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Introduction Data from the “Trattamento Ormonale nello Scompenso CArdiaco” (T.O.S.CA) registry showed that heart failure (HF) represents a complex clinical syndrome with different hormonal alterations. Renal failure represents a frequent complication in HF. We evaluated the relationship between renal function and insuline-like growth factor-1 (IGF-1) deficiency and its impact on cardiovascular mortality (CVM) in patients enrolled in the T.O.S.CA. registry. Methods At the enrolment, all subjects underwent chemistry examinations, including circulating hormones and cardiovascular functional tests. COX regression analysis was used to evaluate factors related to CVM during the follow-up period in all populations, in high-risk patients and in the young-adult population. Also, we evaluate the effects of renal function on the CVM. Results 337 patients (41 deceased) were analyzed. CVM was related to severe renal dysfunction (HR stages IV–V = 4.86), high-risk conditions (HR 2.25), serum IGF-1 (HR 0.42), and HF etiology (HR 5.85 and HR 1.63 for valvular and ischemic etiology, respectively). In high-risk patients, CVM was related to IGF-1 levels, severe renal dysfunction and valvular etiology, whereas in young patients CMV was related to the high-risk pattern and serum IGF-1 levels. Conclusions Our study showed the clinical and prognostic utility of the IGF-1 assay in patients with HF.

Heart failure (HF) and type 2 diabetes mellitus (T2DM) represent two important public health problems, and despite improvements in the management of both diseases, they are responsible for high rates of hospitalizations and mortality. T2DM accelerates physiological cardiac aging through hyperglycemia and hyperinsulinemia. Thus, HF and T2DM are chronic diseases widely represented in elderly people who often are affected by numerous comorbidities with important functional limitations making it difficult to apply the current guidelines. Several antidiabetic drugs should be used with caution in elderly individuals with T2DM. For instance, sulfonylureas should be avoided due to the risk of hypoglycemia associated with its use. Insulin should be used with caution because it is associated with higher risk of hypoglycemia, and may determine fluid retention which can lead to worsening of HF. Thiazolindinediones should be avoided due to the increased risk of fluid retention and HF. Biguanides may lead to a slightly increased risk of lactic acidosis in particular in elderly individuals with impaired renal function. Dipeptidyl peptidase 4 (DPP-4) inhibitors are safe having few side effects, minimal risk of hypoglycemia, and a neutral effect on cardiovascular (CV) outcome, even if it has been reported that saxagliptin treatment is associated with increased risk of hospitalizations for HF (hHF). Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have shown a CV protection without a significant reduction in hHF. On the other hand, sodium-glucose cotransporter 2 (SGLT2) inhibitors have shown a significant improvement in CV outcome, with a strong reduction of hHF and a positive impact on renal damage progression. However, it is necessary to consider the possible some side effects related to their use in elderly individuals including hypotension, bone fractures, and ketoacidosis. It is important to remark that elderly patients, in particular the very elderly, are not sufficiently represented in the trials; thus, the management and treatment of elderly diabetic patients with HF should be mainly based on the integration of scientific evidence with clinical judgment and patients’ condition, with respect to the dignity and quality of life.

Context Metabolic syndrome and elevated high sensitivity C-reactive protein (CRP) levels are associated with risk of cardiovascular diseases (CVD). A reduced myocardial mechano-energetic efficiency (MEE) has been found to be an independent predictor of CVD. Objective To evaluate the association between metabolic syndrome and hsCRP levels with impaired MEE. Methods Myocardial MEE was assessed by a validated echocardiography-derived measure in 1975 non-diabetic and prediabetic individuals subdivided into two groups according to the presence of metabolic syndrome. Results Individuals with metabolic syndrome exhibited increased stroke work and myocardial oxygen consumption estimated by rate pressure product, and a reduced MEE per gram of LV mass (MEEi) as compared to subjects without metabolic syndrome, after adjusting for age, and sex. Myocardial MEEi progressively decreased in parallel with the increase of the number of metabolic syndrome components. In a multivariable regression analysis, both metabolic syndrome and hsCRP contributed to reduced myocardial MEEi independently of sex, total cholesterol, HDL, triglycerides, fasting and 2-h post-load glucose levels. When the study population was divided into 4 groups by the presence or absence of metabolic syndrome and by hsCRP levels above and below 3 mg/L, hsCRP levels ≥3 mg/L were associated with reduced myocardial MEEi both in subjects with metabolic syndrome and in those without the syndrome. Conclusion Non-diabetic and prediabetic individuals with metabolic syndrome exhibit increased stroke work and myocardial oxygen consumption, and an impaired MEEi, an established predictor of adverse cardiovascular events, and elevated hsCRP levels in combination with metabolic syndrome aggravates the myocardial MEEi impairment.

Background. There are scant data about the effectiveness of high flow nasal cannula (HFNC) oxygen therapy in patients hospitalized with severe acute respiratory failure (ARF) in non-intensive medical wards, particularly regarding the effect on arterial oxygenation compared to conventional oxygen therapy (COT) and non-invasive ventilation (NIV) or continuous positive airway pressure (CPAP). Methods. In a retrospective observational study, oxygenation parameters were measured before and immediately after HFNC initiation in 37 consecutive patients hospitalized in a geriatric ward in 2017. Results. HFNC was used as escalation therapy for untreatable hypoxia after failure of NIV/CPAP (n=18) or COT (n=19). Twenty-two patients died, 2 were transferred to the intensive care unit, while 13 were discharged alive. A “do not intubate” status was identified in 17 of the 22 deceased patients. Partial pressure of oxygen (pO2, p< 0.0001), oxygen saturation (SO2, p< 0.0001), pO2/fraction of inspired oxygen ratio (p=0.004) and peripheral SO2 measured by pulse oximetry (p< 0.0001) significantly increased soon after HFNC application. Oxygenation improvements were greater after escalation from NIV/CPAP and in patients discharged alive. Conclusion. HFNC significantly improved oxygenation in severe ARF after failure of COT or NIV/CPAP and may be particularly suitable for older patients hospitalized in non-intensive medical wards.

It’s known that, a not physiological blood pressure (BP) circadian pattern has been associated with increased risk of organ damage and cardiovascular (CV) event. The aim of this study was to assess the association between circadian BP pattern and glucometabolic phenotypes occurring after oral glucose tolerance test (OGTT). We recruited 810 hypertensive Caucasian patients. All participants underwent to OGTT, laboratory test and 24-hours ambulatory BP monitoring (ABPM). The analysis of collected data allowed classifying patients based on nocturnal BP profiles into four categories: dippers, non-dippers, extreme dippers, and inverse dippers. Considering the dipping pattern, the proportion of non-dippers in normal glucose tolerance patients with 1-hour glucose ≥ 155 mg/dL (NGT ≥ 155) (36.4%) was higher than NGT

Background: Impaired myocardial mechano-energetics efficiency (MEEi) was shown to predict incident heart failure, but pathophysiological mechanisms linking impaired MEEi with heart failure have not been elucidated. Endothelial dysfunction is a plausible candidate because it has been associated with heart failure. This study aims to investigate the association between MEEi and endothelium‐dependent vasodilation, among drug-naïve hypertensive individuals with a broad spectrum of glucose tolerance. Methods: 199 drug-naïve hypertensive individuals participating in the CATAnzaro MEtabolic RIsk factors (CATAMERI) study were included. All participants underwent to an oral glucose tolerance test and to an echocardiogram for myocardial MEEi measurement. Endothelial-dependent and endothelial-independent vasodilatation were measured by strain-gauge plethysmography during intra-arterial infusion of acetylcholine and sodium nitroprusside, respectively. A multivariate linear regression analysis was conducted to investigate the independent association between endothelial-dependent vasodilation and MEEi. Results: ACh-stimulated forearm blood flow (FBF) was associated to decreased myocardial MEEi at all the three doses tested: 7.5, 15, and 30 µg/mL-1 x min-1 (β =0.201, P=0.002; β =0.171, P=0.008; β =0.205, P=0.002 respectively) independently of well‐established cardiovascular risk factorsincluding age, sex, BMI, waist circumference, smoking status, total and HDL cholesterol, triglyceride, hsCRP, glucose tolerance status, and HOMA-IR index of insulin resistance. No association was observed between SNP-stimulated vasodilation and MEEi. Conclusions: We found that endothelium-mediated vasodilation contributed to reduced myocardial MEEi independently of several potential confounders. Because diminished myocardial MEE has been associated with incident heart failure, assessment of myocardial MEEi may improve the identification of individuals at risk of heart failure requiring a closer follow-up.

