Search

Background: Anticancer treatments are improving the prognosis of patients fighting cancer. However, anticancer treatments may also increase the cardiovascular (CV) risk by increasing metabolic disorders. Atherosclerosis and atherothrombosis related to anticancer treatments may lead to ischemic heart disease (IHD), while direct cardiac toxicity may induce non-ischemic heart disease. Moreover, valvular heart disease (VHD), aortic syndromes (AoS), and advanced heart failure (HF) associated with CV risk factors and preclinical CV disease as well as with chronic inflammation and endothelial dysfunction may also occur in survivors of anti-carcer treatments. Methods: Public electronic libraries have been searched systematically looking at cardiotoxicity, cardioprotection, CV risk and disease, and prognosis after cardiac surgery in survivors of anticancer treatments. Results: CV risk factors and disease may not be infrequent among survivors of anticancer treatments. As cardiotoxicity of established anticancer treatments has been investigated and is frequently irreversible, cardiotoxicity associated with novel treatments appears to be more frequently reversible, but also potentially synergic. Small reports suggest that drugs preventing HF in the general population may be effective also among survivors of anticancer treatments, so that CV risk factors and disease, and chronic inflammation, may lead to indication to cardiac surgery in survivors of anticancer treatments. There is a lack of substantial data on whether current risk scores are efficient to predict prognosis after cardiac surgery in survivors of anticancer treatments, and to guide tailored decision-making. IHD is the most common condition requiring cardiac surgery among survivors of anticancer treatments. Primary VHD is mostly related to a history of radiation therapy. No specific reports exist on AoS in survivors of anticancer treatments. Conclusions: It is unclear whether interventions to dominate cancer- and anticancer treatment-related metabolic syndromes, chronic inflammation, and endothelial dysfunction, leading to IHD, nonIHD, VHD, HF, and AoS, are as effective in survivors of anticancer treatments as in the general population. When CV diseases require cardiac surgery, survivors of anticancer treatments may be a population at specifically elevated risk, rather than affected by a specific risk factor.

The coronavirus disease 2019 (COVID-19) pandemic has profoundly affected all health care professionals. The outbreak required a thorough reorganization of the Italian regional local health care system to preserve resources such as ventilators, beds in intensive care units and surgical and anaesthesiological staff. Levels of priority were created, together with a rigorous triage procedure for patients with COVID-19, which led to postponement of all elective procedures. Urgent cases were discussed with the local heart team and percutaneous approaches were selected as the first treatment option to reduce hospital stay. COVID-19 and COVID-19-free pathways were created, including adequate preparation of the operating room, management of anaesthesiological procedures, transportation of patients and disinfection. It was determined that patients with chronic diseases were at increased risk of adverse outcomes. Systemic inflammation, cytokine storm and hypercoagulability associated with COVID-19 increased the risk of heart failure and cardiac death. In this regard, the early use of extracorporeal membrane oxygenation could be life-saving in patients with severe forms of acute respiratory distress syndrome or refractory heart failure. The goal of this paper was to report the Italian experience during the COVID-19 pandemic in the setting of cardiovascular surgery., Coronavirus disease 2019 (COVID-19) is a new pandemic infectious disease caused by a novel beta-coronavirus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [1].

Objectives Postoperative hemorrhage in cardiac surgery is a significant cause of morbidity and mortality. Standard laboratory tests fail as predictors for bleeding in the surgical setting. The use of viscoelastic (VE) hemostatic assays thromboelastography (TEG) and rotational thromboelastometry (ROTEM) could be an advantage in patients undergoing cardiac surgery. The objective of this meta-analysis was to analyze the effects (benefits and harms) of VE-guided transfusion practice in cardiac surgery patients. Design A meta-analysis of randomized trials. Setting For this study, PubMed, EMBASE, Scopus, and the Cochrane Collaboration database were searched, and only randomized controlled trials were included. A systematic review and meta-analysis were performed in accordance with the standards set forth by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement, using a random-effects model. Participants The study comprised adult cardiac surgery patients. Interventions VE-hemostatic assays transfusion algorithm compared with transfusion algorithms based on clinicians’ discretion. Measurements and Main Results Seven comparative randomized controlled trials were considered, including a total of 1,035 patients (522 patients in whom a TEG- or ROTEM-based transfusion algorithm was used). In patients treated according to VE-guided algorithms, red blood cell (odds ratio 0.61; 95% confidence interval [CI]: 0.37-0.99; p: 0.04; I2: 66%) and fresh frozen plasma transfusions (risk difference 0.22; 95% CI: 0.11-0.33; p Conclusions This study demonstrated that the use of VE assays in cardiac surgical patients is effective in reducing allogenic blood products exposure, postoperative bleeding at 12 and 24 hours after surgery, and the need for redo surgery unrelated to surgical bleeding.

Over the last 15 years, the management of aortic valve disease has been changed by transcatheter aortic valve replacement, which has become the standard of care across the entire spectrum of surgical risk. As a result of continuous evolution of this technique, several next-generation transcatheter heart valves (THVs) have been developed to minimize procedural complications and improve patient outcomes. This review aims to provide an update on the new generation THVs and delivery systems.

