Gaspare Parrinello

Medium term effects of different dosage of diuretic, sodium, and fluid administration on neurohormonal and clinical outcome in patients with recently compensated heart failure.

Studies have shown that patients with compensated heart failure (HF) receiving high diuretic doses associated with normal sodium diet and fluid intake restrictions demonstrated significant reductions in readmissions and mortality compared with those who received low-sodium diets, and over a 6-month observation period, a reduction in neurohormonal activation was also observed. The aim of this study was to evaluate the effects of different sodium diets associated with different diuretic doses and different levels of fluid intake on hospital readmissions and neurohormonal changes after 6-month follow-up in patients with compensated HF. Four hundred ten consecutive patients with compensated HF (New York Heart Association class II to IV) aged 53 to 86 years, with ejection fractions <35% and serum creatinine <2 mg/dl, were randomized into 8 groups: group A (n = 52): 1,000 ml/day of fluid intake, 120 mmol/day, and 250 mg furosemide twice daily; group B (n = 51): 1,000 ml/day of fluid intake, 120 mmol/day, and 125 mg furosemide twice daily; group C (n = 51): 1,000 ml/day fluid intake, 80 mmol/day, and 250 mg furosemide twice daily; group D (n = 51): 1,000 ml/day fluid intake, 80 mmol/day, and 125 mg furosemide twice daily; group E (n = 52): 2,000 ml/day fluid intake, 120 mmol/day, and 250 mg furosemide twice daily; group F (n = 50): 2,000 ml/day fluid intake, 120 mmol/day, and 125 mg furosemide twice daily; group G (n = 52): 2,000 ml/day fluid intake, 80 mmol/day, and 250 mg furosemide twice daily; and group H (n = 51): 2,000 ml/day fluid intake, 80 mmol/day, and 125 mg furosemide twice daily. All patients received the treatments >or=30 days after discharge and for 180 days afterward. Signs of HF, body weight, blood pressure, heart rate, laboratory parameters, electrocardiograms, echocardiograms, brain natriuretic peptide, aldosterone, and plasma renin activity were examined at baseline and 180 days later. Group A showed the best results, with a significant reduction (p <0.001) in readmissions, brain natriuretic peptide, aldosterone, and plasma renin activity compared with the other groups during follow-up (p <0.001). In conclusion, these data suggest that the combination of a normal-sodium diet with high diuretic doses and fluid intake restriction, compared with different combinations of sodium diets with more modest fluid intake restrictions and conventional diuretic doses, leads to reductions in readmissions, neurohormonal activation, and renal dysfunction.

Effects of high-dose furosemide and small-volume hypertonic saline solution infusion in comparison with a high dose of furosemide as a bolus, in refractory congestive heart failure.

Diuretics, have been accepted as first‐line treatment in refractory heart failure, but a lack of response is a frequent event. A randomised single blind study was performed to evaluate the effects of the combination of high‐dose furosemide and small‐volume hypertonic saline solution (HSS) infusion in the treatment of refractory NYHA class IV congestive heart failure (CHF).

Carotid atherosclerosis and chronic hepatitis C: A prospective study of risk associations

There are contrasting results in studies of cardiovascular risk in patients with genotype 1 chronic hepatitis C (G1 CHC). We evaluated the prevalence of carotid atherosclerosis compared with a control population in order to assess the potential association between atherosclerosis, host and viral factors, and liver histological features. In all, 174 consecutive biopsy‐proven G1 CHC patients were evaluated by anthropometric and metabolic measurements and 174 patients attending an outpatient cardiology unit were used as controls. Intima‐media thickness (IMT) and carotid plaques, defined as focal thickening of >1.3 mm at the level of common carotid, were evaluated using ultrasonography. All G1 CHC biopsies were scored by one pathologist for staging and grading, and graded for steatosis. Carotid plaques were found in 73 (41.9%) G1 CHC patients compared with 40 (22.9%) control patients (P < 0.001). Similarly, G1 CHC patients had a greater IMT compared with control patients (1.04 ± 0.21 versus 0.90 ± 0.16; P < 0.001). Multivariate logistic regression analysis showed that older age (odds ratio [OR] 1.047, 95% confidence interval [CI]: 1.014‐1.082, P = 0.005), and severe hepatic fibrosis (OR 2.177, 95% CI: 1.043‐4.542, P = 0.03), were independently linked to the presence of carotid plaques. In patients ≤55 years, 15/67 cases with F0‐F2 fibrosis (22.3%) had carotid plaques, compared with 11/21 (52.3%) with F3‐F4 fibrosis (P = 0.008). By contrast, in patients >55 years the prevalence of carotid plaques was similar in those with or without severe fibrosis (25/43, 58.1% versus 22/43, 51.1%; P = 0.51). Conclusion: Severe hepatic fibrosis is associated with a high risk of early carotid atherosclerosis in G1 CHC patients. (HEPATOLOGY 2012)

