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Permanent pacemaker implantation (PPI) represents a rare complication after cardiac surgery, with no uniform agreement on timing and no information on follow-up. A multi-center retrospective study was designed to assess pacemaker dependency (PMD) and long-term mortality after cardiac surgery procedures. Between 2004 and 2016, PPI-patients from 18 centers were followed. Time-to-event data were evaluated with semiparametric regression Cox models and semiparametric Fine and Gray model for competing risk framework. Of 859 (0.90%) PPI-patients, 30% were pacemaker independent (PMI) at 6 months. PMD showed higher mortality compared with PMI (10-year survival 80.1% +/- 2.6% and 92.2% +2.4%, respectively, log-rank p-value < 0.001) with an unadjusted hazard ratio for death of 0.36 (95% CI 0.20 to 0.65, p< 0.001 favoring PMI) and an adjusted hazard ratio of 0.19 (95% CI 0.08 to 0.45, p< 0.001 with PMD as reference). Crude cumulative incidence function of restored PMI rhythm at follow-up at 6 months, 1 year and 12 years were 30.5% (95% CI 27.3% to 33.7%), 33.7% (95% CI 30.4% to 36.9%) and 37.2% (95% CI 33.8% to 40.6%) respectively. PMI was favored by preoperative sinus rhythm with normal conduction (SR) (HR 2.37, 95% CI 1.65 to 3.40, p< 0.001), whereas coronary artery bypass grafting and aortic valve replacement were independently associated with PMD (HR 0.63, 95% CI 0.45 to 0.88, p = 0.006 and HR 0.807, 95% CI 0.65 to 0.99, p = 0.047 respectively). Time-to-implantation was not associated with increased rate of PMI. Although 30% of PPI-patients are PMI after 6 months, PMD is associated with higher mortality at long term. (C) 2020 The Author(s). Published by Elsevier Inc.

Background: To assess early and late mortality in patients with isolated acute tricuspid valve infective endocarditis (TVIE) using data from a multicenter registry.Methods: From 1983 to 2018, isolated acute TVIE was surgically treated in 157 (3.8%) patients [mean age 47 +/- 16 years (range 15-86 years), 25% females]. Of these, 142 (90%) had native tricuspid regurgitation, 7 (5%) native tricuspid valve (TV) steno-regurgitation, and 8 (5%) prosthetic TVIE. Intravenous drug use (IVDU) was recorded in 38% of patients, infection involved cardiac implantable electronic device leads in 21%, and vascular catheters for dialysis in 1%; in the remaining cases, the cause was unknown. The primary endpoint was in-hospital outcome, long-term freedom from recurrence and overall survival.Results: Overall, 77 (49%) patients underwent TV repair, 72 (46%) TV replacement, and 8 (5%) prosthetic TV replacement. Early mortality was 11% (n = 17). Expected early mortality according to EndoSCORE was 12%, with age (odds ratio 1.06) and redo (odds ratio 6.64) as risk factors. Late deaths occurred in 31 patients and TVIE recurrences in 4. Survival rates at 10, 20, and 25 years were 66%, 60%, and 44%, respectively. Risk factors were age [hazard ratio (HR) 1.06], mycotic TVIE (HR 4.2), IVDU (HR 4.90), infected prosthesis replacement (HR 4.4), and presence of cardiac implantable electronic device leads (HR 3.0). No significant difference was found in valve repair vs. replacement and in IVDUs vs. non-IVDUs.Conclusions: Patients with isolated acute TVIE undergoing surgical treatment show acceptable early and late outcomes. TVIE recurrence was low, and repair of the affected valve does not seem to confer any advantage either at early or long term up to 25 years. (C) 2019 Elsevier B.V. All rights reserved.

Background: The aim of this multicenter prospective study was to evaluate the prognostic weight of preoperative right ventricular assessment on early mortality in cardiac surgery. Methods: This is a multicenter prospective observational study performed by the Italian Group of Research for Outcome in Cardiac Surgery (GIROC) including 11 centers. From October 2017 to March 2019, out of 923 patients undergoing cardiac surgery, 28 patients with some missing data were excluded and 895 patients were enrolled in the study right ventricular dilatation was defined as a basal end-diastolic diameter >42 mm. The right ventricle (RV) function was assessed using the combination of three parameters: fractional area changing (FAC), tricuspid annular plane systolic excursion (TAPSE), and S'-wave using tissue Doppler imaging (TDI-S'); RV dysfunction was defined as the presence of at least two of the following cutoffs: FAC

OBJECTIVES Our goal was to evaluate the impact of gender on the 10-year outcome of patients after isolated coronary artery bypass grafting (CABG) included in the Italian nationwide PRedictIng long-term Outcomes afteR Isolated coronary arTery bypass surgery (PRIORITY) study. METHODS The PRIORITY project was designed to evaluate the long-term outcomes of patients who underwent CABG and were included in 2 prospective multicentre cohort studies. The primary end point of this analysis was major adverse cardiac and cerebrovascular events. Baseline differences between the study groups were balanced with propensity score matching and inverse probability of treatment. Time to events was analysed using Cox regression and competing risk analysis. RESULTS The study population comprised 10 989 patients who underwent isolated CABG (women 19.6%). Propensity score matching produced 1898 well-balanced pairs. The hazard of major adverse cardiac and cerebrovascular event was higher in women compared to men [adjusted hazard ratio (HR) 1.13, 95% confidence interval (CI) 1.03–1.23; P = 0.009]. The incidence of major adverse cardiac and cerebrovascular event in women was significantly higher at 1 year (HR 1.31, 95% CI 1.11–1.55; P CONCLUSIONS The present study documented an excess of non-fatal cardiac events after CABG among women despite comparable 10-year survival with men. These findings suggest that studies investigating measures of tertiary prevention are needed to decrease the risk of adverse cardiovascular events among women.

OBJECTIVES Endocarditis after the Bentall procedure is a severe disease often complicated by a pseudoaneurysm or mediastinitis. Reoperation is challenging but conservative therapy is not effective. The aim of this study was to assess short- and midterm outcomes of patients reoperated on for Bentall-related endocarditis. METHODS Seventy-three patients with Bentall procedure-related endocarditis were recorded in the Italian registry. The mean age was 57 ± 14 years and 92% were men; preoperative comorbidities included hypertension (45%), diabetes (12%) and renal failure (11%). The logistic EuroSCORE was 25%; the EuroSCORE II was 8%. RESULTS Preoperatively, 12% of the patients were in septic shock; left ventricular-aortic discontinuity was present in 63% and mitral valve involvement occurred in 12%. The most common pathogens were Staphylococcus aureus (22%) and Streptococci (14%). Reoperations after a median interval of 30 months (1–221 months) included a repeat Bentall with a bioconduit (41%), a composite mechanical (33%) or biological valved conduit (19%) and a homograft (6%). In 1 patient, a heart transplant was required (1%); in 12%, a mitral valve procedure was needed. The hospital mortality rate was 15%. The postoperative course was complicated by renal failure (19%), major bleeding (14%), pulmonary failure (14%), sepsis (11%) and multiorgan failure (8%). At multivariate analysis, urgent surgery was a risk factor for early death [hazard ratio 20.5 (1.9–219)]. Survival at 5 and 8 years was 75 ± 6% and 71 ± 7%, with 3 cases of endocarditis relapse. CONCLUSIONS Surgery is effective in treating endocarditis following the Bentall procedure although it is associated with high perioperative mortality and morbidity rates. Endocarditis relapse seems to be uncommon.

SCOPE: It has been proposed that endogenously formed N-nitroso compounds (NOCs) are partly responsible for the link between red meat consumption and colorectal cancer (CRC) risk. As nitrite has been indicated as critical factor in the formation of NOCs, we evaluated the impact of replacing the additive sodium nitrite (E251) by botanical extracts in the PHYTOME project. METHOD AND RESULTS: A human dietary intervention study was conducted in which healthy subjects consumed 300 grams of meat for two weeks, in subsequent order: conventional processed red meat, white meat, and processed red meat with standard or reduced levels of nitrite and added phytochemicals. Consumption of red meat products enriched with phytochemicals leads to a significant reduction in the faecal excretion of NOCs, as compared to traditionally processed red meat products. Gene expression changes identify cell proliferation as main affected molecular mechanism. High nitrate levels in drinking water in combination with processed red meat intake further stimulates NOC formation, an effect that could be mitigated by replacement of E251 by natural plant extracts. CONCLUSION: These findings suggest that addition of natural extracts to conventionally processed red meat products may help to reduce CRC risk, which is mechanistically supported by gene expression analyses.

