Advertisement

Pledgeted versus nonpledgeted sutures in aortic valve replacement: Insights from a prospective multicenter trial

Open AccessPublished:November 04, 2022DOI:https://doi.org/10.1016/j.xjtc.2022.10.016

      Abstract

      Objective

      The objective of this study was to compare short- and midterm clinical and echocardiographic outcomes according to the use of pledgeted sutures during aortic valve replacement.

      Methods

      Patients with aortic stenosis or regurgitation requiring aortic valve replacement were enrolled in a prospective cohort study to evaluate the safety of a new stented bioprosthesis. Outcomes were analyzed according to the use of pledgets (pledgeted group) or no pledgets (nonpledgeted group). The primary outcome was a composite of thromboembolism, endocarditis, and major paravalvular leak at 5 years of follow-up. Secondary outcomes included multiple clinical endpoints and hemodynamic outcomes. Propensity score matching was performed to adjust for prognostic factors, and subanalyses with small valve sizes (<23 mm) and suturing techniques were performed.

      Results

      The pledgeted group comprised 640 patients (59%), and the nonpledgeted group 442 (41%), with baseline discrepancies in demographic characteristics, comorbidities, and stenosis severity. There were no differences between groups in any outcome. After propensity score matching, the primary outcome occurred in 41 (11.7%) patients in the pledgeted and 36 (9.8%) in the nonpledgeted group (P = .51). The effective orifice area was smaller in the pledgeted group (P = .045), whereas no difference was observed for the mean or peak pressure gradient. Separate subanalyses with small valve sizes and suturing techniques did not show relevant differences.

      Conclusions

      In this large propensity score-matched cohort, comprehensive clinical outcomes were comparable between patients who underwent aortic valve replacement with pledgeted and nonpledgeted sutures up to 5 years of follow-up, but pledgets might lead to a slightly smaller effective orifice area in the long run.

      Graphical abstract

      Key Words

      Abbreviations and Acronyms:

      AVR (aortic valve replacement), BMI (body mass index), BSA (body surface area), EOA (effective orifice area), EOAi (effective orifice area indexed), LVOT (left ventricular outflow tract), PERIGON (PERIcardial SurGical AOrtic Valve ReplacemeNt), PPM (prosthesis–patient mismatch), PVL (paravalvular leak), STS (Society of Thoracic Surgeons)
      Figure thumbnail fx2
      Five-year outcomes according to the use of pledgets in the propensity score-matched cohort.
      Clinical outcomes were comparable for patients who underwent aortic valve replacement (AVR) with and without pledgets.
      Whether to use pledgets for surgical AVR is an ongoing debate among surgeons. In a propensity score-matched analysis, comprehensive clinical outcomes were comparable between patients who underwent AVR with pledgeted and nonpledgeted sutures up to 5 years of follow-up. Nevertheless, pledgets might lead to a slight reduction of the EOA in the long run, but this finding requires external validation.
      Aortic valve replacement (AVR) is the second-most commonly performed type of cardiac surgery, and rates are increasing because of an aging population.
      • D'Agostino R.S.
      • Jacobs J.P.
      • Badhwar V.
      • Fernandez F.G.
      • Paone G.
      • Wormuth D.W.
      • et al.
      The Society of Thoracic Surgeons Adult Cardiac Surgery database: 2019 update on outcomes and quality.
      Although AVR has been performed and improved over several decades, there is still debate among surgeons about the optimal implantation technique. An interesting topic that lacks consensus is whether to use pledgeted sutures to secure the prosthetic valve, because the literature shows conflicting results (Table 1).
      Table 1Overview of previous studies regarding the use of pledgets in aortic valve replacement
      Study characteristicsHemodynamic performanceClinical outcomes
      ReferenceDesignValveNFU length, moMPG, mm HgEOA, cm2PVLOperative mortalityTEIE
      Englberger et al.
      • Englberger L.
      • Schaff H.V.
      • Jamieson W.R.
      • Kennard E.D.
      • Im K.A.
      • Holubkov R.
      • et al.
      Importance of implant technique on risk of major paravalvular leak (PVL) after St. Jude mechanical heart valve replacement: a report from the Artificial Valve Endocarditis Reduction Trial (AVERT).
      RCT

      secondary analysis
      Mechanical (aortic/mitral)807601.7% PS vs 5.8% NPS. HR, 0.3 for PS (P < .01)
      LaPar et al.
      • LaPar D.J.
      • Ailawadi G.
      • Bhamidipati C.M.
      • Singh M.
      • Dare D.
      • Kern J.A.
      • et al.
      Use of a nonpledgeted suture technique is safe and efficient for aortic valve replacement.
      Retrospective

      cohort
      Biological, mechanical, homograft80282PS 1.2% vs NPS 0.5% (P = .38)PS 2.3% vs NPS 1.9% (P = .79)
      Tabata et al.
      • Tabata M.
      • Shibayama K.
      • Watanabe H.
      • Sato Y.
      • Fukui T.
      • Takanashi S.
      Simple interrupted suturing increases valve performance after aortic valve replacement with a small supra-annular bioprosthesis.
      Retrospective cohortBiological (19-21 mm)15212Postimplantation:

      PS 1.30 ± 0.28 vs NPS 1.42 ± 0.32 (P = .03).

      1 y:

      No difference (P = .13)
      No difference

      (P > .99)
      Ugur et al.
      • Ugur M.
      • Byrne J.G.
      • Bavaria J.E.
      • Cheung A.
      • Petracek M.
      • Groh M.A.
      • et al.
      Suture technique does not affect hemodynamic performance of the small supra-annular Trifecta bioprosthesis.
      Prospective cohortBiological (19-21 mm)34612PS 8.9 ± 3.9 vs NPS 9.6 ± 4.1 (P = .16)1 y:

      PS 1.53 ± 0.3 vs NPS 1.42 ± 0.3 (P = .04)
      No difference (P = NA)
      Kim et al.
      • Kim H.H.
      • Lee S.
      • Joo H.C.
      • Kim J.H.
      • Youn Y.N.
      • Yoo K.J.
      • et al.
      Impact of suture techniques for aortic valve replacement on prosthesis-patient mismatch.
      Retrospective cohortBiological, mechanical439121 y:

      PS 1.74 ± 1.38 vs NPS 1.70 ± 0.34 vs figure-of-eight 1.7 ± 0.42 (P = .97)
      PS 0.5% vs

      NPS 0% vs figure-of-eight 1% (P = .99)
      PS 2.4% vs NPS 2.5% vs figure-of-eight 5.7% (P = .28)PS 0.5% vs NPS 0.8% vs figure-of-eight 0% (P = .44)
      FU, Follow-up; MPG, mean pressure gradient; EOA, effective orifice area; PVL, paravalvular leak; TE, thromboembolism; IE, infective endocarditis; RCT, randomized controlled trial; PS, pledgeted sutures; NPS, nonpledgeted sutures; HR, hazard ratio; NA, not available.
      Some argue that the use of pledgeted sutures allow for more even distribution of mechanical forces and a tighter connection between the prosthesis and the aortic annulus/root, thereby decreasing the incidence of paravalvular leak (PVL).
      • Englberger L.
      • Schaff H.V.
      • Jamieson W.R.
      • Kennard E.D.
      • Im K.A.
      • Holubkov R.
      • et al.
      Importance of implant technique on risk of major paravalvular leak (PVL) after St. Jude mechanical heart valve replacement: a report from the Artificial Valve Endocarditis Reduction Trial (AVERT).
      However, others believe that pledgets create an additional level of obstruction in the left ventricular outflow tract (LVOT), leading to a higher transvalvular gradient, a smaller effective orifice area (EOA),
      • Tabata M.
      • Shibayama K.
      • Watanabe H.
      • Sato Y.
      • Fukui T.
      • Takanashi S.
      Simple interrupted suturing increases valve performance after aortic valve replacement with a small supra-annular bioprosthesis.
      ,
      • Ugur M.
      • Byrne J.G.
      • Bavaria J.E.
      • Cheung A.
      • Petracek M.
      • Groh M.A.
      • et al.
      Suture technique does not affect hemodynamic performance of the small supra-annular Trifecta bioprosthesis.
      and subsequently more frequent prosthesis–patient mismatch (PPM).
      • Kim H.H.
      • Lee S.
      • Joo H.C.
      • Kim J.H.
      • Youn Y.N.
      • Yoo K.J.
      • et al.
      Impact of suture techniques for aortic valve replacement on prosthesis-patient mismatch.
      Theoretically, the use of pledgets could also induce higher rates of thromboembolism or endocarditis due to extra foreign material.
      Within the PERIcardial SurGical AOrtic Valve ReplacemeNt (PERIGON) Pivotal Trial of the Avalus bioprosthesis (Medtronic), the technical details for implantation were left to the discretion of the surgeon. We aimed to provide insight into the effect of pledgeted sutures during AVR on multiple clinical and hemodynamic outcomes. The primary outcome of interest was a composite of thromboembolism, endocarditis, and major PVL at 5-year follow-up.

