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Traditional and transcatheter surgical treatments of severe aortic valve stenosis (SAVS) are increasing in parallel with the improved life expectancy. Recent randomised controlled trials (RCTs) reported comparable or non-inferior mortality with transcatheter treatments compared with traditional surgery. However, RCTs have the limitation of being a mirror of the predefined inclusion/exclusion criteria, without reflecting the 'real clinical world'. Technological improvements have recently allowed the development of minimally invasive surgical accesses and the use of sutureless valves, but their impact on the clinical scenario is difficult to assess because of the monocentric design of published studies and limited sample size. A prospective multicentre registry including all patients referred for a surgical treatment of SAVS (traditional, through full sternotomy; minimally invasive; or transcatheter; with both 'sutured' and 'sutureless' valves) will provide a 'real-world' picture of available results of current surgical options and will help to clarify the 'grey zones' of current guidelines. Introduction Traditional and transcatheter surgical treatments of severe aortic valve stenosis (SAVS) are increasing in parallel with the improved life expectancy. Recent randomised controlled trials (RCTs) reported comparable or non-inferior mortality with transcatheter treatments compared with traditional surgery. However, RCTs have the limitation of being a mirror of the predefined inclusion/exclusion criteria, without reflecting the 'real clinical world'. Technological improvements have recently allowed the development of minimally invasive surgical accesses and the use of sutureless valves, but their impact on the clinical scenario is difficult to assess because of the monocentric design of published studies and limited sample size. A prospective multicentre registry including all patients referred for a surgical treatment of SAVS (traditional, through full sternotomy; minimally invasive; or transcatheter; with both 'sutured' and 'sutureless' valves) will provide a 'real-world' picture of available results of current surgical options and will help to clarify the 'grey zones' of current guidelines.Methods and analysis European Aortic Valve Registry is a prospective observational open registry designed to collect all data from patients admitted for SAVS, with or without coronary artery disease, in 16 cardiac surgery centres located in six countries (France, Germany, Italy, Spain, Switzerland and UK). Patients will be enrolled over a 2-year period and followed up for a minimum of 5 years to a maximum of 10 years after enrolment. Outcome definitions are concordant with Valve Academic Research Consortium-2 criteria and established guidelines. Primary outcome is 5-year all-cause mortality. Secondary outcomes aim at establishing 'early' 30-day all-cause and cardiovascular mortality, as well as major morbidity, and 'late' cardiovascular mortality, major morbidity, structural and non-structural valve complications, quality of life and echocardiographic results.Ethics and dissemination The study protocol is approved by local ethics committees. Any formal presentation or publication of data will be considered as a joint publication by the participating physician(s) and will follow the recommendations of the International Committee of Medical Journal Editors for authorship.

OBJECTIVES: There are limited reliable data on the long-term survival of patients operated upon with double-valve surgery (DVS) in the literature. In this study, in-hospital mortality and 5-year survival were determined and the potential risk factors for increased mortality were identified and discussed. METHODS: This is a report of an observational retrospective study of 1167 patients undergoing concomitant aortic and mitral valve surgery from 2002 to 2011. Data were prospectively collected in a regional database from Emilia-Romagna (Italy). RESULTS: The overall in-hospital mortality rate for DVS was 6.9%. Both in-hospital and 1-year mortality were statistically significant between age groups. In-hospital mortality was significantly higher for patients with a smaller body mass index (BMI), for those who had concomitant coronary artery bypass grafting (CABG) and those who received mitral valve replacement (MVR) instead of plasty (MVP). Inhospital and 1-year mortality were highest in patients ≥70 who had implantation of mitral and aortic mechanical valves. There were significant differences in 5-year follow-up survival according to age, BMI and concomitant CABG. The choice of MVR and MVP did not affect 5year survival. Multivariable analysis showed that patient-related factors appear to be the major determinant of late survival, irrespective of the type of operation or other intraoperative variables. CONCLUSIONS: Advanced age, smaller BMI and concomitant CABG are significant risk factors for mortality in DVS. MVP provided comparable 5-year outcomes with MVR. Multivariable analysis demonstrates that preoperative and clinical patient-related factors are the real burden in the successful treatment of patients undergoing double-valve procedures.