Background Head and neck squamous cell carcinoma (HNSCC) represents the 6th leading cancer worldwide. In most cases, patients present a locally advanced disease at diagnosis and non-surgical curative treatment is considered the standard of care. Nowadays, [18F]FDG PET/CT is a validated tool in post-treatment evaluation, with a high level of evidence. However, to standardize imaging response, several visual scales have been proposed with none of them approved yet. The study’s aim is a head-to-head comparison between the diagnostic performance of the Hopkins criteria, the Deauville score, and the new proposed Cuneo score, to establish their prognostic role. Secondly, we investigate the possible value of semiquantitative analysis, evaluating SUVmax and ΔSUVmax of the lymph node with the highest uptake on the restaging PET scan. Moreover, we also considered morphological features using the product of diameters measured on the co-registered CT images to assess the added value of hybrid imaging. Methods We performed a retrospective analysis on histologically proven HNSCC patients who underwent baseline and response assessment [18F]FDG PET/CT. Post-treatment scans were reviewed according to Hopkins, Deauville, and Cuneo criteria, assigning a score to the primary tumor site and lymph nodes. A per-patient final score for each scale was chosen, corresponding to the highest score between the two sites. Diagnostic performance was then calculated for each score considering any evidence of locoregional progression in the first 3 months as the gold standard. Survival analysis was performed using the Kaplan–Meier method. SUVmax and its delta, as well as the product of diameters of the lymph node with the highest uptake at post-treatment scan, if present, were calculated. Results A total of 43 patients were finally included in the study. Sensitivity, specificity, PPV, NPV, and accuracy were 87%, 86%, 76%, 92%, and 86% for the Hopkins score, whereas 93%, 79%, 70%, 96%, and 84% for the Deauville score, respectively. Conversely, the Cuneo score reached the highest specificity and PPV (93% and 78%, respectively) but the lowest sensitivity (47%), NPV (76%), and accuracy (77%). Each scale significantly correlated with PFS and OS. The ROC analysis of the combination of SUVmax and the product of diameters of the highest lymph node on the restaging PET scan reached an AUC of 0.822. The multivariate analysis revealed the Cuneo criteria and the product of diameters as prognostic factors for PFS. Conclusions Each visual score statistically correlated with prognosis thus demonstrating the reliability of point-scale criteria in HNSCC. The novel Cuneo score showed the highest specificity, but the lowest sensibility compared to Hopkins and Deauville criteria. Furthermore, the combination of PET data with morphological features could support the evaluation of equivocal cases.

Aim Heart failure (HF) is associated to endothelial dysfunction, a pathological condition characterized by imbalance between the production of vasoconstrictor and vasodilator factors, increase in the production of cytokines, down-regulation of eNOS, platelets activation and increased oxidative stress. Furthermore, endothelial dysfunction promotes the increase of arterial stiffness, augmenting myocardial damage. Sacubitril/Valsartan (sac/val) is used in the treatment of HF reduced ejection fraction (HFrEF) and has been proven effective in reducing CV disease progression and all-cause mortality in HFrEF patients. The aim of the study was to evaluate the effect of sac/val on endothelial dysfunction and arterial stiffness in patients with HFrEF, at baseline and after 6 months of treatment. Moreover, we evaluated the effects of sac/val on oxidative stress levels and platelets activation. Materials Methods We enrolled 46 Caucasian patients (mean age 70.1±7.1), suffering from HFrEF. Inclusion criteria were LVEF Results The mean dose of sac/val was 180.5±110 mg without serious adverse events. At 6 months, data showed a significant improvement in in hemodynamic and clinical parameters such as heart rate (HR) (p Conclusion The treatment with sac/val improved endothelial dysfunction and arterial stiffness, due to reduced levels of oxidative stress, platelet activation and inflammation.

Aim Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) is mainly produced by the liver, but it is also expressed in the heart. It plays a key role in cholesterol's metabolism. Recent studies suggest its possible role in cardiovascular (CV) diseases, promoting vascular inflammation, reactive oxygen species generation and atherosclerotic plaque formation. Global longitudinal strain (GLS), global myocardial work efficiency (GWE), reservoir (PALS) and pump (PACS) atrial function evaluated by speckle-tracking echocardiography are able to identify early subclinical ventricular and atrial myopathy. In the last years PCSK9 inhibitors have been introduced as innovative therapies for LDL plasma levels's reduction. The aim of our study was to investigate PCSK9 inhibitors's effects in secondary prevention's patients, equally assigned to Alirocumab or Evolocumab, who were statin-intolerant and/or not reaching the target of LDL-C Methods We selected 30 patients (24 males and 6 females, mean age 66+8 years old), having several comorbidities: hypertension (97%), ICM (90%), CKD II-III stage (70%), polidistrectual atherosclerosis (67%), T2DM (50%), OSAS-COPD (20%), HF NYHA class II-III (20%). They underwent anthropometrical evaluation, biochemical analysis, oxidative stress markers assessment, liver elastography, and advanced echocardiogram at basal time and after six months of therapy. NOX-2 and Sp-selectin were assessed with ELISA sandwich. Data were analyzed with ANOVA, post-hoc Bonferroni's test and Chi-square. Linear correlation analysis was performed for variables whose variation were statistically significant. Results As expected, lipid profile was greatly improved in all the subjects, reaching the target of LDL-C Conclusions Our study demonstrated for the first time that PCSK9 inhibitors are able to reduce left ventricular filling pressure, to increase atrial function (reservoir and pump), global cardiac performance (GLS and GWE), and eGFR after six months of treatment in high CV risk population. Our results could be partially explained with a reduction of oxidative stress markers, inflammation and cardio-lipotoxicity, probably linked to a modulation of PCSK9's heart expression and its toxic effect on CV and renal function. In addition, we observed a TG/HDL ratio's reduction, related to cardiometabolic and lipid profile improvement. Further studies are necessary to better investigate systemic benefit in a larger population with longer follow-up.

