Performance and Physician Experience of INGEVITY+ Active Fixation Leads: Prospective INGEVITY+ Lead Clinical Study in Korea

Background Boston Scientific INGEVITY+ pacing lead (Boston Scientific, Marlborough, MA, USA) has been upgraded to INGEVITY. The performance of the INGEVITY+ pacing lead has not yet been reported. This study aimed to evaluate the short- and long-term safety, effectiveness, and handling experience of INGEVITY+ leads. Methods Consecutive patients were included from 9 institutions in Korea, where 400 leads (200 right ventricular active fixation leads and 200 right atrial active fixation leads) were implanted or attempted in 200 subjects. Results During the implantation, only one patient required a lead change because of lead screw failure. The handling questionnaires of the lead received very positive feedback with 88% of operators agreeing that it is easy for leads to pass through small vessels or vessels with multiple leads. At the 3-month follow-up, 95.7% of RA leads and 99.5% of RV leads had pacing thresholds less than 1.5 V. A total of 92.4% of atrial leads had amplitudes greater than 1.5 mV, and 96.5% of ventricular leads had sensing amplitudes greater than 5 mV at 3 months. A total of 99.8% had impedances between 300 and 1,300 ohms. The lead-related complication-free rate for all leads during follow-up was 100%, and the overall rates of lead dislodgment, perforation, and pericardial effusion were all 0.0%. Conclusions The INGEVITY+ pacing lead exhibited exceptional clinical performance, with a high complication-free rate throughout the 3-month follow-up period. In addition, the lead displayed excellent electrical characteristics, and the lead-handling experience was reported to be very good.


Introduction
Intracardiac leads play a vital role in transvenous pacemaker systems, serving as an insulated electrical connection between the implantable pulse generator (IPG) and the cardiac tissue.Tese leads face myriad challenges, including enduring biodegradation within the body's environment, withstanding repetitive fexural cycles of the heart, and handling compressive and tensile forces in the extravascular space.Te design requirements for these leads encompass various aspects including ease of implant handling, fuoroscopic visualization, lead body diameter, durability to outlast multiple IPG replacements, low-energy cardiac tissue stimulation, reliable sensing of intrinsic cardiac activity, and considerations for future lead extraction.
Te use of magnetic resonance imaging (MRI) for diagnostic purposes is rapidly increasing in many felds (like the brain, spinal cord, and musculoskeletal system).About 50-70% of patients with cardiac implantable electronic devices are estimated to have an indication for MRI over the lifetime of the device (1) [1].Te incorporation of MRI conditional lead design ofers an added safety beneft, considering the increasing preference for MRI scans in many felds.In the past, MRI scanning was contraindicated for patients with implanted cardiac devices [2,3], but recently, MRI scans have been safely performed in certain patients [4][5][6][7][8][9].Despite these advancements, concerns persist regarding the potential adverse efects of MRI scanners on pacemaker function, such as tissue heating at the lead tip, leading to capture failure or induced arrhythmias due to unintended cardiac stimulation [10,11].Terefore, the MRI lead was modifed to reduce radiofrequency lead tip heating.Tese modifcations resulted in a larger diameter and greater stifness of the leads compared with the conventional non-MRI pacing lead.Consequently, the Medtronic 5086 lead is reportedly associated with increased cardiac perforation and lead dislodgment [12][13][14].
Te Boston Scientifc INGEVITY+ pacing lead (Boston Scientifc, Marlborough, MA, USA) was upgraded to the INGEVITY lead.Te clinical performance of the INGEVITY lead has demonstrated a high lead-related complication-free rate over 12 months of follow-up and excellent electrical characteristics.However, the performance of the INGEV-ITY+ pacing lead has not yet been reported.Tis study aimed to evaluate the short-and long-term safety, efectiveness, and handling experience of INGEVITY+ pacing leads.