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

An increased need of extracorporeal membrane oxygenation (ECMO) support is going to become evident as treatment of SARS-CoV-2 respiratory distress syndrome. This is the first report of the Italian Society for Cardiac Surgery (SICCH) on preliminary experience with COVID-19 patients receiving ECMO support. Data from 12 Italian hospitals participating in SICCH were retrospectively analyzed. Between March 1 and September 15, 2020, a veno-venous (VV) ECMO system was installed in 67 patients (94%) and a veno-arterio-venous ECMO in four (6%). Five patients required VA ECMO after initial weaning from VV ECMO. Thirty (42.2%) patients were weaned from ECMO, while 39 (54.9%) died on ECMO, and six (8.5%) died after ECMO removal. Overall hospital survival was 36.6% (n = 26). Main causes of death were multiple organ failure (n = 14, 31.1%) and sepsis (n = 11, 24.4%). On multivariable analysis, predictors of death while on ECMO support were older age (p = 0.048), elevated pre-ECMO C-reactive protein level (p = 0.048), higher positive end-expiratory pressure on ventilator (p = 0.036) and lower lung compliance (p = 0.032). If the conservative treatment is not effective, ECMO support might be considered as life-saving rescue therapy for COVID-19 refractory respiratory failure. However warm caution and thoughtful approaches for timely detection and treatment should be taken for such a delicate patients population.

Due to its ability to irreversibly inactivate platelet cyclooxygenase, low-dose aspirin (ASA) is the most widely used antithrombotic agent. Although, studies in specific types of patients with cardiovascular disease (CVD) have shown an incomplete inhibition of platelet’s cyclooxygenase, which may increase the variability in drug response. Some aspects of ASA pharmacokinetics (PK) still need further investigation. In this study, we aimed to characterise the contribution of esterase enzymes to ASA hydrolysis in the peripheral blood and to assess their activity in 36 healthy subjects (Ctrl) and 77 CVD patients. To this aim, an in vitro assay testing esterase activity in parallel to a liquid chromatography-tandem mass spectrometry method simultaneously detecting ASA and its main metabolites salicylic (SA) and gentisic acids, have been developed. Michaelis-Menten constant (Km) calculation, ASA esterase isoforms characterisation, and ASA PK study were then achieved. The calculated Km identified plasma esterases as the enzymes with the higher affinity for the substrate compared to the RBC ones. Both rivastigmine and 4-bis-nitrophenyl phosphate inhibited plasma esterase activities, suggesting that acetylcholinesterase and carboxylesterase largely contribute to ASA hydrolysis. The feasibility of the method here developed has been explored in Ctrl and CVD patients. The effect of ASA treatment on enzyme activity was further evaluated on an age, sex and BMI matched subgroup of patients and Ctrl (n = 10 for each subgroup, on and off ASA). No overall variations were evidenced in both CVD and Ctrl groups, even when the effect of ASA treatment was tested. This result suggests the absence of any influence of disease state, drug treatments, and comorbidities on plasma esterase and the inability of ASA intake to induce esterase function. In conclusion, the method here developed allows a better characterisation of ASA esterase activity and could be helpful to define the PK-related determinants of ASA responsiveness in order to personalise regimen in specific pathological conditions.

Objective The aim of this study was to describe the clinical course of a consecutive series of patients operated of urgent cardiac surgery during COVID-19 outbreak. Background In Italy, COVID outbreak has mostly occurred in the metropolitan area of Milan, and in the surrounding region of Lombardy, and previously "conventional" hospitals were converted into COVID spokes to increase ICU beds availability, and to allow only urgent CS procedures. Methods Among urgent CS patients (left main stenosis with unstable angina, acute endocarditis, valvular regurgitation with impending heart failure), 10 patients (mean age = 57 ± 9 years), despite a negative admission triage, developed COVID-pneumonia postoperatively, at a median of 7 days after CS. Results Patients showed typical lymphopenia, higher prothrombotic profile, and higher markers of inflammation (ferritin and interleukin-6 values). At the zenith of pulmonary distress, patients presented with severe hypoxia (median PaO2/FIO2 ratio = 116), requiring advanced noninvasive ventilation (Venturi mask and continuous positive airway pressure) in the majority of cases. All patients were treated with hydroxychloroquine, azithromycin, and low-molecular-weight heparin at anticoagulant dose. Overall in-hospital mortality was 10% (1/10), peaking 25% in patients who developed COVID pneumonia immediately after CS. The remaining patients, with late infection, were all discharged home without oxygen support, at a median of 25 days after symptom onset. Conclusions As postoperative mortality in case of COVID pneumonia is not negligible, meticulous rules (precise triage, safe hospital path, high level of protection for health-care teams, prompt diagnosis of suspicious symptoms) should be strictly followed in patients undergoing CS during COVID pandemic. The role of therapies alternative to CS should be further assessed.

Aims Patients with coronary heart disease (CHD) are at very high risk of recurrent events. A strategy to reduce excess risk might be to deliver structured secondary prevention programmes, but their efficacy has been mostly evaluated in the short term and in experimental settings. This is a retrospective case–control study aimed at assessing, in the real world, the efficacy of a secondary prevention programme in reducing long-term coronary event recurrences after coronary artery bypass surgery (CABG). Methods and results Programme participants (henceforth ‘cases’) were men and women aged Conclusion In a real-world setting, taking part in a structured longstanding secondary prevention programme, in addition to usual cardiology care, meaningfully lowers the risk of coronary recurrences.

Background Contemporary scores for estimating perioperative death have been proposed to also predict also long-term death. The aim of the study was to evaluate the performance of the updated European System for Cardiac Operative Risk Evaluation II, The Society of Thoracic Surgeons Predicted Risk of Mortality score, and the Age, Creatinine, Left Ventricular Ejection Fraction score for predicting long-term mortality in a contemporary cohort of isolated aortic valve replacement (AVR). We also sought to develop for each score a simple algorithm based on predicted perioperative risk to predict long-term survival. Methods Complete data on 1,444 patients who underwent isolated AVR in a 7-year period were retrieved from three prospective institutional databases and linked with the Italian Tax Register Information System. Data were evaluated with performance analyses and time-to-event semiparametric regression. Results Survival was 83.0% ± 1.1% at 5 years and 67.8 ± 1.9% at 8 years. Discrimination and calibration of all three scores both worsened for prediction of death at 1 year and 5 years. Nonetheless, a significant relationship was found between long-term survival and quartiles of scores (p < 0.0001). The estimated perioperative risk by each model was used to develop an algorithm to predict long-term death. The hazard ratios for death were 1.1 (95% confidence interval, 1.07 to 1.12) for European System for Cardiac Operative Risk Evaluation II, 1.34 (95% CI, 1.28 to 1.40) for the Society of Thoracic Surgeons score, and 1.08 (95% CI, 1.06 to 1.10) for the Age, Creatinine, Left Ventricular Ejection Fraction score. Conclusions The predicted risk generated by European System for Cardiac Operative Risk Evaluation II, The Society of Thoracic Surgeons score, and Age, Creatinine, Left Ventricular Ejection Fraction scores cannot also be considered a direct estimate of the long-term risk for death. Nonetheless, the three scores can be used to derive an estimate of long-term risk of death in patients who undergo isolated AVR with the use of a simple algorithm.

OBJECTIVES: We described clinical-epidemiological features of prosthetic valve endocarditis (PVE) and assessed the determinants of early surgical outcomes in multicentre design.METHODS: Data regarding 2823 patients undergoing surgery for endocarditis at 19 Italian Centers between 1979 and 2015 were collected in a database. Of them, 582 had PVE: in this group, the determinants of early mortality and complications were assessed, also taking into account the different chronological eras encompassed by the study.RESULTS: Overall hospital (30-day) mortality was 19.2% (112 patients). Postoperative complications of any type occurred in 256 patients (44%). Across 3 eras (1980-2000, 2001-08 and 2009-14), early mortality did not significantly change (20.4%, 17.1%, 20.5%, respectively, P = 0.60), whereas complication rate increased (18.5%, 38.2%, 52.8%, P -2 mg/dl, chronic pulmonary disease, low ejection fraction, non-streptococcal aetiology, active endocarditis, preoperative intubation, preoperative shock and triple valve surgery were significantly associated with mortality. In multivariable analysis, age (OR = 1.02; P = 0.03), renal insufficiency (OR = 2.1; P = 0.05), triple valve surgery (OR = 6.9; P = 0.004) and shock (OR = 4.5; P CONCLUSIONS: PVE surgery remains a high-risk one. The strongest predictors of early outcome of PVE surgery are related to patient's haemodynamic status and microbiological factors.

