BACKGROUND: In investigational medicinal products testing centers (IMP), reliable methods for monitoring early signs of cardiotoxicity of a potential new drug in healthy volunteers are essential. This study examines what levels of left ventricular ejection fraction (LVEF) variance can be achieved with two-dimensional echocardiography (2DE) in a core laboratory versus a site laboratory. Diurnal variability of LVEF and diastolic parameters were also reviewed. METHODS AND RESULTS: 64 healthy males, (age range 18-40 years), with optimal echo windows were recruited. Two-dimensional and tissue Doppler (TDI) echocardiography was performed by one dedicated sonographer using an Acuson Sequoia C256 machine. Heart rate and blood pressure were recorded simultaneously. Echocardiograms were performed at set time points (0, 1, 4, and 20 hours) on all subjects. The images were analyzed independently by one on-site, unblinded, sonographer reader (site lab) and one experienced off-site blinded physician over reader (core lab). The core lab showed significantly less variance in LVEF measurements than the site lab (5.5% vs. 19.9%). There was no significant diurnal variation in mean blood pressure, LVEF or E:A ratio measurements over 20 hours. CONCLUSIONS: The core lab had better reproducibility and significantly less variance in LVEF measurements by 2DE than the site lab. There was no diurnal variation in LV function measurement.
BACKGROUND: In investigational medicinal products testing centers (IMP), reliable methods for monitoring early signs of cardiotoxicity of a potential new drug in healthy volunteers are essential. This study examines what levels of left ventricular ejection fraction (LVEF) variance can be achieved with two-dimensional echocardiography (2DE) in a core laboratory versus a site laboratory. Diurnal variability of LVEF and diastolic parameters were also reviewed. METHODS AND RESULTS: 64 healthy males, (age range 18-40 years), with optimal echo windows were recruited. Two-dimensional and tissue Doppler (TDI) echocardiography was performed by one dedicated sonographer using an Acuson Sequoia C256 machine. Heart rate and blood pressure were recorded simultaneously. Echocardiograms were performed at set time points (0, 1, 4, and 20 hours) on all subjects. The images were analyzed independently by one on-site, unblinded, sonographer reader (site lab) and one experienced off-site blinded physician over reader (core lab). The core lab showed significantly less variance in LVEF measurements than the site lab (5.5% vs. 19.9%). There was no significant diurnal variation in mean blood pressure, LVEF or E:A ratio measurements over 20 hours. CONCLUSIONS: The core lab had better reproducibility and significantly less variance in LVEF measurements by 2DE than the site lab. There was no diurnal variation in LV function measurement.