Aveir VR real-world performance and chronic pacing threshold prediction using mapping and fixation electrical data

Abstract

Aims

Aveir VR performance and predictors for its pacing threshold (PCT) in a real-world cohort were investigated.

Methods

Electrical measurements at various stages of an Aveir VR implant were prospectively collected. Predictors for 3-month PCT were studied. A retrospective cohort of consecutive 139 Micra implants was used to compare the PCT evolution. High PCT was defined as ≥1.5 V, using a pulse width of 0.4 ms for Aveir and 0.24 ms for Micra. Excellent PCT was defined as ≤0.5 V at the respective pulse width.

Results

Among the 123 consecutive Aveir VR implant attempts, 122 (99.2%) were successful. The majority were of advanced age (mean 79.7) and small body size (mean BSA 1.60). Two patients (1.6%) experienced complications, including one pericardial effusion after device reposition and one intraoperative device dislodgement. Eighty-eight patients reached a 3-month follow-up. Aveir 3-month PCT was correlated with impedance at mapping (P = 0.015), tether mode (P < 0.001), end-of-procedure (P < 0.001), and mapping PCT (P = 0.035), but not with PCTs after fixation (P > 0.05). Tether mode impedance >470 ohms had 88% sensitivity and 71% specificity in predicting excellent 3-month PCT. Although it is more common for Aveir to have high PCT at end of procedure (11.5% for Aveir and 2.2% for Micra, P = 0.004), the rate at 3 months was similar (2.3% for Aveir and 3.1% for Micra, P = 1.000).

Conclusion

Aveir VR demonstrated satisfactory performance in this high-risk cohort. Pacing thresholds tend to improve to a greater extent than Micra after implantation. The PCT after fixation, even after a waiting period, has limited predictive value for the chronic threshold. Low-mapping PCT and high intraoperative impedance predict chronic low PCT.

Graphical Abstract

Graphical Abstract.

Aveir VR pacing threshold tended to improve after implant, while Micra stayed the same. Intraoperative impedance is a good predictor for chronic threshold, while intraoperative threshold was not.

What’s new?

• Aveir VR demonstrated satisfactory performance and safety in a cohort with higher risk profiles.

• In this smaller body size cohort (BMI 22.6 vs 28.7 in Leadless II cohort), snare-assisted implant or right jugular approach may be needed to achieve safe implantation.

• High pacing threshold (PCT) was five times more common in Aveir than Micra at end of procedure, but the rate is similar at 3 months.

• Pre-fixation PCT correlated with 3-month PCT, while post-fixation PCT at tether mode or post-release did not. This was true even after a waiting period for high-threshold cases. Therefore, one should not reposition a fixated Aveir VR solely based on high PCT after fixation, as pericardial effusion may ensue.

• High impedance at all stages of implant strongly predicts excellent 3-month pacing threshold. This is a reassuring sign that electrical measurement will likely improve with resolution of tissue injury.

Introduction

Leadless pacemakers are promising alternatives to transvenous pacing.^1,2 The Micra leadless pacemaker, adopting a passive fixation mechanism, has demonstrated excellent efficacy and safety profile in IDE trial³ and post-approval registries.^4–6 Non-randomized studies also demonstrated its favourable safety profile comparable to transvenous pacing.^6–9

The Aveir leadless pacemaker adopts an active fixation mechanism.¹⁰ It allows electrogram mapping and testing of electrical measurements before fixation.¹⁰ This theoretically reduces the need for device repositioning. While the result of the Leadless II study was promising,^10,11 there were only a few small studies to describe its performance in real-world settings.^12–15 As demonstrated in Micra post-marketing registries, patients implanted with leadless pacemakers in the real world were older and exhibited more comorbidities.⁴ In the Asian population, patients also tend to be of smaller body build, which increases the challenge of achieving a safe implant.¹⁶ This may be particularly relevant for Aveir VR device as it is ∼50% longer than Micra,¹⁷ which may limit the catheter manoeuvrability in small hearts.

