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Invasive electrophysiological testing to predict and guide permanent pacemaker implantation after transcatheter aortic valve implantation: A meta-analysis

Open AccessPublished:October 21, 2022DOI:https://doi.org/10.1016/j.hroo.2022.10.007

      Background

      Atrioventricular conduction abnormalities after transcatheter aortic valve implantation (TAVI) are common. The value of electrophysiological study (EPS) for risk stratification of high-grade atrioventricular block (HG-AVB) and guidance of permanent pacemaker (PPM) implantation is poorly defined.

      Objective

      The purpose of this study was to identify EPS parameters associated with HG-AVB and determine the value of EPS-guided PPM implantation after TAVI.

      Methods

      We performed a systematic review and meta-analysis of studies investigating the value of EPS parameters for risk stratification of TAVI-related HG-AVB and for guidance of PPM implantation among patients with equivocal PPM indications after TAVI.

      Results

      Eighteen studies (1230 patients) were eligible. In 7 studies, EPS was performed only after TAVI, whereas in 11 studies EPS was performed both before and after TAVI. Overall PPM implantation rate for HG-AVB was 16%. AV conduction intervals prolonged after TAVI, with the AH and HV intervals showing the largest magnitude of changes. Pre-TAVI HV >70 ms and the absolute value of the post-TAVI HV interval were associated with subsequent HG-AVB and PPM implantation with odds ratios of 2.53 (95% confidence interval [CI] 1.11–5.81; P = .04) and 1.10 (95% CI 1.03–1.17; P = .02; per 1-ms increase), respectively. In 10 studies, PPM was also implanted due to abnormal EPS findings in patients with equivocal PPM indications post-TAVI (typically new left bundle branch block or transient HG-AVB). Among them, the rate of long-term PPM dependency was 57%.

      Conclusion

      Selective EPS testing may assist in the risk stratification of post-TAVI HG-AVB and in the guidance of PPM implantation, especially in patients with equivocal PPM indications post-TAVI.

      Keywords

      Key Findings
      • The rate of high-grade atrioventricular block (HG-AVB) after transcatheter aortic valve implantation (TAVI) is consistent with previous literature.
      • The HV interval before and after TAVI showed the most consistent association with risk of HG-AVB.
      • In studies in which a permanent pacemaker (PPM) was implanted due to abnormal electrophysiological study (EPS) findings in patients with equivocal PPM indications after TAVI, the rate of PPM dependency at long-term follow-up was 50%.
      • Selective use of EPS testing, especially among patients with equivocal PPM indications, may be helpful in risk stratification for HG-AVB after TAVI.

      Introduction

      Transcatheter aortic valve implantation (TAVI) is now a mainstream approach for the treatment of severe aortic stenosis in elderly patients.
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      2021 ESC/EACTS guidelines for the management of valvular heart disease.
      The number of patients undergoing TAVI is predicted to continue to grow.
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      ,
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      Transcatheter aortic valve implantation vs. surgical aortic valve replacement for treatment of symptomatic severe aortic stenosis: an updated meta-analysis.
      Although high valve frame implantation techniques directly resulted in a significant decrease in the rate of permanent pacemaker (PPM) implantation,
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      Management of conduction disturbances associated with transcatheter aortic valve replacement: JACC scientific expert panel.
      atrioventricular (AV) conduction disturbances after TAVI remain an important limitation.
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      Conduction disturbances after transcatheter aortic valve replacement: current status and future perspectives.
      Despite several known risk factors for post-TAVI PPM requirement,
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      Predictors and clinical outcomes of permanent pacemaker implantation after transcatheter aortic valve replacement: the PARTNER (Placement of AoRtic TraNscathetER Valves) trial and registry.
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      • et al.
      Predictors of permanent pacemaker implantation in patients with severe aortic stenosis undergoing TAVR: a meta-analysis.
      some patients with normal pre-TAVI conduction system still are at risk for high-grade atrioventricular block (HG-AVB). Furthermore, post-TAVI HG-AVB may occur with latency beyond the immediate postprocedural period,
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      Temporal incidence and predictors of high-grade atrioventricular block after transcatheter aortic valve replacement.
      and some new-onset conduction abnormalities, such as left bundle branch block (LBBB), represent management challenges due to uncertainty about the risk of progression to complete AVB.
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      Therefore, identifying patients at risk for persistent HG-AVB post-TAVI remains challenging.
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      A highly predictive risk model for pacemaker implantation after TAVR.
      To address these challenges, various invasively measured electrophysiological (EP) parameters of the conduction system have been investigated as potential predictors of post-TAVI HG-AVB and PPM requirement. However, results have been largely inconclusive, and data supporting the routine use of electrophysiological studies (EPS) for risk stratification of patients undergoing TAVI are sparse.
      The aims of this systematic review and meta-analysis were (1) to synthesize the available evidence on the value of peri-TAVI EPS parameters in the risk stratification of post-TAVI HG-AVB; and (2) to determine their value in guiding PPM implantation among patients with equivocal PPM indications post-TAVI.

      Methods

      The study protocol follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement
      • Page M.J.
      • McKenzie J.E.
      • Bossuyt P.M.
      • et al.
      The PRISMA 2020 statement: an updated guideline for reporting systematic reviews.
      and was registered at the PROSPERO international register of systematic reviews (CRD42019121204). Institutional REVIEW BOARD approval was not required due to the nature of the study, which utilized published data only.

      Search sources and strategy

      We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials using a prespecified search algorithm for each database (Supplemental Material Section 1). After the initial search, we scrutinized the reference lists of potentially eligible articles for relevant entries. Articles published up to March 15, 2022, were considered for inclusion in this systematic review and meta-analysis without language restriction.

      Eligibility criteria and study selection

      We included 2 types of original prospective or retrospective studies: those investigating the association of EPS-derived parameters with HG-AVB and PPM requirement after TAVI; and those investigating an EPS-guided approach to PPM implantation among patients with equivocal PPM indications (without HG-AVB) after TAVI. Further inclusion criteria included TAVI performed for severe stenosis of native aortic valve; EPS performed before and/or after TAVI; and available quantitative data for any EPS parameters before and/or after TAVI, rates of PPM implantation after TAVI, or outcomes of EPS-guided PPM implantation among patients with equivocal post-TAVI PPM indications. We did not apply any restrictions on the study-level number of enrolled patients, type of valve prosthesis, or minimum follow-up duration. Two independent investigators screened search results on title and abstract level and assessed the studies for eligibility in full text. Disagreements between reviewers were resolved by arbitration by a third reviewer.

      Data extraction

      Two investigators independently reviewed the full text and any supplementary material of eligible studies and extracted study-level data into an electronic data abstraction form. Disagreements were resolved by consensus. We summarized the timing of EPS relative to TAVI and the indications and timing (days after TAVI) of PPM implantation. We documented changes of EPS-derived parameters of AV conduction after TAVI. We also extracted any available crude or adjusted risk association estimates (with corresponding 95% confidence interval [CI]) for each EPS-derived parameter as a predictor of PPM requirement. Furthermore, for studies in which patients with equivocal post–transcatheter aortic valve replacement (TAVR) AV conduction abnormalities underwent PPM implantation due to abnormal EPS findings (rather than HG-AVB), we documented the rates of pacemaker dependency, as defined in each study, at the time of post-TAVI follow-up. We also documented rates of sudden cardiac death and subsequent incident PPM implantations among patients with a negative EPS who did not receive a PPM early after TAVI.