Big Data, and the derived analysis techniques, such as artificial intelligence and machine learning, have been considered a revolution in the modern practice of medicine. Big Data comes from multiple sources, encompassing electronic health records, clinical studies, imaging data, registries, administrative databases, patient-reported outcomes and OMICS profiles. The main objective of such analyses is to unveil hidden associations and patterns. In cardiac surgery, the main targets for the use of Big Data are the construction of predictive models to recognize patterns or associations better representing the individual risk or prognosis compared to classical surgical risk scores. The results of these studies contributed to kindle the interest for personalized medicine and contributed torecognize the limitations of randomized controlled trials in representing the real world. However, the main sources of evidence for guidelines and recommendations remain RCTs and meta-analysis. The extent of the revolution of Big Data and new analytical models in cardiac surgery is yet to be determined.

Transcatheter aortic valve replacement (TAVR) is an effective treatment option for patients with severe, symptomatic AS, regardless of the transcatheter heart valve (THV) implanted. Prior studies demonstrated a higher device success with lower paravalvular leak (PVL) using the balloon-expandable (BE) Sapien/XT THV vs. a self-expanding (SE) THV. However, few data are available on the performance of a novel BE THV.to compare early clinical performance and safety of the newly available BE Myval THV (Myval, Meril Life Sciences Pvt. Ltd., India) vs. the commonly used SE (Evolut R, Medtronic) THV.nbsp;A single-center, retrospective cohort analysis was performed withnbsp;166 consecutive patients undergoing TAVR from March 2019 to March 2021 for severe symptomatic AS treated with either the novel BE Myval or the SE Evolut R (ER) bioprosthesis. The primary endpoint was device success at day 30 according to the Valve Academic Research Consortium-3 (VARC-3). Secondary endpoints included 30-day all-cause mortality, cardiovascular mortality, more than mild PVL, permanent pacemaker implantation (PPI) rates and a composite of all-cause mortality and disabling stroke at 6 months.nbsp;Among the 166 included patients, 108 patients received the SE ER THV and 58 patients were treated with the BE Myval THV. At baseline, the two groups showed comparable demographic characteristics. The primary composite endpoint of early device success occurred in 55 patients (94.8%) in the BE Myval group and in 90 patients (83.3%) in the SE ER group (OR 3.667, 95% CI 1.094-12.14;In patients with severe symptomatic AS undergoing TAVR, the novel Myval BE THV provided a comparable performance to the well-known ER SE THV, and it was associated with a lower rate of PPI and ≥moderate PVL within 30 days and 6 months after the procedure. Randomized, head-to-head comparison trials are needed to confirm our results.

The left ventricular (LV) ejection fraction (EF) is the preferred parameter applied for the non-invasive evaluation of LV systolic function in clinical practice. It has a well-recognized and extensive role in the clinical management of numerous cardiac conditions. Many imaging modalities are currently available for the non-invasive assessment of LVEF. The aim of this review is to describe their relative advantages and disadvantages, proposing a hierarchical application of the different imaging tests available for LVEF evaluation based on the level of accuracy/reproducibility clinically required.

A steadying increase of cancer survivors has been observed as a consequence of more effective therapies. However, chemotherapy regimens are often associated with significant toxicity, and cardiac damage emerges as a prominent clinical issue. Many mechanisms sustain chemotherapy-induced cardiac toxicity: direct myocyte damage, arrhythmia induction, coronary vasospasm, and accelerated atherosclerosis. Anthracyclines are the most studied cardiotoxic drugs and represent a clinical model for cardiac damage induced by chemotherapy. In patients suffering from advanced heart failure (HF) because of chemotherapy-related cardiomyopathy, when refractory to optimal medical therapy, mechanical circulatory support or heart transplantation represents an effective treatment. Here, the main mechanisms of cardiac toxicity induced by cancer therapies are analyzed, with a focus on patients requiring intensive care unit (ICU) admission during the course of the disease because of acute cardiac toxicity, takotsubo syndrome, and acute-on-chronic HF in patients suffering from chemotherapy-induced cardiomyopathy. In a subset of patients, cardiac toxicity can be acute and life-threatening, leading to overt cardiogenic shock. The management of critically ill cancer patients poses a unique challenge and requires a multidisciplinary approach. Moreover, no etiologic therapy is available, and only supportive measures can be implemented., Graphical Abstract

An increased need of extracorporeal membrane oxygenation (ECMO) support is going to become evident as treatment of SARS-CoV-2 respiratory distress syndrome. This is the first report of the Italian Society for Cardiac Surgery (SICCH) on preliminary experience with COVID-19 patients receiving ECMO support. Data from 12 Italian hospitals participating in SICCH were retrospectively analyzed. Between March 1 and September 15, 2020, a veno-venous (VV) ECMO system was installed in 67 patients (94%) and a veno-arterio-venous ECMO in four (6%). Five patients required VA ECMO after initial weaning from VV ECMO. Thirty (42.2%) patients were weaned from ECMO, while 39 (54.9%) died on ECMO, and six (8.5%) died after ECMO removal. Overall hospital survival was 36.6% (n = 26). Main causes of death were multiple organ failure (n = 14, 31.1%) and sepsis (n = 11, 24.4%). On multivariable analysis, predictors of death while on ECMO support were older age (p = 0.048), elevated pre-ECMO C-reactive protein level (p = 0.048), higher positive end-expiratory pressure on ventilator (p = 0.036) and lower lung compliance (p = 0.032). If the conservative treatment is not effective, ECMO support might be considered as life-saving rescue therapy for COVID-19 refractory respiratory failure. However warm caution and thoughtful approaches for timely detection and treatment should be taken for such a delicate patients population.

