The study was designed to assess the beat-to-beat variation of ventricular repolarization in patients with myocardial ischemia, hear failure, and in normal subjects. Autonomic tone may alter the dynamic QT/RR interval relation and thus may be involved in ventricular arrhythmia development, especially in the diseased heart. The study included 145 patients (age 16-86 years) with CHF (LVEF < or = 0.30) or unstable angina pectoris (LVEF > 0.60). The control group consisted of healthy volunteers giving physiological baseline measures for the evaluated parameters: cycle length, QT interval, and QT/RR interval ratio during three time periods. In patients with myocardial ischemia (LVEF > 0.60) and healthy subjects the QT/RR interval ratio did not reveal significant differences between both groups (QT/RR(CAD) = 0.36 +/- 0.77 vs QT/RR(controls) = 0.28 +/- 0.83; NS). In sharp contrast, in patients with severe heart failure, RR dependent instantaneous variation of the QT interval was almost missing and regression line analysis disclosed a QT/RR interval slope substantially enhanced by 196% (compared to normal subjects) and 131% (compared to CAD patients; P < 0.05) with a complete loss of circadian modulation (QT/RR(CHF) = 0.83 +/- 0.71 vs QT/RR(CAD) = 0.36 +/- 0.77 vs QT/RR(controls) = 0.28 +/- 0.83; P < 0.05). Beat-to-beat QT interval assessment provides a dynamic parameter of physiological and altered repolarization in defined study groups. Compared to other groups (preserved LVEF), patients with left ventricular impairment exhibited a significantly increased sensitivity of repolarization to cycle length (enhanced QT/RR interval ratio) and a blunted circadian modulation of the QT interval. This is consistent with concept that increased repolarization disparity may be deleterious being a potential pathophysiological basis for enhanced arrhythmic risk.