      Data synthesis

      We visualized the changes in the mean values of the EPS parameters before and after TAVI in paired box plots. We quantified the magnitude of the changes in the mean values of EPS parameters before and after TAVI with the standardized effect size (Cohen's d). The changes were considered small, medium, and large for absolute values of Cohen’s d of 0.2–0.5, 0.5–0.8, and >0.8, respectively. We quantified the variance and calculated the SD of the standardized effect sizes. For data reported as median [interquartile range] or 95% CI, we calculated mean ± SD as previously described.
      • Hozo S.P.
      • Djulbegovic B.
      • Hozo I.
      Estimating the mean and variance from the median, range, and the size of a sample.
      Meta-analysis was performed when at least 2 studies reported the same EPS parameter of interest; otherwise, data were reported only descriptively. We applied random-effects meta-analysis models to summarize crude or adjusted effect estimates of EPS parameters as predictors of PPM implantation due to HG-AVB. We gave preference to adjusted over unadjusted estimates. The summary association metric in the meta-analysis was the odds ratio (OR), and any required transformations were performed as previously described.
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      When can odds ratios mislead?.
      ,
      • Grant R.L.
      Converting an odds ratio to a range of plausible relative risks for better communication of research findings.
      We used random-effects meta-analyses with Hartung-Knapp-Sidik-Jonkman adjustments due to the relatively small number and heterogeneous studies.
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      • Ioannidis J.P.
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      The Hartung-Knapp-Sidik-Jonkman method for random effects meta-analysis is straightforward and considerably outperforms the standard DerSimonian-Laird method.
      ,
      • Rover C.
      • Knapp G.
      • Friede T.
      Hartung-Knapp-Sidik-Jonkman approach and its modification for random-effects meta-analysis with few studies.
      Heterogeneity was assessed by τ2, and the estimator was based on the restricted maximum-likelihood method.
      • Langan D.
      • Higgins J.P.T.
      • Jackson D.
      • et al.
      A comparison of heterogeneity variance estimators in simulated random-effects meta-analyses.
      Values of τ2 approximating 0.04, 0.16, and 0.36 were considered to represent low, moderate, and high heterogeneity, respectively.
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      • Bender R.
      • Dias S.
      • et al.
      On weakly informative prior distributions for the heterogeneity parameter in Bayesian random-effects meta-analysis.
      R Version 4.0.2 was used for all analyses.

