Age Matters? Investigating VARC-3 Outcomes in Surgical Aortic Valve Reoperations: A Multicenter Study

Age Matters? 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Investigating VARC-3 Outcomes in Surgical Aortic Valve Reoperations: A Multicenter Study Nicola Pradegan, Luigi Garufi, Tea Lena, Mariangela Addonizio, and 9 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8534826/v1 This work is licensed under a CC BY 4.0 License Status: Under Revision Version 1 posted 11 You are reading this latest preprint version Abstract Background Redo surgical aortic valve replacement (rSAVR) is known to carry higher operative risk compared with first-time aortic valve surgery. Evidence on how age influences outcomes following rSAVR remains scarce. This study aimed to evaluate clinical outcomes after rSAVR, with particular attention to the role of age. Methods We retrospectively reviewed all adult patients who underwent rSAVR in four centers between January 2015 and December 2022. The primary endpoint was Valve Academic Research Consortium-3 (VARC-3) periprocedural mortality. The impact of age on survival was assessed using univariable Cox regression analysis. Results A total of 215 patients were included (63% male; median age 69 years, IQR 59–75). Previous biological prostheses were present in 165 cases (77%). The median EuroSCORE II was 4.8% (IQR 3.0–8.1). Indications for reoperation included structural valve deterioration in 100 patients (46%), endocarditis in 87 (40%), and paravalvular leak in 14 (7%). Concomitant procedures were performed in 96 patients (45%), and 39 (18%) underwent urgent surgery. A biological valve was implanted in 159 patients (74%). Periprocedural VARC-3 mortality occurred in 22 cases (10%). Age showed no significant effect on periprocedural mortality (HR 0.87, 95% CI 0.53–1.42, p = 0.42). During follow-up (median 4 years, IQR 2–5), overall survival was 86% (95% CI 81–91) at 1 year and 78% (95% CI 72–85) at 5 years. Patients aged ≥ 70 years had a significantly higher risk of late (> 30 days) mortality (HR 2.64, 95% CI 1.04–6.71, p = 0.0012). Conclusions In our multicenter experience, rSAVR remains associated with relevant periprocedural risk. Age does not influence early VARC-3 mortality, but patients aged 70 years or older show increased long-term mortality. Therefore, age may represent an important criterion in patient selection for rSAVR. surgical aortic valve replacement reintervention clinical outcomes structural valve deterioration Figures Figure 1 Figure 2 Background Aortic valve disease is one of the most common structural valvular conditions which requires invasive management 1 – 2 . Over the last two decades, aortic valve replacement (AVR) has dramatically increased, with a significant growth of both bioprosthetic substitutes and transcatheter aortic valve replacement (TAVR) procedures 3 – 4 . Unfortunately, the main disadvantage related to the large-scale diffusion of AVR associated to the increased life expectancy of western countries population, is that survivors remain at risk of structural valve deterioration (SVD), valve thrombosis, and prosthetic valve endocarditis, and frequently require re-interventions 5 . Surgical aortic valve reoperation (rSAVR) shows increased early mortality compared to primary surgical AVR (SAVR), with overall percentages between 5–10% in the rSAVR group 6 – 8 . Even if rSAVR still remains the treatment of choice, Valve-in-Valve TAVR (ViV-TAVR) is an emerging alternative in the SVD subgroup of patients. Among different clinical risk factors which have been associated to worse outcomes after rSAVR 7 , limited data are available regarding the effect of age on outcomes after rSAVR. Current guidelines on valve heart disease 9 , discourage SAVR in elderly patients (> 75 years of age), favoring TAVR; however, rSAVR is not recommended by age group. With this study we aimed to analyze early and late clinical results after rSAVR, with a particular analysis on the effect of age on outcomes. Methods Patient selection We performed a multicenter retrospective observational study involving 4 centers. The study was approved by our local Ethical Committee. We included all patients ≥ 18 years of age who underwent rSAVR between January 2015-December 2022, and who had undergone a previous SAVR. Other inclusion criteria were: combined surgeries (e.g. AVR + coronary artery bypass grafting; AVR + other valve surgery, AVR + aortic surgery, etc.); Bentall operation at the first surgery and/or Bentall surgery at re-intervention. Exclusion criteria were: pediatric patients, valve-sparing aortic valve procedure (e.g. David, Yacoub etc.), aortic valve repair, or Ross operation at the first surgery; previous TAVR. Study protocol Study protocol Clinical and instrumental data available in the computerized health database and paper records of the individual centers participating in the study were collected. Subsequently, each enrolled patient was contacted by phone or e-mail for information on his or her health status according to the variables analyzed in the study. Data were collected in the data collection form and then shared at the pilot center of the survey (Padova University Hospital). Outcome data were defined according to the Valve Academic Research Consortium 3 (VARC-3) criteria 10 . Table 1 summarizes the mortality definition in accordance to VARC-3 criteria. Primary endpoint was VARC-3 periprocedural mortality; secondary endpoints were: VARC-3 early and late mortality, and age effect on VARC-3 periprocedural, early and late death. Etiologies and indications for rSAVR (e.g. SVD, endocarditis, paravalvular leak, patient prosthesis mismatch -PPM- and thrombosis) were defined according to the most recent international guidelines 9 . Table 1 Valve Academic Research Consortium 3 mortality criteria. Periprocedural mortality Death meeting one of the following criteria: - Occurring ≤ 30 days after the index procedure - Occurring > 30 days but during the index hospitalization Early mortality Death occurring > 30 days but ≤ 1 year after the index hospitalization Late mortality Death occurring > 1 year after the index hospitalization Statistical analysis Descriptive statistics were reported as median (interquartile range -IQR-) for continuous variables, and as absolute numbers (percentages) for categorical variables. Univariable logistic regression models were employed to identify predictors of VARC-3 periprocedural death. Survival distribution at follow-up was evaluated using the Kaplan-Meier method. Univariable Cox proportional Hazard model was employed to assess the relationship between VARC-3 periprocedural, early and late mortality, and age at re-intervention. The association between continuous predictors and the outcomes of interest was assessed for non-linearity. If the association was nonlinear, restricted cubic splines were used to estimate the models, and the change-point was identified. Analyses were performed with the R software. P value was set as statistically significant when < 0.05. Results Baseline characteristics A total number of 215 patients fulfilled the inclusion criteria and were included in the study. There were 135 men (63%), with a median age of 69 (IQR 59–75) years. Baseline patient characteristics and comorbidities are listed in Table 2 . The median time interval since the previous aortic valve procedure was 6 (IQR 2–11) years. 165 patients (77%) had a biological valve, and 50 patients (23%) had a mechanical valve. In 96 patients (45%) a combined procedure had been associated at the time of the first AVR. Reason for reintervention was SVD in 100 patients (46%), endocarditis in 87 (40%), paravalvular leaks in 14 (7%), severe PPM in 4 (2%), thrombosis in 4 (2%), and other cause in 6 (3%). 