Aortic Root Surgery in Adults: An Unsolved Problem.

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.

Pacemaker after Sutureless and Rapid-Deployment Prostheses: A Progress Report from the SURD-IR.

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 < 0.001). In the Su cohort, a decrease in age, risk profile, and incidence of bicuspid aortic valve, increased use of anterior right thoracotomy, reduction of cardiopulmonary bypass time and of associated procedures, and more frequent use of smaller prostheses were observed over time. In the RD cohort, the rate of PPI was stable over time (EG = 8.8% vs LG = 9.3%, p = 0.8). In this cohort, a younger age, lower risk profile, and higher incidence of concomitant septal myectomy were observed over time. CONCLUSION: 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.

Transcriptomic profiling of calcified aortic valves in clonal hematopoiesis of indeterminate potential carriers.

Clonal hematopoiesis of indeterminate potential (CHIP) is characterized by the presence of clones of mutated blood cells without overt blood diseases. In the last few years, it has emerged that CHIP is associated with atherosclerosis and coronary calcification and that it is an independent determinant of cardiovascular mortality. Recently, CHIP has been found to occur frequently in patients with calcific aortic valve disease (CAVD) and it is associated with a poor prognosis after valve replacement. We assessed the frequency of CHIP by DNA sequencing in the blood cells of 168 CAVD patients undergoing surgical aortic valve replacement or transcatheter aortic valve implantation and investigated the effect of CHIP on 12 months survival. To investigate the pathological process of CAVD in CHIP carriers, we compared by RNA-Seq the aortic valve transcriptome of patients with or without CHIP and non-calcific controls. Transcriptomics data were validated by immunohistochemistry on formalin-embedded aortic valve samples. We confirm that CHIP is common in CAVD patients and that its presence is associated with higher mortality following valve replacement. Additionally, we show, for the first time, that CHIP is often accompanied by a broad cellular and humoral immune response in the explanted aortic valve. Our results suggest that an excessive inflammatory response in CHIP patients may be related to the onset and/or progression of CAVD and point to B cells as possible new effectors of CHIP-induced inflammation.

The influence of metabolic syndrome in heart valve intervention. A multi-centric study.

BACKGROUND: The effect of metabolic syndrome (MetS), defined as insulin resistance along with two or more of: obesity, atherogenic dyslipidaemia and elevated blood pressure, on postoperative complications after isolated heart valve intervention remains controversial. We hypothesized that MetS may negatively influence the postoperative course in these patients. METHODS: Patients from 10 cardiac units who underwent isolated valve intervention (mitral ± $\pm $ tricuspid repair/replacement (mitral valve surgery [MVS]) or surgical aortic valve replacement (SAVR), or transcatheter aortic valve replacement (TAVR) were included. MetS was defined according to the World Health Organization criteria. Primary outcome was in-hospital mortality and overall postoperative length of stay (LOS). Relevant postoperative complications were also recorded. RESULTS: From 2010 to 2019, 17,283 patients underwent valve intervention. The MVS, SVAR, and TAVR accounted for the 39.4%, 48.2%, and 12.3% respectively of the whole. MetS compared to no-MetS was associated to higher mortality in the MVS group (6.5% vs. 2%, p < .001), but not in the SAVR and TAVR group. In both surgical cohorts, MetS was associated with increased complications including red blood cells transfusion, renal failure, mechanical ventilation time, intensive care and overall postoperative LOS (11 (9) vs. 10 (6), p < .001 and 10 (6) versus 10 (5) days, p = .002, MVS and [SAVR]). No differences were found in the TAVR cohort, with similar mortality and complications. CONCLUSION: MetS was associated to more postoperative complications, with higher mortality in the MVS group. In the TAVR cohort, postoperative complications and mortality rate did not differ between patients with and without MetS, however LOS was longer in the MetS group.

Right ventricle remodeling after transcatheter tricuspid leaflet repair in patients with functional tricuspid regurgitation: Lessons from the surgical experience.

Clinically significant tricuspid regurgitation (TR) is common and associated with excess mortality. At the same time right ventricular (RV) failure is a complex clinical syndrome that results from many causes, but is often associated with long-term prognosis. Whilst results of isolated tricuspid valve (TV) surgery are often unsatisfactory and limited by the prohibitive risk of most patients, the recent development of percutaneous recovery techniques has opened new scenarios. In consideration of the complexity of the mechanisms that lead to right heart failure and RV dysfunction it is important to understand the real advantages that percutaneous TV treatment can offer, more specifically the effect of TR reduction on RV remodeling in the setting of functional tricuspid regurgitation (fTR).

