Left ventricular diastolic function in atrial fibrillation: Methodological implications and clinical considerations.

The assessment of LVDD is routinely included in echocardiographic evaluation because it correlates with cardiac disease progression and its prognostic value. Classic parameters used for assessing LV diastolic function correlate well with invasive measurements which remains the gold standard. Nevertheless, no one echocardiographic parameter alone can completely evaluate LVDD. LV diastolic function evaluation in atrial fibrillation is still challenging, since the E/A ratio, one of the most used parameters in echocardiographic evaluation, cannot be feasible. This is not a good reason to give up measurement. In this review, we analyze the different methods for estimating LV diastolic function in atrial fibrillation, including measurement not dependent on atrial systole and some novel methods that are promising, but not ever available during clinical practice highlighting that this assessment is mandatory for a complete clinical evaluation of the patients.

Chest pain and palpitations in postmenopausal women with mitral valve prolapse: is there a gastro-oesophageal origin?

BACKGROUND AND AIM: Mitral valve prolapse (MVP) is a common disease in women, causing chest pain and palpitation due to structural and functional valve abnormality, and is sometimes associated with gastro-oesophageal reflux disease (GERD). This is a challenging clinical problem in clinical practice and requires targeted diagnostic assessment to identify the underlying causes of the symptoms, because treatment needs to be tailored, according to the causes themselves, to resolve the symptoms. AIM: To assess the prevalence of GERD in a population of postmenopausal women affected by MVP and determine if there is any correlation between the two conditions. METHODS: The MVP diagnosis was performed using echocardiograpy examination, according to American Society Echocardiography criteria. Two hundred and eighty-nine consecutive MVP women, symptomatic for chest pain and palpitation, were included; 250 consecutive women without MVP, symptomatic for chest pain and palpitation, were the control group (CG). The GERD diagnosis was made according to 2013 American College Gastroenterology criteria; women affected by thyroid disorders, all heart disease, including mitral disease with moderate or severe mitral regurgitation, and gastrointestinal diseases assessed using gastroscopy were excluded. RESULTS: Among 289 women with MVP, 31 (11%) women were affected by GERD, and among 250 in the CG, 11 (4.4%) women were affected by GERD: Chi-squared 8.1; odds ratio 2.7; P < 0.0044. Twenty-six (9%) women affected by GERD, with MVP, presented with mild mitral regurgitation, and 7 (2.8%) women in the CG presented with mild mitral regurgitation as well: Chi-squared 8.95; odds ratio 3.4; 95% CI, P < 0.0028. DISCUSSION AND CONCLUSIONS: GERD is relatively common in women with MVP. Moreover, women with MVP are approximately three times more likely to be affected by GERD; the two conditions are correlated in a statistically high significant way. GERD assessment needs to be included into routine follow-up strategies in women with MVP to optimise medical therapy, improvinge symptom relief for better quality of life.

Relative lymphocyte count as an indicator of 3-year mortality in elderly people with severe COPD.

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.

Neutrophil-dependent pentraxin-3 and reactive oxygen species production modulate endothelial dysfunction in haemodialysis patients.

BACKGROUND: The aim of this study was to investigate neutrophil activation and its role in long pentraxin-3 (PTX3) release and oxidative stress generation during haemodialysis (HD) and to correlate neutrophil PTX3 and oxidant expression with endothelial dysfunction. METHODS: Forty-seven uraemic patients on stable HD, 12 healthy subjects and 15 patients with congestive heart failure (New York Heart Association classes III and IV) were enrolled. Neutrophil PTX3 protein expression was evaluated by confocal microscopy. l -selectin expression, intracellular PTX3 localization and reactive oxygen species (ROS) generation in human neutrophils were measured by flow cytometry. NADPH-dependent superoxide generation was investigated by chemiluminescence. PTX3 plasma concentrations were measured by ELISA. Endothelial dysfunction was studied by flow-mediated dilation (FMD). RESULTS: The low baseline levels of FMD significantly improved after HD, but worsened by 24 h. A significant up-regulation of PTX3 protein expression, localized within secondary granules, was detected in neutrophils isolated at 30 and 240 min of HD, along with an increase in l -selectin expression. The up-regulation in intracellular PTX3 in neutrophils was associated with a significant increase in PTX3 plasma concentrations at 240 min. HD increased ROS production and NADPH oxidase activity in neutrophils. In a univariate analysis, pre-treatment with FMD was inversely correlated with PTX3 expression and ROS generation in neutrophils. In a multivariate analysis, both circulating pre-HD PTX3 and intracellular ROS generation by neutrophils were independent predictors of abnormal FMD. CONCLUSIONS: Neutrophil overexpression of PTX3 is associated with ROS overproduction and endothelial dysfunction and may represent an emerging marker of vascular damage progression in HD patients.

