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Nowadays, despite the rapid advancements in interventional cardiology, open surgery still deals with aortic root diseases, to assure the best “ad hoc” treatment. In case of middle-aged adult patients, the optimal operation still represents a matter of debate. A review of the last 10-year literature was conducted, focusing on patients below 65 to 70 years of age. Because of the small sample and the heterogeneity of the papers, no metanalysis was possible. Bentall–de Bono procedure, valve sparing, and Ross operations are the surgical options currently available. The main issues in the Bentall – de Bono operation are lifelong anticoagulation therapy and cavitation in case of mechanical prosthesis implantation and structural valve degeneration in case of biological Bentall. As transcatheter procedures are currently performed as valve in valve, biological prosthesis may be preferable, if the diameter may prevent postoperative high gradients. Conservative techniques, such as remodeling and reimplantation, preferred in the young, guarantee physiologic aortic root dynamics and impose surgical analysis of the aortic root structures to get a durable result. The Ross operation, which shows excellent performance, involves autologous pulmonary valve implantation and is performed only in experienced and high-volume centers. Due to its technical difficulty, it requires a steep learning curve and presents some limitations in specific aortic valve diseases. All three have advantages and downsides, and no ideal solution has still been reported.

BACKGROUND: This study compared clinical and hemodynamic in-hospital outcomes of patients undergoing sutureless vs rapid deployment aortic valve replacement (SURD-AVR) in the large population of the Sutureless and Rapid Deployment International Registry (SURD-IR). METHODS: We examined 4695 patients who underwent isolated or combined SURD-AVR. The "sutureless" Perceval valve (LivaNova PLC, London, United Kingdom) was used in 3133 patients and the "rapid deployment" Intuity (Edwards Lifesciences, Irvine, CA) in 1562. Potential confounding factors were addressed by the use of propensity score matching. After matching, 2 well-balanced cohorts of 823 pairs (isolated SURD-AVR) and 467 pairs (combined SURD-AVR) were created. RESULTS: Patients who received Perceval and Intuity valves showed similar in-hospital mortality and rate of major postoperative complications. Perceval was associated shorter cross-clamp and cardiopulmonary bypass times. In the isolated SURD-AVR group, patients receiving Perceval were more likely to undergo anterior right thoracotomy incision. Postoperative transvalvular gradients were significantly lower for the Intuity valve compared with those of the Perceval valve, either in isolated and combined SURD-AVR. The Intuity valve was associated with a lower rate of postoperative mild aortic regurgitation. CONCLUSIONS: Our results confirm the safety and efficacy of SURD-AVR regardless of the valve type. The Perceval valve was associated with reduced operative times and increased anterior right thoracotomy incision. The Intuity valve showed superior hemodynamic outcomes and a lower incidence of postoperative mild aortic regurgitation. ispartof: ANNALS OF THORACIC SURGERY vol:114 issue:3 pages:758-+ ispartof: location:Netherlands status: published

Background: Recent data suggested that transcatheter aortic valve replacement (TAVR) may be indicated also for low-risk patients. However, robust evidence is still lacking, particularly regarding valve performance at follow-up that confers a limitation to its use in young patients. Moreover, a literature gap exists in terms of 'real-world' data analysis. The aim of this study is to compare the cost-effectiveness of sutureless aortic valve replacement (SuAVR) versus transfemoral TAVR.Methods: Prospectively collected data were retrieved from a centralized database of nine cardiac surgery centers between 2010 and 2018. Follow-up was completed in June 2019. A propensity score matching (PSM) analysis was performed.Results: Patients in the TAVR group (n = 1002) were older and with more comorbidities than SuAVR pa-tients (n = 443). The PSM analysis generated 172 pairs. No differences were recorded between groups in 30-day mortality [SuAVR vs TAVR: n = 7 (4%) vs n = 5 (2.9%); p = 0.7] and need for pacemaker implant [n = 10 (5.8%) vs n = 20 (11.6%); p = 0.1], but costs were lower in the SuAVR group (20486.6 +/- 4188 euro vs 24181.5 +/- 3632 euro ; p < 0.01). Mean follow-up was 1304 +/- 660 days. SuAVR patients had a significantly higher probability of survival than TAVR patients (no. of fatal events: 22 vs 74; p < 0.014). Median follow-up was 2231 days and 2394 days in the SuAVR and TAVR group, respectively.Conclusion: The treatment of aortic valve stenosis with surgical sutureless or transcatheter prostheses is safe and effective. By comparing the two approaches, patients who can undergo surgery after heart team evaluation show longer lasting results and a more favorable cost ratio. (C) 2021 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

Objectives The aim of this study was to investigate the need for postoperative permanent pacemaker implantation (PPI) following sutureless and rapid-deployment aortic valve replacement (SuRD-AVR) in the context of a progress report from a large multicenter international registry (SURD-IR). Methods We retrospectively analyzed 4,166 patients who underwent SuRD-AVR between 2008 and 2019. The primary outcome was the need for PPI before discharge. The study population was analyzed separately according to the implanted prostheses (Su cohort and RD cohort). Each cohort was divided into two groups based on the operation date: an early group (“EG” = 2008–2016) and a late group (“LG” = 2017–2019). Results The rate of PPI decreased significantly in the Su cohort over time (EG = 10.8% vs LG = 6.3%, p Conclusions Our analysis showed a significant decrease in the PPI rate in patients who underwent Su-AVR over time. Patient selection as well as surgical improvements and a more accurate sizing could be correlated with this phenomenon. The RD cohort revealed no significant differences either in patient's characteristics or in PPI rate between the two time periods.

