Background: Although several risk-stratification models have been developed for patients with refractory cardiogenic shock requiring temporary mechanical circulatory support, most primarily predict short- and long-term mortality and do not reliably identify patients who can be successfully weaned from support. Cardiac troponin is routinely measured during the acute phase of myocardial infarction. Cumulative troponin exposure, quantified by the troponin area under the concentration–time curve (T-AUC), correlates with the extent of myocardial necrosis. The objective of this study was to evaluate whether T-AUC could improve prediction of temporary mechanical circulatory support weaning failure. Methods: We conducted a single-centre retrospective cohort study including consecutive adults admitted to our cardiac intensive care unit between January 2014 and September 2025 with acute myocardial infarction-related cardiogenic shock requiring temporary mechanical circulatory support. From serial daily troponin I measurements, cumulative troponin exposure was reconstructed as T-AUC. The primary endpoint was temporary mechanical circulatory support weaning failure, defined as death, durable mechanical circulatory support, or heart transplantation during support or within 30 days after explantation. Results: Among the 159 included patients, 97 (61.0%) reached the primary endpoint. In the adjusted time-dependent Cox model, higher cumulative troponin exposure was independently associated with temporary mechanical circulatory support weaning failure (hazard ratio [HR] 1.40 per 1,000,000 ng/L·day increase, 95% confidence interval [CI] 1.19–1.65; p < 0.0001). Restoration of TIMI 3 flow after revascularisation was associated with a significantly lower risk of failure (HR 0.50, 95% CI 0.31–0.80; p = 0.004). Addition of day-5 T-AUC to the clinical model provided the greatest improvement in discrimination (AUC 0.862, 95% CI 0.797–0.926), followed by peak troponin (AUC 0.848, 95% CI 0.779–0.918). Conclusions: In patients with acute myocardial infarction-related cardiogenic shock requiring temporary mechanical circulatory support, cumulative troponin exposure, quantified by T-AUC, was independently associated with failure to wean from support and provided incremental predictive value beyond established clinical risk factors.

Introduction Cardiac surgery remains a high-risk procedure for bleeding despite advances in patient blood management. Conventional centrifugation-based autotransfusion devices primarily recover red blood cells, losing platelets and coagulation factors. The SAME autotransfusion device (i-SEP, Nantes, France) introduces an innovative filtration-based approach, recovering erythrocytes, leucocytes and platelets to enhance perioperative haemostasis. The main objective is to determine whether the filtration-based SAME device reduces significant perioperative bleeding compared with the centrifugation-based system in high-risk cardiac surgery patients.Methods and analysis The Centrifugation-based vs filtration-based intraOperative cell saLvage on qualiTy of peRioperAtive haemostasis iN cardiac surgEry (COLTRANE) trial is a multicentre, parallel-group, single-blinded, superiority-randomised clinical trial. Conducted over 19 months in 10 French hospitals, the study will target patients at high risk of bleeding undergoing on-pump cardiac surgery via sternotomy. A total of 570 patients (285 per group) are required to achieve 80% statistical power for detecting clinically significant differences. Eligible patients will be randomised to either a centrifugation-based or filtration-based autotransfusion group. Both groups will follow standardised perioperative and cardiopulmonary bypass management, with the devices used only intraoperatively. The primary outcome is the proportion of patients with clinically significant perioperative bleeding defined as classes 2 to 4 of the Universal Definition of Perioperative Bleeding. The secondary outcomes include device efficiency and safety, perioperative haemostasis, lengths of intensive care unit and hospital stays, early postoperative morbidity and 30-day all-cause mortality. Ancillary studies will be performed to evaluate cell recovery and washing performance, the viscoelastic properties of retransfused blood (Quantra Qplus; Stago, Asnières-sur-Seine, France), and the effect of salvaged leucocytes on postoperative inflammation and immune function.Ethics and dissemination This trial has received a favourable opinion from the Committee for the Protection of Persons and authorisation from the French authorities (Comité de protection des personnes Nord Ouest, IDRCB: 2023-A02566-39). Protocol V.1.1 was approved on 22 January 2024. The trial is registered on ClinicalTrials.gov (NCT06425614). The findings will be disseminated through oral communications at national and international scientific meetings and peer-reviewed journal publications. Individual participant data will be made available on reasonable request to qualified researchers, following review and approval by the study sponsor and ethics committee.Trial registration number ClinicalTrials.gov, NCT06425614.

