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Objectives: T1 mapping (T1-map) and cardiac magnetic resonance feature tracking (CMR-FT) techniques have been introduced for the early detection of interstitial myocardial fibrosis and deformation abnormalities. We sought to demonstrate that T1-map and CMR-FT may identify the presence of subclinical myocardial structural changes in patients with mitral valve prolapse (MVP). Methods: Consecutive MVP patients with moderate-to-severe mitral regurgitation and comparative matched healthy subjects were prospectively enrolled and underwent CMR-FT analysis to calculate 2D global and segmental circumferential (CS) and radial strain (RS) and T1-map to determine global and segmental native T1 (nT1) values. Results: Seventy-three MVP patients (mean age, 57 ± 13 years old; male, 76%; regurgitant volume, 57 ± 21 mL) and 42 matched control subjects (mean age, 56 ± 18 years; male, 74%) were included. MVP patients showed a lower global CS (− 16.3 ± 3.4% vs. − 17.8 ± 1.9%, p = 0.020) and longer global nT1 (1124.9 ± 97.7 ms vs. 1007.4 ± 26.1 ms, p < 0.001) as compared to controls. Moreover, MVP patients showed lower RS and CS in basal (21.6 ± 12.3% vs. 27.6 ± 8.9%, p = 0.008, and − 13.0 ± 6.7% vs. − 14.9 ± 4.1%, p = 0.013) and mid-inferolateral (20.6 ± 10.7% vs. 28.4 ± 8.7%, p < 0.001, and − 12.8 ± 6.3% vs. − 16.5 ± 4.0%, p < 0.001) walls as compared to other myocardial segments. Similarly, MVP patients showed longer nT1 values in basal (1080 ± 68 ms vs. 1043 ± 43 ms, p < 0.001) and mid-inferolateral (1080 ± 77 ms vs. 1034 ± 37 ms, p < 0.001) walls as compared to other myocardial segments. Of note, nT1 values were significantly correlated with CS (r, 0.36; p < 0.001) and RS (r, 0.37; p < 0.001) but not with regurgitant volume. Conclusions: T1-map and CMR-FT identify subclinical left ventricle tissue changes in patients with MVP. Further studies are required to correlate these subclinical tissue changes with the outcome. Key Points: • T1 mapping (T1-map) and cardia

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

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.

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 <150 × 10⁹/L and it was considered moderate-severe when preoperative platelet count was <100 × 10⁹/L. Multilevel mixed-effects regression analysis was performed to adjust the effect of thrombocytopenia on outcomes for baseline and operative covariates as well as for interinstitutional differences in patient-blood management. Among 7189 patients included in this analysis, 599 (8.3%) had preoperative thrombocytopenia. Patient with preoperative thrombocytopenia had an increased chest drainage output at 12 h (mean, 519 vs. 456 mL, adjusted coeff. 39, 95%CI 18–60) and rates of severe-massive bleeding (Universal Definition of Perioperative Bleeding (UDPB) severity grades 3–4: 12.7% vs. 8.1%, adjusted OR 1.47, 95%CI 1.11–1.93; E-CABG bleeding severity grades 2–3: 10.4% vs. 6.1%, adjusted OR 1.78, 95%CI 1.30–2.43). Thrombocytopenia was associated with an increased risk of hospital/30-day death (3.2% vs. 1.9%, adjusted OR 2.02, 95%CI 1.20–3.42), 1-year death (5.7% vs. 3.4%, adjusted HR 1.68, 95%CI 1.16–2.44), deep sternal wound infection (3.5% vs. 2.4%, adjusted OR 1.65, 95%CI 1.02–2.66), acute kidney injury (28.1% vs. 22.2%, OR 1.45, 1.18–1.78), and prolonged stay in the intensive care unit (mean, 3.6 vs 2.8 days, adjusted coeff. 0.74, 95%CI 0.40–1.09). Similar results were observed in a subset of patients with moderate-severe thrombocytopenia (51 patients, 0.7%). In particular, these patients had a markedly higher rate of acute kidney injury (40%, adjusted OR, 1.94, 95%CI 1.05–3.57), resternotomy for bleeding (7.8%, adjusted OR 3.49, 95%CI 1.20–10.21), and severe-massive bleeding (UDPB severity grades 3–4

