OBJECTIVE:Mitral valve repair (MVr) is the standard treatment for degenerative mitral regurgitation (MR). However, MR may recur, and reoperation is associated with increased mortality and technical complexity. Microinvasive MVr using the NeoChord technique in redo setting is performed off-pump, offering clear advantages, particularly in high-risk patients. METHODS:This retrospective, multicenter, international registry included 92 patients treated with the NeoChord technique between 2014 and 2025 for recurrent MR after previous MVr across 32 centers. The primary composite end point was freedom from recurrence of severe MR, need for reintervention due to technical failure, and 30-day or cardiovascular mortality. RESULTS:Neochord repair was successful in 91 patients (98.9%); one was converted to open surgery. Mean age was 64.6 ± 11.6; 22 patients (23.9%) were female. Mean left ventricle ejection fraction was 57.4 ± 8.1%; European System for Cardiac Operative Risk Evaluation was 4.3 ± 3.2%. A median of 3 chords was implanted. Mean procedural time was 139 ± 65 minutes. At discharge, MR was mild or less in 93.5%. One patient (1.1%) died on day 8. One life-threatening bleeding and one acute myocardial infarction were reported. Median hospital length-of-stay was 5 days; 47.8% of patients were extubated in the operating room. The primary end point was achieved in 81.3 ± 6.6% of patients at 5 years (Kaplan-Meier analysis). Seven patients (8.6%) underwent re-reintervention; 3 remained with severe MR. In the multivariate analysis, older age was associated with an increased risk (hazard ratio, 1.160; 95% CI, 1.021-1.317), whereas greater hemoglobin levels were protective (hazard ratio, 0.423; 95% CI, 0.233-0.768). CONCLUSIONS:Microinvasive NeoChord repair provides excellent procedural and 5-year outcomes with very low mortality, supporting its role as a valuable option for reoperative mitral valve surgery.

To evaluate the safety and efficacy and report the early multicentre experience of an innovative surgical technique for post–infarction ventricular septal defect (MI–VSD) closure (Figure 1 A-B-C) using two hand–made composite patches (two Teflon layers and one pericardial layer sewed together) parachuted through a transversal aortotomy and a right atriotomy, without left ventriculotomy (Figure 2). Multi–centre retrospective observational study of patients with MI–VSD who underwent surgical repair with this new technique from September 2022 to May 2024. 11 patients – in 8 different hospital institutions – underwent MI–VSD–closure with this new surgical technique. Mean age was 65±9.8yo and 36% were male. 91% had a postero–basal MI–VSD (Ø: 16.7±5.0 mm), due to acute right coronary vessel occlusion, and presented with cardiogenic shock; 10 patients needed preoperatively IABP or ECMO support. Urgent surgery (‹48 hours from presentation) was performed in 6 patients. CPB (84±23.9 min) and X–clamp (60.9±20.2 min) times in isolated MI–VSD–repair were short – even without experience with the technique –. There were no major postoperative complications, including intra–operative mortality, peri–procedural stroke, renal failure requiring permanent dialysis, except for three surgical revisions for bleeding. Overall survival was 55% (6 patients); the main cause of death was cardiac shock due to extremely poor bi–ventricular function. Residual MI–VSD was present in one case, which underwent percutaneous closure with Amplatzer (Figure 3 A-B). Mean discharge time was 13±7.6 days after surgery. Follow–up ranged from 4–20 (mean 8.5±6.1) months: all patients were alive with improved hemodynamics. Echo findings: ejection fraction 49.3±5.6%, no residual MI–VSD and absence of mitral or tricuspid regurgitation due to patch interference. This technique is feasible, safe, simple, and provides good short–term results, in all type of VSD, especially postero–basal ones. Moreover, ventriculotomy is not needed. In early surgery (≤48h), this technique overcomes the problem of how to deal with frail necrotic tissue, saving time before ventricular and organ failure worsens, that are the two most relevant prognostic factors, along with myocardial infarction extension. It could be the first–line approach, and, in case of significant residual shunt, it can be quickly repeated or it can be eventually integrated by a percutaneous closure in a hybrid strategy.Figure 1 Figure 2 Figure 3

Abstract 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. The effect of metabolic syndrome (MetS), defined as insulin resistance along with two or more of: obesity, atherogenic dyslipidaemia and elevated blood pressure, on post-operative complications after isolated heart valve intervention remains controversial. We hypothesized that MetS may negatively influence the post-operative course in these patients. Methods. Patients from 10 cardiac units who underwent isolated valve intervention (mitral ± tricuspid repair/replacement (MVS) or aortic valve replacement (SAVR), or transcatheter aortic valve replacement (TAVR) were included. MetS was defined according to the WHO criteria. Primary outcome was in-hospital mortality and overall post-operative length of stay. Relevant post-operative complications were also recorded. Results. From 2010 to 2019, 17283 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<0.001), 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 post-operative length of stay (11 (9) vs. 10 (6), p<0.001 and 10 (6) vs. 10 (5) days, p=0.002, MVS and SAVR)). No differences were found in the TAVR cohort, with similar mortality and complications. Conclusion. MetS was associated to more post-operative complications, with higher mortality in the MVS group. In the TAVR cohort, post-operative complications and mortality rate did not differ between patients with and without MetS, however length of stay was longer in the MetS group.

