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Background: We analyzed The Society of Thoracic Surgeons Database to investigate risks and optimal timing for coronary artery bypass grafting (CABG) after clopidogrel administration., Methods: Patients were categorized based on clopidogrel use within 5 days and further stratified by days from the last dose (0 to 5 days). Controls were patients who did not receive clopidogrel within 5 days of surgery. The primary outcome was operative mortality, and secondary outcomes included mediastinal reexploration for bleeding and blood product use., Results: Among 148,317 isolated CABG, 19,553 patients (13.2%) received clopidogrel within 5 days. Minimal differences in operative mortality (2.8% vs 2.1%, P < .001), but higher rates of mediastinal reexploration (3.5% vs 2.1%, P < .001) and blood product utilization (72.7% vs 56.8%, P < .001) were observed in the clopidogrel group. The adjusted odds ratio of operative mortality peaked on the day of clopidogrel administration but was comparable to controls thereafter. The odds of reexploration were highest on day 0, decreasing gradually to a plateau after day 3. Patients who underwent operations on day 3 after clopidogrel administration had similar odds of operative mortality and mediastinal reexploration for bleeding and shorter total and preoperative lengths of stay but higher blood product use compared with day 5., Conclusions: CABG within 5 days from clopidogrel is associated with a modest increase in operative mortality and reexploration for bleeding and a substantial increase in blood product use. Risks decreased with increasing time from discontinuation, plateauing after 3 days from clopidogrel. CABG at 3 days yields comparable outcomes as 5 days, reducing the waiting period., Competing Interests: Disclosures Juan Crestanello reports a relationship with Medtronic Inc that includes: consulting or advisory and with Edwards Lifesciences Corporation that includes: consulting or advisory. The other authors have no conflicts of interest to disclose., (Copyright © 2024 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: The effect of hospital-associated SARS-CoV-2 infections in cardiac surgery patients remains poorly investigated, and current data are limited to small case series with conflicting results., Methods: A multicenter European collaboration was organized to analyze the outcomes of patients who tested positive with hospital-associated SARS-CoV-2 infection after cardiac surgery. The study investigators hypothesized that early infection could be associated with worse postoperative outcomes; hence 2 groups were considered: (1) an early hospital-associated SARS-CoV-2 infection group comprising patients who had a positive molecular test result ≤7 days after surgery, with or without symptoms; and (2) a late hospital-associated SARS-CoV-2 infection group comprising patients whose test positivity occurred >7 days after surgery, with or without symptoms. The primary outcome was 30-day mortality. Secondary outcomes included all-cause mortality or morbidity at early follow-up and SARS-CoV-2-related hospital readmission., Results: A total of 87 patients were included in the study. Of those, 30 were in the early group and 57 in the late group. Overall, 30-day mortality was 8%, and in-hospital mortality was 11.5%. The reintubation rate was 11.4%. Early infection was significantly associated with higher mortality (adjusted OR, 26.6; 95% CI, 2, 352.6; P < .01) when compared with the late group. At 6-month follow-up, survival probability was also significantly higher in the late infection group: 91% (95% CI, 83%, 98%) vs 75% (95% CI, 61%, 93%) in the early infection group (P = .036). Two patients experienced COVID-19-related rehospitalization., Conclusions: In this multicenter analysis, hospital-associated SARS-CoV-2 infection resulted in higher than expected postoperative mortality after cardiac surgery, especially in the early infection group., (Copyright © 2024 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Retractions of erroneous and fraudulent papers from the biomedical literature continue to be a major concern. The aim of this analysis is to summarize trends of retractions in the cardiovascular literature over the past four decades., Methods: A review of the Retraction Watch database for retracted articles published between 1978 and 2020 in the cardiovascular literature was performed. Retractions with the term "medicine" in the subject code were selected. Titles and abstracts were reviewed and only retractions of articles in cardiovascular medicine and surgery were included., Results: 459 retraction notices published in 228 journals were identified. The number of retractions increased with time from 1 in 1991 to 48 at the end of 2019 (P < 0.001). Overall, the yearly percentage of retraction increased during the study period (P < 0.001) but decreased after 2015. China