Intestinal Microbiota and Derived Metabolites in Myocardial Fibrosis and Postoperative Atrial Fibrillation.

The high incidence of atrial fibrillation (AFib) following cardiac surgery (postoperative atrial fibrillation, POAF) relies on specific surgical features. However, in the setting of POAF, the role of the microbiome in the modulation of cardiac fibrosis is still not clear. This study aimed to analyze the effect of the microbiome and its main metabolic product (trimethylamine-N-oxide, TMAO) in the fibrosis of myocardial tissue, to investigate its role in POAF. Patients undergoing elective cardiac surgery with cardiopulmonary bypass, central atrio-caval cannulation and no history of AFib, were included. A fragment of the right atrium was analyzed for qualitative and mRNA-quantitative evaluation. A preoperative blood sample was analyzed with enzyme-linked immunosorbent assay (ELISA). A total of 100 patients have been included, with POAF occurring in 38%. Histologically, a higher degree of fibrosis, angiogenesis and inflammation has been observed in POAF. Quantitative evaluation showed increased mRNA expression of collagen-1, collagen-3, fibronectin, and transforming growth factor beta (TGFb) in the POAF group. ELISA analysis showed higher levels of TMAO, lipopolysaccharide and TGFb in POAF, with similar levels of sP-selectin and zonulin. TMAO ≥ 61.8 ng/mL (odds ratio, OR 2.88 [1.35-6.16], p = 0.006), preoperative hemoglobin < 13.1 g/dL (OR 2.37 [1.07-5.24], p = 0.033) and impaired right ventricular function (OR 2.38 [1.17-4.83], p = 0.017) were independent predictors of POAF. Also, TMAO was significantly associated with POAF by means of increased fibrosis. Gut microbiome product TMAO is crucial for myocardial fibrosis, which is a key factor for POAF. Patients in preoperative sinus rhythm who will develop POAF have increased genetic expression of pro-fibrotic genes and enhanced fibrosis in histological staining. Elevated TMAO level (≥61.8 ng/mL) is an independent risk factor for POAF.

A Nomogram for Predicting Long Length of Stay in The Intensive Care Unit in Patients Undergoing CABG: Results From the Multicenter E-CABG Registry.

OBJECTIVE: Many papers evaluated predictive factors for prolonged intensive care unit (ICU) stay after cardiac surgery, but efforts in translating those models in practical clinical tools is lacking. The aim of this study was to build a new nomogram score and test its calibration and discrimination power for predicting a long length of stay in the ICU among patients undergoing coronary artery bypass graft surgery (CABG). DESIGN: Retrospective analysis of an international registry. SETTING: Multicentric. PARTICIPANTS: Based on the european multicenter study on coronary artery bypass grafting (E-CABG) registry (NCT02319083), a total of 7,352 consecutive patients who underwent isolated CABG were analyzed. INTERVENTIONS: A "long length of stay" in the ICU was considered when equal to or more than 3 days. Predictive factors were analyzed through a multivariate logistic regression model that was used for the nomogram. RESULTS: Long length of ICU stay was observed in 2,665 patients (36.2%). Ten independent variables were included in the final regression model: the SYNTAX score class critical preoperative state, left ventricular ejection fraction class, angina at rest, poor mobility, recent potent antiplatelet use, estimated glomerular filtration rate class, body mass index, sex, and age. Based on this 10-risk factors logistic regression model, a nomogram has been designed. CONCLUSION: The authors defined a nomogram model that can provide an individual prediction of long length of ICU stay in cardiovascular surgical patients undergoing CABG. This type of model would allow an early recognition of high-risk patients who might receive different preoperative and postoperative treatments to improve outcomes.

Pressure ulcers in cardiac surgery: Few clinical studies, difficult risk assessment, and profound clinical implications.

