Disease relevance of Heart Block

• We report here that mice lacking the gene encoding Kir6.1 (known as Kcnj8) have a high rate of sudden death associated with spontaneous ST elevation followed by atrioventricular block as seen on an electrocardiogram [1].
• We conclude that the varying degrees of heart block were secondary to hyperthyroxinemia caused by Graves' disease and exogenous thyroid hormone [2].
• Mothers of children with neonatal lupus erythematosus (NLE) and heart block, as well as patients with Sjögren's syndrome (SS) and systemic lupus erythematosus, have serum autoantibodies that recognize SS-A/Ro autoantigens including the 60-kDa ribonucleoprotein [3].
• This work identifies a novel pathway of events, leading to complete heart block and sudden cardiac death, which involves high expression of calreticulin in the heart [4].
• The mean dose of adenosine required to stop the arrhythmia or to induce atrioventricular block in broad complex SVT (0.14 mg/kg, SD 0.04) was higher than in narrow complex SVT (0.11 mg/kg, SD 0.04) [5].

High impact information on Heart Block

• To define these pathways, we generated mice with a ventricular-restricted knockout of Nkx2-5, which display no structural defects but have progressive complete heart block, and massive trabecular muscle overgrowth found in some patients with Nkx2-5 mutations [6].
• Rheumatoid arthritis in the mother of five siblings with congenital heart block [7].
• Association of maternal systemic lupus erythematosus with congenital complete heart block [8].
• High-grade atrioventricular blocks [9].
• Clonidine hydrochloride may be a factor in producing a high-grade atrioventricular block [10].

Chemical compound and disease context of Heart Block

• Evidence for adenosine mediation of atrioventricular block in the ischemic canine myocardium [11].
• Cardiomyocyte overexpression of iNOS in mice results in peroxynitrite generation, heart block, and sudden death [12].
• Heart block in a patient on propranolol and fluoxetine [13].
• Diltiazem and heart block [14].
• First-degree atrioventricular block induced by oral cimetidine [15].

Biological context of Heart Block

• Atenolol and alinidine significantly decreased the basic heart rate without causing more sinus arrest or higher-degree atrioventricular block [16].
• Two patients developed transient atropine-responsive complete heart block and four patients developed transient congestive heart failure with increases in pulmonary capillary wedge pressure [17].
• Despite the near universal association of congenital heart block and maternal Abs to SSA/Ro and SSB/La, the intracellular location of these Ags has made it difficult to substantiate their involvement in pathogenicity [18].
• Sera and IgG-enriched fractions from anti-Ro/SS-A antibody-positive mothers of infants with neonatal lupus erythematosus and congenital heart block bind to neonatal, rather than adult, rabbit cardiac tissue and alter the transmembrane action potential (i.e., inhibit repolarization) [19].
• The duration of diastoles was varied after induction of a heart block with formaldehyde [20].

Anatomical context of Heart Block

• Congenital heart block develops in fetuses after placental transfer of Ro/SSA autoantibodies from rheumatic mothers [21].
• Postoperative development or exacerbation of anatomic tricuspid valve regurgitation occurs in TGA [S,L,L] and may be causally related to surgical complete atrioventricular block [22].
• OBJECTIVE: To assess the true prevalence of congenital complete heart block (CCHB) in infants of anti-Ro/SSA-positive women known to have connective tissue disease (CTD) and, secondarily, to evaluate the prevalence of other electrocardiographic abnormalities in these newborns at birth [23].
• Injection of 25 and 50 micrograms/ml of ethacizin into the atrioventricular (AV) node artery significantly (p less than 0.001) prolonged AV conduction time with occasional second degree heart block [24].
• Cardiac defects included interrupted inferior caval vein in 92%, anomalous pulmonary veins in 56%, atrioventricular septal defect in 49%, pulmonary atresia or stenosis in 28% and aortic coarctation in 16%, with congenital atrioventricular block in 7% [25].

Gene context of Heart Block

• Importantly, DMPK+/- mice develop first-degree heart block, a conduction defect strikingly similar to that observed in DM patients [26].
• Sox6 is a candidate gene for p100H myopathy, heart block, and sudden neonatal death [27].
• Cytokine polymorphisms and histologic expression in autopsy studies: contribution of TNF-alpha and TGF-beta 1 to the pathogenesis of autoimmune-associated congenital heart block [28].
• OBJECTIVES: We hypothesized that neonatal long QT syndrome (LQTS) with 2:1 atrioventricular block (AVB) could be related to HERG mutations [29].
• OBJECTIVES: We investigated the prevalence of lamin A/C (LMNA) gene defects in familial and sporadic dilated cardiomyopathies (DCM) associated with atrioventricular block (AVB) or increased serum creatine-phosphokinase (sCPK), and the corresponding changes in myocardial and protein expression [30].

Analytical, diagnostic and therapeutic context of Heart Block

• Electrocardiography showed evidence of atrial fibrillation and atrioventricular block [31].
• Maternal antibodies to SS-B/La were detected by ELISA in 76% of the heart block group, 73% of the cutaneous neonatal lupus group, 15% of the group with healthy children, and 7% of the fetal death group [32].
• DNA typing of maternal HLA in congenital complete heart block: comparison with systemic lupus erythematosus and primary Sjögren's syndrome [33].
• Risk of congenital complete heart block in newborns of mothers with anti-Ro/SSA antibodies detected by counterimmunoelectrophoresis: a prospective study of 100 women [23].
• CONCLUSIONS: Nonsurgical septal reduction therapy resulted in a significantly higher incidence of complete heart block, but the risk was reduced with contrast echocardiography and slow ethanol injection [34].

References