Search

Objective: Cardiovascular diseases (CVDs) remain a leading cause of mortality globally, emphasizing the need for effective preventive measures. This study aimed to investigate the effects of a multicomponent compared to an aerobic training program on the hemodynamic parameters, physical fitness, psychophysical health status and quality of life (QoL) of adults and elderly with stabilized CVDs. Methods: Thirty-three subjects (19M and 14F; age 69.5 ± 4.9 years; BMI 27.34 ± 4.95 kg/m2) suffering from CVDs voluntarily participated in this 10-week randomized controlled study and were allocated into three groups: multicomponent training group (MTG; 6M, 6F; cardiorespiratory, resistance, flexibility and breathing exercises; 60′, 2d·wk-1), aerobic training group (ATG; 7M, 5F; aerobic-only training; 60′, 2d·wk-1) or a wait-list control group (CG; 6M, 3F; no PA). Hemodynamic parameters were assessed through resting hearth rate (RHR) and peripheral-systolic and diastolic blood pressure (P-SBP/P-DBP). Physical fitness was assessed via a 30” chair stand test (30CST), timed up and go (TUG) test, handgrip strength (HGS) test, and 2’ step test (TMST). The health status, QoL and enjoyment were evaluated with short form-12 (SF-12), world health organization quality of life-bref (WHOQoL-bref) and physical activity enjoyment scale (PACES), respectively. Results: After the intervention, MTG showed significant improvements in hemodynamic parameters (95 % CI, RHR: 2.76 to 9.07; P-SBP: 3.28 to 13.71; P-DBP: 3.56 to 8.94; p 0.05). Significant differences between MTG and ATG were only found in physical fitness variables (95 % CI, 30CST: 3.21 to −0.45, p

Abstract High salt intake and compliance to low-sodium (LS) diets are critical in hypertension. Salt reduction in processed foods can help to achieve the target sodium intake. To verify the hypothesis that an innovative LS formulation of a traditional bread could result in a reduction of sodium intake and blood pressure, we performed a 6-month randomized controlled pilot trial on hypertensive patients. We additionally explored the effects of sodium restriction on blood pressure and fecal cultivable bacteria. Fifty-seven patients were randomized in three groups. Group A (n = 19) followed a free diet using standard bread (750 mg Na/100 g), group B (n = 18) followed a LS diet (2300 mg Na/die) using standard bread, group C (n = 20) followed a LS diet (2300 mg Na/die) using LS bread (280 mg Na/100 g). We measured 24-h urinary sodium, blood pressure, routine parameters, fecal microbial counts (26 patients). After 6 months, as compared to group A, group C showed a reduction of 24-h urinary sodium excretion (-908 mg/24 h), diastolic pressure (-9 mmHg) and microbial counts of Bacteroides, Porphyromonas, Prevotella , Enterobacteriaceae, Staphylococcus, Micrococcus. These results suggest that LS bread could increase the adherence to a LS diet, reducing sodium excretion, diastolic pressure and abundance of some fecal cultivable bacteria. Trial registration Registration nr. NCT03127553, on 25/04/2017.

Cardiac amyloidosis (CA) is a cardiac storage disease caused by the progressive extracellular deposition of misfolded proteins in the myocardium. Despite the increasing interest in this pathology, it remains an underdiagnosed condition. Non-invasive diagnostic techniques play a central role in the suspicion and detection of CA, also thanks to the continuous scientific and technological advances in these tools. The 12-lead electrocardiography is an inexpensive and reproducible test with a diagnostic accuracy that, in some cases, exceeds that of imaging techniques, as recent studies have shown. Echocardiography is the first-line imaging modality, although none of its parameters are pathognomonic. According to the 2023 ESC Guidelines, a left ventricular wall thickness ≥ 12 mm is mandatory for the suspicion of CA, making this technique crucial. Cardiac magnetic resonance provides high-resolution images associated with tissue characterization. The use of contrast and non-contrast sequences enhances the diagnostic power of this imaging modality. Nuclear imaging techniques, including bone scintigraphy and positron emission tomography, allow the detection of amyloid deposition in the heart, and their role is also central in assessing the prognosis and response to therapy. The role of computed tomography was recently evaluated by several studies, above in population affected by aortic stenosis undergoing transcatheter aortic valve replacement, with promising results. Finally, machine learning and artificial intelligence-derived algorithms are gaining ground in this scenario and provide the basis for future research. Understanding the new insights into non-invasive diagnostic techniques is critical to better diagnose and manage patients with CA and improve their survival.

Abstract Background Sudden cardiac death is a major public health concern. The incidence of sudden cardiac death in young adults remains unclear and is generally underestimated. Case presentation This is a case report of a 24-year-old man with a silent pathological history, who suddenly collapsed in a restaurant during dinner with his workmates. Autopsy and ancillary examination revealed focal atrioventricular node fibrosis and thymic hyperplasia. Conclusions Thymic hyperplasia has been considered a cause of sudden death in the past century. The mode of death was explained through nosographic entities such as status lymphaticus or thymic asthma, which are currently consigned to history books. Nevertheless, recent studies have sought to determine the relationship between thymic hyperplasia and sudden unexpected deaths in adults. Moreover, isolated fibrosis of the atrioventricular node is a rare condition that can remain undiagnosed even after a full autopsy. This report aims to provide a concise review of the existing literature concerning sudden cardiac death and discuss the so-called “thymic death” theory, which is now considered a myth. Was the finding of thymic hyperplasia and atrioventricular node fibrosis a coincidence? Should the myth surrounding “thymic death” be re-examined?

Abstract Cangrelor, the first intravenous P2Y12 inhibitor (P2Y12-I), has been approved on the basis of three large RCTs from the CHAMPION program which nevertheless have been criticized for the low bleeding risk of the enrolled patients, the large quote of chronic coronary syndromes, and the use of Clopidogrel as control arm even in the setting of acute coronary syndromes (ACS). We sought to investigate, in the setting of ACS, the comparative performance of Cangrelor in terms of in-hospital ischemic and haemorrhagic outcomes compared with the current gold-standard of oral P2Y12-I. The study retrospectively enrolled 686 consecutive patients admitted to the Divisions of Cardiology of Policlinico of Bari and L. Bonomo Hospital of Andria for ACS and treated with percutaneous coronary intervention. The study population was divided according to the P2Y12-I treatment strategy in two groups: patients given an oral P2Y12-I and patients receiving Cangrelor in the cath lab followed by an oral P2Y12-I. Clinical endpoints included death, ischemic and bleeding events occurring during hospital stay. Cangrelor treated patients presented higher clinical risk profile at presentation and faced higher death rate. However, after PS matching, in-hospital mortality resulted comparable between the groups and Cangrelor use was associated with reduced in-hospital definite stent thrombosis (p = 0.03). Data from our real-world registry highlight that, in the setting of ACS, Cangrelor is prevalently used in patients with very challenging clinical presentations. The adjusted analysis provides for the first time promising data on stent thrombosis reduction associated with Cangrelor use.

