Myocardial Protection during Surgery for Infective Endocarditis: retrospective, single center, risk-adjusted study

Myocardial Protection during Surgery for Infective Endocarditis: retrospective, single center, risk-adjusted study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Myocardial Protection during Surgery for Infective Endocarditis: retrospective, single center, risk-adjusted study Murat Mukharyamov, Tulio Caldonazo, Philine Fleckenstein, Sebastian Freiburger, and 9 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8426492/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 14 You are reading this latest preprint version Abstract Objectives Current evidence does not support superiority of one cardioplegia type over another, but stems from low-risk populations. Therefore, we compared outcomes of multimorbid, high-risk infective endocarditis (IE) patients receiving Custodiol ® crystalloid or Calafiore blood cardioplegia during cardiac surgery. Methods We retrospectively analyzed 553 patients (mean EuroScore II 22.7 ± 21.1) who underwent surgery for IE between 2009 and 2023 and received either cold crystalloid (Custodiol ® , n = 335) or warm blood (Calafiore, n = 218) cardioplegia. The primary endpoint was 1-year mortality. Secondary endpoints included 30-day mortality, postoperative stroke, and new-onset dialysis. Propensity score matching (1:1, 14 covariates) resulted in 175 matched pairs. Statistical analysis included nonparametric and exact tests. Results: In the overall cohort, patients receiving Custodiol ® were higher risk and had higher mortality and morbidity. After matching, there was no significant difference in 1-year mortality between patients receiving Custodiol® and Calafiore (37.1% vs. 28.6%, p = 0.09). Thirty-day mortality trended to be lower in the Calafiore group without reaching statistical significance (22.9% vs. 14.9%, p = 0.057). However, stroke was less frequent (4.6% vs. 10.9%, p = 0.029), ICU stay was shorter (3[ 1 – 8 ] vs. 6[3–12.5] days, p < 0.001) and postoperative dialysis was numerically less common (13.7 vs. 20.6%, p = 0.091). These differences were most evident in procedures with shorter cross-clamp times, such as isolated mitral or aortic valve surgery, where mortality and recovery parameters consistently favored Calafiore. Conclusions In high-risk endocarditis patients warm blood cardioplegia may be superior to cold crystalloid, although differences did not reach statistical significance. However, propensity matching may not have accounted for all differences, which warrants further discussion and investigation. Infective endocarditis cardioplegia myocardial protection Introduction Infective endocarditis (IE) remains a clinical condition associated with high mortality and substantial risk of perioperative complications. Surgical treatment is a key component of the management strategy for many IE patients [ 1 ]. Current IE guidelines provide detailed recommendations on diagnosis, risk stratification and the organization of multidisciplinary endocarditis teams. Yet, they do not offer specific recommendations regarding the choice of cardioplegic solution or myocardial protection strategy in this population, leaving the decision to the surgical team and the operative context [ 1 ]. In parallel, the updated EACTS/EACTAIC/EBCP perfusion guidelines focus on the principles of perfusion (temperature, delivery routes and regimens, hemoconcentration/hemodilution, adjunctive measures), emphasizing the need for a standardized but individualized approach; at the same time, no “best” cardioplegic solution is designated as a universal standard [ 2 ]. This uncertainty is also reflected in real-world practice, with a global survey revealing substantial variability in cardioplegic strategies across centers and regions [ 3 ]. In our recent review on myocardial protection [ 4 ], we demonstrated that the fundamental approaches to cardioplegia have remained largely unchanged over the past decades, whereas the patient profile has markedly shifted towards older age and higher comorbidity. While there is no convincing evidence of the superiority of any solution for “hard” outcomes, most of these data were obtained in low-risk populations. At the same time, other factors such as systemic (extra-cardiac) effects of cardioplegia, incl. vasoplegia or the affection of renal or cerebral function, may be of particular relevance in high-risk groups. Patients with IE may reflect such a high risk group where anatomic and technical factors (aortic regurgitation, root destruction, multiple valve involvement) often require individualized approaches to myocardial protection (e.g., combined or retrograde delivery for variable aortic cross-clamp times). In such situations, potential differences between solutions and regimens (e.g., in vasoplegic profile, degree of hemodilution or frequency of re-dosing) may influence clinical outcomes not only through cardio-specific protection but also via systemic effects — a gap highlighted in our contemporary review and not addressed in current guidelines [ 4 ]. Based on these considerations, the aim of the present study was to assess whether the type of cardioplegia influences the outcomes of IE surgery in a real-world, high-risk cohort, focusing not only on mortality but also on clinically relevant secondary outcomes (stroke, renal dysfunction/dialysis, ICU and hospital length of stay), as well as potential differences across surgical subgroups. Methods Study design and patient population We conducted a retrospective single-center cohort study including all adult patients who underwent surgery for infective endocarditis (IE) at Jena University Hospital between January 2009 and December 2023. The study was approved by the Ethics Committee of Jena University Hospital. Informed consent was waived due to the retrospective design. The study was conducted in compliance with the Declaration of Helsinki. The diagnosis of IE was established according to the Duke criteria 2000 and modified version after 2023 [ 5 , 6 ], integrating clinical presentation, echocardiographic findings, and microbiological evidence from blood cultures and/or valve specimens. Both native and prosthetic valve IE, as well as isolated and combined valve procedures, were eligible. Patients without available cardioplegia data or undergoing surgery without cardiopulmonary bypass (CPB) were excluded. Myocardial protection strategies Two cardioplegia protocols were applied during the study period. First, cold crystalloid cardioplegia (Custodiol® HTK, Köhler Chemie GmbH, Alsbach-Hähnlein, Germany) was administered as a single-dose antegrade infusion (2000 ml) at 4–8°C, with repeat dosing in cases of prolonged aortic cross-clamp time exceeding 90 minutes. Second, intermittent antegrade warm blood cardioplegia was delivered according to the protocol described by Calafiore [ 7 ], at 34–37°C at 20-minute intervals. The choice of strategy was at the surgeon’s discretion. Retrograde or combined delivery was used in cases with severe aortic regurgitation, root destruction, or complex reoperations according to surgeon preference. Data collection and variable definitions All study data were derived from the institutional electronic patient charts. Demographic information included age, sex, and body mass index. Clinical variables comprised relevant comorbidities, preoperative functional status, left ventricular ejection fraction, renal function, and preoperative risk assessment using the EuroSCORE II. Endocarditis-related characteristics included valve localization, vegetation size determined by echocardiography or intraoperative inspection, history of recurrent IE, and microbiological results from blood and/or valve examination. Intraoperative variables included procedure type, cardiopulmonary bypass time, aortic cross-clamp time, total operative time, concomitant procedures, transfusion requirements, and use of inotropes or vasopressors. The primary endpoint was all-cause mortality at 1 year. Secondary endpoints were 30-day mortality, postoperative stroke, new-onset dialysis, intensive care unit (ICU) length of stay, and total postoperative hospital length of stay. A postoperative stroke was defined as a new focal neurological deficit of sudden onset, persisting for at least 24 hours, and confirmed by computed tomography or magnetic resonance imaging. New-onset dialysis was defined as initiation of renal replacement therapy in the postoperative period in patients without preoperative dialysis dependence. Statistical methods Statistical analysis and data visualization were conducted using R 4.5.0 statistical computing environment (R Foundation for Statistical Computing, Vienna, Austria). Descriptive statistics for categorical variables are presented with absolute and relative frequencies. Quantitative variables with symmetrical distributions are described using mean (standard deviation), and variables with skewed distributions are presented with median (1st; 3rd quartiles). Propensity score matching (PSM) was performed using the MatchIt 4.7.1 package. To assess covariate balance of potential confounders, standardized mean difference was used. Logistic regression was employed for PSM, with untransformed covariates included as predictors. The nearest neighbor method without caliper was used for 1 to 1 PSM. For comparing full cohort groups regarding quantitative variables, the Brunner-Munzel test was used, while for comparing groups in terms of binary and categorical variables, the exact Fisher test with mid-p correction and exact version of Pearson's chi-squared test are applied. For comparing matched groups regarding quantitative variables, the Wilcoxon signed-rank test was used, while for comparing groups in terms of binary variables, the exact version of McNemar's test and was applied. A two-sided p-value < 0.05 was considered statistically significant Results Baseline demographic and clinical data are summarized in Table 1 . Patients in the Calafiore group less often had previous cardiac surgery (17.4% vs. 28.7%, p = 0.002), but more frequently presented with NYHA class IV symptoms (35.3% vs. 16.5%, p < 0.001) and LVEF < 50% (46.3% vs. 33.1%, p = 0.002). Other baseline