Objective: Sodium-glucose co-transporter-2 (SGLT2) inhibitors are a novel drug class, able to reduce blood pressure (BP) values and cardiovascular events in type 2 diabetes (T2DM), Though BP and glucose control certainly contribute to the cardiovascular protection mediated by SGLT2-inhibitors, other mechanisms are plausible and not fully elucidated. Aim of this study is to investigate whether dapagliflozin is able to acutely modify systemic and renal vascular function in T2DM. Design and method: 16 T2DM patients, treatment-naïve for BP (age 57 ± 9 years, 11 men, BMI 30.5 ± 6.7, HbA1c 56.0 ± 6.8 mmol/mol) were enrolled. Neuro-hormonal and vascular variables were assessed before (V0) and after (V1) a 2-day treatment with dapagliflozin 10 mg/die per os. 24h-urinary sodium and glucose, diuresis and free-water clearance were measured at V0 and V1. Brachial artery endothelium-dependent and independent vasodilation were assessed by flow-mediated dilation (FMD) and automated image analysis. Pulse wave velocity (PWV), central BP and its augmentation were assessed by applanation tonometry. Renal resistive index (RI) was assessed and renal vasodilating capacity evaluated by administration of low-dose glyceril trinitrate (GTN). Results: 2-day treatment with dapagliflozin induced a significant decrease in brachial systolic BP (130.7 ± 12.8 to 125.4 ± 11.2 mmHg, p < 0.05), an increase in 24h-diuresis (1400[750] to 2000[750] ml, p < 0.05), 24h-urinary glucose (406[3465] to 66239[43780] mg/24 h, p < 0.05), while natriuresis and fasting blood glucose were unchanged. FMD was significantly increased (2.8 ± 2.2 to 4.0 ± 2.1%, p < 0.05), in the presence of unchanged brachial artery diameter, shear rate and response to GTN. PWV was reduced (10.1 ± 1.6 to 8.9 ± 1.6 m/s, p < 0.05); a trend persisted even after correction for mean BP (p = 0.053). RI was reduced (0.62 ± 0.04 to 0.59 ± 0.05, p < 0.05), while RI response to GTN was unmodified. Changes in FMD, PWV and RI were not associated with changes in BP. Conclusions: 2-day treatment with dapagliflozin induce a significant improvement in systemic endothelial function, arterial stiffness and renal vasodilation; this effect is independent of changes in BP and occurrs in the presence of stable blood glucose and natriuresis. These preliminary data suggest that dapagliflozin has a direct beneficial effect on the vasculature, which might translate in reduced cardiovascular risk.

560 Vascular function as a target of cardiovascular therapy?aimed to quantify the influence of this pharmacological substance on the plasma levels of soluble endoglin, versus other antihypertensive drugs, in patients with essential arterial hypertension and endothelial dysfunction.Methods: A total of 351 patients were included in the study: 126 hypertensive patients were treated with Perindopril (4, 8, 5 or 10mg), 120 hypertensive patients with other antihypertensive drugs (such as: metoprolol 50 or 100mg, amlodipine 5 or 10 mg and indapamide 1.5mg, spironolactone 50mg) and 105 normotensive patients (the control group).All the patients from these 3 groups were the same age and gender.The hypertensive had controlled values of blood pressure under medication.Results: Al the patients included in this study had been diagnosed with endothelial dysfunction which was confirmed by classical methods of assessing endothelial dysfunction: FMD or IMT or both.The plasma levels of soluble endoglin were significantly lower in the group of patients treated with Perinfopril compared with the group of patients treated with other antihypertensive drugs and with the control group.Endoglin plasma levels Control group Other antihypertensive drugs group Perindopril group p n=105 n=120 n=126 Endoglin (ng/ml) 5.38±2.965.44±2.324.63±1.41<0.001Conclusions: Perindopril decrease soluble endoglin levels more powerful than other antihypertensive drugs, so we may assume that it has a more potent action in reversing endothelial dysfunction than other antihypertensive drugs.

