Sacubitril/valsartan in COVID-19 patients: the need for trials

We thank Luigi Petramala and Claudio Letizia for their comment1 on our letter about the possible role of sacubitril/valsartan in patients with coronavirus disease 2019 (COVID-19).2 The authors rightly affirm the need for continuing previous therapies with angiotensinconverting enzyme inhibitors (ACE-Is) or sartans in patients with COVID-19, as outlined by recent international consensus papers.3 There is no definite evidence about the harmful or protective use of ACE-Is/sartans in COVID-19 patients.4,5 Dedicated, randomized controlled trials are needed in order to verify the possible worsening of lung infection and/or systemic involvement in patients with COVID-19 who are chronically treated with ACE-Is/sartans. Furthermore, we do not intend to pressurize the indiscriminate change of previous treatments towards sacubitril/valsartan in the absence of evidence from randomized trials. The COVID-19 pandemic forced the scientific community to think about possible, alternative solutions to counteract the multiorgan damage by the virus. We do agree that interrupting specific treatments would increase adverse clinical outcomes in patients, independently from the course of COVID-19, but trying to improve therapeutic solutions is challenging. Sacubitril/ valsartan has already demonstrated superiority over standard therapies in patients suffering from heart failure with reduced ejection fraction (HFrEF), regardless of any comorbidities.6 Moreover, post-hoc analysis from the Comparison of Sacubitril-Valsartan versus Enalapril on Effect on NT-proBNP in Patients Stabilized from an Acute Heart Failure Episode (PIONEER-HF) trial revealed a 42% relative risk reduction in the composite endpoint of death from any cause, re-hospitalization for heart failure, left ventricular assist device implantation, or listing for cardiac transplant, a 42% relative risk reduction in the composite endpoint of cardiovascular death or re-hospitalization for heart failure, and a 39% relative risk reduction in re-hospitalization for heart failure after 8 weeks of treatment with sacubitril/valsartan administered early in patients stabilized during hospitalization for acute decompensated heart failure.7 Furthermore, a significant 50% reduction in NT-proBNP is evident after the first week of treatment with sacubitril/valsartan.8 The need for early administration of sacubitril/valsartan in acute heart failure is probably becoming mandatory in pharmacological management of heart failure patients, although not yet covered by the guidelines. In recent days, the characteristics of cardiac injury during COVID-19 infection have been made available to the medical and scientific community.9,10 In COVID-19 patients, with and without symptoms attributable to pneumonia, there is evidence of a significant increase in NTproBNP, regardless of left ventricular dysfunction. NT-proBNP levels are also the results of acute renal injury and pro-inflammatory molecules such as interleukin-1 and C-reactive protein, which are independent of cardiac function. Shi et al. showed that patients with cardiac injury had a higher rate of mortality during the interval both from symptom onset to admission and from admission to clinical endpoint. Increased death rates were associated with higher levels of NT-proBNP. 9 Gao et al. reported that higher NT-proBNP was an independent risk factor for in-hospital death in patients with severe COVID-19 after adjusting for sex, age, hypertension, coronary heart disease, chronic obstructive pulmonary disease, myoglobin, creatin kinase-MB, high sensitivity troponin-I, white blood cell count, lymphocyte count, C-reactive protein, and procalcitonin.10 Based on the evidence and in relation to the hypotheses generated from our previous correspondence,2 we thought about the possibility of early adoption of sacubitril/valsartan in patients with COVID-19, to maximize the antiinflammatory effects of an enhanced natriuretic peptide system and contain the effects of angiotensin II. Clinical trials in COVID-19 patients are needed in order to validate our hypothesis

Endothelial Function in Pre-diabetes, Diabetes and Diabetic Cardiomyopathy: A Review

