Comparison in Clinical Outcomes Between Leadless and Conventional Transvenous Pacemaker Following Transcatheter Aortic Valve Implantation

Abstract: Objectives. Atrioventricular block is a common complication of transcatheter aortic valve implantation (TAVI). Although conventional transvenous dual-chamber (DDD) pacemaker (PM) is ideal for atrioventricular block, leadless PM, which is less invasive, may be suitable for frail TAVI patients. Little is known about clinical outcomes of this newer device following TAVI. Methods. A total of 330 consecutive patients undergoing TAVI were reviewed. Of these, PM cases without atrial fibrillation were studied. Indication for leadless PM was based on heart team discussion.  Results. PM implantations were performed in 30 patients (9.1%), and 24 patients (7.3%) had no atrial fibrillation. These 24 patients had 14 DDD-PMs and 10 leadless PMs, and formed the two study groups. Baseline characteristics were similar except for ejection fraction: median ages were 83.0 years (IQR, 81.0-87.0 years) vs 86.5 years (IQR, 83.5-90.3) (P=.18); 11 (78.6%) vs 8 (80%) were women (P=.67); Society of Thoracic Surgeons scores were 5.1% (IQR, 3.8%-5.9%) vs 5.3% (IQR, 3.4%-8.5%) (P=.82); and ejection fractions were 68.0% (IQR, 66.0%-70.5%) vs 59.0% (IQR, 52.8%-69.3%) (P=.049), for the DDD-PM and leadless PM groups, respectively. There was 1 case of atrial lead dislodgment in the DDD-PM group; otherwise, no complications related to the implantation procedure were found. The leadless PM group showed numerically shorter hospital stay: 12.5 days (range, 9.0-17.8 day) in the DDD-PM group vs 10.5 days (range, 7.8-15.3 days) in the leadless PM group (P=.44). Six-month follow-up revealed no significant differences in incidence of heart failure rehospitalizations or deaths: 2 (14.3%) in the DDD-PM group vs 2 (25%) in the leadless PM group (P=.47); and 2 (14.3%) in the DDD-PM group vs 0 (0%) in the leadless PM group (P=.39), respectively. Conclusions. Patients with leadless PM following TAVI may have shorter hospital stays, and clinical outcomes can be comparable with DDD-PMs. Leadless PMs may therefore be a reasonable option for frail TAVI patients.

J INVASIVE CARDIOL 2020;32(10):400-404. 

Key words: heart team, pacemakers, transcatheter aortic valve implantation

Atrioventricular block is often seen following transcatheter aortic valve implantation (TAVI). As TAVI devices have progressed, the rate of paravalvular regurgitation has been reduced, but the rate of new permanent pacemaker (PM) implantation remains high. The reported rate of PM implantation following TAVI with early device was 13.9% at 30 days.¹ The incidence of PM implantation after the use of a new-generation TAVI prosthesis ranged between 2.3% and 36.1%.² TAVI procedures are rapidly increasing in number, and the typical patient is shifting to lower surgical risk candidates.^3-5 However, most patients are elderly and frail, and PM implantation requires a subsequent invasive procedure. Considering the invasiveness and high frequency of this procedure, PM implantation post TAVI remains a matter of concern.

The Micra transcatheter pacing system (Medtronic) is a miniaturized, single-chamber PM system that is delivered via catheter through the femoral vein. This system is implanted directly inside the right ventricle of the heart, eliminating the need for a device pocket and insertion of a pacing lead, thereby potentially avoiding some of the complications associated with traditional pacing systems.⁶ The major complication rate of leadless PM is lower than with conventional, transvenous PM.^7,8

Although conventional dual-chamber (DDD) PM implantation is hemodynamically ideal for atrioventricular block in patients with sinus rhythm, the less-invasive leadless PM option may be suitable for frail and vulnerable TAVI patients. Little is known about outcomes of this newer device post TAVI.

Methods

Study population and design. This study retrospectively reviewed 330 consecutive patients undergoing TAVI for symptomatic severe aortic stenosis from January 2016 to March 2019 at a single center in Japan. Patients who underwent PM implantation during the hospitalization for TAVI were selected. Clinical outcomes up to 6-month follow-up were reviewed. Patients were divided into two groups (conventional transvenous DDD-PM and leadless PM) and clinical outcomes were compared. 

