AbstractCOPD is the second most common cause of pulmonary hypertension, and is a common complication of severe COPD with significant implications for both quality of life and mortality. Pulmonary arterial stiffening occurs early in the disease process before the development of overt pulmonary hypertension. Early detection would open this up as a potential therapeutic target before end stage arterial remodeling occurs. Traditionally the assessment of the arterial stiffness required right heart catheterization, however recent advance in MRI are yielding new opportunities to undertake this assessment noninvasively. Pulse wave velocity is one of the most commonly used techniques in the systemic circulation but has been poorly explored in the pulmonary circulation. This thesis was undertaken to test the hypothesis that pulmonary PWV would be elevated in COPD, and that this would correlate with right ventricular mass, and predict future adverse remodeling.
Two commonly used techniques are available for measuring PWV with MRI: the transit time technique and the flow-area technique. These techniques were applied in a cohort of young healthy volunteers (n=10) and older healthy volunteers (n=20). These techniques were repeated using on-table repetition and repetition at 6 months. These were also assessed during exercise in the young healthy volunteers. PWV did not differ between the two age groups (YHV 2.4±0.3 ms-1, OHV 2.9±0.2 ms-1, p=0.1). Using a high temporal resolution sequence through the RPA using the flow-area technique accounting for wave reflections yielded consistently better within-scan, interscan, intraobserver and interobserver reproducibility. Exercise did not result in a change in PWV (mean (95% CI) of the differences: 0.10 (−0.5 to 0.9), p=0.49) despite a significant rise in heart rate (65±2 to 87±3, p<0.0001), blood pressure (113/68 to 130/84, p<0.0001) and cardiac output (5.4±0.4 to 6.7±0.6 L/min, p=0.004).
58 participants with COPD underwent pulmonary function tests, six-minute walk test, and cardiac MRI. These were compared with a cohort of 20 healthy controls. Cardiac MRI was used to quantify right and left ventricular mass and volumes, with phase contrast imaging of the main pulmonary artery in order to calculate pulmonary PWV and of the ascending and abdominal aorta in order to calculate the aortic pulse wave velocity. Those with COPD demonstrated evidence of pulmonary arterial stiffening and pulmonary vascular remodeling with higher pulmonary artery area at end diastole (COPD: 2.36 ± 0.56 cm2/m1.7 vs. HC: 2.14 ± 0.28 cm2/m1.7, p=0.027), reduced pulsatility (COPD: 24.88 ± 8.84 % vs. HC: 30.55 ± 11.28 %, p=0.021), reduced PAT (COPD: 104.0 ± 22.9 ms vs. HC: 128.1 ± 32.2 ms, p<0.001) and higher PWV (COPD: 2.62 ± 1.29 ms-1 vs. HC: 1.78 ± 0.72 ms-1, p=0.001). Those with an elevated PWV did not demonstrate any difference in subjective breathlessness, exercise capacity, or any difference in right ventricular systolic function. Cardiac remodelling in COPD was instead that of a reduced preload with a lower RV end diastolic volume (COPD: 53.6±11.1 ml vs. HC: 59.9±13.0 ml,p=0.037) and RV stroke volume (COPD: 31.9±6.9 ml/m2 vs. HC: 37.1±6.2 m/m2l,p=0.003). Those with COPD had a nonsignificantly higher aortic PWV (COPD: 8.7 ± 2.7 ms-1 vs. HC: 7.4 ± 2.1 ms-1, p=0.06), with aortic PWV correlating with left ventricular remodeling (rho=0.34, p=0.01).
34 participants with COPD underwent repeat imaging at 1 year. While there was a significant increase in pulmonary PWV (Baseline 2.30 ± 0.97, Follow-up: 3.39 ± 1.4 ms-1,
p<0.001) there was no significant change in ventricular mass or volumes.
This thesis has therefore proven its original hypothesis that pulmonary PWV is elevated in those with COPD. However we have seen that this elevation in PWV has no significant
association with right ventricular remodeling either at baseline or at one-year follow-up. Instead we observed a pattern of ventricular remodeling that was more consistent with an under filled condition rather than an overloaded condition. Future work in COPD should thus be targeted at better understanding of the underpinning pathophysiological process behind this.
|Date of Award||2017|
|Add any sponsors of the thesis research||Wellcome Trust|
|Supervisor||Graeme Houston (Supervisor), Allan Struthers (Supervisor) & Brian Lipworth (Supervisor)|
The role of pulmonary arterial stiffness in right ventricular remodelling in COPD
Weir-Mccall, J. (Author). 2017
Student thesis: Doctoral Thesis › Doctor of Philosophy