variables, including sex, renal function, and major comorbidities, did not differ between groups. Table 1 Baseline demographic and clinical data Characteristics Total n = 553 Custodiol n = 335 Calafiore n = 218 p Sex (female) (%) 26.6% 26.6% 26.6% 0.99 Age [years] median (q1;q3) 65 (55; 73) 67 (58; 74) 63 (51.2; 71.8) < 0.001 BMI [kg/m²] median (q1;q3) 26.6 (24.2; 29.8) 26.9 (24.2; 30.8) 26.2 (23.7; 29.3) 0.04 GFR [ml/min] median (q1;q3) 70.8 (44; 94.6) 70.8 (46.4; 92.6) 72.9 (40.4; 101) 0.436 Creatinine [µmol/L] median (q1;q3) 93 (70; 132.8) 92 (70; 128) 97 (74; 143) 0.151 EuroSCORE II mean (SD) 22.7 (21.1) 22.8 (20.9) 22.6 (21.4) 0.789 Pulmonary disease (%) 8.3 9 7.3 0.51 Extracardiac arteriopathy (%) 9.2 9 9.6 0.784 Neurological dysfunction (%) 19.7 20.3 18.8 0.671 Previous cardiac surgery (%) 24.2 28.7 17.4 0.002 Diabetes on insulin (%) 16.6 16.7 16.5 0.955 Critical pre-op state (%) 53.8 53.3 62.5 0.642 Recent MI (%) 4.7 5.7 3.2 0.187 NYHA class IV (%) 23.9 16.5 35.3 < 0.001 LVEF %, median (q1;q3) 55 (50; 60) 56 (50; 63) 54.5 (45; 60) 0.002 LVEF < 50% (%) 38.3 33.1 46.3 0.002 Endocarditis-specific characteristics are shown in Table 2 . Aortic valve IE was more common in patients receiving Calafiore (46.4% vs. 27.1%, p < 0.001), while mitral (29.9% vs. 21.4%, p < 0.001) and multivalve involvement (42.7% vs. 32.3%, p < 0.001) were more frequent in patients with Custodiol®. Median vegetation size was 12.0 to 13.0 mm. Surgery for recurrent IE was less frequent in the Calafiore group (7.7% vs. 30.2%, p < 0.001). Microbiological findings, including Staphylococcus aureus, Enterococcus spp., Candida spp., Streptococcus spp., HACEK, Enterobacteriaceae, and Pseudomonas aeruginosa, showed no relevant differences. Table 2 Endocarditis Details Characteristics Total (n = 553) Custodiol (n = 335) Calafiore (n = 218) p IE localization (%) 15 mm (%) 45.3 48.2 40.6 0.077 Recurrent endocarditis 25.5) 30.2 7.7 < 0.001 Original Microbiology (%) Staphylococcus aureus 26.5 28.3 23.6 0.223 Enterococcus spp. 11.6 11.1 2.3 0.647 Coagulase-negative staphylococci 11.7 11.6 11.9 0.925 Candida spp. 5.7 6.6 4.1 0.205 Streptococcus spp. 9 9.7 7.8 0.437 HACEK group 4 (0.7%) 1 (0.3%) 1.4 0.174 Enterobacteriaceae 0.3 0 0.9 0.142 Pseudomonas aeruginosa 0.2 0 0.5 0.378 Table 3 shows operative data. Calafiore was more often used in aortic valve surgery procedure (46.8% vs. 29.3%, p < 0.001) and less in mitral (21.6% vs. 32.2%, p = 0.006) and Bentall/UFO procedures (6.9% vs. 12.8%, p = 0.024). Minimally invasive access was more frequent in the Custodiol® group (12.8% vs. 5.0%, p = 0.002). CPB, cross-clamp, and total operative times did not differ. Use of fresh frozen plasma and milrinone was more frequent in the warm blood cardioplegia group (Table 3 ), whereas other transfusions and vasopressor use were similar. Table 3 Operative Data Characteristics Total (n = 553) Custodiol (n = 335) Calafiore (n = 218) p Procedure < 0.001 Aortic valve surgery 200 (36.2%) 98 (29.3%) 102/218 (46.8%) < 0.001 Mitral valve surgery 155 (28%) 108 (32.2%) 47/218 (21.6%) 0.006 Double valve surgery 140 (25.3%) 86 (25.7%) 54/218 (24.8%) 0.815 Bentall / UFO 58 (10.5%) 43(12.8%) 15/218 (6.9%) 0.024 Concomitant CABG 79 (14.3%) 46 (13.7%) 33/218 (15.1%) 0.643 MIC 54 (9.8%) 43 (12.8%) 11/218 (5%) 0.002 Time parameters Bypass time (min) 118 (90; 163.5) 119 (93; 166) 113 (84.5; 161) 0.182 Cross-clamp time (min) 77 (58; 107) 77 (59; 107) 77 (54.8; 104.2) 0.638 Total OR time (min) 199 (159; 259) 199 (158; 268) 198.5 (160; 246.5) 0.895 Coagulation and transfusion Red blood cells 259 (44.6%) 152 (42.1%) 107 (48.6%) 0.126 Fresh frozen plasma 89 (15.4%) 26 (7.2%) 63 (28.8%) < 0.001 Platelets 59 (10.2%) 30 (8.3%) 29 (13.3%) 0.059 Fibrinogen 16 (2.8%) 13 (3.6%) 3 (1.4%) 0.113 PPSB 20 (3.4%) 15 (4.2%) 5 (2.3%) 0.237 Factor XIII 11 (1.9%) 9 (2.5%) 2 (0.9%) 0.189 Vasopressors and Inotropic support Noradrenaline 461 (97.9%) 352 (98.1%) 215 (97.3%) 0.632 Adrenaline 136 (28.9%) 100 (27.9%) 70 (32.1%) 0.384 Milrinone 129 (27.4%) 89 (24.8%) 79 (35.7%) 0.027 Table 4 Outcomes (after PSM) Characteristics Custodiol (n = 175) Calafiore (n = 175) p Overall 30-day mortality 40/175 (22.9%) 26/175 (14.9%) 0.057 1-year mortality 65/175 (37.1%) 50/175 (28.6%) 0.09 Postoperative stroke 19/175 (10.9%) 8/175 (4.6%) 0.029 Postoperative dialysis 36/175 (20.6%) 24/175 (13.7%) 0.091 Hospital stay [days (q1;q3)] 20 (13; 30) 15 (11; 26) 0.011 ICU stay [days (q1;q3) ] 6 (3; 12.5) 3 (1; 8) < 0.001 Aortic valve surgery 30-day mortality 13/87 (14.9%) 10/87 (11.5%) 0.513 1-year mortality 22/87 (25.3%) 20/87 (23%) 0.727 Postoperative stroke 6/87 (6.9%) 2/87 (2.3%) 0.171 Postoperative dialysis 9/87 (10.3%) 10/87 (11.5%) 0.814 Hospital stay [median days (q1;q3)] 20 (14; 27.5) 15 (11; 29) 0.09 ICU stay stay [median days (q1;q3)] 6 (3; 10.5) 2 (1; 6) < 0.001 Mitral valve surgery 30-day mortality 10/34 (29.4%) 4/34 (11.8%) 0.083 1-year mortality 16/34 (47.1%) 7/34 (20.6%) 0.024 Postoperative stroke 5/34 (14.7%) 3/34 (8.8%) 0.484 Postoperative dialysis 6/34 (17.6%) 4/34 (11.8%) 0.519 Hospital stay stay [median days (q1;q3)] 19 (10.2; 30.5) 15.5 (10.8; 21.8) 0.217 ICU stay stay [median days (q1;q3)] 6 (3; 12) 2 (0; 5.8) 0.005 Double valve surgery 30-day mortality 13/43 (30.2%) 9/43 (20.9%) 0.338 1-year mortality 21/43 (48.8%) 19/43 (44.2%) 0.673 Postoperative stroke 5/43 (11.6%) 2/43 (4.7%) 0.271 Postoperative dialysis 19/43 (44.2%) 6/43 (14%) 0.002 Hospital stay stay [median days (q1;q3)] 22 (12.5; 34 15 (10.2; 28) 0.201 ICU stay stay [median days (q1;q3)] 10 (4; 13) 4 (2; 11.5) 0.098 Bentall / UFO 30-day mortality 4/11 (36.4%) 3/11 (27.3%) 0.681 1-year mortality 6/11 (54.5%) 4/11 (36.4%) 0.434 Postoperative stroke 3/11 (27.3%) 1/11 (9.1%) 0.338 Postoperative dialysis 2/11 (18.2%) 4/11 (36.4%) 0.392 Hospital stay stay [median days (q1;q3)] 21 (8; 35.5) 15 (8.5; 24) 0.558 ICU stay stay [median days (q1;q3)] 14 (5; 21) 4 (1.5; 8) 0.055 In the overall cohort, no statistically significant differences in 1-year mortality were observed between groups across any surgical category. In aortic valve surgery, patients in the Calafiore group had a shorter ICU (median 2 vs. 5 days, p < 0.001) and hospital stay (15 vs. 19.5 days, p = 0.026); other endpoints, including 30-day mortality, stroke, and dialysis, did not differ. In mitral valve surgery, ICU stay was markedly shorter in patients with Calafiore cardioplegia (1 vs. 6 days, p < 0.001), with no significant differences in survival or other complications. For double valve procedures, dialysis was more frequent (32.6% vs. 14.8%, p = 0.019) and ICU stay was longer (7 vs. 3.5 days, p = 0.043) in the Custodiol® group, while mortality and stroke rates were comparable. In Bentall/UFO operations, outcomes were similar, with a non-significant trend toward shorter ICU stay with Calafiore (4 vs. 8 days, p = 0.148). After propensity score matching using 14 preoperative variables (age, body mass index, NYHA class IV, left ventricular ejection fraction < 50%, recent myocardial infarction < 90 days, diabetes on insulin, pulmonary disease, extracardiac arteriopathy, neurological dysfunction, glomerular filtration rate, previous cardiac surgery, and cross-clamp time), baseline characteristics were well balanced between groups. In aortic valve surgery, ICU stay was again shorter with Calafiore (2 vs. 6 days, p < 0.001) with no significant differences in survival, stroke, or dialysis. In mitral valve surgery, 1-year mortality was lower with Calafiore (20.6% vs. 47.1%, p = 0.024) and ICU stay shorter (2 vs. 6 days, p = 0.005); other outcomes did not differ. For double valve procedures, dialysis remained more frequent with Custodiol® (44.2% vs. 14.0%, p = 0.002), with similar mortality and stroke rates. In Bentall/UFO procedures, there were no significant differences in any endpoint. Discussion We demonstrate in this analysis that in high-risk endocarditis patients, warm blood cardioplegia may be superior to cold crystalloid, although differences did not reach statistical significance. However, propensity matching may not have accounted for all differences, which warrants further discussion and investigation. We used propensity score matching with 13 preoperative variables achieving a good balance with standardized mean differences below 0.1 for all covariates. In this adjusted cohort, 1-year mortality did not differ significantly between the two cardioplegic strategies. This finding aligns with previous reports in mixed cardiac surgical populations, where no clear survival benefit could be attributed to either crystalloid or blood [ 8 ], cold or warm [ 9 ] cardioplegia once baseline risk was accounted for. However, numerically one year mortality was lower with Calafiore. Secondary outcomes also revealed consistent trends suggesting systemic differences between the regimens. Patients receiving warm blood cardioplegia had faster postoperative recovery, shorter ICU stay (2 vs. 6 days, p = 0.001), fewer postoperative strokes (5.0% vs. 9.6%), and less frequent dialysis in double-valve procedures (14.8% vs. 32.6%). These differences were most pronounced in operations with shorter aortic cross-clamp times, particularly isolated aortic and mitral valve procedures. The disappearance of these differences with increasing surgical complexity and cross-clamp time suggests that the observed effects are unlikely to stem from myocardial protection itself, because shorter cross-clamp times require less perfect protection for sufficient endogenous ischemia tolerance. A possible and plausible explanation may therefore lie in the systemic effects of the cardioplegic solution. Custodiol is administered as a single large-volume crystalloid dose and, when allowed to enter the systemic circulation, may induce vasoplegia or contribute to hemodilution. Previous reports demonstrated that active evacuation of Custodiol® from the coronary sinus can attenuate such effects [ 10 ], but this maneuver was rarely performed in our series. In shorter and less complex operations, Calafiore cardioplegia is administered in comparatively smaller volumes, and the systemic impact of its components may therefore play a less prominent role. In infective endocarditis, where septic vasoplegia and endothelial dysfunction