The decision regarding the implantation of a leadless PM was based on heart team discussion and was not randomized. Patients with persistent/chronic atrial fibrillation could receive less benefit with DDD-PM. The implantation of a ventricular-demand (VVI) PM, such as the leadless PM, is the usual clinical strategy for this patient group. Therefore, the cases with persistent/chronic atrial fibrillation were excluded for this analysis comparing DDD with leadless PM. 

The study was conducted with approval from the institutional review board. Patients agreed to participate in the study and written informed consent was obtained from all patients.

Pacemaker indication and leadless pacemaker. PM implantation was decided based on class I or IIa guideline-based indications for pacing, including advanced or complete atrioventricular block and symptomatic bradycardia due to atrial tachyarrhythmia or sinus node dysfunction.

Leadless PM is a single-chamber ventricular PM and is smaller than a conventional transvenous PM system. The device has functionality and features similar to a conventional single-chamber PM, including rate-adaptive pacing, remote monitoring capabilities, and automated pacing capture threshold management, designed to maximize battery longevity.⁷ The transcatheter PM implantation procedure has been described elsewhere.⁸ Briefly, the device sits in a steerable catheter delivery system and is inserted through a femoral vein with a 23 Fr introducer. The catheter is advanced into the right ventricle, and the device is affixed to the myocardium through four electrically inactive nitinol tines located at the distal end of the device. After verification of device fixation and adequate electrical measurements, a tether is cut, and the delivery system is removed. Given this less-invasive implantation procedure compared with the conventional PM procedure, vulnerable patients tended to be implanted with leadless PMs. However, the delivery system of the leadless PM is bulky, and it is difficult to manipulate in a small ventricle. Therefore, a small heart is one reason to select a DDD-PM over a leadless PM. 

Statistical analysis. The data were collected retrospectively, and all analyses were performed using the data from the as-treated population. Quantitative variables were expressed as median value with interquartile range (IQR), and qualitative variables as number with percentage. The Mann-Whitney U-test was used for quantitative variables, and Fisher’s exact test was used for qualitative variables. A P-value ≤.05 was considered statistically significant. The data were analyzed with SPSS software, version 18 (SPSS).

Results

Baseline characteristics. Of 330 consecutive patients who underwent TAVI, 30 PM implantations (9.1%) were performed and 24 cases (7.3%) had no atrial fibrillation. Of these 24 cases, 14 received a transvenous DDD and 10 received a leadless PM (Figure 1). Baseline characteristics were not significantly different, except for ejection fraction of 68.0% (IQR, 66.0%-70.5%) and 59.0% (IQR, 52.8%-69.3%) (P=.049) for the DDD-PM group and leadless PM group, respectively; however, the leadless PM group tended to be higher risk, ie, older and thinner, with higher STS scores and NT-pro BNP levels (Table 1). 

Clinical outcomes and pacemaker implantation-related complications. Compared with the DDD-PM group, the leadless PM group had numerically shorter hospital stays (12.5 days [IQR, 9.0-17.8 days] vs 10.5 days [IQR, 7.8-15.3 days], respectively; P=.44). Neither group had heart failure rehospitalization or death at 1-month follow-up. Six-month follow-up revealed 2 (14.3%) vs 2 (25%) heart failure rehospitalizations (P=.47) and 2 (14.3%) vs 0 (0%) deaths (P=.39) in the DDD-PM group and leadless PM group, respectively; however, the difference between the groups was not statistically significant.

The ventricular lead in DDD-PMs can interfere in the tricuspid valve and cause regurgitation; however, echocardiography at 1 month and 6 months (Table 2) post TAVI revealed that the rate of tricuspid regurgitation ≥moderate was not significantly different between the groups, with 1 (8.3%) in the DDD-PM group vs 2 (25%) in the leadless PM group (P=.34) at 6-month follow-up exam.

In the DDD-PM group, there was 1 case of atrial lead dislodgment. Otherwise, there were no complications related to the PM implantation procedures. During the follow-up period, an 87-year-old man implanted with a transvenous DDD-PM was admitted with systemic infection with bacteremia (Corynebacterium spp) 4 months post implantation. Repeat echocardiography revealed the possibility of a perivalvular abscess of the TAVI valve and prosthetic valve endocarditis was diagnosed. Because of prohibitive risk of surgery, the patient was managed conservatively. Fortunately, he was successfully treated with antibiotics for 4 months and discharged in a stable condition.

