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Survival after aortic root replacement with a stentless xenograft is determined by patient characteristics

Open AccessPublished:July 16, 2021DOI:https://doi.org/10.1016/j.jtcvs.2021.07.011

      Abstract

      Objectives

      Our objective was to examine intermediate-term survival and reinterventions in unselected patients, stratified according to indication, who received a Freestyle (Medtronic Inc, Minneapolis, Minn) bioprosthesis as a full aortic root replacement.

      Methods

      Data from medical records were retrospectively collected for patients who had aortic root replacement using Freestyle bioprostheses between 1999 and 2018 at 6 North-Atlantic centers. Survival status was extracted from national registries and results stratified according to indication for surgery.

      Results

      We included 1030 implantations in 1008 patients with elective indications for surgery: aneurysm (39.8%), small root (8.3%), and other (13.8%), and urgent/emergent indications: endocarditis (26.7%) and Stanford type A aortic dissection (11.4%). Across indications, 46.3% were nonelective cases and 34.0% were reoperations. Median age was 66.0 (interquartile range, 58.0-71.8) years and median follow-up was 5.0 (interquartile range, 2.6-7.9) years. Thirty-day mortality varied from 2.9% to 27.4% depending on indication. Intermediate survival for 90-day survivors with elective indications were not different from the general population standardized for age and sex (P = .95, .83, and .16 for aneurysms, small roots, and other, respectively). In contrast, patients with endocarditis and type A dissection had excess mortality (P < .001). Freedom from valve reinterventions was 95.0% and 94.4% at 5 and 8 years, respectively. In all, 52 patients (5.2%) underwent reinterventions, most because of endocarditis.

      Conclusions

      At intermediate term follow-up this retrospective study provides further support for the use of the Freestyle bioprosthesis in the real-world setting of diverse, complex, and often high-risk aortic root replacement and suggests that outcome is determined by patient and disease, rather than by prosthesis, characteristics.

      Graphical abstract

      Key Words

      Abbreviations and Acronyms:

      BMI (body mass index), CI (confidence interval), CT (computed tomography), EuroSCORE (European System for Cardiac Operative Risk Evaluation), PVE (prosthetic valve infective endocarditis)
      Figure thumbnail fx2
      Survival after aortic root replacement with the Freestyle bioprosthesis (Medtronic Inc, Minneapolis, Minn) versus the Danish general population.
      Survival after Freestyle (Medtronic Inc, Minneapolis, Minn) bioprosthesis aortic root replacement resembles the general population for low-risk cases; outcome is thus explained by patient- and disease-related factors rather than the prosthesis per se.
      This study provides support for the use of the Freestyle (Medtronic Inc, Minneapolis, Minn) bioprosthesis in the diverse indications in the real-world setting of often high-risk aortic root replacement. Our data corroborate the notion that indication influences outcome greatly and show that prosthesis characteristics are compatible with intermediate-term survival in low-risk cases corresponding to the general population.
      See Commentaries on pages 1725 and 1726.
      The Freestyle bioprosthesis (Medtronic Inc, Minneapolis, Minn) is a stentless porcine aortic root xenograft prosthesis that can be used in patients with a range of severe aortic root diseases. These include aneurysms, aortic dissections, and aortic root or prosthetic valve endocarditis, but also in patients in whom aortic root replacement solves technically complex problems such as small annuli and reoperative surgery of the aortic root or valve.
      • Erbel R.
      • Aboyans V.
      • Boileau C.
      • Bossone E.
      • Bartolomeo R.D.
      • Eggebrecht H.
      • et al.
      2014 ESC guidelines on the diagnosis and treatment of aortic diseases: document covering acute and chronic aortic diseases of the thoracic and abdominal aorta of the adult. The task force for the diagnosis and treatment of aortic diseases of the European Society of Cardiology (ESC).
      • Harky A.
      • Wong C.H.M.
      • Hof A.
      • Froghi S.
      • Ahmad M.U.
      • Howard C.
      • et al.
      Stented versus stentless aortic valve replacement in patients with small aortic root: a systematic review and meta-analysis.
      • Habib G.
      • Lancellotti P.
      • Antunes M.J.
      • Bongiorni M.G.
      • Casalta J.P.
      • Del Zotti F.
      • et al.
      2015 ESC guidelines for the management of infective endocarditis: The task force for the management of infective endocarditis of the European Society of Cardiology (ESC). Endorsed by: European Association for Cardio-Thoracic Surgery (EACTS), the European Association of Nuclear Medicine (EANM).
      Stentless xenografts have superior hemodynamics compared with most stented bioprostheses and the Freestyle has shown equal durability and survival compared with other bioprostheses at up to 15 years follow-up.
      • Habib G.
      • Lancellotti P.
      • Antunes M.J.
      • Bongiorni M.G.
      • Casalta J.P.
      • Del Zotti F.
      • et al.
      2015 ESC guidelines for the management of infective endocarditis: The task force for the management of infective endocarditis of the European Society of Cardiology (ESC). Endorsed by: European Association for Cardio-Thoracic Surgery (EACTS), the European Association of Nuclear Medicine (EANM).
      • Bach D.S.
      • Kon N.D.
      Long-term clinical outcomes 15 years after aortic valve replacement with the Freestyle stentless aortic bioprosthesis.
      • El-Hamamsy I.
      • Clark L.
      • Stevens L.M.
      • Sarang Z.
      • Melina G.
      • Takkenberg J.J.
      • et al.
      Late outcomes following Freestyle versus Homograft aortic root replacement.
      • Melina G.
      • De Robertis F.
      • Gaer J.A.
      • Angeloni E.
      • El-Hamamsy I.
      • Bahrami T.
      • et al.
      Long-term survival after xenograft versus homograft aortic root replacement: results from a prospective randomized trial.
      However, the existing literature primarily regards selected populations from highly specialized centers. Hence, Freestyle performance in the most common setting of small-to-medium sized centers with unselected patients has not been determined. We therefore conducted a study including 6 North Atlantic institutions. The objective was to examine clinical outcomes, including overall survival and reinterventions, after Freestyle aortic root replacement, stratified according to indication.

      Methods

      Study Design and Patients

      This observational study included Freestyle aortic root replacements from 1999 to 2018 at 6 institutions: Rigshospitalet, University Hospital of Copenhagen (Copenhagen), Denmark; Karolinska University Hospital (Stockholm), Sweden; Haukeland University Hospital (Bergen), Norway; Linköping University Hospital (Linköping), Sweden; Montreal Heart Institute (Montreal), Canada; and Landspítali University Hospital of Iceland (Reykjavik), Iceland. The participating centers were sole providers of cardiac surgery in each health region. The inclusion criterion was full root implantation of a Freestyle prosthesis in the aortic position. Patients were identified in local registries and those lost to follow-up within 30 days were excluded, thus including patients who died or had a reintervention before 30 days. Medical records were reviewed for baseline and perioperative data. The study was conducted in accordance with the Declaration of Helsinki, and ethical approval was obtained for all sites (Appendix E1).

      Surgical Indications and Technique

      We categorized surgical indications to reflect differences in patient characteristics and operative complexity. Primarily elective categories were: (1) aortic root aneurysm (aneurysm), (2) aortic valve replacement in patients with a small aortic annulus and risk of prosthesis-patient mismatch (small root), (3) predominantly reoperative aortic valve surgery or bail-out solution after failed attempted aortic root or valve procedures, both a priori characterized by long cross-clamp time and technical complexity (other). Urgent categories were: (4) native or prosthetic (PVE) valve infective endocarditis, aortic root abscess formation, or a combination (endocarditis, shown in Video 1); and (5) Stanford type A aortic dissection requiring aortic root replacement (type A dissection). The Freestyle was implanted using a modified Bentall approach with the proximal suture line technique and orientation performed at the surgeon's discretion. Running sutures were used for the coronary buttons and also for the anastomosis distal to the native ascending aorta or to a vascular prosthesis.

      Institutional Characteristics and Practice

      The participating institutions have a yearly volume varying between institutions and over time from 200 to approximately 2000 adult cardiac surgery cases per year and 2-10 surgeons per institution, giving a case load per surgeon ranging from 50 to 300 per year. In all centers, aortic root replacement might be performed by any on-staff surgeon, but complex cases as well as elective aortic root surgery have to a varying degree been concentrated on fewer hands. All participating institutions had the possibility of using a homograft, but most lacked in-house supply throughout the study period and thus generally needed to order a homograft in advance for the specific case. Montreal had access to homografts at all times, Bergen had a local homograft storage up to 2009, and Copenhagen keeps a small storage of only a few grafts in different sizes. The choice ultimately falls on the surgeon. The strategy for postoperative anticoagulation and antiplatelet therapy is similar across institutions; in recent times biological prostheses including the Freestyle patients are only given acetylsalicylic acid but in the first part of the study most institutions gave 2-3 months of warfarin treatment. None of the institutions has differentiated the Freestyle from other biological prostheses in their anticoagulant or antiplatelet regimens.

      Outcomes

      Early complications were reoperation for bleeding or tamponade, perioperative myocardial infarction as defined in Valve Academic Research Consortium-2, postoperative cerebrovascular events, and permanent pacemaker implantation within 30 days from surgery (see definitions in the Appendix E1).
      • Kappetein A.P.
      • Head S.J.
      • Genereux P.
      • Piazza N.
      • van Mieghem N.M.
      • Blackstone E.H.
      • et al.
      Updated standardized endpoint definitions for transcatheter aortic valve implantation: the Valve Academic Research Consortium-2 consensus document.
      Survival status was extracted from civil registries, which guarantee complete and accurate status for domestic residents, except for very recent deaths, which might be registered with a few weeks' delay. Reinterventions were found according to medical record review up until 2019 and divided into those that were secondary to prosthetic valve failure (valve-related) or those caused by coronary artery pathology (coronary). Pseudoaneurysm formation in relation to the Freestyle bioprosthesis was considered valve-related. Because Copenhagen is a national referral site for complex cases, complete Copenhagen reintervention data was ensured using the civil registry number to cross-link with the Danish National Patient Registry in addition to the medical record review. Patients from Copenhagen or Montreal who were also included in a cross-sectional analysis with cardiac computed tomography (CT) were followed up to the date of the study CT imaging, thus not including findings on the CT imaging or ensuing clinical events, all of which have been previously reported.
      • Dagnegård H.H.
      • Sigvardsen P.E.
      • Ihlemann N.
      • Kofoed K.F.
      • El-Hamamsy I.
      • Bekke K.
      • et al.
      Structural abnormalities after aortic root replacement with stentless xenograft.

      Statistical Analysis

      Continuous variables are presented as median with interquartile range, and categorical variables are presented as percentages and frequencies. Body mass index (BMI) is presented as categorical and continuous data. Patients lost to follow-up were censored at the time of their last clinical visit. Kaplan-Meier estimated survival curves were truncated when a minimum of 10% of the group remained at risk and compared using a log rank test. Significant time interaction between indication and time compromised the proportional hazards assumption. We therefore performed a post hoc landmark analysis (ie, survival of all patients up to 90 days after surgery, and for 90 day-survivors to end of follow-up). Cumulative risk of reintervention was visualized using the Aalen-Johansen estimator with death as competing risk. Hazard ratios and 95% confidence intervals (CIs) were estimated using Cox regression, and follow-up time was truncated when all groups had at least 10% remaining at risk. Results were stratified according to indication. Adjusted analysis of the full cohort was enabled using multiple imputation (10 data sets) of missing values (<5%) using fully conditional specification and chained equations (Stef van Buuren, 2020; mice: multivariate imputation by chained equations. R package version 3.9.0) with the use of Rubin's rule, and conditioned on event, event times, and variables known to influence survival and durability: indication, age, center for surgery, sex, preoperative significant coronary artery disease, presence of atrial fibrillation, and estimated glomerular filtration rate. The Danish general population was chosen as a representative reference for the entire study population; survival was obtained from the Human Mortality Database, and standardized for sex, age, and date of birth through the R package CuRe (Lasse Hjort Jakobsen, 2020; CuRe: parametric cure model estimation. R package version 1.0.0.), and compared with study data using the log rank test. Subgroup analysis of survival was performed per sex. All analyses were performed with R version 3.6.1 (R Foundation for Statistical Computing, Vienna, Austria).