Objective In this observational prospective study, we assessed the role of clinical variables and circulating biomarkers in graft occlusion at 18 months to identify a signature for graft occlusion. Methods A total of 330 patients undergoing primary elective coronary artery bypass grafting were enrolled. Blood collection for biomarker assessment was performed before surgery and discharge. Patients were then scheduled to undergo coronary computed tomography angiography at 18 months follow-up, and 179 patients underwent coronary computed tomography angiography 18 ± 2 months postoperatively. Results There were 46 of 503 (9.1%) occluded grafts; of these, 29 (63%) were venous and 17 (37%) were arterial grafts; overall, 43 of 179 patients (24%) had at least 1 occluded graft. Logistic mixed effects model assessing independent factors associated with graft occlusion identified that lower D-dimer levels at baseline (odds ratio [OR], 2.58; 95% confidence interval [CI], 1.36-4.89; P = .00) and total protein content at discharge (OR, 1.09; 95% CI, 1.01-1.19; P = .028) were related to overall graft occlusion at follow-up, along with an arterial graft other than the left internal thoracic artery (OR, 2.92; 95% CI, 1.24-6.9; P = .078); moreover, a venous graft emerged was possibly associated with graft occlusion (OR, 1.51; 95% CI, 0.95-2.39; P = .078). By separately analyzing saphenous vein and arterial grafts, D-dimer levels (OR, 2.67; 95% CI, 1.15-6.2; P = .022 and OR, 2.5; 95% CI, 1.01-7.0; P = .05 for venous and arterial graft, respectively) were still associated with arterial and venous graft occlusion at follow-up. Conclusions We identified D-dimer as a biomarker associated with arterial and venous grafts occlusion. This may help stratify patients at risk of graft failure and identify new molecular targets to prevent this complication.

Cardiopulmonary bypass (CPB) surgery, despite heparin administration, elicits activation of coagulation system resulting in coagulopathy. Anti-inflammatory effects of steroid treatment have been demonstrated, but its effects on coagulation system are unknown. The primary objective of this study is to assess the effects of methylprednisolone on coagulation function by evaluating thrombin generation, fibrinolysis, and platelet activation in high-risk patients undergoing cardiac surgery with CPB. The Steroids In caRdiac Surgery study is a double-blind, randomized, controlled trial performed on 7507 patients worldwide who were randomized to receive either intravenous methylprednisolone, 250 mg at anesthetic induction and 250 mg at initiation of CPB (n = 3755), or placebo (n = 3752). A substudy was conducted in 2 sites to collect blood samples perioperatively to measure prothrombin fragment 1.2 (PF1+2, thrombin generation), plasmin-antiplasmin complex (PAP, fibrinolysis), platelet factor 4 (PF4 platelet activation), and fibrinogen. Eighty-one patients were enrolled in the substudy (37 placebo vs 44 in treatment group). No difference in clinical outcome was detected, including postoperative bleeding and need for blood products transfusion. All patients showed changes of all plasma biomarkers with greater values than baseline in both groups. This reaction was attenuated significantly in the treatment group for PF1.2 (P = 0.040) and PAP (P = 0.042) values at the first intraoperative measurement. No difference between groups was detected for PF4. Methylprednisolone treatment attenuates activation of coagulation system in high-risk patients undergoing CPB surgery. Reduction of thrombin generation and fibrinolysis activation may lead to reduced blood loss after surgery.

Here are reviewed the studies conducted on asbestos-amosite pollution and its effects on the health of workers exposed from 1928 to 1973 at the Collotta-Cis factory of Ledro, Italy. The methods adopted to conduct the initial research, involving the population itself and the local administrations are described. The data summarized include: epidemiological studies of mortality carried out in 1977-85 and updated in 2009; results of the investigations carried out throughout the 1980s on the health consequences on workers, their families and residents near the factory; process of environmental cleanup from asbestos of the industrial area, completed in 1989, and the pollution risk assessment in the whole Ledro Valley. Although this was a small community of about 400 workers, these studies show that exposure to asbestos is responsible for the death of 81 people (22 mesotheliomas, 21 asbestosis, 38 malignant tumors of the lung, digestive system, ovary), for 1400 years of life lost, and for about 100 invalidity pensions, as recognized to former workers by INAIL.

BACKGROUND: Perioperative corticosteroid use may reduce acute kidney injury. We sought to test whether methylprednisolone reduces the risk of acute kidney injury after cardiac surgery. METHODS: We conducted a prespecified substudy of a randomized controlled trial involving patients undergoing cardiac surgery with cardiopulmonary bypass (2007-2014); patients were recruited from 79 centres in 18 countries. Eligibility criteria included a moderate-to-high risk of perioperative death based on a preoperative score of 6 or greater on the European System for Cardiac Operative Risk Evaluation I. Patients (n = 7286) were randomly assigned (1:1) to receive intravenous methylprednisolone (250 mg at anesthetic induction and 250 mg at initiation of cardiopulmonary bypass) or placebo. Patients, caregivers, data collectors and outcome adjudicators were unaware of the assigned intervention. The primary outcome was postoperative acute kidney injury, defined as an increase in the serum creatinine concentration (from the preoperative value) of 0.3 mg/dL or greater (≥ 26.5 μmol/L) or 50% or greater in the 14-day period after surgery, or use of dialysis within 30 days after surgery. RESULTS: Acute kidney injury occurred in 1479/3647 patients (40.6%) in the methylprednisolone group and in 1426/3639 patients (39.2%) in the placebo group (adjusted relative risk 1.04, 95% confidence interval 0.96 to 1.11). Results were consistent across several definitions of acute kidney injury and in patients with preoperative chronic kidney disease. INTERPRETATION: Intraoperative corticosteroid use did not reduce the risk of acute kidney injury in patients with a moderate-to-high risk of perioperative death who had cardiac surgery with cardiopulmonary bypass. Our results do not support the prophylactic use of steroids during cardiopulmonary bypass surgery. Trial registration: ClinicalTrials.gov, no. NCT00427388. ispartof: CANADIAN MEDICAL ASSOCIATION JOURNAL vol:191 issue:9 pages:E247-E256 ispartof: location:Canada status: published

OBJECTIVES The transcarotid (TC) approach for transcatheter aortic valve implantation (TAVI) is potentially an optimal alternative to the transfemoral (TF) approach. Our goal was to compare the safety and efficacy of TC- and TF-TAVI. METHODS Patients who underwent TF-TAVI or TC-TAVI in the prospectively collected FRANCE TAVI registry between January 2013 and December 2015 were compared. Propensity score inverse probability weighting methods were employed to minimize the impact of bias related to non-random treatment assignment. RESULTS Of the 11 033 patients included in the current study, 10 598 (96%) underwent a TF-TAVI and 435 (4.1%) had a TC-TAVI. Patients in the TC-TAVI access group presented with a higher risk profile but were significantly younger. There were no differences in the perioperative and 2-year mortality rates after adjustment [odds ratio (OR) 1.02, 95% confidence interval (CI) 0.62–1.68; P = 0.99 and hazard ratio 1.03, 95% CI 0.7–1.35; P = 0.83). TC-TAVI was associated with a significant risk of stroke (OR 2.42, 95% CI 2.01–2.92; P CONCLUSIONS TC-TAVI is a safe procedure compared to TF-TAVI, although it holds an increased risk of perioperative complications. It should be considered in case of non-femoral peripheral access as the second access choice, to increase the overall safety of TAVI procedures.

Continuous improvement of technologies, devices and drugs needs a renewal and update of current recommendations and guidelines on antithrombotic strategies, especially in those fields where literature lacks of established scientific evidences. Accordingly, the aim of this consensus statement is to provide support for antithrombotic therapy based on current guidelines and the most recent scientific evidences.After an overview on the currently available devices, the appropriate therapy according to type of procedure and implanted device is discussed. The occurrence of postoperative thromboembolic and/or hemorrhagic complications is analyzed, along with the appropriate diagnostic tools and therapeutic approach. A section is dedicated to counseling to pregnancy in women with heart valve prosthesis. Finally, the role of novel oral anticoagulants is discussed, and indications are provided for the management of patients undergoing surgery or interventional procedures on oral anticoagulation therapy.

