Clinical Investigation
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)

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Abstract

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.

Section snippets

MATERIALS AND METHODS

The target population for this trial was patients with NYHA class III HF from ischemic or nonischemic origin. The patients signed informed consent and release of medical information forms before enrolment. The ethical committee approved the protocol only as single-blind study.

RESULTS

Of the 4728 patients consecutively admitted to hospital with worsening HF, 1578 were in NYHA class > III, 158 in NYHA class < III, 143 showed cerebral vascular disease or dementia, 61 cancer, 96 uncompensated diabetes, 85 inability to give informed consent and 63 severe hepatic disease, 186 required pacemaker implantation, 43 had previous cardiac resynchronization therapy implantation and 83 an alcoholic habit. Only 37 patients maintained the NYHA class III at discharge, 139 declined to take

DISCUSSION

The study explores the sodium management in patients with HF both in acute phases (hospitalization) and in chronic phases (after discharge) when the patients had reached a compensated state. Although, in the acute phase, the HSS determined a faster resolution of congestive state without determining renal dysfunction or Na reduction and renin angiotensin aldosterone system (RAAS) activation, in the chronic phases (compensated state), a moderate Na restriction allowed to maintain a good renal

ACKNOWLEDGMENTS

We sincerely thank Prof. Michael H. Alderman for his invaluable contribution and assistance in this manuscript preparation.

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