Pressure ulcers (PUs) are a common complication after cardiac surgery, with almost one third of patients suffering from PUs during hospitalisation. Because of the burden that PUs exert on both the patients and the health care system, prevention is of utmost importance. The first step in successful prevention, however, includes the identification of the main features that render patients prone to PU development. Cardiac surgery population is not adequately addressed in current clinical trials and studies. Few studies focused specifically on cardiac surgery patients, but the majority included cardiac surgery patients within a heterogeneous population of acute or critical care patients. Therefore, additional research is warranted to understand the unique risk profile of patients undergoing cardiac surgery. Intraoperative risk factors that affect tissue tolerance have not been thoroughly investigated but are likely to play an important role, which might explain the epidemiology of a PU. Further research is also needed to better comprehend the risk of PUs among cardiac surgery patients and to design effective and tailored preventative measures with the help of newer tools for risk assessment.

Hybrid Coronary Revascularization: An Attractive Alternative Between Actual Results and Future Trends.

Optimal revascularization strategy in patients with multi-vessel coronary artery disease remains a matter of debate, with advantages and disadvantages in both surgical and percutaneous procedures. A combined approach to achieve coronary revascularization, termed "hybrid coronary revascularization" (HCR), has been recently introduced in clinical practice. HCR is defined as a scheduled combination of surgical left internal mammary artery to left anterior descending (LIMA-LAD) grafting and percutaneous treatment of at least one non-LAD coronary arteries, with both procedures planned and performed within a defined time limit. HCR is indicated in case of both proximal LAD disease eligible to surgical LIMA-LAD grafting and non-LAD disease amenable to percutaneous procedures. Reviews and metanalysis of the literature showed that HCR is non-inferior to conventional surgical myocardial revascularization, and in case of high-risk patients, HCR can be the ideal option. However, the various technical approaches and time-related steps need to be further evaluated. Present and future research in interventional cardiology and cardiac surgery will turn into parallel improvements in HCR procedures. Surgical revascularization with off-pump techniques and minimally-invasive approaches, scoring systems such as SYNTAX II, tools evaluating the hemodynamic significance of atherosclerotic plaques with physiology-based approaches such as fractional flow reserve and instantaneous wave-free ratio, newer generation drug eluting stents, newer antiplatelet agents, and therapies might improve indications and clinical outcomes after HCR procedures. This article reviews the current literature on HCR and aims to provide an overview about future developments.

Successful Valve Prolapse Repair for Ischemic Mitral Regurgitation: Combined Papillary Muscle Approximation and Mitral Chordae System Replacement.

Mitral valve prolapse occurs in 33.6% of patients undergoing surgery for ischemic mitral regurgitation (IMR). In the context of IMR, reparative strategy cannot disregard the underlying mechanism of pathogenesis and the progressive geometric alteration affecting left ventricle and papillary muscles. We present a case of extended mitral prolapse of the posteromedial commissure and A3 concomitant to chordal injury after inferior myocardial infarction. We propose a combined sequential approach including papillary muscle approximation and a mitral chordae system replacement.

Downsizing annuloplasty in ischemic mitral regurgitation: double row overlapping suture to avoid ring disinsertion in valve repair.

The long-term outcomes of undersizing annuloplasty for the treatment of ischemic mitral regurgitation (IMR) is affected by the progressive dilation of the annulus, which carries increased risk for ring disinsertion. Reasons underlying this phenomenon might be found in the excess of physical stress on the annuloplasty sutures during the ventricular remodeling process. We report a technique based on the placement of a double row of overlapping sutures aiming at reducing the potential for ring disinsertion. Eleven patients with IMR undergoing mitral valve repair associated with coronary bypass grafting were treated with this technique and echocardiographically followed up at 6 and 12 months. The overall annular dimension decreased significantly with a significant reduction of the tenting area and no recurrence of mitral regurgitation at 1 year. A double row of overlapping sutures allowed firm attachment of the prosthetic ring while downsizing the annulus in IMR, limiting the consequences of changes in subannular ventricular geometry. This technique might therefore be considered a useful aid during mitral valve repair.

Perioperative Right Ventricular Dysfunction and Abnormalities of the Tricuspid Valve Apparatus in Patients Undergoing Cardiac Surgery.

