Literature DB >> 35837611

Mid- to Long-Term Clinical and Echocardiographic Effects of Post-procedural Permanent Pacemaker Implantation After Transcatheter Aortic Valve Replacement: A Systematic Review and Meta-Analysis.

Shun Xu1, Enrui Zhang1, Zhiyong Qian1, Jinyu Sun1, Fengwei Zou2, Yao Wang1, Xiaofeng Hou1, Jiangang Zou1.   

Abstract

Aims: To date, the prognostic effects of permanent pacemaker implantation (PPI) after transcatheter aortic valve replacement (TAVR) remain controversial. The purpose of this meta-analysis was to investigate the mid- (1 year) to long-term (> 1 year) clinical and echocardiographic effects of post-procedural PPI in patients after TAVR.
Methods: PubMed, Embase, Web of Science, and Cochrane Library databases were systematically searched from the establishment of databases up to 1 December 2021. Studies comparing clinical and echocardiographic outcomes between patients with and without post-TAVR PPI of ≥ 1-year follow-up were collected for further meta-analysis.
Results: A total of 39 studies comprising of 83,082 patients were included in this meta-analysis. At mid-term follow-up (1 year), the pooled results demonstrated a higher risk of all-cause mortality in patients with post-procedural PPI than those without following TAVR (relative risk (RR), 1.17; 95% CI, 1.10-1.24; P < 0.00001). No significant differences were observed in cardiovascular mortality (RR, 0.86; 95% CI, 0.71-1.03; P = 0.10) or heart failure rehospitalization (RR, 0.91; 95% CI, 0.58-1.44; P = 0.69) at 1-year follow-up. At long-term follow-up (> 1 year), post-TAVR PPI had negative effects on all-cause mortality (RR, 1.18; 95% CI, 1.09-1.28; P < 0.0001) and heart failure rehospitalization (RR, 1.42; 95% CI, 1.18-1.71; P = 0.0002). There was no difference in long-term cardiovascular mortality between the two groups (RR, 1.15; 95% CI, 0.97-1.36; P = 0.11). Left ventricular ejection fraction (LVEF) was not significantly different at baseline (mean difference, 1.40; 95% CI, -0.13-2.93; P = 0.07), but was significantly lower in the PPI group at 1-year follow-up (mean difference, -3.57; 95% CI, -4.88 to -2.26; P < 0.00001).
Conclusion: Our meta-analysis provides evidence that post-TAVR PPI has negative clinical and echocardiographic effects on patients at mid- to long-term follow-up. Further studies are urgently needed to explore the cause of these complications and optimize the treatment and management of patients requiring permanent pacing after TAVR. Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021289935], identifier [CRD42021289935].
Copyright © 2022 Xu, Zhang, Qian, Sun, Zou, Wang, Hou and Zou.

Entities:  

Keywords:  heart failure rehospitalization; left ventricular ejection fraction; meta-analysis; mortality; permanent pacemaker implantation; transcatheter aortic valve replacement

Year:  2022        PMID: 35837611      PMCID: PMC9275565          DOI: 10.3389/fcvm.2022.911234

Source DB:  PubMed          Journal:  Front Cardiovasc Med        ISSN: 2297-055X


Introduction

Transcatheter aortic valve replacement (TAVR) has become a well-established therapy for patients with severe aortic stenosis and high risk for surgical aortic valve replacement (1, 2). Recent randomized controlled trials provided evidence to extend the application of TAVR to low-risk patients (3, 4). Despite technological advances and clinical experience accumulation, atrioventricular node, and infranodal tissues remain easily impaired during the implantation of the valve prosthesis. Conduction abnormalities (e.g., high-degree atrioventricular block and new-onset persistent left bundle branch block) are frequently observed after TAVR, and patients often require permanent pacemaker implantation (PPI) (5). The application of post-TAVR PPI was reported in approximately 2.3–37.7% of patients, and the rates largely vary according to the types and generations of the transcatheter valves (6). Cardiac pacing is a recommended therapy to reduce the risk of death related to severe bradycardia arrhythmias. However, traditional right ventricular pacing (RVP) can cause electrical and mechanical dyssynchrony (7, 8), thus increasing the risk of mortality and heart failure hospitalization (9–11). Currently, it remains controversial whether the application of PPI could influence the clinical symptoms and survival outcomes after TAVR (12). Previous meta-analyses were limited by a small number of studies or lack of long-term follow-up (13, 14). This meta-analysis aims to investigate the mid- to long-term clinical and echocardiographic outcomes of post-procedural PPI in patients after TAVR.

