Incremental Prognostic Value of Cardiac Magnetic Resonance Beyond Biomarker Staging in Transthyretin Cardiac Amyloidosis

AIMS: While cardiac magnetic resonance (CMR) provides prognostic value in transthyretin cardiac amyloidosis (ATTR-CA), current ATTR-CA staging relies on serum biomarkers. We evaluated the incremental value of incorporating CMR parameters into the National Amyloidosis Center (NAC) staging and assessed their utility in guiding evaluation for advanced heart failure (HF) therapies and emerging disease-modifying treatments. METHODS AND RESULTS: We retrospectively analyzed a multicenter cohort of 266 ATTR-CA patients who underwent CMR between 2007-2023. Cox regressions were used to assess time to death. A baseline model was constructed using the NAC stage. CMR predictor variables were selected a priori based on clinical relevance and non-collinearity, then refined using stepwise backward elimination regression with NAC stage control; variables retained in ≥60% of 1,000 bootstrapped samples were included. Internal validation was performed via bootstrapping, with performance reported as Harrell's C-statistic and calibration slope. Decision curve analysis evaluated clinical utility.85 patients (32%) died over a median follow up of 20 months (IQR 8-35). Extracellular volume (ECV ≥59%, HR 2.45, 95% CI 1.2-5.2, p = 0.020) and indexed left atrial volume (LAVi ≥54 ml/m2, HR 2.00, 95% CI 1.1-3.7, p = 0.026) were independently associated with mortality after NAC adjustment and improved prognostic accuracy across all biomarker stages. When risk prediction was framed around initiation of advanced HF or emerging disease-modifying therapies, incorporating CMR alongside NAC staging facilitated identification of 28 additional high-risk patients per 1,000. CONCLUSION: CMR-derived ECV and LAVi were associated with incremental prognostic value in ATTR-CA beyond biomarker staging and may inform clinical risk stratification.