ABSTRACT Background Acute kidney injury (AKI) is one of the most common complications after cardiac surgery with cardiopulmonary bypass (CPB). Renal transplant recipients (RTRs) have a higher risk of cardiac surgery–associated AKI (CSA-AKI). A relationship has been strongly suggested between AKI and poor long-term graft survival. The main objective was to evaluate the impact of on-pump cardiac surgery on the 1-year renal allograft survival rate. Methods The study population consisted of 37 RTRs and 56 non-RTRs who underwent cardiac surgery between 1 January 2010 and 31 December 2019. They were matched according to age, sex, preoperative glomerular function, diabetes and type of surgery. The primary composite outcome was renal survival, defined as patient survival without the requirement for permanent dialysis or new kidney transplantation at 1 year after surgery. Results The renal survival rate was significantly lower in the RTR group than in the non-RTR group [81% versus 96%; odds ratio 0.16 (95% confidence interval 0.03–0.82), P = .03]. The proportion of patients who returned to permanent dialysis was higher in the RTR group than in the non-RTR group (12% versus 0%; P = .02). The proportion of patients with severe AKI was also higher in the RTR group. At 1 year after surgery, serum creatinine level, glomerular filtration rate and all-cause mortality rates were comparable between both groups. Conclusion Patients with a functional renal allograft have a low 1-year renal allograft survival rate after cardiac surgery with CPB. In addition, these patients have significant risks of AKI and acute kidney disease after open-heart surgery.

OBJECTIVES: The aim of this study was to investigate the long-term outcomes of concomitant suture bicuspidization to treat mild or moderate tricuspid regurgitation at the time of mitral valve (MV) surgery.METHODS: Data from patients who underwent MV surgery for degenerative MV regurgitation with mild or moderate tricuspid regurgitation and annular dilatation between January 2009 and December 2017 were analysed. The cohort was divided into 2 groups: mitral valve surgery alone (MVA) and MV surgery with concomitant tricuspid valve (TV) repair.RESULTS: A total of 196 patients were included in the study. MVA and MV surgery with concomitant TV repair were performed in 91 (46.4%) and 105 (53.6%) patients, respectively. Propensity score matching analysis identified 54 pairs. In the matched cohort, 30-day mortality (0.0% vs 1.9%, P = 1.0) and new permanent pacemaker implantation (11.1% vs 7.4%, P = 0.740) did not differ significantly between groups. After a mean follow-up of 6.0 (2.8) years, MV surgery with concomitant TV repair was not associated with increased mortality risk compared to MVA (hazard ratio 1.04, 95% confidence interval 0.47-2.28, P = 0.927) with 10-year overall survival rates of 69.9% and 77.2%, respectively. Furthermore, MV surgery with concomitant TV repair was associated with a significantly reduced progression of TV regurgitation (P < 0.001).CONCLUSIONS: Patients undergoing MV surgery with concomitant TV repair had similar 30-day and long-term survival, similar permanent pacemaker implantation rate and reduced progression of TV regurgitation compared to those undergoing MVA.

As the survival after heart transplantation (HTx) is steadily improving, an increasing number of patients with late cardiac pathologies such as valvular disease is expected to rise. Nevertheless, no guidelines for indication of redo cardiac surgery after HTx exists. The aim of the present systematic review is to describe the results reported in the literature of surgical management of severe aortic and/or mitral valve disease. A systematic review was conducted including studies reporting on adult patients with severe mitral or aortic valve pathology needing surgery after their previous HTx. Exclusion criteria consisted in surgery with no left heart valve surgery, concomitant valve surgery during heart transplant, transcatheter interventions, and heterotopic HTx. A total of 35 papers met our inclusion criteria out of 2755 potentially eligible studies with 44 mitral valve surgery patients and 20 aortic valve surgery patients. In the entire population, the mean time from HTx to reintervention was 6.19 ± 5.22 years. After a mean follow-up of 2.78 ± 3.54 years and 1.53 ± 2.26 years from reintervention, 65.6

