Bioprosthetic Total Artificial Heart in Autoregulated Mode Is Biologically Hemocompatible: Insights for Multimers of von Willebrand Factor.

BACKGROUND: Carmat bioprosthetic total artificial heart (Aeson; A-TAH) is a pulsatile and autoregulated device. The aim of this study is to evaluate level of hemolysis potential acquired von Willebrand syndrome after A-TAH implantation. METHODS: We examined the presence of hemolysis and acquired von Willebrand syndrome in adult patients receiving A-TAH support (n=10) during their whole clinical follow-up in comparison with control subjects and adult patients receiving Heartmate II or Heartmate III support. We also performed a fluid structure interaction model coupled with computational fluid dynamics simulation to evaluate the A-TAH resulting shear stress and its distribution in the blood volume. RESULTS: The cumulative duration of A-TAH support was 2087 days. A-TAH implantation did not affect plasma free hemoglobin over time, and there was no association between plasma free hemoglobin and cardiac output or beat rate. For VWF (von Willebrand factor) evaluation, A-TAH implantation did not modify multimers profile of VWF in contrast to Heartmate II and Heartmate III. Furthermore, fluid structure interaction coupled with computational fluid dynamics showed a gradually increase of blood damage according to increase of cardiac output (P<0.01), however, the blood volume fraction that endured significant shear stresses was always inferior to 0.03% of the volume for both ventricles in all regimens tested. An inverse association between cardiac output, beat rate, and high-molecular weight multimers ratio was found. CONCLUSIONS: We demonstrated that A-TAH does not cause hemolysis or AWVS. However, relationship between HMWM and cardiac output depending flow confirms relevance of VWF as a biological sensor of blood flow, even in normal range.

Elevated Circulating Stem Cells Level is Observed One Month After Implantation of Carmat Bioprosthetic Total Artificial Heart.

The Aeson® total artificial heart (A-TAH) has been developed as a total heart replacement for patients at risk of death from biventricular failure. We previously described endothelialization of the hybrid membrane inside A-TAH probably at the origin of acquired hemocompatibility. We aimed to quantify vasculogenic stem cells in peripheral blood of patients with long-term A-TAH implantation. Four male adult patients were included in this study. Peripheral blood mononuclear cells were collected before A-TAH implantation (T0) and after implantation at one month (T1), between two and five months (T2), and then between six and twelve months (T3). Supervised analysis of flow cytometry data confirmed the presence of the previously identified Lin-CD133+CD45- and Lin-CD34+ with different CD45 level intensities. Lin-CD133+CD45-, Lin-CD34+CD45- and Lin-CD34+CD45+ were not modulated after A-TAH implantation. However, we demonstrated a significant mobilization of Lin-CD34+CD45dim (p = 0.01) one month after A-TAH implantation regardless of the expression of CD133 or c-Kit. We then visualized data for the resulting clusters on a uniform manifold approximation and projection (UMAP) plot showing all single cells of the live Lin- and CD34+ events selected from down sampled files concatenated at T0 and T1. The three clusters upregulated at T1 are CD45dim clusters, confirming our results. In conclusion, using a flow cytometry approach, we demonstrated in A-TAH-transplanted patients a significant mobilization of Lin-CD34+CD45dim in peripheral blood one month after A-TAH implantation. Using a flow cytometry approach, we demonstrated in A-TAH transplanted patients a significant mobilization of Lin-CD34+CD45dim in peripheral blood one month after A-TAH implantation. This cell population could be at the origin of newly formed endothelial cells on top of hybrid membrane in Carmat bioprosthetic total artificial heart.

Strength Training: In Search of Optimal Strategies to Maximize Neuromuscular Performance.

Training with low-load exercise performed under blood flow restriction can augment muscle hypertrophy and maximal strength to a similar extent as the classical high-load strength training method. However, the blood flow restriction method elicits only minor neural adaptations. In an attempt to maximize training-related gains, we propose using other protocols that combine high voluntary activation, mechanical tension, and metabolic stress.

Human Aortic Valve Interstitial Cells Display Proangiogenic Properties During Calcific Aortic Valve Disease.

