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In the present study we evaluated the upslope (IUS), downslope (IDS) and terminal slope (ITS) of the QRS complex in both standard and derived ECG leads obtained from spatial QRS loops, either by the vectorcardiogram (VCG) or by principal component analysis (PCA), in 79 patients undergoing prolonged, elective percutaneous coronary intervention (PCI). For each patient, the slope indices IUS, IDS and ITS were evaluated in the PCI recording as well as in a control recording acquired before the PCI procedure, and relative factors of change during PCI were calculated. We showed that IUS and IDS computed over VCG and PCA leads present higher sensitivity to the ischemia-induced changes than the same indices evaluated over the standard 12-lead ECG. Mean relative factors of change were 10.5 and 12.4 for IUS and IDS in PCA, and 7.87 and 13.7, respectively, in VCG, representing an increase in sensitivity of up to 103% for IUS and 46% for IDS compared to measurements obtained in lead V3. We conclude that evaluation of slope indices in leads derived from QRS loops significantly increases their potential value for detection of acute myocardial ischemia.