Heart failure (HF) as defined by the 2021 ESC guidelines, is a clinical syndrome characterized by typical symptoms and signs resulting from structural and/or functional cardiac abnormalities, leading to reduced cardiac output and/or elevated intracardiac pressures ¹ HF continues to represent a major clinical and public health challenge, contributing substantially to hospital admissions and healthcare utilization worldwide. Although advances in cardiovascular care have improved survival, the burden of HF remains high, largely driven by recurrent episodes of congestion. ² From a pathophysiological standpoint, congestion is not a uniform process but rather a complex interaction between circulating plasma volume expansion and elevated venous pressures. These changes promote fluid redistribution across both intravascular and extravascular compartments, ultimately leading to the clinical manifestations of HF. However, this multidimensional nature of congestion is often difficult to capture using routine clinical assessment alone. ^{3, 4}

Traditional measures such as left ventricular ejection fraction (LVEF) play an important role in classifying HF and guiding therapy, yet they do not consistently reflect the degree of volume overload. ⁵ This limitation is particularly evident in patients with preserved ejection fraction, where symptoms may be disproportionate to measurable systolic dysfunction ⁶ In response to these challenges, there has been increasing interest in objective and easily accessible markers of congestion. Estimated plasma volume status (ePVS), derived from standard laboratory parameters, has been proposed as a surrogate for intravascular volume expansion. ⁷ In parallel, the inferior vena cava collapsibility index (IVC-CI), obtained through bedside ultrasound, provides insight into venous return dynamics and right atrial pressure. ^{8, 9}

Despite their growing use, these parameters are typically assessed independently. Considering that congestion in HF involves multiple physiological compartments, ⁵ evaluating these measures together may offer a more comprehensive and clinically relevant perspective. To our knowledge, this study is among the first to integrate estimated plasma volume status and inferior vena cava collapsibility index to characterize congestion across heart failure phenotypes, providing a more practical and multidimensional approach to volume assessment. This study provides a novel integrative approach by simultaneously evaluating intravascular and venous components of congestion using two readily available and non-invasive markers.

A total of 198 patients with heart failure were included in this study. The mean age of patients was 54.88 ± 14.81 years, with a predominance of male patients (67.2%). Hypertension was the most common comorbidity (58.5%), followed by diabetes mellitus (31.8%), coronary artery disease (21.7%), and chronic kidney disease (6.5%) ( Table 1).

At admission, patients demonstrated a mean estimated plasma volume status (ePVS) of 5.26 ± 1.38 and a mean inferior vena cava collapsibility index (IVC-CI) of 19.07 ± 9.65%, indicating the presence of congestion ( Table 2).

When stratified by heart failure phenotype, significant differences were observed in both ePVS and IVC-CI. Patients with reduced ejection fraction (HFrEF) had higher ePVS values compared to HFmrEF and HFpEF (5.51 ± 1.46 vs 4.93 ± 1.19 and 4.75 ± 1.04, respectively; p = 0.007). Conversely, IVC-CI values were lowest in the HFrEF group and progressively higher in HFmrEF and HFpEF (16.24 ± 8.80% vs 22.47 ± 9.42% and 25.17 ± 8.84%, respectively; p < 0.001) ( Table 3).

When further analyzed using post hoc pairwise comparisons with Dunn’s test and Bonferroni correction, significant differences in estimated plasma volume status (ePVS) were observed between specific heart failure phenotypes. Patients with HFrEF had significantly higher ePVS compared to HFmrEF (adjusted p = 0.043) and HFpEF (adjusted p = 0.036). In contrast, no significant difference was observed between HFmrEF and HFpEF (adjusted p = 1.000) ( Table 4).

Similarly, pairwise comparisons for IVC-CI demonstrated that patients with HFrEF had significantly lower values compared to HFmrEF and HFpEF (both adjusted p < 0.001), while no significant difference was found between HFmrEF and HFpEF (adjusted p = 1.000) ( Table 5).

In the subgroup analysis based on renal function, patients with chronic kidney disease had lower IVC-CI values compared to those without CKD (16.00 ± 6.78% vs 19.28 ± 9.80%; p = 0.008), suggesting a greater degree of venous congestion in this population ( Table 6).

Correlation analysis showed no significant association between ePVS and IVC-CI (r = −0.074, p = 0.297), indicating that these two parameters may reflect distinct physiological aspects of congestion ( Table 7).

In this study, we evaluated two accessible markers of congestion—estimated plasma volume status (ePVS) and inferior vena cava collapsibility index (IVC-CI)—in patients with heart failure. Overall, our findings indicate that both parameters reflect different dimensions of congestion and may provide complementary information when used together.

