BACKGROUND:Calcific aortic valve stenosis (AS) affects 3% of older adults and lacks medical treatment. The deacetylase Sirtuin 1 (SIRT1) could be involved in many pathways linked to AS progression. Sodium-glucose co-transporter 2 inhibitors (SGLT2i), glucose-lowering agents, have been shown to reduce cardiovascular events (likely via SIRT1), but their possible benefits in AS are unknown. Our study aims to uncover the role of SIRT1 in AS progression and assess the benefit of SGLT2i to slow down the aortic valve fibro-calcification processes. METHODS:RNA-seq data of human aortic valve specimens were collected from the ARChS4 database. SIRT1 knockdown (SIRT1 KD) and overexpressing (SIRT1 Over) valve interstitial cells (VIC) were generated by CRISPR/Cas9. Real-time PCR, immunofluorescence, and calcification assays were used to characterise mutant VICs. Conditioned medium experiments were implemented to evaluate SGLT2i effect on cellular cross-talk and calcification. Diabetic patients' data from the Lombardy regional healthcare database, treated with sulphonylureas (SU; no effect on SIRT1) and SGLT2i (acting on SIRT1), were selected and matched 1:1 by age, sex, and multisource comorbidity score. Cumulative incidence of hospitalisation for non-rheumatic aortic valve disease was assessed by Kaplan-Meier and Fine and Gray models were used to estimate subdistribution hazard ratios. RESULTS:RNA-seq showed that SIRT1 could be an upstream regulator of multiple AS-related pathways. Functional studies on mutant VICs revealed that SIRT1 directly regulates antioxidant processes, extracellular-matrix remodelling, and calcification by modulating key transcription factors. Moreover, calcification assays further support this role, revealing an increased calcification in SIRT1 KD VICs and a concomitant decrease in VIC SIRT1 Over when compared to wild type. Then, exploring SGLT2i impact on calcification, we showed that VICs cultured in SGLT2i-treated-endothelial medium exhibited reduced calcification associated with endothelial-increased nitric oxide levels, while SIRT1 inhibition enhanced VIC calcification. The real-world data analysis revealed that SGLT2i-treated group had a lower incidence of hospitalised patients for non-rheumatic aortic valve disease compared to SU-treated group. CONCLUSIONS:Our data identify SIRT1 as an upstream regulator of fibro-calcific processes in AS and suggest that SGLT2i may slow the aortic valve degeneration through SIRT1 modulation. These findings support SGLT2i as a potential therapeutic strategy for AS prevention and care.

Background:Fibrocalcific aortic valve disease (FCAVD) is a progressive and multifactorial pathology that remains asymptomatic in its early stages and lacks effective pharmacological therapies. Aortic valve sclerosis (AVSc), the initial phase of FCAVD, is marked by leaflet thickening and early calcium deposition without significant hemodynamic changes. While local inflammation is known to drive valvular remodeling, recent studies suggest that systemic inflammation may also play a critical role, potentially interacting with endothelial (VEC) and interstitial cells (VIC) and thus promoting disease progression. Notably, sex differences in fibrocalcific processes have been identified, yet their mechanistic basis remains understudied. Thus, we hypothesize that systemic inflammation exacerbates endothelial dysfunction and accelerates fibrocalcific remodeling, with distinct processes in men and women, and aim to investigate how these mechanisms contribute to disease progression. Methods:A total of 238 individuals were enrolled across three groups: controls (CTRL n = 80), AVSc (n = 78), and severe aortic stenosis (AS n = 80). A broad panel of circulating cytokines was measured and analyzed with respect to sex and disease stage. To assess the functional impact of key cytokines, in vitro experiments were conducted using human VECs and VICs treated with interleukin-1β (IL-1β) and interferon-β (IFNβ). Cellular responses were evaluated via morphological analyses, gene and protein expression assays, and calcification potential under normal and pro-osteogenic conditions. Results:Cytokine profiling revealed that AVSc patients exhibited significantly elevated levels of IL-1β compared to both CTRL and AS, with IL-1β being consistently higher in males across all stages. In vitro, IL-1β triggered endothelial-to-mesenchymal transition in VECs, promoting a pro-fibrotic and inflammatory phenotype. Sex-stratified analysis of VICs showed that IFNβ enhanced RUNX2 expression and calcification in a dose-dependent manner, with female-derived VICs being more responsive. Conversely, IFNβ exerted anti-fibrotic effects by reducing COL1A1 and ACTA2 expression, more markedly in female cells, particularly at the protein level. Conclusion:Our findings reveal a previously overlooked role of systemic inflammation, primarily driven by IL-1β and IFNβ, in promoting early endothelial activation and sex-specific fibrocalcific remodeling in FCAVD. These cytokines not only serve as markers of disease but also actively influence cell-specific responses, shaping the distinct aortic valve fibrocalcific patterns observed in men and women. Unraveling these mechanisms could open new avenues for developing early monitoring of circulating IL-1β and IFNβ, while informing sex-specific therapeutic strategies to modulate cytokine signaling to slow or prevent FCAVD progression.

