Due to the disease’s complex underlying pathophysiology, optimal volume management in acute heart failure patients is important but complicated. The main goal of decompensated heart failure is to eliminate additional intravascular and extravascular fluid, as well as alleviate congestive signs and symptoms [1].

The peptide hormone, brain natriuretic peptide (BNP), which is secreted primarily by ventricular myocytes in response to cardiac wall stretching and distension, is essential for volume homeostasis. Measurement of plasma brain natriuretic peptide had been proposed as marker of diagnosis of volume overload and prognostication in HF patients [2]. However, the test is costly and not readily available at each healthcare centre.

HCT measurement has been proposed as a suitable surrogate for volume status measurement because it is readily available and less costly than BNP [3]. Achievement of haemoconcentration in hospitalized AHF patients had been shown leading to better survival, compared to those that do not achieve haemoconcentration [3, 4, 5]. However, such data unfortunately remain scarce within most South-East Asian countries, such as Malaysia. As a result, the aim of this research is to see if achieving haemoconcentration prior to discharge is linked to a lower risk of re-admission in inpatient AHF patients.

Heart failure (HF) is a clinical symptom that occurs at the conclusion of most heart diseases. The frequency of HF ranges from 3 to 20 per 1000 population, and it can be as high as 100 per 1000 population in those over the age of 65 [7]. Heart failure can be classified into 3 classes; (i) heart failure with preserve ejection fraction (HFpEF) EF $\ge$50%, (ii) HF with midrange ejection fraction EF 40–49% (HFmrEF), (iii) and Heart failure with reduced ejection fraction, EF 40% (HFrEF) [8].

AHF is described as the onset of new or worsening HF symptoms in a short period of time [9]. Most of time, AHF patients require recurrent hospitalization and urgent therapy to relive their symptoms. In Malaysia, AHF accounts for 6% to 10% of all acute hospital admissions [10].

HF also carries poor prognosis. A landmark registry in United States of America (USA), OPTIMIZE-HF showed that within 3 months of an index HF hospitalization, there is 30% readmission rate and an associated 10% mortality rate [11]. 1-year mortality rate for a patient that been admitted for AHF is around 30% [12].

From a financial perspective, management of HF patients is also associated with increased healthcare expenditures. In 2012, the global economic impact of Heart failure was projected to be $\$$108 billion a year [13]. In Malaysia, the total cost of heart failure was projected to be $\$$USD 194 million (MYR 785 million), with direct and indirect expenses of $\$$USD 12 million (MYR 48.7 million), and $\$$USD 182 million (MYR 740 million) correspondingly, accounting for around 1.8 percent of total health spending [13].

AHF is caused by a variety of causes. The majority of patients hospitalised with AHF exhibit volume overload, according to data from the Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure (OPTIMIZE-HF) [11] and Acute Decompensated Heart Failure Registry (ADHERE) registries [14].

The fluid flow within and outside the vessel maintains a dynamic balance under physiological circumstances. Haemoconcentration occurs when intravascular fluid is lost quicker than it can be replenished by extravascular fluid. Evidence suggested that measurement of BNP in HF patients reflected the intravascular volume status and also disease severity. A study been done by Pimenta et al. [15] in 2010 to investigate the relation of volume status, measured by thoracic fluid content (TFC), with regards to BNP level. The study showed that those with higher TFC value (volume overload) had higher BNP level (BNP $>$1000 pg/mL). Statistically, multivariable linear regression study indicated that TFC is a significant determinant of the BNP level ($\beta$ = 0.043, 95% CI 0.024–0.062, p 0.001). Aside from that, the study discovered that severe systolic dysfunction is a robust predictor of BNP levels (p = 0.001) ($\beta$ = 0.831, 95% CI 0.449–1.212). According to the BNP Consensus Panel, higher BNP levels are inversely proportionate to cardiac output and are strongly connected with intraventricular pressure, pulmonary pressure, prognosis, and New York Heart Association (NYHA) score [16].