Right ventricular (RV) dysfunction frequently occurs after cardiac surgery and is linked to adverse postoperative outcomes, including mortality, reintubation, stroke, and prolonged ICU stays. While various criteria using echocardiography and hemodynamic parameters have been proposed, a consensus remains elusive. Distinctive RV anatomical features include its thin wall, which presents a triangular shape in a lateral view and a crescent shape in a cross-sectional view. Principal causes of RV dysfunction after cardiac surgery encompass ischemic reperfusion injury, prolonged ischemic time, choice of cardioplegia and its administration, cardiopulmonary bypass weaning characteristics, and preoperative risk factors. Post-left ventricular assist device (LVAD) implantation RV dysfunction is common but often transient, with a favorable prognosis upon resolution. There is an ongoing debate regarding the benefits of concomitant surgical repair of the RV in the presence of regurgitation. According to the literature, the gold standard techniques for assessing RV function are cardiac magnetic resonance imaging and hemodynamic assessment using thermodilution. Echocardiography is widely favored for perioperative RV function evaluation due to its accessibility, reproducibility, non-invasiveness, and cost-effectiveness. Although other techniques exist for RV function assessment, they are less common in clinical practice. Clinical management strategies focus on early detection and include intravenous drugs (inotropes and vasodilators), inhalation drugs (pulmonary vasodilators), ventilator strategies, volume management, and mechanical support. Bridging research gaps in this field is crucial to improving clinical outcomes associated with RV dysfunction in the near future.

Nosocomial Extracardiac Infections After Cardiac Surgery.

Purpose of Review: Nosocomial extracardiac infections after cardiac surgery are a major public health issue affecting 3-8.2% of patients within 30-60 days following the intervention. Recent Findings: Here, we have considered the most important postoperative infective complications that, in order of frequency, are pneumonia, surgical site infection, urinary tract infection, and bloodstream infection. The overall picture that emerges shows that they cause a greater perioperative morbidity and mortality with a longer hospitalization time and excess costs. Preventive interventions and corrective measures, diminishing the burden of nosocomial extracardiac infections, may reduce the global costs. A multidisciplinary team may assure a more appropriate management of nosocomial extracardiac infections leading to a reduction of hospitalization time and mortality rate. Summary: The main and most current data on epidemiology, prevention, microbiology, diagnosis, and management for each one of the most important postoperative infective complications are reported. The establishment of an antimicrobial stewardship in each hospital seems to be, at the moment, the more valid strategy to counteract the challenging problems.

3D-Printed Patient-Specific Casts for the Distal Radius in Children: Outcome and Pre-Market Survey.

BACKGROUND: Orthopaedic and Trauma surgery is expected to undergo profound transformation as a result of the adoption of 3D technology. Among the various applications, patient specific manufacturing of splints and casts would appear to be, particularly in children, an interesting implementation. This study aims to assess the safety of patient specific 3D casts obtained with a newly developed 3D-scanning devise in a small case series. We therefore conducted a clinical outcome and pre-marketing study in 10 consecutive patients with distal radius fractures treated at an Academic Level I Pediatric Trauma Center. After the application of the 3D cast, patients underwent three consecutive evaluations in the following 21 days. The main outcome measurements were: pain, skin lesions and general comfort, and acceptance of the cast. The three domains were measured with the Visual Analogue Scale (VAS), the NPUAP/EPUAP classification and the Positive affect-Negative affect Scale for Children (PANAS-C), the Self-Assessment Manikin (SAM) clinical psychology tests and a Likert-type five item questionnaire, respectively. A final mechanical analysis of the cast was carried out to confirm product integrity. RESULTS: The results obtained were consistently positive in the investigated domains of general comfort, efficacy of contention and mechanical integrity of the 3D-printed cast as well as in the practicability of the supply chain. CONCLUSIONS: This study provides Level IV evidence that patient specific 3D printed casts obtained with a specifically designed software were safe in the management of "buckle" fractures of the distal radius in children. These results encourage to extend the technology to the treatment of more demanding fractures.

Aortic valve replacement in a patient with severe nickel allergy.

Nickel allergy can raise clinical problems in patients undergoing cardiac surgery who require sternal closure with stainless steel wire. We describe the case of a 51-year-old woman with severe nickel allergy who underwent aortic valve replacement with a nickel-free ON-X prosthesis and sternal closure by Fiberwire # 2 suture without complications. Considering its biocompatibility and its mechanical characteristics including optimal strength and knot resistance, this suture might be a viable alternative in patients in which the use of stainless steel wire is contraindicated.

