AIM: Aim of this retrospective study was to analyze the effect of closed-loop stimulation (CLS) and DDD pacing mode on autonomic balance, and to evaluate heart rate variability (HRV) during CLS stimulation. METHODS AND MATERIALS: Autonomic balance was estimated by a 24-hour HRV analysis of paced and spontaneous beats in patients implanted with a dual-chamber pacemaker (Inos(2+) CLS-Biotronik GmbH, Berlin, Germany) and randomly assigned to CLS or DDD pacing mode. Patients underwent two 24-hour electrocardiogram Holter recordings at the end of each 3-month pacing mode period. Each Holter recording was automatically scanned to extract sequences of consecutive beats of the same type [atrial paced (Ap)-sequence and atrial spontaneous (As)-sequence], lasting at least 130 beats. RESULTS: Eight hundred and ten sequences were extracted from 15 patients, and the following spectral parameters were evaluated during both CLS and DDD mode: the total power (variance), the absolute and percentage (relative to the total power) powers of the low frequency (LF, 0.04-0.15 Hz) and high frequency (HF, 0.15-0.4 Hz) components, as well as the LF/HF power ratio. DISCUSSION: The two main findings of this study were: in all the patients, CLS seems to mimic short-term physiological HRV, although the variability (total power) was lower than that relative to the spontaneous beats; the HRV of the spontaneous beats had an higher LF/HF when the pacemaker was programmed as DDD respect to CLS, consistent with a shift toward sympathetic predominance.