Objective: Aim of the study is to evaluate the effect of effect of bariatric surgery on vascular and renal biomarkers in morbidly obese, normotensive, non-diabetic patients. Design and method: 25 patients (19 women, age 44 ± 11 years, BMI 45 ± 7 kg/mq) were enrolled. A multidistrict vascular assessment was performed before and 12 months after bariatric surgery, including: aortic stiffness (carotid-femoral pulse wave velocity - PWV), endothelial function (flow-mediated dilation - FMD), carotid intima media thickness (cIMT) and distensibility coefficient (DC), and renal hemodynamics by means of renal resistive index (RI) in resting conditions and after sublingual administration of glyceryl trinitrite 25 mcg s.l. (DRIN) and renal plasma flow (123I-ortho-iodo-ippurate) Results: 20 patients completed the 12-month follow-up, showing a significant reduction in BMI (46 ± 7 to 31 ± 6 kg/mq, p < 0.001), blood pressure (BP - 127 ± 12 / 78 ± 11 to 117 ± 9 / 69 ± 7 mmHg, p < 0.05) and heart rate (71 ± 11 a 61 ± 10 bpm (p = 0.01). HDL was increased (da 41 ± 11 a 52 ± 9, p = 0.009) and triglycerides reduced (da 124 ± 56 to 76 ± 27 mg/dl, p = 0.005). Conversely, blood fasting glucose (100 ± 24 to 87 ± 9 mg/dl, p = 0.29), total cholesterol (da 180 ± 25 a 172 ± 40 mg/dl, p = 0.30) and serum creatinine (0.74 ± 0.17 to 0.69 ± 0.11, p = 0.52) were unmodified. FMD was increased (4.45 ± 2.20 to 6.91 ± 2.30%, p = 0.002), PWV (8.2 ± 1.1 to 7.4 ± 1.2 m/s, p = 0.04) and RI were reduced (0.62 ± 0.06 to 0.59 ± 0.06, p = 0.04), whereas IMT (0.69 ± 0.15 0.62 ± 0.14, p = 0.18), DRIN (−4.4 ± 4.3 to −6.0 ± 3.7%, p = 0.80) and DC (28.8 ± 9.3 to 37.8 ± 15.2, p = 0.11) where unchanged. Absolute changes in PWV, but not in FMD and RI, where directly correlated to changes in mean BP (r = 0.82, p < 0.001). Changes in PWV, FMD and RI were not associated to changes in BMI, HDL and triglycerides. Renal plasma flow before surgery was positively related to RI before surgery (r = 0.65, p = 0.03) and inversely related to changes in RI (p = −0.63, r = 0.04). Conclusions: Bariatric surgery causes an improvement in endothelial function and renal hemodynamics even in morbidly obese, normotensive, non-diabetic individuals with normal renal function, independent of the effect on BMI, BP and lipids. The increased RI observed before surgery may be a feature of hyperperfusion rather than of renal arteriolosclerosis, thus representing a functional and reversible alteration.

Intense physical stress might promote inflammatory responses, whereas a regular physical exercise has positive influence. Little is known on the acute metabolic and inflammatory responses to different levels of strenuous exercise in trained athletes.To compare the short-term effect of two different ultra-endurance competitions on the inflammatory profile in male triathletes.We studied 14 Ironman (IR) and 13 Half Ironman (HIR) before and after their own specific race. We assessed body composition and measured blood cells, lipids, iron metabolism and plasma levels of some acute-phase cytokines and inflammatory markers.After the race, IR showed reduced total body water and fat-free mass, not related with the duration of exercise, and increased white cells and platelets; high-density lipoprotein levels also increased. IR, but not HIR, showed reduced iron levels, increased ferritin and transferrin, reduced % saturated transferrin. HIR showed higher basal interleukin (IL)-6, tumour necrosis factor (TNF)-α, IL-10, IL-1β than IR; however, the post-performance rise was greater in IR. Irisin increased only in HIR and osteocalcin decreased in IR. In the whole study group, delta of white blood cells was directly related with delta of monocyte chemoattractant protein 1, and Δ ferritin was inversely related with Δosteocalcin.A single ultra-endurance competition induces an inflammatory response depending on the duration of physical effort, with increased acute-phase cytokines, and an altered iron metabolism. Irisin, whose biological meaning is still uncertain, seems to be associated with acute variations of some metabolic parameters.