Surgical and pharmacological reassignment: influence on transsexual cardiovascular risk profile.

BACKGROUND/AIM: To evaluate and stratify early cardiovascular risk of transsexuals who underwent pharmacological and/or surgical gender reassignment. METHODS: Fifty-six transsexuals were divided into two groups: group 1 - underwent gonadectomy (orchiectomy for transwomen and hystero-annessiectomy for transmen); group 2 - hormone replacement therapy alone. All participants underwent carotid artery intima-media thickness (C-IMT) and flow-mediated vasodilation (FMD) of brachial artery evaluations. RESULTS: FMD was lower in patients who had undergone gonadectomy compared with non-surgically treated patients (Group 1: 5.711 vs Group 2: 7.339, P < 0.0001). Mean C-IMT was higher in group 1 than group 2 (group 1: 0.733 vs group 2: 0.582). The duration of hormone therapy correlates positively with mean C-IMT (B = 0.001) and negatively with FMD (%) (B = - 0.007). CONCLUSIONS: Cardiovascular risk, which is expressed in terms of endothelial (FMD) and morphological (C-IMT) dysfunction, increases in subjects undergoing gonadectomy compared with those receiving cross-sex reassignment therapy alone.

Carotid stenting versus endarterectomy in the same patient: A "direct" comparison.

The aim of this study was to evaluate outcomes and feasibility of carotid artery stenting versus carotid endarterectomy, both procedures performed in the same patient. Forty-five subjects (33 males, 70 ± 7 years) underwent carotid endarterectomy or carotid artery stenting, the counter procedure on the contralateral carotid performed after a variable period. We evaluated the post-procedural percentage of carotid stenosis at 30, 180 days and one-year follow-up, and the occurrence of acute myocardial infarction, New York Heart Association class progression, stroke, death, cardiovascular death, angina, transient ischemic attack and renal failure. Carotid artery stenting treatment reduced the degree of re-stenosis after 180 days equally to carotid endarterectomy procedure (difference: 0.033%, P = 0.285). No statistically significant differences were observed according to the occurrence of acute myocardial infarction and New York Heart Association class progression, revealing odds ratio (OR) equal to 0.182 ( P = 0.361) for acute myocardial infarction and 0.303 ( P = 0.434) for New York Heart Association class progression. Carotid endarterectomy confirms its efficacy in carotid revascularization, but carotid artery stenting constitutes a good alternative when the procedures are selected based on patient-specific risk factors.

Evaluation of endothelial function and cardiovascular risk in non-obese patients with slight degree of obstructive sleep apnea syndrome.

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.

Rosuvastatin: Beyond the cholesterol-lowering effect.

Rosuvastatin is a fully synthetic statin wich acts by interfering with the endogenous synthesis of cholesterol through competitively inhibiting the 3-hydroxy-3-methylglutaryl coenzyme A reductase, a liver enzyme responsible of the rate-limiting step in cholesterol synthesis. When compared to other molecules of the same class, it shows high efficacy in the improvement of lipid profile, and, thanks to its non-cholesterol-lowering actions (anti-inflammatory, antioxidant and antithrombotic), represents a crucial tool for cardiovascular primary and secondary prevention. Moreover, recent data highlight rosuvastatin beneficial effects in several other fields. In this manuscript we analyzed literature sources in order to better define rosuvastatin features and discuss some critical issues.

Vascular Function and Myocardial Performance Indices in Children Born Small for Gestational Age.