      Methods

      Study Design

      The PERIGON Pivotal Trial (www.clinicaltrials.gov, NCT02088554) is a prospective multicenter trial that is conducted at 38 sites across the United States, Canada, and Europe. In this single-armed trial, clinical and hemodynamic outcomes of the Avalus bioprosthesis (Medtronic), a stented bovine pericardial aortic valve, are evaluated. The study design was previously described in detail.
      • Klautz R.J.M.
      • Kappetein A.P.
      • Lange R.
      • Dagenais F.
      • Labrousse L.
      • Bapat V.
      • et al.
      Safety, effectiveness and haemodynamic performance of a new stented aortic valve bioprosthesis.
      ,
      • Sabik III, J.F.
      • Rao V.
      • Lange R.
      • Kappetein A.P.
      • Dagenais F.
      • Labrousse L.
      • et al.
      One-year outcomes associated with a novel stented bovine pericardial aortic bioprosthesis.
      In short, symptomatic patients with moderate or severe aortic stenosis or chronic, severe aortic regurgitation who were admitted for surgical AVR according to clinical indication were enrolled. Patients with and without concomitant procedures, limited to coronary artery bypass grafting, left atrial appendage ligation, patent foramen ovale closure, ascending aortic aneurysm or dissection repair not requiring circulatory arrest, and subaortic membrane resection not requiring myectomy, were included. In the PERIGON Pivotal Trial protocol, surgical technical details were left to the surgeon's own consideration.
      The trial was conducted according to the Declaration of Helsinki and good clinical practice. At each site, approval of the protocol was obtained from the institutional review board or ethics committee (Table E1), and written informed consent was provided by all patients. All deaths and valve-related adverse events were adjudicated by an independent clinical events committee, and study oversight was provided by an independent data and safety monitoring board (Baim Institute for Clinical Research). All echocardiographic data were evaluated by an independent core laboratory (MedStar).
      In the present study, patients were stratified to noneverted or everted mattress sutures with pledgets (pledgeted group), and noneverted or everted mattress, continuous, or simple interrupted sutures without pledgets (nonpledgeted group). Patients with previous aortic valve implantation (n = 10), figure-of-eight sutures (n = 3), or noncategorized sutures (n = 23) were excluded.

      Follow-up and End Points

      Annual clinical and (transthoracic) echocardiographic evaluations were performed after the first year of follow-up. Patient and procedural characteristics, early outcomes (within 30 days postimplantation), and 5-year outcomes were compared among the pledgeted and nonpledgeted groups. The primary outcome was a composite of thromboembolism, endocarditis, and major PVL at 5-year follow-up. Other clinical parameters included in the early- and midterm outcome analysis consisted of mortality, thromboembolism, endocarditis, all and major hemorrhage, all and major PVL, explant, reintervention, and permanent pacemaker implantation.
      Echocardiographic outcomes consisted of mean and peak pressure gradients calculated using the simplified Bernoulli formula, and EOA, which was determined using the continuity equation. EOA indexed (EOAi) by body surface area (BSA) was used to classify PPM. PPM was defined according to the Valve Academic Research Consortium 3 criteria as insignificant (EOAi >0.85 cm2/m2 or >0.70 cm2/m2), moderate (EOAi between 0.85 and 0.66 cm2/m2 or 0.70 and 0.56 cm2/m2), or severe (EOAi ≤0.65 cm2/m2 or ≤0.55 cm2/m2) for patients with a body mass index (BMI) <30 or ≥30, respectively.
      • Généreux P.
      • Piazza N.
      • Alu M.C.
      • Nazif T.
      • Hahn R.T.
      • Pibarot P.
      • et al.
      Valve Academic Research Consortium 3: updated endpoint definitions for aortic valve clinical research.

      Statistical Analysis

      Continuous variables are presented as mean ± SD and categorical variables as number and percentage. The independent sample t test or Mann–Whitney U test was used to compare continuous variables, and χ2 or Fisher exact test was used for categorical variables. Early and 5-year clinical event rates (including 95% CI) were summarized using the Kaplan–Meier method, and the log rank test was used to calculate P values. An additional evaluation of hemodynamic performance postimplantation and at 5-year follow-up in valve sizes smaller than 23 mm was performed. Furthermore, hemodynamic performance according to suturing techniques within the nonpledgeted group were compared for the “mattress” (noneverted and everted mattress sutures) and “nonmattress” (continuous and simple interrupted sutures) groups to investigate differences not related to the use of pledgets.
      Propensity score matching was performed to account for potential bias arising from the decision to use pledgets. Propensity scores were calculated on the basis of the following variables: age, male sex, BSA, Society of Thoracic Surgeons (STS) risk of mortality, New York Heart Association class III/IV, coronary artery disease, chronic obstructive pulmonary disease, hypertension, previous myocardial infarction, renal dysfunction/insufficiency, diabetes mellitus, atrial fibrillation, peripheral vascular disease, previous stroke/cerebrovascular accident, left ventricular ejection fraction at baseline, mean pressure gradient at baseline, isolated/mixed aortic stenosis, and less invasive approach (hemisternotomy or right anterior thoracotomy). Baseline left ventricular ejection fraction and baseline mean pressure gradient were missing for 225 (20.8%) and 26 (2.4%) patients, respectively. To avoid losing patients in the postmatched analysis, the missing values were imputed with the median before entering propensity score matching. A 5-to-1 digits greedy 1:1 matching algorithm was used to form a propensity score-matched cohort for analysis.
      A 2-sided α level of 0.05 was used in all tests. The balance in baseline characteristics before and after propensity score matching was expressed in standardized mean differences. Statistical analyses were performed with SAS version 9.4 (SAS Institute Inc).

      Results

      Entire Cohort

      Six hundred forty (59%) patients underwent AVR with pledgeted sutures, and 442 (41%) underwent AVR with nonpledgeted sutures. The baseline characteristics are summarized in Table 2. Baseline differences existed in age, BSA, BMI, STS risk of mortality, hypertension, left ventricular hypertrophy, atrial fibrillation, isolated or mixed aortic stenosis as the primary indication for AVR, minimally invasive surgical approach, concomitant procedures, and implanted valve sizes. At 30 days, all clinical and hemodynamic end points were comparable (Table E2). At 5 years of follow-up, the composite outcome of thromboembolism, endocarditis, and major PVL occurred in 9.2% of the pledgeted group and 10.2% of the nonpledgeted group (P = .59; Table E3). Moreover, there were no differences in the separate components of the composite outcome, nor in other clinical or hemodynamic outcomes.
      Table 2Baseline and procedural characteristics according to the use of pledgets for patients who underwent aortic valve replacement in the entire cohort and the propensity score-matched cohort
      Entire cohort (N = 1082)Propensity score-matched cohort (n = 794)
      Pledgets (n = 640)No pledgets (n = 442)SMDPledgets (n = 397)No pledgets (n = 397)SMD
      Age, y69.6 ± 8.571.0 ± 9.40.14870.2 ± 8.370.3 ± 9.20.010
      Male sex494 (77.2)323 (73.1)0.095300 (75.6)295 (74.3)0.029
      Body surface area, m22.01 ± 0.21.96 ± 0.20.2051.98 ± 0.21.98 ± 0.20.019
      Body mass index29.8 ± 5.529.0 ± 5.30.14529.4 ± 5.729.2 ± 5.40.026
      NYHA classification III-IV272 (42.5)189 (42.8)0.005158 (39.8)166 (41.8)0.041
      STS risk of mortality, %1.9 ± 1.22.1 ± 1.60.2111.90 ± 1.201.90 ± 1.240.004
      Diabetes179 (28.0)114 (25.8)0.049108 (27.2)99 (24.9)0.052
      Hypertension510 (79.7)318 (71.9)0.182293 (73.8)291 (73.3)0.011
      Peripheral vascular disease40 (6.3)39 (8.8)0.09826 (6.5)31 (7.8)0.049
      Renal dysfunction/insufficiency65 (10.2)50 (11.3)0.03748 (12.1)40 (10.1)0.064
      Stroke/CVA28 (4.4)16 (3.6)0.03910 (2.5)13 (3.3)0.045
      COPD79 (12.3)48 (10.9)0.04645 (11.3)42 (10.6)0.024
      Left ventricular ejection fraction, %59.8 ± 9.058.6 ± 10.10.12658.67 ± 9.559.71 ± 9.00.112
      Coronary artery disease288 (45.0)183 (41.4)0.073167 (42.1)168 (42.3)0.005
      Left ventricular hypertrophy284 (44.4)161 (36.4)0.163160 (40.3)146 (36.8)0.073
      Atrial fibrillation52 (8.1)59 (13.3)0.16945 (11.3)41 (10.3)0.032
      Isolated/mixed aortic stenosis597 (93.3)425 (96.2)0.129380 (95.7)382 (96.2)0.026
      Minimally invasive surgical approach150 (24.3)70 (16.5)0.20076 (19.1)70 (17.6)0.010
      Concomitant procedure
       None288 (45.0)242 (54.8)0.196175 (44.1)218 (54.9)0.218
       CABG223 (34.8)128 (29.0)0.127145 (36.5)115 (29.0)0.162
       Ascending aortic aneurysm not requiring circulatory arrest48 (7.5)35 (7.9)0.01630 (7.6)32 (8.1)0.019
       Other
      Includes implantable cardiac device, left atrial appendage closure, patent foramen ovale closure, resection of subaortic membrane not requiring myectomy, and dissection repair not requiring circulatory arrest.
      161 (25.2)68 (15.4)0.24592 (23.2)58 (14.6)0.220
      Annular calcification516 (80.6)371 (83.9)0.16320 (80.6)331 (83.4)0.072
      Total bypass time, min104.2 ± 40.6105.6 ± 41.00.035101.7 ± 38.4105.8 ± 41.20.103
      Aortic crossclamp time, min79.2 ± 31.279.5 ± 32.30.01278.2 ± 30.079.9 ± 32.40.052
      Annular diameter
      The annual diameter was determined intraoperatively and corresponds to the size of the replica end of the valve sizer.
      23.7 ± 2.0523.7 ± 2.170.02123.7 ± 2.1323.7 ± 2.190.019
      Valve size implanted
       17 mm0 (0.0)1 (0.2)0.0670 (0.0)0 (0.0)0.000
       19 mm16 (2.5)23 (5.2)0.1418 (2.0)20 (5.0)0.164
       21 mm115 (18.0)88 (19.9)0.05079 (19.9)75 (18.9)0.025
       23 mm226 (35.3)161 (36.4)0.023145 (36.5)147 (37.0)0.010
       25 mm216 (33.8)126 (28.5)0.113125 (31.5)114 (28.7)0.060
       27 mm62 (9.7)36 (8.1)0.05438 (9.6)34 (8.6)0.035
       29 mm5 (0.8)7 (1.6)0.0742 (0.5)7 (1.8)0.119
      Mean pressure gradient, mm Hg41.7 ± 17.043.3 ± 16.80.09643.3 ± 16.943.3 ± 16.70.001
      Effective orifice area, cm20.78 (0.36-4.67)0.75 (0.35-3.43)0.1640.75 (0.36-3.44)0.76 (0.35-3.43)0.013
      Indexed effective orifice area, cm2/m20.39 (0.17-2.52)0.38 (0.18-1.82)0.1310.38 (0.17-1.83)0.39 (0.18-1.82)0.013
      Data are presented as mean ± SD, median (interquartile range), or n (%) except where otherwise noted. SMD, Standardized mean difference; NYHA, New York Heart Association; STS, Society of Thoracic Surgeons; CVA, cerebrovascular accident; COPD, chronic obstructive pulmonary disease; CABG, coronary artery bypass grafting.
      Includes implantable cardiac device, left atrial appendage closure, patent foramen ovale closure, resection of subaortic membrane not requiring myectomy, and dissection repair not requiring circulatory arrest.
      The annual diameter was determined intraoperatively and corresponds to the size of the replica end of the valve sizer.
      After propensity score matching, 794 patients (397 matched pairs) were eligible for the analysis (Figure E1). The groups were similar with regard to comorbidities and hemodynamic parameters, yet differences in concomitant procedures persisted (Table 2). At 30 days, the composite outcome was 2.8% in the pledgeted group and 1.0% in the nonpledgeted group (P = .07; Table E4). The hemodynamic parameters were similar between the 2 groups.
      At 5 years of follow-up (Table 3), the composite outcome of thromboembolism, endocarditis, and major PVL occurred in 11.7% of the pledgeted group and in 9.8% of the nonpledgeted group (P = .51). The separate components were also comparable (Figures 1 and 2). The EOA was smaller in the pledgeted group (P = .045), but no difference was observed for the mean or peak pressure gradient. The mean pressure gradient remained stable over time, whereas the EOA decreased especially in the pledgeted group (Figure E2). The degree of PVL was consistent throughout follow-up (Figure 3). The proportion of patients with any PPM at 5-year follow-up was similar between the groups (Table 3).
      Table 3Clinical outcomes and hemodynamic performance at 5 years of follow-up for patients who underwent aortic valve replacement in the propensity score-matched cohort
      Pledgets (n = 397)No pledgets (n = 397)P value
      P value from log rank test for all clinical outcomes and from independent samples t test, Mann–Whitney U test, or χ2 test for echocardiographic data.
      Composite endpoint (thromboembolism, endocarditis, and major PVL)11.7% (8.7%-15.7%)

