Laboratory-derived inflammatory–nutritional exploratory phenogroups and their associations with functional limitation and 30-day same-center all-cause unplanned readmission in patients with heart failure

Background Heart failure (HF) is characterized by marked clinical heterogeneity, while conventional left ventricular ejection fraction (LVEF)-based classification may not fully capture systemic inflammatory, nutritional, hematologic, and cardiorenal abnormalities. We aimed to identify laboratory-derived inflammatory–nutritional exploratory phenogroups in hospitalized patients with HF and evaluate their associations with functional limitation and 30-day same-center all-cause unplanned readmission. Methods This single-center retrospective cohort included 1,588 hospitalized patients with HF, of whom 1,455 with complete data for 15 prespecified clustering variables were included in the primary analysis. K-means, Gaussian mixture models, and DBSCAN were compared, and K-means with K = 3 was selected based on internal separation, stability, cluster size, and clinical interpretability, with K = 2 used as a sensitivity analysis. Severe functional limitation was defined as NYHA class III–IV, and 30-day same-center all-cause unplanned readmission was evaluated as the short-term clinical outcome. Multivariable logistic regression with HC3 robust standard errors was used to assess these associations, with multiple-imputation and median-imputation sensitivity analyses conducted in the full cohort. Results Three phenogroups were identified: an inflammatory–cardiorenal–nutritional vulnerability phenotype, an anemia–immune dysregulation phenotype, and a relatively preserved laboratory phenotype. LVEF was similar across groups, whereas severe functional limitation and 30-day same-center all-cause unplanned readmission differed significantly. After enhanced adjustment, compared with Cluster 3, the odds ratios for severe functional limitation were 3.814 and 5.594 for Clusters 1 and 2, respectively, and the corresponding odds ratios for 30-day same-center all-cause unplanned readmission were 1.966 and 2.616. Higher quartiles of both ALI and PNI were associated with lower odds of severe functional limitation; higher ALI quartiles and the highest PNI quartile were associated with lower odds of 30-day same-center all-cause unplanned readmission. Conclusion Routine admission laboratory measurements identified three exploratory HF phenogroups with distinct inflammatory, nutritional, hematologic, and cardiorenal profiles. After adjustment for continuous LVEF and NT-proBNP, the two vulnerable phenogroups remained associated with severe functional limitation and 30-day same-center all-cause unplanned readmission, with directionally consistent findings in the full-cohort and K = 2 sensitivity analyses. ALI and PNI reflect laboratory-derived inflammatory–nutritional vulnerability but cannot replace formal nutritional assessment or establish incremental predictive value. These findings remain exploratory and require validation in prospective multicenter cohorts.