      Results

      We included 1030 implantations in 1008 patients (Copenhagen, n = 445; Stockholm, n = 208; Bergen, n = 143; Linköping, n = 98; Montreal, n = 94; and Reykjavik, n = 43). Seven patients were excluded because of unavailable records or <30 days to censoring. Twenty-five nonresidents and emigrants were lost to follow-up (2.5%). Median follow-up of survival was 5.0 years (interquartile range, 2.6-7.9; total range, 0-17.5 years). Elective indication frequencies were: aneurysm 39.8% (n = 410), small root 8.3% (n = 86), and other 13.8% (n = 142). Nonelective were: endocarditis 26.7% (n = 275; of these 46.5% had PVE with root abscess, 24.0% had PVE without abscess, and 25.8% had native valve infective endocarditis with root abscess), and type A dissection (11.4%, n = 117). All indications were represented at all centers, but with varying distribution (Figure E1). Median age was 66.0 years (interquartile range, 58.0-71.8 years); 31.4% of the patients were 60 years or younger. The proportion of nonelective surgery was 46.3%, and 34.0% were reoperations. Tables 1 and E1 shows baseline characteristics per indication, Tables E2 and E3 show them according to sex, and preoperative characteristics are shown in Tables 2 and E4.
      Table 1Preoperative patient characteristics according to indication for unselected aortic root replacement with the Freestyle bioprosthesis at 6 North-Atlantic centers
      % (N)AneurysmSmall rootOtherEndocarditisType A dissectionAllP value
      100 (410)100 (86)100 (141)100 (276)100 (117)100 (1030)
      Age, y
       Median (IQR)67.0 (61.0-72.0)68.0 (58.2-73.0)65 (55.2-71.0)63.0 (51.5-71.0)66.0 (60.0-71.0)66 (58.0-71.8)<.0001
       Range22-8518-8424-8614-8633-8214-86
      Age <60 y22.4 (92)26.7 (23)42.3 (60)42.2 (116)27.4 (32)31.4 (323)<.0001
      Male sex72.2 (296)22.1 (19)57.7 (82)81.8 (225)67.5 (79)68.1 (701)<.0001
      Median BMI (IQR)26.1 (231-28.7)26.2 (23.5-30.5)25.8 (23.2-30.8)25.5 (23.0-29.0)25.5 (23.4-28.0)25.9 (23.13-29.0)
      BMI according to category.08
       <205.2 (21)5.9 (5)4.4 (6)5.3 (14)6.4 (7)5.3 (53)
       20-3077.9 (313)65.9 (56)67.2 (92)75.3 (198)78.2 (86)74.7 (745)
       >3016.9 (68)28.2 (24)28.5 (39)19.4 (51)15.5 (17)20.0 (199)
      Median eGFR (IQR), mL/min78 (64.9-97.6)71 (56.4-85.3)75.4 (61.2-97.1)77.4 (52.7-90.0)71.8 (57.5-82.0)76 (60-90).0006
      Dialysis0.2 (1)1.2 (1)0.7 (1)8.1 (22)0.9 (1)2.5 (26)<.0001
      Diabetes mellitus5.9 (24)15.1 (13)9.9 (14)14.0 (38)3.4 (4)9.1 (93).0002
      Insulin-dependent diabetes1.5 (6)3.5 (3)2.8 (4)2.6 (7)0.9 (1)2.0 (21).52
      Hypertension65.0 (265)59.3 (51)63.4 (90)51.9 (137)60.3 (70)60.3 (613)<.0001
      Hypercholesterolemia42.8 (161)52.9 (45)48.2 (67)35.4 (87)30.5 (32)41.2 (392).002
      Atrial fibrillation17.8 (73)14.1 (12)22.9 (32)27.0 (70)16.2 (19)20.4 (206).01
      Coronary artery disease23.3 (94)33.7 (29)29.7 (41)21.7 (57)12.2 (14)23.4 (235).002
      Chronic lung disease13.3 (54)15.3 (13)11.3 (16)9.6 (26)14.5 (17)12.3 (126).46
      Previous cerebrovascular disease9.0 (37)14.0 (12)14.9 (21)24.3 (66)15.4 (18)15.0 (154)<.0001
      Peripheral vascular disease4.6 (19)9.3 (8)6.4 (9)5.2 (14)5.1 (6)5.5 (56).51
      Bicuspid valve40.9 (167)15.1 (13)15.9 (22)14.3 (39)7.7 (9)24.5 (250)<.0001
      Previous cardiac surgery9.3 (38)9.3 (8)73.9 (105)68.6 (188)9.5 (11)34.0 (350)<.0001
       Aortic surgery8.3 (34)2.4 (2)64.8 (92)64.2 (176)7.8 (9)30.5 (313)
       CABG1.2 (5)0.0 (0)10.6 (15)8.5 (23)1.7 (2)4.4 (45)
       Other0.2 (1)7.0 (6)7.0 (10)4.4 (12)0.0 (0)2.8 (29)
      Previous endocarditis1.7 (7)0.0 (0)14.8 (21)28.2 (77)0.9 (1)10.3 (106)<.0001
      Aortic valve lesion<.0001
       Severe aortic regurgitation64.4 (264)10.5 (9)33.1 (47)33.5 (92)50.4 (59)45.7 (471)
       Severe aortic stenosis17.6 (72)74.4 (64)43.7 (62)14.5 (40)2.6 (3)23.4 (241)
       Mixed lesion0.5 (2)5.8 (5)0.0 (0)0.4 (1)0.0 (0)0.8 (8)
       Competent valve10.7 (44)3.5 (3)9.9 (14)13.8 (38)18.8 (22)11.7 (121)
       Unreported6.8 (28)5.8 (5)13.4 (19)37.8 (104)28.2 (33)18.3 (189)
      LVEF
       Median (IQR), %55 (47-60)60 (55-65)55 (46-60)50 (45-60)55 (50-60)55 (50-60)<.0001
       Range15-7325-8010-7015-8325-6510-83
      NYHA class<.0001
       I34.2 (127)13.0 (10)11.5 (15)23.6 (41)31.7 (20)26.1 (213)
       II40.4 (150)41.6 (32)32.3 (42)20.7 (36)14.3 (9)33.0 (269)
       III-IV25.3 (94)45.5 (35)56.2 (73)55.7 (97)54.0 (34)40.9 (333)
      Surgical priority<.0001
       Elective89.8 (368)89.5 (77)58.2 (82)5.5 (15)7.7 (9)53.7 (551)
       Urgent, emergent, or salvage10.2 (42)10.5 (9)41.8 (59)94.5 (258)92.3 (108)46.3 (476)
      Cardiogenic shock0.0 (0)0.0 (0)3.5 (5)1.8 (5)10.3 (12)2.1 (22)<.0001
      EuroSCORE II
       Median (IQR), %2.4 (1.5-4.2)3.2 (1.9-6.6)8.4 (4.3-16.2)16.7 (10.3-27.8)5.6 (3.5-10.4)5.2 (2.4-13.1)<.0001
       Range1.0-55.81.1-48.11.0-77.31.8-74.21.2-59.11.0-77.3
      All data are reported as % (n) except where otherwise noted. For missing values, see Table E1. IQR, Interquartile range; BMI, body mass index; eGFR, estimated glomerular filtration rate calculated using the Cockcroft-Gault formula; CABG, coronary artery bypass graft; LVEF, left ventricular ejection fraction; NYHA, New York Heart Association functional classification; EuroSCORE, European System for Cardiac Operative Risk Evaluation.
      Table 2Preoperative characteristics according to indication for unselected aortic root replacement with the Freestyle bioprosthesis at 6 North Atlantic centers
      % (N)AneurysmSmall rootOtherEndocarditisType A dissectionAllP value
      100 (410)100 (86)100 (141)100 (276)100 (117)100 (1030)
      Isolated aortic root replacement, % (n)20.6 (84)45.3 (39)45.1 (64)40.7 (111)4.3 (5)29.5 (303)<.0001
      Concomitant procedure, % (n)79.4 (324)54.7 (47)54.9 (78)59.3 (162)95.7 (112)70.5 (723)<.0001
       Ascending aorta only44.6 (182)9.3 (8)15.5 (22)9.5 (26)46.2 (54)28.5 (292)
       CABG (with or without asc ao)
      Including planned and unplanned CABG at the same occasion.
      12.3 (50)25.6 (22)15.5 (22)10.3 (28)17.1 (20)13.8 (142)
       Aortic arch surgery10.8 (44)1.2 (1)2.8 (4)2.2 (6)24.8 (29)8.2 (84)
       Other concomitant procedure13.3 (54)18.6 (16)22.0 (31)37.7 (103)9.4 (11)21.0 (215)
      Implanted valve size in mm, % (n)<.0001
       190.0 (0)5.8 (5)1.4 (2)1.1 (3)0.9 (1)1.1 (11)
       212.7 (11)32.6 (28)17.6 (25)7.3 (20)6.0 (7)8.8 (91)
       2312.0 (49)44.2 (38)26.8 (38)22.2 (61)20.5 (24)20.4 (210)
       2524.1 (99)12.8 (11)28.9 (41)31.6 (87)33.3 (39)26.9 (277)
       2736.6 (150)4.7 (4)14.8 (21)21.1 (58)27.4 (32)25.7 (265)
       2923.4 (96)0.0 (0)5.6 (8)9.5 (26)8.5 (10)13.6 (140)
       Not noted1.2 (5)0.0 (0)4.9 (7)7.3 (20)3.4 (4)3.5 (36)
      Suture technique proximal Freestyle anastomosis, % (n)<.0001
       Running57.3 (235)79.1 (68)47.9 (68)45.1 (124)41.9 (49)52.8 (544)
       Pledgeted U sutures36.1 (148)14.0 (12)33.8 (48)26.5 (73)53.8 (63)33.4 (344)
       Other4.4 (18)4.7 (4)11.3 (16)18.2 (50)1.7 (2)8.7 (90)
       Not noted2.2 (9)2.3 (2)7.0 (10)10.2 (28)2.6 (3)5.0 (52)
      Median cross-clamp time (IQR), min116 (95-138)109 (86-135)147 (112-186)160 (122-198)155 (123-188)130 (103-172)<.0001
       Isolated aortic root replacement104 (88-120)88 (77-112)123 (102-171)127 (109-158)122 (122-134)116 (92-142)
       Concomitant asc ao only112 (95-131)116 (97-123)156 (130-185)182 (161-222)143 (121-173)123 (101-152)
       Concomitant CABG (with or without asc ao)133 (114-172)122 (104-150)134 (123-173)174 (149-200)161 (120-219)144 (117-180)
       Concomitant aortic arch surgery122 (102-162)85 (85-85)266 (247-278)180 (160-193)163 (144-223)152 (118-188)
       Other concomitant procedure129 (90-171)136 (109-152)177 (148-216)192 (142-235)163 (147-187)166 (125-215)
      Median CPB time (IQR)150 (124-187)139 (110-184)196 (155-264)225 (176-287)255 (206-317)181 (139-246)<.0001
       Isolated aortic root replacement125 (113-163)109 (95-137)175 (143-230)180 (149-228)175 (170-233)166 (121-201)
       Concomitant ascending aorta only144 (124-166)136 (117-148)205 (149-269)250 (196-281)242 (201-281)162 (132-217)
       Concomitant CABG (with or without asc ao)179 (147-247)179 (147-204)192 (181-243)254 (215-298)309 (210-399)211 (160-280)
       Concomitant aortic arch surgery191 (149-236)152 (152-152)337 (325-365)328 (289-362)263 (215-340)235 (177-314)
       Other concomitant procedure177 (130-220)168 (133-198)256 (185-313)260 (201-344)305 (269-370)228 (170-308)
      For missing values, see Table E4. CABG, Coronary artery bypass grafting; asc, ascending; ao, aorta; IQR, interquartile range; CPB, cardiopulmonary bypass.
      Including planned and unplanned CABG at the same occasion.

      Overall Survival

      Figure 1 shows Kaplan-Meier survival curves and landmark analyses. Thirty-day mortality rates were 2.9% for aneurysm, 9.3% for small root, 11.2% for other, 14.6% for endocarditis, and 27.4% for type A dissection (Table 3). Survival of the standardized Danish general population overlapped the intermediate-term survival for 90-day survivors of the elective indications (aneurysm, small root, and other), whereas patients with endocarditis and type A dissection had excess mortality, also for 90-day survivors (Figures 1 and E2). Subgroup-analysis of survival according to sex showed similar trends per indication (Figure E3).
      Figure thumbnail gr1
      Figure 1Survival after unselected aortic root replacement with the Freestyle (Medtronic Inc, Minneapolis, Minn) bioprosthesis, according to indication. These 1008 patients underwent aortic root replacement with a stentless xenograft at 6 North Atlantic centers. Survival status follow-up was 100% complete. Survival was stratified for indication for root replacement; curves are truncated at 10% remaining at risk in each indication group, vertical ticks represent censor points and the 95% confidence interval (CI) is visualized as shading. The stapled line represents survival for the age-, sex-, and birth date-standardized Danish general population. A, Kaplan-Meier survival curves. B, Landmark analysis with cutoff at 90 days postoperatively. C, Crude and adjusted hazard ratios (HRs) obtained using Cox proportional hazards regression for overall survival, truncated at 9.61 years where all indications have 10% of patients remaining at risk, at 90 days and at 0.25-9.61 years, respectively. Diss, Dissection; a-fib, atrial fibrillation; eGFR, estimated glomerular filtration rate.
      Table 3Kaplan-Meier analysis of all-cause death after unselected aortic root replacement with the Freestyle bioprosthesis
      % (N)AneurysmSmall rootOtherEndocarditisType A dissectionAll
      100 (410)100 (86)100 (142)100 (275)100 (117)100 (1030)
      % (n)95% CI% (n)95% CI% (n)95% CI% (n)95% CI% (n)95% CI% (n)95% CI
      Early mortality, % (n deaths)
       Periprocedural (<72 h)0.7 (3)0.0-1.62.3 (2)0.0-5.58.2 (11)3.6-12.910.3 (27)6.7-14.020.5 (24)13.2-27.86.6 (67)5.1-8.2
       30-d2.9 (12)1.3-4.69.3 (8)3.2-15.411.2 (15)5.9-16.514.6 (38)10.3-18.827.4 (32)19.3-35.410.4 (105)8.5-12.3
       90-d3.7 (15)1.8-5.510.5 (9)4.0-16.912.7 (17)7.1-18.318.8 (49)14.0-23.531.6 (37)23.2-40.012.6 (127)10.6-14.6
      Late survival, % (n deaths)
       1 y95.4 (19)93.3-97.487.1 (11)80.0-94.285.1 (20)79.0-91.176.2 (62)71.1-81.465.0 (41)56.3-73.684.8 (153)82.6-87.0
       3 y91.3 (35)88.5-94.083.4 (14)75.4-91.383.5 (22)77.2-89.869.0 (80)63.4-74.762.3 (44)53.6-71.180.4 (195)77.9-82.9
       5 y87.7 (47)84.5-91.081.4 (15)72.7-90.177.4 (28)69.9-84.959.3 (100)53.1-65.653.6 (52)44.1-63.074.4 (242)71.6-77.2
       7.5 y80.6 (64)76.1-85.181.4 (15)72.7-90.171.8 (32)63.1-80.654.6 (106)47.7-61.446.4 (56)35.9-56.968.6 (273)65.3-71.8
       10 y71.5 (77)65.4-77.765.8 (18)83.3-48.264.7 (35)53.6-75.851.5 (108)43.8-59.2NA
      Number at risk <10% and therefore not reported.
      61.2 (296)57.1-65.3
      CI, Confidence interval; NA, nonapplicable.
      Number at risk <10% and therefore not reported.