are common, even modest differences in intravascular volume or electrolyte composition may potentially influence postoperative stability and recovery. Placed within this physiological context, these findings gain further clarity when contrasted with outcomes reported in major European multicentre registries. Our outcomes are comparable to those reported by the major contemporary registries of surgically treated infective endocarditis, including the EURO-ENDO registry [ 11 ] and the German multicentre CAMPAIGN [ 12 ] study. Notably, the operative risk in these cohorts was substantially lower—for example, the CAMPAIGN registry reported a median EuroSCORE II of 10–12%, whereas in our study the mean EuroSCORE II was 22.7. Despite this markedly higher risk profile, early mortality in our cohort remained within the range observed in these large registries. Thus, our results can be considered externally valid and potentially generalizable to other centers. Taken together, these findings suggest that systemic factors may influence postoperative morbidity and recovery in high-risk populations. The potential advantage of warm blood cardioplegia in shorter, less complex procedures may therefore reflect attenuation of systemic effects rather than differences in myocardial preservation. Prospective randomized studies are warranted to confirm these hypotheses and to define the optimal myocardial protection strategy for infective endocarditis surgery. In the meantime, it may be advisable to evacuate Custodiuol solutions from the coronary sinus in infective endocarditis patients, a strategy that actually aligns with manufacturer recommendations [ 13 ]. Limitations This was a retrospective single-center analysis, with potential for residual confounding despite propensity matching. Some subgroups, particularly Bentall/UFO, were small and underpowered for detecting modest effects. Declarations Availability of data and materials The datasets generated and/or analyzed during the current study are available from the corresponding author on reasonable request. Competing interests The authors declare that they have no competing interests. Ethics approval and consent to participate The study was approved by the Ethics Committee of Jena University Hospital. Informed consent was waived due to the retrospective and anonymized study design. Consent for publication Not applicable. Authors’ contributions MM and TC contributed equally to study conception, data analysis, and manuscript drafting. PF, SF, HK, and JB contributed to data acquisition and interpretation. MP, SH, SG, MB contributed to clinical expertise and critical revision. MD and TD supervised the study and finalized the manuscript. All authors read and approved the final manuscript. Funding This work was supported by the IKARUS Research College at Jena University Hospital, funded by the Else Kröner-Fresenius-Stiftung. The IKARUS Study Group comprises Prof. Dr. Mathias W. Pletz (Institute of Infectious Diseases and Infection Control); Prof. Dr. Torsten Doenst (Department of Cardiothoracic Surgery); Prof. Dr. Bettina Löffler (Institute of Medical Microbiology); Prof. Dr. Christian Schulze (Department of Internal Medicine I: Cardiology, Angiology, Intensive Care Medicine); Prof. Dr. Regine Heller (Institute of Molecular Cell Biology · Center for Molecular Biomedicine, CMB); Dr. Micha Banz (Department of Internal Medicine IV: Gastroenterology, Hepatology, Infectious Diseases, Interventional Endoscopy); Dr. Jürgen Bogoviku (Department of Internal Medicine I); Dr. Sandesh Dinesh (Department of Internal Medicine I); Dr. Philine Fleckenstein (Department of Cardiothoracic Surgery); Dr. Sebastian Freiburger (Department of Cardiothoracic Surgery); Dr. Stefan Glöckner (Institute of Medical Microbiology); and Dr. Murat Mukharyamov (Department of Cardiothoracic Surgery). 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Last revised October 2022. edn Bensheim, Germany: Dr. Franz Köhler Chemie GmbH; 2022. Additional Declarations No competing interests reported. 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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-8426492","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":585979286,"identity":"6678b592-f281-4199-9674-2b4f75f8f5b3","order_by":0,"name":"Murat Mukharyamov","email":"","orcid":"","institution":"Jena University Hospital, Friedrich Schiller University of Jena","correspondingAuthor":false,"prefix":"","firstName":"Murat","middleName":"","lastName":"Mukharyamov","suffix":""},{"id":585979287,"identity":"0f700f39-469b-45e7-83e0-54dda17d44a3","order_by":1,"name":"Tulio Caldonazo","email":"","orcid":"","institution":"Jena University Hospital, Friedrich Schiller University of Jena","correspondingAuthor":false,"prefix":"","firstName":"Tulio","middleName":"","lastName":"Caldonazo","suffix":""},{"id":585979288,"identity":"04930a14-ba24-4df8-a192-6e56c16bd3c2","order_by":2,"name":"Philine Fleckenstein","email":"","orcid":"","institution":"Jena University Hospital, Friedrich Schiller University of Jena","correspondingAuthor":false,"prefix":"","firstName":"Philine","middleName":"","lastName":"Fleckenstein","suffix":""},{"id":585979289,"identity":"e72df875-31de-43a2-81b8-00016e6d1f25","order_by":3,"name":"Sebastian Freiburger","email":"","orcid":"","institution":"Jena University Hospital, Friedrich Schiller University of Jena","correspondingAuthor":false,"prefix":"","firstName":"Sebastian","middleName":"","lastName":"Freiburger","suffix":""},{"id":585979290,"identity":"46a0ff41-217e-46a8-86c7-cdfce9381d06","order_by":4,"name":"Hristo Kirov","email":"","orcid":"","institution":"Jena University Hospital, Friedrich Schiller University of Jena","correspondingAuthor":false,"prefix":"","firstName":"Hristo","middleName":"","lastName":"Kirov","suffix":""},{"id":585979291,"identity":"e93d859e-c87a-4557-9270-c10572712e84","order_by":5,"name":"Mathias Pletz","email":"","orcid":"","institution":"Jena University Hospital, Friedrich Schiller University of Jena","correspondingAuthor":false,"prefix":"","firstName":"Mathias","middleName":"","lastName":"Pletz","suffix":""},{"id":585979292,"identity":"208c5fbc-cc81-49e1-85f3-4b2399db6a3c","order_by":6,"name":"Stefan Hagel","email":"","orcid":"","institution":"Jena University Hospital, Friedrich Schiller University of Jena","correspondingAuthor":false,"prefix":"","firstName":"Stefan","middleName":"","lastName":"Hagel","suffix":""},{"id":585979293,"identity":"46d3cdba-3f36-4e4d-aac0-b12ec443cf9a","order_by":7,"name":"Jürgen Bogoviku","email":"","orcid":"","institution":"Jena University Hospital, Friedrich Schiller University of Jena","correspondingAuthor":false,"prefix":"","firstName":"Jürgen","middleName":"","lastName":"Bogoviku","suffix":""},{"id":585979294,"identity":"11cbfd85-dd40-4c74-be22-188210c1dff4","order_by":8,"name":"Sandesh Dinesh","email":"","orcid":"","institution":"Jena University Hospital, Friedrich Schiller University of Jena","correspondingAuthor":false,"prefix":"","firstName":"Sandesh","middleName":"","lastName":"Dinesh","suffix":""},{"id":585979295,"identity":"1eeca1e4-a5e8-4879-82b7-cc234a48e916","order_by":9,"name":"Stefan Glöckner","email":"","orcid":"","institution":"Jena University Hospital, Friedrich Schiller University of Jena","correspondingAuthor":false,"prefix":"","firstName":"Stefan","middleName":"","lastName":"Glöckner","suffix":""},{"id":585979296,"identity":"b94a6235-77a5-4206-b583-989eafd24fc3","order_by":10,"name":"Micha Banz","email":"","orcid":"","institution":"Friedrich Schiller University of Jena","correspondingAuthor":false,"prefix":"","firstName":"Micha","middleName":"","lastName":"Banz","suffix":""},{"id":585979297,"identity":"65f630ce-acd5-47e7-87d6-bc666589950a","order_by":11,"name":"Mahmoud Diab","email":"","orcid":"","institution":"Helios University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Mahmoud","middleName":"","lastName":"Diab","suffix":""},{"id":585979298,"identity":"cf343095-6ef4-45e9-b9ef-69de707ca6f9","order_by":12,"name":"Torsten Doenst","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA8UlEQVRIiWNgGAWjYDCCA2DSBogTgNiAgRnM5yGoJSGNdC2HoVpgAJ8WvuPNxx7+/HE+mp89gU26oICBnV+6+QHDmwrcWiTPHEs35km4nTuz5wGb9AygwyTnHDNgnHMGtxaDGzlm0gxALRtuAG3hMfjPbHAjwYCZtw2flvxvkj8SzuXuh2hhYLa/kf6BmfcfXlvYJHgSDuRukIBqMZDIAdrSgNcvZtI8acm5M848bLYGaZG4kVNwcM4x3FqAIfZM8oeNXW5/e/LB2zx/GJL5Z6RvfPCmBrcWJMAIdkwyiDhAlAYYsCNJ9SgYBaNgFIwIAADFOU2aBewEJgAAAABJRU5ErkJggg==","orcid":"","institution":"Jena University Hospital, Friedrich Schiller University of Jena","correspondingAuthor":true,"prefix":"","firstName":"Torsten","middleName":"","lastName":"Doenst","suffix":""}],"badges":[],"createdAt":"2025-12-22 15:38:07","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8426492/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8426492/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":102295786,"identity":"07ea16d0-c85b-4138-af86-a9c5398e1525","added_by":"auto","created_at":"2026-02-10 10:15:05","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":901441,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8426492/v1/84a49e5b-f0c7-4e16-a619-18f350b14289.