      (n = 41)
      9.8% (7.1%-13.4%)

      (n = 36)
      .51
      Thromboembolism5.9% (3.9%-8.9%)

      (n = 22)
      6.1% (4.1%-9.3%)

      (n = 22)
      .95
      Endocarditis6.4% (4.1%-9.9%)

      (n = 20)
      4.2% (2.5%-6.9%)

      (n = 15)
      .35
      Major PVL0.3% (0.0%-1.8%)

      (n = 1)
      0.0% (NA)

      (n = 0)
      .32
      All PVL1.1% (0.4%-2.8%)

      (n = 4)
      1.5% (0.5%-4.0%)

      (n = 4)
      .96
      All-cause mortality13.3% (10.0%-17.6%)

      (n = 45)
      10.5% (7.7%-14.2%)

      (n = 37)
      .30
      Cardiac-related mortality6.8% (4.4%-10.3%)

      (n = 22)
      4.2% (2.5%-7.1%)

      (n = 14)
      .15
      Valve-related mortality2.2% (1.1%-4.4%)

      (n = 8)
      0.5% (0.1%-2.1%)

      (n = 2)
      .06
      Reintervention3.1% (1.7%-5.5%)

      (n = 11)
      3.9% (2.2%-6.7%)

      (n = 13)
      .74
      Explant3.1% (1.7%-5.5%)

      (n = 11)
      3.2% (1.7%-5.7%)

      (n = 11)
      .95
      Permanent pacemaker implantation5.6% (3.7%-8.5%)

      (n = 21)
      6.9% (4.6%-10.1%)

      (n = 25)
      .55
      Mean pressure gradient, mm Hg12.3 ± 4.412.3 ± 4.0.93
      Peak pressure gradient, mm Hg22.0 ± 7.421.9 ± 7.4.93
      EOA, cm21.35 (0.72-2.87)1.44 (0.79-2.58).045
      EOAi, cm2/m20.69 (0.38-1.31)0.73 (0.41-1.31).06
      Prosthesis-patient mismatch.07
       None40 (31.7%)44 (32.6%)
       Moderate46 (36.5%)64 (47.4%)
       Severe40 (31.7%)27 (2.0%)
      Clinical outcomes are reported as 5-year Kaplan–Meier event rates, including 95% CI. Hemodynamic performance is presented either as mean ± SD or median (interquartile range). PVL, Paravalvular leak; NA, not available; EOA, effective orifice area; EOAi, effective orifice area indexed according to body surface area.
      P value from log rank test for all clinical outcomes and from independent samples t test, Mann–Whitney U test, or χ2 test for echocardiographic data.
      Figure thumbnail gr1
      Figure 1Kaplan–Meier event rates according to the use of pledgets for patients who underwent aortic valve replacement in the propensity score-matched cohort. Displayed are event rates for the composite outcome of thromboembolism, endocarditis, and major paravalvular leak (top), and for thromboembolism (bottom). The whiskers represent the 95% CI.
      Figure thumbnail gr2
      Figure 2Kaplan–Meier event rates according to the use of pledgets for patients who underwent aortic valve replacement in the propensity score-matched cohort. Displayed are event rates for endocarditis (top), and for major paravalvular leak (bottom). The whiskers represent the 95% CI.
      Figure thumbnail gr3
      Figure 3Paravalvular leak over time according to the use of pledgets for patients who underwent aortic valve replacement in the propensity score-matched cohort. The frequencies of paravalvular leak severity categories at different time points are displayed as stacked bars.

      Subanalysis: Valve Sizes <23 mm

      The baseline and procedural characteristics of patients with implanted valve sizes <23 mm are presented in Table E5. Pledgets were used in 131 patients, and no pledgets in 112 patients. As observed in the entire cohort, differences among the groups existed in baseline age, STS risk of mortality, concomitant procedures, and implanted valve size. Additionally, the aortic crossclamp time was longer in the pledgeted group than in the nonpledgeted group (78.6 ± 29.4 vs 69.2 ± 31.3 minutes; P = .017). The hemodynamic performance up to 30 days and at 5-year follow-up is shown in Table 4. The mean pressure gradient up to 30 days was lower in the pledgeted group compared with the nonpledgeted group (14.9 ± 4.6 vs 16.4 ± 5.6; P = .027), but this difference was absent at 5-year follow-up. All other parameters were comparable at both follow-up points.
      Table 4Hemodynamic performance at discharge up to 30 days and at 5 years of follow-up in valve sizes <23 mm for patients who underwent aortic valve replacement
      Pledgets (n = 131)No pledgets (n = 112)P value
      Mean pressure gradient, mm Hg
       Discharge up to 30 days14.9 ± 4.616.4 ± 5.6.027
       5 years15.7 ± 5.615.0 ± 4.2.50
      Peak pressure gradient, mm Hg
       Discharge up to 30 days27.5 ± 8.729.8 ± 9.8.07
       5 years27.6 ± 9.226.1 ± 8.0.38
      Effective orifice area, cm2
       Discharge up to 30 days1.31 (0.78-2.54)1.29 (0.70-2.24).43
       5 years1.09 (0.72-1.95)1.10 (0.79-1.70).54
      Indexed effective orifice area, cm2/m2
       Discharge up to 30 days0.72 (0.40-1.33)0.70 (0.31-1.24).81
       5 years0.61 (0.43-1.05)0.64 (0.43-1.04).47
      Prosthesis-patient mismatch
       Discharge up to 30 days.79
      None42 (35.9)28 (31.5)
      Moderate43 (36.8)36 (4.4)
      Severe32 (27.4)25 (28.1)
       5 years.50
      None3 (7.3)6 (12.8)
      Moderate16 (39.0)21 (44.7)
      Severe22 (53.7)20 (42.6)
      Paravalvular leak
       Discharge up to 30 days.60
      None76 (59.8)70 (66.0)
      Trace37 (29.1)27 (25.5)
      Mild14 (11.0)9 (8.5)
      Moderate0 (0.0)0 (.0)
      Severe0 (0.0)0 (.0)
       5 years.33
      None41 (83.7)38 (79.2)
      Trace3 (6.1)7 (14.6)
      Mild5 (10.2)3 (6.3)
      Moderate0 (0.0)0 (0.0)
      Severe0 (0.0)0 (0.0)
      Numerical data are presented as mean ± SD or median (interquartile range) according to their distribution, and categorical data are summarized as n (%). Data were compared using the independent samples t test, Mann–Whitney U test, and χ2 test/Fisher exact test, respectively.

