Research Highlights - Amsterdam Center, Netherlands
The Amsterdam site is building or collaborating with several large cohorts of patients at risk for SCD. One is AGNES (Arrhythmia Genetics in the Netherlands), a unique clinical and DNA dataset generated by medical centers across Holland. AGNES consists of patients either with or without VF during the first 90 minutes after onset of their first MI, and to date almost 1000 patients have been collected. Patients with earlier infarcts or signs of structural heart disease are excluded. An initial analysis (Dekker et al., 2006) found no difference in baseline characteristics, including age, gender, drug use, medical history, and ECG parameters recorded prior to the index infarction; as well, infarct size and location, culprit coronary artery, and the proportion of patients with multivessel disease were similar between groups. However, analysis of ECGs performed at hospital admission for the index STEMI showed that there was greater ST segment elevation among cases (OR per 10-mm ST deviation 1.59, 95% CI 1.25 to 2.02).
In addition, although the prevalence of cardiovascular disease among parents and siblings was similar between cases and controls (73.1% and 73.0%, respectively), there was a significantly higher incidence of a family history of sudden death among cases than controls (43.1% and 25.1%, respectively; OR 2.72, 95% CI 1.84 to 4.03). Thus, in this population of STEMI patients, the risk of primary VF was determined by cumulative ST deviation and a family history of sudden death. This finding not only motivates further genetic analyses, but also suggests that pathways directly involved in generating ST segment elevation are attractive candidates for interrogation at the genomic level.
A second population includes patients recruited after hospitalization for heart failure, and followed prospectively. Recent hospitalization for heart failure is an increasingly well-recognized marker for high risk for SCD. The COACH (Coordinating study evaluating Outcomes of Advising and Counseling in Heart failure) cohort has been recruited at the University of Groningen and its availability to the Network has been confirmed in writing via the Amsterdam centre. COACH is a multi-center trial including 17 centers in the Netherlands, which has the overall goal of assessing the value of nurse-led heart failure management in patients with hospitalization for heart failure. As in other databases, extensive demographic information as well as consented DNA samples are in place.
The Amsterdam site also contributes cases to studies of drug-induced long QT syndrome. In addition, several large families with monogenic arrhythmia syndromes but variable clinical phenotypes have been ascertained, and will be analyzed to identify genes modulating the clinical phenotype. Complementary basic science includes studies of mice with ion channel mutations to identify mechanisms contributing to variable whole heart phenotypes.