Abstract In respiratory infections, anemia is both a consequence of acute inflammation and a predictor of poor clinical outcomes. There are few studies investigating the role of anemia in COVID-19, suggesting a potential role in predicting disease severity. In this study, we aimed to assess the association between the presence of anemia at admission and incidence of severe disease and death in patients hospitalized for COVID-19. Data from all adult patients admitted for COVID-19 in University Hospital “P. Giaccone” Palermo, and University Hospital of Bari, Italy, were retrospectively collected from 1st of September 2020 to 31 August 2022. The association between anemia (defined as Hb

Arrhythmic risk stratification in patients with Lamin A/C gene (LMNA)-related cardiomyopathy influences clinical decisions. An implantable cardioverter defibrillator (ICD) should be considered in patients with an estimated 5-year risk of malignant ventricular arrhythmia (MVA) of ≥10%. The risk prediction score for MVA includes non-missense LMNA mutations, despite their role as an established risk factor for sudden cardiac death (SCD) has been questioned in several studies. The purpose of this study is to investigate cardiac features and find gene–phenotype correlations that would contribute to the evidence on the prognostic implications of non-missense vs. missense mutations in a cohort of LMNA mutant patients. An observational, prospective study was conducted in which 54 patients positive for a Lamin A/C mutation were enrolled, and 20 probands (37%) were included. The median age at first clinical manifestation was 41 (IQR 19) years. The median follow-up was 8 years (IQR 8). The type of LMNA gene mutation was distributed as follows: missense in 26 patients (48%), non-frameshift insertions in 16 (30%), frameshift deletions in 5 (9%), and nonsense in 7 (13%). Among the missense mutation carriers, two (8%) died and four (15%) were admitted onto the heart transplant list or underwent transplantation, with a major adverse cardiovascular event (MACE) rate of 35%. No statistically significant differences in MACE prevalence were identified according to the missense and non-missense mutation groups (p value = 0.847). Our data shift the spotlight on this considerable topic and could suggest that some missense mutations may deserve attention regarding SCD risk stratification in real-world clinical settings.

Objective. We studied the prevalence and major predisposing factors of permanent atrial fibrillation (PAF) in a population of hypertensive post-menopausal (HPMW) women. Materials and Methods. We enrolled 125 consecutive HPMW with PAF, 125 HPMW in sinus rhythm were the control group (CG). Women with valvular heart disease, coronary artery disease, WPW syndrome, left ventricular (LV) ejection fraction

Abstract Acid sphingomyelinase deficiency (ASMD)—also known as Niemann–Pick (NP) disease—is a rare, autosomal recessive disorder which is characterized by deficiency of the lysosomal enzyme acid sphingomyelinase (ASM), resulting in excessive storage of lipids in organs (i.e., spleen, liver, lung, bone marrow, lymph nodes, and vascular system). Only a few cases of moderate-to-severe valvular heart disease due to ASMD are described in the literature, mostly in adulthood. We report here the case of a patient with NP disease subtype B that was diagnosed during adulthood. NP disease in this patient was found to be associated with situs inversus. Specifically, a severe, symptomatic aortic stenosis was identified, and the need for surgical or percutaneous intervention was discussed. The heart team chose transcatheter aortic valvular implantation (TAVI), which was successfully performed with no complications on follow-up.

Background. Chronic depression (CD) is common among postmenopausal women and is associated with an increased risk of cardiovascular disease (CVD). The diagnosis of CD is a challenging problem in clinical practice which is vastly underdiagnosed. CD detection in postmenopausal women with metabolic syndrome (MetS) or hypertension is necessary for CVD prevention. Our study aims to assess the prevalence of CD in postmenopausal women and the relationship between CD and MetS or hypertension. Results. The rate of CD was significantly higher among postmenopausal women with MetS compared with the control group [18% versus 8%; Odds ratio (OR) 2.2, P

Abstract Aims To evaluate endothelial function in subjects with left ventricular assist devices (LVADs), comparing them with subjects with chronic heart failure with reduced ejection fraction on the list for heart transplant (HT) and with HT patients with a normal systolic cardiac function to identify any differences. Methods We enrolled 28 subjects with LVAD, 55 subjects with HT, and 42 subjects with heart failure on the transplant list. The subjects underwent a general physical examination, assessment of laboratory blood parameters, and assessment of endothelial function through flow‐mediated dilation (FMD) of brachial artery. Results The three groups were homogeneous as regards age, gender, smoke abuse, C‐reactive protein (CRP) and FMD parameters (P = ns). In LVAD group percentage of FMD change showed an inverse correlation with CRP (rho: −0.5, P: 0.003), a well‐known marker of inflammation and tissue damage. Conclusions Continuous flow related to LVAD seems to not worsen endothelial function. Endothelial function was not affected by cardiovascular risk factors (hypertension, hypercholesterolaemia, diabetes, obesity, and tobacco habit), by the functional status expressed by New York Heart Association class, by the left ventricular systolic function and by the presence or absence of ischaemic heart disease in all the populations analysed. CRP was the only factor able to influence percentage of FMD change in patient with LVAD, reinforcing the hypothesis that inflammation is the main determinant of endothelial function.

Temporary rapid ventricular pacing (TRVP) is required during transcatheter aortic valve implantation (TAVI) in order to reduce cardiac output and to facilitate balloon aortic valvuloplasty, prosthesis deployment, and post-deployment balloon dilation. The two most frequently used TRVP techniques are right endocardial (RE)-TRVP and retrograde left endocardial temporary rapid ventricular pacing (RLE)-TRVP. The first one could be responsible for cardiac tamponade, one of the most serious procedural complications during TAVI, while the second one could often be unsuccessful. Intracoronary (IC)-TRVP through a coronary guidewire has been described as a safe and efficient procedure that could avoid such complications. We describe two clinical cases in which IC-TRVP has been effectively used during valve-in-valve TAVI with coronary protection via the “chimney technique”, after unsuccessful RLE-TRVP.

Abstract Aims Sodium–glucose co‐transporter‐2 inhibitors (SGLT2i) have been shown to have a relevant role in the prevention of hospitalizations for heart failure and improvement in the life expectancy of patients with diabetes and outpatients with chronic heart failure (CHF) with reduced left ventricular ejection fraction, independently from the presence of type 2 diabetes mellitus (T2DM). The aim of our study was to evaluate in a real‐world population the number of outpatients with CHF who meet the enrolment criteria of the main randomized controlled trials (RCT) published in the last 5 years and consequently identify the percentage of patients who could potential benefit from SGLT2i therapy. Methods and results We retrospectively evaluated all consecutive outpatients referred for CHF. The diagnosis of T2DM was according to the latest European Society of Cardiology Guidelines. Clinical characteristics considered for the enrolment in the RCTs were recorded. We enrolled 515 patients, 384 (75%) of whom had a left ventricular ejection fraction (LVEF) ≤ 40%, 82 (16%) had pre‐diabetes, and 187 (36%) had diabetes. Most of the patients with LVEF ≤ 40% met the criteria for the DAPA‐HF trial (65%), and this percentage was even higher if the serum level of N‐terminal pro‐brain natriuretic peptide was not considered. A high percentage of patients with diabetes and LVEF > 40% met the criteria for the DECLARE (39%), CANVAS (47%), and EMPA‐REG (30%) trials. Patients meeting the enrolment criteria of RCTs evaluating SGLT2i were also characterized by a high risk of heart failure events during follow‐up. Conclusions In spite of a low number of patients actually treated with SGLT2i, we observed that a high prevalence of patients with CHF met the clinical characteristics of RCTs that have demonstrated a beneficial effect of SGLT2i.

Isotretinoin or 13-cis-retinoic acid (RA) is one of the most effective and widely used drugs for the treatment of severe acne vulgaris. Despite being deemed safe, no definite consensus has been reached on the cardiovascular risk of RA derivatives. We report a case of heart failure due to dilated cardiomyopathy (DCM) and concomitant renal infarction occurring after 5 months of isotretinoin use in a previously healthy 18-year-old male. The patient, with a history of acne vulgaris, presented to our emergency department with left iliac fossa pain and effort dyspnea. A trans-thoracic echocardiogram showed DCM and severely reduced left ventricle ejection fraction (LVEF: 29%). During hospitalization, a total body computed tomography (CT) showed an ischemic lesion in the left kidney. Ischemic, autoimmune, infective, and heritable causes of DCM were ruled out. Cardiac magnetic resonance (CMR) evidenced LV circumferential mid-wall late gadolinium enhancement. Heart failure therapy was promptly started and up-titrated, but only poor LVEF improvement was detected overtime. Our case aims to raise awareness on rare life-threatening cardiovascular events possibly associated with isotretinoin use. To the best of our knowledge, this is the first described case of renal thromboembolism and severe DCM leading to implantable cardioverter-defibrillator (ICD) implantation occurring during isotretinoin treatment.

