Baghai et al. Journal of Cardiothoracic Surgery (2021) 16:154 https://doi.org/10.1186/s13019-021-01523-w RESEARCH ARTICLE Open Access Clinical outcomes after implantation of a sutureless aortic bioprosthesis with concomitant mitral valve surgery: the SURE- AVR registry Max Baghai1* , Mattia Glauber2, Raphael Fontaine3, Jose Cuenca Castillo4, Antony H. Walker5, Ugolino Livi6, José Montiel7, Alistair Royse8, Gianluigi Bisleri9, Davide Pacini10, Vincenzo Argano11, Aurelien Roumy12, George Asimakopoulos13, Marco Solinas14, on behalf of the SURE-AVR investigators Abstract Background: Early treatment of aortic valve stenosis is recommended in eligible symptomatic patients with severe aortic valve stenosis who would otherwise have a poor prognosis. The sutureless aortic valve bioprosthesis offers an alternative to standard aortic valve replacement with a sutured valve, but limited data are available in patients who have undergone multiple valve procedures involving the new, sutureless technology. We sought to investigate outcomes in high operative risk patients with previous or concomitant valve surgery who were implanted with a sutureless valve. Methods: SURE-AVR is an ongoing, prospective, multinational registry of patients undergoing aortic valve replacement. In-hospital and post-discharge outcomes up to 5 years were collected. Results: The study population comprised 78 patients (mean ± SD: age 73.6 ± 7.6 years, logistic EuroSCORE 18.0 ± 17.5) enrolled at 13 sites who presented for concomitant or previous mitral valve repair (n = 45) or replacement (n = 33), with or without additional concomitant procedures, and were implanted with a sutureless valve. Mean ± SD overall aortic cross-clamp time was 109 ± 41 min and cardiopulmonary bypass time was 152 ± 49 min. Mean ± SD aortic pressure gradients decreased from 37.6 ± 17.7 mmHg preoperatively to 13.0 ± 5.7 mmHg at hospital discharge, and peak aortic pressure gradient from 61.5 ± 28.7 to 23.4 ± 10.6 mmHg. Early events included 1 death, 1 transient ischaemic attack, and 1 bleed (all 1.3%); a permanent pacemaker implantation was required in 6 patients (7.7%), and 2 reoperations (not valve related) (2.6%) took place. Over a median follow-up of 55.5 months (Q1 13.4, Q3 68.6), 12 patients died (6 cardiovascular and 6 non-cardiovascular, both 2.1% per patient-year). Five-year survival was 81.3%. Late paravalvular leak occurred in 2 patients (0.7% per patient-year) and permanent pacemaker implantation was required in 3 patients (0.1% per patient-year). There was no apparent rise in mean or peak aortic pressure gradient over the study. * Correspondence: mbaghai@nhs.net 1 Department of Cardiovascular Medicine, King’s College Hospital, Brixton, London SE5 9RS, UK Full list of author information is available at the end of the article © The Author(s). 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Baghai et al. Journal of Cardiothoracic Surgery (2021) 16:154 Page 2 of 10 Conclusions: These results suggest that the sutureless implant is a technically feasible procedure during mitral surgery and is associated with good clinical outcomes. Keywords: Aortic valve stenosis, Aortic valve replacement, Aortic valve, Valvular disease Background or malfunctioning native aortic heart valves or pros- Aortic valve stenosis is the most frequent valvular dis- theses. It has a functional component, comprising bovine ease resulting in surgical or catheter intervention in pericardium, stabilized in buffered glutaraldehyde solu- Western countries, and the prevalence is rising due to tion, and a super-elastic metal alloy stent, which has the the ageing population [1]. Early treatment is recom- dual role of valve support and anchoring to the aortic mended in eligible symptomatic patients with severe root with no permanent sutures. Before implantation, aortic valve stenosis, who would otherwise have a poor the prosthesis diameter is reduced to a suitable size for prognosis [1]. loading onto a holder accessory. The valve is then posi- The sutureless aortic valve bioprosthesis offers an al- tioned and released in the aortic root and post-dilated ternative to standard aortic valve replacement (AVR) using a balloon catheter. The device is available in 4 with a sutured valve. It has a shorter cross-clamp