부산대학교 도서관

Background: The non-invasive assessment of volume status in left ventricular systolic dysfunction (LVSD) is challenging. The main thesis objective was to establish the feasibility and potential clinical utility of repeated measures assessment of non-invasive biomarkers in defining changes in volume status within individual volunteers. Methods: Differential volume manipulation protocols were achieved in a three-staged plan of investigation, firstly, in patients with decompensated heart failure receiving intravenous furosemide, secondly, in normal volunteers receiving acute loads of oral water or intravenous saline, and thirdly, in stable LVSD patients on chronic furosemide dosing undergoing staged diuretic withdrawal and resumption. Repeated measures of biomarkers relevant to volume status including blood and urine biomarkers, echocardiographic and bioimepdance measures were performed to assess their sensitivity to the induced volume changes. Results Summary: I demonstrated the smallest variance for bioimpedance measures, and the largest variance for urine biomarkers. In the patients with decompensated heart failure, none of the biomarkers studied showed potential clinical utility at tracking acute volume response to intravenous furosemide. In the normal volunteers, a significant change in estimated blood volume was observed following intravenous saline, but not with acute oral water ingestion. Only whole-body and trunk bioimpedance measures, and to a lesser extent, mitral valve early peak velocity with and without the Valsalva manoeuvre, appeared sensitive enough to map these changes in volume status. In the stable LVSD patients, statistically significant increases in B-type natriuretic peptide, urinary creatinine, urinary kidney injury molecule 1, and in bioimpedance-estimated body water composition were observed with diuretic withdrawal, with levels of these markers reducing following diuretic resumption. However, the amplitude of the changes observed was either lower than the respective within-subject variance or too small to be potentially useful as a marker of volume change. This would thus limit the clinical utility of these biomarkers in the routine monitoring of volume status in LVSD. Conclusion: The repeated measures of biomarkers studied in response to different volume manipulations were interpreted in the context of their within-subject normal variance. None of the biomarkers studied appeared to have the ideal characteristics clinically for the monitoring of subclinical changes in volume status in stable LVSD or in response to acute diuresis in decompensated heart failure. The significant increases in urine biomarkers following diuretic withdrawal in stable LVSD suggested potentially beneficial renal effects of furosemide in stable LVSD.