Tissue requirements for the application of aortic valve neocuspidization - appropriate pericardium properties and homogeneity?

OBJECTIVE: Aortic valve neocuspidization (AVNeo) using autologous pericardium is a promising technique. Expected advantages are reduced immune response, appropriate biomechanics and lower treatment expenses. Nevertheless, autologous pericardium can be affected by patient's age and comorbidities. Usually, glutaraldehyde (GA) - fixed bovine pericardium is the basic material for aortic valve prostheses, easy available and carefully pre-examined in a standardized fabrication process. Aim of the study is the verification of autologous pericardial tissue homogeneity by analysing tissue thickness, biomechanics and extracellular matrix (ECM) composition. METHODS: Segments of human GA-fixed pericardium selected by the surgeon based on visual criteria for cusp pre-cut and remaining after surgical AV replacement were investigated in comparison to bovine standard tissue treated equivalently. Pericardium sampling was performed at up to three positions of each sutured cusp for histological or biomechanical analysis, according to tissue availability. RESULTS AND CONCLUSIONS: Human pericardia exhibited a higher heterogeneity in collagen content, density of vessel structures and elastic moduli. Thickness, vessel density and collagen and elastin content differed significantly between the species. In contrast, significant interindividual differences were detected in most properties investigated for human pericardial samples but only for tissue thickness in bovine tissues. Higher heterogeneity of human pericardium, differing vessel and collagen content compared to bovine state-of-the-art material might be detrimental for long term AV functionality or deterioration and have to be intensely investigated in patients follow up after autologous cusp replacement.

Clinical Outcomes after Multivalve Surgery in Octogenarians: Evaluating the Need for a Paradigm Shift.

(1) Background: this study addresses the lack of comprehensive research on outcomes in octogenarians undergoing cardiac surgery for multivalvular disease, emphasizing the need for a critical examination of the intervention's overall worth in this aging population. (2) Methods: By analyzing short-term and mid-term data from 101 consecutive octogenarian patients undergoing multivalve surgery, the study identifies predictors for in-hospital and one-year mortality. (3) Results: In-hospital mortality increased fourfold with the occurrence of at least one postoperative complication. Octogenarians undergoing multivalve surgery experienced an in-hospital mortality rate of 13.9% and an overall one-year mortality rate of 43.8%. Postoperative delirium was identified as an independent risk factor, contributing to elevated risks of both in-hospital and one-year mortality. Prolonged surgical procedure time emerged as an independent risk factor associated with increased in-hospital mortality. Continuous veno-venous hemodialysis showed an independent impact on in-hospital mortality. Both re-intubation and the transfusion of packed red blood cells were identified as independent risk factors for one-year mortality. (4) Conclusions: This study urges a critical examination of the justification for multivalve surgeries in high-risk elderly patients, emphasizing a paradigm shift. It advocates for interdisciplinary collaboration and innovative strategies, such as staged hybrid procedures, to improve therapeutic approaches for this challenging patient group to achieve a better therapeutic outcome for these patients.

Challenges of aortic valve tissue culture - maintenance of viability and extracellular matrix in the pulsatile dynamic microphysiological system.

BACKGROUND: Calcific aortic valve disease (CAVD) causes an increasing health burden in the 21st century due to aging population. The complex pathophysiology remains to be understood to develop novel prevention and treatment strategies. Microphysiological systems (MPSs), also known as organ-on-chip or lab-on-a-chip systems, proved promising in bridging in vitro and in vivo approaches by applying integer AV tissue and modelling biomechanical microenvironment. This study introduces a novel MPS comprising different micropumps in conjunction with a tissue-incubation-chamber (TIC) for long-term porcine and human AV incubation (pAV, hAV). RESULTS: Tissue cultures in two different MPS setups were compared and validated by a bimodal viability analysis and extracellular matrix transformation assessment. The MPS-TIC conjunction proved applicable for incubation periods of 14-26 days. An increased metabolic rate was detected for pulsatile dynamic MPS culture compared to static condition indicated by increased LDH intensity. ECM changes such as an increase of collagen fibre content in line with tissue contraction and mass reduction, also observed in early CAVD, were detected in MPS-TIC culture, as well as an increase of collagen fibre content. Glycosaminoglycans remained stable, no significant alterations of α-SMA or CD31 epitopes and no accumulation of calciumhydroxyapatite were observed after 14 days of incubation. CONCLUSIONS: The presented ex vivo MPS allows long-term AV tissue incubation and will be adopted for future investigation of CAVD pathophysiology, also implementing human tissues. The bimodal viability assessment and ECM analyses approve reliability of ex vivo CAVD investigation and comparability of parallel tissue segments with different treatment strategies regarding the AV (patho)physiology.

