Lower serum sodium is associated with increased short-term mortality in hospitalized patients with worsening heart failure - Results from the Outcomes of a Prospective Trial of Intravenous Milrinone for Exacerbations of Chronic Heart Failure (OPTIME-CHF) study

University of North Carolina at Chapel Hill, North Carolina, United States
Circulation (Impact Factor: 14.43). 05/2005; 111(19):2454-60. DOI: 10.1161/01.CIR.0000165065.82609.3D
Source: PubMed


The prognostic value of serum sodium in patients hospitalized for worsening heart failure has not been well defined.
The Outcomes of a Prospective Trial of Intravenous Milrinone for Exacerbations of Chronic Heart Failure (OPTIME-CHF) study randomized 949 patients with systolic dysfunction hospitalized for worsening heart failure to receive 48 to 72 hours of intravenous milrinone or placebo in addition to standard therapy. In a retrospective analysis, we investigated the relationship between admission serum sodium and the primary end point of days hospitalized for cardiovascular causes within 60 days of randomization, as well as the secondary end points of in-hospital mortality, 60-day mortality, and 60-day mortality/rehospitalization. The number of days hospitalized for cardiovascular causes was higher in the lowest sodium quartile: 8.0 (4.5, 18.5) versus 6 (4, 13) versus 6 (4, 11.5) versus 6 (4, 12) days (P<0.015 for comparison with the lowest quartile). Lower serum sodium was associated with higher in-hospital and 60-day mortality: 5.9% versus 1% versus 2.3% versus 2.3% (P<0.015) and 15.9% versus 6.4% versus 7.8% versus 7% (P=0.002), respectively. There was a trend toward higher mortality/rehospitalization for patients who were in the lowest sodium quartile. Multivariable-adjusted Cox proportional hazards analysis showed that serum sodium on admission, when modeled linearly, predicted increased 60-day mortality: sodium (per 3-mEq/L decrease) had a hazard ratio of 1.18 with a 95% CI of 1.03 to 1.36 (P=0.018).
In patients hospitalized for worsening heart failure, admission serum sodium is an independent predictor of increased number of days hospitalized for cardiovascular causes and increased mortality within 60 days of discharge.

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Available from: Gary Michael Felker, Dec 12, 2013
    • "As expected and similar with previous studies, the incidence of adverse effects associated with the pharmacological effects of the drug like dry mouth and thirst was seen frequently in patients after receiving tolvaptan.[4567891011121321] This was unusual in our study that some patients had hypernatremia and worsening of renal function after starting tolvaptan treatment. "
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    ABSTRACT: In acute decompensated heart failure (ADHF), diuretic use, the mainstay therapy for congestion, is associated with electrolyte abnormalities and worsening renal function. Vasopressin mediates fluid retention in heart failure. In contrast to diuretics, the vasopressin antagonist tolvaptan may increase net volume loss in heart failure without adversely affecting electrolytes and renal function. Hyponatremia (serum sodium concentration, <135 mEq/L) is a predictor of death among patients with heart failure.
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    • "Hyponatremia has been generally associated with an increased mortality in different conditions such as pneumonia [12], heart failure [13], acute myocardial infarction [14], cirrhosis [15], cancer [14], in the elderly [16], and in intensive care patients [17]. However, whether hyponatremia is an independent risk factor for death or is simply associated with an underlying severe condition that is the cause of death remains to be elucidated [4], [18]. "
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    • "However, these studies have primarily focused on in-hospital and early post-discharge mortality. Moreover, the OPTIME-CHF study, was performed using the patient data derived from a large clinical trial with restricted inclusion criteria, such as markedly reduced LVEF of ≤30%, lower serum creatinine levels of ≤3 mg/dL, and systolic blood pressure ≥80 mmHg[1]. The present study extended the prognostic impact of hyponatremia during the long-term follow-up over 2 years and more importantly to a nonselected HF population encountered in routine clinical practice by analyzing the registry data of hospitalized HF patients in Japan. "
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    ABSTRACT: Hyponatremia is common and is associated with poor in-hospital outcomes in patients hospitalized with heart failure (HF). However, it is unknown whether hyponatremia is associated with long-term adverse outcomes. The purpose of this study was to clarify the characteristics, clinical status on admission, and management during hospitalization according to the serum sodium concentration on admission, and determine whether hyponatremia was associated with in-hospital as well as long-term outcomes in 1677 patients hospitalized with worsening HF on index hospitalization registered in the database of the Japanese Cardiac Registry of Heart Failure in Cardiology (JCARE-CARD). We studied the characteristics and in-hospital treatment in 1659 patients hospitalized with worsening HF by using the JCARE-CARD database. Patients were divided into 2 groups according to serum sodium concentration on admission <135mEq/mL (n=176; 10.6%) or ≥135mEq/mL (n=1483; 89.4%). The mean age was 70.7 years and 59.2% were male. Etiology was ischemic in 33.9% and mean left ventricular ejection fraction was 42.4%. After adjustment for covariates, hyponatremia was independently associated with in-hospital death [adjusted odds ratio (OR) 2.453, 95% confidence interval (CI) 1.265-4.755, p=0.008]. It was significantly associated also with adverse long-term (mean 2.1±0.8 years) outcomes including all-cause death (OR 1.952, 95% CI 1.433-2.657), cardiac death (OR 2.053, 95% CI 1.413-2.983), and rehospitalization due to worsening HF (OR 1.488, 95% CI 1.134-1.953). Hyponatremia was independently associated with not only in-hospital but also long-term adverse outcomes in patients hospitalized with worsening HF.
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