Claudio Napoli,1 Paola Bontempo,2 Vittorio Palmieri,3 Enrico Coscioni,4 Ciro Maiello,5 Francesco Donatelli,6 Giuditta Benincasa1 1Department of Advanced Medical and Surgical Sciences (DAMSS), University of Campania “Luigi Vanvitelli”, Naples, 80138, Italy; 2Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, Naples, 80138, Italy; 3Department of Cardiac Surgery and Transplantation, Heart Transplantation Unit in Adults of the ‘Ospedali dei Colli Monaldi-Cotugno-CTO’, Naples, Italy; 4Department of Cardiac Surgery, Azienda Ospedaliera Universitaria San Giovanni di Dio e Ruggi d’Aragona, Salerno, Italy; 5Department of Cardiovascular Surgery and Transplants, Monaldi Hospital, Azienda dei Colli, Naples, Italy; 6Chair of Cardiac Surgery, Department of Cardiothoracic Center, Istituto Clinico Sant’Ambrogio, University of Milan, Milan, ItalyCorrespondence: Giuditta BenincasaDepartment of Advanced Medical and Surgical Sciences (DAMSS), University of Campania “Luigi Vanvitelli”, Naples, ItalyTel +390815667916Email giuditta.benincasa@unicampania.itAbstract: Despite the current reductionist approach providing an optimal indication for diagnosis and treatment of patients with heart failure with reduced ejection fraction (HFrEF), there are no standard pharmacological therapies for heart failure with preserved ejection fraction (HFpEF). Although in its infancy in cardiovascular diseases, the epigenetic-based therapy (“epidrugs”) is capturing the interest of physician community. In fact, an increasing number of controlled clinical trials isevaluating the putative beneficial effects of: 1) direct epigenetic-oriented drugs, eg, apabetalone, and 2) repurposed drugs with a possible indirect epigenetic interference, eg, metformin, statins, sodium glucose transporter inhibitors 2 (SGLT2i), and omega 3 polyunsaturated fatty acids (PUFAs) in both HFrEF and HFpEF, separately. Apabetalone is the first and unique direct epidrug tested in cardiovascular patients to date, and the BETonMACE trial has reported a reduction in first HF hospitalization (any EF value) and cardiovascular death in patients with type 2 diabetes and recent acute coronary syndrome, suggesting a possible role in secondary prevention. Patients with HFpEF seem to benefit from supplementation to the standard therapy with statins, metformin, and SGLT2i owing to their ability in reducing mortality. In contrast, the vasodilator hydralazine, with or without isosorbide dinitrate, did not provide beneficial effects. In HFrEF, metformin and SGLT2i could reduce the risk of incident HF and mortality in affected patients whereas clinical trials based on statins provided mixed results. Furthermore, PUFAs diet supplementation was significantly associated with reduced cardiovascular risk in both HFpEF and HFrEF. Future large trials will reveal whether direct and indirect epitherapy will remain a work in progress or become a useful way to customize the therapy in the real-world management of HFpEF and HFrEF. Our goal is to discuss the recent advancement in the epitherapy as a possible way to improve personalized therapy of HF.Keywords: heart failure, personalized therapy, epidrugs

Purpose of review Cardiovascular diseases (CVDs) are typically caused by multifactorial events including mutations in a large number of genes. Epigenetic-derived modifications in the cells are normal but can be amended by aging, lifestyle, and exposure to toxic substances. Major epigenetic modifications are DNA methylation, histone modification, chromatin remodeling as well as the noncoding RNAs. These pivotal players are involved in the epigenetic-induced modifications observed during CVDs. Nevertheless, despite impressive efforts capitalized in epigenetic research in the last 50 years, clinical applications are still not satisfactory. Recent findings Briefly, we present some of the recent steps forward in the epigenetic studies of CVDs. There is an increased appreciation for the contribution of epigenetic alterations in the development of CVDs. Now, we have novel epigenetic biomarkers and therapeutic trials with the use of statins, metformin, and some compounds affecting epigenetic pathways including a BET inhibitor apabetalone. The new knowledge of epigenetic regulation is also discussed in the light of precision medicine of CVDs. Summary Epigenetic studies of CVDs have the promise to yield both mechanistic insights as well as adjunct treatments (repurposed drugs and apabetalone). The overall concept of precision medicine is not widely recognized in routine medical practice and the so-called reductionist approach remains the most used way to treat CVD patients.

Several studies have been published describing the clinical and radiographic findings of coronavirus disease 2019-related pneumonia. Therefore, there is currently a lack of pathologic data on its effects in intubated patients. Pneumothorax may occur rarely and results from a combination of fibrotic parenchyma and prolonged high-pressure ventilation. Chest drainage represents first-line treatment. However, in cases of persistent pneumothorax, thoracoscopy and bleb resection may be feasible options to reduce air leak and improve ventilation. This report describes the cases of 2 patients with coronavirus disease 2019 who were successfully treated with thoracoscopy, bleb resection, and pleurectomy for persistent pneumothorax.

Trans-catheter valve-in-valve (ViV) is a treatment option for patients affected by bioprosthetic heart valve (BHV) failure. Both aortic and mitral ViV procedures present several challenges compared to native valve replacement. To date, no data concerning the balloon-expandable MyVal (Meril, Vapi, India) trans-catheter heart valve (THV) use in ViV procedure have been provided. In this case series, we described for the first time its use in five different BHV failures.