Aims Mitral valve prolapse (MVP) has a prevalence of 3% in the general population, affecting > 176 million people worldwide. Despite this, little is known about the molecular and cellular mechanisms involved in the progression of MVP and surgical intervention is the only available option. In this study we investigated the role of osteoprotegerin (OPG) during endothelial to mesenchymal transition (EndMT) in MVP. Methods and results VECs and VICs were isolated from posterior mitral valve leaflets of patients undergoing mitral valve repair (n = 25). Plasma was collected from 57 subjects (29 controls and 28 MVP patients). Overexpression of OPG during EndMT followed by autocrine effects characterised by reactive oxygen species increment and accelerated migration was documented. In addition, OPG increased VIC proliferation. Finally, OPG plasma levels were significantly higher in MVP patients compared to control subjects and the area under the ROC curve was 0.92. Conclusion EndMT has been recognised as a possible pathological mechanism for MVP. For the first time, we report the involvement of OPG in cellular and molecular changes in MVP isolated cells. In addition, we detected elevated circulating OPG levels in MVP patients when compared to controls, which supports the hypothesis that OPG is involved in MVP development and progression.

AIMS Despite several studies reporting a higher mortality rate for women undergoing isolated coronary artery bypass graft (CABG) surgery, this issue has not been completely clarified. The aim of the current study was to determine if sex differences in CABG surgery affect adjusted operative results and operative mortality. METHODS Between January 2005 and December 2012, 3756 consecutive patients (3009 men and 747 women) underwent isolated CABG at our institution. Women presented with older age, smaller BSA and higher rate of preoperative comorbidities. The propensity score methodology was used to obtain risk-adjusted outcome comparisons between the two groups. RESULTS The distribution of preoperative variables among matched pairs (553 patients in both groups) was, on average, equal. Propensity-matched women received a similar number of distal anastomoses (P = 0.56), had similar rate of left internal thoracic artery (LITA) graft (P = 0.73) and comparable extracorporeal circulation (P = 0.61) and aortic cross-clamp (P = 0.39) time as men. Postoperative complications were comparable in the two study groups with the exception of postoperative transfusion rate which was significantly higher in women (P = 0.01). However, operative mortality (3.8 vs. 2.7%; P = 0.20), perioperative acute myocardial infarction (P = 0.50) and stroke (P = 0.75) were not significantly different between the two groups. Interestingly, after adjustment for the other baseline characteristics, female patients with diabetes (P = 0.03), preoperative renal dysfunction (P = 0.07) and obesity (P = 0.07) exhibited a greater operative mortality rate compared with men with the same comorbidities. CONCLUSION After adjustment for preoperative variables, female sex seems not to be an independent risk factor for early mortality in isolated CABG surgery. However, renal impairment, diabetes and obesity seem to play an important role in the operative risk profile of women undergoing isolated CABG.

AIMS Ring annuloplasty is the gold standard of surgical repair in degenerative mitral valve disease. However, prosthetic annuloplasty has some drawbacks and potential hazards. Suture annuloplasty theoretically is able to preserve annular leaflet dynamics and left ventricular performance, but experience is limited. The aim of the study was to review the early and long-term outcome of the posterior double-suture annuloplasty (DSA) technique for degenerative mitral valve repair. METHODS From January 2002 to December 2008, 400 patients underwent primary mitral valve repair for degenerative disease either with posterior DSA [n = 147 (37%)] or with flexible posterior annuloplasty band [n = 253 (63%)]. Differences in patient characteristics were addressed by propensity-score matching (132 pairs). A composite end-point of mitral valve failure (MVF) was calculated as the incidence of mitral valve regurgitation greater than 2+ or need for mitral valve replacement at follow-up. RESULTS After propensity-score matching, the distribution of preoperative variables among matched pairs was, on average, equal. Isolated annuloplasty and leaflet repair techniques were similarly performed in both groups (P = 0.20). In-hospital mortality was comparable between the two study groups (P = 0.48). Predischarge echocardiography showed excellent results regarding valve hemodynamics (P = 0.71). At a mean follow-up of 11 ± 3 years, all-cause mortality (P = 0.12), need for mitral valve replacement (P = 0.49), and cardiac re-hospitalization rate (P = 0.57) resulted comparable between the two groups. Ten-year survival (75 vs. 71%, P = 0.51) and freedom from MVF (92 vs. 84%, P = 0.39) were similar between posterior annuloplasty band and DSA groups. CONCLUSION Suture annuloplasty demonstrated comparable results with posterior flexible band repair and could be a viable option for mitral valve surgery in selected patients, such as in the minimally invasive approach, in endocarditis, and in developing countries.

Background: There is still a wide debate concerning the performance of commonly used risk prediction models in assessing the risk of patients undergoing isolated aortic valve surgery. This study was designed to compare the performances of European System for Cardiac Operative Risk Evaluation (EuroSCORE) II and age, creatinine, and ejection fraction (ACEF) score with those of The Society of Thoracic Surgeons (STS) score and logistic EuroSCORE in patients undergoing isolated aortic valve surgery. Methods: Data on 1,758 consecutive patients who underwent isolated aortic valve replacement in a 6-year period were retrieved from 3 prospective institutional databases. Discriminatory power was assessed using the c-index. Calibration was evaluated with calibration curves and associated statistics. Results: In-hospital mortality rate was 1.4%. The discriminatory power was similar in all algorithms (area under the curve 0.80, 95% confidence interval [CI] 0.72 to 0.88 for logistic EuroSCORE; 0.81, 95% CI 0.73 to -0.88 for EuroSCORE II; 0.78, 95% CI 0.68 to 0.88 for ACEF; 0.85, 95% CI 0.78-0.93 for STS score) and not significantly different (p values > 0.05 for all tests). The EuroSCORE II had a better calibration, being the only score with nonsignificant associated statistics (unreliability test, Hosmer-Lemeshow test, and Spiegelhalter Z-test for calibration accuracy). Nonetheless, EuroSCORE II calibration plot highlighted a trend over under-prediction. Conclusions: The EuroSCORE II is a good predictor of perioperative mortality in isolated aortic valve surgery, with lower discrimination if compared with STS and a better calibration when compared with logistic EuroSCORE, ACEF, and STS scores. Its performance is optimal in the lowest tertile of patients, whereas it under-predicts mortality afterward. None of these algorithms seems suitable for risk estimation in mid and high-risk patients that are the ones who might benefit most from transcatheter procedures. © 2013 The Society of Thoracic Surgeons.

The mitral valve is a highly complex structure which regulates blood flow from the left atrium to the left ventricle (LV) avoiding a significant forward gradient during diastole or regurgitation during systole. The integrity of the mitral valve is also essential for the maintenance of normal LV size, geometry, and function. Significant advances in the comprehension of the biological, functional, and mechanical behavior of the mitral valve have recently been made. However, current knowledge of protein components in the normal human mitral valve is still limited and complicated by the low cellularity of this tissue and the presence of high abundant proteins from the extracellular matrix. We employed here an integrated proteomic approach to analyse the protein composition of the normal human mitral valve and reported confident identification of 422 proteins, some of which have not been previously described in this tissue. In particular, we described the ability of pre-MS separation technique based on liquid-phase IEF and SDS-PAGE to identify the largest number of proteins. We also demonstrated that some of these proteins, e.g. αB-Crystallin, septin-11, four-and-a-half LIM domains protein 1, and dermatopontin, are synthesised by interstitial cells isolated from human mitral valves. These initial results provide a valuable basis for future studies aimed at analysing in depth the mitral valve protein composition and at investigating potential pathogenetic molecular mechanisms. Data are available via ProteomeXchange with identifier PXD004397.

