Wright_whole_thesis.pdf (6.39 MB)
New ultrasound techniques for detection and management of pulmonary vascular disease
thesisposted on 2023-05-27, 09:40 authored by Wright, LM
`Background.` Pulmonary arterial hypertension (PAH), a rare condition of raised blood pressure in the lungs, is a debilitating disease with considerable morbidity and mortality. Clinical diagnosis is through an assessment of pulmonary artery pressures. The condition is treatable, but medications are expensive and not always practical, thus echocardiographic evidence of treatment response is used to rationalise ongoing therapy. However, outcome studies have now shown that invasive and echocardiographic pressures do not strongly associate with outcome. `Aims.` The thesis proposes that a variety of echocardiographic markers, including those of right ventricular (RV) systolic function, are more indicative of patients' clinical status than currently used methods for assessing pressures, and six-minute walk (6MW) distance. Assessment of myocardial deformation (strain) is now accessible at the bedside using echocardiographic speckle tracking. I seek to determine how to use this measure throughout the treatment course, and how RV free wall strain relates to outcome in a clinical setting. The goal of this thesis is to determine where and how strain (especially RV strain) fits in the clinical decision process. `Methods.` A review of echocardiographic methods in regards to RV assessment with echocardiography was undertaken. Following ethics clearance, the majority of patient recruitment was from the Tasmanian Pulmonary Hypertension Registry (Hobart, Australia) Tasmanian Scleroderma Database (Hobart, Australia), and the Princess Alexandra Hospital (Brisbane, Australia). All echocardiographic measurements were performed in accordance with recommended echocardiographic guidelines. Statistical analysis was performed primarily with SPSS (version 21, IBM, Chicago, IL) and MedCalc software version 16.8.4 (MedCalc Software bvba, Ostend, Belgium). \\(Results.\\) First, in PAH, baseline RV function (RVFWS) is a strong predictor of outcome, independent of PASP. Changes throughout therapy appear minimal, and the prognostic value of change appears limited. Second, Afterload changes should be taken into account in the evaluation of RVFWS during PAH follow-up, with the relationship to PASP likely to be linear. Third, RVFWS is more predictive than RVEDA and less variable than FAC in distinguishing acute from chronic RV pressure overload. RVFWS adds incremental and independent information to standard measures of RV function in assessing the acuity of PH. Fourth, RVFWS is strongly associated with exercise capacity in PAH and ise a useful adjunct to the assessment of treatment response. Fifth, RV dysfunction was associated with adverse outcome, independent of and incremental to clinical and LV deformation parameters in SSc. Subclinical LV dysfunction appears to have less prognostic relevance than RV dysfunction. Sixth, the detection of post-capillary PH appears to be better predicted with LV markers than recently recommended algorithms for detecting raised PCWP. Seventh, right atrial strain was significantly different between those with normal versus raised pressure, but it did not identify those with an incorrect echocardiographic assessment of RAP. Eighth, LV markers were associated with changes in PCWP after fluid loading. RV function showed a weak association with raises in PAPm. Myocardial deformation was not associated with a rise in filling pressure after fluid loading. Ninth, microvascular disease appears to be related to be related to RV function in PAH. Macrovascular disease appears to relate to traditional heart disease factors such as LV mass. Endothelial function markers do not appear to be interchangeable in assessing patient outcome. `Conclusions.` New echocardiographic markers of RV systolic function offer a significant increment of prognostic information in PAH. The measurement of RV free wall strain aids in clinical decision-making and integration daily clinical practice is needed. We have found that in a group with a high rate of PAH, current guidelines do not offer strong guidance on the differentiation of LV and pulmonary vascular aetiologies for PH. Although RA speckle tracking is associated with RAP, it did not appear to add in the correction of pressure assessment. Speckle tracking imaging also shows potential in systemic CTD, exposing unique fibrosis patterns in the LV. Vascular function had associations with echocardiographic LV and RV parameters, but heterogeneity in this population hinder its use as a robust discriminative marker. Speckle tracking echocardiography does not appear to detect elevations of invasive PCWP. This work shows that RV free wall strain is now ready for prime time and integration into the clinical decision-making process.
Rights statementCopyright 2017 the author Chapter 3 appears to be, in part, the equivalent of a pre-print version of an article published as: Wright, L., Dwyer, N., Wahi, S., Marwick, T. H., 2018. Relative importance of baseline and longitudinal evaluation in the follow-up of vasodilator therapy in pulmonary arterial hypertension, JACC: cardiovascular imaging, online 17 October 2018, 1-9 Chapter 4 appears to be, in part, the equivalent of a pre-print version of an article published as: Wright, L., Negishi, K., Dwyer, N., Wahi, S., Marwick, T. H., 2017. Afterload dependence of right ventricular myocardial strain, Journal of the American Society of Echocardiography, 30(7), 676-684.e1 Chapter 5 appears to be, in part, the equivalent of a pre-print version of an article published as: Wright, L., Dwyer, N., Power, J., Kritharides, L., Celermajer, D., Marwick, T. H., 2016. Right ventricular systolic function responses to acute and chronic pulmonary hypertension: assessment with myocardial deformation, Journal of the American Society of Echocardiography, 29(3), 259-266 Chapter 7 appears to be, in part, the equivalent of a pre-print version of an article published as: Saito, M., Wright, L., Negishi, K., Dwyer, N., Marwick, T. H., 2018. Mechanics and prognostic value of left and right ventricular dysfunction in patients with systemic sclerosis, EHJ Cardiovascular Imaging, 19(6), 660-667. DOI https://doi.org/10.1007/s10554-018-1368-3 Chapter 9 appears to be, in part, the equivalent of a pre-print version of an article published as: Wright, L. M., Dwyer, N., Wahi, S., Marwick, T. H., 2018. Association with right atrial strain with right atrial pressure: an invasive validation study, International journal of cardiovascular imaging, 34(10), 1541-1548