Aims In the last 15 years, some observations tried to shed light on the dysregulation of the cellular self-digestion process in calcific aortic valve stenosis (CAVS), but the results obtained remain still controversial. This work is aimed to definitively establish the trend of autophagy in patients affected by CAVS, to analyze the putative involvement of other determinants which impact on the mitochondrial quality control mechanisms and to explore possible avenues for pharmacological interventions in the treatment of CAVS. Methods and results This observational study, performed exclusively in ex vivo human samples (cells and serum), by using biochemical approaches and correlations with clinical data, describes new biological features of the calcified valve in terms of mitochondrial dysfunctions. In detail, we unveiled a significant deficiency in mitochondrial respiration and in ATP production coupled to increased production of lactates. In addition, mitochondrial population in the pathologic group is aged with significant alterations in biogenesis and mitophagy pathways. We are also reporting an updated view about autophagy accompanying the calcification process and advanced stages of the disease. We provided evidence for a rapamycin-based therapeutic strategy to revert the calcified phenotype to the wild type one. Conclusions Our data suggest that the Calcific Aortic Valve Stenosis phenotype is featured by defects in mitochondrial quality control mechanisms and that autophagy is not activated enough to counteract cell death and sustain cell functions. Thus, boosting autophagy and mitophagy from short to long-term revert quite all pathological phenotypes. Translational perspective The findings from this study provide evidence for new molecular targets involving mitochondrial quality control mechanisms becoming dysregulated in CAVS. These pathways should be considered as amenable for a combination of new therapies in humans for three reasons: i) no pharmacological treatments are still available to slow down the development of advanced CAVS, ii) being calcification a recurring pathway and iii) the targets proposed are druggable by existing drugs used in the clinic for different purposes. This work also suggests a serum biomarker to be highly related to the stage of disease and the calcification grade of the valve.

OBJECTIVES Sutureless aortic valve prostheses have been introduced to facilitate the implant process, speed up the operating time and improve haemodynamic performance. The goal of this study was to assess the potential advantages of using sutureless prostheses during minimally invasive aortic valve replacement in a large multicentre population. METHODS From 2011 to 2019, a total of 3402 patients in 11 hospitals underwent isolated aortic valve replacement with minimal access approaches using a bioprosthesis. A total of 475 patients received sutureless valves; 2927 received standard valves. The primary outcome was the incidence of 30-day deaths. Secondary outcomes were the occurrence of major complications following procedures performed with sutureless or standard bioprostheses. Propensity matched comparisons was performed based on a multivariable logistic regression model. RESULTS The annual number of sutureless valve implants increased over the years. The matching procedure paired 430 sutureless with 860 standard aortic valve replacements. A total of 0.7% and 2.1% patients with sutureless and standard prostheses, respectively, died within 30 days (P = 0.076). Cross-clamp times [48 (40–62) vs 63 min (48–74); P = 0.001] and need for blood transfusions (27.4% vs 33.5%; P = 0.022) were lower in patients with sutureless valves. No difference in permanent pacemaker insertions was observed in the overall population (3.3% vs 4.4% in the standard and sutureless groups; P = 0.221) and in the matched groups (3.6% vs 4.7% in the standard and sutureless groups; P = 0.364). CONCLUSIONS The use of sutureless prostheses is advantageous and facilitates the adoption of a minimally invasive approach, reducing cardiac arrest time and the number of blood transfusions. No increased risk of permanent pacemaker insertion was observed.

Although aortic valve replacement remains the gold standard treatment for aortic valve diseases like stenosis (AS) or insufficiency, new surgical methods have been developed with a focus in the reconstruction of the aortic valve rather than replacing it. The Ozaki procedure involves a tailored replacement of each individual valvular leaflet with glutaraldehyde-treated autologous pericardium and aims to reproduce the normal anatomy of the aortic valve. Cases of patients with unicuspid aortic valve treated with the Ozaki procedure are uncommon in the litrature and become even more rare when it comes to concomitant diseases like AS and ascending aorta aneurysm. We present the case of a 21-year-old, fit and asymptomatic male, with unicuspid aortic valve with severe stenosis and ascending aorta dilatation, surgically treated with tricuspidization of the aortic valve with glutaraldehyde-treated autologous pericardium and replacement of the ascending aorta with a straight synthetic graft. Postoperative studies showed a fully functional, neo-tailored tricuspid aortic valve with trivial regurgitation. The patient had an uncomplicated recovery, stayed in the intensive care unit for 2 days and was discharged on the 7th postoperative day.

OBJECTIVES Current evidence on sutureless and rapid deployment aortic valve replacement (SURD-AVR) is limited and does not allow for the assessment of the clinical impact and the evolution of procedural and clinical outcomes of this new valve technology. The Sutureless and Rapid Deployment International Registry (SURD-IR) represents a unique opportunity to evaluate the current trends and outcomes of SURD-AVR interventions. METHODS Data from 3682 patients enrolled between 2007 and 2018 were analysed. Patients were divided according to the date of surgery into 6 equal groups and by the type of intervention: isolated SURD-AVR (n = 2472) and combined SURD-AVR (n = 1086). RESULTS Across the 11-year study period, significant changes occurred in patient characteristics including a decrease in age and in estimated surgical risk. Less invasive approaches for isolated SURD-AVR increased considerably from 49.4% to 85.5%. The overall in-hospital mortality rate was 1.6% and 3.9% in isolated and combined procedures, respectively, with no change over time. The rate of perioperative stroke decreased significantly (from 4% to 0.5%), as did the rates of postoperative pacemaker implantation (from 12.8% to 5.9%) and aortic regurgitation (from 17.8% to 2.7%). CONCLUSIONS The present study provides a comprehensive analysis of the current trends and results of SURD-AVR interventions. The most notable changes over time were the increasing implantation of SURD valves in a younger population, with more frequent utilization of less invasive techniques. SURD-AVR demonstrated remarkable improvements in clinical outcomes with a significant reduction in the rates of stroke, pacemaker implantation and postoperative aortic regurgitation.