At admission, patients demonstrated elevated ePVS alongside reduced IVC-CI, suggesting the coexistence of intravascular volume expansion and systemic venous congestion. This observation supports the concept that congestion in heart failure is not confined to a single compartment but instead involves multiple physiological processes that may not be fully captured by clinical examination alone. ^{3, 4} The PARADISE cohort study (2019) demonstrated that higher ePVS values measured from the initial blood sample at admission were associated with an increased likelihood of acute heart failure and higher in-hospital mortality among patients presenting with acute dyspnea. ¹³

When analyzed across LVEF categories, patients with reduced ejection fraction showed higher ePVS values and lower IVC-CI values compared with other groups. This pattern is consistent with the established pathophysiology of HFrEF, where neurohormonal activation contributes to sodium and water retention, ultimately leading to increased plasma volume and elevated filling pressures. ¹⁴ In contrast, patients with HFpEF and HFmrEF appeared to have less pronounced changes in these parameters, although congestion may still be present through different mechanisms, such as impaired ventricular compliance. ¹⁵

An important finding in this study was the lack of a strong association between ePVS and most demographic or clinical variables. There were no significant differences in ePVS across age groups, indicating that age was not a key determinant of plasma volume status. Similarly, sex distribution did not differ across ePVS quartiles, suggesting no direct influence of sex on ePVS ¹⁶ In addition, ePVS values were comparable across comorbid conditions, including hypertension, type 2 diabetes, chronic kidney disease, and coronary artery disease, indicating that plasma volume status was relatively consistent across clinical subgroups. This may suggest that intravascular volume expansion is a common feature across different patient profiles in heart failure. ¹⁷ As a parameter derived from routine laboratory data, ePVS provides a simple and accessible surrogate of plasma volume status, with previous studies demonstrating its association with plasma volume and adverse outcomes in heart failure. ^{13, 18} On the other hand, IVC-CI demonstrated a significant association with chronic kidney disease, with lower values observed in patients with CKD. This finding is clinically plausible, as impaired renal function may exacerbate fluid retention and contribute to increased venous congestion, reflecting the well-recognized interaction between cardiac and renal dysfunction. This further highlights the complex interplay between intravascular and venous components of congestion, reinforcing the need for multidimensional assessment strategies. ^{19, 20}

Notably, the absence of a strong correlation between ePVS and IVC-CI suggests that these measures capture distinct physiological aspects of congestion. While ePVS reflects changes in circulating plasma volume, ²¹ dynamic IVC-CI changes reflecting increased venous pressures, increased venous return, reduced compliance, and increased right-sided filling pressures. ^{22, 23} Taken together, this supports the use of a combined approach, as reliance on a single parameter may underestimate the overall burden of congestion.

From a clinical perspective, these findings highlight the potential value of integrating simple, non-invasive markers into routine assessment. Both ePVS and IVC-CI can be obtained without advanced resources, making them particularly relevant in settings where access to more sophisticated hemodynamic monitoring is limited. ^{24, 25} Their combined use may therefore offer a practical approach to improving the evaluation of volume status in everyday clinical practice. These findings may have important implications for improving bedside congestion assessment, particularly in resource-limited settings. These findings are consistent with recent literature emphasizing the importance of a multidimensional approach to congestion assessment in heart failure, where no single parameter adequately reflects the overall hemodynamic status. Previous studies have highlighted the role of laboratory-based markers such as ePVS in estimating intravascular volume, as well as ultrasound-derived indices like IVC-CI in evaluating venous congestion. ^{26, 27} Our results further support the concept that combining these approaches may provide a more comprehensive and clinically relevant assessment.

This study has several limitations. First, the cross-sectional design does not allow for assessment of temporal changes or causal relationships. Second, as a single-center study, the findings may not be generalizable to other populations. Third, measurement of IVC-CI is operator-dependent and may be influenced by technical variability. Finally, the study did not include longitudinal outcomes, limiting the ability to assess prognostic implications. Residual confounding cannot be excluded. Despite these limitations, this study provides additional insight into the multidimensional nature of congestion in heart failure by evaluating both ePVS and IVC-CI, we demonstrate that these parameters may complement each other and contribute to a more comprehensive assessment of volume status. Future studies are warranted to explore the prognostic value of integrating ePVS and IVC-CI, particularly in predicting clinical outcomes such as rehospitalization and mortality. A longitudinal design may also help clarify how changes in these parameters over time relate to treatment response and disease progression.

Estimated plasma volume status (ePVS) and inferior vena cava collapsibility index (IVC-CI) are practical, non-invasive measures that reflect different aspects of congestion in heart failure. Their combined use may provide a more practical and informative approach to assessing volume status across different heart failure phenotypes.

This study was approved by the Ethics Committee of Hasanuddin University (Approval No: 462/UN4.6.4.5.31/PP36/2025; Date: 1 July 2025). Written informed consent was obtained from all participants prior to inclusion in the study. A template of the informed consent form, along with the ethical approval certificate, has been deposited in the Zenodo repository and is publicly accessible at https://doi.org/10.5281/zenodo.19282344. ²⁸ All patient data were anonymized prior to analysis to ensure confidentiality and privacy.