Mayer Rashtian

Aims: The aim of this analysis was to evaluate the upgradeability of a single-chamber leadless pacemaker (LP) to a dual-chamber system in patients indicated for a dual-chamber pacemaker. Methods and results: A prospective, multicentre study evaluated the safety and performance of a dual-chamber LP. The study included patients with a prior ventricular LP to evaluate its upgradeability. Patients had an attempted atrial LP implant, and if successfully implanted, the LPs were paired to a dual-chamber pacing mode to evaluate upgrade success. Patients were followed for 12 months from the attempted atrial LP implantation. Among 35 patients with an attempted upgrade (62.9% male, average age 70 years), the most common primary indication was sinus node dysfunction (57.1%). Out of 35 patients, 91.4% had successful upgrades. The mean atrial device electrical measurements stabilized within 1 month from the procedure and remained stable through 12 months (capture threshold at 0.4 ms 0.8 ± 0.6 V, sense amplitude 4.5 ± 2.7 mV at 12 months). A total of five (14.3%) patients experienced seven complications, all of which were procedure-related. There were no device or procedure-related deaths. The total estimated battery longevity (accounting for time since implant) evaluated at 12 months was 11.3 ± 4.2 and 5.7 ± 2.6 years for the ventricular and atrial LPs, respectively. One patient required an atrial LP revision 10 months after implantation. The LP was retrieved and replaced. Conclusion: These data confirm the feasibility, safety, and long-term effectiveness of adding an atrial LP in patients with a pre-existing ventricular LP to achieve dual-chamber leadless pacing.

Aims: A dual-chamber leadless pacemaker (LP) system relies on a beat-to-beat, wireless, implant-to-implant (i2i™) communication between implanted devices in the right atrium and right ventricle (A-to-V and V-to-A). Atrioventricular (AV) synchrony was evaluated during an ambulatory 24 h period of daily living to determine if its effectiveness can be maintained under real-world conditions. Methods and results: A prospective, single-arm, multicentre clinical study (ClinicalTrials.gov identifier NCT05252702) evaluated the overall safety and performance of the dual-chamber LPs in patients with standard indications for dual-chamber pacing. Following the 3-month visit, eligible patients wore 12-lead Holter monitors for 24 h while resuming the activities of daily living while under clinically driven programmed settings. Leadless pacemaker diagnostic data were interrogated when patients returned to the clinic. An independent Holter core laboratory adjudicated the proportion of synchronous beats (PR intervals within paced and sensed AV delay bounds). Relationships between AV synchrony and i2i communication success rate, implant indication, heart rate, and AV event type were evaluated. Among 47 analysable patients, mean AV synchrony was achieved in 96.7% of beats, exceeding mean A-to-V and V-to-A transmission success rates of 93.4% and 92.1%, respectively. There were no significant differences in AV synchrony between sinus node and AV block patients. Across all AV paced/sensed cycle combinations and heart rate ranges (including >100 b.p.m.), AV synchrony was sustained >90% in an ambulatory real-world setting. Conclusion: A dual-chamber leadless pacing system demonstrated >96% overall AV synchrony for a 24 h period of daily living while programmed to clinically appropriate settings, thus showing that true dual-chamber DDD(R) pacing can be maintained in a real-world environment.

Background: A dual‐chamber leadless pacemaker (LP) system has been developed, employing distinct atrial leadless pacemaker (ALP) and ventricular leadless pacemaker (VLP) devices that maintain atrioventricular synchrony via wireless implant‐to‐implant (i2i) communication with each beat. A new i2i communication‐free programming option was introduced to extend battery longevity and minimize unnecessary ventricular pacing by providing rate‐modulated atrial pacing with backup ventricular pacing when needed (AAI(R) + VVI). The clinical safety and longevity improvement have not been evaluated commercially. Methods: Patients indicated for dual‐chamber pacing with new or existing dual‐chamber LP implants were enrolled in this prospective, nonblinded, interventional study. Device diagnostics and battery longevity were interrogated before and after 6 months (6 M) of AAI(R) + VVI programming, with any programming‐related complications or symptoms noted. Total ALP and VLP longevities were compared for DDD(R) at enrollment versus AAI(R) + VVI at 6 M. Results: Dual‐chamber LP systems in 139 patients at six centers were evaluated (76 ± 11 years; 53% male; PR 210 ± 56 ms; 80% sinus node dysfunction, 16% AV block of any degree), including 16% new and 84% existing implants (enrolled 7.9 ± 7.5 months postimplant). The 84 patients completing the study ( n = 55 did not return) demonstrated a complication‐free rate of 100.0% and a symptom‐free rate of 97.6% ( n = 2; fatigue, dizziness, shortness of breath). In the 32 patients enrolled with existing implants already in DDD(R) mode who also completed the 6 M visit, AAI(R) + VVI extended the longevities of ALPs by 93% (5.8 ± 1.1 to 11.1 ± 2.7 years, p < 0.001) and VLPs by 61% (10.9 ± 2.1 to 16.9 ± 1.2 years, p < 0.001). Conclusion: Clinical use of AAI(R) + VVI programming in dual‐chamber LPs over 6 M resulted in no complications, minimal symptoms, and significantly extended ALP and VLP battery longevities.