A retrospective multicentre study on dalbavancin effectiveness and cost-evaluation in sternotomic wound infection treatment: DALBA SWIT Study.

OBJECTIVE: To evaluate the cost-effectiveness of dalbavancin compared with standard of care (SoC) treatment as daptomycin or teicoplanin in patients with sternal wound infections (SWI). METHODS: Multicentre retrospective study of patients diagnosed with SWI from January 2016 to December 2019 at two cardiac surgery facilities treated with dalbavancin, teicoplanin or daptomycin. Patients with SWI treated with dalbavancin were compared with SoC to evaluate resolution of infection at 90 and 180 days from infection diagnosis, length of stay (LoS) and management costs. RESULTS: 48 patients with SWI were enrolled, 25 (50%) male, median age 67 (60-73) years, Charlson index score 5 (4-7). Fifteen patients were treated with dalbavancin (31%) and 33 with SoC (69%): teicoplanin in 21 (63%), and daptomycin in 12 (37%). Staphylococcus species were the most frequent isolates (44, 92%), mostly (84%) resistant to methicillin. All patients were treated with surgical debridement followed by negative pressure wound therapy. Wound healing at day 90 and 180 was achieved in 46 (95.8%) and 34 (82.9%) of patients, respectively. A shorter length of hospitalization in patients treated with dalbavancin compared with SoC [12 (7-18) days vs 22 (12-36) days, p:0.009] was found. Treatment with dalbavancin resulted in total cost savings of €16 026 (95% CI 5976-26 076, P < 0.001). Savings were mainly related to the LoS that was significantly shorter in the dalbavancin group, generating significantly lower cost compared to SoC group. CONCLUSION: Dalbavancin treatment of sternal wound infections is effective and seems to reduce hospitalization length, leading to significantly lower costs.

Sutureless and rapid deployment versus sutured aortic valve replacement: a propensity-matched comparison from the Sutureless and Rapid Deployment International Registry.

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 < 0.001), no difference was found in more recent year period (relative risk 1.66, P = 0.08; P for heterogeneity 0.003). Group 1 was associated with reduced rates of postoperative low cardiac output syndrome, atrial fibrillation and mild aortic regurgitation. New pacemaker implant was three-fold higher in group 1. 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.

Periareolar approach in female patients undergoing mitral and tricuspid valve surgery: An almost invisible surgical access.

BACKGROUND AND AIM OF THE STUDY: Periareolar minithoracotomy represents an interesting option in minimally invasive cardiac surgery and it is our preferred approach for women. Our aim is to assess the results in female patients, in terms of nipple postoperative pain, local sensitivity, and eventual alterations in mammography after surgery. METHODS: Fifty-seven female patients underwent periareolar incision, as minithoracotomy approach, from December 2018 to December 2021. Their mean age was 56 ± 12 years, their body mass index was 22.5 ± 4.8; their surgery was elective in 93%, with mean Euroscore II about 2 ± 1.3. RESULTS: Of 57 patients, 87.7% (50 patients) underwent mitral valve repair, whose six with associated procedures; 8.8% (five patients) underwent mitral valve replacement whose two with tricuspid annuloplasty associated and 3.5% (two patients) had isolated tricuspid surgery. The cardiopulmonary bypass and aortic cross-clamp time were 123.2 ± 30.2 and 101.3 ± min respectively. There were no conversions to either full sternotomy or larger thoracotomy approach. There were no in-hospital and follow-up deaths. No strokes or wound infections were observed. Mean follow-up was 16± 9 months. Within the investigated follow-up, 100% of the patients were satisfied with the esthetic result, no remarkable postoperative pain was reported, two patients had slight hyposensitivity in the nipple area. About 50% IThad mammography as prevention screening after surgery and no abnormalities were found. CONCLUSIONS: Periareolar minithoracotomy is a feasible surgical option in female patients, with excellent healing and cosmetic results and preserving the tissues of the mammary gland.

Standardized Aortic Valve Neocuspidization for Treatment of Aortic Valve Diseases.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Surgical aortic valve replacement for low-gradient aortic stenosis.