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Myocardial Protection during Surgery for Infective Endocarditis: retrospective, single center, risk-adjusted study","fulltext":[{"header":"Introduction","content":"\u003cp\u003eInfective endocarditis (IE) remains a clinical condition associated with high mortality and substantial risk of perioperative complications. Surgical treatment is a key component of the management strategy for many IE patients [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Current IE guidelines provide detailed recommendations on diagnosis, risk stratification and the organization of multidisciplinary endocarditis teams. Yet, they do not offer specific recommendations regarding the choice of cardioplegic solution or myocardial protection strategy in this population, leaving the decision to the surgical team and the operative context [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. In parallel, the updated EACTS/EACTAIC/EBCP perfusion guidelines focus on the principles of perfusion (temperature, delivery routes and regimens, hemoconcentration/hemodilution, adjunctive measures), emphasizing the need for a standardized but individualized approach; at the same time, no \u0026ldquo;best\u0026rdquo; cardioplegic solution is designated as a universal standard [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. This uncertainty is also reflected in real-world practice, with a global survey revealing substantial variability in cardioplegic strategies across centers and regions [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn our recent review on myocardial protection [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e], we demonstrated that the fundamental approaches to cardioplegia have remained largely unchanged over the past decades, whereas the patient profile has markedly shifted towards older age and higher comorbidity. While there is no convincing evidence of the superiority of any solution for \u0026ldquo;hard\u0026rdquo; outcomes, most of these data were obtained in low-risk populations. At the same time, other factors such as systemic (extra-cardiac) effects of cardioplegia, incl. vasoplegia or the affection of renal or cerebral function, may be of particular relevance in high-risk groups.\u003c/p\u003e \u003cp\u003ePatients with IE may reflect such a high risk group where anatomic and technical factors (aortic regurgitation, root destruction, multiple valve involvement) often require individualized approaches to myocardial protection (e.g., combined or retrograde delivery for variable aortic cross-clamp times). In such situations, potential differences between solutions and regimens (e.g., in vasoplegic profile, degree of hemodilution or frequency of re-dosing) may influence clinical outcomes not only through cardio-specific protection but also via systemic effects \u0026mdash; a gap highlighted in our contemporary review and not addressed in current guidelines [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eBased on these considerations, the aim of the present study was to assess whether the type of cardioplegia influences the outcomes of IE surgery in a real-world, high-risk cohort, focusing not only on mortality but also on clinically relevant secondary outcomes (stroke, renal dysfunction/dialysis, ICU and hospital length of stay), as well as potential differences across surgical subgroups.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eStudy design and patient population\u003c/p\u003e \u003cp\u003eWe conducted a retrospective single-center cohort study including all adult patients who underwent surgery for infective endocarditis (IE) at Jena University Hospital between January 2009 and December 2023. The study was approved by the Ethics Committee of Jena University Hospital. Informed consent was waived due to the retrospective design. The study was conducted in compliance with the Declaration of Helsinki.\u003c/p\u003e \u003cp\u003eThe diagnosis of IE was established according to the Duke criteria 2000 and modified version after 2023 [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e], integrating clinical presentation, echocardiographic findings, and microbiological evidence from blood cultures and/or valve specimens. Both native and prosthetic valve IE, as well as isolated and combined valve procedures, were eligible. Patients without available cardioplegia data or undergoing surgery without cardiopulmonary bypass (CPB) were excluded.\u003c/p\u003e \u003cp\u003eMyocardial protection strategies\u003c/p\u003e \u003cp\u003eTwo cardioplegia protocols were applied during the study period. First, cold crystalloid cardioplegia (Custodiol\u0026reg; HTK, K\u0026ouml;hler Chemie GmbH, Alsbach-H\u0026auml;hnlein, Germany) was administered as a single-dose antegrade infusion (2000 ml) at 4\u0026ndash;8\u0026deg;C, with repeat dosing in cases of prolonged aortic cross-clamp time exceeding 90 minutes. Second, intermittent antegrade warm blood cardioplegia was delivered according to the protocol described by Calafiore [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e], at 34\u0026ndash;37\u0026deg;C at 20-minute intervals. The choice of strategy was at the surgeon\u0026rsquo;s discretion. Retrograde or combined delivery was used in cases with severe aortic regurgitation, root destruction, or complex reoperations according to surgeon preference.\u003c/p\u003e \u003cp\u003eData collection and variable definitions\u003c/p\u003e \u003cp\u003eAll study data were derived from the institutional electronic patient charts. Demographic information included age, sex, and body mass index. Clinical variables comprised relevant comorbidities, preoperative functional status, left ventricular ejection fraction, renal function, and preoperative risk assessment using the EuroSCORE II. Endocarditis-related characteristics included valve localization, vegetation size determined by echocardiography or intraoperative inspection, history of recurrent IE, and microbiological results from blood and/or valve examination. Intraoperative variables included procedure type, cardiopulmonary bypass time, aortic cross-clamp time, total operative time, concomitant procedures, transfusion requirements, and use of inotropes or vasopressors.\u003c/p\u003e \u003cp\u003eThe primary endpoint was all-cause mortality at 1 year. Secondary endpoints were 30-day mortality, postoperative stroke, new-onset dialysis, intensive care unit (ICU) length of stay, and total postoperative hospital length of stay. A postoperative stroke was defined as a new focal neurological deficit of sudden onset, persisting for at least 24 hours, and confirmed by computed tomography or magnetic resonance imaging. New-onset dialysis was defined as initiation of renal replacement therapy in the postoperative period in patients without preoperative dialysis dependence.\u003c/p\u003e \u003cp\u003eStatistical methods\u003c/p\u003e \u003cp\u003eStatistical analysis and data visualization were conducted using R 4.5.0 statistical computing environment (R Foundation for Statistical Computing, Vienna, Austria). Descriptive statistics for categorical variables are presented with absolute and relative frequencies. Quantitative variables with symmetrical distributions are described using mean (standard deviation), and variables with skewed distributions are presented with median (1st; 3rd quartiles). Propensity score matching (PSM) was performed using the MatchIt 4.7.1 package. To assess covariate balance of potential confounders, standardized mean difference was used. Logistic regression was employed for PSM, with untransformed covariates included as predictors. The nearest neighbor method without caliper was used for 1 to 1 PSM. For comparing full cohort groups regarding quantitative variables, the Brunner-Munzel test was used, while for comparing groups in terms of binary and categorical variables, the exact Fisher test with mid-p correction and exact version of Pearson's chi-squared test are applied. For comparing matched groups regarding quantitative variables, the Wilcoxon signed-rank test was used, while for comparing groups in terms of binary variables, the exact version of McNemar's test and was applied. A two-sided p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eBaseline demographic and clinical data are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Patients in the Calafiore group less often had previous cardiac surgery (17.4% vs. 28.7%, p\u0026thinsp;=\u0026thinsp;0.002), but more frequently presented with NYHA class IV symptoms (35.3% vs. 16.5%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and LVEF\u0026thinsp;\u0026lt;\u0026thinsp;50% (46.3% vs. 33.1%, p\u0026thinsp;=\u0026thinsp;0.002). Other baseline variables, including sex, renal function, and major comorbidities, did not differ between groups.\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\u003eBaseline demographic and clinical data\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\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 \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;553\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCustodiol\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;335\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCalafiore\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;218\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex (female) (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e26.6%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e26.6%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e26.6%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.99\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge [years] median (q1;q3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e65 (55; 73)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e67 (58; 74)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e63 (51.2; 71.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI [kg/m\u0026sup2;] median (q1;q3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e26.6 (24.2; 29.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e26.9 (24.2; 30.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e26.2 (23.7; 29.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.04\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGFR [ml/min] median (q1;q3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e70.8 (44; 94.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e70.8 (46.4; 92.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e72.9 (40.4; 101)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.436\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCreatinine [\u0026micro;mol/L] median (q1;q3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e93 (70; 132.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e92 (70; 128)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e97 (74; 143)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.151\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEuroSCORE II mean (SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e22.7 (21.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22.8 (20.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e22.6 (21.