Background: In situ laser-fenestrated thoracic aortic endovascular repair (FTEVAR) has emerged as a valuable alternative for aortic arch management. This review assessed the early and follow-up outcomes of in situ laser-FTEVAR in aortic arch pathologies. Methods: The PRISMA statement was followed. The English literature was searched, via Ovid, until 15 October 2022. Observational studies, published after 2000, reporting on early and follow-up outcomes for the in situ laser-FTEVAR were eligible. The Newcastle–Ottawa Scale was used to assess the risk of bias. Primary outcomes were the technical success, stroke, and mortality at 30-days, and the secondary were the mortality and reintervention during follow-up. Results: Six retrospective studies from 591 and 247 patients were included. Fifty-nine (23.9%) patients were managed for aortic arch aneurysms and 146 (59.1%) for dissections; 22.6% of them for type A. Technical success was at 98% (range 90–100%). Eight patients died (3.2%) and 11 cases presented any type of stroke (4.5%) during the 30-day follow-up. The mean follow-up was 15 months (1–40 months). Ten deaths were reported (4.2%); one was aortic-related (10%). Thirteen re-interventions (6.0%) were performed. Conclusions: In situ laser-FTEVAR for aortic arch repair may be performed with high technical success and low 30-day and midterm follow-up mortality, stroke, and re-intervention rates when applied in well selected patients and performed by experienced teams.

Heart failure is the final common stage of most cardiopathies. Cardiomyocytes (CM) connect with others via their extremities by intercalated disk protein complexes. This planar and directional organization of myocytes is crucial for mechanical coupling and anisotropic conduction of the electric signal in the heart. One of the hallmarks of heart failure is alterations in the contact sites between CM. Yet no factor on its own is known to coordinate CM polarized organization. We have previously shown that PDZRN3, an ubiquitine ligase E3 expressed in various tissues including the heart, mediates a branch of the Planar cell polarity (PCP) signaling involved in tissue patterning, instructing cell polarity and cell polar organization within a tissue. PDZRN3 is expressed in the embryonic mouse heart then its expression dropped significantly postnatally corresponding with heart maturation and CM polarized elongation. A moderate CM overexpression of Pdzrn3 ( Pdzrn3 OE) during the first week of life, induced a severe eccentric hypertrophic phenotype with heart failure. In models of pressure-overload stress heart failure, CM-specific Pdzrn3 knockout showed complete protection against degradation of heart function. We reported that Pdzrn3 signaling induced PKC ζ expression, c-Jun nuclear translocation and a reduced nuclear ß catenin level, consistent markers of the planar non-canonical Wnt signaling in CM. We then show that subcellular localization (intercalated disk) of junction proteins as Cx43, ZO1 and Desmoglein 2 was altered in Pdzrn3 OE mice, which provides a molecular explanation for impaired CM polarization in these mice. Our results reveal a novel signaling pathway that controls a genetic program essential for heart maturation and maintenance of overall geometry, as well as the contractile function of CM, and implicates PDZRN3 as a potential therapeutic target for the prevention of human heart failure.

Background: While endothelial dysfunction is suggested to contribute to heart failure with preserved ejection fraction pathophysiology, understanding the importance of the endothelium alone, in the pathogenesis of diastolic abnormalities has not yet been fully elucidated. Here, we investigated the consequences of specific endothelial dysfunction on cardiac function, independently of any comorbidity or risk factor (diabetes or obesity) and their potential effect on cardiomyocyte. Methods: The ubiquitine ligase Pdzrn3 , expressed in endothelial cells (ECs), was shown to destabilize tight junction. A genetic mouse model in which Pdzrn3 is overexpressed in EC (iEC-Pdzrn3) in adults was developed. Results: EC-specific Pdzrn3 expression increased cardiac leakage of IgG and fibrinogen blood-born molecules. The induced edema demonstrated features of diastolic dysfunction, with increased end-diastolic pressure, alteration of dP/dt min, increased natriuretic peptides, in addition to limited exercise capacity, without major signs of cardiac fibrosis and inflammation. Electron microscopic images showed edema with disrupted EC-cardiomyocyte interactions. RNA sequencing analysis of gene expression in cardiac EC demonstrated a decrease in genes coding for endothelial extracellular matrix proteins, which could be related to the fragile blood vessel phenotype. Irregularly shaped capillaries with hemorrhages were found in heart sections of iEC- Pdzrn3 mice. We also found that a high-fat diet was not sufficient to provoke diastolic dysfunction; high-fat diet aggravated cardiac inflammation, associated with an altered cardiac metabolic signature in EC- Pdzrn3 mice, reminiscent of heart failure with preserved ejection fraction features. Conclusions: An increase of endothelial permeability is responsible for mediating diastolic dysfunction pathophysiology and for aggravating detrimental effects of a high-fat diet on cardiac inflammation and metabolism.