BACKGROUND AND AIM:A certain degree of impaired kidney function is related to an increased cardiovascular risk. The cardiovascular protection exerted in the postmenopausal state by the hormone replacement therapy (HRT) is debated. No studies have so far explored the relationship between menopause, renal function and cardiovascular risk profile in healthy menopausal women in relation with HRT. SUBJECTS AND METHODS:A total of 362 postmenopausal healthy women with normal albumin excretion rate were recruited and divided into two groups (HRT+ and HRT-) according to the presence or absence of HRT. All participants underwent a complete routine biochemical analyses and an echocardiogram. RESULTS:Clinical characteristics of the two groups were similar, but HRT+ showed a significantly higher estimated glomerular filtration rate (GFR; by CKD-EPI formula). Regarding the heart ultrasonography, HRT+ had a significantly lower size of the aortic root and left atrium diameter (p = 0.038 and p = 0.012, respectively); no differences were found in the ejection fraction and Left Ventricular Mass Index (LVMI). In the whole study group, eGFR correlated inversely with LVMI and with the size of the aortic root (both p < 0.0001), being GFR the only determinant of the former by a stepwise regression. Dividing the study population according to an eGFR cut-off (> 80 and < 80 ml/min/1.73 m(2)); > 80 women, in comparison with < 80, showed a significantly lower LVMI and lower size of aortic bulb, further reduced in the HRT+. CONCLUSION:In a cohort of healthy, drug-naïve, postmenopausal women, HRT seems to positively affect glomerular filtration and is associated with lower values of left ventricular mass and aortic root size, thus offering a further mechanism through female hormones exert cardioprotection.

This study was undertaken to elucidate the still debated question of the relationship between cardiac volume and QRS voltage amplitude. The authors studied 14 healthy men, aged 24-61 years (mean age, 41.2 +/- 12.1 years). They underwent a reduction in venous return, produced by simultaneously inflating sphygmomanometric cuffs placed around the most proximal portion of each of the four limbs. In basal conditions and 5 minutes after cuff inflation, two-dimensional and M-mode echocardiograms were recorded with vectorcardiographic loops and scalar Frank leads. The reduction of the venous return to the heart induced a significant decrease of the end-diastolic left ventricular diameter (from 52.4 +/- 4.2 to 48.5 +/- 4.6 mm, P < .001), of the R wave amplitude in leads X and Y, of the sum of the R wave amplitudes in the three leads,and of the maximal vector in the frontal and horizontal planes. No significant changes in the heart rate or arterial blood pressure were observed. These results support Brody's theory concerning the relationship between cardiac blood volume and QRS voltage.

The aim of this study was to evaluate the effects of preload reduction on the Doppler transmitral flow pattern in the presence of diastolic dysfunction (hypertensive patients) and normal diastolic function (normal subjects) to identify, if present, one or more indexes of abnormal diastolic ventricular filling independent of variations in preload. For this purpose Doppler echocardiography was performed in 17 patients with hypertension and in 18 normal subjects under basal conditions and after 5 minutes of blood pressure cuff inflation at the root of the four limbs. The two groups showed a similar response to preload reduction: a significant reduction in peak velocity and the time-velocity integral of the E wave and in the ratio of peak velocities of E and A waves. Therefore the differences in left ventricular filling patterns between hypertensive and normal subjects observed under basal conditions were still present after preload reduction. The comparison between normal subjects after preload reduction and hypertensive patients in the basal state showed a higher peak velocity and time-velocity integral of the A wave in the latter (61.2 ± 16.2 vs 46.2 ± 9 cm/sec [p < 0.002] and 5.4 ± 1.8 vs 3.7 ± 1 cm [p < 0.002], respectively) with no differences in the ratios of peak velocities and time-velocity integrals of the E and A waves. It was concluded that the response of the Doppler transmitral flow pattern to preload reduction appears to be similar in normal subjects and patients with hypertension, irrespective of the presence of diastolic dysfunction, and the peak velocity and time-velocity integral of the A wave may be considered indexes of diastolic dysfunction independent of preload reduction.

The normal values of the systolic time intervals (STI) in children and their possible relationship with heart rate have not been studied thoroughly. From a group of 9760 healthy school-children 10-12 years old, 488 subjects of both sexes were randomly selected in order to measure the STI and calculate the respective indices. The final population study was composed of 479 children, 249 males and 230 females, aged from 10/1 to 12/2 years/months (mean age 11/1 +/- 0/4 years/months). In each child, the following STI were measured: total electromechanical systole (Q-S2), left ventricular ejection time (LVET), mechanical systole (S1-S2), preejection period (PEP), PEP/LVET ratio and isovolumic contraction time (ICT). For each parameter, the regression equation with heart rate was calculated using a linear model and was verified if a real difference existed between linear regressions of males and females. Moreover, for each parameter, the index from the respective regression equation was calculated as well as its normal value and the standard deviation. Finally, the diastolic time (% diastole) and its correlation with heart rate were calculated. Our results demonstrate that in children, a close correlation exists between the STI and heart rate, although less striking than in adults; only the PEP/LVET ratio appears independent from heart rate, as in adults. The % diastole versus heart rate non-linear relationship shows the same behaviour as in adults. Finally, in agreement with other authors, our results show that in childhood the relationship between the STI and heart rate behaves alike in males and females.