Aside from BNP, pulmonary artery catheterization measurements (central venous pressure, pulmonary capillary wedge pressure) [17] and tracer methods (i.e., I131-tagged albumin) can be employed to assess intravascular volume status [18]. However, these procedures are frequently invasive, time-consuming, and costly, and they are not easily available in every healthcare facility.

Haemoconcentration, defined as a rise in haemoglobin (Hb), HCT, or plasma albumin, has been proposed as a suitable surrogate for assessing volume status changes [3, 4]. Studies showed that achievement of haemoconcentration is linked with better result.

Testani et al. [3] analysed the landmark ESCAPE study [19] and found that patients with haemoconcentration got larger doses of loop diuretics, lost more weight/fluid, and had bigger decreases in filling pressures (p 0.05 for all), but at the risk of decreasing renal function (OR = 5.3, p 0.001). They also discovered that people in the haemoconcentration group had a decreased 180-day death rate (HR = 0.31, p = 0.013).

Van der Meer et al. [4] found that an increase in Hb is linked to increase in HCT (p 0.01), greater weight loss (p 0.01), and improved 180-day survival (p = 0.002, 95% confidence interval: 0.51 to 0.86, hazard ratio: 0.66) [20]. However, they also discovered that this group of patients is at risk of deteriorating renal function (p = 0.01, percentage change in creatinine +6.4 $\pm$ 26 vs. +3.1 $\pm$ 26).

According to a study by Zhou et al. [6], Increased HCT during hospitalisation is related with a decreased risk of all-cause mortality compared to those who do not demonstrate an increase in HCT [p 0.001, 95% confidence interval (CI) 0.24–0.63, hazard ratio (HR) 0.39]. They discovered that decreasing renal function did not differ substantially between the two groups (p = 0.15).

This present study has demonstrated that change in HCT and ejection fraction is strong predictors for readmission due to AHF among patients hospitalized with acute heart failure. We found that patients that do not achieve hemoconcentration prior to discharge had higher risk of readmission due to AHF, when compared to those that achieved hemoconcentration. This finding is consistent with previous studies showing patients hospitalized for HF that achieved hemoconcentration had more favorable outcome, when compared to those without hemoconcentration [3, 4, 5, 6].

When compared to HFpEF, patients with HFrEF had a greater risk of readmission, but HFmrEF appeared to be a protective factor against readmission. Interestingly, previous data on readmission risk had shown conflicting results when taking EF as a predictor for readmission.

For example, Cheng et al. [21] discovered that in the HFrEF population, HF-specific readmissions were greater than in the HFpEF population, with 30.9% vs. 24.3% at 1 year respectively and 9.0% vs. 6.1% at 30 days (p 0.001).

However, a metaanalysis by Altaie et al. [22] in the HFmrEF population found that the probability of an heart failure associated readmission was identical in HFmrEF compared to HFpEF or HFrEF. according to a recent research by Santas et al. [23], when compared to patients with HFrEF or HFpEF, patients with HFmrEF had a similar rehospitalization cost and a similar likelihood of recurring all-cause and heart failure-related admissions after an Acute heart failure stay.

In HFrEF patients, improvement in EF has been found to be a positive prognostic measure. Ghimire et al. [24] found that HF with recovery EF (HFrecEF) , defined as EF improvement of $\ge$10% on the follow-up echocardiagram, demonstrated lower rates per 1000 patient years of mortality (aHR 0.70 [0.62–0.79], adjusted hazard ratio, 106 vs. 164), cardiac transplantation or left ventricular assist device implantation (aHR 0.21 [0.10–0.45], 2 vs. 10), all-cause emergency room (ER) visits (aHR 0.88 [0.81–0.95], 569 vs. 799), and all-cause hospitalizations (aHR 0.87 [0.79–0.95], 300 vs. 428) compared to patients with persistent HFrEF.