This study aims to evaluate the safety and performance of Aveir VR in a real-world population with small body size. From this cohort, we sought to identify predictors for good electrical measurement. A Micra cohort would be used as a comparison arm to illustrate the different procedural characteristics.

Methods

Study design

This was an investigator-driven, non-randomized cohort study. No sponsorship from industry was involved. The study was approved by local institutional ethics review board. Consecutive patients undergoing Aveir VR pacemakers at Prince of Wales Hospital and Queen Elizabeth Hospital in Hong Kong were included in the study. The implantation procedure characteristics were prospectively collected. This included the number of mapping positions and serial electrical measurements during mapping, fixation, tether mode, and after release. Commanded electrograms (CEGMs) were also collected at each phase of implant. Follow-up electrical measurements were performed at the first week post-implant (Days 1–7) and at 3 months. The performance of Aveir VR was compared with a cohort of consecutive patients undergoing Micra VR.

Aveir VR implantation procedure

The implantation technique was standard, apart from additional serial electrical measurements mandated by the implantation protocol (Table 1). For patients on anticoagulation, new oral anticoagulations (NOACs) were stopped for at least 24 h before implant, or warfarin interrupted until international normalized ratio (INR) <1.5. Implantations were attempted via the right femoral vein. If implantation could not be achieved by this access, right jugular venous access would be attempted. The mapping electrical measurements and CEGMs were saved for analysis. When a site with good electrical measurements was identified, the device was fixated by slow clockwise rotation of the delivery catheter handle, during which clicks would be felt for each 45° rotation of the handle. The number of clicks to achieve 0.25, 0.5, 0.75, 1, 1.25, and 1.5 turns was recorded. In addition, CEGM and impedance measurement would be performed at 0.5, 1, and 1.25–1.5 turns. After 1.25–1.5 turns, the device would go into tether mode. Then deflection stress test would be performed to ensure secure fixation. At this stage, full electrical measurements and CEGM would be collected. If pacing threshold (PCT) was higher than 2V@0.4, measurements were repeated after a 3-min interval. Repositioning would be at implanter’s discretion, taking into account the electrical measurement, CEGM recordings, and fixation security demonstrated in the deflection test. After device release, the measurement was repeated. If pacing threshold was higher than 1.5V@0.4 ms, a repeat measurement would be made 3 min later. Snaring of device would be considered if pacing threshold was persistently high. After implantation, the femoral wound was managed with a figure-of-eight skin suture. Electrical measurements were repeated after wound closure.

Table 1.

Aveir VR electrical measurement protocol.

Mapping phase

Measurement of CEGM, impedance, sensing, and pacing threshold at each site

Fixation phase

0.5 turn: CEGM and impedance

1 turn: CEGM and impedance

1.25–1.5 turns: CEGM and impedance

Tether mode phase

After deflection test

Measurement of CEGM, impedance, sensing, and pacing threshold

If pacing threshold > 2V@0.4 ms, wait 3 min and repeat measurement

Additional 3-min wait encouraged if pacing threshold remains high

Release at the discretion of implanter, taking into account all electrical measurements, deflection test stability

Post-release phase

Measurement of CEGM, impedance, sensing and pacing threshold

If pacing threshold > 1.5V@0.4 ms, wait 3 minutes and repeat measurement

Additional 3 minutes wait encouraged if pacing threshold remains high

Accept device position at the discretion of implanter, taking into account all electrical measurements

CEGM, commanded electrogram.

Follow-up

The device would be checked the first week after implant (1–7 days post-implant). Commanded electrogram collection and electrical measurements would be performed. Another check at 3 months post-implant was performed. Any complications related to the device would be recorded.

Micra VR comparison cohort

The Micra cohort consisted of consecutive patients undergoing Micra VR implantation between the years 2015 and 2018 at the Prince of Wales Hospital. Number of device repositioning and electrical measurements at end of procedure were documented and retrospectively collected. Procedural complications were recorded. Follow-up measurements at the first week and 3 months were retrieved.