OBJECTIVE: The study's aim was to analyze the capacity of human valve interstitial cells (VICs) to participate in aortic valve angiogenesis. Approach and Results: VICs were isolated from human aortic valves obtained after surgery for calcific aortic valve disease and from normal aortic valves unsuitable for grafting (control VICs). We examined VIC in vitro and in vivo potential to differentiate in endothelial and perivascular lineages. VIC paracrine effect was also examined on human endothelial colony-forming cells. A pathological VIC (VICp) mesenchymal-like phenotype was confirmed by CD90+/CD73+/CD44+ expression and multipotent-like differentiation ability. When VICp were cocultured with endothelial colony-forming cells, they formed microvessels by differentiating into perivascular cells both in vivo and in vitro. VICp and control VIC conditioned media were compared using serial ELISA regarding quantification of endothelial and angiogenic factors. Higher expression of VEGF (vascular endothelial growth factor)-A was observed at the protein level in VICp-conditioned media and confirmed at the mRNA level in VICp compared with control VIC. Conditioned media from VICp induced in vitro a significant increase in endothelial colony-forming cell proliferation, migration, and sprouting compared with conditioned media from control VIC. These effects were inhibited by blocking VEGF-A with blocking antibody or siRNA approach, confirming VICp involvement in angiogenesis by a VEGF-A dependent mechanism. CONCLUSIONS: We provide here the first proof of an angiogenic potential of human VICs isolated from patients with calcific aortic valve disease. These results point to a novel function of VICp in valve vascularization during calcific aortic valve disease, with a perivascular differentiation ability and a VEGF-A paracrine effect. Targeting perivascular differentiation and VEGF-A to slow calcific aortic valve disease progression warrants further investigation.

Multidimensional Proteomic Approach of Endothelial Progenitors Demonstrate Expression of KDR Restricted to CD19 Cells.

Endothelial progenitor cells (EPCs) are involved in vasculogenesis and cardiovascular diseases. However, the phenotype of circulating EPCs remains elusive but they are more often described as CD34+KDR+. The aim of the study was to extensively characterize circulating potential vasculogenic stem cell candidates in two populations of patients with cardiovascular disease by powerful multidimensional single cell complementary cytometric approaches (mass, imaging and flow). We identified cellular candidates in one patient before and after bioprosthetic total artificial heart implantation and results were confirmed in healthy peripheral and cord blood by mass cytometry. We also quantified cellular candidates in 10 patients with different COVID-19 severity. Both C-TAH implantation and COVID-19 at critical stage induce a redistribution of circulating CD34+ and CD19+ sub-populations in peripheral blood. After C-TAH implantation, circulating CD34+ progenitor cells expressed c-Kit stem marker while specific subsets CD34+CD133-/+CD45-/dimc-Kit+KDR- were mobilized. KDR was only expressed by CD19+ B-lymphocytes and CD14+ monocytes subpopulations in circulation. We confirmed by mass cytometry this KDR expression on CD19+ in healthy peripheral and cord blood, also with a VE-cadherin expression, confirming absence of endothelial lineage marker on CD34+ subtypes. In COVID-19, a significant mobilization of CD34+c-Kit+KDR- cells was observed between moderate and critical COVID-19 patients regardless CD133 or CD45 expression. In order to better evaluate EPC phenotype, we performed imaging flow cytometry measurements of immature CD34+KDR+ cells in cord blood and showed that, after elimination of non-circular events, those cells were all CD19+. During COVID-19, a significant mobilization of CD19+KDR+ per million of CD45+ cells was observed between moderate and critical COVID-19 patients regardless of CD34 expression. CD34+c-Kit+ cells are mobilized in both cardiovascular disease described here. KDR cells in peripheral blood are CD19 positive cells and are not classic vasculogenic stem and/or progenitor cells. A better evaluation of c-Kit and KDR expressing cells will lead to the redefinition of circulating endothelial progenitors.Graphical abstract Central illustration figure. Multidimensional proteomic approach of endothelial progenitors demonstrate expression of KDR restricted to CD19 cells. Endothelial progenitor cells (EPCs) are involved in cardiovascular diseases, however their phenotype remains elusive. We elucidated here EPCs phenotype by a deep characterization by multidimensional single cell complementary cytometric approaches after Bioprosthetic total artificial heart implantation and during COVID-19. We showed a redistribution of circulating CD34+ and CD19+ sub-populations in both situations. None of the immature cell population expresses KDR. Mobilized CD34+ expressed c-Kit. Imaging flow cytometry demonstrated that CD34+KDR+ cells, after elimination of non-circular events, are all CD19+. Our results suggest a new definition of circulating EPCs and emphasize involvement of CD19 cells in cardiovascular disease.

