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Title: Genetic and functional studies of osteoarthritis susceptibility at COL11A1 and GDF5
Author: Dodd, Andrew William
Awarding Body: University of Newcastle Upon Tyne
Current Institution: University of Newcastle upon Tyne
Date of Award: 2013
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Background: Non-invasive cardiac imaging provides important diagnostic and prognostic information in cardiovascular disease. Assessment of ventricular function remains the fundamental imaging request in clinical practice. Cardiac magnetic resonance (CMR) is now the recognised reference standard for quantification of left and right ventricular systolic function, but not diastolic filling. Due to cost and limited availability of CMR, echocardiography remains the first line imaging modality for assessing ventricular function in most cases. Several echocardiographic methods are available for quantifying global ventricular function however despite significant advances in cardiac imaging techniques, visual assessment of ventricular systolic function remains the standard by which ventricular function is reported in many centres. This method is subjective and introduces inter-observer bias. In an era of multi-modal imaging, accurate, reproducible and widely available methods for quantifying ventricular function, which exhibit good inter-modal inter-technique concordance, are desirable. The overall aim of this thesis was to examine the accuracy and reproducibility of several new echocardiographic imaging techniques for quantifying left and right ventricular systolic function, indexed against CMR reference standards, and to examine a novel CMR technique for assessing diastolic function, indexed against current reference standards (invasive catheter recording of left ventricular end diastolic filling pressure (LVEDP)), in a heterogeneous cohort of patients as seen in clinical practice. Methods: All imaging modalities were performed within three hours of each other. Study 1 was designed to compare the accuracy of speckle tracking strain echocardiography for quantifying LV systolic function against biplane Simpson’s rule (SR) and 3D-echocardiography, using CMR LV ejection fraction (LVEF) as the reference standard. Study 2 was designed to investigate the accuracy of a novel modified regional wall motion scoring index (RWMSI) for calculating LVEF, and compare its accuracy against SR and CMR LVEF. Study 3 was designed to explore the clinical utility of velocity encoded (VEC) CMR for diagnosing LV diastolic dysfunction. VEC CMR E/Em velocity ratio was compared to LVEDP recorded during left heart catheterisation. Study 4 was a head-to-head comparison of 10 echocardiographic non-volumetric indices of right ventricular systolic function, based on current European Association of Echocardiography recommendations, indexed against CMR RVEF as the reference standard. Results: In study 1 we demonstrate that speckle tracking strain may be superior to SR for quantifying LV systolic function. In study 2 we suggest that, when specialist imaging software is unavailable, a modified RWMSI may be superior to SR for calculating LVEF. In study 3, we demonstrate a significant correlation between VEC-CMR E/Em ratios and LVEDP, and conclude that VEC-CMR may be a useful tool to diagnose diastolic dysfunction, especially in patients with preserved LVEF. In study 4, we demonstrate that RV free wall strain has a closer correlation to CMR-RVEF than nine alternative echocardiographic indices of RV function, and may be the method of choice for assessing RV systolic function by 2D-echocardiography in the future. Conclusions: This series of studies has confirmed that novel non-invasive cardiac imaging techniques may be used to accurately quantify cardiac ventricular function, and may confer significant advantage over current methods.
Supervisor: Not available Sponsor: Cardiovascular Research Centre, Adelaide
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available