      Reinterventions

      Fifty-two patients (5.2%) had valve-related reinterventions during follow-up (Figure 2, A), most occurred among the endocarditis patients. There were 29 (2.9%) reinterventions because of endocarditis including 20 cases with recurrent infection. Thirteen reinterventions (1.3%) were because of pseudoaneurysms and 8 (0.8%) were because of structural valve deterioration (all of them with aortic regurgitation). One reintervention (0.1%) was because of valve thrombosis. Three valve-related interventions were performed as transcatheter valve-in-valve procedures.
      Figure thumbnail gr2
      Figure 2Valve-related and coronary reinterventions occurring after unselected aortic root replacement with the Freestyle (Medtronic Inc, Minneapolis, Minn) bioprosthesis, according to indication of index Freestyle implantation. This observational study included 1008 patients from 6 North Atlantic centers. Freedom from reintervention was estimated by Aalen-Johansen analysis with death as competing risk (reported in ) stratified for indication for root replacement; curves are truncated at 10% remaining at risk in each indication group, vertical ticks represent censor points, and the 95% confidence interval (CI) is visualized as shading. A, Freedom from valve-related reinterventions including valve dysfunction, pseudoaneurysms, endocarditis, and thromboses requiring reintervention. B, Freedom from coronary reinterventions including percutaneous interventions and coronary artery bypass grafting. C, Crude and adjusted hazard ratios (HRs) obtained using Cox proportional hazards regression. Adjusted according to age at surgery, center for surgery, ischemic heart disease, atrial fibrillation (a-fib), estimated glomerular filtration rate (eGFR), valve size, and suture technique.
      Overall freedom from valve-related reinterventions was 95.0 (95% CI, 93.6-96.5) at 5 years and 94.4% (95% CI, 92.6-96.1) at 8 years. Eighteen patients (1.8%) had postoperative coronary revascularizations (Figure 2, B). Nine of these occurred early (0-42 days postoperatively), among patients operated for small root (n = 4), aneurysm (n = 3), and endocarditis (n = 2). All early revascularizations were in patients with confirmed or suspected proximal coronary lesions. The remaining 9 occurred for all indications in 0.4-5.8 years postoperatively; the coronary lesions were distal (n = 2), proximal (n = 5), or combined (n = 2). Eight patients had known survival status but unknown revascularization status because of inaccessible records and were lost-to-follow-up for this analysis.

      Early Complications

      Perioperative myocardial infarction occurred in 11 (13.3%) patients with small roots; other groups ranged from 3.2% to 9.0% (Table 4). Four patients had their prosthesis replaced early because of continued bleeding (n = 1) or early suspicion of recurrent endocarditis (n = 3).
      Table 4Early complications
      Within 30 days from surgery.
      after unselected aortic root replacement with the Freestyle bioprosthesis
      %, NAneurysmSmall rootOtherEndocarditisType A dissectionAll
      100 (410)100 (86)100 (142)100 (275)100 (117)100 (1030)
      Early reoperation for bleeding or tamponade, % (n)10.7 (44)2.3 (2)16.2 (23)15.6 (43)27.4 (32)14.0 (144)
      Median ICU stay (IQR), d1 (1-2)1 (1-3)2 (1-5)2 (1-6)4 (1-8)1 (1-4)
       Missing (n)112710030
      Perioperative myocardial infarction, % (n)
      VARC-2-criteria.
      3.2 (13)13.3 (11)6.7 (9)3.6 (9)9.0 (9)5.2 (51)
       Missing (n)738231758
      Postoperative cerebrovascular event, % (n)
      Defined as all new-onset neurological symptoms, including TIA.
      5.2 (21)3.7 (3)6.0 (8)10.2 (26)22.4 (22)8.2 (80)
       Missing (n)648211958
      Permanent pacemaker implantation, % (n)4.7 (19)7.5 (6)19.4 (26)23.6 (60)5.1 (5)12.0 (116)
       Missing (n)968211862
      ICU, Intensive care unit; IQR, interquartile range.
      Within 30 days from surgery.
      VARC-2-criteria.
      Defined as all new-onset neurological symptoms, including TIA.

      Discussion

      In this report we describe the outcomes in to our knowledge, the largest published Freestyle aortic root replacement cohort, so far. It testifies to the wide range of aortic root pathologies for which this stentless bioprosthesis is used. Furthermore, because survival of aneurysm patients was similar to the general population, outcome seems determined by patient, more than by prosthesis, characteristics. A summary of the study is shown Figure 3. Our findings reflect a heterogenous cohort of diverse and high-risk patients, represented by the various indication groups, most of which are characterized by well known risk factors for adverse outcome, including nonelective, reoperative, concomitant, and endocarditis surgery.
      • Di Marco L.
      • Pacini D.
      • Pantaleo A.
      • Leone A.
      • Barberio G.
      • Marinelli G.
      • et al.
      Composite valve graft implantation for the treatment of aortic valve and root disease: results in 1045 patients.
      • Berretta P.
      • Di Marco L.
      • Pacini D.
      • Cefarelli M.
      • Alfonsi J.
      • Castrovinci S.
      • et al.
      Reoperations versus primary operation on the aortic root: a propensity score analysis.
      • Dhurandhar V.
      • Parikh R.
      • Saxena A.
      • Vallely M.P.
      • Wilson M.K.
      • Black D.A.
      • et al.
      The aortic root replacement procedure: 12-year experience from the Australian and New Zealand Society of Cardiac and Thoracic Surgeons database.
      • Musci M.
      • Weng Y.
      • Hubler M.
      • Chavez T.
      • Qedra N.
      • Kosky S.
      • et al.
      Predictors of early mortality in patients with active infective native or prosthetic aortic root endocarditis undergoing homograft aortic root replacement.
      • Ostergaard L.
      • Valeur N.
      • Ihlemann N.
      • Bundgaard H.
      • Gislason G.
      • Torp-Pedersen C.
      • et al.
      Incidence of infective endocarditis among patients considered at high risk.
      • Leontyev S.
      • Borger M.A.
      • Modi P.
      • Lehmann S.
      • Seeburger J.
      • Walther T.
      • et al.
      Redo aortic valve surgery: influence of prosthetic valve endocarditis on outcomes.
      In previously reported mixed aortic root replacement cohorts, nonelective surgery accounted for 4%-28% of included cases compared with 46% in the current study, and reoperative surgery accounted for 4%-27% of cases compared with 34% in our study.
      • Harky A.
      • Wong C.H.M.
      • Hof A.
      • Froghi S.
      • Ahmad M.U.
      • Howard C.
      • et al.
      Stented versus stentless aortic valve replacement in patients with small aortic root: a systematic review and meta-analysis.
      ,
      • Di Marco L.
      • Pacini D.
      • Pantaleo A.
      • Leone A.
      • Barberio G.
      • Marinelli G.
      • et al.
      Composite valve graft implantation for the treatment of aortic valve and root disease: results in 1045 patients.
      • Berretta P.
      • Di Marco L.
      • Pacini D.
      • Cefarelli M.
      • Alfonsi J.
      • Castrovinci S.
      • et al.
      Reoperations versus primary operation on the aortic root: a propensity score analysis.
      • Dhurandhar V.
      • Parikh R.
      • Saxena A.
      • Vallely M.P.
      • Wilson M.K.
      • Black D.A.
      • et al.
      The aortic root replacement procedure: 12-year experience from the Australian and New Zealand Society of Cardiac and Thoracic Surgeons database.
      • Musci M.
      • Weng Y.
      • Hubler M.
      • Chavez T.
      • Qedra N.
      • Kosky S.
      • et al.
      Predictors of early mortality in patients with active infective native or prosthetic aortic root endocarditis undergoing homograft aortic root replacement.
      ,
      • Zehr K.J.
      • Orszulak T.A.
      • Mullany C.J.
      • Matloobi A.
      • Daly R.C.
      • Dearani J.A.
      • et al.
      Surgery for aneurysms of the aortic root: a 30-year experience.
      • Mataraci I.
      • Polat A.
      • Kiran B.
      • Caliskan A.
      • Tuncer A.
      • Erentug V.
      • et al.
      Long-term results of aortic root replacement: 15 years' experience.
      • Bach D.S.
      • Kon N.D.
      • Dumesnil J.G.
      • Sintek C.F.
      • Doty D.B.
      Ten-year outcome after aortic valve replacement with the Freestyle stentless bioprosthesis.
      • Byrne J.G.
      • Gudbjartsson T.
      • Karavas A.N.
      • Mihaljevic T.
      • Phillips B.J.
      • Aranki S.F.
      • et al.
      Biological vs. mechanical aortic root replacement.
      • Kuwaki K.
      • Amano A.
      • Inaba H.
      • Yamamoto T.
      • Matsumura T.
      • Dohi S.
      • et al.
      Predictors of early and mid-term results in contemporary aortic valve replacement for aortic stenosis.
      • Ennker I.C.
      • Albert A.
      • Dalladaku F.
      • Rosendahl U.
      • Ennker J.
      • Florath I.
      Midterm outcome after aortic root replacement with stentless porcine bioprostheses.
      • Mookhoek A.
      • Korteland N.M.
      • Arabkhani B.
      • Di Centa I.
      • Lansac E.
      • Bekkers J.A.
      • et al.
      Bentall procedure: a systematic review and meta-analysis.
      • Schneider A.W.
      • Putter H.
      • Hazekamp M.G.
      • Holman E.R.
      • Bruggemans E.F.
      • Versteegh M.I.M.
      • et al.
      Twenty-year experience with stentless biological aortic valve and root replacement: informing patients of risks and benefits.
      • El-Hamamsy I.
      • Ibrahim M.
      • Stevens L.M.
      • Witzke H.
      • Clark L.
      • Yacoub M.H.
      Early and long-term results of reoperative total aortic root replacement with reimplantation of the coronary arteries.
      • Esaki J.
      • Leshnower B.G.
      • Binongo J.N.
      • Lasanajak Y.
      • McPherson L.
      • Thourani V.H.
      • et al.
      Reoperative aortic root replacement: outcome in a contemporary series.
      • Di Eusanio M.
      • Berretta P.
      • Cefarelli M.
      • Folesani G.
      • Petridis F.D.
      • Di Marco L.
      • et al.
      Reoperative aortic root replacement: short- and long-term outcomes in 111 patients [in Italian].
      • Leontyev S.
      • Borger M.A.
      • Davierwala P.
      • Walther T.
      • Lehmann S.
      • Kempfert J.
      • et al.
      Redo aortic valve surgery: early and late outcomes.
      • Jassar A.S.
      • Bavaria J.E.
      • Szeto W.Y.
      • Moeller P.J.
      • Maniaci J.
      • Milewski R.K.
      • et al.
      Graft selection for aortic root replacement in complex active endocarditis: does it matter?.
      • Sabik J.F.
      • Lytle B.W.
      • Blackstone E.H.
      • Marullo A.G.
      • Pettersson G.B.
      • Cosgrove D.M.
      Aortic root replacement with cryopreserved allograft for prosthetic valve endocarditis.
      • Schneider A.W.
      • Hazekamp M.G.
      • Versteegh M.I.
      • Bruggemans E.F.
      • Holman E.R.
      • Klautz R.J.
      • et al.
      Stentless bioprostheses: a versatile and durable solution in extensive aortic valve endocarditis.
      • Leshnower B.G.
      • Chen E.P.
      When and how to replace the aortic root in type A aortic dissection.
      • Di Eusanio M.
      • Trimarchi S.
      • Peterson M.D.
      • Myrmel T.
      • Hughes G.C.
      • Korach A.
      • et al.
      Root replacement surgery versus more conservative management during type A acute aortic dissection repair.
      • Castrovinci S.
      • Pacini D.
      • Di Marco L.
      • Berretta P.
      • Cefarelli M.
      • Murana G.
      • et al.
      Surgical management of aortic root in type A acute aortic dissection: a propensity-score analysis.
      Also, complex endocarditis was our second most common indication, and 70% of these patients had PVE. Last, in all groups except aneurysm, the most prevalent New York Heart Association functional classification was III-IV, which is strongly associated with mortality and morbidity after cardiac surgery.
      • Di Marco L.
      • Pacini D.
      • Pantaleo A.
      • Leone A.
      • Barberio G.
      • Marinelli G.
      • et al.
      Composite valve graft implantation for the treatment of aortic valve and root disease: results in 1045 patients.
      ,
      • Leontyev S.
      • Borger M.A.
      • Modi P.
      • Lehmann S.
      • Seeburger J.
      • Walther T.
      • et al.
      Redo aortic valve surgery: influence of prosthetic valve endocarditis on outcomes.
      ,
      • Kuwaki K.
      • Amano A.
      • Inaba H.
      • Yamamoto T.
      • Matsumura T.
      • Dohi S.
      • et al.
      Predictors of early and mid-term results in contemporary aortic valve replacement for aortic stenosis.
      The overall high level of disease severity in the current study is further reflected by the high proportion of young patients who received a bioprosthesis. This suggests that the surgeons prioritized operative success, and confidence to the Freestyle as a surgical solution, over long-term durability. A summary of publications for the purpose of comparison of our results with suitable study populations is presented in Table 5.
      • Harky A.
      • Wong C.H.M.
      • Hof A.
      • Froghi S.
      • Ahmad M.U.
      • Howard C.
      • et al.
      Stented versus stentless aortic valve replacement in patients with small aortic root: a systematic review and meta-analysis.
      ,
      • Di Marco L.
      • Pacini D.
      • Pantaleo A.
      • Leone A.
      • Barberio G.
      • Marinelli G.
      • et al.
      Composite valve graft implantation for the treatment of aortic valve and root disease: results in 1045 patients.
      • Berretta P.
      • Di Marco L.
      • Pacini D.
      • Cefarelli M.
      • Alfonsi J.
      • Castrovinci S.
      • et al.
      Reoperations versus primary operation on the aortic root: a propensity score analysis.
      • Dhurandhar V.
      • Parikh R.
      • Saxena A.
      • Vallely M.P.
      • Wilson M.K.
      • Black D.A.
      • et al.
      The aortic root replacement procedure: 12-year experience from the Australian and New Zealand Society of Cardiac and Thoracic Surgeons database.
      • Musci M.
      • Weng Y.
      • Hubler M.
      • Chavez T.
      • Qedra N.
      • Kosky S.
      • et al.
      Predictors of early mortality in patients with active infective native or prosthetic aortic root endocarditis undergoing homograft aortic root replacement.
      ,
      • Zehr K.J.
      • Orszulak T.A.
      • Mullany C.J.
      • Matloobi A.
      • Daly R.C.
      • Dearani J.A.
      • et al.
      Surgery for aneurysms of the aortic root: a 30-year experience.
      • Mataraci I.
      • Polat A.
      • Kiran B.
      • Caliskan A.
      • Tuncer A.
      • Erentug V.
      • et al.
      Long-term results of aortic root replacement: 15 years' experience.
      • Bach D.S.
      • Kon N.D.
      • Dumesnil J.G.
      • Sintek C.F.
      • Doty D.B.
      Ten-year outcome after aortic valve replacement with the Freestyle stentless bioprosthesis.
      • Byrne J.G.
      • Gudbjartsson T.
      • Karavas A.N.
      • Mihaljevic T.
      • Phillips B.J.
      • Aranki S.F.
      • et al.
      Biological vs. mechanical aortic root replacement.
      • Kuwaki K.
      • Amano A.
      • Inaba H.
      • Yamamoto T.
      • Matsumura T.
      • Dohi S.
      • et al.
      Predictors of early and mid-term results in contemporary aortic valve replacement for aortic stenosis.
      • Ennker I.C.
      • Albert A.
      • Dalladaku F.
      • Rosendahl U.
      • Ennker J.
      • Florath I.
      Midterm outcome after aortic root replacement with stentless porcine bioprostheses.
      • Mookhoek A.
      • Korteland N.M.
      • Arabkhani B.
      • Di Centa I.
      • Lansac E.
      • Bekkers J.A.
      • et al.
      Bentall procedure: a systematic review and meta-analysis.
      • Schneider A.W.
      • Putter H.
      • Hazekamp M.G.
      • Holman E.R.
      • Bruggemans E.F.
      • Versteegh M.I.M.
      • et al.
      Twenty-year experience with stentless biological aortic valve and root replacement: informing patients of risks and benefits.
      • El-Hamamsy I.
      • Ibrahim M.
      • Stevens L.M.
      • Witzke H.
      • Clark L.
      • Yacoub M.H.
      Early and long-term results of reoperative total aortic root replacement with reimplantation of the coronary arteries.
      • Esaki J.
      • Leshnower B.G.
      • Binongo J.N.
      • Lasanajak Y.
      • McPherson L.
      • Thourani V.H.
      • et al.
      Reoperative aortic root replacement: outcome in a contemporary series.
      • Di Eusanio M.
      • Berretta P.
      • Cefarelli M.
      • Folesani G.
      • Petridis F.D.
      • Di Marco L.
      • et al.
      Reoperative aortic root replacement: short- and long-term outcomes in 111 patients [in Italian].
      • Leontyev S.
      • Borger M.A.
      • Davierwala P.
      • Walther T.
      • Lehmann S.
      • Kempfert J.
      • et al.
      Redo aortic valve surgery: early and late outcomes.
      • Jassar A.S.
      • Bavaria J.E.
      • Szeto W.Y.
      • Moeller P.J.
      • Maniaci J.
      • Milewski R.K.
      • et al.
      Graft selection for aortic root replacement in complex active endocarditis: does it matter?.
      • Sabik J.F.
      • Lytle B.W.
      • Blackstone E.H.
      • Marullo A.G.
      • Pettersson G.B.
      • Cosgrove D.M.
      Aortic root replacement with cryopreserved allograft for prosthetic valve endocarditis.
      • Schneider A.W.
      • Hazekamp M.G.
      • Versteegh M.I.
      • Bruggemans E.F.
      • Holman E.R.
      • Klautz R.J.
      • et al.
      Stentless bioprostheses: a versatile and durable solution in extensive aortic valve endocarditis.
      • Leshnower B.G.
      • Chen E.P.
      When and how to replace the aortic root in type A aortic dissection.
      • Di Eusanio M.
      • Trimarchi S.
      • Peterson M.D.
      • Myrmel T.
      • Hughes G.C.
      • Korach A.
      • et al.
      Root replacement surgery versus more conservative management during type A acute aortic dissection repair.
      • Castrovinci S.
      • Pacini D.
      • Di Marco L.
      • Berretta P.
      • Cefarelli M.
      • Murana G.
      • et al.
      Surgical management of aortic root in type A acute aortic dissection: a propensity-score analysis.
      Figure thumbnail gr3
      Figure 3Study summary. This was a retrospective, observational North Atlantic multicenter study of survival and reinterventions after aortic root replacement with the stentless xenograft Freestyle (Medtronic Inc, Minneapolis, Minn) bioprosthesis. It included 1008 unselected patients from Copenhagen, Stockholm, Bergen, Montreal, Linköping, and Reykjavik. Results were stratified for the elective indications aneurysm, small root and other and emergent indications, complex endocarditis, and Stanford type A aortic dissection requiring root replacement. In this study survival differed significantly in between indications. Early mortality was high for acknowledged high-risk cases. For 90-day survivors, survival after elective indications resembled that of the sex- and age-standardized Danish general population, whereas those with type A dissection and endocarditis had continued excess mortality. Thus, prosthesis characteristics allow intermediate-term survival corresponding to the background population, and outcome after aortic root replacement with the Medtronic xenograft Freestyle bioprosthesis is determined by patient—rather than by prosthesis—characteristics. It is therefore useful, safe, and durable in the intermediate term in low-risk as well as complex and high-risk surgery. Type A Diss, Type A aortic dissection.
      Table 5Excerpts from publications on ARR with specified indications and procedures: survival and reinterventions
      First authorreferenceDesign and contentsN
      The number of patients on which the following numbers are based might be a subgroup of ARR in a study containing also other procedures. If the included number (and associated results) includes any of these other procedures it is reflected in the proportion of ARR, presented in the following column.
      ARR, %
      Percentage of the patients represented under “N” and the reported results – if the cited study contained subgroups that were not relevant and results were reported separately, only ARR cases are included in the table.
      Mean age ± SD or median (IQR)NYHA class III-IV, %Concomitant CABG, %Redo, %Priority, %Population specification, %30-d mortality, %Survival, %Freedom from reinterventions, %
      5-yOther10-y5-yOther10-y
      Zehr
      • Zehr K.J.
      • Orszulak T.A.
      • Mullany C.J.
      • Matloobi A.
      • Daly R.C.
      • Dearani J.A.
      • et al.
      Surgery for aneurysms of the aortic root: a 30-year experience.
      Retrospective, composite ARR vs VSRR for root aneurysm: subcohort of ARR14910054 ± 1611134El: 96