Cardiac Surgery for Treatment of COVID-19-Associated Infectious Endocarditis.

BACKGROUND: Significant uncertainty exists about the optimal timing of surgery for infectious endocarditis (IE) surgery in patients with active SARS-CoV-2 infection. This case series and a systematic review of the literature were carried out to evaluate the timing of surgery and postsurgical outcomes for patients with COVID-19-associated IE. METHODS: The PubMed database was searched for reports published from June 20, 2020, to June 24, 2021, that contained the terms infective endocarditis and COVID-19. A case series of 8 patients from the authors' facility was also added. RESULTS: A total of 12 cases were included, including 4 case reports that met inclusion criteria in addition to a case series of 8 patients from the authors' facility. Mean (SD) patient age was 61.9 (17.1) years, and patients were predominantly male (91.7%). Being overweight was the main comorbidity among patients studied (7/8 [87.5%]). Among all patients evaluated in this study, dyspnea (n = 8 [66.7%]) was the leading symptom, followed by fever (n = 7 [58.3%]). Enterococcus faecalis and Staphylococcus aureus caused 75.0% of COVID-19-associated IE. The mean (SD) time to surgery was 14.5 (15.6) days (median, 13 days). In-hospital and 30-day mortality for all evaluated patients was 16.7% (n = 2). CONCLUSION: Clinicians must carefully assess patients diagnosed with COVID-19 to prevent missing underlying diseases such as IE. If IE is suspected, clinicians should avoid postponement of crucial diagnostic and treatment steps.

Hemocompatibility tuning of an innovative glutaraldehyde-free preparation strategy using riboflavin/UV crosslinking and electron irradiation of bovine pericardium for cardiac substitutes.

Hemocompatibility tuning was adopted to explore and refine an innovative, GA-free preparation strategy combining decellularization, riboflavin/UV crosslinking, and low-energy electron irradiation (SULEEI) procedure. A SULEEI-protocol was established to avoid GA-dependent deterioration that results in insufficient long-term aortic valve bioprosthesis durability. Final SULEEI-pericardium, intermediate steps and GA-fixed reference pericardium were exposed in vitro to fresh human whole blood to elucidate effects of preparation parameters on coagulation and inflammation activation and tissue histology. The riboflavin/UV crosslinking step showed to be less efficient in inactivating extracellular matrix (ECM) protein activity than the GA fixation, leading to tissue-factor mediated blood clotting. Intensifying the riboflavin/UV crosslinking with elevated riboflavin concentration and dextran caused an enhanced activation of the complement system. Yet activation processes induced by the previous protocol steps were quenched with the final electron beam treatment step. An optimized SULEEI protocol was developed using an intense and extended, trypsin-containing decellularization step to inactivate tissue factor and a dextran-free, low riboflavin, high UV crosslinking step. The innovative and improved GA-free SULEEI-preparation protocol results in low coagulant and low inflammatory bovine pericardium for surgical application.

Virulence of Staphylococcus Infection in Surgically Treated Patients With Endocarditis : A Multicenter Analysis.