Endpoint definition

The pacing threshold during mapping was defined as the last pacing threshold taken before fixation. The pacing threshold during tether mode was defined as the last pacing threshold obtained during tether mode, after deflection test and following a waiting period for high pacing threshold cases. Similarly, the pacing threshold at the end of procedure was defined as the pacing threshold after device release and following a waiting period for high pacing threshold cases. Excellent pacing threshold was defined as ≤0.5V@0.4 ms for Aveir VR cases. High pacing threshold was defined as ≥1.5@0.4 ms for Aveir VR and ≥1.5V@0.24 ms for Micra VR.

Statistical analysis

Categorical variables were presented in frequency tables and compared using Pearson’s χ² test if all cell sizes were >5, or Fisher’s exact test if otherwise. Parametric and non-parametric continuous variables were expressed as mean ± SD and median (interquartile range) and were compared using Student’s t-test and Mann–Whitney U test, respectively. Spearman’s correlation test was used to study the correlation between pacing threshold and implant characteristics. All statistic tests were two tailed. A P < 0.05 was considered statistically significant. Receiver operating characteristic (ROC) analysis was performed to identify predicting power of variables. All statistical analyses were performed using SPSS version 29.0.

Results

Patient characteristics

From March to December 2023, 123 consecutive patients underwent implantation of Aveir VR leadless pacemakers in the two centres. The first week follow-up data were available for all these patients. Eighty-eight patients reached 3-month follow-up. The patient characteristics are summarized in Table 2. The cohort has a mean age of 79.7, BMI 22.5, and BSA 1.60.

Table 2.

Characteristics of Aveir VR cohort.

Patient characteristics	Mean ± SD or frequency (percentage)
Age	79.7 ± 8.0
BMI	22.5 ± 3.7
BSA	1.60 ± 0.17
Indication
Sick sinus syndrome	61 (49.6%)
AV block	62 (50.4%)
Chronic obstructive pulmonary disease	7 (5.7%)
Renal impairment	67 (54%)
Heart failure	42 (34%)
Atrial fibrillation	62 (50%)
On antiplatelets	36 (29%)
On anticoagulation (but interrupted)	57 (46%)
Dialysis	6 (4.9%)
Previous cardiac implantable device infection	1 (1%)
Coronary artery disease	31 (25%)

BMI, body mass index; BSA, body surface area; AV, atrioventricular.

Aveir VR implantation results

One hundred and twenty-three patients underwent Aveir VR implantation attempts, of which 122 (99.2%) were successfully implanted with a functional device. Among these patients, two required snare-assisted implantation (see Supplementary material online, Figure S1) and two required jugular vein access. For the case with unsuccessful implant, the patient was eventually diagnosed with retroperitoneal fibrosis with atresia of both superior and inferior venae cavae in CT. The hepatic vein was accessed percutaneously, and a single-chamber pacemaker was implanted with generator of device placed at right lateral abdominal wall (see Supplementary material online, Figure S2).

Among the successful implant cases, 13 (10.7%) patients required repositioning of device, of which 12 (9.8%) patients had successful implant after first repositioning, and 1 (0.8%) patient had repositioned twice. The implant pacing threshold, sensing, and impedance trend during are shown in Figure 1. During acute fixation, we observed a trend of rise in impedance and drop of pacing threshold. After implantation, the pacing threshold continued to improve, with rise of R-wave sensing and drop of impedance. At 3-month follow-up, the pacing threshold improved from 0.81 ± 0.54 to 0.62 ± 0.47 V. Impedance fell from 731 ± 288 to 563 ± 149 ohms. The R-wave sensing also improved from 7.46 ± 3.84 to 11.15 ± 4.21 mV.

Figure 1.

Electrical measurement of Aveir at various stages of implant and follow-up.

High pacing threshold (≥1.5V@0.4 ms) was observed in 25.0% patients on mapping, 19.2% patients on tether mode, and 11.5% patients at end of procedure, but only 2 patients on the first week (1.6%, n = 122) and 2 patients (2.3%, n = 88) at 3 months (Graphical Abstract).