Aim Non Valvular Atrial fibrillation (NVAF) is an independent predictor of cardiovascular (CV) mortality and morbidity. The incidence and prevalence increase in proportion to age and comorbidity burden. Non vitamin K oral anticoagulants (NOACs) are as effective as VKAs with a better safety profile, ensuring a lower incidence of major bleeding. NVAF and Chronic Kidney Disease (CKD) are mutually connected and often coexist in the elderly patient. NVAF is a risk factor for the progression of CKD, the prevalence and incidence of NVAF increase with decrease in renal function, CKD also increases the risk of bleeding and thromboembolism, making risk stratification and treatment difficult. All available NOACs are partially eliminated by the kidneys therefore, renal function inevitably influences our therapeutic strategies. The aim of this work is to evaluate any differences between VKAs versus NOACs patient's on the decline of renal function in elderly population with NVAF and important comorbidities. Materials and Methods We enrolled 411 Caucasian patients aged ≥70 years, affected by NVAF with important comorbidities; 135 patients receiving VKAs and 276 receiving NOACs, median age was 77.2 years (IQR 72.7-81.6). Patients underwent clinical-instrumental and laboratory evaluation for a follow-up of 6.9±2.5 years. Patients with severe hepatic impairment or ClCr Results During an average follow-up of 6.9±2.5 years there were statistically significantly differences between NOACs and VKAs in: eGFR values 48.2 (IQR 40.3-58.6) vs. 39.7 (IQR 32.4-47.8) ml/min/1.73 m2, p=0.0001; Delta eGFR -9.1 (IQR -14.3/-5.2) vs -29.8 (IQR -40.9/-18.9) ml/min/1.73 m2, p=0.0001; Delta eGFR/year -1.6 (IQR -2.6/-0.9) vs 2.9 (IQR -5.0/-2.0) ml/min/1.73 m2, p=0.0001; and in glycaemia (p Conclusions The data from the present study confirm a better safety profile of NOACs compared with VKAs on the occurrence of rapid decline in renal function in an elderly population with numerous comorbidities, despite the NOACs group having lower baseline eGFR values than VKAs.

Condition being studied: Review efficacy and safety of minimally-invasive treatments for Low Urinary Tract Symptoms (LUTS) in patients affected by Benign Prostate Hyperplasia (BPH). These minimally invasive techniques represent a valid alternative for patients who can no longer continue medical therapy or are ineligible to surgery. Eligibility criteria: The inclusion criteria concern the most relevant clinical trials on minimally invasive interventions for Benign Prostatic Hyperplasia (BPH) from January 1993 to January 2022.

Background Findings from the T.O.S.CA. Registry recently reported that patients with concomitant chronic heart failure (CHF) and impairment of insulin axis (either insulin resistance—IR or diabetes mellitus—T2D) display increased morbidity and mortality. However, little information is available on the relative impact of IR and T2D on cardiac structure and function, cardiopulmonary performance, and their longitudinal changes in CHF. Methods Patients enrolled in the T.O.S.CA. Registry performed echocardiography and cardiopulmonary exercise test at baseline and at a patient-average follow-up of 36 months. Patients were divided into three groups based on the degree of insulin impairment: euglycemic without IR (EU), euglycemic with IR (IR), and T2D. Results Compared with EU and IR, T2D was associated with increased filling pressures (E/e′ratio: 15.9 ± 8.9, 12.0 ± 6.5, and 14.5 ± 8.1 respectively, p 2) in TD2 vs EU and IR patients was recorded (respectively, 15.8 ± 3.8 ml/Kg/min, 18.4 ± 4.3 ml/Kg/min and 16.5 ± 4.3 ml/Kg/min, p 2 in the T2D group (+ 13% increase in RV dimension, − 21% decline in TAPSE/PAPS ratio and − 20% decrease in peak VO2). Conclusion The higher risk of death and CV hospitalizations exhibited by HF-T2D patients in the T.O.S.CA. Registry is associated with progressive RV ventricular dysfunction and exercise impairment when compared to euglycemic CHF patients, supporting the pivotal importance of hyperglycaemia and right chambers in HF prognosis. Trial registration ClinicalTrials.gov identifier: NCT023358017

Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) levels have been suggested as novel atherosclerotic biomarker. PCSK9 plays important roles in the pathogenesis of atherosclerosis by regulating the degradation of low-density lipoprotein receptor as well as different inflammatory pathways. Considering the important prognostic role of arterial stiffness in cardiovascular disease (CVD), the aim of the study is to investigate the correlation between PCSK9 levels and arterial stiffness in a cohort of diabetic patients, without previous CV events.This cross-sectional analysis enrolled 401 Caucasian patients with type II diabetes mellitus (T2DM). PCSK9 levels were measured by ELISA test, arterial stiffness was estimated by measuring carotid-femoral pulse wave velocity (PWV).Patients were divided in three tertiles according to increasing value of PCSK9. From the I to the III tertiles, there was a significant increase in high sensitivity C-reactive protein (hs-CRP), fibrinogen and white blood cells (WBC) and a reduction in estimated glomerular filtration rate (e-GFR). Patients with higher levels of PCSK9 presented increased systolic, diastolic blood pressure, pulse pressure and PWV. PWV was significantly and directly correlated with PCSK9, fibrinogen, age, BMI and PP, and indirectly correlated with diet, lifestyle and e-GFR. Serum PCSK9 was the major predictor of PWV, justifying a 16.9% of its variation.Our study demonstrates a close association between circulating PCSK9 levels and PWV in T2DM subjects without previous CV events even after adjusting for well-known CV risk factor and pharmacological medications. Serum PCSK9 could be a useful biomarker for CV risk stratification in diabetic subjects.

Background Heart failure with reduced ejection fraction (HFrEF) is a clinical condition frequently diagnosed in clinical practice. In patients affected by HFrEF, sleep apnea (SA) can be detected among the most frequent comorbidities. Sacubitril–valsartan (sac/val) association has been proven to be effective in reducing disease progression and all-cause mortality in HFrEF patients. Sac/val treatment can potentially attenuate SA development via several pathophysiologic mechanisms, including improvement of global hemodynamics, reduction of extracellular fluid overload, and decrease of sympathetic neural activity. Purpose The aim of this work is to evaluate the effects of a 6-month therapy with sac/val on hemodynamic and metabolic parameters, as well as on the occurrence of apnea/hypopnea and oxygen saturation in patients with HFrEF and SA, already treated with CPAP. Methods We recruited 132 patients affected by HFrEF and SA, already under treatment with continuous positive airway pressure (CPAP), which was discontinued 24 hours before the scheduled study timepoints. Physical examination, echocardiography, nocturnal cardio-respiratory monitoring, and laboratory tests were performed in each patient at baseline and after a 6-month treatment with sac/val. Results After 6 months, sac/val induced statistically significant changes in clinical, hemodynamic, biohumoral (NT-proBNP, serum electrolytes, creatinine and uric acid), and echocardiographic parameters. In particular, cardiac index (CI), both atrial and ventricular volumes and global longitudinal strain (GLS) improved. Moreover, polysomnography, carried out during a temporary CPAP interruption, revealed a significant reduction in global apnea-hypopnea index (AHI) value (p Conclusions Our results suggest that treatment with sac/val is able to significantly improve the cardiorespiratory performance of patients with HFrEF and SA, integrating the positive impact of CPAP. Thus, both CPAP and sac/val therapy may synergistically contribute to lower the risks of both cardiac and pulmonary complications in HFrEF patients with SA. Funding Acknowledgement Type of funding sources: None.

Background Non Valvular Atrial fibrillation (NVAF) is an independent predictor of cardiovascular (CV) mortality and morbidity. The incidence and prevalence increase in proportion to age and comorbidity burden especially in elderly patients in whom oral anticoagulant therapy (OAT) is difficult to manage, and it is often underused for limitations of efficacy and safety presented by vitamin K antagonists (AVK). Direct oral coagulation inhibitors (DOACs) are as effective as AVKs with a better safety profile, ensuring a lower incidence of major bleeding. NVAF and Chronic Kidney Disease (CKD) are mutually connected and often coexist in the elderly patient. AF is a risk factor for the progression of CKD, the prevalence and incidence of AF increase with decrease in renal function, CKD also increases the risk of bleeding and thromboembolism, making risk stratification and treatment difficult. All available DOACs are partially eliminated by the kidneys therefore, renal function inevitably influences our therapeutic strategies. Purpose The aim of this work is to evaluate any differences between AVK versus DOACs patient's on the decline of renal function in elderly population with NVAF and important comorbidities. Methods We enrolled 411 Caucasian patients aged ≥70 years, affected by NVAF with important comorbidities; 135 patients receiving VKA and 276 receiving DOACs, median age was 77.2 years (IQR 72.7–81.6). Patients underwent clinical-instrumental and laboratory evaluation for a follow-up of 6.9±2.5 years. Patients with severe hepatic impairment or ClCr Results During an average follow-up of 6.9±2.5 years there were statistically significantly differences between VKA and NOAC in eGFR (p Conclusion The present study confirms a better safety profile of DOACs compared to AVKs on the decline of renal function in elderly and multimorbid population, even though patients receiving DOACs had a greater burden of comorbidities that negatively affect renal function such as arterial hypertension, COPD, heart failure; and at baseline a significantly lower eGFR value than the AVK group. Funding Acknowledgement Type of funding sources: None.

