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      The prognosis of heart failure patients: Does sodium level play a significant role?

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          Abstract

          Introduction

          Heart failure (HF), a major cardiovascular disorder, remains a grievous clinical condition regardless of advances in medical care. Hyponatremia is classified as a serum sodium concentration of <135 mEq/L, and the prevalence, clinical impact and prognostic factor of hyponatremia in heart failure patients varies widely. The current study was conducted with the aim of assessing the prevalence of hyponatremia in patients hospitalized with a diagnosis of HF and comparing baseline clinical characteristic of HF patients based on their sodium status. Survival difference between patients with hyponatremia and normonatremia was also assessed and the clinical prognostic indicators of overall mortality in HF patients were evaluated.

          Method

          A retrospective cohort study was conducted to assess medical records of heart failure patients who were admitted to Gondar University Referral Hospital. Patients were categorized based on their sodium level status at their first admission to the internal medicine department. Each patient was assigned to either of the following groups: hyponatremia if sodium < 135 mmol/L, or normonatremia if sodium ≥ 135 mmol/L.

          Result

          Among 388 participants, the prevalence of hyponatremia in the study cohorts was 51.03%. Kaplan-Meier survival curves showed that there was a significant difference in survival status of HF patients among the two cohorts (Log—Rank test, P <0.0001). Hence, patients with normal sodium levels had a higher chance of survival over hyponatremic patients. Multivariate Cox regression has revealed a statistically significant association of mortality with the following variables: advanced age (AHR = 1.035 (1.012–1.058), P = 0.003), hyponatremia (AHR = 4.003 (1.778–9.009), P = 0.001), higher creatinine level (AHR = 1.929 (1.523–2.443), P = <0.0001) and, prescription of angiotensin-converting enzyme inhibitors (AHR = 0.410 (0.199–0.842), P = 0.015) and spironolactone (AHR = 0.511 (0.275–0.949), P = 0.033.

          Conclusion

          In conclusion, hyponatremia is one of the crucial factors in the clinical prognosis of heart failure patients. However, as other prognostic factors (i.e. medication, creatine level, and age) also played vital roles in overall survival, well-controlled clinical trials (complete with medication dosing, laboratory outputs and long-term prospective follow up) are required to further study the impact of hyponatremia in HF patient’s prognosis in low income nations.

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          Most cited references51

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          Epidemiology and risk profile of heart failure.

          Heart failure (HF) is a major public health issue, with a prevalence of over 5.8 million in the USA, and over 23 million worldwide, and rising. The lifetime risk of developing HF is one in five. Although promising evidence shows that the age-adjusted incidence of HF may have plateaued, HF still carries substantial morbidity and mortality, with 5-year mortality that rival those of many cancers. HF represents a considerable burden to the health-care system, responsible for costs of more than $39 billion annually in the USA alone, and high rates of hospitalizations, readmissions, and outpatient visits. HF is not a single entity, but a clinical syndrome that may have different characteristics depending on age, sex, race or ethnicity, left ventricular ejection fraction (LVEF) status, and HF etiology. Furthermore, pathophysiological differences are observed among patients diagnosed with HF and reduced LVEF compared with HF and preserved LVEF, which are beginning to be better appreciated in epidemiological studies. A number of risk factors, such as ischemic heart disease, hypertension, smoking, obesity, and diabetes, among others, have been identified that both predict the incidence of HF as well as its severity. In this Review, we discuss key features of the epidemiology and risk profile of HF.
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            The effect of digoxin on mortality and morbidity in patients with heart failure.

            (1997)
            The role of cardiac glycosides in treating patients with chronic heart failure and normal sinus rhythm remains controversial. We studied the effect of digoxin on mortality and hospitalization in a randomized, double-blind clinical trial. In the main trial, patients with a left ventricular ejection fraction of 0.45 or less were randomly assigned to digoxin (3397 patients) or placebo (3403 patients) in addition to diuretics and angiotensin-converting-enzyme inhibitors (median dose of digoxin, 0.25 mg per day; average follow-up, 37 months). In an ancillary trial of patients with ejection fractions greater than 0.45, 492 patients were randomly assigned to digoxin and 496 to placebo. In the main trial, mortality was unaffected. There were 1181 deaths (34.8 percent) with digoxin and 1194 deaths (35.1 percent) with placebo (risk ratio when digoxin was compared with placebo, 0.99; 95 percent confidence interval, 0.91 to 1.07; P=0.80). In the digoxin group, there was a trend toward a decrease in the risk of death attributed to worsening heart failure (risk ratio, 0.88; 95 percent confidence interval, 0.77 to 1.01; P=0.06). There were 6 percent fewer hospitalizations overall in that group than in the placebo group, and fewer patients were hospitalized for worsening heart failure (26.8 percent vs. 34.7 percent; risk ratio, 0.72; 95 percent confidence interval, 0.66 to 0.79; P<0.001). In the ancillary trial, the findings regarding the primary combined outcome of death or hospitalization due to worsening heart failure were consistent with the results of the main trial. Digoxin did not reduce overall mortality, but it reduced the rate of hospitalization both overall and for worsening heart failure. These findings define more precisely the role of digoxin in the management of chronic heart failure.
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              Effects of oral tolvaptan in patients hospitalized for worsening heart failure: the EVEREST Outcome Trial.

