Type III collagen formation is significantly associated with risk of outcome in HFpEF patients but loses its significant association with underlying AF

Heart failure with preserved ejection fraction (HFpEF) is the most common type of heart failure, associated with high morbidity and mortality. Atrial fibrillation (AF) has been associated with structural remodelling and fibrosis and can coexist with HFpEF. Type III collagen is the second most abundant collagen in the heart wall and has been associated with cardiac fibrosis. It has been previously shown that type III collagen formation, measured by PRO-C3, is prognostic for all-cause mortality in HFpEF.

In this study, we aimed at investigating if the prognostic power of PRO-C3 in relation to all-cause mortality would be affected by underlying AF in HFpEF patients.

The analysis included 166 individuals with hypertensive HFpEF. The patients were classified in three groups according to NYHA classification, 43.2% in NYHA Class II, 52.5% NYHA Class III and 2.5% NYHA Class IV. A previous history of AF was present in 53.4% of the patients. Cardiac function was assessed by echocardiography and standard clinical measures. Type III collagen formation was evaluated by means of ELISA with the biomarker PRO-C3, which targets the released N-terminal pro-peptide of type III collagen.

Levels of PRO-C3 were significantly elevated in HFpEF patients with AF (p=0.0063). PRO-C3 was significantly predictive of all-cause mortality in HFpEF patients (AUC=0.643, p=0.0053), but lost its significant association when factoring in AF (AUC=0.581, p=0.235). There was an increased risk of all-cause mortality (p=0.0089) but not statistically significant differences in HFpEF patients with AF (p=0.178) with increasing tertiles of PRO-C3.

Type III collagen formation as measured by PRO-C3, was increased in patients with HFpEF and previously diagnosed AF. However, while PRO-C3 can be predictive of all-cause mortality in HFpEF patients, it lacks predicting ability when AF is considered. The presented data suggest a potential role of increased type III collagen formation in HFpEF patients with adverse outcomes, which is consistent with the presence of increased fibrosis, and can potentially be used as a tool of risk stratification.

Type of funding sources: Private company. Main funding source(s): Nordic Bioscience A/S