The aim of this study was to evaluate the relationship between anaemia and biomarkers of central/peripheral congestion in heart failure (HF) and the impact on mortality. We retrospectively evaluated 434 acute/chronic HF (AHF/CHF) patients. Anaemia was defined as haemoglobin levels p < 0.001) and showed a significant correlation with the NYHA functional class and renal function. BNP and HI were significantly higher in patients with anaemia than in those without anaemia. Independent predictors of anaemia included BNP, estimated creatinine clearance (eCrCL), and HI. The all-cause mortality rate was 21%, which was significantly higher in patients with anaemia than in those without anaemia (30% vs. 14%, p < 0.001; hazard ratio: 2.6). At multivariate Cox regression analysis, BNP, eCrCL, and HI were independent predictors for mortality (Hazard ratios: 1.0002, 0.97, and 1.05, respectively), while anaemia was not. Anaemia correlates with HF status, functional class, renal function, BNP, and HI. Anaemia was not an independent predictor for mortality, acting as a disease severity marker in congestive patients rather than as a predictor of death.

The impact of coronary artery disease (CAD) on all-cause mortality and overall disabilities is well-established. Percutaneous and/or surgical coronary revascularization procedures dramatically reduced the occurrence of adverse cardiovascular events in patients suffering from atherosclerosis. Specifically, guidelines from the European Society of Cardiology on the management of myocardial revascularization promoted coronary artery by-pass graft (CABG) intervention in patients with specific alterations in the coronary tree due to the higher beneficial effects of this procedure as compared to the percutaneous one. The left internal mammary artery (LIMA) is one of the best-performing vessels in CABG procedures due to its location and its own structural characteristics. Nevertheless, the non-invasive assessment of its patency is challenging. Doppler ultrasonography (DU) might perform as a reliable technique for the non-invasive evaluation of the patency of LIMA. Data from the literature revealed that DU may detect severe (>70%) stenosis of the LIMA graft. In this case, pulsed-wave Doppler might show peak diastolic velocity/peak systolic velocity < 0.5 and diastolic fraction < 50%. A stress test might also be adopted for the evaluation of patency of LIMA through DU. The aim of this narrative review is to evaluate the impact of DU on the evaluation of the patency of LIMA graft in patients who undergo follow-up after CABG intervention.

The application of imaging to cardiovascular diseases fosters the diagnosis, clinical management, and risk stratification of patients, thus leading to the early detection of cardiac and vascular diseases [...]

Childhood acute lymphoblastic leukemia (ALL) survivors who underwent chemotherapy with anthracyclines have an increased cardiovascular risk. The aim of the study was to evaluate left and right cardiac chamber performances and vascular endothelial function in childhood ALL survivors. Fifty-four ALL survivors and 37 healthy controls were enrolled. All patients underwent auxological evaluation, blood pressure measurements, biochemical parameters of endothelial dysfunction, flow-mediated dilatation (FMD) of the brachial artery, mean common carotid intima-media thickness (c-IMT), antero-posterior diameter of the infra-renal abdominal aorta (APAO), and echocardiographic assessment. The ALL subjects had significantly lower FMD (p = 0.0041), higher left (p = 0.0057) and right (p = 0.0021) echocardiographic/Doppler Tei index (the non-invasive index for combined systolic and diastolic ventricular function) as compared to controls. Tricuspid annular plane excursion (TAPSE) was 16.9 ± 1.2 mm vs. 24.5 ± 3.7 mm, p < 0.0001. Cumulative anthracycline doses were related to TAPSE (p < 0.001). The ALL survivors treated with anthracyclines demonstrated systo/diastolic alterations of the right ventricle and reduced endothelial function compared with healthy controls. The early recognition of subclinical cardiac and vascular impairment during follow up is of utmost importance for the cardiologist to implement strategies preventing overt cardiovascular disease considering the growing number of young adults cured after childhood ALL.

Circulating parathyroid hormone (PTH) concentrations increase in heart failure (HF) and are related to disease severity. The relationship between PTH and congestion is still a matter of debate. The objective of this analysis was to evaluate the role of PTH as a marker of congestion and prognosis in HF. We enrolled 228 patients with HF. Intact PTH concentrations and HYDRA score (constituted by: B-type natriuretic peptide, blood urea nitrogen–creatinine ratio, estimated plasma volume status, and hydration status) were evaluated. The study endpoint was all-cause mortality. PTH levels were higher in acute compared with chronic HF and in patients with clinical signs of congestion (i.e., peripheral oedema and orthopnea). PTH concentrations significantly correlated with NYHA class and HYDRA score. At multivariate analysis of HYDRA score, estimated glomerular filtration rate (eGFR), and corrected serum calcium were independently determinants of PTH variability. Fifty patients (22%) died after a median follow-up of 408 days (interquartile range: 283–573). Using univariate Cox regression analysis, PTH concentrations were associated with mortality (hazard ratio [HR]: 1.003, optimal cut-off: >249 pg/mL—area under-the-curve = 0.64). Using multivariate Cox regression analysis, PTH was no longer associated with death, whereas HYDRA score, left ventricular ejection fraction, and eGFR acted as independent predictors for mortality (HR: 1.96, 0.97, and 0.98, respectively). Our study demonstrated that intact PTH was related to clinical and subclinical markers of congestion. However, intact PTH did not act as an independent determinant of all-cause death in HF patients.

Heart failure (HF) is a worrisome cardiac pandemic with a negative prognostic impact on the overall survival of individuals. International guidelines recommend up-titration of standardized therapies in order to reduce symptoms, hospitalization rates, and cardiac death. Hyperkalemia (HK) has been identified in 3–18% of HF patients from randomized controlled trials and over 25% of HF patients in the “real world” setting. Pharmacological treatments and/or cardio-renal syndrome, as well as chronic kidney disease may be responsible for HK in HF patients. These conditions can prevent the upgrade of pharmacological treatments, thus, negatively impacting on the overall prognosis of patients. Potassium binders may be the best option in patients with HK in order to reduce serum concentrations of K+ and to promote correct upgrades of therapies. In addition to the well-established use of sodium polystyrene sulfonate (SPS), two novel drugs have been recently introduced: sodium zirconium cyclosilicate (SZC) and patiromer. SZC and patiromer are gaining a central role for the treatment of chronic HK. SZC has been shown to reduce K+ levels within 48 h, with guaranteed maintenance of normokalemia for up to12 months. Patiromer has resulted in a statistically significant decrease in serum potassium for up to 52 weeks. Therefore, long-term results seemed to positively promote the implementation of these compounds in clinical practice due to their low rate side effects. The aim of this narrative review is to delineate the impact of new potassium binders in the treatment of patients with HF by providing a critical reappraisal for daily application of novel therapies for hyperkalemia in the HF setting.

