Journal of the American College of Cardiology · 2025
Myocardial Amyloid Burden in Transthyretin Amyloidosis.
СтатьяНазвание и аннотация: Перевод в очереди
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Sheikh Awais, Achten Anouk, Aimo Alberto, Razvi Yousuf, Mansell Josephine, Rauf Muhammad U, Porcari Aldostefano, Patel Rishi, Venneri Lucia, Martinez-Naharro Ana, Whelan Carol, Quarta Cristina, Virsinskaite Ruta, Feffer Barak Daniel, Wechalekar Ashutosh, Lachmann Helen, Knight Daniel, Kotecha Tushar, Kellman Peter, Manisty Charlotte, Moon James, Emdin Michele, Solomon Scott D, Hawkins Philip N, Gillmore Julian, Fontana Marianna
Аннотация
BACKGROUND: Stabilizers/silencers limit new transthyretin amyloid formation, whereas emerging agents aim to clear existing deposits. Cardiovascular magnetic resonance (CMR) extracellular volume (ECV) reflects myocardial amyloid and may provide a quantitative framework for therapeutic planning OBJECTIVES: The aim was to define calibrated ECV thresholds, evaluate their diagnostic and prognostic value, and explore how CMR-ECV could provide a quantitative framework for disease staging and therapeutic planning.
METHODS: We studied 1,541 subjects undergoing CMR for transthyretin amyloidosis (ATTR) classified as TTR-variant carriers (n = 123), extracardiac ATTR (n = 41), early-stage ATTR-CM (n = 70), or overt ATTR-CM (n = 1,308). The endpoint was all-cause mortality.
RESULTS: ECV was similar in carriers and extracardiac ATTR but rose from early-stage to ATTR-cardiomyopathy (CM). Associations with biomarkers, National Amyloidosis Centre (NAC) stage, Perugini grade, and echocardiographic measures were modest, with wide overlap. Diagnostic performance was excellent: ECV <30% excluded and ≥40% confirmed cardiac involvement, whereas 30% to 39% indicated early infiltration. Over a median follow-up of 2.8 years (IQR: 1.4-4.3 years), 612 patients (40%) died. Prognostically, ECV independently predicted mortality (HR: 1.22 per 10% increase; 95% CI: 1.10-1.34 per 10% increase; P < 0.001) after multivariable analysist. Stratifying patients by ECV categories (degree of infiltration: none <30%; mild = 30%-39%; moderate = 40%-49%; moderate-to-severe = 50%-59%; severe ≥60%) showed monotonic risk increase across categories. ECV retained prognostic value across hs-troponin and N-terminal pro-B-type natriuretic peptide (NT-proBNP) strata, Perugini grades 1 to 3, and left ventricular mass index (LVMI) tertiles, with steeper gradients in low-biomarker/low-LVMI strata.
CONCLUSIONS: ECV directly quantifies myocardial amyloid load and, for the first time, defines reproducible thresholds that stratify burden and refine risk prediction beyond stage, biomarkers, and imaging, providing a quantitative framework for staging and therapeutic planning in ATTR amyloidosis.
METHODS: We studied 1,541 subjects undergoing CMR for transthyretin amyloidosis (ATTR) classified as TTR-variant carriers (n = 123), extracardiac ATTR (n = 41), early-stage ATTR-CM (n = 70), or overt ATTR-CM (n = 1,308). The endpoint was all-cause mortality.
RESULTS: ECV was similar in carriers and extracardiac ATTR but rose from early-stage to ATTR-cardiomyopathy (CM). Associations with biomarkers, National Amyloidosis Centre (NAC) stage, Perugini grade, and echocardiographic measures were modest, with wide overlap. Diagnostic performance was excellent: ECV <30% excluded and ≥40% confirmed cardiac involvement, whereas 30% to 39% indicated early infiltration. Over a median follow-up of 2.8 years (IQR: 1.4-4.3 years), 612 patients (40%) died. Prognostically, ECV independently predicted mortality (HR: 1.22 per 10% increase; 95% CI: 1.10-1.34 per 10% increase; P < 0.001) after multivariable analysist. Stratifying patients by ECV categories (degree of infiltration: none <30%; mild = 30%-39%; moderate = 40%-49%; moderate-to-severe = 50%-59%; severe ≥60%) showed monotonic risk increase across categories. ECV retained prognostic value across hs-troponin and N-terminal pro-B-type natriuretic peptide (NT-proBNP) strata, Perugini grades 1 to 3, and left ventricular mass index (LVMI) tertiles, with steeper gradients in low-biomarker/low-LVMI strata.
CONCLUSIONS: ECV directly quantifies myocardial amyloid load and, for the first time, defines reproducible thresholds that stratify burden and refine risk prediction beyond stage, biomarkers, and imaging, providing a quantitative framework for staging and therapeutic planning in ATTR amyloidosis.