The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal Mendelian Long QT Syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals we identified 35 common variant QT interval loci, that collectively explain ∼8-10% of QT variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 novel QT loci in 298 unrelated LQTS probands identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode for proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies novel candidate genes for ventricular arrhythmias, LQTS,and SCD.

Objectives. To investigate the relationship between cardiac repolarization (QT interval duration) and intima media thickness (IMT) of the carotid arteries as surrogate measures of subclinical atherosclerosis. Design. Prospective study with consecutive subjects enrolled in the SAPHIR program (Salzburg Atherosclerosis Prevention Program in Subjects at High Individual Risk). Setting. The analysis of the material was performed at the departments of medicine and neurology of a university hospital. Subjects. The study cohort comprises a populationbased sample of 1199 clinically healthy subjects (851 men and 348 women; age 39-66 years). Exclusion criteria were cardiovascular disease, diabetes, atrial fibrillation, bundle branch block and use of medication affecting QT interval duration. Main outcome measures. IMT of common (CCA) and internal carotid arteries (ICA) was measured by B-mode ultrasound. QT interval duration was determined in the resting 12-lead electrocardiogram by an automatic analysis program. The QT intervals were corrected for heart rate with five standard equations (QTc-Bazett, -Fridericia, -Framingham, -Hodges and -Rautaharju) and tested for their relationship with carotid IMT after adjustment for clinical and metabolic variables. Results. Females had higher heart rates than males (64 ± 10 b min )1 vs. 60 ± 9 b min )1 , P < 0.0005), with longer mean QT (410 ± 28 ms vs. 404 ± 28 ms, P ¼ 0.003) and QTc intervals in all correction formulae (P < 0.0005). Significant correlations between QT/QTc and ICA IMT (r ¼0.14-0.16) were found in males. In the general linear model the association between QTc (except for Bazett) and ICA IMT remained significant after adjusting for age, BMI and further cardiovascular risk factors. In females the crude correlations between QT/QTc and ICA IMT were lower than those with CCA IMT. Only the correlation between uncorrected QT and CCA IMT (r ¼ 0.15, P ¼ 0.006) remained significant after adjustment for covariates. Conclusions. The results of the present study demonstrate that QT and QTc prolongation are in part associated with IMT of carotid arteries, which is an established risk marker of subclinical atherosclerosis. In men the data support the hypothesis of an association between QTc and ICA IMT. In women a statistically significant relationship was found between the uncorrected QT interval and CCA IMT. These findings suggest that differences in carotid IMT and ventricular repolarization between genders might be related to hormonal and nonhormonal effects.

For frailty assessment implementation of validated standardized test protocols based on well-established assessment tools, covering all domains of frailty among TAVR centers is crucial for patient selection. Secondly, validated cutoffs and scoring systems are essential.

The PPM implantation rate of about 20 % after TAVI is comparable to previously published data. The need for permanent pacing is linked to the valve type and preexistence of a right bundle branch block. At short-term more than half of the patients implanted with a device were not strictly PM-dependent, but presented an underlying intrinsic rhythm, indicating that temporary AV conduction disturbances may recover over time. This might justify a more conservative approach in some patients under watchful waiting. From another point of view, ventricular pacing at a regular or sensor-modulated rate may provide rhythm stability and chronotropy during the short-term period post-TAVI.