The impact of sex on the assessment of congestion in acute heart failure (AHF) is still a matter of debate. The objective of this analysis was to evaluate sex differences in the evaluation of congestion at admission in patients hospitalized for AHF. We consecutively enrolled 494 AHF patients (252 female). Clinical congestion assessment, B-type natriuretic peptide levels analysis, blood urea nitrogen to creatinine ratio (BUN/Cr), plasma volume status estimate (by means of Duarte or Kaplam-Hakim PVS), and hydration status evaluation through bioimpedance analysis were performed. There was no difference in medications between men and women. Women were older (79 ± 9 yrs vs. 77 ± 10 yrs, p = 0.005), and had higher left ventricular ejection fraction (45 ± 11% vs. 38 ± 11%, p < 0.001), and lower creatinine clearance (42 ± 25 mL/min vs. 47 ± 26 mL/min, p = 0.04). The prevalence of peripheral oedema, orthopnoea, and jugular venous distention were not significantly different between women and men. BUN/Cr (27 ± 9 vs. 23 ± 13, p = 0.04) and plasma volume were higher in women than men (Duarte PVS: 6.0 ± 1.5 dL/g vs. 5.1 ± 1.5 dL/g, p < 0.001; Kaplam–Hakim PVS: 7.9 ± 13% vs. −7.3 ± 12%, p < 0.001). At multivariate logistic regression analysis, female sex was independently associated with BUN/Cr and PVS. Female sex was independently associated with subclinical biomarkers of congestion such as BUN/Cr and PVS in patients with AHF. A sex-guided approach to the correct evaluation of patients with AHF might become the cornerstone for the correct management of these patients.

Abstract Background Prognostic stratification of elderly patients with chronic obstructive pulmonary disease (COPD) is difficult due to the wide inter-individual variability in the course of the disease. No marker can exactly stratify the evolution and natural history of COPD patients. Studies have shown that leukocyte count is associated with increased risk of mortality in COPD patients. The aim of this study was to evaluate the possible role of relative lymphocyte count as a risk marker for mortality in elderly patients with COPD. Methods and results This is a3-year prospective study. A total of 218patients, mean age 75.2±7 years, with moderate to severe COPD and free from conditions affecting lymphocyte count were enrolled. The population was divided into two groups according to the relative lymphocyte count, with a cut-off of 20%. Eighty-five patients (39%) had a relative lymphocyte count ≤20%. Three-year mortality rates from any cause in patients with relative lymphocyte count ≤ or > 20% were 68 and 51%, respectively (p = 0.0012). Survival curve analysis showed higher mortality in patients with relative lymphocyte count ≤20% (p = 0.0005). After adjustment for age and sex, the hazard ratio for mortality risk according to lymphocyte count was 1.79 (95% confidence interval [CI]: 1.26–2.57, p = 0.0013), even in the analysis limited to the 171 patients without congestive heart failure (1.63; 95% CI: 1.03–2.58, p = 0.038). Conclusions Low relative lymphocyte count was associated with higher mortality in elderly patients with severe COPD.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) commonly complicates with coagulopathy. A syndrome called Long-COVID-19 is emerging recently in COVID-19 survivors, characterized, in addition to the persistence of symptoms typical of the acute phase, by alterations in inflammatory and coagulation parameters due to endothelial damage. The related disseminated intravascular coagulation (DIC) can be associated with high death rates in COVID-19 patients. It is possible to find a prothrombotic state also in Long-COVID-19. Early administration of anticoagulants in COVID-19 was suggested in order to improve patient outcomes, although exact criteria for their application were not well-established. Low-molecular-weight heparin (LMWH) was commonly adopted for counteracting DIC and venous thromboembolism (VTE), due to its pharmacodynamics and anti-inflammatory properties. However, the efficacy of anticoagulant therapy for COVID-19-associated DIC is still a matter of debate. Thrombin and Factor Xa (FXa) are well-known components of the coagulation cascade. The FXa is known to strongly promote inflammation as the consequence of increased cytokine expression. Endothelial cells and mononuclear leucocytes release cytokines, growth factors, and adhesion molecules due to thrombin activation. On the other hand, cytokines can activate coagulation. The cross-talk between coagulation and inflammation is mediated via protease-activated receptors (PARs). These receptors might become potential targets to be considered for counteracting the clinical expressions of COVID-19. SARS-CoV-2 is effectively able to activate local and circulating coagulation factors, thus inducing the generation of disseminated coagula. LMWH may be considered as the new frontier in the treatment of COVID-19 and Long-COVID-19. Indeed, direct oral anticoagulants (DOACs) may be an alternative option for both early and later treatment of COVID-19 patients due to their ability to inhibit PARs. The aim of this report was to evaluate the role of anticoagulants—and DOACs in particular in COVID-19 and Long-COVID-19 patients. We report the case of a COVID-19 patient who, after administration of enoxaparin developed DIC secondary to virosis and positivity for platelet factor 4 (PF4) and a case of Long-COVID with high residual cardiovascular risk and persistence of blood chemistry of inflammation and procoagulative state.

Primary malignant cardiac tumors are rare, with a prevalence of about 0.01% among all cancer histotypes. At least 60% of them are primary soft tissue sarcomas of the heart (pSTS-h) that represent almost 1% of all STSs. The cardiac site of origin is the best way to classify pSTS-h as it is directly linked to the surgical approach for cancer removal. Indeed, histological differentiation should integrate the classification to provide insights into prognosis and survival expectancy of the patients. The prognosis of pSTS-h is severe and mostly influenced by the primary localization of the tumor, the difficulty in achieving complete surgical and pharmacological eradication, and the aggressive biological features of malignant cells. This review aims to provide a detailed literature overview of the most relevant issues on primary soft tissue sarcoma of the heart and highlight potential diagnostic and therapeutic future perspectives.

Background: The aim of the study was to evaluate the efficacy and safety of direct oral anticoagulants (DOACs) in a subgroup of patients with atrial fibrillation (AF), CHADS2 score ≥3, advanced age, and heart failure (HF) coming from the main DOACs randomized clinical trials.Methods: We searched MEDLINE, MEDLINE In-Process, and Other Non-Indexed Citations, EMBASE, PubMed, and the Cochrane Central Register of Controlled Trials. English-language articles published from 2002 to March 2019 dealing with DOACs for preventing thrombotic events in AF were considered. We did not conduct any statistical analyses, as indirect comparison between DOACs represents hypothesis generators.Results: This systematic review was restricted to the subgroup of patients with CHADS2 score ≥3 (n = 31,203), elderly (n = 24,788), and with HF (n = 29,297) derived from the pivotal trials. Risk index (RI) was calculated. The RI for stroke/systemic embolism was similar in all of the patients treated with DOACs or warfarin. The lowest RI was in rivaroxaban patients (CHADS2 score ≥3: RI = 0.04; elderly: RI = 0.09; HF: RI = 0.05). The RIs for bleeding were higher in patients treated with dabigatran (CHADS2 score ≥3: RI110 = 0.23; elderly: RI110 = 0.22; HF: RI110 = 0.16; CHADS2score ≥3: RI150 = 0.30; elderly: RI150 = 0.24; HF: RI150 = 0.16). The bleeding RIs were higher with apixaban (CHADS2 score ≥3: RI = 0.23; elderly: RI = 0.25; HF: RI = 0.14) and dabigatran (CHADS2 score ≥3: RI = 0.28; elderly: RI = 0.21; HF: RI = 0.19).Conclusions: The use of DOACs is a reasonable alternative to vitamin K antagonists in AF patients with CHADS2 score ≥3, advanced age, and HF. The RI constitutes a useful, additional tool to facilitate clinicians in choosing DOACs or warfarin in particular category of AF patients.