OBJECTIVES The need for concomitant tricuspid surgery in patients who need mitral valve surgery casts doubt on its feasibility via a minimally invasive approach. Our goal was to evaluate the short-term outcomes of patients undergoing concomitant mitral and tricuspid valve surgery either with a standard full sternotomy (full-MTS) or a minimally invasive approach (mini-MTS). METHODS The outcomes of patients who had combined mitral and tricuspid valve surgery in 11 centres were retrospectively evaluated. The primary outcome was the incidence of 30-day mortality. A propensity score matched cohort was selected to create 2 comparable groups stratified by surgery (valve replacement or repair). RESULTS During the study period, 1048 consecutive patients had combined mitral and tricuspid valve surgery (730 full-MTS, 318 mini-MTS). The matching procedure paired 192 full-MTS to 192 mini-MTS procedures. After matching, mini-MTS was associated with longer cardiopulmonary bypass [123 min, standard deviation (SD) 46, vs 102 min, SD 36, P = 0.001] and cross-clamping times (89 min, SD 34, vs 78 min, SD 29, P = 0.003). Although the hospital length of stay was shorter (8 days, interquartile range 7-12 vs 9 days, interquartile range 7–14, P = 0.034) with mini-MTS before matching, this difference disappeared after matching. No differences in other major complications or in 30-day mortality were observed: 48 deaths (4.6%), 36 of which (4.9%) occurred in patients who had a full-MTS and 12 (3.8%), in patients who had a mini-MTS (4.7% in both approaches paired by propensity). CONCLUSIONS The mini-MTS approach proved to be safe and effective in patients requiring concomitant mitral and tricuspid surgery. We could not demonstrate any difference in short-term outcomes between the 2 surgical approaches, indicating that there is not a preferred surgical approach.

OBJECTIVES To compare procedural and in-hospital outcomes of patients undergoing sutureless (Perceval, Livanova PLC, London, UK) and rapid deployment (Intuity Elite, Edwards Lifesciences, Irvine, CA, USA) aortic valve replacement (group 1) versus sutured aortic valve replacement (group 2). METHODS Patients receiving isolated aortic valve replacement between 2014 and 2020 were analysed using data from the Sutureless and Rapid Deployment International Registry. Patients in group 1 and group 2 were propensity-score matched in a 1:1 ratio. RESULTS A total of 7708 patients were included in the study. After matching, 2 groups of 2643 each were created. Patients in group 1 were more likely to undergo minimally invasive approaches and were associated with shorter operative times when compared with group 2. Overall in-hospital mortality was similar between groups. While an increased risk of stroke was observed in group 1 in the first study period (2014–2016; relative risk 3.76, P CONCLUSIONS Our findings showed significant differences in procedural and clinical outcomes between the study groups. These results suggest that sutureless and rapid deployment aortic valve replacement should be considered as part of a comprehensive valve programme. The knowledge of the respective post-aortic valve replacement benefits for different valve technologies may result in patient-tailored valve selection with improved clinical outcomes.

Aortic valve replacement is the traditional surgical treatment for aortic valve diseases, yet standardized aortic valve neocuspidization (AVNeo) is a promising alternative that is gaining popularity. The purpose of this article is to review the available published literature of AVNeo using glutaraldehyde-treated autologous pericardium, also known as the Ozaki procedure, including indications, outcomes, potential benefits, and modes of failure for the reconstructed valve.A comprehensive literature search was performed using keywords related to aortic valve repair, AVNeo, or Ozaki procedure. All articles describing performance of AVNeo were reviewed.Reported early mortality after AVNeo varies from 0% to 5.88%. The largest cohort of patients in the literature includes 850 patients with an inhospital mortality rate of 1.88%. Cumulative incidence of aortic valve reoperation was 4.2% in the largest series. Reoperation was uncommon and mainly due to infective endocarditis or degeneration of the reconstructed valve (most commonly due to aortic valve regurgitation, rather than stenosis).Aortic valve neocuspidization is a versatile and standardized alternative to aortic valve replacement with a biological prosthesis. Early to midterm outcomes from a number of centers are excellent and demonstrate the safety and durability of the procedure. Long-term outcomes and clinical trial data are necessary to determine which patients benefit the most from this procedure.

OBJECTIVES: The impact of sutureless and rapid deployment (SURD) valves on the clinical outcomes of patients undergoing minimally invasive aortic valve replacement (MI-AVR) has still to be defined. The aim of this study was to assess clinical characteristics and in-hospital results of patients receiving SURD-AVR through less invasive approaches in the large population of the Sutureless and Rapid Deployment International Registry (SURD-IR). METHODS: Of the 1935 patients who received primary isolated SURD-AVR between 2009 and 2018, a total of 1418 (73.3%) underwent MI interventions and were included in this analysis. SURD-AVR was performed using upper ministernotomy in 56.4% (n = 800) of cases and anterior right thoracotomy in 43.6% (n = 618). Perceval S was implanted in 1011 (71.3%) patients and Edwards Intuity or Intuity Elite in 407 (28.7%) patients. RESULTS: Overall in-hospital mortality and stroke rates were 1.7% and 2%, respectively. A definitive pacemaker implantation was reported in 9% of cases and significantly decreased over the observational period, from 20.6% to 5.6% (P = 0.002). The Perceval valve was associated with shorter operative times and was more frequently implanted in patients receiving anterior right thoracotomy incision. The Intuity valve was preferred in younger patients and revealed superior postoperative haemodynamic results. CONCLUSIONS: SURD-AVR was largely performed through less invasive approaches and can be considered as a primary indication in MI surgery. In the SURD-IR cohort, MI SURD-AVR using both Perceval and Intuity valves appeared a safe and reproducible procedure associated with promising early results.

Summary: Preclinical models of ischemia/reperfusion injury (RI) demonstrate the deleterious effects of permeability transition pore complex (PTPC) opening in the first minutes upon revascularization of the occluded vessel. The ATP synthase c subunit (Csub) influences PTPC activity in cells, thus impacting tissue injury. A conserved glycine-rich domain in Csub is classified as critical because, when mutated, it modifies ATP synthase properties, protein interaction with the mitochondrial calcium (Ca2+) uniporter complex, and the conductance of the PTPC. Here, we document the role of a naturally occurring mutation in the Csub-encoding ATP5G1 gene at the G87 position found in two ST-segment elevation myocardial infarction (STEMI) patients and how PTPC opening is related to RI in patients affected by the same disease. We report a link between the expression of ATP5G1G87E and the response to hypoxia/reoxygenation of human cardiomyocytes, which worsen when compared to those expressing the wild-type protein, and a positive correlation between PTPC and RI.