39 patients (18%) were scheduled with an urgent indication and 4 (2%) with an emergent one. Table 2 Baseline patients’ characteristics. N = 215 Age at redo surgery, median (IQR), years 69 (59–75) Age at first operation, median (IQR), years 62 (48–70) Gender (male), n (%) 135 (63) Bicuspid aortic valve, n (%) 49 (34) Type of prosthesis at first operation, n (%) Biological 165 (77) Mechanical 50 (23) Type of bioprosthetic valve, n (%) Stented pericardial 122 (75) Stentless pericardial 7 (4) Sutureless 4 (2) Stentless porcine 4 (2) Stented porcine 28 (17) Prosthesis diameter n (%) (n = 197) 19 24 (12) 21 56 (28) 23 71 (36) 25 27 (14) 27 16 (8) 29 3 (2) Hypertension n (%) 111 (52) Diabetes n (%) 41 (19) Active tabagism n (%) 46 (22) Hypercholesterolemia n (%) 84 (39) COPD n (%) 13 (6) CKD with eGFR 55% n (%) 152 (71) Severe AR before rSAVR n (%) 104 (48) Previously endocarditis medically treated n (%) 38(18) Euroscore II, median (IQR) 4.8 (3.0- 8.1) Cause of reintervention n (%) SVD 100 (46) Severe PPM 4 (2) Endocarditis 87 (40) Paravalvular leak 14 (7) Thromboses 4 (2) Other 6 (3) Combined Surgery at first operation (%) 96 (45) CABG 31 (16) Bentall 19 (10) Supracommisural ascending aorta replacement 31 (16) Aortic arch replacement 3 (2) Mitral valve surgery 34 (17) Tricuspid valve repair 7 (4) Urgent Surgery 39 (18) Emergent Surgery 4 (2) Pre-op V-A ECMO 2 (1) Legend: BMI: Body Mass Index; COPD: Chronic Obstructive Pulmonary Disease; CKD: Chronic Kidney Disease CABG: Coronary Artery Bypass Graft; eGFR: estimated Glomerular Filtration Rate; CAD: Coronary Artery Disease; NYHA: New York Heart Association; ACS: Acute coronary syndrome; LVEF: Left Ventricle Ejection Fraction; MR: Mitral Regurgitation; Gmed: median Gradient; SVD: structural valve degeneration; PPM patient-prostheses mismatch; V-A ECMO: Veno-arterious ExtraCorporeal Membrane Oxygenaton. Intraoperative characteristics All the patients were reoperated with a full sternotomy approach. No fatal re-entry injuries occurred. The mean duration of cardiopulmonary bypass (CPB) and aortic cross-clamp time were 119 (IQR 86–166) and 90 (IQR 68–122) minutes, respectively. In 159 patients (74%) the previous aortic prosthesis was replaced with a new biological prosthesis and in 56 patients (26%) with a mechanical valve. Another surgical procedure was associated with the aortic valve replacement in 99 patients (46%), while 5 patients (2%) had aortic annulus enlargement (either with the Nicks or Manouguian technique). Details of intraoperative features are listed in Table 3 . Table 3 Intraoperative clinical features. Intraoperative Features N = 215 CPB, mean minutes 119 (86–166) Cross-clamp time 90 (68–122) Type of prostheses (%) Biological 159 (74) Mechanical 56 (26) Type of bioprosthetic valve (%) Stented bovine pericardial 115 (72) Stentless bovine pericardial 17 (11) Sutureless 13 (8) Stentless porcine pericardial 9 (6) Stented porcine pericardial 5 (3) Prosthesis diameter (%) 17 7 (4) 19 35 (18) 21 55 (28) 23 49 (26) 25 34 (17) 27 12 (6) 29 1 (1) Combined Surgery (%) 99 (46) CABG 13 (6) Bentall 48 (22) Supracommisural ascending aorta replacement 24 (11) Aortic arch replacement 2 (1) Mitral valve surgery 30 (14) Tricuspid valve repair 19 (9) Annulus enlargement (%) 5 (2) Nicks 1 (0.5) Manouguian 4 (2) Legend: CPB: Cardiopulmonary Bypass Time CABG: Coronary Artery Bypass Graft. Postoperative outcomes Valve Academic Research Consortium 3 periprocedural death was 10% (22 patients). We found no association between VARC-3 periprocedural mortality and the previous type of prosthesis (biological or mechanical, p = 0.38). Patients with a LVEF of 40% or less showed greater mortality, even if not statistically significant (p = 0.07). Periprocedural mortality according to VARC-3 criteria was higher in patients with chronic kidney disease (CKD) and an estimated glomerular filtration rate (eGFR) < 60ml/min, but it was not statistically significant (p = 0.74). After performing a univariate analysis on VARC-3 periprocedural risk factors, patients operated in urgent or emergent status had a significantly higher periprocedural mortality rate than those operated electively (p = 0.006 and p = 0.004, respectively). Details of univariate analysis are listed on Table 4 . The median intubation time was 9 hours (IQR 6–20). The median ICU time was 2 days (IQR 2–5) and the median in hospital stay was 12 days (IQR 8–18). 16 patients (8%) underwent surgical revision for bleeding; 23 patients (11%) had acute kidney failure leading to temporary dialysis. Twenty-seven patients (13%) required a definitive pacemaker (PM) implantation. Details of postoperative outcomes are listed in Table 5 . Age at reoperation did not affect VARC-3 periprocedural death (p = 0.42) (Fig. 1 A). Table 4 Univariate analysis on Valve Academic Research Consortium 3 periprocedural death risk factors. Variable HR (CI 95%) P value Gender (M) 0.82 (0.33–2.02) 0.67 Urgent Case 3.76 (1.48–9.58) < 0.01* Emergent Case 30.32 (3.00-305.95) < 0.01* Endocarditis 3.96 (1.37–11.40) 0.01* Type of prosthesis used (mechanical vs biological) 0.60 (0.19–1.86) 0.38 Chronic kidney disease with eGFR < 60ml/min 1.19 (0.41–3.49) 0.74 Preop ejection fraction < 40% 3.11 (0.86–10.87) 0.07 EuroSCORE II (3◊8) 1.95 (1.43–2.67) 0.68 Legend: eGFR: expected glomerular filtration rate. Table 5 Post-operative characteristics. Post-operative characteristics Stroke, n (%) 17(8) AMI, n (%) 5 (2) CRRT, n (%) 23 (11) Bleeding with surgical re-exploration 16 (8) VARC3 vascular and access related complications, n (%) 7 (3) VARC3 cardiac structural complication, n (%) 8 (4) Sternal dehiscence (%) 4 (2) Permanent PM, n (%) 27 (13) New onset AF, n (%) 32 (15) Blood Transfusion, n (%) 96 (82) Post-op MCS (%) IABP 10 (5) V-A ECMO 12 (6) Intubation duration, median (IQR), hours 9 (6–20) ICU stay, median (IQR), days 2 (2–5) Hospital stay, median (IQR), days 12 (8–18) VARC-3 periprocedural death, n (%) 22 (10) Gmed at discharge, median (IQR), mmHg 13 (10–17) Paravalvular leak grade n (%) Zero 131 (83) One 25 (16) Two 2 (1) LVEF at discharge, median (IQR), (%) 55 (48–60%) Legend: AMI: CRRT: Continous Renal Replacement Therapy; VARC: Valvular Academic Research Consortium 3; PM: Pacemaker; AF: Atrial Fibrillation; MCS: Mechanical Circulatory Support; IABP: Intraortic balloon pump; V-A ECMO: Veno-arterious ExtraCorporeal Membrane Oxygenaton; ICU: Intensive Care Unit; Gmed: median gradient; LVEF: Left Ventricle Ejection Fraction Follow-up outcomes Median duration of follow-up was 4 years (IQR 2–5). Overall survival was 86% (CI 95% 81–91) at 1 year, 78% (CI 95% 72–85) at 5 years (Fig. 2 A). Age at reoperation > 70 years was found to be a significant risk factor for increased VARC-3 early and late mortality (p = 0.0012). Figure 1 B shows how age marked a significant change point for mortality > 30 days. Patients who required surgery for endocarditis had a significant lower survival probability than patients operated on with other indications (p = 0.0013) during follow-up. Figure 2 B summarizes the overall survival between rSAVR due to SVD vs. endocarditis according to Kaplan-Meier method. Discussion This retrospective multicenter study analyzed the clinical outcome of 215 patients who required rSAVR at 4 different high-volume centers. The great majority of patients underwent a bioprosthetic replacement at first SAVR, and SVD and endocarditis accounted for more than 80% of the etiologies for rSAVR. These data are in line with other retrospective analyses 11 – 13 , and reflect the epidemiology of the main causes of reoperation. Patients were at lower risk according to EuroSCORE II preoperative predictive score, and this might justify why patients were selected for surgery instead of ViV-TAVR (at least in the SVD group). At the time of rSAVR, there was a small increase in the number of patients who required a mechanical prosthesis, and there was an increase in the smallest prosthesis diameters (≤ 19mm). These two technical aspects might be explained with the fact that not infrequently the aortic annulus after prosthesis explant is stiff and bulging and cannot accept the same diameter implanted at first SAVR. Unfortunately, only 2% of rSAVR underwent annulus enlargement. This might be explained by the variable surgical expertise of surgeons who performed the procedures. Regarding post-operative outcomes, the main complications showed percentages similar to other rSAVR groups which included both SVD and endocarditis. A different retrospective analysis by Yousef et al. 14 limited to SVD cases, showed a lower incidence of post-operative complications, probably due to the fact that urgent cases and endocarditis were excluded by this analysis. When comparing our data to current largest literature experiences with ViV-TAVR, results are questionable: in fact, in regard to PM implantation, the VIVID registry 15 showed an overall rate of permanent PM of 6%, while a large meta-analysis from 2021 evaluating more than 16000 patients 16 found a lower incidence of PM need compared to rSAVR. This might be due to the conduction system protection provided by surgical valve ring. However, given a 40% of endocarditis (which usually