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Background It has been demonstrated that cyclic variation of ultrasonic integrated backscatter (CVIBS) may be useful in detecting altered physical conditions in the heart. However, no previous study has examined serial changes of CVIBS in the myocardium during the development of left ventricular dysfunction. Methods and Results We examined alterations of CVIBS in pacing-induced cardiac dysfunction. Eight pigs (36±2 kg) were studied before and sequentially during sustained rapid ventricular pacing (225±9 beats per minute). CVIBS was measured in the IVS and left ventricular PLW before pacing and daily for 4 days after onset of pacing. Five additional pigs (35±10 kg) were examined after 14 days of pacing. Regional function and CVIBS were assessed with pacemakers inactivated. A quantitative integrated backscatter imaging system (two-dimensional format) was used. Over 4 days of pacing, the magnitude of CVIBS progressively decreased in the PLW but was unchanged in the IVS, findings that persisted at 14 days. Percent wall thickening in the PLW progressively decreased to a greater degree than percent wall thickening in the IVS. A linear relation between the magnitude of CVIBS and percent wall thickening was found. At 14 days, blood flow to the two regions was similar but regional differences in CVIBS persisted. Conclusions Rapid left ventricular pacing produces abnormalities of regional myocardial function within 48 hours of pacing. Regional myocardial dysfunction is accompanied by a reduction in CVIBS in the same region.