A dying neonate with congenital complete atrioventricular block underwent an emergency temporary pacing via the umbilical vein 1 h after birth. Implantation of a permanent epicardial pacemaker system was performed at the age of 10 days. During the follow-up period of 3 months, the child had been growing well with the VVIR pacemaker.

This study was performed to investigate the feasibility and effectiveness of left bundle branch area pacing (LBBaP) used in young children. MethodsFrom September 2020 to May 2021, total of thirty-one children (≤ 7 years old) with complete atrioventricular block were included. All patients were intended to receive the operation of LBBaP. The pacing parameters, cardiac function and cardiac synchrony were evaluated during follow-up. ResultsLBBaP succeeded in twenty-two children (3.3 ± 2.1 years old), with a success rate of 70.9%. LBBaP had failed in nine children, these children received right ventricular septal pacing (RVSP) eventually. The average postoperative QRS duration in patients of LBBaP group was narrower than that of RVSP group: 100.9 ± 9.1 versus 114.2 ± 11.9 ms (P = 0.002). The median time of follow-up was 12 (IQR 6-15) months.At last time of follow-up, the capture threshold of ventricular electrode in patients of LBBaP group were signi cantly lower than that of RVSP group (0.70 ± 0.25 versus 1.39 ± 0.94 V, P = 0.011). The echo-LVEF in patients of LBBaP group were better than that of RVSP group (66.1 ± 3.3 versus 63.1 ± 2.2%, P = 0.025). Additionally, the intraventricular and interventricular synchrony parameters in patients of LBBaP group were better than that of RVSP group: the standard deviation of time to peak strain (38.1 ± 5.3 versus 50.3 ± 7.0 ms, P = 0.000) and the interventricular mechanical delay time (38.4 ± 19.9 versus 65.0 ± 31.1 ms, P = 0.012) respectively. ConclusionLBBaP could be safely and effectively for young children. Satisfactory pacing parameters, narrow QRS duration and well cardiac synchrony parameters could be obtained.

28L-type calcium (CaV1) channels regulate gene expressions via the cascade of excitation-29 transcription coupling, or directly as standalone CCAT (Calcium Channel Associated 30Transcriptional-regulator) peptides encoding distal carboxyl-terminus (DCT) of CaV1, both 31 evidenced in dendritogenesis signaling in neurons. We here discover that DCT peptides opposedly 32 mediate these two sets of transcription signals, all tunable in accordance to C-terminus mediated 33 inhibition (CMI) of Ca 2+ /CaV1 influx. By electrophysiology, neurite morphology, and FRET 2-34 hybrid binding analyses, we systematically examined native and derived DCT peptides across CaV1, 35 unveiling that the overall balance between cytosolic inhibition versus nuclear facilitation is spatially 36 and temporally tuned by CMI of each DCT variant. Our findings not only resolve several 37 controversies existing to DCT variants, but also propose a de novo scheme of CaV1-centric gene 38 regulation: two concurrent routes of transcription signals initiated from either membrane CaV1 39 channels or nuclear CaV1-encoded peptides are subject to autonomous feedback tuning by 40 peptide/channel interactions. 41 42 43 (CDI) (Liu, Yang et al. 2017). It is postulated that CMI should downregulate Ca 2+ /CaV1 signaling 64 along the cascade of excitation-transcription coupling in neurons, in that the conventional inhibitor 65 dihydropyridine (DHP) indeed tunes down CaV1-dependent transcriptional signaling (Redmond, 66 Kashani et al. 2002, Wheeler, Groth et al. 2012). However, if the above hypothesis gets proved, 67 the actual roles of DCT would encounter an apparent dilemma: promotion of neurite outgrowth by 68 regulating related genes as nuclear TF, in direct opposition to inhibition of Ca 2+ influx and 69 presumably also neurite outgrowth as channel inhibitor. In this work, we undertook the mission to 70 elucidate the above controversy regarding CaV1-encoded peptides. 71In neurons, there are two independent sources of peptides encoding DCT fragments. One is 72 from the activation of a cryptic promoter in the coding region of CACNA1C (CaV1.2). Such DCT 73 fragment is termed as calcium channel associated transcriptional regulator (CCATC) and contains 74 intact proximal C-terminal regulatory domain, nuclear retention domain and distal C-terminal 75 regulatory domain (PCRD, NRD and DCRD, respectively) (Figure 2-figure supplement 1) 76 (Gomez-Ospina, Panagiotakos et al. 2013). Here NRD is an indispensable region for Ca 2+ -77 dependent nuclear transport (Gomez-Ospina, Tsuruta et al. 2006), whereas PCRD and DCRD serve 78 as key elements for CMI (Liu, Yang et al. 2017). Two putative transcription activation domains of 79 DCT fragments are distributed on PCRD-NRD junction and DCRD (Gomez-Ospina, Tsuruta et al. 80 2006), the latter of which appears to have more contributions (Gomez-Ospina, Panagiotakos et al. 81 2013). Alternatively, DCT peptides could be generated from proteolytic cleavage of the full-length 82 CaV1. The cleavage sites of amino acid sequences NNAN ...