Background: Postoperative hyperglycemia is associated with increased rate of surgical site infection, renal failure, and cardiovascular events. The study of insulin sensitivity state before surgery could help in treating postoperative hyperglycemia and preventing iatrogenic hypoglycemia. We studied the postoperative insulin secretion in patients who have a low insulin sensitivity (IR) before surgery compared to patients with normal preoperative insulin sensitivity (IS). Materials and methods: Forty-two consecutive patients, undergoing abdominal surgery, underwent preoperative sequential hyperglycemic-euglycemic clamp (SHEC) in order to measure insulin secretion and to screen patients with low insulin sensitivity (IR) or with normal insulin sensitivity (IS). Patients had been randomized to receive either general anesthesia with epidural or PCA. Results: Postoperative insulin secretion in IR patients is decreased compared to IS (P = 0.059) and to IR before surgery regardless to the type of analgesia (P < 0.001). In the IS group, postoperative insulin secretion depends on type of analgesia. It is increased when using PCA and decreased when using epidural (P < 0.05). Blood glucose increased after surgery in both IS an IR (P < 0.001). Patients with preoperative insulin resistance had a higher glycemia before and after surgery (P < 0.001). Blood glucose levels were comparable between PCA and epidural patients (P = 0.450). Conclusion: Insulin secretion is reduced in IR regardless the type of anesthesia. PCA increases insulin secretion, whereas epidural decreases it in patients with normal insulin sensitivity. These findings implicate that after surgery insulin administration is advisable in patients with preoperative insulin resistance while it should be given cautiously in those with normal preoperative insulin sensitivity

Type 1 diabetes (T1D) is an irreversible degenerative disease with severe complications such as heart disease, nephropathy, neuropathy, and retinopathy. Although exogenous insulin administration is a life-saving therapy, it does not cure the disease. This review addresses the epigenetic mechanisms responsible for the development of T1D and discusses epigenetic-based strategies for prevention and treatment of the disease. We describe novel epigenetic biomarkers for the identification of susceptible individuals and the establishment of innovative therapies with epidrugs and cell therapy to regenerate the lost β-cells. Despite the wealth of promising data regarding the potential benefits of epigenetic tools to reduce the burden of T1D, clinical trials are still very few, and this issue needs to be resolved in the near future.

Almost all known conventional cytotoxic anticancer drugs are less effective in killing tumor cells grown as multicellular spheroids than in killing tumor cells grown as monolayer cell cultures. This“ multicellular resistance” reflects the relative intrinsic drug-resistant phenotype of most solid tumors growing in vivo and is due to factors such as limited drug penetration or reduced fractions of proliferating cells. Proteasome inhibitors such as PS-341, a dipeptide boronic acid analogue, represent an interesting new class of potential anticancer drugs, which are entering early-phase clinical trials. PS-341 has been found to have good broad-spectrum cytotoxic activity in the 60-monolayer cell line National Cancer Institute screen. However, because its relative potency has not been tested in spheroid systems, we analyzed the activity of PS-341 in a spheroid/solid tumor context using four different human ovarian carcinoma cell lines and three prostate carcinoma cell lines, respectively. We found, with one exception, that PS-341 showed equal or greater activity in spheroids than in the respective monolayer cell cultures, even in a prostate cancer spheroid model with a very low growth fraction. PS-341 induced apoptotic cell death in carcinoma cells in both culture systems. We also noted a decrease in XIAP protein, a member of the inhibitor of apoptosis (IAP) family of apoptosis inhibitors, and phosphorylation of Bcl-XL in PS-341-treated ovarian carcinoma cells. Furthermore, DNA fragmentation, a hallmark of apoptosis (in this case, induced by PS-341), was completely inhibited by the caspase inhibitor N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (Z-VAD). Taken together, the results indicate that unlike most other known anticancer cytotoxic drugs, PS-341 appears to be as effective in killing tumor cells grown in the form of multicell spheroids as in killing tumor cells grown in monolayer cell culture. Hence, this compound has the potential to circumvent multicellular drug resistance and, as such, may show promising activity against solid tumors with low growth fractions invivo, which are frequently intrinsically resistant to conventional cytotoxic anticancer drugs.

Heart failure (HF) management is challenging due to high clinical heterogeneity of this disease which makes patients responding differently to evidence-based standard therapy established by the current reductionist approach. Better understanding of the genetic and epigenetic interactions may clarify molecular signatures underlying maladaptive responses in HF, including metabolic shift, myocardial injury, fibrosis, and mitochondrial dysfunction. DNA methylation, histone modifications and micro-RNA (miRNAs) may be major epigenetic players in the pathogenesis of HF. DNA hypermethylation of the kruppel-like factor 15 (KLF15) gene plays a key role in switching the failing heart from oxidative to glycolytic metabolism. Moreover, hypomethylation at H3K9 promoter level of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) genes also leads to reactivation of fetal genes in man. The role of miRNAs has been investigated in HF patients undergoing heart transplantation, for whom miR-10a, miR-155, miR-31, and miR-92 may be putative useful prognostic biomarkers. Recently, higher RNA methylation levels have been observed in ischemic human hearts, opening the era of "epitranscriptome" in the pathogenesis of HF. Currently, hydralazine, statins, apabetalone, and omega-3 polyunsatured fatty acids (PUFA) are being tested in clinical trials to provide epigenetic-driven therapeutic interventions. Moreover, network-oriented analysis could advance current medical practice by focusing on protein-protein interactions (PPIs) perturbing the "cardiac" interactome. In this review, we provide an epigenetic map of maladaptive responses in HF patients. Furthermore, we propose the "EPi-transgeneratIonal network mOdeling for STratificatiOn of heaRt Morbidity" (EPIKO-STORM), a clinical research strategy offering novel opportunities to stratify the natural history of HF.

