Low-dose ventricular radiotherapy was well tolerated in five patients with ATTRwt-CA, with 0 grade ≥3 adverse events over 6 months and a directional decrease in amyloid PET uptake.
Does low-dose ventricular radiotherapy reduce cardiac amyloid burden and is it safe in patients with wild-type transthyretin cardiac amyloidosis?
Low-dose ventricular radiotherapy appears safe and well-tolerated in a small first-in-human cohort of ATTRwt-CA patients, with early signals of reduced amyloid PET uptake warranting further study.
Absolute Event Rate: 0% vs 0%
Wild-type transthyretin cardiac amyloidosis (ATTRwt-CA) causes heart failure through myocardial deposition of misfolded transthyretin (TTR) fibrils. Radiotherapy has been explored in localized amyloid deposition in other organs, but its potential role in ATTRwt-CA remains unexplored. Eligible patients with ATTRwt-CA underwent low-dose radiotherapy (LD-RT) (10 Gy in 5 daily fractions) targeting the left ventricle. Cardiac amyloid burden was assessed using 18F-Flutemetamol amyloid PET (tissue-to-background ratio (TBR) in the septal and lateral LV walls) and cardiac magnetic resonance (CMR) imaging (extracellular volume and T1 mapping) at baseline and 12 weeks. Additionally, New York Heart Association (NYHA) class, cardiac biomarkers, transthoracic echocardiography, 6-minute walk test (6MWT) and the Short-Form 36-Item Health Survey (SF-36) were evaluated at baseline and at weeks 3, 6, 12, and 6 months post-LD-RT. Safety was assessed through systematic clinical follow-up and monitoring of patient-reported symptoms potentially attributable to LD-RT. Five patients with ATTRwt-CA (mean age 87 years) received focused LD-RT; two received concomitant tafamidis. No grade ≥ 3 treatment-related adverse events occurred over 6 months. At 12 weeks, clinical, biomarker, and functional changes were heterogeneous. A directional decrease in amyloid PET uptake ratio was observed in most patients, irrespective of tafamidis exposure, whereas native T1 values and left ventricular mass index on CMR showed no improvement. In this small exploratory cohort, cardiac radiotherapy was well tolerated. Although no efficacy conclusions can be drawn, the observed PET signal warrants cautious evaluation in adequately powered studies.
Guijarro et al. (Tue,) reported a other. Low-dose ventricular radiotherapy was well tolerated in five patients with ATTRwt-CA, with 0 grade ≥3 adverse events over 6 months and a directional decrease in amyloid PET uptake.