BACKGROUND: A dual-chamber leadless pacemaker can provide bradycardia therapy to most patients with pacemaker indications without the complications associated with a lead or pulse generator. We sought to confirm whether previously reported 3-month safety and performance outcomes were sustained through 12 months by determining whether 12-month complication-free and performance success rates exceeded their prespecified performance goals. METHODS: Patients were enrolled in the prospective, single-group Aveir DR i2i Study if they had a standard indication for dual-chamber pacing. Enrolled patients were implanted with an Aveir DR dual-chamber leadless pacemaker system, which comprised 2 communicating leadless pacemakers (1 in the right atrium and 1 in the right ventricle). The primary safety outcome evaluated whether freedom from serious device- or procedure-related events through 365 days exceeded the predetermined performance goal of 76.5%. The primary performance outcome determined whether the composite of atrial capture threshold (≤3.0 V at 0.4 ms) and sensing amplitude (P-wave ≥1.0 mV) at the 12-month visit exceeded the predetermined performance goal of 80.0%. RESULTS: Sites attempted implantation in 300 subjects, where 63.3% had sinus-node dysfunction and 33.3% had atrioventricular block as their primary pacing indication. The primary safety end point was achieved, with a Kaplan-Meier 12-month complication-free rate of 88.6% (95% CI, 84.5–91.8; P P <0.001). CONCLUSIONS: Both primary safety and performance end points were met after 1 year, demonstrating consistency with previously reported 3-month outcomes of a dual-chamber leadless pacemaker. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT05252702.

BACKGROUND: A dual-chamber leadless pacemaker system has been designed for atrioventricular synchronous pacing using wireless, beat-to-beat, implant-to-implant (i2i) communication between distinct atrial and ventricular leadless pacemakers. The atrioventricular synchrony achieved across various ambulatory scenarios has yet to be systematically evaluated. METHODS: A prospective, single-arm, unblinded, multicenter, international clinical trial of the leadless pacemaker system was conducted in patients with a conventional dual-chamber pacing indication enrolled from February 2022 to March 2023. Leadless pacemaker systems were implanted, and 12-lead Holter electrocardiographic recordings were collected 3 months after implantation over various postures/activities: sitting, supine, left lateral recumbent, right lateral recumbent, standing, normal walk, and fast walk. An independent Holter core laboratory performed a manual adjudication of the percent of atrioventricular synchronous beats using the standard 300-millisecond PR interval limit. Atrium-to-ventricle and ventricle-to-atrium i2i communication success rates were also assessed. Post hoc summary statistics describing the relationships between atrioventricular synchrony and i2i success, posture/activity, implantation indication, atrioventricular event, and heart rate were calculated. RESULTS: In the evaluable population (n=384 of 464 enrolled [83%]; 61% male; age, 70 years; weight, 82 kg; 60% ejection fraction; 95% of beats evaluable), the mean atrioventricular synchrony of 98% of beats observed across all postures using the standard 300-millisecond limit was greater than both atrial-to-ventricular i2i (94%) and ventricular-to-atrial i2i (94%; P 95% of evaluable beats across all postures/activities, implantation indications, atrioventricular paced/sensed event combinations, and heart rate ranges (including >100 bpm). CONCLUSIONS: This dual-chamber leadless pacemaker system demonstrated atrioventricular synchrony in 98% of evaluable beats at 3 months after implantation. Atrioventricular synchrony was maintained across postures/activities and remained robust for heart rates >100 bpm.

