Native T1 for Diagnosis and Risk Prediction in Amyloid Transthyretin Cardiomyopathy: An Observational Study on 1,675 Subjects.
Abstract
Background
Native T1 mapping is a contrast-free cardiac magnetic resonance (CMR) marker of myocardial amyloid infiltration, but center-specific diagnostic cutoffs and prognostic strata remain incompletely defined across transthyretin amyloidosis (ATTR).
Objectives
This study aims to define native T1 thresholds and risk strata across the ATTR spectrum and compare its diagnostic and prognostic performance with extracellular volume (ECV).
Methods
In a cohort at a national referral amyloidosis center (2011-2025), 1,675 individuals undergoing CMR for suspected or confirmed ATTR were classified as asymptomatic TTR-variant carriers (n = 125), extracardiac ATTR (n = 44), early ATTR-CM (n = 73), or overt ATTR-CM (n = 1,433). Diagnostic targets were: 1) any cardiac involvement (early/overt ATTR-CM); and 2) overt vs early ATTR-CM. All-cause mortality from national records was analyzed with Cox models; native T1 strata were calibrated to predefined ECV strata using 3-year mortality.
Results
Native T1 rose stepwise across disease categories and correlated with ECV (r = 0.62), with weaker coupling in advanced disease. Over a median 3.3 years, 822 of 1,675 (49%) participants died. Native T1 ≤1,050 ms (z-score +1.14) identified a low likelihood of cardiac involvement with 93% sensitivity and 84% specificity, whereas native T1 ≥1,100 ms (z-score +2.40) identified overt ATTR-CM with 75% sensitivity and 88% specificity. Calibration against ECV strata yielded native T1 risk categories that reproduced a stepwise 3-year mortality gradient, with a stronger gradient at low to intermediate T1 and relative plateauing at higher T1; adding native T1 strata improved prognostic information beyond clinical variables.
Conclusions
Native T1 can provide pragmatic diagnostic supportive thresholds, whereas ECV-calibrated native T1 strata reproduced a graded 3-year mortality risk. Native T1 offers a practical contrast-free approach to support diagnosis and risk stratification, although ECV remains the preferred quantitative marker when contrast CMR is available. Thresholds and z-score based approaches still require local recalibration and external validation before adoption at other centers.