Transthyretin amyloid cardiomyopathy: natural history and treatment response assessed by cardiovascular magnetic resonance

转甲状腺素蛋白淀粉样变性心肌病:心血管磁共振评估其自然病程和治疗反应

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Abstract

BACKGROUND AND AIMS: Cardiovascular magnetic resonance (CMR) and extracellular volume (ECV) mapping can measure amyloid burden in vivo. This study sought to assess the natural history of transthyretin amyloid cardiomyopathy (ATTR-CM) in terms of amyloid deposition burden (ECV) over time, changes in cardiac amyloid load following treatment with patisiran, and the association between change in ECV and mortality. METHODS: All 189 patients (untreated = 119, patisiran = 70) underwent assessment with CMR at baseline, 160 patients (untreated = 94, patisiran = 66) had a 1-year follow-up CMR and 75 patients (untreated = 42, patisiran = 33) had a 2-year follow-up CMR, of whom 36 patients (untreated = 17, patisiran = 29) had follow-up CMR at both timepoints. CMR response was graded by change in ECV: progression (≥5% increase), stable (<5% change) and regression (≥5% decrease). RESULTS: In untreated patients, 36% progressed at 1 year which significantly increased to 62% at 2 years. Mean increase in ECV of 4.1% (after 1 year) and 6.8% (after 2 years) was observed and associated with significant worsening in biomarkers and structural parameters. No significant difference in mean ECV was observed following treatment with patisiran at both timepoints. Stable ECV was observed in 88% of patients (after 1 year) and 100% of patients (after 2 years). Structural parameters remained stable following treatment. ECV progression after 1 year was independently associated with mortality after adjusting for known predictors (hazard ratio 2.021; 95% confidence interval 1.081-3.781; P = .028). CONCLUSIONS: CMR with ECV mapping can track changes in cardiac amyloid burden and treatment response in ATTR-CM, with changes in ECV being independently associated with outcomes.

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