Systematic Analysis of Gene Expression Differences between Left and Right Atria in Different Mouse Strains and in Human Atrial Tissue

Background: Normal development of the atria requires left-right differentiation during embryonic development. Reduced expression of Pitx2c (paired-like homeodomain transcription factor 2, isoform c), a key regulator of left-right asymmetry, has recently been linked to atrial fibrillation. We therefore systematically studied the molecular composition of left and right atrial tissue in adult murine and human atria. Methods: We compared left and right atrial gene expression in healthy, adult mice of different strains and ages by employing whole genome array analyses on freshly frozen atrial tissue. Selected genes with enriched expression in either atrium were validated by RT-qPCR and Western blot in further animals and in shock-frozen left and right atrial appendages of patients undergoing open heart surgery. Results: We identified 77 genes with preferential expression in one atrium that were common in all strains and age groups analysed. Independent of strain and age, Pitx2c was the gene with the highest enrichment in left atrium, while Bmp10, a member of the TGFb family, showed highest enrichment in right atrium. These differences were validated by RT-qPCR in murine and human tissue. Western blot showed a 2-fold left-right concentration gradient in PITX2 protein in adult human atria. Several of the genes and gene groups enriched in left atria have a known biological role for maintenance of healthy physiology, specifically the prevention of atrial pathologies involved in atrial fibrillation, including membrane electrophysiology, metabolic cellular function, and regulation of inflammatory processes. Comparison of the array datasets with published array analyses in heterozygous Pitx2c+/2 atria suggested that approximately half of the genes with left-sided enrichment are regulated by Pitx2c. Conclusions: Our study reveals systematic differences between left and right atrial gene expression and supports the hypothesis that Pitx2c has a functional role in maintaining ‘‘leftness’’ in the atrium in adult murine and human hearts

Health-related quality of life in adults with tetralogy of Fallot repair: A systematic review and meta-analysis

Background: With the advancement in diagnostics and clinical management, patients with Tetralogy of Fallot (ToF) are surviving till adulthood. Hence, assessing the impact of ToF repair on health-related quality of life (HRQOL) of these patients is becoming increasingly important. The objective of this paper is to conduct a systematic review and meta-analysis of the HRQOL in patients who have undergone ToF repair.Methods: A systematic search was conducted using PubMed, CINAHL, Medline and Web of Science databases. Studies that compared the HRQOL of adult patients (mean age ≥ 18 years) who had previously undergone ToF repair with healthy controls were included. Analysis was done via Revman V5.3 using a random effects model.Results: The 16 studies (15 using SF-36) included in the meta-analysis, comprised 1818 patients and 50,265 healthy controls. There was a higher proportion of males (59%). The mean ages at surgery and at HRQOL assessment were 5.37 years and 30.3 years, respectively. We found that repaired ToF patients had a statistically significantly lower score in the physical component summary (SMD = - 0.92 CI = - 1.54, - 0.30) and physical functioning (SMD = - 0.27 CI = - 0.50, - 0.03) compared to healthy controls. However, these patients had statistically significantly higher scores in the bodily pain domain (SMD = 0.35 CI = 0.12, 0.58) and social functioning (SMD = 0.23 CI = 0.01, 0.46), while there was no significant difference in other domains.Conclusion: Overall, physical domain of HRQOL was statistically significantly lower in repaired ToF patients compared to healthy controls. However, repaired ToF patients scored significantly higher on bodily pain and Social Functioning. There was additionally no difference in the HRQOL between the two groups in other domains of HRQOL