BACKGROUND:Atrial fibrillation (AF) detection following ischemic stroke is critical to guide management. Echocardiography (echo) is commonly performed poststroke and may help identify candidates for prolonged rhythm monitoring. The PER DIEM trial randomized poststroke patients without known AF to 12-months of implantable loop recorder (ILR) monitoring versus 30-days of external rhythm monitoring and demonstrated higher AF detection rates using ILR. AIMS:This substudy of the PER DIEM trial investigated the association between baseline echo parameters and poststroke AF detection. METHODS:PER DIEM trial participants with complete transthoracic echo performed at the time of ischemic stroke were included. Demographic, clinical, and echocardiographic parameters were compared between those with and without AF. RESULTS:Nineteen (12.4%) of the 153 patients included had poststroke AF. AF patients were significantly older and had higher CHA2DS2-VASc scores. Patients with AF had higher left atrial volume index (LAVI), lower absolute left ventricular global longitudinal strain (LV GLS) and lower contractile LA strain compared to those without AF. Univariate analysis showed that a higher LAVI (OR 1.30 per 5 mL/m2 increase, 95%CI 1.03-1.64, p = 0.025) and lower absolute LV GLS (OR 2.73 per 5% decrease, 95%CI 1.37-6.04, p = 0.007) were significantly associated with poststroke AF, with optimal cutoff values of 32.12 mL/m2 and 15.5%, respectively. CONCLUSIONS:In patients with ischemic stroke, LAVI and LV GLS were significantly associated with subsequent AF detection. These findings may help risk stratify AF monitoring strategies for postischemic stroke management.

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.

Leadless pacemakers (LP) with the capability to obtain electrical measurements such as impedance and electrograms (EGM) can provide early feedback on implant site selection, before committing to fixation and therefore minimizing the need to reposition the LP. The objective was to utilize intraoperative features of the electrogram (EGM) and paced impedance measurements to predict pacing capture thresholds (PCT) at the 3-month follow-up. This is a retrospective study of a leadless pacemaker clinical trial (NCT#:05252702), including patients with complete sets of impedance measurements and intracardiac EGMs collected during the mapping phase and while in tether mode, and a capture threshold obtained at the 3-month follow-up. A computerized algorithm was developed to quantify features of the EGM signal: amplitudes of the R-wave, S-wave, and COI, the slope of the upstroke and downstroke, and the sharpness of the R-wave peak (calculated as average slope of points within 1 sample of the peak). Linear regression was performed to identify significant predictors of the chronic PCT. Binary logistic regression models were constructed by converting the 3-month PCT into a binary outcome using a cutoff of 1.5V and analyzed using receiver operating characteristic (ROC) curves. 88 patients were included. PCT at 3-months was 0.73±0.84 V. 8 patients had PCT >1.5V at 3 months. In univariate linear regression, impedance during mapping and tether, the sharpness of the R-wave during mapping, and the R-wave amplitude during tether were significant predictors of 3-month PCT (p=0.04, <0.01, 0.05, 0.03, respectively). Two logistic regression models were identified: 1) using only mapping variables (COI and impedance), 2) including both mapping COI and tether impedance. The mapping logistic regression model included COI (p=0.01) and impedance (p=0.1) during mapping and produced an area under the curve (AUC) of 0.88 with sensitivity and specificity of 100% and 70%, respectively. A logistic regression model including COI (mapping, p=0.04) and impedance (tether, p=0.03) produced an AUC of 0.92 with sensitivity and specificity of 100% and 81%, respectively. Test of the Χ2 statistic vs. constant model had p<0.01 in both models. We developed a computerized prediction model using intraoperative EGM and impedance to predict 3-month PCT of a leadless pacemaker. This may be useful in enhancing procedural efficacy and efficiency.Linear Regression Results Binary Logistic Regression ROC Curves

