Cardiovascular Magnetic Resonance (Cmr) in Transthyretin Amyloid Cardiomyopathy - a Study of Natural History and Treatment Repsonse

Abstract

Introduction Cardiovascular magnetic resonance (CMR) and extracellular volume (ECV) mapping can quantify amyloid burden in patients with cardiac amyloidosis. At present, there is a paucity of data on tracking changes in amyloid deposition in both untreated and treated cohorts with transthyretin (ATTR) disease. Our aim was to use CMR and ECV mapping to characterise the natural history of untreated ATTR amyloidosis, measure the response to treatment with patisiran, and correlate ECV with changes in structural and functional cardiac parameters. Materials and Methods In total, 119 untreated patients and 70 patients treated with patisiran were assessed with serial biomarkers, echocardiography and CMR with ECV mapping at baseline, 1 year, and 2 years where possible. CMR response was categorized by changes in ECV as either: disease progression (>=3% increase), stable (=3% decrease). Results In untreated patients, 57% had disease progression at 1 year which significantly increased to 70% at 2 years (p<0.05). Mean increase in ECV of 4.0% after 1 year and 6.8% after 2 years was observed, and associated with significant worsening in biomarkers, ventricular wall thickness and global longitudinal strain at each timepoint. Left ventricular (LV) ejection fraction, indexed stroke volume and LV mass significantly worsened after 2 years. Following treatment with patisiran, no significant difference in mean ECV was observed at both timepoints. Disease stability was observed in 66% and 64% of patients and ECV regression observed in 17% and 21% of patients after 1 and 2 years of treatment with patisiran respectively. In all patients followed up at 1 year (n=160), reduction in ECV was not associated with a change in biomarkers or imaging parameters. ECV stability or progression was associated with significant worsening in wall thickness, LV volumes and biventricular longitudinal function. Conclusion CMR with ECV mapping demonstrates that cardiac amyloid deposition increases over time in ATTR amyloidosis and is associated with worsening cardiac structure and function. Although treatment with patisiran is associated with disease stability in the majority, stabilisation of cardiac structural and functional parameters is only observed in those with ECV regression, highlighting the importance of achieving a significant treatment response.