OBJECTIVE: Infective endocarditis (IE) caused by Staphylococcus species (spp.) is believed to be associated with higher morbidity and mortality rates. We hypothesize that Staphylococcus spp. are more virulent compared with other commonly causative bacteria of IE with regard to short-term and long-term mortality. BACKGROUND: It remains unclear if patients suffering from IE due to Staphylococcus spp. should be referred for surgical treatment earlier than other IE patients to avoid septic embolism and to optimize perioperative outcomes. MATERIALS AND METHODS: The database of the CAMPAIGN registry, comprising 4917 consecutive patients undergoing heart valve surgery, was retrospectively analyzed. Patients were divided into 2 groups with regard to the identified microorganisms: Staphylococcus group and the non- Staphylococcus group. The non- Staphylococcus group was subdivided for further analyses: Streptococcus group, Enterococcus group, and all other bacteria groups. RESULTS: The respective mortality rates at 30 days (18.7% vs 11.8%; P <0.001), 1 year (24.7% vs 17.7%; P <0.001), and 5 years (32.2% vs 24.5%; P <0.001) were significantly higher in Staphylococcus patients (n=1260) compared with the non- Staphylococcus group (n=1787). Multivariate regression identified left ventricular ejection fraction <30% ( P <0.001), chronic obstructive pulmonary disease ( P =0.045), renal insufficiency ( P =0.002), Staphylococcus spp. ( P =0.032), and Streptococcus spp. ( P =0.013) as independent risk factors for 30-day mortality. Independent risk factors for 1-year mortality were identified as: age ( P <0.001), female sex ( P =0.018), diabetes ( P =0.018), preoperative stroke ( P =0.039), chronic obstructive pulmonary disease ( P =0.001), preoperative dialysis ( P <0.001), and valve vegetations ( P =0.004). CONCLUSIONS: Staphylococcus endocarditis is associated with an almost twice as high 30-day mortality and significantly inferior long-term outcome compared with IE by other commonly causative bacteria. Patients with Staphylococcus infection are more often female and critically ill, with >50% of these patients suffering from clinically relevant septic embolism. Early diagnosis and referral to a specialized center for surgical treatment are strongly recommended to reduce the incidence of preoperative deterioration and stroke due to septic embolism.

Infrared Spectroscopic Verification of a α-Helical Collagen Structure in Glutaraldehyde-Free Crosslinked Bovine Pericardium for Cardiac Implants.

The degeneration of heart valve bioprostheses due to calcification processes is caused by the intercalation of calciumhydroxyapatite in pericardium collagen bundles. Variations of the protein secondary structure of biomaterials according to preparation are relevant for this mineralization process and thus the structural characterization of innovative bioprostheses materials is of great importance. The gold standard for prostheses preparation is glutaraldehyde (GA)-fixation of bovine pericardium that adversely promotes calcification. The novel GA-free SULEEI-treatment of bovine pericardium includes decellularization, UV-crosslinking, and electron beam sterilization. The aim of this study is the structural characterization of SULEEI-treated and GA-fixed bovine pericardium. IR spectroscopic imaging combined with multivariate data and curve fit analysis was applied to investigate the amide I and amide II regions of SULEEI-treated and GA-fixed samples. The spectroscopic images of GA-fixed pericardial tissue exhibited a generally high content of amine groups and side chains providing nucleation points for calcification processes. In contrast, in SULEEI-treated tissue, the typical α-helical structure was retained and was supposed to be less prone to deterioration.

Redo surgery for noninfective isolated mitral valve disease: Initial outcome and further follow-up compared to primary surgery.