Background Heart failure (HF) is associated to endothelial dysfunction, a pathological condition characterized by imbalance between the production of vasoconstrictor and vasodilator factors, increase in the production of cytokines, down-regulation of eNOS, platelets activation and increased oxidative stress. Furthermore, endothelial dysfunction promotes the increase of arterial stiffness, augmenting myocardial damage. Sacubitril/Valsartan (sac/val) is used in the treatment of HF reduced ejection fraction (HFrEF) and has been proven effective in reducing CV disease progression and all-cause mortality in HFrEF patients. Purpose The aim of the study was to evaluate the effect of sac/val on endothelial dysfunction and arterial stiffness in patients with HFrEF, at baseline and after 6 months of treatment. Moreover, we evaluated the effects of sac/val on oxidative stress levels and platelets activation. Methods We enrolled 46 Caucasian patients (mean age 70.1±7.1), suffering from HFrEF. Inclusion criteria were EF Results The mean dose of sac/val was 180.5±110 mg without serious adverse events. At 6 months, data showed a significant improvement in in hemodynamic and clinical parameters such as heart rate (HR) (p Conclusion The treatment with sac/val improved endothelial dysfunction and arterial stiffness, due to reduced levels of oxidative stress, platelet activation and inflammation. Funding Acknowledgement Type of funding sources: None.

Background Atrial fibrillation (AF) and cancer are frequently coexisting in elderly patients. Pooled metanalytic data on the impact of cancer on outcomes in AF patients are lacking. Purpose We want to investigate the impact of cancer in patients with AF, particularly in relation to the incidence of bleeding and ischemic events Methods Systematic review and meta-regression analysis of clinical studies retrieved from Medline (PubMed) and Cochrane (CENTRAL) databases according to PRISMA guidelines. Safety endpoints included any, major, gastrointestinal (GI) bleeding and intracranial haemorrhage (ICH). Efficacy endpoints included myocardial infarction (MI), ischemic stroke/systemic embolism (IS/SE), cardiovascular (CV) and all-cause death. Results 15 studies were included in the metanalysis: 4 prospective, 3 randomized clinical trials and 8 retrospective studies with 2,868,010 AF patients, of whom 479,571 (16.7%) had cancer. The pooled HR for cancer was 1.43 (95% CI 1.42–1.44) for any bleeding, 1.27 (95% CI 1.26–1.29) for major bleeding, 1.17 (95% CI 1.14–1.19) for GI bleeding, and 1.07 (95% CI 1.04–1.11) for ICH. The risk of major bleeding increased with the proportion of breast cancer. Cancer increased the risk of all-cause death (HR 2.00, 95% CI 1.99–2.02) whereas no association with MI (HR 0.97, 95% CI 0.94–1.01) and CV death (HR 1.01, 95% CI 0.99–1.03) was found. Patients with AF and cancer were less likely to suffer from IS/SE (HR 0.91, 95% CI 0.89–0.94). Conclusion The presence of cancer modifies the clinical history of AF patients, mainly increasing the risk of bleeding. Further analyses according to the type and stage of cancer is necessary to better stratify bleeding risk in these patients. Funding Acknowledgement Type of funding sources: None.

Background: Alterations in myocardial mechano-energetic efficiency (MEEi), which represents the capability of the left ventricles to convert the chemical energy obtained by oxidative metabolism into mechanical work, have been associated with cardiovascular disease. Although whole-body insulin resistance has been related to impaired myocardial MEEi, it is unknown the relationship between cardiac insulin resistance and MEEi. Aim of this study was to evaluate the relationship between insulin-stimulated myocardial glucose metabolic rate (MrGlu) and myocardial MEEi in subjects having different degrees of glucose tolerance. Methods: We evaluated insulin-stimulated myocardial MrGlu using cardiac dynamic positron emission tomography (PET) with 18F-Fluorodeoxyglucose (18F-FDG) combined with euglycemic-hyperinsulinemic clamp, and myocardial MEEi in 57 individuals without history of coronary heart disease having different degrees of glucose tolerance. The subjects were stratified into tertiles according to their myocardial MrGlu values. Results: After adjusting for age, gender and BMI, subjects in I tertile showed a decrease in myocardial MEEi (0.31±0.05 vs 0.42±0.14 ml/sec*g, P=0.02), and an increase in myocardial oxygen consumption (MVO2) (10153±1375 vs 7816±1229 mmHg*bpm, P2. In a multivariate regression analysis running a model including several CV risk factors, the only variable that remained significantly associated with MEEi was myocardial MrGlu (b 0.346; P=0.01). Conclusions: These data suggest that an impairment in insulin-stimulated myocardial glucose metabolism is an independent contributor of depressed myocardial MEEi in subjects without history of CHD.

Chronic kidney disease is a risk factor for cardiovascular events. Smoking and chronic obstructive pulmonary disease (COPD) are risk factors for renal impairment. The aim of this study was to test the combined effect of smoking and COPD on renal function decline in hypertensives. We enrolled 1728 hypertensives stratified by smoking status and presence/absence of COPD. To test the mutual effect modification by both smoking and COPD and e-GFR, we performed crude and adjusted linear regression analyses, these latter taking into account potential confounders. Smokers displayed significantly lower e-GFR values than non-smokers (90 ± 24 vs. 121 ± 35 ml/min/1.73 m

Lung hyperinflation and systemic inflammation are currently believed to be the most important causes of right heart alterations in chronic obstructive pulmonary disease (COPD) patients. A multicentre observational study was performed to assess the morphological and functional parameters of right ventricle (RV) in COPD subjects, as well as to evaluate the potential prognostic impact on the development of major cardiovascular adverse events (MACEs).For this retrospective study, from 1 January 2010 to 31 December 2021, we enrolled COPD patients on the basis of their airflow limitation. In particular, we selected subjects spanning across GOLD 1 and 2 functional stages. Clinical, laboratory and functional parameters were collected at baseline. Echocardiography was routinely performed in all COPD patients. RV dysfunction was defined on the basis of tricuspid annular plane systolic excursion (TAPSE) values. MACE occurrence (non-fatal ischemic stroke, non-fatal myocardial infarction, cardiac revascularization or coronary bypass surgery and cardiovascular death) was evaluated during a median follow-up of 55 (36-72) months.Among the 749 enrolled patients, 408 subjects had a TAPSE value ≥20 mm, while the remaining 341 had a TAPSE value20 mm. In patients with TAPSE ≥20 mm the observed MACEs were 1.9 events/100 patient-year, while in the group with a worse right heart function there were 4.2 events/100 patient-year (p .0001). The multivariate analysis model confirmed the association between RV dysfunction and MACE. Indeed, a 1-mm increase in TAPSE value and the intake of long-acting βThe results of this study showed that in patients with mild COPD there is an association between right heart dysfunction and the risk of MACE during follow-up.

