The present study clearly demonstrates that hyponatremia is the most prevalent electrolyte disturbance in patients hospitalized for HF [7, 8, 10]. Based on information on vital signs and symptoms at admission, this study also shows that patients with hyponatremia presented with more severe disease and their prognosis, in term of in-hospital mortality, was also worse. Compared to patients without hyponatremia during hospitalization, peripheral edema and ascites at admission were found to be more prevalent in patients who developed hyponatremia during hospitalization. Patients with more severe HF would potentially have these symptoms as a result of poor cardiac function, i.e. more severe ventricular dysfunction. Left ventricular ejection fraction (LVEF) has been well known as an indicator of cardiac pump function, in which lower LVEF indicates poorer cardiac pump function . In this study, the average of LVEF is not significantly different between patients with normonatremia and patients with hyponatremia during hospitalization, but the average was calculated from only 47.6 % and 43.4 % of patients with and without hyponatremia during hospitalization, respectively. In their research, Sato et al. reported signs of a difference LVEF between these groups but this was not significant .
This study found that a higher proportion of patients developing hyponatremia during hospitalization had a history of hospitalization for cardiac diseases but the disease was not mentioned specifically in medical records. Previous published studies also reported that more hyponatremic patients have previous hopstalization for HF compared to nonhyponatremic patients [8, 13] and this might be related to the poorer condition of HF in hyponatremic patients. Renal failure was the only one concomitant diagnosis found in this study with a significant correlation between hyponatremic and non-hyponatremic patients but serum creatinine of both groups was found not significantly different. However, the average of blood urea nitrogen in hyponatremic patients was found higher than non-hyponatremic patients. In acute conditions, serum creatinine of HF patients may be increased owing to hypoperfusion and congestion  and worsening renal function in HF patients with congestion has been found as a predictor for poorer prognosis . Liver function abnormality, detected by AST and ALT, was also found higher in patients with hyponatremia during hospitalization in this study. In HF patients, liver function abnormalities indicate the presence of cardio-hepatic syndrome and, specifically, higher level of AST and or ALT indicates ischemia within hepatocytes that should be considered both in managing the patients and predicting of long-term outcome .
In term of medication administered during hospitalization, patients with hyponatremia during hospitalization received less ACEIs or ARBs compared to patients with normonatremia. In contrast, patients with hyponatremia received more amiodarone, heparin, insulin and antibiotics. This information on medication might also indicate more severe condition of patients with hyponatremia. The most used ACEIs or ARBs are administered orally and patients with severe condition would have difficulty to take oral medication. In contrast, amiodarone and heparin are administered parenterally and mostly used in patients with severe conditions. However, the rate of overall use of ACEIs or ARBs found in this study at 75 % is higher compared to the rate reported by Callender et al.  in their systematic review on HF in low-middle income countries and Siswanto et al.  in their study on HF in Indonesia, 57 % and 68 %, respectively.
Other than patient’s condition before and at admission, this study found that medication administered during hospitalization could also worsen hyponatremia. While higher serum sodium level at admission and history of hypertension lowers the risk of hyponatremia during hospitalization, history of fatigue before admission and the presence of ascites at admission conversely increase the risk. Patients received heparin and antibiotics in this study appeared to have around a three fold higher risk of developing hyponatremia during hospitalization with odds ratio 3.85 (95 % CI 1.78-8.31) and 3.08 (1.71-5.53), respectively. While heparin has been known can induce hyponatremia , administration of antibiotics might induce hyponatremia by involving a complex association with pathophysiological process of infection.
The overall in-hospital mortality rate found in this study is 11 % and this is higher than the average of in-hospital mortality rates reported by Siswanto, et al. in their report on behalf of The Acute Decompensated Heart Failure National Registry (ADHERE) research team in Indonesia at 6.7 % .
This is also higher compared to in-hospital mortality rates of HF patients in developing countries reported by Callender, et al.  and in Asia Pacific reported by Atherton, et al. , 8 % and 4.8 %, respectively. The higher in-hospital mortality rate found in this study might be due to more severe conditions of the patients included in this study. In their report, Siswanto, et al. found that patients hospitalized for HF in Indonesia tend to have severe symptoms and lower LVEF . It is a challenge for primary care providers and general practitioners in Indonesia to improve management of HF so that patients with HF will be not delayed to receive appropriate treatment .
While previous studies have revealed the association between hyponatremia on admission and in-hospital mortality in patients hospitalized for HF [8, 26, 27], the results of this study are slightly different. Instead of hyponatremia on admission, hyponatremia during hospitalization was found to have an association with in-hospital mortality as shown in Table 4. In this study, only 56 % of patients developing hyponatremia during hospitalization were hyponatremic on admission and this means that 45 out of 464 patients (9.7 %) included in this study developed hospital-acquired hyponatremia. In a study with unselected patients, hospital-acquired hyponatremia was found in around one third of hospitalized patients and the condition was associated with increase of length of hospital stay and in-hospital mortality . Therefore, factors associated with increased risk of developing hyponatremia during hospitalization in patients hospitalized for HF are important to be studied.
Other than serum sodium levels several other factors should be considered to assess the hyponatremic status of a patient hospitalized for HF. Although HF patients have a high probability of developing hypervolemic hyponatremia, the possibility of the occurrence of pseudo-hyponatremia and other types of hyponatremia need also to be considered in order to administer appropriate management. Pseudo-hyponatremia, for instance, should be considered in HF patients with hyperglycemia or hypercholesterolemia .
As the use of arginine vasopressin receptor antagonists, also known as the vaptans, in patients with HF have been approved, American College Cardiology Foundation/American Heart Association put these drugs on their recommendation for managing HF patients developing hypervolemic hyponatremia . However, role of the vaptans in reducing all-cause mortality and cardiovascular mortality in patients with HF, including their acceptability for long-term use, are still questionable [31–33].
While the vaptans are now might be available in some developed countries, it is not easy to provide these drugs in developing countries due to the cost of the medication. Therefore, the first strategy to minimize hyponatremia-related problem in patients hospitalized for HF should be to optimize guideline-driven therapy and to assess hyponatremia more appropriately [34–37]. Furthermore, conventional options for managing hyponatremia such as the use of saline solution, either isotonic or hypertonic, are still important to be considered [29, 38, 39].
This study was conducted in a single tertiary referral hospital, as the number of tertiary hospitals in Indonesia are more limited compared to secondary hospitals, this study might not be true representation of the whole population hospitalized for HF In Indonesia. Hence, further studies involving more centers and secondary hospitals need to be conducted to get better picture on hyponatremia in patients hospitalized for HF in Indonesia.
Patients included in this study were only HF patients hospitalized with code I50.0 as their main diagnosis in which the code is only for patients with congestive HF and patients with right ventricular failure (secondary to left HF). Therefore, other types of HF were not included in this study.
Furthermore, hyponatremia in this study was only assessed by serum sodium level. Hence, patients’ hyponatremic status could not be differentiate whether it was euvolemic, hypervolemic or might be pseudo-hyponatremia.
As frequently occurrs with retrospective studies, some important information, such as information on medication history before hospitalization, could not also be gathered in this study.