AIMS:Intraoperative use of an antibacterial envelope during surgery for cardiac implantable electronic device (CIED) surgery reduces infection risk at increased procedural costs. The objective of this systematic review was to synthesize the published economic literature on the cost-effectiveness of the antibacterial envelope. METHODS AND RESULTS:A systematic review of the published literature was conducted to identify economic evaluations (i.e. cost-utility, cost-effectiveness, and cost-benefit studies) comparing the antibacterial envelope compared with standard of care in preventing post-operative CIED infection. Systematic review best practices were followed, and study quality was assessed. Of 142 unique citations, 7 studies met the inclusion criteria for qualitative synthesis. All cost-effectiveness studies were conducted from the healthcare payer perspective of high-income countries. The base case analysis of most economic studies (5/7) reported a cost per quality-adjusted life year gained that exceeded country-specific societal thresholds for good value in healthcare. Cost-effectiveness was highly dependent on the baseline infection risk. That is, at current pricing, the antibacterial envelope may be cost-effective at base infection rates of greater than 3%, and cost-savings at infection rates that exceed 6%. CONCLUSION:Routine use of an antibacterial envelope in patients undergoing CIED procedures (implantation or revision) is unlikely to be cost-effective except among those at high risk for post-operative infection. Individualized risk assessment may help guide efficient and value-based use of this technology.

AIMS:A dual-chamber leadless pacemaker (LP) system that employs distinct atrial and ventricular LP devices (ALP, VLP) has been introduced to clinical practice. Proprietary, low-energy, implant-to-implant (i2i) communication at each beat enables the devices to maintain synchronous atrioventricular sensing and pacing. We evaluated device longevities and contributing factors, such as i2i communication. METHODS AND RESULTS:Patients meeting dual-chamber pacing indications received the dual-chamber LP system as part of a prospective, multi-centre, international clinical trial (Aveir DR i2i Study, NCT05252702). Programming and diagnostics were interrogated from all de novo, non-revised, dual-chamber programmed devices at 12 months post-implant. This analysis included 302 patients (65% male; age 70 ± 13 years; weight 80 ± 19 kg; intrinsic heart rate 55 ± 7 bpm; 58% sinus node dysfunction, 27% atrioventricular block). At 12 months, devices were programmed to dual-chamber pacing (DDD(R) or DDI(R)) at a median 60 bpm rate, median 1.25 V pulse amplitude in ALP and 1.5 V in VLP, median 0.4 ms pulse width, and median i2i signal setting level 5 out of 7. Median ALP and VLP remaining battery longevities at 12 months were 4.3 and 9.1 years, with median total ALP and VLP longevities of 5.3 and 9.9 years. Base rate, pulse amplitude, pacing percentage, event rate, impedance, and i2i setting level all exhibited significant correlations with ALP and VLP longevities (P < 0.001). Programming i2i setting levels below 7 produced the greatest longevity savings. CONCLUSION:The first dual-chamber LP demonstrated adequate projected battery longevity after 12 months of use. Patient-specific device programming considerations, unique to leadless devices, may extend longevity.

Background The growing use of leadless pacemaker (LP) technology requires safe and effective solutions for retrieving and removing these devices over the long term. Objectives This study sought to evaluate retrieval and removal of an active helix-fixation LP studied in worldwide regulatory clinical trials. Methods Subjects enrolled in the LEADLESS II phase 1 investigational device exemption, LEADLESS Observational, or LEADLESS Japan trials with an attempted LP retrieval at least 6 weeks postimplantation were included. The retrieval success rate was evaluated for all attempted retrievals. Site-reported complications associated with LP retrievals were quantified, with the severity and relationship adjudicated by an independent clinical events committee. Results There were 1,423 successful LP implants and 234 chronic LP retrieval attempts in 233 subjects. The overall retrieval success rate was 87.6% (205 of 234 attempts). The most common reason for failed retrieval (86.2%, 25 of 29 attempts) was inability to access the LP docking button. The mean time from implantation to attempted retrieval was 3.2 years (range 0.2-9.0 years) and did not significantly influence the retrieval success (P = 0.71). The clinical events committee adjudicated 11 complications in 9 subjects as being retrieval related (3.9%, 9 of 233 subjects). Conclusions The safety and efficacy of chronic LP retrieval of an active helix-fixation device was demonstrated in an international clinical trial setting, with implant durations up to 9 years.