There was one case of pericardial tamponade, which happened after unscrewing a fixated device in response to high pacing threshold during tether mode. Emergency pericardiocentesis was performed. After stabilization, the procedure was continued with a successful implant. The pericardial drain was removed on the next day, and the patient was discharged on Day 2 post-implant. There was one case of intraoperative device dislodgement, attributed to a difficult device release. The device was snared out percutaneously with two loop snares. The same device was reloaded to the delivery catheter and reimplanted successfully. There was no post-operative dislodgement, vascular complications, deep vein thrombosis, or procedure-related death. The overall complication rate was 1.6%.

Predicting factors for 3-month pacing threshold in Aveir VR

Correlation between implant electrical measurements and 3-month pacing threshold is summarized in Table 3. Three-month pacing threshold was inversely correlated with mapping impedance (P = 0.015), tether impedance (P < 0.001), and final impedance (P < 0.001). It was correlated to pacing threshold at mapping (P = 0.035) but was not correlated with tether or final pacing threshold (P > 0.05).

Table 3.

Correlation between Aveir 3-month pacing threshold and intraoperative measurements

Variables	Correlation coefficient	P-value
Mapping phase
Pacing threshold	0.231	0.035*
Impedance	−0.267	0.015*
Sensing	−0.077	0.496
Tether phase
Pacing threshold	0.093	0.403
Impedance	−0.385	<0.001**
Sensing	0.029	0.794
End of procedure
Pacing threshold	0.175	0.115
Impedance	−0.371	<0.001**
Sensing	−0.121	0.280

* denotes P value < 0.05, ** denotes P value < 0.001.

Impedance at any stage of fixation was a good predictor for excellent 3-month pacing threshold. The ROC area under the curve (AUC) was 0.72 for mapping impedance, 0.82 for tether mode impedance, and 0.80 for final impedance (Figure 2, Graphical Abstract). Tether mode impedance >470 ohms had 88% sensitivity and 71% specificity to predict excellent 3-month pacing threshold (Figure 3).

Figure 2.

Receiver operative characteristic analysis on 3-month pacing threshold and intraoperative impedance and pacing threshold. The area under the curve for impedance at mapping, tether mode, and end of procedure was 0.72, 0.82, and 0.80, respectively, indicating good predicting power. The area under the curve for pacing threshold at mapping, tether mode, and end of procedure was 0.65, 0.56, and 0.64, respectively, indicating poor predicting power. ROC, receiver operative characteristic.

Figure 3.

Scatter plot of 3-month pacing threshold against impedance at tether mode. Tether mode impedance >470 ohms had 88% sensitivity and 71% specificity in predicting excellent 3-month pacing threshold.

Micra cohort

A cohort of 139 consecutive Micra implants were used to compare with the Aveir cohort. They were implanted between the years 2015 and 2018 at Prince of Wales Hospital, Hong Kong. Patients had a mean age of 80.5 ± 8.73, BMI 23.7 ± 3.68, and BSA 1.60 ± 0.18. Implantation was successful in 137 (98.6%) patients, with two failed implantations due to inadequate electrical measurements after repeated repositioning attempts. Transvenous pacemakers were implanted for these two patients. There were two cases of pericardial effusion, of which one required percutaneous drainage and one settled with observation. There was a case of early peri-procedural death of uncertain cause. 24.5% of the patients required Micra repositioning, with 7.9% requiring more than one repositioning attempt (up to 10 repositions). The mean pacing thresholds at implant and 3 months were 0.60 ± 0.33 V and 0.57 ± 0.40V@0.24 ms, respectively. R-wave sensing were 9.63 ± 4.32 mV at implant and 13.26 ± 4.85 mV at 3 months. Impedance was 745 ± 198 ohms at implant and 586 ± 113 ohm at 3 months. High pacing threshold, defined as a pacing threshold of ≥1.5V@0.24 ms, was observed in 3 (2.2%) patients at implant and 4 (3.1%, n = 130) patients in 3 months.

