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Updated: Sep 28, 2026
Genetic Analysis of Hereditary Transthyretin Ala97Ser Related Amyloidosis
Published on: June 9, 2018
Native T1 for Diagnosis and Risk Prediction in Amyloid Transthyretin Cardiomyopathy: An Observational Study on 1,675
Alberto Aimo1, Awais Sheikh2, Sorayya Kakhi2
1Interdisciplinary Center for Health Sciences, Scuola Superiore Sant'Anna, Pisa, Italy; Cardiology Division, Fondazione Toscana Gabriele Monasterio, Pisa, Italy.
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.