Aim Hyperglycemia status induces endothelial dysfunction, although the underlying pathogenic mechanisms are not fully understood. There are several studies connecting sugar/sweetened beverages to the cardiovascular disease. Currently, many sweeteners have been extensively introduced into lifestyle to normalize blood glucose levels without altering the sweet taste. However, there is growing concern for their impact on metabolic health. Methods Human endothelial cells were treated with Glucose, Fructose, Aspartame, Rebaudioside A, Stevioside, or Steviol. Morphological characteristics, in vitro angiogenesis and array gene expression were analyzed. Results High-glucose and fructose concentrations significantly decreased cell features such as angiogenic capability. Interestingly, non-caloric sweeteners did not significantly modified all cell characteristics and they did not compromised cell angiogenic ability. Array gene expression analysis revealed that the chemokine fractalkine (CX3CL1) and the enzyme transferase (HPRT1) were always significantly upregulated and downregulated respectively, after glucose and fructose treatments (P > .05), whereas they were non-differentially expressed with all the other sweeteners. Interestingly, both genes are considered as cardiovascular disease risk biomarkers. Specifically, upregulation of CX3CL1/CX3CR1 occurs in the human placenta and serum levels of the ligand are associated with markers of insulin resistance in GDM. Conclusions Differently from glucose and fructose, steviol glycosides do not damage endothelial cells. Prospective preclinical studies and clinical trials are warranted to confirm the long-term safety of such compounds.

Cardiac herniation is a rare complication of intrapericardial lung resection, typically occurring within the first twenty-four hours. Considering that this condition carries a high mortality rate despite prompt management, early diagnosis is key. Since clinical manifestations can be variable, the use of imaging modalities coupled with a high index of suspicion is critical to making the correct diagnosis. In this article, a case of acute cardiac herniation post left pneumonectomy diagnosed with the help of an intraoperative transesophageal echocardiography (TEE) is presented.

Although venous thromboembolism (VTE) shows a polygenic nature, the crossroad between genome and environment is not fully understood. Genetics explains only a part of VTE hereditability and not defined molecular causes are found in approximately 50% of thrombotic patients. Thus, a major understanding of molecular mechanisms may clarify the missing hereditability. Concerning epigenetics, a particular histone modification (citrullination) plays a key role in increasing the rate of venous occlusive events by inducing neutrophil apoptosis and expulsion of neutrophil extra-cellular traps (NETs), which may be useful biomarkers of active disease. Moreover, an over-expression of miR-320a/b, miR-582, miR-195, miR-424-5p, and miR-532, or a down-regulation of miR495, miR-136-5p and miR-26a may improve the accuracy of VTE diagnosis. No clinical studies have focused on DNA methylation in VTE. Nowadays, no validated epigenetics biomarkers are routinely used for diagnosis and prevention of VTE. In the era of personalized therapy, several clinical trials are investigating the putative role of statins, a class of lipid-lowering epigenetic-based drugs, as additional therapeutic agents in VTE. Furthermore, single nucleotide polymorphisms (SNPs) in CYP2C9, VKORC1, and MIR133 genes can help physicians to predict individual warfarin dose requirement. Consequently, a comprehensive understanding of the mechanisms involved in the control of blood clot development is crucial to design novel therapeutic strategies. This review summarizes the current clinical concepts both in genetic and epigenetic VTE framework. Furthermore, we discuss the contribution of the innovative network medicine paradigm into advancing our knowledge about molecular underpinnings needed to support novel VTE diagnostic and therapeutic options.

Rationale Although there have been several studies describing clinical and radiographic features about the novel coronavirus (COVID-19) infection, there is a lack of pathologic data conducted on biopsies or autopsies. Patient concerns A 56-year-old and a 70-year-old men with fever, cough, and respiratory fatigue were admitted to the intensive care unit and intubated for respiratory distress. Diagnosis The nasopharyngeal swab was positive for COVID-19 and the chest Computed Tomography (CT) scan showed the presence of peripheral and bilateral ground-glass opacities. Interventions Both patients developed pneumothoraces after intubation and was managed with chest tube. Due to persistent air leak, thoracoscopies with blebs resection and pleurectomies were performed on 23rd and 16th days from symptoms onset. Outcomes The procedures were successful with no evidence of postoperative air-leak, with respiratory improvement. Pathological specimens were analyzed with evidence of diffuse alveolar septum disruption, interstitium thickness, and infiltration of inflammatory cells with diffuse endothelial dysfunction and hemorrhagic thrombosis. Lessons Despite well-known pulmonary damages induced by the COVID-19, the late-phase histological changes include diffused peripheral vessels endothelial hyperplasia, in toto muscular wall thickening, and intravascular hemorrhagic thrombosis.

