Assessment of Ventricular Function in Normal and Failing Hearts Using 4D Flow CMR

Heart failure is a common disorder and a major cause of illness and death in the population, creating an enormous health-care burden. It is a complex condition, representing the end-point of many cardiovascular diseases. In general heart failure progresses slowly over time and once it is diagnosed it has a poor prognosis which is comparable with that of many types of cancer. The heart has an ability to adapt in response to long lasting increases in hemodynamic demand; the heart conforms its shape and size in order to maintain adequate cardiac output. This process is called remodeling and can be triggered by pathologies such as hypertension or valvular disease. When the myocardial remodeling is maintained chronically it becomes maladaptive and is associated with an increased risk of heart failure. In many cases, heart failure is associated with left bundle branch block (LBBB). This electrical disturbance leads to dyssynchronous left ventricular (LV) contraction and relaxation which may contribute to cardiac dysfunction and ultimately heart failure. Mechanical dyssynchrony can be treated with cardiac resynchronization therapy (CRT). However, many heart failure patients do not demonstrate clinical improvement despite CRT. Blood flow plays an important role in the normal development of the fetal heart. However, flow-induced forces may also induce changes in the heart cells that could lead to pathological remodeling in the adult heart. Until recently, measurement tools have been inadequate in describing the complex three-dimensional and time-varying characteristics of blood flow within the beating heart. 4D (3D + time) flow cardiovascular magnetic resonance (CMR) enables acquisition of three-dimensional, three-directional, time-resolved velocity data from which visualization and quantification of the blood flow patterns over a complete cardiac cycle can be performed. In this thesis, novel 4D Flow CMR based methods are used to study the intraventricular blood flow in healthy subjects and heart failure patients with and without ventricular dyssynchrony in order to gain new knowledge of the ventricular function. Different flow components were assessed in normal heart ventricles. It was found that inflowing blood that passes directly to outflow during the same heartbeat (the Direct Flow component) was larger and possessed more kinetic energy (KE) than other flow components. Diastolic flow through the normal heart appears to create favorable conditions for effective systolic ejection. This organized blood flow pattern within the normal LV is altered in heart failure patients and is associated with decreased preservation of KE which might be unfavorable for efficient LV ejection. Inefficient flow of blood through the heart may influence diastolic wall stress, and thus contribute to pathological myocardial remodeling. In dyssynchronous LVs of heart failure patients with LBBB, Direct Flow showed even more reduced preservation of KE compared to similarly remodeled LVs without LBBB. Furthermore, in LBBB patients, LV filling hemodynamic forces, acting on the myocardium, were more orthogonal to the main flow direction compared to patients without LBBB. Deviation of LV flow forces and reduction of KE preservation and may reflect impairment of LV diastolic function and less efficient ensuing ejection related to dyssynchrony in these failing ventricles. Blood flow patterns were also studied with respect to fluctuations of the velocity of the flow (turbulent flow) in normal and failing LVs. In failing hearts, turbulent kinetic energy (TKE) was higher during diastole than in healthy subjects. TKE is a cause of energy loss and can thus be seen as a measure of flow inefficiency. Elucidating the transit of multidimensional blood flow through the heart chambers is fundamental in understanding the physiology of the heart and to detect abnormalities in cardiac function. The 4D Flow CMR parameters presented in this thesis can be utilized to detect altered intracardiac blood flow and may be used as markers of deteriorating cardiac function, pathological remodeling and mechanical dyssynchrony in heart failure.