BACKGROUND:Compression garments are a relatively inexpensive and easy-to-implement treatment, but the longer term benefits of abdominal compression in a real-world setting are not known. In this study we sought to evaluate commercially available abdominal compression garments in a real-world setting in patients with postural orthostatic tachycardia syndrome (POTS). METHODS:Participants completed four 10-minute active stand tests, with and without an abdominal compression garment, in the morning (Test #1: AM-OFF; Test #2: AM-ON) and afternoon (Test #3: PM-ON; Test #4: PM-OFF). Participants held medication that could augment heart rate (HR) and blood pressure during this 1-day study. A Holter monitor was used to record HR and participants recorded their symptoms using the Vanderbilt Orthostatic Symptom Score at the end of each standing test (range 0-90, where 0 = no symptoms). Continuous data are presented as median (25th-75th percentile). RESULTS:Standing HR (103 [91-114] vs 118 [99-134], P = 0.002) and change in HR with upright posture compared with supine (27 [19-42] vs 41 [26-48], P < 0.001) were reduced, and symptoms improved (29 [16-45] vs 35 [25-60], P = 0.005), during AM-ON compared with AM-OFF. When the garment was removed after several hours of use (PM-ON vs PM-OFF), standing HR (P = 0.04), ΔHR (P = 0.01), and symptoms (P = 0.02) increased. CONCLUSIONS:Commercially available abdominal compression garments reduced HR and improved symptoms both acutely and after several hours of use. Abdominal compression garments may provide a good alternative to full waist-high compression garments in patients with POTS. CLINICAL TRIAL REGISTRATION:NCT04881318.

BACKGROUND:Initial results were recently reported for the AVEIR DR i2i study, which involved the percutaneous implantation of a novel dual-chamber leadless pacemaker (LP) system, with right atrial and right ventricular LPs delivering atrioventricular synchronous pacing. OBJECTIVE:The purpose of this study was to evaluate procedural outcomes and learning curve for de novo implantation of the dual-chamber LP (AVEIR DR, Abbott, Abbott Park, IL). METHODS:Implant procedure metrics collected during the study were analyzed, including procedural complications within 30 days of implantation. Procedural outcomes were evaluated according to implanter experience: 1-4 vs 9+ dual-chamber LP implant procedures (ie, initial vs advanced implant experience). RESULTS:De novo dual-chamber LPs were successfully implanted in 446 of 452 patients (99%) by 126 physicians. Mean procedural duration metrics included 90±37 minutes of introducer sheath insertion-to-removal time, 74±32 minutes of dual-chamber procedure duration, 26±17 minutes of right ventricular LP procedure duration, 42±24 minutes of right atrial LP procedure duration, and 20±13 minutes of fluoroscopy duration; between initial and advanced implant experience, there were reductions of 19%-36% (P<.05) in these duration metrics. There were 62 procedural complications in 50 of 452 patients (11.1%) (ie, 88.9% complication free), predominantly involving cardiac arrhythmias (ie, atrial fibrillation/flutter or complete atrioventricular block; 16 of 452 [3.5%]). Freedom from complications significantly improved from 89% to 98% of patients (P<.05) when comparing initial and advanced implant experience. CONCLUSION:In a pivotal investigational study, implantation of a dual-chamber LP system was successful in 99% of patients. Advanced implant experience was accompanied by improvements in procedural outcomes including reduced procedural times (introducer sheath insertion to removal, dual-chamber procedure, ventricular LP and atrial LP procedures, and fluoroscopy) and improved freedom from complications. TRIAL REGISTRATION:ClinicalTrials.gov identifier: NCT05252702.

