Accelerated Cardiac Rhabdomyoma Regression with Everolimus in Infants with Tuberous Sclerosis Complex.

Tuberous sclerosis complex is associated with benign tumors such as cardiac rhabdomyomas (RHM) caused by the disinhibition of the mammalian target of rapamycin (mTOR) protein. Recent reports on everolimus, an mTOR inhibitor, have shown size reduction of RHM. We compared cases recently treated with everolimus to historic controls whose first echocardiography was within first month of life. The largest dimension of the largest RHM was reported as a percentage compared to the earliest echocardiography study. Treatment of the four cases was started at a median age of 6.5 days (range 2-20) with an initial enteral dose of 0.1 mg daily, aiming at a therapeutic serum trough level of 5-15 ng/mL. Median duration of everolimus treatment was 73 days (range 34-138). Compared to 10 historic controls, everolimus-treated patients had 11.8 times faster RHM size regression rate (slope -0.0285 vs. -0.0024; p < 0.001). The average time to 50% size reduction was 1.13 ± 0.33 month (range 0.66-1.4 months) with everolimus versus 72.9 ± 53.03 months in controls (p = 0.026). Following treatment with everolimus, one case was operated for congenital heart disease, without requirement of RHM resection, two others had the massive left ventricle RHM shrink to non-consequential size. The latter had a disappearance of RHM, but everolimus therapy was maintained to prevent the regrowth of a significant cerebral tumor. Everolimus is efficacious for size reduction of RHM during the neonatal period. With limited safety data, this approach should be used with caution in selective cases.

Prenatal markers of atypical neurodevelopment in children with congenital heart defects.

BACKGROUND: A growing body of literature demonstrates that survivors of congenital heart defects (CHD) are at increased risk of neurodevelopmental delay, which frequently manifests as motor delay during the first year of life. OBJECTIVE: The aim of this study was to determine prenatal predictors of an early atypical neurodevelopment. This information could help assist decision-making during prenatal counseling. STUDY DESIGN: In this retrospective cohort study, we evaluated the records of 75 children with CHD followed at the Clinique d'Investigation Neuro-Cardiaque (CINC) of the CHU Ste-Justine born between 2013 and 2016. The neurodevelopmental outcome was determined using the Alberta Infant Motor Scale (AIMS) at 4 months. Associations between prenatal factors and atypical neurodevelopment (AIMS < 10th percentile) were assessed using bivariate and multivariate analyses. RESULTS: Forty-four infants (58.7%) had atypical neurodevelopment. When there was no extra cardiac anomaly seen on prenatal ultrasound, a head to abdominal ratio (HC/AC) below 1.1 was associated with a four-fold increased risk of atypical neurodevelopment (OR = 4.54; 95% CI = 1.24-16.64 p = .023). There was no difference in identified genetic anomaly in both groups. However, there was a trend toward more extra cardiac anomalies in infants with atypical neurodevelopment (27.3%) compared to 9.7% in those with typical neurodevelopment (p = .061). CONCLUSION: Our study shows that early atypical neurodevelopment affects the majority of children with CHD and highlights the importance of post-natal monitoring by a specialized team. A thorough prenatal ultrasound is important to screen for those at higher risk i.e. those with extra cardiac anomaly and HC/AC below 1.1. A larger cohort is needed to validate those results.

Pericardial effusion in severe hypothyroidism in children.

Pleural and pericardial effusion is a rare complication of severe hypothyroidism in children but can be present in 10 to 30% of adults. Most pediatric cases have been in children with Down syndrome. In this report, six cases of pericardial effusion in children with severe hypothyroidism with and without trisomy 21 are presented. In all patients, the pericardial effusion was managed successfully without pericardiocentesis. The effusions resolved completely in 2 to 12 months after initiation of thyroxin replacement. In conclusion, hypothyroidism should be considered in any child with unexplained pericardial or pleural effusions. Early recognition and treatment with thyroid hormone replacement could eliminate the need for unnecessary diagnostic procedures and invasive treatment measures and reduce the risk of progression to cardiac tamponade.

In Vitro Feasibility and Accuracy of Three-Dimensional Echocardiography for Ventricular Volume Assessment in Very Small Hearts.