Methods

Search Strategy

We performed a systematic literature search in PubMed, Embase, Web of Science, and Cochrane Library from the establishment of databases up to 1 December 2021 by two investigators (Shun Xu and Enrui Zhang) independently. The following strategy was used in PubMed: ((((((“Transcatheter Aortic Valve Replacement” [Mesh]) OR (Transcatheter Aortic Valve Replacement [Title/Abstract])) OR (Transcatheter Aortic Valve Implantation [Title/Abstract])) OR (TAVR [Title/Abstract])) OR (TAVR [Title/Abstract]))) AND (((((“Cardiac Pacing, Artificial” [Mesh]) OR (pacing [Title/Abstract])) OR (pace [Title/Abstract])) OR ((“Pacemaker, Artificial” [Mesh]) OR (pacemaker [Title/Abstract])))). The searching strategies for Embase, Web of Science, and Cochrane Library were provided in Supplementary Table 1. We also manually screened reference lists of retrieved reviews, reports, and other relevant publications to identify additional pertinent studies.

Study Design

The protocol of this meta-analysis has been registered in PROSPERO (Registration ID: CRD42021289935). Clinical studies were eligible if they met the following inclusion criteria: (1) studies comparing clinical and echocardiographic outcomes between patients with and without post-procedural PPI after TAVR, including all-cause mortality, cardiovascular mortality, heart failure rehospitalization, and left ventricular ejection fraction (LVEF); (2) studies with a follow-up of ≥ 1 year; (3) studies with full texts published in English in peer-reviewed journals. We only included the study containing the most data for multiple publications of the same trial. We excluded review articles, case reports, letters, editorials, articles lacking outcomes of interest, studies without detailed data, and studies with a follow-up of < 1 year. Importantly, we also excluded studies that failed to distinguish patients with PPI before TAVR. Two independent investigators (Shun Xu and Enrui Zhang) assess eligibility by screening and reviewing article titles, abstracts, and full texts. Any disagreement about eligibility was clarified via consulting a third investigator (Jinyu Sun).

Data Extraction and Quality Assessment

Two investigators (Shun Xu and Enrui Zhang) independently extracted data for each eligible study. Any disagreement was resolved through discussion with a third investigator (Jinyu Sun) to reach a consensus. The following characteristics were included: first author, year of publication, inclusion period, number and region of centers, sample size, PPI criteria, patient demographic characteristics, and the following mid-term (1 year) to long-term (> 1 year) outcomes, including all-cause mortality, cardiovascular mortality, heart failure rehospitalization, and LVEF. The quality of studies involved was assessed by two investigators (Shun Xu and Enrui Zhang) independently using the Newcastle-Ottawa Scale (NOS). The NOS tool involved three aspects, and a maximum of 9 stars can be allotted to each study: the selection of cohorts (0–4 stars), the comparability of cohorts (0–2 stars), and the assessment of the outcome (0–3 stars). A NOS score ≥ 6 stars indicated moderate-to-high quality, while a NOS score < 6 stars indicated low quality. Discrepancies were resolved by consulting a third investigator (Jinyu Sun) to reach a consensus.

Statistical Analysis

Continuous variables were presented as mean ± standard deviation, and categorical variables were presented as frequencies or percentages. Relative risk (RR) with corresponding 95% confidence intervals (CIs) for each endpoint was calculated and analyzed for categorical variable outcomes. Continuous data were summarized as a mean difference with 95% CI. P-value < 0.05 was considered statistically significant. The heterogeneity between studies was quantified by I-squared (I2) statistic, with a fixed-effects model adopted when the I2-value was < 50% and a random-effects model applied otherwise. Review Manager version 5.3 was used for all the statistical analyses. The meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (15).