INTRODUCTION: Isolated redo-mitral valve replacement (iMVR) is underreported and often mixed up with endocarditis in the present literature. The present study compares first with redo iMVR in noninfective mitral disease. PATIENTS AND METHODS: A total of 3821 mitral valve procedures were analyzed. The study was restricted to isolated and noninfective mitral valve replacements done by sternotomy. Finally, 402 patients are included, consisting of 102 redo- and 300 first surgeries. The mean patient's age was 65.9 ± 10.4 years; the mean EuroSCORE II was 3.0 ± 2.2%. Median follow-up was 221 days, ranging up to 9.9 years with a total of 367 patient-years. RESULTS: Redo's had higher EuroSCORE II (5.1 ± 2.9% vs. 2.3 ± 1.4%; p < .01), more atrial fibrillation (31.1% vs. 46.1%; p = .01), chronic obstructive pulmonary disease (7.3% vs. 17.6%; p = .05), coronary artery disease (7.3% vs. 17.6%; p = .03) and more frequently reduced ejection fraction < 30% (3.0% vs. 11.8%; p = .02). Main outcomes showed comparable 30-days mortality (first: 4.1%, redo: 6.9%; p = .813). Postoperative morbidity of the redo's was associated with increased postoperative bleeding (p < .01) resulting in increased transfusions of packed red blood cells and fresh frozen plasma (each p < .01), more re-explorations (p < .01) and longer primary intensive care unit stay (p < .01). Postoperative occurrence of stroke, respiratory or renal failure, and myocardial infarction as well as hospital stay differed not significantly. Estimated 5-years survival was 65.5 ± 12.3% for all patients with no significant differences between the groups. Multivariate logistic regression respiratory failure as relevant for hospital (odds ratio [OR]: 12.3 [1.1-158]; p = .029) and stroke (OR: 4.8 [1.1-12.3]; p = .021) as relevant for long-term mortality. CONCLUSION: iMVR for noninfective reasons is infrequent and rare. Compared to primary surgery, redo's suffer mainly from bleeding-associated morbidity. This does not translate into prolonged hospital stay or inferior immediate or long-term outcomes. Redo mitral valve replacement can be performed at no significantly increased surgical risk compared with first surgery and the results are particularly not limited by the surgery itself.

Aortic root reinforcement in aortic valve endocarditis with annular abscess: The Calamari procedure.

Treatment of infective endocarditis can often prove challenging due to its wide range of anatomical presentations. When complicated by an aortic root abscess, patients may require extensive root surgery, which on its own leads to a worse outcome. We present our experience with a surgical technique for reinforcing the aortic annulus with a ring from a Dacron aortic prosthesis placed in the left ventricular outflow tract to avoid the need for root replacement procedures or patch closures of the defect. The technique described in this paper provides a viable alternative to the standard techniques used for the treatment of annular abscesses in aortic valve endocarditis. Due to the relative simplicity and ease of use, this approach may present a means of reducing operation time and possibly postoperative complications of this severe condition.

Impact of the 2009 ESC Guideline Change on Surgically Treated Infective Endocarditis.

BACKGROUND: In 2009, updated European Society of Cardiology guidelines on the prevention, diagnosis, and treatment of infective endocarditis (IE) were released and restricted the use of antibiotic prophylaxis to high-risk patients only. The aim of this study was to analyze the effect of the restrictive antibiotic regimen on the incidence and manifestations of surgically treated IE before and after the guideline change. METHODS: This study retrospectively analyzed data of 4917 patients who underwent valve surgical procedures for IE between 1994 and 2018 in 6 German cardiac surgery centers. Potential risk factors for 30-day mortality were assessed using logistic regression. Interrupted time series regression was used to evaluate the effect of the guideline change on the manifestation of IE. RESULTS: A total of 2014 patients (41%) underwent surgical procedures before the guideline change, and 2903 patients (59%) underwent surgical procedures after the change. After 2009, patients were older (67.0 years [interquartile range, 56.0-74.0 years] vs 64.0 years [interquartile range, 52.0-71.0 years]; P < .001), and they presented with more comorbidities, such as hypertension (56.9% vs 41.7%; P < .001), diabetes (27.4% vs 24.4%; P = .020), peripheral artery disease (8.5% vs 6.5%; P = .011), and preoperative acute kidney injury (42.8% vs 31.9%; P < .001). Patients had worse clinical outcomes with respect to 30-day mortality (18.1% vs 14.3%; P = .001) and 1-year mortality (37.1% vs 29.1%; P < .001). An increase in Streptococcus-related IE (P = .002) and an increase in mitral valve IE (P = .035) were observed after the guideline change. CONCLUSIONS: Since 2009, there has been a significant increase in the incidence of mitral valve IE and Streptococcus-related IE. Patients undergoing surgical procedures for IE present with more comorbidities, which contribute to high mortality rates.