Six-Month Echocardiographic Study in Patients With Submassive Pulmonary Embolism and Right Ventricle Dysfunction: Comparison of Thrombolysis With Heparin

Introduction:The aim of this study was to assess the effect of thrombolysis versus heparin treatment on echocardiographic parameters and clinical outcome, during hospitalization and within the first 180 days after admission, in patients with first episode of submassive pulmonary embolism (SPE) and right ventricle dysfunction (RVD). Methods:Consecutive patients (age, 18–75 years) with a first episode of SPE, symptoms onset since no more than 6 hours, normal blood pressure (>100 mm Hg), echocardiographic evidence of RVD and positive lung spiral computed tomography were double-blind randomized: 1 group received 100 mg of alteplase (10-mg bolus, followed by a 90-mg intravenous infusion over a period of 2 hours), while the other group received matching placebo. In addition to alteplase or placebo, both groups received an unfractionated heparin treatment. Echocardiogram was performed at admission, at 24, 48 and 72 hours, at discharge and at 3 and at 6 months after randomization. Results:Seventy-two patients were included into the study; 37 were assigned to thrombolysis and 35 to placebo. Both groups were well matched with regard to features and clinical presentation. Thrombolysis group showed a significant early improvement of RV function compared with heparin group, and this improvement was observed also during the follow-up (180 days). The same group also showed significant reduction in clinical events during the hospitalization and follow-up. Conclusions:Our data suggest that, in hemodynamically stable patients with SPE, thrombolysis shows an earliest reduction of RVD and a more favorable trend in clinical outcome, so, it could merit consideration in SPE.

Short-Term Effects of Hypertonic Saline Solution in Acute Heart Failure and Long-Term Effects of a Moderate Sodium Restriction in Patients With Compensated Heart Failure With New York Heart Association Class III (Class C) (SMAC-HF Study)

Introduction:Hypertonic saline solution (HSS) and a moderate Na restriction plus high furosemide dose showed beneficial effects in compensated heart failure (HF), in short and long terms. The study was aimed to verify the effects of this combination on hospitalization time, readmissions and mortality in patients in New York Heart Association (NYHA) class III. Method:Chronic ischemic or nonischemic cardiomyopathy uncompensated patients with HF in NYHA III functional class with ejection fraction <40%, serum creatinine <2.5 mg/dL, blood urea nitrogen <60 mg/dL and reduced urinary volume were single-blind randomized in 2 groups: the first group received a 30-minute intravenous infusion of furosemide (250 mg) plus HSS (150 mL) twice daily and a moderate Na restriction (120 mmol); the second group received furosemide intravenous bolus (250 mg) twice a day, without HSS and a low Na diet (80 mmol); both groups received a fluid intake of 1000 mL/d. After discharge, the HSS group continued with 120 mmol Na/d; the second group continued with 80 mmol Na/d. Results:A total of 1771 patients (881 HSS group and 890 without HSS group) met inclusion criteria: the first group (881 patients), compared with the second (890 patients), showed an increase in diuresis and serum Na levels, a reduction in hospitalization time (3.5 + 1 versus 5.5 + 1 days, P < 0.0001) and, during follow-up (57 + 15 months), a lower rate in readmissions (18.5% versus 34.2%, P < 0.0001) and mortality (12.9% versus 23.8%, P < 0.0001); the second group also showed a significant increase in blood urea nitrogen and serum creatinine. Conclusion:This study suggests that in-hospital HSS administration, combined with moderate Na restriction, reduces hospitalization time and that a moderate sodium diet restriction determines long-term benefit in patients with NYHA class III HF.

The Usefulness of Bioelectrical Impedance Analysis in Differentiating Dyspnea Due to Decompensated Heart Failure

