Advertisement

Prognostic Implications of Change in Left Ventricular Ejection Fraction After Transcatheter Aortic Valve Implantation

Open AccessPublished:June 09, 2022DOI:https://doi.org/10.1016/j.amjcard.2022.04.060
      Reduced left ventricular (LV) systolic function is associated with worse prognosis in patients with severe aortic stenosis (AS) treated with transcatheter aortic valve implantation (TAVI). We aimed to examine the changes in left ventricular ejection fraction (LVEF) after TAVI among patients with varying baseline LVEF. Moreover, variables associated with lack of LVEF improvement were identified and the association with long-term outcomes was investigated. A total of 560 patients (age 80 ± 7 years, 53% men) with severe AS who underwent transfemoral TAVI between 2007 and 2019 were selected. LVEF was assessed from transthoracic echocardiography at baseline (before TAVI) and at 6 and 12 months after TAVI. Patients were stratified according to baseline LVEF: (1) LVEF ≥50%, (2) LVEF 40% to 49%, and (3) LVEF <40%. The clinical end point was ≥5% LVEF improvement. The primary outcome was all-cause mortality. Patients with baseline LVEF<40% showed greater increase in LVEF than those with baseline LVEF 40% to 49% and LVEF ≥50% (from 33% ± 6% to 43% ± 10%, p <0.001; from 45% ± 3% to 52% ± 8%, p <0.001; and from 58% ± 5% to 59% ± 7%, p = 0.012, respectively, p for interaction <0.001). Coronary artery disease (odds ratio [OR] 1.80 [95% confidence interval (CI) 1.06 to 3.06], p = 0.031), myocardial infarction (OR 2.07 [95% CI 1.19 to 3.61], p = 0.010), and permanent pacemaker (OR: 1.93 [95% CI 1.25 to 3.00], p = 0.003) were independently associated with the lack of ≥5% LVEF improvement. During a median follow-up of 3.8 (interquartile range 2.6 to 5.2) years, 176 patients died (31%). Patients with ≥5% LVEF improvement had similar outcomes compared with those with <5% LVEF improvement (log-rank p = 0.89). In conclusion, patients with severe AS and baseline LVEF <40% had the greatest improvement in LVEF at 1-year follow-up after TAVI. Coronary artery disease, myocardial infarction, and permanent pacemaker were associated with lack of LVEF improvement. However, LVEF improvement at 12 months was not associated with long-term outcomes.
      Severe aortic stenosis (AS) may have a significant impact on left ventricular (LV) function. Increased afterload caused by AS may lead to LV remodeling, resulting in LV hypertrophy and impaired LV function.
      • Otto CM
      • Prendergast B.
      Aortic-valve stenosis–from patients at risk to severe valve obstruction.
      ,
      • Grossman W
      • Jones D
      • McLaurin LP.
      Wall stress and patterns of hypertrophy in the human left ventricle.
      Approximately 1/3 of patients with severe AS present with LV systolic dysfunction.
      • Baron SJ
      • Arnold SV
      • Herrmann HC
      • Holmes DR
      • Jr Szeto WY
      • Allen KB
      • Chhatriwalla AK
      • Vemulapali S
      • O'Brien S
      • Dai D
      • Cohen DJ
      Impact of ejection fraction and aortic valve gradient on outcomes of transcatheter aortic valve replacement.
      ,
      • Elmariah S
      • Palacios IF
      • McAndrew T
      • Hueter I
      • Inglessis I
      • Baker JN
      • Kodali S
      • Leon MB
      • Svensson L
      • Pibarot P
      • Douglas PS
      • Fearon WF
      • Kirtane AJ
      • Maniar HS
      • Passeri JJ
      PARTNER Investigators. Outcomes of transcatheter and surgical aortic valve replacement in high-risk patients with aortic stenosis and left ventricular dysfunction: results from the Placement of Aortic transcatheter Valves (PARTNER) trial (cohort A).
      Moreover, LV systolic dysfunction has been linked with worse prognosis in patients with severe AS who were treated medically or underwent surgical aortic valve replacement.
      • Passeri JJ
      • Elmariah S
      • Xu K
      • Inglessis I
      • Baker JN
      • Alu M
      • Kodali S
      • Leon MB
      • Svensson LG
      • Pibarot P
      • Fearon WF
      • Kirtane AJ
      • Vlahakes GJ
      • Palacios IF
      • Douglas PS
      • Investigators PARTNER
      Transcatheter aortic valve replacement and standard therapy in inoperable patients with aortic stenosis and low EF.
      • Dahl JS
      • Eleid MF
      • Michelena HI
      • Scott CG
      • Suri RM
      • Schaff HV
      • Pellikka PA.
      Effect of left ventricular ejection fraction on postoperative outcome in patients with severe aortic stenosis undergoing aortic valve replacement.
      • Halkos ME
      • Chen EP
      • Sarin EL
      • Kilgo P
      • Thourani VH
      • Lattouf OM
      • Vega JD
      • Morris CD
      • Vassiliades T
      • Cooper WA
      • Guyton RA
      • Puskas JD.
      Aortic valve replacement for aortic stenosis in patients with left ventricular dysfunction.
      Transcatheter aortic valve implantation (TAVI) has become an alternative to surgical aortic valve replacement in patients with severe symptomatic AS.
      • Siontis GCM
      • Overtchouk P
      • Cahill TJ
      • Modine T
      • Prendergast B
      • Praz F
      • Pilgrim T
      • Petrinic T
      • Nikolakopoulou A
      • Salanti G
      • Søndergaard L
      • Verma S
      • Jüni P
      • Windecker S.
      Transcatheter aortic valve implantation vs. surgical aortic valve replacement for treatment of symptomatic severe aortic stenosis: an updated meta-analysis.
      Similarly, reduced baseline LV ejection fraction (LVEF) is associated with an increased risk of all-cause and cardiovascular mortality after TAVI.
      • Eleid MF
      • Goel K
      • Murad MH
      • Erwin PJ
      • Suri RM
      • Greason KL
      • Nishimura RA
      • Rihal CS
      • Holmes Jr, DR
      Meta-analysis of the prognostic impact of stroke volume, gradient, and ejection fraction after transcatheter aortic valve implantation.
      • Furer A
      • Chen S
      • Redfors B
      • Elmariah S
      • Pibarot P
      • Herrmann HC
      • Hahn RT
      • Kodali S
      • Thourani VH
      • Douglas PS
      • Alu MC
      • Fearon WF
      • Passeri J
      • Malaisrie SC
      • Crowley A
      • McAndrew T
      • Genereux P
      • Ben-Yehuda O
      • Leon MB
      • Burkhoff D.
      Effect of baseline left ventricular ejection fraction on 2-year outcomes after transcatheter aortic valve replacement: analysis of the PARTNER 2 trials.
      • Sannino A
      • Gargiulo G
      • Schiattarella GG
      • Brevetti L
      • Perrino C
      • Stabile E
      • Losi MA
      • Toscano E
      • Giugliano G
      • Scudiero F
      • Chiacchio E
      • Trimarco B
      • Esposito G.
      Increased mortality after transcatheter aortic valve implantation (TAVI) in patients with severe aortic stenosis and low ejection fraction: a meta-analysis of 6898 patients.
      LVEF is an important parameter for the assessment of LV systolic function and is relevant in the management of patients with asymptomatic severe AS according to current guidelines.
      • Vahanian A
      • Beyersdorf F
      • Praz F
      • Milojevic M
      • Baldus S
      • Bauersachs J
      • Capodanno D
      • Conradi L
      • De Bonis M
      • De Paulis R
      • Delgado V
      • Freemantle N
      • Gilard M
      • Haugaa KH
      • Jeppsson A
      • Jüni P
      • Pierard L
      • Prendergast BD
      • Sádaba JR
      • Tribouilloy C
      • Wojakowski W
      ESC/EACTS Scientific Document Group. 2021 ESC/EACTS Guidelines for the management of valvular heart disease.
      ,
      • Otto CM
      • Nishimura RA
      • Bonow RO
      • Carabello BA
      • Erwin 3rd, JP
      • Gentile F
      • Jneid H
      • Krieger EV
      • Mack M
      • McLeod C
      • O'Gara PT
      • Rigolin VH
      • Sundt 3rd, TM
      • Thompson A
      • Toly C
      2020 ACC/AHA guideline for the management of patients With valvular heart disease: A report of the American College of Cardiology/American Heart Association joint committee on clinical practice guidelines.
      Previous studies showed that LV systolic function improved after TAVI in patients with reduced LVEF.
      • Takagi H
      • Ando T
      • Umemoto T
      ALICE (All-Literature Investigation of Cardiovascular Evidence) Group. A meta-analysis of effects of transcatheter versus surgical aortic valve replacement on left ventricular ejection fraction and mass.
