Multiparametric congestion phenotypes in elderly patients with acute HFpEF: clinical profiles and short-term prognostic implications. A subanalysis of the NACLOCRo study
J Campos, F Croset, A Perez-Nieva, C Perez-Medina, M Garcia-Melero, M Vergara, B Del Hoyo, J R-Oyuela, P Cevallos, C Fernandez, M Fabregate, E Perez-Pison, P Llacer, L ManzanoAbstract
Background
Heart failure with preserved ejection fraction (HFpEF) is the most prevalent form of heart failure, and congestion is the main driver of acute decompensation and early adverse outcomes. In elderly and comorbid patients, conventional clinical assessment often underestimates the burden and distribution of congestion. Multiparametric strategies integrating biomarkers and point-of-care ultrasound may help identify distinct congestion phenotypes with prognostic relevance.
Purpose
To characterize clinical, biomarker, and ultrasound profiles of multiparametric congestion phenotypes in patients hospitalized with acute HFpEF and to explore their association with 30-day outcomes.
Methods
We conducted a prospective, single-center observational study within the NACLOCRo project, including patients admitted with acute HFpEF. Congestion was assessed using biomarkers (BNP and CA125) and extended ultrasound evaluation (lung ultrasound and venous congestion assessment). Using an exploratory, data-driven algorithm, patients were classified into pulmonary, systemic, or mixed congestion phenotypes. Associations with 30-day outcomes—including a composite of all-cause mortality or heart failure readmission—were analyzed using multivariable logistic regression. Model discrimination was assessed with receiver operating characteristic (ROC) curves.
Results
Seventy patients were included (median age 88 years; 72.9% women). Conventional clinical congestion signs and EVEREST scores did not differ across phenotypes. The pulmonary phenotype showed higher systolic blood pressure, more B-lines, higher BNP, lower CA125, and a more favorable natriuretic response. The systemic phenotype was characterized by predominant serosal and visceral congestion, high rates of pleural effusion, markedly elevated CA125, greater hepatic and renal involvement, and a trend toward longer hospital stay. The mixed phenotype combined pulmonary and systemic features and exhibited the worst renal profile. Congestion phenotype was significantly associated with the 30-day composite outcome (p=0.029). Compared with the pulmonary phenotype, systemic congestion showed an OR of 6.44 (95% CI 0.99–41.87; p=0.051) and the mixed phenotype an OR of 8.30 (95% CI 1.26–54.56; p=0.028). No significant associations were found for mortality or readmission alone. The model showed good discrimination for the composite endpoint (AUC 0.815).
Conclusions
In elderly patients hospitalized with acute HFpEF, multiparametric congestion phenotyping identified distinct clinical entities with different short-term prognostic implications. A mixed pulmonary–systemic congestion pattern was associated with the highest 30-day risk, while isolated pulmonary congestion was linked to more favorable early outcomes. These findings support integrating biomarkers and ultrasound into routine assessment to improve risk stratification and individualized congestion management in HFpEF.Baseline characteristicsFor image description, please refer to the figure legend and surrounding text.Biomarkers across phenotypesFor image description, please refer to the figure legend and surrounding text.