Background: We evaluated perioperative bleeding after coronary artery bypass grafting (CABG) in patients preoperatively treated with ticagrelor or clopidogrel, stratified by discontinuation of these P2Y₁₂ inhibitors. Methods: All patients from the prospective, European Multicenter Registry on Coronary Artery Bypass Grafting (E-CABG) treated with ticagrelor or clopidogrel undergoing isolated primary CABG were eligible. The primary outcome measure was severe or massive bleeding defined according to the Universal Definition of Perioperative Bleeding, stratified by P2Y₁₂ inhibitor discontinuation. Secondary outcome measures included four additional definitions of major bleeding. Propensity score matching was performed to adjust for differences in preoperative and perioperative covariates. Results: Of 2,311 patients who were included, 1,293 (55.9%) received clopidogrel and 1,018 (44.1%) ticagrelor preoperatively. Mean time between discontinuation and the operation was 4.5 ± 3.2 days for clopidogrel and 4.9 ± 3.0 days for ticagrelor. In the propensity score–matched cohort, ticagrelor-treated patients had a higher incidence of major bleeding according to Universal Definition of Perioperative Bleeding when ticagrelor was discontinued 0 to 2 days compared with 3 days before the operation (16.0% vs 2.7%, p = 0.003). Clopidogrel-treated patients had a higher incidence of major bleeding according to the Universal Definition of Perioperative Bleeding when clopidogrel was discontinued 0 to 3 days compared with 4 to 5 days before the operation (15.6% vs 8.3%, p = 0.031). Conclusions: In patients receiving ticagrelor 2 days before CABG and in those receiving clopidogrel 3 days before CABG, there was an increased rate of severe bleeding. Postponing nonemergent CABG for at least 3 days after discontinuation of ticagrelor and 4 days after clopidogrel should be considered.

The perioperative bleeding risk in patients receiving fondaparinux versus low-molecular weight heparin before coronary artery bypass grafting has not been reported. We evaluated perioperative coronary artery bypass grafting -related bleeding in patients with acute coronary syndrome preoperatively treated with fondaparinux or low-molecular weight heparin. All patients with acute coronary syndrome from the prospective, European multicenter registry on Coronary Artery Bypass Grafting (E-CABG) preoperatively treated with fondaparinux or lowmolecular weight heparin undergoing isolated primary CABG were eligible. The primary outcome measure was severe or massive bleeding defined according to the Universal Definition of Perioperative Bleeding stratified by P2Y12 inhibitor discontinuation. Secondary outcome measures included three additional definitions of major bleeding used in cardiac surgery trials. Propensity score matching was performed to adjust for differences in pre- and perioperative covariates. 1525 patients were included, of whom 276 (18.1%) received fondaparinux and 1249 (81.9%) low-molecular weight heparin preoperatively. In the propensity score-matched cohort (245 pairs), the risk of major bleeding according to the Universal Definition of Perioperative Bleeding severe or massive bleeding (11.8 versus 9.0%, p = 0.285) and the three other major bleeding definitions was similar between the fondaparinux and low-molecular weight heparin cohorts. In conclusion, preoperative treatment with fondaparinux compared to low-molecular weight heparin was associated with similar incidence of perioperative bleeding in patients with acute coronary syndrome undergoing coronary artery bypass grafting.

Background: Bilateral internal mammary artery (BIMA) grafting is increasingly used in elderly patients without evidence of its risks or benefits compared with single internal mammary artery (SIMA) grafting. Methods: In all, 2,899 patients aged 70 years or older (855 [29.5%] underwent BIMA grafting) operated on from January 2015 to December 2016 and included in the prospective multicenter Outcome After Coronary Artery Bypass Grafting (E-CABG) study were considered in this analysis. Results: One-to-one propensity matching resulted in 804 pairs with similar preoperative risk profile. Propensity score matched analysis showed that BIMA grafting was associated with a nonstatistically significant increased risk of inhospital death (2.7% versus 1.6%, p = 0.117). The BIMA grafting cohort had a significantly increased risk of any sternal wound infection (7.7% versus 5.1%, p = 0.031) as well as higher risk of deep sternal wound infection/mediastinitis (4.0% versus 2.2%, p = 0.048). The BIMA grafting cohort required more frequently extracorporeal membrane oxygenation (1.0% versus 0.1%, p = 0.02), and the intensive care unit stay (mean 3.6 versus 2.6 days, p < 0.001) and inhospital stay (mean 11.3 versus 10.0 days, p < 0.001) were significantly longer compared with the SIMA grafting cohort. Test for interaction showed that urgent operation in patients undergoing BIMA grafting was associated with higher risk of inhospital death (5.6% versus 1.3%, p = 0.009). Conclusions: Bilateral internal mammary artery grafting in elderly patients seems to be associated with a worse early outcome compared with SIMA grafting, particularly in patients undergoing urgent operation. Until more conclusive results are gathered, BIMA grafting should be reserved only for elderly patients with stable coronary artery disease, without significant baseline comorbidities and with long life expectancy.

