Phenotypic Presentation and Longitudinal Characterization of Hereditary ATTRv Amyloidosis in Previously Undiagnosed Family Members

作者：Luca Fazzini, Matteo Castrichini, Li Yan, Jose De Melo, Marta Figueiral, Jenny J Cao, Eric W. Klee, Christian Cadeddu Dessalvi, Martha Grogan, Angela Dispenzieri, Naveen L. Pereira · 发表于：JACC Advances · 年份：2025 · DOI：10.1016/j.jacadv.2025.102036 · 被引用次数：5 · 研究领域：Amyloidosis: Diagnosis, Treatment, Outcomes、Parathyroid Disorders and Treatments、Dermatological and Skeletal Disorders

BACKGROUND: Clinical characteristics, cardiac disease progression, and outcomes of "previously undiagnosed" family members of patients with hereditary transthyretin amyloid cardiomyopathy (ATTRv-CM) with pathogenic or likely pathogenic transthyretin (TTR) variants (genotype positive or G+) are unknown despite prognostic and therapeutic implications. OBJECTIVES: The objectives of this study are to describe the phenotypic presentation and report longitudinal assessment, including cardiac imaging of ATTRv G+ family members. METHODS: Demographic, electrocardiographic, genetic, and imaging (echocardiography, cardiac technetium-99m pyrophosphate, and magnetic resonance imaging) data were abstracted and analyzed from the electronic health records. RESULTS: There were 85 G+ family members, with the most common genotypes being Val50Met (29.4%) and Thr60Ala (28.2%). The mean age was 48.5 ± 11.7 years, 38.8% were male, and 17.9% and 15.5% had a diagnosis of peripheral neuropathy and carpal tunnel syndrome, respectively. The median follow-up was 6.8 years (Q1-Q3: 4.1-9.7), over which 55 patients had follow-up imaging studies. Left ventricular ejection fraction reduction (63 ± 4 to 61 ± 4, P = 0.014) and progressive septal wall thickening (9.4 ± 1.6 to 10.2 ± 2.4, P = 0.037) were observed. There were only 6 (10.9%) patients who developed at least 2 abnormal echocardiographic changes consistent with cardiac disease progression. The risk of developing peripheral neuropathy during follow-up ...