had the highest percentage of retractions when compared to other countries (P < 0.001). The majority of articles were retracted for scientific misconduct (n = 289, 63.0%); retractions due to scientific misconduct increased significantly over the study period (P = 0.04) but decreased after 2015. The median time from publication to retraction was 1.4 years (interquartile range [IQR]: 0.6-3.8) and decreased significantly over time (P < 0.001). The median number of citations of retracted articles was 8.0., Conclusions: The number of retractions and the yearly percentage of retraction in the cardiovascular literature increased significantly during the study period, although a decrease was seen after 2015. Scientific misconduct represents the most common reason for retraction, although a reduction has been observed in the last five years., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Patient-reported outcomes (PROs) are reports of a person's health status that provide a global perspective of patient well-being. PROs can be classified into 4 primary domains: global, mental, physical, and social health. In this descriptive review, we focus on how PROs can be used in cardiac clinical trials, with an emphasis on cardiac surgical trials for patients with coronary heart disease and heart failure. We also highlight ongoing challenges and provide specific suggestions and novel opportunities to advance cardiac clinical trials. Current challenges include the long-term measurement of PROs in clinical trials beyond 1 year, inconsistency in the choice of the outcome measures among studies, and the lack of measurement of PROs across multiple domains. Opportunities for advancement include measuring PROs using consumer health informatics tools, including returning information back to participants in formats that they can understand using visualization. Future opportunities include quantifying cohort-specific minimal clinically important differences for PROs., (Copyright © 2021 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background: Contemporary outcomes of open repair of thoracoabdominal aortic aneurysms (TAAAs) and descending thoracic aortic aneurysms (DTAs) have not been analyzed in an inclusive meta-analysis., Methods: After a systematic literature search, studies from 2008 to 2018 reporting outcomes of open repair of DTAs or TAAAs were pooled in a single-arm meta-analysis performed using the generic inverse variance method. Primary outcome was operative mortality. Secondary outcomes were late mortality, postoperative stroke, permanent and temporary spinal cord injury, renal failure, respiratory failure, and myocardial infarction., Results: Fifty-four studies with 12,245 patients were included. Pooled operative mortality for open repair was 10.4% (95% confidence interval [CI], 8.3-12.8): 6.6% (95% CI, 3.7-11.6) for DTA and 10.5% (95% CI, 7.5-14.5) for TAAA. Pooled incidence rate of late mortality was 0.6% (95% CI, 0.5-0.8) per person-year. Pooled rates for postoperative outcomes were 4.9% (95% CI, 3.9-6.1) for stroke; 5.7% (95% CI, 4.3-7.5) and 3.0% (95% CI, 2.1-4.2) for permanent and temporary spinal cord injury, respectively; 13.2% (95% CI, 9.9-17.3) for renal failure; 23.3% (95% CI, 17.5-30.4) for respiratory failure; and 2.7% (95% CI, 1.8-4.1) for myocardial infarction. At metaregression, year of publication, use of the clamp-and-sew technique, and use of the cerebrospinal fluid drain were associated with lower operative mortality. Ruptured aneurysms were associated with higher operative mortality., Conclusions: Despite improvement, open repair of DTAs and TAAAs continues to be associated with a considerable risk for operative death and perioperative complications. Use of the cerebrospinal fluid drain is associated with better outcomes., (Copyright © 2020 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Fractional flow reserve (FFR) provides an objective measurement of the severity of ischemia caused by coronary stenoses in downstream myocardial regions. Data from the interventional cardiology realm have suggested benefits of a FFR-guided percutaneous coronary intervention (PCI) strategy. Limited evidence is available on the use of FFR to guide coronary artery bypass grafting (CABG). The most recent data have shown that FFR might simplify CABG procedures and optimize patency of arterial grafts without any clear impact on clinical outcomes. The aim of this review was to summarize the available data on FFR-based CABG and discuss the rationale and potential consequences of a switch toward FFR-based surgical revascularization strategy., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: There is uncertainty whether venoarterial extracorporeal membrane oxygenation (VA-ECMO) should be used in older patients with cardiopulmonary failure after cardiac surgery., Methods: This was a retrospective multicenter study of 781 patients who required postcardiotomy