Possible Link Between the ABO Blood Group of Bioprosthesis Recipients and Specific Types of Structural Degeneration.

Background Pigs/bovines share common antigens with humans: α-Gal, present in all pigs/bovines close to the human B-antigen; and AH-histo-blood-group antigen, identical to human AH-antigen and present only in some animals. We investigate the possible impact of patients' ABO blood group on bioprosthesis structural valve degeneration (SVD) through calcification/pannus/tears/perforations for patients ≤60 years at implantation. Methods and Results This was a single-center study (Paris, France) that included all degenerative bioprostheses explanted between 1985 and 1998, mostly porcine bioprostheses (Carpentier-Edwards second/third porcine bioprostheses) and some bovine bioprostheses. For the period 1998 to 2014, only porcine bioprostheses with longevity ≥13 years were included (total follow-up ≥29 years). Except for blood groups, important predictive factors for SVD were prospectively collected (age at implantation/longevity/number/site/sex/SVD types) and analyzed using logistic regression. All variables were available for 500 explanted porcine bioprostheses. By multivariate analyses, the A group was associated with an increased risk of: tears (odds ratio[OR], 1.61; P=0.026); pannus (OR, 1.5; P=0.054), pannus with tears (OR, 1.73; P=0.037), and tendency for lower risk of: calcifications (OR, 0.63; P=0.087) or isolated calcification (OR, 0.67; P=0.17). A-antigen was associated with lower risk of perforations (OR 0.56; P=0.087). B-group patients had an increased risk of: perforations (OR, 1.73; P=0.043); having a pannus that was calcified (OR, 3.0, P=0.025). B-antigen was associated with a propensity for calcifications in general (OR, 1.34; P=0.25). Conclusions Patient's ABO blood group is associated with specific SVD types. We hypothesize that carbohydrate antigens, which may or may not be common to patient and animal bioprosthetic tissue, will determine a patient's specific immunoreactivity with respect to xenograft tissue and thus bioprosthesis outcome in terms of SVD.

Autoregulation of Pulsatile Bioprosthetic Total Artificial Heart is Involved in Endothelial Homeostasis Preservation.

Pulsatile Carmat bioprosthetic total artificial heart (C-TAH) is designed to be implanted in patients with biventricular end-stage heart failure. Since flow variation might contribute to endothelial dysfunction, we explored circulating endothelial biomarkers after C-TAH implantation in seven patients and compared the manual and autoregulated mode. Markers of endothelial dysfunction and regeneration were compared before and during a 6- to 9-month follow-up after implantation. The follow-up was divided into three periods (< 3, 3-6, and > 6 months) and used to estimate the temporal trends during the study period. A linear mixed model was used to analyze repeated measures and association between tested parameters according to the mode of C-TAH and the time. Relevance of soluble endoglin (sEndoglin) level increase has been tested on differentiation and migration potential of human vasculogenic progenitor cells (endothelial colony forming cells [ECFCs]). Normal sEndoglin and soluble endothelial protein C receptor (sEPCR) levels were found in patients after implantation with autoregulated C-TAH, whereas they significantly increased in the manual mode, as compared with pretransplant values (p = 0.005 and 0.001, respectively). In the autoregulated mode, a significant increase in the mobilization of cytokine stromal cell-derived factor 1 was found (p = 0.03). After adjustment on the mode of C-TAH, creatinine or C-reactive protein level, sEndoglin, and sEPCR, were found significantly associated with plasma total protein levels. Moreover, a significant decrease in pseudotubes formation and migration ability was observed in vitro in ECFCs receiving sEndoglin activation. Our combined analysis of endothelial biomarkers confirms the favorable impact of blood flow variation achieved with autoregulation in patients implanted with the bioprosthetic total artificial heart.

Hemocompatibility and safety of the Carmat Total Artifical Heart hybrid membrane.