      Subanalysis: Nonpledgeted Sutures

      Stratification of patients within the nonpledgeted group resulted in 180 patients in the mattress subgroup and 205 in the nonmattress subgroup. Their baseline characteristics are summarized in Table E6. Differences were observed in BMI, New York Heart Association class III/IV, diabetes mellitus, hypertension, renal dysfunction/insufficiency, stroke/cerebrovascular accident, chronic obstructive pulmonary disease, coronary artery disease, left ventricular hypertrophy, and concomitant procedures. The hemodynamic performance up to 30 days and at 5-year follow-up is presented in Table E7. At both time points, no differences related to suturing technique were found in echocardiographic variables, PPM, or PVL.

      Discussion

      In a propensity score-matched analysis of a large international cohort, clinical outcomes at 30 days and 5 years of follow-up were comparable among patients who underwent surgical AVR with and without pledgeted sutures. Comparisons of pledgeted with nonpledgeted sutures in AVR in previous literature have mainly focused on hemodynamic performance (Table 1). Hence, insight into clinical outcomes is scarce. A potential disadvantage of pledgeted sutures is an increased risk of infection, pannus, or thrombus formation due to the presence of extra foreign material. A single study
      • Kim H.H.
      • Lee S.
      • Joo H.C.
      • Kim J.H.
      • Youn Y.N.
      • Yoo K.J.
      • et al.
      Impact of suture techniques for aortic valve replacement on prosthesis-patient mismatch.
      evaluated thromboembolism rates, whereas endocarditis has never been studied to our knowledge. In our analysis, both adverse events rarely occurred within 30 days of follow-up and were comparable at 5 years. Thus, there was no evidence of higher rates of these events when pledgets were used.
      PVL is another important variable in the choice whether to use pledgeted sutures. Several studies have investigated this parameter but have reported conflicting results. Englberger and colleagues
      • Englberger L.
      • Schaff H.V.
      • Jamieson W.R.
      • Kennard E.D.
      • Im K.A.
      • Holubkov R.
      • et al.
      Importance of implant technique on risk of major paravalvular leak (PVL) after St. Jude mechanical heart valve replacement: a report from the Artificial Valve Endocarditis Reduction Trial (AVERT).
      reported a reduction in PVL in the pledgeted sutures group. On the contrary, others reported no differences compared with nonpledgeted or figure-of-eight sutures.
      • Tabata M.
      • Shibayama K.
      • Watanabe H.
      • Sato Y.
      • Fukui T.
      • Takanashi S.
      Simple interrupted suturing increases valve performance after aortic valve replacement with a small supra-annular bioprosthesis.
      • Ugur M.
      • Byrne J.G.
      • Bavaria J.E.
      • Cheung A.
      • Petracek M.
      • Groh M.A.
      • et al.
      Suture technique does not affect hemodynamic performance of the small supra-annular Trifecta bioprosthesis.
      • LaPar D.J.
      • Ailawadi G.
      • Bhamidipati C.M.
      • Singh M.
      • Dare D.
      • Kern J.A.
      • et al.
      Use of a nonpledgeted suture technique is safe and efficient for aortic valve replacement.
      • Kim H.H.
      • Lee S.
      • Joo H.C.
      • Kim J.H.
      • Youn Y.N.
      • Yoo K.J.
      • et al.
      Impact of suture techniques for aortic valve replacement on prosthesis-patient mismatch.
      Our findings were in line with the latter studies.
      Regarding other hemodynamic performance measures such as the EOA, previous results were ambiguous, too. Tabata and colleagues
      • Tabata M.
      • Shibayama K.
      • Watanabe H.
      • Sato Y.
      • Fukui T.
      • Takanashi S.
      Simple interrupted suturing increases valve performance after aortic valve replacement with a small supra-annular bioprosthesis.
      observed a smaller EOA postimplantation in the pledgeted group that disappeared at 1 year, whereas Ugur and colleagues
      • Ugur M.
      • Byrne J.G.
      • Bavaria J.E.
      • Cheung A.
      • Petracek M.
      • Groh M.A.
      • et al.
      Suture technique does not affect hemodynamic performance of the small supra-annular Trifecta bioprosthesis.
      described a larger EOA at that time point. In the current study, the EOA was equal between the groups at short-term follow-up; however, at 5 years a difference appeared as a result of a smaller EOA in the pledgeted group. This phenomenon might be due to subvalvular obstruction caused by the pledgets and tissue (pannus) formation/ingrowth developing over time, which could lead to elevated velocities in the LVOT. Theoretically, such obstruction would be more profound in a small LVOT because pledgets have a fixed size, but in our subanalysis of valve sizes <23 mm, the EOAs were similar between the pledgeted and nonpledgeted groups (Table 4). Another explanation could be related to measurement error because the smaller EOA was not reflected by the mean or peak pressure gradient. Measurement of the LVOT diameter is prone to error and has a drastic effect on the EOA value because this diameter is squared to obtain the LVOT area for the continuity equation. The presence of pledgets might complicate the echocardiographic measurement of the LVOT diameter even more when it is examined in close proximity to the aortic annulus. Because the absolute difference in EOA was <0.1 cm2, the difference was absent in small valve sizes, and other hemodynamic parameters were equal between the groups, the clinical relevance of this difference in EOA is questionable. External validation of this finding and longer follow-up could provide valuable insights. A derivative of the indexed EOA is PPM. Because previous PERIGON substudies challenged the clinical relevance of this concept by outlining shortcomings regarding correspondence with elevated gradient and disproportional normalization by BSA,
      • Vriesendorp M.D.
      • Deeb G.M.
      • Reardon M.J.
      • Kiaii B.
      • Bapat V.
      • Labrousse L.
      • et al.
      Why the categorization of indexed effective orifice area is not justified for the classification of prosthesis-patient mismatch.
      • Vriesendorp M.D.
      • Groenwold R.H.H.
      • Herrmann H.C.
      • Head S.J.
      • De Lind Van Wijngaarden R.A.F.
      • Vriesendorp P.A.
      • et al.
      The clinical implications of body surface area as a poor proxy for cardiac output.
      • Velders B.J.J.
      • Vriesendorp M.D.
      • Herrmann H.C.
      • Klautz R.J.M.
      The ratio fallacy of prosthesis-patient mismatch.
      we chose to mainly elaborate on primary echocardiographic parameters rather than PPM in this study.
      Although similar pressure gradients at 5 years were observed, a difference with lower values in the pledgeted group was found at 30 days, however, this dissimilarity was <1 mm Hg. Hence, it was not considered clinically important. To further investigate differences related to suturing technique, a subanalysis was executed within the nonpledgeted group. This analysis did not show any difference in the mattress and nonmattress suturing techniques.
      Hemodynamic outcomes have received specific attention in smaller valve sizes. Two earlier studies reported similar hemodynamic parameters for pledgeted and nonpledgeted sutures.
      • Tabata M.
      • Shibayama K.
      • Watanabe H.
      • Sato Y.
      • Fukui T.
      • Takanashi S.
      Simple interrupted suturing increases valve performance after aortic valve replacement with a small supra-annular bioprosthesis.
      ,
      • Ugur M.
      • Byrne J.G.
      • Bavaria J.E.
      • Cheung A.
      • Petracek M.
      • Groh M.A.
      • et al.
      Suture technique does not affect hemodynamic performance of the small supra-annular Trifecta bioprosthesis.
      Our results are in agreement with these findings.

      Strengths and Limitations

      A major advantage of the current study was that all 1082 patients received the same bioprosthetic valve, which eliminated any bias due to the type of prosthesis. Furthermore, the prospective design with independent adverse event adjudication and core laboratory assessment of echocardiograms enabled robust and consistent data-gathering up to 5 years of follow-up. Despite these strengths, there were limitations. Even though there was apparent harmony in patient characteristics after propensity score-matching, the study design could not guarantee complete comparability because adjustment was possible only for measured confounders. Specifically, we did not adjust for surgeon bias, and it is possible that surgeons who opted for one technique versus another might have different skills, leading to an inextricable confounding effect. The 1082 AVR procedures in this analysis were performed by 132 surgeons, some of whom solely used pledgeted (54 surgeons) or nonpledgeted sutures (33 surgeons). Hence, we did not incorporate surgeon data in the propensity score matching. To achieve complete comparability, randomized treatment allocation would have been a prerequisite, which was not the case. Furthermore, no correction methods were applied to the subanalyses, in which the statistical power was also decreased because of smaller sample sizes. Therefore, these results should be interpreted in the context of these limitations. An increased length of follow-up might have revealed more profound differences in outcomes. It would be of interest to observe whether the difference in EOA will persist and eventually lead to differences in clinical outcomes such as reintervention. Important aspects that remain unknown to the discussion of whether to use pledgeted sutures for surgical AVR are the feasibility of reoperations and future valve-in-valve transcatheter AVR for degenerated bioprostheses. Unfortunately, no quantitative claims can be made on the basis of data from the current study. For future studies on this topic, these issues are highly relevant.