Results

Study Selection and Quality Assessment

Figure 1 shows the flow chart of the study selection. A total of 9,852 records were initially identified from the databases according to the searching strategies, including 1,842 from PubMed, 4,782 from Embase, 3,053 from Web of Science, and 175 from Cochrane Library. After title and abstract screening, a total of 4,321 duplicates and 5,461 irrelevant records were excluded, the remaining 70 full-text articles to be reviewed for eligibility. Of those, 22 studies were excluded for having no outcomes of interest or without provided data. Two studies were excluded due to failing to distinguish patients with PPI before TAVR. One study was excluded because the follow-up duration was less than 1 year. Six case reports were also excluded. Finally, 39 studies containing 83,082 patients were included for further analysis (16–54) (Table 1).
FIGURE 1

Flowchart of study selection based on the Preferred Reported Items for Systematic Reviews and Meta-Analysis (PRISMA) statement.

TABLE 1

Summary of studies evaluating mid- to long-term clinical and echocardiographic effects of post-TAVR PPI.

ReferencesYearRegionCentersInclusion periodSamplePPI criteriaTime of PPI
Rück et al. (16)2021Sweden8Jan 2008–Dec 20183420NA≤30 days
Rajah et al. (17)2021Arabia1Jan 2010–Jan 2019170NA≤30 days
Schoechlin et al. (18)2021Germany1Jan 2014–Dec 2016767Restrictive or liberal strategyAfter TAVR
Van Mieghem et al. (19)2021International53Jan 2016–Dec 2016886NA≤30 days
Clementy et al. (20)2021FranceNAJan 2010–Jun 201923060NA≤30 days
Weferling et al. (21)2021Germany1Jan 2010–Apr 20191846ESC 2013 guidelinesMedian 3 days
Nicolas et al. (22)2021Europe and United States19Jan 2013–Dec 2015922ESC 2013 guidelinesAfter TAVR
Alperi et al. (23)2021International>180Apr 2007–Apr 20201987NABefore discharge
Ashraf et al. (24)2020United States1Jan 2012–Jul 2018243ACC/AHA/HRS guidelines≤30 days
Duet al. (25)2020China1Mar 2013–Oct 2018256ACC/AHA/HRS 2012 guidelines≤30 days
Fujita et al. (26)2020GermanyNA2011–201520872NABefore discharge
Costa et al. (27)2019Italy1Jun 2007–Feb 20181116ESC 2013 guidelines≤30 days
Meduri et al. (28)2019International55Sep 2014–Dec 2015688NA≤30 days
Maeno et al. (29)2019United States1Jan 2013–Dec 2015659NABefore discharge
Jørgensen et al. (30)2019Denmark1Aug 2007–Sep 2017816NA≤30 days
Gonska et al. (31)2018Germany1Feb 2014–Sep 2016532NAAfter TAVR
Nadeem et al. (32)2018United States12011–2017672NAAfter TAVR
Alasti et al. (33)2018Australia1Apr 2012–Oct 2016152High-degree AVB, first-degree AVB with LBBB, AF with slow ventricular rate and SSS≤30 days
Walther et al. (34)2018International12Dec 2011–Sep 2015198NA≤1 year
Rogers et al. (35)2018United States1Jan 2013–Dec 2015614NAAfter TAVR
Aljabbary et al. (36)2018Canada10Apr 2010–Mar 20151257NABefore discharge
Chamandi et al. (37)2018International9May 2007–Feb 20151629ACC/AHA/HRS 2012 guidelines≤30 days
López-Aguilera et al. (38)2018Spain1Apr 2008–Dec 2015217Third-degree AVB, LBBB or new first-degree AVB with persistent severe bradycardia (< 40 bpm) and developed syncopeAfter TAVR
Nijenhuis et al. (39)2017Netherlands1Jun 2007–Jun 2015155ESC 2007/2013 guidelines8 (6–14) days
Engborg et al. (40)2017Denmark1Mar 2008–Sep 2012128High-degree AVB, SSS, LBBB combined with first-degree AVB≤30 days
Fadahunsi et al. (41)2016United States229Nov 2011–Sep 20149785NA≤30 days
Giustino et al. (42)2016International4Nov 2005–Dec 2011947ACC/AHA/HRS 2012 guidelinesAfter TAVR
Dizon et al. (43)2015International25May 2007–Aug 20091945NA≤30 days
Mouillet et al. (44)2015France29Jan 2010–Oct 2011833NAAfter TAVR
Kawaguchi et al. (45)2015France1Feb 2010–Jun 2012160NAAfter TAVR
Schymik et al. (46)2015Germany1May 2008–Apr 2012634ESC 2013 guidelinesAfter TAVR
Nazif et al. (47)2015International25NA1973High-degree AVB, SSS, and other bradycardias≤30 days
Urena et al. (48)2014International8Jan 2005–Feb 20131556ACC/AHA/HRS 2008 guidelines≤30 days
Biner et al. (49)2014Israel1NA230Pre-TAVR RBBB, post-TAVR high-degree AVB, alternating BBB, and new LBBB with PR-interval prolongation ≥ 280 msAfter TAVR
Pereira et al. (50)2013Portugal1Aug 2007–May 201158ESC 2007 guidelinesRange 1–9 days
Houthuizen et al. (51)2012Netherlands8Nov 2005–Dec 2010797NAAfter TAVR
De Carlo et al. (52)2012Italy3Sep 2007–Jul 2010275ESC 2007 guidelinesRange 0–12 days
Buellesfeld et al. (53)2012Switzerland and Germany2Aug 2007–Mar 2010305High-degree AVB, new LBBB with PR interval prolongation ≥ 300 ms, and AF with inadequate escape rhythm≤30 days
D’Ancona et al. (54)2011Germany1Apr 2008–Mar 2011322High-degree AVB and symptomatic bradycardia≤30 days