Diabetes mellitus worsens cardiovascular risk profile of affected individuals. Its worldwide increasing prevalence and its negative influences on vascular walls morphology and function are able to induce the expression of several morbidities which worsen the clinical conditions of the patients getting them running towards a reduced survival curve. Although overt diabetes increases the mortality rate of individuals due to its pathogenesis, poor information are in literature about the role of pre-diabetes and family history of diabetes mellitus in the outcome of general population. This emphasizes the importance of early detection of vascular impairment in subjects at risk of developing diabetes. The identification of early stages of atherosclerotic diseases in diabetic persons is a fundamental step in the risk stratification protocols followed-up by physicians in order to have a complete overview about the clinical status of such individuals. Common carotid intima-media thickness, flow-mediated vasodilatation, pulse wave velocity are instrumental tools able to detect the early impairment in cardiovascular system and stratify cardiovascular risk of individuals. The aim of this review is to get a general perspective on the complex relationship between cardiovascular diseases onset, pre-diabetes and family history of diabetes. Furthermore, it points out the influence of diabetes on heart function till the expression of the so-called diabetic cardiomyopathy

Nutraceuticals and dyslipidaemia: Beyond the common therapeutics

Dyslipidaemia accelerates the atherosclerotic process and its morbid consequences; statins represent the evidence-based treatment of choice for reducing low-density lipoprotein cholesterol levels and decreasing cardiovascular events. Unfortunately, statins are frequently not available for several reasons, including intolerance, side effects or, simply, patient preference. Nutraceuticals and functional food ingredients that are beneficial to vascular health may represent useful compounds that are able to reduce the overall cardiovascular risk induced by dyslipidaemia by acting parallel to statins or as adjuvants in case of failure or in situations where statins cannot be used. The mechanisms underlying such actions are not fully understood but may be related to reducing 7a-hydroxylase, increasing faecal excretion of cholesterol, decreasing 3-hydroxy-3-methylglutaryl-CoA reductase mRNA levels or reducing the secretion of very low-density lipoprotein. This contribution provides an overview of the mechanism of action of nutraceuticals and functional food ingredients on lipids and their role in the management of lipid disorders

Early and Late Infections in Newborns: Where Do We Stand? A Review

Neonatal sepsis still represents an important cause of mortality and morbidity among infants. According to the onset, we can distinguish "early onset sepsis" when microbiological cultures positive for external pathogens come from newborns during the first 7 days of life (maternal intrapartum transmission); "late onset sepsis" when microbiological cultures positive for external pathogens come from newborns after the first 7 days from delivery (postnatal acquisition). In this review we synthesize the incidence, risk factors, clinical manifestations, and methods of diagnosis and treatment of each type of neonatal infection, in order to better define such a pathological condition which is of great importance in common clinical practice

Primary Prevention Of Cardiovascular Risk In Octogenarians By Risk Factors Control

Primary prevention of cardiovascular events in older adults is a relevant problem, because of lack of evidence for safe and efficacious therapy, its costs and elderly quality of life, Italy's aging population is constantly increasing, so cardiovascular disease (CVD) primary prevention in the elderly is a prime objective. Life expectancy has dramatically increased over the last 2 decades,the proportion of individuals aged 80 years and older has grown rapidly in Europe and United States,but cost / effective ratio of CVD prevention through risk factors control is debated. It is therefore important to implement cardiovascular risk factors estimation in the elderly to maximize quality of life of patients and to lengthen their healthy life expectancy, choosing the better treatment for each patient sharing the choice with himself when it is possible, always remembering that elderly patients often have multiple co-morbidities that require a high number of concurrent medications; this may increase the risk for drug-drug interactions, thereby reducing the potential benefits of CVD prevention therapy. Anyway CVD are not an inevitable concomitant of aging. Sometimes autopsy in the elderly reveals atheroma-free coronary arteries,a normal-sized heart and unscarred valves. All primary prevention strategy decisions should consider estimated life expectancy and overall function not only cardiovascular event risks, magnitude and time to benefit or harm, potentially altered adverse effect profiles, and informed patient preferences.CVD primary prevention need to be more implemented in the elderly, this might contribute to improve health status and quality of life in this growing population if correctly performed

Anteroposterior diameter of the infrarenal abdominal aorta is higher in women with polycystic ovary syndrome