      U:4
      4.093798886
      Mataraci
      • Mataraci I.
      • Polat A.
      • Kiran B.
      • Caliskan A.
      • Tuncer A.
      • Erentug V.
      • et al.
      Long-term results of aortic root replacement: 15 years' experience.
      Retrospective study of all Bentall de Bono, indication 93% aneurysm25410048 ± 1534157El: 91

      U: 9
      Hypoth cardiac arrest: 21

      A-diss: 20
      11.88495
      Composite end point with survival.
      93
      Composite end point with survival.
      Doty
      • Doty D.B.
      • Cafferty A.
      • Cartier P.
      • Huysmans H.A.
      • Kon N.D.
      • Krause A.H.
      • et al.
      Aortic valve replacement with Medtronic Freestyle bioprosthesis: 5-year results.
      /Bach
      • Bach D.S.
      • Kon N.D.
      • Dumesnil J.G.
      • Sintek C.F.
      • Doty D.B.
      Ten-year outcome after aortic valve replacement with the Freestyle stentless bioprosthesis.
      Prospective, Freestyle in ao valve lesions, subcohort of full roots (early results, here in bold, were reported by Doty and colleagues)17810070 ± 873/79NAAS: 38

      Mix: 43

      AR: 18
      7.173479892
      Byrne
      • Byrne J.G.
      • Gudbjartsson T.
      • Karavas A.N.
      • Mihaljevic T.
      • Phillips B.J.
      • Aranki S.F.
      • et al.
      Biological vs. mechanical aortic root replacement.
      Observational, all elective ARR to compare bio vs mech2219653302413El: 100Arch: 7

      A-diss: 0

      IE: 0 (3.6 “cold” IE)
      1.8 (in-hospital mortality)91“Low”
      Kuwaki
      • Kuwaki K.
      • Amano A.
      • Inaba H.
      • Yamamoto T.
      • Matsumura T.
      • Dohi S.
      • et al.
      Predictors of early and mid-term results in contemporary aortic valve replacement for aortic stenosis.
      Observational, AVR with or without CABG to evaluate STS and risk factors209069 ± 9533303.888.6
      Harky
      • Harky A.
      • Wong C.H.M.
      • Hof A.
      • Froghi S.
      • Ahmad M.U.
      • Howard C.
      • et al.
      Stented versus stentless aortic valve replacement in patients with small aortic root: a systematic review and meta-analysis.
      Meta-analysis of 7 observational studies of stented vs stentless AVR in the small root965075 vs 7256 vs 8027 vs 180EScII 2.1 vs 2.55.3 vs 4.489 vs 80
      Ennker
      • Ennker I.C.
      • Albert A.
      • Dalladaku F.
      • Rosendahl U.
      • Ennker J.
      • Florath I.
      Midterm outcome after aortic root replacement with stentless porcine bioprostheses.
      Observational, full root Freestyle for all indications. Primarily aneurysm and small roots30210072 ± 946234Em: 2Ascending ao surgery: 31

      IE: 1
      5.0749-y: 5399.293.6
      Di Marco
      • Di Marco L.
      • Pacini D.
      • Pantaleo A.
      • Leone A.
      • Barberio G.
      • Marinelli G.
      • et al.
      Composite valve graft implantation for the treatment of aortic valve and root disease: results in 1045 patients.
      Retrospective, all composite (aneurysm 62%)104510059 ± 1434.21112El: 89

      U/Em: 11
      A-diss: 15.5

      IE: 1.3
      5.38466Ca 9694
      Mookhoek
      • Mookhoek A.
      • Korteland N.M.
      • Arabkhani B.
      • Di Centa I.
      • Lansac E.
      • Bekkers J.A.
      • et al.
      Bentall procedure: a systematic review and meta-analysis.
      Meta-analysis of mechanical Bentall762997.850NA1216Em: 15.8A-diss: 15.3

      IE: 2
      5.6LOC: 2.02
      Dhurandhar
      • Dhurandhar V.
      • Parikh R.
      • Saxena A.
      • Vallely M.P.
      • Wilson M.K.
      • Black D.A.
      • et al.
      The aortic root replacement procedure: 12-year experience from the Australian and New Zealand Society of Cardiac and Thoracic Surgeons database.
      Retrospective multicenter, all ARR (48% aneurysm)95410056 ± 15272121El: 75

      U/Em/S: 26
      A-diss: 9.5

      IE: 8.5
      El: 3.6

      U/Em/S: 12.7

      A-diss: 15.8
      84
      Schneider
      • Schneider A.W.
      • Putter H.
      • Hazekamp M.G.
      • Holman E.R.
      • Bruggemans E.F.
      • Versteegh M.I.M.
      • et al.
      Twenty-year experience with stentless biological aortic valve and root replacement: informing patients of risks and benefits.
      Retrospective, all full root Freestyle40310062 (51-70)271527U: 20

      Em: 8
      AS: 35

      AR 45

      A-diss: 8

      IE: 14
      All: 7.9

      El: 6.1
      8-y: 59
      Berretta
      • Berretta P.
      • Di Marco L.
      • Pacini D.
      • Cefarelli M.
      • Alfonsi J.
      • Castrovinci S.
      • et al.
      Reoperations versus primary operation on the aortic root: a propensity score analysis.
      Retrospective single-center, repeat ARR (only previous ao surgery) vs primary ARR180 vs 108710057 vs 6023 vs 2813U/Em: 18.9 vs 10.7IE: 12.2 vs 0.7

      Ao arch: 34 vs 14.1
      11.1 vs 4.1

      (OR 2.9)
      El-Hamamsy
      • El-Hamamsy I.
      • Ibrahim M.
      • Stevens L.M.
      • Witzke H.
      • Clark L.
      • Yacoub M.H.
      Early and long-term results of reoperative total aortic root replacement with reimplantation of the coronary arteries.
      Retrospective single surgeon, repeat ARR (only previous ARR procedures)8410038 ± 153812100Em/U: 12IE: 152.4898197
      Esaki
      • Esaki J.
      • Leshnower B.G.
      • Binongo J.N.
      • Lasanajak Y.
      • McPherson L.
      • Thourani V.H.
      • et al.
      Reoperative aortic root replacement: outcome in a contemporary series.
      Observational, redo ARR (all previous cardiac/ao surgery)28010053 ± 1424100Em: 4.6IE: 18

      A-diss: 2
      14.37495.4
      Di Eusanio
      • Di Eusanio M.
      • Berretta P.
      • Cefarelli M.
      • Folesani G.
      • Petridis F.D.
      • Di Marco L.
      • et al.
      Reoperative aortic root replacement: short- and long-term outcomes in 111 patients [in Italian].
      Observational, redo ARR (all previous cardiac/ao surgery)11110055100Em/U: 2212.672519286
      Leontyev
      • Leontyev S.
      • Borger M.A.
      • Modi P.
      • Lehmann S.
      • Seeburger J.
      • Walther T.
      • et al.
      Redo aortic valve surgery: influence of prosthetic valve endocarditis on outcomes.
      Retrospective, redo AVR with or without root replacement85 vs 694558 ± 1342100El: 37

      U: 41

      Em: 21
      IE: 27

      A-diss: 2.6
      ca. 5.4 both groups668-y: 68878-y: 82
      Jassar
      • Jassar A.S.
      • Bavaria J.E.
      • Szeto W.Y.
      • Moeller P.J.
      • Maniaci J.
      • Milewski R.K.
      • et al.
      Graft selection for aortic root replacement in complex active endocarditis: does it matter?.
      Retrospective, ARR for endocarditis, compare bio, mech, and homograft13410058 ± 15591269U/Em: 72Root abscess: 82