Aortic Thrombosis following COVID-19: A Systematic Review.

BACKGROUND: Arterial and venous thromboses associated with the coronavirus disease 2019 (COVID-19) have been well described. These events are caused by a hypercoagulable state due to endotheliopathy and infection-driven coagulopathy. There has been an ever-increasing number of documented cases of aortic thrombosis (AoT) in COVID-19 patients. We conducted a systematic review of current scientific literature to identify and consolidate evidence of AoT in COVID-19 patients. METHODS: A systematic review of literature was conducted between March 15, 2020, and May 1, 2021, on PubMed and Cochrane databases. Additionally, a case from our facility was included. RESULTS: A total of 38 studies (12 case series and 26 case reports) and a case from our facility describing AoT in 56 COVID-19 patients were included. Patients were aged 64.8 ± 10.5 years, were predominantly male (75%), and had several comorbidities. AoT was symptomatic in 82,14% of patients; however, when D dimers were reported, they were significantly elevated even in otherwise asymptomatic patients. Most patients had no previous history of aortic disease. Thrombosis was described in all parts of the aorta, with several cases reporting multiple locations. The median reported time until development of AoT was 10 days. Peripheral thrombosis occurred in 73.21% of cases, most commonly causing lower limb ischemia. Mortality rate was 30.4%. CONCLUSIONS: AoT can occur with no clinical symptoms or as a primary symptom in otherwise asymptomatic COVID-19 patients. D dimers are a highly sensitive diagnostic tool. Diagnosis of this condition prior to development of complications could be instrumental in saving many lives.

Sterilization and Cross-Linking Combined with Ultraviolet Irradiation and Low-Energy Electron Irradiation Procedure: New Perspectives for Bovine Pericardial Implants in Cardiac Surgery.

BACKGROUND: Bovine pericardium is the major natural source of patches and aortic valve substitutes in cardiac repair procedures. However, long-term tissue durability and biocompatibility issues lead to degeneration (e.g., calcification) that requires reoperation. Tissue preparation strategies, including glutaraldehyde fixation, are reasons for the deterioration of pericardial tissues. We describe a pretreatment procedure involving sterilization and cross-linking combined with ultraviolet (UV) irradiation and low-energy electron irradiation (SULEEI). This innovative, glutaraldehyde-free protocol improves the mechanical aspects and biocompatibility of porcine pericardium patches. METHODS: We adopted the SULEEI protocol, which combines decellularization, sterilization, and cross-linking, along with UV irradiation and low-energy electron irradiation, to pretreat bovine pericardium. Biomechanics, such as ultimate tensile strength and elasticity, were investigated by comparing SULEEI-treated tissue with glutaraldehyde-fixed analogues, clinical patch materials, and an aortic valve substitute. Histomorphological and cellular aspects were investigated by histology, DNA content analysis, and degradability. RESULTS: Mechanical parameters, including ultimate tensile strength, elasticity (Young's modulus), and suture retention strength, were similar for SULEEI-treated and clinically applied bovine pericardium. The SULEEI-treated tissues showed well-preserved histoarchitecture that resembled all pericardial tissues investigated. Fiber density did not differ significantly. DNA content after the SULEEI procedure was reduced to less than 10% of the original tissue material, and more than 50% of the SULEEI-treated pericardium was digested by collagenase. CONCLUSION: The SULEEI procedure represents a new treatment protocol for the preparation of patches and aortic valve prostheses from bovine pericardial tissue. The avoidance of glutaraldehyde fixation may lessen the tissue degeneration processes in cardiac repair patches and valve prostheses.

