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Objectives: The aim of this research was to evaluate right ventricular pacing effects on left ventricular function., Background: Right ventricular pacing alters the ventricular activation sequence and reduces left ventricular ejection fraction (EF). It is unclear whether the observed reduction in EF can be completely attributed to the alteration in activation sequence., Methods: Twelve subjects (eight women), mean age 68 +/- 12 years, with transvenous dual-chamber pacemakers, normal left ventricular function, and intact atrioventricular (AV) conduction were studied with serial-gated blood pool studies. Left ventricular EF was measured at a fixed rate after at least 1 week of atrial pacing only (baseline), during short-term (2 h) and mid-term (1 week) AV sequential pacing with a short AV delay, and after short- and mid-term AV pacing., Results: Baseline EF was 66.5 +/- 4.5%. Short-term AV pacing resulted in a decrease in EF to 60.3 +/- 5.2% (p < 0.0002). After one week of AV pacing, there was a further decline in EF to 52.9 +/- 8.3% (p < 0.0001). After cessation of mid-term pacing, EF was 57.3 +/- 5.9% (p < 0.0001 vs. baseline). A total of 2, 5, 8, and 24 h later, EF remained depressed (59% to 60%, p < 0.007). At 32 h, EF was 62.9 +/- 7.6% (p < 0.11 compared with baseline)., Conclusions: The abnormal activation sequence resulting from right ventricular pacing accounts for only part of the reduction in EF as mid-term pacing is associated with a lower EF than short-term pacing, and EF remains depressed after cessation of AV pacing. Changes in ventricular function induced by right ventricular pacing may account for some of its associated adverse effects.