Introduction

Heart failure with reduced ejection fraction (HFrEF), a major global health challenge, is associated with increased risk of cardiovascular (CV) mortality and frequent HF-related hospitalizations. The New York Heart Association (NYHA) functional classification with a high prognostic value is instrumental in evaluating symptom severity in this patient population. However, there is an increasing demand for accessible, objective markers that would improve outcome prediction. The C-reactive protein-albumin-lymphocyte (CALLY) index, derived from C-reactive protein (CRP), albumin, and lymphocyte count, presents a composite measure, reflecting systemic inflammation, nutritional status, and immune function of the patient. 

Aim

To ascertain the association between the CALLY index, NYHA class, and all-cause mortality in patients with HFrEF.

Patient Profile

• Patients diagnosed with HFrEF (age > 18 years). The diagnosis of HFrEF was based on the clinical evaluation and echocardiographic assessment [left ventricular ejection fraction (LVEF ≤ 40%) accompanied by clinical manifestations and/ or symptoms indicative of HF].
• The study subjects were categorized as survivors or non-survivors. Clinical characteristics, laboratory findings, and NYHA functional class were systematically compared between the two groups.

Methods

Study Design

CALLY Index Calculation

[serum albumin (g/L) × lymphocyte count (cells/μL)]/[CRP level (mg/L) ×10⁴]. 

Assessments

• A univariate and multivariate logistic regression analyses were both conducted to explore factors independently associated with mortality
• Additionally, the prognostic performance of the CALLY index was assessed using receiver operating characteristic (ROC) curve analysis.

Results

• The study population comprised of 146 patients diagnosed with HFrEF. Of these, 29 (19.8%) died. 
• Compared with survivors, non-survivors were older (61.8 yrs vs. 66.55 yrs) and had significantly lower LVEF (34.01 vs. 30.69).
• Non-survivors also had significantly higher levels of inflammatory and cardiac biomarkers, including CRP, troponin-T, and pro-brain natriuretic peptide, as compared to survivors. 
• Advanced heart failure symptoms (NYHA class 3-4) were more common among non-survivors vs. survivors (31.0% vs. 10.3%; p=0.008).
• The mortality group had significantly lower CALLY index (1.33 vs 4.02, p < 0.001), highlighting its potential role a prognostic biomarker. 
• As per the univariate analysis, diminished LVEF was significantly associated with death, [odds ratio (OR): 0.946; 95% confidence interval (CI): 0.896-0.998; p=0.044]. The presence of advanced HF symptoms (as indicated by NYHA class 3-4), strongly predicted mortality, emphasizing the clinical importance of symptom burden in this population (OR: 3.937; 95% CI: 1.466-10.573; p=0.007). The CALLY index had a significant inverse association with mortality; higher values were associated with improved survival (OR: 0.763; 95% CI: 0.626-0.981; p=0.034).
• As per the multivariate logistic regression analysis, LVEF remained a significant protective factor: higher LVEF was associated with a reduced risk of mortality. Presence of advanced HF symptoms (classified as NYHA class 3-4) independently predicted increased mortality risk. The CALLY index had a significant inverse association with mortality, highlighting its potential as a valuable prognostic biomarker (Table 1).

Table 1: Predictors of all-cause mortality as per the multivariable analysis

Table 2: CALLY index in the patients as per their NYHA class

• ROC curve analysis showed the CALLY index had strong predictive value for all‑cause mortality and moderate value for NYHA class III–IV, supporting its utility as a practical tool in clinical risk assessment.
• The CALLY index predicted all‑cause mortality with AUC 0.728 (95% CI 0.633–0.823; p<0.001). A cutoff of 0.869 had sensitivity of 66.7% and specificity of 71.4%. CRP showed moderate value (AUC 0.702; p=0.001), while albumin (AUC 0.606; p=0.090) and lymphocytes (AUC 0.596; p=0.127) had weaker discrimination.

Conclusions

• The study demonstrated the CALLY index was an independent predictor of all‑cause mortality and advanced impairment (NYHA III–IV) in patients with HFrEF. 
• Lower values correlated with adverse outcomes, underscoring its role as a cost‑effective, accessible risk tool. By integrating nutritional and inflammatory markers, it offers holistic prognostic insight beyond conventional models. Validation in larger, diverse cohorts is warranted. 

Med J Bakirkoy 2025;21(4):436-443.DOI: 10.4274/BMJ.galenos.2025.2025.9-7