Impact of Surgeon Experience and Centre Volume on Outcome After Off-Pump Coronary Artery Bypass Surgery: Results From the European Multicenter Study on Coronary Artery Bypass Grafting (E-CABG) Registry.

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

Glycated ACE2 reduces anti-remodeling effects of renin-angiotensin system inhibition in human diabetic hearts.

BACKGROUND: High glycated-hemoglobin (HbA1c) levels correlated with an elevated risk of adverse cardiovascular outcomes despite renin-angiotensin system (RAS) inhibition in type-2 diabetic (T2DM) patients with reduced ejection fraction. Using the routine biopsies of non-T2DM heart transplanted (HTX) in T2DM recipients, we evaluated whether the diabetic milieu modulates glycosylated ACE2 (GlycACE2) levels in cardiomyocytes, known to be affected by non-enzymatic glycosylation, and the relationship with glycemic control. OBJECTIVES: We investigated the possible effects of GlycACE2 on the anti-remodeling pathways of the RAS inhibitors by evaluating the levels of Angiotensin (Ang) 1-9, Ang 1-7, and Mas receptor (MasR), Nuclear-factor of activated T-cells (NFAT), and fibrosis in human hearts. METHODS: We evaluated 197 first HTX recipients (107 non-T2DM, 90 T2DM). All patients were treated with angiotensin-converting enzyme inhibitor (ACE-I) or angiotensin receptor blocker (ARB) at hospital discharge. Patients underwent clinical evaluation (metabolic status, echocardiography, coronary CT-angiography, and endomyocardial biopsies). Biopsies were used to evaluate ACE2, GlycACE2, Ang 1-9, Ang 1-7, MasR, NAFT, and fibrosis. RESULTS: GlycACE2 was higher in T2DM compared tonon-T2DM cardiomyocytes. Moreover, reduced expressions of Ang 1-9, Ang 1-7, and MasR were observed, suggesting impaired effects of RAS-inhibition in diabetic hearts. Accordingly, biopsies from T2DM recipients showed higher fibrosis than those from non-T2DM recipients. Notably, the expression of GlycACE2 in heart biopsies was strongly dependent on glycemic control, as reflected by the correlation between mean plasma HbA1c, evaluated quarterly during the 12-month follow-up, and GlycACE2 expression. CONCLUSION: Poor glycemic control, favoring GlycACE2, may attenuate the cardioprotective effects of RAS-inhibition. However, the achievement of tight glycemic control normalizes the anti-remodeling effects of RAS-inhibition. TRIAL REGISTRATION: https://clinicaltrials.gov/ NCT03546062.

Dissecting the correlates of N-terminal prohormone brain natriuretic peptide in acute infective endocarditis.

PURPOSE: To explore the prognostic value and the correlates of NT-proBNP in patients with acute infective endocarditis, a life-threatening disease, with an often unpredictable outcome given by the lack of reliable prognostic parameters. METHODS: We retrospectively studied 337 patients admitted to our centre between January 1, 2006 and September 30, 2020 with available NT-proBNP level at admission. Our analyses were performed considering NT-proBNP as both a categorical variable, using the median value as the cut-off level, and numerical variable. Study end points were in-hospital mortality, cardiac surgery and 1 year survival. RESULTS: NT-proBNP was an independent predictor of in-hospital mortality (OR 14.9 [95%C.I. 2.46-90.9]; P = .003). Levels below 2926 pg/mL were highly predictive of a favorable in-hospital outcome (negative predictive value 96.6%). Patients with higher NT-proBNP levels showed a significantly lower survival rate at 1 year follow-up (log-rank P = .005). NT-proBNP was strongly associated with chronic kidney disease (P < .001) and significantly higher in patients with prior chronic heart failure (P = .001). NT-proBNP was tightly related to staphylococcal IE (P = .001) as well as with higher CRP and hs-troponin I (P = 0.023, P < .001, respectively). CONCLUSION: Our results confirm the remarkable prognostic role of NT-proBNP in patients with IE and provide novel evidences of its multifaceted correlates in this unique clinical setting. Our data strongly support the incorporation of NT-proBNP into the current diagnostic work-up of IE.

Prognostic value of SARS-CoV-2 on patients undergoing cardiac surgery.

