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

Background: Postoperative atrial fibrillation (POAF) occurs in 30% to 50% of patients undergoing cardiac surgery and is associated with increased morbidity and mortality. Prospective identification of structural/molecular changes in atrial myocardium that correlate with myocardial injury and precede and predict risk of POAF may identify new molecular pathways and targets for prevention of this common morbid complication. Methods: Right atrial appendage samples were prospectively collected during cardiac surgery from 239 patients enrolled in the OPERA trial (Omega-3 Fatty Acids for Prevention of Post-Operative Atrial Fibrillation), fixed in 10% buffered formalin, and embedded in paraffin for histology. We assessed general tissue morphology, cardiomyocyte diameters, myocytolysis (perinuclear myofibril loss), accumulation of perinuclear glycogen, interstitial fibrosis, and myocardial gap junction distribution. We also assayed NT-proBNP (N-terminal pro-B-type natriuretic peptide), hs-cTnT, CRP (C-reactive protein), and circulating oxidative stress biomarkers (F2-isoprostanes, F3-isoprostanes, isofurans) in plasma collected before, during, and 48 hours after surgery. POAF was defined as occurrence of postcardiac surgery atrial fibrillation or flutter of at least 30 seconds duration confirmed by rhythm strip or 12-lead ECG. The follow-up period for all arrhythmias was from surgery until hospital discharge or postoperative day 10. Results: Thirty-five percent of patients experienced POAF. Compared with the non-POAF group, they were slightly older and more likely to have chronic obstructive pulmonary disease or heart failure. They also had a higher European System for Cardiac Operative Risk Evaluation and more often underwent valve surgery. No differences in left atrial size were observed between patients with POAF and patients without POAF. The extent of atrial interstitial fibrosis, cardiomyocyte myocytolysis, cardiomyocyte diameter, glycogen score or Cx43 distribution at the time of surgery was not significantly associated with incidence of POAF. None of these histopathologic abnormalities were correlated with levels of NT-proBNP, hs-cTnT, CRP, or oxidative stress biomarkers. Conclusions: In sinus rhythm patients undergoing cardiac surgery, histopathologic changes in the right atrial appendage do not predict POAF. They also do not correlate with biomarkers of cardiac function, inflammation, and oxidative stress. Graphic Abstract: A graphic abstract is available for this article.

Background: Fractional flow reserve (FFR) is a reliable tool for the functional assessment of coronary stenoses. FFR computed tomography (CT) derived (FFR CT ) has shown to be accurate, but its clinical usefulness in patients with complex coronary artery disease remains to be investigated. The present study sought to determine the impact of FFR CT on heart team’s treatment decision-making and selection of vessels for revascularization in patients with 3-vessel coronary artery disease. Methods: The trial was an international, multicenter study randomizing 2 heart teams to make a treatment decision between percutaneous coronary interventions and coronary artery bypass grafting using either coronary computed tomography angiography or conventional angiography. The heart teams received the FFR CT and had to make a treatment decision and planning integrating the functional component of the stenoses. Each heart team calculated the anatomic SYNTAX score, the noninvasive functional SYNTAX score and subsequently integrated the clinical information to compute the SYNTAX score III providing a treatment recommendation, that is, coronary artery bypass grafting, percutaneous coronary intervention, or equipoise coronary artery bypass grafting-percutaneous coronary intervention. The primary objective was to determine the proportion of patients in whom FFR CT changed the treatment decision and planning. Results: Overall, 223 patients were included. Coronary computed tomography angiography assessment was feasible in 99% of the patients and FFR CT analysis in 88%. FFR CT was available for 1030 lesions (mean FFR CT value 0.64±13). A treatment recommendation of coronary artery bypass grafting was made in 24% of the patients with coronary computed tomography angiography with FFR CT . The addition of FFR CT changed the treatment decision in 7% of the patients and modified selection of vessels for revascularization in 12%. With conventional angiography as reference, FFR CT assessment resulted in reclassification of 14% of patients from intermediate and high to low SYNTAX score tertile. Conclusions: In patients with 3-vessel coronary artery disease, a noninvasive physiology assessment using FFR CT changed heart team’s treatment decision-making and procedural planning in one-fifth of the patients. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02813473.

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.

Background Leaflet resection represents the reference standard for surgical treatment of mitral valve (MV) regurgitation. New approaches recently proposed place emphasis on respecting, rather than resecting, the leaflet tissue to avoid the drawbacks of the 'resection' approach. Objectives The lateral dislocation of mid portion of mitral posterior leaflet (P2) technique for MV repair is a nonresectional technique in which the prolapsed P2 segment is sutured to normal P1 segment. Our study evaluates the effectiveness of this technique. Patients and methods We performed the procedure on seven patients. Once ring annular sutures were placed, the prolapsed P2 segment was dislocated toward the normal P1 segment with a rotation of 90° and without any resection. If present, residual clefts between P2 and P3 segments were closed. Once the absence of residual mitral regurgitation is confirmed by saline pressure test, ring annuloplasty was completed. The valve was evaluated using transesophageal echocardiography in the operating room and by transthoracic echocardiography before discharge. Results At the last follow-up visit, transthoracic echocardiography revealed no mitral regurgitation and normal TRANSVALVULAR gradients. Conclusion The lateral dislocation of P2 is an easily fine-tuned technique for isolated P2 prolapse, with the advantage of short aortic cross-clamp and cardiopulmonary bypass times. We think it might be very favorable in older and frail patients. Long-term follow-up is necessary to assess the durability of this technique.

