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Updated: Jan 9, 2026
Genetic Analysis of Hereditary Transthyretin Ala97Ser Related Amyloidosis
Published on: June 9, 2018
Global Longitudinal Strain for Prognostic Staging in Wild-Type Transthyretin Cardiac Amyloidosis
Philippe Debonnaire1, Wouter L'Hoyes1, Erwan Donal2
1Cardiology Department, AZ Sint-Jan Brugge, Belgium (P.D., W.L., E.C., R.T., I.B., S.T.).
Background:
A formal prognostic staging system in wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM), based on echocardiographic imaging, is lacking. We evaluated the prognostic performance of global longitudinal strain (GLS) staging in a large cohort of patients with ATTRwt-CM, including under tafamidis treatment and relative to National Amyloidosis Center (NAC) biomarker staging.
Methods:
A multicentric, international ATTRwt-CM patient cohort with baseline GLS (distribution quartiles), evaluated by echocardiography, was studied, related to all-cause mortality.
Results:
The study comprised 816 patients with ATTRwt-CM, median age of 81.5 years, 83% males, and 72% tafamidis initiated. During a 2.2-year median follow-up, 29.7% of patients died. GLS worsened with increasing NAC disease stage (I: -14.3%, II: -11.6%, III: -11.4%; P<0.001). Median survival per baseline GLS quartile stage 1 (<-15.8%), 2 (-15.8 to -12.9%), 3 (-12.8 to -10.0%), and 4 (GLS >-10.0%) was not met, 6.7, 4.6, and 3.4 years, respectively (P<0.001). The median GLS -12.8% cutoff predicted 1-year mortality with 74% sensitivity, 52% specificity (area under the curve, 0.73 [95% CI, 0.66-0.80]; P<0.001). GLS was the only independent echocardiographic and strong mortality predictor, independent of other predictors, including age, New York Heart Association class symptoms, NAC stage, and tafamidis treatment (hazard ratio, 1.08 [95% CI, 1.04-1.12]; P<0.001), also when restricted to 591 tafamidis-treated subjects (hazard ratio, 1.15 [95% CI, 1.08-1.22]; P<0.001). Baseline GLS -12.8% cutoff value provided further prognostic discriminative ability for mortality within each NAC disease stage stratum (all P<0.050). Likelihood ratio test indicated incremental prognostic value of GLS (staging) over baseline NAC staging (P<0.001).
Conclusions:
GLS is a strong, independent mortality predictor in ATTRwt-CM, irrespective of tafamidis treatment, that may be an adjunct or complementary to biomarker staging.