BACKGROUND: Small-for-gestational-age (SGA) children have increased cardiovascular risk, but the mediating factors are poorly understood. We hypothesized that birth size could affect the cardiovascular system since childhood in the absence of other risk factors. We investigated endothelial and myocardial function in SGA children with regular catch-up growth. METHODS AND RESULTS: Biochemical markers, blood pressure, flow-mediated vasodilation (FMD), common carotid intima-media thickness (cIMT), anteroposterior diameter of the infrarenal abdominal aorta (APAO) and echocardiographic parameters of left and right ventricular (LV and RV) function were studied in 27 SGA and 25 appropriate-for-gestational-age (AGA) subjects. SGA subjects had a higher homeostasis model assessment index than controls (2.61±1.27 vs. 1.56±0.40, P=0.01), higher cIMT (0.51±0.04 mm vs. 0.45±0.07 mm, P=0.007) and APAO (1.31±1.35 cm vs. 1.30±0.16 cm, P=0.005), and lower FMD (10.11±4.17% vs. 12.34±4.28, P=0.04) than controls. On echocardiography SGA had higher Tei index both at LV and RV than controls (P=0.001). Reduced RV systolic function was also observed in SGA subjects. CONCLUSIONS: SGA subjects had vascular morphological and function abnormalities compared with AGA, which increase their cardiovascular risk profile. Furthermore, a subtle cardiac alteration in both RV and LV functions was seen in SGA patients compared with AGA.

Echocardiographic diagnosis of the different phenotypes of hypertrophic cardiomyopathy.

Hypertrophic Cardiomyopathy (HCM) is an inherited cardiovascular disorder of great genetic heterogeneity and has a prevalence of 0.1 - 0.2 % in the general population. Several hundred mutations in more than 27 genes, most of which encode sarcomeric structures, are associated with the HCM phenotype. Then, HCM is an extremely heterogeneous disease and several phenotypes have been described over the years. Originally only two phenotypes were considered, a more common, obstructive type (HOCM, 70 %) and a less common, non-obstructive type (HNCM, 30 %) (Maron BJ, et al. Am J Cardiol 48:418 -28, 1981). Wigle et al. (Circ 92:1680-92, 1995) considered three types of functional phenotypes: subaortic obstruction, midventricular obstruction and cavity obliteration. A leader american working group suggested that HCM should be defined genetically and not morphologically (Maron BJ, et al. Circ 113:1807-16, 2006). The European Society of Cardiology Working Group on Myocardial and Pericardial Diseases recommended otherwise a morphological classification (Elliott P, et al. Eur Heart J 29:270-6, 2008). Echocardiography is still the principal tool for the diagnosis, prognosis and clinical management of HCM. It is well known that the echocardiographic picture may have a clinical and prognostic impact. For this reason, in this article, we summarize the state of the art regarding the echocardiographic pattern of the HCM phenotypes and its impact on clinical course and prognosis.

Focus on alirocumab: A PCSK9 antibody to treat hypercholesterolemia.

Statin treatment represents the gold standard in the reduction of low-density lipoprotein cholesterol and cardiovascular risk. Although statin therapy is generally well tolerated, some patients fail to achieve the target level of low-density lipoprotein cholesterol or discontinue the treatment for the occurrence of adverse events. In recent years new lipid-modifying agents have been studied to overcome these limitations and to reduce low-density lipoprotein cholesterol plasma levels. Alirocumab is a fully human monoclonal antibody that inhibits proprotein convertase subtilisin/kexin type 9, thereby preventing its interaction with low density lipoprotein receptors. Several trials have been conducted in the last few years to evaluate long-term effects of this new molecule on low-density lipoprotein cholesterol levels and cardiovascular risk.

Correlation between inflammatory markers of atherosclerosis and carotid intima-media thickness in Obstructive Sleep Apnea.

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.

Effects of low-sodium bread on dietary compliance and fecal cultivable bacteria in a randomized controlled pilot trial in hypertensive subjects.

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.

Dietary intake of carotenoids and their antioxidant and anti-inflammatory effects in cardiovascular care.

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 (ß-carotene, α-carotene, ß-cryptoxanthin, lycopene, lutein, zeaxanthin, and astaxanthin).

Impact of sleep respiratory disorders on endothelial function in children.

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.

HCN channels and heart rate.

Hyperpolarization and Cyclic Nucleotide (HCN) -gated channels represent the molecular correlates of the "funny" pacemaker current (I(f)), 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.

The Prognostic Role of ST2L and sST2 in Patients Who Underwent Carotid Plaque Endarterectomy: A Five-Year Follow-Up Study.

