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A Study of Regional and Global Myocardial Morphology and Function in Various Substrates of Cardiac Remodelling

In contemporary clinical cardiology practice, echocardiography plays a leading role in the diagnosis and management guidance of various forms of myocardial remodelling. Furthermore, it is the most commonly used diagnostic technique in the elucidation of the underlying substrates and pathophysiologic mechanisms of heart failure as a consequence of ventricular remodelling. Due to its widespread availability, non-invasiveness, user-friendliness and relatively low cost, echocardiography is still irreplaceable by other cardiac imaging methods which should rather be seen as complementary diagnostic tools. This thesis sought to study several types of ventricular remodelling and their consequences on regional and global myocardial function, employing different echocardiographic tools and dedicated signal and image analysis algorithms in the detection of ventricular dysfunction. Recent echocardiographic techniques based on Myocardial Velocity Imaging have provided the possibility of a more detailed and integrated insight to cardiac (dys-) function. Based on novel understandings, we first gave an original integrated overview on ‘cardiac function’, distinguishing intrinsic myocyte function (often referred to as contractility) and ventricular pump function as well as the main components of function, namely force development and deformation. Additionally, the boundary conditions in which the heart functions, which determine the interactions between these components were defined as: a) wall properties such as tissue composition/elasticity, fibre structure and global geometry, and b) interaction between the heart and peripheral circulation, mostly described as (pressure & volume) loading conditions. Furthermore, Doppler echocardiography data were analyzed in a study addressing flow remodelling as a consequence of cellular and force remodelling in ischaemically remodelled hearts. A dedicated automated quantification of the CW outflow Doppler traces was used to define specific trace parameters indicative of myocardial dysfunction. It was shown that decreased overall contractility results in a more symmetrical outflow velocity profile, which would suggest that the global development of contractile force has been remodelled to cope with the decreased output resulting from decreased contractility. Similar automatic quantification of the aortic instantaneous peak velocities was further employed in patients with hypertrophic remodelling due to aortic stenosis. This study has shown that the values of trace asymmetry before surgery are predictive of the change in EF pre- and postoperatively: all of the patients with markedly symmetric preoperative instantaneous peak velocities showed stagnation or deterioration of EF postoperatively. Furthermore, the study has proven that the symmetry of the shape of the instantaneous peak velocities is a more reliable predictor of functional improvement after the valve replacement procedure as compared to mean aortic gradient and aortic valve area which are widely used in preoperative assessment of patients with aortic stenosis. An intraoperative Doppler myocardial imaging study was performed along with standard echocardiography in an analysis of electrical remodelling in patients with LBBB during the CRT implantation procedure. In addition to confirming the septal flash as a mechanical consequence of the underlying electrical problem and a valid marker of intraventricular dyssynchrony, an acute contractility recruitment, resolution of the septal flash as well as reverse remodelling immediately following CRT device activation was shown in these patients. As opposed to remodelling induced by changes in loading conditions, evidence of hypertrophy and hypercontractility without an additional change in afterload resulting in increased cardiac output and inducing additional signs of vascular remodelling was demonstrated in patients with early stage acromegaly. Finally, a comprehensive view on the changing role of echocardiography in the diagnosis of hypertrophic myopathies is presented. Previous knowledge as well as regional deformation data (including deformation pattern analysis) are combined to provide an indicator toward the disease underlying hypertrophic ventricular remodelling: in hypertensive heart disease LVH is predominantly localized in the basal septal region showing reduced systolic strain values with post-systolic shortening ; systemic diseases such as Fabry’s disease often affect a specific region - the basal (infero)lateral segment in which post-systolic deformation is often present. Hypertrophic cardiomyopathy is associated with regions of local fibre disarray, in which no myocardial deformation is present at all, while in the surrounding segments (often showing similar thickness) deformation is reduced, but almost normal as compared to undiseased hearts. The absence of deformation is mostly associated with the thickest segments. Amyloidosis seems to provide an exception in which the impairment of systolic function affects the myocardium globally – it is presented with global LVH and diffuse, severe reduction of longitudinal strain, while the radial strain is still preserved, but of low values.

Myocardial morphology; Myocardial function; Cardiac remodelling; Coronary artery disease; aortic stenosis; hypertrohic myopathies; Doppler echocardiography; Doppler myocardial imaging

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