OBJECTIVES Female sex is an established risk factor for postoperative complications after heart surgery, but the influence of sex on outcomes after minimally invasive cardiac surgery (MICS) for valvular replacement/repair remains controversial. We examined whether the role of sex as a risk factor varies by surgical approach [MICS vs conventional sternotomy (ST)] and further assessed outcomes among female patients including in-hospital mortality and postoperative complications by surgical approach. METHODS We analysed data from a multicentre registry for patients who underwent isolated aortic valve and mitral surgery with MICS or ST. The primary outcome was in-hospital mortality. Propensity score matching was used to minimize between-group differences. RESULTS Among the 15 155 patients included in the study, 7674 underwent MICS (50.6%). Female sex was equally distributed in the MICS and ST groups (47.3% vs 47.6%, respectively). Risk for surgery was higher in the ST group than in the MICS group {EuroSCORE II: 4.0 [standard deviation (SD): 6.8] vs 3.7 [SD: 6.4]; P = 0.005}, including among female patients only [ST vs MICS 4.6 (SD: 6.9) vs 4.2 (SD: 6.3); P = 0.04]. Mortality did not significantly vary by procedure among women [MICS vs ST, 2.4% vs 2.8%; hazard ratio 1.09, 95% confidence interval 0.71–1.73; P (surgical approach × sex) = 0.51]. The results also did not vary after adjusting for confounders. CONCLUSIONS Female sex was associated with higher mortality in patients undergoing valve surgery, regardless of surgical approach. In female patients, MICS did not provide any benefits over ST in terms of in-hospital deaths or postoperative complications. Subject collection 117, 125.

BACKGROUND: Benefits of sutureless and rapid deployment (SURD) bioprostheses in bicuspid aortic valves (BAV) are controversial. The aim of this study is to report the outcomes of patients undergoing aortic valve replacement (AVR) for BAV from the Sutureless and Rapid-Deployment Aortic Valve Replacement International Registry (SURD-IR). METHODS: Of the 4,636 patients who received primary isolated SURD-AVR between 2007 and 2018, 191 (4.1%) BAV patients underwent AVR with SURD valve. RESULTS: Overall 30-day mortality was 1.6%. The Intuity valve was implanted in 53.9% of cases, whereas the Perceval was implanted in 46.1%. Rate of stroke for isolated AVR was 4.2%. No case of endocarditis, thromboembolism, myocardial infarction, valve dislocation or structural valve deterioration was reported in the early phase. Rate of pacemaker implantation and moderate-severe aortic regurgitation (AR) were 7.9% and 3.7%, respectively. CONCLUSIONS: BAV is not considered a contraindication for the implantation of SURD valves. However, detailed information of aortic root geometry as well as the knowledge of some technical considerations are mandatory for a good outcome. ispartof: ANNALS OF CARDIOTHORACIC SURGERY vol:9 issue:4 pages:298-304 ispartof: location:China status: published

Surgical mitral valve reintervention is associated with significant morbidity and mortality, and repeat repair is not always feasible. We examine the clinical outcomes of the NeoChord procedure after failed conventional mitral valve repair. A total of 312 patients were treated with the NeoChord repair procedure between January 2014 and December 2018 at 5 European centers. Clinical and echocardiographic data were reviewed to identify patients who had a prior surgical mitral valve repair procedure. The primary endpoint (Patient Success) was a composite of placement of at least 2 neochordae and end-procedure mitral valve regurgitation (MR) ≤ mild, freedom from death, stroke, structural or functional procedure failure (MR > moderate), procedure or device-related unplanned procedures, cardiac-related rehospitalization, or worsening NYHA functional class at 1 and 2-year FU. Fifteen (15) patients were identified who required reoperation for failed surgical mitral valve repair. Mean time-to-reoperation was 2.7 years (2.2–6.1). Median intensive care unit stay was 24 hours and median hospitalization time was 7 days (6–8). No in-hospital deaths were observed. At discharge, mitral regurgitation was ≤ mild in 13 patients (86.7%). Patient success and freedom from more than mild MR were 92.3 ± 7.4% and 83.9 ± 10.4% at 1 and 2-year follow-up respectively. One high-risk patient presented with severe recurrent MR and died during surgical reintervention due to an acute aortic dissection. Selected patients can be successfully treated with the NeoChord procedure after failed surgical mitral valve repair. These results support a wider adoption of the NeoChord procedure as a first-line minimally invasive, alternative therapy to treat failed mitral valve repair.

BACKGROUND: Patients with liver cirrhosis (LC) undergoing cardiac surgery (CS) face perioperative high mortality and morbidity, but extensive studies on this topic are lacking.METHODS: All adult patients with LC undergoing a CS procedure between 2000 and 2017 at 10 Italian Institutions were included in this retrospective cohort study. LC was classified according to preoperative Child-Turcotte-Pugh (CTP) score and Model for End-Stage Liver Disease (MELD) score. Early-term and medium-term outcomes analysis was performed in the overall population and according to CTP classes.RESULTS: The study population included 144 patients (mean age 66 ± 9 years, 69% male). Ninety-eight, 20, and 26 patients were in CTP class A, in early CTP class B (MELD score 12), respectively. The main LC etiologies were viral (43%) and alcoholic (36%). Liver-related clinical presentation (ascites, esophageal varices, and encephalopathy) and laboratory values (estimated glomerular filtration rate, serum albumin, and bilirubin, platelet count) significantly worsened across the CTP classes (P= .001). Coronary artery bypass grafting or valve surgery (87% bioprosthesis) were performed in 36% and 50%, respectively. Postoperative complications (especially acute kidney injury, liver complication, and length of stay) significantly worsened in advanced CTP class B (P= .001). Notably, observed mortality was 3-fold or 4-fold higher than the EuroSCORE (European System for Cardiac Operative Risk Evaluation) II-predicted mortality, in the overall population, and in the subgroups. At Kaplan-Meier analysis, 1-year and 5-year cumulative survival in the overall population was 82% ± 3% and 77% ± 4%, respectively. The 5-year survival in CTP class A, early CTP class B, and advanced CTP class B was 72% ± 5%, 68% ± 11%, and 61% ± 10%, respectively (P= .238).CONCLUSIONS: CS outcomes in patients with LC are significantly affected in relation to the extent of preoperative liver dysfunction, but in early CTP classes, medium-term survival is acceptable. Further analysis are needed to better estimate the preoperative risk stratification of these patients.