BACKGROUND Acute dyspnea poses a diagnostic challenge for physicians, and the current methods in differentiating cardiac from non-cardiac causes have been limited to date. Recently, the brain natriuretic peptide (BNP) rapid test has been validated in the emergency room. Nevertheless, the early accumulation of fluid in the interstitial space in the body and in the lungs, which characterizes patients with ADHF, is well estimated by BIA. We investigate whether bioelectrical impedance analysis (BIA) can serve as a noninvasive diagnostic tool in the differential diagnosis of acute decompensated heart failure (ADHF) in the emergency department (ED). METHODS AND RESULTS A total of 292 patients presenting with acute dyspnea to the ED were evaluated by using a conventional diagnostic strategy and rapid BNP measures. Segmental (Seg) and whole-body (WB) BIA resistance (Rz) and reactance (Xc) on entry were immediately detected. After hospital discharge, an expert team classified enrolled patients into ADHF and non-ADHF. A total of 58.9% of patients had ADHF, whereas 41.1% were non-ADHF. ADHF patients showed significantly (P < .001) higher BNP values (591.8 +/- 501 versus 69.5 +/- 42 pg/mL), a significant (P < .001) reduction of Seg (35.5 + 8.2 versus 66.4 + 10.5) and WB (402.3 + 55.5 versus 513.2 + 41.8) Rz (Ohm), and a significant correlation (P < .0001) between BNP and Seg (r = -0,62) and WB (r = -0.63) bioelectrical Rz was also identified. Multiple regression analysis revealed that whole body and segmental BIA were strong predictors of ADHF alone or in combination with BNP. CONCLUSIONS Our data suggest that Seg and WB BIA are a useful, simple, rapid, and noninvasive diagnostic adjunct in the early diagnosis of dyspnea from ADHF.

Long-Term Effects of Dietary Sodium Intake on Cytokines and Neurohormonal Activation in Patients With Recently Compensated Congestive Heart Failure

BACKGROUND A growing body of evidence suggests that the fluid accumulation plays a key role in the pathophysiology of heart failure (HF) and that the inflammatory and neurohormonal activation contribute strongly to the progression of this disorder. METHODS AND RESULTS The study evaluated the long-term effects of 2 different sodium diets on cytokines neurohormones, body hydration and clinical outcome in compensated HF outpatients (New York Heart Association Class II). A total of 173 patients (105 males, mean age 72.5+/-7) recently hospitalized for worsening advanced HF and discharged in normal hydration and in clinical compensation were randomized in 2 groups (double blind). In Group 1, 86 patients received a moderate restriction in sodium (120mmol to 2.8g/day) plus oral furosemide (125 to 250mg bid); in Group 2, 87 patients: received a low-sodium diet (80mmol to 1.8g/day) plus oral furosemide (125 to 250mg bid). Both groups were followed for 12 months and the treatment was associated with a drink intake of 1000mL daily. Neurohormonal (brain natriuretic peptide, aldosterone, plasma rennin activity) and cytokines values (tumor necrosis factor-alpha, interleukin-6) were significantly reduced with a significant increase of the anti-inflammatory cytokine interleukin-10 at 12 months in normal, P < .0001) than low-sodium group. The low-sodium diet showed a significant activation of neurohormones and cytokines and worsening the body hydration, whereas moderate sodium restriction maintained dry weigh and improved outcome in the long term. CONCLUSIONS Our results appear to suggest a surprising efficacy of a new strategy to improve the chronic diuretic response by increasing Na intake and limiting fluid intake. This counterintuitive approach underlines the need for a better understanding of factors that regulate sodium and water handling in chronic congestive HF. A larger sample of patients and further studies are required to evaluate whether this is due to the high dose of diuretic used or the low-sodium diet.

Central obesity and hypertension: The role of plasma endothelin

Hypertension and central obesity are two conditions closely linked, but the mechanisms responsible for obesity-associated hypertension are still unclear. In the last few years, several studies addressed the role of endothelin-1 (ET-1) in the development and maintenance of hypertension. This study was designed to evaluate plasma ET-1 in normotensive and hypertensive central obese subjects compared with a lean healthy group. Our final goal was to analyze the relationship between plasma ET-1, blood pressure, and left ventricular structure and function in central obese subjects (both normotensives and hypertensives). ET-levels have been assessed by the radioimmunoassay method in 20 lean normotensives and in 57 central obese subjects; 30 of them were hypertensives and 27 of them were normotensives. Twenty-four-hour mean blood pressure (MBP/24 h) by noninvasive ambulatory blood pressure monitoring, left ventricular mass/ height (LVM/H), and left ventricular ejection fraction (LVEF) by echocardiography and peak filling rate (PFR) by radionuclide study were also measured. ET levels were significantly (P < .05) higher in obese hypertensives and obese normotensives than in lean normotensives. In addition, ET levels were significantly (P < .05) higher in obese hypertensives than in obese normotensives. ET were directly related to LVM/ H (r = 0.86; P < .001) and MBP/24 h (r = 0.48; P < .009) but only in obese hypertensives. Multiple regression analysis indicated that ET-1 plasma levels remain an independent predictor of MBP/ 24 h and LVM/H also when age was included in the analysis. These data suggest that obesity-associated hypertension is characterized by an endothelial dysfunction that may contribute to the higher cardiovascular risk detectable in these patients.

