Underdiagnosis of Conditions Associated with Sudden Cardiac Death in Children--Is it the Absence of a Comprehensive Screening Program or a True Low Prevalence?

This study aimed to assess the prevalence of conditions associated with sudden cardiac death (SCD) among all children and children with sudden infant death syndrome (SIDS) in the State of Hawai'i, where no comprehensive screening program is conducted for such conditions. A retrospective chart review was conducted from the single tertiary pediatric hospital in Hawai'i, from offices of all pediatric cardiologists in Hawai'i, and the Hawai'i State Department of Health from 1/1/2000 to 12/31/2013. Children aged 0-18 years were included in the study. A subset of the study analyzed records of infants aged 0-12 months. SIDS rate was calculated and compared to national data. Prevalence was calculated for known conditions associated with SCD. The identified prevalence was compared to the established prevalence of conditions associated with SCD. In Hawai'i, the infant SIDS rate (66.4/100,000) was similar to the national rate (54.4/100,000). Over 14 years, only 51 children were diagnosed with a condition associated with SCD; 28 with a cardiomyopathy and 21 with a channelopathy. A 14-year retrospective analysis in the State of Hawai'i revealed that less than 1 in 30 children, who are expected to harbor a SCD-associated condition, had been appropriately diagnosed. The underdiagnosis of conditions associated with SCD reflects that in the absence of a comprehensive screening program, conditions without obvious signs and symptoms are difficult to diagnose. Many children with these conditions will remain at risk of SCD.

IAPP aggregation and cellular toxicity are inhibited by 1,2,3,4,6-penta-O-galloyl-ß-D-glucose.

The polyphenol, 1,2,3,4,6-penta-O-galloyl-ß-D-glucose (PGG) has been found to exhibit a host of positive pharmacologic activities, including anti-cancer and anti-diabetic. Little is known about the mode of action of PGG in yielding these positive activities. We show here that PGG is a potent inhibitor of IAPP (islet amyloid polypeptide, amylin) aggregation. Preventing the initial aggregation event of IAPP is one strategy for slowing, and possibly preventing, the toxic effects of IAPP oligomeric intermediates. Equal molar ratios of PGG to IAPP substantially reduced the ability of IAPP to bind thioflavin T. Atomic force microscopy revealed that PGG prevented amyloid-based fiber formation under rigorous conditions conducive to forming IAPP aggregates. PGG was also found to protect PC12 rat cells from toxic IAPP. PGG was compared to the known amyloid inhibitors (and structural relatives); tannic acid and gallic acid. In every test, PGG was far superior to tannic and gallic acids at inhibiting amyloid aggregation. These results indicate that PGG is a potent inhibitor of IAPP amyloid aggregation and a potential lead molecule for development of an amyloid inhibiting therapeutic.