Dataset Information

Familial Clustering of Cardiac Conduction Defects and Pacemaker Insertion.

ABSTRACT: BACKGROUND:The etiopathogenesis of electrocardiographic bundle branch and atrioventricular blocks is not fully understood. We investigated familial clustering of cardiac conduction defects and pacemaker insertion in the FHS (Framingham Heart Study). Additionally, we assessed familial clustering of pacemaker insertion in the Danish general population. METHODS:In FHS, we used multivariable-adjusted logistic regression models to investigate the association of parental atrioventricular block (PR interval, ?0.2 s), complete bundle branch block (QRS, ?0.12 s), or pacemaker insertion with the occurrence of cardiac conduction abnormalities in their offspring. The Danish nationwide administrative registries were interrogated to assess the relations of parental pacemaker insertion with offspring pacemaker insertion. RESULTS:In FHS (n=371 cases with first-degree atrioventricular block, complete bundle branch block, or pacemaker insertion, and 1471 age- and sex-matched controls), individuals with at least 1 affected parent with a conduction defect had a 1.65-fold odds (odds ratio, 95% CI, 1.32-2.07) for manifesting an atrioventricular block and a 1.62-fold odds (95% CI, 1.08-2.42) for developing a complete bundle branch block. If at least 1 parent had any electrocardiographic conduction defect or pacemaker insertion, the offspring had a 1.62-fold odds (95% CI, 1.31-2.00) for experiencing any of these conditions. In Denmark (n=2?824?199 individuals; 5397 incident pacemaker implantations), individuals with at least 1 first-degree relative with history of pacemaker insertion had a multivariable-adjusted 1.68-fold (incidence rate ratio, 95% CI, 1.49-1.89) risk of undergoing a pacemaker insertion. If the affected relative was ?45 years of age, the incidence rate ratio was markedly increased to 51.0 (95% CI, 32.7-79.9). CONCLUSIONS:Cardiac conduction blocks and risk for pacemaker insertion cluster within families. A family history of conduction system disturbance or pacemaker insertion should trigger increased awareness of a similar propensity in other family members, especially so when the conduction system disease occurs at a younger age.

SUBMITTER: Kaess BM

PROVIDER: S-EPMC6588168 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Familial Clustering of Cardiac Conduction Defects and Pacemaker Insertion.

Kaess Bernhard M BM Andersson Charlotte C Duncan Meredith S MS Larson Martin G MG Aasbjerg Kristian K Gislason Gunnar H GH Torp-Pedersen Christian C Vasan Ramachandran S RS

Circulation. Arrhythmia and electrophysiology 20190620 7

<h4>Background</h4>The etiopathogenesis of electrocardiographic bundle branch and atrioventricular blocks is not fully understood. We investigated familial clustering of cardiac conduction defects and pacemaker insertion in the FHS (Framingham Heart Study). Additionally, we assessed familial clustering of pacemaker insertion in the Danish general population.<h4>Methods</h4>In FHS, we used multivariable-adjusted logistic regression models to investigate the association of parental atrioventricula ...[more]

PMID: 31216886

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Project description:Renin-angiotensin (RAS) system activation is associated with an increased risk of sudden death. Previously, we used cardiac-restricted angiotensin-converting enzyme (ACE) overexpression to construct a mouse model of RAS activation. These ACE 8/8 mice die prematurely and abruptly. Here, we have investigated cardiac electrophysiological abnormalities that may contribute to early mortality in this model. In ACE 8/8 mice, surface ECG voltages are reduced. Intracardiac electrograms showed atrial and ventricular potential amplitudes of 11% and 24% compared with matched wild-type (WT) controls. The atrioventricular (AV), atrio-Hisian (AH), and Hisian-ventricular (HV) intervals were prolonged 2.8-, 2.6-, and 3.9-fold, respectively, in ACE 8/8 vs. WT mice. Various degrees of AV nodal block were present only in ACE 8/8 mice. Intracardiac electrophysiology studies demonstrated that WT and heterozygote (HZ) mice were noninducible, whereas 83% of ACE 8/8 mice demonstrated ventricular tachycardia with burst pacing. Atrial connexin 40 (Cx40) and connexin 43 (Cx43) protein levels, ventricular Cx43 protein level, atrial and ventricular Cx40 mRNA abundances, ventricular Cx43 mRNA abundance, and atrial and ventricular cardiac Na(+) channel (Scn5a) mRNA abundances were reduced in ACE 8/8 compared with WT mice. ACE 8/8 mice demonstrated ventricular Cx43 dephosphorylation. Atrial and ventricular L-type Ca(2+) channel, Kv4.2 K(+) channel alpha-subunit, and Cx45 mRNA abundances and the peak ventricular Na(+) current did not differ between the groups. In isolated heart preparations, a connexin blocker, 1-heptanol (0.5 mM), produced an electrophysiological phenotype similar to that seen in ACE 8/8 mice. Therefore, cardiac-specific ACE overexpression resulted in changes in connexins consistent with the phenotype of low-voltage electrical activity, conduction defects, and induced ventricular arrhythmia. These results may help explain the increased risk of arrhythmia in states of RAS activation such as heart failure.

Dataset Information

Familial Clustering of Cardiac Conduction Defects and Pacemaker Insertion.

Publications

Familial Clustering of Cardiac Conduction Defects and Pacemaker Insertion.

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