Background: Genome-wide association studies have revealed robust associations of common genetic polymorphisms in an intron of the PHACTR-1 (phosphatase and actin regulator 1) gene (chr6p24), with cervical artery dissection, spontaneous coronary artery dissection, and fibromuscular dysplasia. The aim was to assess its role in the pathogenesis of cervical artery dissection or fibromuscular dysplasia. Methods: Using various tissue-specific Cre-driver mouse lines, Phactr1 was deleted either in endothelial cells using 2 tissue-specific Cre-driver (PDGFB [platelet-derived growth factor B]-CreERT2 mice and Tie2 [tyrosine kinase with immunoglobulin and EGF homology domains]-Cre) and smooth muscle cells (smooth muscle actin-CreERT2) with a third tissue-specific Cre-driver. Results: To test the efficacy of the Phactr1 deletion after cre-induction, we confirmed first, a decrease in Phactr1 transcription and Phactr1 expression in endothelial cell and smooth muscle cell isolated from Phactr1iPDGFB and Phactr1iSMA mice. Irrespective to the tissue or the duration of the deletion, mice did not spontaneously display pathological phenotype or vascular impairment: mouse survival, growth, blood pressure, large vessel morphology, or actin organization were not different in knockout mice than their comparatives littermates. Challenging vascular function and repair either by angiotensin II–induced hypertension or limb ischemia did not lead to vascular morphology or function impairment in Phactr1-deleted mice. Similarly, there were no more consequences of Phactr1 deletion during embryogenesis in endothelial cells. Conclusions: Loss of PHACTR-1 function in the cells involved in vascular physiology does not appear to induce a pathological vascular phenotype. The in vivo effect of the intronic variation described in genome-wide association studies is unlikely to involve downregulation in PHACTR-1 expression.

OBJECTIVES:The hypothermic circulatory arrest is a major limitation of the frozen elephant trunk (FET) technique, associated with a high incidence of postoperative mobility and mortality. The aim of this study was to evaluate the surgical outcomes of patients suffering from different aortic arch diseases treated with the release and perfuse technique (RPT).METHODS:We retrospectively reviewed the records of patients who had undergone aortic arch repair with the RPT at our Institution between October 2019 and September 2021. Preoperative, intra-operative, and postoperative data were collected.RESULTS:A total of 18 patients undergoing aortic arch surgery with the use of RPT were analyzed. Twelve of them (67%) were males, and the median age of the entire cohort was 67 (56-73) years. The primary indications for surgery included acute type A aortic dissection (50%), chronic type B aortic dissection (33%), and chronic aneurysms (17%). The median cardiopulmonary bypass-, aortic cross-clamp- and circulatory arrest times were 163 (147-213) min, 69 (51-120) min, and 10 (8-13) min, respectively. The median intensive care unit and hospital stay were 4 (2-7) and 12 (11-16) days, respectively. One patient (6%) died during the first 30 days after surgery.CONCLUSIONS:Considering the anatomical limitations related to the use of this technique, the RPT can be safely performed and could represent a promising strategy to reduce the circulatory arrest time during aortic arch surgery. Nevertheless, further studies are required to demonstrate its efficacy.

(1) Background: Although transcatheter technology is rapidly growing and represents a promising strategy, the surgical approach remains the best way to repair a degenerative mitral valve regurgitation. In this context, robotic surgery is technologically the most advanced method of minimally invasive mitral valve repair. The aim of this study is to present the preliminary results of the initial single-center experience with a new robotic mitral valve repair program. (2) Methods: We retrospectively reviewed the records of patients who underwent robotic mitral valve repair at our Institution between January and September 2021. (3) Results: A total of 29 patients underwent mitral valve repair with annuloplasty and chordal implantation to treat degenerative mitral regurgitation. The procedure's success was achieved in 97% of patients. The 30-day cardiac-related mortality was 0%. The median CPB and cross-clamp times were 189 and 111 min, respectively, with a progressive reduction from the beginning of the robotic program. (4) Conclusions: Considering all the limitations related to the small sample, the presented results of robotic mitral valve repair appear to be encouraging and acceptable. A careful patient selection, a dedicated team, and a robust experience in surgical mitral valve repair are the fundamentals to start a new robotic mitral surgery program.