      PVE: 67
      2259
      Sabik
      • Sabik J.F.
      • Lytle B.W.
      • Blackstone E.H.
      • Marullo A.G.
      • Pettersson G.B.
      • Cosgrove D.M.
      Aortic root replacement with cryopreserved allograft for prosthetic valve endocarditis.
      Retrospective, all homograft replacements because of prosthetic endocarditis (Cleveland clinic)10310057 ± 15100Root abscess: 783.97356
      Musci
      • Musci M.
      • Weng Y.
      • Hubler M.
      • Chavez T.
      • Qedra N.
      • Kosky S.
      • et al.
      Predictors of early mortality in patients with active infective native or prosthetic aortic root endocarditis undergoing homograft aortic root replacement.
      Observational single-center, homograft ARR for native valve endocarditis vs PVE99 vs 12210050 vs 60El: 6 vs 9

      U: 70 vs 75

      Em: 24 vs 16
      Root abscess: 78 vs 9216.2 vs 25.467 vs 4847 vs 35
      Schneider
      • Schneider A.W.
      • Hazekamp M.G.
      • Versteegh M.I.
      • Bruggemans E.F.
      • Holman E.R.
      • Klautz R.J.
      • et al.
      Stentless bioprostheses: a versatile and durable solution in extensive aortic valve endocarditis.
      Retrospective, full root Freestyle for endocarditis with extensive root involvement5410061 ± 131863NAPVE 541170 (CI, 52-82)
      Leshnower
      • Leshnower B.G.
      • Chen E.P.
      When and how to replace the aortic root in type A aortic dissection.
      Review of A-diss with dissection of the root12.3-288565
      Di Eusanio
      • Di Eusanio M.
      • Trimarchi S.
      • Peterson M.D.
      • Myrmel T.
      • Hughes G.C.
      • Korach A.
      • et al.
      Root replacement surgery versus more conservative management during type A acute aortic dissection repair.
      Retrospective registry study (IRAD), comparing CRR vs ARR for A diss69910057 ± 1533 Shock14Mix VSRR/ARR21.33-y:92
      For hospital survivors.
      3-y: 99
      Castrovinci
      • Castrovinci S.
      • Pacini D.
      • Di Marco L.
      • Berretta P.
      • Cefarelli M.
      • Murana G.
      • et al.
      Surgical management of aortic root in type A acute aortic dissection: a propensity-score analysis.
      Retrospective single-centre, comparing CRR vs ARR in A-diss11910060 ± 11NA87Ao. arch: 2621717-y:63Prox: 96
      The table contains a selection of publications regarding ao root replacement, or alternative procedures to treat similar pathology. The table illustrates the differences in the baseline characteristics, including proportion of surgical priority and redo surgery, as well as the related results. “Small root” indicates 21-mm annulus or prosthetic size. “Repeat ARR” indicates second-time aortic root surgery. ARR, Aortic root replacement; SD, standard deviation; IQR, interquartile range; NYHA, New York Heart Association; CABG, coronary artery bypass grafting; redo, reoperative cardiac surgery (ie, redo sternotomy and dissection from adherences); VSRR, valve-sparing root replacement; El, elective; U, urgent; Hypoth, hypothermic; A-diss, type A aortic dissection; NA, Nonapplicable; AS, aortic stenosis; AR, aortic regurgitation; bio, bioprosthetic; mech, mechanical prosthesis; IE, infective endocarditis; AVR, aortic valve replacement; STS, The Society of Thoracic Surgeons; EScII, European System for Cardiac Operative Risk Evaluation II; Em, emergent; ca, circa; LOC, linearized occurrence rates; S, salvage; Ao, aortic; PVE, prosthetic valve endocarditis; CI, 95% confidence interval; IRAD, The International Registry of Acute Aortic Dissection; CRR, conservative root management; Prox, proximal (reoperations).
      The number of patients on which the following numbers are based might be a subgroup of ARR in a study containing also other procedures. If the included number (and associated results) includes any of these other procedures it is reflected in the proportion of ARR, presented in the following column.
      Percentage of the patients represented under “N” and the reported results – if the cited study contained subgroups that were not relevant and results were reported separately, only ARR cases are included in the table.
      Composite end point with survival.
      § For hospital survivors.

      Survival

      Early mortality after aortic root replacement or similar procedures for severe aortic root disease ranges between 1.8% and 28% (Table 5).
      • Harky A.
      • Wong C.H.M.
      • Hof A.
      • Froghi S.
      • Ahmad M.U.
      • Howard C.
      • et al.
      Stented versus stentless aortic valve replacement in patients with small aortic root: a systematic review and meta-analysis.
      ,
      • Di Marco L.
      • Pacini D.
      • Pantaleo A.
      • Leone A.
      • Barberio G.
      • Marinelli G.
      • et al.
      Composite valve graft implantation for the treatment of aortic valve and root disease: results in 1045 patients.
      • Berretta P.
      • Di Marco L.
      • Pacini D.
      • Cefarelli M.
      • Alfonsi J.
      • Castrovinci S.
      • et al.
      Reoperations versus primary operation on the aortic root: a propensity score analysis.
      • Dhurandhar V.
      • Parikh R.
      • Saxena A.
      • Vallely M.P.
      • Wilson M.K.
      • Black D.A.
      • et al.
      The aortic root replacement procedure: 12-year experience from the Australian and New Zealand Society of Cardiac and Thoracic Surgeons database.
      • Musci M.
      • Weng Y.
      • Hubler M.
      • Chavez T.
      • Qedra N.
      • Kosky S.
      • et al.
      Predictors of early mortality in patients with active infective native or prosthetic aortic root endocarditis undergoing homograft aortic root replacement.
      ,
      • Zehr K.J.
      • Orszulak T.A.
      • Mullany C.J.
      • Matloobi A.
      • Daly R.C.
      • Dearani J.A.
      • et al.
      Surgery for aneurysms of the aortic root: a 30-year experience.
      • Mataraci I.
      • Polat A.
      • Kiran B.
      • Caliskan A.
      • Tuncer A.
      • Erentug V.
      • et al.
      Long-term results of aortic root replacement: 15 years' experience.
      • Bach D.S.
      • Kon N.D.
      • Dumesnil J.G.
      • Sintek C.F.
      • Doty D.B.
      Ten-year outcome after aortic valve replacement with the Freestyle stentless bioprosthesis.
      • Byrne J.G.
      • Gudbjartsson T.
      • Karavas A.N.
      • Mihaljevic T.
      • Phillips B.J.
      • Aranki S.F.
      • et al.
      Biological vs. mechanical aortic root replacement.
      • Kuwaki K.
      • Amano A.
      • Inaba H.
      • Yamamoto T.
      • Matsumura T.
      • Dohi S.
      • et al.
      Predictors of early and mid-term results in contemporary aortic valve replacement for aortic stenosis.
      • Ennker I.C.
      • Albert A.
      • Dalladaku F.
      • Rosendahl U.
      • Ennker J.
      • Florath I.
      Midterm outcome after aortic root replacement with stentless porcine bioprostheses.
      • Mookhoek A.
      • Korteland N.M.
      • Arabkhani B.
      • Di Centa I.
      • Lansac E.
      • Bekkers J.A.
      • et al.
      Bentall procedure: a systematic review and meta-analysis.
      • Schneider A.W.
      • Putter H.
      • Hazekamp M.G.
      • Holman E.R.
      • Bruggemans E.F.
      • Versteegh M.I.M.
      • et al.
      Twenty-year experience with stentless biological aortic valve and root replacement: informing patients of risks and benefits.
      • El-Hamamsy I.
      • Ibrahim M.
      • Stevens L.M.
      • Witzke H.
      • Clark L.
      • Yacoub M.H.
      Early and long-term results of reoperative total aortic root replacement with reimplantation of the coronary arteries.
      • Esaki J.
      • Leshnower B.G.
      • Binongo J.N.
      • Lasanajak Y.
      • McPherson L.
      • Thourani V.H.
      • et al.
      Reoperative aortic root replacement: outcome in a contemporary series.
      • Di Eusanio M.
      • Berretta P.
      • Cefarelli M.
      • Folesani G.
      • Petridis F.D.
      • Di Marco L.
      • et al.
      Reoperative aortic root replacement: short- and long-term outcomes in 111 patients [in Italian].
      • Leontyev S.
      • Borger M.A.
      • Davierwala P.
      • Walther T.
      • Lehmann S.
      • Kempfert J.
      • et al.
      Redo aortic valve surgery: early and late outcomes.
      • Jassar A.S.
      • Bavaria J.E.
      • Szeto W.Y.
      • Moeller P.J.
      • Maniaci J.
      • Milewski R.K.
      • et al.
      Graft selection for aortic root replacement in complex active endocarditis: does it matter?.
      • Sabik J.F.
      • Lytle B.W.
      • Blackstone E.H.
      • Marullo A.G.
      • Pettersson G.B.
      • Cosgrove D.M.
      Aortic root replacement with cryopreserved allograft for prosthetic valve endocarditis.
      • Schneider A.W.
      • Hazekamp M.G.
      • Versteegh M.I.
      • Bruggemans E.F.
      • Holman E.R.
      • Klautz R.J.
      • et al.
      Stentless bioprostheses: a versatile and durable solution in extensive aortic valve endocarditis.
      • Leshnower B.G.
      • Chen E.P.
      When and how to replace the aortic root in type A aortic dissection.
      • Di Eusanio M.
      • Trimarchi S.
      • Peterson M.D.
      • Myrmel T.
      • Hughes G.C.
      • Korach A.
      • et al.
      Root replacement surgery versus more conservative management during type A acute aortic dissection repair.
      • Castrovinci S.
      • Pacini D.
      • Di Marco L.
      • Berretta P.
      • Cefarelli M.
      • Murana G.
      • et al.
      Surgical management of aortic root in type A acute aortic dissection: a propensity-score analysis.
      Our data compare well with the literature; early and late mortality varies significantly with indication for surgery, with 30-day mortality ranging from 3% for aneurysms to 27% for type A dissections. In all studies, including the present, high rates of mortality occur primarily among patients with type A dissection and those with complex endocarditis. The rather high mortality rate in these groups might be explained by the extended surgical aortic root injury in aortic dissection patients and with invasive root abscess formation or redo setting in patients with endocarditis. The relatively low early mortality rate of our elective aneurysm patients is also in line with established knowledge.
      • Di Marco L.
      • Pacini D.
      • Pantaleo A.
      • Leone A.
      • Barberio G.
      • Marinelli G.
      • et al.
      Composite valve graft implantation for the treatment of aortic valve and root disease: results in 1045 patients.
      ,
      • Dhurandhar V.
      • Parikh R.
      • Saxena A.
      • Vallely M.P.
      • Wilson M.K.
      • Black D.A.
      • et al.
      The aortic root replacement procedure: 12-year experience from the Australian and New Zealand Society of Cardiac and Thoracic Surgeons database.
      ,
      • Zehr K.J.
      • Orszulak T.A.
      • Mullany C.J.
      • Matloobi A.
      • Daly R.C.
      • Dearani J.A.
      • et al.
      Surgery for aneurysms of the aortic root: a 30-year experience.
      ,
      • Mataraci I.
      • Polat A.
      • Kiran B.
      • Caliskan A.
      • Tuncer A.
      • Erentug V.
      • et al.
      Long-term results of aortic root replacement: 15 years' experience.
      ,
      • Byrne J.G.
      • Gudbjartsson T.
      • Karavas A.N.
      • Mihaljevic T.
      • Phillips B.J.
      • Aranki S.F.
      • et al.
      Biological vs. mechanical aortic root replacement.
      ,
      • Ennker I.C.
      • Albert A.
      • Dalladaku F.
      • Rosendahl U.
      • Ennker J.
      • Florath I.
      Midterm outcome after aortic root replacement with stentless porcine bioprostheses.
      • Mookhoek A.
      • Korteland N.M.
      • Arabkhani B.
      • Di Centa I.
      • Lansac E.
      • Bekkers J.A.
      • et al.
      Bentall procedure: a systematic review and meta-analysis.
      • Schneider A.W.
      • Putter H.
      • Hazekamp M.G.
      • Holman E.R.
      • Bruggemans E.F.
      • Versteegh M.I.M.
      • et al.
      Twenty-year experience with stentless biological aortic valve and root replacement: informing patients of risks and benefits.
      ,
      • Doty D.B.
      • Cafferty A.
      • Cartier P.
      • Huysmans H.A.
      • Kon N.D.
      • Krause A.H.
      • et al.
      Aortic valve replacement with Medtronic Freestyle bioprosthesis: 5-year results.
      Still, the small root group had a 30-day mortality of 9.3% (n = 8), which is higher than the 4.4% reported in a recent meta-analysis of patients with small aortic roots.
      • Harky A.
      • Wong C.H.M.
      • Hof A.
      • Froghi S.
      • Ahmad M.U.
      • Howard C.
      • et al.
      Stented versus stentless aortic valve replacement in patients with small aortic root: a systematic review and meta-analysis.
      Only 1 case was related to an early revascularization, but 4 had perioperative myocardial infarctions. Four of the 8 deceased patients were emergent or urgent cases and the median European System for Cardiac Operative Risk Evaluation (EuroSCORE) II of the 8 patients was 10.7% (range, 2.2%-48.1%; only 1 patient had a EuroSCORE II <7%); hence our 30-day mortality rate is not completely unexpected but an over-representation of coronary reimplantation complications as a contributing factor cannot be out-ruled. Intermediate-term survival of patients with elective indications (aneurysm, small root, and other) was comparable or slightly lower than previously reported (Tables 3 and E1).
      • Harky A.
      • Wong C.H.M.
      • Hof A.
      • Froghi S.
      • Ahmad M.U.
      • Howard C.
      • et al.
      Stented versus stentless aortic valve replacement in patients with small aortic root: a systematic review and meta-analysis.
      ,
      • Di Marco L.
      • Pacini D.
      • Pantaleo A.
      • Leone A.
      • Barberio G.
      • Marinelli G.
      • et al.
      Composite valve graft implantation for the treatment of aortic valve and root disease: results in 1045 patients.
      • Berretta P.
      • Di Marco L.
      • Pacini D.
      • Cefarelli M.
      • Alfonsi J.
      • Castrovinci S.
      • et al.
      Reoperations versus primary operation on the aortic root: a propensity score analysis.
      • Dhurandhar V.
      • Parikh R.
      • Saxena A.
      • Vallely M.P.
      • Wilson M.K.
      • Black D.A.
      • et al.
      The aortic root replacement procedure: 12-year experience from the Australian and New Zealand Society of Cardiac and Thoracic Surgeons database.
      • Musci M.
      • Weng Y.
      • Hubler M.
      • Chavez T.
      • Qedra N.
      • Kosky S.
      • et al.
      Predictors of early mortality in patients with active infective native or prosthetic aortic root endocarditis undergoing homograft aortic root replacement.
      ,
      • Zehr K.J.
      • Orszulak T.A.
      • Mullany C.J.
      • Matloobi A.
      • Daly R.C.
      • Dearani J.A.
      • et al.
      Surgery for aneurysms of the aortic root: a 30-year experience.
      • Mataraci I.
      • Polat A.
      • Kiran B.
      • Caliskan A.
      • Tuncer A.
      • Erentug V.
      • et al.
      Long-term results of aortic root replacement: 15 years' experience.
      • Bach D.S.
      • Kon N.D.
      • Dumesnil J.G.
      • Sintek C.F.
      • Doty D.B.
      Ten-year outcome after aortic valve replacement with the Freestyle stentless bioprosthesis.
      • Byrne J.G.
      • Gudbjartsson T.
      • Karavas A.N.
      • Mihaljevic T.
      • Phillips B.J.
      • Aranki S.F.
      • et al.
      Biological vs. mechanical aortic root replacement.
      • Kuwaki K.
      • Amano A.
      • Inaba H.
      • Yamamoto T.
      • Matsumura T.
      • Dohi S.
      • et al.
      Predictors of early and mid-term results in contemporary aortic valve replacement for aortic stenosis.
      • Ennker I.C.
      • Albert A.
      • Dalladaku F.
      • Rosendahl U.
      • Ennker J.
      • Florath I.
      Midterm outcome after aortic root replacement with stentless porcine bioprostheses.
      • Mookhoek A.
      • Korteland N.M.
      • Arabkhani B.
      • Di Centa I.
      • Lansac E.
      • Bekkers J.A.
      • et al.
      Bentall procedure: a systematic review and meta-analysis.
      • Schneider A.W.
      • Putter H.
      • Hazekamp M.G.
      • Holman E.R.
      • Bruggemans E.F.
      • Versteegh M.I.M.
      • et al.
      Twenty-year experience with stentless biological aortic valve and root replacement: informing patients of risks and benefits.
      • El-Hamamsy I.
      • Ibrahim M.
      • Stevens L.M.
      • Witzke H.
      • Clark L.
      • Yacoub M.H.
      Early and long-term results of reoperative total aortic root replacement with reimplantation of the coronary arteries.
      • Esaki J.
      • Leshnower B.G.
      • Binongo J.N.
      • Lasanajak Y.
      • McPherson L.
      • Thourani V.H.
      • et al.
      Reoperative aortic root replacement: outcome in a contemporary series.
      • Di Eusanio M.
      • Berretta P.
      • Cefarelli M.
      • Folesani G.
      • Petridis F.D.
      • Di Marco L.
      • et al.
      Reoperative aortic root replacement: short- and long-term outcomes in 111 patients [in Italian].
      • Leontyev S.
      • Borger M.A.
      • Davierwala P.
      • Walther T.
      • Lehmann S.
      • Kempfert J.
      • et al.
      Redo aortic valve surgery: early and late outcomes.
      • Jassar A.S.
      • Bavaria J.E.
      • Szeto W.Y.
      • Moeller P.J.
      • Maniaci J.
      • Milewski R.K.
      • et al.
      Graft selection for aortic root replacement in complex active endocarditis: does it matter?.
      • Sabik J.F.
      • Lytle B.W.
      • Blackstone E.H.
      • Marullo A.G.
      • Pettersson G.B.
      • Cosgrove D.M.
      Aortic root replacement with cryopreserved allograft for prosthetic valve endocarditis.
      • Schneider A.W.
      • Hazekamp M.G.
      • Versteegh M.I.
      • Bruggemans E.F.
      • Holman E.R.
      • Klautz R.J.
      • et al.
      Stentless bioprostheses: a versatile and durable solution in extensive aortic valve endocarditis.
      • Leshnower B.G.
      • Chen E.P.
      When and how to replace the aortic root in type A aortic dissection.
      • Di Eusanio M.
      • Trimarchi S.
      • Peterson M.D.
      • Myrmel T.
      • Hughes G.C.
      • Korach A.
      • et al.
      Root replacement surgery versus more conservative management during type A acute aortic dissection repair.
      • Castrovinci S.
      • Pacini D.
      • Di Marco L.
      • Berretta P.
      • Cefarelli M.
      • Murana G.
      • et al.
      Surgical management of aortic root in type A acute aortic dissection: a propensity-score analysis.
      In a landmark analysis with cutoff at 90 days, survival rates up to 10 years for aneurysm, small root, and other were indistinguishable, and furthermore comparable with a reference group from the Danish general population. This is contrary to the survival in patients after conventional aortic valve replacement, which have been shown to exhibit a small but significant late excess mortality, especially in this younger age group, compared with the general population.
      • Glaser N.
      • Persson M.
      • Jackson V.
      • Holzmann M.J.
      • Franco-Cereceda A.
      • Sartipy U.
      Loss in life expectancy after surgical aortic valve replacement: SWEDEHEART study.
      This is especially reassuring in light of the previously reported high rates of pseudoaneurysm formation.
      • Dagnegård H.H.
      • Sigvardsen P.E.
      • Ihlemann N.
      • Kofoed K.F.
      • El-Hamamsy I.
      • Bekke K.
      • et al.
      Structural abnormalities after aortic root replacement with stentless xenograft.
      ,
      • Englum B.R.
      • Pavlisko E.N.
      • Mack M.C.
      • Ganapathi A.M.
      • Schechter M.A.
      • Hanna J.M.
      • et al.
      Pseudoaneurysm formation after Medtronic Freestyle porcine aortic bioprosthesis implantation: a word of caution.
      However, our data seem to support previous reports of continued excess mortality for endocarditis patients and implies that this could also apply to patients with type A dissection (Figure 1, B, Table 5, and Figure E2, F and L).
      • Ostergaard L.
      • Valeur N.
      • Ihlemann N.
      • Bundgaard H.
      • Gislason G.
      • Torp-Pedersen C.
      • et al.
      Incidence of infective endocarditis among patients considered at high risk.
      ,
      • Thuny F.
      • Grisoli D.
      • Cautela J.
      • Riberi A.
      • Raoult D.
      • Habib G.
      Infective endocarditis: prevention, diagnosis, and management.
      On this note, late survival for type A dissection appears to be lower than previously reported for root-involving type A dissection, but because our patients were 6-9 years older at the time of surgery than the patients in studies representing comparably complex cases (Table 5), the true difference is probably small. Still, it cannot be ruled out that pseudoaneurysm formation and rupture is a possible mechanism for this excess mortality, although an association between pseudoaneurysms and indication for Freestyle implantation has not been identified.
      • Dagnegård H.H.
      • Sigvardsen P.E.
      • Ihlemann N.
      • Kofoed K.F.
      • El-Hamamsy I.
      • Bekke K.
      • et al.
      Structural abnormalities after aortic root replacement with stentless xenograft.
      A subgroup analysis showed no marked difference between sexes but was underpowered to refute such a difference with certainty.