PNPLA3 GG Genotype and Carotid Atherosclerosis in Patients with Non-Alcoholic Fatty Liver Disease

Background and Aim To evaluate if the presence of carotid atherosclerosis in patients with NAFLD, could be related to gene variants influencing hepatic fat accumulation and the severity of liver damage. Methods We recorded anthropometric, metabolic and histological data(Kleiner score) of 162 consecutive, biopsy-proven Sicilian NAFLD patients. Intima-media thickness(IMT), IMT thickening(IMT≥1 mm) and carotid plaques(focal thickening of >1.3 mm at the level of common carotid artery) were evaluated using ultrasonography. IL28B rs12979860 C>T, PNPLA3 rs738409 C>G, GCKR rs780094 C>T, LYPLAL1 rs12137855 C>T, and NCAN rs2228603 C>T single nucleotide polymorphisms were also assessed. The results were validated in a cohort of 267 subjects with clinical or histological diagnosis of NAFLD from Northern Italy, 63 of whom had follow-up examinations. Results Carotid plaques, IMT thickening and mean maximum IMT were similar in the two cohorts, whereas the prevalence of diabetes, obesity, NASH, and PNPLA3 GG polymorphism(21%vs.13%, p = 0.02) were significantly higher in the Sicilian cohort. In this cohort, the prevalence of carotid plaques and IMT thickening was higher in PNPLA3 GG compared to CC/CG genotype(53%vs.32%, p = 0.02; 62%vs.28%, p<0.001, respectively). These associations were confirmed at multivariate analyses (OR2.94;95%C.I. 1.12–7.71, p = 0.02, and OR4.11;95%C.I. 1.69–9.96, p = 0.002, respectively), although have been observed only in patients <50years. Also in the validation cohort, PNPLA3 GG genotype was independently associated with IMT thickening in younger patients only (OR: 6.00,95%C.I. 1.36–29, p = 0.01), and to IMT progression (p = 0.05) in patients with follow-up examinations. Conclusion PNPLA3 GG genotype is associated with higher severity of carotid atherosclerosis in younger patients with NAFLD. Mechanisms underlying this association, and its clinical relevance need further investigations.

Central obesity and hypertensive renal disease: association between higher levels of BMI, circulating transforming growth factor beta1 and urinary albumin excretion.

Objective: In this study, the relationship between circulating transforming growth factor β1 (TGFβ1) and urinary albumin excretion (UAE) has been investigated in non‐obese and central obese hypertensive patients. Design and Patients: Fifty‐eight consecutive hypertensive outpatients both lean and with central obesity were enrolled and divided in three groups, according to their body mass index (BMI) values. Group A: 16 lean hypertensives (men with BMI <25 kg/m 2 and women with BMI <24.7 kg/m 2 ); Group B: 16 overweight hypertensives (men with BMI ≥25 kg/m 2 and <30 kg/m 2 and women with BMI ≥24.7 kg/m 2 and <27.3 kg/m 2 ); Group C: 26 obese hypertensives (men with BMI ≥30 kg/m 2 and women with BMI ≥27.3 kg/m 2 ). Measures: In all patients, UAE, by immunonephelometric assay, circulating TGFβ1 by a solid‐phase specific sandwich enzyme‐linked immunosorbent assay (ELISA) technique, blood urea nitrogen (BUN) and creatinine, by routine laboratory methods, were determined. In addition, left ventricular telediastolic internal diameter (LVIDd), interventricular septum diastolic (IVSTd), posterior wall thickness (PWT), total and normalized to height 2.7 left ventricular mass (LVM, LVM/h 2.7 ), relative wall thickness (RWT) and left ventricular ejection fraction (EF) by M‐B Mode echocardiography were calculated. Results: Overweight and obese hypertensives had significantly (p < 0.05) higher BMI, waist–hip ratio (WHR), UAE and TGFβ1 than lean hypertensives. Obese hypertensives had significantly (p < 0.05) higher total and indexed LVM values than lean hypertensives. Obese hypertensives had significantly (p < 0.05) higher BMI, UAE and TGFβ1 than overweight hypertensives. In all subjects, TGFβ1 correlated directly with BMI (r = 0.52; p < 0.0001), WHR (r = 0.48; p < 0.003), MBP (r = 0.31; p < 0.02) and UAE (r = 0.57; p < 0.0001). Multiple regression analysis indicated that BMI, MBP and UAE were able to explain the 47.9% TGFβ1 variability (r = 0.69; p < 0.0001), and that TGFβ1 was the best predictor of UAE changes (r = 0.60; p < 0.0001). Conclusion: Our data suggest that TGFβ1 levels are positively associated with BMI, MBP and UAE in hypertensive subjects. This also indicates that TGFβ1 overproduction might be considered a pathophysiology mechanism of progressive renal function impairment in obese hypertensives.