The investigation of biological processes involved in cardiovascular diseases and the study of new cardioprotective strategies and therapeutic targets in human specimens are challenging to date. This is partly due to the almost absent availability of control cardiac samples caused by stringent ethical guidelines of the interested country and the continual development of semi-invasive percutaneous procedures, which make it difficult to perform and process the cardiac biopsy for experiments on viable myocytes. Real and attractive alternatives may exist, such as the creation of pathological models with immortalised ventricular human myocytes and the direct reprogramming of human endogenous cells into cardiomyocytes using induced pluripotent stem cell technology, but these methods also include limitations.1 The obstacles to developing an appropriate cell model to study a given pathology are not limited to the cardiovascular field. Several studies, including mitochondrial disorders and neurodegenerative diseases,2-4 have adopted alternative and more feasible experimental models, such as skin-biopsy-derived fibroblasts, to perform functional analyses on a pathological phenotype. In our previous publication5 to which this short letter refers, we showed a strong and positive correlation between the mitochondrial permeability transition pore (mPTP) opening measured in fibroblasts from ST-segment elevation myocardial infarction (STEMI) patients and reperfusion injury (RI) evaluated by cardiac magnetic resonance imaging of the same patients. Moreover, we found significant intersubject variability in mPTP opening, and the patients with hyperresponsive mPTP opening also had greater reperfusion damage.5 This was an interesting finding considering the fact that, to the best of our knowledge, no data on mPTP and RI in humans are available to date. However, the question of how mPTP measured in fibroblasts reflects the reperfusion damage of a given patient, as well as how mPTP function (or other biological readouts) can be assessed directly in patients affected by cardiac ischaemia–reperfusion (I/R), remains unanswered. mPTP is a multiprotein complex with channel function.6-11 It is of great interest in the cardiovascular field because it is a key step in cell death during I/R episodes (i.e., in MI) in its “open state” and is considered one of the main culprits of RI. For these reasons, it constitutes an important target for cardioprotection, as already shown in cells and animal models.8, 12, 13 Here, in an effort to explain our findings mentioned above, we provide an update on the differences that may occur between cardiomyocytes and fibroblasts in the analysis of mPTP activity in ischaemic patients. Indeed, with this pilot study, we detected negligible differences in mPTP function between both cell lines. This study is part of a larger project aimed to provide genetic and functional information on the mPTP in the RI directly in humans and refers to our previous publication. Simultaneous evaluation of the mPTP in CaRdiOmyocytes and FibroblasTs in patients undergoing cardiac surgery (CROFT) was a single-centre, investigator-driven, prospective study conducted at the cardiac surgery unit of Maria Cecilia Hospital of Cotignola, Ravenna, Italy. The trial was performed according to the Declaration of Helsinki and approved by the local ethics committee (Comitato Etico Area Vasta Emilia Romagna). Patients with a surgical indication for cardiac revascularisation or heart valve surgery, >18 years old, and with documented coronary artery disease upon coronary artery angiography were enrolled. The exclusion criteria were as follows: refused informed consent, contraindication to statin therapy, known haemorrhagic disease, known disease of the mitochondria, neoplasia treated <5 years ago, chemotherapy <5 years ago, life expectancy <1 year, suspected neoplasia, use of oral contraceptives, pregnancy or breast feeding. All enrolled patients underwent a skin biopsy to obtain a fibroblast culture and myocardial biopsy to obtain atrial cardiomyocyte cultures. As a basic research pilot study, sample size calculation was not feasible.14 Considering similar studies, we enrolled 20 patients in whom the twofold biopsy (skin fibroblasts and atrial cardiomyocytes) was performed. Patients undergoing coronary artery bypass graft needed the packaging of one or more saphenous or autologous mammary bypasses. Thus, a skin biopsy was performed at the site of the autologous saphenous bypass or at the level of the thoracic skin incision. The skin tissue was collected with a clamp and introduced into a sterile container prefilled with an adequate quantity of preservative solution. Fibroblasts were isolated from the epidermis, dermis and hypodermis. After the surgical intervention, the cutaneous biopsy tissue was stored overnight in HBSS containing 3% penicillin–streptomycin (PS) and 1% amphotericin B. After being washed and minced into smaller pieces, the tissues were arranged in 25-cm2 flasks covered by a thin layer of FBS. Then, for the following 10 days, every day, 500 µl of DMEM with 50% FBS was added to the culture. After approximately 15 days, fibroblasts were removed from the biopsy samples and trypsinised and amplified for experiments. A single tissue sample was collected at the