International audience; OBJECTIVE: To verify the rate of thromboembolic and hemorrhagic complications during the first 6 months after mitral valve repair and to assess whether the type of antithrombotic therapy influenced clinical outcome. METHODS: Retrospective data were retrieved from 19 centers. Inclusion criteria were isolated mitral valve repair with ring implantation. Exclusion criteria were ongoing or past atrial fibrillation and any combined intraoperative surgical procedures. The study cohort consisted of 1882 patients (aged 58 +/- 15 years; 36% women), and included 1517 treated with an oral anticoagulant (VKA group) and 365 with antiplatelet drugs (APLT group). Primary efficacy outcome was the incidence of arterial thromboembolic events within 6 months and primary safety outcome was the incidence of major bleeding within 6 months. Propensity matching was performed to obtain 2 comparable cohorts (858 vs 286). RESULTS: No differences were detected for arterial embolic complications in matched cohort (1.6% VKA vs 2.1% APLT; P = .50). Conversely, patients in the APLT group showed lower incidence of major bleeding complications (3.9% vs 0.7%; P = .01). Six-month mortality rate was significantly higher in the VKA group (2.7% vs 0.3%; P = .02). Multivariable analysis in the matched cohort found VKA as independent predictor of major bleeding complications and mortality at 6 months. CONCLUSIONS: Vitamin K antagonist therapy was not superior to antiplatelet therapy to prevent thromboembolic complications after mitral valve repair. Our data suggest that oral anticoagulation may carry a higher bleeding risk compared with antiplatelet therapy, although these results should be confirmed in an adequately powered randomized controlled trial

On-pump cardiac surgery may trigger inflammation and accelerate platelet cyclooxygenase-1 renewal, thereby modifying low-dose aspirin pharmacodynamics. Thirty-seven patients on standard aspirin 100 mg once-daily were studied before surgery and randomized within 36 hours postsurgery to 100 mg once-daily, 100 mg twice-daily, or 200 mg once-daily for 90 days. On day 7 postsurgery, immature and mature platelets, platelet mass, thrombopoietin, glycocalicin, leukocytes, C-reactive protein, and interleukin-6 significantly increased. Interleukin-6 significantly correlated with immature platelets. At day 7, patients randomized to 100 mg once-daily showed a significant increase in serum thromboxane (TX)B

Aims Epidemiological studies strongly suggest a link between stress, depression, and cardiovascular diseases (CVDs); the mechanistic correlation, however, is poorly understood. A single-nucleotide polymorphism in the BDNF gene (BDNFVal66Met), associated with depression and anxiety, has been proposed as a genetic risk factor for CVD. Using a knock-in mouse carrying the BDNFVal66Met human polymorphism, which phenocopies psychiatric-related symptoms found in humans, we investigated the impact of this SNP on thrombosis. Methods and results BDNFMet/Met mice displayed a depressive-like phenotype concomitantly with hypercoagulable state and platelet hyperreactivity. Proteomic analysis of aorta secretome from BDNFMet/Met and wild-type (WT) mice showed differential expression of proteins involved in the coagulation and inflammatory cascades. The BDNF Met allele predisposed to carotid artery thrombosis FeCl3-induced and to death after collagen/epinephrine injection. Interestingly, transfection with BDNFMet construct induced a prothrombotic/proinflammatory phenotype in WT cells. SIRT1 activation, using resveratrol and/or CAY10591, prevented thrombus formation and restored the physiological levels of coagulation and of platelet markers in BDNFMet/Met mice and/or cells transfected with the Met allele. Conversely, inhibition of SIRT1 by sirtinol and/or by specific siRNA induced the prothrombotic/proinflammatory phenotype in WT mice and cells. Finally, we found that BDNF Met homozygosity is associated with increased risk of acute myocardial infarction (AMI) in humans. Conclusion Activation of platelets, alteration in coagulation pathways, and changes in vessel wall protein expression in BDNFMet/Met mice recapitulate well the features occurring in the anxiety/depression condition. Furthermore, our data suggest that the BDNFVal66Met polymorphism contribute to the individual propensity for arterial thrombosis related to AMI.

Background Malignant cardiac tumors are rare and have an extremely poor prognosis even when complete resection is attempted. The aim of this study was to review the experience of primary malignant cardiac tumors in 2 Italian academic hospitals. Methods The hospital records were searched to identify patients with primary malignant cardiac tumors who underwent surgery between January 1979 and December 2012. Secondary cardiac tumors, whether metastatic or invasive, were excluded as were primary sarcomas of the great arteries. Fourteen patients selected from our institution’s surgical series were identified. Eleven (78.6%) were men and 3 (21.4%) were women, and the mean age at surgery was 47.4 years. Results The most common histological type was angiosarcoma (28.6%). The mean survival was 28.8 ± 28 months and it was better in men than in women (30.5 ± 8.7 vs. 21.1 ± 3.2 months). Patients with a radical resection at the first surgery had a longer survival compared to patients with a partial resection (39.9 ± 23.2 vs. 24 ± 4 months). Conclusions The treatment outcome for patients affected by primary malignant heart tumors remains poor. Aggressive surgery alone does not provide good results in terms of survival rate. A new multidisciplinary approach is mandatory to improve long-term survival.

OBJECTIVES: We investigated whether oxidative stress and the arginine/nitric oxide pathway differ in control subjects and in adult patients who are candidates for the three most common cardiac surgical operations: coronary bypass surgery, aortic valve replacement for calcific non-rheumatic aortic stenosis or mitral valve repair for degenerative mitral insufficiency. METHODS: In this prospective observational study, we studied 165 consecutive patients undergoing surgery from January to June 2011 (coronary bypass surgery, n = 63; aortic valve replacement for calcific non-rheumatic aortic stenosis, n = 51; mitral valve repair for degenerative mitral insufficiency, n = 51). Thirty-three healthy subjects with cardiovascular risk factors similar to surgery patients were also studied (Controls). Oxidative stress (the ratio of reduced and oxidized glutathione and urinary isoprostane), antioxidants (alpha- and gamma tocopherol) and factors involved in nitric oxide synthesis (arginine, symmetric and asymmetric dimethylarginine) were measured before surgery. Analysis of variance general linear models and principal component analysis were used for statistical analysis. RESULTS: Surgical patients had increased levels of oxidative stress and decreased levels of antioxidants. Increased levels of nitric oxide inhibitor asymmetric dimethylarginine were detected in surgical candidates, suggesting arginine/nitric oxide pathway impairment. Concerning the differences among surgical procedures, higher oxidative stress and a major imbalance of the ratio between substrate and inhibitors of nitric oxide synthesis were evidenced in patients who were candidates for mitral valve repair with respect to coronary bypass surgery patients and patients with calcific non-rheumatic aortic stenosis. CONCLUSIONS: Patients undergoing cardiac surgery have increased oxidative stress and a trend towards an impaired arginine/nitric oxide pathway with respect to Controls. Patients affected by mitral valve regurgitation show more pronounced perturbations in these pathways. The clinical implications of these findings need to be investigated. © The Author 2013. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Aims Aortic valve sclerosis (AVSc) is a hallmark of several cardiovascular conditions ranging from chronic heart failure and myocardial infarction to calcific aortic valve stenosis (AVS). AVSc, present in 25–30% of patients over 65 years of age, is characterized by thickening of the leaflets with marginal effects on the mechanical proprieties of the valve making its presentation asymptomatic. Despite its clinical prevalence, few studies have investigated the pathogenesis of this disease using human AVSc specimens. Here, we investigate in vitro and ex vivo BMP4-mediated transdifferentiation of human valve interstitial cells (VICs) towards an osteogenic-like phenotype in AVSc. Methods and results Human specimens from 60 patients were collected at the time of aortic valve replacement (AVS) or through the heart transplant programme (Controls and AVSc). We show that non-calcified leaflets from AVSc patients can be induced to express markers of osteogenic transdifferentiation and biomineralization through the combinatory effect of BMP4 and mechanical stimulation. We show that BMP4 antagonist Noggin attenuates VIC activation and biomineralization. Additionally, patient-derived VICs were induced to transdifferentiate using either cell culture or a Tissue Engineering (TE) Aortic Valve model. We determine that while BMP4 alone is not sufficient to induce osteogenic transdifferentiation of AVSc-derived cells, the combinatory effect of BMP4 and mechanical stretch induces VIC activation towards a phenotype typical of late calcified stage of the disease. Conclusion This work demonstrates, for the first time using AVSc specimens, that human sclerotic aortic valves can be induced to express marker of osteogenic-like phenotype typical of advanced severe aortic stenosis.