OBJECTIVE: To analyze Italian Cardiac Surgery experience during the pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) identifying risk factors for overall mortality according to coronavirus disease 2019 (COVID-19) status. METHODS: From February 20 to May 31, 2020, 1354 consecutive adult patients underwent cardiac surgery at 22 Italian Centers; 589 (43.5%), patients came from the red zone. Based on COVID-19 status, 1306 (96.5%) were negative to SARS-CoV-2 (COVID-N), and 48 (3.5%) were positive to SARS-CoV-2 (COVID-P); among the COVID-P 11 (22.9%) and 37 (77.1%) become positive, before and after surgery, respectively. Surgical procedures were as follows: 396 (29.2%) isolated coronary artery bypass grafting (CABG), 714 (52.7%) isolated non-CABG procedures, 207 (15.3%) two associate procedures, and three or more procedures in 37 (2.7%). Heart failure was significantly predominant in group COVID-N (10.4% vs. 2.5%, p = .01). RESULTS: Overall in-hospital mortality was 1.6% (22 cases), being significantly higher in COVID-P group (10 cases, 20.8% vs. 12, 0.9%, p < .001). Multivariable analysis identified COVID-P condition as a predictor of in-hospital mortality together with emergency status. In the COVID-P subgroup, the multivariable analysis identified increasing age and low oxygen saturation at admission as risk factors for in-hospital mortality. CONCLUSION: As expected, SARS-CoV-2 infection, either before or soon after cardiac surgery significantly increases in-hospital mortality. Moreover, among COVID-19-positive patients, older age and poor oxygenation upon admission seem to be associated with worse outcomes.

Coronary Artery Bypass Grafting in Patients With High Risk of Bleeding.

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<0.001), had a longer stay in the intensive care unit (on-pump: 4.4 [95% CI 3.6-8.1] days; off-pump: 3.2 [95% CI 2.0-4.4] days; p=0.049), and a higher rate of postoperative atrial fibrillation (on-pump: 46.5% [95% CI 34.9-58.1]; off-pump: 31.3% [95% CI 21.7-40.9]; p=0.025). Furthermore, on-pump patients showed a trend towards a higher rate of postoperative stroke (on-pump: 2.4% [95% CI 0.9-4.1]; off-pump: 1.1 [95% CI 0.2-2.7]; p=0.094). CONCLUSION: Our data suggest that in patients with an increased risk of bleeding, the use of cardiopulmonary bypass is associated with higher morbidity. These patients may benefit from off-pump surgery if complete revascularisation can be ensured.

Glycated ACE2 receptor in diabetes: open door for SARS-COV-2 entry in cardiomyocyte.

RATIONALE: About 50% of hospitalized coronavirus disease 2019 (COVID-19) patients with diabetes mellitus (DM) developed myocardial damage. The mechanisms of direct SARS-CoV-2 cardiomyocyte infection include viral invasion via ACE2-Spike glycoprotein-binding. In DM patients, the impact of glycation of ACE2 on cardiomyocyte invasion by SARS-CoV-2 can be of high importance. OBJECTIVE: To evaluate the presence of SARS-CoV-2 in cardiomyocytes from heart autopsy of DM cases compared to Non-DM; to investigate the role of DM in SARS-COV-2 entry in cardiomyocytes. METHODS AND RESULTS: We evaluated consecutive autopsy cases, deceased for COVID-19, from Italy between Apr 30, 2020 and Jan 18, 2021. We evaluated SARS-CoV-2 in cardiomyocytes, expression of ACE2 (total and glycosylated form), and transmembrane protease serine protease-2 (TMPRSS2) protein. In order to study the role of diabetes on cardiomyocyte alterations, independently of COVID-19, we investigated ACE2, glycosylated ACE2, and TMPRSS2 proteins in cardiomyocytes from DM and Non-DM explanted-hearts. Finally, to investigate the effects of DM on ACE2 protein modification, an in vitro glycation study of recombinant human ACE2 (hACE2) was performed to evaluate the effects on binding to SARS-CoV-2 Spike protein. The authors included cardiac tissue from 97 autopsies. DM was diagnosed in 37 patients (38%). Fourth-seven out of 97 autopsies (48%) had SARS-CoV-2 RNA in cardiomyocytes. Thirty out of 37 DM autopsy cases (81%) and 17 out of 60 Non-DM autopsy cases (28%) had SARS-CoV-2 RNA in cardiomyocytes. Total ACE2, glycosylated ACE2, and TMPRSS2 protein expressions were higher in cardiomyocytes from autopsied and explanted hearts of DM than Non-DM. In vitro exposure of monomeric hACE2 to 120 mM glucose for 12 days led to non-enzymatic glycation of four lysine residues in the neck domain affecting the protein oligomerization. CONCLUSIONS: The upregulation of ACE2 expression (total and glycosylated forms) in DM cardiomyocytes, along with non-enzymatic glycation, could increase the susceptibility to COVID-19 infection in DM patients by favouring the cellular entry of SARS-CoV2.