time sizes (small, medium, large, extra-large, corresponding than traditional valves, and hence a shorter myocardial to prosthesis heights of 31.0, 33.0, 35.5, and 37.5 mm, re- ischaemia time [2], and is associated with better clinical spectively). Implantation could be performed using a outcomes and reduced hospital costs [3]. In a meta- traditional surgical approach [14, 15] or through minim- analysis involving 84 studies, reductions in aortic cross- ally invasive cardiac surgery [16–18]. clamp and cardiopulmonary bypass times were reported Patients were enrolled in a sequential and prospective with the Perceval sutureless valve (LivaNova plc, manner and were treated based on the standard of care London, UK) versus a traditional sutured prosthesis. at participating sites. All patients received a unique Limited data, restricted to small, single-centre, short- registry number in the electronic data capture system to term cohorts, are available in patients who have under- guarantee their anonymity. Participation was voluntary, gone multiple valve procedures involving the new, and patients could withdraw from participating at any sutureless technology [4–8]. In elderly high-risk patients time. with isolated AVR, rates of operative mortality range Baseline data were entered into an electronic case re- from 0 to 3% for sutureless AVR and from 4 to 10% for port form by trained study coordinators, and included conventional AVR [2, 9–12]. However, higher rates have demographic, clinical, echocardiographic, and surgical been reported in patients undergoing complex concomi- data. Follow-up visits were performed according to the tant procedures (5.3–7.4% for sutureless AVR and 15.6% centres’ usual practices (by telephone call, referring for conventional AVR) [7, 13]. We therefore sought to physician, or clinical visit) at 1 year and annually there- investigate early and late outcomes in high operative risk after to 5 years, with follow-up at 7 and 10 years in se- patients with previous or concomitant valve surgery who lected centres. The results presented herein are limited were implanted with the sutureless valve, using data to 5-year follow-up. from the Sorin Universal REgistry on Aortic Valve An electronic data capture system was used to allow Replacement (SURE-AVR). specific quality control checks. The sponsor’s project team also applied checks to ensure an appropriate level Patients and methods of quality and compliance of the data. No source verifi- SURE-AVR is an ongoing, prospective, observational cation visits were conducted. Before enrolling patients, registry being conducted at 60 sites in 18 countries in staff at each participating centre underwent training on Europe, Canada, and Australia (ClinicalTrials.gov identi- the protocol, electronic case report form, and electronic fier: NCT02679404). Patients implanted with any of the data capture system. commercially available LivaNova aortic products are eli- The design and conduct of the registry are overseen by a gible for enrolment. This analysis focuses on patients study coordinating committee comprising representatives implanted with the Perceval sutureless aortic valve who from the different regions involved in the study. The com- presented at 13 sites for concomitant or previous mitral mittee is responsible for registry oversight, including study valve repair or replacement with or without additional progress, patient safety, and data quality and integrity. concomitant procedures. The Perceval (LivaNova plc, London, UK) sutureless Clinical outcomes valve is a self-anchoring, self-expanding, surgical aortic Data on multiple procedural and hospital discharge vari- bioprosthesis indicated for the replacement of damaged ables were collected, including implant success, cross- Baghai et al. Journal of Cardiothoracic Surgery (2021) 16:154 Page 3 of 10 clamp time, length of stay in the intensive care unit, and Before the sutureless implant, 11.5% of patients had total length of hospitalization. Clinical success was de- undergone aortic valve replacement, 11.5% mitral valve fined as a successful valve implantation without the oc- replacement, 10.3% coronary artery bypass graft (CABG), currence of major adverse events by the time of and 7.7% mitral valve repair (Table 