Emergent expansion of clinical epigenetics in patients with cardiovascular diseases.

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.

Precision medicine in distinct heart failure phenotypes: Focus on clinical epigenetics.

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.

Viscoelastic Blood Tests Use in Adult Cardiac Surgery: Meta-Analysis, Meta-Regression, and Trial Sequential Analysis.

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 < 0.0001; I2: 79%) use was reduced; platelets transfusion was not reduced (odds ratio 0.61; 95% CI: 0.32-1.15; p: 0.12; I2 74%). 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.

Postoperative insulin secretion is decreased in patients with preoperative insulin resistance.

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.

Risk Factors for Permanent Pacemaker after Implantation of Surgical or Percutaneous Self-Expanding Aortic Prostheses.

BACKGROUND: 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). METHODS: 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. RESULTS: 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, p<0.001) 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. CONCLUSIONS: 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.

Case report of snaring-assisted TAVR under cerebral embolic protection: the "Chaperone" with "Top Hat" technique.

Symptomatic severe aortic stenosis (AS) in patients with intermediate-to-high surgical risk is currently being treated with transcatheter aortic valve replacement (TAVR). We present a case of a TAVR in a severe calcific AS with porcelain aorta and 'gothic' aortic arch. Pre-operative thoraco-abdominal computed tomography angiography showed also severe calcification at the sinotubular junction with protruding huge calcified nodules extending in ascending aorta and multiple calcific stenosis of both iliac-femoral vessels, severely tortuous. The choice of the interventional access was not easy and the high risk of an acute intra-procedural brain event guided the procedural planning. To our knowledge, this is the first case of TAVR with complete cerebral protection with Triguard system device and 'snaring-assisted' valve advancement.

Case report: Self-expanding transcatheter valve implantation (Acurate Neo 2) in a very small native aortic annulus.

Transcatheter aortic valve replacement (TAVR) is a treatment of choice in patients with symptomatic severe aortic valve stenosis (AS) and intermediate-to-high surgical risk. The presence of a small aortic annulus (SAA) has been associated with a higher incidence of prosthesis-patient mismatch (PPM) when surgical aortic valve replacement (sAVR) is performed. TAVR might be a treatment option offering better hemodynamics with a lower incidence of PPM. When a severe AS with a SAA is treated, TAVR-related risk as the coronary obstruction and the annulus rupture, must be also prevented. We present a case of a TAVR in a very small aortic annulus; to our knowledge, this is the smallest native aortic annulus treated percutaneously in a tricuspid stenotic aortic valve with a Self-Expanding Transcatheter Heart Valve (THV) Acurate Neo 2.

Percutaneous treatment of abdominal aortic aneurysm and aortic valve stenosis with 'staged' EVAR and TAVR: a case series.

Symptomatic aortic valve stenosis (AS) and abdominal aortic aneurysm (AAA) are critical clinical conditions, increasingly more prevalent with aging of the population. Calcific aortic stenosis is the most common structural cardiac disease in the elderly population, and medical management of severe aortic stenosis of the elderly population is associated with poor outcomes as compared to surgical treatment. Transcatheter aortic valve replacement (TAVR) is a treatment of choice in inoperable, often elderly, patients with symptomatic severe AS and in intermediate-to-high surgical risk patients. It is not yet clarified the incidence of AAA and its impact on procedural and clinical outcomes among patients undergoing TAVR. It is known that after AS resolution with aortic valve replacement or TAVR there is an increase in blood pressure that increases the risk of dissection or abdominal aortic aneurysm rupture if AAA repair is delayed. The purpose of this report is to describe the anatomical details and technical and procedural considerations when proposing totally endovascular strategies dedicated to the treatment of patients with AS and AAA.

Cardiotoxicity, Cardioprotection, and Prognosis in Survivors of Anticancer Treatment Undergoing Cardiac Surgery: Unmet Needs.

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.

Artificial intelligence, big data and heart transplantation: Actualities.