      Results

      Study characteristics

      The literature search identified 657 potentially eligible studies, of which 24 were further evaluated in full text. A total of 18 studies
      • Rubin J.M.
      • Avanzas P.
      • del Valle R.
      • et al.
      Atrioventricular conduction disturbance characterization in transcatheter aortic valve implantation with the CoreValve prosthesis.
      • Akin I.
      • Kische S.
      • Paranskaya L.
      • et al.
      Predictive factors for pacemaker requirement after transcatheter aortic valve implantation.
      • Eksik A.
      • Gul M.
      • Uyarel H.
      • et al.
      Electrophysiological evaluation of atrioventricular conduction disturbances in transcatheter aortic valve implantation with Edwards SAPIEN prosthesis.
      • Rivard L.
      • Schram G.
      • Asgar A.
      • et al.
      Electrocardiographic and electrophysiological predictors of atrioventricular block after transcatheter aortic valve replacement.
      • Shin D.I.
      • Merx M.W.
      • Meyer C.
      • et al.
      Baseline HV-interval predicts complete AV-block secondary to transcatheter aortic valve implantation.
      • Eksik A.
      • Yildirim A.
      • Gul M.
      • et al.
      Comparison of Edwards Sapien XT versus Lotus valve devices in terms of electrophysiological study parameters in patients undergoing TAVI.
      • Kostopoulou A.
      • Karyofillis P.
      • Livanis E.
      • et al.
      Permanent pacing after transcatheter aortic valve implantation of a CoreValve prosthesis as determined by electrocardiographic and electrophysiological predictors: a single-centre experience.
      • Lopez-Aguilera J.
      • Segura Saint-Gerons J.M.
      • Mazuelos Bellido F.
      • et al.
      Atrioventricular conduction changes after corevalve transcatheter aortic valve implantation.
      • Tovia-Brodie O.
      • Ben-Haim Y.
      • Joffe E.
      • et al.
      The value of electrophysiologic study in decision-making regarding the need for pacemaker implantation after TAVI.
      • Badenco N.
      • Chong-Nguyen C.
      • Maupain C.
      • et al.
      Respective role of surface electrocardiogram and His bundle recordings to assess the risk of atrioventricular block after transcatheter aortic valve replacement.
      • Makki N.
      • Dollery J.
      • Jones D.
      • Crestanello J.
      • Lilly S.
      Conduction disturbances after TAVR: Electrophysiological studies and pacemaker dependency.
      • Rogers T.
      • Devraj M.
      • Thomaides A.
      • et al.
      Utility of invasive electrophysiology studies in patients with severe aortic stenosis undergoing transcatheter aortic valve implantation.
      • Knecht S.
      • Schaer B.
      • Reichlin T.
      • et al.
      Electrophysiology testing to stratify patients with left bundle branch block after transcatheter aortic valve implantation.
      • Krishnaswamy A.
      • Sammour Y.
      • Mangieri A.
      • et al.
      The utility of rapid atrial pacing immediately post-TAVR to predict the need for pacemaker implantation.
      • Reiter C.
      • Lambert T.
      • Kellermair J.
      • et al.
      Intraprocedural dynamics of cardiac conduction during transcatheter aortic valve implantation: assessment by simultaneous electrophysiological testing.
      • Bourenane H.
      • Galand V.
      • Boulmier D.
      • et al.
      Electrophysiological study-guided permanent pacemaker implantation in patients with conduction disturbances following transcatheter aortic valve implantation.
      • Nauchi M.
      • Yamawaki M.
      • Nakano T.
      • et al.
      Bedside Electrophysiological study using a temporary pacemaker may predict recurrence of atrioventricular block after transcatheter aortic valve replacement.
      • Ferreira T.
      • Da Costa A.
      • Cerisier A.
      • et al.
      Predictors of high-degree conduction disturbances and pacemaker implantation after transcatheter aortic valve replacement: prognostic role of the electrophysiological study.
      with 1230 patients (mean 68 patients per study) reporting on nonoverlapping patient populations were considered eligible (Supplemental Material Section 2). The characteristics of the included studies and patients are summarized in Tables 1 and 2. Thirteen studies were prospective, and 1 was multicenter. Most studies (n = 13) included patients without pre-existing PPM undergoing peri-TAVI EPS, whereas 5 studies were restricted only to patients undergoing EPS because of an equivocal indication for PPM after TAVI, such as transient HG-AVB and new LBBB. Seven studies included only self-expanding prostheses, and 11 studies included both self-expanding and balloon-expandable prostheses. In 11 studies, EP testing was performed both before and after TAVI, and in 7 studies it was only performed after TAVI. Pre-TAVI EPS typically was performed immediately before valve deployment. Timing of post-TAVI EP testing ranged from immediately post–valve deployment to 7 days later. Reported follow-up ranged from 2 days to 30 months after the index hospitalization.
      Table 1Baseline characteristics of the included studies
      StudyPublication yearEnrollment periodDesignCentersNo. of patientsAge (y)Male [n (%)]Self-/balloon-expandable prosthesis [n (%)]Follow-up
      EPS performed in all patients for prognostication before and/or after TAVI
      Rubin et al
      • Rubin J.M.
      • Avanzas P.
      • del Valle R.
      • et al.
      Atrioventricular conduction disturbance characterization in transcatheter aortic valve implantation with the CoreValve prosthesis.
      2011Dec 2009–Aug 2010ProspectiveSingle1885 ± 34 (22)18 (100)/012 mo
      Akin et al
      • Akin I.
      • Kische S.
      • Paranskaya L.
      • et al.
      Predictive factors for pacemaker requirement after transcatheter aortic valve implantation.
      2012Jan 2007–Jan 2008RetrospectiveSingle4582 ± 718 (40)45 (100)/06 mo
      Eksik et al
      • Eksik A.
      • Gul M.
      • Uyarel H.
      • et al.
      Electrophysiological evaluation of atrioventricular conduction disturbances in transcatheter aortic valve implantation with Edwards SAPIEN prosthesis.
      2013Oct 2010–Feb 2012ProspectiveSingle2878 ± 511 (39)28 (100)/02 d
      Rivard et al
      • Rivard L.
      • Schram G.
      • Asgar A.
      • et al.
      Electrocardiographic and electrophysiological predictors of atrioventricular block after transcatheter aortic valve replacement.
      2015Jan 2009–Jul 2012ProspectiveSingle7582 ± 748 (64)64 (85)/11 (15)24 mo
      Shin et al
      • Shin D.I.
      • Merx M.W.
      • Meyer C.
      • et al.
      Baseline HV-interval predicts complete AV-block secondary to transcatheter aortic valve implantation.
      2015Oct 2011–Mar 2012ProspectiveSingle25N/AN/A25 (100)/010 mo
      Eksik et al
      • Eksik A.
      • Yildirim A.
      • Gul M.
      • et al.
      Comparison of Edwards Sapien XT versus Lotus valve devices in terms of electrophysiological study parameters in patients undergoing TAVI.
      2016Jun 2012–Mar 2016ProspectiveSingle5577 ± 723 (42)25 (45)/30 (55)5 mo
      Kostopoulou et al
      • Kostopoulou A.
      • Karyofillis P.
      • Livanis E.
      • et al.
      Permanent pacing after transcatheter aortic valve implantation of a CoreValve prosthesis as determined by electrocardiographic and electrophysiological predictors: a single-centre experience.
      2016Jan 2010–Feb 2012ProspectiveSingle3081 ± 518 (60)30 (100)/017 mo
      Lopez-Aguilera et al
      • Lopez-Aguilera J.
      • Segura Saint-Gerons J.M.
      • Mazuelos Bellido F.
      • et al.
      Atrioventricular conduction changes after corevalve transcatheter aortic valve implantation.
      2016Ap 2008–Dec 2013ProspectiveSingle13178 ± 560 (46)131 (100)/05 d
      Badenco et al
      • Badenco N.
      • Chong-Nguyen C.
      • Maupain C.
      • et al.
      Respective role of surface electrocardiogram and His bundle recordings to assess the risk of atrioventricular block after transcatheter aortic valve replacement.
      2017Jan 2013–Dec 2014ProspectiveSingle8483 ± 934 (41)56 (67)/28 (33)7 d
      Makki et al
      • Makki N.
      • Dollery J.
      • Jones D.
      • Crestanello J.
      • Lilly S.
      Conduction disturbances after TAVR: Electrophysiological studies and pacemaker dependency.
      2017Nov 2011–Jan 2016RetrospectiveSingle7N/AN/A5 (71)/2 (29)3 mo
      Krishnaswamy et al
      • Krishnaswamy A.
      • Sammour Y.
      • Mangieri A.
      • et al.
      The utility of rapid atrial pacing immediately post-TAVR to predict the need for pacemaker implantation.
      2020Jan 2016–Aug 2018ProspectiveMulticenter28481 [75–85]154 (54)68 (24)/216 (76)1 mo
      Reiter et al
      • Reiter C.
      • Lambert T.
      • Kellermair J.
      • et al.
      Intraprocedural dynamics of cardiac conduction during transcatheter aortic valve implantation: assessment by simultaneous electrophysiological testing.
      2020Jan 2017–Jan 2019ProspectiveSingle10880 ± 542 (39)108 (100)/01 mo
      Ferreira et al
      • Ferreira T.
      • Da Costa A.
      • Cerisier A.
      • et al.
      Predictors of high-degree conduction disturbances and pacemaker implantation after transcatheter aortic valve replacement: prognostic role of the electrophysiological study.
      2021Jun 2018–Jul 2019ProspectiveSingle7482 ± 636 (48)35 (48)/39 (52)3–6 mo
      EPS performed in patients with equivocal pacing indication post-TAVR
      Tovia-Brodie et al
      • Tovia-Brodie O.
      • Ben-Haim Y.
      • Joffe E.
      • et al.
      The value of electrophysiologic study in decision-making regarding the need for pacemaker implantation after TAVI.
      2016Mar 2009–May 2015RetrospectiveSingle2682 [65–94]10 (39)19 (73)/7 (27)12 mo
      Rogers et al
      • Rogers T.
      • Devraj M.
      • Thomaides A.
      • et al.
      Utility of invasive electrophysiology studies in patients with severe aortic stenosis undergoing transcatheter aortic valve implantation.
      2018Jan 2013–Dec 2015ProspectiveSingle9580 ± 951 (54)47 (49)/48 (51)30 mo
      Knecht et al
      • Knecht S.
      • Schaer B.
      • Reichlin T.
      • et al.
      Electrophysiology testing to stratify patients with left bundle branch block after transcatheter aortic valve implantation.
      2020N/AProspectiveSingle5682 ± 623 (41)40 (71)/16 (29)12 mo
      Bourenane et al
      • Bourenane H.
      • Galand V.
      • Boulmier D.
      • et al.
      Electrophysiological study-guided permanent pacemaker implantation in patients with conduction disturbances following transcatheter aortic valve implantation.
      2021Jun 2017–Jul 2020RetrospectiveSingle7884 [80–86]48 (61)15 (20)/63 (80)5 mo
      Nauchi et al
      • Nauchi M.
      • Yamawaki M.
      • Nakano T.
      • et al.
      Bedside Electrophysiological study using a temporary pacemaker may predict recurrence of atrioventricular block after transcatheter aortic valve replacement.
      2021Jun 2019–Oct 2020RetrospectiveSingle1187 ± 81 (9)6 (54)/5 (46)3 mo
      Values are given as absolute number (n) with percentage (%), mean ± SD, or median [interquartile range] as reported in the primary studies.
      EPS = electrophysiological study; N/A = not applicable/available; TAVI = transcatheter aortic valve implantation; TAVR = transcatheter aortic valve replacement.
      Table 2Study-level inclusion criteria, criteria for permanent pacemaker implantation, and timing of EPS
      StudyPatient populationCriteria for PPMTiming of EPS
      EPS performed in all patients for prognostication before and/or after TAVI
      Rubin et al
      • Rubin J.M.
      • Avanzas P.
      • del Valle R.
      • et al.
      Atrioventricular conduction disturbance characterization in transcatheter aortic valve implantation with the CoreValve prosthesis.
      Patients undergoing TAVI without pre-existing PPMHigh-grade AVBImmediately before TAVI