International audience; BK virus (BKV) reactivation has been increasingly associated with the occurrence of late-onset hemorrhagic cystitis (HC) after allogeneic hematopoietic SCT (allo-HSCT) resulting in morbidity and sometimes mortality. We investigated the incidence, risk factors and outcome of BKV-HC in 323 consecutive adult patients undergoing allo-HSCT over a 5-year period. BK viremia values for HC staging were evaluated, as well as the medico-economic impact of the complication. Forty-three patients developed BKV-HC. In univariate analysis, young age (P=0.028), unrelated donor (P=0.0178), stem cell source (P=0.0001), HLA mismatching (P=0.0022) and BU in conditioning regimen (P=0.01) were associated with a higher risk of developing BKV-HC. In multivariate analysis, patients receiving cord blood units (CBUs) (P=0.0005) and peripheral blood stem cells (P=0.011) represented high-risk subgroups for developing BKV-HC. BK viremia was directly correlated to HC severity (P=0.011) with a 3 to 6-log peak being likely associated with grades 3 or 4 HC. No correlation was found between BKV-HC and acute graft versus host disease or mortality rate. Patients with BKV-HC required a significantly longer duration of hospitalization (P\textless0.0001), more RBC (P=0.0003) and platelet transfusions (P\textless0.0001). Over the 5-year study period, the financial cost of the complication was evaluated at \\[euro]2 376 076 (\3 088 899). Strategies to prevent the occurrence of late-onset BKV-HC after allo-HSCT are urgently needed, especially in CBU and peripheral blood stem cell recipients. BK viremia correlates with the severity of the disease. Prospective studies are required to test prophylactic approaches.

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.

The therapeutic landscape of chronic myeloid leukemia (CML) has profoundly changed over the past 7 years. Most patients with chronic phase (CP) now have a normal life expectancy. Another goal is achieving a stable deep molecular response (DMR) and discontinuing medication for treatment-free remission (TFR). The European LeukemiaNet convened an expert panel to critically evaluate and update the evidence to achieve these goals since its previous recommendations. First-line treatment is a tyrosine kinase inhibitor (TKI; imatinib brand or generic, dasatinib, nilotinib, and bosutinib are available first-line). Generic imatinib is the cost-effective initial treatment in CP. Various contraindications and side-effects of all TKIs should be considered. Patient risk status at diagnosis should be assessed with the new EUTOS long-term survival (ELTS)-score. Monitoring of response should be done by quantitative polymerase chain reaction whenever possible. A change of treatment is recommended when intolerance cannot be ameliorated or when molecular milestones are not reached. Greater than 10% BCR-ABL1 at 3 months indicates treatment failure when confirmed. Allogeneic transplantation continues to be a therapeutic option particularly for advanced phase CML. TKI treatment should be withheld during pregnancy. Treatment discontinuation may be considered in patients with durable DMR with the goal of achieving TFR. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons. org/licenses/by/4.0/.

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: Bilateral internal mammary artery (BIMA) grafting largely is underutilized in patients undergoing coronary artery bypass grafting (CABG), partly because of the perceived increased complexity of the procedure. Aims: In this study, we evaluated whether BIMA grafting can safely be performed also in centers, where this revascularization strategy infrequently is adopted. Methods: Out of 6,783 patients from the prospective multicenter E-CABG study, who underwent isolated non-emergent CABG from January 2015 to December 2016, 2,457 underwent BIMA grafting and their outcome was evaluated in this analysis. Results: The mean number of BIMA grafting per center was 82 cases/year and hospitals were defined as high or low volume, according to this cutoff value. Six hospitals were considered as centers with a high volume of BIMA grafting (no. of procedures ranging from 120 to 267/year; overall: 2,156; prevalence: 62.2%) and nine hospitals as centers with a low volume of BIMA grafting (no. of procedures ranging from 2 to 39/year; overall: 301; prevalence: 9.1%). Multilevel mixed-effects regression analysis showed that the low- and high-volume cohorts had similar outcomes. Propensity score one-to-one matching analysis of 292 pairs showed that the low-volume cohort had a significantly shorter intensive care unit stay (2.2 ± 2.3 versus 2.9 ± 4.8 days, P = .020). The rates of in-hospital death (1.0% versus 0.3%, P = .625), deep sternal wound infection/mediastinitis (3.8% versus 3.1%, P = .824), and 1-year survival (98.1% versus 99.7%, P = .180) as well as other outcomes were similar between the high- and low-volume cohorts. Conclusions: BIMA grafting can be safely performed also in centers in which this revascularization strategy is infrequently performed.

Background: Postoperative bleeding after cardiac surgery is associated with increased morbidity and mortality. We tested the hypothesis that patients with a preoperatively estimated high risk of severe perioperative bleeding may have impaired early outcome after on-pump versus off-pump coronary artery bypass grafting (CABG). Method: Data from 7,352 consecutive patients who underwent isolated CABG from January 2015 to May 2017 were included in the multicentre European Coronary Artery Bypass Grafting registry. The postoperative bleeding risk was estimated using the WILL-BLEED risk score. Of all included patients, 3,548 had an increased risk of severe perioperative bleeding (defined as a WILL-BLEED score ≥4) and were the subjects of this analysis. We compared the early outcomes between patients who underwent on-pump or off-pump CABG using a multivariate mixed model for risk-adjusted analysis. Results: Off-pump surgery was performed in 721 patients (20.3%). On-pump patients received more packed red blood cell units (on-pump: 1.41 [95% confidence interval {CI}, 0.99–1.86]; off-pump: 0.86 [95% CI, 0.64–1.08]; p