In the last few years, alterations in transmitral diastolic flow pattern have been used to assess changes in left ventricular diastolic properties. However, since diastolic flow primarily reflects the atrioventricular pressure gradient, loading conditions, as well as intrinsic left ventricular properties, should be able to affect this pattern. This study was selectively designed to decrease preload (a major determinant of the atrioventricular pressure gradient) in normal subjects to observe the effects on the Doppler transmitral flow pattern without pharmacologic interventions that may also affect left ventricular diastolic properties. In 12 normal subjects, preload was reduced by inflation of blood pressure cuffs placed at the level of the root of the 4 limbs. The peak velocity of early mitral flow (E wave) decreased from 62 ± 8 to 51 ±7 cm/s (p < 0.001), while no changes were found in the maximal velocity after atrial contraction; this caused a significant decrease in the ratio of these 2 velocities (the E to A ratio) from 1.5 ± 0.3 to 1.1 ± 0.1 (p < 0.001). The time-velocity integral of early diastolic inflow decreased from 7.8 ± 1.3 to 6.1 ± 1.3 cm (p < 0.001) with no significant changes of the time-velocity integral of inflow after atrial contraction. Therefore, preload reduction in normal subjects significantly reduces transmitral flow in early diastole with preserved late ventricular filling, producing a pattern that can mimic the changes previously described in left ventricular diastolic dysfunction.

Beta-endorphin and beta-lipotropin plasma concentrations were evaluated in 24 patients with congestive heart failure (CHF) (10 patients had chronic CHF and 14 an acute episode superimposing on chronic CHF), and in 35 age matched controls. Beta-endorphin and beta-lipotropin were significantly lower (P less than 0.005 and P less than 0.001 respectively) in patients with CHF than in controls. A significant decrease of both peptides vs controls was observed also in the two subgroups of patients, with chronic and acute CHF, without statistical differences between the subgroups. Beta-endorphin and beta-lipotropin showed a close and significant correlation (r = 0.88, P less than 0.001) amongst the whole series of patients as well as in both subgroups with chronic and acute CHF. In consideration of the long duration of the disease the decreased concentrations of beta-endorphin and beta-lipotropin can be considered to be due to a depletion of the releasable pool of the peptides, as it was previously shown for chronic stress.

The effects of ibopamine and furosemide on renal function given alone and in combination at single doses were studied in 6 men and 6 women aged 45 to 73 years with chronic congestive heart failure of NYHA class II. After 3 days of dietary stabilization, the patients received either ibopamine 200 mg, furosemide 40 mg, or furosemide 40 mg plus ibopamine 200 mg with 2-day washout between treatments, according to a double-blind, balanced three-way crossover design using all possible treatment sequences. On each treatment day urine collections were performed at 2-hourly intervals from 2 h before to 6 h after dosing, and urine volume and Na+, K+, Cl-, and creatinine concentrations were measured for every period. The patients received a standardized breakfast 3 h before treatment and then were allowed 250 ml tap water to drink before starting each urine collection period. Venous blood samples were taken before breakfast and midway between each urine collection period for analysis of serum Na+, K+, Cl-, creatinine, and glucose. Heart rate, blood pressure, and physical signs were recorded 2, 1 h, immediately before, and then 0.5, 1, 2, 3, 4, 5, and 6 h after treatment. At the same times the patients were asked for any symptoms. The time course of the diuretic effect of furosemide 40 mg was consistent with the data reported by other authors.(ABSTRACT TRUNCATED AT 250 WORDS)

In order to investigate the prevalence of vectorcardiographic bites, expression of small areas of fibrosis, atrophy or degeneration of the myocardium, we studied, using the vectorcardiograms (VCG) of 101 diabetic patients (35 with insulin-dependent and 66 with non-insulin-dependent diabetes mellitus, aged from 25 to 60 years, without hypertension, coronary artery disease, or intraventricular conduction defects) and 228 normal control subjects, matched for age and sex. The prevalence of bites was 38.6% in diabetic patients and 10.0% in the control group (p<0.001). Diabetic patients were also subdivided into groups according to age, sex, metabolic control, risk factors for coronary heart disease, type of diabetes, duration of diabetes and diabetic microangiopathy. No correlation was found between any of the variables investigated nor of a combination of these, and the presence of bites. We conclude that VCG is a sensitive test for cardiac involvement in diabetic patients but that it cannot be used to identify any specific factor able to influence the onset and evolution of this involvement.

