The efficacy of flecainide versus digoxin in the management of fetal supraventricular tachycardia

Fetal supraventricular tachycardia (SVT) can be successfully treated transplacentally, but in cases where fetal hydrops develops there is considerable morbidity and mortality. The present study was carried out to establish whether the introduction of flecainide altered obstetric management and fetal outcome. A retrospective analysis took place of 51 singleton pregnancies which were referred to the division of prenatal diagnosis because of fetal tachycardia between 1982 and 1993. SVT was documented in 50 out of 51 fetuses, one of which displayed a combination of extensive rhabdomyomas and severe hydrops and died shortly after referral. In the other fetus ventricular tachycardia was diagnosed. Of the remaining 49 fetuses, 14 did not receive any prenatal treatment, but nine needed postnatal treatment. Transplacental treatment of SVT took place in 35 fetuses, of which 22 presented without hydrops and 13 with hydrops. These subsets differed significantly with respect to restoration of normal sinus rhythm (73% vs. 30%; p<0.001) and mortality (0% vs. 46%; p<0.001). Digoxin was effective in restoring sinus rhythm in 55 per cent of the non‐hydropic fetuses but in only eight per cent of the hydropic fetuses. Flecainide was effective in restoring sinus rhythm in all non‐hydropic fetuses where digoxin treatment failed, and in 43 per cent of hydropic fetuses. Administration of flecainide resulted in a significantly reduced mortality (p<0.001) compared with digoxin treatment. No adverse effects were seen. Postnatal anti‐arrhythmic treatment was necessary in 23 infants. Treatment could be withdrawn within one year in all cases but one. Copyrigh

Low agreement between cardiologists diagnosing left ventricular hypertrophy in children with end-stage renal disease

Background: Monitoring of the appearance of left ventricular hypertrophy (LVH) by echocardiography is currently recommended for in the management of children with End-stage renal disease (ESRD). In order to investigate the validity of this method in ESRD children, we assessed the intra- and inter-observer reproducibility of the diagnosis LVH. Methods. Echocardiographic measurements in 92 children (0-18 years) with ESRD, made by original analysists, were reassessed offline, twice, by 3 independent observers. Smallest detectable changes (SDC) were calculated for continuous measurements of diastolic interventricular septum (IVSd), Left ventricle posterior wall thickness (LVPWd), Left ventricle end-diastolic diameter (LVEDd), and Left ventricle mass index (LVMI). Cohen's kappa was calculated to assess the reproducibility of LVH defined in two different ways. LVHWT was defined as Z-value of IVSd and/or LVPWd>2 and LVHMI was defined as LVMI> 103 g/m 2 for boys and >84 g/m2 for girls. Results: The intra-observer SDCs ranged from 1.6 to 1.7 mm, 2.0 to 2.6 mm and 17.7 to 30.5 g/m2 for IVSd, LVPWd and LVMI, respectively. The inter-observer SDCs were 2.6 mm, 2.9 mm and 24.6 g/m2 for IVSd, LVPWd and LVMI, respectively. Depending on the observer, the prevalence of LVHWT and LVHMI ranged from 2 to 30% and from 8 to 25%, respectively. Kappas ranged from 0.4 to 1.0 and from 0.1 to 0.5, for intra-and inter- observer reproducibility, respectively. Conclusions: Changes in diastolic wall thickness of less than 1.6 mm or LVMI less than 17.7 g/m2 cannot be distinguished from measurement error in individual children, even when measured by the same observer. This limits the use of echocardiography to detect changes in wall thickness in children with ESRD in routine practice

Mucopolysaccharidosis: Cardiologic features and effects of enzyme-replacement therapy in 24 children with MPS I, II and VI