Brillouin confocal microscopy to determine biomechanical properties of SULEEI-treated bovine pericardium for application in cardiac surgery.

BACKGROUND: Heart valves are exposed to a highly dynamic environment and underlie high tensile and shear forces during opening and closing. Therefore, analysis of mechanical performance of novel heart valve bioprostheses materials, like SULEEI-treated bovine pericardium, is essential and usually carried out by uniaxial tensile tests. Nevertheless, major drawbacks are the unidirectional strain, which does not reflect the in vivo condition and the deformation of the sample material. An alternative approach for measurement of biomechanical properties is offered by Brillouin confocal microscopy (BCM), a novel, non-invasive and three-dimensional method based on the interaction of light with acoustic waves. OBJECTIVE: BCM is a powerful tool to determine viscoelastic tissue properties and is, for the first time, applied to characterize novel biological graft materials, such as SULEEI-treated bovine pericardium. Therefore, the method has to be validated as a non-invasive alternative to conventional uniaxial tensile tests. METHODS: Vibratome sections of SULEEI-treated bovine pericardium (decellularized, riboflavin/UV-cross-linked and low-energy electron irradiated) as well as native and GA-fixed controls (n = 3) were analyzed by BCM. In addition, uniaxial tensile tests were performed on equivalent tissue samples and Young's modulus as well as length of toe region were analyzed from stress-strain diagrams. The structure of the extracellular matrix (ECM), especially collagen and elastin, was investigated by multiphoton microscopy (MPM). RESULTS: SULEEI-treated pericardium exhibited a significantly higher Brillouin shift and hence higher tissue stiffness in comparison to native and GA-fixed controls (native: 5.6±0.2 GHz; GA: 5.5±0.1 GHz; SULEEI: 6.3±0.1 GHz; n = 3, p < 0.0001). Similarly, a significantly higher Young's modulus was detected in SULEEI-treated pericardia in comparison to native tissue (native: 30.0±10.4 MPa; GA: 31.8±10.7 MPa; SULEEI: 42.1±7.0 MPa; n = 3, p = 0.027). Native pericardia showed wavy and non-directional collagen fibers as well as thin, linear elastin fibers generating a loose matrix. The fibers of GA-fixed and SULEEI-treated pericardium were aligned in one direction, whereat the SULEEI-sample exhibited a much denser matrix. CONCLUSION: BCM is an innovative and non-invasive method to analyze elastic properties of novel pericardial graft materials with special mechanical requirements, like heart valve bioprostheses.

Role of Concomitant Coronary Artery Bypass Grafting in Valve Surgery for Infective Endocarditis.

BACKGROUND: It is current practice to perform concomitant coronary artery bypass grafting (CABG) in patients with infective endocarditis (IE) who have relevant coronary artery disease (CAD). However, CABG may add complexity to the operation. We aimed to investigate the impact of concomitant CABG on perioperative outcomes in patients undergoing surgery for IE. METHODS: We retrospectively used data of surgically treated IE patients between 1994 and 2018 in six German cardiac surgery centers. We performed inverse probability weighting (IPW), multivariable adjustment, chi-square analysis, and Kaplan-Meier survival estimates. RESULTS: CAD was reported in 1242/4917 (25%) patients. Among them, 527 received concomitant CABG. After adjustment for basal characteristics between CABG and no-CABG patients using IPW, concomitant CABG was associated with higher postoperative stroke (26% vs. 21%, p = 0.003) and a trend towards higher postoperative hemodialysis (29% vs. 25%, p = 0.052). Thirty-day mortality was similar in both groups (24% vs. 23%, p = 0.370). Multivariate Cox regression analysis after IPW showed that CABG was not associated with better long-term survival (HR: 1.00, 95% CI: 0.82-1.23, p = 0.998). CONCLUSION: In endocarditis patients with CAD, adding CABG to valve surgery may be associated with a higher likelihood of postoperative stroke without adding long-term survival benefits. Therefore, in the absence of critical CAD, concomitant CABG may be omitted without impacting outcome. The results are limited due to a lack of data on the severity of CAD, and therefore there is a need for a randomized trial.