      • Ewe SH
      • Ajmone Marsan N
      • Pepi M
      • Delgado V
      • Tamborini G
      • Muratori M
      • Ng AC
      • van der Kley F
      • de Weger A
      • Schalij MJ
      • Fusari M
      • Biglioli P
      • Bax JJ
      Impact of left ventricular systolic function on clinical and echocardiographic outcomes following transcatheter aortic valve implantation for severe aortic stenosis.
      • Ribeiro HB
      • Lerakis S
      • Gilard M
      • Cavalcante JL
      • Makkar R
      • Herrmann HC
      • Windecker S
      • Enriquez-Sarano M
      • Cheema AN
      • Nombela-Franco L
      • Amat-Santos I
      • Muñoz-García AJ
      • Garcia Del Blanco B
      • Zajarias A
      • Lisko JC
      • Hayek S
      • Babaliaros V
      • Le Ven F
      • Gleason TG
      • Chakravarty T
      • Szeto WY
      • Clavel MA
      • de Agustin A
      • Serra V
      • Schindler JT
      • Dahou A
      • Puri R
      • Pelletier-Beaumont E
      • Côté M
      • Pibarot P
      • Rodés-Cabau J
      Transcatheter aortic valve replacement in patients With low-flow, low-gradient aortic stenosis: the TOPAS-TAVI registry.
      • Kamperidis V
      • Joyce E
      • Debonnaire P
      • Katsanos S
      • van Rosendael PJ
      • van der Kley F
      • Sianos G
      • Bax JJ
      • Ajmone Marsan N
      • Delgado V
      Left ventricular functional recovery and remodeling in low-flow low-gradient severe aortic stenosis after transcatheter aortic valve implantation.
      However, data on the change of LVEF after TAVI in patients with varying LVEF at baseline are scarce. Additionally, the impact of LVEF improvement on outcomes after TAVI is not clear. Accordingly, the aims of this study were to investigate the potential improvement of LVEF after TAVI in patients with preserved baseline LVEF (LVEF ≥50%), midrange LVEF (LVEF 40% to 49%), and reduced LVEF (LVEF <40%). Moreover, the variables associated with lack of LVEF improvement were identified. Finally, the association between LVEF improvement with long-term outcomes after TAVI was evaluated.

      Methods

      Patients with severe AS who were treated with TAVI at the Leiden University Medical Center (Leiden, The Netherlands) between 2007 and 2019 were included in this retrospective analysis. Patients who underwent transapical TAVI or a valve-in-valve procedure and those whose echocardiographic data at baseline and/or follow-up were lacking were excluded. All patients underwent standard routine follow-up transthoracic echocardiography. Patients were stratified according to baseline (pre-TAVI) LVEF as appointed in the 2016 European Society of Cardiology heart failure guidelines
      • Ponikowski P
      • Voors AA
      • Anker SD
      • Bueno H
      • Cleland JGF
      • Coats AJS
      • Falk V
      • González-Juanatey JR
      • Harjola VP
      • Jankowska EA
      • Jessup M
      • Linde C
      • Nihoyannopoulos P
      • Parissis JT
      • Pieske B
      • Riley JP
      • Rosano GMC
      • Ruilope LM
      • Ruschitzka F
      • Rutten FH
      • van der Meer P.
      2016 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure.
      : patients with preserved LVEF (LVEF ≥50%), midrange LVEF (LVEF 40% to 49%), and reduced LVEF (LVEF <40%). Demographic and clinical characteristics at the time of TAVI were collected from the electronic patient records (EPD-vision, Leiden University Medical Center). Clinical characteristics included co-morbidities, cardiac risk factors, previous coronary revascularization, and medication use. The estimated glomerular filtration rate was calculated using the Chronic Kidney Disease Epidemiology Collaboration formula and renal impairment was defined as an estimated glomerular filtration rate <60 ml/min/1.73 m2. This retrospective analysis complies with the Declaration of Helsinki and was approved by the institutional review board, which waived the need for written informed consent owing to the retrospective study design.
      TAVI eligibility and feasibility and decision making on the access route and valve type were decided by the local heart team. Multidetector-row computed tomography measurements of the aortic annulus were used to select the transcatheter heart valve size, as previously described.
      • Delgado V
      • Ng AC
      • van de Veire NR
      • van der Kley F
      • Schuijf JD
      • Tops LF
      • de Weger A
      • Tavilla G
      • de Roos A
      • Kroft LJ
      • Schalij MJ
      • Bax JJ.
      Transcatheter aortic valve implantation: role of multi-detector row computed tomography to evaluate prosthesis positioning and deployment in relation to valve function.
      The TAVI procedure was performed according to standard practice.
      • Otto CM
      • Kumbhani DJ
      • Alexander KP
      • Calhoon JH
      • Desai MY
      • Kaul S
      • Lee JC
      • Ruiz CE
      • Vassileva CM.
      2017 ACC Expert Consensus decision pathway for transcatheter aortic valve replacement in the management of adults With aortic stenosis: A report of the American College of Cardiology task force on clinical expert consensus documents.
      Balloon- and self-expandable valves that were used included Edwards SAPIEN, SAPIEN XT, and SAPIEN 3 (Edwards Lifesciences, Irvine, California) and Medtronic (Minneapolis, Minnesota) CoreValve Evolut R and Evolut Pro (Medtronic).
      Transthoracic 2-dimensional echocardiographic examinations were performed before TAVI (to evaluate AS severity, LV systolic function, and LV dimensions) and during routine follow-up: immediately after TAVI (prosthetic valve hemodynamics) and at 6- and 12-month follow-up (prosthetic valve hemodynamics, LV function, and LV dimensions). All echocardiographic examinations were acquired by experienced echocardiographers using commercially available ultrasound systems (Vivid-7, E9 or E95, General Electric Vingmed, Horten, Norway), equipped with 3.5 MHz or M5S transducers. The echocardiographic examinations were performed with patients at rest and data were obtained from the parasternal, apical, and subcostal views. All echocardiographic examinations were reported according to current recommendations.
      • Lancellotti P
      • Pibarot P
      • Chambers J
      • Edvardsen T
      • Delgado V
      • Dulgheru R
      • Pepi M
      • Cosyns B
      • Dweck MR
      • Garbi M
      • Magne J
      • Nieman K
      • Rosenhek R
      • Bernard A
      • Lowenstein J
      • Vieira ML
      • Rabischoffsky A
      • Vyhmeister RH
      • Zhou X
      • Zhang Y
      • Zamorano JL
      • Habib G.
      Recommendations for the imaging assessment of prosthetic heart valves: a report from the European Association of Cardiovascular Imaging endorsed by the Chinese Society of Echocardiography, the Inter-American Society of Echocardiography, and the Brazilian Department of Cardiovascular Imaging.
      ,
      • Lang RM
      • Badano LP
      • Mor-Avi V
      • Afilalo J
      • Armstrong A
      • Ernande L
      • Flachskampf FA
      • Foster E
      • Goldstein SA
      • Kuznetsova T
      • Lancellotti P
      • Muraru D
      • Picard MH
      • Rietzschel ER
      • Rudski L
      • Spencer KT
      • Tsang W
      • Voigt JU.
      Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging.
      Echocardiographic analysis was performed offline, using commercially available software (EchoPac version 113.0.3 and 203; GE Medical Systems, Horten, Norway). Peak and mean transvalvular gradients were calculated from continuous-wave Doppler recordings of the apical 3- or 5-chamber views according to the Bernoulli equation. Aortic valve area (AVA) was calculated using the continuity equation and indexed to body surface area (indexed AVA [AVAi]). Severe AS was defined as an AVA <1.0 cm
      • Grossman W
      • Jones D
      • McLaurin LP.
      Wall stress and patterns of hypertrophy in the human left ventricle.
      or AVAi <0.6 cm2/m2 and a mean transvalvular pressure gradient ≥40 mm Hg or peak aortic jet velocity ≥4 m/s at rest or during dobutamine stress echocardiography.
      • Vahanian A
      • Beyersdorf F
      • Praz F
      • Milojevic M
      • Baldus S
      • Bauersachs J
      • Capodanno D
      • Conradi L
      • De Bonis M
      • De Paulis R
      • Delgado V
      • Freemantle N
      • Gilard M
      • Haugaa KH
      • Jeppsson A
      • Jüni P
      • Pierard L
      • Prendergast BD
      • Sádaba JR
      • Tribouilloy C
      • Wojakowski W
      ESC/EACTS Scientific Document Group. 2021 ESC/EACTS Guidelines for the management of valvular heart disease.