Background Aortic stenosis is the most common valvular disease and has a dismal prognosis without surgical treatment. The aim of this meta‐analysis was to quantitatively assess the comparative effectiveness of the Perceval (LivaNova) valve versus conventional aortic bioprostheses. Methods and Results A total of 6 comparative studies were identified, including 639 and 760 patients who underwent, respectively, aortic valve replacement with the Perceval sutureless valve (P group) and with a conventional bioprosthesis (C group). Aortic cross‐clamping and cardiopulmonary bypass duration were significantly lower in the P group. No difference in postoperative mortality was shown for the P and C groups (2.8% versus 2.7%, respectively; odds ratio [OR]: 0.99 [95% confidence interval ( CI ), 0.52–1.88]; P =0.98). Incidence of postoperative renal failure was lower in the P group compared with the C group (2.7% versus 5.5%; OR: 0.45 [95% CI , 0.25–0.80]; P =0.007). Incidence of stroke (2.3% versus 1.7%; OR: 1.34 [95% CI , 0.56–3.21]; P =0.51) and paravalvular leak (3.1% versus 1.6%; OR : 2.52 [95% CI , 0.60–1.06]; P =0.21) was similar, whereas P group patients received fewer blood transfusions than C group patients (1.16±1.2 versus 2.13±2.2; mean difference: 0.99 [95% CI , −1.22 to −0.75]; P =0.001). The incidence of pacemaker implantation was higher in the P than the C group (7.9% versus 3.1%; OR : 2.45 [95% CI , 1.44–4.17]; P =0.001), whereas hemodynamic Perceval performance was better (transvalvular gradient 23.42±1.73 versus 22.8±1.86; mean difference: 0.90 [95% CI , 0.62–1.18]; P =0.001), even during follow‐up (10.98±5.7 versus 13.06±6.2; mean difference: −2.08 [95% CI , −3.96 to −0.21]; P =0.030). We found no difference in 1‐year mortality. Conclusions The Perceval bioprosthesis improves the postoperative course compared with conventional bioprostheses and is an option for high‐risk patients.

Objectives The aim of this meta-analysis was to compare outcomes of patients undergoing transcatheter aortic valve implantation (TAVI) with those undergoing surgical aortic valve replacement using sutureless valves. Methods A systematic review and meta-analysis in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement was performed. Results No randomized controlled trials were identified. Six comparative studies using propensity score matching met the inclusion criteria. This meta-analysis identified 1462 patients in that 731 patients underwent surgical aortic valve replacement using sutureless valves (SU) and 731 patients underwent a TAVI. The 30-day or in-hospital mortality was lower in the SU group [odds ratio (OR) 0.54, 95% confidence interval (CI) 0.36-0.80; P = 0.003]. In the TAVI group, the incidence of postoperative stroke was higher (OR 0.36, 95% CI 0.17-0.79; P = 0.01). The incidence of moderate or severe paravalvular regurgitation was higher in the TAVI group (OR 0.22, 95% CI 0.14-0.35; P = 0.001). There were neither differences in the postoperative renal failure (OR 1.44, 95% CI 0.46-4.58; P = 0.53) nor in the number of patients requiring postoperative pacemaker implantation (OR 1.06, 95% CI 0.54-2.08; P = 0.86). Patients in the SU group required more transfusions (OR 4.47, 95% CI 2.77-7.21; P = 0.0001), whereas those in the TAVI group had higher major vascular complications (OR 0.06, 95% CI 0.01-0.25; P = 0.0001). Intensive care unit stay was not different (mean difference 0.99, 95% CI - 1.22 to 1.40; P = 0.53). One-year survival was better in the SU group (Peto OR 0.35, 95% CI 0.18-0.67; P = 0.001), as was the 2-year survival (Peto OR 0.38, 95% CI 0.17-0.86; P = 0.001). Conclusions Surgical aortic valve replacement using sutureless valves is associated with better early and mid-term outcomes compared with TAVI in high- or intermediate-risk patients.

The use of transcatheter aortic valve implantation (TAVI) following the introduction of Nitinol autoexpandable devices has spread rapidly during recent years. In addition, cardiac surgery has been revolutionized due to the use of Nitinol-based sutureless prostheses for aortic valve replacement (AVR). During the same period, however, permanent pacemaker (PPM) implantation has emerged as a frequent complication. The study aim was to identify the risk factors of PPM following the implantation of a Nitinol self-expanding prosthesis (for AVR or TAVI).A study group was created between two institutions experienced in the use of nitinol devices, and a pool of 336 patients (56.6% CoreValve - Medtronic; 43.4% Perceval - Sorin) was available for a retrospective analysis. Pre-procedural clinical and electrocardiography (ECG) variables and postprocedural ECG variables were compared between the PPM group and control patients who had not received a PPM during their index hospitalization.A PPM was required in 12.8% of patients (TAVI 17.5% versus AVR 6.8%, p = 0.007). PPM patients had a higher logistical EuroSCORE (median 20.77% versus 15.59%, p = 0.015), a lower use of statins (18.6% versus 34.2%, p = 0.04), a pre-procedural longer QRS interval (median 117 ms versus 98 ms, p = 0.002), and a higher incidence of conduction disturbances (29.3% versus 16.8%, p = 0.034), with a prevalence of right bundle branch block. At the first postprocedural ECG, non-stimulated PPM patients had a longer QRS interval (median 150 ms versus 113 ms, p0.001) and a longer QTc interval (487.3 ± 46 ms versus 510.8 ± 53.8 ms, p = 0.005). Prevalent intra-ventricular conduction disorders in both groups included left bundle branch block. AVR patients received a PPM later than the TAVI group (median 6 days versus 3 days, p = 0.01). TAVI was an independent predictor of PPM at logistic regression analysis (OR 3.18; 95% CI 1.19-8.48, p = 0.021), but the significance disappeared after incorporating post-procedural ECG variables.Nitinol technology is a ground-breaking option for aortic valve procedures. However, the radial forces of the self-expandable mechanism may be implicated in the increased need for PPM, mostly in cases of TAVI compared to AVR, that most likely are due to displacement of the stent provoked by in situ calcium clusters. Given the clinical and economic impact of PPM, new parameters are required to understand the stent/tissue interaction and to help with device selection.