While the use of antibiotic prophylaxis is clearly advantageous to prevent streptococcal infection, it alters the composition of the gut microbiota in mothers and infants. Enterococcus faecium L3 is one of the best studied probiotic strains and shows strong antagonistic activity against Streptococcus agalactiae due to the production of bacteriocins able to inhibit common gut and vaginal pathogens.We tested an L3-based probiotic formula (iNatal®) on 127 pregnant women attending our gynaecological unit in 2015. We compared the study subjects with 279 pregnant women enrolled in the same year and with 892 other pregnant women who attended our gynaecological unit in 2013 and 2014.The findings demonstrate: (a) the safety profile of the product; (b) its ability to reduce gut disorders; (c) a 6% decrease in the incidence of streptococcal colonization; (d) an approximately 30% decline in episodes of premature rupture of membranes; (e) fewer caesarean sections during labour; and (f) a reduction in pathological umbilical cord blood pH.Our results demonstrate that a probiotic treatment during pregnancy could have unexpected but favourable clinical results. Further randomized, double-blind, placebo controlled studies are now needed to confirm our preliminary findings.

OBJECTIVES: Age, creatinine, ejection fraction (ACEF) score is a simplified algorithm for prediction of mortality after elective cardiac surgery. Although mainly conceived for elective cardiac surgery, no information is available on its performance in non-elective surgery and on comparison with the new EuroSCORE II. This study was undertaken to compare the performance of ACEF score and EuroSCORE II within classes of urgency. METHODS: Complete data on 13 871 consecutive patients who underwent major cardiac surgery in a 6-year period were retrieved from three prospective institutional databases. Discriminatory power was assessed using the c-index and h with Delong, bootstrap and Venkatraman methods. Calibration was evaluated with calibration curves and associated statistics. RESULTS: The in-hospital mortality rate was 2.5%. The discriminatory power of ACEF score within elective and non-elective surgery was similar (area under the curve (AUC) 0.71, 95% confidence interval (CI) 0.67-0.74 and AUC 0.68, 95% CI 0.62-0.73, respectively) but significantly lower than that of EuroSCORE II (AUC 0.80, 95% CI 0.77-0.83 for elective surgery; AUC 0.82, 95% CI 0.78-0.85 for non-elective surgery). The calibration patterns were different in the two subgroups, but the summary statistics underscored a miscalibration in both of them (U-statistic and Spiegelhalter Z-test P-values

Background Multidetector computed tomography (MDCT) is useful in evaluation of coronary artery bypass graft (CABG). However, radiation exposure is a reason for concern. We compared diagnostic performance and effective dose of a new dedicated post-processing reconstruction algorithm with BMI-adapted scanning protocol (MDCT-XTe) vs. standard prospective ECG-triggering protocol (MDCT-XT) and retrospective ECG-triggering (MDCT-Helical), compared to invasive coronary angiography (ICA), in the assessment of grafts and nongrafted or distal runoff coronary arteries. Methods One hundred and nineteen patients with 277 grafts were randomized to Group 1 based on BMI-adapted scanning protocol with prospective ECG-triggering (40 patients), Group 2 with prospective ECG-triggering (39 patients) and Group 3 (40 patients) with retrospective ECG-triggering. Data were acquired using 64-slice MDCT. Results MDCT correctly assessed the patency of all CABG in 3 groups. After comparison with ICA, MDCT was able to correctly detect the occlusion or stenosis of CABG in all groups, with the exception of one case of Group 3. In Group 3 sensitivity, specificity, positive predictive value, negative predictive value and accuracy of CABG evaluation were 100%, 98.4%, 96.7%, 100% and 98.9%, respectively. In Groups 1 and 2 the diagnostic accuracy of CABG evaluation was 100%. Effective radiation dose was 3.5±1.4mSv in Group 1 vs. 7.4±2.6mSv in Group 2 vs. 27.8±9.4mSv in Group 3. Conclusions Our results indicated that MDCT-XTe and MDCT-XT have a diagnostic performance in the evaluation of CABG similar to MDCT-Helical, with a significant reduction of radiation exposure, specially for MDCT-XTe.

SummaryEarly post-operative aspirin improves survival in patients undergoing coronary artery bypass graft (CABG). However, most patients do not benefit of aspirin after CABG, still remaining at risk of thrombotic events due to insufficient platelet inhibition, specifically via the thromboxane (TX) pathway. We evaluated the effect of two aspirin doses (100 or 325 mg daily, enteric coated formulations) on platelet function and TX biosynthesis in patients after CABG and assessed whether the incidence of residual platelet reactivity could be reduced by the higher dose. Fifty-six patients undergoing CABG were randomly assigned to 100 or 325 mg aspirin daily for five days in a prospective single-centre study. Treatment effect was assessed by measuring either platelet function (light-transmission aggregometry and point-of-care PFA-100®) or TX biosynthesis in collagen-stimulated platelets, serum, urine, and in lipopolysaccharide (LPS)-cultured whole blood (WB). An insufficient TX inhibition was observed with 100 mg aspirin but not with the higher dose. The different effect of the two doses was, however, highlighted by either TX (platelet- or serum-derived) or by PFA-100® but not by the other assays. In conclusion, early after CABG, the incidence of residual platelet activity was lower in patients who received 325 mg aspirin. Moreover, evidence was provided that different methods yield different results in the detection of aspirin resistance, rendering them not interchangeable.

The performances of the OXY-SCORE, a summary index of oxidative stress, and of its individual components (plasma malondialdehyde (MDA), oxidized and reduced glutathione, individual antioxidant capacity, alpha- and gamma-tocopherol and urinary isoprostanes) were assessed in 47 patients undergoing coronary surgery, randomly assigned to cardiopulmonary bypass (CPB) or off-pump procedure (OPCAB) associated with less oxidative stress. The ability of the OXY-SCORE to classify correctly the patients was high (area under the ROC curve 0.90). Only free MDA showed a similar performance, but it was insensitive to the minor variations of the oxidative balance in the OPCAB group.

Background This study sought to assess inflammation activation in the follow-up (up to one month) of coronary bypass surgery performed both on- (CABG) and off-pump (OPCAB). Methods Thirty patients, candidates for coronary surgery, were randomized to undergo CABG (n = 16) or OPCAB (n = 14). Blood samples were collected before the intervention, after protamine administration, and 4, 8, and 30 days after surgery. Results Plasma tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) levels significantly increased with respect to baseline from protamine administration up to eight postoperative days, whereas high-sensitivity C-reactive protein (hs-CRP) and fibrinogen increased after surgery up to eight postoperative days in both groups. On the other hand, neutrophil elastase levels were higher than baseline from protamine administration up to four postoperative days in CABG, and at the time point eight days after surgery in OPCAB. The only significant differences between CABG and OPCAB in inflammatory markers occurred intraoperatively, after protamine administration, when TNF-α and elastase levels were higher in CABG, whereas no differences were detected between CABG and OPCAB at any postoperative time point. Postoperative increases in fibrinogen and hs-CRP were positively correlated with increases in IL-6, but not with postoperative changes in TNF-α both in CABG and OPCAB. Conclusions After coronary bypass surgery, there is a protracted postoperative activation of inflammation persisting several days after surgery; this postoperative activation is not affected by the surgical strategy (on-pump or off-pump).

A prospective trial was designed to evaluate the effect of hyperbaric oxygen (HBO) therapy on organ/space sternal surgical site infections (SSIs) following cardiac surgery that requires sternotomy.A total of 32 patients who developed postoperative organ/space sternal SSI were enrolled in this study from 1999 through 2005. All patients were offered HBO therapy. Group 1 included the patients who accepted and were able to undergo HBO therapy (n = 14); group 2 included patients who refused HBO therapy or had contraindications to it (n = 18).The two groups were well matched at baseline with comparable preoperative clinical characteristics and operative factors. Staphylococcus was the most common pathogen for both groups. The duration of infection was similar in groups 1 and 2 (31.8 7.6 vs. 29.3 5.7 days, respectively, p = 0.357). The infection relapse rate was significantly lower in group 1 (0% vs. 33.3%, p = 0.024). Moreover, the duration of intravenous antibiotic use (47.8 +/- 7.4 vs. 67.6 +/- 25.1 days, p = 0.036) and total hospital stay (52.6 +/- 9.1 vs. 73.6 +/- 24.5 days, p = 0.026) were both significantly shorter in group 1.Hyperbaric oxygen is a valuable addition to the armamentarium available to physicians for treating postoperative organ/space sternal SSI.

