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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.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.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.

Coronary artery calcium (CAC) scoring has emerged as a marker of the burden of atheromatous disease and has been included in scoring systems. The practice of myocardial revascularization, considering percutaneous procedures or surgical strategies, is dramatically changing over years and the prognostic significance of CAC scoring is gradually being conceived. In this interdisciplinary scenario, vessel specific calcium scoring, mapping of coronary calcification and its integration with functional assessment of coronary artery disease might change the future decisions in the catheterization lab and operative theaters. This article summarizes CAC evaluation techniques and its implications in clinical practice.

Purpose. Statins are a class of drugs widely used in clinical practice for their lipid-lowering and pleiotropic effects. In recent years, a correlation between statins and platelet function has been unveiled in the literature that might introduce new therapeutic indications for this class of drugs. This review is aimed at summarizing the mechanisms underlying statin-platelet interaction in the cardiologic scenario and building the basis for future in-depth studies. Methods. We conducted a literature search through PubMed, Embase, EBSCO, Cochrane Database of Systematic Reviews, and Web of Science from their inception to June 2020. Results. Many pathways could explain the interaction between statins and platelets, but the specific effect depends on the specific compound. Some could be mediated by enzymes that allow the entry of drugs into the cell (OATP2B1) and others by enzymes that mediate their activation (PLA2, MAPK, TAX2, PPARs, AKT, and COX-1), recruitment and adhesion (LOX-1, CD36, and CD40L), or apoptosis (BCL2). Statins also appear to have a synergistic effect with aspirin and low molecular weight heparins. Surprisingly, they seem to have an antagonistic effect with clopidogrel. Conclusion. There are many pathways potentially responsible for the interactions between statins and platelets. Their effect appears to be closely related, and each single effect can be barely measured. Also, the same compound might have complex downstream signaling with potentially opposite effects, i.e., beneficial or deleterious. The multiple clinical implications that can be derived as a result of this interaction, however, represent an excellent reason to develop future in-depth studies.

Wound healing process after surgical procedure plays a crucial role to prevent blood loss and infections. Hypertrophic scars might occur after surgery and are generally associated with an inflammatory burden. Cardiac surgery is intrinsically related to a strong systemic inflammatory state that might favor hypertrophic scarring. Besides lipid-lowering effects, statins are known for their pleiotropic and anti-inflammatory activity. The aim of this study was to investigate the impact of statins in the healing process after median sternotomy in patients undergoing cardiac surgery. All patients undergoing major cardiac surgery with median sternotomy and cardiopulmonary bypass, and subsequently evaluated in the outpatient clinic after discharge, were included in this study. A total of 930 Caucasian patients were retrospectively reviewed. At outpatient visit, 276 patients (29.7%) showed the formation of hypertrophic scars. Patients with hypertrophic scars tended to be younger (P = .001) and nonstatin users (P = .001). Logistic regression analysis confirmed the protective role of statins (odds ratio 0.39, 95% confidence interval 0.29-0.53, P = .001), after adjustment for age. A dose-dependent effect was confirmed, showing a more intensive protective effect for higher doses of statins. Statin use might be correlated with reduced hypertrophic scars after cardiac surgery through median sternotomy. A dose-dependent effect has been shown, and statin effect seems to be independent of age in a selected population undergoing surgery with an elevated inflammatory burden. Although further studies are warranted to elucidate the biologic mechanisms, the concept of using statins as anti-scarring agents is novel and should be investigated with tailored studies.

Background Twelve-lead ECG represents the most common diagnostic tool in clinical cardiology and allows an immediate screening of left ventricular hypertrophy (LVH), but current criteria might have poor clinical usefulness in everyday clinical practice due to lack of sensitivity. Methods The current study aims to review and compare the clinical performance of known ECG criteria of LVH in a real-life setting; 2134 patients had ECG and echocardiographic exams performed during the same hospitalization. All traces were retrospectively analysed, and the amplitudes of the waves were manually measured. Transthoracic echocardiography was considered as the gold standard to assess LVH. Results LVH had a prevalence of 58%. Considering the diagnostic performance of ECG criteria for LVH, the Cornell voltage carried the best area under the receiver operating characteristic curve (0.678), while RaVF (R wave in aVF lead) had the poorer result (0.440). The R5/R6 criterion had the best sensitivity (60%), but with the worst specificity (37.4%). The 'Q or S aVR' had the best specificity (99.9%) but lacks sensitivity (0.80%). The Peguero Lo Presti criterion had a sensitivity of 42.3% and a specificity of 75.8%. The Cornell voltage and the Cornell product had similar area under the receiver operating characteristic curve values which were found to be significantly greater compared with other criteria. Conclusion Current ECG criteria of LVH have low sensitivity despite an acceptable specificity. Among these, Cornell voltage and Cornell product criteria were equally found to have a more accurate diagnostic performance compared with other criteria. To overcome the intrinsic limitations of the current ECG LVH criteria, a new paradigm in the analysis of electrocardiographic data might be necessary.