Device Characteristics.
Te INGEVITY+ pacing leads were 6F (2.0 mm) steroid-eluting endocardial pace/sense leads designed for permanent implantation in atrial or ventricular applications.Tese leads use an active fxation mechanism that employs an extendable or retractable helix for secure placement.INGEVITY+ was built on the established INGEVITY platform and incorporates specifc design features for MRI conditional safety.Te leads had three layers of insulation between the conductors and the polyurethane lead body to ensure optimal electrical performance and safety.Te inner coil design of the leads is triflar, providing consistent, low, and repeatable turn counts during helix extension and retraction.Tese leads incorporate design aspects for MRI conditional safety.Te inner coil of the MRI lead was modifed to have a higher inductance to prevent heating during MRI scanning, which was achieved through the uniflar design of the inner coils of the INGEVITY leads [13,15,16].However, because torque transfer decreased in a uniflar inner coil, the INGEVITY+ leads were upgraded to a triflar coil design.Tese leads feature an IS-1 bipolar connector for seamless integration with the pacing systems.Te tip of the lead was designed with fexibility in mind, incorporating an iridium oxide (IROX ™ ) coating on the tip of the electrode to improve the electrical performance and lead longevity.Te lead design is illustrated in Figure 1.Tis study was approved by the Institutional Review Board of Severance Hospital (1-2021-0011), and all patients provided written informed consent.For endpoint analyses, only leads that were implanted or attempted last during the initial implantation procedure in each chamber were considered.Te safety evaluation of INGEVITY+ leads focused on the complication-free rate (CFR) related to leads from the time of lead implantation until the 3-month follow-up.CFR was determined based on complications specifcally related to INGEVITY+ lead.Complications related to the leads include permanent loss of pacing therapy, injury, invasive intervention, or death.Tese are based on the AdvaMed document, "Industry Guidance for Uniform Reporting of Clinical Performance of Cardiac Rhythm Management Pulse Generators and Leads," which sets standards for lead performance reporting and specifcally addressed the reporting of active registry performance data.
Clinical efectiveness was assessed by evaluating the sensing and pacing performance at the 3-month postimplantation mark.Te primary efectiveness endpoint involved measuring bipolar pacing thresholds, which refers to the minimum electrical stimulation required to consistently initiate cardiac depolarization.Tis measurement was taken in volts (V) using a 0.5-ms pulse.In addition to the pacing threshold measurement, other lead electrical performance parameters were assessed at diferent time points, including predischarge and 3-month follow-ups.
All lead defciencies were documented and reported to the Institutional Review Board.Te handling experiences of the implanting physicians were collected to gain insights into their experiences with the new lead.Specifc aspects of interest include the radiopacity of the active fxation lead helix, which aids in confrming the full extension of the helix during implantation.Te overall handling of the lead and other related questions were part of the feedback assessment.

Statistical Methods. Descriptive statistics (mean ± SD)
were reported for lead electrical data.Comparisons between groups were performed using a 2-sample t-test or Fisher's exact test.Te 95% lower pointwise confdence limit of the lead-related CFR was determined using the log-log methodology.Tese values were compared with the predefned performance goals, which were set at 91.4% for the safety endpoint.An α level of 0.05 was used for each analysis.Data assembly and statistical analyses were performed using SPSS version 22 (IBM Inc., Armonk, NY, USA).

2
Cardiology Research and Practice All patients in this study required pacemaker implantation as part of their medical treatment.Te patient demographic characteristics are presented in Table 1.Notably, 43.5% of the enrolled patients were men, while 56.5% were women.Te mean age of the patients was 70.2 ± 9.1 years, with an age range spanning from 27.0 to 86.0 years.Te indications for pacemaker implantation were sinus node dysfunction (40.5%) and atrioventricular (AV) block (39.0%).

Results
Figure 2 shows the number of INGEVITY+ lead implantation according to physicians and the experience of physician.Most implantations (83%) were performed by physicians with INGEVITY+ lead implantation more than four (Figure 2).

Follow-Up and Complication-Free Rate (CFR) Related
with Leads.From enrollment to the 3-month follow-up, all subjects survived and remained in the study.During the implantation procedure, one patient required a lead change because of lead screw failure.
Te INGEVITY+ study successfully achieved predefned safety endpoints, and the lead-related CFR was 100% at three months.No instances of lead dislodgment were observed in any participant, resulting in an overall dislodgment rate of 0%.Additionally, the study recorded no occurrences of lead perforation (0.0%) or pericardial efusion (0.0%).

Pacing Treshold.
Troughout the 3 months, the pacing threshold of INGEVITY+ leads remained consistently low and stable.Te mean pacing threshold for active fxation in the RV was 0.92 ± 0.53 V, whereas that in the RA was 0.93 ± 0.54 V.A total of 95.7% of the RA leads and 99.5% of the RV leads exhibited pacing thresholds less than 1.5 V (Figure 3(a)).

Sensing Amplitude.
At the 3-month evaluation, the mean sensed amplitude of the INGEVITY+ leads in the RA was recorded as 4.2 ± 2.4 mV.For leads in the RV, the mean sensed amplitude was 16.9 ± 6.3 mV.Remarkably, 92.4% of the RA leads exhibited amplitudes >1.5 mV, whereas 96.5% of the RV leads exhibited amplitudes >5 mV (Figure 3(b)).