The Carmat bioprosthetic total artificial heart (C-TAH) is a biventricular pump developed to minimize drawbacks of current mechanical assist devices and improve quality of life during support. This study aims to evaluate the safety of the hybrid membrane, which plays a pivotal role in this artificial heart. We investigated in particular its blood-contacting surface layer of bovine pericardial tissue, in terms of mechanical aging, risks of calcification, and impact of the hemodynamics shear stress inside the ventricles on blood components. Hybrid membranes were aged in a custom-designed endurance bench. Mechanical, physical and chemical properties were not significantly modified from 9 months up to 4 years of aging using a simulating process. Exploration of erosion areas did not show no risk of oil diffusion through the membrane. Blood contacting materials in the ventricular cavities were subcutaneously implanted in Wistar rats for 30 days as a model for calcification and demonstrated that the in-house anti-calcification pretreatment with Formaldehyde-Ethanol-Tween 80 was able to significantly reduce the calcium concentration from 132 µg/mg to 4.42 µg/mg (p < 0.001). Hemodynamic simulations with a computational model were used to reproduce shear stress in left and right ventricles and no significant stress was able to trigger hemolysis, platelet activation nor degradation of the von Willebrand factor multimers. Moreover, explanted hybrid membranes from patients included in the feasibility clinical study were analyzed confirming preclinical results with the absence of significant membrane calcification. At last, blood plasma bank analysis from the four patients implanted with C-TAH during the feasibility study showed no residual glutaraldehyde increase in plasma and confirmed hemodynamic simulation-based results with the absence of hemolysis and platelet activation associated with normal levels of plasma free hemoglobin and platelet microparticles after C-TAH implantation. These results on mechanical aging, calcification model and hemodynamic simulations predicted the safety of the hybrid membrane used in the C-TAH, and were confirmed in the feasibility study.

Assessment of energy expenditure during high intensity cycling and running using a heart rate and activity monitor in young active adults.

OBJECTIVE: Although high intensity physical activities may represent a great proportion of the total energy expenditure in active people, only sparse studies have investigated the accuracy of wearable monitors to assess activity related energy expenditure (AEE) during high intensity exercises. Therefore, the purpose of the present study was to investigate the accuracy of the Actiheart, a light portable monitor estimating AEE based on heart rate (HR) and activity counts (ACT), during two popular activities (running and cycling) performed at high intensities. The benefit of an individual calibration of the HR-AEE relationship established during a preliminary maximal test was also evaluated. METHODS: AEE was estimated in eighteen active adults (4 women and 14 men; 25 ± 4 yr) with indirect calorimetry using a respiratory gas analysis system (reference method) and the Actiheart during 5-min running and cycling at 60, 75 and 85% of maximal oxygen uptake (VO2max) previously determined during a maximal test performed on a treadmill or cycle ergometer. For the Actiheart, AEE was estimated either using the group or individual calibrated equations available in the dedicated software, and their respective HR, ACT or combined HR/ACT algorithms. RESULTS: When the HR algorithm was used for cycling and the HR or HR/ACT algorithms for running, AEE measured by the Actiheart increased proportionally to exercise intensity from 60 to 85% VO2max (P<0.001). Compared to indirect calorimetry, the Actiheart group calibrated equations slightly to moderately underestimated (3 to 20%) AEE for the three exercise intensities (P<0.001). Accuracy of AEE estimation was greatly improved by individual calibration of the HR-AEE relationship (underestimation below 5% and intraclass correlation coefficient [ICC]: 0.79-0.93) compared to group calibration (ICC: 0.64-0.79). CONCLUSION: The Actiheart enables to assess AEE during high intensity running and cycling when the appropriate algorithm is applied. Since an underestimation was present for group calibration, an individual and sport-specific calibration should be performed when a high accuracy is required.

Decline in abundance and apparent survival rates of fin whales (Balaenoptera physalus) in the northern Gulf of St. Lawrence.

Estimates of abundance and survivorship provide quantifiable measures to monitor populations and to define and understand their conservation status. This study investigated changes in abundance and survival rates of fin whales (Balaenoptera physalus) in the northern Gulf of St. Lawrence in the context of anthropogenic pressures and changing environmental conditions. A long-term data set, consisting of 35 years of photo-identification surveys and comprising more than 5,000 identifications of 507 individuals, formed the basis of this mark-recapture study. Based on model selection using corrected Akaike Information Criterion, the most parsimonious Cormack-Jolly-Seber model included a linear temporal trend in noncalf apparent survival rates with a sharp decline in the last 5 years of the study and a median survival rate of 0.946 (95% confidence interval (CI) 0.910-0.967). To account for capture heterogeneity due to divergent patterns of site fidelity, agglomerative hierarchical cluster analysis was employed to categorize individuals based on their annual and survey site fidelity indices. However, the negative trend in survivorship remained and was corroborated by a significant decline in the estimated super-population size from 335 (95% CI 321-348) individuals in 2004-2010 to 291 (95% CI 270-312) individuals in 2010-2016. Concurrently, a negative trend was estimated in recruitment to the population, supported by a sharp decrease in the number of observed calves. Ship strikes and changes in prey availability are potential drivers of the observed decline in fin whale abundance. The combination of clustering methods with mark-recapture represents a flexible way to investigate the effects of site fidelity on demographic variables and is broadly applicable to other individual-based studies.

