PhD defence R. (Roy) Huurman

Below is a brief summary of the dissertation:

We first leveraged extensive genetic data, from which we concluded that the specific variant location can explain cellular differences between subjects with the same variant. Furthermore, we constructed a polygenic risk score which explains, in part, the large disease variability seen in HCM patient cohorts. We investigated the utility of novel imaging markers on echo and cardiac magnetic resonance (CMR) imaging and discovered that CMR has excellent performance in distinguishing genotype-positive subjects compared to healthy controls. We answered a number of real-world clinical challenges focusing on various imaging and monitoring modalities, showcasing their value in several scenarios, including chest pain, sudden cardiac death prediction and apical aneurysms. Importantly, we tested the value of CMR on top of electrocardiography and echo in the work-up of subjects referred for cardiac screening following genetic testing. We showed that CMR has clear value, judging by the large number of subjects that did not have hypertrophic cardiomyopathy on echo who were reclassified following CMR. We investigated if survival after myectomy is different between men and women, revealing that that outcome was similar, despite women seemingly having worse disease on echo. Our results suggest that male-female differences have a biological basis, which include the role of sex hormones in development of hypertrophy. Lastly, we look toward the future by showing several ongoing national collaborative efforts.