The overall aim of the project is to study risk factors for repolarization disturbances, fatal and non-fatal drug-induced ventricular arrhythmia, and to study genetic and metabolic effect modifiers. Furthermore, we aim to develop and assess novel electrocardiographic measures as risk indicators and develop a risk score for ventricular arrhythmia (Sudden Cardiac Death) that incorporates clinical and other risk factors.
The project is divided in four topics.
Topic 1: Magnitude of the problem
The goal of this topic was to gain insights in the magnitude of the problem. First, we have assessed the incidence of SCD in the general population and showed that the incidence is declining. Second, within a population-based cohort of persons aged 45 years and older we studied the association between concomitant use of multiple QTc-prolonging drugs and repolarization duration. Third, tri-cyclic anti-depressants were studied for their perceived association with QT interval. We showed that this association is driven by a heart rate effect that is insufficiently corrected for.
Topic 2: Genetic and metabolic effect modifiers
Genetic and metabolic effect modifiers were studied extensively. For example, we wrote a paper that provides an update on the pharmacogenetics of drug-induced QT interval prolongation. During the project we continue to work in a consortium using genome wide analysis approaches to elucidate the missing heritability. We have published multiple papers on gene variants in relation to the risk of sudden cardiac death and their effects on heart rate. In the area of metabolic effect modifiers we studied the association between thyroid function and cardiovascular disease as a risk factor for sudden cardiac death. Finally, we are studying other risk factors for association with SCD namely subclinical echocardiographic abnormalities and Chronic Obstructive Pulmonary Disease (COPD).
Topic 3: ECG-derived risk indicators
We studied multiple ECG parameter and their value as risk indicators. Part of the research focussed on the eWe have developed a new algorithm to measure QT variability, which enables large-scale assessment.
Topic 4: Risk score development
We study a risk score that contains clinical risk factors and ECG-related risk factors for Sudden Cardiac Death.