TAVR, transcatheter aortic valve replacement; PPI, permanent pacemaker implantation; NA, not available; ESC, European Society of Cardiology; ACC, American College of Cardiology; AHA, American Heart Association; HRS, Heart Rhythm Society; AVB, atrioventricular block; SSS, sick sinus syndrome; AF, atrial fibrillation; LBBB, left bundle branch block; RBBB, right bundle branch block; BBB, bundle branch block.

Flowchart of study selection based on the Preferred Reported Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. Summary of studies evaluating mid- to long-term clinical and echocardiographic effects of post-TAVR PPI. TAVR, transcatheter aortic valve replacement; PPI, permanent pacemaker implantation; NA, not available; ESC, European Society of Cardiology; ACC, American College of Cardiology; AHA, American Heart Association; HRS, Heart Rhythm Society; AVB, atrioventricular block; SSS, sick sinus syndrome; AF, atrial fibrillation; LBBB, left bundle branch block; RBBB, right bundle branch block; BBB, bundle branch block. All included studies had moderate-to-high quality while none had less than 6 points according to NOS: two with 9 points, nineteen with 8 points, six with 7 points, and 12 with 6 points. The details of the quality assessment are shown in Table 2.
TABLE 2

Quality assessment of the included studies according to the Newcastle-Ottawa Scale (NOS).