VA-ECMO for cardiopulmonary failure after adult cardiac surgery from 2010 to 2018 at 19 cardiac surgery centers. A parallel systematic review with meta-analysis of the literature was performed., Results: The hospital mortality in the overall Postcardiotomy Venoarterial Extracorporeal Membrane Oxygenation (PC-ECMO) series was 64.4%. A total of 255 patients were 70 years old or older (32.7%), and their hospital mortality was significantly higher than in younger patients (76.1% vs 58.7%; adjusted odds ratio, 2.199; 95% confidence interval [CI], 1.536 to 3.149). Arterial lactate level greater than 6 mmol/L before starting VA-ECMO was the only predictor of hospital mortality among patients 70 years old or older in univariate analysis (82.6% vs 70.4%; P = .029). Meta-analysis of current and previous studies showed that early mortality after postcardiotomy VA-ECMO was significantly higher in patients aged 70 years or older compared with younger patients (odds ratio, 2.09; 95% CI, 1.59 to 2.75; 5 studies including 1547 patients; I 2 , 5.9%). The pooled early mortality rate among patients aged 70 years or older was 78.8% (95% CI, 74.1 to 83.5; 6 studies including 617 patients; I 2 , 41.8%). Two studies reported 1-year mortality (including hospital mortality) of 79.9% and 75.6%, respectively, in patients 70 years old or older., Conclusions: Advanced age should not be considered a contraindication for postcardiotomy VA-ECMO. However, in view of the high risk of early mortality, meaningful scrutiny is needed before using VA-ECMO after cardiac surgery in older patients., (Copyright © 2019 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Despite the progressive expansion of clinical indications for percutaneous coronary intervention and the increasingly high risk profile of referred patients, coronary artery bypass grafting (CABG) remains the mainstay in multivessel disease, providing good long-term outcomes with low complication rates. Multiple arterial grafting, especially if associated with anaortic techniques, might provide the best longer-term outcomes. A surgical approach individualized to the patients' clinical and anatomic characteristics, and surgeon and team experience, are key to excellent outcomes. Current evidence regarding patient selection, indications, graft selection, and potential strategies to optimize outcomes in patients treated with CABG is summarized., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The recent literature on transcatheter aortic valve replacement (TAVR) is shedding new light on the perspective to extend this procedure to other lower risk-category of patients, leading in fact to a potential erosion of the current guidelines. Notwithstanding the warnings provided in the literature regarding the risk of severely impairing complications, unclear survival advantage, and cost-inefficiency, many observational studies, especially performed in high-volume centers, support a general drive toward the recruitment of intermediate-low risk patients in the expectation of clinical advantages versus standard surgical replacement. It appears that, in combination with the development of more refined technologies, medical groups with matured experience and centers able to successfully manage patients with different profiles have been progressively "selected" and emerged pushing further the limits of the procedure itself. On the surgeon side, involved in the surgical assistance of TAVR procedures or in the standby-coverage in case of major complications, the expansion of indications and the interventionists' overconfidence have relevant implications. Considerations on the actual long-term effectiveness of the procedure on younger lower-risk patients in terms of actual hemodynamic durability and inability to deal with functional and morphological aspects of annular calcifications should be made. Also, it seems that other technologies enabling annulus decalcification, such as sutureless valve, have been totally overlooked and trials sponsored by industrial leaders in the market have taken the lead. Such a rapid expansion of TAVR indications should be better understood considering that in the surgical field valve bioprostheses needed to undergo a much longer validation period and the appearance of data on their 20 years follow-up after implantation was required before the application in younger patients., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: In patients with ischemic mitral regurgitation, leaflet prolapse requires an accurate evaluation since surgical approach depends on valvular and subvalvular characteristics. This study aims to describe a cohort of patients over a long-term follow up, analyzing survival, reoperation and predictive factors of surgical outcomes., Methods and Results: From March 1994 to June 2011, 75 patients with ischemic mitral regurgitation and leaflet prolapse underwent surgical myocardial revascularization