Continuous-flow left ventricular assist devices (LVADs) represent a leading option in the treatment of end-stage heart failure (HF), provided that right ventricular (RV) contractile function is sufficiently preserved to ensure cardiac output after LVAD implantation. In this context, evaluating the RV before surgery is crucial, as the onset of early right heart failure (RHF) following LVAD placement is linked to increased mortality and morbidity. Unfortunately, the contractile performance of the RV is a difficult issue to evaluate and requires a multimodal approach based on the application of multiple diagnostic tools, including clinical assessment, echocardiography, right heart catheterization (RHC), and risk models, all of which have variable predictive power in the currently available literature. Pre-implantation RV assessment is even more challenging and misleading in patients with hemodynamic instability under extracorporeal membrane oxygenation (ECMO) support, a situation characterized by complete right heart unloading, which renders most assessment techniques unreliable. The present paper proposes a simple and comprehensive preoperative appraisal strategy for the RV, which is adapted to the clinical status (critical or more stable) of the patient, based on a review of the advantages and limitations of each diagnostic modality and derived parameters.

We present the first worldwide case of a hybrid surgical-percutaneous procedure involving transvenous lead extraction, concomitant tricuspid valve repair, implantation of an atrioventricular (AV) leadless pacemaker, and extravascular implantable cardioverter-defibrillator placement with suturing of the defibrillation lead to the heart wall. Multiple interventions were necessary as a result of active endocarditis, congenital complete AV block, and ventricular arrhythmia secondary prevention.

We present the first worldwide case of a hybrid surgical-percutaneous procedure involving transvenous lead extraction, concomitant tricuspid valve repair, implantation of an atrioventricular (AV) leadless pacemaker, and extravascular implantable cardioverter-defibrillator placement with suturing of the defibrillation lead to the heart wall. Multiple interventions were necessary as a result of active endocarditis, congenital complete AV block, and ventricular arrhythmia secondary prevention.

Introduction: Mitral valve calcifications increase the complexity of valvular repair. Major calcifications have a known impact on the outcomes, while minor calcifications are less studied. We aim to define the role of minor mitral valve calcification on long term results of valvular repair. Methods: Retrospective study on patients who underwent mitral valve repair between 2001 and 2010. Patients who had a degenerative mitral valve disease, minor calcification at pre-operative echocardiogram confirmed at surgical inspection and no employment of decalcification techniques were included. A control group was selected using a 1:2 match using propensity score. Kaplan-Meier curves estimated long term survival and mitral valve events (recurrent mitral regurgitation>2+, mitral valve reintervention, endocarditis and cardiac death. Cox- model estimated the unadjusted and adjusted hazard ratio. Results: A total of 1052 patients underwent mitral valve repair and 42(3.99%) met the inclusion criteria. 76 patients were selected to form the Control Group. The only significant preoperative difference among the two groups was the presence of coronaropathy, which was more common in the group with mitral calcification (p-value 0.0283). At follow-up, 30 patients developed the study endpoint (Control Group: n=13, 17.1%; Group with mitral calcification: n=17, 40.5%; p=0.0053). The 19-year survival by Kaplan–Meier analysis showed that mitral valve calcification is associated with a worse survival (HR: 2.538 [1.520-4.238], p=0.0004), even after adjusting for preoperative coronary disease. Conclusions: Minor mitral calcifications are associated with a worse outcome, even after adjusting for preoperative coronary disease. Minor calcification should be taken into account when planning surgery and follow up.