BACKGROUND: As diagnostic and prognostic models developed by traditional statistics perform poorly in real-world, artificial intelligence (AI) and Big Data (BD) may improve the supply chain of heart transplantation (HTx), allocation opportunities, correct treatments, and finally optimize HTx outcome. We explored available studies, and discussed opportunities and limits of medical application of AI to the field of HTx. METHOD: A systematic overview of studies published up to December 31st, 2022, in English on peer-revied journals, have been identified through PUBMED-MEDLINE-WEB of Science, referring to HTx, AI, BD. Studies were grouped in 4 domains based on main studies' objectives and results: etiology, diagnosis, prognosis, treatment. A systematic attempt was made to evaluate studies by the Prediction model Risk Of Bias ASsessment Tool (PROBAST) and the Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD). RESULTS: Among the 27 publications selected, none used AI applied to BD. Of the selected studies, 4 fell in the domain of etiology, 6 in the domain of diagnosis, 3 in the domain of treatment, and 17 in that of prognosis, as AI was most frequently used for algorithmic prediction and discrimination of survival, but in retrospective cohorts and registries. AI-based algorithms appeared superior to probabilistic functions to predict patterns, but external validation was rarely employed. Indeed, based on PROBAST, selected studies showed, to some extent, significant risk of bias (especially in the domain of predictors and analysis). In addition, as example of applicability in the real-world, a free-use prediction algorithm developed through AI failed to predict 1-year mortality post-HTx in cases from our center. CONCLUSIONS: While AI-based prognostic and diagnostic functions performed better than those developed by traditional statistics, risk of bias, lack of external validation, and relatively poor applicability, may affect AI-based tools. More unbiased research with high quality BD meant for AI, transparency and external validations, are needed to have medical AI as a systematic aid to clinical decision making in HTx.

[SICI-GISE/SICOA Consensus document: Clinical follow-up of patients after acute coronary syndrome or percutaneous coronary intervention]. / Documento di consenso SICI-GISE/SICOA: La gestione del follow-up del paziente dopo sindrome coronarica acuta e/o angioplastica coronarica.

In the last decades, advances in percutaneous coronary intervention (PCI) strategies have significantly reduced the risk of procedural complications and in-hospital mortality of patients with acute coronary syndromes (ACS), thus increasing the population of stable post-ACS patients. This novel epidemiological scenario emphasizes the importance of implementing secondary preventive and follow-up strategies. The follow-up of patients after ACS or elective PCI should be based on common pathways and on the close collaboration between hospital cardiologists and primary care physicians. However, the follow-up strategies of these patients are still poorly standardized. This SICI-GISE/SICOA consensus document was conceived as a proposal for the long-term management of post-ACS or post-PCI patients based on their individual residual risk of cardiovascular adverse events. We defined five patient risk classes and five follow-up strategies including medical visits and examinations according to a specific time schedule. We also provided a short guidance for the selection of the appropriate imaging technique for the assessment of left ventricular ejection fraction and of non-invasive anatomical or functional tests for the detection of obstructive coronary artery disease. Physical and pharmacological stress echocardiography was identified as the first-line imaging technique in most of cases, while cardiovascular magnetic resonance should be preferred when an accurate evaluation of left ventricular ejection fraction is needed. The standardization of the follow-up pathways of patients with a history of ACS or elective PCI, shared between hospital doctors and primary care physicians, could result in a more cost-effective use of resources and potentially improve patient's long-term outcome.

Parenteral amino acids v. dextrose infusion: an anabolic strategy to minimise the catabolic response to surgery while maintaining normoglycaemia in diabetes mellitus type 2 patients.

Loss of body protein and hyperglycaemia represent typical features of the stress response to surgery and anaesthesia. This appears to be particularly pronounced in patients with diabetes mellitus type 2. The aim of the present study was to highlight the greater benefit of amino acids (AA) as represented by positive protein balance and maintenance of blood glucose homoeostasis compared with dextrose (DEX) in diabetic patients after colorectal surgery. A total of thirteen patients underwent a 5 h stable isotope infusion study (2 h fasted, 3 h fed with an infusion of AA (n 6) or DEX (n 7)) on the second post-operative day. Glucose and protein kinetics were assessed by using the stable isotopes l-[1-¹³C]leucine and [6,6-²H2]glucose. The transition from fasted to fed state decreased endogenous glucose production (P < 0·001) in both groups, with a more profound effect in the DEX group (P = 0·031). In contrast, total glucose production was increased by the provision of DEX while being lowered by AA (P = 0·021). Feeding decreased protein oxidation (P = 0·009) and protein synthesis in the AA group, whereas DEX infusion did not affect oxidation and even decreased protein synthesis. Therefore, only AA shifted protein balance to a positive value, while patients in the DEX group remained in a catabolic state (P < 0·001). Parenteral nutritional support with AA rather than with DEX is an effective strategy to achieve a positive protein balance while maintaining normoglycaemia in diabetic patients after colorectal surgery.