Sacubitril/Valsartan (Sac-Val) has improved clinical prognosis in patients affected by heart failure (HF) with reduced ejection fraction (HFrEF). Comorbidities have a crucial impact on clinical presentation and prognosis in HF patients. Cognitive impairment (CoI) and Depression are a very common comorbidity in patients with HF and is widely recognized as a specific determinant of chronic disability, and HF patients with poor physical functional performance in Short physical performance battery (SPPB) showed a worse prognosis. The aim of the present study was to evaluate the potential effects of Sac-Val on functional, humoral, and cognitive aspects, evaluated by performing comprehensive geriatric assessment (CGA), in a cohort of elderly HFrEF. We studied 61 patients (51 men and 10 women, mean age 76.4 ± 5.1 years) suffering from HFrEF. After 6 months follow-up, we observed a significant improvement in humoral and functional parameters of CGA, renal function, NTpro-BNP levels and echocardiographic parameters. In the whole population, multivariate analysis shows that changes of Cardiac Index, NT-proBNP and Respiratory rate contributed for 26.0%, 9.7% and 4.8% to GDS variability, respectively, and the whole model accounted for a 41.1% of GDS variation; moreover changes of Global longitudinal strain, estimated glomerular filtration rate, Cardiac Index and BMI contributed for 23.9%, 11.7%, 5.4% and 4.0% to SPPB variability, respectively, and the whole model accounted for a 45% of SPPB variation. This represents the first real-world study carried out in an elderly population suffering from chronic HFrEF with numerous comorbidities, in which treatment with Sac-Val for 6 months induced important improvements in clinical, humoral, hemodynamic, and functional outcomes, without adverse effects on cognitive performance.

To determine whether treatment with empagliflozin was able to affect the myocardial glucose metabolic rate, as assessed by cardiac dynamicTo further investigate the cardioprotective mechanism of sodium-glucose co-transporter-2 inhibitors, we performed a 26-week, randomized, open-label, crossover, active-comparator study to determine the effects of empagliflozin 10 mg versus glimepiride 2 mg daily on the myocardial glucose metabolic rate assessed by cardiac dynamicCompared with glimepiride, treatment with empagliflozin resulted in a greater reduction in the myocardial glucose metabolic rate from baseline to 26 weeks (adjusted difference -6.07 [-8.59, -3.55] μmol/min/100 g; P .0001). Moreover, compared with glimepiride, empagliflozin led to significant reductions in left atrial diameter, left ventricular end-systolic and end-diastolic volumes, N-terminal pro b-type natriuretic peptide levels, blood pressure, heart rate, stroke work, and myocardial oxygen consumption estimated by the rate pressure product, and increases in ejection fraction, myocardial mechano-energetic efficiency, red blood cells, and haematocrit and haemoglobin levels.The present study provides evidence that empagliflozin treatment in subjects with type 2 diabetes without coronary artery disease leads to a significant reduction in the myocardial glucose metabolic rate.

Background: Acutely ill medical patients experience deep venous thrombosis (DVT) during the hospitalization, however the time course of DVT is still unclear. Objectives: To evaluate risk factors in acutely ill hospitalized medical patients for asymptomatic DVT (ADVT) and symptomatic DVT (SDVT) within 48 hours from admission and at discharge and comparing prophylaxis treatment with (group A) and without (group B) low-molecular weight heparin (LMWH) Patients/Methods: Consecutive acutely ill medical patients underwent duplex color compression ultrasonography (CUS) of proximal lower limb veins within 48 hours from admission and at discharge to screen for ADVT and to document SDVT. Primary end-point of the multicentric study was the incidence of all DVT. Biographical characteristics at hospitalization, D-Dimer and DD-improve score at entry and at discharge were analyzed by univariate and multivariate analysis to identify variables associated with DVT and compared between groups.Results: Of 2,100 patients (1002 females, 998 males, age 71±16) included 58 (2.7%) (31 females. 27 males, age 77±14) had ADVT at admission. A binary logistic regression analysis showed that age (O.R.: 1.03, 95% C.I. 1.007-1.05, p=0.008), thrombophilia (O.R.: 10,95% C.I. 3-34, pConclusions: The incidence of ADVT and of SDVT was high (3%) upon admission of acutely ill medical patients upon hospitalization. Advanced age, active cancer, thrombophilia, elevated D-dimer and IMPROVE-DD score greater than 2.5 were risk factors for ADVT should analyzed upon hospitalization for decision of treatment with LMWH. The benefit of therapeutic dose of anticoagulation needs to be investigated in patients with ADVT and specific risk factors. Trial registration: NCT03157843

Background Obesity and Obstructive Sleep Apnea Syndrome (OSAS) has been recognized as two of the major cardiac risk factors and they often coexist in one patient. OSAS increase the risk of as myocardial infarction, heart failure and arrhythmias. On the other hand, obesity is and independent predictor of cardiovascular mortality since it causes insulin resistance, dyslipidemia, sympathetic hyperactivation, chronic inflammation and endothelial dysfunction. Aim To evaluate cardiometabolic profile, echocardiographic alterations and the presence of arrhythmias in obese patients with Obstructive Sleep Apnea Syndrome and non obese patients. Patients and Methods 67 obese patients (37 male/30 female) and 52 non obese patients (40 male/12 female) were enrolled. All subjects underwent anthropometrical evaluation and a venous blood sample for biochemical and hormonal determinations including fasting plasma glucose, fasting plasma insulin, Hba1c and OGTT to 5 hours. The insulin resistance was evaluated by HOMA–IR. All the patients underwent echocardiographic examination, polysomnographic evaluation, in order to diagnose the OSAS, and a simultaneous 12–lead Holter ECG to evaluate the presence of nocturnal arrhythmias. Results As expected, we found a better antropometrics profile in non obese patients. Obese patients display a severe OSAS compared to non–obese patient as shown by higher values of AHI (26.37 ±24.95 vs 16.58 ±14.07; P 3 sec during apnea. In obese population alone we demonstrated a significant negative correlation between AHI and E–wave (r= –0.3; P = 0.04) and a positive correlation with interventricular septum (r = 0.38; P = 0.01) and left ventricular mass (r = 0.32; P = 0.02). Post–hoc analysis shown how these findings maintained statistical significance even when the obese patients were stratified in subgroups according to the severity of OSAS. Conclusions Our data, even if preliminary, seem to indicate that OSAS is not only linked to obesity but it also acts as a negative factor on the cardiometabolic risk.

Background Sacubitril/Valsartan has been shown to improve mortality and reduce hospitalizations in patients with heart failure with reduced ejection fraction (HFrEF). Moreover Sacubitril/Valsartan showed a significantly reduction in the HbA1c in diabetic patients. The effect of Sacubitril/Valsartan on metabolic parameter and insulin resistence in both, non obese and non diabetic patients, have not been previously described. Aim We evaluated the effects of the Sacubitril/Valsartan on both glycaemic and metabolic parameter, on HOMA–IR and on echocardiographic parameters in patients with HFrEF. Methods A total of 59 non obese and non diabetic patients with a diagnosis of HFrEF (EF Results Data analysis demostrated a significant reduction in fasting plasma glucose (111.4 + 11.5 vs 106 + 10 mg/dl, P = 0.03), fasting plasma insulin (13.6 + 5.9 vs 10.5 + 4.4 µUI/ml), HbA1c value (6.14 + 0.5% vs 5.9 + 0.3%, P Conclusions Our data, even if preliminary, seem to indicate that sacubitril/valsartan might enhance glycaemic control and improve insulin resistance in non obese/non diabetic patients with HFrEF. Also, our data confirm that sacubitril/valsartan treatment is able to improve ejection fraction in HFrEF patients.