Background: The aim of this study was to assess the role of cardiac and vascular parameters as all-cause mortality determinants in patients suffering from gynecological cancers. Methods: This was an observational, prospective, non-randomized, and non-controlled study. Forty-seven consecutive patients (mean age: 58 ± 13 years) were enrolled after cancer staging. All patients underwent evaluation of vascular (common carotid intima-media thickness (mean C-IMT), flow-mediated dilation of the brachial artery (FMD), and antero-posterior diameter of the infrarenal abdominal aorta (APAO)) and cardiac function and morphology before cancer-related interventions. A 6-year follow-up was carried out to assess the overall survival of the whole population. Results: Twenty patients (42%) died by the time of the 6-year follow-up. The brachial artery FMD values were higher in the survivors than the non-survivors (9.71 ± 3.53% vs. 6.13 ± 2.62%, p < 0.001), as well as the LVEF (60.8 ± 3.0% vs. 57.8 ± 4.4%, p = 0.009). There were no differences in the mean C-IMT, APAO, and other echocardiographic parameters. ROC curve analysis identified a baseline LVEF < 57% and FMD value < 5.8% as the best cut-offs. Kaplan–Meier evaluation showed that the LVEF, tricuspid annular plane systolic excursion, and FMD were the best predictors of all-cause mortality, although only the LVEF and FMD were confirmed in multivariate Cox regression analysis. Conclusions: The LVEF and brachial artery FMD are independent prognostic determinants in patients with gynecological cancers.

Background: The long-term efficacy of low-dose aspirin for primary prevention of cardiovascular (CV) events in postmenopausal women with type-2 diabetes is controversial. Therefore, it is recommended only on an individual basis, recommendation of grade C. Methods: We enrolled 275 consecutive postmenopausal women with type-2 diabetes, without an increased bleeding risk and without preexisting CV disease as coronary artery disease, stroke, and peripheral vascular disease, but with a high risk assessed by score >10%, aged 60–69 years. All were receiving aspirin (75–100 mg daily), aspirin group (AG). 170 postmenopausal women with type-2 diabetes and without preexisting cardiovascular (CV) disease, but not on aspirin treatment, despite a high risk assessed by score >10%, were control group (CG). Mean age was 66 ± 4 years for AG and 65 ± 7 years for CG. Our goal was to identify the prevalence of low-dose aspirin prescriptions in these populations according to different clinical conditions. Results: Women with only high risk were 41/275 (15%) on AG and 72/170 (42.3%) on CG, Chi-squared 41, Odds ratio 0.2, c.i. 95%, P < 0.0001. Women affected by metabolic syndrome were 105/275 (38.1%) on AG and 47/170 (27.6%) on CG, Chi-squared 5.1, Odds ratio 1.6, c.i. 95%, P < 0.02. Women affected by metabolic cardiomyopathy were 111/275 (40.3%) on AG and 44/170 (25.9%) on CG, Chi-squared 8, Odds ratio 1.8, c.i. 95%, P < 0.004. Women affected by diabetic cardiomyopathy were 18/275 (6.6%) on AG and 7/170 (4.2%) on CG, Chi-squared 1.2, Odds ratio 16, c.i. 95%, P < 0.2 n.s. Conclusions: Low-dose aspirin in our population is prescribed preferentially in postmenopausal women with type-2 diabetes when affected by metabolic syndrome or metabolic cardiomyopathy, at the opposite women with only high risk have lower chance to receive aspirin.

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.

We explored the significance of the L-Arginine/asymmetric dimethylarginine (L-Arg/ADMA) ratio as a biomarker of endothelial dysfunction in stroke patients. To this aim, we evaluated the correlation, in terms of severity, between the degree of endothelial dysfunction (by L-Arg/ADMA ratio), the methylene tetrahydrofolate reductase (MTHFR) genotype, and the interatrial septum (IAS) phenotype in subject with a history of stroke. Methods and Results: L-Arg, ADMA, and MTHFR genotypes were evaluated; the IAS phenotype was assessed by transesophageal echocardiography. Patients were grouped according to the severity of IAS defects and the residual enzymatic activity of MTHFR-mutated variants, and values of L-Arg/ADMA ratio were measured in each subgroup. Of 57 patients, 10 had a septum integrum (SI), 38 a patent foramen ovale (PFO), and 9 an ostium secundum (OS). The L-Arg/ADMA ratio differed across septum phenotypes (p ≤ 0.01), and was higher in SI than in PFO or OS patients (p ≤ 0.05, p ≤ 0.01, respectively). In the PFO subgroup a negative correlation was found between the L-Arg/ADMA ratio and PFO tunnel length/height ratio (p ≤ 0.05; r = − 0.37; R2 = 0.14). Interestingly, the L-Arg/ADMA ratio varied across MTHFR genotypes (p ≤ 0.0001) and was lower in subgroups carrying the most impaired enzyme with respect to patients carrying the conservative MTHFR (p ≤ 0.0001, p ≤ 0.05, respectively). Consistently, OS patients carried the most dysfunctional MTHFR genotypes, whereas SI patients the least ones. Conclusions: A low L-Arg/ADMA ratio correlates with impaired activity of MTHFR and with the jeopardized IAS phenotype along a severity spectrum encompassing OS, PFO with long/tight tunnel, PFO with short/large tunnel, and SI. This infers that genetic MTHFR defects may underlie endothelial dysfunction-related IAS abnormalities, and predispose to a cryptogenic stroke. Our findings emphasize the role of the L-Arg/ADMA ratio as a reliable marker of stroke susceptibility in carriers of IAS abnormalities, and suggest its potential use both as a diagnostic tool and as a decision aid for therapy.

Background: In chronic heart failure (CHF) patients there is a wide variability in the minimal effective diuretic dose. The aim of this study is to evaluate whether renal resistance index (RRI) is associated to baseline diuretic dose and the changes at one year. Methods and results: 250 outpatients in a stable condition and in conventional therapy were enrolled. Baseline RRI was calculated by renal arterial Doppler. The total daily dose of loop diuretics was assessed at baseline and after one year. High diuretic dose (HDD) was defined as a daily furosemide equivalent dose >100 mg. RRI was independently associated with baseline HDD at univariate (OR 1.39; 95% CI: 1.233–1.58; p

Recently, it has been clearly described an independent relationship between obstructive sleep apnea syndrome (OSAS) and cardiovascular risk, with underlying mechanisms also including endothelial dysfunction. We enrolled 32 consecutive non-obese patients (mean age of 39.5±11.5 years), of which 16 with mild OSAS and 16 snoring without OSAS. Mild OSAS is defined by an AHI index between 5 and 15. We have investigated if whether there was a relationship between mild OSAS, endothelial function and carotid intima-media thickness (C-IMT). The population was divided into two groups: Group 1 (16 simple snorer patients with an average age of 39.4±12.1 years) and Group 2 (16 subjects with mild OSAS with an average age of 39.6±11.2 years). Each group underwent cardiovascular investigation including measurement of flow-mediated dilation (FMD) of the brachial artery and C-IMT. Both groups comprised non-obese subjects. Patients with mild OSAS had serum total cholesterol values statistically significantly higher than simple snores patients (178.6±24.9 vs 159.2±25.3; p=0.038). OSAS patients had also a trend towards higher values of maximum C-IMT compared to simple snorer patients (0.70±0.15 vs 0.65±0.16), although below the level of significance. Between the two groups, no difference was found for FMD values. The present results on mild OSAS strengthen the importance of a diagnosis of OSAS as soon as possible, in order to encourage all primary prevention interventions to correct risk factors responsible for disease progression and the occurrence of cardiovascular diseases, not excluding the use of therapies of non-invasive ventilation even in the early stages of the disease.