Atrial myxomas arise from multipotent cardiac stem cells.

AIMS: Cardiac myxomas usually develop in the atria and consist of an acid-mucopolysaccharide-rich myxoid matrix with polygonal stromal cells scattered throughout. These human benign tumours are a valuable research model because of the rarity of cardiac tumours, their clinical presentation and uncertain origin. Here, we assessed whether multipotent cardiac stem/progenitor cells (CSCs) give rise to atrial myxoma tissue. METHODS AND RESULTS: Twenty-three myxomas were collected and analysed for the presence of multipotent CSCs. We detected myxoma cells positive for c-kit (c-kitpos) but very rare Isl-1 positive cells. Most of the c-kitpos cells were blood lineage-committed CD45pos/CD31pos cells. However, c-kitpos/CD45neg/CD31neg cardiac myxoma cells expressed stemness and cardiac progenitor cell transcription factors. Approximately ≤10% of the c-kitpos/CD45neg/CD31neg myxoma cells also expressed calretinin, a characteristic of myxoma stromal cells. In vitro, the c-kitpos/CD45neg/CD31neg myxoma cells secrete chondroitin-6-sulfate and hyaluronic acid, which are the main components of gelatinous myxoma matrix in vivo. In vitro, c-kitpos/CD45neg/CD31neg myxoma cells have stem cell properties being clonogenic, self-renewing, and sphere forming while exhibiting an abortive cardiac differentiation potential. Myxoma-derived CSCs possess a mRNA and microRNA transcriptome overall similar to normal myocardium-derived c-kitpos/CD45neg/CD31negCSCs , yet showing a relatively small and relevant fraction of dysregulated mRNA/miRNAs (miR-126-3p and miR-335-5p, in particular). Importantly, myxoma-derived CSCs but not normal myocardium-derived CSCs, seed human myxoma tumours in xenograft's in immunodeficient NOD/SCID mice. CONCLUSION: Myxoma-derived c-kitpos/CD45neg/CD31neg CSCs fulfill the criteria expected of atrial myxoma-initiating stem cells. The transcriptome of these cells indicates that they belong to or are derived from the same lineage as the atrial multipotent c-kitpos/CD45neg/CD31neg CSCs. Taken together the data presented here suggest that human myxomas could be the first-described CSC-related human heart disease.

Prospective validation of the International Warfarin Pharmacogenetics Consortium algorithm in high-risk elderly people (VIALE study).

We assessed the predictive accuracy of the Warfarin Pharmacogenetics Consortium (IWPC) algorithm in a prospective cohort of 376 high-risk elderly patients (≥65 years) who required new treatment with warfarin for either medical (non valvular atrial fibrillation) or surgical conditions (heart valve replacement), had ≥1 comorbid conditions, and regularly used ≥2 other drugs. Follow-up visits were performed according to clinical practice and lasted for a maximum of 1 year. Two hundred and eighty-three (75%) patients achieved a stable maintenance dose. Warfarin maintenance doses were low on average (median 20.3 mg/week, interquartile range, 14.1-27.7 mg/week) and were substantially overestimated by the IWPC algorithm. Overall the percentage of patients whose predicted dose of warfarin was within 20% of the actual stable dose was equal to 37.5%, (95% CI 32.0-43.3%). IWPC algorithm explained only 31% of the actual warfarin dose variability. Modifications of the IWPC algorithm are needed in high-risk elderly people.

Hospital Volume and Outcome after Bilateral Internal Mammary Artery Grafting.

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.

Polyamines and microbiota in bicuspid and tricuspid aortic valve aortopathy.