Higher preoperative left atrial volume index predicts lack of mitral regurgitation improvement after transcatheter aortic valve replacement.

BACKGROUND: Moderate-to-severe mitral regurgitation is present in 20-35% of patients undergoing transcatheter aortic valve replacement (TAVR) and the current literature lacks simple echocardiographic parameters, which can predict post-TAVR changes in mitral regurgitation. The aim of this study is to investigate the echocardiographic predictors of improvement or worsening of mitral regurgitation in patients undergoing TAVR with moderate-to-severe mitral regurgitation. METHODS: This retrospective study included 113 patients who underwent TAVR with preoperative mitral regurgitation grade at least 2. Patients with concomitant coronary artery disease requiring treatment were excluded. Mitral regurgitation was related to the annular dilatation or tethering mechanism in all patients. Preoperative and postoperative echocardiographies were compared in terms of mitral regurgitation and other commonly measured parameters. RESULTS: After TAVR, a reduction in mitral regurgitation was observed in 62.8% of cases. On the basis of the difference between postoperative and preoperative echocardiograms, 71 patients had improved mitral regurgitation, whereas 42 patients had stable or worsened mitral regurgitation. After analyzing preoperative echocardiographic parameters with regard to this group difference, left atrial volume index (LAVI) was the only variable that was different between groups (33.4 ±â€Š4.8 ml/m in improved mitral regurgitation vs. 39.8 ±â€Š3.0 ml/m in not improved mitral regurgitation, P < 0.001). In a multivariable logistic regression model, a LAVI increase was associated with lack of an acute reduction in mitral regurgitation (odds ratio = 1.41, P < 0.001) after adjustment for age and preoperative serum creatinine. CONCLUSION: Higher preoperative LAVI is a determinant predictor of lack of an acute reduction in mitral regurgitation after TAVR, and LAVI could be used as a stratifying tool to tailor the treatment strategy and the timing of the procedures. However, validation of these results and long-term outcomes are warranted to support those conclusions.

Predictive scores for major bleeding after coronary artery bypass surgery in low operative risk patients.

BACKGROUND: Cardiac surgery is associated with perioperative bleeding and carries high risk of allogeneic blood transfusion. Recently new scores for prediction of severe bleeding have been developed. This study aims to compare the WILL-BLEED, CRUSADE, PAPWORTH, TRUST, TRACK and ACTION scores in predicting major bleeding after CABG in patients with low estimated operative risk. METHODS: A multicenter observational study included 1391 patients who underwent isolated CABG from July 2015 to January 2018. We tested the hypothesis that the WILL-BLEED score, specifically designed for CABG, would perform at least as well as the CRUSADE, PAPWORTH, TRUST, TRACK and ACTION scores in predicting postoperative major bleeding in low operative risk patients. The primary endpoint was the performance of known bleeding risk scores after CABG. The secondary endpoint was the evaluation of in-hospital mortality. RESULTS: Mean age was 68.2±9.4 years and median Euroscore II value was 1.69% (IQR 1.15-2.81%). Mean blood losses in the first 12 postoperative hours was 339.75 mL. Seventy-three (5.2%) subjects underwent administration of blood products. The rate of severe-massive bleeding according to UDPB grades 3-4 was 1.5%. WILL-BLEED, TRUST, TRACK and ACTION scores were significantly associated with severe postoperative bleeding. WILL-BLEED presented the best c-index (AUC: 0.658; 95% CI: 0.600,0.716). Reclassification analysis showed a worsening in sensitivity and significant negative reclassification of CRUSADE, PAPWORTH, TRACK and ACTION scores when compared with WILL-BEED. The combination of WILL-BLEED and TRUST scores improved the prediction ability (AUC: 0.673; 95% CI: 0.615-0.732). Overall in-hospital mortality was 1.65%. Early mortality in patients with severe versus no-severe bleeding was found to be 11.8% vs. 1.0% Severe bleeding (OR: 13.26; P value<0.001) was found to be significantly associated with early mortality. CONCLUSIONS: Severe bleeding after CABG is a harmful event associated with adverse outcomes. WILL-BLEED Score has the better performance in predicting severe-massive bleeding after CABG. The TRUST Score, although suboptimal, represents a valuable alternative in this setting.