Oat and barley beta-glucans are prebiotic fibers known for their cholesterol-lowering activity, but their action on the human gut microbiota metabolism is still under research. Although the induction of short-chain fatty acids (SCFA) following their ingestion has previously been reported, no study has investigated their effects on proteolytic uremic toxins p-cresyl sulfate (pCS) and indoxyl sulfate (IS) levels, while others have failed to demonstrate an effect on the endothelial function measured through flow-mediated dilation (FMD).The aim of our study was to evaluate whether a nutritional intervention with a functional pasta enriched with beta-glucans could promote a saccharolytic shift on the gut microbial metabolism and improve FMD.We carried out a pilot study on 26 healthy volunteers who underwent a 2-month dietary treatment including a daily administration of Granoro "Cuore Mio" pasta enriched with barley beta-glucans (3g/100g). Blood and urine routine parameters, serum pCS/IS and FMD were evaluated before and after the dietary treatment.The nutritional treatment significantly reduced LDL and total cholesterol, as expected. Moreover, following beta-glucans supplementation we observed a reduction of serum pCS levels and an increase of FMD, while IS serum levels remained unchanged.We demonstrated that a beta-glucans dietary intervention in healthy volunteers correlates with a saccharolytic shift on the gut microbiota metabolism, as suggested by the decrease of pCS and the increase of SCFA, and associates with an improved endothelial reactivity. Our pilot study suggests, in addition to cholesterol, novel pCS-lowering properties of beta-glucans, worthy to be confirmed in large-scale trials and particularly in contexts where the reduction of the microbial-derived uremic toxin pCS is of critical importance, such as in chronic kidney disease.

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 7α-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.

Obstructive Sleep Apnea (OSA) is a sleep-related breathing disorder associated with the development of cardiovascular diseases and atherosclerosis. Systemic inflammation plays an important role in the development of cardiovascular complications in OSA patients. The aim of the study was to evaluate the relationship between carotid intima-media thickness (cIMT) and inflammatory markers plasma levels in OSA patients. We enrolled 80 OSA patients and 40 controls matched for age and body mass index (BMI). The presence and severity of sleep apnea was determined by in-laboratory portable monitoring (PM). Demographic data, blood pressure, heart rate, and cIMT were measured. High-sensitive C-Reactive Protein (hsCRP), interleukin (IL)-6, tumor necrosis factor (TNF)-α and pentraxin (PTX)-3 serum concentrations were detected. cIMT was higher in OSA patients than controls (0.89 ± 0.13 mm vs. 0.65 ± 0.1 mm, p < 0.01). Moderate-severe OSA patients (0.95 ± 0.09 mm) had significantly increased cIMT than mild OSA (0.76 ± 0.1 mm; p < 0.01) and control (0.65 ± 0.1 mm; p < 0.01). hsCRP, IL-6, TNF-α, and PTX-3 in patients with OSA (1.67 ± 0.66 mg/L, 2.86 ± 1.39 pg/mL, 20.09 ± 5.39 pg/mL, 2.1 ± 0.59 ng/mL, respectively) were significantly higher than in controls (1.08 ± 0.53 mg/L, p < 0.01; 1.5 ± 0.67 pg/mL, p < 0.01; 12.53 ± 3.48 pg/mL, p < 0.01; 1.45 ± 0.41 ng/mL, p < 0.01, respectively). Carotid IMT was significantly correlated to CRP (r = 0.44; p < 0.01), IL-6 (r = 0.42; p < 0.01), TNF-α (r = 0.53; p < 0.01), and PTX-3 (r = 0.49; p < 0.01). OSA patients showed increased cIMT, CRP, IL-6, TNF-α, and PTX-3 levels. Inflammatory markers levels are correlated to cIMT in OSA patients.

Cardiovascular diseases (CVD) are the major cause of death worldwide. The identification of markers able to detect the early stages of such diseases and/or their progression is fundamental in order to adopt the best actions in order to reduce the worsening of clinical condition. Brain natriuretic peptide (BNP) and NT-proBNP are the best known markers of heart failure (HF), while troponins ameliorated the diagnosis of acute and chronic coronary artery diseases. Nevertheless, many limitations reduce their accuracy. Physicians have tried to develop further detectable molecules in order to improve the detection of the early moments of CVD and prevent their development. Soluble ST2 (suppression of tumorigenicity 2) is a blood protein confirmed to act as a decoy receptor for interleukin-33. It seems to be markedly induced in mechanically overloaded cardiac myocytes. Thus, HF onset or worsening of a previous chronic HF status, myocardial infarct able to induce scars that make the myocardium unable to stretch well, etc, are all conditions that could be detected by measuring blood levels of soluble ST2. The aim of this review is to explore the possible role of ST2 derived-protein as an early marker of cardiovascular diseases, above all in heart failure and ischemic heart diseases.

ST2 (suppression of tumorigenity) has been described as a receptor for the interleukin-33, a member of the IL-1 family of cytokines. It is associated to coronary artery disease, all-causes mortality and cardiovascular mortality.The present study was designed to assess the immunohistochemical expression of the ST2 receptor (ST2L/Il-1R) in atherosclerotic plaques of formalin fixed paraffin-embedded internal carotid arteries of patients with and without cerebro-vascular symptoms.The study involved 41 cases (23 asymptomatic and 18 symptomatic). All the clinical and morphological parameters examined were uniformly distributed between the two groups, with a mild predominance of degree of calcification in asymptomatic cases (p = 0.01). ST2L expression was found to be more evident as a membrane pattern in macrophages when observing carotid atherosclerotic plaques of symptomatic patients, rather than in asymptomatic patients' plaques (77.7% vs 39.1%; p = 0.015), and its expression was particularly remarkable in VI type plaque (AHA). Significantly, ST2L was marked by the endothelium of neoangiogenetic vessels on the shoulder region of the plaque, but not (apart from a few cases) in the endothelium covering the residual lumen of the vessel.The ST2L immunohistochemical expression was for the first time investigated in a large number of human carotid atherosclerotic plaques, as for its pattern of distribution in the different plaque cell populations. Furthermore, ST2L was particularly remarkable on macrophages, as a membrane pattern, of symptomatic patients' plaque. Considering our data, we hypothesize that ST2L/IL33 axis could drive the mechanism of plaque development and eventually rupture.

Hyperpolarization and Cyclic Nucleotide (HCN) -gated channels represent the molecular correlates of the “funny” pacemaker current (If), a current activated by hyperpolarization and considered able to influence the sinus node function in generating cardiac impulses. HCN channels are a family of six transmembrane domain, single pore-loop, hyperpolarization activated, non-selective cation channels. This channel family comprises four members: HCN1-4, but there is a general agreement to consider HCN4 as the main isoform able to control heart rate. This review aims to summarize advanced insights into the structure, function and cellular regulation of HCN channels in order to better understand the role of such channels in regulating heart rate and heart function in normal and pathological conditions. Therefore, we evaluated the possible therapeutic application of the selective HCN channels blockers in heart rate control.