Pacing Impedance.
Te mean pacing impedance measured at 3 months was 628.0 ± 123.7 ohms for RA and 765.2 ± 131.1 ohms for RV.Te ventricular leads showed a decreasing impedance trend from the time of implantation to the 3-month follow-up (p < 0.001).In contrast, the atrial leads exhibited consistent impedances between the time of implantation and the 3-month evaluation (p � 0.219).Te impedances were between 300 and 1,300 ohms in 99.8% of leads (Figure 3(c)).

Handling Experiences.
In the lead-handling questionnaires, the radiopacity quality of the extendable/retractable helix markers, as well as the handling and maneuverability of the stylet and lead, were rated as "very good" or exceeded expectations in 68.5% and 68% of cases, respectively.Regarding the overall handling performance of the leads, 66.5% of the respondents graded it as "very good" or "excellent," while 32.0%considered it as "good," and 1.5% found it to meet their expectations.Furthermore, a signifcant majority   (88%) of operators agreed or strongly agreed that the leads were easy to navigate through small vessels or vessels with multiple leads (Figure 4).
To achieve a higher inductance, the inner coil was reduced from a multiflar design in the MRI-noncompatible model, leading to a 1-2 flar design [13,15].Te two-flar inner conductor coil design of the Medtronic 5086 lead increased the inductance, thereby reducing lead tip heating caused by radiofrequency (RF) energy.It has a 7F diameter, which requires an 8F introducer.However, its tip stifness, which can be an indicator of lead perforation, is greater than that of the Medtronics 5076 model [13,15].Terefore, the Medtronic 5086 lead has been reported to be associated with increased cardiac perforation, tamponade, death, and lead dislodgment [12][13][14].Delayed lead perforation may be associated with leads featuring a decreased diameter, resulting in higher force per unit area [19,20].
In the case of the INGEVITY and INGEVITY+ studies, which evaluated the 6-French lead design, no increase in the perforation rate was observed.Moreover, the INGEVITY+ data did not indicate a higher incidence of lead-related complications.However, it is usually recommended that a softer stylet be used when siting the MRI leads in an apical position and that the stylet is not fully seated when the lead is positioned against the myocardium.Another major diference between the leads is the number of rotations required to fully deploy the helix in the myocardium.To facilitate the transfer of torque and prevent sudden exit of the helix, manufacturers advise that the proximal portion of the lead should be maintained in a straightened position and that one 4 Cardiology Research and Practice turn per second be applied.Fluoroscopy is the only reliable method for confrming extension of the helix.Te movement of the radiographic markers at the lead tip indicates that the helix has been successfully deployed [13,15].Torque transfer was lower in a uniflar inner coil than in a similarly designed multiflar coil [12,13].In handling experience, INGEVITY+ lead-handling experience was reported to be very good.

Study
Limitations.Tis study was designed as an observational, single-arm investigation, thus limiting direct comparisons with historical control groups.Tis study included high-volume pacemaker centers with experienced operators.Te annual pacemaker implantation volume was inversely related to early surgical complications and early lead dislocations.Terefore, the outcomes observed in this study may difer in real-world settings, with fewer experienced operators and lower overall procedure volumes.Tese factors may introduce potential limitations to the generalizability of the fndings to diverse clinical environments [12,21].

Conclusion
Te study fndings unequivocally established the safety and efectiveness of the INGEVITY+ pacemaker lead, which exceeded the predefned endpoints.Continuous surveillance will be maintained to ensure the ongoing assessment of lead durability and long-term performance.

2. 2 .
Clinical Evaluation.Tis study evaluated the safety and efectiveness of INGEVITY+ pacemaker leads over a 3-month follow-up period.Tese leads were implanted in the right atrial (RA) and/or right ventricular (RV) region as part of a single chamber (SC) or dual chamber (DC) pacemaker.Patients eligible for the study had Class I or Class II indications for device implantation as per the reference guidelines.

Figure 1 :
Figure 1: INGEVITY+ pacing lead design.INGEVITY+ lead has three layers of insulation between conductors and a polyurethane lead body.Te triflar inner coil design provides consistent, low, and repeatable turn counts when extending and retracting the helix2.

Figure 2 :Figure 3 :
Figure 2: Number of implantation according to physicians (a) and the experience of physician (b).
We enrolled 200 subjects from nine centers in Korea from June 2021 to September 2022.All enrolled patients underwent implantation or attempted implantation with an INGEVITY+ lead, and all patients in this group received the lead.Te lead implantation procedure involved placement of both atrial and ventricular INGEVITY+ leads.Specifcally, 200 RV and 200 RA active fxation leads were implanted in the study population. 3.1.Patients.

Table 1 :
Baseline characteristics of patients.