presents with peri-anular infection/abscess) and considering that 22% of patients required a Bentall operation, the higher percentage of PM implantation might be only influenced by the cause of reoperation. According to this meta-analysis, stroke, major bleedings and acute kidney injury requiring replacement therapy are also less frequent in ViV-TAVR. Nevertheless, ViV-TAVR patients are usually reported at higher risk and compass only the specific SVD group, which is just a part of the entire group. Periprocedural overall VARC-3 mortality was high, but similar to other studies with a similar methodology, and affected by the nature of the etiology: in fact, endocarditis is usually scheduled for surgery on an emergent/urgent basis, and it is associated to increased in-hospital mortality. Indeed, endocarditis still negatively affects mid-term follow-up. The effect of age on post-operative outcomes had already been correlated to worse outcomes at follow-up after rSAVR by different authors 17 – 18 . Unlikely a previous retrospective study 7 , in our cohort we did not find any correlation between older age and early death. This aspect was also in contrast to a more recent analysis involving more than 3000 rSAVR in the United Kingdom 19 , in which age was significantly correlated to in-hospital death; In this study, this result was obtained after a multivariate analysis corrected for several variables, while in our experience we used a univariable method, which might have limited our data. Nevertheless, the previous studies did not analyze age as a continuous variable. Thanks to this statistical strategy, we were able to assess more accurately at which age time, mid-term follow-up is mainly affected. Despite emerging evidence that rSAVR shows excellent outcomes also in octogenarian patients 20 , these results are just limited to in-hospital mortality and in elective cases. Consequently, according to our cohort of patients, older age should disfavor rSAVR for the worse mid-term survival rate and, when feasible, might be oriented towards a transcatheter treatment. On the other side, patients < 70 years of age can undergo rSAVR without any significant effect on late overall mortality. However, while current studies on ViV-TAVR progressively extend their follow-up 21 , comparison analyses between rSAVR and ViV-TAVR would be mandatory to assess the effect of age on these two procedures in order to select the most appropriate therapeutic option for each patient. The present study shows several limitations: first, it is a retrospective analysis on a limited group of patients, and it involved different centers with different diagnostic and surgical policy. Consequently, surgeons’ variability might have affected in-hospital and outpatient outcomes. Second, follow-up time is limited, and longer follow-up results might give more precise conclusions. Third, we selectively analyzed rSAVR, and a comparison study to a ViV-TAVR cohort might give intriguing results on these two different therapies. Fourth, we analyzed several types of rSAVR (in terms of substitute type and etiology of re-intervention) and this variability might have affected the results. Conclusions In conclusion, according to our study, rSAVR represents a treatment option which is more frequently related to prosthetic degeneration or infection, and it is associated to increased overall VARC-3 periprocedural mortality, even if endocarditis is the main risk factor for this type of mortality. Age does not affect VARC-3 periprocedural death, but patients ≥ 70 years are at significantly increased risk of out-of-hospital mortality > 30 days. Consequently, age might become a selection criterium for rSAVR in specific etiologies. Further studies are required to establish when rSAVR might be preferable compared to ViV-TAVR. Declarations Ethics approval and consent to participate: our ethical committee (Ethical Committee Padova University Hospital) approved the present manuscript; participants gave consent to participate. Our study adheres to the Declaration of Helsinki. Informed consent was waived the above-mentioned ethical committee and according to the Italian rules. Availability of data and materials: data are available on request to the corresponding author (Nicola Pradegan, MD, [email protected] ). Consent for Publication : patients gave consent to present publication. Competing interests: none. Funding: none. Authors' contributions: N.P. ideation, writing; L.G. data collection, writing; T.L. data collection; M.A. data collection; O.B. data collection; L.L. data collection; M.A. data collection; M.D.E. draft revision; D.M. draft revision; R.D.P. draft revision; G.L. data collection, statistical analysis, manuscript writing; D.G. statistical analysis, revision; V.T. ideation, draft revision. Acknowledgements: none. References Peters AS, Duggan JP, Trachiotis GD, Antevil JL. Epidemiology of Valvular Heart Disease. Surg Clin North Am. 2022;102(3):517–528. 10.1016/j.suc.2022.01.008 . PMID: 35671771. Grave C, Juillière Y, Tuppin P, Weill A, Gabet A, Tribouilloy C, Olié V. Epidemiological Features of Aortic Stenosis in a French Nationwide Study: 10-Year Trends and New Challenges. J Am Heart Assoc. 2020;9(23):e017588. 10.1161/JAHA.120.017588 . Epub 2020 Nov 23. PMID: 33222585; PMCID: PMC7763773. 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Valve-in-valve transcatheter aortic valve implantation versus repeat surgical aortic valve replacement in patients with a failed aortic bioprosthesis. EuroIntervention. 2022;17(15):1227–37. 10.4244/EIJ-D-21-00472 . PMID: 34521614; PMCID: PMC9724873. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Revision Version 1 posted Editorial decision: Revision requested 18 Feb, 2026 Reviews received at journal 14 Feb, 2026 Reviewers agreed at journal 06 Feb, 2026 Reviewers agreed at journal 04 Feb, 2026 Reviews received at journal 03 Feb, 2026 Reviewers agreed at journal 29 Jan, 2026 Reviewers invited by journal 28 Jan, 2026 Editor assigned by journal 28 Jan, 2026 Editor invited by journal 16 Jan, 2026 Submission checks completed at journal 14 Jan, 2026 First submitted to journal 14 Jan, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8534826","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":587612226,"identity":"d8a7ed7a-ace5-471d-a17d-94c04be79d2e","order_by":0,"name":"Nicola Pradegan","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABAElEQVRIiWNgGAWjYDACZiB+AGEagAg5BgbGBgYeBgn8WhKQtBjDtODRg6YlsQFE8jDgtsacnfnhg4Qahjzz9sMbH36puZO+4XZz24M3DBZ1uLRYNrMZGyQcYyiWOZNWbCxz7FnuhjsH2w3n4HGYwWEeNokENobEGQw5ZtISbIdzN9xIbJPG5xeIln9ALfxvzH9L/DucbkCUlsQ2oBaJHDPGj22HE4jQAvRLYp9EsYTEs2Jpxr7DhjNvJAL9YiAh2YBLy/nDDx98+GaTJ8GfvPHjj2+H5flupD978Kaijh+XLVAgkQAimXkgPDZoHOEHYC2MP+BaRsEoGAWjYBQgAAAcd1QOF57u/QAAAABJRU5ErkJggg==","orcid":"","institution":"University of Padova","correspondingAuthor":true,"prefix":"","firstName":"Nicola","middleName":"","lastName":"Pradegan","suffix":""},{"id":587612227,"identity":"ebcf1858-39ec-4031-b0a5-3f9853063aea","order_by":1,"name":"Luigi Garufi","email":"","orcid":"","institution":"San Camillo Hospital","correspondingAuthor":false,"prefix":"","firstName":"Luigi","middleName":"","lastName":"Garufi","suffix":""},{"id":587612228,"identity":"c5da0019-c788-478a-9ff3-0260ec4b1907","order_by":2,"name":"Tea Lena","email":"","orcid":"","institution":"University of Padova","correspondingAuthor":false,"prefix":"","firstName":"Tea","middleName":"","lastName":"Lena","suffix":""},{"id":587612229,"identity":"96294790-68c6-499c-9469-2d528741374b","order_by":3,"name":"Mariangela Addonizio","email":"","orcid":"","institution":"University of Padova","correspondingAuthor":false,"prefix":"","firstName":"Mariangela","middleName":"","lastName":"Addonizio","suffix":""},{"id":587612230,"identity":"1eb58107-c549-4679-b6f6-913a24e98bd4","order_by":4,"name":"Olimpia Bifulco","email":"","orcid":"","institution":"Polytechnic University of Marche","correspondingAuthor":false,"prefix":"","firstName":"Olimpia","middleName":"","lastName":"Bifulco","suffix":""},{"id":587612231,"identity":"ad9d8dc4-8394-4260-a27a-b44074c07e45","order_by":5,"name":"Lorenzo Longinotti","email":"","orcid":"","institution":"Ospedale dell' Angelo","correspondingAuthor":false,"prefix":"","firstName":"Lorenzo","middleName":"","lastName":"Longinotti","suffix":""},{"id":587612232,"identity":"52b69adf-45f6-4488-ad87-947ad1726a97","order_by":6,"name":"Marco Andreis","email":"","orcid":"","institution":"University