Aim: Hybrid coronary revascularization (HCR) for multivessel coronary artery disease (CAD) integrates coronary artery bypass grafting (CABG) and percutaneous intervention in a planned revascularization strategy. This systematic review summarizes the state of this art of this technique. Methods: Major databases searched until October 2021. Results: The available literature on HCR includes three randomized trials, ten meta-analysis and 27 retrospective studies. The greatest benefits are observed in patients with low-to-intermediate risk and less complex coronary anatomy; highly complex disease and the presence of risk factors favored conventional CABG in terms of adverse events and survival. Conclusion: HCR is an interesting approach for multivessel CAD but should not be considered a ‘one-size-fits-all’ procedure. Further studies will specify the subset of patients likely to benefit most from this hybrid approach.

(1) Background: Bicuspid aortic valve (BAV) is the most frequent congenital cardiac disease. Alteration of ascending aorta diameter is a consequence of shear stress alterations due to haemodynamic abnormalities developed from inadequate valve cusp coaptation. (2) Objective: This narrative review aims to discuss anatomical, pathophysiological, genetical, ultrasound, and radiological aspects of BAV disease, focusing on BAV classification related to imaging patterns and flux models involved in the onset and developing vessel dilatation. (3) Methods: A comprehensive search strategy was implemented in PubMed from January to May 2022. English language articles were selected independently by two authors and screened according to the following criteria. (4) Key Contents and Findings: Ultrasound scan is the primary step in the diagnostic flowchart identifying structural and doppler patterns of the valve. Computed tomography determines aortic vessel dimensions according to the anatomo-pathology of the valve. Magnetic resonance identifies hemodynamic alterations. New classifications and surgical indications derive from these diagnostic features. Currently, indications correlate morphological results, dissection risk factors, and genetic alterations. Surgical options vary from aortic valve and aortic vessel substitution to aortic valve repair according to the morphology of the valve. In selected patients, transcatheter aortic valve replacement has an even more impact on the treatment choice. (5) Conclusions: Different imaging approaches are an essential part of BAV diagnosis. Morphological classifications influence the surgical outcome.

Purpose Post-pericardiotomy syndrome (PPS) is a common complication of cardiac surgery. This systematic review aimed to investigate the efficacy of colchicine, indomethacin, and dexamethasone in the treatment and prophylaxis of PPS. Methods Literature research was carried out using PubMed. Studies investigating ≥ 10 patients with clinically PPS treated with colchicine, dexamethasone, and indomethacin and compared with placebo were included. Animal or in vitro experiments, studies on Results Seven studies were included. Among studies with postoperative colchicine treatment, two of them demonstrated a significant reduction of PPS. In the single pre-surgery colchicine administration study, a decrease of PPS cases was registered. Indomethacin pre-surgery administration was linked to a reduction of PPS. No significant result emerged with preoperative dexamethasone intake. Conclusion Better outcomes have been registered when colchicine and indomethacin were administered as primary prophylactic agents in preventing PPS and PE. Further RCT studies are needed to confirm these results.

Background: Endothelial injury occurring during cardiopulmonary bypass is a major contributing factor in the development of organ dysfunction, which leads to many of the postoperative complications occurring during cardiac surgery. Objective: This narrative review aims to summarize the main mechanisms of cardiopulmonary bypass - related disease, evaluating the unfavorable events leading to tissue injury, with a description of current pharmacologic and non-pharmacologic mechanisms to reduce CPB-related injury. Methods: A Medline/Pubmed/Scopus search was conducted using clinical queries with the key terms "cardiac surgery", “cardiopulmonary bypass”, "inflammation" and “endothelial injury”, and related MeSH terms, until July 2019. The search strategy included meta-analyses, randomized controlled trials, clinical trials, reviews and pertinent references. Patents were searched using the same key terms from https://patents.google.com/, www.uspto.gov, and www.freepatentsonline.com. Results: In this review, we discuss the current knowledge of the mechanisms of vascular endothelial cell injury, the acute inflammatory response, and the regulatory factors that control the extent of vascular injury during extracorporeal circulation, summarizing the main target of anti-inflammatory pharmacologic and non-pharmacologic strategies. Conclusion: Inflammatory response and endothelial dysfunction following cardiopulmonary bypass are the prices to pay for the benefits offered during cardiac surgery procedures. Counteracting the detrimental effect of extracorporeal circulation appears to be crucial to improve clinical outcomes in pediatric and adult cardiac surgery. The intrinsic complexity and the tight interplay of the factors involved might require a holistic approach against inflammation and endothelial response.