Pacemaker check-up and ventricular pacing rate. Routine PM check-up was arranged 1 month after PM implantation, and every year thereafter. Check-ups were performed in 13 of the 14 patients in the DDD-PM group and 9 of the 10 patients in the leadless PM group; however, the records of ventricular pacing rates were available in 7 patients and 9 patients, respectively. The rate of ventricular pacing tended to be higher in the transvenous DDD-PM group, but was not significantly different from the leadless PM group (97% [IQR,13.0%-99.0%] vs 50.5% [IQR, 45.5%-70.5%], respectively; P=.79). All patients who underwent PM check-up showed low and stable pacing capture threshold.

Discussion

Although the rates of paravalvular regurgitation have been reduced as TAVI devices have improved, the rate of new permanent PM implantation remains high. Paravalvular regurgitation is associated with higher mortality rates; thus, newer-generation TAVI devices offer features, such as a sealing skirt, to reduce this complication. However, there is still controversy regarding the impact of new PM implantation on outcomes, and no specific feature has developed to reduce the new conduction disorders. PMs are associated with prolonged hospital stay and costs, and require an additional invasive implantation procedure.^9-11 Considering these factors, along with the invasiveness and high frequency of this procedure, PM implantation post TAVI remains a matter of concern.

This is the first study to compare DDD-PM with leadless PM post TAVI. The leadless PM group showed numerically shorter hospital stay, and clinical outcomes comparable with the DDD-PM group. Moreover, the leadless PM group had no complications, although there was 1 atrial lead dislodgment and 1 prosthetic valve endocarditis in the DDD-PM group.  

A conventional transvenous PM has been an established treatment for symptomatic bradycardia for a long time; however, approximately 1 in 8 patients still has an early complication, related to the leads or to the subcutaneous pocket.¹² A leadless system has been pursued in order to reduce these complications. There are some studies reporting the major complication rates following leadless PM implantation. Roberts et al reported a major complication rate of 1.51%, which trended lower than the control (odds ratio, 0.58; 95% CI, 0.27-1.25; P=.16).⁷ Reynolds et al reported 28 major complications in 25 patients (out of a total 725 patients), which was significantly fewer than the conventional transvenous PM group (hazard ratio, 0.49; 95% CI, 0.33-0.75; P<.01).⁸ The less invasive procedure and low complication rate renders leadless PMs suitable for frail patients. Indeed, one of the major reasons for the selection of VVI pacing for leadless PMs was advanced patient age (18.2%) in the previous study. Their post hoc analysis comparing leadless with transvenous PM revealed that the leadless study group was older and had more coexisting conditions.⁸ Their findings were consistent with our study.

In the present study, there was 1 case of bacteremia at 4 month post transvenous DDD-PM implantation. Conversely, there were no infectious complications related to the device in the leadless group. In the study by Roberts et al, leadless PM showed no infections requiring extraction of the PM.⁷ The reason hypothesized was that the small size, lack of proximity to a cutaneous incision, and late encapsulation might have influenced a reduced infection rate. In TAVI patients, a prosthetic valve is already implanted prior to the PM procedure. Managing the risk of infection is a crucial aspect. 

TAVI and leadless PM implantation are relatively novel technologies. Although the comparatively less invasiveness procedure potentially benefits aged and frail TAVI candidates, there were only 2 reported cases of leadless PM implantation following TAVI in the literature.^13,14 The first reported case was a frail 75-year-old woman who underwent TAVI with a 23 mm CoreValve (Medtronic). Two weeks post discharge, she suffered a complete atrioventricular block. Leadless PM implantation was selected in order to avoid complications. The second case was a 91-year-old man who experienced sinus arrest a few hours after TAVI with a 26 mm Sapien 3 valve (Edwards Lifesciences). Leadless PM implantation was selected due to the patient’s old age and frailty. The present study is small, but is nonetheless the first data on a group of patients who underwent leadless PM implantation post TAVI.

