Contrast echo washout curves from the left ventricle: Application of basic principles of indicator-dilution theory and calculation of ejection fraction

Time-intensity curves can be obtained from contrast echocardiography of the left ventricle. The purposes of this study were: 1) to verify whether these curves conform to the basic principles of indicator-dilution theory; and 2) to derive indexes of left ventricular ejection fraction from curve analysis. In seven closed chest dogs, 31 doses of the polysaccharide agent SHU-454 were injected into the left ventricular cavity during apical four chamber two-dimensional echocardiography. Data were obtained at different levels of ejection fraction, which were induced by changes in preload, afterload and contractility, and measured by single plane Simpson's rule analysis of digital subtraction left ventriculograms. In a subset of two dogs, eight incremental doses (from 1 to 8 ml) of SHU were injected in the basal state. Contrast echocardiograms were digitized off-line, the mean gray level/pixel of a region of interest inside the left ventricular cavity was measured, and the average value for three systolic frames of each beat was used to obtain time-intensity curves. A good correlation was observed between the peak of the time-intensity curve and the quantity of contrast injected (correlation coefficient r = 0.91 by a logarithmic fit). The echo intensities observed in each animal were subsequently transformed in quantity of contrast according to these functions and their natural logarithm was calculated both with and without background subtraction. All curves relating time and the natural logarithm of the corrected intensity exhibited a descending rectilinear portion (washout) in which the correlation was very good (r = 0.97 ± 0.02 = mean ± SD) and which was not significantly affected by background subtraction. The validity of this fit was also un affected by heart rate (55 to 158 beats/min) and angiographic ejection fraction (22 to 74%), and only minimally influenced by duration of contrast washout (3.3 to 14.6 seconds). Ejection fraction was calculated by an algorithm derived from indicator-dilution theory: ejection fraction = [1 − e^−bd] × 100, where b = slope of the curve and d = cardiac cycle duration. Linear regression analysis between values of ejection fraction derived by angiography and contrast echo yielded r = 0.73. A second index, based on b and d, was derived by multiple regression analysis. Linear regression analysis of this index and angiographic ejection fraction yielded a correlation of r = 0.87. In conclusion, these data indicate that: 1) the washout phase of contrast echo time-intensity curves conforms to a monoexponential function; and 2) estimates of angiographic ejection fraction can be obtained by this method independent of geometric assumptions and without the necessity for precise identification of the ventricular endocardium.