of Padova","correspondingAuthor":false,"prefix":"","firstName":"Marco","middleName":"","lastName":"Andreis","suffix":""},{"id":587612233,"identity":"b01ef298-6ee3-4e21-91d3-f54adab369f0","order_by":7,"name":"Marco Eusanio","email":"","orcid":"","institution":"Polytechnic University of Marche","correspondingAuthor":false,"prefix":"","firstName":"Marco","middleName":"","lastName":"Eusanio","suffix":""},{"id":587612234,"identity":"81ffd6d3-f40b-4b38-8721-1d8a094e1a82","order_by":8,"name":"Domenico Mangino","email":"","orcid":"","institution":"Ospedale dell' Angelo","correspondingAuthor":false,"prefix":"","firstName":"Domenico","middleName":"","lastName":"Mangino","suffix":""},{"id":587612235,"identity":"0d56f656-7483-40d1-863f-122fd107b60b","order_by":9,"name":"Ruggero Paulis","email":"","orcid":"","institution":"European Hospital of Rome","correspondingAuthor":false,"prefix":"","firstName":"Ruggero","middleName":"","lastName":"Paulis","suffix":""},{"id":587612236,"identity":"7cb431e9-77a7-4c4e-af33-7ac24350e4ba","order_by":10,"name":"Giulia Lorenzoni","email":"","orcid":"","institution":"Padova University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Giulia","middleName":"","lastName":"Lorenzoni","suffix":""},{"id":587612238,"identity":"b154eb61-6cf0-485b-a599-889a0090063a","order_by":11,"name":"Dario Gregori","email":"","orcid":"","institution":"Padova University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Dario","middleName":"","lastName":"Gregori","suffix":""},{"id":587612239,"identity":"778e58da-04c7-427f-afb4-a8a10f617ed1","order_by":12,"name":"Vincenzo Tarzia","email":"","orcid":"","institution":"University of Padova","correspondingAuthor":false,"prefix":"","firstName":"Vincenzo","middleName":"","lastName":"Tarzia","suffix":""}],"badges":[],"createdAt":"2026-01-06 20:38:16","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8534826/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8534826/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":102375315,"identity":"392459cf-06c0-4aca-bee3-d6785599e605","added_by":"auto","created_at":"2026-02-11 05:19:03","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":554129,"visible":true,"origin":"","legend":"\u003cp\u003eUnivariable Cox proportional Hazard model to assess the effect of age (as a continuous variable) to Valve Academic Research Consortium 3 (VARC-3) periprocedural death (Panel A), and to VARC-3 early and late mortality (Panel B).\u003c/p\u003e","description":"","filename":"figure1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8534826/v1/b763b016bd538d8ab402f44e.jpeg"},{"id":102375316,"identity":"ab9c6517-8bc5-42d7-bf14-6a23f5f4afd3","added_by":"auto","created_at":"2026-02-11 05:19:03","extension":"jpeg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":513735,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan-Meier analysis showing follow-up overall survival (Panel A), and follow-up survival among the structural valve deterioration (SVD) and the endocarditis group (Panel B).\u003c/p\u003e","description":"","filename":"figure2.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8534826/v1/0e07e413f065db31507cefd3.jpeg"},{"id":102375340,"identity":"e9e4d8b7-ee04-46fe-bb41-c4fe1983634d","added_by":"auto","created_at":"2026-02-11 05:19:08","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1915134,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8534826/v1/f6635417-3064-44f0-b430-8356a2ec827a.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Age Matters? Investigating VARC-3 Outcomes in Surgical Aortic Valve Reoperations: A Multicenter Study","fulltext":[{"header":"Background","content":"\u003cp\u003eAortic valve disease is one of the most common structural valvular conditions which requires invasive management\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e. Over the last two decades, aortic valve replacement (AVR) has dramatically increased, with a significant growth of both bioprosthetic substitutes and transcatheter aortic valve replacement (TAVR) procedures\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e. Unfortunately, the main disadvantage related to the large-scale diffusion of AVR associated to the increased life expectancy of western countries population, is that survivors remain at risk of structural valve deterioration (SVD), valve thrombosis, and prosthetic valve endocarditis, and frequently require re-interventions\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eSurgical aortic valve reoperation (rSAVR) shows increased early mortality compared to primary surgical AVR (SAVR), with overall percentages between 5\u0026ndash;10% in the rSAVR group\u003csup\u003e\u003cspan additionalcitationids=\"CR7\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e. Even if rSAVR still remains the treatment of choice, Valve-in-Valve TAVR (ViV-TAVR) is an emerging alternative in the SVD subgroup of patients. Among different clinical risk factors which have been associated to worse outcomes after rSAVR\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e, limited data are available regarding the effect of age on outcomes after rSAVR. Current guidelines on valve heart disease\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e, discourage SAVR in elderly patients (\u0026gt;\u0026thinsp;75 years of age), favoring TAVR; however, rSAVR is not recommended by age group.\u003c/p\u003e \u003cp\u003eWith this study we aimed to analyze early and late clinical results after rSAVR, with a particular analysis on the effect of age on outcomes.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003ePatient selection\u003c/h2\u003e \u003cp\u003eWe performed a multicenter retrospective observational study involving 4 centers. The study was approved by our local Ethical Committee. We included all patients\u0026thinsp;\u0026ge;\u0026thinsp;18 years of age who underwent rSAVR between January 2015-December 2022, and who had undergone a previous SAVR. Other inclusion criteria were: combined surgeries (e.g. AVR\u0026thinsp;+\u0026thinsp;coronary artery bypass grafting; AVR\u0026thinsp;+\u0026thinsp;other valve surgery, AVR\u0026thinsp;+\u0026thinsp;aortic surgery, etc.); Bentall operation at the first surgery and/or Bentall surgery at re-intervention. Exclusion criteria were: pediatric patients, valve-sparing aortic valve procedure (e.g. David, Yacoub etc.), aortic valve repair, or Ross operation at the first surgery; previous TAVR.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eStudy protocol\u003c/h3\u003e\n\u003cdiv class=\"Heading\"\u003eStudy protocol\u003c/div\u003e \u003cp\u003eClinical and instrumental data available in the computerized health database and paper records of the individual centers participating in the study were collected. Subsequently, each enrolled patient was contacted by phone or e-mail for information on his or her health status according to the variables analyzed in the study. Data were collected in the data collection form and then shared at the pilot center of the survey (Padova University Hospital). Outcome data were defined according to the Valve Academic Research Consortium 3 (VARC-3) criteria\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e. Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e summarizes the mortality definition in accordance to VARC-3 criteria. Primary endpoint was VARC-3 periprocedural mortality; secondary endpoints were: VARC-3 early and late mortality, and age effect on VARC-3 periprocedural, early and late death. Etiologies and indications for rSAVR (e.g. SVD, endocarditis, paravalvular leak, patient prosthesis mismatch -PPM- and thrombosis) were defined according to the most recent international guidelines\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eValve Academic Research Consortium 3 mortality criteria.