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<0.001). The primary performance end point was achieved in 92.8% of patients (95% CI, 89.7-95.8; 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.

In a pivotal trial (NCT05252702), the AVEIR DR (Abbott) leadless pacemaker system was found to be safe and effective in delivering DDDR synchronous atrial and ventricular pacing. This dual-chamber system employs 2 leadless pacemakers with implant-to-implant communication. Although implantation of the ventricular device as a single-chamber pacemaker has been well described, there are additional considerations surrounding the dual-chamber implantation procedure. Herein, we review the dual-chamber leadless pacemaker implantation workflow while providing guidance to optimize safe and effective implantation procedures.

BACKGROUND:Compression garments reduce heart rate and symptoms in patients with postural orthostatic tachycardia syndrome in an acute laboratory setting. Patients taking medications controlling heart rate have less benefit from compression than those not on medications. The effectiveness of commercially available garments in a community-based setting, with and without medication use, is not known. OBJECTIVES:The authors sought to evaluate commercially available compression tights in a community-based setting both with, and without, medications modulating heart rate, using a clinical trial with 2 before-after protocols conducted in a randomized crossover fashion. METHODS:Participants (N = 26) held medications during protocol #1 and took medications as normal during protocol #2. For each, participants completed 4, 10-minute active stand tests in the morning (AM) and afternoon (PM) with the garments on (ON) and off (OFF) (AM-OFF, AM-ON, PM-ON, and PM-OFF). Heart rate (Holter monitor) and symptoms (Vanderbilt Orthostatic Symptom Score [VOSS]) were measured for each standing test. RESULTS:Protocol #1: Standing heart rate was reduced (105 [99-116] beats/min vs 119 [105-130] beats/min; P < 0.001) and symptoms improved (P < 0.001), during AM-ON vs AM-OFF. Standing heart rate (P = 0.04) and symptoms (P = 0.004) increased when compression was removed after several hours. Protocol #2: Standing heart rate was reduced (84 [77-90] beats/min vs 89 [84-100] beats/min; P < 0.001), and symptoms improved (P = 0.03), during AM-ON vs AM-OFF. Standing heart rate (P = 0.02) and symptoms (P < 0.001) increased when compression was removed after several hours. CONCLUSIONS:Commercially available compression tights reduced heart rate and symptoms both acutely and after several hours of use. This additional benefit persisted whether concomitant medications were used. (Compression Garments in the Community With POTS [COM-COM-POTS]; NCT04881318).

BACKGROUND:The Resynchronization-Defibrillation for Ambulatory Heart Failure Trial (RAFT) showed a greater benefit with respect to mortality at 5 years among patients who received cardiac-resynchronization therapy (CRT) than among those who received implantable cardioverter-defibrillators (ICDs). However, the effect of CRT on long-term survival is not known. METHODS:We randomly assigned patients with New York Heart Association (NYHA) class II or III heart failure, a left ventricular ejection fraction of 30% or less, and an intrinsic QRS duration of 120 msec or more (or a paced QRS duration of 200 msec or more) to receive either an ICD alone or a CRT defibrillator (CRT-D). We assessed long-term outcomes among patients at the eight highest-enrolling participating sites. The primary outcome was death from any cause; the secondary outcome was a composite of death from any cause, heart transplantation, or implantation of a ventricular assist device. RESULTS:The trial enrolled 1798 patients, of whom 1050 were included in the long-term survival trial; the median duration of follow-up for the 1050 patients was 7.7 years (interquartile range, 3.9 to 12.8), and the median duration of follow-up for those who survived was 13.9 years (interquartile range, 12.8 to 15.7). Death occurred in 405 of 530 patients (76.4%) assigned to the ICD group and in 370 of 520 patients (71.2%) assigned to the CRT-D group. The time until death appeared to be longer for those assigned to receive a CRT-D than for those assigned to receive an ICD (acceleration factor, 0.80; 95% confidence interval, 0.69 to 0.92; P = 0.002). A secondary-outcome event occurred in 412 patients (77.7%) in the ICD group and in 392 (75.4%) in the CRT-D group. CONCLUSIONS:Among patients with a reduced ejection fraction, a widened QRS complex, and NYHA class II or III heart failure, the survival benefit associated with receipt of a CRT-D as compared with ICD appeared to be sustained during a median of nearly 14 years of follow-up. (RAFT ClinicalTrials.gov number, NCT00251251.).