      ,
      • Otto CM
      • Nishimura RA
      • Bonow RO
      • Carabello BA
      • Erwin 3rd, JP
      • Gentile F
      • Jneid H
      • Krieger EV
      • Mack M
      • McLeod C
      • O'Gara PT
      • Rigolin VH
      • Sundt 3rd, TM
      • Thompson A
      • Toly C
      2020 ACC/AHA guideline for the management of patients With valvular heart disease: A report of the American College of Cardiology/American Heart Association joint committee on clinical practice guidelines.
      LV volumes (end-diastolic and end-systolic) were measured using planimetry in the apical 2- and 4-chambers views and were indexed to body surface area. LVEF was calculated using Simpson biplane method. LV dimensions (end-diastolic diameter, intraventricular septum thickness, and posterior wall thickness) were obtained in the parasternal long-axis views at end-diastole.
      • Lang RM
      • Badano LP
      • Mor-Avi V
      • Afilalo J
      • Armstrong A
      • Ernande L
      • Flachskampf FA
      • Foster E
      • Goldstein SA
      • Kuznetsova T
      • Lancellotti P
      • Muraru D
      • Picard MH
      • Rietzschel ER
      • Rudski L
      • Spencer KT
      • Tsang W
      • Voigt JU.
      Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging.
      LV mass was calculated using the Devereux formula and indexed to body surface area.
      • Lang RM
      • Badano LP
      • Mor-Avi V
      • Afilalo J
      • Armstrong A
      • Ernande L
      • Flachskampf FA
      • Foster E
      • Goldstein SA
      • Kuznetsova T
      • Lancellotti P
      • Muraru D
      • Picard MH
      • Rietzschel ER
      • Rudski L
      • Spencer KT
      • Tsang W
      • Voigt JU.
      Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging.
      The presence of postprocedural aortic regurgitation and paravalvular leakage was detected and severity was graded according to current recommendations: mild (grade 1), moderate (grade 2), moderate to severe (grade 3), and severe (grade 4).
      • Zoghbi WA
      • Asch FM
      • Bruce C
      • Gillam LD
      • Grayburn PA
      • Hahn RT
      • Inglessis I
      • Islam AM
      • Lerakis S
      • Little SH
      • Siegel RJ
      • Skubas N
      • Slesnick TC
      • Stewart WJ
      • Thavendiranathan P
      • Weissman NJ
      • Yasukochi S
      • Zimmerman KG.
      Guidelines for the evaluation of valvular regurgitation after percutaneous valve repair or replacement: A report from the American Society of Echocardiography developed in collaboration with the Society for Cardiovascular Angiography and Interventions, Japanese Society of Echocardiography, and Society for Cardiovascular Magnetic Resonance.
      Significant paravalvular leakage was defined by a grade ≥2.
      Changes in LVEF and LV volumes over time are presented as absolute numbers and LV volumes also as percentual reduction compared with baseline. Additional echocardiographic end points included the increase in LVEF ≥5% and ≥10% (as percent point) at follow-up. An increase of LVEF ≥5% was the primary end point, as used previously.
      • Bax JJ
      • Poldermans D
      • Elhendy A
      • Cornel JH
      • Boersma E
      • Rambaldi R
      • Roelandt JR
      • Fioretti PM.
      Improvement of left ventricular ejection fraction, heart failure symptoms and prognosis after revascularization in patients with chronic coronary artery disease and viable myocardium detected by dobutamine stress echocardiography.
      Variables linked with the lack of ≥5% LVEF improvement were identified. Additionally, patients were followed up for the occurrence of all-cause mortality after TAVI and survival time was restricted to 5 years. Data on mortality were collected from the departmental electronic patient files, which were linked with the Social Security Death Index and were acquired for all patients.
      Continuous variables following a normal distribution are presented as mean ± SD and were compared using the 1-way analysis of variance test. Non-normally distributed continuous variables are presented as median with 25% to 75% interquartile range and were compared using the Kruskal-Wallis test. Bonferroni post hoc analysis was performed to assess between-group differences in case of a significant difference in the overall 3 group comparison. Distribution of continuous variables was evaluated using histograms and Q-Q plots. Categoric variables are presented as absolute numbers and percentages and were compared using the chi-square test or Fisher exact test. General linear models with repeated measures analysis were used to evaluate changes in echocardiographic variables over time and to test differences between the groups of baseline LVEF. The Greenhouse-Geisser correction was used if the sphericity assumption was violated and Bonferroni post hoc analysis was performed in case of a significant difference in the overall 3 group comparison. Additional analyses were performed to correct for potential confounders (age, gender, hypertension, diabetes mellitus, coronary artery disease, previous myocardial infarction, concomitant moderate or severe mitral- or aortic regurgitation, moderate or severe paravalvular leakage, permanent pacemaker [before and after TAVI], atrial fibrillation, pre-TAVI AV mean gradient, and pre-TAVI LVEF) on the change of the LV parameters over time and were included as covariates in the general linear models.
      • Ngo A
      • Hassager C
      • Thyregod HGH
      • Søndergaard L
      • Olsen PS
      • Steinbrüchel D
      • Hansen PB
      • Kjærgaard J
      • Winther-Jensen M
      • Ihlemann N.
      Differences in left ventricular remodelling in patients with aortic stenosis treated with transcatheter aortic valve replacement with corevalve prostheses compared to surgery with porcine or bovine biological prostheses.
      Univariable and multivariable binary logistic regression models were used to evaluate the variables that were associated with lack of ≥5% LVEF improvement. All variables with a p <0.10 in the univariable analysis were included in the multivariable model. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated and reported. Kaplan-Meier curves were generated to estimate the cumulative survival rates of all-cause mortality and the log-rank test was used to compare patients with ≥5% LVEF improvement at follow-up. Multivariable Cox proportional hazards regression analysis was used to evaluate the association of improvement in LVEF (as continuous and dichotomous variables) at follow-up with all-cause mortality. Potential confounders including age, gender, cardiac risk factors, coronary artery disease, previous myocardial infarction, previous stroke/transient ischemic attack, peripheral vascular disease, chronic obstructive pulmonary disease, previous coronary revascularization, chronic kidney disease, pre-TAVI AV mean gradient, and pre-TAVI LVEF were incorporated in the multivariable Cox proportional hazard model. Hazard ratios (HRs) and 95% CI were calculated and reported. A 2-sided p <0.05 was considered significant. Data analyses were performed with SPSS version 25.0 (IBM SPSS Statistics, IBM Corporation, Armonk, New York).

      Results

      A total of 560 patients (age 80 ± 7 years, 53% men) with severe AS were included in the analysis (Figure 1). The distribution of the different groups of LV systolic function before TAVI and at 6- and 12-month follow-up are shown in Figure 2. Before TAVI, 350 patients (62%) had preserved LVEF (LVEF ≥50%), 122 patients (22%) had midrange LVEF (LVEF 40% to 49%), and reduced LVEF (LVEF <40%) was present in 88 patients (16%). Baseline (pre-TAVI) demographic and clinical characteristics of the overall population and according to baseline LVEF are presented in Table 1. Patients with reduced baseline LVEF had a more frequent history of myocardial infarction, NYHA class 3 to 4, concomitant moderate or severe mitral or aortic regurgitation, and permanent pacemaker compared with patients with preserved and midrange baseline LVEF, whereas hypertension was less common. Accordingly, patients with reduced baseline LVEF were more frequently using diuretics, mineralocorticoid receptor antagonists, and oral anticoagulation and less calcium antagonists. Additionally, patients with reduced baseline LVEF had a higher logistic EuroSCORE and worse kidney function than patients with midrange and preserved baseline LVEF. However, the frequency of reduced kidney function was comparable between the groups (50% vs 52% vs 45%, respectively, p = 0.42).
      Figure 2
      Figure 2Distribution of LVEF before TAVI and at follow-up. Pie chart displaying the distribution of patients with preserved LVEF ≥50% (green), midrange LVEF 40% to 49% (blue), and reduced LVEF <40% (red) at baseline and 6 and 12 months after transcatheter aortic valve implantation.