AIMS: Low-gradient aortic stenosis is a challenging entity that needs accurate preoperative evaluation. For this high-risk patient population, ad hoc predictive scores are not available and profile risk is currently revealed by the EuroSCOREs. Aims of this study are to verify the suitability of the ES II as predictor of mortality in low-gradient aortic stenosis and to analyse the role of surgery as a treatment. METHODS: From June 2013 to August 2019, 414 patients underwent surgical aortic valve replacement for low-gradient aortic stenosis. Mean age was 75.78 ±â€Š6.77 years and 190 were women. The prognostic value of Logistic EuroSCORE and EuroSCORE II were compared by receiver-operating characteristics (ROC) curve analysis. RESULTS: In-hospital, 30-day and 1-year mortality rates were respectively 3.4, 2.9 and 4.8% (14, 12 and 20 patients over 414). In-hospital mortality risk calculated by the Additive EuroSCORE was 7.2 ±â€Š2.7%, by the Logistic EuroSCORE was 9 ±â€Š5.2% and by the ES II was 4.13 ±â€Š2.56%. The prognostic values of the EuroSCORE II and of the EuroSCORE were analysed in a ROC curve analysis for the prediction of in-hospital mortality [area under the curve (AUC): 0.62 vs. 0.58], 30-day mortality (AUC: 0.63 vs. 0.64) and 1-year mortality (AUC: 0.79 vs. 0.65). Both scores did not show significant differences with the only exception of 1-year mortality, for which EuroSCORE II had a better predictive ability than the Logistic EuroSCORE (P < 0.05). CONCLUSION: In low-gradient aortic stenosis undergoing surgery, the EuroSCORE II is a strong predictor of 1-year mortality.

Comparison of a full sternotomy with a minimally invasive approach for concomitant mitral and tricuspid valve surgery.

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.

Impact of comorbidities on older patients undergoing open heart surgery.

BACKGROUND: The number of elderly patients undergoing cardiac surgery is increasing. Age greater than 80 years has been identified as a strong independent risk factor for shortand long-term survival. The current study is aimed to identify the impact of preoperative comorbidities on early and late outcomes in older patients undergoing cardiac surgery. METHODS: Baseline characteristics, procedurals and postoperative complications of all patients undergoing cardiac surgery at our institution are collected. The current analysis is focused on patients aged at least 80 years at the time of intervention and treated from January 2010 to December 2019. RESULTS: In-hospital mortality resulted as 6.3%. Redo intervention [odds ratio (OR) 2.49, 95% confidence interval (CI) 1.13-5.48], chronic obstructive pulmonary disease (COPD) (OR 2.99, 95% CI 1.75-5.12) and peripheral arterial disease (PAD) (OR 2.23, 95% CI 1.30-3.81) were independent baseline predictors of outcome in the multivariate analysis. Prolonged extracorporeal circulation time, need for transfusion and prolonged intubation time strongly and independently predicted in-hospital mortality. During a mean follow-up of 3.6 years 34.3% of patients died and unplanned admission (HR 1.33, 95% CI 1.05-1.67), NYHA class III-IV (HR 1.35, 95% CI 1.12-1.64), diabetes (HR 1.27, 95% CI 1.01-1.59), COPD (HR 1.60, 95% CI 1.25-2.04) and PAD (HR 1.32, 95% CI 1.03-1.71) resulted as independent predictors of all-cause death. CONCLUSION: Cardiac surgery is feasible in octogenarians, with an acceptable risk of mortality. Chronological age itself should not be the main determinant of choice while referring patients for cardiac surgical intervention. Comorbidities such as COPD, PAD and diabetes need to be taken into account for risk stratification.

Sutureless Versus Rapid Deployment Aortic Valve Replacement: Results From a Multicenter Registry.

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.

Sex-specific differences and postoperative outcomes of minimally invasive and sternotomy valve surgery.

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.

Impairment of mitophagy and autophagy accompanies calcific aortic valve stenosis favouring cell death and the severity of disease.

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 analyse 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 increase 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. CONCLUSION: Our data suggest that the CAVS 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 reverts quite all pathological phenotypes.

Sutureless versus transcatheter aortic valve replacement: A multicenter analysis of "real-world" data.

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 patients (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€ vs 24181.5±3632€; 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.

Biological Characterization of Human Autologous Pericardium Treated with the Ozaki Procedure for Aortic Valve Reconstruction.

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.

Minimally invasive aortic valve replacement: short-term efficacy of sutureless compared with stented bioprostheses.

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.

A naturally occurring mutation in ATP synthase subunit c is associated with increased damage following hypoxia/reoxygenation in STEMI patients.

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.