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"1\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePeriprocedural mortality\u003c/p\u003e \u003cp\u003eDeath meeting one of the following criteria:\u003c/p\u003e \u003cp\u003e- Occurring\u0026thinsp;\u0026le;\u0026thinsp;30 days after the index procedure\u003c/p\u003e \u003cp\u003e- Occurring\u0026thinsp;\u0026gt;\u0026thinsp;30 days but during the index hospitalization\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eEarly mortality\u003c/b\u003e\u003c/p\u003e \u003cp\u003eDeath occurring\u0026thinsp;\u0026gt;\u0026thinsp;30 days but \u0026le;\u0026thinsp;1 year after the index hospitalization\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLate mortality\u003c/b\u003e\u003c/p\u003e \u003cp\u003eDeath occurring\u0026thinsp;\u0026gt;\u0026thinsp;1 year after the index hospitalization\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eDescriptive statistics were reported as median (interquartile range -IQR-) for continuous variables, and as absolute numbers (percentages) for categorical variables. Univariable logistic regression models were employed to identify predictors of VARC-3 periprocedural death. Survival distribution at follow-up was evaluated using the Kaplan-Meier method. Univariable Cox proportional Hazard model was employed to assess the relationship between VARC-3 periprocedural, early and late mortality, and age at re-intervention. The association between continuous predictors and the outcomes of interest was assessed for non-linearity. If the association was nonlinear, restricted cubic splines were used to estimate the models, and the change-point was identified. Analyses were performed with the R software. P value was set as statistically significant when \u0026lt;\u0026thinsp;0.05.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eBaseline characteristics\u003c/h2\u003e \u003cp\u003eA total number of 215 patients fulfilled the inclusion criteria and were included in the study. There were 135 men (63%), with a median age of 69 (IQR 59\u0026ndash;75) years. Baseline patient characteristics and comorbidities are listed in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. The median time interval since the previous aortic valve procedure was 6 (IQR 2\u0026ndash;11) years. 165 patients (77%) had a biological valve, and 50 patients (23%) had a mechanical valve. In 96 patients (45%) a combined procedure had been associated at the time of the first AVR. Reason for reintervention was SVD in 100 patients (46%), endocarditis in 87 (40%), paravalvular leaks in 14 (7%), severe PPM in 4 (2%), thrombosis in 4 (2%), and other cause in 6 (3%). 39 patients (18%) were scheduled with an urgent indication and 4 (2%) with an emergent one.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBaseline patients\u0026rsquo; characteristics.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eN\u0026thinsp;=\u0026thinsp;215\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge at redo surgery, median (IQR), years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e69 (59\u0026ndash;75)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge at first operation, median (IQR), years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e62 (48\u0026ndash;70)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGender (male), n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e135 (63)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBicuspid aortic valve, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e49 (34)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eType of prosthesis at first operation, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBiological\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e165 (77)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMechanical\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e50 (23)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eType of bioprosthetic valve, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStented pericardial\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e122 (75)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStentless pericardial\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSutureless\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStentless porcine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStented porcine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e28 (17)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProsthesis diameter n (%) (n\u0026thinsp;=\u0026thinsp;197)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24 (12)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e56 (28)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e71 (36)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e27 (14)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16 (8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypertension n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e111 (52)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiabetes n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e41 (19)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eActive tabagism n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e46 (22)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypercholesterolemia n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e84 (39)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCOPD n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13 (6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCKD with eGFR\u0026thinsp;\u0026lt;\u0026thinsp;60 ml/min n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e42 (21)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrevious stroke n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17 (8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePeripheral Arterial Disease n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e22 (10)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCAD n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e51 (24)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePre-op ACS (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePre-op NYHA 3\u0026ndash;4 Class n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e97 (45)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePre-op LVEF\u0026thinsp;\u0026gt;\u0026thinsp;55% n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e152 (71)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSevere AR before rSAVR n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e104 (48)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePreviously endocarditis medically treated n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e38(18)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEuroscore II, median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.8 (3.0- 8.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCause of reintervention n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSVD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e100 (46)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSevere PPM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEndocarditis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e87 (40)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eParavalvular leak\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14 (7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eThromboses\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCombined Surgery at first operation (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e96 (45)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCABG\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e31 (16)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBentall\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e19 (10)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSupracommisural ascending aorta replacement\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e31 (16)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAortic arch replacement\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMitral valve surgery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e34 (17)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTricuspid valve repair\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUrgent Surgery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e39 (18)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEmergent Surgery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePre-op V-A ECMO\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"2\"\u003eLegend: BMI: Body Mass Index; COPD: Chronic Obstructive Pulmonary Disease; CKD: Chronic Kidney Disease CABG: Coronary Artery Bypass Graft; eGFR: estimated Glomerular Filtration Rate; CAD: Coronary Artery Disease; NYHA: New York Heart Association; ACS: Acute coronary syndrome; LVEF: Left Ventricle Ejection Fraction; MR: Mitral Regurgitation; Gmed: median Gradient; SVD: structural valve degeneration; PPM patient-prostheses mismatch; V-A ECMO: Veno-arterious ExtraCorporeal Membrane Oxygenaton.