Global longitudinal strain for prognostic staging in wild-type transthyretin cardiac amyloidosis, including under tafamidis treatment

Background A formal prognostic staging system in wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM) based on echocardiographic imaging is currently lacking. Purpose We evaluated the prognostic performance of GLS staging in a large ATTRwt-CM patient cohort, relative to National Amyloidosis Centre (NAC) biomarker staging, including under tafamidis treatment. Methods A multicentric, international ATTRwt-CM patient cohort with baseline GLS evaluated by echocardiography was studied, related to all-cause mortality. Results The study comprised 816 ATTRwt-CM patients, median age 81.5 years, 83% males, 72% tafamidis initiated. During 2.2 years 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). GLS -12.8% cut-off predicted mortality with 73% sensitivity, 60% specificity, AUC 0.70 (95%CI 0.66-0.74, p<0.001). GLS was the only echocardiographic and a strong mortality predictor, independent of other predictors, including age, NYHA class symptoms, NAC disease stage and tafamidis treatment (HR 1.07, 95%CI 1.03-1.11, p=0.001), also when restricted to 591 tafamidis treated subjects (HR 1.14, 95%CI 1.07-1.21, p<0.001). Baseline GLS -12.8% cut-off 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, including under tafamidis treatment, that may be used as an adjunct or alternative to biomarker staging. GLS stages survival