Welcome to the Risk Project 

The contribution of ventricular arrhythmia to morbidity and mortality in the elderly is substantial. Sudden cardiac death (SCD) is one of the most important causes of cardiovascular death with an incidence rate of one per 1000 patient years. SCD and non-fatal ventricular arrhythmia as a consequence of repolarization disturbances are frequent adverse effects of many commonly used drugs (e.g. antiarrhythmics, antidepressants, antipsychotics, antihistamines, certain antibiotics) in the elderly.

QT interval prolongation is the main parameter measured to assess the arrhythmogenic potential of drugs, but fails to adequately predict the risk of sudden cardiac death associated with drug use. Several other ECG parameters have been proposed, e.g, beat-to-beat changes of the QT interval, and heart rate variability. In addition, there are other effect modifiers, e.g., genetic variants and metabolic parameters.

 

The objective of the Risk-Project is to improve the insight in risk factors for Sudden Cardiac Death

 

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Risk-project main contributors:

Mark Eijgelsheim, PhD (project lead)

Peter Rijnbeek, PhD (project lead)

Maartje N Den Besten-Niemeijer (PhD Student)

Marten E van den Berg (PhD Student)

Gerard van Herpen (Cardiologist)

Jan Kors, PhD (Senior Researcher)

Prof Bruno Stricker (Promotor)

 

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Contact Information

The Risk-project is lead by the Department of Medical Informatics and the

Department of Epidemiology the Erasmus Medical Center Rotterdam.

 

For more information please contact:

Peter Rijnbeek

email: p.rijnbeek-add-erasmusmc.nl

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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.

 

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