Plasma Biomarkers Associated with HF Hospitalization in Atrial Fibrillation

Patients with atrial fibrillation occupy a well-recognized intersection of thromboembolic and heart failure risk, but the biological signals that precede decompensation remain ill-defined.

In a recent analysis of the ARISTOTLE biomarker substudy, investigators evaluated 268 circulating proteins to clarify which pathways are most closely tied to subsequent heart failure hospitalization. The cohort included 596 patients who experienced hospitalization for heart failure and 4029 control patients without heart failure, with biomarker measurements obtained at baseline using high-throughput proteomic assays.

Take a look at the findings below.

Established Markers Still Dominate
Among all candidates, natriuretic peptides and cardiac troponin had the strongest associations with future hospitalization. NT-proBNP, BNP, and high-sensitivity troponin T (hs-cTnT) consistently ranked highest across machine learning and regression models, even after adjustment for clinical variables and renal function. Their persistence reinforces a central clinical reality: myocardial stretch and injury remain the dominant measurable signals preceding decompensation in atrial fibrillation populations.

However, reliance on these markers alone appears incomplete. After accounting for them, a subset of additional biomarkers remained independently associated with risk, suggesting parallel biological processes that aren’t fully captured by traditional cardiac metrics.

Multisystem Signals Beyond the Myocardium Revealed
10 biomarkers met stringent statistical thresholds after multiplicity adjustment, extending beyond conventional cardiac pathways. These included fibroblast growth factor 23 (FGF-23), spondin 1, insulin-like growth factor binding protein 7 (IGFBP-7), soluble urokinase-type plasminogen activator receptor, osteopontin, pentraxin-related protein 3 (PTX3), and transferrin receptor protein 1.

The pattern that emerges is multidimensional. Signals of cardiorenal dysfunction, inflammation, extracellular matrix remodeling, fibrinolysis, and iron metabolism all appear related to hospitalization risk, emphasizing that failure in atrial fibrillation is rarely driven by a single mechanism.

Distinguishing Biology Across HF Subtypes
The study also examined biomarker differences between heart failure phenotypes in patients with established disease at baseline. Distinct profiles separated patients with reduced ejection fraction from preserved ejection fraction.

Those with reduced ejection fraction demonstrated higher levels of natriuretic peptides, troponin, renin, ACE2, GDF-15, and interleukin-6. This constellation reflects physiology dominated by myocardial injury, neurohormonal activation, and systemic inflammation.

In contrast, preserved ejection fraction was associated with higher levels of stem cell factor and leptin. These markers point toward processes involving adipose signaling, tissue repair, and metabolic inflammation, aligning with the known clinical association between HFpEF and obesity-related phenotypes.

The separation isn’t absolute, though it’s directionally consistent with differing pathophysiologic drivers rather than a single disease spectrum.

Applying the Findings to Clinical Strategy
The dataset benefits from scale, standardized biomarker acquisition, and rigorous statistical filtering. At the same time, its interpretation requires attention to context. Heart failure hospitalization wasn’t centrally adjudicated, left ventricular function classification relied on available imaging reports, and atrial fibrillation itself can elevate natriuretic peptides, potentially complicating signal attribution.

The findings reinforce that risk stratification in atrial fibrillation cannot be reduced to a single biomarker axis. A layered biological model emerges: myocardial stress markers anchor risk while inflammatory, renal, and metabolic pathways refine it. This multidomain signal suggests that future clinical tools may need to integrate panels rather than individual markers to better anticipate decompensation and guide targeted intervention.

Reference

Pol T, Lindbäck J, Oldgren J, et al. Plasma biomarkers associated with heart failure hospitalization among patients with atrial fibrillation and subtypes of heart failure. J Am Heart Assoc. 2026;15:e045970. doi:10.1161/JAHA.125.045970