Median sternotomy remains the most common access to perform cardiac surgery procedures. However, the experience of the operating surgeon remains a crucial factor during sternal closure to avoid potential complications related to poor sternal healing, such as mediastinitis. Considering the lack of major randomized controlled trials and the heterogeneity of the current literature, this narrative review aims to summarize the different techniques and approaches to sternal closure with the aim to investigate their reflections into clinical outcomes and to inform the choice on the most effective closure method after median sternotomy. A literature search through PubMed, Embase, EBSCO, Cochrane database of systematic reviews, and Web of Science from its inception up to April 2019 using the following search keywords in various combinations: sternal, sternotomy, mediastinitis, deep sternal wound infection, cardiac surgery, closure. Single wire fixation methods, at present, seems the most useful method to perform sternal closure in routine patients, although patients with a fragile sternum might benefit more from a figure-of-eight technique. In high-risk patients (e.g. chronic pulmonary disease, obesity, bilateral internal mammary artery harvesting, diabetes, off-midline sternotomy), rigid plate fixation is currently the most effective method, if available; alternatively, weave techniques could be used. The choice among the sternal closure techniques should be mainly inspired and tailored on the patient’s characteristics, and correct judgement and experience play a pivotal role. A decisional algorithm has been proposed as an attempt to overcome the absence of specific guidelines and to guide the operative approach. This operative approach might be used also in non-cardiac procedure in which median sternotomy is required, such as in case of thoracic surgery.

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.

Three-dimensional (3D) printing is emerging as an innovative tool for a tailored approach to endovascular or open procedures. The efforts of different specialists and data analysis can be used to fabricate patient-specific implants, which might have significant impact even in life-saving procedures such as aortic dissections or aortic arch aneurysm. 3D printing is gradually changing the traditional pattern of diagnosis and treatment. This innovative approach allows a perfect match between the patient's anatomy and the prosthetic graft, ideally resulting in better hemodynamics and improved long-term patency related to reduced turbulent flow. Future applications of 3D printing in the cardiovascular field combined with tissue engineering will enhance the therapeutic features of bioprinted tissues and scaffolds for regenerative medicine. This review will summarize the clinical significance of 3D printing in cardiovascular disease, exploring current applications, translational outlooks and future perspectives.

Objective: Procalcitonin (PCT) has been associated with adverse outcomes after cardiac surgery. Nevertheless, there is no consensus on thresholds and timing of PCT measurement to predict adverse outcomes. Materials & methods: A total of 960 patients undergoing elective cardiac surgery were retrospectively evaluated. PCT levels were measured from the first to the seventh postoperative day (POD). The onset of complications was recorded. Results: Complications occurred in 421 (44%) patients. PCT on the third POD was associated with the occurrence of any kind of complications (odds ratio: 1.06; p: 0.037), and noninfectious complications (odds ratio: 1.05; p: 0.035), after adjusting. PCT above the median value at the third POD (>0.33 μg/l) predicted postoperative complications (incidence rate ratio: 1.13; p = 0.035). Conclusion: PCT seems to predict postoperative complications in cardiac surgery. The determination at the third POD yields the greatest sensitivity and specificity.

The use of wearable sensors for health monitoring is rapidly growing. Over the past decade, wearable technology has gained much attention from the tech industry for commercial reasons and the interest of researchers and clinicians for reasons related to its potential benefit on patients’ health. Wearable devices use advanced and specialized sensors able to monitor not only activity parameters, such as heart rate or step count, but also physiological parameters, such as heart electrical activity or blood pressure. Electrocardiogram (ECG) monitoring is becoming one of the most attractive health-related features of modern smartwatches, and, because cardiovascular disease (CVD) is one of the leading causes of death globally, the use of a smartwatch to monitor patients could greatly impact the disease outcomes on health care systems. Commercial wearable devices are able to record just single-lead ECG using a couple of metallic contact dry electrodes. This kind of measurement can be used only for arrhythmia diagnosis. For the diagnosis of other cardiac disorders, additional ECG leads are required. In this study, we characterized an electronic interface to be used with multiple contactless capacitive electrodes in order to develop a wearable ECG device able to perform several lead measurements. We verified the ability of the electronic interface to amplify differential biopotentials and to reject common-mode signals produced by electromagnetic interference (EMI). We developed a portable device based on the studied electronic interface that represents a prototype system for further developments. We evaluated the performances of the developed device. The signal-to-noise ratio of the output signal is favorable, and all the features needed for a clinical evaluation (P waves, QRS complexes and T waves) are clearly readable.