Polyamines are small aliphatic cationic molecules synthesized via a highly regulated pathway and involved in general molecular and cellular phenomena. Both mammalian cells and microorganisms synthesize polyamines, and both sources may contribute to the presence of polyamines in the circulation. The dominant location for microorganisms within the body is the gut. Accordingly, the gut microbiota probably synthesizes most of the polyamines in the circulation in addition to those produced by the mammalian host cells. Polyamines are mandatory for cellular growth and proliferation. Established evidence suggests that the polyamine spermidine prolongs lifespan and improves cardiovascular health in animal models and humans through both local mechanisms, involving improved cardiomyocyte function, and systemic mechanisms, including increased NO bioavailability and reduced systemic inflammation. Higher levels of polyamines have been detected in non-dilated aorta of patients affected by bicuspid aortic valve congenital malformation, an aortopathy associated with an increased risk for thoracic ascending aorta aneurysm. In this review, we discuss metabolism of polyamines and their potential effects on vascular smooth muscle and endothelial cell function in vascular pathology of the thoracic ascending aorta associated with bicuspid or tricuspid aortic valve.

Pericoronary fat inflammation and Major Adverse Cardiac Events (MACE) in prediabetic patients with acute myocardial infarction: effects of metformin.

BACKGROUND/OBJECTIVES: Pericoronary adipose tissue inflammation might lead to the development and destabilization of coronary plaques in prediabetic patients. Here, we evaluated inflammation and leptin to adiponectin ratio in pericoronary fat from patients subjected to coronary artery bypass grafting (CABG) for acute myocardial infarction (AMI). Furthermore, we compared the 12-month prognosis of prediabetic patients compared to normoglycemic patients (NG). Finally, the effect of metformin therapy on pericoronary fat inflammation and 12-months prognosis in AMI-prediabetic patients was also evaluated. METHODS: An observational prospective study was conducted on patients with first AMI referred for CABG. Participants were divided in prediabetic and NG-patients. Prediabetic patients were divided in two groups; never-metformin-users and current-metformin-users receiving metformin therapy for almost 6 months before CABG. During the by-pass procedure on epicardial coronary portion, the pericoronary fat was removed from the surrounding stenosis area. The primary endpoints were the assessments of Major-Adverse-Cardiac-Events (MACE) at 12-month follow-up. Moreover, inflammatory tone was evaluated by measuring pericoronary fat levels of tumor necrosis factor-α (TNF-α), sirtuin 6 (SIRT6), and leptin to adiponectin ratio. Finally, inflammatory tone was correlated to the MACE during the 12-months follow-up. RESULTS: The MACE was 9.1% in all prediabetic patients and 3% in NG-patients. In prediabetic patients, current-metformin-users presented a significantly lower rate of MACE compared to prediabetic patients never-metformin-users. In addition, prediabetic patients showed higher inflammatory tone and leptin to adiponectin ratio in pericoronary fat compared to NG-patients (P < 0.001). Prediabetic never-metformin-users showed higher inflammatory tone and leptin to adiponectin ratio in pericoronary fat compared to current-metformin-users (P < 0.001). Remarkably, inflammatory tone and leptin to adiponectin ratio was significantly related to the MACE during the 12-months follow-up. CONCLUSION: Prediabetes increase inflammatory burden in pericoronary adipose tissue. Metformin by reducing inflammatory tone and leptin to adiponectin ratio in pericoronary fat may improve prognosis in prediabetic patients with AMI. Trial registration Clinical Trial NCT03360981, Retrospectively Registered 7 January 2018.

Is there a role for autophagy in ascending aortopathy associated with tricuspid or bicuspid aortic valve?

Autophagy is a conserved process by which cytoplasmatic elements are sequestered in vesicles and degraded after their fusion with lysosomes, thus recycling the precursor molecules. The autophagy-mediated removal of redundant/harmful/damaged organelles and biomolecules plays not only a replenishing function, but protects against stressful conditions through an adaptive mechanism. Autophagy, known to play a role in several pathological conditions, is now gaining increasing attention also in the perspective of the identification of the pathogenetic mechanisms at the basis of ascending thoracic aortic aneurysm (TAA), a localized or diffused dilatation of the aorta with an abnormal widening greater than 50 percent of the vessel's normal diameter. TAA is less frequent than abdominal aortic aneurysm (AAA), but is encountered with a higher percentage in patients with congenital heart disease or known genetic syndromes. Several biological aspects of TAA pathophysiology remain to be elucitated and therapeutic needs are still widely unmet. One of the most controversial and epidemiologically important forms of TAA is that associated with the congenital bicuspid malformation of the aortic valve (BAV). Dysregulated autophagy in response, for example, to wall shear stress alterations, has been demonstrated to affect the phenotype of vascular cells relevant to aortopathy, with potential consequences on signaling, remodeling, and angiogenesis. The most recent findings and hypotheses concerning the multiple aspects of autophagy and of its dysregulation are summarized, both in general and in the context of the different vascular cell types and of TAA progression, with particular reference to BAV-related aortopathy.