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eIntraoperative characteristics\u003c/h2\u003e \u003cp\u003eAll the patients were reoperated with a full sternotomy approach. No fatal re-entry injuries occurred. The mean duration of cardiopulmonary bypass (CPB) and aortic cross-clamp time were 119 (IQR 86\u0026ndash;166) and 90 (IQR 68\u0026ndash;122) minutes, respectively. In 159 patients (74%) the previous aortic prosthesis was replaced with a new biological prosthesis and in 56 patients (26%) with a mechanical valve. Another surgical procedure was associated with the aortic valve replacement in 99 patients (46%), while 5 patients (2%) had aortic annulus enlargement (either with the Nicks or Manouguian technique). Details of intraoperative features are listed in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eIntraoperative clinical features.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIntraoperative Features\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eN\u0026thinsp;=\u0026thinsp;215\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCPB, mean minutes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e119 (86\u0026ndash;166)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCross-clamp time\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e90 (68\u0026ndash;122)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eType of prostheses (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBiological\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e159 (74)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMechanical\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e56 (26)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eType of bioprosthetic valve (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStented bovine pericardial\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e115 (72)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStentless bovine pericardial\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17 (11)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSutureless\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13 (8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStentless porcine pericardial\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStented porcine pericardial\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProsthesis diameter (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e35 (18)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e55 (28)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e49 (26)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e34 (17)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12 (6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCombined Surgery (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e99 (46)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCABG\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13 (6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBentall\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e48 (22)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSupracommisural ascending aorta replacement\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24 (11)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAortic arch replacement\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMitral valve surgery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e30 (14)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTricuspid valve repair\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e19 (9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnnulus enlargement (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNicks\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (0.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eManouguian\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eLegend: CPB: Cardiopulmonary Bypass Time CABG: Coronary Artery Bypass Graft.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003ePostoperative outcomes\u003c/h3\u003e\n\u003cp\u003eValve Academic Research Consortium 3 periprocedural death was 10% (22 patients). We found no association between VARC-3 periprocedural mortality and the previous type of prosthesis (biological or mechanical, p\u0026thinsp;=\u0026thinsp;0.38). Patients with a LVEF of 40% or less showed greater mortality, even if not statistically significant (p\u0026thinsp;=\u0026thinsp;0.07). Periprocedural mortality according to VARC-3 criteria was higher in patients with chronic kidney disease (CKD) and an estimated glomerular filtration rate (eGFR)\u0026thinsp;\u0026lt;\u0026thinsp;60ml/min, but it was not statistically significant (p\u0026thinsp;=\u0026thinsp;0.74). After performing a univariate analysis on VARC-3 periprocedural risk factors, patients operated in urgent or emergent status had a significantly higher periprocedural mortality rate than those operated electively (p\u0026thinsp;=\u0026thinsp;0.006 and p\u0026thinsp;=\u0026thinsp;0.004, respectively). Details of univariate analysis are listed on Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e. The median intubation time was 9 hours (IQR 6\u0026ndash;20). The median ICU time was 2 days (IQR 2\u0026ndash;5) and the median in hospital stay was 12 days (IQR 8\u0026ndash;18). 16 patients (8%) underwent surgical revision for bleeding; 23 patients (11%) had acute kidney failure leading to temporary dialysis. Twenty-seven patients (13%) required a definitive pacemaker (PM) implantation. Details of postoperative outcomes are listed in Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e. Age at reoperation did not affect VARC-3 periprocedural death (p\u0026thinsp;=\u0026thinsp;0.42) (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eA).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eUnivariate analysis on Valve Academic Research Consortium 3 periprocedural death risk factors.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHR (CI 95%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGender (M)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.82 (0.33\u0026ndash;2.02)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.67\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUrgent Case\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.76 (1.48\u0026ndash;9.58)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.01*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEmergent Case\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e30.32 (3.00-305.95)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.01*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEndocarditis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.96 (1.37\u0026ndash;11.40)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.01*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eType of prosthesis used (mechanical vs biological)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.60 (0.19\u0026ndash;1.86)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.38\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChronic kidney disease with eGFR\u0026thinsp;\u0026lt;\u0026thinsp;60ml/min\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.19 (0.41\u0026ndash;3.49)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.74\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePreop ejection fraction\u0026thinsp;\u0026lt;\u0026thinsp;40%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.11 (0.86\u0026ndash;10.87)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.07\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEuroSCORE II (3\u0026loz;8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.95 (1.43\u0026ndash;2.67)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.68\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"3\"\u003eLegend: eGFR: expected glomerular filtration rate.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePost-operative characteristics.