2). discharge. Major adverse events (investigator reported) were defined as death (all-cause, non-cardiovascular, and Surgical procedures cardiovascular [including deaths of unknown cause]), The majority (76.9%) of patients underwent a median stroke, and reintervention (surgery or other cardiac inva- sternotomy approach and a large-size valve was im- sive therapy). Serious valve-related adverse events in- planted in 46.2% (Table 3). A concomitant procedure cluded bleeding, thromboembolism, valve thrombosis, was reported in 89.7% of the patients, with CABG per- endocarditis, non-structural dysfunction, and structural formed in 16.7% and tricuspid repair in 16.7%. The valve deterioration. All adverse events are defined ac- sutureless valve was successfully implanted in all cording to the Valve Academic Research Consortium-2 patients. criteria [19]. Severity of valve dysfunction was classified Mean ± SD overall aortic cross-clamp time was 109 ± as mild (grade 1+), moderate (2+), moderate to severe 41 min (median 105, Q1 84, Q3 132 min) and the (3+) or severe (4+). Improvement in clinical status was mean ± SD cardiopulmonary bypass time was 152 ± 49 defined as an improvement of ≥1 in the New York Heart min (median 145, Q1 124, Q3 173 min) (Table 3). Mean Association (NYHA) classification from baseline (before length of stay in the intensive care unit was 3.1 ± 4.1 days the procedure), measured annually throughout the study. (median 2.0, Q1 1.0, Q3 3.5 days); total length of hospital Echocardiographic and haemodynamic data were col- stay was 14.2 ± 9.4 days (median 11.0, Q1 8.0, Q3 16.0 lected. Early outcomes were defined as those occurring days). up to 30 days after the procedure and late outcomes as those occurring > 30 days after the procedure. Early outcomes Mean ± SD effective orifice area was 0.7 ± 0.3 cm2 before surgery and 1.4 ± 0.3 cm2 at discharge (Fig. 1). Mean aor- Statistical analysis tic pressure gradient decreased from 37.6 ± 17.7 mmHg Variables are described as mean ± standard deviation preoperatively to 13.0 ± 5.7 mmHg at discharge from (SD) or median (quartile [Q1, Q3]; range) for quantita- hospital, and peak aortic pressure gradient from 61.5 ± tive variables and as number (%) for qualitative variables. 28.7 mmHg to 23.4 ± 10.6 mmHg. Outcomes are reported as descriptive statistics. The Early outcomes are detailed in Table 4. There was 1 rates of early adverse events were calculated as the num- death (due to septicaemia), 1 transient ischaemic attack, ber of events divided by the number of patients. Linear- and 1 case of bleeding (all 1.3%). There were no cases of ized complication rates were calculated as the number of endocarditis, myocardial infarction, or structural valve late events divided by the number of patient-years. The deterioration. Mild non-structural valve dysfunction (not statistical analyses were performed using SAS® (Release requiring intervention) was reported in 10 patients 9.4, by SAS Institute Inc., Cary, NC, USA). (12.8%). Mild paravalvular leak occurred in 1 patient (1.3%). A permanent pacemaker implantation was re- Results quired in 6 patients (7.7%), due to third-degree atrioven- A total of 1134 patients (482 men and 652 women) im- tricular block in 4 patients and for unspecified planted with a sutureless valve were prospectively en- conduction disorders in 2 patients. Two reoperations rolled in the SURE-AVR registry between March 2011 (not valve related) (2.6%) took place, 1 due to subtampo- and March 2019. Of these, 78 patients (enrolled at 13 nade pericardial effusion and 1 to superior vena cava sites) had undergone a previous and/or concomitant mi- syndrome. No explants were reported. tral valve procedure: 45 mitral valve repair and 33 mitral valve replacement. Late outcomes The characteristics of the study population are detailed Median study follow-up duration was 55.5 months (Q1 in Table 1. Most patients were female (74.4%) and the 13.4, Q3 68.6 months), with a cumulative follow-up of mean ± SD age at surgery was 73.6 ± 7.6 years. The main 289.2 patient-years (including 282.5 patient-years). Late indication for a sutureless implant was aortic valve sten- outcomes are detailed in Table 4. Mean effective orifice osis (59.0%). A diagnosis of mitral regurgitation was re- area