A Possible Early Biomarker for Bicuspid Aortopathy: Circulating Transforming Growth Factor ß-1 to Soluble Endoglin Ratio.

RATIONALE: The pathogenesis of bicuspid aortic valve (BAV)-associated aortopathy is poorly understood, and no prognostic biomarker is currently available. OBJECTIVE: We aimed to identify putative circulating biomarkers pathogenetically and prognostically linked to bicuspid aortopathy. METHODS AND RESULTS: By reverse transcription polymerase chain reaction, we evaluated gene expression variations (versus normal aorta) of transforming growth factor-ß1 (TGF-ß1), connective tissue growth factor, matrix metalloproteinase-2 (MMP-2), MMP-14, endoglin (ENG), and superoxide dismutase 3 in ascending aorta samples from 50 tricuspid and 70 patients with BAV undergoing surgery for aortic stenosis (aorta diameter ≤45 mm: BAVnon-dil or >45 mm: BAVdil). Expression changes of the TGF-ß1 active dimer and ENG were analyzed also by Western blot in ascending aorta samples from other 10 tricuspid aortic valve, 10 BAVnon-dil, and 10 BAVdil patients. The serum concentration of study targets was assessed through ELISA and the ratio of serum TGF-ß1/ENG (T/E) was evaluated. All BAVnon-dil patients underwent follow-up echocardiography to assess aortic growth rate. In BAVnon-dil patients, TGF-ß1 and MMP-2 gene expression increased significantly, whereas MMP-14 and ENG expression decreased versus controls. Expression changes were confirmed at protein level for TGF-ß1 and ENG. TGF-ß1 serum concentration significantly decreased in tricuspid aortic valve and BAVnon-dil patients versus healthy subjects. ENG serum concentration decreased in all patients, more markedly in BAVdil. A significant increase of the T/E ratio versus healthy subjects was unique of patients with BAV. In BAVnon-dil patients, a T/E ≥9 was independently associated in multivariable analysis with higher MMP-2 and lower superoxide dismutase 3 gene expression, independent of age and aortic diameter. A significant correlation was observed between baseline T/E ratio and aortic diameter growth rate in BAVnon-dil patients (r=0.66, P<0.001). CONCLUSIONS: The novel evidence of a possible value of the T/E ratio as a biomarker of BAV aortopathy was presented: further validation studies are warranted.

Impact of preoperative thrombocytopenia on the outcome after coronary artery bypass grafting.

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: 23.5%, adjusted OR 3.08, 95%CI 1.52-6.22; E-CABG bleeding severity grades 2-3: 23.5%, adjusted OR 4.43, 95%CI 2.15-9.15) compared to patients with normal preoperative platelet count. Mild preoperative thrombocytopenia is associated with increased risk of severe-massive bleeding, mortality, and other major adverse events after CABG. Such risks are markedly increased in patients with moderate-severe preoperative thrombocytopenia.

Comparative Analysis of Prothrombin Complex Concentrate and Fresh Frozen Plasma in Coronary Surgery.

BACKGROUND: Recent studies suggested that prothrombin complex concentrate (PCC) might be more effective than fresh frozen plasma (FFP) to reduce red blood cell (RBC) transfusion requirement after cardiac surgery. METHODS: This is a comparative analysis of 416 patients who received FFP postoperatively and 119 patients who received PCC with or without FFP after isolated coronary artery bypass grafting (CABG). RESULTS: Mixed-effects regression analyses adjusted for multiple covariates and participating centres showed that PCC significantly decreased RBC transfusion (67.2% vs. 87.5%, adjusted OR 0.319, 95%CI 0.136-0.752) and platelet transfusion requirements (11.8% vs. 45.2%, adjusted OR 0.238, 95%CI 0.097-0.566) compared with FFP. The PCC cohort received a mean of 2.7±3.7 (median, 2.0, IQR 4) units of RBC and the FFP cohort received a mean of 4.9±6.3 (median, 3.0, IQR 4) units of RBC (adjusted coefficient, -1.926, 95%CI -3.357-0.494). The use of PCC increased the risk of KDIGO (Kidney Disease: Improving Global Outcomes) acute kidney injury (41.4% vs. 28.2%, adjusted OR 2.300, 1.203-4.400), but not of KDIGO acute kidney injury stage 3 (6.0% vs. 8.0%, OR 0.850, 95%CI 0.258-2.796) when compared with the FFP cohort. CONCLUSIONS: These results suggest that the use of PCC compared with FFP may reduce the need of blood transfusion after CABG.