      Table 1Baseline (pre-TAVI) demographical and clinical characteristics of the overall population and according to baseline left ventricular ejection fraction
      VariableOverall population (n=560)Left ventricular ejection fraction ≥50% (n=350)Left ventricular ejection fraction 40-49% (n=122)Left ventricular ejection fraction <40% (n=88)p-Value
      Age (years)80 ± 780 ± 780 ± 679 ± 90.46
      Male sex296 (53%)178 (51%)68 (56%)50 (57%)0.47
      Body mass index (kg/m2)26.7 ± 4.626.7 ± 4.827.0 ± 4.226.4 ± 4.40.67
      Logistic EuroSCORE12.3 [8.6-20.1]10.7 [7.9-17.1]13.4 [9.5-21.6]*21.9 [13.8-31.9]*,†<0.001
      eGFR (ml/min)61 ± 2063 ± 1958 ± 21*57 ± 21*,†0.007
      Hypertension407 (73%)266 (76%)88 (72%)53 (60%)0.009
      Hypercholesterolemia338 (61%)206 (59%)80 (66%)52 (59%)0.43
      Diabetes mellitus159 (28%)97 (28%)35 (29%)27 (31%)0.86
      Smoker76 (14%)47 (14%)14 (12%)15 (18%)0.58
      CAD351 (63%)208 (60%)80 (66%)63 (72%)0.089
      Previous myocardial infarction112 (20%)55 (16%)30 (25%)27 (31%)0.003
      Previous revascularization293 (52%)172 (49%)67 (55%)54 (61%)0.099
      PCI173 (31%)108 (31%)36 (30%)29 (33%)0.22
      CABG120 (21%)64 (18%)31 (25%)25 (28%)
      NYHA class
       I-II231 (41%)156 (45%)50 (41%)25 (28%)0.020
       III-IV327 (59%)192 (55%)72 (59%)63 (72%)
       Previous stroke/TIA103 (19%)62 (18%)23 (19%)18 (21%)0.86
       Peripheral vascular disease100 (18%)56 (16%)24 (20%)20 (23%)0.28
       Atrial fibrillation147 (26%)76 (22%)42 (34%)29 (33%)0.007
       Chronic obstructive pulmonary disease101 (18%)63 (18%)17 (14%)21 (24%)0.19
       Concomitant mitral/aortic regurgitation ≥grade 2148 (26%)64 (18%)45 (37%)39 (44%)<0.001
       Permanent pacemaker83 (15%)37 (11%)23 (19%)23 (26%)<0.001
      Medication
       Beta-blocker326 (58%)207 (60%)72 (59%)47 (53%)0.58
       ACE-I / ARB II290 (52%)178 (51%)61 (50%)51 (58%)0.46
       Calcium antagonist136 (24%)81 (23%)41 (34%)14 (16%)0.010
       Diuretics295 (53%)159 (46%)75 (62%)61 (69%)<0.001
       MR antagonist57 (10%)27 (8%)14 (12%)16 (18%)0.014
       Statins349 (63%)222 (64%)79 (65%)48 (55%)0.24
       Antiplatelet325 (58%)204 (58%)71 (58%)50 (57%)0.97
       Anticoagulation211 (38%)111 (32%)51 (43%)49 (56%)<0.001
      Data are presented as mean ± SD, median [25-75% interquartile range] and n (%).
      ACE-I = angiotensin-converting enzyme; ARB II = angiotensin-II receptor blocker; CABG = coronary artery bypass grafting; CAD = coronary artery disease; CKD-EPI = Chronic Kidney Disease Epidemiology Collaboration; eGFR = estimated glomerular filtration rate; MR = mineralocorticoid receptor; NYHA = New York Heart Association; PCI = percutaneous coronary intervention; TIA = transient ischemic attack.
      *p<0.05 vs group ‘Left Ventricular Ejection Fraction ≥50%’ with Bonferroni's post-hoc analysis.
      p<0.05 vs group ‘Left Ventricular Ejection Fraction 40-49%’ with Bonferroni's post-hoc analysis.
      Baseline (pre-TAVI) echocardiographic data are presented in Table 2. LV volumes and LV mass index were larger in patients with reduced LVEF than those with midrange and preserved LVEF before TAVI. In contrast, AV peak and mean gradient and stroke volume index were lower in patients with reduced baseline LVEF. AVAi was comparable between patients with reduced, midrange, and preserved baseline LVEF.
      Table 2Baseline (pre-TAVI) echocardiographic data of the overall population and according to baseline left ventricular ejection fraction
      VariableOverall population (n=560)Left ventricular ejection fraction ≥50% (n=350)Left ventricular ejection fraction 40-49% (n=122)Left ventricular ejection fraction <40% (n=88)p-Value
      LVEF (%)51 ± 1158 ± 545 ± 3*33 ± 6*,<0.001
      AV peak gradient (mmHg)66 ± 2570 ± 2563 ± 26*55 ± 25*,<0.001
      AV mean gradient (mmHg)42 ± 1745 ± 1641 ± 1835 ± 15*,<0.001
      AVA (cm2)0.80 ± 0.280.82 ± 0.280.78 ± 0.270.75 ± 0.300.13
      AVAi (cm2/m2)0.43 ± 0.150.44 ± 0.150.42 ± 0.150.41 ± 0.160.19
      LVEDVi (ml/m2)44 [36-54]40 [34-48]47 [36-54]*60 [50-74]*,<0.001
      LVESVi (ml/m2)20 [15-29]17 [14-20]25 [20-30]*41 [33-50]*,<0.001
      SVi (ml/m2)39 ± 1241 ± 1237 ± 12*32 ± 10*,<0.001
      LV mass index (g/m2)119 ± 32112 ± 27126 ± 36*138 ± 34*,<0.001
      LVEDD (mm)47.7 ± 7.445.7 ± 6.549.0 ± 7.2*53.9 ± 7.1*,<0.001
      IVST (mm)13.1 ± 1.813.2 ± 1.713.2 ± 2.112.5 ± 1.7*,0.004
      PWT (mm)12.2 ± 2.112.3 ± 2.112.5 ± 2.111.9 ± 2.00.12
      RWT0.52 ± 0.130.54 ± 0.130.51 ± 0.120.44 ± 0.10*,<0.001
      Data are presented as mean ± SD, median [25-75% interquartile range] and n (%).
      AV = aortic valve; AVA = aortic valve area; AVAi = indexed aortic valve area; IVST = intraventricular septum thickness; LV = left ventricular; LVEDVi = left ventricular end-diastolic volume index; LVEDD = left ventricular end-diastolic diameter; LVEF = left ventricular ejection fraction; LVESVi = left ventricular end-systolic volume index; PWT = posterior wall thickness; RWT = relative wall thickness; SVi = stroke volume index.
      *p<0.05 vs group ‘Left Ventricular Ejection Fraction ≥50%’ with Bonferroni's post-hoc analysis.
      p<0.05 vs group ‘Left Ventricular Ejection Fraction 40-49%’ with Bonferroni's post-hoc analysis.
      All patients underwent TAVI using the transfemoral approach. The majority of patients received balloon-expandable valves: Edwards SAPIEN 3,341 (61%), SAPIEN XT 46 (8%), SAPIEN 36 (6%), and SAPIEN Ultra 3 (0.5%). Self-expandable valves were used in 133 patients (24%). Prothesis size ranged from 23 to 31 mm, with 26 mm being most frequent in 221 patients (40%).
      LVEF improved significantly during follow-up (from 51 ± 11% to 54 ± 10% at 6 months and to 55 ±10% at 12 months, p <0.001). The changes in LVEF according to baseline LVEF are displayed in Figure 3. The largest increase in LVEF after TAVI was noted in patients with reduced baseline LVEF versus those with midrange LVEF (from 33 ± 6% to 42 ± 10% at 6 months and to 43 ± 10% at 12 months, p <0.001; and from 45 ± 3% to 51 ± 8% at 6 months and to 52 ± 8% at 12 months, p <0.001, respectively), and a modest improvement in LVEF was noted in patients with preserved baseline LVEF (from 58 ± 5% to 58 ± 7% at 6 months and to 59 ± 7% at 12 months, p = 0.012; p for interaction <0.001). LV volumes decreased significantly after TAVI. The largest decrease in LV end-diastolic volume index was noted in patients with reduced LVEF compared with patients with preserved baseline LVEF (from 60 [50 to 74] ml/m2 to 51 [43 to 70] ml/m2 at 6 months and to 55 [38 to 67] ml/m2 at 12 months, p <0.001; and from 40 [34 to 48] ml/m2 to 39 [32 to 47] ml/m2 at 6 months and to 38 [30 to 45] ml/m2 at 12 months, p <0.001, respectively), whereas LV end-diastolic volume index was not significantly decreased among patients with midrange baseline LVEF (from 47 [36 to 54] ml/m2 to 44 [38 to 55] ml/m2 at 6 months and to 43 [34 to 50] ml/m2 at 12 months, p = 0.055; p for interaction = 0.001). Similarly, patients with decreased LVEF had the largest reduction in LV end-systolic volume index after TAVI compared with those with midrange LVEF and preserved LVEF (reduced LVEF: from 41 [33 to 50] ml/m2 to 32 [23 to 41] ml/m2 at 6 months and to 30 [21 to 41] ml/m2 at 12 months, p <0.001; midrange LVEF: from 25 [20 to 30] ml/m2 to 22 [17 to 27] ml at 6 months and to 20 [16 to 25] ml/m2 at 12 months, p <0.001; and preserved LVEF: from 17 [14 to 20] ml/m2 to 16 [13 to 20] ml/m2 at 6 months and to 15 [11 to 19] ml/m2 at 12 months, p< 0.001; p for interaction <0.001). LV mass index regressed significantly after TAVI (from 119 ± 32 g/m2 to 105 ± 26 g/m2 at 6 months and to 99 ± 26 g/m2 at 12 months, p <0.001) and was comparable between the varying groups of baseline LVEF over time (p for interaction = 0.48). Prosthetic AV mean gradient was similar during follow-up (from 9 ± 4 mm Hg immediately after TAVI to 10 ± 5 mm Hg at 6 months and to 10 ± 5 mm Hg at 12 months) without significant changes between groups over time (p for interaction = 0.48). Additional analysis was performed to correct for confounders of the change in LVEF after TAVI and showed similar results (Supplementary Table 1). The absolute change in LVEF and LV volumes and mass at 6- and 12-month follow-up are shown in Supplementary Table 2.