Bicuspid aortic valve (BAV) disease is the most common congenital abnormality and is characterized by a risk of premature aortic valve disease, predominantly aortic stenosis. Surgery remains the treatment of choice for patients with symptomatic BAV disease, but, in patients who are unsuitable for surgical aortic valve replacement, transcatheter aortic valve replacement (TAVR) is currently used as an alternative to surgery, although there is no official recommendation for their management, since BAV patients with severe aortic stenosis have been excluded from the major TAVR randomized clinical trials. Patients with BAV stenosis present anatomic challenges for treatment with TAVR. The BAV annulus often has an elliptical shape and is larger than the tricuspid valve, and is more likely to exhibit severe eccentric calcification. In addition, BAV is often associated with a dilated, horizontal ascending aorta, and effaced sinuses. The calcified raphe may also place differential stress on the expansion of the transcatheter valve, increasing the risk of suboptimal positioning and consequently the risk of paravalvular leakage, new pacemaker implantation, new-onset left bundle branch block, and annular rupture. Moreover, coronary obstruction may occur when leaflet fusion results in a longer leaflet. Although some of these challenges have been successfully overcome using new-generation devices, the complication rate is still relatively high and requires a deeper understanding of the patient’s specific complex and variable anatomy. Selection of the type and size of the transcatheter valve according to the patient’s individual anatomy is critical to achieving successful results. Therefore, given the increasing frequency of BAV stenosis in younger patients, and the worldwide expansion in the application of TAVR in younger and lower surgical-risk patients, preprocedural multimodality imaging involving CT scan and three-dimensional echocardiography is mandatory to understand the complex and variable anatomy of BAV disease and improve both procedural results and short- and long-term outcomes in these patients.

Mitral valve repair is the gold standard for treatment of degenerative mitral regurgitation, such as that caused by leaflet prolapse, flail or annular dilatation. A variety of surgical techniques allow surgeons to achieve a high rate of success with mitral valve repair, even in complex cases, and mitral valve repair is associated with better long-term outcomes than valve replacement. However, in the setting of mitral valve surgical repair, systolic anterior motion (SAM) is a complication that determines the dynamic anterior movement of the mitral valve towards the interventricular septum during systole, and creates a left ventricular outflow tract obstruction associated with residual mitral regurgitation. Awareness of risk factors for SAM influences operative planning for repair. Predictors of SAM are known and can be definitively evaluated with intraoperative transesophageal echocardiography, but SAM still complicates mitral valve repair and, if untreated, negatively impacts short-term and long-term outcomes. A stepwise approach in SAM correction is advocated, consisting of medical therapy with aggressive volume-loading and beta-adrenoceptor blockade, but severe or persistent SAM requires surgical revision with a second cross-clamping or a redo procedure. The correct choice of surgical technique requires a deep understanding of the anatomical substrate of SAM, as SAM can be due to different mechanisms that require tailored surgical correction to avoid ineffective or potentially dangerous procedures. This paper reviews the mechanisms and predictors of SAM and summarizes the current concepts of intraoperative and postoperative SAM management.

Maintenance of physiologically balanced levels of autophagy is crucial for cellular homeostasis and in the normal vessel wall, balanced autophagy can be considered a cytoprotective mechanism that preserves endothelial function and prevents cardiovascular disease. Recent studies pointed out the importance of the modulation of the autophagic flux in the pathogenesis of aortic dissection and aneurysms of the ascending aorta. Notably, shear stress (and its receptor p62), IL-6, Rab7 and Atg5/IRE1α pathways of autophagy may be considered the novel super-selective therapeutic target for the preventive and postoperative treatment of aortic aneurysm and aortic dissection. This review intends to summarize current evidences in this field trying to enlighten new avenues for future researches.

Median sternotomy is the most common access for cardiac surgery. Deep surgical wound infection (DSWI) and mediastinitis after median sternotomy remain significant clinical problems after cardiac surgery in terms of mortality, morbidity and healthcare-associated costs. Despite recent advances in medical management and consensus papers, their incidence ranges from 1% to 5%, and the associated mortality ranges from 20% to 50%. Recent studies in this field are providing excellent outcomes with promising results for the near future. The choice of sternal closure technique plays a crucial role in the prevention of DSWI and mediastinitis and should be tailored to the patient's characteristics, as clinical judgement and experience play a pivotal role. Early aggressive surgical debridement, vacuum-assisted closure (VAC) therapy, muscle flap and newer technologies are revolutionizing the paradigm of treatment of DSWI. Also, recent advances in tissue engineering have been refining potential approaches to tissue regeneration or substitution for enhanced wound repair. This editorial aims to briefly summarize the current and future techniques in DSWI prevention and treatment after cardiac surgery.

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.

The management of antithrombotic therapy in patients undergoing percutaneous coronary intervention (PCI) with an indication for long-term oral anticoagulant therapy (OAT) is still a matter of debate. We aim to evaluate the safety and the efficacy of dual therapy (DT) compared to triple therapy (TT) in this clinical setting.A study level meta-analysis and a review of randomized trials selected using PubMed, Embase, EBSCO, Cochrane database of systematic reviews, Web of Science, and abstract from major cardiology congresses. Six randomized trials with 12,156 patients evaluating the strategy of DT vs. TT in patients treated with PCI with indication for long-term OAT were included.Patients treated with DT demonstrated a 45% relative reduction in the risk of TIMI major bleeding (1.71% vs. 2.99%; OR 0.55, 95% CI 0.41-0.71; P0.0001) and TIMI minor bleeding compared to TT arm (4.67% vs 7.83%, OR 0.55 95% CI 0.39-0.78, P = 0.0007). All-cause mortality was similar in two arms (3.95% vs 3.77%, P = 0.92), as well as cardiovascular mortality (2.21% vs 2.19%, P = 0.97). DT was associated with a borderline increase of ST (1.02% vs 0.67%, P = 0.07). No significant differences were observed in occurrence of MI and stroke.Our findings suggest that DT is safer than TT with regard to occurrence of major bleeding. DT with a direct oral anticoagulant plus clopidogrel at discharge could be effective in most patients, maintaining aspirin in periprocedural phase and as longer "tailored" treatment for patients at higher ischemic risk.

