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Genetic variation at the human connexin 43 locus but not at the connexin 40 locus is associated with left bundle branch block.

ABSTRACT: Background: Bundle branch block (BBB) has been regarded as a disease of the conduction system, but occurs in mice lacking connexin 40 (expressed in atria, proximal conduction system) or connexin 43 (expressed in Purkinje cells, cardiomyocytes).

Objective: The aim of this paper is to explore whether BBB is heritable, and whether polymorphisms at connexin 40 and connexin 43 loci are associated with BBB.

Methods: To assess BBB heritability, we screened descendants of men with BBB in the population cohort 'The Study of Men Born 1913'. DNA samples from 80-year-old men with extreme QRS-duration phenotypes were used to search for polymorphisms at connexin 40 and 43 loci. Associations between identified polymorphisms and BBB were evaluated in an independent cohort (INTERGENE).

Results: Seventy-seven men from 'The Study of Men Born 1913' with BBB had 116 descendants. Among the 76 participating descendants, 2 sons (6.4%) had BBB at 54?years of age. At the same age, 0.9% of men born in 1913 had BBB. We identified 6 single nucleotide polymorphisms (SNPs) in connexin 40 and 1 polymorphism in connexin 43. In the INTERGENE cohort, the connexin 43 polymorphism was associated with left BBB (LBBB) (4 of 35 LBBB vs 16 of 232 without BBB, ?(2)=7.4, p=0.03), but not with right BBB (RBBB) or overall BBB. None of the connexin 40 SNPs or haplotypes were associated with LBBB or RBBB.

Conclusions: These findings indicate that conduction by connexin 43 within the ventricular muscle distal to the specialised conduction system may be important for LBBB development.

SUBMITTER: Ladenvall P

PROVIDER: S-EPMC4395834 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Genetic variation at the human connexin 43 locus but not at the connexin 40 locus is associated with left bundle branch block.

Ladenvall Per P Andersson Björn B Dellborg Mikael M Hansson Per-Olof PO Eriksson Henry H Thelle Dag D Eriksson Peter P

Open heart 20150410 1

<h4>Background</h4>Bundle branch block (BBB) has been regarded as a disease of the conduction system, but occurs in mice lacking connexin 40 (expressed in atria, proximal conduction system) or connexin 43 (expressed in Purkinje cells, cardiomyocytes).<h4>Objective</h4>The aim of this paper is to explore whether BBB is heritable, and whether polymorphisms at connexin 40 and connexin 43 loci are associated with BBB.<h4>Methods</h4>To assess BBB heritability, we screened descendants of men with BBB ...[more]

PMID: 25893100

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Project description:BackgroundComplete bundle branch block in individuals without structural heart disease is known as isolated complete bundle branch block. Isolated complete left bundle branch block (CLBBB) is correlated with ventricular dysfunction secondary to dyssynchrony; however, few studies have investigated isolated complete right bundle branch block (CRBBB), which was previously considered benign but was recently found to be associated with adverse cardiovascular outcomes. This study aimed to evaluate cardiac mechanical synchrony, and systolic and diastolic function in patients with isolated CRBBB and compare cardiac synchrony and function to patients with isolated CLBBB.MethodsThis cross-sectional study was conducted at The First Hospital of China Medical University in Shenyang, China, from 2020 to 2021. A total of 44 isolated CRBBB patients, 44 isolated CLBBB patients, and 42 healthy subjects were enrolled in the study. Transthoracic echocardiography was performed in all subjects. Synchrony parameters, including the mechanical dispersion of the right ventricle [the standard deviation of time to the peak longitudinal strain of six right ventricular (RV) segments] and atrioventricular dyssynchrony parameter [the ratio of left ventricular (LV) diastolic filling time to the time interval between two adjacent R waves (RR interval) measured by tissue Doppler imaging]. RV and LV function were assessed by the global longitudinal strain (GLS) of six RV segments and 18 LV segments, and the ratio of the peak early diastolic flow velocity to annular velocity (E/e') of the tricuspid valve and mitral valve. Statistical analyses were performed, including an analysis of variance, Pearson correlation analysis, and linear regression analysis.ResultsCompared with the healthy subjects, the mechanical dispersion of the right ventricle was significantly increased, and ventricular function was impaired as evidenced by the decreased RV GLS and LV GLS, and the increased E/e' of the tricuspid valve and mitral valve in the isolated CRBBB patients (all P<0.001). Moreover, compared with the isolated CLBBB patients, the mechanical dispersion of the right ventricle and E/e' of the tricuspid valve were increased, and RV GLS was significantly reduced in the isolated CRBBB patients (all P<0.001). Mechanical dispersion of the right ventricle was independently associated with RV GLS [coefficient, 0.13; 95% confidence interval (CI): 0.004-0.26; P=0.04] in the isolated CRBBB patients. RV GLS (coefficient, 0.10; 95% CI: 0.01-0.20; P=0.03) and the ratio of the LV diastolic filling time to the RR interval measured (coefficient, -0.30; 95% CI: -0.53 to -0.07; P=0.01) were independent factors of LV GLS.ConclusionsThe isolated CRBBB patients had impaired cardiac mechanical synchrony and ventricular function, and more decreased RV synchrony and function than the isolated CLBBB patients. Right intraventricular synchrony was independently associated with RV systolic dysfunction in patients with isolated CRBBB. Atrioventricular synchrony and RV systolic function were independently associated with the LV systolic function. Therefore, comprehensive evaluations of echocardiography results and close monitoring is required for isolated CRBBB patients.

Project description:AimTo evaluate ventricular synchronization and function in patients with right bundle-branch block after left bundle-branch-area pacing (LBBAP) by echocardiography.MethodsForty patients who successfully received LBBAP were selected and divided into the right bundle-branch block group (RBBB group) and the non-RBBB group by pre-operation ECG. Echocardiography and follow-up were performed 1 month after operation. Interventricular synchronization was evaluated by tissue Doppler (TDI), tissue mitral annular displacement (TMAD), and interventricular mechanical delay. The tricuspid annular plane systolic excursion (TAPSE), right ventricular fractional area change (RVFAC), tricuspid annulus sidewall systolic velocity (TV-s'), left ventricular global ventricular longitudinal strain (GLS), right ventricular free wall longitudinal strain (LS-RV), standard deviation of left ventricular 18 segments peak time difference (SDt-L) and standard deviation of right ventricular free wall 3 segments peak time difference (SDt-R) were applied to evaluate intraventricular synchronization and ventricular function.ResultsThe difference of displacement peak time of the tricuspid and mitral valves, namely ΔPTTV-MV measured by TMAD, the difference of systolic time to peak of the tricuspid and mitral valves, namely ΔTsTV-MV measured by TDI, were statistically different between the two groups (P < 0.05). Compared with the non-RBBB group, there were no statistically significant differences in the GLS, RVFAC, LS-RV, TAPSE, TV-s', SDt-L, SDt-R (P > 0.05).ConclusionEchocardiography technology including two-dimensional speckle tracking imaging (2D-STI), TDI, and TMAD can effectively analyze interventricular synchronization, intraventricular synchronization, and ventricular function. Although the movement of the right ventricular myocardium in the RBBB group was slightly later than that of the left ventricular myocardium after LBBAP, LBBAP could still be applied in RBBB patients with pacing indication.

Dataset Information

Genetic variation at the human connexin 43 locus but not at the connexin 40 locus is associated with left bundle branch block.

Publications

Genetic variation at the human connexin 43 locus but not at the connexin 40 locus is associated with left bundle branch block.

Similar Datasets

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