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.789\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePulmonary disease (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.51\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eExtracardiac arteriopathy (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.784\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeurological dysfunction (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e19.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e18.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.671\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrevious cardiac surgery (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e17.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.002\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiabetes on insulin (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e16.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.955\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCritical pre-op state (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e53.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e53.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e62.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.642\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRecent MI (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.187\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNYHA class IV (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e35.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLVEF %, median (q1;q3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e55 (50; 60)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e56 (50; 63)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e54.5 (45; 60)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.002\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLVEF\u0026thinsp;\u0026lt;\u0026thinsp;50% (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e38.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e33.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e46.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.002\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eEndocarditis-specific characteristics are shown in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. Aortic valve IE was more common in patients receiving Calafiore (46.4% vs. 27.1%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), while mitral (29.9% vs. 21.4%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and multivalve involvement (42.7% vs. 32.3%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) were more frequent in patients with Custodiol\u0026reg;. Median vegetation size was 12.0 to 13.0 mm. Surgery for recurrent IE was less frequent in the Calafiore group (7.7% vs. 30.2%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Microbiological findings, including Staphylococcus aureus, Enterococcus spp., Candida spp., Streptococcus spp., HACEK, Enterobacteriaceae, and Pseudomonas aeruginosa, showed no relevant differences.\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\u003eEndocarditis Details\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\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 \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003cp\u003e\u003cem\u003e(n\u0026thinsp;=\u0026thinsp;553)\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCustodiol\u003c/p\u003e \u003cp\u003e\u003cem\u003e(n\u0026thinsp;=\u0026thinsp;335)\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCalafiore\u003c/p\u003e \u003cp\u003e\u003cem\u003e(n\u0026thinsp;=\u0026thinsp;218)\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep\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\u003eIE localization (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMitral\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e26.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e29.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e21.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAortic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e34.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e27.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e46.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMore or equal to 2 valves\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e38.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e42.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e32.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTricuspid\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVegetation size (mm) median (q1;q3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12 (2; 25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13 (2; 27)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12 (2; 19.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.002\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVegetation\u0026thinsp;\u0026gt;\u0026thinsp;15 mm (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e45.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e48.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e40.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.077\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRecurrent endocarditis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e30.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eOriginal Microbiology (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStaphylococcus aureus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e26.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e23.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.223\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEnterococcus spp.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.647\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCoagulase-negative staphylococci\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.925\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCandida spp.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.205\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStreptococcus spp.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.437\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHACEK group\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (0.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (0.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.174\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEnterobacteriaceae\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.142\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePseudomonas aeruginosa\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.378\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e shows operative data. Calafiore was more often used in aortic valve surgery procedure (46.8% vs. 29.3%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and less in mitral (21.6% vs. 32.2%, p\u0026thinsp;=\u0026thinsp;0.006) and Bentall/UFO procedures (6.9% vs. 12.8%, p\u0026thinsp;=\u0026thinsp;0.024). Minimally invasive access was more frequent in the Custodiol\u0026reg; group (12.8% vs. 5.0%, p\u0026thinsp;=\u0026thinsp;0.002). CPB, cross-clamp, and total operative times did not differ. Use of fresh frozen plasma and milrinone was more frequent in the warm blood cardioplegia group (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e), whereas other transfusions and vasopressor use were similar.\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\u003eOperative Data\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\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 \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003cp\u003e\u003cem\u003e(n\u0026thinsp;=\u0026thinsp;553)\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCustodiol\u003c/p\u003e \u003cp\u003e\u003cem\u003e(n\u0026thinsp;=\u0026thinsp;335)\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCalafiore\u003c/p\u003e \u003cp\u003e\u003cem\u003e(n\u0026thinsp;=\u0026thinsp;218)\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep\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\u003eProcedure\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAortic valve surgery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e200 (36.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e98 (29.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e102/218 (46.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\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\u003e155 (28%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e108 (32.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e47/218 (21.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.006\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDouble valve surgery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e140 (25.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e86 (25.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e54/218 (24.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.815\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBentall / UFO\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e58 (10.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e43(12.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e15/218 (6.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.024\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eConcomitant CABG\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e79 (14.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e46 (13.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e33/218 (15.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.643\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMIC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e54 (9.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e43 (12.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11/218 (5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.002\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTime parameters\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBypass time (min)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e118 (90; 163.