In order to more clearly understand the electrocardiographic manifestations of early transmural ischemia, we studied electrocardiograms (ECGs) in patients undergoing balloon angioplasty. Decisions regarding reperfusion strategies in patients with acute myocardial infarction rely largely on the presence of ST-segment elevation (STE) in the ECG, consequently with significant limitations. Studies of the "ischemic cascade" show that ST-segment changes occur well after the onset of wall motion abnormalities. We prospectively analyzed ECGs obtained at 20-s intervals in 74 patients undergoing elective balloon angioplasty. The ECGs were analyzed using 3 methodologies. In 74 patients, the ST-segment, the T-wave, and the QT-interval were analyzed using the MUSE (General Electric HC, Menomonee Falls, Wisconsin) automated system (MUSE). Fifty patients were also analyzed using the Interval Editor automated system (IE; General Electric HC). In 20 patients, measurements were made manually. Transmural ischemia prolonged the QTc interval (using the Bazett's formula) in 100% of patients. In all 74 patients analyzed with MUSE, QTc interval prolonged from 423 +/- 25 ms to 455 +/- 34 ms (p < 0.001). In the 50 patients analyzed with IE, QTc interval prolonged in 50 of 50 (100%) patients (from 424 +/- 27 ms to 458 +/- 33 ms [p < 0.001]). Mean time to maximal QTc interval prolongation, changes in T-wave polarity, > or =1 mm STE, and ST-segment depression (STD) were 22, 24, 29, and 35 s, respectively. Although QTc interval prolonged in 100% of patients, T-wave changes, STE, and STD (> or =1 mm) occurred in 7%, 15%, and 7%, respectively. The QTc interval prolongs in 100% of patients with early transmural ischemia. When compared with clinically accepted indexes of transmural ischemia (i.e., STD and STE [> or =1 mm]) it is the earliest ECG abnormality.