was 1.4 ± 0.4 cm2, mean aortic pressure gradient ported for 64.1% of the patients. Tricuspid regurgitation was 12.5 ± 6.0 mmHg, and peak aortic pressure gradient was diagnosed in 61.5% of the patients. Most of the pa- was 21.4 ± 10.7 mmHg at 5 years (Fig. 1). tients (87.0%) were in NYHA class II or III. Mean ± SD Six cardiovascular deaths (2.1% per patient-year) were logistic EuroSCORE I was 18.0 ± 17.5. reported as late outcomes, 1 caused by worsening heart Baghai et al. Journal of Cardiothoracic Surgery (2021) 16:154 Page 4 of 10 Table 1 Baseline demographics and clinical characteristics in overall population and according to type of mitral valve surgery Characteristic Overall population (n = 78) Mitral repair (n = 45) Mitral replacement (n = 33) Women, n (%) 58 (74.4) 31 (68.9) 27 (81.8) Age at surgery (years), mean ± SD 73.6 ± 7.6 73.0 ± 8.3 74.5 ± 6.5 Range 55–88 55–88 60–87 Body surface area (m2), mean ± SD 1.7 ± 0.2 1.8 ± 0.2 1.7 ± 0.2 Diagnosis, n (%) Aortic valve stenosis 46 (59.0) 28 (62.2) 18 (54.5) Aortic steno-regurgitation 16 (20.5) 7 (15.6) 9 (27.3) Aortic regurgitation 15 (19.2) 10 (22.2) 5 (15.2) Mitral stenosis 7 (9.0) 3 (6.7) 4 (12.1) Mitral steno-regurgitation 10 (12.8) 2 (4.4) 8 (24.2) Mitral regurgitation 50 (64.1) 36 (80.0) 14 (42.4) Tricuspid regurgitation (mild to severe) 48 (61.5) 28 (62.2) 20 (60.6) Risk factors, n (%) Diabetes mellitus 23 (29.5) 15 (33.3) 8 (24.2) Coronary artery disease 28 (35.9) 16 (35.6) 12 (36.4) Endocarditis 6 (7.7) 3 (6.7) 3 (9.1) Renal insufficiency 12 (15.4) 7 (15.6) 5 (15.2) Cerebrovascular events 4 (5.1) 4 (8.9) 0 Chronic lung disease 9 (11.5) 7 (15.6) 2 (6.1) NYHA class (n = 77) (n = 45) (n = 32) I 1 (1.3) 1 (2.2) 0 II 35 (45.5) 24 (53.3) 11 (34.4) III 32 (41.6) 15 (33.3) 17 (53.1) IV 9 (11.7) 5 (11.1) 4 (12.5) Left ventricular ejection fraction (%) (n = 25) (n = 15) (n = 10) Mean ± SD 53.1 ± 9.6 50.4 ± 8.8 57.0 ± 9.7 Median (quartile 1, quartile 3) 55.0 (45.4; 60.0) 53.7 (45.0; 57.0) 57.5 (50.0; 62.0) Logistic EuroSCORE I (n = 50) (n = 29) (n = 21) Mean ± SD 18.0 ± 17.5 15.9 ± 17.7 20.9 ± 17.3 Median (quartile 1, quartile 3) 11.5 (7.5; 21.5) 9.1 (6.6; 18.5) 15.7 (9.1; 24.4) NYHA New York Heart Association, SD standard deviation Table 2 Previous cardiac surgery in the overall population and according to type of mitral valve surgerya Surgery, n (%) Overall population (n = 78) Mitral repair (n = 45) Mitral replacement (n = 33) Coronary artery bypass graft 8 (10.3) 1 (2.2) 7 (21.2) Repair procedure 10 (12.8) 5 (11.1) 5 (15.2) Aortic valve repair 5 (6.4) 3 (6.7) 2 (6.1) Mitral valve repair 6 (7.7) 3 (6.7) 3 (9.1) With ring 3/6 (50.0) 2/3 (66.7) 1/3 (33.3) Valve replacement 15 (19.2) 3 (6.7) 12 (36.4) Aortic valve replacement 9 (11.5) 3 (6.7) 6 (18.2) Mitral valve replacement 9 (11.5) 0 9 (27.3) a Some patients may have undergone more than one previous cardiac surgery Baghai et al. Journal of Cardiothoracic Surgery (2021) 16:154 Page 5 of 10 Table 3 Procedural characteristics in the overall population and according to type of mitral valve surgery Characteristic, n (%) Overall population (n = 78) Mitral repair (n = 45) Mitral replacement (n = 33) Surgical approach Median sternotomy 60 (76.9) 30 (66.7) 30 (90.9) Minimally invasive cardiac surgery 18 (23.1) 15 (33.3) 3 (9.1) Mini thoracotomy 17 (21.8) 15 (33.3) 2 (6.1) Mini sternotomy 1 (1.3) 0 1 (3.0) Valve size (aortic annulus diameter) Small (19–21 mm) 9 (11.5) 5 (11.1) 4 (12.1) Medium (21–23 mm) 29 (37.2) 14 (31.1) 15 (45.5) Large (23–25 mm) 36 (46.2) 23 (51.1) 13 (39.4) Extra large (25–27 mm) 4 (5.1) 3 (6.7) 1 (3.0) Concomitant procedures 70 (89.7) 42 (93.3) 28 (84.8) CABG 13 (16.7) 11 (24.4) 2 (6.1) Atrial fibrillation ablation 3 (3.8) 2 (4.4) 1 (3.0) Mitral surgery 69 (88.5) 42 (93.3) 27 (81.8) Repair procedure 43/69 (62.3) 42/42 (100.0) 1/27 (3.7) Replacement procedure 26/69 (37.7) 0 26/27 (96.3) Tricuspid surgery 13 (16.7) 6 (13.3) 7 (21.2) Repair procedure 13/13 (100.0) 6/6 (100.0) 7/7 (100.0) Replacement procedure 0 0 0 Implant successful 78 (100.0) 45 (100.0) 33 (100.0) Cross-clamp time (min) Mean ± SD 109 ± 41 107 ± 28 113 ± 55 Median (quartile 1, quartile 3) 105 (84; 132) 105 (85; 125) 106 (77; 136) Cardiopulmonary bypass time (min) Mean ± SD 152 ± 49 147 ± 32 159 ± 68 Median (quartile 1, quartile 3) 