The long-term follow-up of large-diameter Dacron® vascular grafts in surgical practice: a review.

Synthetic grafts have been widely used in cardiac and vascular surgery since the mid-1970s. Considering the relative lack of randomized clinical trials or systematic analyses in the field of prosthetic large vessel diameter replacement, we reviewed the literature on the long-term performance and surgical management of complications of Dacron® grafts in both thoracic and abdominal aorta reconstruction and in the pediatric population. MedLine, Embase and Cochrane Library databases were searched for meta-analyses, reviews, clinical trials, and case reports pertinent to the study object. Aortic replacement with Dacron® prostheses is widely performed with acceptable outcome and a relatively low rate of graft-related and postimplantation complications, such as rupture, infection and fistulization. However, progressive dilation and mechanical failure of the grafts represent the most worrisome complication in all the districts analyzed. The emerging concept of the mismatch in the biomechanical properties between the prosthetic material and native aorta is thought to be at the root of these complications leading to even more daunting consequences when the ascending aorta is involved. Indeed introduction of a non-compliant prosthesis in place of the native ascending aorta can exert detrimental effects not only at the level of the anastomosis, leading to pseudoaneurysm, but also can influence the optimal performance of the aortic root complex with consequent valve dysfunction and ventricular hypertrophy. Albeit confirming their overall successful performance, this review launches a warning on the current liberal use of non-compliant grafts in aortic position, remarking the need for alternative vascular conduits mimicking the native artery compliance.

Preoperative atorvastatin reduces bleeding and blood transfusions in patients undergoing elective isolated aortic valve replacement.

OBJECTIVES: Minimization of bleeding to reduce the use of blood products is of utmost importance in cardiac surgery. Statins are known for their pleiotropic effects beyond lipid-lowering properties, and the use of atorvastatin preoperatively is associated with reduced risk of bleeding and blood product use after coronary surgery. However, no studies have investigated if this beneficial effect also extends to aortic valve surgery. METHODS: In this retrospective cohort study, 1145 consecutive patients undergoing elective primary isolated aortic valve replacement meeting the inclusion and exclusion criteria were selected from January 2009 to December 2017 (547 in the atorvastatin group, 598 in the control group). Postoperative bleeding, blood product use, and complications were monitored during hospitalization. RESULTS: Postoperative bleeding was significantly lower in the atorvastatin group compared with the controls in the first 12 h after surgery (372 ± 137 vs 561 ± 219 ml; P = 0.001) and considering overall bleeding (678 ± 387 vs 981 ± 345 ml, P = 0.001). A total of 32.3% of controls and 26.3% of atorvastatin users received packed red blood cells (P = 0.027), and major surgical complications were similar between the groups. Postoperative length of stay was shorter in the atorvastatin group with an average reduction of 1 day of hospitalization (6.0 ± 1.4 vs 6.9 ± 2.1 days; P = 0.001). Postoperative bleeding among the atorvastatin-treated patients was significantly greater in those taking lower doses compared to those taking higher doses of atorvastatin with a 20% between-group difference (P = 0.001). CONCLUSIONS: Preoperative treatment with atorvastatin might reduce postoperative bleeding and transfusion of packed red blood cells in patients undergoing elective isolated aortic valve replacement. This result might translate into faster recovery after surgery and reduced hospitalization costs.

Primary cardiac MYC/BCL6 double hit non-Hodgkin lymphoma.