Soluble suppressor of tumorigenicity (sST)-2 plasma concentration is related to atherosclerosis. The aim of this study was to assess the prognostic impact of sST2 and its membrane-associated form (ST2L) in patients with carotid atherosclerotic plaque who underwent endarterectomy (CEA). Eighty-two consecutive patients (age range: 48−86 years) who underwent CEA were enrolled. Anthropometric, clinical, instrumental, and laboratory evaluations were gathered. Thirty-seven (45%) patients were symptomatic of cerebrovascular diseases. Patients underwent a five-year follow-up. Phone calls and the analysis of national and regional databases were performed in order to evaluate the occurrence of the primary outcome (all-cause mortality). The population was divided according to survival status. Statins were administered in 81% and 87.5% of survivors and non-survivors, respectively. sST2 levels were higher in non-survivors than in survivors (117.0 ± 103.9 vs. 38.0 ± 30.0 ng/mL, p < 0.001) and in symptomatic individuals, compared with asymptomatic (80.3 ± 92.1 ng/mL vs. 45.4 ± 41.4 ng/mL, p = 0.02). ROC curve analysis identified sST2 cut-off: >98.44 ng/mL as the best predictor for mortality. At the one-year follow-up, the survival rate decreased up to 20% in patients with sST2 higher than the cut-off value. A multivariate regression analysis revealed that only sST2 (HR: 1.012, 95% CI: 1.008−1.016, p < 0.0001) and triglycerides plasma levels (HR: 1.008, 95% CI: 1.002−1.015, p = 0.0135) remained significantly associated with all-cause mortality. ST2L was not associated with all-cause mortality risk. sST2 may act as an independent prognostic determinant of all-cause mortality and symptomatic cerebrovascular diseases in patients with carotid atherosclerotic plaque who underwent CEA.

Correlation between coronary artery disease severity, left ventricular mass index and carotid intima media thickness, assessed by radio-frequency.

BACKGROUND: Intima-media thickness of the common carotid artery (CCA-IMT) is a validated marker of systemic atherosclerosis process. The aim of this study was to evaluate the association between coronary artery disease (CAD), left ventricular hypertrophy (LVH) and CCA-IMT, assessed by Radio Frequency-Quality Intima Media Thickness (RFQIMT) method, the next generation of IMT real-time measurement, based on the direct analysis of the radiofrequency signal and endowed with high accuracy and reproducibility in early detection of arterial wall thickness. METHODS: 115 patients (76 men, mean age: 65.1 ± 12 years) referred to our department and shown significant (≥ 70% luminal obstruction) stenosis at least in one major epicardial coronary artery were studied. Coronary angiograms were divided for severity and extent of the disease: 79 patients (69%) had one, 24 patients (21%) two, 12 patients (10%) three major epicardial coronary arteries with ≥ 70% stenosis. All patients underwent echocardiography and carotid ultrasound examination, assessed by RF. RESULTS: Dividing RFQIMT data in tertiles, dyslipidaemia (31 patients with IMT ≥ 1.20 mm vs 16 with IMT = 0.91-1.19 vs 25 with IMT ≤ 0.9, p = 0.004), LVMI (153.5 ± 20.6 g/m² in IMT ≥ 1.20 mm vs 131.2 ± 8.4 g/m² in IMT = 0.91-1.19 mm vs 114.3 ± 11.1 g/m² in IMT ≤ 0.9 mm, P < 0.001) and number of high stenosed coronary arteries (IMT ≥ 1.20 mm population more often showed three vessel diseases than IMT ≤ 0.90 mm one, P < 0.001) seemed to be significantly related to CCA-IMT increases. Furthermore, LVMI is positively related to IMT (r = 0.91; P < 0.001). In a multivariate regression model (R2 = 0.88), RFQIMT remained significantly associated with the dyslipidemia (regression coefficient ± standard error [SE]: 0.057 ± 0.023; p = 0.017), LVMI (regression coefficient ± SE: 0.01 ± 0.001; P < 0.0001) and number of damaged coronaries (regression coefficient ± SE: 0.0174 ± 0.028; P < 0.0001). CONCLUSIONS: RFQIMT is a sophisticated method for carotid ultrasound evaluation. Its evaluation in patients with at least one important major epicardial coronary vessel stenosis would help the accuracy in the general assessment of the number of coronary lesions in these patients.