145 (121; 173) 141 (124; 168) 148 (118; 191) CABG coronary artery bypass graft, SD standard deviation failure, 1 due to a possible cardiac cause, and 4 of an un- any haemodynamic consequences). Permanent pace- known cause. Six non-cardiovascular deaths (2.1% per maker implantation was required in 3 patients (1.1% per patient-year) occurred, 3 as a result of neoplasia, 2 due patient-year), due to atrioventricular block III in 1 pa- to other non − valve-related causes (1 urosepsis, 1 un- tient and other unspecified conduction disorders in 2 known [the patient died while abroad and based on the patients. A transcatheter valve (0.4% per patient-year) information provided, their doctor classified the death as was implanted in 1 patient after 873 days, due to moder- non-cardiovascular]), and 1 due to renal failure. Survival ate/severe regurgitation. Two sutureless valves were at 5-year follow-up was 81.3% in the overall population, explanted (0.7% per patient-year), 1 due to endocarditis 83.8% in the mitral repair group, and 77.9% in the mitral and 1 to non-structural valve dysfunction. There was no replacement group (Fig. 2). Two cases of bleeding (0.7% apparent rise in either the mean aortic or peak gradient per patient-year) and 1 case each of transient ischaemic over the course of the study (Fig. 1). attack, non-disabling stroke, and endocarditis (all 0.4% per patient-year) occurred. No cases of myocardial in- Discussion farction, thrombosis, or structural valve deterioration In this population of patients at high operative risk who were reported. In addition to the 2 cases requiring re- had undergone a previous and/or concomitant valvular intervention described above, mild non-structural valve procedure, the sutureless biological aortic valve was a dysfunction (intra-prosthetic regurgitation) was reported technically feasible procedure during mitral surgery and in 9 patients (3.2% per patient-year), none of which re- was associated with good clinical outcomes, both early quired intervention. Paravalvular leak occurred in 2 pa- after the procedure and up to 5 years of follow-up. Im- tients (0.7% per patient-year) (mild regurgitation without plantation of the sutureless aortic valve in the presence Baghai et al. Journal of Cardiothoracic Surgery (2021) 16:154 Page 6 of 10 Fig. 1 a Effective orifice area and b mean aortic pressure gradient, preoperatively and up to 5 years of follow-up. Vertical lines indicate standard error of a previously implanted prosthesis in the mitral pos- reporting outcomes in patients undergoing isolated ition or with a concomitant mitral valve procedure sutureless AVR or with concomitant cardiac procedures, appears to be a viable option. but most are relatively small, retrospective in design, Limited comparative data are currently available in pa- have no comparator arm, or involve lower-risk patients tients undergoing multiple valve procedures with stented [7, 13, 21]. In the recently published prospective, ran- or sutureless valves. One of the largest is the Epic study domized PERSIST-AVR study [22], 910 patients with se- [20], which enrolled an elderly all-comer population vere symptomatic aortic valve stenosis were randomized undergoing aortic, mitral, or double-valve replacement to undergo implantation with a sutureless valve or a with a stented porcine xenograft during 2001 to 2012 standard aortic valve, using a conventional or minimally and followed them for a mean ± SD of 4.5 ± 3.5 years. Of invasive approach. The study showed that in patients 2544 patients enrolled, 347 underwent mitral valve re- undergoing isolated AVR or AVR plus CABG, the placement, 27.6% of whom had undergone previous car- sutureless valve reduced operative time and was nonin- diac surgery and 39.6% were undergoing additional ferior to conventional bioprostheses for 1-year major cardiac procedures. More recent studies are available, complications (a composite of all-cause death, myocar- comparing sutureless with conventional AVR in patients dial infarction, stroke, or valve reintervention). The rate undergoing concomitant cardiac procedures, or of concomitant surgical procedures in the PERSIST- Baghai et al. Journal of Cardiothoracic Surgery (2021) 16:154 Page 7 of 10 Table 4 Early and late adverse events in the