Cardiac and pericardial involvement by malignant lymphoma is a rare condition. The present case report describes a case of primary cardiac MYC/BCL6 double hit non-Hodgkin lymphoma in the pericardium, and highlights the importance of a prompt diagnosis and aggressive pharmacologic treatment of this disease. In a symptomatic patient, a minimally invasive 3 cm sub-xiphoidal incision was performed under deep sedation with spontaneous ventilation to perform a pericardial biopsy. A 5 cm × 3 cm portion of pericardium was removed from above the right ventricle, thus ameliorating the extrinsic compression on the right chambers. The patient received 6 cycles of immuno-chemotherapy (rituximab plus cyclophosphamide, vincristine, and methylprednisolone), with no complications, achieving complete remission with no symptoms. Malignancies must be excluded in every case of acute pericardial disease with imaging techniques, and lymphomas should be always considered in the differential diagnosis of cardiac tumors. Complete surgical removal of the tumor is not necessary to achieve complete remission, and minimally invasive surgical approaches are an effective tool to confirm diagnosis and allow a precise histologic characterization. .

Single-territory incomplete surgical revascularization improves regional wall motion of remote ventricular areas: results from a propensity-matched study.

OBJECTIVE: Basic science studies demonstrated a general intramyocardial angiogenetic response potentially responsible for the creation of a microvascular neocapillaries network assisting myocardial function. We hypothesized that the benefit provided by the reperfusion of left anterior descending (LAD) territories and the biological angiogenetic drive triggered by the revascularization could translate in a global improvement in ventricular contractility, not restricted to the grafted area. METHODS: High-risk patients with multivessel coronary artery disease and preoperative wall motion abnormalities were retrospectively analyzed to compare outcomes and regional ventricular function of those who received optimal medical therapy (OMT) versus those who underwent off-pump coronary artery bypass grafting (OPCABG) and received an incomplete myocardial revascularization using left internal mammary artery (LIMA) on LAD (OPCABG group). From January 2007 to December 2014, 206 patients (OMT, n = 136, OPCABG, n = 70) were propensity-score matched to have 70 matched pairs. Variables included in propensity score analyses were ejection fraction (EF), left ventricular end diastolic volume (LVEDVi), EuroSCORE II. Primary endpoint was the variation in the global wall motion score index (ΔWMSI) as evaluated by transthoracic echocardiography. Follow up was completed at 3 years from surgery or hospital discharge. RESULTS: Regional analysis of ventricular function revealed a regional WMSI improvement in the OPCABG group not only for LAD territories but also for non-LAD regions, associated with a reduction in the negative left ventricular ischemic remodeling, compared to patients discharged in optimal medical therapy. Global ΔWMSI was negative in OPCABG group (-3.4 ± 2.8%) and positive in the OMT group (5.9 ± 3.1%), indicating a better wall motion score for OPCAB patients. Surprisingly, regional WMSI improved also in non-grafted territories in the off-pump CABG group with a delta value of -3.7 ± 5.3% for left circumflex artery (LCX) area and -3.5 ± 5.4% for right coronary artery (RCA) area. CONCLUSIONS: In patients with multivessel coronary artery disease, LIMA-to-LAD grafting is associated with an improvement in the WMSI involving also the surrounding non-LAD ungrafted segments and with the attenuation of negative global and regional ischemic ventricular remodeling.

Heart rate variability: a new tool to predict complications in adult cardiac surgery.

Heart rate variability (HRV) refers to the variations between consecutive heartbeats, which depend on the continuous modulation of the sympathetic and parasympathetic branches of the autonomic nervous system. HRV has been shown to be effective as a predictor of risk after myocardial infarction and an early warning sign of diabetic neuropathy, and in the cardiology setting is now recognized to be a useful tool for risk-stratification after hospital admission and after discharge. Recent evidences suggest that HRV analysis might predict complications even in patients undergoing cardiac surgery, and the present review summarizes the importance of HRV analysis in adult cardiac surgery and the perspectives for HRV use in current clinical practice. Although future larger studies are warranted before HRV can be included into daily clinical practice in adult cardiac surgery, HRV is a novel tool which might detect autonomic instability in the early postoperative phase and during hospital stay, thus predicting or prompt-diagnosing many of the post-operative complications.

Preoperative atorvastatin reduces bleeding and blood products use in patients undergoing on-pump coronary artery bypass grafting.

