The negative U wave: A pathogenetic enigma but a useful, often overlooked bedside diagnostic and prognostic clue in ischemic heart disease

The pathogenesis of U-wave inversion and its clinical value are still not clear, although the U wave was described by Einthoven together with the other electrocardiographic (ECG) waves. Not considered a useful diagnostic clue, it is not usually mentioned in ECG reports. In recent years, stimulated by the long QT syndromes and by the discovery of U-wave changes in some pathologic, mostly cardiac states, this neglected wave has attracted new interest. This review focuses on the negativity of the U wave in ischemic heart disease. The discovery of M cells and their electrophysiology has established the cellular basis for repolarization and has contributed to our knowledge of U-wave genesis. Hemodynamic changes during diastole in acute ischemia also furnish interesting elements for the interpretation of U-wave changes, and some experimental and clinical studies, besides designating stretch as a cause of U-wave changes, have also proved their value for more accurate bedside diagnosis and prognosis. They may indicate the extent of myocardial ischemia, the presence of collateral circulation, and the possible territory and vessel involved. When U-wave changes are the first and only sign of ischemia, they may contribute to a decision regarding the hospital admission of a patient without typical ischemic symptoms. Furthermore, U-wave changes during exercise tests increase their sensitivity.