      Conclusions

      In a propensity score-matched analysis, comprehensive clinical outcomes were comparable between patients who underwent AVR with pledgeted and nonpledgeted sutures up to 5 years of follow-up (Figure 4). Nevertheless, pledgets might lead to a slight reduction of the EOA in the long run, but this finding requires external validation.
      Figure thumbnail gr4
      Figure 4Pledgeted versus nonpledgeted sutures in aortic valve replacement: insights from a prospective multicenter trial. Outcomes were compared according to the use of pledgeted sutures. Propensity score matching was used to adjust for baseline differences. The images showing the suturing techniques were reproduced from Kirali and colleagues,
      • Kirali K.
      • Yerlikhan Ö.A.
      Conventional aortic valve surgery (open surgical approaches).
      with permission from Elsevier. AVR, Aortic valve replacement.

      Conflict of Interest Statement

      Bart J. J. Velders: institutional research grant and speaker fees paid to his department by Medtronic. Michiel D. Vriesendorp: institutional research grant and reimbursement of travel expenses from Medtronic. Joseph F. Sabik III: North American Principal Investigator of the PERIGON Pivotal Trial for Medtronic. Francois Dagenais: speaker and consultant for Medtronic, COOK Medical, and Edwards Lifesciences. Louis Labrousse: research grant from Medtronic, Edwards Lifesciences, and Abbott. Vinayak Bapat: consultant for Medtronic, Edwards Lifesciences, and Abbott. Yaping Cai: employee of Medtronic. Robert J. M. Klautz: research support, consultation fees, and European Principal Investigator of the PERIGON Pivotal Trial for Medtronic. All other authors reported no conflicts of interest.
      The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest.

      Appendix E1

      Table E1IRB, IRB, and EC approval information—PERIGON Pivotal Trial
      SiteIRB/REB/EC informationDate of IRB/REB/EC approvalIRB/REB/EC approval No.
      United States
       Cleveland Clinic

      Cleveland, Ohio
      Cleveland Clinic IRB

      9500 Euclid Ave HSb 103

      Cleveland, OH 44195
      January 13, 201514-1537
       Piedmont Hospital

      Atlanta, Georgia
      Western IRB (WIRB)

      1019 39th Ave SE

      Ste 120

      Puyallup, WA 98374
      September 10, 201420141211
       University of Maryland Medical Center

      Baltimore, Maryland
      Maryland School of Medicine IRB

      Human Research Protections Office

      800 W Baltimore Street, Suite 100

      Baltimore, MD 21201
      April 30, 2015HP-00063749
       ProMedica Physicians Group

      Toledo, Ohio
      Western IRB (WIRB)

      1019 39th Ave SE Ste 120

      Puyallup, WA 98374
      August 28, 201420141211
       Oklahoma Heart Hospital

      Oklahoma City, Oklahoma
      Western IRB (WIRB)

      1019 39th Ave SE Ste 120

      Puyallup, WA 98374
      October 17, 201420141211
       Aurora Medical Group Cardiovascular and Thoracic Surgery

      Milwaukee, Wisconsin
      Aurora Heath Care IRB Office

      945 North 12th Street

      PO Box 342 W310

      Milwaukee, WI 53201
      August 19, 201414-77
       Maimonides Medical Center

      Brooklyn, New York
      Maimonides Medical Center IRB/Research Committee

      4802 Tenth Ave

      Brooklyn, NY 11219
      September 26, 20142014-08-17
       University of Michigan Cardiovascular Center

      Ann Arbor, Michigan
      University of Michigan, Office of Research

      University of Michigan Medical School

      4107 Medical Science Building I

      1301 Catherine Street SPC 5624

      Ann Arbor, MI 48109-5624
      September 11, 2014IRB00001995
       Cardiothoracic and Vascular Surgeons

      Austin, Texas
      St David's Health Care IRB

      St David's Medical Center

      919 East 32nd Street

      Austin, TX 78705
      January 9, 201514-12-02
       University of Colorado

      Aurora, Colorado
      Colorado Multiple Institutional Review Board

      Campus Mailbox F490

      13001 E 17th Place, Room N3214

      Aurora, CO 80045
      January 9, 201514-1348
       University of Southern California Los Angeles, CaliforniaUSC OPRS—Office for the Protection of Research Subjects

      General Hospital

      Suite 4700

      1200 North State Street

      Los Angeles, CA 90033
      September 15, 2014HS-14-00527
       University of Florida-Shands

      Gainesville, Florida
      Western IRB

      1019 39th Ave SE Ste 120

      Puyallup, WA 98374
      November 4, 201420141211
       Houston Methodist Hospital

      Houston, Texas
      Houston Methodist Institutional Review Board

      6565 Fannin Street

      #MGJ6-014

      Houston, TX 77030
      September 9, 20140714-0157
       University of Washington

      Seattle, Washington
      Western IRB

      1019 39th Ave SE Ste 120

      Puyallup, WA 98374
      November 30, 201420141211
       Massachusetts General Hospital

      Boston, Massachusetts
      Partners Human Research Committee

      116 Huntington Avenue Ste 1002

      Boston, MA 02116
      January 28, 20152014P001477
       Riverside Methodist Hospital

      Columbus, Ohio
      Western IRB (WIRB)

      1019 39th Ave SE Ste 120

      Puyallup, WA 98374
      August 21, 201420141211
       Minneapolis Heart Institute Foundation

      Minneapolis, Minnesota
      Quorum Review IRB

      1501 Fourth Avenue Ste 800

      Seattle, WA 98101
      August 29, 201429584/1
       New York Presbyterian Hospital/Columbia University Medical Center

      New York, New York
      Columbia University IRB

      154 Haven Ave, 1st Floor

      New York, NY 10032
      May 22, 2015IRB-AAAO9403
       Mount Sinai Medical Center

      New York, New York
      Program for the Protection of Human Subjects

      345 E 102nd St

      Suite 200-2nd Floor

      New York, NY 10029
      June 9, 2015HS No: 15-00331
       Stanford University

      Stanford, California
      Research Compliance Office, Stanford University

      3000 El Camino Real

      Five Palo Alto Square

      4th Floor

      Palo Alto, CA 94306
      November 17, 20154593
       Hartford Hospital Hartford, ConnecticutHuman Research Protection Program

      80 Seymour Street

      PO Box 5037

      Hartford, CT 06102-5037
      December 3, 2020HHC-2020-0335
      Canada
       University of Ottawa Heart Institute

      Ottawa, Ontario, Canada
      Ottawa Health Science Network Research Ethics Board (OHSN-REB)

      Ottawa Hospital, Civic Campus

      725 Parkdale Avenue

      Civic Box 411

      LOEB Building

      Ottawa, Ontario K1Y 4E9, Canada
      August 18, 201420140100-01H
       Toronto General Hospital

      Toronto, Ontario, Canada
      UHN Research Ethics Board

      700 University Ave

      Hyaro Building, Suite 1056

      Toronto, Ontario M5G 1Z5, Canada
      July 7, 201414-7354-A
       Institut Universitaire de Cardiologie et de Pneumologie de Québec (IUCPQ)

      Quebec, Quebec, Canada
      Comité d'ethique de la recherche IUCPQ

      Room U-4733, IRB

      2725 chemin Ste-Foy

      Quebec G1V 4G5, Canada
      June 30, 20142014-2354
       Montreal Heart Institute

      Montreal, Quebec, Canada
      Comité D’éthique de la Recherché Montreal Heart

      5000 Rue Belanger est

      Montreal, Quebec H1T 1C8, Canada
      July 17, 20142014-1686
       London Health Sciences Centre

      London, Ontario, Canada
      Western University Health Sciences Research Ethics Board

      1393 Western Rd Support Services Building, Room 5182

      London, Ontario N6G 1G9, Canada
      June 7, 2016107602
      Europe
       Medizinische Hochschule Hannover

      Hannover, Germany
      Central EC:

      Ethikkommission an der Technischen Universität München

      Ismaninger Straβe 22

      81675 München, Germany

      Local EC:

      Ethikkommission der MHH

      Carl-Neuberg-Straβe 1

      30625 Hannover, Germany
      June 3, 2014Reference: 36/14Mf-AS

      EUDAMED: CIV-14-01
       Ospedale San Raffaele

      Milano, Italy
      Comitato lini dell’ Ospedale

      San Raffaele

      Via Olgettina, 60

      20132 Milano, Italy
      March 6, 2014Approval number not specified in approval letter
       Hôpital Bichat—Claude Bernard

      Paris, France
      Comité de protection des personnes Sud-Ouest et outre mer III

      Service de pharmacologie linique

      Groupe Hospitalier Pellegrin

      Bât 1A

      Place Amélie Raba Léon

      33076 Bordeaux Cedex,

      France
      January 29, 2014ANSM number: 2013-A00897-38/4
       Universitätsspital Zürich