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e119 (93; 166)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e113 (84.5; 161)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.182\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCross-clamp time (min)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e77 (58; 107)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e77 (59; 107)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e77 (54.8; 104.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.638\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal OR time (min)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e199 (159; 259)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e199 (158; 268)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e198.5 (160; 246.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.895\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCoagulation and transfusion\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRed blood cells\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e259 (44.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e152 (42.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e107 (48.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.126\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFresh frozen plasma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e89 (15.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e26 (7.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e63 (28.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePlatelets\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e59 (10.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e30 (8.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e29 (13.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.059\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFibrinogen\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16 (2.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13 (3.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3 (1.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.113\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePPSB\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20 (3.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15 (4.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5 (2.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.237\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFactor XIII\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11 (1.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9 (2.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (0.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.189\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eVasopressors and Inotropic support\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNoradrenaline\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e461 (97.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e352 (98.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e215 (97.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.632\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAdrenaline\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e136 (28.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e100 (27.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e70 (32.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.384\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMilrinone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e129 (27.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e89 (24.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e79 (35.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.027\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \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\u003eOutcomes (after PSM)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\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 \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCustodiol\u003c/p\u003e \u003cp\u003e\u003cem\u003e(n\u0026thinsp;=\u0026thinsp;175)\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCalafiore\u003c/p\u003e \u003cp\u003e\u003cem\u003e(n\u0026thinsp;=\u0026thinsp;175)\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ep\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOverall\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e30-day mortality\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e40/175 (22.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e26/175 (14.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.057\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1-year mortality\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e65/175 (37.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e50/175 (28.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.09\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePostoperative stroke\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e19/175 (10.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8/175 (4.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.029\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePostoperative dialysis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e36/175 (20.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24/175 (13.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.091\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHospital stay [days (q1;q3)]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20 (13; 30)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15 (11; 26)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.011\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eICU stay [days (q1;q3) ]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (3; 12.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (1; 8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAortic valve surgery\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e30-day mortality\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13/87 (14.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10/87 (11.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.513\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1-year mortality\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e22/87 (25.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20/87 (23%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.727\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePostoperative stroke\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6/87 (6.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2/87 (2.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.171\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePostoperative dialysis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9/87 (10.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10/87 (11.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.814\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHospital stay [median days (q1;q3)]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20 (14; 27.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15 (11; 29)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.09\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eICU stay stay [median days (q1;q3)]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (3; 10.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (1; 6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMitral valve surgery\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e30-day mortality\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10/34 (29.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4/34 (11.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.083\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1-year mortality\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16/34 (47.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7/34 (20.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.024\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePostoperative stroke\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5/34 (14.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3/34 (8.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.484\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePostoperative dialysis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6/34 (17.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4/34 (11.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.519\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHospital stay stay [median days (q1;q3)]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e19 (10.2; 30.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15.5 (10.8; 21.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.217\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eICU stay stay [median days (q1;q3)]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (3; 12)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (0; 5.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.005\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDouble valve surgery\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e30-day mortality\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13/43 (30.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9/43 (20.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.338\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1-year mortality\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21/43 (48.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19/43 (44.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.673\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePostoperative stroke\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5/43 (11.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2/43 (4.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.271\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePostoperative dialysis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e19/43 (44.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6/43 (14%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.002\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHospital stay stay [median days (q1;q3)]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e22 (12.5; 34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15 (10.2; 28)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.201\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eICU stay stay [median days (q1;q3)]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10 (4; 13)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (2; 11.