International audience; Heart transplantation (HTx) is a valuable option in eligible patients with end-stage heart failure. The most significant complication in the immediate post-operative period is early graft failure (EGF), with a mean incidence of 20–25%. EGF is a major risk factor for death and accounts for 40–50% of early mortality after HTx. Despite the use of inotropes, EGF may persist and require temporary mechanical circulatory support. Extracorporeal membrane oxygenation (ECMO) has been investigated over the years and has proved to be a reliable strategy in patients with EGF after HTx. This study aims to review the contemporary literature on this topic. Considering short-term outcomes, 45–80% of patients were discharged alive from hospital. Duration of support is variable, with a mean duration of 4–8 days. Cannulation strategy and device selection have no differences with respect to short-term outcomes. The main causes of death are multi-organ failure, bleeding, heart failure, stroke and sepsis. Considering long-term outcomes, ECMO survivors appear to have similar survival rates to HTx patients who did not experience EGF. Also, ECMO-treated EGF, among survivors, has no detrimental effect for graft function. In conclusion, ECMO is a reliable therapeutic option to support patients with severe graft failure after HTx, providing adequate support with either central or peripheral arteriovenous cannulation. Further studies will be needed to establish the correct threshold for ECMO support and to provide long-term results.

Background Mitral valve repair (MVr) combined with papillary muscle approximation (PMA) may improve repair durability in severe ischemic mitral regurgitation (MR), when compared with MVr alone. We sought to identify preoperative transthoracic echocardiographic markers associated with MR recurrence after MVr with PMA. Methods A post-hoc analysis was performed on patients with severe ischemic MR who underwent coronary artery bypass graft surgery with MVr with PMA in the papillary muscle approximation randomized trial. The PMA was performed utilizing a 4-mm polytetrafluoroethylene graft placed around the papillary muscles. Linear regression analyses and receiver-operating characteristic curves were used to identify echocardiographic variables and diagnostic models associated with recurrent MR. Results There were 48 patients with a mean age of 63 ± 7 years, a left ventricular ejection fraction of 35% ± 5%, and a left ventricular end-diastolic diameter of 63 ± 3 mm. Of these, 37 patients had baseline and 5-year follow-up echocardiograms, with moderate-to-severe MR recurring in 27%. Linear regression analyses revealed associations between preoperative pulmonary artery systolic pressure (standardized beta coefficient, β = 0.49/mm Hg, p = 0.002), MV tenting area (β = 0.47/cm2, p = 0.004), a symmetric MV tethering pattern (β = 0.44, p = 0.007), and left ventricular end-diastolic diameter (β = 0.37/mm, p = 0.02) with follow-up MR grade. The presence of both MV tenting area 3.1 cm2 or greater (area under the curve 0.822) and left ventricular end-diastolic diameter of 64 mm or greater (area under the curve 0.801) was the most robust discriminative model for moderate-to-severe MR recurrence (specificity 92%, sensitivity 69%, area under the curve 0.804, p = 0.003). Conclusions In patients undergoing coronary artery bypass graft surgery with MVr plus PMA, the extent of baseline MV apparatus and left ventricle geometric remodeling identifies patients at increased risk for MR recurrence.

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.

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

Objective The most efficient surgical approach to severe aortic valve disease in the young adult is still debated: cryopreserved aortic allograft offers excellent hemodynamic and avoid anticoagulation, but long-term durability is influenced by structural valve deterioration (SVD). This study aimed to describe long-term results of aortic allografts and to identify factors influencing long-term durability. Methods From January 1993 to August 2010, 210 patients underwent aortic allograft replacement via the free-hand subcoronary implantation technique (N = 55) or root replacement with coronary reimplantation (N = 155). Clinic and echocardiographic follow-up was updated to April 2016. Results Overall mortality and cardiac mortality occurred in 80 (38.1%) and 64 (30.5%) patients, respectively. Reoperation was required in 69 cases (32.8%), whereas SVD required reoperation in 57 cases (27.1%). No early endocarditis occurred, whereas late endocarditis occurred in 4 patients. The free-hand technique seems to be associated with improved left ventricular remodeling compared with the root-replacement technique, and smaller allograft size represents a predictor of reoperation independently on the surgical technique used. In the overall population, there were 44 women of childbearing age, and 37 patients remained pregnant during the follow-up of the study. No differences were found in the clinical outcomes among women who had children and who did not. Conclusions Cryopreserved allograft is a valid option, especially in complex infective endocarditis and in women of childbearing age. A careful choice of allograft size and implantation technique can reduce the risk of SVD.