Background Obesity is associated with cardiac remodeling resulting in hypertrophy of the left ventricle (LV) with a predominantly concentric pattern. LV remodeling and fibrosis induce mechanical and electrical dysfunction of the myocardial tissue, an increase in cardiac output, an increase of myocardial workload and mean arterial pressure. Objective To evaluate the impact of bariatric surgery, and therefore of anthropometric and cardio–metabolic variations, on cardiac structure and function. Methods Twenty–six obese patients treated with bariatric surgery were enrolled. All the patients at baseline and at 6 and 12 months underwent a complete anthropometrical evaluation, laboratory determinations and echocardiogram evaluation. The IR has been assessed by HOMA–IR. The patients were divided into two groups: the first group (8 patients) carried out a follow–up at 6 months post–surgery; the second group (18 patients) at 12 months post–surgery. Results As expected, an improvement in the anthropometric and metabolic profile in patients treated with bariatric surgery was observed. Echocardiographic data showed a significant increase in the Ejection Fraction (P Conclusions Our data showed an increase of the systolic function, an increase of the left ventricular diastolic compliance and a reduction in subclinical cardiac organ damage. Therefore, significant weight loss obtained with bariatric surgery may lead to reverse cardiac remodeling, associated with beneficial effects on myocardial structure and systo-diastolic function.

Background Obesity cardiomyopathy is a heart failure unexplained by others etiologies that can vary from a subclinical left ventricular dysfunction to overt dilated cardiomyopathy. Aim To evaluate the changes in echocardiogram in both normotensive and hypertensive obese and to evaluate obesity and/or hypertension impact on cardiomyopathy. Methods 383 subjects (236F–147M) were enrolled. They were divided into two groups based on BMI: non–obese subjects (BMI30kg/m2). The obese subjects were divided in different degrees (groups) of obesity according with obesity classification: group 1= BMI >303540 kg/m2. 208 of 383 enrolled subjects were hypertensive. All subjects underwent to an echocardiogram with evalutation of left atrial diameter (LAD), left ventricular end–diastolic diameter (LVEDD), left ventricular end–systolic diameter (LVESD), ventricular septum, cardiac mass and left ventricular mass index (LVMI). Results Obese subjects showed a progressive increase in left atrial diameter (LAD)(P = 0.000), left ventricular end–diastolic diameter (LVEDD)(P = 0.000), left ventricular end–systolic diameter (LVESD)(P = 0.001), ventricular septum (P = 0.000) and cardiac mass (P = 0.000) according to the degree of obesity. Subjects in the 3° group of obesity showed higher value of LAD and LVESD when compared with subjects in first two groups (P = 0.000; P = 0.032; P = 0.000; P = 0.001, respectively). Similarly, subjects in the 3° group of obesity showed higher value of ventricular septum and cardiac mass when compared with the first two groups of obesity (P = 0.005; P = 0.002; P = 0.000; P = 0.005; respectively). LAD, LVEDD, LVESD, ventricular septum and cardiac mass were positively related with the obesity degree. In order to avoid that echocardiographic modifications were caused by hypertension, data were adjusted for hypertension so linear regression documented that degree of obesity predicts echocardiographic changes (LAD, LVEDD, LVESD) better than hypertension. Conclusions Our data suggested that the in obese subjects the severity of cardiomyopathy is correlated with degree of obesity and that the degree of obesity is a better predictor than hypertension for echocardiographic changes.

IntroductionGut microbiota are a complex ecosystem harboring our intestine. They maintain human body equilibrium, while their derangement, namely, “dysbiosis“, has been associated with several gastrointestinal diseases, such as liver steatosis (NAFLD) and liver cirrhosis. Small intestinal bacterial overgrowth (SIBO) is an example of dysbiosis of the upper gastrointestinal (GI) tract.AimThe aim of this study is to evaluate the relationship between SIBO and levels of endotoxemia and grade of liver steatosis (LS) and liver fibrosis (LF) in hepatologic patients.Materials and MethodsConsecutive outpatients referred to our hepatology clinic were tested for SIBO by the lactulose breath test (LBT) and peripheral blood levels of endotoxemia; LS grading and LF were assessed by abdominal ultrasound and transient elastography, respectively.ResultsFifty-two consecutive patients (17 with alcohol abuse (4.5 ± 0.8 alcohol units per day), 4 with HCV and 2 with HBV infection, 24 of metabolic origin, 2 of autoimmune origin, and 3 with cholangiopathies; mean age 54.7 ± 8.3 years, 31 F, BMI 24.1 ± 1.1 Kg/m2) and 14 healthy volunteers (HV) (mean age 50.1 ± 4.3 years, 9 F, BMI 23.3 ± 1.1 Kg/m2) were enrolled. SIBO prevalence was significantly higher in cirrhotic (LC) vs. non-cirrhotic (LNC) patients and vs. HV (all, p < 0.05), with a significant positive trend according to Child-Pugh status (all, p < 0.05). SIBO prevalence was not correlated with LS stages (all, p = NS). Consensually, endotoxin levels were significantly higher in LC vs. LNC and vs. HV (all, p < 0.05) and significantly correlated with LF in patients with LC, according to Child-Pugh status (all, p < 0.05).ConclusionThis study shows that SIBO prevalence and relative endotoxin blood levels seem to be significantly associated with the grade of LF vs. LS in LC. SIBO is also present under pre-cirrhotic conditions, but its prevalence seems to correlate with liver disease irreversible derangement.

Metabolic syndrome is a condition characterized by a clustering of metabolic abnormalities associated with an increased risk of type 2 diabetes and cardiovascular disease. An impaired insulin-stimulated myocardial glucose metabolism has been shown to be a risk factor for the development of cardiovascular disease in patients with type 2 diabetes. Whether cardiac insulin resistance occurs in subjects with metabolic syndrome remains uncertain. To investigate this issue, we evaluated myocardial glucose metabolic rate using cardiac dynamic

Interleukin-4 (IL-4) and interleukin-13 (IL-13) are key cytokines involved in the pathophysiology of both immune-inflammatory and structural changes underlying type 2 asthma. IL-4 plays a pivotal role in Th2 cell polarization, immunoglobulin E (IgE) synthesis and eosinophil recruitment into the airways. IL-13 synergizes with IL-4 in inducing IgE production and also promotes nitric oxide (NO) synthesis, eosinophil chemotaxis, bronchial hyperresponsiveness and mucus secretion, as well as the proliferation of airway resident cells such as fibroblasts and smooth muscle cells. The biological effects of IL-4 and IL-13 are mediated by complex signaling mechanisms activated by receptor dimerization triggered by cytokine binding to the α-subunit of the IL-4 receptor (IL-4Rα). The fully human IgG4 monoclonal antibody dupilumab binds to IL-4Rα, thereby preventing its interactions with both IL-4 and IL-13. This mechanism of action makes it possible for dupilumab to effectively inhibit type 2 inflammation, thus significantly reducing the exacerbation of severe asthma, the consumption of oral corticosteroids (OCS) and the levels of fractional exhaled NO (FeNO). Dupilumab has been approved not only for the add-on therapy of severe asthma, but also for the biological treatment of atopic dermatitis and nasal polyposis.