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<0.001), exceeding both i2i values in 95% of patients. Atrioventricular synchrony was achieved in >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:Postural orthostatic tachycardia syndrome (POTS) is a chronic form of orthostatic intolerance that primarily affects female patients. Despite the severity of POTS, there are no approved medications for use in patients with this disorder. Compression garments are a commonly prescribed nonpharmacological treatment, but little is known about the patient experience with compression. In this study we aimed to evaluate the patient experience with compression garments using a structured survey and semistructured telephone interviews. Methods:A focused survey was designed as a component of a larger clinical trial on compression garment use in patients diagnosed with POTS. Building on the survey, semistructured telephone interviews were conducted with POTS patients. Recorded interviews were transcribed and coded in a thematic analysis using a descriptive-interpretive approach. Results:A total of 27 participants completed the survey, and 20 participants completed the telephone interview. Patient experiences with compression were variable, with some participants experiencing significant benefits, and others reporting minimal to no benefits. Six themes that influenced garment use were identified: the potential benefit of the garment to improve symptoms, specific activities patients will be undertaking, environmental conditions, garment attributes, psychological and cognitive aspects, and financial considerations. Conclusions:Participants engage in a daily cost-benefit analysis when making decisions to use a compression garment. Clinicians should be aware of the benefits of and factors that limit use of compression garments as a treatment for POTS.

BACKGROUND:The first dual-chamber leadless pacemaker (DC-LP) system consists of 2 separate atrial and ventricular devices that communicate to maintain synchronous atrioventricular pacing and sensing. The initial safety and efficacy were previously reported. OBJECTIVE:The purpose of this study was to evaluate the chronic electrical performance of the DC-LP system. METHODS:Patients meeting standard dual-chamber pacing indications were enrolled and implanted with the DC-LP system (Aveir DR, Abbott), including right atrial and ventricular helix-fixation LPs (atrial leadless pacemaker [ALP], ventricular leadless pacemaker [VLP]). Pacing capture threshold, sensed amplitude, and pacing impedance were collected using the device programmer at prespecified timepoints from 0-6 months postimplant. RESULTS:De novo devices were successfully implanted in 381 patients with complete 6-month data (62% male; age 69 ± 14 years; weight 82 ± 20 kg; 65% sinus nodal dysfunction, 30% atrioventricular block). ALPs were implanted predominantly in the right atrial appendage anterior base and VLPs primarily at the mid-to-apical right ventricular septum. From implant to 1 month, pacing capture thresholds (0.4-ms pulse width) improved in both ALPs (2.4 ± 1.5 V to 0.8 ± 0.8 V; P <.001) and VLPs (0.8 ± 0.6 V to 0.6 ± 0.4 V; P <.001). Sensed amplitudes improved in both ALPs (1.8 ± 1.3 mV to 3.4 ± 1.9 mV; P <.001) and VLPs (8.8 ± 4.0 mV to 11.7 ± 4.2 mV; P <.001). Impedances were stable in ALPs (334 ± 68 Ω to 329 ± 52 Ω; P = .17) and reduced in VLPs (789 ± 351 Ω to 646 ± 190 Ω; P <.001). Electrical measurements remained relatively stable from 1-6 months postimplant. No differences in electrical metrics were observed among ALP or VLP implant locations. CONCLUSION:This first in-human evaluation of the new dual-chamber leadless pacemaker system demonstrated reliable electrical performance throughout the initial 6-month evaluation period.