Multidetector computed tomography has been shown to be useful in the evaluation of coronary artery bypass grafts in previous studies. We studied the accuracy of multidetector computed tomography in the detection of patency and significant stenosis of both grafts and native postanastomotic coronary arteries.Ninety-six patients with 216 grafts (98 left mammary artery, 8 right mammary artery, 8 radial artery, and 102 venous grafts) were investigated by 16-slice computed tomography. Native postanastomotic coronary arteries were also evaluated. Patients unable to maintain a breath hold of 40 s were excluded. Computed tomography data were compared with the results of conventional angiography.On a segment-based model, the overall feasibility of computed tomography was 98.1% (212 of 216 grafts) for bypass grafts and 93.1% (201 of 216 segments) for postanastomotic coronary arteries. The leading cause of unfeasibility for postanastomotic coronary arteries was the small diameter of the examined vessel (1.5 mm). Computed tomography correctly diagnosed all the 25 occluded grafts. Of the 33 significant stenoses of grafts, computed tomography correctly diagnosed 31. Sensitivity, specificity, positive predictive value, and negative predictive value were 100%, 98.5%, 96.5%, and 100%, respectively, for bypass graft; and 100%, 97.7%, 85%, and 100%, respectively, for coronary arteries. On a patient-based model, the feasibility, sensitivity, specificity, positive predictive value, and negative predictive value were 89.4% (86 of 96 patients), 100%, 93%, 86.4%, and 100%, respectively.Multidetector computed tomography allows a very accurate assessment of arterial and venous conduits and of postanastomotic native coronary arteries in patients with previous bypass graft. Despite high feasibility (93.1%), limitations of the method were breath-hold duration (35 to 40 s) and postanastomotic assessment of small vessels (which, however, precluded the analysis in only 4.6% of cases).

OBJECTIVES To assess the early and mid-term outcomes and related predictors in a consecutive series of patients who underwent surgical ventricular restoration (SVR) combined with additional mitral valve (MV) repair. METHODS From January 2001 to October 2014, 626 patients underwent SVR; of these, 175 (28%, median age 65) had an additional MV repair. Anterior, inferior or diffuse remodelling was present in 124 (71%), 41 (23%) and 10 (6%) patients, respectively. The median ejection fraction was 30%, whereas mitral regurgitation grade was 3.3 ± 0.8. Multivariable logistic regression and Cox regression analyses were used to identify predictors of early and mid-term mortality. RESULTS Operative death occurred in 25 patients (14.3%). Independent predictors of early mortality were age, creatinine and ejection fraction score [odds ratio (OR) = 5.1, 95% confidence interval (CI) 2.5-10.3], previous stroke (OR = 8.0, 95% CI 1.5-44), unstable angina (OR = 8.8, 95% CI 1.5-53) and diffuse remodelling (OR = 5.8, 95% CI 1.02-33). Average follow-up was 42 ± 37 months. The actuarial survival rate of the whole patient population at 3, 5 and 8 years was 72 ± 4, 65 ± 4 and 45 ± 6%, respectively. Risk factors for late mortality were preoperative creatinine (OR = 2.6, 95% CI 1.5-4.4), previous implantation of cardioverter defibrillator (OR = 4.7, 95% CI 1.6-5.8), whereas the absence of angina at the time of surgery emerged as protective factor (OR = 0.46, 95% CI 0.23-0.89). CONCLUSIONS MV repair combined with SVR is a complex and challenging procedure that can be performed with acceptable early and mid-term results. Interestingly, angina features predict both early and late outcome, with unstable angina at the time of surgery being a predictor of poor early outcome and the absence of angina at surgery, a predictor of favourable outcome at mid-term follow-up.

The radiofrequency maze procedure achieves sinus rhythm in 45%–95% of patients treated for atrial fibrillation. This retrospective study evaluates mid-term results of the radiofrequency maze—performed concomitant to elective cardiac surgery—to determine sinus-rhythm predictive factors, and describes the evolution of patients' echocardiographic variables. From 2003 through 2011, 247 patients (mean age, 64 ± 9.5 yr) with structural heart disease (79.3% mitral disease) and atrial fibrillation underwent a concomitant radiofrequency modified maze procedure. Patients were monitored by 24-hour Holter at 3, 6, 12, and 24 months, then annually. Eighty-four mitral-valve patients underwent regular echocardiographic follow-up. Univariate and multivariate analysis for risk factors of maze failure were identified. The in-hospital mortality rate was 1.2%. During a median follow-up of 39.4 months, the late mortality rate was 3.6%, and pacemaker insertion was necessary in 26 patients (9.4%). Sinus rhythm was present in 63% of patients at the latest follow-up. Predictive factors for atrial fibrillation recurrence were arrhythmia duration (hazard ratio [HR]=1.296, P=0.045) and atrial fibrillation at hospital discharge (HR=2.03, P=0.019). The monopolar device favored maze success (HR=0.191, P Concomitant radiofrequency maze procedure provided remarkable outcomes. Shorter preoperative atrial fibrillation duration, monopolar device use, and prompt treatment of arrhythmia recurrences increase the midterm success rate. Early sinus rhythm restoration seems to result in better left ventricular ejection fraction recovery.

The euroSCORE II has recently been developed to increase the performance of the older versions that have been demonstrated to be miscalibrated. 1 Although the core of the algorithm is similar, some new pieces have been added, among them a different classification of operations and a novel categorization of number of procedures. Nonetheless, no data are available regarding the potential relationship between euroSCORE II performance and surgical procedures. The purpose of this study was to evaluate the impact of surgical procedures on euroSCORE II calibration by modeling the receiver operating characteristic (ROC) curve with a generalized linear model. MATERIALS AND METHODS Data on13,871consecutivepatientswhounderwentcardiacsurgeryina 6-year period were retrieved from the institutional databases that are prospectively collected within the departments of cardiac surgery of two university hospitals and one regional hospital in Italy. The relevant institutional review boards approved the data set’s use for research. The Institutional Ethical Committees approved the study, and the requirement for informed written consent was waived on the condition that subjects’ identities remain masked. Data from the three centers were matched and stored in a dedicated data set. The euroSCORE II was tested on the prediction of in-hospital mortality. Discriminative power was assessed with the c-index (area under the ROC curve [AUC]). To analyze the effect of type of surgery on discriminative power, we modeled the ROC curve with a parametric generalized linear model, with a binormal mode. 2 Two-sided statisticswereperformed.Forallanalyses,theR2.15.1softwarewasused. 3 RESULTS The mean value of euroSCORE II was 3.0 4.1, and the observed mortality was 2.5% (335 patients). The mean age of the study group was 67.4 11.7 years, and 31.4% (4359 patients) were female. A majority of the group underwent isolated or associated coronary artery bypass grafting (CABG; 7449 patients, 53.7%). A preliminary nonparametric analysis of discrimination showed a worse performance of the euroSCORE II in the surgical subgroups not included in the algorithm, such as aortic valve surgery, mitral valve surgery, tricuspid valve surgery (AUC 0.80, 95% confidence interval [CI] 0.77-0.83 vs AUC 0.87, 95% CI 0.83-0.91 for procedures included in the algorithm; Figure 1) The multivariable direct parametric modeling of ROC curves with generalized linear model methodology demonstrated that surgery of the mitral valve significantly lowers the discriminative performance of the euroSCORE II by affecting both parameters that define the ROC curve (intercept 0.38 0.16; 95% CI 0.68 to 0.05; slope 0.36 0.10, 95% CI 0.57 to 0.15; Table 1), leading to a curve that is closer to the diagonal line. The effect of other procedures is not significant, and the performances for these subgroups of patients are comparable to that for patients undergoing CABG. DISCUSSION

ATP acts as a neurotransmitter via seven P2X receptor-channels for Na(+) and Ca(2+), and eight G-protein-coupled P2Y receptors. Despite evidence suggesting roles in human heart, the map of myocardial P2 receptors is incomplete, and their involvement in chronic heart failure (CHF) has never received adequate attention. In left myocardia from five to nine control and 5-12 CHF subjects undergoing heart transplantation, we analyzed the full repertoire of P2 receptors and of 10 "orphan" P2Y-like receptors. All known P2Y receptors (i.e. P2Y(1,2,4,6,11,12,13,14)) and two P2Y-like receptors (GPR91 and GPR17) were detected in all subjects. All known P2X(1-7) receptors were also detected; of these, only P2X(6) was upregulated in CHF, as confirmed by quantitative real time-PCR. The potential significance of this change was studied in primary cardiac fibroblasts freshly isolated from young pigs. Exposure of cardiac fibroblasts to ATP or its hydrolysis-resistant-analog benzoylATP induced apoptosis. TNFalpha (a cytokine implicated in CHF progression) exacerbated cell death. Similar effects were induced by ATP and TNFalpha in a murine cardiomyocytic cell line. In cardiac fibroblasts, TNFalpha inhibited the downregulation of P2X(6) mRNA associated to prolonged agonist exposure, suggesting that, by preventing ATP-induced P2X(6) desensitization, TNFalpha may abolish a defense mechanism meant at avoiding Ca(2+) overload and, ultimately, Ca(2+)-dependent cell death. This may provide a basis for P2X(6) upregulation in CHF. In conclusion, we provide the first characterization of P2 receptors in the human heart and suggest that the interaction between TNFalpha and the upregulated P2X(6) receptor may represent a novel pathogenic mechanism in CHF.