Summary The antiplatelet agent ticagrelor has recently been found to have bactericidal activity, demonstrated in vitro and in an in vivo mouse model, which warrants further clinical investigations. The aim of this study was to evaluate infectious complications after coronary artery bypass grafting in patients pre-operatively treated with ticagrelor or clopidogrel. In a multi-centre trial, all adult patients who were pre-operatively treated with ticagrelor or clopidogrel prior to isolated primary coronary artery bypass grafting were eligible. Propensity score matching was used. Outcome measures were any sternal wound infection, deep sternal wound infection, and any in-hospital use of postoperative antibiotics. Of 2311 patients who were included, 1293 (55.9%) received clopidogrel and 1018 (44.1%) ticagrelor pre-operatively. In both overall and propensity score matched analyses, ticagrelor was associated with a similar incidence of infectious complications compared to clopidogrel. Our findings do not support a clinically relevant bactericidal effect of ticagrelor in patients undergoing coronary artery bypass grafting.

Objective: The aim of this multicenter study was to evaluated whether cold or warm cardioplegia are associated with postoperative atrial fibrillation (POAF) and the prognostic role of the latter on early stroke and neurological mortality.Method: This was a retrospective analysis of prospective collected data from 9 cardiac centers in Italy and the United States including patients undergoing surgery between 2010 and 2018. From the 9 institutional databases, 17,231 patients underwent isolated CABG on-pump, using either warm cardioplegia (n = 7730) or cold cardioplegia (n = 9501); among the latter group blood and crystalloid cardioplegia were used in 691 and 8810 patients, respectively. After matching, two pairs of 4162 patients (overall cohort 8324) were analyzed.Results: In matched population, the rate of POAF was 18% (1472 cases), 15% (608) in warm group versus 21% (864) in cold group (p < 0.001). Multivariable analysis confirmed that cold cardioplegia was associated with higher rate of POAF, along with age, hypercholesterolemia, LVEF, reoperation, preoperative IABP, previous stroke, cardiopulmonary and cross-clamp. Moreover, cold cardioplegia as well as POAF increased the rate of postoperative stroke as well as early mortality and neurological mortality Propensity-weighted cohort included 11,830 (70%) patients out of 17,231. After adjustment, both cold blood and cold crystalloid cardioplegia negatively influenced POAF, stroke and neurological mortality.Conclusions: Warm cardioplegia may reduce the rate of POAF in CABG patients with respect to cold cardioplegia, either blood or crystalloid. This has a prognostic impact on postoperative stroke and neurological mortality. (C) 2020 Elsevier B.V. All rights reserved.

Aims Triple valve surgery (TVS) may still be considered a challenge in cardiac surgery, and is still associated with a not negligible mortality and morbidity. This study analyzed retrospectively patients' data from RERIC (Registro Regionale degli Interventi Cardiochirurgici) registry, to evaluate early and mid-term results of TVS. Methods From April 2002 to December 2013, data from n = 44 211 cardiac surgical procedures were collected from six Cardiac Surgery Departments (RERIC). Two hundred and eighty patients undergoing TVS were identified, including aortic and mitral replacement with tricuspid repair in 211 patients (75.3%), aortic replacement with mitral and tricuspid repair in 64 (22.9%) and triple valve replacement in 5 (1.8%). Univariate and multivariate analyses were performed to identify predictors of overall mortality or adverse outcomes. Results The mean age of the patients was 67.5 ± 12.2. Overall in-hospital mortality rate was 7.9%: in-hospital mortality was 10.9% in mitral valve repair and 6.6% in mitral valve replacement, respectively. Tricuspid valve replacement was associated with the highest mortality rate (40%). Independent predictors of in-hospital mortality were serum creatinine greater than 2 mg/dl [odds ratio (OR) 4.5; P = 0.03], concomitant coronary artery bypass graft (CABG) (OR 3.8; P = 0.01) and previous cardiac surgery (OR 5.1; P = 0.04). Overall cumulative mortality rate at 1, 3 and 5 years was 14.7, 24.1 and 28.9%, respectively. Mitral valve replacement associated with tricuspid valve repair showed better survival rate (hazard ratio 0.1; P = 0.007). Conclusion TVS has demonstrated satisfactory results in terms of in-hospital and mid-term mortality rate. Renal failure, reoperations and concomitant CABG resulted as risk factors for mortality; moreover, we could not demonstrate a mid-term better survival rate of mitral valve repair compared with the replacement.