The proliferation of transcatheter aortic valve implantation has alerted clinicians to a specific type of prosthetic degeneration represented by thrombosis. The pathogenesis of this clinical or subclinical phenomenon, which can occur in up to 15% of both surgical and percutaneous procedures, is poorly understood, as is its potential impact on patient prognosis and long-term bioprosthesis durability. Based on this lack of knowledge about the real meaning and importance of bioprosthetic valve thrombosis, the aim of the present review is to draw the clinicians’ attention to its existence, starting from the description of predisposing factors that may require a closer follow-up in such categories of patients, to an in-depth overview of all available imaging modalities with their respective pros and cons. Finally, a glimpse into the future of technology and biomarker development is presented. The hope is to increase the rate of bioprosthetic diagnosis, especially of the subclinical one, in order to understand (thanks to a strict and prolonged follow-up) if it can only be considered as an incidental tomographic entity without significant clinical consequences, or, on the contrary, if it is associated with neurological events or accelerated bioprosthetic degeneration. Nevertheless, despite the technical advances of echocardiography and cardiac tomography in terms of accurate bioprosthesis thrombosis detection, several diagnostic and therapeutic issues remain unresolved, including possible prevention strategies, tailored treatment protocols, and follow-up modalities.

We present the first worldwide case of a hybrid surgical-percutaneous procedure involving transvenous lead extraction, concomitant tricuspid valve repair, implantation of an atrioventricular (AV) leadless pacemaker, and extravascular implantable cardioverter-defibrillator placement with suturing of the defibrillation lead to the heart wall. Multiple interventions were necessary as a result of active endocarditis, congenital complete AV block, and ventricular arrhythmia secondary prevention.

Background Acute mitral regurgitation due to papillary muscle rupture is a severe complication of acute myocardial infarction. Transcatheter edge-to-edge repair is emerging as an effective alternative to surgical treatment, with encouraging outcomes. Leaflet adverse events are rare and are associated with relapse of significant mitral regurgitation.Case summary A 54-year-old man arrived at our hospital with a late presentation of ST-elevation myocardial infarction. During primary percutaneous coronary intervention of the circumflex coronary artery, a partial papillary muscle rupture occurred with acute severe mitral regurgitation and cardiogenic shock. Due to the severe haemodynamic instability, the patient underwent an emergent transcatheter edge-to-edge repair with MitraClip device during Impella support with mitral regurgitation resolution and haemodynamic stabilization. At 2-month follow-up, an interclip leaflet tear occurred with relapse of severe mitral regurgitation, requiring a mitral valve replacement surgery.Discussion Acute mitral regurgitation due to papillary muscle rupture is a serious complication of acute myocardial infarction. Management is based on haemodynamic stabilization and surgery. The transcatheter edge-to-edge repair is emerging as a therapeutic alternative in high-risk cases. Leaflet adverse events rarely occur during the transcatheter edge-to-edge repair procedure or before patient discharge. Our case is the first to report a late leaflet adverse event, occurring two months after the procedure and, interestingly, after an acute myocardial infarction conditioning an ischaemic mitral regurgitation. This event may be the result of the progressive adverse remodelling of left ventricular inferolateral akinetic wall, with consequent increase of tethering forces on the posterior leaflet, tensioned in the opposite direction by the clip. 10.1093/ehjcr/ytae533_video1 Video Abstract ytae533media1 6362428009112

The case presents a traumatic ventricular perforation of a girl, accidentally felt on a sharp instrument. The uniqueness of the case presented is due to the very high infrequency of injuries with this type of sharp object. The 7-year-old girl was transported to the hospital after accidentally falling on a sharp instrument. The child had no signs of heart failure. On opening the chest, it was found that the metal object was lodged in the right ventricle. Quickly proceeded to remove the object and suture the entry hole. After a short hospitalization, the child was discharged completely cured.

BACKGROUND:Up to 50% of patients with advanced small-intestinal neuroendocrine tumors (SI-NETs) and carcinoid syndrome (CS) develop carcinoid heart disease (CHD). However, the true frequency and prognostic markers for CHD in CS are lacking. We described the real-world management of patients in two NET referral centers in this clinical context and relationships between clinical features, including CHD and overall survival (OS). PATIENTS AND METHODS:This is a retrospective analysis of patients with stage IV SI-NET and CS, treated at the European Institute of Oncology in Milan and Uppsala University in Sweden between 2015 and 2021. CHD was defined as at least one moderate right-sided heart valve defect. Median OS and cumulative incidence of CHD were estimated from the diagnosis of metastatic disease, and the association between clinical parameters with both OS and occurrence of CHD was evaluated. RESULTS:We included 165 patients, with 97% having low-intermediate-grade SI-NETs and 86% having synchronous liver metastases. Ninety-eight patients (59%) became refractory to full label dose of somatostatin analogues and 25% developed a CHD. At CHD diagnosis, baseline urine 5-hydroxyindoleacetic acid (24-h u5-HIAA) value and plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) value were known in 76% of patients. Moderate-to-severe tricuspid insufficiency was the most common alteration of CHD. Prognosis was significantly impaired by CHD (multivariable hazard ratio for OS = 2.85, P < 0.001). The median OS from the CHD diagnosis was 4.5 years [95% confidence interval (CI) 2.1-7.2 years], and the 5-year survival rate was 34% (95% CI 13% to 57%). CONCLUSIONS:In our study population of SI-NET patients with CS, more than half had a refractory carcinoid syndrome (RCS) and one-quarter developed a CHD, with a negative impact on OS. Therefore, it is recommended to screen and monitor patients with CS for CHD, ideally with a combination of u5-HIAA, NT-proBNP values, and echocardiography at CS baseline, preferably in NET referral centers.