Efficacy of a new strength training design: the 3/7 method.

AIM: This study investigated the efficacy of a new strength training method on strength gain, hypertrophy, and neuromuscular fatigability. METHODS: The training exercise consisted of elbow flexion against a load of ~ 70% of one repetition maximal (1RM). A new method (3/7 method) consisting of five sets of an increasing number of repetitions (3 to 7) during successive sets and brief inter-set intervals (15 s) was repeated two times after 150 s of recovery and compared to a method consisting of eight sets of six repetitions with an inter-set interval of 150 s (8 × 6 method). Subjects trained two times per week during 12 weeks. Strength gain [1RM load and maximal isometric voluntary contraction (MVC)], EMG activity of biceps brachii and brachioradialis, as well as biceps' brachii thickness were measured. Change in neuromuscular fatigability was assessed as the maximal number of repetitions performed at 70% of 1RM before and after training. RESULTS: Both 3/7 and 8 × 6 methods increased 1RM load (22.2 ± 7.4 and 12.1 ± 6.6%, respectively; p < 0.05) and MVC force (15.7 ± 8.2 and 9.5 ± 9.5%; p < 0.05) with a greater 1RM gain (p < 0.05) for the 3/7 method. Normalized (%Mmax) EMG activity of elbow flexors increased (p < 0.05) similarly (14.5 ± 23.2 vs. 8.1 ± 20.5%; p > 0.05) after both methods but biceps' brachii thickness increased to a greater extent (9.6 ± 3.6 vs. 5.5 ± 3.7%; p < 0.05) for the 3/7 method. Despite subjects performing more repetitions with the same absolute load after training, neuromuscular fatigability increased (p < 0.05) after the two training methods. CONCLUSION: The 3/7 method provides a better stimulus for strength gain and muscle hypertrophy than the 8 × 6 method.

The Cape Town Declaration on Access to Cardiac Surgery in the Developing World.

Mission: to urge all relevant entities within the international cardiac surgery, industry and government sectors to commit to develop and implement an effective strategy to address the scourge of rheumatic heart disease in the developing world through increased access to life-saving cardiac surgery.

Arterial Pulsatility and Circulating von Willebrand Factor in Patients on Mechanical Circulatory Support.

BACKGROUND: The main risk factor for bleeding in patients with continuous-flow mechanical circulatory support (CF-MCS) is the acquired von Willebrand factor (VWF) defect related to the high shear-stress forces developed by these devices. Although a higher bleeding rate has been reported in CF-MCS recipients who had reduced pulsatility, the relation between pulsatility and the VWF defect has never been studied. OBJECTIVES: The purpose of this study was to investigate the relation between pulsatility and VWF under CF-MCS. METHODS: We assessed the effect of 2 CF-MCS on VWF multimer degradation in a mock circulatory loop (model 1). Using these devices, we investigated in a dose-effect model (model 2) 3 levels of pulsatility in 3 groups of swine. In a cross-over model (model 3), we studied the effects of sequential changes of pulsatility on VWF. We reported the evolution of VWF multimerization in a patient undergoing serial CF-MCS and/or pulsatile-MCS. RESULTS: We demonstrated the proteolytic degradation of VWF multimers by high shear CF-MCS in a circulatory loop without pulsatility. We observed both in swine models and in a patient that the magnitude of the VWF degradation is modulated by the pulsatility level in the high shear-stress level condition, and that the restoration of pulsatility is a trigger for the endothelial release of VWF. CONCLUSIONS: We demonstrated that the VWF defect reflects the balance between degradation induced by the shear stress and the endothelial release of new VWF triggered by the pulsatility. This modulation of VWF levels could explain the relationship between pulsatility and bleeding observed in CF-MCS recipients. Preservation of pulsatility may be a new target to improve clinical outcomes of patients.

Feasibility of Bioengineered Tracheal and Bronchial Reconstruction Using Stented Aortic Matrices.