Background: Patients with increased glycated hemoglobin (HbA1c) seem to be at increased risk of sternal wound infection (SWI) after coronary artery bypass grafting (CABG). However, it is unclear whether increased baseline HbA1c levels may affect other postoperative outcomes. Material and methods: Data on preoperative levels of HbA1c were collected from 2606 patients undergoing elective isolated CABG from 2015 to 2016 and included in the prospective, multicenter E-CABG registry. Results: The prevalence of HbA1c ≥ 53 mmol/mol (7.0%) among non-diabetics was 5.3%, among non-insulin dependent diabetics was 53.5% and among insulin dependent diabetics was 67.1% (p < 0.001). The prevalence of HbA1c > 75 mmol/mol (9.0%) among non-diabetics was 0.5%, among non-insulin dependent diabetics was 5.8% and among insulin dependent diabetics was 10.6% (p < 0.001). Baseline levels of HbA1c ≥ 53 mmol/mol (7.0%) was a significant predictor of any SWI (10.7% vs. 3.3%, adjusted p-value

Background The impact of the coronary artery bypass grafting ( CABG ) technique (on‐ versus off‐pump, single versus multiple aortic clamping) on postoperative neurological outcome remains a matter of controversy. The aim of this study was to assess the association between the incidence of postoperative stroke and the degree of aortic manipulation in one of the largest contemporary CABG series. Methods and Results A retrospective, multicenter, international study was conducted in 25 388 patients undergoing isolated CABG procedures with on‐pump CABG ( ONCAB ) or off‐pump CABG ( OPCAB ) technique including single or multiple aortic clamping. Postoperative stroke was defined as a postoperative neurological deficit lasting more than 24 hours and associated with evidence of a brain lesion on computed tomography. The degree of aortic manipulation was assumed to be higher for on‐pump versus off‐pump surgery and for multiple versus single or no aortic clamping. Logistic regression and propensity matching were used. ONCAB procedures were performed in 17 231 cases and OPCAB in 8157. The incidence of postoperative stroke was significantly lower in the OPCAB group even after propensity matching (0.4% OPCAB versus 1.2% ONCAB , P =0.02). In the ONCAB group (but not in the OPCAB arm) the use of single aortic clamping was associated with significantly reduced postoperative stroke rate (odds ratio, 0.05; 95% CI , 0.008 to 0.07 [ P Conclusions OPCAB and the use of single aortic clamping in the ONCAB arm were associated with a reduced incidence of postoperative stroke. Our data confirm a strong association between aortic manipulation and neurological outcome after CABG surgery.

Purpose: The introduction of transcatheter aortic valves has focused attention on the results of conventional aortic valve surgery in high-risk patients. The aim of the study was to evaluate 5-years outcomes in this category of patients in the current surgical era. Methods: This is an observational retrospective study of 581 high-risk patients undergoing aortic valve replacement from 2008 to 2013,with a mean logistic EuroSCORE of 26.6% ± 14.6%. Data were prospectively collected in a database of Emilia-Romagna region (Italy). Results: Overall 30-day mortality was 9.3%. Stroke rate was 1.5%. At 1-,3-,and 5-years overall mortality was 18.2%,30.4%,and 42.2%,cardiac death rate was 3.9%,9.2%,and 12.9%,stroke rate 2.5%,7.7%,and 10.2%,re-operation occurrence 0.2%,0.9% and 1.3%,and new pacemaker implantation was 2.3%,5.1% and 7.8%. At multivariate analysis,urgency,hemodynamic instability,LVEF ≤30%,NYHA III-IV,severe chronic obstructive pulmonary disease (COPD),extra-cardiac arteriopathy,cerebrovascular disease,and creatinine >2.0 mg/dL remained independent predictors of 5-year mortality. Conclusion: The results of the current study add weight to the evidence that traditional aortic valve replacement can be performed in high-risk patients with satisfactory 5-year mortality and morbidity. Our study may help to improve decision-making in this category of high-risk patients with aortic valve disease. © 2016 The Editorial Committee of Annals of Thoracic and Cardiovascular Surgery. All rights reserved.