      Immediately after TAVI
      Akin et al
      • Akin I.
      • Kische S.
      • Paranskaya L.
      • et al.
      Predictive factors for pacemaker requirement after transcatheter aortic valve implantation.
      Patients undergoing TAVI without pre-existing PPMHigh-grade AVB

      Abnormal EPS
      Immediately before TAVI

      Immediately after TAVI

      7 d after TAVI
      Eksik et al
      • Eksik A.
      • Gul M.
      • Uyarel H.
      • et al.
      Electrophysiological evaluation of atrioventricular conduction disturbances in transcatheter aortic valve implantation with Edwards SAPIEN prosthesis.
      Patients undergoing TAVI without pre-existing PPMHigh-grade AVBImmediately before TAVI

      Immediately after TAVI
      Rivard et al
      • Rivard L.
      • Schram G.
      • Asgar A.
      • et al.
      Electrocardiographic and electrophysiological predictors of atrioventricular block after transcatheter aortic valve replacement.
      Patients undergoing TAVI without pre-existing PPMHigh-grade AVBImmediately before TAVI

      Immediately after TAVI
      Shin et al
      • Shin D.I.
      • Merx M.W.
      • Meyer C.
      • et al.
      Baseline HV-interval predicts complete AV-block secondary to transcatheter aortic valve implantation.
      Patients undergoing TAVI without pre-existing PPMHigh-grade AVBImmediately before TAVI

      Immediately after TAVI
      Eksik et al
      • Eksik A.
      • Yildirim A.
      • Gul M.
      • et al.
      Comparison of Edwards Sapien XT versus Lotus valve devices in terms of electrophysiological study parameters in patients undergoing TAVI.
      Patients undergoing TAVI without pre-existing PPMHigh-grade AVBImmediately before TAVI

      Immediately after TAVI
      Kostopoulou et al
      • Kostopoulou A.
      • Karyofillis P.
      • Livanis E.
      • et al.
      Permanent pacing after transcatheter aortic valve implantation of a CoreValve prosthesis as determined by electrocardiographic and electrophysiological predictors: a single-centre experience.
      Patients undergoing TAVI without pre-existing PPMHigh-grade AVB

      New LBBB plus abnormal EPS
      Immediately before TAVI

      2 d after TAVI
      Lopez-Aguilera et al
      • Lopez-Aguilera J.
      • Segura Saint-Gerons J.M.
      • Mazuelos Bellido F.
      • et al.
      Atrioventricular conduction changes after corevalve transcatheter aortic valve implantation.
      Patients undergoing TAVI without pre-existing PPMHigh-grade AVBImmediately before TAVI

      30 min after TAVI
      Badenco et al
      • Badenco N.
      • Chong-Nguyen C.
      • Maupain C.
      • et al.
      Respective role of surface electrocardiogram and His bundle recordings to assess the risk of atrioventricular block after transcatheter aortic valve replacement.
      Patients undergoing TAVI without pre-existing PPMHigh-degree AVB

      Abnormal EPS
      Immediately before TAVI

      Immediately after TAVI

      2 d after TAVI for Edwards Sapien and 5 d after procedure for CoreValve
      Makki et al
      • Makki N.
      • Dollery J.
      • Jones D.
      • Crestanello J.
      • Lilly S.
      Conduction disturbances after TAVR: Electrophysiological studies and pacemaker dependency.
      Patients undergoing TAVI without pre-existing PPM but underwent in-hospital PPM implantationLBBB and abnormal EPSPerformed a median of 6 (range 2–210) d after TAVI
      Krishnaswamy et al
      • Krishnaswamy A.
      • Sammour Y.
      • Mangieri A.
      • et al.
      The utility of rapid atrial pacing immediately post-TAVR to predict the need for pacemaker implantation.
      Patients undergoing TAVI in the absence of pre-existing PPM, AF, or persistent intraprocedural AVBHigh-grade AVBImmediately after TAVI
      Reiter et al
      • Reiter C.
      • Lambert T.
      • Kellermair J.
      • et al.
      Intraprocedural dynamics of cardiac conduction during transcatheter aortic valve implantation: assessment by simultaneous electrophysiological testing.
      Patients undergoing TAVI without pre-existing pacemaker or persistent AFHigh-grade AVBImmediately before TAVI

      After balloon predilation

      Immediately after TAVI
      Ferreira et al
      • Ferreira T.
      • Da Costa A.
      • Cerisier A.
      • et al.
      Predictors of high-degree conduction disturbances and pacemaker implantation after transcatheter aortic valve replacement: prognostic role of the electrophysiological study.
      Patients undergoing TAVI without pre-existing PPMHigh-grade AVB

      Abnormal EPS
      Day 1–7 before TAVI

      Day 4–5 after TAVI
      EPS performed in patients with equivocal pacing indication post-TAVR
      Tovia-Brodie et al
      • Tovia-Brodie O.
      • Ben-Haim Y.
      • Joffe E.
      • et al.
      The value of electrophysiologic study in decision-making regarding the need for pacemaker implantation after TAVI.
      Patients undergoing TAVI without pre-existing PPM plus one of the following:

