Prevalence of interatrial block in patients with Friedreich's ataxia.

UNLABELLED: Interatrial block is a predictor of atrial arrhythmias. Aim of the present study was to estimate the prevalence of interatrial block (IAB) in Friedreich's Ataxia (FA) compared to controls and correlate it with echocardiographic and genetic features. METHODS: IAB, defined as an electrocardiographic (ECG) derived P-wave duration >120 ms, echocardiographic variables and genetic markers were evaluated in 23 FA patients with no manifestation of cardiac involvement and were compared to 23 sex- and age-matched controls. RESULTS: IAB was significantly more frequent among FA patients compared to controls (11/23 vs 1/23, p<0.005 respectively). However, no correlations with echocardiographic parameters or Guanine-Adenine-Adenine (GAA) trinucleotide repeat lengths could be established. CONCLUSION: Early recognition of IAB could allow the identification of asymptomatic FA patients who are prone to develop potentially life-threatening arrhythmias.

Deficient zebrafish ether-à-go-go-related gene channel gating causes short-QT syndrome in zebrafish reggae mutants.

BACKGROUND: Genetic predisposition is believed to be responsible for most clinically significant arrhythmias; however, suitable genetic animal models to study disease mechanisms and evaluate new treatment strategies are largely lacking. METHODS AND RESULTS: In search of suitable arrhythmia models, we isolated the zebrafish mutation reggae (reg), which displays clinical features of the malignant human short-QT syndrome such as accelerated cardiac repolarization accompanied by cardiac fibrillation. By positional cloning, we identified the reg mutation that resides within the voltage sensor of the zebrafish ether-à-go-go-related gene (zERG) potassium channel. The mutation causes premature zERG channel activation and defective inactivation, which results in shortened action potential duration and accelerated cardiac repolarization. Genetic and pharmacological inhibition of zERG rescues recessive reg mutant embryos, which confirms the gain-of-function effect of the reg mutation on zERG channel function in vivo. Accordingly, QT intervals in ECGs from heterozygous and homozygous reg mutant adult zebrafish are considerably shorter than in wild-type zebrafish. CONCLUSIONS: With its molecular and pathophysiological concordance to the human arrhythmia syndrome, zebrafish reg represents the first animal model for human short-QT syndrome.

Familial progressive sinoatrial and atrioventricular conduction disease of adult onset with sudden death, dilated cardiomyopathy, and brachydactyly. A new type of heart-hand syndrome?

We identified a family with 10 affected members in four generations suffering from adult-onset progressive sinoatrial and atrioventricular conduction disease, sudden death due to ventricular tachyarrhythmia, dilated cardiomyopathy, and a unique type of brachydactyly with mild hand involvement (short distal, middle, proximal phalanges and clinodactyly) and more severe foot involvement (short distal, proximal phalanges and metatarsal bones, short or absent middle phalanges, terminal symphalangism, duplication of the bases of the second metatarsals, extra ossicles, and syndactyly). The phenotype differences from other reported genetic abnormalities and linkage exclusion of Holt-Oram syndrome, ulnar-mammary syndrome, brachydactyly type B or Robinow syndrome, and cardiac conduction disease or Brugada syndrome loci suggest that we report on a new hereditary heart-hand syndrome.

Cardiac involvement and CTG expansion in myotonic dystrophy.

Although cardiac complications are well known in myotonic dystrophy (DM), patients rarely manifest symptoms of cardiac disease, and if so they most often show conduction abnormalities or arrhythmia. In this study, specific cardiac findings were reviewed in 79 patients with DM. No correlation was found between the cardiac assessments and the CTG expansion. Thus, for a single patient the cardiac involvement in the disease can not be predicted from the findings of the genetic investigation. On the other hand, a clear positive relationship of the PR interval with the QRS duration was revealed, as well as a positive correlation between the age of the DM patient and the QRS duration, which increases with 0,54 ms/year. Systolic dysfunction, evaluated by transthoracic echocardiography, seems to be quite uncommon. In 32 % of the patients with a normal ECG, the 24 h Holter monitoring showed arrhythmias and conduction abnormalities. Based on these findings we recommend a follow up of DM patients not only based on the ECG, but also through 24 h Holter monitoring.

Conduction disturbances and increased atrial vulnerability in Connexin40-deficient mice analyzed by transesophageal stimulation.

BACKGROUND: Recently, it has been reported that connexin40 (Cx40) deficiency in targeted mouse mutants is associated with a prolongation of P-wave and QRS complex duration on surface electrograms. The specific effects of Cx40 deficiency on sinus node function, sinoatrial, and atrioventricular conduction properties as well as on atrial vulnerability have not yet been investigated systematically by electrophysiological analysis. METHODS AND RESULTS: Fifty-two mice (18 Cx40(+/+), 15 Cx40(+/-), and 19 Cx40(-/-) mice) were subjected to rapid atrial transesophageal stimulation after anesthesia with avertin. A significant prolongation of sinus node recovery time was noticed in Cx40(-/-) mice compared with Cx40(+/-) and Cx40(+/+) mice (287.8+/-109.0 vs 211.1+/-61.8 vs 204.4+/-60.9 ms; P<0.05). In addition, Wenckebach periodicity occurred at significantly longer atrial pacing cycle lengths in Cx40(-/-) mice than in Cx40(+/-) or Cx40(+/+) mice (93. 3+/-11.8 vs 83.9+/-9.7 vs 82.8+/-8.0 ms, P<0.05). Analysis of 27 Cx40(-/-) mice showed a significant increase in intra-atrial conduction time and atrioventricular conduction time compared with 52 Cx40(+/-) and 31 wild-type (Cx40(+/+)) mice. Furthermore, in Cx40(-/-) mice, atrial tachyarrhythmias could be induced frequently by atrial burst pacing, whereas no atrial arrhythmias were inducible in heterozygous or wild-type mice. CONCLUSIONS: This study demonstrates that Cx40 deficiency is associated with sinoatrial, intra-atrial, and atrioventricular conduction disturbances. In atrial myocardium of the mouse, Cx40 deficiency results in increased atrial vulnerability and might contribute to arrhythmogenesis.

[Adult familial idiopathic binodal block]. / Le bloc binodal idiopathique et familial de l'adulte.

Four brothers with a maximum age difference of 20 years, the eldest of whom has been re-examined after a 10 year interval, have sinoatrial block, a supra-hisian atrioventricular block and paroxysmal atrial arrhythmias which have led to partial atrial standstill in the eldest: left anterior hemiblock is also present in the two youngest brothers. The condition is very well tolerated. This family is compared to the other 12 reported cases of familial idiopathic binodal block in the adult, an autosomal dominant condition with variable penetration. The diagnosis is reserved and justifies endocavitary investigation of the sinus node function and atrioventricular conduction in the four brothers and the most exposed members of their family. The mechanism of the condition is unknown. It seems to arise from variable degrees of nonspecific of the nodal and atrial tissues.