Background: The Ozaki procedure is an innovative surgical technique aiming at reconstructing aortic valves with human autologous pericardium. Even if this procedure is widely used, a comprehensive biological characterization of the glutaraldehyde (GA)-fixed pericardial tissue is still missing. Methods: Morphological analysis was performed to assess the general organization of pericardium subjected to the Ozaki procedure (post-Ozaki) in comparison to native tissue (pre-Ozaki). The effect of GA treatment on cell viability and nuclear morphology was then investigated in whole biopsies and a cytotoxicity assay was executed to assess the biocompatibility of pericardium. Finally, human umbilical vein endothelial cells were seeded on post-Ozaki samples to evaluate the influence of GA in modulating the endothelialization ability in vitro and the production of pro-inflammatory mediators. Results: The Ozaki procedure alters the arrangement of collagen and elastic fibers in the extracellular matrix and results in a significant reduction in cell viability compared to native tissue. GA treatment, however, is not cytotoxic to murine fibroblasts as compared to a commercially available bovine pericardium membrane. In addition, in in vitro experiments of endothelial cell adhesion, no difference in the inflammatory mediators with respect to the commercial patch was found. Conclusions: The Ozaki procedure, despite alteration of ECM organization and cell devitalization, allows for the establishment of a noncytotoxic environment in which endothelial cell repopulation occurs.

During embryonic development, new arteries and veins form from preexisting vessels in response to specific angiogenic signals. Angiogenic signaling is complex since not all endothelial cells exposed to angiogenic signals respond equally. Some cells will be selected to become tip cells and acquire migration and proliferation capacity necessary for vessel growth while others, the stalk cells become trailer cells that stay connected with pre-existing vessels and act as a linkage to new forming vessels. Additionally, stalk and tip cells have the capacity to interchange their roles. Stalk and tip cellular responses are mediated in part by the interactions of components of the Delta/Notch and Vegf signaling pathways. We have identified in zebrafish, that the transmembrane protein Tmem230a is a novel regulator of angiogenesis by its capacity to regulate the number of the endothelial cells in intersegmental vessels by co-operating with the Delta/Notch signaling pathway. Modulation of Tmem230a expression by itself is sufficient to rescue improper number of endothelial cells induced by aberrant expression or inhibition of the activity of genes associated with the Dll4/Notch pathway in zebrafish. Therefore, Tmem230a may have a modulatory role in vessel-network formation and growth. As the Tmem230 sequence is conserved in human, Tmem230 may represent a promising novel target for drug discovery and for disease therapy and regenerative medicine in promoting or restricting angiogenesis. This article is protected by copyright. All rights reserved

Background: Aortic valve endocarditis remains a life-threatening condition, especially in cases of periannular complications. Aorto-ventricular discontinuity associated with proximal false aneurysm represents a more severe picture secondary to an extensive tissue disruption and is usually associated with prosthetic valve infection. Complex surgical repair is required in these cases and continues to be associated with high mortality and morbidity rates. Methods: We retrieved information for 32 patients undergoing operation for infective aortic valve/ prosthesis endocarditis complicated by pseudoaneurysm arising from aorto-ventricular discontinuity. Patients were relatively young, mostly male and most of them had a prior cardiac operation. Aortic root replacement with valve graft conduit was performed in all cases; it was associated with other procedures in seven patients: CABG (n=2), MV surgery (n=3), MV surgery + CABG (n=1) and pulmonary valve replacement (n=1). We reported and analysed patient outcomes at early and mid-term follow-up. Results: Pre-discharge mortality was 22% (n=7). The postoperative course was complicated in 24 (75%) cases. Eighteen patients (56%) sustained low cardiac output resulting in multiple organ failure syndrome and death in five cases. One patient (3%) experienced a major neurologic deficit with a permanent cerebral stroke. Acute kidney injury complicated the course in 12 cases (37%), continuous renal replacement therapy was necessary in four patients (12%). Overall survival and freedom from endocarditis and reoperation at 5-years was 59% and 89%, respectively. Conclusions: Patients with complicated aortic valve endocarditis presented generally in a poor preoperative state. Surgical treatment poses a non-negligible risk of postoperative mortality and morbidity but provides an acceptable survival rate and a satisfactory recovery at mid-term.

OBJECTIVES Surgical aortic valve replacement (AVR) can be performed via a full sternotomy or a minimal access approach (mini-AVR). Despite long-term experience with the procedure, mini-AVR is not routinely adopted. Our goal was to compare contemporary outcomes of mini-AVR and conventional AVR in a large multi-institutional national cohort. METHODS A total of 5801 patients from 10 different centres who had a mini-AVR (2851) or AVR (2950) from 2011 to 2017 were evaluated retrospectively. Standard aortic prostheses were used in all cases. The use of the minimally invasive approach has increased over the years. The primary outcome is the incidence of 30-day deaths following mini-AVR and AVR. Secondary outcomes are the occurrence of major complications following both procedures. Propensity-matched comparisons were performed based on the multivariable logistic regression model. RESULTS In the overall population patients who had AVR had an increased surgical risk based on the EuroSCORE, and the 30-day mortality rate was higher (1.5% and 2.3% in mini-AVR and AVR, respectively; P = 0.048). Propensity scores identified 2257 patients per group with similar baseline profiles. In the matched groups, patients who had mini-AVR, despite longer cardiopulmonary bypass (81 ± 32 vs 76 ± 28 min; P = 0.004) and cross-clamp (64 ± 24 vs 59 ± 21 min; P ≤ 0.001) times, had lower 30-day mortality rates (1.2% vs 2.0%; P = 0.036), reduced low cardiac output (0.8% vs 1.4%; P = 0.046) and reduced postoperative length of stay (9 ± 8 vs 10 ± 7 days; P = 0.004). Blood transfusions (36.4% vs 30.8%; P ≤ 0.001) and atrial fibrillation (26.0% vs 21.5%, P ≤ 0.001) were higher in patients who had the mini-AVR. CONCLUSIONS In a large multi-institutional recent cohort, minimal access approach aortic valve replacement is associated with reduced 30-day mortality rates and shorter postoperative lengths of stay compared to standard sternotomy. A prospective randomized trial is needed to overcome the possible biases of a retrospective study.