Aims No data exists on inter-institutional differences in terms of adherence to international guidelines regarding the discontinuation of antithrombotics and rates of severe bleeding in coronary artery bypass grafting (CABG). Methods and results This is an analysis of 7118 patients from the prospective multicentre European CABG (E-CABG) registry who underwent isolated CABG in 15 European centres. Preoperative pause of P2Y12 receptor antagonists shorter than that suggested by the 2017 ESC guidelines (overall 11.6%) ranged from 0.7% to 24.8% between centres (adjusted P < 0.0001) and increased the rate of severe-massive bleeding [E-CABG bleeding grades 2-3, OR 1.66, 95% confidence interval (CI) 1.27-2.17; Universal Definition of Perioperative Bleeding (UDPB) bleeding grades 3-4, OR 1.50, 95% CI 1.16-1.93]. The incidence of resternotomy for bleeding (overall 2.6%) ranged from 0% to 6.9% (adjusted P < 0.0001), and surgical site bleeding (overall 59.6%) ranged from 0% to 84.6% (adjusted P = 0.003). The rate of the UDPB bleeding grades 3-4 (overall 8.4%) ranged from 3.7% to 22.3% (P < 0.0001), and of the E-CABG bleeding grades 2-3 (overall 6.5%) ranged from 0.4% to 16.4% between centres (P < 0.0001). Resternotomy for bleeding (adjusted OR 5.04, 95% CI 2.85-8.92), UDPB bleeding grades 3-4 (adjusted OR 6.61, 95% CI 4.42-9.88), and E-CABG bleeding grades 2-3 (adjusted OR 8.71, 95% CI 5.76-13.15) were associated with an increased risk of hospital/30-day mortality. Conclusions Adherence to the current guidelines on the early discontinuation of P2Y12 receptor antagonists is of utmost importance to reduce excessive bleeding and early mortality after CABG. Inter-institutional variation should be considered for a correct interpretation of the results in multicentre studies evaluating perioperative bleeding and use of blood products.

The impact of thrombocytopenia on postoperative bleeding and other major adverse events after cardiac surgery is unclear. This issue was investigated in a series of patients who underwent isolated coronary artery bypass grafting (CABG) from the prospective, multicenter E-CABG registry. Preoperative thrombocytopenia was defined as preoperative platelet count

Ponatinib has potent activity against native and mutant BCR-ABL1, including BCR-ABL1T315I. The pivotal phase 2 Ponatinib Ph+ ALL and CML Evaluation (PACE) trial evaluated efficacy and safety of ponatinib at a starting dose of 45 mg once daily in 449 patients with chronic myeloid leukemia (CML) or Philadelphia chromosome–positive acute lymphoblastic leukemia (ALL) resistant/intolerant to dasatinib or nilotinib, or with BCR-ABL1T315I. This analysis focuses on chronic-phase CML (CP-CML) patients (n = 270) with 56.8-month median follow-up. Among 267 evaluable patients, 60%, 40%, and 24% achieved major cytogenetic response (MCyR), major molecular response (MMR), and 4.5-log molecular response, respectively. The probability of maintaining MCyR for 5 years was 82% among responders. Dose reductions were implemented in October 2013 to decrease the risk of arterial occlusive events (AOEs); ≥90% of CP-CML patients who had achieved MCyR or MMR maintained response 40 months after elective dose reductions. Estimated 5-year overall survival was 73%. In CP-CML patients, the most common treatment-emergent adverse events were rash (47%), abdominal pain (46%), thrombocytopenia (46%), headache (43%), dry skin (42%), and constipation (41%). The cumulative incidence of AOEs in CP-CML patients increased over time to 31%, while the exposure-adjusted incidence of new AOEs (15.8 and 4.9 per 100 patient-years in years 1 and 5, respectively) did not increase over time. These final PACE results demonstrate ponatinib provides durable and clinically meaningful responses, irrespective of dose reductions, in this population of heavily pretreated CP-CML patients. This trial was registered at www.clinicaltrials.gov as #NCT01207440.

Background Multiple percutaneous coronary interventions ( PCIs ) are considered determinant of poor outcome in patients undergoing coronary artery bypass grafting ( CABG ), but scarce data exist to substantiate this. Methods and Results Patients who underwent CABG without history of prior PCI or with PCI performed >30 days before surgery were selected for the present analysis from the prospective, multicenter E‐CABG (European Multicenter Study on Coronary Artery Bypass Grafting) registry. Out of 6563 patients with data on preoperative SYNTAX (Synergy between PCI With Taxus and Cardiac Surgery) score, 1181 patients (18.0%) had undergone PCI >30 days before CABG . Of these, 11.6% underwent a single PCI , 4.4% 2 PCI s, and 2.1% ≥3 PCI s. PCI of a single main coronary vessel was performed in 11.3%, of 2 main vessels in 4.9%, and of 3 main vessels in 1.6% of patients. Multivariable analysis showed that differences in early mortality and other outcomes were not significantly different in the study cohorts. The adjusted hospital/30‐day mortality rate was 1.8% in patients without history of prior PCI , 1.9% in those with a history of 1 PCI , 1.4% after 2 PCI s, and 2.5% after ≥3 PCI s (adjusted P =0.8). The adjusted hospital/30‐day mortality rate was 2.0% in those who had undergone PCI of 1 main coronary vessel, 1.3% after PCI of 2 main vessels, and 3.1% after PCI of 3 main coronary vessels (adjusted P =0.6). Conclusions Multiple prior PCI s are not associated with increased risk of early adverse events in patients undergoing isolated CABG . The present results are conditional to survival after PCI and should not be viewed as a support for a policy of multiple PCI as opposed to earlier CABG . Clinical Trial Registration URL : http://www.Clinicaltrials.gov . Unique identifier: NCT 02319083.

