Skeletal and cardiac muscle disorders are associated with substantial morbidity and mortality. Despite many improvements in the medical and surgical management of these disorders, development of... Show moreSkeletal and cardiac muscle disorders are associated with substantial morbidity and mortality. Despite many improvements in the medical and surgical management of these disorders, development of effective treatments has proven to be challenging. This is because of the limited suitability of existing experimental models for acquiring a thorough understanding of the mechanisms underlying skeletal and cardiac muscle diseases and the lack of efficiency and specificity of many of the currently available therapeutic interventions. Therefore, the aim of this thesis was to establish and use dedicated cellular models in combination with genetic interventions to study the biology of skeletal and cardiac muscles in healthy and diseased states and thereby identify potential targets for future therapeutic interventions. The experiments described in this thesis indeed emphasized the importance of cellular models for (i) elucidating the mechanisms underlying skeletal and cardiac muscle diseases and (ii) identification of novel therapeutic targets. This thesis also underlined the usefulness of viral vector-mediated gene transfer technology for development of biological assays and the evaluation of therapeutic targets. In conclusion, application of in vitro models in combination with genetic interventions can improve our understanding of skeletal and cardiac muscle diseases and aid development of new therapies for these disorders. Show less
Radiofrequency catheter ablation (RFCA) has become an important treatment option in the management of supraventricular arrhythmias such as atrioventricular (nodal) re-entry tachycardia, atrial... Show moreRadiofrequency catheter ablation (RFCA) has become an important treatment option in the management of supraventricular arrhythmias such as atrioventricular (nodal) re-entry tachycardia, atrial tachycardia, atrial flutter and atrial fibrillation (AF). Particularly in the management of AF the number of RFCA procedures performed is growing rapidly. Three-dimensional electroanatomical mapping combined with non-invasive imaging is currently a state of the art technique to guide RFCA for complex arrhythmias such as AF ablation, providing information on anatomical landmarks and arrhythmogenic substrate with higher accuracy and with less radiation exposure than fluoroscopy or conventional catheter based mapping. Importantly, accurate characterization of the arrhythmogenic substrate and the underlying mechanisms of the arrhythmia as well as visualization of anatomical landmarks are pivotal to optimize the results of RFCA. Comprehensive pre-procedural evaluation may help to identify the appropriate substrate as well as to identify patients with a high likelihood to benefit from a RFCA procedure. Show less