      Figure 3
      Figure 3Evolution of LVEF after transcatheter aortic valve implantation. Changes in LVEF of patients with preserved baseline LVEF ≥50% (green line), midrange LVEF 40% to 49% (blue line), and patients with reduced LVEF <40% (red line) from baseline to 6 months and 12 months follow-up after transcatheter aortic valve implantation. *Shows p-value for interaction between the varying groups of baseline LVEF over time. Error bars indicate 95% confidence intervals.
      An improvement in LVEF ≥5% at follow-up was noted in 233 patients (42%) and was most frequently observed among patients with reduced LVEF (67%), followed by patients with midrange LVEF (58%) and those with preserved baseline LVEF (29%, p <0.001). Similarly, ≥10% LVEF improvement was observed in 121 patients (22%) and most common in patients with reduced baseline LVEF (48% vs 32% vs 11%, respectively, p <0.001). A scatterplot of LVEF at baseline versus follow-up according to ≥5% LVEF improvement is displayed in Figure 4.
      Figure 4
      Figure 4Scatterplot of LVEF before transcatheter aortic valve implantation and at follow-up. Blue dots represent patients with ≥5% LVEF improvement; red dots represent patients with <5% LVEF improvement.
      Patients with ≥5% LVEF improvement at follow-up had less hypertension than those with <5% LVEF improvement (68% vs 77%, p = 0.021) and less coronary artery disease (55% vs 68%, p = 0.001), less myocardial infarction (15% vs 24%, p = 0.007), less previous percutaneous coronary interventions (25% vs 35%, p = 0.016), and less permanent pacemaker implantation (25% vs 35%, p = 0.021). In contrast, atrial fibrillation (32% vs 22%, p = 0.012) and concomitant moderate or severe mitral or aortic regurgitation (31% vs 23%, p = 0.026) were more frequent in patients with ≥5% LVEF improvement. Similar results were noted in the comparison of patients with ≥10% LVEF improvement. Additionally, the baseline clinical and echocardiographic characteristics of patients with LVEF <50% at baseline and follow-up versus patients with preserved LVEF at baseline and follow-up among patients with <5% LVEF improvement are summarized in Supplementary Table 3.
      The baseline clinical and echocardiographic variables associated without ≥5% LVEF improvement are displayed in Table 3. Baseline LVEF <50% was independently associated with ≥5% LVEF improvement at follow-up (OR for lack of ≥5% LVEF improvement 0.22 [95% CI 0.15 to 0.35], p <0.001), whereas coronary artery disease (OR 1.80 [95% CI 1.06 to 3.06], p = 0.031), myocardial infarction (OR 2.07 [95% CI 1.19 to 3.61], p = 0.010), and need for permanent pacemaker (OR 1.93 [95% CI 1.25 to 3.00], p = 0.003) were independently associated with lack of ≥5% LVEF improvement after TAVI.
      Table 3Uni- and multivariable logistic regression of clinical and echocardiographic parameters associated without ≥5% LVEF improvement after transcatheter aortic valve implantation
      UnivariableMultivariable
      VariableOR95% CIp-ValueOR95% CIp-Value
      Age0.9950.971-1.0190.66
      Male sex1.2720.908-1.7820.16
      Body mass index1.0210.983-1.0600.28
      Logistic EuroSCORE0.9830.966-1.0000.0560.9890.967-1.0110.33
      eGFR<60ml/min1.2100.864-1.6960.27
      Hypertension1.5551.068-2.2650.0211.2810.825-1.9900.27
      Hypercholesterolemia1.1980.850-1.6890.30
      Diabetes mellitus0.9700.668-1.4070.87
      CAD1.7761.254-2.5150.0011.7961.055-3.0570.031
      Previous myocardial infarction1.8331.176-2.8580.0072.0721.189-3.6110.010
      PCI1.5781.087-2.2910.0160.9760.571-1.6700.93
      CABG1.3010.858-1.9730.22
      Previous stroke/TIA1.0120.655-1.5640.96
      Peripheral vascular disease0.8040.520-1.2420.33
      Atrial fibrillation0.6180.423-0.9020.0130.7610.486-1.1900.23
      Chronic obstructive pulmonary disease0.8270.536-1.2760.39
      Concomitant mitral/aortic regurgitation ≥grade 20.9380.550-1.6010.82
      Baseline LVEF<50%0.2570.179-0.368<0.0010.2240.145-0.346<0.001
      Paravalvular leakage ≥moderate (grade 2)1.4430.637-3.2720.38
      Permanent pacemaker1.5481.066-2.2490.0221.9311.245-2.9950.003
      CABG = coronary artery bypass grafting; CAD = coronary artery disease; CKD-EPI = Chronic Kidney Disease Epidemiology Collaboration; eGFR = estimated glomerular filtration rate; LVEF = left ventricular ejection fraction; PCI = percutaneous coronary intervention; TIA = transient ischemic attack.
      During a median follow-up of 3.8 (interquartile range 2.6 to 5.2) years, 176 patients died (31%). Kaplan-Meier analysis demonstrated similar outcomes for patients with versus without ≥5% LVEF improvement after TAVI (log-rank chi-square: 0.19, p = 0.89; Figure 5). Moreover, long-term survival was comparable for patients with and without ≥5% LVEF improvement after TAVI among patients with preserved baseline LVEF (log-rank chi-square: 0.002, p = 0.97), baseline LVEF <50% (n = 210; log-rank chi-square: 0.27, p = 0.60), and among patients with reduced baseline LVEF (log-rank chi-square: 0.18, p = 0.68; Figure 5). Additionally, baseline LVEF (as a continuous variable, HR 0.995 [95% CI 0.980 to 1.009], p = 0.47), a 1% improvement in LVEF after TAVI (HR 0.996 [95% CI 0.979 to 1.013], p = 0.64), ≥5% LVEF improvement (HR 0.927 [95% CI 0.670 to 1.283], p = 0.65), and ≥10% LVEF improvement (HR 1.129 [95% CI 0.776 to 1.643], p = 0.53) were not associated with all-cause mortality after TAVI in multivariable Cox regression analysis.
      Figure 5
      Figure 5Kaplan-Meier curves demonstrating the event-free survival for all-cause mortality according to ≥5% improvement in LVEF of the overall population (A) and among patients with baseline preserved LVEF (LVEF>50%, B), LVEF <50% (C), and reduced LVEF (LVEF<40%, D).

      Discussion

      In patients with severe AS, LVEF improved significantly at 1-year follow-up after TAVI. Patients with reduced baseline LVEF showed the greatest improvement in LVEF. Additionally, coronary artery disease, myocardial infarction, and need for a permanent pacemaker were independently associated with lack of LVEF improvement after TAVI. However, improvement in LVEF at 1-year follow-up was not associated with long-term outcomes.
      LV systolic dysfunction is common among patients with severe AS; this may be secondary to severe AS or coexistent cardiomyopathy. In severe AS, the LV myocardium may remodel and develop LV hypertrophy, as a consequence of the chronic LV pressure overload associated with severe AS, to normalize wall stress and maintain cardiac output.
      • Otto CM
      • Prendergast B.
      Aortic-valve stenosis–from patients at risk to severe valve obstruction.
      ,
      • Dweck MR
      • Boon NA
      • Newby DE.
      Calcific aortic stenosis: a disease of the valve and the myocardium.
      However, with AS progression, this compensation mechanism may fail and subsequently lead to heart failure and mortality.
      • Bing R
      • Cavalcante JL
      • Everett RJ
      • Clavel MA
      • Newby DE
      • Dweck MR.
      Imaging and impact of myocardial fibrosis in aortic stenosis.
      ,
      • Hein S
      • Arnon E
      • Kostin S
      • Schönburg M
      • Elsässer A
      • Polyakova V
      • Bauer EP
      • Klövekorn WP
      • Schaper J.
      Progression from compensated hypertrophy to failure in the pressure-overloaded human heart: structural deterioration and compensatory mechanisms.