ReferencesSelectionComparabilityOutcomeTotal stars
Rück et al. (16)4228
Rajah et al. (17)4228
Schoechlin et al. (18)4026
Van Mieghem et al. (19)4026
Clementy et al. (20)4026
Weferling et al. (21)4037
Nicolas et al. (22)4228
Alperi et al. (23)4127
Ashraf et al. (24)4026
Du et al. (25)4228
Fujita et al. (26)4026
Costa et al. (27)4228
Meduri et al. (28)4228
Maeno et al. (29)4228
Jørgensen et al. (30)4026
Gonska et al. (31)4239
Nadeem et al. (32)4228
Alasti et al. (33)4228
Walther et al. (34)4127
Rogers et al. (35)4026
Aljabbary et al. (36)4026
Chamandi et al. (37)4127
López-Aguilera et al. (38)4228
Nijenhuis et al. (39)4228
Engborg et al. (40)4228
Fadahunsi et al. (41)4127
Giustino et al. (42)4127
Dizon et al. (43)4026
Mouillet et al. (44)4228
Kawaguchi et al. (45)4228
Schymik et al. (46)4026
Nazif et al. (47)4228
Urena et al. (48)4228
Biner et al. (49)4228
Pereira et al. (50)4026
Houthuizen et al. (51)4026
De Carlo et al. (52)4228
Buellesfeld et al. (53)4239
D’Ancona et al. (54)4228
Quality assessment of the included studies according to the Newcastle-Ottawa Scale (NOS).

Mid-Term (1 Year) Clinical Effects of Post-procedural Permanent Pacemaker Implantation After Transcatheter Aortic Valve Replacement

The risk of mid-term all-cause mortality was pooled from 27 studies that included 49,579 patients, and 7,235 patients were implanted with permanent pacemakers after TAVR. There were 1,197 of 7,235 (16.54%) cases of all-cause mortality in the PPI group while 6,285 of 42,344 (14.84%) cases in the no PPI group. The pooled results demonstrated that patients with PPI had a higher risk of death than those without PPI following TAVR (RR, 1.17; 95% CI, 1.10–1.24; P < 0.00001; I2 = 22%; Figure 2A). After pooling the results from nine studies, no significant difference in mid-term cardiovascular death was observed (RR, 0.86; 95% CI, 0.71–1.03; P = 0.10; I2 = 0%; Figure 2B). The risk of 1-year heart failure rehospitalization was assessed in five studies using a random-effects model. As shown in Figure 2C, no significant difference was observed in heart failure rehospitalization (RR, 0.91; 95% CI, 0.58–1.44; P = 0.69; I2 = 83%).
FIGURE 2

Forest plot of the risk of mid-term (1 year) (A) all-cause mortality, (B) cardiovascular mortality, and (C) heart failure rehospitalization in patients with post-procedural permanent pacemaker implantation (PPI) after transcatheter aortic valve replacement (TAVR).

Forest plot of the risk of mid-term (1 year) (A) all-cause mortality, (B) cardiovascular mortality, and (C) heart failure rehospitalization in patients with post-procedural permanent pacemaker implantation (PPI) after transcatheter aortic valve replacement (TAVR).

Long-Term (> 1 Year) Clinical Effects of Post-procedural Permanent Pacemaker Implantation After Transcatheter Aortic Valve Replacement

Long-term mortality between patients with and without PPI after TAVR was reported in 18 studies enrolling 39,172 patients with a mean follow-up period of 2.59 years. A random-effects model was applied, and patients with PPI after TAVR had a higher risk of all-cause mortality than those without PPI after TAVR (RR, 1.18; 95% CI, 1.09–1.28; P < 0.0001; I2 = 57%; Figure 3A). However, there was no statistical difference in long-term risk of cardiovascular mortality between the two groups (RR, 1.15; 95% CI, 0.97–1.36; P = 0.11; I2 = 59%; Figure 3B) after a mean follow-up of 2.12 years. Seven studies demonstrated a deleterious effect of PPI on heart failure rehospitalization after a mean follow-up of 2.16 years (RR, 1.42; 95% CI, 1.18–1.71; P = 0.0002; I2 = 76%; Figure 3C).
FIGURE 3

Forest plot of the risk of long-term (> 1 year) (A) all-cause mortality, (B) cardiovascular mortality, and (C) heart failure rehospitalization in patients with post-procedural PPI after TAVR.

Forest plot of the risk of long-term (> 1 year) (A) all-cause mortality, (B) cardiovascular mortality, and (C) heart failure rehospitalization in patients with post-procedural PPI after TAVR.