OBJECTIVES The aim of this study was to assess the impact of frailty on the outcome after coronary artery bypass grafting (CABG) and whether it may improve the predictive ability of European System for Cardiac Operative Risk Evaluation (EuroSCORE II). METHODS The Clinical Frailty Scale (CFS) was assessed preoperatively in patients undergoing isolated CABG from the multicentre E-CABG registry, and patients were stratified into 3 classes: scores 1-2, scores 3-4 and scores 5-7. RESULTS Of the 6156 patients enrolled, 39.2% had CFS scores 1-2, 57.6% scores 3-4, and 3.2% scores 5-7. Logistic regression adjusted for multiple covariates showed that the CFS was an independent predictor of hospital/30-day mortality [CFS scores 3-4, odds ratio (OR) 3.95, 95% confidence interval (CI) 2.19-7.14; CFS scores 5-7, OR 5.90, 95% CI 2.67-13.05] and resulted in an Integrated Improvement Index of 1.3 (P

Cardiovascular disease is the leading cause of mortality in the US and in westernized countries with ischemic heart disease accounting for the majority of these deaths. Paradoxically, the improvements in the medical and surgical treatments of acute coronary syndrome are leading to an increasing number of "survivors" who are then developing heart failure. Despite considerable advances in its management, the gold standard for the treatment of end-stage heart failure patients remains heart transplantation. Nevertheless, this procedure can be offered only to a small percentage of patients who could benefit from a new heart due to the limited availability of donor organs. The aim of this review is to evaluate the safety and efficacy of innovative approaches in the diagnosis and treatment of patients refractory to standard medical therapy and excluded from cardiac transplantation lists. © 2015 Giulio Agnetti et al.

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.

BACKGROUND Excessive bleeding and blood transfusion are associated with adverse outcome after cardiac surgery, but their mechanistic effects are difficult to disentangle in patients with increased operative risk. This study aimed to evaluate the incidence and prognostic impact of bleeding and transfusion of blood products in low-risk patients undergoing coronary artery bypass grafting (CABG). STUDY DESIGN AND METHODS Sixteen tertiary European centers of cardiac surgery contributed to the prospective European registry of CABG (E-CABG). The severity of bleeding was defined by the E-CABG bleeding severity classification and universal definition of perioperative bleeding (UDPB) classification. RESULTS Of 1213 patients with EuroSCORE II of less than 2% (mean, 1.1 ± 0.4%), 18.5% suffered from mild bleeding (E-CABG bleeding Grade 1) and 3.4% experienced severe bleeding (E-CABG bleeding Grade 2-3). Similarly, 19.7% had UDPB Class 2 and 5.9% had UDPB Classes 3 and 4. Mild and severe bleeding defined by the E-CABG and UDPB classifications were associated with an increased risk of several adverse events as adjusted by multiple covariates. The risk of death, stroke, and acute kidney injury was particularly increased in patients with severe bleeding. CONCLUSION Severe bleeding is rather uncommon in low-risk patients undergoing CABG, but it is associated with an increased risk of major adverse events. Prevention of excessive perioperative bleeding and patient blood management may improve the outcome of cardiac surgery also in low-risk patients.

Glycated hemoglobin (HbA1c) is a suspected risk factor for sternal wound infection (SWI) after CABG.Methods and Results:Data on preoperative HbA1c and SWI were available in 2,130 patients undergoing isolated CABG from the prospective E-CABG registry. SWI occurred in 114 (5.4%). Baseline HbA1c was significantly higher in patients with SWI (mean, 54±17 vs. 45±13 mmol/mol, P0.0001). This difference was also observed in patients without a diagnosis of diabetes (P=0.027), in insulin-dependent diabetic (P=0.023) and non-insulin-dependent diabetic patients (P=0.034). In the overall series, HbA1c70 mmol/mol (NGSP units, 8.6%) was associated with the highest risk of SWI (20.6% vs. 4.6%; adjusted OR, 5.01; 95% CI: 2.47-10.15). When dichotomized according to the cut-off 53 mmol/mol (NGSP units, 7.0%) as suggested both for diagnosis and optimal glycemic control of diabetes, HbA1c was associated with increased risk of SWI in the overall series (10.6% vs. 3.9%; adjusted OR, 2.09; 95% CI: 1.24-3.52), in diabetic patients (11.7% vs. 5.1%; adjusted OR, 2.69; 95% CI: 1.38-5.25), in patients undergoing elective surgery (9.9% vs. 2.7%; adjusted OR, 2.09; 95% CI: 1.24-3.52) and in patients with bilateral mammary artery grafts (13.7% vs. 4.8%; adjusted OR, 2.35; 95% CI: 1.17-4.69).Screening for HbA1c before CABG may identify untreated diabetic patients, as well as diabetic patients with suboptimal glycemic control, at high risk of SWI.