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePost-operative characteristics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStroke, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17(8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAMI, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCRRT, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23 (11)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBleeding with surgical re-exploration\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16 (8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVARC3 vascular and access related complications, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVARC3 cardiac structural complication, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8 (4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSternal dehiscence (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePermanent PM, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e27 (13)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNew onset AF, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e32 (15)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBlood Transfusion, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e96 (82)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePost-op MCS (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIABP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10 (5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eV-A ECMO\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12 (6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIntubation duration, median (IQR), hours\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (6\u0026ndash;20)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eICU stay, median (IQR), days\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (2\u0026ndash;5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHospital stay, median (IQR), days\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12 (8\u0026ndash;18)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVARC-3 periprocedural death, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e22 (10)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGmed at discharge, median (IQR), mmHg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13 (10\u0026ndash;17)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eParavalvular leak grade n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eZero\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e131 (83)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOne\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25 (16)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTwo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLVEF at discharge, median (IQR), (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e55 (48\u0026ndash;60%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"2\"\u003eLegend: AMI: CRRT: Continous Renal Replacement Therapy; VARC: Valvular Academic Research Consortium 3; PM: Pacemaker; AF: Atrial Fibrillation; MCS: Mechanical Circulatory Support; IABP: Intraortic balloon pump; V-A ECMO: Veno-arterious ExtraCorporeal Membrane Oxygenaton; ICU: Intensive Care Unit; Gmed: median gradient; LVEF: Left Ventricle Ejection Fraction\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e\n\u003ch3\u003eFollow-up outcomes\u003c/h3\u003e\n\u003cp\u003eMedian duration of follow-up was 4 years (IQR 2\u0026ndash;5). Overall survival was 86% (CI 95% 81\u0026ndash;91) at 1 year, 78% (CI 95% 72\u0026ndash;85) at 5 years (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eA).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eAge at reoperation\u0026thinsp;\u0026gt;\u0026thinsp;70 years was found to be a significant risk factor for increased VARC-3 early and late mortality (p\u0026thinsp;=\u0026thinsp;0.0012). Figure\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eB shows how age marked a significant change point for mortality\u0026thinsp;\u0026gt;\u0026thinsp;30 days.\u003c/p\u003e \u003cp\u003ePatients who required surgery for endocarditis had a significant lower survival probability than patients operated on with other indications (p\u0026thinsp;=\u0026thinsp;0.0013) during follow-up. Figure\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eB summarizes the overall survival between rSAVR due to SVD vs. endocarditis according to Kaplan-Meier method.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis retrospective multicenter study analyzed the clinical outcome of 215 patients who required rSAVR at 4 different high-volume centers.\u003c/p\u003e \u003cp\u003eThe great majority of patients underwent a bioprosthetic replacement at first SAVR, and SVD and endocarditis accounted for more than 80% of the etiologies for rSAVR. These data are in line with other retrospective analyses\u003csup\u003e\u003cspan additionalcitationids=\"CR12\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e, and reflect the epidemiology of the main causes of reoperation. Patients were at lower risk according to EuroSCORE II preoperative predictive score, and this might justify why patients were selected for surgery instead of ViV-TAVR (at least in the SVD group).\u003c/p\u003e \u003cp\u003eAt the time of rSAVR, there was a small increase in the number of patients who required a mechanical prosthesis, and there was an increase in the smallest prosthesis diameters (\u0026le;\u0026thinsp;19mm). These two technical aspects might be explained with the fact that not infrequently the aortic annulus after prosthesis explant is stiff and bulging and cannot accept the same diameter implanted at first SAVR. Unfortunately, only 2% of rSAVR underwent annulus enlargement. This might be explained by the variable surgical expertise of surgeons who performed the procedures.\u003c/p\u003e \u003cp\u003eRegarding post-operative outcomes, the main complications showed percentages similar to other rSAVR groups which included both SVD and endocarditis. A different retrospective analysis by Yousef et al.\u003csup\u003e14\u003c/sup\u003e limited to SVD cases, showed a lower incidence of post-operative complications, probably due to the fact that urgent cases and endocarditis were excluded by this analysis. When comparing our data to current largest literature experiences with ViV-TAVR, results are questionable: in fact, in regard to PM implantation, the VIVID registry\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e showed an overall rate of permanent PM of 6%, while a large meta-analysis from 2021 evaluating more than 16000 patients\u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e found a lower incidence of PM need compared to rSAVR. This might be due to the conduction system protection provided by surgical valve ring. However, given a 40% of endocarditis (which usually presents with peri-anular infection/abscess) and considering that 22% of patients required a Bentall operation, the higher percentage of PM implantation might be only influenced by the cause of reoperation. According to this meta-analysis, stroke, major bleedings and acute kidney injury requiring replacement therapy are also less frequent in ViV-TAVR. Nevertheless, ViV-TAVR patients are usually reported at higher risk and compass only the specific SVD group, which is just a part of the entire group. Periprocedural overall VARC-3 mortality was high, but similar to other studies with a similar methodology, and affected by the nature of the etiology: in fact, endocarditis is usually scheduled for surgery on an emergent/urgent basis, and it is associated to increased in-hospital mortality. Indeed, endocarditis still negatively affects mid-term follow-up.\u003c/p\u003e \u003cp\u003eThe effect of age on post-operative outcomes had already been correlated to worse outcomes at follow-up after rSAVR by different authors\u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e. Unlikely a previous retrospective study\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e, in our cohort we did not find any correlation between older age and early death. This aspect was also in contrast to a more recent analysis involving more than 3000 rSAVR in the United Kingdom\u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e, in which age was significantly correlated to in-hospital death; In this study, this result was obtained after a multivariate analysis corrected for several variables, while in our experience we used a univariable method, which might have limited our data. Nevertheless, the previous studies did not analyze age as a continuous variable. Thanks to this statistical strategy, we were able to assess more accurately at which age time, mid-term follow-up is mainly affected. Despite emerging evidence that rSAVR shows excellent outcomes also in octogenarian patients\u003csup\u003e\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e, these results are just limited to in-hospital mortality and in elective cases. Consequently, according to our cohort of patients, older age should disfavor rSAVR for the worse mid-term survival rate and, when feasible, might be oriented towards a transcatheter treatment. On the other side, patients\u0026thinsp;\u0026lt;\u0026thinsp;70 years of age can undergo rSAVR without any significant effect on late overall mortality. However, while current studies on ViV-TAVR progressively extend their follow-up\u003csup\u003e21\u003c/sup\u003e, comparison analyses between rSAVR and ViV-TAVR would be mandatory to assess the effect of age on these two procedures in order to select the most appropriate therapeutic option for each patient.