Native T1 for diagnosis and risk prediction in amyloid transthyretin cardiomyopathy

Abstract

Importance: Stabilizers/silencers limit new transthyretin amyloid formation, while emerging agents aim to clear existing deposits. Extracellular volume (ECV) mapping reflects myocardial amyloid burden but is gadolinium-dependent; native T1 offers a contrast-free alternative.

Objective

To define calibrated native T1 thresholds and strata across the ATTR spectrum and assess whether native T1 provides diagnostic and prognostic information comparable to ECV.

Design

Prospective observational cohort of individuals undergoing cardiovascular magnetic resonance (CMR) for suspected or confirmed ATTR from 2011 to 2025.

Setting

National referral amyloidosis center.

Participants

1,675 participants (median age, 79 years): asymptomatic TTR-variant carriers (n=125), extra-cardiac ATTR (n=44), early-stage ATTR-CM (n=73), and overt ATTR-CM (n=1,433).

Exposures

Native T1 and ECV.

Main Outcomes and Measures: Diagnostic targets were 1) any cardiac involvement and 2) overt vs early ATTR-CM. Prognostic analyses used Cox regression for all-cause mortality. Native T1 was calibrated against predefined ECV strata using 3-year mortality.

Results

Native T1 increased stepwise from carriers and extra-cardiac ATTR to overt ATTR-CM and correlated with ECV in the whole cohort (r=0.62), with weaker correlations in more advanced disease. Over a median 3.3 years, 822 of 1,675 participants (49%) died. For any cardiac involvement, a native T1 ≤1,041 ms yielded 95% sensitivity and 78% specificity, whereas a threshold ≥1,101 ms for overt ATTR-CM yielded 73% sensitivity and 96% specificity; pragmatic rounded cut-offs of 1,050 and 1,100 ms preserved similar performance. Native T1 was calibrated against ECV strata (<30%, 30–39%, 40–49%, 50–59%, ≥60%) to derive four T1 categories (<980, 980–1,029, 1,030–1,049, ≥1,050 ms) that reproduced a stepwise 3-year mortality gradient. ECV showed an approximately linear relationship with mortality across its range, whereas native T1 exhibited a strong risk gradient at low–intermediate levels with a relative plateau in the highest category. Adding native T1 strata to the clinical model including National Amyloidosis Centre stage provided independent prognostic information and improved risk reclassification.

Conclusions and Relevance

Native T1 mapping provides a contrast-free quantitative marker of myocardial amyloid load with pragmatic diagnostic thresholds and calibrated risk strata that align with ECV-based classification, particularly in earlier disease stages.For image description, please refer to the figure legend and surrounding text.