BACKGROUND Reoperation for aortic valve replacement can be challenging and is usually associated with an increased risk for complications and mortality. The study aim was to report the results of a multicenter cohort of patients who underwent minimally invasive reoperative aortic valve replacement with a sutureless or rapid-deployment prosthesis. METHODS From 2007 to 2018 data from 3651 patients were retrospectively collected from the Sutureless and Rapid-Deployment Aortic Valve Replacement International Registry. Of them, 63 patients who had previously undergone cardiac surgery represented the study population. In-hospital clinical and echocardiographic outcomes were recorded. RESULTS Mean age of the selected 63 patients was 75.3 ± 7.8 years and logistic EuroSCORE 10.1. Surgery was performed by ministernotomy in 43 patients (68.3%) and by anterior right thoracotomy in 20 (31.7%); 31 patients (49.2%) received the Perceval valve (Livanova PLC, London, UK) and 32 (50.8%) the Intuity valve (Edwards Lifesciences, Irvine, CA). Mean cross-clamp time was 57.8 ± 23.2 minutes and cardiopulmonary bypass time 95.0 ± 34.3 minutes. Neither conversion to full sternotomy nor in-hospital deaths occurred. Postoperative events were ischemic cerebral events in 3 patients (4.8%), need for pacemaker implantation in 2 (3.6%), bleeding requiring reoperation in 5 (8.9%), and dialysis in 1 (1.6%). Median intensive care unit stay was 1 day, and median length of hospital stay was 10 days. On echocardiographic evaluation 1 patient showed a significant postoperative aortic regurgitation. CONCLUSIONS Minimally invasive reoperative aortic valve replacement with a sutureless or rapid-deployment prosthesis is a safe and feasible treatment strategy, resulting in fast recovery and improved postoperative outcome with no mortality and an acceptable complication rate.

Objectives Treatment of aortic valve stenosis is evolving, indications for transcatheter approach (TAVI) have increased but also surgical valve replacement has changed with the use of minimally invasive approaches. Comparisons between TAVI and surgery have rarely been done with minimally invasive techniques (mini-SAVR) in the surgical arm. Aim of the present study is to compare mini-SAVR and TAVI in a multicenter recent cohort. Methods Evaluated were 2904 patients undergone mini-SAVR (2407) or TAVI (497) in 10 different centers in the period 2011–2016. The Heart Team approved treatment for complex cases. The primary outcome is the incidence of 30-day mortality following mini-SAVR and TAVI. Secondary outcomes are the occurrence of major complications following both procedures. Propensity matched comparisons was performed based on multivariable logistic regression model. Results In the overall population TAVI patients had increased surgical risk (median EuroSCORE II 3.3% vs. 1.7%, p ≤ 0.001) and 30-day mortality was higher (1.5% and 2.8% in mini-SAVR and TAVI respectively, p = 0.048). Propensity score identified 386 patients per group with similar baseline profile (median EuroSCORE II ~3.0%). There was no difference in 30-day mortality (3.4% in mini-SAVR and 2.3% in TAVI; p = 0.396) and stroke, surgical patients had more blood transfusion, kidney dysfunction and required longer ICU and hospital length of stay while TAVI patients had more permanent pace maker insertion. Conclusions Mini-SAVR and TAVI are both safe and effective to treat aortic stenosis in elderly patients with comorbidities. A joint evaluation by the heart-team is essential to direct patients to the proper approach., Highlights • A comparison between TAVI and minimally invasive techniques has rarely been done • In a propensity-matched comparison from 10 different hospitals, TAVI and mini-SAVR provided optimal short-term outcome. • 30-day mortality was 3.4% in mini-SAVR and 2.3% in TAVI (p = 0.396) • Mini-SAVR and TAVI are both safe and effective to treat aortic stenosis in elderly patients with comorbidities.

OBJECTIVES The ideal strategy for the treatment of severe aortic valve stenosis in patients of varying risk categories has become a debated topic in the last years: should the transcatheter or surgical approach be adopted? The aim of this study was to evaluate the outcomes of low-, intermediate-, high- and very high-risk patients undergoing sutureless, rapid deployment aortic valve replacement. METHODS From 2007 to 2017, data on a total of 3651 patients were collected from the Sutureless and Rapid Deployment Aortic Valve Replacement International Registry (SURD-IR). Of these, 2057 patients who underwent primary isolated aortic valve replacement were considered for this analysis and classified as being at low (EuroSCORE 20; n = 156) preoperative risk. RESULTS Overall, a less invasive approach was used in 74.1% of patients and represented the most frequent (>50%) approach in all risk categories. The Perceval prosthesis was used more frequently than other devices, especially in patients at high and very high risk. Hospital mortality was 1.6%, 0.8%, 1.9% and 2.7% in low-, intermediate-, high- and very high-risk patients, respectively, with no significant differences among subgroups. Similarly, postoperative complication rates were similar across the different risk categories. CONCLUSIONS Surgical aortic valve replacement using sutureless, rapid deployment biological valve prostheses is associated with excellent results and represents a safe and effective treatment option for patients with severe aortic valve stenosis. This seems to be particularly true in patients with a higher risk profile.

Objective: The Ozaki procedure consists of aortic valve reconstruction using autologous pericardium. The aim of this study is to report our initial single centre experience and to evaluate the earl...

Objective: Recent advances in device design have resulted in a variety of transcatheter treatment options for patients affected by primary or secondary mitral valve disease. Mitral valve repair for...