Background: Neuroendocrine tumors (NET) are known to be associated with development of heart valve disease, the Hedinger syndrome. This is due to the release of vasoactive substances inducing endocardial plaques of fibrous tissues. The disease may be associated with increased mortality. Methods: Herein we analyzed the early and mid-term outcomes of patients who underwent surgery for NET-related heart valve disease at our Institution from March 2019 to March 2024. Results: The present study includes 11 consecutive patients with a mean age of 66.2±7.0 years, of whom eight (72.7%) patients were females. Ten patients underwent replacement of the tricuspid valve, and 6 patients underwent replacement of the pulmonary valve. None of the patients underwent surgery for aortic valve or mitral valve disease. One patient underwent concomitant coronary surgery. One (9.0%) patient died during the index hospitalization because of sepsis. None of the other patients experienced neurological complications, severe bleeding or stage 3 acute kidney disease. At 3-year, all-cause mortality was 57.6%. Conclusions: Surgery for NET-related heart valve disease is associated with relatively low risk of early mortality and morbidity, but in this series more than half of patients have died at 3-year.

Tables number: 0Funding statement: no funding Disclosures: none TEXT Mitral valve prolapse (MVP) affects 2% to 3% of the population and it represents first cause of 2 primary chronic mitral regurgitation (MR) (1). Although as "an abnormal systolic protrusion mitral valve in the left atrium", MVP includes a wide spectrum of anatomical conditions, 4 ranging from Barlow's disease to fibroelastic deficiency (FED). Barlow's disease patients are younger, 5 present redundant myxoid leaflets and elongated (rarely ruptured) chordae, whereas FED is associated 6 with translucent tissue, chordal rupture and flail leaflet in older patients(2). 7Despite thousands of articles on MVP, such pathological entity still presents some blind spots: a full 8 comprehension of its underlying biological bases is far from achievement(3), as well as the rising 9 evidence of a link between MVP, mitral annular disjunction (MAD) and malignant arrhythmias(4). 10Given the excellent results of surgical repair(5), indications to treatment are in continuous evolution 11 aiming at weighing the predicted risk, repair feasibility and precocious markers of cardiac 12 impairment(6). This trend translates into a parallel effort to combine all diagnostic tools for detecting 13 as early as possible criteria of MR severity and their possible impact on heart function.

Abstract Objectives  The aim of the present study was to evaluate the results of isolated coronary artery bypass grafting (CABG) with or without revascularization of the occluded right coronary artery (RCA). Methods  Patients undergoing isolated CABG were included in a prospective European multicenter registry. Outcomes were adjusted for imbalance in preoperative variables with propensity score matching analysis. Late outcomes were evaluated with Kaplan–Meier's method and competing risk analysis. Results  Out of 2,948 included in this registry, 724 patients had a total occlusion of the RCA and were the subjects of this analysis. Occluded RCA was not revascularized in 251 (34.7%) patients with significant variability between centers. Among 245 propensity score-matched pairs, patients with and without revascularization of occluded RCA had similar early outcomes. The nonrevascularized RCA group had increased rates of 5-year all-cause mortality (17.7 vs. 11.7%, p  = 0.039) compared with patients who had their RCA revascularized. The rates of myocardial infarction and repeat revascularization were only numerically increased but contributed to a significantly higher rate of MACCE (24.7 vs. 15.7%, p  = 0.020) at 5 year among patients with nonrevascularized RCA. Conclusion  In this multicenter study, one-third of totally occluded RCAs was not revascularized during isolated CABG for multivessel coronary artery disease. Failure to revascularize an occluded RCA in these patients increased the risk of all-cause mortality and MACCEs at 5 years.