According to the European Medicine Agency (EMA) regulatory frameworks, Advanced Therapy Medicinal Products (ATMP) represent a new category of drugs in which the active ingredient consists of cells, genes, or tissues. ATMP-CD133 has been widely investigated in controlled clinical trials for cardiovascular diseases, making CD133+cells one of the most well characterized cell-derived drugs in this field. To ensure high quality and safety standards for clinical use, the manufacturing process must be accomplished in certified facilities following standard operative procedures (SOPs). In the present work, we report the fully compliant GMP-grade production of ATMP-CD133 which aims to address the treatment of chronic refractory ischemic heart failure. Starting from bone marrow (BM), ATMP-CD133 manufacturing output yielded a median of 6.66 × 106of CD133+cells (range 2.85 × 106–30.84 × 106), with a viability ranged between 96,03% and 99,97% (median 99,87%) and a median purity of CD133+cells of 90,60% (range 81,40%–96,20%). Based on these results we defined our final release criteria for ATMP-CD133: purity ≥ 70%, viability ≥ 80%, cellularity between 1 and 12 × 106cells, sterile, and endotoxin-free. The abovementioned criteria are currently applied in our Phase I clinical trial (RECARDIO Trial).

Context It is not known whether statin treatment improves clinical outcomes and reduces aortic stenosis progression in non-rheumatic calcific aortic stenosis. Objective A meta-analysis of studies was performed comparing statin therapy with placebo or no treatment on outcomes and on aortic stenosis progression echocardiographic parameters. Data sources The authors searched Medline and Pubmed up to January 2010. Data extraction Two independent reviewers independently abstracted information on study design (prospective vs retrospective or randomised vs non-randomised), study and participant characteristics. Fixed and random effects models were used. A-priori subanalyses assessed the effect of statins on low-quality (retrospective or non-randomised) and on high-quality (prospective or randomised) studies separately. Results Meta-analysis identified 10 studies with a total of 3822 participants (2214 non-statin-treated and 1608 statin-treated); five studies were classified as prospective and five as retrospective; concerning randomisation, three trials were randomised whereas seven were not. No significant differences were found in all-cause mortality, cardiovascular mortality or in the need for aortic valve surgery. Lower-quality (retrospective or non-randomised) studies showed that, in statin-treated patients, the annual increase in peak aortic jet velocity and the annual decrease in aortic valve area were lower, but this was not confirmed by the analysis in high-quality (prospective or randomised) studies. Statins did not significantly affect the progression over time of peak and mean aortic gradient. Conclusions Currently available data do not support the use of statins to improve outcomes and to reduce disease progression in non-rheumatic calcific aortic valve stenosis.

Mitral valve prolapse (MVP) represents a common degenerative disease, often requiring surgery. If untreated, MVP with considerable valve incompetence can lead to cardiovascular and systemic complications causing substantial morbidity and mortality. In contrast with the wide knowledge concerning clinical and physiological features, currently available data regarding its molecular bases are very limited. We review current knowledge concerning MVP biological mechanisms, focusing on specific aspects of haemostasis, platelet function, oxidative stress, extracellular matrix remodeling and genomics. In particular, available evidence supports the role played by tissue remodeling processes in determining MVP onset and progression. Moreover, even if a consistent although controversial perturbation of haemostatic system and alterations of the oxidative stress equilibrium have been proposed to influence disease development, it is unknown whether these changes precede or follow MVP occurrence. Consequently, the complete knowledge of all the biochemical pathways involved are far from complete. In addition, changes in the regulation pattern of adrenergic and renin-angiotensin-aldosterone systems have been described in MVP syndrome, a condition characterized by the association of MVP with other peculiar neurological and general symptoms, but it is unknown whether these abnormalities are shared by "traditional" MVP. In conclusion, MVP is probably a multi-factorial process, and many aspects still need to be clarified. As surgery can only correct the damaged valve but not the underlying mechanisms, a more complete knowledge of the involved molecular pathways is necessary, as it may allow the discovery of targeted therapeutic strategies aimed at modifying or slackening MVP natural course in the early phases. © 2010 Elsevier Ireland Ltd.

Background: The European System for Cardiac Operative Risk Evaluation (EuroSCORE) was developed to predict immediate outcomes after adult cardiac operations, but less than 30% of the cases used to develop this score were valve procedures. We studied EuroSCORE performance in valve procedures. Methods: We performed a meta-analysis of published studies reporting the assessment of discriminatory power of the EuroSCORE by receiver operating characteristics (ROC) curve analysis in adult valve operations. A comparison of observed and predicted mortality rates was also performed. Results: A literature search identified 37 potentially eligible studies, and 12 were selected for meta-analysis comprising 26,621 patients with 1250 events (mortality rate, 4.7%). Meta-analysis of these studies provided an average area under the curve (AUC) value of 0.730 (95% confidence interval [CI], 0.717 to 0.743). The same results were obtained when meta-analyses were performed separately in studies categorized on reliability of uncertainty estimation: in the seven studies reporting reliable uncertainty estimation (8175 patients with 358 events; mortality rate, 4.4%), the ROC curve provided an average AUC value of 0.724 (95% CI, 0.699 to 0.749). The five studies not reporting reliable uncertainty estimation (18,446 patients with 892 events; mortality rate, 4.8%) had an average AUC of 0.732 (95% CI, 0.717 to 0.747). We documented a constant trend to overpredict mortality by EuroSCORE, both in the additive and especially in the logistic form. Conclusions: The EuroSCORE has low discrimination ability for valve surgery, and it sensibly overpredicts risk. Alternative risk scoring algorithms should be seriously considered. © 2010 The Society of Thoracic Surgeons.