Multi-Biomarker Profiling and Recurrent Hospitalizations in Heart Failure

Antoni Bayes-Genis, Julio Núñez, Eduardo Núñez, Jaume Barallat Martínez, Maria-Cruz Pastor Ferrer, Marta de Antonio, Elisabet Zamora, Juan Sanchis, Josep Lupón Rosés

Despite advances in pharmacologic therapy and devices, patients with heart failure (HF) continue to have significant rehospitalization rates and risk prediction remains challenging. We sought to explore the value of a multi-biomarker panel [including NT-proBNP, high-sensitivity cardiac troponin T (hs-TnT), and ST2] on top of clinical assessment for long-term prediction of recurrent hospitalizations in HF. NT-proBNP, hs-TnT, and ST2 (suppression of tumorigenicity-2) levels were measured in 891 consecutive ambulatory HF patients. The independent association between the multi-biomarker panel and recurrent hospitalizations was assessed through a multivariable negative binomial regression and expressed as incidence rates ratios. McFadden pseudo-R(2) and goodness-of-fit measures were also used. The total number of unplanned hospitalizations [all-cause, cardiovascular (CV)-, and HF-related] were selected as the primary endpoints. At a mean follow-up of 4.2 ± 2.1 years, 1623 all-cause hospitalizations in 498 patients (55.9%), 710 CV-related hospitalizations in 331 patients (37.2%), and 444 HF-related hospitalizations in 214 patients (24.1%) were registered. The crude incidence of all-cause, CV-, and HF-related recurrent hospitalizations was significantly higher for patients with the multi-biomarker panel above the cut-point (hs-TnT > 14 ng/L, NT-proBNP > 1000 ng/L, and ST2 > 35 ng/mL) (all P < 0.001). For all-cause, CV-, and HF-related recurrent hospitalizations, the McFadden R(2), Akaike information criterion, and Bayesian information criterion supported the superiority of incorporating the multi-biomarker panel into a clinical predictive model. A multi-biomarker approach based on NT-proBNP, hs-TnT, and ST2 better identifies HF patients at risk for recurrent hospitalizations as compared to approaches entailing just one or two of these biomarkers. Elucidation of new biophysiological predictors for recurrent hospitalizations may identify patient profiles for focused intervention.