Aim The aim of this study was to assess the impact of surgeon experience and centre volume on early operative outcomes in patients undergoing off-pump coronary artery bypass (OPCAB) surgery.Method Of 7,352 patients in the European Multicenter Study on Coronary Artery Bypass Grafting (E-CABG) registry, 1,549 underwent OPCAB and were included in the present analysis. Using adjusted regression analysis, we compared major early adverse events after procedures performed by experienced OPCAB surgeons (i.e., >20 cases per year; n=1,201) to those performed by non-OPCAB surgeons (n=348). Furthermore, the same end points were compared between procedures performed by OPCAB surgeons in high OPCAB volume centres (off-pump technique used in >50% of cases; n=894) and low OPCAB volume centres (n=307).Results In the experienced OPCAB surgeon group, we observed shorter procedure times (I3 -43.858, 95% confidence interval [CI] -53.322 to -34.393; p<0.001), a lower rate of conversion to cardiopulmonary bypass (odds ratio [OR] 0.284, 95% CI 0.147-0.551; p<0.001), a lower rate of prolonged inotrope or vasoconstrictor use (OR 0.492, 95% CI 0.371-0.653; p<0.001), a lower rate of early postprocedural percutaneous coronary in-terventions (OR 0.335, 95% CI 0.169-0.663; p=0.002), and lower 30-day mortality (OR 0.423, 95% CI 0.194-0.924; p=0.031). In high OPCAB volume centres, we found a lower rate of prolonged inotrope use (OR 0.584, 95% CI 0.419-0.814; p=0.002), a lower rate of postprocedural acute kidney injury (OR 0.382, 95% CI 0.198-0.738; p=0.004), shorter duration of intensive care unit (I3 -1.752, 95% CI -2.240 to -1.264; p<0.001) and hospital (I3 -1.967; 95% CI -2.717 to -1.216; p<0.001) stays, and lower 30-day mortality (OR 0.316, 95% CI 0.114-0.881; p=0.028).Conclusions Surgeon experience and centre volume may play an important role on the early outcomes after OPCAB surgery.

In cardiogenic shock various short-term mechanical assistances may be employed, including an Extra Corporeal Membrane Oxygenator and other non-dischargeable devices. Once hemodynamic stabilization is achieved and the patient evolves towards a persisting biventricular dysfunction or an underlying long-standing end-stage disease is present, aside from Orthotopic Heart Transplantation, a limited number of long-term therapeutic options may be offered. So far, only the Syncardia Total Artificial Heart and the Berlin Heart EXCOR (which is not approved for adult use in the United States unlike in Europe) are available for extensive implantation. In addition to this, the strategy providing two continuous-flow Left Ventricular Assist Devices is still off-label despite its widespread use. Nevertheless, every solution ensures at best a 70% survival rate (reflecting both the severity of the condition and the limits of mechanical support) with patients suffering from heavy complications and a poor quality of life. The aim of the present paper is to summarize the features, implantation techniques, and results of current devices used for adult Biventricular Mechanical Circulatory Support, as well as a glance to future options.

We would like to thank Lin Chen et al. [...].

Objectives: The aim of the present study was to evaluate the risk of late mortality and major adverse cardiovascular and cerebral events after coronary artery bypass grafting (CABG) in patients with prior percutaneous coronary intervention (PCI). Methods: A total of 2948 patients undergoing isolated CABGs were included in a prospective multicenter registry. Outcomes were adjusted for multiple covariates in logistic regression, Cox proportional hazards analysis and competing risk analysis. Results: In all, 2619 patients fulfilled the inclusion criteria of this analysis. Of them, 2199 (79.1%) had no history of PCI and 420 (20.9%) had a prior PCI. An adjusted analysis showed that a single prior PCI and multiple prior PCIs did not increase the risk of 30-day and 5-year mortality. Patients with multiple prior PCIs had a significantly higher risk of 5-year myocardial infarction (SHR 2.566, 95%CI 1.379–4.312) and repeat revascularization (SHR 1.774, 95%CI 1.140–2.763). Similarly, 30-day and 5-year mortality were not significantly increased in patients with prior PCI treatment of single or multiple vessels. Patients with multiple vessels treated with PCI had a significantly higher risk of 5-year myocardial infarction (SHR 2.640, 95%CI 1.497–4.658), repeat revascularization (SHR 1.648, 95%CI 1.029–2.638) and stroke (SHR 2.215, 95%CI 1.056–4.646) at 5-year. The risk for repeat revascularization was also increased with a prior single vessel PCI, but not for other outcomes. Conclusions: Among patients undergoing CABGs, multiple prior PCIs seem to increase the risk of late myocardial infarction and the need for repeat revascularization, but not the risk of mortality.