level of the auricula where the tobacco pouch was made for venous cannulation. The tissue was collected with a clamp and introduced into a sterile container prefilled with an adequate quantity of preservative solution. Cardiomyocytes were isolated from the myocardium. The procedure was performed in accordance with standard procedures widely described in the literature.15 Briefly, within 20 min after myocardial biopsy, atrial appendages were digested using a two-step protocol involving first 30 min of protease XXIV followed by 60 min of collagenase II digestion in a buffer with low calcium at 37°C and continuously oxygenated. The digestion product was filtered with a 300-μm nylon mesh and carefully centrifuged at 100 g for 5 min. Cells were counted and seeded on 24-mm glass coverslips, and a laminin coating was applied on these coverslips to promote cell attachment. All experiments, from sample collection to cell attachment on the coverslips, were performed within 6 h. As mPTP opening leads to the loss of the proton gradient across mitochondrial membranes, it can be measured with tetramethylrhodamine methyl ester (TMRM), a chemical, cationic and cell-permeable dye that accumulates in the mitochondrial matrix. The opening of the mPTP triggers the efflux of TMRM from the organelle in a short time, resulting in a progressive decrease in fluorescence intensity (Figure 1A). This change in fluorescence, in addition to the basal TMRM intensity loaded by the cell at resting conditions, can be monitored and recorded with confocal microscopy to obtain kinetics (Figure 1A). These data were analysed considering the slope (excel function) of the kinetics from the time of the stimulus administration until the end of the live imaging. In detail, cells were loaded with 20 nM TMRM for 30 min at 37°C; once on the microscope, TMRM basal intensity was first acquired at resting conditions for 30 s. Then, mPTP opening was stimulated by Ca2+ (10 nM ionomycin)- and oxidative stress (500 μM H2O2)-dependent conditions in living cardiomyocytes and fibroblasts (Figure 1A). TMRM assay was sensitive to mPTP-dependent stimuli as its fluorescence decreased after their addition, but also to Cyclosporin A (CsA), as the cells pretreated with the mPTP inhibitor and then stimulated with Ca2+ overload and pro-oxidants did not experience TMRM fluorescence decrease in the same extend of the first case (Figure 1A). Imaging was performed with a Nikon Eclipse Ti confocal microscope with a 40 ×/0.60 SPlanFluor objective. On average, 15 cardiomyocytes and 40 fibroblasts per patient were evaluated. The Shapiro–Wilk test was used to check data for normality. The results are shown as the median ± range. Statistical significance was investigated by the Mann–Whitney test for two-group comparisons and by the Kruskal–Wallis test for comparisons of more than two groups. A Bland–Altman plot was used to analyse the agreement between two different measures. A correlation analysis was performed by applying the Spearman rank test. The CROFT study initially involved 20 patients undergoing cardiac surgery. In these samples, we performed mPTP functional analysis by analysing the mitochondrial membrane potential under Ca2+- and oxidative stress-dependent conditions, as previously described and shown in Figure 1A. Indeed, it was impossible to perform the more direct calcein–cobalt assay in myocytes due to the toxicity of the CoCl2 reagent needed for the test or longer protocols due to the short viability of cells after extraction. Samples from 4 out of 20 enrolled patients were used to set experimental conditions; thus, they were excluded from the study. In the remaining 16 patients (Table 1), by measuring mPTP opening in both fibroblasts and myocytes, we reported a significant intersubject variability of the channel (p < 0.0001 for myocytes and p < 0.0001 for fibroblasts) (Figure 1B). This finding confirmed the results obtained in5 and supported the hypothesis that this functional difference may have a pathological implication. Although the values obtained from patient ID11 differ significantly between myocytes and fibroblasts and considering that different cellular types can have different sensitivities to either Ca2+- or ROS-dependent stimuli, overall, the analysis of the agreement between both measures confirms that they are interchangeable. Indeed, the Bland–Altman test (Figure 1C) yielded a bias = 0.15 and a narrow range of 95% limits of agreement (dotted lines), and all values fell within that limit, suggesting that the differences between mPTP opening in myocytes and fibroblasts are close to 0. In addition, the recorded values showed a positive correlation (Spearman's r = 0.61, p = 0.01) (Figure 1D). Overall, as shown in Figure 1E, patients with lower mPTP activity recorded in fibroblasts (mPTP of fibroblasts below the median value) also had lower mPTP activity in myocytes than other patients. Taken together, these data highlighted fibroblasts from skin biopsies as a feasible model for obtaining crucial information on mPTP function in cardiovascular diseases where cardiac biopsies cannot be collected (i.e., MI). Obtaining and processing heart samples for experimental research are challenging, even considering the continual development of semi-invasive percutaneous procedures in the treatment