PhD defence S. (Sven) Geurts

Summary:

The human heart (myocardium) is a fascinating and powerful fist-sized muscular organ that pumps around blood through the cardiovascular system. The heart is located in the middle compartment of the chest called the mediastinum. The heart is anatomically divided into four chambers: two upper chambers called the left and right atria and two lower chambers called the left and right ventricle. At rest the heart beats around 60-80 times per minute whereas during physical exertion it may beat up to 180-200 times per minute, depending on the metabolic needs of the body. The pump function and its frequency is further regulated by the sinoatrial node, located in the upper right atrium, which is the orchestrator of the cardiac rhythm. In a physiological setting, electrical activity is initiated by pacemaker cells in the sinoatrial node. These very specialized cells generate an electrical current that travels in series from the sinoatrial node to the atrioventricular node to the bundle of His and ends at the Purkinje fibers located in the ventricles. This travelling electrical current causes the atria and ventricles to contract sequentially which makes blood flow from the atria to the ventricles to the cardiovascular system. In atrial fibrillation, this normal cardiac rhythm is disturbed by chaotic electrical activity in the atria. This chaotic atrial electrical activity or excitation leads to unproductive atrial contraction and may subsequently cause an irregularly irregular ventricular excitation and contraction. atrial fibrillation is the most common cardiac arrhythmia worldwide and its prevalence has reached epidemic proportions due to aging of the general population and the increasing prevalence of atrial fibrillation risk factors such as obesity, hypertension, diabetes mellitus, coronary heart disease, and heart failure. In the past decades, the scientific community propelled the knowledge regarding the epidemiology, prediction, pathophysiology, and treatment of atrial fibrillation. Despite this global scientific effort in the past decades to better understand this complex and polygenetic disorder, the atrial fibrillation etiology remains unclear. As one can imagine this complexity further complicates the prediction, prevention, and management of atrial fibrillation. Generating new evidence is therefore warranted to reduce the disease burden of atrial fibrillation. Therefore, we mainly investigated the etiology of atrial fibrillation in participants from the Rotterdam Study, the UK Biobank, and several large-scale genomic consortia.