Neonates and infants requiring life-long cardiac pacing: How reliable are epicardial leads through childhood?

BACKGROUND: In the literature, data is lacking on mid-term results of epicardial pacemaker implantation in neonates and infants. Our aim was to evaluate the mid-term results of epicardial pacemakers implanted in infants under 1 year of age. METHODS AND RESULTS: We conducted a retrospective review of patients who underwent pacemaker implantation between 2000 and 2017. Pacemaker and lead parameters were reviewed at discharge, 2, 4 and more than 5 years after implantation. A total of 71 patients aged 4 ±â€¯3 months and weighing 4 ±â€¯2 kg were included in the study. Indications for pacemaker implantation were: acquired AV-block (n = 44), congenital AV block (n = 22), sick sinus syndrome (n = 4) and AV block type Mobitz II (n = 1). Median follow-up time was 5 years (range: 1 month-17 years). At 5 years of follow-up, atrial lead energy threshold for pacing decreased significantly (0.72 ±â€¯0.71 µJ to 0.45 ±â€¯0.35 µJ; P < 0.001) but was stable for ventricular leads (0.57 µJ [0.05; 39.47] to 0.64 µJ [0.13; 9.45], P = 0.97). Atrial lead impedance increased significantly (569 ±â€¯137 Ω to 603 ±â€¯134 Ω, P < 0.001), whereas ventricular lead impedance decreased (603 ±â€¯202 Ω to 490 ±â€¯150 Ω, P < 0.001) after 5 years. Repeat operations were required for generator change (n = 55), lead exchange (n = 17) and infection (n = 1). At 2, 5 and 10 years, atrial lead survival was 96%, 91% and 76% and ventricular lead survival was 94%, 82% and 75%, respectively (P = 0.45). CONCLUSION: Stable pacing thresholds after 5 years indicated that epicardial pacemakers are safe for infants under 1 year of age until at least school enrolment age. However, due to stimulation at higher heart rates in infancy, battery depletion is a frequent occurrence.

The C/EBP homologous protein CHOP (GADD153) is an inhibitor of Wnt/TCF signals.

CHOP (GADD153) is a protein of the C/EBP family of transcriptional regulators, which dimerizes with other C/EBP members and changes their DNA-binding and transactivation properties. It induces growth arrest and apoptosis after endoplasmatic reticulum stress or DNA damage. CHOP is also expressed during early embryogenesis and upregulated in tumour tissues with defective Wnt signals. We report here that CHOP functions as a specific inhibitor of Wnt/T-cell factor (TCF) signalling. CHOP inhibits TCF-dependent transcription in human embryonic and colon cancer cell lines. Injection of CHOP mRNA into early Xenopus laevis embryos suppresses dorsal organizer formation and inhibits secondary axis formation and TCF-dependent transcription in response to Wnt-8, Dishevelled, beta-Catenin and TCF-VP16. In embryos and human cells, this inhibition depends on the N-terminal transactivation domain of CHOP, whereas the C-terminal dimerization domain is dispensable. CHOP binds to TCF factors, thereby preventing the binding of TCF to its DNA recognition site. Our findings demonstrate a novel function of CHOP as a Wnt repressor.

Conditional expression of RNA polymerase II in mammalian cells. Deletion of the carboxyl-terminal domain of the large subunit affects early steps in transcription.

The carboxyl-terminal domain (CTD) of the large subunit of mammalian RNA polymerase II contains 52 repeats of a heptapeptide that is the target of a variety of kinases. The hyperphosphorylated CTD recruits important factors for mRNA capping, splicing, and 3'-processing. The role of the CTD for the transcription process in vivo, however, is not yet clear. We have conditionally expressed an alpha-amanitin-resistant large subunit with an almost entirely deleted CTD (LS*Delta5) in B-cells. These cells have a defect in global transcription of cellular genes in the presence of alpha-amanitin. Moreover, pol II harboring LS*Delta5 failed to transcribe up to the promoter-proximal pause sites in the hsp70A and c-fos gene promoters. The results indicate that the CTD is already required for steps that occur before promoter-proximal pausing and maturation of mRNA.