An active fixation quadripolar left ventricular lead for cardiac resynchronization therapy with reduced postoperative complication rates

Abstract Background The rate of left ventricular (LV) lead displacement after cardiac resynchronization therapy (CRT) remains high despite improvements in lead technology. In 2017, a novel quadripolar lead with active fixation technology became available in the UK. Methods This was a retrospective, observational study analyzing device complications in 476 consecutive patients undergoing successful first‐time implantation of a CRT device at a tertiary center from 2017 to 2020. Results Both active (n = 135) and passive fixation (n = 341) quadripolar leads had similar success rates for implantation (99.3% vs. 98.8%, p = 1.00), although the pacing threshold (0.89 [0.60–1.25] vs. 1.00 [0.70–1.60] V, p = .01) and lead impedance (632 [552–794] vs. 730 [636–862] Ohms, p < .0001) were significantly lower for the active fixation lead. Patients receiving an active fixation lead had a reduced incidence of lead displacement at 6 months (0.74% vs. 4.69%, p = .036). There was no significant difference in the rate of right atrial (RA) and right ventricular (RV) lead displacement between the two groups (RA: 1.48% vs. 1.17%, p = .68; RV: 2.22% vs. 1.76%, p = .72). Reprogramming the LV lead after displacement was unsuccessful in most cases (successful reprogramming: Active fix = 0/1, Passive fix = 1/16) therefore nearly all patients required a repeat procedure. As a result, the rate of intervention within 6 months for lead displacement was significantly lower when patients were implanted with the active fixation lead (0.74% vs. 4.40%, p = .049). Conclusion The novel active fixation lead in our study has a lower incidence of lead displacement and re‐intervention compared to conventional quadripolar leads for CRT.


| INTRODUCTION
Cardiac resynchronization therapy (CRT) has become the gold standard treatment for heart failure patients with severely reduced ejection fraction and left bundle branch block. Studies have consistently demonstrated an improvement in symptoms and left ventricular (LV) ejection fraction in the majority of patients, as well as a reduction in mortality after CRT insertion. 1,2 Nonetheless, CRT is limited by several complications, many of which relate to the insertion of the LV lead. 3 The placement of a pacing lead within the coronary venous system for CRT can be technically challenging and subsequent LV lead displacement is a well-recognized postprocedural complication. 4 This typically results in an increase in pacing threshold and a loss of LV capture, thus negating the benefit of resynchronization therapy. LV lead displacement can also cause inadvertent stimulation of the phrenic nerve, leading to uncomfortable diaphragmatic excitation. Whilst the advent of quadripolar LV leads allows for re-programming around phrenic nerve stimulation, 5 if LV lead displacement results in loss of capture from all the available pacing vectors, a repeat procedure to replace the lead is required.
Standard LV leads rely on a passive fixation technique which involves advancing the lead tip distally into the target vessel.
With quadripolar leads, this can allow for the lead to be positioned more apically for better stability, but with pacing from more basal electrodes closer to the site of the latest activation. 6 Quadripolar leads are associated with more effective resynchronization and a reduction in heart failure hospitalization and mortality compared to bipolar leads. 5,[7][8][9] In 2017, a novel quadripolar LV lead-containing active fixation mechanism was made available in the UK. This lead has a specifically designed side-helix which actively fixes the lead body to the target vessel.
Initial experience with the lead has demonstrated a high rate of procedural insertion success (96.8%) and a low rate of LV leadrelated complications (2.3%). 10 However, no study to date has made a direct comparison between this active fixation lead and conventional quadripolar LV leads. In this study, we use observational data from a large tertiary UK hospital to assess lead implantation success, pacing characteristics, and complication rates when compared to conventional passive fixation quadripolar LV leads, with a focus on the rate of lead displacement at 6 months and the need for invasive re-intervention. between a vein and the nearest artery is 1 mm) 11 leaving a fourfold safety margin for insertion. Furthermore, the helix incorporates a mechanical stop that activates after four rotations to prevent the lead from becoming over-torqued.

| Study design
We performed an observational study using registry data from a UK tertiary center to compare the complication rates for patients undergoing CRT insertion with the active fixation lead and those who received conventional passive fixation quadripolar leads. All patients gave written informed consent, and the study was locally approved and Boston Scientific = 9). All CRT devices were implanted according to guidelines published by the European Society of Cardiology. 12 The decision to insert a passive or active fixation LV lead was made before the procedure by the implanting physician. Preimplantation characteristics such as patient demographics, ejection fraction, and electrophysiological parameters were collected from available clinical data. Procedural characteristics such as the position of the LV lead, and lead capture threshold were collected using our local catheter-lab reporting system. Complete data sets were available for all parameters except for lead electrical characteristics are at the discretion of the operator but are also optimized to produce the narrowest QRS duration of the best morphology. Multi-point™ or MultiSite™ pacing is not routinely programmed at implant in our institution but considered at 6 months in non-responders. 13 Electronic patient records were used to identify patients that experienced complications within 6 months, such as phrenic nerve stimulation and lead displacement. If there was an unacceptable rise in pacing thresholds, lack of ventricular capture, or new phrenic nerve stimulation, then patients would undergo a chest X-ray to look for evidence of displacement. A lead displacement was defined as a change in the lead position as documented on chest radiography in two orthogonal planes associated with a change in pacing parameters from that observed at the implant. All complications were reviewed monthly at a morbidity and mortality meeting, and annually via further audit as approved by our institution.

