Rare genetic variants previously associated with congenital forms of long QT syndrome have little or no effect on the QT interval.

AIMS: We studied whether variants previously associated with congenital long QT syndrome (cLQTS) have an effect on the QTc interval in a Danish population sample. Furthermore, we assessed whether carriers of variants in cLQTS-associated genes are more prone to experience syncope compared with non-carriers and whether carriers have an increased mortality compared with non-carriers. METHODS AND RESULTS: All genetic variants previously associated with cLQTS were surveyed using the Human Gene Mutation Database. We screened a Danish population-based sample with available whole-exome sequencing data (n = 870) and genotype array data (n = 6161) for putative cLQTS genetic variants. In total, 33 of 1358 variants previously reported to associate with cLQTS were identified. Of these, 10 variants were found in 8 or more individuals. Electrocardiogram results showed normal mean QTc intervals in carriers compared with non-carriers. Syncope data analysis between variant and non-variant carriers showed that 4 of 227 (1.8%) and 95 of 5861 (1.6%) individuals, respectively, had experienced syncope during follow-up (P = 0.80). There was no significant difference in overall mortality rates between carriers [7/217 (3.2%)] and non-carriers [301/6453 (4.7%)] (P = 0.24). CONCLUSION: We present QTc data and register data, indicating that 26 cLQTS-associated variants neither had any effect on the QTc intervals nor on syncope propensity or overall mortality. Based on the frequency of individual gene variants, we suggest that the 10 variants frequently identified, assumed to relate to cLQTS, are less likely to associate with a dominant monogenic form of the disease.

Role of PR-Interval In Predicting the Occurrence of Atrial Fibrillation.

The identification of individuals at high risk of developing atrial fibrillation (AF) is important to prevent potentially lethal and invalidating complications of this arrhythmia. Recently, several studies have investigated the association between PR-interval and the risk of AF and have tested the value of PR-interval in personalized risk scores for AF. However, the results of these studies are generally conflicting. When looking for an association between a prolonged PR-interval (first-degree atrioventricular [AV] block vs. normal PR-interval) and an increased risk of AF, not all studies were able to find a consistent and statistically significant association. In two recent studies, however, the investigators were able to show an increased risk of AF for individuals with PR-intervals in the short range compared with individuals in the middle range. The existence of a true U-shaped relationship could potentially explain part of the conflicting results from investigators only looking for an increased risk for longer PR-intervals. However, regardless of these speculations, the association seems relatively weak. The significance of PR-interval in risk prediction of AF has been tested in three independent risk scores where model selection primarily was based on improvement in c-statistics. In one risk score, PR-interval improved the predictive value of the risk model, whereas it did not in the other two risk scores. Further studies are warranted before any final conclusion can be drawn, although based on the current evidence, it is reasonable to conclude that the predictive value of PR-interval in AF risk prediction is limited.