Twelve patients with chronic cor pulmonale due to chronic obstructive pulmonary disease have been examined with 2D echocardiography, performing four-chamber view by apical and subcostal approaches, and the right ventricular outflow tract view by the subcostal approach. These views have permitted evaluation of right ventricular volumes, and hence right ventricular ejection fraction, by the use of three different geometrical formulae: the biplane area-length method, Simpson's rule and the pyramidal method. The ejection fraction values obtained from each method have been compared to those obtained by equilibrium radionuclide angiocardiography. Four-chamber apical and subcostal views were satisfactorily recorded in 10 of the 12 patients (83.3%), and right ventricular outflow tract view in 8 patients (66.6%). No significant statistical differences have been found between measurements obtained from the three different echocardiographic examinations performed on each subject by the same operator, so demonstrating a satisfactory reproducibility of the technique. The highest correlation coefficient for ejection fraction was shown by Simpson's rule (r = 0.96, p less than 0.001), with a very narrow confidence intervals, while the r values for the biplane area-length method was 0.63 (p less than 0.05) and for the pyramidal method 0.50 (not statistically significant), with increasingly wider confidence intervals. The statistically significant difference between the three correlation coefficients demonstrates the higher accuracy of Simpson's rule for the determination of right ventricular ejection fraction.

In the aim to clarify the magnitude and features of alterations in left ventricular function observed in patients with mitral valve prolapse syndrome (MVPS), we studied 41 patients with MVPS with M-mode echocardiography and computerized reading of recordings (with particular regard to the diastolic phase), and compared them with a control group of 15 healthy subjects matched for age and sex. Routine morphological and functional echocardiographic parameters were evaluated and, in addition, peak rates of movement of left ventricular endocardia, of wall thicknesses change and of cavity dimensions variations were obtained. Finally, a detailed analysis of various diastolic phases have been performed, according to the method proposed by Hanrath et al. There were no significant statistical differences in the morphological echocardiographic parameters (ventricular diameters, wall thicknesses) between the two groups. Patients with MVPS showed (compared to the control group) a significant increase in the peak rate of posterior wall endocardium movement during systole (1.64 +/- 0.42 vs 1.29 +/- 0.30, p less than 0.01) and a reduction of peak rate of interventricular septum thickening (1.21 +/- 0.36 vs 1.45 +/- 0.46, p less than 0.05). The comparison of all other systolic function parameters did not show statistical differences. As far as diastolic phase is concerned, no significant differences were found in the analysis of the peak velocities. However, evaluation of the diastolic phases demonstrated, in MVPS group, a significantly shorter slow filling period, both in absolute value (185.88 +/- 78.91 vs 303.15 +/- 117.58, p less than 0.001) and in percent of the whole diastole (37.42 +/- 11.88 vs 52.50 +/- 10.61, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Thyroid function alterations induced by amiodarone treatment (200-400 mg/day for 5 days/week) were studied in 50 patients with heart disease (age 34-75 years, mean age 55.5 +/- 11.8) for 25.6 +/- 15.0 months. Statistical analysis was made of the results obtained from the 14 patients who underwent all of the schedule examinations during the same 16-month period. A reduction in T3 was observed after 7 days' treatment; this became statistically significant at 12 and 16 months. FT3 fell significantly only after 7 days; rT3 showed an opposite trend to that of T3 (low T3 syndrome), with significant increases at all observation times. TSH rose at 7 days, then fell gradually to below baseline values after 12 months. No evidence of clinical hyperthyroidism accompanied the significant increases of T4 and FT4 observed at 1, 3, 6, and 16 months; when this complication occurred (in 6% of the cases) it was associated with a rise or lack of reduction in T3 levels. In these cases treatment was withdrawn. Amiodarone was also discontinued in 2 other cases (4%) with elevated thyroid function indices but without clinical symptoms. Seven patients who showed an isolated increase of FT3 were carefully monitored; only in one case did clinical hyperthyroidism develop with a simultaneous rise in the T3 level. A diagnosis of hypothyroidism may be considered only if there is a reduction in T4 levels, since an isolated increase in TSH is not as reliable; treatment had to be suspended for this reason in 2 cases (4%), both without clinical symptoms.(ABSTRACT TRUNCATED AT 250 WORDS)