      Aortic valve replacement results in immediate relief of LV afterload and is associated with LV reverse remodeling and improvement in LV systolic function.
      • Takagi H
      • Ando T
      • Umemoto T
      ALICE (All-Literature Investigation of Cardiovascular Evidence) Group. A meta-analysis of effects of transcatheter versus surgical aortic valve replacement on left ventricular ejection fraction and mass.
      ,
      • Pai RG
      • Kapoor N
      • Bansal RC
      • Varadarajan P.
      Malignant natural history of asymptomatic severe aortic stenosis: benefit of aortic valve replacement.
      The present study evaluated the development of LVEF after TAVI among patients with varying baseline LVEF. The greatest improvement in LVEF at 1-year follow-up was noted in patients with reduced LVEF (<40%), despite a higher prevalence of ischemic heart disease, which potentially could limit LV reverse remodeling. Patients with reduced LV function may have the greatest potential for LV recovery after TAVI, as confirmed by the present results.
      Ewe et al
      • Ewe SH
      • Ajmone Marsan N
      • Pepi M
      • Delgado V
      • Tamborini G
      • Muratori M
      • Ng AC
      • van der Kley F
      • de Weger A
      • Schalij MJ
      • Fusari M
      • Biglioli P
      • Bax JJ
      Impact of left ventricular systolic function on clinical and echocardiographic outcomes following transcatheter aortic valve implantation for severe aortic stenosis.
      evaluated the LV systolic function of 147 patients with severe AS who underwent TAVI with preserved baseline LVEF and impaired LVEF (<50%). In line with our findings, patients with impaired LVEF showed significant improvement in LVEF at follow-up. However, LVEF was comparable in patients with preserved baseline LVEF at follow-up, whereas in the present study, including more patients and longer echocardiographic follow-up, a modest but significant improvement in LVEF was noted in patients with preserved baseline LVEF at 1-year after TAVI. Similarly, a study including 505 patients with severe AS who underwent TAVI demonstrated that patients with severe LV dysfunction (<35%) had the greatest improvement in LVEF at 6-month follow-up compared with those with moderate LV dysfunction (35% to 50%).
      • Elhmidi Y
      • Bleiziffer S
      • Deutsch MA
      • Krane M
      • Mazzitelli D
      • Lange R
      • Piazza N.
      Transcatheter aortic valve implantation in patients with LV dysfunction: impact on mortality and predictors of LV function recovery.
      Moreover, a meta-analysis including 26 articles reported significant improvement in LVEF among patients with severe AS and low baseline LVEF (<50%) at 30 days, 6 months, and at 1 year after TAVI.
      • Sannino A
      • Gargiulo G
      • Schiattarella GG
      • Brevetti L
      • Perrino C
      • Stabile E
      • Losi MA
      • Toscano E
      • Giugliano G
      • Scudiero F
      • Chiacchio E
      • Trimarco B
      • Esposito G.
      Increased mortality after transcatheter aortic valve implantation (TAVI) in patients with severe aortic stenosis and low ejection fraction: a meta-analysis of 6898 patients.
      Next, the variables related to lack of LVEF improvement were evaluated. Permanent pacemaker implantation, more specifically right ventricular pacing, is known to affect LV function and LV recovery after TAVI.
      • Ngo A
      • Hassager C
      • Thyregod HGH
      • Søndergaard L
      • Olsen PS
      • Steinbrüchel D
      • Hansen PB
      • Kjærgaard J
      • Winther-Jensen M
      • Ihlemann N.
      Differences in left ventricular remodelling in patients with aortic stenosis treated with transcatheter aortic valve replacement with corevalve prostheses compared to surgery with porcine or bovine biological prostheses.
      ,
      • Urena M
      • Webb JG
      • Tamburino C
      • Muñoz-García AJ
      • Cheema A
      • Dager AE
      • Serra V
      • Amat-Santos IJ
      • Barbanti M
      • Immè S
      • Briales JH
      • Benitez LM
      • Al Lawati H
      • Cucalon AM
      • García Del Blanco B
      • López J
      • Dumont E
      • Delarochellière R
      • Ribeiro HB
      • Nombela-Franco L
      • Philippon F
      • Rodés-Cabau J
      Permanent pacemaker implantation after transcatheter aortic valve implantation: impact on late clinical outcomes and left ventricular function.
      The present analysis showed that the majority of patients with a permanent pacemaker did not improve in LVEF at follow-up. Additionally, coronary artery disease and myocardial infarction were also associated with lack of LVEF improvement, whereas baseline LVEF <50% was linked with LVEF improvement that is similar to previous studies.
      • Elhmidi Y
      • Bleiziffer S
      • Deutsch MA
      • Krane M
      • Mazzitelli D
      • Lange R
      • Piazza N.
      Transcatheter aortic valve implantation in patients with LV dysfunction: impact on mortality and predictors of LV function recovery.
      ,
      • Dauerman HL
      • Reardon MJ
      • Popma JJ
      • Little SH
      • Cavalcante JL
      • Adams DH
      • Kleiman NS
      • Oh JK.
      Early recovery of left ventricular systolic function after CoreValve transcatheter aortic valve replacement.
      LV systolic function yields important prognostic information in patients with severe AS who underwent surgical aortic valve replacement.
      • Dahl JS
      • Eleid MF
      • Michelena HI
      • Scott CG
      • Suri RM
      • Schaff HV
      • Pellikka PA.
      Effect of left ventricular ejection fraction on postoperative outcome in patients with severe aortic stenosis undergoing aortic valve replacement.
      Similarly, it has been shown that baseline LVEF is an independent predictor of outcomes after TAVI.
      • Eleid MF
      • Goel K
      • Murad MH
      • Erwin PJ
      • Suri RM
      • Greason KL
      • Nishimura RA
      • Rihal CS
      • Holmes Jr, DR
      Meta-analysis of the prognostic impact of stroke volume, gradient, and ejection fraction after transcatheter aortic valve implantation.
      • Furer A
      • Chen S
      • Redfors B
      • Elmariah S
      • Pibarot P
      • Herrmann HC
      • Hahn RT
      • Kodali S
      • Thourani VH
      • Douglas PS
      • Alu MC
      • Fearon WF
      • Passeri J
      • Malaisrie SC
      • Crowley A
      • McAndrew T
      • Genereux P
      • Ben-Yehuda O
      • Leon MB
      • Burkhoff D.
      Effect of baseline left ventricular ejection fraction on 2-year outcomes after transcatheter aortic valve replacement: analysis of the PARTNER 2 trials.
      • Sannino A
      • Gargiulo G
      • Schiattarella GG
      • Brevetti L
      • Perrino C
      • Stabile E
      • Losi MA
      • Toscano E
      • Giugliano G
      • Scudiero F
      • Chiacchio E
      • Trimarco B
      • Esposito G.
      Increased mortality after transcatheter aortic valve implantation (TAVI) in patients with severe aortic stenosis and low ejection fraction: a meta-analysis of 6898 patients.
      However, data on LVEF improvement versus long-term outcomes after TAVI are scarce. In a cohort of patients with severe AS and reduced LVEF (<45%) who underwent TAVI, Angelillis et al
      • Angelillis M
      • Giannini C
      • De Carlo M
      • Adamo M
      • Nardi M
      • Colombo A
      • Chieffo A
      • Bedogni F
      • Brambilla N
      • Tamburino C
      • Barbanti M
      • Bruschi G
      • Colombo P
      • Poli A
      • Martina P
      • Violini R
      • Presbitero P
      • Petronio AS.
      Prognostic significance of change in the left ventricular ejection fraction after transcatheter aortic valve implantation in patients with severe aortic stenosis and left ventricular dysfunction.
      reported that a ≥10% increase in LVEF at 1-month follow-up was associated with improved outcomes, although patients with previous coronary revascularization were excluded from the analysis. Similarly, Dauerman et al
      • Dauerman HL
      • Reardon MJ
      • Popma JJ
      • Little SH
      • Cavalcante JL
      • Adams DH
      • Kleiman NS
      • Oh JK.
      Early recovery of left ventricular systolic function after CoreValve transcatheter aortic valve replacement.
      evaluated early LV recovery after TAVI in patients with severe AS and reduced LVEF (<40%) with high operative risk. Patients with a ≥10% increase in LVEF at 1-month follow-up had fewer adverse events, although not statistically different possibly because of small patient numbers. In the present study, which includes more patients, an improvement of ≥5% in LVEF at 6- or 12-month follow-up after TAVI was not associated with long-term outcomes, even in the patients with reduced baseline LVEF.
      Several limitations should be acknowledged. First, this is a single-center retrospective analysis, with inherent limitations related to the study design. Second, patients without echocardiographic follow-up have been excluded from the analysis, which may have caused selection bias. However, the baseline clinical characteristics of this population versus the study population are comparable (Supplementary Table 4). Third, the group of patients with reduced LVEF was limited. Finally, the present study used LVEF as a marker of LV systolic function, where LV strain may be a more sensitive marker to assess LV dysfunction.