LVAD implantation in patients with a recently diagnosed cardiomyopathy has been poorly investigated. This work aims at describing the characteristics and outcomes of patients receiving a LVAD within 30 days following the diagnosis of cardiomyopathy. Patients from the ASSIST-ICD study was divided into recently and remotely diagnosed cardiomy-opathy based on the time from initial diagnosis of cardiomyopathy to LVAD implantation using the cut point of 30 days. The primary end point of the study was all-cause mortality at 30-day and during follow-up. A total of 652 patients were included and followed during a median time of 9.1 (2.5 to 22.1) months. In this population, 117 (17.9%) had a recently diagnosed cardiomyopathy and had LVAD implantation after a median time of 15.0 (9.0 to 24.0) days following the diagnosis. This group of patients was significantly younger, with more ischemic cardiomyopathy, more sudden cardiac arrest (SCA) events at the time of the diagnosis and were more likely to receive temporary mechanical support before LVAD compared with the remotely diagnosed group. Postoperative in-hospital survival was similar in groups, but recently diagnosed patients had a better long-term survival after hospital discharge. SCA before LVAD and any cardiac surgery combined with LVAD implantation were identified as 2 independent predictors of postoperative mortality in recently diagnosed patients. In conclusion, rescue LVAD implantation for recently diagnosed severe cardiomyopathy is common in clinical practice. Such patients experience a relatively low postoperative mortality and have a better long-term survival compared with remotely diagnosed patients. (C) 2021 Elsevier Inc. All rights reserved.

We aimed at characterizing the impact of low and high body mass index (BMI) on outcomes after left-ventricular assist device (LVAD) surgery and define the predictors of mortality in patients with abnormal BMI (low/high). This study was conducted in 19 centers from 2006 to 2016. Patients were divided based on their baseline BMI into 3 groups of BMI: low (BMI <= 18.5 kg/m(2)); normal (BMI = 18.5 to 24.99 kg/m(2)) and high (BMI >= 25 kg/ m(2)) (including overweight (BMI = 25 to 29.99 kg/m2), and obesity (BMI >= 30 Kg/m(2))). Among 652 patients, 29 (4.4%), 279 (42.8%) and 344 (52.8%) had a low-, normal-, and high BMI, respectively. Patients with high BMI were significantly more likely men, with more co-morbidities and more history of ventricular/supra-ventricular arrhythmias before LVAD implantation. Patients with abnormal BMI had significantly lower survival than those with normal BMI. Notably, those with low BMI experienced the worst survival whereas overweight or obese patients had similar survival. Four predictors of mortality for LVAD candidates with abnormal BMI were defined: total bilirubin >= 16 mmol/L before LVAD, hypertension, destination therapy, and cardiac surgery with LVAD. Depending on the number of predictor per patients, those with abnormal BMI may be divided in 3 groups of 1-year mortality risk, i.e., low (0 to 1 predictor: 29% and 31%), intermediate (2 to 3 predictors, 51% and 52%, respectively), and high (4 predictors: 83%). In conclusion, LVAD recipients with abnormal BMI experience lower survival, especially underweight patients. Four predictors of mortality have been identified for LVAD population with abnormal BMI, differentiating those a low-, intermediate-, and high risks of death. (c) 2020 Elsevier Inc. All rights reserved.

To develop a reproducible and stable closed chest model of ischemic cardiogenic shock in sheep, with high survival rate and potential insight into human pathology. We established a protocol for multi-step myocardial alcoholisation of the left anterior descending coronary artery by percutaneous ethanol injection. A thorough hemodynamic assessment was obtained by invasive and non-invasive monitoring devices. Repeated blood samples were obtained to determine haemoglobin and alcohol concentration, electrolytes, blood gas parameters and cardiac troponin I. After sacrifice, tissue was excised for quantification of infarction and histology. Cardiogenic shock was characterized by a significant decrease in mean arterial pressure (− 33%), cardiac output (− 29%), dP/dtmax (− 28%), carotid blood flow (− 22%), left ventricular fractional shortening (− 28%), and left ventricle end-systolic pressure–volume relationship (− 51%). Lactate and cardiac troponin I levels increased from 1.4 ± 0.2 to 4.9 ± 0.7 mmol/L (p = 0.001) and from 0.05 ± 0.02 to 14.74 ± 2.59 µg/L (p = 0.001), respectively. All haemodynamic changes were stable over a three-hour period with a 71% survival rate. The necrotic volume (n = 5) represented 24.0 ± 1.9% of total ventricular mass. No sham exhibited any variation under general anaesthesia. We described and characterized, for the first time, a stable, reproducible sheep model of cardiogenic shock obtained by percutaneous intracoronary ethanol administration.