Objective This study investigated whether the activation of coagulation, fibrinolysis, and endothelium occurring during the first postoperative month after on-pump coronary artery bypass surgery differs from that after off-pump coronary artery bypass grafting. Methods Thirty-five patients candidates to coronary surgery were randomized to undergo on-pump (n = 18) or off-pump (n = 17) coronary artery bypass grafting. Blood samples were collected before the intervention and to 1 month after surgery. Results Prothrombin fragment F1.2, thrombin-antithrombin complex, and D-dimer increased after surgery and were persistently higher than preoperative values as late as 30 postoperative days in both on- and off-pump groups; higher levels of these variables were detected after on-pump surgery relative to off-pump surgery only at the time point after termination of cardiopulmonary bypass (fragment F1.2 and thrombin-antithrombin complex) or from bypass end to 8 postoperative days (D-dimer). Fibrinogen levels decreased after surgery and then increased in parallel in both groups to 8 days after surgery. The von Willebrand factor level increased postoperatively in both groups and returned to baseline 30 days after surgery; it was higher after on-pump surgery from bypass end to 8 postoperative days. Soluble vascular cell adhesion molecule 1 was increased significantly from baseline in both groups 30 days after surgery, with no difference between groups. Conclusion Patients undergoing off-pump surgery showed protection against activation of coagulation and fibrinolysis and against endothelial injury only during the intraoperative period; this was followed by the development of a prothrombotic pattern comparable to that of patients undergoing on-pump surgery lasting at least as late as 30 days after surgery.

It is uncertain whether mitral valve replacement is really inferior to mitral valve repair for the treatment of chronic ischemic mitral regurgitation. This multicenter study aimed at providing a contribution to this issue. METHODS: Of 1006 patients with chronic ischemic mitral regurgitation and impaired left ventricular function (ejection fraction < 40%) operated on at 13 Italian institutions between 1996 and 2011, 298 (29.6%) underwent mitral valve replacement whereas 708 (70.4%) received mitral valve repair. Propensity scores were calculated by a nonparsimonious multivariable logistic regression, and 244 pairs of patients were matched successfully using calipers of width 0.2 standard deviation of the logit of the propensity scores. The postmatching median standardized difference was 0.024 (range, 0-0.037) and in none of the covariates did it exceed 10%. RESULTS: Early deaths were 3.3% (n = 8) in mitral valve repair versus 5.3% (n = 13) in mitral valve replacement (P = .32). Eight-year survival was 81.6% ± 2.8% and 79.6% ± 4.8% (P = .42), respectively. Actual freedom from all-cause reoperation and valve-related reoperation were 64.3% ± 4.3% versus 80% ± 4.1%, and 71.3% ± 3.5% versus 85.5% ± 3.9 in mitral valve repair and mitral valve replacement, respectively (P < .001). Actual freedom from all valve-related complications was 68.3% ± 3.1% versus 69.9% ± 3.3% in mitral valve repair and mitral valve replacement, respectively (P = .78). Left ventricular function did not improved significantly, and it was comparable in the 2 groups postoperatively (36.9% vs 38.5%, P = .66). At competing regression analysis, mitral valve repair was a strong predictor of reoperation (hazard ratio, 2.84; P < .001). CONCLUSIONS: Mitral valve replacement is a suitable option for patients with chronic ischemic mitral regurgitation and impaired left ventricular function. It provides better results in terms of freedom from reoperation with comparable valve-related complication rates.

Background: The development of acute kidney injury (AKI) after adult cardiac surgery is associated with increased morbidity and mortality. Our aim was to assess the risk factors for postoperative AKI and whether the addition of perioperative management variables can improve AKI prediction. Methods: We studied 3,219 patients operated from January 2006 to December 2009. The AKI was defined as proposed by the Acute Kidney Injury Network. Patient preoperative characteristics, as well as intraoperative, cardiopulmonary bypass (CPB), and postoperative management variables, were evaluated for association with AKI with logistic regression analysis. The model including all variables was assessed first, then separate models including only preoperative variables followed by the sequential addition of intraoperative, CPB, and postoperative management variables were tested; receiver operating characteristic analysis was used to evaluate and compare models' discriminatory power. Results: The AKI occurred in 288 of 3,219 patients (8.9%). Logistic regression analysis identified 15 predictors of AKI; 4 were preoperative (age, diabetes, smoking, and serum creatinine), 4 intraoperative (inotropes, erythrocytes transfusion, cross-clamp time, and need of a new pump run), 2 CPB-related (urine output and furosemide administration during CPB), and 5 postoperative (erythrocytes transfusion, administration of vasoconstrictors, inotropes, diuretics, and antiarrhythmics). Model-discrimination performance improved from an area under the curve of 0.830 (95% confidence interval 0.807 to 0.854) for the model including only preoperative variables to an area under the curve of 0.904 (95% confidence interval 0.886 to 0.921) for the model including all variables (p < 0.001). Conclusions: Several factors influence AKI development after cardiac surgery and perioperative patient management significantly affects AKI occurrence. Predictive models can be sensibly improved by the addition of these variables. © 2012 The Society of Thoracic Surgeons.

Increased oxidative stress in a failing heart may contribute to the pathogenesis of heart failure (HF). The aim of this study was to identify the oxidised proteins in the myocardium of HF patients and analyse the consequences of oxidation on protein function. The carbonylated proteins in left ventricular tissue from failing (n = 14) and non-failing human hearts (n = 13) were measured by immunoassay and identified by proteomics. HL-1 cardiomyocytes were incubated in the presence of stimuli relevant for HF in order to assess the generation of reactive oxygen species (ROS), the induction of protein carbonylation, and its consequences on protein function. The levels of carbonylated proteins were significantly higher in the HF patients than in the controls (p

The purpose of this study was to compare early and late outcomes after inflammatory and noninflammatory abdominal aortic aneurysm (AAA) repair with emphasis on graft-related complications. Of 625 consecutive patients submitted to AAA repair, 18 were classified as having inflammatory AAAs (group 1). The results of this group were compared with those of 54 patients (group 2) retrospectively drawn from patients who underwent aortic replacement for noninflammatory AAAs. A computer-assisted matching system was used to match patients according to date of birth, gender, and surgical priority. All patients of both groups were followed by periodic clinical and instrumental examinations. Patients in group 1 complained more frequently of aneurysm-related symptoms (72% vs. 20%; p = 0.0001), and their erythrocyte sedimentation rate was elevated more often (78% vs. 19%; p < 0.0001). Surgical morbidity and mortality rates were not different. The mean lengths of follow-up were 61 +/- 47 months (group 1) and 71 +/- 38 months (group 2). The 10-year overall survival rates did not differ significantly between the two groups (49.1% +/- 16.9% for group 1 vs. 61.6% +/- 13.8% for group 2; p = 0.26, log-rank test). In contrast, the free from paraanastomotic aneurysm survival rates were significantly lower in group 1 (57.3% +/- 20.2% vs. 97.8% +/- 2.5% at 10 years; p = 0.025, log-rank test). Long-term outcomes showed a higher incidence of graft-related complications in group 1. As inflammatory aneurysms might represent a risk factor for the development of paraanastomotic aneurysms, routine imaging surveillance of graft aortic healing after inflammatory AAA repair is warranted.