Optical coherence tomography and multiphoton microscopy offer new options for the quantification of fibrotic aortic valve disease in ApoE-/- mice.

Aortic valve sclerosis is characterized as the thickening of the aortic valve without obstruction of the left ventricular outflow. It has a prevalence of 30% in people over 65 years old. Aortic valve sclerosis represents a cardiovascular risk marker because it may progress to moderate or severe aortic valve stenosis. Thus, the early recognition and management of aortic valve sclerosis are of cardinal importance. We examined the aortic valve geometry and structure from healthy C57Bl6 wild type and age-matched hyperlipidemic ApoE-/- mice with aortic valve sclerosis using optical coherence tomography (OCT) and multiphoton microscopy (MPM) and compared results with histological analyses. Early fibrotic thickening, especially in the tip region of the native aortic valve leaflets from the ApoE-/- mice, was detectable in a precise spatial resolution using OCT. Evaluation of the second harmonic generation signal using MPM demonstrated that collagen content decreased in all aortic valve leaflet regions in the ApoE-/- mice. Lipid droplets and cholesterol crystals were detected using coherent anti-Stokes Raman scattering in the tissue from the ApoE-/- mice. Here, we demonstrated that OCT and MPM, which are fast and precise contactless imaging approaches, are suitable for defining early morphological and structural alterations of sclerotic murine aortic valves.

Surgical results for prosthetic versus native valve endocarditis: A multicenter analysis.

OBJECTIVES: Prosthetic valve endocarditis is associated with worse outcomes compared with native valve endocarditis. Our aim was to evaluate the impact of native valve endocarditis versus prosthetic valve endocarditis on postoperative outcomes and long-term survival and to identify preoperative risk factors in a large cohort of 4300 patients with infective endocarditis. METHODS: This retrospective cohort study was conducted in 5 German Cardiac Surgery Centers: the Clinical Multicenter Project of Analysis of Infective Endocarditis in Germany. Data of 4300 patients undergoing valve surgery for native valve endocarditis and prosthetic valve endocarditis were retrospectively analyzed. Univariable and multivariable analyses were used for risk stratification, Kaplan-Meier analysis for long-term survival. In addition, we performed Cox proportional hazards regression with multivariable adjustment. RESULTS: Between 1994 and 2016, 3143 patients (73.1%) underwent surgery for native valve endocarditis and 1157 patients (26.9%) underwent surgery for prosthetic valve endocarditis. Patients with prosthetic valve endocarditis were older (69 [60-75] vs 63 [52-72] years; P < .001) and had more comorbidities, such as hypertension (55% vs 46%; P < .001), diabetes (28% vs 25%; P = .020), coronary artery disease (32% vs 23%; P < .001), and preoperative acute kidney injury (41% vs 32%; P < .001). Kaplan-Meier analysis revealed significantly decreased long-term survival of patients undergoing surgery for prosthetic valve endocarditis compared with native valve endocarditis (P < .001). However, after multivariable adjustment, there was no significant difference in long-term survival between patients undergoing cardiac surgery with prosthetic valve endocarditis compared with native valve endocarditis. CONCLUSIONS: After adjusting for preoperative comorbidities, long-term survival for prosthetic valve endocarditis and native valve endocarditis is comparable. Thus, our large cohort study provides evidence that prosthetic valve endocarditis alone should not be a contraindication for redo operations.

Treatment with XAV-939 prevents in vitro calcification of human valvular interstitial cells.