Background A sutureless aortic valve can be inserted through a right anterior minithoracotomy (RAMT) with consistent decreased cross-clamping time and ease of insertion. We report the experience of RAMT implantation of the 3f Enable (Medtronic, Inc, Minneapolis, Minn) self-expanding sutureless bioprosthesis, performed in 2 European cardiac surgery centers. Method From September 2012 to April 2014, a total of 71 patients with severe aortic stenosis were selected to receive an aortic valve replacement via RAMT using the sutureless valve. Hemodynamic parameters and clinical outcome were assessed at discharge and up to 16 months postoperatively. Results All the patients received the prosthesis with success. One conversion to median sternotomy was necessary, owing to severe pleural adhesions. Overall in-hospital mortality was 2.8%. Mean cardiopulmonary bypass and cross-clamping time were, respectively, 91 ± 29 minutes and 66 ± 19 minutes. Reclamping was necessary in 4 cases (5.6%). Early incidences of grade I or lower paravalvular leakages and pacemaker implantation were, respectively, 4.2% and 5.6%. No paravalvular leakage greater than grade I was registered. The mean follow-up time was 8.1 months; the mean transvalvular gradient was, at discharge and at 6-12 months, respectively, 10.7 ± 4.3 mm Hg and 9.6 ± 3.1 mm Hg. The degree of regurgitation remained stable in all cases. Freedom from all-cause and valve-related mortality was 97% and 99%, respectively, at 1 year. Conclusions Aortic valve replacement via RAMT with the 3f Enable valve is a reproducible procedure, as it provides satisfactory hemodynamics, and a low valve-related complication rate. Greater experience is needed to compare the performance of the 3f Enable valve with that of other sutureless valves implanted via the same RAMT procedure.

Surgical aortic valve replacement (SAVR) with extracorporeal circulation (ECC) is currently the treatment of choice for patients with severe aortic stenosis, but high-risk patients may benefit from reduced ECC and cross-clamping times (CCTs) and a minimally invasive approach. A new generation of ‘sutureless’ (SU) bioprostheses has recently been introduced into clinical practice. Sutureless fixation of the valve combines the advantages of open SAVR (i.e. complete removal of pathological tissue) with reduced ECC and CCT, and facilitates small incision surgery. Between November 2012 and August 2014, we operated on 49 consecutive patients with aortic valve stenosis, using SU valves. Patients (18 males, mean age 78.9 ± 6.3 years, range 63–91) had a mean logistic EuroSCORE of 10.9 ± 10.8. Thirty-nine patients received a Medtronic 3f Enable and 10 a Sorin Perceval S valve; 24 patients underwent minithoracotomy, 11 ministernotomy, and 14 full sternotomy. Valve implantation resulted in a significant improvement in symptoms; mean preoperative and postoperative transvalvular gradients were 60 (120–40) mmHg and 8.5 (17–7) mmHg, respectively. Cross-clamping time was 55.6 ± 14.4 min, mean ECC time 71 ± 19.8 min, and mean implant time 9 min. There was no 30-day mortality. Early incidence of grade I paravalvular leakages and pacemaker implantation was, respectively, 2.0 and 4%. No perivalvular leak >grade I was registered. Aortic valve replacement with SU aortic bioprosthesis represents a safe and effective treatment for aortic valve stenosis, providing excellent haemodynamic and clinical results. A larger study is needed to confirm these initial promising results.

OBJECTIVES The Sutureless and Rapid-Deployment Aortic Valve Replacement International Registry (SURD-IR) was established by a consortium of 18 research centres-the International Valvular Surgery Study Group (IVSSG)-to overcome limitations of the literature and provide adequately powered evidence on sutureless and rapid-deployment aortic valves replacement (SURD-AVR). METHODS Data from 3343 patients undergoing SURD-AVR over a 10-year period (2007-2017) were collected in the registry. The mean age of the patients was 76.8 ± 6.7 years, with 36.4% being 80 years or older. The average logistic EuroSCORE was 11.3 ± 9.7%. RESULTS Isolated SURD-AVR was performed in 70.7% (n = 2362) of patients using full sternotomy (35.3%) or less invasive approaches (64.8%). Overall hospital mortality was 2.1%, being 1.4% in patients who had isolated SURD-AVR and 3.5% in those who had concomitant procedures (P

Off-pump direct coronary artery bypass grafting through a left anterior small thoracotomy is widely utilized for minimally invasive myocardial revascularization. More recently, a novel technique for transapical off-pump mitral valve repair with the NeoChord device is demonstrating its efficacy. This report describes a case of an 84-year-old male patient with coronary artery disease involving the left anterior descending coronary artery and acute severe mitral regurgitation secondary to posterior leaflet flail who underwent both off-pump coronary artery bypass and mitral valve repair with the transapical implantation of artificial chordae using the NeoChord DS 1000 system through the same anterolateral small thoracotomy.

This study provides early results of re-operations after the prior surgical treatment of acute type A aortic dissection (AAD) and identifies risk factors for mortality. Between May 2003 and January 2014, 117 aortic re-operations after an initial operation for AAD (a mean time from the first procedure was 3.98 years, with a range of 0.1–20.87 years) were performed in 110 patients (a mean age of 59.8 ± 12.6 years) in seven European institutions. The re-operation was indicated due to a proximal aortic pathology in ninety cases: twenty aortic root aneurysms, seventeen root re-dissections, twenty-seven aortic valve insufficiencies and twenty-six proximal anastomotic pseudoaneurysms. In fifty-eight cases, repetitive surgical treatment was subscripted because of distal aortic pathology: eighteen arch re-dissections, fifteen arch dilation and twenty-five anastomotic pseudoaneurysms. Surgical procedures comprised a total of seventy-one isolated proximals, thirty-one isolated distals and fifteen combined interventions. In-hospital mortality was 19.6 % (twenty-three patients); 11.1 % in patients with elective/urgent indication and 66.6 % in emergency cases. Mortality rates for isolated proximal, distal and combined operations regardless of the emergency setting were 14.1 % (10 pts.), 25.8 % (8 pts.) and 33.3 % (5 pts.), respectively. The causes of death were cardiac in eight, neurological in three, MOF in five, sepsis in two, bleeding in three and lung failure in two patients. A multivariate logistic regression analysis revealed that risk factors for mortality included previous distal procedure (p = 0.04), new distal procedure (p = 0.018) and emergency operation (p