Importance: Airway transplantation could be an option for patients with proximal lung tumor or with end-stage tracheobronchial disease. New methods for airway transplantation remain highly controversial. Objective: To establish the feasibility of airway bioengineering using a technique based on the implantation of stented aortic matrices. Design, Setting, and Participants: Uncontrolled single-center cohort study including 20 patients with end-stage tracheal lesions or with proximal lung tumors requiring a pneumonectomy. The study was conducted in Paris, France, from October 2009 through February 2017; final follow-up for all patients occurred on November 2, 2017. Exposures: Radical resection of the lesions was performed using standard surgical techniques. After resection, airway reconstruction was performed using a human cryopreserved (-80°C) aortic allograft, which was not matched by the ABO and leukocyte antigen systems. To prevent airway collapse, a custom-made stent was inserted into the allograft. In patients with proximal lung tumors, the lung-sparing intervention of bronchial transplantation was used. Main Outcomes and Measures: The primary outcome was 90-day mortality. The secondary outcome was 90-day morbidity. Results: Twenty patients were included in the study (mean age, 54.9 years; age range, 24-79 years; 13 men [65%]). Thirteen patients underwent tracheal (n = 5), bronchial (n = 7), or carinal (n = 1) transplantation. Airway transplantation was not performed in 7 patients for the following reasons: medical contraindication (n = 1), unavoidable pneumonectomy (n = 1), exploratory thoracotomy only (n = 2), and a lobectomy or bilobectomy was possible (n = 3). Among the 20 patients initially included, the overall 90-day mortality rate was 5% (1 patient underwent a carinal transplantation and died). No mortality at 90 days was observed among patients who underwent tracheal or bronchial reconstruction. Among the 13 patients who underwent airway transplantation, major 90-day morbidity events occurred in 4 (30.8%) and included laryngeal edema, acute lung edema, acute respiratory distress syndrome, and atrial fibrillation. There was no adverse event directly related to the surgical technique. Stent removal was performed at a postoperative mean of 18.2 months. At a median follow-up of 3 years 11 months, 10 of the 13 patients (76.9%) were alive. Of these 10 patients, 8 (80%) breathed normally through newly formed airways after stent removal. Regeneration of epithelium and de novo generation of cartilage were observed within aortic matrices from recipient cells. Conclusions and Relevance: In this uncontrolled study, airway bioengineering using stented aortic matrices demonstrated feasibility for complex tracheal and bronchial reconstruction. Further research is needed to assess efficacy and safety. Trial Registration: clinicaltrials.gov Identifier: NCT01331863.

Multiple reoperations on the aortic valve: outcomes and implications for future potential valve-in-valve strategy.

OBJECTIVES: Surgical mortality and long-term outcomes are important considerations when determining strategies for multiple reoperations on the aortic valve (AV). With the rise of percutaneous valve-in-valve, we sought to evaluate the current outcomes of conventional surgery for AV reoperation, focusing first on the effect of the number of previous AV interventions with a subsequent analysis of the risk factors for adverse outcomes. METHODS: From January 2007 to December 2016, 316 consecutive patients underwent an open redo operation (replacement) on their AV at a single centre. It was the first AV reintervention in 263 patients (Group 1), second in 42 patients (Group 2) and third or more in 11 patients (Group 3). RESULTS: There were 230 men and 86 women, with a median age of 58 (Q1-Q3: 46-70) years. Structural valve deterioration (SVD) of the bioprosthesis (n = 136, 44%), endocarditis (n = 57, 18%) and prosthetic valve dehiscence (n = 41, 13%) were the most common reasons for reintervention. Overall, in-hospital mortality was 7.3%: 7.2% in Group 1, 4.76% in Group 2 and 18.2% in Group 3 (P = 0.233) and ranged from 3.7% for SVD to 14.0% when endocarditis was the reason for reintervention. Higher preoperative New York Heart Association (NYHA) class (III/IV) [odds ratio (OR) 15.9, P = 0.011], injury during re-entry (OR 16.9, P = 0.015), endocarditis (OR 3.7, P = 0.038) and concomitant mitral valve replacement (OR 5.6, P = 0.006) were independent risk factors for in-hospital mortality. Survival at 8 years was 79.0 ± 3.0% for the entire cohort and 88.4 ± 3.2% for re-replacement after SVD. CONCLUSIONS: Multiple AV reoperations carry an acceptable risk of early postoperative mortality, particularly for isolated valve replacements of SVD.