OBJECTIVE This study sought to evaluate control mechanism of the varying left ventricular performance in atrial fibrillation. BACKGROUND Atrial fibrillation is characterized by a randomly irregular ventricular response, resulting in continuous variation in left ventricular beat-to-beat mechanical behavior and hemodynamic variables. METHODS Fourteen patients with chronic nonvalvular atrial fibrillation were studied, using a nonimaging computerized nuclear probe linked to a personal computer. Left ventricular ejection fraction, end-diastolic and end-systolic volume counts, stroke volume counts and filling time were calculated on a beat-to-beat basis during 500 consecutive RR intervals. Multiple regression analysis was used to assess how ejection fraction was predicted by these variables. RESULTS The preceding RR interval and end-diastolic volume showed a positive relation, and prepreceding interval and end-systolic volume an inverse relation, with ejection fraction (all p < 0.001). Sensitivity analysis suggested that the preceding interval and the end-diastolic volume were equally important in predicting ejection fraction. There was a relatively strong interaction between the preceding interval and end-diastolic volume, indicating that the influence of the end-diastolic volume on ejection fraction was diminished after long intervals. A second interaction showed that the effect of end-diastolic volume on ejection fraction was attenuated after short prepreceding cycles. CONCLUSIONS Cycle length-dependent contractile mechanisms, including postextrasystolic potentiation and mechanical restitution, determine the varying left ventricular systolic performance during atrial fibrillation over the entire range of intervals. Beat-to-beat changes in preload, consistent with the Frank-Starling mechanism, also play a role, but their influence is diminished after long preceding and short prepreceding intervals.