To evaluate the in vitro accuracy of three-dimensional echocardiography (3-DE) for estimation of ventricular volume in very small hearts, left ventricular (LV) volume was determined by 3-DE in the excised hearts of 10 guinea pigs and 10 rabbits, and right ventricular (RV) volume was determined in 20 rabbits. The effect of edge enhancement, Sigma filter, and slice distance (1 mm versus 0.5 mm) was assessed in each heart. True volumes were obtained from ventricular casts. Mean cast volume was 1.38 +/- 0.83 mL for LVs and 1.63 +/- 1.01 mL for RVs. Correlations between 3-DE and true volumes were r > 0.99 (P < 0.0001) for both ventricles. Accuracy was not affected by ventricular type, slice distance, or Sigma filter. Mean percent difference from true volume was significantly less (P = 0.03) with edge enhancement. Ventricular volume can be assessed reliably by 3-DE in very small hearts. The edge enhancement feature improved the accuracy of the measurements.

Propranolol in the treatment of problematic infantile hemangioma: review of 35 consecutive patients from a vascular anomalies clinic.

BACKGROUND: Propranolol, a nonselective ß-blocker, has been reported as efficient for controlling the growth of complicated infantile hemangiomas (IHs). No uniformly accepted protocol exists regarding the administration of oral propranolol for IH. OBJECTIVE: We sought to share our experience using propranolol for problematic IH and to evaluate the efficacy of this treatment modality. METHODS: A retrospective chart review analysis was performed for 35 consecutive children treated with propranolol as an oral solution on an outpatient basis in our dermatology/vascular anomalies clinic. A protocol was established with the help of our pediatric cardiologists, including pretreatment electrocardiography and echocardiography. Medical photographs taken after 2 months of treatment were rated by two independent evaluators. RESULTS: We treated 31 girls and 4 boys with a median age of 3.5 months. Rapid improvement was reported in the first days of treatment in 34 patients. Mean improvement after 2 months was 61.5%. No serious adverse effects were reported. CONCLUSION: Propranolol was effective in controlling the proliferative phase of problematic IH. It was well tolerated in our study. Outpatient treatment is possible if parents follow strict guidelines. Propranolol should be a first-line treatment for problematic IH in carefully selected patients.

Propranolol in the treatment of problematic infantile hemangioma: review of 35 consecutive patients from a vascular anomalies clinic.

BACKGROUND: Propranolol, a nonselective ß-blocker, has been reported as efficient for controlling the growth of complicated infantile hemangiomas (IHs). No uniformly accepted protocol exists regarding the administration of oral propranolol for IH. OBJECTIVE: We sought to share our experience using propranolol for problematic IH and to evaluate the efficacy of this treatment modality. METHODS: A retrospective chart review analysis was performed for 35 consecutive children treated with propranolol as an oral solution on an outpatient basis in our dermatology/vascular anomalies clinic. A protocol was established with the help of our pediatric cardiologists, including pretreatment electrocardiography and echocardiography. Medical photographs taken after 2 months of treatment were rated by two independent evaluators. RESULTS: We treated 31 girls and 4 boys with a median age of 3.5 months. Rapid improvement was reported in the first days of treatment in 34 patients. Mean improvement after 2 months was 61.5%. No serious adverse effects were reported. CONCLUSION: Propranolol was effective in controlling the proliferative phase of problematic IH. It was well tolerated in our study. Outpatient treatment is possible if parents follow strict guidelines. Propranolol should be a first-line treatment for problematic IH in carefully selected patients.

Fetal echocardiographic screening of pregnancies of mothers with anti-Ro and/or anti-La antibodies.

The objectives of this study are to assess the incidence of congenital complete heart block (CCHB) in pregnant women who are anti-Ro and/or La positive. Between January, 1988 and July 1997, 118 pregnancies in 105 women were assessed by fetal echo at 18, 24, and 32 weeks' gestation. Of these 105, 96 had no history of a previous fetus with CCHB; 11(12 pregnancies) a history of a pregnancy with CCHB; and 4 a previous child with cutaneous neonatal lupus erythematosus (CNLE). The 102 pregnancies in 96 women with anti-Ro and/or anti-La antibodies and no history of a previous child with NLB, resulted in 100 live-births with no CCHB. There was 1 dilated cardiomyopathy at 6 months, 1 child with CCHB, and 1 with sclerosis of the endocardium. No case of CCHB was observed in 102 pregnancies without a previous history of CCHB. These results suggest that the risks of CCHB, without a prior history are low.