and mitral valve repair (90.7%) or replacement (9.3%). Our cohort was followed up until April 2015, with a mean follow up of 7 ± 3 years. Cardiac-related deaths occurred in 26 patients, with a mean survival of 114.2 months, including eight patients with in-hospital mortality. Reoperation was performed in 14 patients, due to valve repair failure. Twenty-six patients experienced moderate-to-severe mitral regurgitation. A preoperative LVEDD > 62 mm, LVESD > 52 mm, previous anteroseptal myocardial infarction, diffuse coronary artery disease, papillary anatomy type 1, partial rupture of the papillary muscle, A1-A2 scallop prolapse and postoperative mitral valve configuration (tenting area, tenting height, alfa-1 angle and alfa-2 angle) were identified as independent predictors of poor outcome. An index quantifying the stress on the annulus imparted by annuloplasty was elaborated and predicted endpoints., Conclusion: Leaflet prolapse is an important entity in patients with ischemic mitral regurgitation, and its pathogenic mechanism mostly relies on papillary muscle lesion or elongation. Perioperative parameters describing geometric features of left ventricle, valvular and subvalvular components should be considered to provide a tailored approach for mitral valve repair, or to opt for immediate replacement in case of unfavorable geometry., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: Supravalvular pulmonary stenosis (SPS) remains a worrisome complication in the long term of simple transposition of the great arteries. Issues of scar formation and inability to grow are considered at the base of this phenomenon. We pioneered the use of a tissue engineering approach to guide the maturation and the growth of pulmonary autograft in the Ross procedure with encouraging results. We therefore sought to investigate the use of a similar approach in the reconstruction of neopulmonary trunk (NPT) with the aim to recreate a vascular conduit that retains the structural architecture and the same biological potential of native pulmonary artery and prevents long-term SPS., Methods: A model of NPT reconstruction in growing lambs was used. NPT was constructed with autologous pericardium and reinforced with a four-layered knitted polydioxanone mesh (PDS n=10) or left unreinforced (control n=10). Animals were left growing for 6 months and angiographic and transesophageal echocardiographic measurements were performed at day 1 and at the end of the study together with histological analysis., Results: Control group developed SPS while PDS reinforcement allowed a progressive increase in diameter with an optimal size to match the pulmonary artery of healthy growing controls. Histological analysis showed in the control group disruption of endothelial lining with fibrosis, while demonstrated in the PDS group a trilaminar vessel-like structure., Conclusions: The bioresorbable reinforcement induced the formation over time of a neopulmonary conduit able to both face the hemodynamic load of the pulmonary system and guarantee a harmonious increase in size during the somatic growth., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background Aims: Follistatin (FST) and the related proteins FSTL1 and FSTL3 are crucial modulators of the transforming growth factor (TGF)-beta superfamily and function by neutralizing activins, a group of proteins implicated in many biologic processes, such as cell proliferation and differentiation, immune responses, various endocrine activities, wound repair, inflammation and fibrosis. Activins are increased in the serum of heart failure patients and in cardiomyocytes after experimental myocardial infarction, suggesting the involvement of activins in heart failure pathogenesis. FST is considered to be a key modulator in muscle development, differentiation and regeneration, and it has been implicated in the repair of mesodermal- and endodermal-derived tissues, promoting cell proliferation and hampering fibrogenesis. We have previously demonstrated that electrostimulation (ES) induces cardiomyocyte pre-commitment of both stem and non-stem cells in vitro. In this study, we evaluated whether applying ES to human mesenchymal stromal cells (hMSC) modulated FST production., Methods: hMSC were electrostimulated with 10 and 40 V for 12 h. FST production was assessed by immunostaining, Western blot and flow cytometry., Results: FST was up-regulated in hMSC after ES and was associated with cardiomyogenic differentiation of hMSC by short-term ES., Conclusions: The possibility of stimulating the production of FST, a key regulator of mesodermal differentiation, in adult stem cells, while avoiding the drawbacks of conditioned media, dangerous drugs and gene delivery, has relevant potential therapeutic clinical applications. Additionally, this simple differentiation system could be useful for elucidating the molecular mechanisms driving the stem cell-differentiation process.

