Philippe Debonnaire, Wouter L’Hoyes, Erwan Donal, Nicolas Verheyen, Delphine Vervloet, Karl Dujardin, Anne–Catherine Pouleur, Raluca Dulgheru, Victor Sarli Issa, Steven Droogmans, Ruxandra Jurcuţ, Madelien V. Regeer, Matthias Dupont, Antoine Bondue, Philippe Timmermans, Alexandre Bohyn, Emma Christiaen, Nicolas Wyseure, Mélanie Bézard, David Zach, Nora Schwegel, Robbe Knapen, L Buytaert, Nils de Marneffe, Robert Adam, Nina Ajmone Marsan, René Tavernier, Ian Buysschaert, Sander Trenson
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.