Salvatore Paterna

Normal-sodium diet compared with low-sodium diet in compensated congestive heart failure: is sodium an old enemy or a new friend?

The aim of the present study was to evaluate the effects of a normal-sodium (120 mmol sodium) diet compared with a low-sodium diet (80 mmol sodium) on readmissions for CHF (congestive heart failure) during 180 days of follow-up in compensated patients with CHF. A total of 232 compensated CHF patients (88 female and 144 male; New York Heart Association class II-IV; 55-83 years of age, ejection fraction <35% and serum creatinine <2 mg/dl) were randomized into two groups: group 1 contained 118 patients (45 females and 73 males) receiving a normal-sodium diet plus oral furosemide [250-500 mg, b.i.d. (twice a day)]; and group 2 contained 114 patients (43 females and 71 males) receiving a low-sodium diet plus oral furosemide (250-500 mg, b.i.d.). The treatment was given at 30 days after discharge and for 180 days, in association with a fluid intake of 1000 ml per day. Signs of CHF, body weight, blood pressure, heart rate, laboratory parameters, ECG, echocardiogram, levels of BNP (brain natriuretic peptide) and aldosterone levels, and PRA (plasma renin activity) were examined at baseline (30 days after discharge) and after 180 days. The normal-sodium group had a significant reduction (P<0.05) in readmissions. BNP values were lower in the normal-sodium group compared with the low sodium group (685+/-255 compared with 425+/-125 pg/ml respectively; P<0.0001). Significant (P<0.0001) increases in aldosterone and PRA were observed in the low-sodium group during follow-up, whereas the normal-sodium group had a small significant reduction (P=0.039) in aldosterone levels and no significant difference in PRA. After 180 days of follow-up, aldosterone levels and PRA were significantly (P<0.0001) higher in the low-sodium group. The normal-sodium group had a lower incidence of rehospitalization during follow-up and a significant decrease in plasma BNP and aldosterone levels, and PRA. The results of the present study show that a normal-sodium diet improves outcome, and sodium depletion has detrimental renal and neurohormonal effects with worse clinical outcome in compensated CHF patients. Further studies are required to determine if this is due to a high dose of diuretic or the low-sodium diet.

Angiotensin-Converting Enzyme Gene Deletion Polymorphism Determines an Increase in Frequency of Migraine Attacks in Patients Suffering from Migraine without Aura

Many authors have reported an association between the angiotensin-converting enzyme (ACE)-D allele and coronary heart disease and other cardiovascular diseases. The mechanism underlying the positive associations between the ACE-D alleles and diseases are not yet clear. Previous reports showed an association between migraine without aura and ACE-D allele polymorphism. The study is aimed to evaluate if the DD genotype could also be associated with the frequency and duration of migraine without aura. In 302 patients suffering from migraine without aura (at least for 1 year), with no history of cardiovascular diseases and major risk factors for ischemic events, the genotypes of the ACE gene, plasma ACE activity, and the frequency (weekly) and duration of migraine attacks were evaluated. No drugs were given before (4 weeks) and during the study. The same evaluations were performed in 201 subjects without migraine. The molecular biologist and the physician evaluating the patient data were blinded to the clinical history and ACE-DD gene determination. Genotypes were determined by polymerase chain reaction amplification. Plasma ACE activity was performed by the HPLC method. The groups were similar for sex, age and smoking habit (migraines: 302 patients (200 F/102 M), mean age 37.8 ± 8.2 years; control: 201 subjects (127 F/74 M), mean age 37.5 ± 9.3 years). Patients with migraine without aura showed higher incidence of the ACE-DD gene (48.34%) than control subjects (37.32%), p < 0.05. The frequency of migraine (average attacks per week) was higher in patients with DD (2.11 ± 1.9) than in patients with ID (1.54 ± 1.44), p < 0.05. No difference in duration of migraine attacks (hours per week) was observed. Plasma ACE activity was increased in patients with the ACE-DD gene. Our data suggest that ACE-DD gene polymorphism could have an important role in determining migraine attacks and the frequency of these attacks. Further data are needed through further studies, especially on the biomolecular level.

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).

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.