      Zürich, Switzerland
      Central EC:

      Kantonale Ethikkommission Bern (KEK)

      Institut für Pathophysiologie

      Hörsaaltrakt Pathologie, Eingang 43A, Büro H372

      Murtenstrasse 31

      3010 Bern, Switzerland

      Local EC:

      Kantonale Ethikkommission Zürich Stampfenbachstrasse 121

      8090 Zürich, Switzerland
      May 16, 2014CEC number 010/14; SNCTP 17

      CEC–ZH number: 2014–0068
       Inselspital—Universitätsspital Bern

      Bern, Switzerland
      Kantonale Ethikkommission Bern (KEK)

      Institut für Pathophysiologie

      Hörsaaltrakt Pathologie, Eingang 43A, Büro H372

      Murtenstrasse 31 3010 Bern,

      Switzerland
      May 16, 2014CEC number: 010/14; SNCTP 17

      CEC–ZH number: 2014–0068
       Hôpital Haut-Lévêque—CHU de Bordeaux

      Bordeaux, France
      Comité de protection des personnes Sud-Ouest et outre mer III

      Service de pharmacologie linique

      Groupe Hospitalier Pellegrin

      Bât. 1A

      Place Amélie Raba Léon

      33076 Bordeaux Cedex,

      France
      January 29, 20142013-A000897-38
       Leids Universitair Medisch Centrum

      Leiden, The Netherlands
      Medisch-Ethische Toetsingscommissie Leiden Den Haag Delft

      PO Box 9600

      2300 RC Leiden, The Netherlands
      March 21, 2014P14.009/NL45419.058.13
       Erasmus Medical Centre

      Rotterdam, The Netherlands
      Medisch Ethische toetsings Commissie Erasmus MC

      Westzeedijk 353 Room Ae-337

      3015 AA Rotterdam, The Netherlands
      June 5, 2014MEC-2014-272/NL45419.058.13
       Universitätsklinikum Frankfurt

      Klinik für Thorax-, Herz- und Thorakale Gefäβchirurgie

      Frankfurt, Germany
      Central EC:

      Ethikkommission der Fakultät für Medizin der Technischen Universität München

      Ismaninger Straβe 22

      81675 München, Germany

      Local EC:

      Ethik- Kommission der Universitätsklinikum Frankfurt

      Theodor-Stern-Kai-7

      60590 Frankfurt, Germany
      June 3, 2014Reference: 36/14Mf-AS

      EUDAMED: CIV-14-01
       Guy's & St Thomas' NHS Foundation Trust–St Thomas' Hospital

      London, United Kingdom
      NRES Committee London–Dulwich

      Health Research Authority

      Skipton House

      80 London Road

      London SE1 6LH, United Kingdom
      April 28, 2014REC reference: 14/LO/0353

      IRAS project ID: 134481
       Universitätsklinikum Köln

      Köln, Germany
      Central EC:

      Ethikkommission der Fakultät für Medizin der Technischen Universität München

      Ismaninger Straβe 22

      81675 München, Germany

      Local EC:

      Ethikkommission der Medizinischen Fakultät der Universität zu Köln

      Kerpener Straβe 62

      50937 Köln, Germany
      June 3, 2014Reference: 36/14Mf-AS

      EUDAMED: CIV-14-01
       Herzzentrum Leipzig–Universitätsklinik

      Leipzig, Germany
      Central EC:

      Ethikkommission der Fakultät für Medizin der Technischen Universität München

      Ismaninger Straβe 22

      81675 München

      Germany

      Local EC:

      Ethikkommission an der Medizinischen Fakultät der Universität Leipzig

      Käthe-Kollwitz-Straβe 82

      04109 Leipzig

      Germany
      June 3, 2014Reference: 36/14Mf-AS

      EUDAMED: CIV-14-01
       Deutsches Herzzentrum München

      Klinik an der TU München

      München, Germany
      Ethikkommission der Fakultät für Medizin der Technischen Universität München

      Ismaninger Straβe 22

      81675 München, Germany
      June 3, 2014Reference: 36/14Mf-AS

      EUDAMED: CIV-14-01
      Adapted from Klautz and colleagues,
      • Klautz R.J.M.
      • Kappetein A.P.
      • Lange R.
      • Dagenais F.
      • Labrousse L.
      • Bapat V.
      • et al.
      Safety, effectiveness and haemodynamic performance of a new stented aortic valve bioprosthesis.
      an Open Access article distributed under the terms of the Creative Commons Attribution-Noncommercial License. IRB, Institutional review board; REB, research ethics board; EC, ethics committee; ANSM, french national agency for medicines and health products safety; CEC, central ethics committee; SNCTP, swiss national clinical trials portal; REC, research ethics committee; IRAS, integrated research application system; EUDAMED, European database on medical devices.
      Table E2Clinical outcomes and hemodynamic performance at 30 days in the entire cohort
      Pledgets (n = 640)Nonpledgets (n = 442)P value
      P value from log rank test for all clinical outcomes and from an independent samples t test or Mann–Whitney U test for echocardiographic data.
      Composite endpoint (thromboembolism, endocarditis, and major PVL)1.9% (1.1%-3.3%)

      (n = 12)
      1.1% (0.5%-2.7%)

      (n = 5)
      .34
      Thromboembolism1.4% (0.7%-2.7%)

      (n = 9)
      1.1% (0.5%-2.7%)

      (n = 5)
      .70
      Endocarditis0.3% (0.1%-1.2%)

      (n = 2)
      0.0% (NA)

      (n = 0)
      .24
      Major PVL0.2% (0.0%-1.1%)

      (n = 1)
      0.0% (NA)

      (n = 0)
      .41
      All PVL0.2% (0.0%-1.1%)

      (n = 1)
      0.2% (0.0%-1.6%)

      (n = 1)
      .79
      Major hemorrhage1.1% (0.5%-2.3%)

      (n = 7)
      0.9% (0.3%-2.4%)

      (n = 4)
      .76
      All-cause mortality0.8% (0.3%-1.9%)

      (n = 5)
      1.1% (0.5%-2.7%)

      (n = 5)
      .55
      Cardiac-related mortality0.6% (0.2%-1.7%)

      (n = 4)
      0.5% (0.1%-1.8%)

      (n = 2)
      .71
      Valve-related mortality0.0% (NA)

      (n = 0)
      0.0% (NA)

      (n = 0)
      NA
      Reintervention0.6% (0.2%-1.7%)

      (n = 4)
      0.0% (NA)

      (n = 0)
      .10
      Explant0.6% (0.2%-1.7%)

      (n = 4)
      0.0% (NA)

      (n = 0)
      .10
      Permanent pacemaker implantation3.3% (2.2%-5.0%)

      (n = 21)
      4.8% (3.1%-7.2%)

      (n = 21)
      .22
      Mean pressure gradient, mm Hg12.9 ± 4.413.4 ± 5.0.14
      Peak pressure gradient, mm Hg23.7 ± 7.924.3 ± 8.8.25
      EOA, cm21.60 ± 0.381.58 ± 0.38.46
      EOAi, cm2/m20.80 ± 0.190.81 ± 0.20.79
      Prosthesis-patient mismatch, n (%).36
       None269 (49.9)170 (45.1)
       Moderate193 (35.8)148 (39.3)
       Severe77 (14.3)59 (15.6)
      Clinical outcomes are reported as 5-year Kaplan–Meier event rates including 95% CI. Hemodynamic performance is presented either as mean ± SD or median (interquartile range). PVL, Paravalvular leak; NA, not applicable; EOA, effective orifice area; EOAi, effective orifice area indexed according to body surface area.
      P value from log rank test for all clinical outcomes and from an independent samples t test or Mann–Whitney U test for echocardiographic data.
      Table E3Clinical outcomes and hemodynamic performance at 5 years of follow-up in the entire cohort
      Pledgets (n = 640)Nonpledgets (n = 442)P value
      P value from log rank test for all clinical outcomes and from an independent samples t test, Mann–Whitney U test, or χ2 test for echocardiographic data.
      Composite endpoint (thromboembolism, endocarditis, and major PVL)9.2% (7.1%-12.0%)

      (n = 53)
      10.2% (7.6%-13.6%)

      (n = 41)
      .59
      Thromboembolism4.5% (3.1%-6.4%)

      (n = 27)
      6.9% (4.8%-10.0%)

      (n = 27)
      .17
      Endocarditis5.0% (3.4%-7.3%)

      (n = 26)
      3.8% (2.3%-6.2%)

      (n = 15)
      .55
      Major PVL0.3% (0.1%-1.3%)

      (n = 2)
      0.0% (NA)

      (n = 0)
      .24
      All PVL1.0% (0.4%-2.2%)

      (n = 6)
      1.3% (0.5%-3.6%)

      (n = 4)
      .92
      All-cause mortality12.0% (9.5%-15.1%)

      (n = 67)
      12.0% (9.1%-15.6%)

      (n = 48)
      .93
      Cardiac-related mortality5.8% (4.1%-8.3%)

      (n = 31)
      5.7% (3.8%-8.6%)

      (n = 22)
      .98
      Valve-related mortality1.7% (0.9%-3.2%)

      (n = 10)
      1.0% (0.4%-2.6%)