Unlike all the results of landmark studies and guideline, we found that prescription of the standard medical therapies drugs, namely renin-angiotensin system (RAS) blockade [25], beta blocker (BB) [26], aldosterone antagonist [27] and diuretic [28], were not significantly associated with reduction in readmission. This might be described by the differences in study designs patients’, concomitant medical therapy, and background. For example, the MERIT-HF study [26] investigated patients with chronic and stabile with LVEF $\le$40 as opposed to all (HFrEF, HFpEF and HFmrEF) hospitalised acute decompensated HF patients in our study. Studies of Left Ventricular Dysfunction (SOLVD) Treatment Trial [25] on the other hand, due to its strict exclusion criteria comprises only 6.4% patients with HFrEF compared to our study of 63.7%. Furthermore, we found sub-optimal prescribing rate especially in RAS blocker in our study patients. The low prescription rate in RAS blockade is also seen our Malaysian national cardiovascular database registry for ACS which shows RAS blockage prescription rate of only around 50% [29, 30]. The possible limiting factors would be hypotension, worsening kidney function or physician’s cautions in prescribing RAS blockage in patients with impaired kidney function.

Time to event analysis results showed that those with haemoconcentration tend to be readmitted earlier after discharge, compared to those that did not achieve haemoconcentration, despite haemoconcentration is a protective factor from readmission. So far there is no comparable data available. We hypothesized that this is maybe because of other unmeasurable confounding factors, such as fluid restriction and also patient’s compliance to medication. Further studies are needed to further determine this association.

Our study has limitation that need to be emphasised. This research was a retrospective single-centred analysis, which may not give the full picture of all AHF admission. Furthermore, using HCT change as a substitute for direct measures of plasma volume to check for changes in volume status may be insufficiently precise. In example, compared to volume overload state in AHF which leads to low HCT level (haemodilution), HCT level also will be low in a case of gastrointestinal bleed, which in this situation, patient will be in volume depleted state. According to Van der Meer et al. [4] remaining congestion was seen in 41% of patients with haemoconcentration and 53% of patients without haemoconcentration. This demonstrates that despite haemoconcentration, a large number of patients have clinically persisting congestion. We were also unable to eliminate out any measured and unmeasured confounding variables that may have influenced the results. Compliance to medications, fluid and salt restrictions and achievement of optimum doses of guideline- recommended drugs were not taken into analysis. Finally, further additional relevant data to support the assessment of plasma volume such as serum albumin level, NYHA class status, clinical decongestion assessment at discharge and total net fluid balance were not available.

Our study found that haematocrit change is a reliable predictor for AHF readmission and potential therapeutic target in HF. Patients with AHF who achieve haemoconcentration before to release are less likely to be readmitted for AHF within 90 days. We also found that patients with reduced EF are more likely to be readmitted for AHF compared to other groups. Therefore, we recommend on practice of monitoring of the haematocrit level prior to discharge among all AHF patients. Those that do not achieve haemoconcentration likely will benefit from higher dosage of diuretics and earlier follow up. We also recommend on active measures to improve patients’ EF, either medically (optimize anti-failure as per GDMT) or invasively (percutaneous angiogram, left ventricle assist device) to improve overall outcome. Additional large-scale, prospective, randomised controlled trials are needed to validate and describe the link between short-term changes in HCT and prognosis, as well as to establish effective volume management techniques for AHF patients.

MZAS and HMI designed the study. The study and data analysis were carried out by MDI and ZMAM. Editorial modifications in the manuscript were made by all writers. The final manuscript was reviewed and approved by all authors.

All patients gave their informed consent for inclusion before they participated in the study. The study was conducted in accordance with the Declaration of Helsinki, and the protocol was approved by the University Malaya Medical Centre Ethics Committee (20201126-9539).

We would like to thank everyone who assisted us throughout the research and drafting of this publication. Thank you to all of the peer reviewers who contributed their ideas and opinions.

This study received no external funding.

The authors declare no conflict of interest.