Comparison between Aveir and Micra cohorts

Repositioning was less common in the Aveir cohort (10.8% vs. 24.6% for Micra, P = 0.005 by Pearson’s χ² test). At end of procedure, more patients in Aveir had a high pacing threshold compared with Micra (11.5% vs. 2.2%, P = 0.004 by Fisher’s exact test). However, by 3 months, the probability of high pacing threshold was similar between Aveir and Micra (2.3% vs. 3.1%, P = 1.000 by Fisher’s exact test; Graphical Abstract).

Discussion

The Aveir VR has the unique mapping capability before fixation. Our study took advantage of Aveir VR’s unique mapping capability to study the serial electrical measurement evolution of a helix-fixation leadless pacemaker. This allows us to investigate predictors of satisfactory long-term electrical measurement. This study is also the first real-world report of Aveir VR in a high-risk small body size cohort.

The main findings are as follows:

1. Aveir VR demonstrated satisfactory performance and safety in a cohort with higher risk profiles.

2. In this smaller body size cohort (BMI 22.6 vs. 28.7 in Leadless II cohort), snare-assisted implant or right jugular approach may be needed to achieve safe implantation.

3. High pacing threshold was five times more common in Aveir than Micra at end of procedure, but the rate is similar at 3 months.

4. Pre-fixation PCT correlated with 3-month PCT while post-fixation PCT at tether mode or post-release did not. This was true even after a waiting period of at least 3 min for high-threshold cases. Therefore, one should not reposition a fixated Aveir VR solely based on high PCT after fixation, as pericardial effusion may ensue.

5. High impedance at all stages of implant strongly predicts excellent 3-month pacing threshold. This is a reassuring sign that electrical measurement will likely improve with resolution of tissue injury.

Implantation in patients with small body size

It was demonstrated in Micra studies that small body size is an important risk factor for complications.^16,18 The mean BMI was 27–28 in the Micra IDE trial³ and 28.7 in the Leadless II trial Phase 1 for Nanostim.¹⁹ This current study presents a cohort of much smaller body sizes, with a mean BMI of 22.5 and BSA of 1.6. The longer Aveir VR device length may limit the catheter manoeuvrability in small hearts. There was also a concern that patients with smaller hearts may have increased pericardial effusion risk, especially if the screw-in fixation was inadvertently at the thinner right ventricular apex or free wall. This study demonstrates that the procedure can be performed safely in this group of patients. However, special techniques may be required for about 4% of these patients, such as snare-assisted implantation or a trans-jugular approach. The technique of snared-assisted implantation is described in the Supplementary material. Trans-jugular implantation of Aveir VR pacemaker was described by Ip.²⁰

Strategy to prevent cardiac perforation

Repositioning of leadless pacemakers was an independent risk factor for cardiac perforation.²¹ The repositioning of a helix-fixed leadless pacemaker may theoretically create more tissue injury than a tine-fixed one. In this cohort, the only cardiac tamponade case happened after a repositioning attempt. In the Leadless II Phase 2 trial,¹⁰ the pericardial effusion rate was 1.5%. The pericardial effusion rate in our cohort is 0.8%. The lower pericardial effusion rate may be contributed by a lower reposition rate (10.8% in this cohort compared with 16.8% in the Leadless II Phase 2 study¹⁰).

Strategies to minimize repositioning and achieve good electrical measurements

Comparing with Micra highlights the difference in pacing threshold evolution. Our study shows the pacing threshold of Aveir VR improves by a greater extent after acute implant. This is consistent with findings in the Leadless II trial¹⁰ (mean pacing threshold improved from 0.85 V to 0.54V@0.4 ms at 6 months). In contrast, the pacing threshold stayed stably low in the Micra IDE trial with less improvement (from 0.63 V improved to 0.54V@0.24 ms at 6 months).³ The unique electrical measurement collection protocol of this study demonstrates that high pacing threshold was rather common at the mapping phase (25.0%) and tether mode (19.2%). This suggests that we should not reposition a device solely based on high pacing threshold test after fixation, especially if the pacing threshold before fixation is low.