      New-onset LBBB

      Old LBBB and PR increase >20 ms

      Slow AF(<100/min) in presence of old or new-onset LBBB
      Abnormal EPSAfter TAVI (median 6 d)
      Rogers et al
      • Rogers T.
      • Devraj M.
      • Thomaides A.
      • et al.
      Utility of invasive electrophysiology studies in patients with severe aortic stenosis undergoing transcatheter aortic valve implantation.
      Patients with equivocal indication for pacing after TAVI (high-degree AVB, LBBB, sinus nodal dysfunction, other)Abnormal EPSBefore hospital discharge (>24 h post-TAVI)
      Knecht et al
      • Knecht S.
      • Schaer B.
      • Reichlin T.
      • et al.
      Electrophysiology testing to stratify patients with left bundle branch block after transcatheter aortic valve implantation.
      Patients with LBBB (new or pre-existing) undergoing TAVIAbnormal EPS<24 h after TAVI
      Bourenane et al
      • Bourenane H.
      • Galand V.
      • Boulmier D.
      • et al.
      Electrophysiological study-guided permanent pacemaker implantation in patients with conduction disturbances following transcatheter aortic valve implantation.
      Patients with equivocal indication for pacing after TAVI (LBBB, transient AVB, other)Abnormal EPS2–5 d after TAVI
      Nauchi et al
      • Nauchi M.
      • Yamawaki M.
      • Nakano T.
      • et al.
      Bedside Electrophysiological study using a temporary pacemaker may predict recurrence of atrioventricular block after transcatheter aortic valve replacement.
      Patients with transient AVB after TAVIAbnormal EPSDuring hospitalization after TAVI
      AF = atrial fibrillation; AVB = atrioventricular block; LBBB = left bundle branch block; PPM = permanent pacemaker; other abbreviations as in Table 1.
      In 10 of the included studies, EPS parameters were used to guide PPM decisions post-TAVI.
      • Tovia-Brodie O.
      • Ben-Haim Y.
      • Joffe E.
      • et al.
      The value of electrophysiologic study in decision-making regarding the need for pacemaker implantation after TAVI.
      ,
      • Rogers T.
      • Devraj M.
      • Thomaides A.
      • et al.
      Utility of invasive electrophysiology studies in patients with severe aortic stenosis undergoing transcatheter aortic valve implantation.
      ,
      • Knecht S.
      • Schaer B.
      • Reichlin T.
      • et al.
      Electrophysiology testing to stratify patients with left bundle branch block after transcatheter aortic valve implantation.
      ,
      • Bourenane H.
      • Galand V.
      • Boulmier D.
      • et al.
      Electrophysiological study-guided permanent pacemaker implantation in patients with conduction disturbances following transcatheter aortic valve implantation.
      ,
      • Nauchi M.
      • Yamawaki M.
      • Nakano T.
      • et al.
      Bedside Electrophysiological study using a temporary pacemaker may predict recurrence of atrioventricular block after transcatheter aortic valve replacement.
      In 5 of these studies, EPS was only performed among patients with equivocal post-TAVR pacing indication. The indications for EPS were new or pre-existing LBBB in 4 studies and transient intraprocedural HG-AVB in 3 studies. Other miscellaneous reasons, including sinus nodal dysfunction, were also considered in 2 of these studies. The criteria for PPM were prolonged HV interval (threshold varying from 55 to 75 ms per study) in 3 studies and induction of intrahisian or infrahisian block in 3 studies. In the remaining 5 studies in which EPS was performed in all patients undergoing TAVI,
      • Akin I.
      • Kische S.
      • Paranskaya L.
      • et al.
      Predictive factors for pacemaker requirement after transcatheter aortic valve implantation.
      ,
      • Kostopoulou A.
      • Karyofillis P.
      • Livanis E.
      • et al.
      Permanent pacing after transcatheter aortic valve implantation of a CoreValve prosthesis as determined by electrocardiographic and electrophysiological predictors: a single-centre experience.
      ,
      • Badenco N.
      • Chong-Nguyen C.
      • Maupain C.
      • et al.
      Respective role of surface electrocardiogram and His bundle recordings to assess the risk of atrioventricular block after transcatheter aortic valve replacement.
      ,
      • Makki N.
      • Dollery J.
      • Jones D.
      • Crestanello J.
      • Lilly S.
      Conduction disturbances after TAVR: Electrophysiological studies and pacemaker dependency.
      ,
      • Ferreira T.
      • Da Costa A.
      • Cerisier A.
      • et al.
      Predictors of high-degree conduction disturbances and pacemaker implantation after transcatheter aortic valve replacement: prognostic role of the electrophysiological study.
      , the criteria for PPM implantation were new LBBB plus prolonged HV interval in 3 studies and isolated prolonged HV interval in 2 studies (threshold varying from 55 to 80 m across studies).

      Changes of EPS parameters before and after TAVI

      Data on EPS parameters before and after TAVI (in patients without immediate AVB) were available for the AH interval, HV interval, anterograde Wenckebach cycle length, and anterograde AV nodal effective refractory period. The changes in these parameters in each study are summarized in Figure 1. Changes were consistent across studies, with the majority showing an increase in the absolute values of all intervals after TAVI. The changes were statistically significant and of large magnitude for the AH interval (mean pre-TAVI 104 ms; mean post-TAVI 119 ms; Cohen’s d 0.91; P = .004) and the HV interval (mean pre-TAVI 52 ms; mean post-TAVI 63 ms; Cohen’s d 1.88; P <.001).
      Figure thumbnail gr1
      Figure 1Summary mean changes of atrioventricular conduction parameters before and after transcatheter aortic valve implantation (TAVI). A: Atrium to His (AH) interval. B: His to ventricle (HV) interval. C: Anterograde Wenckebach cycle length (AWB). D: Effective refractory period (ERP) (atrioventricular node). ∗Paired sample t test. CI = confidence interval; EPS = electrophysiological study.