              Vasopressin mediates fluid retention in heart failure. Tolvaptan, a vasopressin V2 receptor blocker, shows promise for management of heart failure. To investigate the effects of tolvaptan initiated in patients hospitalized with heart failure. The Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study With Tolvaptan (EVEREST), an event-driven, randomized, double-blind, placebo-controlled study. The outcome trial comprised 4133 patients within 2 short-term clinical status studies, who were hospitalized with heart failure, randomized at 359 North American, South American, and European sites between October 7, 2003, and February 3, 2006, and followed up during long-term treatment. Within 48 hours of admission, patients were randomly assigned to receive oral tolvaptan, 30 mg once per day (n = 2072), or placebo (n = 2061) for a minimum of 60 days, in addition to standard therapy. Dual primary end points were all-cause mortality (superiority and noninferiority) and cardiovascular death or hospitalization for heart failure (superiority only). Secondary end points included changes in dyspnea, body weight, and edema. During a median follow-up of 9.9 months, 537 patients (25.9%) in the tolvaptan group and 543 (26.3%) in the placebo group died (hazard ratio, 0.98; 95% confidence interval [CI], 0.87-1.11; P = .68). The upper confidence limit for the mortality difference was within the prespecified noninferiority margin of 1.25 (P<.001). The composite of cardiovascular death or hospitalization for heart failure occurred in 871 tolvaptan group patients (42.0%) and 829 placebo group patients (40.2%; hazard ratio, 1.04; 95% CI, 0.95-1.14; P = .55). Secondary end points of cardiovascular mortality, cardiovascular death or hospitalization, and worsening heart failure were also not different. Tolvaptan significantly improved secondary end points of day 1 patient-assessed dyspnea, day 1 body weight, and day 7 edema. In patients with hyponatremia, serum sodium levels significantly increased. The Kansas City Cardiomyopathy Questionnaire overall summary score was not improved at outpatient week 1, but body weight and serum sodium effects persisted long after discharge. Tolvaptan caused increased thirst and dry mouth, but frequencies of major adverse events were similar in the 2 groups. Tolvaptan initiated for acute treatment of patients hospitalized with heart failure had no effect on long-term mortality or heart failure-related morbidity. clinicaltrials.gov Identifier: NCT00071331
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Writing – original draft
                Role: Data curationRole: InvestigationRole: Writing – original draftRole: Writing – review & editing
                Role: Data curationRole: Methodology
                Role: SupervisionRole: Writing – review & editing
                Role: Data curationRole: Investigation
                Role: Data curationRole: MethodologyRole: Supervision
                Role: SupervisionRole: Writing – review & editing
                Role: InvestigationRole: MethodologyRole: SoftwareRole: Supervision
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                8 November 2018
                2018
                : 13
                : 11
                : e0207242
                Affiliations
                [1 ] Department of Clinical Pharmacy, School of Pharmacy, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia
                [2 ] Department of Learning, Informatics, Management, and Ethics (LIME), Karolinska Institutet, Solna, Sweden
                [3 ] Department of Internal Medicine, United Arab Emirates University, Al Ain, United Arab Emirates
                [4 ] School of Pharmacy, University of Queensland, Brisbane, Australia
                Osaka University Graduate School of Medicine, JAPAN
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                http://orcid.org/0000-0002-9367-7592
                http://orcid.org/0000-0002-9205-9442
                Article
                PONE-D-18-18280
                10.1371/journal.pone.0207242
                6224129
                30408132
                d5690013-86a0-4dfc-8946-8da0e9813c6d
                © 2018 Abebe et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 13 August 2018
                : 26 October 2018
                Page count
                Figures: 1, Tables: 4, Pages: 14
                Funding
                The authors received no specific funding for this work.
                Categories
                Research Article
                Medicine and Health Sciences
                Cardiology
                Heart Failure
                Biology and Life Sciences
                Biochemistry
                Biomarkers
                Creatinine
                Medicine and Health Sciences
                Diagnostic Medicine
                Prognosis
                Medicine and Health Sciences
                Cardiovascular Medicine
                Cardiovascular Diseases
                Medicine and Health Sciences
                Pharmacology
                Drugs
                Diuretics
                Biology and Life Sciences
                Population Biology
                Population Metrics
                Death Rates
                Medicine and Health Sciences
                Cardiology
                Arrhythmia
                Atrial Fibrillation
                Medicine and Health Sciences
                Cardiology
                Custom metadata
                All relevant data are within the paper and its Supporting Information files.

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                Uncategorized

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