Performance of an active fixation bipolar left ventricular lead vs passive fixation quadripolar leads in cardiac resynchronization therapy, a randomized trial

Abstract Background Usage of active fixation bipolar left ventricular (LV) leads represents an alternative approach to the more commonly used passive fixation quadripolar leads in cardiac resynchronization therapy (CRT). We compared a bipolar LV lead with a side screw for active fixation and passive fixation quadripolar LV leads. Methods Sixty‐two patients were before CRT implantations randomly allocated to receive a bipolar (n = 31) or quadripolar (n = 31) LV leads. Speckle‐tracking radial strain echocardiography was used to define the LV segment with latest mechanical activation as the target LV segment. The electrophysiological measurements and the capability to obtain a proximal position in a coronary vein placed over the target segment were assessed. Results Upon implantation, the quadripolar lead demonstrated a lower pacing capture threshold than the bipolar lead, but at follow‐up, there was no difference. There were no differences in the LV lead implant times or radiation doses. The success rate in reaching the target location was not significantly different between the two LV leads. Conclusions The pacing capture thresholds were low, with no significant difference between active fixation bipolar leads and quadripolar leads. Active fixation leads did not promote a more proximal location of the stimulating electrode or a higher grade of concordance to the target segment than passive fixation leads.

nonoptimal position of the left ventricular (LV) lead is a major reason for an inferior response to CRT. 4,5 Placement of the LV lead in a segment remote from the region with the latest mechanical activation or in a segment with a myocardial scar predicts a high risk for nonresponse. Echocardiographic speckle-tracking two-dimensional (2D) radial strain imaging has the ability to identify the LV segment with the latest mechanical activation. LV lead implantation guided by this robust echocardiographic method has been shown to augment the clinical outcomes of CRT compared with those of unguided LV lead placement. 6,7 The optimal location for LV pacing may be different from the best position for lead stability and may be compromised to achieve a stable lead position with a low risk of lead dislodgement.
Available quadripolar LV leads provide multiple options of different pacing vector and are particularly useful for eliminating postoperative phrenic nerve stimulation (PNS) by reprogramming lead configuration. 8,9 Active fixation mechanisms of LV leads facilitate stable lead positions in a wide range of venous anatomies. 10 The aim of the current study was to compare a bipolar LV lead with a side helix for active fixation and a quadripolar LV lead with passive fixation regarding the electrophysiological performance, the stability, and the ability to reach the target position.

| Study design
In this prospective, randomized, single-center trial, patients with symptomatic heart failure and an indication for CRT implantation in accordance with current guidelines were included. The study was approved by the regional committee for medical and health research ethics (Reference 2015/1507), and all patients gave their written informed consent. The patients were blinded and randomly assigned to receive either an active fixation lead or a quadripolar passive fixation lead. For patients randomized to receive a quadripolar lead, the operators were free to choose between three different shapes.
Prior to randomization, the patients were stratified into two cohorts based on whether they received a CRT device either with a defibrillator (CRT-D) or without a defibrillator (CRT-P). The decision of implanting a CRT-D or a CRT-P was done individually based on etiology of the heart failure and the patient's comorbidity.

| Patient population
Between February 2016 and November 2017, 62 patients were included and randomized. The inclusion criteria, which were based on current guidelines, were symptomatic heart failure; New York Heart Association (NYHA) functional class II or III or ambulant class IV; LV ejection fraction ≤35%; and left bundle branch block (LBBB) with a QRS duration ≥120 ms or non-LBBB with a QRS duration ≥150 ms The baseline clinical characteristics and comorbidities of the patients are described in Table 1. No significant differences were found between the two patient groups with respect to sex, QRS duration, LV ejection fraction, NYHA functional class, medication, and comorbidities. The average NYHA functional class was 2.7 in both patient groups.

| Echocardiographic imaging
The LV ejection fraction was measured by echocardiography using the biplane modified Simpson's method (GE Vivid E9, Vingmed Ultrasound, Horten, Norway). Transthoracic echocardiography with 2D speckle-tracking radial strain (ST-RS) measurements of the LV was performed prior to the implantation procedures. All images were processed offline (EchoPac 202 GE Medical System, Horten, Norway). Intraventricular LV dyssynchrony was determinated using ST-RS echocardiography from 2D images in a mid-LV parasternal short-axis view with a frame rate ≥50 Hz. Time-strain curves were computed for the different LV segments. Left ventricular segments with a strain rate <10% were excluded because this finding was considered to indicate a high level of transmural scarring. 11,12 The time from Q-wave onset on the electrocardiogram to the maximal radial strain in the anterior, lateral, and posterior LV segments was

| Cardiac resynchronization therapy device implantation
The devices were implanted under local anesthesia. The right atrial

| Lead characteristics
The active fixation lead was a soft bipolar steroid-eluting lead (Attain

| Statistical analysis
Analyses were conducted according to the intention-to-treat con-

