 to March 2011): Double inlet single ventricle (DISV) (n = 16), tricuspid valve atresia (TA) (n = 18), Mitral valve atresia and hypoplastic left heart syndrome (HLHS) (n = 75), hypoplastic right-heart syndrome (HRHS) (n = 16) and heteroataxy syndrome with common auriculoventricular valve (HS) (n = 3). The results of fetal echocardiography were compared with the diagnoses at postnatal echocardiography or anatomopatologic findings. Postnatal surgical outcome of survival patients was reviewed. Results: We had 81 terminations of pregnancy (TOP) (63.1%: 50% DISV; 50% TA; 69% HLHS; 50% HRHS and 100% HS) and 2 intrauterine fetal death. Anatomical findings were correlated in 91% of cases. In 7 morphology of the predominant ventricle was not identified. Diagnostic accuracy was present in visceral situs, presence of pulmonary or aortic outflow tract obstruction and presence of obstructed pulmonary venous outflow (sensitivity 100%). However, the ability to predict a ductal dependent pulmonary circulation was poor (sensitivity 63%). Of the 45 newborns, intervention was elected in 40 (88%), nonintervention in 5, and 9 died after intervention (6 after Norwood procedure). Of the cohort of operated newborns 71% are presently alive after various stages of intervention. Conclusions: Accurate diagnosis of the fetal single ventricle heart is possible, and outcome is improving. The rate of TOP is high in single ventricle anomalies. Caution must be taken in judging ventricular morphology and in predicting ductal dependent pulmonary circulation.

P08.12: Fetal and neonatal clinical evolution of isolated congenital heart disease and associated with major extracardiac malformations or genetic syndromes

in imaging protocols. The detection rates in in-born babies was considerably higher than in out-born babies. There was close correlation between antenatal and post-natal findings. Conclusions: We have demonstrated an improvement in overall detection rates over a 10 year period, however rates are still not close to 100%. The next step is to implement an educational plan for our rural and regional hospitals and hope to then demonstrate a further improvement in detection levels, in order to reduce the incidence or out-born babies.

OP27.05: Hypoplastic left ventricle (HLHS): in utero evolution and treatment

Objectives: To evaluate the potential use of the lung-head ratio (LHR) for the prediction of neonatal outcome in severe left congenital diaphragmatic hernia (CDH) after fetal tracheal occlusion (FETO). Methods: Between January 2006 and December 2009, 20 fetuses with severe, isolated left CDH (LHR < 1.0 and liver-up) were submitted to FETO between 26–30 weeks of gestation. The LHR was evaluated before (26–28 ws) and after (32 ws) FETO procedure and then correlated with neonatal outcome (deaths). Results: Neonatal deaths occurred in 9/20 (45.0%) cases. Significantly lower values of LHR were observed in those cases that died before (0.6 ± 0.3) and after (0.9 ± 0.4) FETO procedures in comparison to those that survived (0.8 ± 0.3 and 1.6 ± 0.4; respectively, P < 0.05). Conclusions: The LHR may be useful to predict neonatal outcome in fetuses with severe left CDH submitted to FETO procedures.