Rotation, Velocity and Deformation Imaging in Hypertrophic Cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is regarded as one of the most common inherited cardiac diseases. In a number of population studies the prevalence of HCM is estimated in the general population to be at least 1 in 500. HCM is inherited with an autosomal dominant Mendelian pattern, variable expressivity, and age-related (and incomplete) penetrance. Clinical diagnosis of HCM requires confirmation of phenotypic expression, that is an unexplained increase in left ventricular (LV) wall thickness (≥15 mm in adults) associated with a nondilated LV chamber with cardiac imaging (usually echocardiography). Phenotype positive patients may show different patterns of LV hypertrophy: reverse septal curvature, sigmoidal and apical forms have been described. Relatives identified with pathogenic mutations (gene carriers) but without evidence of the disease phenotype comprise a new HCM subgroup, designated as genotype positive-phenotype negative individuals. The risk of eventually developing LV hypertrophy in this group is currently uncertain. In this thesis we investigated the value of speckle tracking echocardiographically (STE)-derived global and regional LV rotation and strain in HCM mutation gene carriers and patients, both in systole and diastole.
In the first part of this thesis STE analysis of myocardial velocity, rotation and strain in systole and diastole is introduced. In Chapter 2 a literature review of LV twist mechanics in cardiomyopathies is presented. Analysis of LV twist mechanics may provide substantial pathophysiological understanding in a variety of cardiomyopathies.
In the second part of this thesis the feasibility of STE is studied. In Chapter 3 it is shown with a moving phantom model that mitral annular velocities can be accurately determined by STE in an angle independent way. In Chapter 4 the feasibility, observer variability and test-retest variability of LV twist measurements by STE is described. The method appeared to be feasible in approximately two thirds of the subjects with good observer variability and temporal reproducibility, potentially allowing to study changes in LV twist over time in an individual patient.
The third part of this thesis is dedicated to the value of STE in HCM carriers and patients. In Chapter 5 it is shown that in HCM patients, LV basal rotation is increased, whereas apical rotation was normal, resulting in increased LV twist. The increased basal rotation may be explained by loss of counteraction of the subendocardial fibre helix, caused by endocardial ischemia due to microvascular dysfunction. LV apical rotation and twist were dependent on the pattern of LV hypertrophy. In patients with a sigmoidal septal curvature, LV apical rotation and twist are increased as compared to patients with a reverse septal curvature. This may be partly explained by the degree of subendocardial ischemia since patients with a sigmoidal septal curvature more often had LV outflow tract obstruction. The extravascular compressive forces caused by gradients due to the outflow obstruction may lead to more extensive microvascular dysfunction and subendocardial ischemia. In Chapter 6 differences in regional basal rotation in HCM patient with a typical reverse septal curvature are described. Basal septal and anterior segments, the segments mostly involved in the hypertrophic process, showed increased rotation compared to other segments where re-rotation rate, the diastolic LV back rotation velocity, is decreased in the septal segment of the basal LV. In Chapter 7 it is shown that although systolic twist is increased in HCM patients LV untwist is delayed, impairing diastolic filling. In a pilot study described in Chapter 8 we tried to investigate the feasibility and value of LV systolic and diastolic strain and rotation (twist) parameters during exercise in patients with HCM, with emphasize on the reserve as clinical exercise-related symptoms in patients with HCM but without LV outflow-tract obstruction are presumed to be related to diastolic dysfunction. Although in this study a blunted diastolic longitudinal functional reserve as assessed by tissue Doppler and STE analysis in HCM patients during exercise is shown, the principal finding of this study is that the feasibility of STE during upright bicycle testing is very limited. In Chapter 9 the relation between resting diastolic deformation indices and subjective (NYHA Class) and objective (ergometry) exercise tolerance in HCM patients is studied. Although the conventional early diastolic myocardial lengthening velocity parameter (e’) is the strongest predictor for exercise workload in HCM patients also STE deformation parameters like strain, unstrain and untwist showed independent correlations to exercise workload. In the final two chapters we investigated the possibilities of STE in detecting preclinical HCM in family members of HCM patients as an alternative for genetic testing, comparable to prior studies using TDI in which conflicting results were reported, potentially caused by the angle-dependency of TDI. In Chapter 10 increased peak late diastolic annular velocities in HCM genetically affected subjects without LV hypertrophy were shown with STE analysis. In contrast, peak early diastolic values could not differentiate genotype (+) from genotype (-) individuals. Finally, in Chapter 11 it is shown that in HCM mutation carriers untwist and unstrain rates are also decreased and delayed indicating early diastolic abnormalities.