Prognostic Impact of Asymptomatic Carotid Artery Stenosis in Patients Undergoing Coronary Artery Bypass Grafting.

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-operative screening of asymptomatic CS before CABG may not be justified. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov. Unique identifier: NCT02319083.

Ascending aortas from heart donors and CABG patients are not equivalent as control in aortopathy studies.

OBJECTIVES: A careful selection of reference samples in studies on the pathogenesis of thoracic ascending aorta (TAA) dilation is crucial for reliability, consistency and reproducibility of experimental results. Several studies include control TAA samples from heart donors. Others include samples harvested during coronary artery bypass graft (CABG) procedures or a mix of samples from heart donors and CABG patients. We verified the equivalence/homogeneity of TAA samples from heart donors and CABG patients in terms of basal gene expression and thus their reliability as reference groups in aortopathy studies. DESIGN: We analysed by RT-PCR and Western blot the differential expression of smoothelin, α-smooth muscle actin (α-SMA) and transforming growth factor-ß1 (TGF-ß1), selected as major players in smooth muscle cell and myofibroblast phenotype and remodelling. The mean age and comorbidities of subjects were consistent with data routinely seen in clinical practice. RESULTS: Data revealed the loss of smoothelin in samples from CABG patients, together with a significant increase of α-SMA, while TGF-ß1 dimer showed a marked increase in CABG patients versus heart donors, accompanied by a decrease of the corresponding mRNA. Differences in gene expression were maintained after adjustment for age. However, TGF-ß1 mRNA and CABG patients' age showed a positive correlation (ρ = 0.89, p < .05), while α-SMA mRNA and age showed a negative correlation (ρ = -0.85, p < .05). CONCLUSIONS: We revealed the non-equivalence of samples from heart donors and CABG patients, presumably for the presence of microscopic atherosclerotic lesions in CABG patients, suggesting the necessity of a careful selection of control groups in aortopathy studies.

Polyamine concentration is increased in thoracic ascending aorta of patients with bicuspid aortic valve.

Polyamines are cationic molecules synthesized via a highly regulated pathway, obtained from the diet or produced by the gut microbiota. They are involved in general molecular and cellular phenomena that play a role also in vascular disease. Bicuspid aortic valve (BAV) is a congenital malformation associated to a greater risk of thoracic ascending aorta (TAA) aneurysm, whose pathogenesis is not yet well understood. We focused on differential analysis of key members of polyamine pathway and on polyamine concentration in non-dilated TAA samples from patients with either stenotic tricuspid aortic valve (TAV) or BAV (diameter ≤ 45 mm), vs. normal aortas from organ donors, with the aim of revealing a potential involvement of polyamines in early aortopathy. Changes of gene expression in TAA samples were evaluated by RT-PCR. Changes of ornithine decarboxylase 1 (ODC1), a key enzyme in polyamine formation, and cationic amino acid transporter 1 (SLC7A1/CAT-1) expression were analyzed also by Western blot. ODC1 subcellular localization was assessed by immunohistochemistry. Polyamine concentration in TAA samples was evaluated by HPLC. BAV TAA samples showed an increased concentration of putrescine and spermidine vs. TAV and donor samples, together with a decreased mRNA level of polyamine anabolic enzymes and of the putative polyamine transporter SLC7A1/CAT-1. The catabolic enzyme spermidine/spermine N1-acetyltransferase 1 showed a significant mRNA increase in TAV samples only, together with a decreased concentration of spermine. The decreased expression of SLC7A1/CAT-1 and ODC1 mRNAs in BAV corresponded to increased or unchanged expression of the respective proteins. ODC was located mainly in smooth muscle cell (SMC) nucleus in TAV and donor samples, while it was present also in SMC cytoplasm in BAV samples, suggesting its activation. In conclusion, BAV, but not TAV non-dilated samples show increased polyamine concentration, accompanied by the activation of a regulatory negative feedback mechanism.