      EPS parameters as predictors of HG-AVB post-TAVI

      Across 12 studies in which a PPM was implanted for a standard, unequivocal indication (HG-AVB), a total of 153 of 957 patients (16%) received a PPM. The timing of HG-AVB and PPM implantation was before hospital discharge in most studies, although occasionally it occurred up to 30 days post-TAVI. PPM implantation rates for HG-AVB ranged from 4% to 32% among studies (Table 3).
      Table 3PPM implantation for high-grade AVB after TAVI
      StudyNo. of patientsPPM implanted for high-grade AVBTiming of AVB and PPM implantation
      Rubin et al
      • Rubin J.M.
      • Avanzas P.
      • del Valle R.
      • et al.
      Atrioventricular conduction disturbance characterization in transcatheter aortic valve implantation with the CoreValve prosthesis.
      184 (22)3 before hospital discharge and 1 at 10 d
      Akin et al
      • Akin I.
      • Kische S.
      • Paranskaya L.
      • et al.
      Predictive factors for pacemaker requirement after transcatheter aortic valve implantation.
      4510 (22)Within 7 d post-TAVI
      Eksik et al
      • Eksik A.
      • Gul M.
      • Uyarel H.
      • et al.
      Electrophysiological evaluation of atrioventricular conduction disturbances in transcatheter aortic valve implantation with Edwards SAPIEN prosthesis.
      281 (4)Before hospital discharge
      Rivard et al
      • Rivard L.
      • Schram G.
      • Asgar A.
      • et al.
      Electrocardiographic and electrophysiological predictors of atrioventricular block after transcatheter aortic valve replacement.
      7514 (19)Median 2 d (range 0–30)
      Shin et al
      • Shin D.I.
      • Merx M.W.
      • Meyer C.
      • et al.
      Baseline HV-interval predicts complete AV-block secondary to transcatheter aortic valve implantation.
      258 (32)Before hospital discharge
      Eksik et al
      • Eksik A.
      • Yildirim A.
      • Gul M.
      • et al.
      Comparison of Edwards Sapien XT versus Lotus valve devices in terms of electrophysiological study parameters in patients undergoing TAVI.
      558 (15)Before hospital discharge
      Kostopoulou et al
      • Kostopoulou A.
      • Karyofillis P.
      • Livanis E.
      • et al.
      Permanent pacing after transcatheter aortic valve implantation of a CoreValve prosthesis as determined by electrocardiographic and electrophysiological predictors: a single-centre experience.
      307 (23)Median 2 d post-TAVI (range 2–24)
      Lopez-Aguilera et al
      • Lopez-Aguilera J.
      • Segura Saint-Gerons J.M.
      • Mazuelos Bellido F.
      • et al.
      Atrioventricular conduction changes after corevalve transcatheter aortic valve implantation.
      13133 (25)Within 72 h post-TAVI
      Badenco et al
      • Badenco N.
      • Chong-Nguyen C.
      • Maupain C.
      • et al.
      Respective role of surface electrocardiogram and His bundle recordings to assess the risk of atrioventricular block after transcatheter aortic valve replacement.
      8417 (20)Before hospital discharge
      Krishnaswamy et al
      • Krishnaswamy A.
      • Sammour Y.
      • Mangieri A.
      • et al.
      The utility of rapid atrial pacing immediately post-TAVR to predict the need for pacemaker implantation.
      28419 (7)N/A
      Reiter et al
      • Reiter C.
      • Lambert T.
      • Kellermair J.
      • et al.
      Intraprocedural dynamics of cardiac conduction during transcatheter aortic valve implantation: assessment by simultaneous electrophysiological testing.
      10816 (15)Within 30 d post-TAVI
      Ferreira et al
      • Ferreira T.
      • Da Costa A.
      • Cerisier A.
      • et al.
      Predictors of high-degree conduction disturbances and pacemaker implantation after transcatheter aortic valve replacement: prognostic role of the electrophysiological study.
      7416 (22)Within 5 d post-TAVI
      Data are given absolute number (n) with percentage (%) as reported in the primary studies.
      Abbreviations as in Tables 1 and 2.
      Figure 2 and Supplemental Material Section 3 show the random-effects summary estimates for each examined EPS parameter in association with post-TAVI HG-AVB requiring PPM. The pre-TAVI HV interval >70 ms was significantly associated with an increased risk of HG-AVB and PPM implantation (OR 2.53; 95% CI 1.11–5.81; P = .04; heterogeneity τ2 <0.001). Furthermore, among patients without immediate AVB, the absolute value of the HV interval post-TAVI was also statistically significantly associated with subsequent HG-AVB and PPM requirement (OR 1.10; 95% CI 1.03–1.17; P = .02; τ2 <0.001; per 1-ms increase). Other parameters, including pre- and post-TAVI AH, anterograde Wenckebach cycle length, delta AH, and delta HV, did not show significant associations with post-TAVI HG-AVB.
      Figure thumbnail gr2
      Figure 2Random-effects meta-analysis of EPS-derived predictors for permanent pacemaker implantation following TAVI. All estimates are reported per millisecond of change of the EPS parameter except for HV >70 ms pre-TAVI and HV >70 ms post-TAVI, which are shown as categorical estimates. dAH = delta AH; dHV = delta HV; OR = odds ratio; PPM = permanent pacemaker; TAVR = transcatheter aortic valve replacement; other abbreviations as in .

      EPS parameters to guide PPM implantation post-TAVI

      In 10 studies (506 patients), PPM implantation decision-making was guided by post-TAVI EPS findings. Table 4 lists the EPS criteria composing the indications for PPM implantation in each study. In these studies, the prevalence of post-TAVI LBBB ranged from 21% to 100%, and the prevalence of intraprocedural transient AVB ranged from 9% to 100% (Table 4). A total of 124 of 506 patients (25%) received a PPM for that indication before hospital discharge.
      Table 4PPM implantation guided by abnormal EPS
      StudyNo. of patientsNo. with LBBB post-TAVRNo. with transient intraoperative AVBCriteria for PPM implantationTiming of PPM implantationPPM implanted for abnormal EPSLong-term PPM dependency in patients implanted for abnormal EPSDefinition of PPM dependency
      Akin et al
      • Akin I.
      • Kische S.
      • Paranskaya L.
      • et al.
      Predictive factors for pacemaker requirement after transcatheter aortic valve implantation.
      4520 (44)N/ANew LBBB plus HV ≥75 msWithin 7 d post-TAVI13 (29)Not assessedN/A
      Kostopoulou et al
      • Kostopoulou A.
      • Karyofillis P.
      • Livanis E.
      • et al.
      Permanent pacing after transcatheter aortic valve implantation of a CoreValve prosthesis as determined by electrocardiographic and electrophysiological predictors: a single-centre experience.
      3014 (47)N/ANew LBBB plus HV >70 msMedian 2 d post-TAVI (range 2-24)1 (3)1/1 (100)Asystole or HG-AVB with or without escape rhythm after cessation of pacing
      Tovia-Brodie et al
      • Tovia-Brodie O.
      • Ben-Haim Y.
      • Joffe E.
      • et al.
      The value of electrophysiologic study in decision-making regarding the need for pacemaker implantation after TAVI.
      2681 (100)N/AIntrahisian block

      HV interval ≥75 ms

      Second-degree infranodal block during incremental atrial pacing at a cycle length <400 ms
      N/A8 (31)Not assessedN/A
      Badenco et al
      • Badenco N.
      • Chong-Nguyen C.
      • Maupain C.
      • et al.
      Respective role of surface electrocardiogram and His bundle recordings to assess the risk of atrioventricular block after transcatheter aortic valve replacement.
      8430 (36)13 (15)HV interval >80 mBefore hospital discharge9 (11)1/9 (11)Persistent HG-AVB
      Makki et al
      • Makki N.
      • Dollery J.
      • Jones D.
      • Crestanello J.
      • Lilly S.
      Conduction disturbances after TAVR: Electrophysiological studies and pacemaker dependency.
      75 (71)N/ALBBB and HV interval >55 ms or elicitation of complete heart blockN/A7 (100)1/7 (14)(1) >50% pacing on PPM interrogation

      (2) Underlying HG-AVB

      (3) Underlying asystole >5 s

      (4) Symptoms in the setting of bradycardia (rate <50 bpm)
      Rogers et al
      • Rogers T.
      • Devraj M.
      • Thomaides A.
      • et al.
      Utility of invasive electrophysiology studies in patients with severe aortic stenosis undergoing transcatheter aortic valve implantation.
      9520 (21)N/AIntrahisian or infrahisian block with decremental atrial pacing with or without isoproterenol challengeN/A28 (29)Not assessedN/A
      Knecht et al
      • Knecht S.
      • Schaer B.
      • Reichlin T.
      • et al.
      Electrophysiology testing to stratify patients with left bundle branch block after transcatheter aortic valve implantation.
      5656 (100)N/AHV interval >55 msN/A15 (27)8/15 (53)HG-AVB on 12-lead ECG and/or ventricular pacing >1% despite algorithms to minimize pacing
      Bourenane et al
      • Bourenane H.
      • Galand V.
      • Boulmier D.
      • et al.
      Electrophysiological study-guided permanent pacemaker implantation in patients with conduction disturbances following transcatheter aortic valve implantation.
      7863 (81)7 (9)HV interval >70 ms