Pacing threshold at tether mode and end of procedure both had poor correlation with the 3-month pacing threshold. This was true even after a waiting period of 3–9 min for high-threshold cases. Acute tissue injury can cause a reversible increase in pacing threshold, and this can be contributed by both direct catheter pressure and active fixation. Mapping pacing thresholds tend to correlate with 3-month pacing threshold (P = 0.035). This is reasonable as pacing threshold at mapping is least affected by tissue injury, compared with pacing threshold at tether mode or after device release.

Higher impedance at any stage of implant strongly correlates with low pacing threshold at 3 months. This is in-line with previous study on Micra.²² However, impedance monitoring is even more important for Aveir. Unlike in the case of Micra, where one can rely on pacing threshold at tether phase to guide repositioning decisions, the tether mode threshold for Aveir has little predicting value on chronic threshold (AUC for ROC = 0.534 only). Based on findings from this study, impedance >385 ohms at mapping phase and >470 ohms at tether mode suggests that the high pacing threshold for this device is transient, and the 3-month pacing threshold will likely be excellent (≤0.5V@0.4 ms). When the acute pacing threshold after fixation is high, a high impedance is a reassuring sign that the pacing threshold will likely improve after procedure.

Long-term electrical performance depends on good myocardial tissue quality and a secure fixation. Myocardial tissue quality is best measured by the mapping phase pacing threshold, before it is confounded by tissue injury caused by fixation. Device–tissue contact can be evaluated by mapping phase impedance. Fixation security can be quantified by tether mode impedance. Implanters are advised to consider all these factors before deciding whether to accept a device position.

Limitation of study

Firstly, though this study recruited patients from two centres, the sample size was still relatively small compared with the existing Micra registry. However, this is the largest post-marketing cohort to date for this relatively new device. Inclusion of consecutive patients of multiple risk factors also ensures that the study represented implants in real-world settings.

Secondly, a direct comparison with the Micra cohort may be confounded by the non-randomized study design. The Micra cohort represented an early phase in the Micra implantation learning curve, which should compare fairly with the current Aveir cohort. However, recent publications have provided guidance on enhancing Micra implant efficacy and safety. For example, impedance was found to be useful in guiding the decision to reposition Micra,²² and a mid-septal implantation approach was advocated to prevent cardiac perforation.²³ In addition, the default pulse width used for Micra pacing is different from Aveir. Therefore, one should be cautious in interpreting the direct electrical comparison between the two leadless pacemakers. Nonetheless, it was evident that the Micra pacing threshold tended to stay stably low after implant, while the Aveir pacing threshold started higher and tended to improve. While operator experience is a critical factor for safety of leadless pacemaker implantation,²⁴ our research highlights the pitfall of directly translating one’s experience with Micra into Aveir implantation. This comparison also demonstrates that Aveir repositioning is much less commonly required.

Lastly, although CEGM was collected by this study protocol, its predicting value on long-term pacing threshold was not analysed. It is expected that studying CEGM features would improve our understanding of cases with high pacing threshold. Further research is needed to elucidate how to define and quantify injury current in CEGM and how to make use of this information to guide implantation.

Conclusions

Aveir VR has a favourable performance in this high-risk real-world cohort. Intraoperative high pacing threshold is more common than Micra implantations. To reduce repositioning, one should take into account all electrical measurements collected during various stages of implant. In particular, high impedance at mapping, tether mode, and after release all predicts excellent pacing threshold on follow-up. This should deter the repositioning of a fixated Aveir VR even if post-fixation pacing threshold is high.

Supplementary material

Supplementary material is available at Europace online.

Funding

This study was funded by department funding from the Division of Cardiology, Department of Medicine and Therapeutics, The Chinese University of Hong Kong.

Data availability

The data underlying this article will be shared upon reasonable request to the corresponding author.