Right ventricular adaptation to chronic abnormal loading: and implications for patients with tetralogy of Fallot

Tetralogy of Fallot is a congenital heart disease, named after the French physician Étienne Fallot. Without treatment, this is a disease with high morbidity and early mortality. Fortunately, survival into adulthood is excellent when cardiac surgery is performed in the first year of life. However, important sequels of the disease and the operation put a burden on these patients later in life: patients are at risk of progressive enlargement (dilatation) of the right heart chamber, possibly resulting in right heart failure or even death. Also, patients are at risk of cardiac arrhythmia, which can be both stressful and life threatening. In this thesis, we have studied various mechanisms of cardiac adaptation to chronic abnormal loading, as can be the case in tetralogy of Fallot, by means of experimental studies. Such insights are important to determine future targets of treatment. Also, we established that female sex is associated with favorable function and outcome. Next, by means of MRI-images of the heart of patients, we established several predicting factors for cardiac arrhythmia, and demonstrated that the female heart is relatively smaller, compared to the male heart. This has consequences for the indication of treatment. In conclusion, this thesis adds to our understanding of cardiac adaptation to chronic abnormal loading, both in experimental studies and imaging-based studies in patients. Herewith we aim to earlier identify patients at increased risk, and to guide future studies for new treatment options.