of I/R-based pathologies. In vitro models to study the molecular mechanisms of human cardiac diseases exist, but they include several limitations. Moreover, clinical studies involving both basic and translational research lines are still scarce.16 Thus, it is necessary to explore additional routes to investigate the molecular pathways behind the phenotype, as was done in the past by several research groups in other fields. The most widespread, already used for mitochondrial disorders or neurodegenerative pathologies where human specimens are rare or impossible to be taken, is skin biopsy-derived fibroblasts.2-4 In line with this previous literature and in understanding how the function of mPTP activity measured in fibroblasts from STEMI patients correlates with RI, we analysed the activity of mPTP both in fibroblasts and myocytes in ischaemic patients undergoing cardiac surgery. We believe this addendum may provide at least one more explanation in support of those findings. Overall, in the CROFT study, we first confirmed our previous results about the significant intersubject variability of mPTP opening, which further supports the hypothesis that this functional difference may have a pathological implication in the clinical outcome of those patients (such as RI). Second, we detected negligible differences in terms of mPTP activity between fibroblasts and cardiomyocytes recorded in patients undergoing cardiac surgery. Indeed, the trend of variation in mPTP activity between fibroblasts and cardiomyocytes among patients was positively and significantly correlated. The fact that ID11 assumes statistically significant values between cell lines may on the one hand confirm the fact that different cell types sense stimuli in different ways; on the other hand, it further validates our data output; indeed, although the cohort is small, only one sample differed from the overall trend. Nevertheless, the comparative analyses represented by the Bland–Altman test and the correlation analysis provide a link between fibroblasts and cardiomyocytes in terms of mPTP opening under certain pathological conditions. We are aware that our study contains some limitations. The small population size is affected by restrictions due to ethical guidelines. Further studies should be conducted to broaden the findings of this pilot study. Another limitation is the evaluation of mPTP activity using only one assay. Unfortunately, the cardiac tissues allowed were small, and explanted myocytes were viable only for a few hours after cardiac surgery, in agreement with the literature in the field. Thus, longer experimental protocols were not applicable, and the more direct assay (calcein–cobalt technique) for analysing mPTP was excluded due to the toxicity of the CoCl2 reagent. P.P. is grateful to Camilla degli Scrovegni for continuous support. The Signal Transduction Laboratory (www.unife.it/labs/signaltransduction) was supported by the Italian Association for Cancer Research (AIRC: IG-23670 to P.P. and IG-19803 to C.G.), A-ROSE, Progetti di Rilevante Interesse Nazionale (PRIN2017E5 L5P3 to P.P. and PRIN20177E9EPY to C.G.), the Italian Ministry of Health (GR-2013-02356747 to C.G.), the European Research Council (ERC; 853057-InflaPML to C.G.) and local funds from the University of Ferrara to P.P. and C.G. G.M. was supported by the Italian Ministry of Health (GR-2019-12369862). M.R.W. was supported by the Polish National Science Centre (Grants: UMO-2014/15/B/NZ1/00490 and UMO-2018/29/B/NZ1/00589). The authors declare that they have no conflicts of interest.

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 x 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.

BACKGROUND This study compared clinical and hemodynamic in-hospital outcomes of patients undergoing suture -less 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 Life -sciences, 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 post-operative 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. (Ann Thorac Surg 2022;114:758-66) (c) 2022 by The Society of Thoracic Surgeons

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.

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 euro 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.(c) 2022 The Authors. Published by Elsevier Ltd on behalf of International Society for Antimicrobial Chemotherapy. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ )

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 ± 6.77 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 ± 2.7%, by the Logistic EuroSCORE was 9 ± 5.2% and by the ES II was 4.13 ± 2.56%. 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.

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.

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.

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).

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.

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 endo-carditis 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.(Ann Thorac Surg 2022;114:1108-17)(c) 2022 by The Society of Thoracic Surgeons

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.

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.

The present case highlights the crucial role of hybrid setting for diagnosis and treatment of refractory coronary spasms.