Objective: This study examines the outcomes of the cryopreserved mitral homograft in 110 patients prospectively followed with clinical, echocardiographic and structural valve deterioration (SVD) assessments. Methods: The etiology of mitral disease was: rheumatic disease (n=70), endocarditis (n=33), and others (n=7). There were 31 partial homografts and 79 total homografts. Mitro-aortic homograft valve replacement was performed in 29 cases.Results:Mean follow-up was 9.8W6.3 years (up to 19.2 years). There were seven early (

Objective: This study reports the outcomes of the cryopreserved mitral homograft in 119 patients prospectively followed with clinical, echocardiographic and structural valve deterioration assessments. Methods: 119 patients undergoing mitral and aortic homograft implantation. Patient’s causes of mitral disease were: rheumatic disease (n = 75), endocarditis (n = 37) and others (n = 7). There were 40 partial homografts and 88 total homografts. Mitro-aortic homograft valve replacement was performed in 29 cases. Results: Mean follow-up was 9.8 ± 6.3 years (up to 19.2 yrs). There were 7 early (2 p

Aging results in functional and structural changes in the cardiovascular system, translating into a progressive increase of mechanical vessel stiffness, due to a combination of changes in micro-RNA expression patterns, autophagy, arterial calcification, smooth muscle cell migration and proliferation. The two pivotal mechanisms of aging-related endothelial dysfunction are oxidative stress and inflammation, even in the absence of clinical disease. A comprehensive understanding of the aging process is emerging as a primary concern in literature, as vascular aging has recently become a target for prevention and treatment of cardiovascular disease. Change of life-style, diet, antioxidant regimens, anti-inflammatory treatments, senolytic drugs counteract the pro-aging pathways or target senescent cells modulating their detrimental effects. Such therapies aim to reduce the ineluctable burden of age and contrast aging-associated cardiovascular dysfunction. This narrative review intends to summarize the macrovascular and microvascular changes related with aging, as a better understanding of the pathways leading to arterial aging may contribute to design new mechanism-based therapeutic approaches to attenuate the features of vascular senescence and its clinical impact on the cardiovascular system.

The surgical treatment of aortic valve endocarditis (AVE) is generally performed using conventional mechanical or biological xenograft prosthesis, with limited use of aortic homograft (Ao-Homo) or pulmonary autograft (PA). Clinical evidence has demonstrated a clear contradiction between the proven benefits of Ao-Homo and PA in the context of infection and the very limited use of allogenic or autologous tissue in everyday clinical practice. This review aims to summarize the most recent and relevant literature in order to foster the scientific debate on the use of the use of allogenic and autologous tissue to treat AVE. The decisional process of the Heart Team should also include the preferences of the patient, his/her family, the general cardiologist or primary care physician. The use of allogenic or autologous valve substitute is beneficial if there is a high risk of recurrence of infection, avoiding extensive adhesiolysis and debridement of synthetic material. In any case, those procedures should be performed by highly trained centers to optimize outcomes.

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.

Background Molecular mechanisms underlying abdominal aneurysm (AAA) formation and rupture are not well understood. Early detection and repair of AAA may reduce the high mortality rates associated with rupture. Serum proteomics allows the detection of alterations in the expression of proteins, guiding further studies on these target molecules as potential markers. Analysis of proteomic profile of asymptomatic patients with AAA allows the identification of reliable predictors or markers of disease presence or progression. Methods A proteomics approach based on two-dimensional electrophoresis and mass spectrometry was used to compare serum proteomic profiles of patients with AAA who are candidates for surgical repair compared with healthy controls. We analyzed in parallel the proteomic profile of subjects with cardiac heart failure to discriminate these two pathologies, which show similar pattern of systemic inflammation process. Results We identified in AAA subjects four serum proteins that show altered expression profile and that could be specifically linked to AAA pathology. We discuss the role of our identified proteins with their possible implications in disease outcome. Conclusions This approach could provide an initial screening tool that may drive the basis for further research in the field of cardiovascular diseases. These results need to be validated in larger studies to find potential markers of AAA presence or progression to use in clinical settings. Summary A proteomics approach was used to compare serum proteomic profiles of patients with abdominal aortic aneurysm who are candidates for surgical repair compared with healthy controls. Four serum proteins showed altered expression profile that could be correlated with the pathology. This approach could provide an initial screening tool that may drive the basis for further research in the field of cardiovascular diseases.