Aim of the study: In chronic heart failure (CHF) patients, renal congestion plays a key role in determining the progression of renal dysfunction and a worse prognosis. The aim of this study was to define the role of Doppler venous patterns reflecting renal congestion that predict heart failure progression. Methods: We enrolled outpatients affected by CHF, in stable clinical conditions and in conventional therapy. All patients underwent a clinical evaluation, routine chemistry, an echocardiogram and a renal echo-Doppler. Pulsed Doppler flow recording was performed at the level of interlobular renal right veins in the tele-expiratory phase. The venous flow patterns were divided into five groups according to the fluctuations of the flow. Type A and B were characterized by a continuous flow, whereas type C was characterized by a short interruption or reversal flow during the end-diastolic or protosystolic phase. Type D and E were characterized by a wide interruption and/or reversal flow. The occurrence of death and/or of heart transplantation and/or of hospitalization due to heart failure worsening was considered an event during follow-up. Results: During a median follow-up of 38 months, 126 patients experienced the considered end-point. Venous pattern C (HR 4.04; 95% CI: 2.14⁻7.65; p < 0.001), pattern D (HR 7.16; 95% CI: 3.69⁻13.9; p < 0.001) and pattern E (HR 8.94; 95% CI: 4.65⁻17.2; p < 0.001) were all associated with events using an univariate Cox regression analysis. Moreover, both the presence of pattern C (HR: 1.79; 95% CI: 1.09⁻2.97; p: 0) and of pattern D or E (HR: 1.90; 95% CI: 1.16⁻3.12; p: 0.011) remained significantly associated to events using a multivariate Cox regression analysis after correction for a reference model with an improvement of the overall net reclassification index (0.46; 95% CI 0.24⁻0.68; p < 0.001). Conclusions: Our findings demonstrate the independent and incremental role of Doppler venous patterns reflecting renal congestion in predicting HF progression among CHF patients, thus suggesting its possible utility in daily clinical practice to better characterize patients with cardio-renal syndrome.

Marco Matteo Ciccone1, Ambrogio Aquilino2, Francesca Cortese1, Pietro Scicchitano1, Marco Sassara1, Ernesto Mola3, Rodolfo Rollo4,Pasquale Caldarola5, Francesco Giorgino6, Vincenzo Pomo2, Francesco Bux21Section of Cardiovascular Disease, Department of Emergency and Organ Transplantation, School of Medicine, University of Bari, Bari, Italy; 2Agenzia Regionale Sanitaria – Regione Puglia (ARES), Apulia, Italy; 3ASL, Lecce, Italy; 4ASL, Brindisi, Italy; 5Cardiologia, Ospedale “Sarcone”, Terlizzi, Italy; 6Section of Endocrinology, Department of Emergency and Organ Transplantation, School of Medicine, University of Bari, Bari, ItalyPurpose: Project Leonardo represented a feasibility study to evaluate the impact of a disease and care management (D&CM) model and of the introduction of “care manager” nurses, trained in this specialized role, into the primary health care system. Patients and methods: Thirty care managers were placed into the offices of 83 general practitioners and family physicians in the Apulia Region of Italy with the purpose of creating a strong cooperative and collaborative “team” consisting of physicians, care managers, specialists, and patients. The central aim of the health team collaboration was to empower 1,160 patients living with cardiovascular disease (CVD), diabetes, heart failure, and/or at risk of cardiovascular disease (CVD risk) to take a more active role in their health. With the support of dedicated software for data collection and care management decision making, Project Leonardo implemented guidelines and recommendations for each condition aimed to improve patient health outcomes and promote appropriate resource utilization.Results: Results show that Leonardo was feasible and highly effective in increasing patient health knowledge, self-management skills, and readiness to make changes in health behaviors. Patient skill-building and ongoing monitoring by the health care team of diagnostic tests and services as well as treatment paths helped promote confidence and enhance safety of chronic patient management at home.Conclusion: Physicians, care managers, and patients showed unanimous agreement regarding the positive impact on patient health and self-management, and attributed the outcomes to the strong “partnership” between the care manager and the patient and the collaboration between the physician and the care manager. Future studies should consider the possibility of incorporating a patient empowerment model which considers the patient as the most important member of the health team and care managers as key health care collaborators able to enhance and support services to patients provided by physicians in the primary health care system.Keywords: partnerships, health team, patient empowerment, care coordination

Marco Matteo Ciccone1, Stefano Favale1, Anish Bhuva4, Pietro Scicchitano1, Vito Caragnano1, Cristina Lavopa2, Giovanni De Pergola3, Giuseppe Loverro21Department of Cardiology; 2Department of Gynecology and Obstetrics; 3Section of Internal Medicine, Endocrinology, Andrology, and Metabolic Diseases, University of Bari, DETO, Italy; 4University College of London, London, UKBackground: 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.Keywords: polycystic ovary syndrome, antero-posterior diameter, infrarenal abdominal aorta, intimia-media thickness

The aims of this study were: i) analysis of clinical severity evolution in multiple sclerosis patients; ii) identification of temporal indicators for clinical worsening. We investigated by echo-color-Doppler (ECD) 789 patients (490 female plus 299 male), aged 45.4 years, with chronic cerebro-spinal venous insufficiency (CCSVI) and multiple sclerosis (MS). All patients tested positive for CCSVI by ECD assessment were divided into three groups, namely: type 1 CCSVI (371) presenting an endo-vascular obstacle to the venous drainage; type 2 CCSVI (40) presenting an extra-vascular obstacle to the venous drainage, for external compression of the vessel; type 3 CCSVI (315) presenting both venous endo-vascular and extra-vascular obstructed drains. We analyzed the morphological and hemodynamic data recorded on computerized map (MEM-net). All data were collected by respecting the Italian Privacy Laws and they are available on the National Epidemiological Observatory on CCSVI website (www.osservatorioccsvi.org). We focused in the three main parameters in all studied patients. First parameter was expanded disability status scale (EDSS) score; second parameter was illness duration; third parameter was CCSVI type. The MS duration values stratified by EDSS grouped values in CCSVItype- 1 and CCSVI-type-3 patients shows that the differences were statistical significant by Kruskal-Wallis test: H=44.2829; degree of freedom= 1 for CCSVI-type-1 (P

The aim of our work is to describe the Memnet program’s use and potential and to show the data of Italian Chronic Cerebrospinal Venous Insufficiency (CCSVI)-National Epidemiological Observatory (NEO) activity in the first three years (http://www.osservatorioccsvi. org). From 2011 to 2014, all echo-color- Doppler (ECD) assessments were stored by Mem-net program into CCSVI-NEO web site (http://www.mem-net.it). Mem-net is a tool for multicenter data collection based on the International Society for Neurovascular Disease consensus and position statement, where we can insert patients (pts) history, neurological visits, ECD assessments, different examinations, therapies and surgical procedures. The website provides an epidemiological and statistical program for data analysis in real time. At present, 7 medical centers, affiliated to CCSVI-NEO, input their symptomatic and asymptomatic subjects with CCSVI. Data were storage using the Mem-net program. We analyzed data of only four centers on seven (Rome, Bari, Cagliari and Benevento). Total pts number with multiple sclerosis (MS) was 1109, mean age 46.0±13.4 [male 422 (38.05%); female 687 (61.95%)]. CCSVI positive pts were 937 (84.49%), CCSVI negative pts were 172 (15.51%). The CCSVI type 1 subjects were 530 (56.56%), CCSVI type 2 subjects were 20 (2.13%), CCSVI type 3 subjects were 387 (41.30%). We found 800 (85.38%) pts with criterion 1; 725 (77.37%) with criterion 2; 519 (55.39%) with criterion 3; 483 (51.55%) with criterion 4; 88 (9.39%) with criterion 5. The venous hemodynamic insufficiency severity score mean score was 3.8; the CCSVI mean score was 2.8; the MEM mean score was 34.7; the expanded disability status scale mean score was 4.5; the disease mean duration was 12.5±5.7 years. MS clinical types were divided as follows: relapsing-remitting pts were 449 (47.92%), Secondary progressive pts were 144 (15.37%), primary progressive pts were 72 (7.68%). The CCSVI-NEO database and Memnet software may be useful medical and researching tools for recording, storing, analyzing and studying ECD and vascular data. Preliminary data of NEO show an elevated prevalence of CCSVI in MS.