The 6-month follow-up echocardiography in the current study revealed that the rate of tricuspid regurgitation ≥ moderate was not significantly different between the groups, with 1 (8.3%) in the transvenous DDD-PM group vs 2 (25%) in the leadless PM group (P=.34). A study by Bonner et al¹⁵ compared leadless and transvenous PM in an animal model, which showed no difference in the degree of tricuspid regurgitation between the two groups. They hypothesized that the combination of young, healthy animals and the short duration of implantation contributed to the lack of increased tricuspid regurgitation in the leaded animals. 

Study limitations. This was a single-center study, with a small study population. In addition, the study was retrospective in nature and no randomization was performed. Further analysis with a larger, multicenter, long-term study is warranted.

Conclusion

Patients with leadless PM implantation post TAVI tend to have shorter hospital stays and similar clinical outcomes when compared with patients undergoing DDD-PM implantation. Leadless PM implantation may be a reasonable option for frail and vulnerable TAVI patients.

From the Division of Cardiology, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Japan.

Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. The authors report no conflicts of interest regarding the content herein.

Manuscript accepted February 28, 2020.

Address for correspondence: Kazuaki Okuyama, MD, Division of Cardiology, Department of Internal Medicine, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki, 216-8511, Japan. Email: kazu-823@hotmail.co.jp

1. Genereux P, Head SJ, Van Mieghem NM, et al. Clinical outcomes after transcatheter aortic valve replacement using Valve Academic Research Consortium definitions: a weighted meta-analysis of 3,519 patients from 16 studies. J Am Coll Cardiol. 2012;59:2317-2326.
2. van Rosendael PJ, Delgado V, Bax JJ. Pacemaker implantation rate after transcatheter aortic valve implantation with early and new-generation devices: a systematic review. Eur Heart J. 2018;39:2003-2013.
3. Leon MB, Smith CR, Mack MJ, et al. Transcatheter or surgical aortic-valve replacement in intermediate-risk patients. N Engl J Med. 2016;374:1609-1620.
4. Mack MJ, Leon MB, Thourani VH, et al. Transcatheter aortic valve replacement with a balloon-expandable valve in low-risk patients. N Engl J Med. 2019;380:1695-1705.
5. Popma JJ, Deeb GM, Yakubov SJ, et al. Transcatheter aortic valve replacement with a self-expanding valve in low-risk patients. N Engl J Med. 2019;380:1706-1715.
6. Ritter P, Duray GZ, Zhang S, et al. The rationale and design of the Micra transcatheter pacing study: safety and efficacy of a novel miniaturized pacemaker. Europace. 2015;17:807-813.
7. Roberts PR, Clementy N, Al Samadi F, et al. A leadless pacemaker in the real-world setting: the Micra transcatheter pacing system post-approval registry. Heart Rhythm. 2017;14:1375-1379.
8. Reynolds DW, Ritter P. A leadless intracardiac transcatheter pacing system. N Engl J Med. 2016;374:2604-2605.
9. Urena M, Rodes-Cabau J. Permanent pacemaker implantation following transcatheter aortic valve replacement: still a concern? JACC Cardiovasc Interv. 2015;8:70-73.
10. Toggweiler S, Kobza R. Pacemaker implantation after transcatheter aortic valve: why is this still happening? J Thor Dis. 2018;10(Suppl 30):S3614-S3619.
11. Toggweiler S, Stortecky S, Holy E, et al. The electrocardiogram after transcatheter aortic valve replacement determines the risk for post-procedural high-degree AV block and the need for telemetry monitoring. JACC Cardiovasc Interv. 2016;9:1269-1276.
12. Udo EO, Zuithoff NP, van Hemel NM, et al. Incidence and predictors of short- and long-term complications in pacemaker therapy: the FOLLOWPACE study. Heart Rhythm. 2012;9:728-735.
13. Shikama T, Miura M, Shirai S, et al. Leadless pacemaker implantation following transcatheter aortic valve implantation using SAPIEN 3. Korean Circ J. 2018;48:534-535.
14. Kypta A, Blessberger H, Lichtenauer M, Steinwender C. Dawn of a new era: the completely interventionally treated patient. BMJ Case Reports. 2016;2016:bcr2015214268.
15. Bonner M, Eggen M, Haddad T, Sheldon T, Williams E. Early performance and safety of the Micra transcatheter pacemaker in pigs. PACE. 2015;38:1248-1259.