We determined the cardiologic features of children with MPS I, II and VI, and evaluated the effect of enzyme-replacement therapy (ERT) on cardiac disease. Twenty-four children aged 1-18 years with MPS I, II or VI were prospectively evaluated with echocardiogram and electrocardiogram from the start of enzyme-replacement therapy up to 6 years of treatment. At start of therapy, 66% had abnormal cardiac geometric features. Left-ventricular mass index (LVMI) was increased in half of the patients, due mainly to concentric hypertrophy in MPS I and II and to eccentric hypertrophy in MPS VI. Regurgitation was most severe in a subgroup of young MPS VI patients ( 2. LVMI Z-scores decreased significantly in patients with MPS I and MPS II (p = 0.04 and p = 0.032). Despite ERT, valve regurgitation increased in 60% of the patients. We conclude that all our MPS patients have cardiac abnormalities. The most severe cardiac disease was observed in a subgroup of young MPS VI patients. While ERT had an effect on LVMI and IVSd, it apparently had little or none on valve regurgitation

Cardiac outcome in classic infantile Pompe disease after 13\xe2\x80\xafyears of treatment with recombinant human acid alpha-glucosidase

Background: Cardiac failure is the main cause of death in untreated classic infantile Pompe disease, an inheritable metabolic myopathy characterized by progressive hypertrophic cardiomyopathy. Since the introduction of enzyme replacement therapy (ERT), survival has increased significantly due to reduced cardiac hypertrophy and improved cardiac function. However, little is known about ERT\'s long-term effects on the heart. Methods: Fourteen patients were included in this prospective study. Cardiac dimensions, function, conduction and rhythm disturbances were evaluated at baseline and at regular intervals thereafter. Results: Treatment duration ranged from 1.1 to 13.9 years (median 4.8 years). At baseline, all patients had increased left ventricular mass index (LVMI) (median LVMI 226 g/m2, range 98 to 599 g/m2, Z-score median 7, range 2.4\xe2\x80\x9312.4). During the first four weeks, LVMI continued to increase in six patients. Normalization of LVMI was observed in 13 patients (median 30 weeks; range 3 to 660 weeks). After clinical deterioration, LVMI increased again slightly in one patient. At baseline, PR interval was shortened in all patients; it normalized in only three. A delta-wave pattern on ECG was seen in six patients and resulted in documented periods of supraventricular tachycardias (SVTs) in three patients, two of whom required medication and/or ablation. One patient had severe bradycardia (35 beats/min). Conclusion: This study shows that ERT significantly reduced LVMI, and sustained this effect over a period of 13.9 years. The risk for rhythm disturbances remains. Regular cardiac evaluations should be continued, also after initially good response to ERT

ADAMTS19-associated heart valve defects: Novel genetic variants consolidating a recognizable cardiac phenotype

Recently, ADAMTS19 was identified as a novel causative gene for autosomal recessive heart valve disease (HVD), affecting mainly the aortic and pulmonary valves. Exome sequencing and data repository (CentoMD) analyses were performed to identify patients with ADAMTS19 variants (two families). A third family was recognized based on cardiac phenotypic similarities and SNP array homozygosity. Three novel loss of function (LoF) variants were identified in six patients from three families. Clinically, all patients presented anomalies of the aortic/pulmonary valves, which included thickening of valve leaflets, stenosis and insufficiency. Three patients had (recurrent) subaortic membrane, suggesting that ADAMTS19 is the first gene identified related to discrete subaortic stenosis. One case presented a bi-commissural pulmonary valve. All patients displayed some degree of atrioventricular valve insufficiency. Other cardiac anomalies included atrial/ventricular septal defects, persistent ductus arteriosus, and mild dilated ascending aorta. Our findings confirm that biallelic LoF variants in ADAMTS19 are causative of a specific and recognizable cardiac phenotype. We recommend considering ADAMTS19 genetic testing in all patients with multiple semilunar valve abnormalities, particularly in the presence of subaortic membrane. ADAMTS19 screening in patients with semilunar valve abnormalities is needed to estimate the frequency of the HVD related phenotype, which might be not so rare