Trans-Catheter Valve-in-Valve Implantation for the Treatment of Aortic Bioprosthetic Valve Failure.

Aortic valve-in-valve (ViV) procedure is a valid treatment option for patients affected by bioprosthetic heart valve (BHV) degeneration. However, ViV implantation is technically more challenging compared to native trans-catheter aortic valve replacement (TAVR). A deep knowledge of the mechanism and features of the failed BHV is pivotal to plan an adequate procedure. Multimodal imaging is fundamental in the diagnostic and pre-procedural phases. The main challenges associated with ViV TAVR consist of a higher risk of coronary obstruction, severe post-procedural patient-prosthesis mismatch, and a difficult coronary re-access. In this review, we describe the principles of ViV TAVR.

An Update on New Generation Transcatheter Aortic Valves and Delivery Systems.

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 in cardiac surgery: real world and perspectives.

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 to recognize 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.

Clinical Comparison of a Novel Balloon-Expandable Versus a Self-Expanding Transcatheter Heart Valve for the Treatment of Patients with Severe Aortic Valve Stenosis: The EVAL Registry.

BACKGROUND: 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. PURPOSE: 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. METHODS:  A single-center, retrospective cohort analysis was performed with 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. RESULTS:  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; p = 0.048). At day 30, the BE Myval THV group exhibited a significantly lower incidence of more than mild PVL (BE Myval 3.45% vs. SE ER 14.8%, OR 0.2, 95% CI 0.05-0.8; p = 0.0338), along with a lower rate of PPI (BE Myval 11% vs. SE ER 24.2%, OR 0.38, 95% CI 0.15-0.99; p = 0.0535). At the 6-month follow-up, the incidence of all-cause mortality and disabling stroke did not significantly differ between the two groups, while the incidence of PPI (BE Myval 11% vs. SE ER 27.5%, OR 0.32, CI 95% 0.1273-0.8; p = 0.02) and ≥moderate PVL (BE Myval 6.9% vs. SE ER 19.8%, OR 0.31, 95% CI 0.1-0.94; p = 0.0396) was significantly lower in the BE Myval group. CONCLUSIONS: 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.

Current Use of Oral Anticoagulation Therapy in Elderly Patients with Atrial Fibrillation: Results from an Italian Multicenter Prospective Study-The ISNEP Study.

Background: Atrial fibrillation (AF) is the most common heart arrhythmia, and its prevalence increases with age. Oral Anticoagulant Therapy (OAT) with non-vitamin K antagonist oral anticoagulants (NOACs) or vitamin K antagonists (VKAs) is essential to avoid thromboembolic events in AF. However, this treatment is associated with a high risk of bleeding and low adherence in elderly patients. Aim: The aim was to evaluate the real-world use of OAT in a population of patients aged ≥80 years in twenty-three Italian centers and to investigate the tolerance of and patient satisfaction with this therapy. Methods: The ISNEP Study is a multicenter cross-sectional study enrolling patients with AF and aged ≥80 years and treated with either NOACs or VKAs. A written questionnaire was administered to each patient to evaluate the adherence to and patient satisfaction with this therapy. Results: The study included 641 patients with a mean age of 85 (82−87) years. The use of NOACs was reported in 93.0% of cases, with the remaining 7.0% treated with VKAs. A history of stroke events was reported in five (11.1%) and one (0.2%) patients in the VKA and NOAC groups, respectively. The rate of referred ecchymosis/epistaxis was significantly higher in the VKA group compared to the NOAC group (p < 0.001). Patients receiving NOACs reported a substantial improvement in their quality of life compared to the VKA group. Conclusions: A small, but not negligible, proportion of elderly AF patients is still treated with VKAs. Patients treated with NOAC have a higher level of satisfaction with the therapy and complete adherence.

Preoperative glucose and protein metabolism: the influence of diabetes mellitus type 2 in patients with colorectal tumors.

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.