Item does not contain fulltext AIMS: Cryoballoon ablation (CBA; Arctic Front, Medtronic) has proven very effective in achieving pulmonary vein isolation. Real-time three-dimensional transoesophageal echocardiography (RT 3D TEE) is a novel technology, which permits detailed visualization of cardiac structures in a 3D perspective. The aim of the present study was to assess the feasibility, advantages, and safety of RT 3D TEE in guiding CBA in a series of patients affected by paroxysmal atrial fibrillation. METHODS AND RESULTS: Forty-five patients (34 males, mean age: 63 +/- 12 years) underwent CBA guided by 3D TEE. A total of 190 veins could be documented by TEE. Real-time three-dimensional transoesophageal echocardiography successfully guided the operator to position the CB in the pulmonary vein (PV) ostium and obtain complete occlusion in all 190 (100%) veins. Transoesophageal echocardiography identified leakages in 25 (13%) veins led to successful elimination of PV-left atrium (LA) backflow by guiding correct balloon repositioning. In four (2%) veins, this imaging tool led to perform successful pull-down manoeuvres. After a mean 2.6 +/- 1.4 applications, isolation could be documented in 190 (100%) PVs. Median procedural and fluoroscopy times were 145 and 24 min. During a median follow-up of 278 days, 37 (82%) patients did not experience atrial fibrillation recurrence following a 3-month blanking period. CONCLUSION: Cryoballoon ablation is safe and feasible under RT 3D TEE guidance. This imaging tool permits perfect visualization of all PV ostia and neighbouring LA structures. Most importantly, it proved very efficient in guiding the operator to achieve complete occlusion and successful isolation in all veins.

The HER family of tyrosine kinase receptors includes several members that are clinically important targets in cancer therapies, in particular HER1 (the EGF receptor) and HER2, other members include HER3 and HER4. Trastuzumab, a humanized monoclonal antibody and lapatinib, a tyrosine kinase inhibitor, are drugs that target HER2, which is highly expressed in 20-30% of breast cancers. Trastuzumab is recommended as an adjuvant therapy for lymph node positive, HER2-positive breast cancers, or node-negative cancer with high-risk of recurrence, as well as in stage IV cancers. One serious side effect of trastuzumab is cardiomyocyte dysfunction, resulting in reduced heart contractile efficiency. The incidence of collateral effects on the heart with trastuzumab therapy increases in people with cardiovascular risk factors, heart disease and when combined with other chemotherapeutics. When cardiotoxicity was observed with trastuzumab, several studies have addressed potential cardiac damage of trastuzumab itself and lapatinib. The differences in cardiovascular effects of these two compounds are somewhat unexpected and suggest distinct mechanisms of action, which have clear implications in clinical application and prevention of cardiotoxicity in cardio-oncological approaches.

Hypermetabolism, abnormal plasma amino acid profiles, increased gluconeogenesis, and changes in liver and muscle protein turnover are well-described undesirable effects in patients with cancer and diabetes mellitus type 2 (DM2) The aim of the present study was to analyze the specific impact and interaction of these 2 disease patterns on patients' preoperative glucose and protein metabolism. Eight nondiabetic and 8 diabetic patients devoid of cachexia underwent a stable isotope infusion study on the day before surgery for colorectal cancer or adenoma with high-grade dysplasia. Protein and glucose kinetics were assessed in a fasted state by L-[1-(13)C]leucine and [6,6(2)H(2)]glucose. In diabetic patients, glucose metabolism was found to be elevated as the plasma glucose level increased (P = 0.013) and endogenous rate of appearance of glucose tended to be higher compared to nondiabetic patients (P = 0.083). Protein metabolism was not affected by the metabolic state of the 2 groups. Resting energy expenditure was higher in diabetic patients (P = 0.028). Under postabsorptive conditions, noncachectic patients with DM2 suffering from colorectal tumors showed an elevated turnover in glucose metabolism whereas the nondiabetic counterparts failed to demonstrate any metabolic changes due solely to malignancy.

PURPOSE: The pathogenic role of angiotensin-converting enzyme (ACE) inhibition in hypertensive patients regarding endothelial progenitor-cell (EPC) function is still poorly understood. The aim of the study was to evaluate EPC number, function, and relationship to carotid intima media thickness (IMT) progression. METHODS: We studied 36 newly diagnosed mildly hypertensive patients free of cardiovascular disease and related risk factors without prior or concurrent therapy with ACE inhibitors. Patients were randomized to receive enalapril 20 mg/day (n = 18) or zofenopril 30 mg/day (n = 18). EPC number and migrating capacity, plasma nitrite and nitrate (NOx), and isoprostane concentrations were evaluated. Carotid IMT was determined by ultrasonography at baseline and after 1 and 5 years of follow-up. RESULTS: EPC number increased during the follow-up, with no statistical differences between treatment groups. There was an inverse correlation between circulating EPCs and IMT increase over time. Plasma NOx decreased during the study without evident differences between treatment groups. Isoprostanes decreased more markedly in zofenopril-treated patients. Multiple linear regression model demonstrated that carotid IMT was significantly inversely correlated with EPC but not with migratory cells after adjusting for confounders. CONCLUSIONS: The study demonstrated that EPC levels increased during the follow-up in both groups of newly diagnosed hypertensive patients treated with ACE inhibitors. These drugs prevented progression of vascular damage, with an inverse correlation between circulating EPC levels and IMT values.

