PhD defence J.I. (Jaap) van Waning

Noncompaction cardiomyopathy (NCCM) is a rare disease. NCCM is characterized by hypertrabeculation of myocardium the left ventricle. Recent improvements in cardiac imaging techniques led to an increasing in detection and showed that NCCM occurs less frequently than hypertrophic (HCM) and dilated cardiomyopathy (DCM). The noncompaction phenotype is hypothesized to be a morphologic expression of different pathophysiologic mechanisms in patients with a cardiomyopathy. Interestingly signs of hypertrabeculation may be observed in healthy population without signs of cardiomyopathy, for instance in athletes or in women during pregnancy. In these cases cardiac overload might be related to localized hypertrabeculation of the left ventricle. In patients diagnosed with NCCM the clinical symptoms range from mild to severe outcomes. Heritability plays an important role in NCCM. In around one third of NCCM patients a genetic defect can be identified. In an additional 15% there is familial disease without a known genetic cause. In around 50% of the NCCM patients there is no evidence for a genetic disease; no mutation in a cardiomyopathy gene or familial disease. These cases may have yet unknown (complex) genetic cause(s) carrying small risk for relatives. Alternatively, NCCM may be attributed to non-genetic, secondary causes for hypertrabeculation. Finding a genetic cause for NCCM is of importance for patients and their families, enabling to predict genetic risk and perform family cascade screening. This allows accurate identification of relatives which have an increased risk of developing a cardiomyopathy and it also offers the possibility to reassure relatives who do not carry the genetic risk variant. It is important to know if specific causes are related to outcome. In this thesis we investigated if the genotype is of additional value for clinical management. More precisely whether specific genetic defects could predict the clinical features and the outcome (i.e. the risk of severe cardiac complications) in NCCM.

The public defence will take place at the Senatehall, 1st floor of the Erasmus Building, Campus Woudestein. The ceremony will begin exactly at 09.30 hrs. In light of the solemn nature of the ceremony, we recommend that you do not take children under the age of 6 to the first part of the ceremony.