Sternal synthesis after median sternotomy, a conventional access practice in thoracic and cardiac surgery, is at the basis of severe complications, often impairing the clinical outcome of surgical interventions. In this work, we propose the use of an acellular biomaterial scaffold, to be interposed across the fracture rime during closure operations, directly exposing the biomaterial to bone marrow, in order to expedite healing process. A rabbit model of median sternotomy was performed and an electrospun scaffold composed of a hydroxyapatite-loaded absorbable biopolymer (poly-L: -lactide), shaped into a fibrillar structure, was used. CT follow-up confirmed a complete healing in the scaffold-treated group 1 week before the control. Histological evaluation demonstrated presence of newly formed bone trabeculae among scaffold fibers showing a higher degree of maturity with respect to the control untreated group. The proposed approach is able to both guide a more rapid healing and modulate inflammatory response across the wound site, resulting in improved healing and tissue remodeling with respect to conventional closure technique.

Anomalous origin of the left coronary artery originating from the opposite sinus of Valsalva is a coronary anomaly with a consistently low prevalence rate. Different patterns have been described for this type of anomaly with respect to the position and course of the coronary arteries. The interarterial type can be considered a malignant variant, as it is characterized by a left main coronary artery that is positioned between the aortic root and the pulmonary artery root, and it frequently presents with syncope or aborted sudden cardiac death. Other symptoms or clinical presentations include the presence or development of angina, acute myocardial infarction and ventricular tachycardia. We present the case of a 49-year old man who presented with a new onset of chest pain; a coronary angiogram showed an anomalous left main coronary artery arising from the right Valsalva sinus, accompanied by a long and severe stenosis. It was found that multi-scan cardiac tomography is very useful in identifying the position of the coronary arteries when coronary anomalies occur.

Aims: Current limitations of tissue-engineered vascular grafts include timing for the scaffold preparation, cell type, cell differentiation and growth inside the construct, and thrombogenicity of the final device. To surmount these shortcomings, we developed a heparin-releasing poly-L-lactide (PLLA) scaffold using the electrospinning technique, to guide the differentiation of human mesenchymal stem cells towards the endothelial phenotype and to deliver a useful drug in the management of the postimplantation period. Materials & methods: The heparin-releasing PLLA scaffold was produced by means of the electrospinning technique in a tubular shape. The scaffold was seeded with human mesenchymal stem cells and cultured for up to 1 week. Cell viability and cytotoxicity assays were performed, and cell differentiation was evaluated by immunofluorescence with confocal microscopy, cytofluorometry and western blotting. Heparin release was assayed by Azure A method and biological effectiveness of the drug was assessed by activated clotting time measurements. Results: The scaffold exhibited a morphology favorable to cell attachment. Heparin release showed an initial burst within the first 24 h, followed by a further sustained release profile. After 48 h of culturing, the construct demonstrated adequate engraftment and viability. Increased proliferation compared with the control scaffold in bare PLLA, suggested the induction of a favorable microenvironment. A shift towards CD31 positivity and modifications in cell morphology were observed in the heparin-releasing PLLA scaffold. Conclusion: By exploiting the biological effects of heparin, we developed an ad hoc differentiating device towards the endothelial phenotype for autologous stem cell seeding and, at the same time, we were able to facilitate and optimize the management of the construct once in clinical settings.

Myocardial infarction and its consequences represent one of the most demanding challenges in cell therapy and regenerative medicine. Transfer of skeletal myoblasts into decompensated hearts has been performed through intramyocardial injection. However, the achievements of both cardiomyocyte differentiation and precise integration of the injected cells into the myocardial wall, in order to augment synchronized contractility and avoid potentially life-threatening alterations in the electrical conduction of the heart, still remain a major target to be pursued. Recently, granulocytes colony-stimulating factor (G-CSF) fuelled the interest of researchers for its direct effect on cardiomyocytes, inhibiting both apoptosis and remodelling in the failing heart and protecting from ventricular arrhythmias through the up-regulation of connexin 43 (Cx43). We propose a tissue engineering approach concerning the fabrication of an electrospun cardiac graft functionalized with G-CSF, in order to provide the correct signalling sequence to orientate myoblast differentiation and exert important systemic and local effects, positively modulating the infarction microenvironment. Poly-(l-lactide) electrospun scaffolds were seeded with C2C12 murine skeletal myoblast for 48 hrs. Biological assays demonstrated the induction of Cx43 expression along with morphostructural changes resulting in cell elongation and appearance of cellular junctions resembling the usual cardiomyocyte arrangement at the ultrastructural level. The possibility of fabricating extracellular matrix-mimicking scaffolds able to promote myoblast pre-commitment towards myocardiocyte lineage and mitigate the hazardous environment of the damaged myocardium represents an interesting strategy in cardiac tissue engineering.