overall population and according to type of mitral valve surgery Event Early events (≤30 days), n (%) Late events (> 30 days), n (rate per 100 patient-years) Overall Mitral Mitral Overall population Mitral repair (n = Mitral replacement population repair replacement (n = 78; 282.5 45; 160.6 patient- (n = 33; 122.2 (n = 78) (n = 45) (n = 33) patient-years) years) patient-years) Death 1 (1.3) 0 1 (3.0) 12 (4.2) 6 (3.7) 6 (4.9) Cardiovascular 0 0 0 6 (2.1) 3 (1.9) 3 (2.5) a b Non-cardiovascular 1 (1.3) 0 1 (3.0) 6 (2.1) 3 (1.9) 3 (2.5) Reintervention 2 (2.6) 0 2 (6.1) 4 (1.4) 3 (1.9) 1 (0.8) Valve related 0 0 0 3 (1.1)c 2 (1.2) 1 (0.8) Not valve related 2 (2.6) 0 2 (6.1) 1 (0.4) 1 (0.6) 0 Cerebrovascular accident 1 (1.3) 1 (2.2) 0 2 (0.7) 1 (0.6) 1 (0.8) Stroke 0 0 0 1 (0.4)d 0 1 (0.8) Transient ischaemic attack 1 (1.3) 1 (2.2) 0 1 (0.4) 1 (0.6) 0 Bleeding 1 (1.3) 0 1 (3.0) 2 (0.7) 2 (1.2) 0 Minore 0 0 0 1 (0.4) 1 (0.6) 0 Majorf 0 0 0 0 0 0 Not classified 1 (1.3) 0 1 (3.0) 1 (0.4) 1 (0.6) 0 Non-structural valve dysfunction 10 (12.8) 1 (2.2) 9 (27.3) 13 (4.6) 8 (5.0) 5 (4.1) Intra-prosthetic regurgitation (1+) 6 (7.7) 0 6 (18.2) 9 (3.2) 6 (3.7) 3 (2.5) Paravalvular leak 1 (1.3) 1 (2.2) 0 2 (0.7) 1 (0.6) 1 (0.8) Paravalvular leak plus intra- 3 (3.8) 0 3 (9.1) 2 (0.7) 1 (0.6) 1 (0.8) prosthetic leak (no haemo- dynamic consequences) Permanent pacemaker implant, due 6 (7.7) 3 (6.7) 3 (9.1) 3 (1.1) 1 (0.6) 2 (1.6) to: Atrioventricular block (third 4 (5.1) 3 (6.7) 1 (3.0) 1 (0.4) 0 1 (0.8) degree) Other reason 2 (2.6) 0 2 (6.1) 2 (0.7) 1 (0.6) 1 (0.8) a Due to septicaemia b Due to neoplasia (3 patients) in mitral replacement group, renal failure (1 patient) and non − valve-related death (2 patients) in mitral repair group c 1 endocarditis, 2 non-structural valve disease d Non-disabling stroke e Any bleeding worthy of clinical mention (e.g. access site haematoma) that does not qualify as life-threatening, disabling, or major [19] f Overt bleeding either associated with a drop in the haemoglobin level of ≥3.0 g/dL or requiring transfusion of 2 or 3 units of whole blood/RBC, or causing hospitalization or permanent injury, or requiring surgery AND does not meet criteria of life-threatening or disabling bleeding [19] AE adverse event AVR study was, however, much lower than in our reported longer operative times in their study of 70 present study (30% vs 89.7%, respectively), high-risk elderly patients undergoing sutureless AVR Prolonged aortic cross-clamping during AVR is associ- plus other cardiac procedures (76.3% of whom under- ated with higher mortality and morbidity in patients went CABG), with a mean ± SD cross-clamp time of undergoing cardiac surgery [23]. Flameng et al. [2], in a 78 ± 28 min and a cardiopulmonary bypass time of population of 32 patients (median logistic EuroSCORE 119 ± 42 min, both of which were statistically signifi- 9.99) requiring AVR with or without concomitant cantly shorter than with conventional AVR using a su- CABG, reported that a sutureless stent-mounted aortic tured valve (122 ± 38 min and 166 ± 50 min, respectively; valve could be implanted in less than 20 min of aortic both P = 0.001). In the Epic study [20], the mean ± SD cross-clamping, and in 23 min for AVR plus CABG. In a aortic cross-clamp time was 84 ± 44 min and the cardio- retrospective study of 314 patients undergoing AVR with pulmonary bypass time was 142 ± 60 min. The operative a sutureless bioprosthesis (29.9% of whom underwent times were longer in the present study (cross-clamp CABG), the mean ± SD aortic cross-clamp time was 109 ± 41 min and cardiopulmonary bypass 152 ± 49 min), 39 ± 15 min for isolated AVR and 52 ± 26 min for AVR reflecting the high rate of mitral (88.5%) and tricuspid with concomitant CABG [13]. Hanedan et al. [7] (16.7%) repair and replacement procedures in this Baghai et al. Journal of Cardiothoracic Surgery (2021) 16:154 Page 8 of 10 Fig. 2 a Overall survival and b freedom from reintervention in patients who underwent mitral repair or mitral replacement Baghai et al. Journal of Cardiothoracic Surgery (2021) 16:154 Page 9 of 10 complex and high-risk population, but still appeared Limitations shorter than reported for conventional aortic valve re- This study is limited by the small population size, the