      In conclusion, LVEF improved significantly in patients with severe AS at 1-year follow-up after TAVI. Patients with reduced baseline LVEF revealed the greatest improvement in LVEF. Coronary artery disease, myocardial infarction, and the need for a permanent pacemaker were independently associated with lack of LVEF improvement. However, LVEF improvement at 12-month follow-up was not associated with long-term outcomes.

      Disclosures

      The Department of Cardiology of Leiden University Medical Center in Leiden, The Netherlands has received unrestricted research grants from Abbot Vascular, Bayer, Bioventrix, GE Healthcare, Ionis, Medtronic, Biotronik, Boston Scientific, and Edwards Lifesciences. Dr. Butcher reports a relation with European Society of Cardiology that includes funding grants. Juhani Knuuti reports a relation with AstraZeneca and GE Healthcare that includes consulting or advisory fees and a relation with GE Healthcare, Bayer, Lundbeck, Boehringer-Ingelheim, Pfizer, and Merck that includes: speaking and lecture fees. Dr. Pibarot reports a relation with Edwards Lifesciences Corp that includes funding grants and a relation with Edwards Lifesciences and Medtronic that includes: echocardiography core laboratory research contracts. Dr. Marsan reports a relation with Abbott Vascular and GE Healthcare that includes speaking and lecture fees. Dr. Delgado reports a relation with Abbott Vascular, Edwards Lifesciences, GE Healthcare, Merck Sharp & Dohme, Novartis, and Medtronic that includes speaking and lecture fees. Dr. Bax reports a relation with Abbott Vascular that includes speaking and lecture fees. The remaining authors have no conflicts of interest to declare.

      Appendix. Supplementary materials

      References

        • Otto CM
        • Prendergast B.
        Aortic-valve stenosis–from patients at risk to severe valve obstruction.
        N Engl J Med. 2014; 371: 744-756
        • Grossman W
        • Jones D
        • McLaurin LP.
        Wall stress and patterns of hypertrophy in the human left ventricle.
        J Clin Invest. 1975; 56: 56-64
        • Baron SJ
        • Arnold SV
        • Herrmann HC
        • Holmes DR
        • Jr Szeto WY
        • Allen KB
        • Chhatriwalla AK
        • Vemulapali S
        • O'Brien S
        • Dai D
        • Cohen DJ
        Impact of ejection fraction and aortic valve gradient on outcomes of transcatheter aortic valve replacement.
        J Am Coll Cardiol. 2016; 67: 2349-2358
        • Elmariah S
        • Palacios IF
        • McAndrew T
        • Hueter I
        • Inglessis I
        • Baker JN
        • Kodali S
        • Leon MB
        • Svensson L
        • Pibarot P
        • Douglas PS
        • Fearon WF
        • Kirtane AJ
        • Maniar HS
        • Passeri JJ
        PARTNER Investigators. Outcomes of transcatheter and surgical aortic valve replacement in high-risk patients with aortic stenosis and left ventricular dysfunction: results from the Placement of Aortic transcatheter Valves (PARTNER) trial (cohort A).
        Circ Cardiovasc Interv. 2013; 6: 604-614
        • Passeri JJ
        • Elmariah S
        • Xu K
        • Inglessis I
        • Baker JN
        • Alu M
        • Kodali S
        • Leon MB
        • Svensson LG
        • Pibarot P
        • Fearon WF
        • Kirtane AJ
        • Vlahakes GJ
        • Palacios IF
        • Douglas PS
        • Investigators PARTNER
        Transcatheter aortic valve replacement and standard therapy in inoperable patients with aortic stenosis and low EF.
        Heart. 2015; 101: 463-471
        • Dahl JS
        • Eleid MF
        • Michelena HI
        • Scott CG
        • Suri RM
        • Schaff HV
        • Pellikka PA.
        Effect of left ventricular ejection fraction on postoperative outcome in patients with severe aortic stenosis undergoing aortic valve replacement.
        Circ Cardiovasc Imaging. 2015; 8e002917
        • Halkos ME
        • Chen EP
        • Sarin EL
        • Kilgo P
        • Thourani VH
        • Lattouf OM
        • Vega JD
        • Morris CD
        • Vassiliades T
        • Cooper WA
        • Guyton RA
        • Puskas JD.
        Aortic valve replacement for aortic stenosis in patients with left ventricular dysfunction.
        Ann Thorac Surg. 2009; 88: 746-751
        • Siontis GCM
        • Overtchouk P
        • Cahill TJ
        • Modine T
        • Prendergast B
        • Praz F
        • Pilgrim T
        • Petrinic T
        • Nikolakopoulou A
        • Salanti G
        • Søndergaard L
        • Verma S
        • Jüni P
        • Windecker S.
        Transcatheter aortic valve implantation vs. surgical aortic valve replacement for treatment of symptomatic severe aortic stenosis: an updated meta-analysis.
        Eur Heart J. 2019; 40: 3143-3153
        • Eleid MF
        • Goel K
        • Murad MH
        • Erwin PJ
        • Suri RM
        • Greason KL
        • Nishimura RA
        • Rihal CS
        • Holmes Jr, DR
        Meta-analysis of the prognostic impact of stroke volume, gradient, and ejection fraction after transcatheter aortic valve implantation.
        Am J Cardiol. 2015; 116: 989-994
        • Furer A
        • Chen S
        • Redfors B
        • Elmariah S
        • Pibarot P
        • Herrmann HC
        • Hahn RT
        • Kodali S
        • Thourani VH
        • Douglas PS
        • Alu MC
        • Fearon WF
        • Passeri J
        • Malaisrie SC
        • Crowley A
        • McAndrew T
        • Genereux P
        • Ben-Yehuda O
        • Leon MB
        • Burkhoff D.
        Effect of baseline left ventricular ejection fraction on 2-year outcomes after transcatheter aortic valve replacement: analysis of the PARTNER 2 trials.
        Circ Heart Fail. 2019; 12e005809
        • Sannino A
        • Gargiulo G
        • Schiattarella GG
        • Brevetti L
        • Perrino C
        • Stabile E
        • Losi MA
        • Toscano E
        • Giugliano G
        • Scudiero F
        • Chiacchio E
        • Trimarco B
        • Esposito G.
        Increased mortality after transcatheter aortic valve implantation (TAVI) in patients with severe aortic stenosis and low ejection fraction: a meta-analysis of 6898 patients.
        Int J Cardiol. 2014; 176: 32-39
        • Vahanian A
        • Beyersdorf F
        • Praz F
        • Milojevic M
        • Baldus S
        • Bauersachs J
        • Capodanno D
        • Conradi L
        • De Bonis M
        • De Paulis R
        • Delgado V
        • Freemantle N
        • Gilard M
        • Haugaa KH
        • Jeppsson A
        • Jüni P
        • Pierard L
        • Prendergast BD
        • Sádaba JR
        • Tribouilloy C
        • Wojakowski W
        ESC/EACTS Scientific Document Group. 2021 ESC/EACTS Guidelines for the management of valvular heart disease.
        Eur J Cardiothorac Surg. 2021; 60: 727-800
        • Otto CM
        • Nishimura RA
        • Bonow RO
        • Carabello BA
        • Erwin 3rd, JP
        • Gentile F
        • Jneid H
        • Krieger EV
        • Mack M
        • McLeod C
        • O'Gara PT
        • Rigolin VH
        • Sundt 3rd, TM
        • Thompson A
        • Toly C
        2020 ACC/AHA guideline for the management of patients With valvular heart disease: A report of the American College of Cardiology/American Heart Association joint committee on clinical practice guidelines.
        Circulation. 2021; 143: e72-e227
        • Takagi H
        • Ando T
        • Umemoto T
        ALICE (All-Literature Investigation of Cardiovascular Evidence) Group. A meta-analysis of effects of transcatheter versus surgical aortic valve replacement on left ventricular ejection fraction and mass.
        Int J Cardiol. 2017; 238: 31-36
        • Ewe SH
        • Ajmone Marsan N
        • Pepi M
        • Delgado V
        • Tamborini G
        • Muratori M
        • Ng AC
        • van der Kley F
        • de Weger A
        • Schalij MJ
        • Fusari M
        • Biglioli P
        • Bax JJ
        Impact of left ventricular systolic function on clinical and echocardiographic outcomes following transcatheter aortic valve implantation for severe aortic stenosis.