Background: Women affected by polycystic ovary syndrome (PCOS) are known to be at higher risk of cardiovascular disease. The aim of this study was to identify the artery that first is affected by early pre-atherosclerotic changes in PCOS. Methods: Twenty-nine women with PCOS aged 17 to 27 years and 26 healthy nonhyperandrogenic volunteers with regular menses (control women) aged 16 to 28 years were enrolled. All PCOS patients were overweight or obese (body mass index [BMI]  25). Diagnosis of PCOS was performed in line with the 2003 Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Accordingly, PCOS was defined when at least two of the following three features were present after exclusion of other etiologies: 1) oligomenorrhea and or anovulation; 2) hyperandrogenism and/or hyperandrogenemia; and 3) polycystic ovaries visible at ultrasound. Androgen excess or related disorders were excluded. The intima-media thickness (IMT) of common carotid arteries and common femoral arteries and the anteroposterior diameter of the infrarenal abdominal aorta were measured by ultrasound. Lutenizing hormone (LH), follicle-stimulating hormone(FSH), estradiol, total testosterone, androstenedione, and sex hormone-binding globulin (SHBG) serum levels were measured between the 3rd and the 6th day of spontaneous or progestin-induced menstrual cycle. Our study was performed in the absence of any medical treatment. Results: Women with PCOS showed a higher LH to FSH ratio (p < 0.01), increased fasting insulin (p < 0.001), total testosterone (p < 0.001), and androstenedione (p < 0.001) levels, and lower SHBG concentrations (p < 0.001) compared to control women. BMI and waist-to-hip ratio were also higher in women with PCOS (p < 0.000 and p < 0.001, respectively). Women with PCOS also showed increased total cholesterol (p < 0.001), triglyceride (p < 0.001), and apolipoprotein B (p < 0.001) levels. Vascular data showed women with PCOS had a higher anteroposterior diameter than control women (p < 0.005). However, when analysis of covariance was performed and BMI was entered into the model as a covariate, anteroposterior diameter did not maintain a significant association with PCOS. Conclusion: This study shows that anteroposterior diameter of the infrarenal abdominal aorta, but not IMT of common carotid arteries or common femoral arteries, is higher in women with PCOS than in women without this disease. This represents the earliest atherosclerotic change in women with PCOS. However, this alteration seems to be due to body weight secondary to PCOS and not due to PCOS per se

Doppler ultrasound venous mapping of the lower limbs

Aldo Innocente Galeandro1, Giovanni Quistelli2, Pietro Scicchitano2, Michele Gesualdo2, Annapaola Zito2, Paola Caputo2, Rosa Carbonara2, Giuseppe Galgano3, Francesco Ciciarello4, Sandro Mandolesi4, Claude Franceschi5, Marco Matteo Ciccone21Centro Diagnostica Globale and ASL-TA, Taranto, Italy; 2Cardiovascular Diseases Section, Department of Emergency and Organ Transplantation (DETO), University of Bari, Bari, Italy; 3Cardiovascular Diseases Section, Ente Ecclesiastico Ospedale Generale Regionale F Miulli, Acquaviva delle Fonti, Bari, Italy; 4Cardiology Department, Policlinico Umberto I, Sapienza University of Rome, Italy; 5Vascular Laboratories of Hospitals Saint Joseph and Piti&amp;eacute;-Salp&amp;eacute;tri&amp;egrave;re, Paris, FranceBackground: The study aim was to test the accuracy (intra and interobserver variability), sensitivity, and specificity of a simplified noninvasive ultrasound methodology for mapping superficial and deep veins of the lower limbs.Methods: 62 consecutive patients, aged 62 &amp;plusmn; 11 years, were enrolled. All underwent US-examinations, performed by two different investigators, of both legs, four anatomical parts, and 17 veins, to assess the interobserver variability of evaluation of superficial and deep veins of the lower limbs.Results: Overall the agreement between the second versus the first operator was very high in detecting reflux (sensitivity 97.9, specificity 99.7, accuracy 99.5; P = 0.80 at McNemar test). The higher CEAP classification stages were significantly associated with reflux (odds ratio: 1.778, 95% confidence interval: 1.552&amp;ndash;2.038; P &amp;lt; 0.001) as well as with thrombosis (odds ratio: 2.765, 95% confidence interval: 1.741&amp;ndash;4.389; P &amp;lt; 0.001). Thus, our findings show a strict association between the symptoms of venous disorders and ultrasound evaluation results for thrombosis or reflux.Conclusion: This study demonstrated that our venous mapping protocol is a reliable method showing a very low interobserver variability, which makes it accurate and reproducible for the assessment of the morphofunctional status of the lower limb veins.Keywords: venous mapping, new methodology, sensitivity, specificity, accurac