Gamma-glutamyltransferase independently predicts mortality and heart failure hospitalization in cardiac transthyretin amyloidosis.

Abstract

Transthyretin cardiac amyloidosis (ATTR-CA) is a leading cause of heart failure (HF). Although transthyretin is synthesized in the liver, overt liver disease is uncommon in ATTR-CA. We characterised hepatic involvement in patients with ATTR-CA, and identified the correlates and prognostic value of elevated gamma-glutamyl transferase (GGT), the most prominently deranged biomarker. We examined 528 patients from four centers, using scintigraphy, cardiovascular magnetic resonance, and circulating biomarkers to assess liver function. The primary endpoint was all-cause mortality; secondary endpoints included HF hospitalization alone or combined with all-cause mortality. The cohort comprised predominantly older men (86 % male; median age 81 years). Scintigraphy showed no abnormal hepatic uptake, but liver extracellular volume was elevated (median 0.69; clinically significant cutoff 0.40). Median GGT was 49 U/L, with 48 % exceeding sex-specific upper reference limits. By comparison, elevated aspartate and alanine transaminases, total bilirubin, and alkaline phosphatase were observed in 26 %, 9 %, 33 %, and 1 % of patients, respectively. Patients with GGT ≥82 U/L displayed indicators of more advanced cardiac disease, hepatic injury, and venous congestion. During a median follow-up of 2.6 years, 39 % died and 33 % were hospitalized for HF. In multivariable analysis, GGT remained predictive of all-cause mortality and HF hospitalization beyond the National Amyloidosis Centre score (hazard ratio [HR] 1.15, 95 % confidence interval [CI] 1.01-1.31; p = 0.045, and HR 1.17, 95 % CI 1.03-1.32; p = 0.016, respectively). Elevated GGT is associated with greater disease severity and predicts worse outcomes in ATTR-CA. GGT measurement may improve risk stratification and guide treatment decision-making.