Background: The clinical impact of prior percutaneous coronary intervention (PCI) in patients requiring coronary artery bypass grafting (CABG) remains unsettled. We sought to determine whether prior PCI is associated with adverse outcome after CABG. Methods and Results: Data from the prospective E-CABG (European Multicenter Study on Coronary Artery Bypass Grafting) conducted between January 2015 and March 2016 at 16 European centres were analyzed using propensity weighted methodology to adjust for confounding. A parallel systematic review/meta-analysis (MEDLINE, Embase, SCOPUS, and Cochrane Library) through September 2017 was accomplished. Of a total of 3641 adult patients included in the E-CABG study, 685 (19%) patients had a history of PCI. At multivariable level, prior PCI was not associated with an increased hospital mortality in both unweighted and weighted patient groups (odds ratio, 0.73; 95% confidence interval, 0.29–1.38; P=0.33 and odds ratio, 0.90; 95% confidence interval, 0.39–2.08; P=0.81, respectively). Subgroup analyses confirmed that prior PCI had no impact on hospital mortality and morbidity, including reexploration for bleeding, blood transfusion, hospital resource use, and neurological, renal, and cardiac complications. The systematic review provided a total of 71 366 individuals and showed a trend toward higher in-hospital/30-day mortality (adjusted odds ratio, 1.30; 95% confidence interval, 0.99–1.70; I²=43.1%) in patients with prior PCI. Conclusions: Our prospective multicenter study showed that prior PCI was not associated with an increased risk of mortality or other adverse outcomes in patients undergoing CABG. In light of a trend toward increased mortality observed in the meta-analysis, further studies are needed to ascertain the prognostic impact of prior PCI in the outcome after CABG.

Objectives: The aim of this study was to evaluate the prognostic impact of untreated asymptomatic carotid artery stenosis (CS) in patients undergoing isolated coronary artery bypass grafting (CABG). Methods: This was a post hoc analysis of data from a prospective multicentre observational study. Patients without history of stroke or transient ischaemic attack from the multicentre E-CABG registry who were screened for CS before isolated CABG were included. Results: Among 2813 patients screened by duplex ultrasound and who did not undergo carotid intervention for asymptomatic CS, 11.1% had a stenosis of 50–59%, 6.0% of 60–69%, 3.1% of 70–79%, 1.4% of 80–89%, 0.5% of 90–99%, and 1.1% had carotid occlusion. In the screened population post-operative stroke occurred in 25 patients (0.9%), with an incidence of 1.5% among patients with CS ≥ 50% (n = 649). Pre-operative screening had not found a relevant CS in 15 of 25 patients suffering stroke after CABG. Brain imaging identified cerebral ischaemic injury in 20 patients, which was bilateral in five patients (25%), ipsilateral to a CS ≥ 50% in six (30%), and ipsilateral to a CS ≥ 70% in three (15%). In univariable analysis, the severity of CS was associated with a significantly increased risk of stroke (CS < 50%, 0.7%; 50–59%, 1.0%; 60–69%, 0.6%; 70–79%, 1.2%; 80–89%, 5.1%; 90–99%, 7.7%; occluded, 6.7%, p < .001). In multivariable analysis, a CS of 90–99% (OR 12.03, 95% CI 1.34–108.23) and the presence of an occluded internal carotid artery (OR 8.783, 95% CI 1.820–42.40) were independent predictors of stroke along with urgency of the procedure, severe massive bleeding according to the E-CABG classification, and the presence of a porcelain ascending aorta. Conclusions: Among screened patients with untreated asymptomatic patients, CS ≥ 90% was an independent predictor of post-operative stroke. As this condition has a low prevalence and when left untreated is associated with a relatively low rate of stroke, pre-o

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 < 0.001) and a Net Reclassification Index of 55.6 (P < 0.001) for prediction of hospital/30-day mortality. Adding the CFS classes to EuroSCORE II resulted in an Integrated Improvement Index of 0.9 (P < 0.001) and Net Reclassification Index of 59.6 (P < 0.001) for prediction of hospital/30-day mortality with a significantly larger area under the receiver operating characteristics curve (0.809 vs 0.781, P = 0.028). The CFS was an independent predictor of mid-term mortality [CFS scores 3–4, hazard ratio (HR) 2.05, 95% CI 1.43–2.85; CFS scores 5–7, HR 3.05, 95% CI 1.83–5.06]. Conclusions: The CFS predicted early- and mid-term mortality in patients undergoing isolated CABG. Further studies are needed to evaluate whether frailty may improve the estimation of the operative risk of patients undergoing adult cardiac surgery.

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)B2within the 24-hour dosing interval and urinary TXA2metabolite (TXM) excretion. Aspirin 100 mg twice-daily lowered serum TXB2and prevented postsurgery TXM increase (P < 0.01), without affecting prostacyclin metabolite excretion. After cardiac surgery, shortening the dosing interval, but not doubling the once-daily dose, rescues the impaired antiplatelet effect of low-dose aspirin and prevents platelet activation associated with acute inflammation and enhanced platelet turnover.

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 reg