Background and Aims. It is widely accepted that obstructive sleep apnea (OSA) is independently associated with atherosclerosis. Similar to OSA, hypertension (HTN) is a condition associated with atherosclerosis. However, to date, the impact of the simultaneous presence of OSA and HTN on the risk of atherosclerosis has not been extensively studied. The aim of this study was to evaluate the consequences of the coexistence of OSA and HTN on carotid intima-media thickness (IMT) and on inflammatory markers of atherosclerosis (such as interleukin- [IL-] 6 and pentraxin- [PTX-] 3). Methods. The study design allowed us to define 4 groups: (1) controls (n=30); (2) OSA patients without HTN (n=30); (3) HTN patients without OSA (n=30); (4) patients with OSA and HTN (n=30). In the morning after portable monitoring (between 7 am and 8 am), blood samples were collected, and carotid IMT was measured. Results. Carotid IMT, IL-6, and PTX-3 in OSA normotensive patients and in non-OSA HTN subjects were significantly higher compared to control subjects; in addition, in OSA hypertensive patients they were significantly increased compared to OSA normotensive, non-OSA HTN, or control subjects. Conclusions. OSA and HTN have an additive role in the progression of carotid atherosclerosis and in blood levels of inflammatory markers for atherosclerosis, such as interleukin-6 and pentraxin-3.

Background. Hepatitis C virus (HCV) infection can exert proatherogenic activities due to its direct action on vessel walls and/or via the chronic inflammatory process involving the liver. Aims. To clarify the role of HCV in atherosclerosis development in monoinfected HCV patients at different degrees of liver fibrosis and with no risk factors for coronary artery disease. Methods. Forty-five patients were included. Clinical, serological, and anthropometric parameters, liver fibrosis (transient liver elastometry (fibroscan) and aspartate aminotransferase to platelet ratio index (APRI)), carotid intima-media thickness (c-IMT), and brachial artery flow-mediated vasodilatation (FMD) were assessed. Patients were divided into 3 tertiles according to fibroscan values. Results. Patients in the third tertile (fibroscan value >11.5 KPa) showed FMD values were significantly lower than second and first tertiles (4.7±1.7% versus 7.1±2.8%, p=0.03). FMD values were inversely related to liver elastomeric values. c-IMT values were normal. The risk for endothelial dysfunction development in the third tertile (p=0.02) was 6.9 higher than the first tertile. A fibroscan value >11.5 KPa had a positive predictive power equal to 79% for endothelial dysfunction. Conclusions. HCV advanced liver fibrosis promotes atherosclerosis by inducing endothelial dysfunction independently of common cardiovascular risk factors.

Galectin-3 and ST2 are emerging biomarkers involved in myocardial fibrosis. We evaluate the relevance of a multiparametric biomarker approach based on increased serum levels of NT-proBNP, galectin-3, and ST2 in stratifying the prognosis of chronic heart failure (CHF) outpatients. In 315 CHF outpatients in stable clinical condition clinical and echocardiographic evaluations were performed. Routine chemistry and serum levels of NT-proBNP, galectin-3, and ST2 were also assessed. During a 12 month follow-up, cardiovascular death, and/or heart failure (HF) occurred in 64 patients. The presence of NT-proBNP, galectin-3, and ST2 were higher than the recommended cutoffs and were all associated with events at univariate Cox regression analysis, as well as in a multivariate analysis including the three biomarkers. When a score based on the number of biomarkers above the recommended cut-offs was used (in a range of 0–3), it was associated with events both with respect to the univariate (HR 2.96, 95% CI 2.21–3.95, p < 0.001, C-index 0.78) and the multivariate (HR 1.52, 95% CI 1.06–2.17, p: 0.023, C-index 0.87) analyses, after correction for the variables of a reference model. Our results suggest that an easy prognostic approach based on the combination of three biomarkers, although with partially-overlapping pathophysiological mechanisms, is able to identify patients with the highest risk of heart failure progression.

Objective. Our study investigates major common cardiovascular risk factors relation with aortic stiffness on 269 postmenopausal women by global pulse wave velocity (PWVg), useful to relate PWVg to risk of major cardiovascular events. Patients and Methods. Women were categorized as hypertensive (H), hypercholesterolemic (C), or diabetic (D). Aortic stiffness was assessed by PWVg measured with pulsed Doppler, at the left ventricular outflow tract (LVOT) and at the right common femoral artery. Results. All population mean PWVg was 8.2 m/s. 85 (26.5%) women were H; mean PWVg was 7.9 m/s. HC women were 118 (36.7%), with mean PWVg 8.3 m/s. HD women were 30 (9.5%), with mean PWVg 7.8 m/s. HDC women were 36 (11.2%), with mean PWVg 9.3 m/s. 52 (16.1%) menstruate women without risk factor were control group (CG), with mean PWVg 6.5 m/s. Highly significant was the statistical difference in PWVg between HDC women and each other group: P

Obstructive sleep apnea syndrome (OSAS) in children can induce endothelial dysfunction, a well-known early marker of atherosclerosis. The study aimed to evaluate a link among endothelial function (measured by flow-mediated vasodilation (FMD)), obesity (evaluated by body mass index (BMI)), and sleep disordered breathing (SDB), assessed with apnoea/hypopnoea index (AHI), in a paediatric population. We demonstrated that our little OSAS patients showed an impaired endothelial function as compared to controls. In particular, the higher the AHI, the worst the FMD values and thus the endothelial function. Although the population sample is small, this study demonstrated that OSAS could impair endothelial function and worsen cardiovascular risk profile since childhood.

Cardiovascular disease related to atherosclerosis represents nowadays the largest cause of morbidity and mortality in developed countries. Due to inflammatory nature of atherosclerosis, several studies had been conducted in order to search for substances with anti-inflammatory activity on arterial walls, able to exert beneficial roles on health. Researches investigated the role of dietary carotenoids supplementation on cardiovascular disease, due to their free radicals scavenger properties and their skills in improving low-density lipoprotein cholesterol resistance to oxidation. Nevertheless, literature data are conflicting: although some studies found a positive relationship between carotenoids supplementation and cardiovascular risk reduction, others did not find any positive effects or even prooxidant actions. This paper aimed at defining the role of carotenoids supplementation on cardiovascular risk profile by reviewing literature data, paying attention to those carotenoids more present in our diet (β-carotene, α-carotene, β-cryptoxanthin, lycopene, lutein, zeaxanthin, and astaxanthin).

Background: Galectin-3 (Gal-3) is a novel biomarker reflecting inflammation status and fibrosis involving worsening of both cardiac and renal functions. Objectives: The aim of this study was to evaluate the relationship between Gal-3 serum levels and microalbuminuria in a group of chronic heart failure (CHF) outpatients. Patients and Methods: We enrolled CHF outpatients having stable clinical conditions and receiving conventional therapy. All patients underwent clinical evaluation, routine chemistry analysis, echocardiography, and evaluation of the urinary albumin/creatinine ratio (UACR). Results: Among the patients enrolled, 61 had microalbuminuria (UACR, 30-299) and 133 normoalbuminuria (UACR, < 30). Patients with normoalbuminuria showed significantly higher levels of Gal-3 than those without (19.9 ± 8.8 vs. 14.6 ± 5.5 ng/mL). The stepwise regression analysis indicated that Gal-3 was the first determinant of microalbuminuria (odds ratio [OR]: 1.08; 95% confidence interval [CI]: 1.02 - 1.14, P = 0.012), followed by diabetes (OR 2.14; 95% CI: 1.00 - 4.57; P = 0.049) and high central venous pressure (OR 2.80; 95% CI: 1.04 - 7.58; P= 0.042). Conclusions: Our findings indicate an independent association between Gal-3 levels and microalbuminuria, an early marker of altered renal function. This suggests the possible role of Gal-3 in the progression of cardiorenal syndrome in CHF outpatients.