Surgical injury provokes a stress response that is thought to be pronounced in patients with diabetes mellitus type 2 (DM2) leading to intensified catabolism. The aim of this study was to compare the effects of perioperative epidural analgesia (EDA) versus patient controlled analgesia (PCA) and amino acid infusion on postoperative metabolism in patients with and without DM2.For this study, 12 nondiabetic patients and 12 diabetic patients undergoing colorectal surgery were randomly assigned to 4 groups (n = 6 per group) receiving either EDA (nondiabetic EDA and diabetic EDA [DEDA group]) or PCA with morphine (nondiabetic PCA and diabetic PCA) for perioperative pain control. Protein and glucose kinetics were measured on the second postoperative day using L-[1-13C]leucine and [6,6-2H2]glucose infusion during a fasted state and a 3-hr fed state with amino acid infusion.The transition from the fasted to fed state suppressed endogenous rate of appearance (Ra) of glucose (P G 0.001) with a distinct effect for the DEDA group (P G 0.001). The Ra of leucine and the endogenous rate of appearance of leucine tended to be lower in the DEDA group(P = 0.056 and P = 0.07). Leucine oxidation was more suppressed in the DEDA group (P = 0.02) and when receiving amino acids(P = 0.001). Diabetic patients achieved a higher protein balance than nondiabetic patients (P = 0.032) and when receiving EDA instead of PCA (P = 0.012) or infusion of amino acids (P = 0.014).A short-term infusion of amino acids reduced protein breakdown, increased protein synthesis, and rendered protein balance positive. This anabolic effect was pronounced in diabetic patients with EDA compared with nondiabetic patients or PCA, respectively, and prevented an undesirable hyperglycemia.

Objective: Post-infarction ventricular remodelling has been graded (I—III) according to the loss of systolic left ventricular silhouette curvaturechanges.Althoughsurgicalventricularrestoration(SVR)hasbeenextendedtotypeIIIischaemiccardiomyopathy,theresultsareless satisfactory. We sought to identify geometric and functional predictors of late outcome after SVR. Methods: Among 144 patients who underwent SVR since 1998, a subgroup of 31 patients (age: 65.2 7.6 years) was analysed. Inclusion criteria were: type III cardiomyopathy, no associated procedure except coronary artery bypass grafting, prior anterior infarction, absent-to-2+ mitral regurgitation, elective operation, follow-up 18 months (mean: 44 26; longest: 96 months). Probability of events was estimated with the Kaplan—Meier method. A Cox multivariable regression model was constructed selecting eight potential predictors of four adverse events: death, cardiac death, recurrent heart failure (New York Heart Association class III or IV) and left ventricular re-remodelling, defined as a 25% increase of end-systolic volume index after SVR, or an end-systolic volume index 50 mlm 2 . Results: Early and late mortality were zero and 6% (2/31 patients, one cardiacrelated death). NYHA class and all echocardiographic functional variables significantly improved early after SVR. Freedom (standard error (SE)) from heart failure was 97% 3%, 93% 5%, 77% 11% and 64% 15%, whereas freedom from left ventricular re-remodelling was 97% 3%, 80% 8%, 60% 12% and 39% 15%, respectively, 1, 3, 5 and 7 years after SVR. Multivariable analysis identified baseline mitral regurgitation degree and sphericity index as independent predictors of recurrent heart failure (p = 0.025; hazard ratio (HR) = 7.80 (95% confidence intervals (CIs): 1.29—47.19)) and left ventricular re-remodelling (p = 0.047; HR = 2.84 (95% CIs: 1.01—7.95)). Both predictors also correlated with a higher recurrence of end-systolic volume index 50 mlm 2 at late follow-up.Conclusions: Despite advanced cardiomyopathy, SVR determines left ventricular volume reduction and improved systolic function. Baselineabsent-to-moderate mitral regurgitation and a more spherical left ventricular geometry predict a less favourable clinical and functional outcome, suggesting a possible rationale for wider indications for combined correction of 2+ mitral regurgitation and undersizing of the mitral annulus, particularly in patients with sphericity index 0.75. # 2009 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

Background: Cardiopulmonary-bypass (CPB) induces hyperglycemia. There is growing evidence that perioperative maintenance of blood glucose within the physiological range improves patients' outcome. Nevertheless, perioperative normoglycemia is often difficult to achieve during surgery with CPB and the response to insulin infusion is characterized by a considerable variability. The aim of this study was to determine to what extent the presence of pre-operative metabolic syndrome (MS) influences the blood glucose and insulin response during cardiac surgery. Methods: Forty-five patients scheduled for elective cardiac surgery were screened for the presence of MS according to the International Diabetes Federation definition. Patients were then assigned to two groups: those with metabolic syndrome (MSP) and those without (control). During surgery, blood glucose levels were measured in all patients and hyperglycemia was treated with a standard protocol of continuous insulin infusion. Results: The mean blood glucose levels during CPB increased only in the MSP group (P