placement [7]. Owing to the lack of a matched cohort, it heterogeneous population, the lack of a control group, is difficult to demonstrate a shorter operative time with and high enrolment at 1 centre. the sutureless versus sutured valve. In the present study, one patient (1.3%) died Conclusion within 30 days of the procedure, which compares This study, in high operative risk patients implanted with 1.9% in a single-centre experience of 617 pa- with a sutureless valve in the presence of a previously tients using the same sutureless valve [24]. Higher implanted prosthesis in the mitral position or with a rates of 30-day death were reported by Hanedan concomitant mitral valve procedure, confirms that the et al. [7] (5.3% for sutureless AVR and 15.6% for sutureless implant is a technically feasible procedure conventional AVR). Rubino et al. reported a 1.4% during multivalvular surgery and is associated with good in-hospital mortality rate after an isolated aortic clinical outcomes. valve procedure (1.4%), which increased to 7.4% when performed alongside CABG [13]. Five-year Abbreviations AVR: Aortic valve replacement; CABG: Coronary artery bypass graft; survival rates were markedly higher in our study CI: Confidence interval; NYHA: New York Heart Association; Q: Quartile; than in Epic [20] (81.3% vs 39.3% with double valve SD: Standard deviation; SURE-AVR: Sorin Universal REgistry on Aortic Valve replacement) whereas bleeding was similar (2.6% vs Replacement 2.9% after double valve replacement). Only 1 patient Acknowledgements (1.3%) had a cerebrovascular accident (no strokes SURE-AVR investigators (number of patients enrolled into the study). were reported) during the early postoperative Dr. Marco Solinas, Ospedale del Cuore G. Pasquinucci, Massa (n = 15). period, compared with 9.1% with double valve re- Dr. Raphael Fontaine, CHR Namur, Namur (n = 5). Mr. Max Baghai, King’s College Hospital, London (n = 5). placement in Epic [20]. Dr. Jose Cuenca Castillo, Hospital Juan Canalejo, A Coruña (n = 4). The need for permanent pacemaker implantation re- Mr. Antony H Walker, Blackpool Teaching Hospitals NHS Foundation Trust, mains a concern with the use of sutureless valves, with Blackpool (n = 3). Prof Ugolino Livi, Az. Osp. Univ. S. Maria della Misericordia, Udine (n = 2). postoperative incidence rates of 5% [24] and 10.8% [25]. Dr. Josep Maria Padrò, Hospital de la Santa Creu i Sant Pau, Barcelona (n = 2). The rate of permanent pacemaker implantation after Dr. Alistair Royse, Melbourne Private Hospital, Melbourne (n = 1). transcatheter AVR with new-generation devices is highly Dr. Gianluigi Bisleri, Kingston Health Sciences Centre, Kingston (n = 1). Prof Davide Pacini, Policlinico Sant’Orsola, Bologna (n = 1). variable (ranging from 2.3 to 36.1% in a recent systematic Prof Vincenzo Argano, AOU Policlinico “Paolo Giaccone”, Palermo (n = 1). review [26]), and is influenced by electrical, anatomical, Dr. Aurelien Roumy, Centre Hospitalier Universitaire Vaudois, Lausanne and procedural factors. In the current study, 6 patients (n = 1). Mr. George Asimakopoulos, Royal Brompton Hospital, London (n = 1). (7.7%) underwent permanent pacemaker implantation Dr. Mattia Glauber, Clinico Sant’Ambrogio, Milan (n = 0). within 30 days of the procedure, 4 due to third-degree Sophie Rushton-Smith, PhD (MedLink Healthcare Communications) provided atrioventricular block. By late follow-up, 3 further patients medical writing assistance, under the direction of the authors, and was funded by LivaNova. (1.1% per patient-year) had undergone pacemaker im- plantation (third-degree atrioventricular block: 0.4% per Authors’ contributions patient-year). Our results show a lower rate of pacemaker Max Baghai made substantial contributions to the conceptualization, methods, writing and reviewing of the manuscript. All other authors implantation compared with the Epic study, which re- participated in the formal analysis, in the writing, reviewing and editing. The ported an 11.6% rate during hospitalization after double authors read and approved the final manuscript. valve replacement [20]. Our findings are consistent with a large study of 658 patients, in which the rate of pacemaker Funding This work was supported by LivaNova. implantation at 1 year for