Echocardiographic Effects of Post-procedural Permanent Pacemaker Implantation After Transcatheter Aortic Valve Replacement

Two studies reported LVEF both at baseline and 1-year follow-up. Figure 4A shows no significant difference in LVEF between the two groups at baseline (mean difference, 1.40; 95% CI, –0.13 to 2.93; P = 0.07; I2 = 0%). LVEF at 1-year follow-up after TAVR was assessed using a fixed-effect model, and the overall value of LVEF was significantly greater in the no PPI group than in the PPI group (mean difference, –3.57; 95% CI, –4.88 to –2.26; P < 0.00001; I2 = 0%; Figure 4B).
FIGURE 4

Forest plot of left ventricular ejection fraction at baseline (A) and 1-year follow-up (B) between patients with and without post-procedural PPI after TAVR.

Forest plot of left ventricular ejection fraction at baseline (A) and 1-year follow-up (B) between patients with and without post-procedural PPI after TAVR.

Discussion

The results of this meta-analysis can be summarized as follows: (1) patients with post-procedural PPI show a higher risk of all-cause mortality at mid-term follow-up after TAVR; (2) post-TAVR PPI is associated with an increased risk of all-cause mortality and heart failure rehospitalization at long-term follow-up; and (3) post-procedural PPI adversely affect LVEF recovery on patients undergoing TAVR. Twenty years after the first procedure in 2002 (55), TAVR has become a first-line treatment for patients with symptomatic severe aortic stenosis regardless of the estimated surgical risk (1–4). Although TAVR technology has matured significantly over the years, conduction abnormalities remain one of the major complications to be resolved. Currently, there is insufficient evidence to support that the newer-generation devices could reduce the rate of post-procedural PPI (56, 57). The underlying pathophysiological mechanisms compose of direct trauma, hemorrhage, inflammation, and ischemic injury of the conduction system during the expansion of the valve prosthesis (5). With accumulating TAVR cases, it is important to investigate the mid- to long-term clinical and echocardiographic outcomes of post-procedural PPI after TAVR. Numerous studies have confirmed that RVP can negatively impact left ventricular function and increase the risk of the occurrence of atrial fibrillation (10, 58–60). The detrimental effects of RVP may elevate the risk of mortality and heart failure rehospitalization. As shown in our study, the pooled results revealed that patients undergoing PPI after TAVR had a higher risk of death at both mid- and long-term follow-up. They were also more likely to be hospitalized for heart failure during long-term follow-up. Similarly, a recent study containing the largest sample size reported that PPI after TAVR was independently associated with higher mortality and heart failure rehospitalization rate during follow-up, which was based on the entire France nationwide-level population (20). We observed no significant difference in cardiovascular mortality and 1-year risk of heart failure rehospitalization between the two groups in our meta-analysis. The potential protective effects of PPI with respect to lethal bradyarrhythmias may counterbalance the negative effects of ventricular pacing. After the improvement of aortic stenosis, hemodynamic improvement of left ventricular function may compensate for the potential deleterious effects of ventricular pacing in such patients. In addition, implanting biventricular pacemakers in patients after TAVR may partially offset adverse effects linked to RVP. Inconsistent with our results, few previous meta-analyses showed significant impacts of PPI after TAVR on clinical outcomes (13, 61, 62), except for a study by Faroux et al. (14), which was the first meta-analysis to reveal a significantly higher risk of all-cause death and heart failure rehospitalization in patients with PPI post-TAVR at 1-year follow-up. There are several explanations underlying the conflicting results in different studies. The small number of samples and short follow-up time may account for the distinct results. The occurrence and severity of pacing-induced cardiomyopathy are associated with ventricular pacing burden and duration, especially in patients with long-term pacing percentage ≥ 40% (11, 63, 64). Studies on TAVR have shown that new-onset conduction disturbances after TAVR may recover during follow-up, and about half of the patients requiring post-TAVR PPI are not pacing-dependent eventually (65–67). This may also partly explain why there was no significant difference in 1-year heart failure rehospitalization rates between the two groups. Conduction disturbances occur commonly after TAVR, and an expert consensus algorithm was provided for managing post-TAVR conduction disturbances, but the optimal management of this complication is still unknown (68, 69). Schoechlin et al. (18) compared patients’ outcomes between different PPI implantation indications and revealed that the restrictive PPI strategy they adopted reduces the PPI rate significantly and is safe after a follow-up of 3 years. In consideration of the mid- to long-term negative effects demonstrated in our meta-analysis, we recommended adopting a relatively restrictive PPI strategy after TAVR, but the detailed indications and management need to be further explored. Furthermore, His-Purkinje system pacing (HPSP) allows for electrical stimulation signaling through the physiological conduction system, which has the potential to prevent pacing-induced dyssynchrony, heart failure hospitalization, and mortality (70–73). Previous studies have confirmed the feasibility and safety of HPSP in patients after TAVR. De Pooter et al. (74) found that the valve prosthesis can serve as an anatomical landmark for the implantation of the His-bundle lead. A multicenter study by Vijayaraman et al. (75) revealed that left bundle branch pacing had a higher success rate than His-bundle pacing after TAVR, with more ideal pacing parameters. Eleven patients with reduced left ventricular function who underwent HPSP successfully in this study showed significant LVEF improvement from 35 to 42% during follow-up. However, there is no systematic large-scale study evaluating the clinical and echocardiographic effects of HPSP in patients undergoing TAVR. Therefore, further studies are needed to focus on this area.