Background/Introduction: The first global dual-chamber leadless pacemaker (DR-LP) study included a group of subjects with a pre-existing upgradeable ventricular single chamber leadless pacemaker (VR-LP) in whom the addition of an atrial leadless pacemaker (AR-LP) was undertaken to allow upgrading to a dual chamber leadless pacing (DR-LP) system. Purpose: Summarize success rates of single to dual chamber leadless pacemaker upgrades, as well as device and i2i throughput measurements, serious adverse device effects (SADEs) and mortality in this cohort. Methods: Subjects with a pre-existing VR-LP who were indicated for a dual-chamber pacemaker were included. Upgrade procedures included downloading firmware to existing VR-LP, placing AR-LP, and pairing the devices to operate in a DR-LP mode. Electrical and i2i throughput measurements were collected at implant, pre-discharge, 1-mo, 3-mo, 6-mo, and 12-mo. Upgrade success rate was defined as an AR-LP upgrade procedure that resulted in a functional DR-LP system. SADEs included all reported events that were adjudicated as serious and possibly, probably or causally related to the procedure or system. SADEs and deaths were adjudicated by an independent clinical events committee. Results: Out of 36 enrolled subjects (61.1% male, 70.4 ± 13.8 yrs., 55.6% sinus node dysfunction, 38.9% AV block), 35 had an attempted implant, and 32 of these were successful (91.4%). The 3 unsuccessful upgrade attempts were related to unsuccessful placement of the AR-LP due to complications during the procedure (n = 2) or an inability to implant an AR-LP (n = 1). Figure 1 illustrates a declining early mean pacing capture threshold, rising early P-wave amplitudes, and stable impedance for the AR-LP over the 12 months. Mean i2i throughput for communication from the RV to RA and the RA to RV improved from pre-discharge to 3 months and remained stable through the subsequent 9 months (Figure 2). A total of 5 subjects (5 of 36; 13.9%) experienced 7 SADEs (all procedure-related; 2 related to the AR-LP and 2 to the delivery catheter). One non-cardiovascular, non-device, non-procedure related death occurred in the upgrade population. Conclusions: The single to dual-chamber upgrade cohort demonstrated a high upgrade success rate (91.4%), stable atrial and ventricular electrical measurements and consistently high i2i communication throughout the 12 months. AV synchrony (AVS) was not specifically measured in this upgrade cohort, but data from the main DR-LP study suggest that i2i throughput correlates with, but significantly underestimates AVS. Further, the rate of complications was acceptable (13.9%) and limited to the procedure. These data confirm the feasibility, safety and longer-term effectiveness of adding an atrial LP in patients with a pre-existing ventricular LP order to achieve effective dual chamber pacing.Fig. 1: Upgrade Electrical measurementsFig. 2: i2i communication for Upgrades

Background/Introduction: A dual-chamber leadless pacemaker system has been developed to provide atrial and ventricular pacing and maintain atrioventricular (AV) synchrony. The device demonstrated an ability to maintain consistent AV synchrony in an in-clinic setting when tested through a series of postures and gaits under some programming restrictions. Assessing AV synchrony within real-world conditions is needed to understand the device’s performance under wider variations in activity and over a longer period. Purpose: Assess a dual-chamber leadless pacemaker’s ability to maintain AV synchrony in an ambulatory environment of daily living under clinically driven programmed settings. Methods: Implanted de novo subjects, who had at least 25% atrial pacing after 3-months post-implant, wore a 12-lead Holter monitor for a minimum of 24 hours during normal daily activities and completed a symptom diary. Devices were programmed to a dual chamber pacing mode and clinically appropriate settings then interrogated pre- and post-assessment. An independent Core Laboratory evaluated AV Synchrony, based on a configurable sampling window approach at repeated intervals, and defined synchronous cycles based on whether PR intervals fell within a 50 ms margin of the programmed Paced AV Delay. Results: Among the 50 subjects who were administered the assessment, 48 of their Holters were analyzable (mean age 71.4 ± 10.9 years; 66.7% male), and 47 subjects had paired device interrogation data available. The analyzable population was predominantly indicated for sinus node dysfunction (83.3%) with a minority indicated for AV block (16.7%). The mean ± standard deviation of the programmed paced AV delay was 260.0 ± 47.6 ms, and mean PR interval was 241.4 ± 35.1 ms. An atrial paced beat and ventricular paced beat were each present in 69.5% and 22.5% of the evaluable cardiac cycles in the population, respectively. Mean AV Synchrony was maintained above 97% (95% CI: 95.5, 98.8) in the entire cohort and was sustained at high rates within each sub-population. Device metrics that diagnose the rate of directional implant-to-implant (i2i) communication also confirmed device data average throughput rates above 90% (Picture 1). There were no reported episodes of oversensing, undersensing, loss of capture, or pauses. Conclusion: Among subjects with standard pacemaker indications, the dual-chamber leadless pacemaker system maintains very high rates of AV synchrony, exceeding i2i throughput, within real-world conditions utilizing clinically appropriate programmed settings.AV Synchrony and i2i by Indication

Background: Leadless pacemakers (LPs) can mitigate conventional pacemaker complications related to the transvenous leads and subcutaneous pocket surrounding the pulse generator. Although single-chamber leadless pacing has been established, multichamber pacing requires wireless bidirectional communication across multiple LPs to maintain synchrony. This preclinical study demonstrates the chronic performance of implant-to-implant (i2i) communication that achieves synchronous, dual-chamber pacing with 2 LPs. Methods: The i2i communication modality employs subthreshold electrical signals conducted between implanted LPs through the blood and myocardial tissue on a beat-by-beat basis. Right atrial and right ventricular LPs were implanted in 9 ovine subjects. The i2i transmission performance was evaluated 13 weeks after implant. Results: Right atrial and right ventricular LPs were implanted successfully and without complication in 9 ovine subjects. A total of 8715±457 right atrial-to-right ventricular and right ventricular-to-right atrial transmissions were sent per hour, with a success rate of 99.2±0.9%. Of periods with i2i communication failure when DDD pacing was not possible, 97.3±1.8% were resolved within 6 s. Conclusions: For the first time, synchronized, dual-chamber pacing has been demonstrated in a chronic preclinical feasibility study by 2 leadless pacemakers using beat-to-beat, wireless communication, achieving a success rate of 99.2%.