New modalities to monitor and interfere with cardiac remodeling

This thesis describes new modalities to monitor and interfere with cardiac remodeling. Current disease management mainly consists of drug treatments; however the effects are not always as hoped for and the need for new strategies exists. In part one of this thesis we describe new interference strategies to prevent structural remodelling and arrhythmias. We investigated CaMKII inhibition in genetically modified mice in combination with the anti-fibrotic drug eplerenone, which was able to reduce structural remodelling and deterioration of function. We also describe gene therapy introducing the skeletal sodium channels after myocardial infarction (MI) in dogs to prevent abnormal conduction in the epicardial border zone of the infarct. We conclude that the chosen delivery modality is of great importance for anti-arrhythmic potential. In part two we describe new modalities to monitor cardiac remodelling after MI and in arrhythmogenic cardiomyopathy (ACM). We investigated the potential of circulating biomarkers of fibrotic turnover and a new echocardiography analysis to predict scar size after a MI in patients compared to late gadolinium enhancement MRI routinely used to measure scar size. Although we found a correlation of our new modalities with scar size these techniques are not yet applicable in clinical practice. In patients with ACM we identified decreased myocardial plakoglobin expression. We investigated the use of buccal mucosa cells (BCM) to replace cardiac biopsies for plakoglobin screening. On population level we found significant reductions in plakoglobin expression in BCM, but on individual level changes appeared too subtle to use as diagnostic tool.