Limitations

Several limitations of our meta-analysis should be acknowledged. First, most studies included in our meta-analysis were retrospective observational studies. Thus, prospective, multi-center, randomized comparative studies are urgently needed. Second, TAVR technology has developed over time, and the types of valve prostheses are different. Patients included in the prior studies might have different PPI inclusion criteria compared with later ones so the heterogeneity among studies was relatively high in our study. Third, we had inadequate numbers of studies reporting ventricular pacing percentage to assess any significance of pacing-induced cardiomyopathy. We also do not have enough information to study other complications of PPI, such as infection, pneumothorax, and pocket hematoma, which may result in significant clinical consequences outside of mortality. Last but not least, our study is a meta-analysis, and we lack access to individual patient data which may provide more information.

Conclusion

The present meta-analysis provides evidence that post-TAVR PPI has negative clinical and echocardiographic effects at mid- to long-term follow-up. This study highlights the importance of identifying patients at high risk of developing conduction disturbances and requiring PPI after TAVR. Cardiologists should optimize treatment strategies and management of these patients. TAVR technology should also improve to reduce the incidence of such complications.

Data Availability Statement

The original contributions presented in this study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding author/s.

Author Contributions

SX, EZ, JS, and JZ contributed to the conception and designed the study. SX, EZ, and JS extracted the data and evaluated the quality. SX and EZ analyzed the data and wrote the manuscript. ZQ, FZ, YW, XH, and JZ critically reviewed and revised the manuscript. All authors have read and approved the final version of the manuscript.

Conflict of Interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Publisher’s Note

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.
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Authors:  Simon Biner; Yoav Michowitz; Eran Leshem-Rubinow; Yan Topilsky; Eyal Ben-Assa; Jason Shimiaie; Shmuel Banai; Gad Keren; Arie Steinvil; Ariel Finkelstein
Journal:  Am J Cardiol       Date:  2013-10-04       Impact factor: 2.778

9.  Outcomes associated with pacemaker implantation following transcatheter aortic valve replacement: A nationwide cohort study.

Authors:  Nicolas Clementy; Arnaud Bisson; Alexandre Bodin; Julien Herbert; Thibaud Lacour; Christophe Saint Etienne; Bertrand Pierre; Pierre Deharo; Dominique Babuty; Laurent Fauchier
Journal:  Heart Rhythm       Date:  2021-06-17       Impact factor: 6.343

10.  Influence of permanent pacemaker implantation after transcatheter aortic valve implantation with new-generation devices.

Authors:  B Gonska; M Keßler; J Wöhrle; W Rottbauer; J Seeger
Journal:  Neth Heart J       Date:  2018-12       Impact factor: 2.380

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