Effect of physical training on exercise capacity, gas exchange and N-terminal pro-brain natriuretic peptide levels in patients with chronic heart failure

Background Decreased exercise capacity is the main factor restricting the daily life of patients with chronic heart failure. N-terminal pro-brain natriuretic peptide (NT pro-BNP) is strongly related to the severity of and is an independent predictor of outcome in chronic heart failure. Design The study aimed to evaluate the effect of exercise training on functional capacity and on changes in NT pro-BNP levels and to assess the effect of exercise training on quality of life. Materials and methods Sixty patients (45 men/15 women, mean age 52.7 years; ±5.3 SD), with stable heart failure (45 ischaemic/hypertensive and 15 idiopathic patients), in New York Heart Association (NYHA) functional class II (n = 35) to III (n = 25), with an ejection fraction less than 40%, were randomly assigned to a training (n = 30) and a control group (n = 30). The training group (30 patients) performed 3 months of supervised physical training programme using a bicycle ergometer for 30 min three times a week at a load corresponding to 60–70% of their oxygen consumption (Vo2) peak. The control group did not change their previous physical activity. A graded maximal exercise test with respiratory gas analysis and an endurance test with constant workload corresponding to 85% of the peak oxygen load at the baseline and after 3 months were performed, and at the same times NT pro-BNP levels were measured. Results The exercise capacity increased from 15.8 (±2.3 SD) to 29.9 (±2.1 SD) min (P<0.0001) and the peak Vo2 tended to improve from 14.5 (±1.4 SD) to 17.7 (±2.6 SD) ml/kg per min (P<0.0001) during the supervised training period. Vo2 at the anaerobic threshold increased from 12.9 (±1.0 SD) to 15.5 (±1.7 SD) ml/kg per min (P<0.0001). NT pro-BNP levels decreased from 3376 (±3133 SD) to 1434 (±1673 SD) pg/ml (P=0.043). The positive training effects were associated with an improvement in the NYHA functional class. Conclusion Physical training of moderate intensity significantly improves the exercise capacity and neurohormonal modulation in patients with chronic heart failure. This is associated with an alleviation of symptoms and improvement in quality of life.

Impact of ‘‘Off-Label’’ Use of Ivabradine on Exercise Capacity, Gas Exchange, Functional Class, Quality of Life, and Neurohormonal Modulation in Patients With Ischemic Chronic Heart Failure

Background: Epidemiologic studies indicate that elevated heart rate (HR) is an independent risk factor for mortality and morbidity in patients (pts) with chronic heart failure (CHF). Clinical trials with β-blockers suggest that HR reduction is an important mechanism of their benefit in pts with stable CHF. Pharmacologic inhibition of the If current now provides the opportunity of pure HR reduction. The purpose of this study was to evaluate the impact of ‘‘Off-Label’’ use of ivabradine on exercise capacity, gas exchange, functional class, quality of life, and neurohormonal modulation in pts with ischemic CHF. Methods: Between January 2008 and June 2008, a graded maximal exercise test with respiratory gas analysis and an endurance test with constant workload corresponding to 85% of the peak VO2 at the baseline and after 3 months were performed, and at the same times, N-terminal probrain natriuretic peptide (NT-proBNP) levels were also measured, in 60 pts (45 M, 15 F, mean age 52.7 ± 5.3 years), with stable ischemic CHF, New York Heart Association (NYHA) functional classes II (n = 35)—III (n = 25), with left ventricular ejection fraction (LVEF) ≤ 40%, randomized to a ‘‘off-label’’ ivabradine use (n = 30) and a control group (n = 30). Results: The exercise capacity increased from 14.8 ± 2.5 to 28.2 ± 3.5 min (P < .0001) and the peak oxygen consumption tended to improve from 13.5 ± 1.3 to 17.9 ± 2.4 mL/kg per minute (P < .0001) in ivabradine group. Oxygen consumption at the anaerobic threshold (AT) increased from 11.9 ± 1.4 to 15.3 ± 1.4 mL/kg per minute (P < .0001). NTproBNP levels decreased from 2356 ± 2113 pg/mL to 1434 ± 1273 pg/mL (P = .045). No significant differences were found in control group at 3 months. The positive ivabradine effects were also associated with an improvement in the NYHA functional class and quality of life. Conclusion: The ‘‘Off-Label’’ use of ivabradine significantly improves the exercise capacity, gas exchange, functional heart failure class, quality of life, and neurohormonal modulation in pts with ischemic CHF.