third-degree atrioventricular block was 9.6% for the sutureless valve [21]. Availability of data and materials Haemodynamic data – in terms of effective orifice area The datasets used and/or analysed during the current study are available and mean and peak aortic pressure gradients – were from the corresponding author on reasonable request. good and remained stable through 5 years of follow-up. Declarations Further, the rates of paravalvular leakage were low, com- prising mild regurgitation with no haemodynamic conse- Ethics approval and consent to participate The registry is being conducted according to the International Conference quences, and there was no apparent structural valve on Harmonization guidelines, Good Clinical Practice, and local regulations. deterioration. These findings − consistent with a previ- Ethics committee and/or institutional review board approval was obtained as ous study in patients undergoing isolated sutureless aor- required by local regulations. All patients gave informed consent to participate. tic valve procedures [27] − are reassuring, as the current labelling for the Perceval sutureless valve includes a pre- Consent for publication caution about its use in concomitant mitral procedures. Not applicable. Baghai et al. Journal of Cardiothoracic Surgery (2021) 16:154 Page 10 of 10 Competing interests 13. Rubino AS, Santarpino G, De Praetere H, Kasama K, Dalen M, Sartipy U, et al. Max Baghai, Mattia Glauber, Gianluigi Bisleri, George Asimakopoulos, and Early and intermediate outcome after aortic valve replacement with a Marco Solinas are proctors for LivaNova. The other authors declare they have sutureless bioprosthesis: results of a multicenter study. J Thorac Cardiovasc no competing interests. Surg. 2014;148(3):865–71; discussion 871. https://doi.org/10.1016/j.jtcvs.2014. 03.052. Author details 14. Pfeiffer S, Sirch J, Vogt F, Fischlein T, Santarpino G. Implantation of the Sorin 1 Department of Cardiovascular Medicine, King’s College Hospital, Brixton, Perceval(R) sutureless aortic valve: a step by step approach. Minerva London SE5 9RS, UK. 2U.O. Cardiochirurgia Mininvasiva, Istituto Clinico Cardioangiol. 2017;65(2):184–92. https://doi.org/10.23736/S0026-4725.16.04 Sant’Ambrogio, Milan, Italy. 3Chirurgie Cardiaque CHR Namur, Namur, 085-8. Belgium. 4Cirugía Cardiaca, Hospital Juan Canalejo, A Coruña, Spain. 15. Vasanthan V, Kent W, Gregory A, Maitland A, Cutrara C, Bouchard D, Asch F, 5 Cardiothoracic Surgery, Blackpool Teaching Hospitals NHS Foundation Trust, Adams C. Perceval Valve Implantation: Technical Details and Blackpool, UK. 6Cardiochirurgia, Az. Osp. Univ. S. Maria della Misericordia, Echocardiographic Assessment. Ann Thorac Surg. 2019;107(3):e223–e5. Udine, Italy. 7Cirurgia Cardiaca, Hospital de la Santa Creu i Sant Pau, 16. Glauber M, Moten SC, Quaini E, Solinas M, Folliguet TA, Meuris B, et al. Barcelona, Spain. 8Cardiovascular department, The University of Melbourne, International expert consensus on Sutureless and rapid deployment valves Melbourne, Australia. 9Division of Cardiac Surgery, University of Toronto, in aortic valve replacement using minimally invasive approaches. Toronto, Canada. 10Cardiochiurgia, Policlinico Sant’Orsola, Bologna, Italy. Innovations (Phila). 2016;11(3):165–73. https://doi.org/10.1097/imi. 11 U.O.C. Cardiochirurgia, AOU Policlinico “Paolo Giaccone”, Palermo, Italy. 0000000000000287. 12 Service de chirurgie cardio-vasculaire, Centre Hospitalier Universitaire 17. Miceli A, Murzi M, Gilmanov D, Fuga R, Ferrarini M, Solinas M, et al. Vaudois, Lausanne, Switzerland. 13Heart Surgery, Royal Brompton Hospital, Minimally invasive aortic valve replacement using right minithoracotomy is London, UK. 14U.O.C Cardiochirurgia Adulti, Ospedale del Cuore G. associated with better outcomes than ministernotomy. 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Publisher’s Note 12. Shrestha M, Folliguet TA, Pfeiffer S, Meuris B, Carrel T, Bechtel M, et al. Aortic Springer Nature remains neutral with regard to jurisdictional claims in valve replacement and concomitant procedures with the Perceval valve: published maps and institutional affiliations. results of European trials. Ann Thorac Surg. 2014;98(4):1294–300. https://doi. org/10.1016/j.athoracsur.2014.05.033.