      (n = 4)
      .34
      Reintervention2.7% (1.7%-4.5%)

      (n = 16)
      3.5% (2.0%-6.0%)

      (n = 13)
      .70
      Explant2.6% (1.6%-4.3%)

      (n = 15)
      2.9% (1.6%-5.2%)

      (n = 11)
      .91
      Permanent pacemaker implantation6.9% (5.2%-9.3%)

      (n = 42)
      7.5% (5.3%-10.6%)

      (n = 31)
      .76
      Mean pressure gradient, mm Hg12.7 ± 4.912.3 ± 4.1.48
      Peak pressure gradient, mm Hg22.5 ± 8.322.0 ± 7.6.54
      EOA, cm21.40 ± 0.331.45 ± 0.36.19
      EOAi, cm2/m20.71 ± 0.160.75 ± 0.18.06
      Prosthesis-patient mismatch, n (%).21
       None64 (33.3)49 (32.2)
       Moderate70 (36.5)68 (44.7)
       Severe58 (30.2)35 (23.0)
      Clinical outcomes are reported as 5-year Kaplan–Meier event rates including 95% CI. Hemodynamic performance is presented either as mean ± SD or median (interquartile range). PVL, Paravalvular leak; NA, not applicable; EOA, effective orifice area; EOAi, effective orifice area indexed according to body surface area.
      P value from log rank test for all clinical outcomes and from an independent samples t test, Mann–Whitney U test, or χ2 test for echocardiographic data.
      Table E4Clinical outcomes and hemodynamic performance at 30 days in the propensity score-matched cohort
      Pledgets (n = 397)Nonpledgets (n = 397)P value
      P value from log rank test for all clinical outcomes and from an independent samples t test, Mann–Whitney U test, or χ2 test for echocardiographic data.
      Composite endpoint (thromboembolism, endocarditis, and major PVL)2.8% (1.5%-5.0%)

      (n = 11)
      1.0% (0.4%-2.7%)

      (n = 4)
      .07
      Thromboembolism2.0% (1.0%-4.0%)

      (n = 8)
      1.0% (0.4%-2.7%)

      (n = 4)
      .25
      Endocarditis0.5% (0.1%-2.0%)

      (n = 2)
      0.0% (NA)

      (n = 0)
      .16
      Major PVL0.3% (0.0%-1.8%)

      (n = 1)
      0.0% (NA)

      (n = 0)
      .34
      All PVL0.3% (0.0%-1.8%)

      (n = 1)
      0.3% (0.0%-1.8%)

      (n = 1)
      >.99
      Major hemorrhage0.8% (0.2%-2.3%)

      (n = 3)
      1.0% (0.4%-2.7%)

      (n = 4)
      .71
      All-cause mortality1.0% (0.4%-2.7%)

      (n = 4)
      1.0% (0.4%-2.7%)

      (n = 4)
      .99
      Cardiac-related mortality1.0% (0.4%-2.7%)

      (n = 4)
      0.3% (0.0%-1.8%) (n = 1).18
      Valve-related mortality0.0% (NA)

      (n = 0)
      0.0% (NA)

      (n = 0)
      NA
      Reintervention0.8% (0.2%-2.3%)

      (n = 3)
      0.0% (NA)

      (n = 0)
      .08
      Explant0.8% (0.2%-2.3%)

      (n = 3)
      0.0% (NA)

      (n = 0)
      .08
      Permanent pacemaker implantation2.3% (1.2%-4.3%)

      (n = 9)
      4.3% (2.7%-6.8%)

      (n = 17)
      .11
      Mean pressure gradient, mm Hg12.7 ± 4.413.5 ± 5.1.010
      Peak pressure gradient, mm Hg23.3 ± 7.924.6 ± 9.0.027
      EOA, cm21.55 (0.80-2.84)1.54 (0.70-3.01).99
      EOAi, cm2/m20.79 (0.38-1.41)0.79 (0.31-1.50).88
      Prosthesis-patient mismatch, n (%).87
       None158 (47.2)155 (45.2)
       Moderate127 (37.9)134 (39.1)
       Severe50 (14.9)54 (15.7)
      Clinical outcomes are reported as 5-year Kaplan–Meier event rates including 95% CI. Hemodynamic performance is presented either as mean ± SD or median (interquartile range). PVL, Paravalvular leak; NA, not available; EOA, effective orifice area; EOAi, effective orifice area indexed according to body surface area.
      P value from log rank test for all clinical outcomes and from an independent samples t test, Mann–Whitney U test, or χ2 test for echocardiographic data.
      Table E5Baseline and procedural characteristics in valve sizes <23 mm
      Pledgets (n = 131)Nonpledgets (n = 112)P value
      Age, y70.9 ± 7.173.4 ± 10.3.035
      Male sex51 (38.9)40 (35.7).61
      Body surface area, m21.8 ± 0.21.8 ± 0.2.19
      Body mass index29.3 ± 5.928.8 ± 6.6.49
      NYHA classification III-IV63 (48.1)54 (48.2).98
      STS risk of mortality, %2.1 ± 1.32.8 ± 1.9.002
      Diabetes42 (32.1)26 (23.2).13
      Hypertension99 (75.6)84 (75.0).92
      Peripheral vascular disease11 (8.4)7 (6.3).52
      Renal dysfunction/insufficiency12 (9.2)17 (15.2).15
      Stroke/CVA11 (8.4)5 (4.5).22
      COPD9 (6.9)13 (11.6).20
      Left ventricular ejection fraction, %62.7 ± 7.261.6 ± 7.1.35
      Coronary artery disease59 (45.0)44 (39.3).37
      Left ventricular hypertrophy55 (42.0)34 (30.4).06
      Atrial fibrillation10 (7.6)14 (12.5).21
      Isolated/mixed aortic stenosis126 (96.2)111 (99.1).22
      Minimally invasive surgical approach36 (27.9)22 (20.0).16
      Concomitant procedures
       None64 (48.9)73 (65.2).011
       CABG45 (34.4)28 (25.0).11
       Ascending aortic aneurysm not requiring circulatory arrest5 (3.8)0 (.0).06
       Other
      Includes implantable cardiac device, left atrial appendage closure, patent foramen ovale closure, resection of subaortic membrane not requiring myectomy, and dissection repair not requiring circulatory arrest.
      32 (24.4)18 (16.1).11
      Annular calcification111 (84.7)95 (84.8).98
      Total bypass time, min102.8 ± 37.593.1 ± 39.2.05
      Aortic crossclamp time, min78.6 ± 29.469.2 ± 31.3.017
      Valve size implanted.042
       17 mm0 (0.0)1 (.9)
       19 mm16 (12.2)23 (2.5)
       21 mm115 (87.8)88 (78.6)
      Mean pressure gradient, mm Hg42.9 ± 16.946.5 ± 17.3.11
      Effective orifice area, cm21.17 (0.65-2.14)1.17 (0.68-1.73).86
      Indexed effective orifice area, cm2/m20.38 (0.19-1.19)0.39 (0.20-1.22).74
      Data are presented as either mean ± SD, median (interquartile range), or n (%) and compared with the independent samples t test, Mann–Whitney U test, or χ2/Fisher exact test, respectively. NYHA, New York Heart Association; STS, Society of Thoracic Surgeons; CVA, cerebrovascular accident; COPD, chronic obstructive pulmonary disease; CABG, coronary artery bypass grafting.
      Includes implantable cardiac device, left atrial appendage closure, patent foramen ovale closure, resection of subaortic membrane not requiring myectomy, and dissection repair not requiring circulatory arrest.
      Table E6Baseline and procedural characteristics within the nonpledgeted subgroups
      Mattress
      The mattress group consisted of everting and noneverting mattress sutures.
      (n = 180)
      Nonmattress
      The nonmattress group comprised simple interrupted and continuous sutures.
      (n = 205)
      P value
      Age, y71.0 ± 8.672.3 ± 8.9.15
      Male sex134 (74.4)149 (72.7).70
      Body surface area, m22.0 ± 0.21.9 ± 0.2.14
      Body mass index29.2 ± 5.328.2 ± 5.1.046
      NYHA classification III-IV96 (53.3)82 (40.0).009
      STS risk of mortality, %2.2 ± 1.52.3 ± 1.7.50
      Diabetes56 (31.1)43 (21.0).023
      Hypertension140 (77.8)134 (65.4).007
      Peripheral vascular disease18 (10.0)17 (8.3).56
      Renal dysfunction/insufficiency26 (14.4)12 (5.9).005
      Stroke/CVA12 (6.7)4 (2.0).037
      COPD13 (7.2)30 (14.6).021
      Left ventricular ejection fraction, %59.9 ± 8.457.7 ± 11.5.06
      Coronary artery disease91 (50.6)70 (34.1).001
      Left ventricular hypertrophy56 (31.1)91 (44.4).008
      Atrial fibrillation29 (16.1)24 (11.7).21
      Isolated/mixed aortic stenosis175 (97.2)199 (97.1).93
      Minimally invasive surgical approach23 (12.9)27 (13.2).93
      Concomitant procedures
       None83 (46.1)133 (64.9)<.001
       CABG60 (33.3)59 (28.8).33
       Ascending aortic aneurysm not requiring circulatory arrest16 (8.9)5 (2.4).005
       Other
      Includes implantable cardiac device, left atrial appendage closure, patent foramen ovale closure, resection of subaortic membrane not requiring myectomy, and dissection repair not requiring circulatory arrest.
      41 (22.8)14 (6.8)<.001
      Annular calcification153 (85.0)167 (81.5).36
      Total bypass time, min103.3 ± 42.4103.2 ± 37.7.97
      Aortic crossclamp time, min79.4 ± 34.677.2 ± 30.7.51
      Valve size implanted.40
       17 mm1 (0.6)0 (0.0)
       19 mm6 (3.3)15 (7.3)
       21 mm41 (22.8)39 (19.0)
       23 mm64 (35.6)82 (4.0)
       25 mm53 (29.4)55 (26.8)
       27 mm13 (7.2)13 (6.3)
       29 mm2 (1.1)1 (0.5)
      Mean pressure gradient, mm Hg43.4 ± 16.845.2 ± 16.6.30
      Effective orifice area, cm20.78 (0.35-2.79)0.73 (0.38-3.43).41
      Indexed effective orifice area, cm2/m20.39 (0.20-1.65)0.38 (0.18-1.82).48
      Data are presented as either mean ± standard deviation, median (interquartile range), or n (%) and compared with the independent samples t test, Mann–Whitney U test, or χ2/Fisher exact test, respectively, except where otherwise noted. NYHA, New York Heart Association; STS, Society of Thoracic Surgeons; CVA, cerebrovascular accident; COPD, chronic obstructive pulmonary disease; CABG, coronary artery bypass grafting.
      The mattress group consisted of everting and noneverting mattress sutures.
      The nonmattress group comprised simple interrupted and continuous sutures.
      Includes implantable cardiac device, left atrial appendage closure, patent foramen ovale closure, resection of subaortic membrane not requiring myectomy, and dissection repair not requiring circulatory arrest.
      Table E7Hemodynamic performance at discharge up to 30 days and at 5 years of follow-up within the nonpledgeted subgroups
      Mattress
      The mattress group consisted of everting and noneverting mattress sutures.
      (n = 180)
      Nonmattress
      The nonmattress group comprised simple interrupted and continuous sutures.
      (n = 205)
      P value
      Mean pressure gradient, mm Hg
       Discharge up to 30 days13.2 ± 5.113.9 ± 5.0.18
       5 years12.5 ± 4.312.6 ± 4.1.84
      Peak pressure gradient, mm Hg
       Discharge up to 30 days23.8 ± 8.725.0 ± 9.1.20
       5 years22.4 ± 7.222.5 ± 8.2.90
      Effective orifice area, cm2
       Discharge up to 30 days1.60 (0.70-3.01)1.51 (0.80-2.64).16
       5 years1.44 (0.86-2.44)1.38 (0.79-2.44).20
      Indexed effective orifice area, cm2/m2
       Discharge up to 30 days0.79 (0.31-1.50)0.78 (0.41-1.62).44
       5 years0.78 (0.41-1.31)0.72 (0.45-1.18).25
      Prosthesis-patient mismatch
       Discharge up to 30 days.85
      None72 (46.8)77 (44.0)
      Moderate58 (37.7)71 (4.6)
      Severe24/154 (15.6)27/175 (15.4)
       5 years.60
      None22 (36.1)20 (28.2)
      Moderate27 (44.3)34 (47.9)
      Severe12 (19.7)17 (23.9)
      Paravalvular leak
       Discharge up to 30 days.46
      None125 (73.5)154 (77.8)
      Trace30 (17.6)32 (16.2)
      Mild15 (8.8)11 (5.6)
      Moderate0 (0.0)1 (.5)
      Severe0 (0.0)0 (.0)
       5 years.22
      None60 (88.2)70 (85.4)
      Trace3 (4.4)9 (11.0)
      Mild5 (7.4)3 (3.7)
      Moderate0 (0.0)0 (0.0)
      Severe0 (0.0)0 (0.0)
      Numerical data are presented as mean ± SD or median (interquartile range) according to their distribution, and categorical data are summarized as n (%); data were compared using the independent samples t test, Mann–Whitney U test, and χ2 test/Fisher exact test, respectively.
      The mattress group consisted of everting and noneverting mattress sutures.
      The nonmattress group comprised simple interrupted and continuous sutures.
      Figure thumbnail fx3
      Figure E1Consolidated Standards of Reporting Trials diagram of patients who underwent surgical aortic valve replacement with or without pledgeted sutures. The Avalus bioprosthesis is from Medtronic. SAVR, Surgical aortic valve replacement; PERIGON, PERIcardial SurGical AOrtic Valve ReplacemeNt; AVR, aortic valve replacement.
      Figure thumbnail fx4
      Figure E2Hemodynamic performance over time according to the use of pledgets for patients who underwent aortic valve replacement in the propensity score-matched cohort. The box plots depict the (A) mean aortic gradient and (B) effective orifice area over time. Data are core lab reported. The boxes are centered at the median, with upper and lower bounds of the box being the 75th and 25th percentiles, respectively. The upper and lower ends of the whiskers represent maximum and minimum values. The circle represents the mean.