      Reinterventions

      Reintervention rates compare well with previous reports of aortic root replacement for similar indications, regardless of the type of prosthesis used (Table 5). Most of the valve-related reinterventions were because of recurrent endocarditis in the group of endocarditis, again likely reflecting the underlying pathophysiology and comorbidity rather than the choice of prosthesis. Overall freedom from valve-related reintervention during the first 8 years was generally high (94.4%). Reinterventions because of structural valve deterioration were rare. Coronary reinterventions primarily occurred among small root patients, who had a 5-year freedom of 90% (Figure 2, B). Of note, 4 of 7 revascularizations in this group were perioperative and represented 4 of the 7 early revascularizations in the entire study unit. Thus, the small root appears particularly prone to coronary reimplantation complications such as, for example, a kink of the proximal coronary artery, but all early revascularizations must be considered likely complications to coronary artery reimplantation. Even so, all but 1 of the four small root patients and 2 of the 7 patients in all, survived this complication. In all, the authors consider the perioperative risk of kink or other ostial obstruction in relation to aortic root replacement admissible, but the results do underline the importance of coronary positioning when reimplanting the coronary buttons, especially under the narrow conditions seen, for example, in the small root setting. Most of the late coronary lesions were proximal and might represent a complication to the coronary reimplantation.

      Early Complications

      Overall complication frequencies are shown in Table 4; they reflect patient characteristics, disease severity, and surgical complexity. The rate of most early complications, including reoperation for bleeding or tamponade, was comparable with previous reports.
      • Harky A.
      • Wong C.H.M.
      • Hof A.
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      • et al.
      Stented versus stentless aortic valve replacement in patients with small aortic root: a systematic review and meta-analysis.
      ,
      • Di Marco L.
      • Pacini D.
      • Pantaleo A.
      • Leone A.
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      • Marinelli G.
      • et al.
      Composite valve graft implantation for the treatment of aortic valve and root disease: results in 1045 patients.
      • Berretta P.
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      • Pacini D.
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      • Castrovinci S.
      • et al.
      Reoperations versus primary operation on the aortic root: a propensity score analysis.
      • Dhurandhar V.
      • Parikh R.
      • Saxena A.
      • Vallely M.P.
      • Wilson M.K.
      • Black D.A.
      • et al.
      The aortic root replacement procedure: 12-year experience from the Australian and New Zealand Society of Cardiac and Thoracic Surgeons database.
      ,
      • Leontyev S.
      • Borger M.A.
      • Modi P.
      • Lehmann S.
      • Seeburger J.
      • Walther T.
      • et al.
      Redo aortic valve surgery: influence of prosthetic valve endocarditis on outcomes.
      • Zehr K.J.
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      • Matloobi A.
      • Daly R.C.
      • Dearani J.A.
      • et al.
      Surgery for aneurysms of the aortic root: a 30-year experience.
      • Mataraci I.
      • Polat A.
      • Kiran B.
      • Caliskan A.
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      • Erentug V.
      • et al.
      Long-term results of aortic root replacement: 15 years' experience.
      ,
      • Byrne J.G.
      • Gudbjartsson T.
      • Karavas A.N.
      • Mihaljevic T.
      • Phillips B.J.
      • Aranki S.F.
      • et al.
      Biological vs. mechanical aortic root replacement.
      ,
      • Kuwaki K.
      • Amano A.
      • Inaba H.
      • Yamamoto T.
      • Matsumura T.
      • Dohi S.
      • et al.
      Predictors of early and mid-term results in contemporary aortic valve replacement for aortic stenosis.
      ,
      • Mookhoek A.
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      • Arabkhani B.
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      • Lansac E.
      • Bekkers J.A.
      • et al.
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      • et al.
      Twenty-year experience with stentless biological aortic valve and root replacement: informing patients of risks and benefits.
      • El-Hamamsy I.
      • Ibrahim M.
      • Stevens L.M.
      • Witzke H.
      • Clark L.
      • Yacoub M.H.
      Early and long-term results of reoperative total aortic root replacement with reimplantation of the coronary arteries.
      • Esaki J.
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      • Binongo J.N.
      • Lasanajak Y.
      • McPherson L.
      • Thourani V.H.
      • et al.
      Reoperative aortic root replacement: outcome in a contemporary series.
      ,
      • Leontyev S.
      • Borger M.A.
      • Davierwala P.
      • Walther T.
      • Lehmann S.
      • Kempfert J.
      • et al.
      Redo aortic valve surgery: early and late outcomes.
      • Jassar A.S.
      • Bavaria J.E.
      • Szeto W.Y.
      • Moeller P.J.
      • Maniaci J.
      • Milewski R.K.
      • et al.
      Graft selection for aortic root replacement in complex active endocarditis: does it matter?.
      • Sabik J.F.
      • Lytle B.W.
      • Blackstone E.H.
      • Marullo A.G.
      • Pettersson G.B.
      • Cosgrove D.M.
      Aortic root replacement with cryopreserved allograft for prosthetic valve endocarditis.
      • Schneider A.W.
      • Hazekamp M.G.
      • Versteegh M.I.
      • Bruggemans E.F.
      • Holman E.R.
      • Klautz R.J.
      • et al.
      Stentless bioprostheses: a versatile and durable solution in extensive aortic valve endocarditis.
      ,
      • Di Eusanio M.
      • Trimarchi S.
      • Peterson M.D.
      • Myrmel T.
      • Hughes G.C.
      • Korach A.
      • et al.
      Root replacement surgery versus more conservative management during type A acute aortic dissection repair.
      ,
      • Castrovinci S.
      • Pacini D.
      • Di Marco L.
      • Berretta P.
      • Cefarelli M.
      • Murana G.
      • et al.
      Surgical management of aortic root in type A acute aortic dissection: a propensity-score analysis.
      ,
      • Easo J.
      • Weymann A.
      • Holzl P.
      • Horst M.
      • Eichstaedt H.
      • Mashhour A.
      • et al.
      Hospital results of a single center database for stentless xenograft use in a full root technique in over 970 patients.
      However, the number of cerebrovascular events in the type A dissection and endocarditis groups were 22.4% and 10.2%, respectively, compared with up to 10% observed in other studies of these indications.
      • Jassar A.S.
      • Bavaria J.E.
      • Szeto W.Y.
      • Moeller P.J.
      • Maniaci J.
      • Milewski R.K.
      • et al.
      Graft selection for aortic root replacement in complex active endocarditis: does it matter?.
      ,
      • Di Eusanio M.
      • Trimarchi S.
      • Peterson M.D.
      • Myrmel T.
      • Hughes G.C.
      • Korach A.
      • et al.
      Root replacement surgery versus more conservative management during type A acute aortic dissection repair.
      ,
      • Castrovinci S.
      • Pacini D.
      • Di Marco L.
      • Berretta P.
      • Cefarelli M.
      • Murana G.
      • et al.
      Surgical management of aortic root in type A acute aortic dissection: a propensity-score analysis.
      Some studies included only permanent stroke whereas others did not specify inclusion (eg, transient ischemic attacks or stroke without sequelae). The current study included all cerebrovascular events whether they were due to the underlying disease, or real intra- or postoperative events, perhaps explaining the higher rate. The high rate of perioperative myocardial infarction (13.3%; n = 11) appears less surprising when the high proportion of coronary artery disease within the small root group (33.7%) is considered, corroborated by the need for concomitant coronary artery bypass grafting (25.6%) and later increased risk of revascularization (hazard ratio, 12.01; 95% CI, 1.99-72.39). However, the perioperative myocardial infarction and the late revascularizations might represent a particular, technical difficulty of coronary reimplantation among the small root patients.