Background: The main purpose of this study was to evaluate the impact of gender on outcomes after isolated coronary artery bypass grafting, in terms of 5-year rates of overall death, cardiac-related death, myocardial infarction, re-hospitalization, repeat percutaneous or surgical revascularization, stroke, new pacemaker implantation, postoperative renal failure, heart failure and need for long-term care. Methods: Two propensity-score matched cohorts, each of 1331 patients, undergoing isolated surgical coronary revascularization at the regional public and private centers of Emilia-Romagna region (Italy) from January 1st 2003 to December 31th 2013, were used to compare long-term outcomes of male (5976 patients) versus female gender (1332 patients). Results: In the matched cohort, males received significantly more bypass grafts (3.0 ± 1.0 vs 2.8 ± 1.0, p = 0.001). Left internal mammary artery use and total arterial revascularization were similarly performed in both matched subgroups. Both groups reported similar cumulative rate of all-cause, cardiac-related mortality and stroke at five years. Females experienced significantly higher rate of myocardial infarction, and not significantly higher occurrence of heart failure, and need for long-term care. Males experienced significantly higher rate of cumulative re-hospitalization and higher need for pacemaker implantation. Female gender was not an independent predictor of death at long-term follow-up. Conclusions: Women are more likely to be readmitted with myocardial infarction and congestive heart failure after CABG but experience survival similar to that observed in men. Female gender was not an independent risk factor for mortality. Prevention of new occurrence of postoperative myocardial infarction and enhancement of complete coronary revascularization should be future endpoints. © 2016 The Author(s).

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

OBJECTIVES: The aim of this study was to compare 5-year rates of overall death, cardiac-related death, myocardial infarction, repeat revascularization, stroke and new occurrence of postoperative renal failure in a large cohort of patients with coronary disease, treated with on- or off-pump coronary artery bypass grafting (CABG). METHODS: Two propensity score-matched cohorts, each of 560 patients, undergoing isolated surgical coronary revascularization at the regional public and private centres of Emilia-Romagna region (Italy) over the period 1 January 2003 - 31 December 2013, were used to compare long-term outcomes of on-pump CABG (6711 patients) and off-pump CABG (597 patients). RESULTS: The matched on-pump group received significantly more bypass grafts than the matched off-pump group (2.4 ± 1.1 vs 1.6 ± 0.9, P < 0.0001). The on-pump group reported statistically significant lower cardiac-related mortality. There was a trend towards higher overall mortality and the need for repeat revascularization procedures in the off-pump group. No difference was found for myocardial infarction, stroke or new occurrence of postoperative renal failure between groups in the follow-up. The multivariate analysis of significant predictors of mortality in the overall population confirmed that the off-pump revascularization strategy was an independent predictor of death at long-term follow-up. On-pump CABG reported significantly better results in terms of mortality in the subgroups of patients with a depressed left ventricular ejection fraction and in patients with three-vessel disease. CONCLUSIONS: In patients undergoing elective isolated CABG, on-pump strategy conferred a long-term survival advantage compared with off-pump strategy, particularly for patients with more extensive coronary disease. No benefits were found in terms of reduction of postoperative morbidity with the off-pump strategy. On-pump surgery should be the preferred revascularization technique, and off-pump surgery reserved for patients for whom the perioperative risk of cardiopulmonary bypass is greater than the risk of a less complete coronary revascularization. © The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Background The aim of this study was to compare 7-year rates of all-cause death, cardiac death, myocardial infarction, target vessel revascularization, and stroke in a large cohort of octogenarians with left main coronary artery or multivessel disease, treated with coronary artery bypass grafting or percutaneous coronary intervention. Methods Two propensity score-matched cohorts of patients undergoing revascularization procedures at regional public and private centers of Emilia-Romagna, Italy, from July 2002 to December 2008 were used to compare long-term outcomes of percutaneous coronary intervention (947 patients) and coronary artery bypass grafting (441 patients). Results There were no significant differences between groups in 30-day mortality. In the follow-up the overall and the matched percutaneous coronary intervention population experienced significantly worse outcomes in terms of cardiac mortality, myocardial infarction, and target vessel revascularization. No difference was found for stroke between treatment groups. Percutaneous coronary intervention was an independent predictor of increased death at long-term follow-up. The subgroups in which coronary artery bypass grafting reduced more clearly the risk of death were age 80 to 85 years, previous myocardial infarction, history of cardiac heart failure, chronic renal failure, peripheral vascular disease, and patients with three-vessel disease associated with the left main coronary artery. Conclusions In this real-world setting, surgical coronary revascularization remains the standard of care for patients with left main or multivessel disease. The long-term outcomes of current percutaneous coronary intervention technology in octogenarians are yet to be determined with adequately powered prospective randomized studies. © 2015 The Society of Thoracic Surgeons.