      High-grade infrahisian block during incremental atrial pacing at rate ≤100 bpm
      N/A35 (45)27/35 (77)Ventricular pacing >1%
      Nauchi et al
      • Nauchi M.
      • Yamawaki M.
      • Nakano T.
      • et al.
      Bedside Electrophysiological study using a temporary pacemaker may predict recurrence of atrioventricular block after transcatheter aortic valve replacement.
      11N/A11 (100)Induction of AVB with RV apical pacing at 100 per min for 1 min with or without IV procainamide (10 mg/kg) for 10 minN/A3 (27)2/3 (67)Persistent HG-AVB
      Ferreira et al
      • Ferreira T.
      • Da Costa A.
      • Cerisier A.
      • et al.
      Predictors of high-degree conduction disturbances and pacemaker implantation after transcatheter aortic valve replacement: prognostic role of the electrophysiological study.
      7433 (45)N/AHV interval ≥95 ms

      High-grade infrahisian block during atrial pacing at rate ≤150 bpm
      Within 5 d post-TAVI5 (7)Not assessedN/A
      Values are given as absolute number (n) with percentage (%) as reported in the primary studies.
      ECG = electrocardiogram; HG-AVB = high-grade atrioventricular block; IV = intravenous; RV = right ventricle; other abbreviations as in Tables 1 and 2.
      Six studies reported rates of pacemaker dependency during follow-up among patients receiving PPM for abnormal EPS findings. The definitions of pacemaker dependency in each of the 6 studies are listed in Table 4. Of 70 patients, 40 (57%) were PPM-dependent during variable follow-up ranging from 7 days to 17 months in different studies. Furthermore, 6 studies reported that the postdischarge rate of sudden cardiac death or PPM implantation for HG-AVB among patients with a negative post-TAVI EPS was 1.7% (4/229 patients) during follow-up of 3–12 months.

      Discussion

      PPM implantation for HG-AVB after TAVI is associated with longer hospitalization, higher readmission rates, and possibly increased morbidity and mortality.
      • Nazif T.M.
      • Dizon J.M.
      • Hahn R.T.
      • et al.
      Predictors and clinical outcomes of permanent pacemaker implantation after transcatheter aortic valve replacement: the PARTNER (Placement of AoRtic TraNscathetER Valves) trial and registry.
      ,
      • Aljabbary T.
      • Qiu F.
      • Masih S.
      • et al.
      Association of clinical and economic outcomes with permanent pacemaker implantation after transcatheter aortic valve replacement.
      ,
      • Kawsara A.
      • Sulaiman S.
      • Alqahtani F.
      • et al.
      Temporal trends in the incidence and outcomes of pacemaker implantation after transcatheter aortic valve replacement in the United States (2012-2017).
      Electrocardiographic predictors of post-TAVI AVB based on the preprocedure ECG, as well as procedural and anatomic characteristics, can guide procedural planning and patient counseling for PPM risk.
      • Nazif T.M.
      • Dizon J.M.
      • Hahn R.T.
      • et al.
      Predictors and clinical outcomes of permanent pacemaker implantation after transcatheter aortic valve replacement: the PARTNER (Placement of AoRtic TraNscathetER Valves) trial and registry.
      ,
      • Siontis G.C.
      • Juni P.
      • Pilgrim T.
      • et al.
      Predictors of permanent pacemaker implantation in patients with severe aortic stenosis undergoing TAVR: a meta-analysis.
      However, uncertainty exists regarding the management of patients with equivocal PPM indications after TAVI. This uncertainty is reflected by the broad range of guidance in the 2020 ACC Expert Consensus Decision Pathway on Management of Conduction Disturbances in Patients Undergoing Transcatheter Aortic Valve Replacement wherein “monitoring, and consideration for EPS and PPM are advised for patients with new, progressive or pre-existing conduction disturbance that changes post-procedure.”
      • Lilly S.M.
      • Deshmukh A.J.
      • Epstein A.E.
      • et al.
      2020 ACC expert consensus decision pathway on management of conduction disturbances in patients undergoing transcatheter aortic valve replacement: a report of the American College of Cardiology Solution Set Oversight Committee.
      In this meta-analysis of 18 studies reporting the value of peri-TAVI EPS to predict HG-AVB, we found the rate of PPM implantation for HG-AVB was 16%. The AH and HV intervals showed the most consistent absolute increases after TAVI. The HV interval pre- and post-TAVI was significantly associated with subsequent HG-AVB and PPM requirement. Furthermore, among patients without early HG-AVB who received a PPM for abnormal EPS findings after TAVI, half were PPM-dependent during posthospitalization follow-up. Among patients with a normal EPS after TAVI who did not receive a PPM, the rate of sudden cardiac death or HG-AVB after hospital discharge was very low.
      Most PPM implantations after TAVI are unavoidable and clearly indicated. However, some patients with new AV conduction disease without definite PPM indications may receive a prophylactic PPM because of concern for progression to higher-grade AVB, and many more patients undergo prolonged ambulatory rhythm monitoring after hospital discharge. Up to 10% of patients without an immediate PPM indication may develop delayed, posthospitalization HG-AVB, with first-degree AVB and bundle branch blocks being predictors of delayed AVB.
      • El-Sabawi B.
      • Welle G.A.
      • Cha Y.M.
      • et al.
      Temporal incidence and predictors of high-grade atrioventricular block after transcatheter aortic valve replacement.
      ,
      • Ream K.
      • Sandhu A.
      • Valle J.
      • et al.
      Ambulatory rhythm monitoring to detect late high-grade atrioventricular block following transcatheter aortic valve replacement.
      However, in a study using 30-day continuous ambulatory monitoring in post-TAVI patients, only 14% of patients with new LBBB progressed to second- or third-degree AVB.
      • Tian Y.
      • Padmanabhan D.
      • McLeod C.J.
      • et al.
      Utility of 30-day continuous ambulatory monitoring to identify patients with delayed occurrence of atrioventricular block after transcatheter aortic valve replacement.
      Therefore, EP testing may offer useful information in refining risk stratification for patients before TAVI but also for those with equivocal PPM indications post-TAVI, such as new LBBB or right bundle branch block with or without first-degree AVB or atrial fibrillation, and transient intraprocedural HG-AVB.
      The current analysis allows synthesis of evidence across studies with diverse patient populations and practice patterns and amplifies the statistical power to detect associations between EPS parameters and TAVI-related AVB. We found the pre- and post-TAVI HV interval was a significant predictor of AVB and PPM requirement. The HV interval is an integral measure of intrahisian and infrahisian system function, with an interval ≥55 ms considered abnormal. We found less robust evidence for the pre- or post-TAVI AH interval. This is not surprising considering that the compact AV node and its fast pathway input are less likely to be injured during TAVI, as opposed to the His bundle and proximal left bundle branch.
      • Kawashima T.
      • Sato F.
      Visualizing anatomical evidences on atrioventricular conduction system for TAVI.
      Furthermore, unlike the HV interval, the AH interval varies significantly depending on autonomic input, thus providing a less reproducible measure of AV conduction status.
      The approach of EPS-guided PPM implantation after TAVI was specifically tested in 10 of the included studies. Using various criteria to define abnormal EPS, this approach resulted in 1 in 4 patients receiving a PPM after EPS before hospital discharge. Outside of the TAVI setting, HV >70 ms in patients with syncope and bundle branch block is an indication for a PPM.
      • Kusumoto F.M.
      • Schoenfeld M.H.
      • Barrett C.
      • et al.
      2018 ACC/AHA/HRS guideline on the evaluation and management of patients with bradycardia and cardiac conduction delay: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines, and the Heart Rhythm Society.
      Similarly, pacing- or procainamide-induced infrahisian block is a PPM indication in most settings. Two of the studies in this meta-analysis used an HV interval threshold of 55 ms to recommend PPM implantation. It is reasonable to individually consider PPM for HV interval between 55 and 70 ms depending also on other patient-specific factors and preferences. Even though the pre-TAVI HV interval had prognostic significance in our study, pre-TAVI EPS is not included in the proposed algorithm because it would be unlikely to impact management unless AV conduction changes occur after valve deployment.
      More than half of the patients who received a PPM for an abnormal EPS were pacemaker-dependent (defined as persistent HG-AVB or non-negligible ventricular pacing percentage among studies) when long-term follow-up PPM data were available. This is a large value that supports the use of EPS-guided PPM implantation in some patients. PPM utilization could be improved by fine-tuning patient criteria and EPS parameter thresholds to increase their specificity for subsequent HG-AVB. In addition, conduction changes after TAVI can evolve over a period of days, particularly for self-expanding valves, and the optimal timing of EPS after TAVI needs further investigation. Noteworthy, the very low rate of subsequent PPM requirement or sudden cardiac death in patients with reassuring EPS results who did not receive a PPM before hospital discharge further highlights the potential value of peri-TAVR EPS.
      The implications of EPS on TAVI-related costs and resource utilization merit consideration. Payment and reimbursement models for TAVI vary across health systems, and the cost-effectiveness of EPS requires further study. There is also a theoretical concern for prolonged hospital stay in patients undergoing EPS after TAVI. However, in one of the largest studies by Rogers et al
      • Rogers T.
      • Devraj M.
      • Thomaides A.
      • et al.
      Utility of invasive electrophysiology studies in patients with severe aortic stenosis undergoing transcatheter aortic valve implantation.
      included in this meta-analysis, patients with a negative EPS had comparable length of hospital stay as patients without any conduction disturbance. Similarly, Krishnaswamy et al
      • Krishnaswamy A.
      • Sammour Y.
      • Mangieri A.
      • et al.
      The utility of rapid atrial pacing immediately post-TAVR to predict the need for pacemaker implantation.
      reported a similar length of hospital stay in patients with positive and negative EPS. Selective use of EPS when it can meaningfully impact decision-making ultimately may reduce costs of care and adverse outcomes by reducing over- and underutilization of ambulatory rhythm monitoring and PPM. However, because of the heterogeneity in existing evidence, the current data do not support the broad adoption of EPS-guided decision-making in clinical practice. Further research is needed to determine actionable thresholds of key AV conduction parameters, optimal EPS protocols, and patient subgroups who will benefit the most.