\u003c/p\u003e \u003cp\u003eThe present study shows several limitations: first, it is a retrospective analysis on a limited group of patients, and it involved different centers with different diagnostic and surgical policy. Consequently, surgeons\u0026rsquo; variability might have affected in-hospital and outpatient outcomes. Second, follow-up time is limited, and longer follow-up results might give more precise conclusions. Third, we selectively analyzed rSAVR, and a comparison study to a ViV-TAVR cohort might give intriguing results on these two different therapies. Fourth, we analyzed several types of rSAVR (in terms of substitute type and etiology of re-intervention) and this variability might have affected the results.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eIn conclusion, according to our study, rSAVR represents a treatment option which is more frequently related to prosthetic degeneration or infection, and it is associated to increased overall VARC-3 periprocedural mortality, even if endocarditis is the main risk factor for this type of mortality. Age does not affect VARC-3 periprocedural death, but patients\u0026thinsp;\u0026ge;\u0026thinsp;70 years are at significantly increased risk of out-of-hospital mortality\u0026thinsp;\u0026gt;\u0026thinsp;30 days. Consequently, age might become a selection criterium for rSAVR in specific etiologies. Further studies are required to establish when rSAVR might be preferable compared to ViV-TAVR.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate:\u0026nbsp;\u003c/strong\u003eour ethical committee (Ethical Committee Padova University Hospital) approved the present manuscript; participants gave consent to participate. Our study adheres to the Declaration of Helsinki. Informed consent was waived the above-mentioned ethical committee and according to the Italian rules.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials:\u0026nbsp;\u003c/strong\u003edata are available on request to the corresponding author (Nicola Pradegan, MD, [email protected]).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for Publication\u003c/strong\u003e: patients gave consent to present publication.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests:\u0026nbsp;\u003c/strong\u003enone.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u0026nbsp;\u003c/strong\u003enone.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors' contributions:\u0026nbsp;\u003c/strong\u003eN.P. ideation, writing; L.G. data collection, writing; T.L. data collection; M.A. data collection; O.B. data collection; L.L. data collection; M.A. data collection; M.D.E. draft revision; D.M. draft revision; R.D.P. draft revision; G.L. data collection, statistical analysis, manuscript writing; D.G. statistical analysis, revision; V.T. ideation, draft revision.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements:\u0026nbsp;\u003c/strong\u003enone.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003ePeters AS, Duggan JP, Trachiotis GD, Antevil JL. 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PMID: 34521614; PMCID: PMC9724873.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-cardiovascular-disorders","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcar","sideBox":"Learn more about [BMC Cardiovascular Disorders](http://bmccardiovascdisord.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcar/default.aspx","title":"BMC Cardiovascular Disorders","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"surgical aortic valve replacement, reintervention, clinical outcomes, structural valve deterioration","lastPublishedDoi":"10.21203/rs.3.rs-8534826/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8534826/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eRedo surgical aortic valve replacement (rSAVR) is known to carry higher operative risk compared with first-time aortic valve surgery. Evidence on how age influences outcomes following rSAVR remains scarce. This study aimed to evaluate clinical outcomes after rSAVR, with particular attention to the role of age.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003e We retrospectively reviewed all adult patients who underwent rSAVR in four centers between January 2015 and December 2022. The primary endpoint was Valve Academic Research Consortium-3 (VARC-3) periprocedural mortality. The impact of age on survival was assessed using univariable Cox regression analysis.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eA total of 215 patients were included (63% male; median age 69 years, IQR 59\u0026ndash;75). Previous biological prostheses were present in 165 cases (77%). The median EuroSCORE II was 4.8% (IQR 3.0\u0026ndash;8.1). Indications for reoperation included structural valve deterioration in 100 patients (46%), endocarditis in 87 (40%), and paravalvular leak in 14 (7%). Concomitant procedures were performed in 96 patients (45%), and 39 (18%) underwent urgent surgery. A biological valve was implanted in 159 patients (74%). Periprocedural VARC-3 mortality occurred in 22 cases (10%). Age showed no significant effect on periprocedural mortality (HR 0.87, 95% CI 0.53\u0026ndash;1.42, p\u0026thinsp;=\u0026thinsp;0.42). During follow-up (median 4 years, IQR 2\u0026ndash;5), overall survival was 86% (95% CI 81\u0026ndash;91) at 1 year and 78% (95% CI 72\u0026ndash;85) at 5 years. Patients aged\u0026thinsp;\u0026ge;\u0026thinsp;70 years had a significantly higher risk of late (\u0026gt;\u0026thinsp;30 days) mortality (HR 2.64, 95% CI 1.04\u0026ndash;6.71, p\u0026thinsp;=\u0026thinsp;0.0012).\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eIn our multicenter experience, rSAVR remains associated with relevant periprocedural risk. Age does not influence early VARC-3 mortality, but patients aged 70 years or older show increased long-term mortality. Therefore, age may represent an important criterion in patient selection for rSAVR.\u003c/p\u003e","manuscriptTitle":"Age Matters? Investigating VARC-3 Outcomes in Surgical Aortic Valve Reoperations: A Multicenter Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-02-11 05:18:49","doi":"10.21203/rs.3.rs-8534826/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-02-18T08:22:23+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-02-14T08:38:13+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"94812210436968722720408919444692429357","date":"2026-02-06T19:31:19+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"89789738666989597461540010605519889878","date":"2026-02-04T16:38:45+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-02-03T11:14:39+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"294524435884715768437955077630519572749","date":"2026-01-29T06:49:31+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-01-29T04:50:06+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-01-29T04:49:04+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-01-16T05:40:55+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-01-14T13:19:48+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Cardiovascular Disorders","date":"2026-01-14T12:42:50+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-cardiovascular-disorders","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcar","sideBox":"Learn more about [BMC Cardiovascular Disorders](http://bmccardiovascdisord.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcar/default.aspx","title":"BMC Cardiovascular Disorders","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"6e475ee2-dc37-4538-a1df-d5a6918335b5","owner":[],"postedDate":"February 11th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"in-revision","subjectAreas":[],"tags":[],"updatedAt":"2026-05-05T09:26:15+00:00","versionOfRecord":[],"versionCreatedAt":"2026-02-11 05:18:49","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8534826","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8534826","identity":"rs-8534826","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}