Background Ponatinib is a potent oral tyrosine kinase inhibitor of unmutated and mutated BCR-ABL, including BCR-ABL with the tyrosine kinase inhibitor–refractory threonineto-isoleucine mutation at position 315 (T315I). We conducted a phase 2 trial of ponatinib in patients with chronic myeloid leukemia (CML) or Philadelphia chromosome– positive acute lymphoblastic leukemia (Ph-positive ALL). Methods We enrolled 449 heavily pretreated patients who had CML or Ph-positive ALL with resistance to or unacceptable side effects from dasatinib or nilotinib or who had the BCR-ABL T315I mutation. Ponatinib was administered at an initial dose of 45 mg once daily. The median follow-up was 15 months. Results Among 267 patients with chronic-phase CML, 56% had a major cytogenetic response (51% of patients with resistance to or unacceptable side effects from dasatinib or nilotinib and 70% of patients with the T315I mutation), 46% had a complete cytogenetic response (40% and 66% in the two subgroups, respectively), and 34% had a major molecular response (27% and 56% in the two subgroups, respectively). Responses were observed regardless of the baseline BCR-ABL kinase domain mutation status and were durable; the estimated rate of a sustained major cytogenetic response of at least 12 months was 91%. No single BCR-ABL mutation conferring resistance to ponatinib was detected. Among 83 patients with accelerated-phase CML, 55% had a major hematologic response and 39% had a major cytogenetic response. Among 62 patients with blast-phase CML, 31% had a major hematologic response and 23% had a major cytogenetic response. Among 32 patients with Ph-positive ALL, 41% had a major hematologic response and 47% had a major cytogenetic response. Common adverse events were thrombocytopenia (in 37% of patients), rash (in 34%), dry skin (in 32%), and abdominal pain (in 22%). Serious arterial thrombotic events were observed in 9% of patients; these events were considered to be treatment-related in 3%. A total of 12% of patients discontinued treatment because of an adverse event.

Background: The study compares five-year clinical outcomes of CABG vs PCI in a real world population of diabetic patients with multivessel coronary disease since it is not clear whether to prefer surgical or percutaneous revascularization. Methods: Between July 2002 and December 2008, 2885 multivessel coronary diabetic patients underwent revascularization (1466 CABG and 1419 PCI) at hospitals in Emilia-Romagna Region, Italy and were followed for 1827±617 days by record linkage of two clinical registries with the regional administrative database of hospital admissions and the mortality registry. Five-year incidences of MACCE (mortality, acute myocardial infarction [AMI], stroke, and repeat revascularization [TVR]) were assessed with Kaplan-Meier estimates, Cox proportional hazards regression and cumulative incidence functions of death and TVR, to evaluate the competing risk of AMI on death and TVR. The same analyses were applied to the propensity score matched subgroup of patients undergoing CABG or PCI with DES and with complete revascularization. Results: PCI had higher mortality for all causes (HR: 1.8, 95% CI 1.4-2.2 p

OBJECTIVES: Few data exist on contemporary outcomes after conventional aortic valve replacement (AVR) in the elderly. Accordingly, we evaluated contemporary outcomes and identified predictors of reduced survival in a large series of octogenarians undergoing AVR. METHODS: The Regione Emilia Romagna Cardiac Surgery registry (RERIC) database (n = 2 6938) was queried for clinical features, hospital and mid-term outcomes of octogenarians undergoing AVR between 2003 and 2009. Predictors of hospital and mid-term mortality were identified. RESULTS: The study population consisted of 638 patients. NYHA class III-IV, congestive heart failure, cerebrovascular disease, extra-cardiac arteriopathy, mostly exacerbated patients' clinical profile. Mean log-EuroSCORE was 13.0%. Overall hospital mortality and stroke rates were 4.5% and 1.3%, respectively. Other post-operative complications included renal failure (4.9%), intubation time >48 h (3.4%), complete atrio-ventricular block (4.4%). NYHA III-IV (OR = 2.7; CI 95%:1.2-6.7) and CCS III-IV (OR = 3.1; CI 95%:1.1-9.4) emerged as independent predictors of hospital mortality on multivariate analysis. At 6 years, octogenarians' survival rate was similar to the expected survival of the age- and sex-matched regional population. CCS III-IV (HR = 2.1; CI 95%:1.2-4), preoperative creatinine > 2.1 (HR = 2.8; CI 95%:1.4-5.9), extra-cardiac arteriopathy (HR = 1.5; CI 95%:1.1-2.1) and peripheral neurological dysfunction (HR = 3.8; CI 95%:1.4-10.4) emerged as independent risk factors for decreased 6 years' survival. CONCLUSIONS: This study, showing that contemporary outcomes after AVR are excellent, may help to improve treatment decision-making in elderly patients with aortic valve disease.