Is elabela/toddler a poor prognostic marker in heart failure patients?

Background: Elabela/toddler (ELA-32) is a recently identified endogenous apelin receptor ligand. ELA levels are known to rise in heart failure (HF) patients. However, the association between elevated ELA levels and prognosis in these patients remains unknown. We aimed to investigate whether ELA plasma levels are correlated with prognosis in heart failure patients with reduced ejection fraction (HFrEF).

Methods: This case-control cross-sectional study enrolled 150 patients, including 73 HFrEF patients and 77 age- and gender-matched healthy volunteers. We collected a blood sample at hospital admission to measure ELA-32 levels. The study endpoint was cardiovascular mortality or HF-related hospitalization. We followed up all patients in the study for a mean of 7.48 ± 2.73 months.

Results: In patients with HFrEF, ELA-32 levels were higher than those in controls. The levels of ELA-32 showed a significant increase at advanced New York Heart Association stages. In the receiver operating characteristics curve analysis, a cut-off value of the serum ELA-32 level of 8.25 ng/mL showed a sensitivity of 76 % and specificity of 82 % for predicting the study endpoint [area under the curve: 0.84; 95 % confidence interval (CI): 0.72-0.98; p <0.001]. Cardiovascular mortality (p =0.042) and HF-related hospitalization (p <0.001) were statistically more significant in patients with ELA-32 levels greater than 8.25. Age [Hazard ratio (HR) =1.023; 95 % CI: 0.964-1.230, p =0.039], N-terminal pro-brain natriuretic peptide (HR =1.300; 95 % CI: 1.017-1.874, p =0.017), left ventricular end-diastolic volume (HR =1.142; 95 % CI 1.022-1.547, p =0.028), and ELA-32 ≥8.25 (HR =2.556; 95 % CI: 1.078-3.941, p <0.001) remained independently associated with the risk of study endpoint.

Conclusion: For the first time, HF-related hospitalizations and cardiovascular mortality are independently associated with increased ELA-32 levels in patients with HFrEF. HIPPOKRATIA 2023, 27 (4):126-131.