In last few years, Online Social Networks (OSNs) have become one of the most used platforms for sharing data (e.g., pictures, short texts) on the Internet. Nowadays Facebook and Twitter are the most popular OSN providers, though they implement different social models. However, independently from the social model they implement, OSN platforms have become a widespread repository of personal information. All these data (e.g., profile information, shared elements, users’ likes) are stored in a centralized repository that can be exploited for data mining and marketing analysis. With this data collection process, lots of sensitive information are gathered by OSN providers that, in time, have become more and more targeted by malicious attackers. To overcome this problem, in this paper we present an architectural framework that, by means of a Social Application registered in Facebook, allows users to move their data (e.g., relationships, resources) outside the OSN realm and to store them in the public Cloud. Given that the public Cloud is not a secure and private environment, our proposal provides users security and privacy guarantees over their data by encrypting the resources and by anonymizing their social graphs. The presented framework enforces Relationship-Based Access Control (ReBAC) rules over the anonymized social graph, providing OSN users the possibility to selectively share information and resources as they are used to do in Facebook.

Background: Surgical aortic valve replacement (SAVR) with extracorporeal circulation (ECC) is currently the treatment of choice for patients with severe aortic stenosis. High-risk patients may benefit from reduced ECC time, crossclamp time (CCT) and a minimally-invasive approach. Minimally invasive aortic valve replacement (MIAVR) was first described by Cosgrove and Sabik [1] and have increasingly gained acceptance in the surgical realm, with the aim of achieving equivalent or superior out- comes compared with conventional AVR (CAVR). A new generation of “suture less” bioprostheses has recently been introduced in clinical practice. Sutureless fixation of the valve combines the advantages of open SAVR, i.e. complete removal of pathological tissue, with reduced ECC and CCT, and facilitates small incision surgery. Methods: Between November 2012 and October 2015 we operated on 70 consecutive patients with aortic valve stenosis, using suture less valves. Patients (25 males, mean age 77.9 ± 6.3 years, range 63-91) had a mean logistic Euro SCORE of 11.9 ± 10.8. Fifty-five patients received a Medtronic 3f Enable and 15 a Sorin Perceval S valve; 48 patients were operated through minithoracotomy, and 22 through ministernotomy. Results: Valve implantation resulted in a significant improvement in patients’ symptoms; mean preoperative and postoperative transvalvular gradient was 60 mmHg (120-40) and 8.5 mmHg (17-7), respectively. CCT time was66 ± 14.4 min, mean ECC time 71 ± 19.8 min, mean implant time 9 min. 30-day mortality was 1,5%. Early incidence of grade I paravalvular leakages and pacemaker implantation was, respectively, 2.0 % and 4%. 1 late PVL grade 2 was registered. Conclusion: MIAVR with suture less aortic bioprosthesisin high risk patients represents a safe and effective treatment for aortic valve stenosis, providing excellent hemodynamic and clinical results. A larger study is needed to confirm these initial promising results.

Objectives Aortic valve replacement through conventional sternotomy still represents the gold-standard surgical approach for aortic valve disease. However, given the increasing number of patients with comorbidities, strategies that can improve operative results are always sought. Minimally invasive aortic valve surgery, although related to a steep learning curve, might be associated with improved postoperative outcomes. The main aim of this study was to assess whether significant differences exist in terms of operative and early results between a mini-sternotomy and a right mini-thoracotomy approach for isolated aortic valve replacement without sutureless technologies. Methods This is an observational retrospective multicentre study from nine Italian cardiac centres that analyses prospectively collected data of patients who underwent isolated minimally invasive aortic valve replacement between January 2010 and December 2014. Two approaches are considered (mini-sternotomy and mini-thoracotomy) and compared in terms of operative and early outcomes. Results After interrogation of the centralized database, a total of 1130 patients were retrieved (854 mini-sternotomy and 276 mini-thoracotomy). Patients in the mini-sternotomy group had a higher risk profile. There was no difference in terms of early mortality; cardiopulmonary bypass and cross-clamp time did not differ significantly between the groups; and a significantly higher number of reoperations for bleeding was observed in the right mini-thoracotomy group. Conclusions Both mini-sternotomy and mini-thoracotomy could be performed safely, with low mortality and postoperative morbidity. The mini-thoracotomy approach was associated with a significantly higher rate of reoperation for bleeding. Uptake among cardiac centres was low. Sutureless technologies could potentially increase surgical volume by simplifying the mini-thoracotomy procedure.

The mammary gland, the unique organ that primarily form at puberty, is an ideal model to study the functions of homeobox (HB) genes in both development and tumorigenesis. HB genes comprise a large family of developmental regulators that have a critical role in cell growth and differentiation. In the normal mammary gland, homeobox genes are involved in ductal formation, epithelial branching, and lobulo-alveolar development by regulating epithelial proliferation and differentiation. The HB genes are controlled in a spatial and temporal manner in both stromal and epithelial cells. They are coordinately regulated by hormones and extracellular matrix, suggesting that many signaling pathways are involved in homeobox gene functions. When homeobox genes are misexpressed in animal models, different defects are displayed in mammary gland development. Aberrant expression of homeobox genes, overexpressed or downregulated, is found in primary carcinomas and in breast cancer. The Otx1 HB gene is a classic regulatory of nervous system development during embryogenesis. Postnatally Otx1 is transcribed in the anterior pituitary gland, where activates transcription of the pituitary hormones, and plays a role in hematopoiesis, enhancing pluripotent cells, and erythroid differentiation. Otx1 can still be detected in mature cells of the erythroid and megacaryocytic lineage. During cyclical development of mammary gland, the Otx1 gene is overexpressed in lactation, confirming a role of this transcription factor in cell differentiation. Recent studies report that Otx1 is overexpressed in breast cancer. Otx1 is expressed during embryogenesis, and it is expressed again during carcinogenesis, implying its possible function in differentiation of neoplastic cells.