Aims Endothelial dysfunction and heart failure are associated, but no prospective studies demonstrated that impaired endothelium‐dependent vasodilation predicts incident heart failure. We designed this study to test whether endothelial dysfunction is associated with incident heart failure in a group of hypertensives. Methods and results We enrolled 735 White never‐treated hypertensive outpatients free from heart failure, diabetes, chronic kidney disease, and previous cardiovascular events. Endothelium‐dependent vasodilation was investigated by intra‐arterial infusion of acetylcholine, and laboratory determinations were obtained by standard procedures. During the follow‐up [median 114 months (range 26–206)], there were 208 new cases of heart failure (3.1 events/100 patient‐years). Dividing the study population in progressors and non‐progressors, we observed that progressors were older, showed a higher prevalence of being female, and had a higher baseline heart rate, glucose, insulin, Homeostatic Model Assessment (HOMA), creatinine, and high‐sensitivity C‐reactive protein (hs‐CRP) mean values, while estimated glomerular filtration rate and maximal acetylcholine‐stimulated forearm blood flow were lower. In the multiple Cox regression analysis, female gender [hazard ratio (HR) = 1.454, 95% CI = 1.067–1.981], fasting glucose (HR = 1.186, 95% CI = 1.038–1.357), hs‐CRP (HR = 1.162, 95% CI = 1.072–1.259), HOMA (HR = 1.124, 95% CI = 1.037–1.219), acetylcholine‐stimulated forearm blood flow (HR = 0.779, 95% CI = 0.695–0.874), and estimated glomerular filtration rate (HR = 0.767, 95% CI = 0.693–0.849) maintained an independent association with the outcome. Successively, testing the interaction between forearm blood flow and hs‐CRP, we observed that patients who have hs‐CRP values above the median and forearm blood flow under the median show a higher risk of developing heart failure (HR = 7.699, 95% CI = 4.407–13.451). Conclusions The present data demonstrate that an impaired endothelium‐dependent vasodilation and hs‐CRP predict development of incident heart failure in hypertensives.

AIMS: To investigate the decline of estimated glomerular filtration rate (eGFR) in patients with atrial fibrillation (AF) treated with vitamin K antagonists (VKAs) or non‐VKA oral anticoagulants (NOACs). METHODS: Multicentre prospective cohort study including 1667 patients with nonvalvular AF. The eGFR was assessed by the CKD‐EPI formula at baseline and during follow‐up. The primary endpoint of the study was the median annual decline of eGFR according to VKA (n = 743) or NOAC (n = 924) use. As secondary endpoints, we analysed the transition to eGFR

BackgroundHeart failure with reduced ejection fraction (HFrEF) is a clinical condition frequently diagnosed in clinical practice. In patients affected by HFrEF, sleep apnea (SA) can be detected among the most frequent comorbidities. Sacubitril–valsartan (sac/val) association has been proven to be effective in reducing disease progression and all-cause mortality in HFrEF patients. Sac/val treatment can potentially attenuate SA development via several pathophysiologic mechanisms, including improvement of global hemodynamics, reduction of extracellular fluid overload, and decrease of sympathetic neural activity.MethodsWe recruited 132 patients affected by HFrEF and SA, already under treatment with continuous positive airway pressure (CPAP), which was discontinued 24 h before the scheduled study timepoints. Physical examination, echocardiography, nocturnal cardio-respiratory monitoring, and laboratory tests were performed in each patient at baseline and after a 6-month treatment with sac/val.ResultsAfter 6 months, sac/val induced statistically significant changes in clinical, hemodynamic, biohumoral (NT-proBNP, serum electrolytes, creatinine, and uric acid), and echocardiographic parameters. In particular, cardiac index (CI), both atrial and ventricular volumes and global longitudinal strain (GLS) improved. Moreover, polysomnography, carried out during a temporary CPAP interruption, revealed a significant reduction in global apnea-hypopnea index (AHI) value (p < 0.0001), central AHI (p < 0.0001), obstructive AHI (p < 0.0001), oxygen desaturation index (ODI) (p < 0.0001), and percentage time of saturation below 90% (TC90) (p < 0.0001). The changes of CI, estimated glomerular filtration rate (eGFR), NT-proBNP, and tricuspid annular plane excursion (TAPSE) contributed to 23.6, 7.6, 7.3, and 4.8% of AHI variability, respectively, and the whole model accounted for a 43.3% of AHI variation.ConclusionsOur results suggest that treatment with sac/val is able to significantly improve the cardiorespiratory performance of patients with HFrEF and SA, integrating the positive impact of CPAP. Thus, both CPAP and sac/val therapy may synergistically contribute to lower the risks of both cardiac and pulmonary complications in HFrEF patients with SA.

Data from the "Trattamento Ormonale nello Scompenso CArdiaco" (T.O.S.CA) registry showed that heart failure (HF) represents a complex clinical syndrome with different hormonal alterations. Renal failure represents a frequent complication in HF. We evaluated the relationship between renal function and insuline-like growth factor-1 (IGF-1) deficiency and its impact on cardiovascular mortality (CVM) in patients enrolled in the T.O.S.CA. registry.At the enrolment, all subjects underwent chemistry examinations, including circulating hormones and cardiovascular functional tests. COX regression analysis was used to evaluate factors related to CVM during the follow-up period in all populations, in high-risk patients and in the young-adult population. Also, we evaluate the effects of renal function on the CVM.337 patients (41 deceased) were analyzed. CVM was related to severe renal dysfunction (HR stages IV-V = 4.86), high-risk conditions (HR 2.25), serum IGF-1 (HR 0.42), and HF etiology (HR 5.85 and HR 1.63 for valvular and ischemic etiology, respectively). In high-risk patients, CVM was related to IGF-1 levels, severe renal dysfunction and valvular etiology, whereas in young patients CMV was related to the high-risk pattern and serum IGF-1 levels.Our study showed the clinical and prognostic utility of the IGF-1 assay in patients with HF.

Background: The association of circulating asymmetric dimethylarginine (ADMA) levels with cardiovascular risk and arterial stiffness has been reportedly demonstrated, although the causal involvement of ADMA in the pathogenesis of these conditions is still debated. Dimethylaminohydrolase 2 (DDAH2) is the enzyme responsible for ADMA hydrolysis in the vasculature, and carriers of the polymorphism rs9267551 C in the 5′-UTR of DDAH2 have been reported to have higher DDAH2 expression and reduced levels of serum ADMA.Approach and Results: We genotyped rs9267551 in 633 adults of European ancestry and measured their carotid–femoral pulse wave velocity (cfPWV), the gold-standard method to estimate arterial stiffness. cfPWV resulted significantly lower in rs9267551 C allele carriers (Δ = −1.12 m/s, P < 0.01) after correction for age, sex and BMI, and a univariate regression showed that the presence of rs9267551 C variant was negatively associated with cfPWV (β = −0.110, P < 0.01). In a multivariable regression model, subjects carrying the rs9267551 C allele manifested significantly lower cfPWV than GG carriers (β = −0.098, P = 0.01) independently from several potential confounders. We measured circulating ADMA levels in a subset of 344 subjects. A mediation analysis revealed that the effect of DDAH2 rs9267551 genotype on cfPWV was mediated by the variation in ADMA levels.Conclusions: These evidences hint that the presence of rs9267551 C allele may explain, at least in part, a reduction in vessel rigidity as measured by cfPWV, and support the attribution of a causative role to ADMA in the pathogenesis of arterial stiffness.

This review is a brief overview of the current status and the potential role of robotics in interventional radiology. Literature published in the last decades, with an emphasis on the last 5 years, was reviewed and the technical developments in robotics and navigational systems using CT-, MR- and US-image guidance were analyzed. Potential benefits and disadvantages of their current and future use were evaluated. The role of fusion imaging modalities and artificial intelligence was analyzed in both percutaneous and endovascular procedures. A few hundred articles describing results of single or several systems were included in our analysis.