AIMS: Statins are a widely recognized weapon in the primary and secondary prevention of coronary artery disease for their pleiotropic effects. However, recent reports from the cerebrovascular and pharmacological literature are insinuating concerns about a potential increase in the haemorrhagic risk among statin users.The effect of statins in postoperative bleeding should be carefully investigated in major cardiac surgery that exposes per se to risk of bleeding. METHODS: In this retrospective cohort study, we evaluated 441 patients who received atorvastatin until surgery and 213 patients who had never been treated with statins, undergoing elective primary isolated on-pump coronary artery bypass grafting. Postoperative bleedings, blood products use and complications were monitored during hospitalization. RESULTS: Preoperative and intraoperative variables were similar between groups. Early and overall postoperative bleedings were reduced among statin users, who had lower C-reactive protein values in the first postoperative day. Atorvastatin carries a strong protective effect against major bleedings, with a propensity score-adjusted odds ratio of 0.28 (P < 0.01). Also, blood products use for statin-treated patients was lower compared with controls, with fewer transfused patients and fewer red-packed cells units per transfused patient. CONCLUSION: Preoperative atorvastatin use is associated with reduced risk of bleeding and blood products use after coronary artery bypass grafting, likely due to a reduction in the postoperative inflammatory response. Statin continuation at the highest tolerable dose should be encouraged before cardiac surgery. The preoperative use of statins in cardiac surgery as 'bleeding-preventers' might have profound clinical implications.

The role of extracellular matrix in age-related conduction disorders: a forgotten player?

Cardiovascular aging is a physiological process gradually leading to structural degeneration and functional loss of all the cardiac and vascular components. Conduction system is also deeply influenced by the aging process with relevant reflexes in the clinical side. Age-related arrhythmias carry significant morbidity and mortality and represent a clinical and economical burden. An important and unjustly unrecognized actor in the pathophysiology of aging is represented by the extracellular matrix (ECM) that not only structurally supports the heart determining its mechanical and functional properties, but also sends a biological signaling regulating cellular function and maintaining tissue homeostasis. At the biophysical level, cardiac ECM exhibits a peculiar degree of anisotropy, which is among the main determinants of the conductive properties of the specialized electrical conduction system. Age-associated alterations of cardiac ECM are therefore able to profoundly affect the function of the conduction system with striking impact on the patient clinical conditions. This review will focus on the ECM changes that occur during aging in the heart conduction system and on their translation to the clinical scenario. Potential diagnostic and therapeutical perspectives arising from the knowledge on ECM age-associated alterations are further discussed.

Simvastatin attenuates the endothelial pro-thrombotic shift in saphenous vein grafts induced by Advanced glycation endproducts.

BACKGROUND: Advanced glycation endproducts (AGEs) and its receptors (RAGEs) are heterogeneous signaling proteins associated to diabetes and responsible of endothelial alterations leading to atherosclerosis progression and graft failure. The aim of this study was to investigate the role of statin in reducing AGEs related endothelial damage. METHODS: Endothelial cell(EC) obtained from leftovers of saphenous vein grafts of non-diabetic patients were incubated with AGEs (2 and 20 µM) and subsequently treated with Simvastatin. Neutrophils (PNM) adherence, ROS production and RAGE and peroxisome proliferator-activated receptors-gamma (PPAR-γ) expression were analyzed. As clinical validation of the in vitro findings, ECs of diabetic patients in optimized glycaemic control administered with a 3 weeks Simvastatin regimen were similarly processed. RESULTS: Simvastatin blunted the rise in PMN adhesion and ROS generation following stimulation of saphenous vein EC culture with AGEs in vitro. This effect was time dependent and was associated to an increase in PPAR-γ induction paralleled by a decrease in RAGEs expression. Parallely, data from diabetic patients administered with Simvastatin showed a similar significant reduction in PNM adhesion and ROS generation. Simvastatin treatment significantly decreased RAGEs expression in ECs from diabetic patients and determined a slight increase in PPAR-γ expression but the latter failed to reach statistical significance. Interference in the function of these two crucial pathways might be at the root of the statin antinflammatory and antithrombotic effect in the context of AGEs-associated damage. CONCLUSIONS: Despite the recently raised warning on the use of statins in the diabetic population, this study elucidates their cornerstone position in endothelial homeostasis of saphenous grafts in patients with controlled diabetes.