The development of a substance or inhibitor-based treatment strategy for the prevention of aortic valve stenosis is a challenge and a main focus of medical research in this area. One strategy may be to use the tankyrase inhibitor XAV-939, which leads to Axin stabilisation and subsequent destruction of the ß-catenin complex and dephosphorylation of ß-catenin. The dephosphorylated active form of ß-catenin (non-phospho-ß-catenin) then promotes nuclear transcription that leads to osteogenesis. The aims of the present study were to develop an experimental system for inducing in vitro calcification of human aortic valvular interstitial cells (VICs) to investigate the potential anti-calcific effect of XAV-939 and to analyse expression of the Wnt signalling proteins and Sox9, a chondrogenesis regulator, in this model. Calcification of human VIC cultures was induced by cultivation in an osteogenic medium and the effect of co-incubation with 1µM XAV-939 was monitored. Calcification was quantified when mineral deposits were visible in culture and was histologically verified by von Kossa or Alizarin red staining and by IR-spectroscopy. Protein expression of alkaline phosphatase, Axin, ß-catenin and Sox9 were quantified by western blotting. In 58% of the VIC preparations, calcification was induced in an osteogenic culture medium and was accompanied by upregulation of alkaline phosphatase. The calcification induction was prevented by the XAV-939 co-treatment and the alkaline phosphatase upregulation was suppressed. As expected, Axin was upregulated, but the levels of active non-phospho-ß-catenin were also enhanced. Sox9 was induced during XAV-939 treatment but apparently not as a result of downregulation of ß-catenin signalling. XAV-939 was therefore able to prevent calcification of human VIC cultures, and XAV-939 treatment was accompanied by upregulation of active non-phospho-ß-catenin. Although XAV-939 does not downregulate active ß-catenin, treatment with XAV-939 results in Sox9 upregulation that may prevent the calcification process.

Stabilization and Sterilization of Pericardial Scaffolds by Ultraviolet and Low-Energy Electron Irradiation.

IMPACT STATEMENT: Pericardium-based tissue transplantation is a lifesaving treatment. Commercial glutaraldehyde-treated pericardial tissue exhibits cytotoxicity, which is associated with the accelerated graft failure. Replacement of glutaraldehyde has been suggested to overcome those drawbacks. In this study, we report a toxin-free method that combines tissue stabilization with a terminal sterilization. Our data indicate that the SULEEI procedure, which is part of an issued patent, may be a promising first step toward glutaraldehyde-free pericardium-based tissue transplants. Thus, our results may contribute to improving cardiovascular treatment strategies.

Movat Pentachrom stain reveals unexpected high osteogenesis rate in aortic valves.

BACKGROUND AND AIM OF THE STUDY: Aortic valve (AV) stenosis is the most common valvular heart disease with an incidence of 3% for people ≥ 65years in the industrialized world with indication for a surgical or transcatheter valve replacement. Researchers suppose osteogenic processes as key mechanisms in calcific aortic valve stenosis. Recently, Torre et al. published impressive histological analyses and detected osseous and/or chondromatous metaplasia in 15.6% of 6685 native calcified aortic valves. Therefore one HE section per valve originated from the area with the greatest extent of calcification was analyzed. Aim of our experimental setup was to identify regions of neo-osteogenesis and to determine the rate of specimens with active mineralization in human aortic valve tissue by Movat Pentachrom staining of sections of lager tissue segments. METHODS: Operational replaced aortic valves of 35 patients, 15 female and 20 male with an average age of 66.2 years were formalin fixed and decalcified using Osteosoft®-solution. Tissue samples were cut and 2µm specimens were stained with Movat Pentachrom to visualize osteogenic regions. Instead of screening a large number of sections, tissue samples were cut up to five times with at least 100µm space each if no region of osseous and/or chondromatous metaplasia was visible. RESULTS/CONCLUSIONS: Using this setup, a region of osseous metaplasia was detected in 25 (71.4%) of 35 samples analyzed. In some cases, these regions were small sized and only visible due to the bright color of Movat Pentachrom stain. This leads to the suggestion that a higher rate of calcified aortic valve samples would be classified as cusps with areas of neo-osteogenesis after staining with Movat Pentachrom stain and by the systematic analysis of larger parts of the tissue blocks.