| Data analysis
All continuous nonparametric data is reported as a median and interquartile range. Analysis was performed using a Mann-Whitney U test. Categorical data were reported as n (%) and analyzed using a χ 2 test, except for where there was a small number of reported events, under which circumstances a Fisher's exact test was used.
Statistical significance is accepted at p < .05.

| Clinical characteristics
The clinical characteristics of the 476 patients who successfully received an LV lead are shown in Table 1. Patients receiving either an active or passive fixation quadripolar lead were well matched with respect to sex, heart failure etiology, and left ventricular ejection fraction. Furthermore, there were no significant differences between the two groups with respect to the QRS duration or underlying electrical rhythm. However, patients receiving the active fixation lead were on average slightly older.

| Procedural characteristics
Procedural success in inserting an LV lead was similarly high regardless of the type of LV lead that was selected (Active fixation = 135/136 (99.3%); Passive fixation = 341/345 (98.8%), p = 1.00). For successful lead insertions, the procedural characteristics for each implantation are shown in Table 2. A similar proportion of active fixation CRT procedures incorporated a defibrillator when compared with the passive fixation group, although a slightly higher proportion were de novo insertions rather than an upgrade of an existing pacemaker. LV lead pulse width (t, seconds) was the same for both groups. Whilst the capture threshold (V) was significantly lower with the active fixation lead, the impedance (I) was similarly lower, therefore there were no significant differences in the threshold energy between the two groups. Documentation of the final LV lead position obtained using our cath-lab reporting system demonstrated that there was no significant difference in the anatomical positioning of active and passive fixation LV leads.
There was no significant difference in the rate of displacement of right atrial and right ventricular leads between the two groups. Furthermore, there was no significant difference between the displace-  Table 3).
Rates of phrenic nerve stimulation for the two leads were similar.
There was no significant difference between the rates of other procedural complications requiring revision such as wound hematoma and infection (Table 3). Furthermore, the rates of coronary sinus dissection were similar for both groups, and there were no incidences of cardiac tamponade resulting from the placement of an LV lead.

| DISCUSSION
Here we report the first study to directly compare outcomes of a novel  However, before our study, no direct comparison has been made against a control group comprised of patients who underwent insertion of conventional LV quadripolar leads.
In our study, it is notable that both active and passive quadripolar leads had a similarly high success rate for implantation reflecting the improvement in delivery catheters, sub-selectors, guide wires, stylets, and lead design over the last 20 years. The active fixation lead had a significantly lower pacing threshold and lead impedance which may reflect the better contact obtained from the active fixation mechanism, and/or the fact that all four poles on this lead have steroid eluting electrodes. However, given that pacing energy was similar between active and passive fixation leads, it is unlikely these differences will alter overall battery longevity.
We also demonstrate that there is a significant reduction in the rate of LV lead displacement at 6 months postimplant with the active fixation lead when compared with conventional passive fixation LV leads. Furthermore, reprogramming the device to overcome the issues associated with lead displacement is rarely successful. Out of the 16 patients in the passive fixation group who experienced a lead displacement, 15 were offered a repeat procedure to revise or replace the lead. This represents a significantly higher rate of re-intervention compared to that when an active fixation lead is inserted in the initial procedure.
In addition to reduced rates of lead displacement, active fixation leads may facilitate LV lead insertion into targeted vein segments and reduce rates of intraoperative displacement, allowing the operator more flexibility in terms of where to position the lead. 18,19 This is encouraging, since positioning the LV lead at the latest point of activation of the ventricle has been shown to improve clinical outcomes such as mortality and heart failure hospital admission. 15,20,21 In most cases, targeting the lead to a postero-lateral, mid-to-basal LV segment can achieve pacing at the latest point of activation. 22 There have previously been concerns expressed about the potential difficulties of extracting chronically implanted active fixation leads. 23,24 This arose from the analysis of a small number of attempted transvenous extractions of the Medtronic StarFix leads, where powered sheaths and aggressive techniques were required for removal. However, the Attain Stability lead employs a very different mechanism for active fixation into the vessel wall which has been reported to be safe and without procedural complexity in sheep. 25 Furthermore, there have been successful cases of uncomplicated extraction of the 20066 active fixation bipolar lead, which uses the same technology as the Attain Stability lead. 26,27 In our study, one active fixation lead required extraction and was done so without complication. Nonetheless, further information about the long-term extractability of active fixation leads will need to be recorded.

| Limitations
This large observational study of 476 patients is based on real-world data which reflects the routine clinical practice in our center. It is therefore nonrandomized and prone to the effects of possible confounding variables. There was a trend towards older age in the active fixation group. However, it is unlikely that these factors limit the interpretations of our findings given that the key outcome was the rate of lead displacement. Additionally, this is a single-center study, albeit at a hospital with substantial experience of inserting active fixation leads.

| CONCLUSIONS
The novel active fixation LV lead in our study has a significantly lower rate of lead displacement at 6 months when compared to conventional LV leads. Subsequently, the proportion of patients requiring a repeat procedure to revise the LV lead is also significantly decreased with the active fixation lead.

ACKNOWLEDGEMENT
This study received no specific funding.