BIO|STREAM.CSP CLS

This study, BIO|STREAM.CSP CLS, is a prospective, observational submodule of the ongoing BIO|STREAM.CSP registry. It is designed to collect real-world clinical data from patients who receive BIOTRONIK dual-chamber pacemakers using conduction system pacing (CSP), with a specific focus on the combination of left bundle branch area pacing (LBBAP) and Closed Loop Stimulation (CLS).

Permanent cardiac pacing is a standard therapy for patients with sinus node dysfunction (SND), a condition in which the heart's natural pacemaker does not function properly. A considerable proportion of these patients also have atrioventricular (AV) conduction disorders, which impair the electrical connection between the atria and ventricles. In such cases, dual-chamber pacemakers are typically implanted to maintain appropriate heart rhythm and coordination.

Traditional right ventricular (RV) pacing, while effective in maintaining heart rate, has been associated with non-physiological activation of the heart and may contribute to an increased risk of atrial fibrillation (AF), especially when pacing burden is high. Device-detected atrial fibrillation (DDAF) is a clinically relevant outcome, as it is associated with increased risk of stroke, heart failure, and other cardiovascular complications.

Closed Loop Stimulation (CLS) is an advanced pacemaker feature designed to provide more physiological heart rate adaptation by continuously monitoring cardiac contractility and adjusting the pacing rate accordingly. In previous studies, including the B3 trial, CLS demonstrated a reduction in DDAF incidence in patients with SND. However, this benefit was not observed in patients with AV block, likely due to the adverse effects of frequent RV pacing.

Conduction system pacing, and in particular left bundle branch area pacing (LBBAP), is an emerging pacing strategy that stimulates the heart's intrinsic conduction pathways, resulting in a more physiological and synchronized ventricular activation. This approach has the potential to reduce the negative effects associated with RV pacing.

The BIO|STREAM.CSP CLS submodule aims to investigate whether the combination of LBBAP and CLS can reduce the incidence of DDAF in patients with both SND and AV conduction disorders in routine clinical practice. The study will follow approximately 150 patients over a 24-month period after pacemaker implantation. Patients included are those enrolled in the BIO|STREAM.CSP registry who receive a de novo dual-chamber pacemaker with activated CLS and LBBAP, and who have no prior history of atrial fibrillation.

The primary objective of this exploratory submodule is to assess the incidence and timing of DDAF episodes following activation of CLS, using device-based diagnostics over the follow-up period. The study will evaluate multiple thresholds of AF episode duration (e.g., ≥6 minutes, ≥6 hours, ≥24 hours, and ≥7 days), as well as the time to first occurrence and overall AF burden. Secondary analyses will explore how CLS modulates heart rate in patients with conduction system pacing, including the distribution of paced and sensed heart rates over time.

As an observational study without a control group, BIO|STREAM.CSP CLS is intended to generate hypothesis-generating, real-world evidence rather than to test a predefined hypothesis. The findings are expected to provide insights into the clinical performance of CLS in combination with LBBAP and to support optimization of device programming strategies.

Overall, this study seeks to improve understanding of how advanced pacing technologies can be used together to deliver more physiological cardiac pacing, with the goal of reducing atrial arrhythmias and improving long-term outcomes in patients requiring permanent pacemakers.

Inclusion criteria

• Enrolled in the BIO|STREAM.CSP registry
• Standard indication for dual-chamber pacing due to any form of sinus node disease according to guidelines
• DDD-CLS pacing mode activated
• Either ≥ II degree AV block, or native PR interval ≥ 200 ms at baseline ECG with expected RVP ≥ 20%

Exclusion criteria

• Implantation dates back more than 90 days
• History of clinical AF
• Patients intended to receive, or already received a pacing lead for traditional RV pacing, His bundle pacing or right bundle branch pacing
• Upgrade from previous pacemaker system
• Patients transitioning from the BIO|MASTER.CSP study
• DDAF episodes present in the device memory at the time of registration