        Am Heart J. 2010; 160: 1113-1120
        • Ribeiro HB
        • Lerakis S
        • Gilard M
        • Cavalcante JL
        • Makkar R
        • Herrmann HC
        • Windecker S
        • Enriquez-Sarano M
        • Cheema AN
        • Nombela-Franco L
        • Amat-Santos I
        • Muñoz-García AJ
        • Garcia Del Blanco B
        • Zajarias A
        • Lisko JC
        • Hayek S
        • Babaliaros V
        • Le Ven F
        • Gleason TG
        • Chakravarty T
        • Szeto WY
        • Clavel MA
        • de Agustin A
        • Serra V
        • Schindler JT
        • Dahou A
        • Puri R
        • Pelletier-Beaumont E
        • Côté M
        • Pibarot P
        • Rodés-Cabau J
        Transcatheter aortic valve replacement in patients With low-flow, low-gradient aortic stenosis: the TOPAS-TAVI registry.
        J Am Coll Cardiol. 2018; 71: 1297-1308
        • Kamperidis V
        • Joyce E
        • Debonnaire P
        • Katsanos S
        • van Rosendael PJ
        • van der Kley F
        • Sianos G
        • Bax JJ
        • Ajmone Marsan N
        • Delgado V
        Left ventricular functional recovery and remodeling in low-flow low-gradient severe aortic stenosis after transcatheter aortic valve implantation.
        J Am Soc Echocardiogr. 2014; 27: 817-825
        • Ponikowski P
        • Voors AA
        • Anker SD
        • Bueno H
        • Cleland JGF
        • Coats AJS
        • Falk V
        • González-Juanatey JR
        • Harjola VP
        • Jankowska EA
        • Jessup M
        • Linde C
        • Nihoyannopoulos P
        • Parissis JT
        • Pieske B
        • Riley JP
        • Rosano GMC
        • Ruilope LM
        • Ruschitzka F
        • Rutten FH
        • van der Meer P.
        2016 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure.
        Rev Esp Cardiol (Engl Ed). 2016; 69: 1167
        • Delgado V
        • Ng AC
        • van de Veire NR
        • van der Kley F
        • Schuijf JD
        • Tops LF
        • de Weger A
        • Tavilla G
        • de Roos A
        • Kroft LJ
        • Schalij MJ
        • Bax JJ.
        Transcatheter aortic valve implantation: role of multi-detector row computed tomography to evaluate prosthesis positioning and deployment in relation to valve function.
        Eur Heart J. 2010; 31: 1114-1123
        • Otto CM
        • Kumbhani DJ
        • Alexander KP
        • Calhoon JH
        • Desai MY
        • Kaul S
        • Lee JC
        • Ruiz CE
        • Vassileva CM.
        2017 ACC Expert Consensus decision pathway for transcatheter aortic valve replacement in the management of adults With aortic stenosis: A report of the American College of Cardiology task force on clinical expert consensus documents.
        J Am Coll Cardiol. 2017; 69: 1313-1346
        • Lancellotti P
        • Pibarot P
        • Chambers J
        • Edvardsen T
        • Delgado V
        • Dulgheru R
        • Pepi M
        • Cosyns B
        • Dweck MR
        • Garbi M
        • Magne J
        • Nieman K
        • Rosenhek R
        • Bernard A
        • Lowenstein J
        • Vieira ML
        • Rabischoffsky A
        • Vyhmeister RH
        • Zhou X
        • Zhang Y
        • Zamorano JL
        • Habib G.
        Recommendations for the imaging assessment of prosthetic heart valves: a report from the European Association of Cardiovascular Imaging endorsed by the Chinese Society of Echocardiography, the Inter-American Society of Echocardiography, and the Brazilian Department of Cardiovascular Imaging.
        Eur Heart J Cardiovasc Imaging. 2016; 17: 589-590
        • Lang RM
        • Badano LP
        • Mor-Avi V
        • Afilalo J
        • Armstrong A
        • Ernande L
        • Flachskampf FA
        • Foster E
        • Goldstein SA
        • Kuznetsova T
        • Lancellotti P
        • Muraru D
        • Picard MH
        • Rietzschel ER
        • Rudski L
        • Spencer KT
        • Tsang W
        • Voigt JU.
        Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging.
        J Am Soc Echocardiogr. 2015; 28 (e14): 1-39
        • Zoghbi WA
        • Asch FM
        • Bruce C
        • Gillam LD
        • Grayburn PA
        • Hahn RT
        • Inglessis I
        • Islam AM
        • Lerakis S
        • Little SH
        • Siegel RJ
        • Skubas N
        • Slesnick TC
        • Stewart WJ
        • Thavendiranathan P
        • Weissman NJ
        • Yasukochi S
        • Zimmerman KG.
        Guidelines for the evaluation of valvular regurgitation after percutaneous valve repair or replacement: A report from the American Society of Echocardiography developed in collaboration with the Society for Cardiovascular Angiography and Interventions, Japanese Society of Echocardiography, and Society for Cardiovascular Magnetic Resonance.
        J Am Soc Echocardiogr. 2019; 32: 431-475
        • Bax JJ
        • Poldermans D
        • Elhendy A
        • Cornel JH
        • Boersma E
        • Rambaldi R
        • Roelandt JR
        • Fioretti PM.
        Improvement of left ventricular ejection fraction, heart failure symptoms and prognosis after revascularization in patients with chronic coronary artery disease and viable myocardium detected by dobutamine stress echocardiography.
        J Am Coll Cardiol. 1999; 34: 163-169
        • Ngo A
        • Hassager C
        • Thyregod HGH
        • Søndergaard L
        • Olsen PS
        • Steinbrüchel D
        • Hansen PB
        • Kjærgaard J
        • Winther-Jensen M
        • Ihlemann N.
        Differences in left ventricular remodelling in patients with aortic stenosis treated with transcatheter aortic valve replacement with corevalve prostheses compared to surgery with porcine or bovine biological prostheses.
        Eur Heart J Cardiovasc Imaging. 2018; 19: 39-46
        • Dweck MR
        • Boon NA
        • Newby DE.
        Calcific aortic stenosis: a disease of the valve and the myocardium.
        J Am Coll Cardiol. 2012; 60: 1854-1863
        • Bing R
        • Cavalcante JL
        • Everett RJ
        • Clavel MA
        • Newby DE
        • Dweck MR.
        Imaging and impact of myocardial fibrosis in aortic stenosis.
        JACC Cardiovasc Imaging. 2019; 12: 283-296
        • Hein S
        • Arnon E
        • Kostin S
        • Schönburg M
        • Elsässer A
        • Polyakova V
        • Bauer EP
        • Klövekorn WP
        • Schaper J.
        Progression from compensated hypertrophy to failure in the pressure-overloaded human heart: structural deterioration and compensatory mechanisms.
        Circulation. 2003; 107: 984-991
        • Pai RG
        • Kapoor N
        • Bansal RC
        • Varadarajan P.
        Malignant natural history of asymptomatic severe aortic stenosis: benefit of aortic valve replacement.
        Ann Thorac Surg. 2006; 82: 2116-2122
        • Elhmidi Y
        • Bleiziffer S
        • Deutsch MA
        • Krane M
        • Mazzitelli D
        • Lange R
        • Piazza N.
        Transcatheter aortic valve implantation in patients with LV dysfunction: impact on mortality and predictors of LV function recovery.
        J Invasive Cardiol. 2014; 26: 132-138
        • Urena M
        • Webb JG
        • Tamburino C
        • Muñoz-García AJ
        • Cheema A
        • Dager AE
        • Serra V
        • Amat-Santos IJ
        • Barbanti M
        • Immè S
        • Briales JH
        • Benitez LM
        • Al Lawati H
        • Cucalon AM
        • García Del Blanco B
        • López J
        • Dumont E
        • Delarochellière R
        • Ribeiro HB
        • Nombela-Franco L
        • Philippon F
        • Rodés-Cabau J
        Permanent pacemaker implantation after transcatheter aortic valve implantation: impact on late clinical outcomes and left ventricular function.
        Circulation. 2014; 129: 1233-1243
        • Dauerman HL
        • Reardon MJ
        • Popma JJ
        • Little SH
        • Cavalcante JL
        • Adams DH
        • Kleiman NS
        • Oh JK.
        Early recovery of left ventricular systolic function after CoreValve transcatheter aortic valve replacement.
        Circ Cardiovasc Interv. 2016; 9e003425
        • Angelillis M
        • Giannini C
        • De Carlo M
        • Adamo M
        • Nardi M
        • Colombo A
        • Chieffo A
        • Bedogni F
        • Brambilla N
        • Tamburino C
        • Barbanti M
        • Bruschi G
        • Colombo P
        • Poli A
        • Martina P
        • Violini R
        • Presbitero P
        • Petronio AS.
        Prognostic significance of change in the left ventricular ejection fraction after transcatheter aortic valve implantation in patients with severe aortic stenosis and left ventricular dysfunction.
        Am J Cardiol. 2017; 120: 1639-1647