Recent studies demonstrated that in normoglucose-tolerant subjects (NGT), 1-h post load plasma glucose value ≥155 mg/dL, during OGTT, identifies a worse cardio-metabolic risk profile with increased risk for Type 2 Diabetes Mellitus (T2DM). T2DM patients present increased oxidative stress, due to high blood glucose levels, which plays a central role in the development of CV events. The aim of our study was to evaluate the correlation between oxidative stress and subclinical myocardial damage, assessed with speckle tracking echocardiography, in NGT patients with 1-h post load ≥155 mg/dL vs. NGT

The circadian rhythm regulates biological processes that occur within 24 h in living organisms. It plays a fundamental role in maintaining biological functions and responds to several inputs, including food intake, light/dark cycle, sleep/wake cycle, and physical activity. The circadian timing system comprises a central clock located in the suprachiasmatic nucleus (SCN) and tissue-specific clocks in peripheral tissues. Several studies show that the desynchronization of central and peripheral clocks is associated with an increased incidence of insulin resistance (IR) and related diseases. In this review, we discuss the current knowledge of molecular and cellular mechanisms underlying the impact of circadian clock dysregulation on insulin action. We focus our attention on two possible mediators of this interaction: the phosphatases belonging to the pleckstrin homology leucine-rich repeat protein phosphatase family (PHLPP) family and the deacetylase Sirtuin1. We believe that literature data, herein summarized, suggest that a thorough change of life habits, with the return to synchronized food intake, physical activity, and rest, would doubtless halt the vicious cycle linking IR to dysregulated circadian rhythms. However, since such a comprehensive change may be incompatible with the demand of modern society, clarifying the pathways involved may, nonetheless, contribute to the identification of therapeutic targets that may be exploited to cure or prevent IR-related diseases.

Background and objectives: COVID-19 is associated with an aberrant inflammatory response that may trigger new-onset cardiac arrhythmias. The aim of this study was to assess the mortality risk in hospitalized COVID-19 patients according to IL-6 serum levels and new-onset atrial fibrillation (AF) according to PaO2/FiO2 stratification. Materials and Methods: 175 COVID-19 patients (25 new-onset AF, 22 other types of AF and 128 no-AF) were included in this single-center, retrospective study; clinical and demographic data, vital signs, electrocardiograms and laboratory results were collected and analyzed. The primary outcome of the study was to evaluate the mortality rate in new-onset AF patients according to IL-6 serum levels and PaO2/FiO2 stratification. Results: The incidence of new-onset AF in the study population was 14.2%. Compared to the no-AF group, new-onset AF patients were older with a positive history of chronic kidney disease and heart failure, had higher IL-6, creatinine and urea serum levels whereas their platelet count was reduced. After PaO2/FiO2 stratification, 5-days mortality rate was higher in new-onset AF patients compared to patients with other types of AF and no-AF patients, and mortality risk increases 5.3 fold compared to no-AF (p = 0.0014) and 4.8 fold compared to other forms of AF (p = 0.03). Conclusions: New-onset AF is common in COVID-19 patients and is associated with increased IL-6 serum levels and early mortality. Further studies are needed to support the use of IL-6 as an early molecular target for COVID-19 patients to reduce their high rate of mortality.

Background: The association of circulating asymmetric dimethylarginine (ADMA) levels with cardiovascular risk and arterial stiffness has been reportedly demonstrated, although the causal involvement of ADMA in the pathogenesis of these conditions is still debated. Dimethylaminohydrolase 2 (DDAH2) is the enzyme responsible for ADMA hydrolysis in the vasculature, and carriers of the polymorphism rs9267551 C in the 5′-UTR of DDAH2 have been reported to have higher DDAH2 expression and reduced levels of serum ADMA. Approach and Results: We genotyped rs9267551 in 633 adults of European ancestry and measured their carotid–femoral pulse wave velocity (cfPWV), the gold-standard method to estimate arterial stiffness. cfPWV resulted significantly lower in rs9267551 C allele carriers (Δ = −1.12 m/s, P < 0.01) after correction for age, sex and BMI, and a univariate regression showed that the presence of rs9267551 C variant was negatively associated with cfPWV (β = −0.110, P < 0.01). In a multivariable regression model, subjects carrying the rs9267551 C allele manifested significantly lower cfPWV than GG carriers (β = −0.098, P = 0.01) independently from several potential confounders. We measured circulating ADMA levels in a subset of 344 subjects. A mediation analysis revealed that the effect of DDAH2 rs9267551 genotype on cfPWV was mediated by the variation in ADMA levels. Conclusions: These evidences hint that the presence of rs9267551 C allele may explain, at least in part, a reduction in vessel rigidity as measured by cfPWV, and support the attribution of a causative role to ADMA in the pathogenesis of arterial stiffness.

Aging with multimorbidity and polytherapy are the most significant factors that could led to inappropriate prescribing of contraindicated medications in patients with chronic kidney disease (CKD). The aim of this study was to evaluate the prescriptions of contraindicated drugs in older adults in CKD and to identify their associated factors in a hospital context. An observational retrospective study was carried out considering all patients ≥65 years with at least one serum creatinine value recorded into the REPOSI register into 2010–2016 period. The estimated glomerular filtration rate (eGFR) was applied to identify CKD. A descriptive analysis was performed to compare demographic and clinical characteristics; logistic regression models were used to estimate factors of inappropriate and percentage changes of drug use during hospitalization. A total of 4,713 hospitalized patients were recorded, of which 49.8% had an eGFR 2; the 21.9% were in treatment with at least one inappropriate drug at the time of hospital admission with a decrease of 3.0% at discharge (p = 0.010). The probability of using at least one contraindicated drug was significantly higher in patients treated with more several drugs (OR 1.21, 95% CI 1.16–1.25, p p < 0.001; G5: 19.38, 11.51–32.64, p < 0.001). Low-dose acetylsalicylic acid was the contraindicated drug mainly used at the time of admission, reducing 1.2% at discharge. An overall increase in therapeutic appropriateness in hospitalized older patients with CKD was observed, despite a small percentage of therapeutic inappropriateness at discharge that underlines the need for a closer collaboration with the pharmacologist to improve the drug management.

Background Non-Alcoholic Fatty Liver Disease (NAFLD) represents an increasing cause of liver disease worldwide. Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in these patients. Although NAFLD pathophysiology is not fully understood alterations in fat metabolism seem to play a role. Autoantibodies against apolipoprotein A-1 (anti-apoA-1 IgG) are a novel cardiovascular risk factor to which have been recently attributed a metabolic role in addition to a well-established macrophage-mediated inflammatory effect and have a function as a disruptor of the cholesterol pathway. Purpose This study aims at evaluating a possible role of anti-apoA-1 IgG in NAFLD. Methods Serum from 137 NAFLD patients were tested for anti-apoA-1 IgG prevalence. In vitro, SREBP1, SREBP2 expressions were assessed in the human hepatic cell line HepaRG by western blot analysis and bodipy staining was used to evaluate the lipid droplet content. Mescoscale technology platform was used to measure TNF-α, IL-6 and IL-8 cytokines/chemokines in HepaRG supernatants. Oil Red O staining was used to detect lipid accumulation in liver sections from ApoE−/− mice. Results Elevated anti-apoA-1 IgG seropositivity was found in patients with NAFLD (46%). In vitro, anti-apoA-1 IgG and not control IgG induced lipid accumulation in hepatic cells (5.9 vs 2.5, P=0.0008) and this lipid overload was associated with a high SREBP1 but not SREBP2 expression. Furthermore, anti-apoA-1 IgG and not control antibodies caused a significant large increase of the proinflammatory cytokines IL-6 (680 vs. 163 pg/mL, P=0.03) and TNF-α (391 vs 266 pg/mL, P=0.04) as well as of the chemokine IL-8 (174.1 vs. 72.6 ng/mL, P=0.03) detected in the hepatic cell supernatants. In vivo, anti-apoA-1 IgG and not control IgG also induced higher lipid accumulation in the livers of ApoE−/− mice (1.23 vs 0.53, P=0.03). Conclusion Anti-apoA-1 IgG are frequent in NAFLD, cause a strong inflammatory response and promote lipid accumulation through SREBP1 activation in human hepatic cells. We hypothesize that anti-apoA1 IgG may be a potential contributor in the development of NAFLD. Funding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): Geneva University Hospital

INTRODUCTION AND OBJECTIVE:Although MRI targeted biopsies (TBx) have been demonstrated to provide high accuracy in detecting clinically signicant prostate cancer (PCa), the addition of systematic b...