Biomarker-based clinical evaluation in ATTR-CM: plasma fibroblast-growth-factor-23 assessment

Introduction Fibroblast Growth Factor 23 (FGF23) is a hormone involved in phosphate and mineral metabolism and has recently gained attention for its role in heart failure disease. Elevated FGF23 contributes to myocardial remodeling, left ventricular hypertrophy, and increased atrial filling pressures. While its role has been comprehensively demonstrated in heart failure with reduced ejection fraction (HFrEF), its contribution to transthyretin amyloid cardiomyopathy (ATTR-CM) remains unclear. Given the growing need for new biomarkers in ATTR-CM, this study investigates FGF23 levels in ATTR-CM patients, focusing on their potential clinical and diagnostic relevance. Purpose The aim of this study is to determine the clinical significance of FGF23 in ATTR-CM by comparing plasma levels with those in heart failure patients. Methods We conducted a prospective, observational age-matched study. Plasma biomarker sampling and clinical evaluation was done in all patients. FGF23 levels were measured and analyzed for differences between groups, using statistical methods to assess sensitivity and specificity. Results A total number of 105 participants (ATTR-CM: n = 32, mean age = 80.3 years; heart failure controls: n = 73, mean age = 76.8 years) mean age of 80.6 years were included in this study. The cutoff for distinguishing ATTR-CM from HFrEF was 102.5 pg/mL, achieving high sensitivity (95-100%), although specificity decreased to below 50% at higher levels. When comparing ATTR-CM with a broader heart failure cohort (including HFrEF, HFmrEF, and HFpEF), the optimal cutoff slightly decreased to 99.5 pg/mL, maintaining high sensitivity (95-100%) but with reduced specificity (~30%). Conclusion Our study demonstrates that plasma FGF23 levels are elevated in ATTR-CM patients compared to those with HFrEF, suggesting its potential role in disease characterization.