Young Investigator Abstract SessionIs there a signal-averaged ECG phenotype in patients with Brugada syndrome?Critical role of microRNA miR-26 in atrial electrical remodelling in experimental atrial fibrillationLeft ventricular systolic and diastolic function in paediatric patients with definitive pacemakerRadiologically observed lead placement complications seen after pacemaker implantation in 526 subjects: a compelling case for leadless pacing systems

# Is there a signal-averaged ECG phenotype in patients with Brugada syndrome? {#article-title-2} Background and objectives Electrocardiographic manifestations of Brugada syndrome (BS) have been attributed to one of the two basic mechanisms: conduction delay and premature repolarization. The possible contribution of signal-averaged ECG (SAECG) to BS diagnosis is indefinite, and this study tests the hypothesis that these patients have a distinct SAECG phenotype. Methods Seventy-two adults were included, 52 from the same family with Brugada [25 with positive genetic test (G+) and 27 with negative genetic test (G−)]. Twenty unrelated healthy individuals were the control group (CG). Late potentials (LPs) were defined when at least two of the following were present: (i) filtered QRS duration (fQRS) >114ms; (ii) root-mean square voltage of terminal 40 ms of QRS (RMS40) 38 ms. Results The prevalence of LPs was 15, 26, and 61%, respectively, in CG, G− , and G+ group ( P < 0.05). G+ presented a higher percentage of patients with abnormal parameters, particularly RMS40 (61.5 vs. 26.9% and 20%, respectively, in G− and CG, P = 0.005) and LAS (69.2 vs. 26% and 15%, respectively, in G− and CG, P < 0.001). Conclusion Brugada patients appear to have an SAECG characteristic phenotype, defined by fragmented activity within the terminal portion of the QRS (essentially LAS and RMS40) without a major change in its length (fQRS). # Critical role of microRNA miR-26 in atrial electrical remodelling in experimental atrial fibrillation {#article-title-3} Background Increase in inward rectifier K+ current I K1 is a hallmark of atrial fibrillation (AF)-related electrical remodelling. However, the underlying mechanism remains largely unknown. Recent studies have highlighted the important roles of microRNAs (miRNAs) in various heart diseases. Hence, this study aims to investigate the potential roles of miRNAs in AF by targeting ion channels, specifically I K1. Methods The canine AF model was induced by atrial tachypacing; the miRNA expression level was determined by Q-PCR; the effect of miR-26 on KCNJ2 was examined by luciferase assay and western blot; I K1 currents were recorded by whole cell patch clamp; adenovirus carrying miR-26 was constructed to in vivo over express miR-26; and endogenous miR-26 was knocked down by LNA knockdown oligo. Results We first found miR-26 being significantly down-regulated by >50% in AF. We subsequently verified KCNJ2 encoding Kir2.1 protein for I K1 as a cognate target for miR-26. Transfection of miR-26 reduced the Kir2.1 protein level, whereas knocking down miR-26 by its antisense oligomers (AMO-26) caused a robust increase in the Kir2.1 level. Accordingly, miR-26 depressed whilst AMO-26 enhanced, I K1 current density. We further characterized the core promoter regions of miR-26 genes and identified NFAT, a well-implicated transcription factor in AF, as a transcriptional repressor of miR-26 genes. More interestingly, application of in vivo knockdown oligo against miR-26 to mice greatly enhanced the AF vulnerability while overexpressing miR-26 largely reduced AF inducibility. Conclusion Our study revealed that miRNAs are critically involved in AF and the associated atrial electrical remodelling and may serve as therapeutic target for AF treatment. # Left ventricular systolic and diastolic function in paediatric patients with definitive pacemaker {#article-title-4} Background Chronic right ventricular pacing is associated with deleterious effects in left ventricular form and function. Alternative sites of stimulation could avoid the cardiac remodelling and ventricular dysfunction. Objective Compare the effects of chronic right and left ventricular pacing in children with structurally normal hearts. Methods Echocardiographic data were retrospectively and prospectively obtained from patients with structurally normal hearts that required the implantation of definitive pacemakers at right ventricle epicardium ( n = 7), at right ventricle endocardium ( n = 30), and at left ventricle epicardium ( n = 18), between 1 January2000 and 31 December 2009. Fractional shortening and fractional ejection were calculated as a measure of left ventricular systolic function, Doppler mitral inflow, pulmonary vein flow, and tissue Doppler were estimated to diastolic function analysis; left ventricular end-diastolic diameter and left ventricular end-systolic diameter were also determined. Echocardiographic evaluations were made before pacemaker implantation, immediately after and regularly during a medium-term follow-up. Results Left ventricular diastolic function did not change in any site pacing during the follow-up; left ventricular fractional shortening and fractional ejection were higher in left ventricular epicardium pacing (42 ± 8, 73 ± 6) than in right ventricular endocardium paced group (36 ± 4, 66 ± 5) and right ventricular epicardium paced patients (34 ± 6, 64 ± 5). Left ventricular end-diastolic and end-systolic diameters were increased as a result of depressed systolic function in both right ventricular pacing. Conclusion Left ventricular form and function are better in paediatric patients with structurally normal hearts and chronic left ventricular pacing when compared with children with chronic right ventricular pacing. # Radiologically observed lead placement complications seen after pacemaker implantation in 526 subjects: a compelling case for leadless pacing systems {#article-title-5} Background Despite technical advances, cardiac pacing is still associated with problems attributable to poor lead placement. Lead problems may be caused by operator experience, technical performance, and logistics. Elimination of leads and the utilization of alternate energy are the only way to avoid these complications. In this QA analysis, we sought to define and quantify post-procedure lead X-ray configurations to assess the potential benefit of emerging leadless technology. Methods and results Post-procedure chest X-rays of 526 patients after pacemaker implantation were reviewed. Final atrial lead (AL) positions (433) were categorized according to quadrants in the frontal projection: A (right upper-ideal), B (right lower), C (left lower), and D (left upper). Final ventricular lead (VL) locations (526) were also analysed. Septal and epicardial leads were excluded. In 433 patients, AL were non-ideal in 29.3% (Quadrant B −10.6%, C −1.2%, D −18.7%). Atrial lead looping was recorded in 10.4% cases. Ventricular lead placements were considered suboptimal in 15%. Return to theatre for early lead revision occurred in <10%. Clinical correlates were analysed. Conclusions This large radiographic series highlights the technical difficulties producing sub-optimal lead configurations after pacemaker implants. Not all lead malpositions cause immediate clinical problems, but the risks of delayed complications such as further migration, atrial fibrillation, and mal-sensing remain. This analysis quantifies the potential benefit proffered by a leadless pacing system.