Stem-cell therapy has become a promising therapeutic tool for myocardial repair. Cardiac pre-committed cells, which complete their differentiation in the myocardium, may reduce fibrosis and restore muscle function. However, many questions concerning a precise, functional integration of injected cells remain unanswered. Fibroblasts regulate the cardiac extracellular matrix and are the most abundant cell population in an infarcted area. Electrostimulation is a well-known trophic factor and can induce phenotypic changes in myoblasts. The objective of this study was to evaluate the effectiveness of electrical stimulation to induce pre-commitment of fibroblasts into cardiomyocytes in vitro. Using short-time electrostimulation in a cytokine-free culture system, we induced pre-commitment of two fibroblast cell lines to a cardiomyocyte phenotype. This partial differentiation in vitro may facilitate further differentiation within the cardiac environment and result in better electro-mechanical integration of the therapeutically introduced cells.

Objectives: To evaluate the relationship between CD40/CD40L system and increased thrombogenesis in AF, and to test the effects of simvastatin treatment., Methods: In vitro study using human tissue, University Hospital (tertiary referral center). Experiments on right atrial segments obtained before the onset of cardiopulmonary bypass were done in either presence or absence of 5 microM simvastatin. Two groups of patients in either chronic atrial fibrillation or sinus rhythm at the time of cardiac surgery. The endocardial expression of CD40, the release of CD40L, and adhesion of platelets to endocardium. Additionally, the thickness of platelet aggregates and the platelet distribution on the endocardium were also evaluated., Results: Atrial fibrillation was associated with a significant increase of endocardial CD40 expression (293.1+/-55.1 pg/ml vs. 230.9+/-53.3 pg/ml, p<0.01), and platelet-endocardial adhesion compared with sinus rhythm atria (10.8+/-2.2 vs. 5.2+/-1.3 platelet CD41 AU p<0.01). At immunofluorescence about 62% of fibrillating endocardium was covered by platelets, compared with 12% of not sinus rhythm atria. Addition of simvastatin significantly reduced CD40 expression as well as platelet adhesion to fibrillating atria; its efficacy was not reversed by the addition of mevalonic acid., Conclusions: Chronic atrial fibrillation acutely upregulates CD40 expression as well as platelet adhesion to the endocardium. Simvastatin is effective in modulating this expression, thus it may potentially contribute to reduce the risk of intra-atrial thrombus formation.

Background: Neutrophils play a central role in systemic inflammatory reaction after cardiopulmonary bypass. Apoptosis is significantly delayed, and this might exacerbate systemic and myocardial damage. We tested the hypothesis of whether pretreatment with simvastatin increases the apoptotic rate of neutrophils and hence reduces the entity of inflammatory reaction., Methods: Thirty patients undergoing coronary surgery with cardiopulmonary bypass were randomized to treatment with either simvastatin (40 mg/day) or placebo for 3 weeks before surgery. A group of 15 patients undergoing off-pump coronary surgery served as controls. Blood samples for detection of serum cytokine levels were obtained before anesthesia, at the end of surgery, and at 4, 24, 48, and 72 hours postoperatively. Apoptosis and indices of activation were assessed in cultured neutrophils., Results: Simvastatin significantly reduced the postoperative peak values of interleukin (IL)-6 and IL-8. The neutrophil apoptotic rate was significantly higher among neutrophils obtained from patients pretreated with simvastatin (p < 0.05 at both 8 and 24 hours) compared with placebo. Neutrophils from the statin group had depressed functional activity, as underscored by significantly lower values of CD11b (p < 0.01 at 24 hours) and a significantly less percentage of cells positive for nitro-blue tetrazolium (p < 0.01 at 12 and 24 hours) compared with placebo., Conclusions: This randomized, double-blind study indicates that statin therapy before cardiopulmonary bypass is associated with reduction of circulating markers of inflammation and increased neutrophil apoptosis. These data support a routine inclusion of statins as an adjuvant pharmacologic therapy before cardiopulmonary bypass surgery.