BACKGROUND Diabetic patients exhibit an increased risk of saphenous graft occlusion after coronary bypass. Advanced glycation end products (AGEs) are ubiquitous signalling proteins that are associated with vascular and neurological complication of diabetes. The aim of this study is to verify whether AGE levels may promote endothelial cell alterations responsible for vein graft failure. METHODS Segments of saphenous vein were obtained from both normal people and diabetic patients (HbA(1c) < 6.0%) at the time of coronary surgery. Cultured endothelial cells were incubated in the absence/presence of AGEs (2 and 20 microM), and mRNA and protein for both receptor of AGEs (RAGE) and peroxisome proliferator-activated receptors-gamma (PPAR-gamma) were analysed by real-time polymerised chain reaction (PCR) and Western blot analysis. In the same fashion, the cell release of reactive oxygen species (ROS) was estimated in the absence/presence of AGEs by spectrofluorimetric analysis. Finally, neutrophil-endothelial adhesion was evaluated in saphenous vein segments with and without the addition of AGEs. RESULTS AGEs activated in a dose-dependent manner the expression of RAGE and inhibited PPAR-gamma expression in endothelial cells as testified by both reverse transcription-PCR (RT-PCR) and Western blot analysis. Stimulation of cultured endothelial cells with AGEs significantly enhanced intracellular ROS formation in a dose-dependent manner. Finally, neutrophil-endothelial adhesion was significantly increased after incubation of control veins with AGEs. CONCLUSIONS These findings indicate that even in diabetic patients with HbA(1c) < 6.0%, elevated serum levels of AGE determine a sort of a pro-thrombotic state, providing a common mechanism that could explain the increased rate of vein graft occlusion in this population.

Secondary alcohol metabolites and reactive oxygen species mediate cardiomyopathy induced by cumulative doses of antitumor anthracyclines, such as doxorubicin and epirubicin. Epirubicin exhibits a defective conversion to both toxic species, thereby inducing cardiotoxicity at doses higher than equiactive to doxorubicin; however, the gain in cardiac tolerability seems to be marginal compared with the magnitude of the metabolic defects of epirubicin. Cardiomyopathy may occur independent of toxic metabolites if a given anthracycline tends to accumulate in the heart; therefore, we characterized whether epirubicin showed an unusual accumulation in human myocardial strips incubated in plasma. Epirubicin exhibited a higher uptake and reached myocardial levels 2 times higher than those of doxorubicin. Epirubicin also showed a unique metabolization to doxorubicinolone, the product of epirubicin deglycosidation and carbonyl reduction. In diffusing from the strips to plasma, doxorubicinolone caused membrane permeation effects that augmented epirubicin elimination. Experiments with purified doxorubicinolone showed that the efflux of 1 mol doxorubicinolone promoted the concomitant elimination of as many as approximately 40 mol epirubicin. Doxorubicinolone could also diffuse from plasma back to the strips, causing a permeation effect that promoted epirubicin reuptake; however, this reverse process was slower and less potent. On balance, doxorubicinolone efflux diminished the epirubicin to doxorubicin accumulation ratio to approximately 1.5. These results suggest that the cardiac tolerability of epirubicin is limited by its accumulation in the heart and that such accumulation would be even higher in the absence of doxorubicinolone formation and efflux. These results may also serve guidelines for developing noncardiotoxic anthracyclines.

Management of preoperative antiplatelet therapy in coronary artery bypass grafting (CABG) is variable among surgeons: guidelines collide with prejudices because replacement of aspirin with low-molecular-weight heparin is still performed because of a presumed minor bleeding risk. This study aims to analyze postoperative bleedings and complications in patients scheduled for elective primary isolated on-pump CABG, depending on preoperative aspirin treatment or its replacement with enoxaparin. In this cohort study, we propensity score matched 200 patients in whom aspirin was stopped at least 5 days before CABG and replaced with enoxaparin and 200 patients who continued aspirin therapy until the day before surgery. Postoperative bleedings and complications were monitored during hospitalization. Among patients who continued aspirin treatment, mean overall bleeding was 701.0 ± 334.6 ml, whereas in the matched enoxaparin group, it was significantly greater (882.6 ± 64.6 ml, p value

Diabetes is a major risk factor for cardiovascular disease, and recent advances in research indicate that a detailed understanding of the pathophysiology of its effects is mandatory to reduce diabetes-related mortality and morbidity. Advanced Glycation End Products (AGEs) play a central role in the genesis and progression of complications of both type 1 and type 2 diabetes mellitus, and have been found to be important even in non-diabetic patients as a marker of cardiovascular disease. AGEs have a profound impact on patient's prognosis regardless of the glycemic control, and therefore pharmacologic approaches against AGEs accumulation have been proposed over the years to treat cardiovascular diseases, parallel to a more detailed understanding of AGEs pathophysiology. Compounds with anti-AGEs effects are currently under investigation in both pre-clinical and clinical scenarios, and many of the drugs previously used to treat specific diseases have been found to have AGE-inhibitory effects. Some products are still in "bench evaluation", whereas others have been already investigated in clinical trials with conflicting evidences. This review aims at summarizing the mechanisms of AGEs formation and accumulation, and the most relevant issues in pre-clinical and clinical experiences in anti-AGEs treatment in cardiovascular research.