| RE SULTS
Initial successful implantation was obtained in 31 patients (100%) and 30 patients (97%) in the active fixation bipolar group and the quadripolar group, respectively. In 1 patient, the quadripolar lead dislodged repeatedly during implantation, and this could not be avoided by switching to the bipolar active fixation lead. Finally, an alternate thicker bipolar LV lead was implanted successfully. In three patients, LV lead dislodgement occurred, all in the active fixation group. For two of these three patients, the LV lead dislodged some hours after implantation, and the third instance of dislocation was recognized after 2 months. In all three patients, the same lead was repositioned successfully to the same coronary vein. We compared the size of target veins (Table 2). There was no difference in vein size at the active electrode or at the distal electrode. The average vein dimension at the proximal electrode was larger at the qauadripolar lead, corresponding with a more proximal position. During FU, there were no additional instances of reoperation, and there were no cases of device infection. All patients were alive the 12 month FU. Table 2 summarizes the characteristics of the 62 implantation procedures.
The locations of the targeted LV segments were anterior (10%), anterolateral (11%), lateral (44%), posterolateral (30%), and posterior (5%). The distribution of the locations of the selected stimulating electrodes for each LV lead is shown in Figure 1. The target LV lead placement, which was defined as a position in a concordant or adjacent LV segment, was achieved in the majority of the patients with no statistically significant differences between the patient groups (Table 3). For both LV lead groups, the selected active electrodes were stimulating the LV from a position close to the distal part of the basal segments in majority of the patients. The proximal electrode of the quadripolar LV lead was closer to the CS than that of the active fixation LV lead. However, there was no statistically significant difference between the active fixation group and the quadripolar group concerning the proximity of the stimulating electrode to the coronary sinus, neither in absolute values nor in distance as a percentage of the distance from the CS to the apex.

F I G U R E 3
A, The bipolar lead with distal angled shape has an exposed side screw for fixation located 15 mm proximal to the proximal electrode. The electrode separation is 21.0 mm. The maximum lead body diameter is 3.9 Fr. B, Demonstrates a close range view of the exposed side screw. C, The quadripolar leads: An S-shaped lead, a straight lead with tines and a dual bend lead. The distances between the electrodes are 21 mm (LV1-LV2), 1. The electrical performance was recorded at implantation and at the 2-, 6-and 12 month FU periods ( at one time or another after discharge from the hospital experienced some kind of discomfort from PNS. Six of those patients (19%) were in the active fixation group, and three (10%) were in the quadripolar group. In all cases, the PNS was resolved by reprogramming the device. trial that compared active fixation LV leads with quadripolar LV leads reported noninferior clinical outcomes for the active fixation leads. 16 Our trial is the only randomized clinical trial comparing active fixation LV leads with quadripolar LV leads. At implantation, the PCT was lower in the quadripolar group than in the active fixation group, but the difference decreased later, and there were no significant differences at the 6-and 12 month FUs. The pacing impedance was significantly higher (approximately 20%) in the active fixation group than in the quadripolar group and may lead to a moderate increase in battery longevity compared to devices with quadripolar LV leads.

| D ISCUSS I ON
Our hypothesis was that in large veins, an active fixation bipolar LV lead will enable a more proximal position of the stimulating electrode compared to a quadripolar lead. We aimed to achieve a position of the stimulating LV lead electrode as far from the apex as possible.
Nevertheless, we did not find any significant difference between the two types of LV leads concerning the proximity of the ultimately selected stimulating electrode to the coronary sinus. Thus, the active fixation lead did not promote a more basal placement of the stimulating electrode. An explanation for this may be that in many cases of quadripolar leads, it was possible to wedge the lead tip in an early side branch to stabilize the stimulation electrode in a basal LV segment.
Furthermore, the electrically inactive helix of the active fixation bipolar lead was placed proximal to the proximal electrode, thus prohibiting placement of the proximal electrodes in the vein close to the coronary sinus. The PCT for the proximal electrode was significantly higher for the quadripolar lead than for the active fixation lead (2.84 vs 1.42 V).
This may be because of the lower amount of pressure toward the wall for the passive leads than for the active fixation leads in the proximal vein segment. On the contrary, the PCTs for the distal electrodes were lower for the quadripolar leads at implantation. An explanation for this may be that the S-shape or dual bend shape and the larger body diameter of the quadripolar lead may cause more tension toward the vein wall than that of the distal end of the active fixation lead. Quadripolar leads with active fixation were not available when the current trial was performed, but later, a quadripolar active fixation lead with a similar helix for fixation was approved (Medtronic lead model 4798). In this quadripolar version, the fixation mechanism is located between electrodes 3 and 4, which may potentially improve the lead stability and reduce the PCT for the most proximal electrodes, even in large coronary veins. The LV lead dislodgement rate is low in recent trials with quadripolar leads, and in the Performa Trial, a dislodgement rate of 1.4% was reported. 17 In the current trial, which was not powered to show differences in the rate of lead dislodgement, there were no dislodgements of the quadripolar leads; however, in the active fixation group, two postoperative dislodgments and one late dislodgment occurred. These three patients were retrospectively evaluated. One patient had a large-diameter coronary vein (16.5 Fr at the point of helix fixation) and needed four fixation attempts at the primary operation. The other 2 patients with LV lead dislodgement showed no unusual vein-anatomy and only one fixation attempt was needed initially. The present trial did not prove that adding an active fixation mechanism to bipolar lead makes them more stable than passive fixation quadripolar leads. The new location of the fixation helix between electrodes 3 and 4 in the Medtronic lead model 4798 may potentially further augment the stability of the active fixation lead. 18 There is an obvious concern about the extractability of active fixation LV lead. Unlike the leads with side lobes of the lead, the Attain Stability is fixated with a side helix constructed to uncoil in response to retractive force. However, the data on extraction safety are limited and this must be taken into account when choosing an LV lead.
In this randomized trial, comparing an active fixation bipolar lead and quadripolar passive fixation leads, no important differences in implantation variables or long-term electrical performance were found. Furthermore, there were no differences in the ability to reach a proximal concordant or adjacent LV segment for targeted LV stimulation.

| Study limitations
The study was a single-center study with a relatively small sample size. Therefore, the extension of the validity of these results to other centers and implanters is not possible. The clinical findings, as changes in NYHA classification or echocardiographic response, were not compared in the present study.

CO N FLI C T O F I NTE R E S T S
The authors have no conflict of interest, financial or otherwise.