Hospital Outcome and Risk Indices of Mortality after redo-mitral valve surgery in Potential Candidates for Transcatheter Procedures: Results From a European Registry.

OBJECTIVE: Transcatheter mitral valve-in-valve/valve-in-ring procedures (TM-VIVoR) are increasing. The authors aimed to identify independent predictors for hospital mortality in redo mitral valve surgery as possible future selection criteria for TM-VIVoR. DESIGN: Retrospective multicenter registry. SETTING: Tertiary university and community hospitals. PARTICIPANTS: Two-hundred and sixty patients (out of 920 enrolled) who are potentially candidates for TM-VIVoR undergoing redo-surgery. INTERVENTIONS: Redo mitral surgery. MEASUREMENTS AND MAIN RESULTS: Regression analyzes and receiver operating characteristic (ROC) curves identified independent predictors of death. Patients potentially candidates for TM-VIVoR reported significant hospital mortality (9.2%; EuroSCORE II: 13.2 ± 13.1, Society of Thoracic Surgeons [STS] score: 6.2 ± 3.1) and major morbidity (3.8% acute myocardial infarction, 5% stroke, 16.9% perioperative respiratory failure, 16.5% acute renal insufficiency, 25% massive transfusions). EuroSCORE II (odds ration [OR] 1.06; confidence interval [CI] 1.01-1.10; p = 0.005), STS score (OR 1.58; CI 1.27-1.97; p = 0.001), age at surgery (OR 1.05; CI 1.00-1.15; p = 0.05), preoperative dialysis (OR 2.5; CI 1.8-12.6; p = 0.042), left ventricular ejection fraction (LVEF) <30% (OR 4.8; CI 1.12-37.1; p = 0.021), severe pulmonary hypertension (OR 7.5; CI 1.9-29.4; p = 0.003), and previous coronary artery bypass grafting (CABG) (OR 11.8; CI 1.7-36.9; p = 0.002) were independent predictors of hospital mortality. ROC analyses reported good prediction for EuroSCORE II (AUC: 0.76; cut-off value: >13.1; 70.8% sensitivity and 68.2% specificity) and better prediction for STS score (AUC: 0.81; cut-off value: 7.4; 75.0% sensitivity and 66.2% specificity). Quintiles stratification identified EuroSCORE II ≥18.7 (5th quintile, observed mortality: 19.3%) and STS score >9.1 as strong predictors of death within each risk-categorization (OR 5.9 and 12.1, respectively). CONCLUSIONS: High EuroSCORE II and STS scores, advanced age at surgery, LVEF <30%, previous CABG, severe pulmonary hypertension or preoperative dialysis might represent in the future preferred indications for TM-VIVoR in the redo-mitral surgery scenario.

Prognostic Impact of Prolonged Cross-Clamp Time in Coronary Artery Bypass Grafting.

BACKGROUND: The prognostic impact of cross-clamp time (XCT) in patients undergoing isolated coronary artery bypass grafting (CABG) has not been thoroughly investigated. MATERIAL AND METHODS: 2957 patients who underwent on-pump isolated CABG from the prospective multicentre E-CABG study were the subjects of this analysis. RESULTS: The mean XCT in this series was 58±25minutes Cross-clamp time was >60 minutes in 1134 patients (38.3%), >75minutes in 619 patients (20.9%) and >90minutes in 296 patients (10.0%). Multivariate analysis showed that XCT was an independent predictor of 30-day mortality (p<0.0001, OR 1.027, 95%CI 1.015-1.039) along with age (p<0.0001), female gender (p=0.001), pulmonary disease (p=0.001), poor mobility (p=0.002), urgency status (p=0.007), critical preoperative status (p=0.002) and participating centres (p=0.015). Adjusted risk of 30-day mortality was highest for XCT >75minutes (2.9% vs. 1.7%, p=0.002, OR 3.479, 95%CI 1.609-7.520). Analysis of 428 propensity score matched pairs showed that XCT >75minutes was associated with significantly increased risk of early mortality, prolonged use of inotropes, postoperative use of intra-aortic balloon pump, use of extracorporeal membrane oxygenation, atrial fibrillation, prolonged stay in the intensive care unit and of composite major adverse events. CONCLUSIONS: Isolated CABG is currently performed with prolonged XCT in a significant number of patients and this seems to be a determinant of poor early outcome.