      Strengths and Limitations

      The multicenter design, large study population, and complete follow-up were strengths of the study. Although our study was limited by lack of cause of death, the comparison of the survival of our cohort with that of the standardized general population allows interpretation of the prosthesis implantation's influence on mortality. The main limitations, additional to those inherent to the retrospective study design, included the lack of detailed serial follow-up echocardiographic data. This prohibited estimation of biological valve failure according to the guideline of the 2017 European Association of Percutaneous Cardiovascular Interventions/European Society of Cardiology/European Association for Cardio-Thoracic Surgery consensus report because of the inability to identify structural valve deterioration not causing reintervention.
      • Capodanno D.
      • Petronio A.S.
      • Prendergast B.
      • Eltchaninoff H.
      • Vahanian A.
      • Modine T.
      • et al.
      Standardized definitions of structural deterioration and valve failure in assessing long-term durability of transcatheter and surgical aortic bioprosthetic valves: a consensus statement from the European Association of Percutaneous Cardiovascular Interventions (EAPCI) endorsed by the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS).
      Furthermore, proper evaluation of prosthesis-patient mismatch was not possible, information on functional status and quality of life was sparse, and duration of follow-up was limited.

      Conclusions

      In this study of more than 1000 unselected Freestyle full aortic root implantations in patients from 6 small- to medium-sized and comparable centers, survival was equal to that of previous reports of similar cohorts of aortic root procedures, and for elective indications also for that of the general population.
      Considering the indications for Freestyle aortic root replacement and the known risk factors for death, the high early mortality rate in high-risk cases might be acceptable. Intermediate-term reintervention rates (valve and coronary) were low and primarily because of recurrent endocarditis. In conclusion, the present intermediate-term study provides further support for the use of the Freestyle full root bioprosthesis in the real-world setting of diverse, complex, and often high-risk aortic root replacement, and suggests that outcome is determined by patient and disease, rather than by prosthesis, characteristics.

      Conflict of Interest Statement

      The 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.
      The authors thank Jørgen Brekke Vennemo for his valuable contributions in the acquisition of data.

      Supplementary Data

      • Video 1

        This is a video of a redo aortic root replacement in a 76-year-old woman who received an aortic valve bioprosthesis 2 months previously because of aortic valve stenosis. The postoperative course was complicated by mediastinitis, and she has now presented with prosthetic valve endocarditis including vegetations on the valve and in the left ventricular outflow tract. The video shows the explantation of the bioprosthesis and the resection of infected tissue. It then moves on to the reconstruction of the resulting defect in the left ventricular outflow tract and left atrial roof with a bovine pericardial patch. This is followed by the implantation of a full root Freestyle (Medtronic Inc, Minneapolis, Minn) bioprosthesis including the fashioning and reimplantation of the coronary buttons (the coronary ostia, with a cuff of aortic tissue). The case exemplifies one of the complex endocarditis cases, which are included in the endocarditis group in this article. Video available at: https://www.jtcvs.org/article/S0022-5223(21)01042-4/fulltext.

      Appendix E1. Ethical Approval

      The study was approved by the Ethics Committee, Copenhagen Denmark (H-16047065); the local Ethics Committee, Montreal Heart Institute (2017-2336); the Swedish Ethical Review Authority (2017/1198-31/2); the Norwegian regional committee for ethical medical and health research (2018/1548/REK vest); and The National Bioethics Committee, Iceland (VSN-10-009-V8-S1).