      Study limitations

      The included studies had variations in procedural characteristics, EPS protocols and timing, and actionable thresholds of EPS parameters. Similarly, there was a mix of patients undergoing self-expanding and balloon-expandable TAVI in the cumulative data analyzed. The value of EPS in predicting short- and longer-term PPM requirement likely differs in the 2 groups. We did not have the data required to investigate the value of EPS parameters in different subgroups, including those with various pre- or post-TAVI conduction abnormalities (such as LBBB). The overlap in enrollment periods across studies and the limited or absent study-level information on EPS parameters stratified by the different TAVI systems and implantation techniques did not allow us to investigate the value of EPS parameters over time in correlation with evolving TAVI technology and techniques. Furthermore, with the exception of the small randomized study by Kostopoulou et al,
      • Kostopoulou A.
      • Karyofillis P.
      • Livanis E.
      • et al.
      Permanent pacing after transcatheter aortic valve implantation of a CoreValve prosthesis as determined by electrocardiographic and electrophysiological predictors: a single-centre experience.
      all other included studies were observational and findings may have been affected by confounders. Large randomized trials of an EPS-guided vs conventional approach to post-TAVI PPM implantation are needed to inform on the outcomes of patients with equivocal pacing indications after TAVI.

      Conclusion

      Invasive EPS parameters can offer useful insights in the risk stratification for HG-AVB after TAVI. Selective utilization of EPS for assessment of the AV conduction system in patients with borderline PPM indications after TAVI can be considered within the context of the limitations of the currently available data. Future randomized studies comparing EPS-guided and standard-of-care approaches in patients with new, non–high-grade AV conduction disturbances after TAVI are needed to definitively assess the impact on patient outcomes, resource utilization, and costs before broader adoption of EPS in the peri-TAVI setting can be justified.

      Funding Sources

      No funding was obtained for this study.

      Disclosures

      Dr Pilgrim received research grants to the institution from Biotronik, Boston Scientific, and Edwards Lifesciences; and speaker fees/consultancy/advisory board from Biotronik, Boston Scientific, HigLife SAS, and Medtronic. Dr Roten received consulting honoraria and speaker fees from Abbott and Medtronic. Dr Reichlin reports research grants from the Goldschmidt-Jacobson Foundation, the Swiss National Science Foundation, the Swiss Heart Foundation, the European Union Eurostars (9799)—ALVALE, and the Professor Max Cloëtta Foundation, all for work outside the submitted study; speaker/consulting honoraria or travel support from Abbott/SJM, AstraZeneca, Brahms, Bayer, Biosense Webster, Biotronik, Boston Scientific, Daiichi Sankyo, Medtronic, Pfizer BMS, and Roche, all for work outside the submitted study; and support for his institution’s fellowship program from Abbott/SJM, Biosense Webster, Biotronik, Boston Scientific, and Medtronic for work outside the submitted study. Dr Windecker serves as unpaid advisory board member and/or unpaid member of the steering/executive committee for trials funded by Abbott, Abiomed, Amgen, AstraZeneca, Bristol Myers Squibb, Boston Scientific, Biotronik, Cardiovalve, Edwards Lifesciences, MedAlliance, Medtronic, Novartis, Polares, Sinomed, V-Wave, and Xeltis, but has not received personal payments by pharmaceutical companies or device manufacturers; and is a member of the steering/executive committee for several investigator-initiated trials that receive funding by industry without impact on personal remuneration. All other authors have no conflicts to disclose.

      Authorship

      All authors attest they meet the current ICMJE criteria for authorship.

      Ethics Statement

      The study protocol follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement and was registered at the PROSPERO international register of systematic reviews (CRD42019121204). Institutional review board approval was not required due to the nature of the study, which utilized published data only.

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