Atrial high-rate episodes predict clinical outcome in patients with cardiac resynchronization therapy

Objectives. Up to 50% of patients qualified for cardiac resynchronization therapy (CRT) have documented atrial fibrillation (AF) prior to CRT-implantation. This finding is associated with worse prognosis but few studies have evaluated the importance of post-implant device-detected AF. This study aimed to assess the prognostic impact of device-detected atrial high-rate episodes (AHRE), as a surrogate for AF. Design. Data were retrospectively obtained from consecutive patients receiving CRT. Baseline clinical data and data from CRT device-interrogations, performed at a median of 12.2 months after CRT-implantation, were evaluated with regard to prediction of the composite endpoint of death, heart transplant or appropriate shock therapy. Median follow-up time was 51 months post-implant. Results. The study included 377 patients. Preoperative AF was present in 49% and associated with worse outcome. The cumulative burden of AHRE at 12 months post-implant was an independent predictor of the primary endpoint. During the first 12 months after CRT-implantation, AHRE were detected in 25% of the patients with no preoperative diagnosis of AF. This finding was not associated with worse outcome. Conclusions. In CRT recipients, the cumulative burden of AHRE during the first year of follow-up was associated with worse long-term clinical outcome. Prospective trials are needed to determine if a rhythm control strategy is to be preferred in patients with CRT.     

Test-retest reliability of knee kinesthesia in healthy adults

Background  

Sensory information from mechanoreceptors in the skin, muscles, tendons, and joint structures plays an important role in joint stability. A joint injury can lead to disruption of the sensory system, which can be measured by proprioceptive acuity. When evaluating proprioception, assessment tools need to be reliable. The aim of this study was to assess the test-retest reliability of a device designed to measure knee proprioception.     

Polymorphisms in the calcineurin genes are associated with the training responsiveness of cardiac phenotypes in Chinese young adults

We studied the association of 55 polymorphisms in the PPP3CA, PPP3CB, PPP3CC, PPP3R1 and PPP3R2 genes with both (1) the pre-training levels and (2) responsiveness to endurance training (18 weeks), of echocardiographic variables. The latter were measured both before and after the training program at each of the following time points: before (rest), during and after cycle-ergometry exercise. Subjects were healthy young Chinese men of Han origin [n = 102; mean (SD) age: 19 ± 1 years]. To assess genotype:phenotype associations at pre-training, we used a one-factor (genotype) ANOVA for each polymorphism. To assess the association between each polymorphism and the training responsiveness of cardiac phenotypes, we used a two-factor (genotype x training) ANOVA with repeated measures. All multiple comparisons were corrected for mass significance. For genotype:phenotype associations at pre-training, we only found a significant association between the rs3763679 polymorphism (PPP3CB) and resting heart rate. As for genotype associations with trainability of cardiac phenotypes, we found the following significant associations (i.e. significant genotype × training interaction effect): (1) rs1879793, rs1075534, rs7430, rs2461483 and rs10108011 (PPP3CC) and cardiac output/stroke volume after exercise; and (2) rs1407877 (PPP3R2) and ejection fraction at 50 W. The findings suggest that polymorphisms in the calcineurin genes might be among the numerous potential genetic variant candidates that can help explaining human variations in the pre-training levels or trainability of cardiac phenotype traits.     

Overweight, obesity and body fat composition in spanish adolescents. The AVENA Study

OBJECTIVE: To describe the prevalence of overweight and obesity in the Spanish adolescent population and its relationship with the socioeconomic status, and to assess their body fat composition and compare these results with previous data from our own country. DESIGN: Cross-sectional multicenter study conducted in five Spanish cities (Granada, Madrid, Murcia, Santander and Zaragoza) in 2000-2002. SUBJECTS: 2,320 adolescents with complete set of anthropometric measurements, 1,192 boys and 1,128 girls. MEASUREMENTS: Body mass index calculated from weight and height measurements, and body fat percentage calculated from skinfold thickness measurements. RESULTS: Overweight + obesity prevalences were 25.69 and 19.13% in boys and girls, respectively. Overweight + obesity prevalence increased in boys from high to medium-low socioeconomic status categories (p = 0.015); meanwhile, there was not a significant effect of socioeconomic status in girls. In males, overweight + obesity prevalence changed from 1985 to 2000-2002 from 13 to 35% and in females from 16 to 32%. The rate of change in overweight + obesity prevalences seems to increase in the last years; from 0.88 (1985 to 1995) to 2.33%/year (1995 to 2000-2002) in males and from 0.5 (1985 to 1995) to 1.83%/year (1995 to 2000-2002) in females. The rate of body fat percentage increase was similar between 1980 and 1995 and between 1995 and 2000-2002: 0.26 and 0.23%/year, respectively, at 13 years of age, and 0.16 and 0.17%/year, respectively, at 14 years of age. CONCLUSION: We observed elevated overweight and obesity prevalences in Spanish adolescents, similar to those observed in other European countries. There is a significant inverse relationship between socioeconomic status and overweight + obesity, but only in boys. The rate of change in overweight prevalence in Spanish adolescents seems to increase, and the rate of increase of body fat percentage seems to be similar as in previous years.     

Reduced cell surface levels of GPI‐linked markers in a new case with PIGG loss of function

Glycosylphosphatidylinositol (GPI) is a glycolipid that tethers more than 150 different proteins to the cell surface. Aberrations in biosynthesis of GPI anchors cause congenital disorders of glycosylation with clinical features including intellectual disability (ID), seizures, and facial dysmorphism. Here, we present two siblings with ID, cerebellar hypoplasia, cerebellar ataxia, early‐onset seizures, and minor facial dysmorphology. Using exome sequencing, we identified a homozygous nonsense variant (NM_001127178.1:c.1640G>A, p.Trp547*) in the gene Phosphatidylinositol Glycan Anchor Biosynthesis, Class G (PIGG) in both the patients. Variants in several other GPI anchor synthesis genes lead to a reduced expression of GPI‐anchored proteins (GPI‐APs) that can be measured by flow cytometry. No significant differences in GPI‐APs could be detected in patient granulocytes, consistent with recent findings. However, fibroblasts showed a reduced global level of GPI anchors and of specific GPI‐linked markers. These findings suggest that fibroblasts might be more sensitive to pathogenic variants in GPI synthesis pathway and are well suited to screen for GPI‐anchor deficiencies. Based on genetic and functional evidence, we confirm that pathogenic variants in PIGG cause an ID syndrome, and we find that loss of function of PIGG is associated with GPI deficiency.