      Early Complications

      Early complications were defined as occurring within 30 days from surgery. We included all reoperations within 30 days for which the indication was drainage output, pericardial exudate, or tamponade symptoms.
      Perioperative myocardial infarction was defined according to the Valve Academic Research Consortium-2 criteria
      • Kappetein A.P.
      • Head S.J.
      • Genereux P.
      • Piazza N.
      • van Mieghem N.M.
      • Blackstone E.H.
      • et al.
      Updated standardized endpoint definitions for transcatheter aortic valve implantation: the Valve Academic Research Consortium-2 consensus document.
      :
      • New ischemic symptoms (eg, chest pain or shortness of breath), or
      • New ischemic signs (eg, ventricular arrhythmias, new or worsening heart failure, new ST-segment changes, hemodynamic instability, new pathological Q-waves in at least 2 contiguous leads, imaging evidence of new loss of viable myocardium, or new wall motion abnormality), and
      • Elevated cardiac biomarkers (preferable creatinine kinase myocardial band [CK-MB]) within 72 hours after the index procedure, consisting of at least 1 sample post procedure with a peak value exceeding 15 times the upper reference limit for troponin or 5 times for CK-MB. If cardiac biomarkers are increased at baseline (>99th percentile), a further increase in at least 50% post procedure is required and the peak value must exceed the previously stated limit.
      If the diagnosis perioperative myocardial infarction was posed clinically, but information was not sufficient to assess the previously listed criteria, the event was included.
      A postoperative cerebrovascular event was defined as
      • Radiologically verified new cerebral lesion, or
      • New neurological symptoms (not recurrence of previous symptoms) to ensure inclusion of all relevant events, also in the absence of the detailed information used in the Valve Academic Research Consortium-2 criteria.
      Permanent pacemaker implantation: new implantation of a permanent pacemaker.
      Figure thumbnail fx4
      Figure E1Distribution of indications for aortic root replacement with the Freestyle (Medtronic Inc, Minneapolis, Minn) bioprosthesis. All indications were represented at all institutions, but the distribution varied substantially. In the total study population the proportions were: aneurysm (aortic root aneurysm): 39.8% (n = 410) , small root (patients with an aortic valve lesion at risk of prosthesis-patient mismatch): 8.3% (n = 86), other (technically challenging cases such as redo aortic valve or root, or bailout surgery for aortic root remodeling or reimplantation): 13.8% (n = 142), complex endocarditis (primarily prosthetic valve endocarditis or aortic root abscess) 26.7% (n = 275), and Stanford type A aortic dissection (type A Diss), requiring root replacement (eg, because of dissection involving the coronary or reaching the aortic valve): 11.4% (n = 117). LNKPG, Linköping University Hospital; HUS, Haukeland University Hospital; IS, Landspítali University Hospital of Iceland; MHI, Montreal Heart Institute; KS, Karolinska University Hospital; RH, Rigshospitalet, University Hospital of Copenhagen.
      Figure thumbnail fx5a
      Figure E2All-cause survival for all and for 90-day survivors after aortic root replacement (ARR) with the Freestyle (Medtronic Inc, Minneapolis, Minn) bioprosthesis, compared with the Danish general population. Overall (A and B) and per indication: aneurysm (C and D), small root (E and F), other (G and H), endocarditis (I and J), and type A dissection (K and L). Shading indicates 95% confidence interval. Curves are truncated when 10% of the population remains at risk, vertical ticks represent censor points. Data for the general population were obtained from the publicly available Human Mortality Database (www.mortality.org), and standardized according to sex and age at year of surgery.
      Figure thumbnail fx5b
      Figure E2All-cause survival for all and for 90-day survivors after aortic root replacement (ARR) with the Freestyle (Medtronic Inc, Minneapolis, Minn) bioprosthesis, compared with the Danish general population. Overall (A and B) and per indication: aneurysm (C and D), small root (E and F), other (G and H), endocarditis (I and J), and type A dissection (K and L). Shading indicates 95% confidence interval. Curves are truncated when 10% of the population remains at risk, vertical ticks represent censor points. Data for the general population were obtained from the publicly available Human Mortality Database (www.mortality.org), and standardized according to sex and age at year of surgery.
      Figure thumbnail fx6
      Figure E3Survival according to sex. In this study of 1008 patients who had undergone aortic root replacement with the Freestyle (Medtronic Inc, Minneapolis, Minn) bioprosthesis we investigated intermediate-term survival. In this study, an excessive mortality in patients who were operated for type A aortic dissection and endocarditis was shown, but a survival close to the general population in the primarily elective indications of aneurysm, small root, and “other” (consisting among other things of reoperative surgery and bailout surgery for failed aortic valve or root procedures). A subgroup analysis of men (A) and women (B) showed similar trends for both sexes. It appears as though female survival rates might be lower than that of the age- and sex-standardized general population, but because the confidence interval (CI) of all of the elective indications overlaps the curve of the general population for most of the period, this is not certain. A difference between sexes is shown in the group “others,” however, taking into consideration the heterogenicity and low number of patients in this group, this alone cannot be interpreted as a true sex-mediated difference (C shows hazard ratios [HRs] obtained using Cox proportional hazards regression analysis per sex). The excessive mortality in the group “endocarditis” might be less pronounced in the female group but is nonetheless significantly worse than for aneurysm patients, in accordance with the male group (C). Further research is needed to further understand the influence of sex on aortic root replacement with the Freestyle bioprosthesis. Diss, Dissection; a-fib, atrial fibrillation; eGFR, estimated glomerular filtration rate.
      Figure thumbnail fx7
      Figure E4Death before (A) valve-related and (B) coronary reintervention, as competing risk in the Aalen-Johnson model. Curves of “cause-2” (ie, death) from competing risk analyses of reinterventions after aortic root replacement with the Freestyle (Medtronic Inc, Minneapolis, Minn) bioprosthesis. Curves are truncated at 10% of the group population remaining at risk, censor times are marked with ticks and 95% confidence interval is indicated by shading. See for inverted cumulative incidence curves for (A) valve-related reinterventions and (B) coronary reinterventions. Aneurysm indicates aortic root aneurysm, small root indicates patients with aortic valve lesion at risk for patient-prosthesis mismatch, other represents primarily reoperative cases (with eg, aortic valve dysfunction, and bail-out for eg, aortic valve plasties), and endocarditis indicates complex endocarditis such as prosthetic endocarditis or root abscess. Diss, Dissection.
      Table E1Preoperative patient characteristics according to indication, including missing data
      % (n)AneurysmSmall rootOtherEndocarditisType A dissectionAll
      100 (410)100 (86)100 (142)100 (275)100 (117)100 (1030)
      Age at surgery
       Median (IQR), y67 (61-72)68 (58.2-73.0)65 (55.2-71.0)63 (51.5-71.0)66 (60-71)66 (58.0-71.8)
       Range, y22-8518-8424-8614-8633-8214-86
       Missing, n000000
      Age <60 y22.4 (92)26.7 (23)42.3 (60)42.2 (116)27.4 (32)31.4 (323)
      Male sex72.2 (296)22.1 (19)57.7 (82)81.8 (225)67.5 (79)68.1 (701)
       Missing, n000000
      BMI
       <205.2 (21)5.9 (5)4.4 (6)5.3 (14)6.4 (7)5.3 (53)
       20-3077.9 (313)65.9 (56)67.2 (92)75.3 (198)78.2 (86)74.7 (745)
       >3016.9 (68)28.2 (24)28.5 (39)19.4 (51)15.5 (17)20.0 (199)
       Missing, n81512733
      Median eGFR (IQR), mL/min78 (64.9-97.6)71 (56.4-85.3)75.4 (61.2-97.1)77.4 (52.7-90.0)71.8 (57.5-82.0)76 (60-90)
       Missing, n7108420
      Dialysis0.2 (1)1.2 (1)0.7 (1)8.1 (22)0.9 (1)2.5 (26)
       Missing, n002406
      Diabetes mellitus5.9 (24)15.1 (13)9.9 (14)14.0 (38)3.4 (4)9.1 (93)
       Missing, n100405
      Insulin-dependent diabetes1.5 (6)3.5 (3)2.8 (4)2.6 (7)0.9 (1)2.0 (21)
       Missing, n100405
      Hypertension65.0 (265)59.3 (51)63.4 (90)51.9 (137)60.3 (70)60.3 (613)
       Missing, n000000
      Hypercholesterolemia42.8 (161)52.9 (45)48.2 (67)35.4 (87)30.5 (32)41.2 (392)
       Missing, n3413291279
      Atrial fibrillation17.8 (73)14.1 (12)22.9 (32)27.0 (70)16.2 (19)20.4 (206)
       Missing, n11216020
      Coronary artery disease23.3 (94)33.7 (29)29.7 (41)21.7 (57)12.2 (14)23.4 (235)
       Missing, n60412224
      Chronic lung disease13.3 (54)15.3 (13)11.3 (16)9.6 (26)14.5 (17)12.3 (126)
       Missing, n410409
      Previous cerebrovascular disease9.0 (37)14.0 (12)14.9 (21)24.3 (66)15.4 (18)15.0 (154)
       Missing, n001304
      Peripheral vascular disease4.6 (19)9.3 (8)6.4 (9)5.2 (14)5.1 (6)5.5 (56)
       Missing, n001506
      Bicuspid valve40.9 (167)15.1 (13)15.9 (22)14.3 (39)7.7 (9)24.5 (250)
       Missing, n204208
      Previous cardiac surgery9.3 (38)9.3 (8)73.9 (105)68.6 (188)9.5 (11)34.0 (350)
       Aortic surgery8.3 (34)2.4 (2)64.8 (92)64.2 (176)7.8 (9)30.5 (313)
       CABG1.2 (5)0.0 (0)10.6 (15)8.5 (23)1.7 (2)4.4 (45)
       Other0.2 (1)7.0 (6)7.0 (10)4.4 (12)0.0 (0)2.8 (29)
       Missing, n000112
      History of endocarditis1.7 (7)0.0 (0)14.8 (21)28.2 (77)0.9 (1)10.3 (106)
       Missing, n000213
      Data are presented as % (n) except where otherwise noted. IQR, Interquartile range; BMI, body mass index; eGFR, estimated glomerular filtration rate; CABG, coronary artery bypass graft.
      Table E2Preoperative patient characteristics according to indication and sex: men
      N (%)AneurysmSmall rootOtherEndocarditisType A dissectionAllP value
      296 (100)19 (100)82 (100)225 (100)79 (100)701 (100)
      Age at surgery
       Median (IQR), y66 (60-70)58 (51.0-67.5)65 (57.0-70.8)63 (50-71)65 (60-70)65 (58-70).0002
       Range22-8518-7824-8214-8637-8214-86
       Missing, n000000
      Age <60 y25.3 (75)57.9 (11)41.5 (34)42.7 (96)26.6 (21)33.8 (237)<.0001
      Median BMI continuous (IQR)26.6 (23.8-28.8)25.1 (23.4-28.7)27.0 (23.1-29.1)25.7 (23.1-29.1)25.8 (23.9-28.0)26.2 (23.7-29.0).04
      BMI categorical
       <203.4 (10)5.3 (1)1.2 (1)5.1 (11)6.8 (5)4.1 (28)
       20-3079.0 (229)73.7 (14)65.0 (52)73.1 (158)80.8 (59)75.5 (512)
       >3017.6 (51)21.1 (4)33.8 (27)21.8 (47)12.3 (9)20.4 (138)
       Missing, n6029623
      Median eGFR (IQR), mL/min83.8 (68.8-103.1)83.3 (72.0-95.2)84 (64.1-101.8)78 (53-90)72 (57.2-82.0)79.8 (62.3-97.3).0001
       Missing, n4005413
      Dialysis0.0 (0)5.3 (1)0.0 (0)6.7 (15)1.3 (1)2.4 (17)<.0001
       Missing, n002204
      Diabetes mellitus5.1 (15)15.8 (3)8.5 (7)14.7 (33)5.1 (4)8.9 (62).002
       Missing, n100102
      Insulin-dependent diabetes1.0 (3)0.0 (0)1.2 (1)3.1 (7)1.3 (1)1.7 (12).40
       Missing, n100102
      Hypertension64.6 (190)36.8 (7)68.3 (56)51.8 (113)63.3 (50)60.1 (416).02
       Missing, n000000
      Hypercholesterolemia43.0 (117)36.8 (7)48.1 (39)34.5 (70)30.6 (22)39.4 (255).07
       Missing, n240122754
      Atrial fibrillation18.6 (55)10.5 (2)20.0 (16)27.8 (59)17.7 (14)21.3 (146).07
       Missing, n00213015
      Coronary artery disease25.4 (74)21.1 (4)38.3 (31)22.2 (48)15.6 (12)24.7 (169).01
       Missing, n5019217
      Chronic lung disease11.3 (33)0.0 (0)12.2 (10)9.8 (22)12.7 (10)10.8 (75).55
       Missing, n400105
      Previous cerebrovascular disease9.5 (28)5.3 (1)15.9 (13)21.9 (49)11.4 (9)14.3 (100).001
       Missing, n000101
      Peripheral vascular disease5.4 (16)5.3 (1)6.1 (5)5.8 (13)6.3 (5)5.7 (40)1.00
       Missing, n000202
      Bicuspid valve42.5 (125)36.8 (7)18.5 (15)16.6 (37)10.1 (8)27.6 (192)<.0001
       Missing, n201205
      Previous cardiac surgery10.5 (31)15.8 (3)72.0 (59)67.4 (151)14.1 (11)36.5 (255)<.0001
       Aortic surgery9.5 (28)0.0 (0)63.4 (52)63.4 (142)11.5 (9)33.1 (231)
       CABG1.0 (3)0.0 (0)14.6 (12)9.0 (20)2.5 (2)5.3 (37)
       Other0.3 (1)15.8 (3)4.9 (4)4.0 (9)0.0 (0)2.4 (17)
       Missing, n000112
      History of endocarditis1.4 (4)0.0 (0)19.5 (16)29.9 (67)1.3 (1)12.6 (88)<.0001
       Missing, n000112
      Data are presented as % (n) except where otherwise noted. IQR, Interquartile range; BMI, body mass index; eGFR, estimated glomerular filtration rate; CABG, coronary artery bypass graft.
      Table E3Preoperative patient characteristics according to indication and sex: women
      N (%)AneurysmSmall rootOtherEndocarditisType A dissectionAllP value
      114 (100)69 (100)63 (100)50 (100)38 (100)329 (100)
      Age at surgery [y]
       Median (IQR)68 (64-74)69 (62.0-74.5)63 (54.8-72.0)63.5 (54.5-70.8)67 (59.0-72.5)68 (59-73).0008
       Range37-8319-8431-8625-8433-7719-86
       Missing, n000000
      Age <60 y14.9 (17)17.9 (12)43.3 (26)40.0 (20)28.9 (11)26.1 (86)<.0001
      Median BMI continuous (IQR)25 (22-28)26.4 (23.6-30.9)24 (21.4-28.8)24.2 (22.3-28.7)24.5 (22.3-29.4)24.8 (22.2-28.9).002
      BMI categorical.18
       <209.8 (11)6.1 (4)8.8 (5)6.4 (3)5.4 (2)7.8 (25)
       20-3075.0 (84)63.6 (42)70.2 (40)85.1 (40)73.0 (27)73.0 (233)
       >3015.2 (17)30.3 (20)21.1 (12)8.5 (4)21.6 (8)19.1 (61)
       Missing, n2133110
      Median eGFR (IQR), mL/min68.4 (55.0-85.7)68.4 (56.1-83.0)69.6 (57.8-90.0)66.2 (51.6-90.0)71.4 (59.2-83.8)68.6 (55.7-86.9).66
       Missing, n310307
      Dialysis0.9 (1)0.0 (0)1.7 (1)14.6 (7)0.0 (0)2.8 (9)<.0001
       Missing, n000202
      Diabetes mellitus7.9 (9)14.9 (10)11.7 (7)10.6 (5)0.0 (0)9.5 (31).14
       Missing, n000303
      Insulin-dependent diabetes2.6 (3)4.5 (3)5.0 (3)0.0 (0)0.0 (0)2.8 (9).37
       Missing, n000303
      Hypertension65.8 (75)65.7 (44)56.7 (34)52.2 (24)54.1 (20)60.8 (197).004
       Missing, n000000
      Hypercholesterolemia42.3 (44)57.6 (38)48.3 (28)39.5 (17)30.3 (10)45.1 (137).09
       Missing, n10127525
      Atrial fibrillation15.9 (18)15.2 (10)26.7 (16)23.4 (11)13.2 (5)18.5 (60).28
       Missing, n110305
      Coronary artery disease17.7 (20)37.3 (25)17.5 (10)19.1 (9)5.3 (2)20.5 (66).001
       Missing, n103307
      Chronic lung disease18.4 (21)19.7 (13)10.0 (6)8.5 (4)18.4 (7)15.7 (51).29
       Missing, n010304
      Previous cerebrovascular disease7.9 (9)16.4 (11)13.6 (8)35.4 (17)23.7 (9)16.6 (54).0004
       Missing, n001203
      Peripheral vascular disease2.6 (3)10.4 (7)6.8 (4)2.1 (1)2.6 (1)4.9 (16).12
       Missing, n001304
      Bicuspid valve36.8 (42)9.0 (6)12.3 (7)4.0 (2)2.6 (1)17.8 (58)<.0001
       Missing, n003003
      Previous cardiac surgery6.1 (7)7.5 (5)76.7 (46)74.0 (37)0.0 (0)28.9 (95)<.0001
       Aortic surgery5.3 (6)3.0 (2)66.7 (40)68.0 (34)0.0 (0)24.9 (82)
       CABG1.8 (2)0.0 (0)5.0 (3)6.2 (3)0.0 (0)2.4 (8)
       Other0.0 (0)4.5 (3)10.0 (6)6.0 (3)0.0 (0)3.6 (12)
       Missing, n000000
      History of endocarditis2.6 (3)0.0 (0)8.3 (5)20.4 (10)0.0 (0)5.5 (18)<.0001
       Missing, n000101
      IQR, Interquartile range; BMI, body mass index; eGFR, estimated glomerular filtration rate; CABG, coronary artery bypass graft.
      Table E4Surgical characteristics according to indication, including missing data
      % (n)AneurysmSmall rootOtherEndocarditisType A dissectionAll
      100 (410)100 (86)100 (142)100 (275)100 (117)100 (1030)
      Isolated aortic root replacement20.6 (84)45.3 (39)45.1 (64)40.7 (111)4.3 (5)29.5 (303)
      Concomitant procedure79.4 (324)54.7 (47)54.9 (78)59.3 (162)95.7 (112)70.5 (723)
       Asc ao only44.6 (182)9.3 (8)15.5 (22)9.5 (26)46.2 (54)28.5 (292)
       CABG (with or without asc ao)12.3 (50)25.6 (22)15.5 (22)10.3 (28)17.1 (20)13.8 (142)
       Aortic arch surgery10.8 (44)1.2 (1)2.8 (4)2.2 (6)24.8 (29)8.2 (84)
       Other13.3 (54)18.6 (16)22.0 (31)37.7 (103)9.4 (11)21.0 (215)
       Missing, n200204
      Implanted valve size in mm
       190.0 (0)5.8 (5)1.4 (2)1.1 (3)0.9 (1)1.1 (11)
       212.7 (11)32.6 (28)17.6 (25)7.3 (20)6.0 (7)8.8 (91)
       2312.0 (49)44.2 (38)26.8 (38)22.2 (61)20.5 (24)20.4 (210)
       2524.1 (99)12.8 (11)28.9 (41)31.6 (87)33.3 (39)26.9 (277)
       2736.6 (150)4.7 (4)14.8 (21)21.1 (58)27.4 (32)25.7 (265)
       2923.4 (96)0.0 (0)5.6 (8)9.5 (26)8.5 (10)13.6 (140)
       Not noted1.2 (5)0.0 (0)4.9 (7)7.3 (20)3.4 (4)3.5 (36)
      Suture technique, proximal Freestyle anastomosis
       Running57.3 (235)79.1 (68)47.9 (68)45.1 (124)41.9 (49)52.8 (544)
       Pledgeted U-sutures36.1 (148)14.0 (12)33.8 (48)26.5 (73)53.8 (63)33.4 (344)
       Other4.4 (18)4.7 (4)11.3 (16)18.2 (50)1.7 (2)8.7 (90)
       Not noted2.2 (9)2.3 (2)7.0 (10)10.2 (28)2.6 (3)5.0 (52)
      Median cross-clamp time (IQR), min116 (95-138)109 (86-135)147 (112-186)160 (122-198)155 (123-188)130 (103-172)
       Isolated aortic root replacement104 (88-120)88 (77-112)123 (102-171)127 (109-158)122 (122-134)116 (92-142)
       Concomitant asc ao only112 (95-131)116 (97-123)156 (130-185)182 (161-222)143 (121-173)123 (101-152)
       Concomitant CABG (with or without asc ao)133 (114-172)122 (104-150)134 (123-173)174 (149-200)161 (120-219)144 (117-180)
       Concomitant aortic arch surgery122 (102-162)85 (85-85)266 (247-278)180 (160-193)163 (144-223)152 (118-188)
       Other concomitant procedure129 (90-171)136 (109-152)177 (148-216)192 (142-235)163 (147-187)166 (125-215)
       Missing, n40510221
      Median CPB time (IQR), min150 (124-187)139 (110-184)196 (155-264)225 (176-287)255 (206-317)181 (139-246)
       Isolated aortic root replacement125 (113-163)109 (95-137)175 (143-230)180 (149-228)175 (170-233)166 (121-201)
       Concomitant asc ao only144 (124-166)136 (117-148)205 (149-269)250 (196-281)242 (201-281)162 (132-217)
       Concomitant CABG (with or without asc ao)179 (147-247)179 (147-204)192 (181-243)254 (215-298)309 (210-399)211 (160-280)
       Concomitant aortic arch surgery191 (149-236)152 (152-152)337 (325-365)328 (289-362)263 (215-340)235 (177-314)
       Other concomitant procedure177 (130-220)168 (133-198)256 (185-313)260 (201-344)305 (269-370)228 (170-308)
       Missing, n40510221
      Data are presented as % (n) except where otherwise noted. Freestyle bioprosthesis is from Medtronic Inc (Minneapolis, Minn). asc ao, Ascending aorta; CABG, coronary artery bypass graft; IQR, interquartile range; CPB, cardiopulmonary bypass.

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      Linked Article

      • Commentary: Posting up for the stentless
        The Journal of Thoracic and Cardiovascular SurgeryVol. 164Issue 6
        • Preview
          In the United States, stentless roots comprise 31% of aortic root replacements (ARRs).1 From a standalone report on use of the Freestyle porcine root prosthetic for ARR, Dagnegård and colleagues2 provide insight into several aspects of this biologic root substitute This study has implications for patients of all ages. In both elderly3 and younger populations,4 there has been a trend toward biologic valve replacements relative to mechanical valves.4 A study of aortic root operations linking the Society of Thoracic Surgeons database with Centers for Medicare & Medicaid Services data found that longer-term survival was superior with stentless bioprosthetic Bentall compared with mechanical Bentall (adjusted hazard ratio, 0.70).
        • Full-Text
        • PDF
      • Commentary: Stentless root takes root in real world
        The Journal of Thoracic and Cardiovascular SurgeryVol. 164Issue 6
        • Preview
          Dagnegård and colleagues1 present the largest study to date of aortic root replacement using a stentless porcine root (Freestyle, Medtronic, Minneapolis, Minn)—1008 patients had 1030 operations. Having been 1 of only 2 principal investigators in the initial worldwide investigation (begun in 1992) to consistently use full root method of implantation,2 it is gratifying to see the technique validated in a wide variety of root pathologies. Including small-to medium-size programs gives a “real-world” context, but each center is in truth a regional aortic surgery referral center.
        • Full-Text
        • PDF