Defining the magnitude of measurement variability in the virtual histology analysis of acute coronary syndrome plaques

BACKGROUND: Previous intravascular ultrasound-based virtual histology (IVUS-VH) measurement variability studies have been confined to single-frame or short-segment analysis in stable patients with minimal disease. We sought to determine the magnitude of human measurement variability in acute coronary syndrome (ACS) plaques. METHODS AND RESULTS: Prior to percutaneous coronary intervention, we performed IVUS-VH analysis in troponin-positive ACS culprit lesions. A total of 3840 IVUS-VH frames were analysed by two operators to determine intra- and inter-observer variability. The plaque constituent area and volumes were compared using intra-class correlation coefficient (ICC); within-subjects standard deviation (WSSD, mm(2) or mm(3)) and the repeatability coefficient (RCO) to quantify the magnitude of operator error that 95% of future measurements should not exceed. The majority of intra- and inter-observer measurements had ICC of >0.92 confirming excellent agreement. Only the fibrous area (0.86), fibro-fatty (FF) area (0.72) and FF volume (0.87) had ICC levels suggesting an operator error >10%. However, the mean RCO and the percentage this represents in single-frame analysis (area error) varied across the plaque subtypes: fibrous area = 1.64 mm(2) (59%); FF area = 0.49 mm(2) (140%); necrotic core (NC) area = 0.39 mm(2) (21.3%); dense calcium (DC) area = 0.29 mm(2) (33.7%). For full lesion pullbacks (volume error): fibrous volume = 8.14 mm(3) (9.9%); FF volume = 5.63 mm(3) (53.8%); NC volume = 3.78 mm(3) (6.9%) and DC = 2.4 mm(3) (9.6%) CONCLUSION: As in previous studies, intra- and inter-observer ICC suggests good agreement between observers. However, this can still represent large measurement error values and percentages. These findings could impact on the interpretation of previous studies and influence future studies using IVUS-VH measurements as endpoints.