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.098\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBentall / UFO\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e30-day mortality\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4/11 (36.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3/11 (27.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.681\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1-year mortality\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6/11 (54.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4/11 (36.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.434\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePostoperative stroke\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3/11 (27.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1/11 (9.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.338\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePostoperative dialysis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2/11 (18.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4/11 (36.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.392\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHospital stay stay [median days (q1;q3)]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21 (8; 35.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15 (8.5; 24)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.558\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eICU stay stay [median days (q1;q3)]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14 (5; 21)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (1.5; 8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.055\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eIn the overall cohort, no statistically significant differences in 1-year mortality were observed between groups across any surgical category. In aortic valve surgery, patients in the Calafiore group had a shorter ICU (median 2 vs. 5 days, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and hospital stay (15 vs. 19.5 days, p\u0026thinsp;=\u0026thinsp;0.026); other endpoints, including 30-day mortality, stroke, and dialysis, did not differ. In mitral valve surgery, ICU stay was markedly shorter in patients with Calafiore cardioplegia (1 vs. 6 days, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), with no significant differences in survival or other complications. For double valve procedures, dialysis was more frequent (32.6% vs. 14.8%, p\u0026thinsp;=\u0026thinsp;0.019) and ICU stay was longer (7 vs. 3.5 days, p\u0026thinsp;=\u0026thinsp;0.043) in the Custodiol\u0026reg; group, while mortality and stroke rates were comparable. In Bentall/UFO operations, outcomes were similar, with a non-significant trend toward shorter ICU stay with Calafiore (4 vs. 8 days, p\u0026thinsp;=\u0026thinsp;0.148).\u003c/p\u003e \u003cp\u003eAfter propensity score matching using 14 preoperative variables (age, body mass index, NYHA class IV, left ventricular ejection fraction\u0026thinsp;\u0026lt;\u0026thinsp;50%, recent myocardial infarction\u0026thinsp;\u0026lt;\u0026thinsp;90 days, diabetes on insulin, pulmonary disease, extracardiac arteriopathy, neurological dysfunction, glomerular filtration rate, previous cardiac surgery, and cross-clamp time), baseline characteristics were well balanced between groups.\u003c/p\u003e \u003cp\u003eIn aortic valve surgery, ICU stay was again shorter with Calafiore (2 vs. 6 days, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) with no significant differences in survival, stroke, or dialysis. In mitral valve surgery, 1-year mortality was lower with Calafiore (20.6% vs. 47.1%, p\u0026thinsp;=\u0026thinsp;0.024) and ICU stay shorter (2 vs. 6 days, p\u0026thinsp;=\u0026thinsp;0.005); other outcomes did not differ. For double valve procedures, dialysis remained more frequent with Custodiol\u0026reg; (44.2% vs. 14.0%, p\u0026thinsp;=\u0026thinsp;0.002), with similar mortality and stroke rates. In Bentall/UFO procedures, there were no significant differences in any endpoint.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eWe demonstrate in this analysis that in high-risk endocarditis patients, warm blood cardioplegia may be superior to cold crystalloid, although differences did not reach statistical significance. However, propensity matching may not have accounted for all differences, which warrants further discussion and investigation.\u003c/p\u003e \u003cp\u003eWe used propensity score matching with 13 preoperative variables achieving a good balance with standardized mean differences below 0.1 for all covariates. In this adjusted cohort, 1-year mortality did not differ significantly between the two cardioplegic strategies. This finding aligns with previous reports in mixed cardiac surgical populations, where no clear survival benefit could be attributed to either crystalloid or blood [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e], cold or warm [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e] cardioplegia once baseline risk was accounted for. However, numerically one year mortality was lower with Calafiore.\u003c/p\u003e \u003cp\u003eSecondary outcomes also revealed consistent trends suggesting systemic differences between the regimens. Patients receiving warm blood cardioplegia had faster postoperative recovery, shorter ICU stay (2 vs. 6 days, p\u0026thinsp;=\u0026thinsp;0.001), fewer postoperative strokes (5.0% vs. 9.6%), and less frequent dialysis in double-valve procedures (14.8% vs. 32.6%). These differences were most pronounced in operations with shorter aortic cross-clamp times, particularly isolated aortic and mitral valve procedures.\u003c/p\u003e \u003cp\u003eThe disappearance of these differences with increasing surgical complexity and cross-clamp time suggests that the observed effects are unlikely to stem from myocardial protection itself, because shorter cross-clamp times require less perfect protection for sufficient endogenous ischemia tolerance. A possible and plausible explanation may therefore lie in the systemic effects of the cardioplegic solution. Custodiol is administered as a single large-volume crystalloid dose and, when allowed to enter the systemic circulation, may induce vasoplegia or contribute to hemodilution. Previous reports demonstrated that active evacuation of Custodiol\u0026reg; from the coronary sinus can attenuate such effects [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e], but this maneuver was rarely performed in our series. In shorter and less complex operations, Calafiore cardioplegia is administered in comparatively smaller volumes, and the systemic impact of its components may therefore play a less prominent role. In infective endocarditis, where septic vasoplegia and endothelial dysfunction are common, even modest differences in intravascular volume or electrolyte composition may potentially influence postoperative stability and recovery.\u003c/p\u003e \u003cp\u003ePlaced within this physiological context, these findings gain further clarity when contrasted with outcomes reported in major European multicentre registries. Our outcomes are comparable to those reported by the major contemporary registries of surgically treated infective endocarditis, including the EURO-ENDO registry [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e] and the German multicentre CAMPAIGN [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e] study. Notably, the operative risk in these cohorts was substantially lower\u0026mdash;for example, the CAMPAIGN registry reported a median EuroSCORE II of 10\u0026ndash;12%, whereas in our study the mean EuroSCORE II was 22.7. Despite this markedly higher risk profile, early mortality in our cohort remained within the range observed in these large registries. Thus, our results can be considered externally valid and potentially generalizable to other centers.\u003c/p\u003e \u003cp\u003eTaken together, these findings suggest that systemic factors may influence postoperative morbidity and recovery in high-risk populations. The potential advantage of warm blood cardioplegia in shorter, less complex procedures may therefore reflect attenuation of systemic effects rather than differences in myocardial preservation. Prospective randomized studies are warranted to confirm these hypotheses and to define the optimal myocardial protection strategy for infective endocarditis surgery. In the meantime, it may be advisable to evacuate Custodiuol solutions from the coronary sinus in infective endocarditis patients, a strategy that actually aligns with manufacturer recommendations [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e].\u003c/p\u003e"},{"header":"Limitations","content":"\u003cp\u003eThis was a retrospective single-center analysis, with potential for residual confounding despite propensity matching. Some subgroups, particularly Bentall/UFO, were small and underpowered for detecting modest effects.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets generated and/or analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was approved by the Ethics Committee of Jena University Hospital. Informed consent was waived due to the retrospective and anonymized study design.\u003c/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eMM and TC contributed equally to study conception, data analysis, and manuscript drafting. PF, SF, HK, and JB contributed to data acquisition and interpretation. MP, SH, SG, MB contributed to clinical expertise and critical revision. MD and TD supervised the study and finalized the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by the IKARUS Research College at Jena University Hospital, funded by the Else Kr\u0026ouml;ner-Fresenius-Stiftung. The IKARUS Study Group comprises Prof. Dr. Mathias W. Pletz (Institute of Infectious Diseases and Infection Control); Prof. Dr. Torsten Doenst (Department of Cardiothoracic Surgery); Prof. Dr. Bettina L\u0026ouml;ffler (Institute of Medical Microbiology); Prof. Dr. Christian Schulze (Department of Internal Medicine I: Cardiology, Angiology, Intensive Care Medicine); Prof. Dr. Regine Heller (Institute of Molecular Cell Biology \u0026middot; Center for Molecular Biomedicine, CMB); Dr. Micha Banz (Department of Internal Medicine IV: Gastroenterology, Hepatology, Infectious Diseases, Interventional Endoscopy); Dr. J\u0026uuml;rgen Bogoviku (Department of Internal Medicine I); Dr. Sandesh Dinesh (Department of Internal Medicine I); Dr. Philine Fleckenstein (Department of Cardiothoracic Surgery); Dr. Sebastian Freiburger (Department of Cardiothoracic Surgery); Dr. Stefan Gl\u0026ouml;ckner (Institute of Medical Microbiology); and Dr. Murat Mukharyamov (Department of Cardiothoracic Surgery).