      References

        • D'Agostino R.S.
        • Jacobs J.P.
        • Badhwar V.
        • Fernandez F.G.
        • Paone G.
        • Wormuth D.W.
        • et al.
        The Society of Thoracic Surgeons Adult Cardiac Surgery database: 2019 update on outcomes and quality.
        Ann Thorac Surg. 2019; 107: 24-32
        • Englberger L.
        • Schaff H.V.
        • Jamieson W.R.
        • Kennard E.D.
        • Im K.A.
        • Holubkov R.
        • et al.
        Importance of implant technique on risk of major paravalvular leak (PVL) after St. Jude mechanical heart valve replacement: a report from the Artificial Valve Endocarditis Reduction Trial (AVERT).
        Eur J Cardio Thorac Surg. 2005; 28: 838-843
        • LaPar D.J.
        • Ailawadi G.
        • Bhamidipati C.M.
        • Singh M.
        • Dare D.
        • Kern J.A.
        • et al.
        Use of a nonpledgeted suture technique is safe and efficient for aortic valve replacement.
        J Thorac Cardiovasc Surg. 2011; 141: 388-393
        • Tabata M.
        • Shibayama K.
        • Watanabe H.
        • Sato Y.
        • Fukui T.
        • Takanashi S.
        Simple interrupted suturing increases valve performance after aortic valve replacement with a small supra-annular bioprosthesis.
        J Thorac Cardiovasc Surg. 2014; 147: 321-325
        • Ugur M.
        • Byrne J.G.
        • Bavaria J.E.
        • Cheung A.
        • Petracek M.
        • Groh M.A.
        • et al.
        Suture technique does not affect hemodynamic performance of the small supra-annular Trifecta bioprosthesis.
        J Thorac Cardiovasc Surg. 2014; 148: 1347-1351
        • Kim H.H.
        • Lee S.
        • Joo H.C.
        • Kim J.H.
        • Youn Y.N.
        • Yoo K.J.
        • et al.
        Impact of suture techniques for aortic valve replacement on prosthesis-patient mismatch.
        Ann Thorac Surg. 2020; 109: 661-667
        • Klautz R.J.M.
        • Kappetein A.P.
        • Lange R.
        • Dagenais F.
        • Labrousse L.
        • Bapat V.
        • et al.
        Safety, effectiveness and haemodynamic performance of a new stented aortic valve bioprosthesis.
        Eur J Cardio Thorac Surg. 2017; 52: 425-431
        • Sabik III, J.F.
        • Rao V.
        • Lange R.
        • Kappetein A.P.
        • Dagenais F.
        • Labrousse L.
        • et al.
        One-year outcomes associated with a novel stented bovine pericardial aortic bioprosthesis.
        J Thorac Cardiovasc Surg. 2018; 156: 1368-1377.e5
        • Généreux P.
        • Piazza N.
        • Alu M.C.
        • Nazif T.
        • Hahn R.T.
        • Pibarot P.
        • et al.
        Valve Academic Research Consortium 3: updated endpoint definitions for aortic valve clinical research.
        Eur Heart J. 2021; 42: 1825-1857
        • Vriesendorp M.D.
        • Deeb G.M.
        • Reardon M.J.
        • Kiaii B.
        • Bapat V.
        • Labrousse L.
        • et al.
        Why the categorization of indexed effective orifice area is not justified for the classification of prosthesis-patient mismatch.
        J Thorac Cardiovasc Surg. 2022; 164: 822-829.e6
        • Vriesendorp M.D.
        • Groenwold R.H.H.
        • Herrmann H.C.
        • Head S.J.
        • De Lind Van Wijngaarden R.A.F.
        • Vriesendorp P.A.
        • et al.
        The clinical implications of body surface area as a poor proxy for cardiac output.
        Structural Heart. 2021; 5: 582-587
        • Velders B.J.J.
        • Vriesendorp M.D.
        • Herrmann H.C.
        • Klautz R.J.M.
        The ratio fallacy of prosthesis-patient mismatch.
        JACC Cardiovasc Interv. 2022; 15: 901
        • Kirali K.
        • Yerlikhan Ö.A.
        Conventional aortic valve surgery (open surgical approaches).
        in: Ţintoiu I.C. Ursulescu A. Elefteriades J.A. Underwood M.J. Droc I. New Approaches to Aortic Diseases from Valve to Abdominal Bifurcation. Academic Press, 2018: 257-275