Novel echocardiographic modalities for evaluation of pathophysiology and diagnostic in heart failure with normal ejection fraction

Abstract

This thesis is focused on studies investigating the role of novel echocardiographic modalities for the evaluation of LV diastolic function in heart failure with a normal ejection fraction. New non-invasive techniques have been validated against the invasive gold standard catheterization method in order to provide the diagnostic and prognostic accuracy of HFNEF. Despite of high prevalence and mortality in HFNEF, the exact pathomechanisms are still uncertain and diagnostic procedures unreliable. Conventional echocardiography, a widespread non-invasive method of choice yielded low sensitivity and specificity in direct comparison with pressure-volume relationship analysis. Novel tissue Doppler diastolic velocity parameters provided strong correlation with LV relaxation and stiffness, crucial haemodynamic determinants of diastolic dysfunction. They showed significantly higher diagnostic accuracy in early and mild forms of LV dysfunction. In particular, the LV filling index E/E’ correlated with passive cardiac properties like the LV stiffness coefficient. An additional study demonstrated that tissue Doppler velocities including E/E’ index were associated with myocardial collagen amounts and the level of cardiac fibrosis obtained from endomyocardial biopsies, which have impact on LV stiffness. Besides tissue Doppler imaging, further echocardiographic modality, and deformation imaging also reflected intrinsic myocardial changes which showed a significant correlation of diastolic strain rate with relaxation index and LV stiffness. By this, deformation parameters were not found to be superior to the tissue Doppler imaging in diagnostic HFPEF. However, in the settings of clinical routine where extended echocardiographic analysis is not available, a simple diagnostic tool with an additional determination of NT-proBNP level to the conventional echocardiography improved the diagnostic accuracy up to the level of tissue Doppler imaging and showed a prognostic value by predicting a re- hospitalisation rate involving HFNEF. New techniques extended the understanding of pathophysiology in HFNEF as evidenced by their relation to cardiac fibrosis, and by their clarifying diastolic ventricular interactions in primary pulmonary arterial hypertension. The bottom line of these evaluated studies is that novel echocardiographic methods optimize diagnostic accuracy in HFNEF based on an improved characterization of intrinsic myocardial properties.

Im Mittelpunkt dieser kumulativen Habilitationsschrift stehen Arbeiten, die die Rolle der neuen echokardiographischen Modalitäten für die Beurteilung der LV diastolischen Funktion bei Herzinsuffizienz mit normaler Ejektionsfraktion untersuchen. Die neuen nicht-invasiven Techniken wie gewebedoppler, myokardiale Deformationsimaging inklusiv strain rate und speckle tracking analyse, sowie auch neue Biomarker für Herzinsuffizienz wurden gegen invasive Goldstandard Katheterverfahren mit linksventrikulärer Druck-Volumen Analyse validiert, um die diagnostische und prognostische Genauigkeit der Methoden bei HFNEF zu überprüfen. Es wurden nicht nur neue nicht-invasive diagnostische tools evaluiert sondern auch neue pathophysiologische mechanismen wie der Enfluss von kardialen Fibrose und primärer pulmonaler Hypertonie auf die LV diastoliche Funktion und Symptomatik bei HFNEF postuliert und analysiert. Die Quintessenz der vorgelegten Arbeiten ist es, dass neue echokardiographische Methoden eine diagnostische Zuverläßigkeit bei HFNEF Patienten optimieren, basierend auf verbesserter Charakterisierung der intrinsischen myokardialen Eigenschaften.