\u003cbr\u003e \u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eDelgado V, Ajmone Marsan N, de Waha S, Bonaros N, Brida M, Burri H et al. 2023 \u003cem\u003eESC Guidelines for the management of endocarditis: Developed by the task force on the management of endocarditis of the European Society of Cardiology (ESC) Endorsed by the European Association for Cardio-Thoracic Surgery (EACTS) and the European Association of Nuclear Medicine (EANM)\u003c/em\u003e. European Heart Journal 2023;44:3948\u0026ndash;4042.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWahba A, Kunst G, De Somer F, Agerup Kildahl H, Milne B, Kjellberg G et al. 2024 EACTS/EACTAIC/EBCP Guidelines on cardiopulmonary bypass in adult cardiac surgery. Eur J Cardiothorac Surg 2025;67.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAli JM, Miles LF, Abu-Omar Y, Galhardo C, Falter F. Global Cardioplegia Practices: Results from the Global Cardiopulmonary Bypass Survey. J Extra Corpor Technol. 2018;50:83\u0026ndash;93.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMukharyamov M, Schneider U, Kirov H, Caldonazo T, Doenst T. \u003cem\u003eMyocardial protection in cardiac surgery\u0026mdash;hindsight from the 2020s\u003c/em\u003e. European Journal of Cardio-Thoracic Surgery 2023;64.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLi JS, Sexton DJ, Mick N, Nettles R, Fowler VG Jr., Ryan T, et al. Proposed modifications to the Duke criteria for the diagnosis of infective endocarditis. Clin Infect Dis. 2000;30:633\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFowler VG, Durack DT, Selton-Suty C, Athan E, Bayer AS, Chamis AL, et al. The 2023 Duke-International Society for Cardiovascular Infectious Diseases Criteria for Infective Endocarditis: Updating the Modified Duke Criteria. Clin Infect Dis. 2023;77:518\u0026ndash;26.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCalafiore AM, Teodori G, Mezzetti A, Bosco G, Verna AM, Di Giammarco G, Lapenna D. Intermittent antegrade warm blood cardioplegia. Ann Thorac Surg. 1995;59:398\u0026ndash;402.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGuru V, Omura J, Alghamdi AA, Weisel R, Fremes SE. Is blood superior to crystalloid cardioplegia? A meta-analysis of randomized clinical trials. Circulation. 2006;114:I331\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFan Y, Zhang AM, Xiao YB, Weng YG, Hetzer R. Warm versus cold cardioplegia for heart surgery: a meta-analysis. Eur J Cardiothorac Surg. 2010;37:912\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBusch T, Sirbu H, Kazmaier S, Aleksic I, Friedrich M, Dalichau H, Buhre W. Single atriocaval cannulation is associated with increased incidence of hypercirculatory failure after cardiopulmonary bypass. Ann Thorac Cardiovasc Surg. 2001;7:210\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHabib G, Erba PA, Iung B, Donal E, Cosyns B, Laroche C, et al. Clinical presentation, aetiology and outcome of infective endocarditis. Results of the ESC-EORP EURO-ENDO (European infective endocarditis) registry: a prospective cohort study. Eur Heart J. 2019;40:3222\u0026ndash;32.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAckermann P, Marin-Cuartas M, Weber C, De La Cuesta M, Lichtenberg A, Petrov A et al. Sex-related differences in patients with infective endocarditis requiring cardiac surgery: insights from the CAMPAIGN Study Group. Eur J Cardiothorac Surg 2024;66.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGmbH DFKC. \u003cem\u003eCustodiol\u0026reg; (HTK) L\u0026ouml;sung \u0026ndash; Gebrauchsinformation / Instructions for Use. Version V11/07.23\u003c/em\u003e. Official Instructions for Use (IFU), regulatory document for Custodiol HTK. Document code 10500226. Last revised October 2022. edn Bensheim, Germany: Dr. Franz K\u0026ouml;hler Chemie GmbH; 2022.\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":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"journal-of-cardiothoracic-surgery","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"jcts","sideBox":"Learn more about [Journal of Cardiothoracic Surgery](http://cardiothoracicsurgery.biomedcentral.com)","snPcode":"13019","submissionUrl":"https://submission.nature.com/new-submission/13019/3","title":"Journal of Cardiothoracic Surgery","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Infective endocarditis, cardioplegia, myocardial protection","lastPublishedDoi":"10.21203/rs.3.rs-8426492/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8426492/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eObjectives\u003c/h2\u003e \u003cp\u003eCurrent evidence does not support superiority of one cardioplegia type over another, but stems from low-risk populations. Therefore, we compared outcomes of multimorbid, high-risk infective endocarditis (IE) patients receiving Custodiol\u003cb\u003e\u0026reg;\u003c/b\u003e crystalloid or Calafiore blood cardioplegia during cardiac surgery.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eWe retrospectively analyzed 553 patients (mean EuroScore II 22.7\u0026thinsp;\u0026plusmn;\u0026thinsp;21.1) who underwent surgery for IE between 2009 and 2023 and received either cold crystalloid (Custodiol\u003cb\u003e\u0026reg;\u003c/b\u003e, n\u0026thinsp;=\u0026thinsp;335) or warm blood (Calafiore, n\u0026thinsp;=\u0026thinsp;218) cardioplegia. The primary endpoint was 1-year mortality. Secondary endpoints included 30-day mortality, postoperative stroke, and new-onset dialysis. Propensity score matching (1:1, 14 covariates) resulted in 175 matched pairs. Statistical analysis included nonparametric and exact tests.\u003c/p\u003e\u003ch2\u003eResults:\u003c/h2\u003e \u003cp\u003eIn the overall cohort, patients receiving Custodiol\u003cb\u003e\u0026reg;\u003c/b\u003e were higher risk and had higher mortality and morbidity. After matching, there was no significant difference in 1-year mortality between patients receiving Custodiol\u0026reg; and Calafiore (37.1% vs. 28.6%, p\u0026thinsp;=\u0026thinsp;0.09). Thirty-day mortality trended to be lower in the Calafiore group without reaching statistical significance (22.9% vs. 14.9%, p\u0026thinsp;=\u0026thinsp;0.057). However, stroke was less frequent (4.6% vs. 10.9%, p\u0026thinsp;=\u0026thinsp;0.029), ICU stay was shorter (3[\u003cspan additionalcitationids=\"CR2 CR3 CR4 CR5 CR6 CR7\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e] vs. 6[3\u0026ndash;12.5] days, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and postoperative dialysis was numerically less common (13.7 vs. 20.6%, p\u0026thinsp;=\u0026thinsp;0.091). These differences were most evident in procedures with shorter cross-clamp times, such as isolated mitral or aortic valve surgery, where mortality and recovery parameters consistently favored Calafiore.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eIn high-risk endocarditis patients warm blood cardioplegia may be superior to cold crystalloid, although differences did not reach statistical significance. However, propensity matching may not have accounted for all differences, which warrants further discussion and investigation.\u003c/p\u003e","manuscriptTitle":"Myocardial Protection during Surgery for Infective Endocarditis: retrospective, single center, risk-adjusted study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-02-06 16:03:55","doi":"10.21203/rs.3.rs-8426492/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-04-05T12:54:55+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-02-21T16:24:27+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-02-10T02:21:40+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-02-07T15:31:14+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"327605697193375361465403055738724202252","date":"2026-02-07T14:18:03+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"140221783303560854785279272202764775776","date":"2026-02-06T20:35:05+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-02-04T23:07:29+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"308584503373664427962773999269621918786","date":"2026-02-04T19:45:45+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"128724539055543994027383461066126444789","date":"2026-02-04T15:35:45+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"45424040706874766526512359778541851890","date":"2026-02-04T12:54:31+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-02-04T11:52:44+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-12-29T02:29:23+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-12-29T02:28:18+00:00","index":"","fulltext":""},{"type":"submitted","content":"Journal of Cardiothoracic Surgery","date":"2025-12-22T15:13:50+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"journal-of-cardiothoracic-surgery","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"jcts","sideBox":"Learn more about [Journal of Cardiothoracic Surgery](http://cardiothoracicsurgery.biomedcentral.com)","snPcode":"13019","submissionUrl":"https://submission.nature.com/new-submission/13019/3","title":"Journal of Cardiothoracic Surgery","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"fb9ab15c-8e23-459e-8af7-bafc4bbda6be","owner":[],"postedDate":"February 6th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-04-21T13:25:37+00:00","versionOfRecord":[],"versionCreatedAt":"2026-02-06 16:03:55","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8426492","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8426492","identity":"rs-8426492","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}