Reduction in ^99mTc-DPD myocardial uptake with therapy of ATTR cardiomyopathy

Abstract

Aims: Novel ribonucleic acid interference (RNAi) therapeutics such as patisiran and inotersen have been shown to benefit neurologic disease course and quality of life in patients with hereditary transthyretin amyloidosis (ATTRv). We aimed to determine the impact of RNAi therapeutics on myocardial amyloid load using quantitative single photon emission computed tomography/computed tomography (SPECT/CT) imaging in patients with ATTRv-related cardiomyopathy (ATTRv-CM). We furthermore compared them with wild-type ATTR-CM (ATTRwt-CM) patients treated with tafamidis.

Methods and results: ATTRv-CM patients underwent [^99mTc]-radiolabeled diphosphono-1,2-propanodicarboxylic acid (^99mTc-DPD) scintigraphy and quantitative SPECT/CT imaging before and after 12 months (IQR: 11.0–12.0) of treatment with RNAi therapeutics (patisiran: n = 5, inotersen: n = 4). RNAi treatment significantly reduced quantitative myocardial uptake as measured by standardised uptake value (SUV) retention index (baseline: 5.09 g/mL vs. follow-up: 3.19 g/mL, p = .028) in ATTRv-CM patients without significant improvement in cardiac function. Tafamidis treatment resulted in a significant reduction in SUV retention index (4.96 g/mL vs. 3.27 g/mL, p < .001) in ATTRwt-CM patients (historical control cohort: n = 40) at follow-up [9.0 months (IQR: 7.0–10.0)] without beneficial impact on cardiac function.

Conclusions: RNAi therapeutics significantly reduce quantitative myocardial uptake in ATTRv-CM patients, comparable to tafamidis treatment in ATTRwt-CM patients, without impact on cardiac function. Serial ^99mTc-DPD SPECT/CT imaging may be a valuable tool to quantify and monitor response to disease-specific therapies in both ATTRv-CM and ATTRwt-CM.

Keywords:

• Inotersen
• patisiran
• RNA interference
• SPECT/CT
• tafamidis
• transthyretin cardiac amyloidosis
• treatment monitoring

Disclosure statement

R.R. received speaker fees and congress support from Akcea, Alnylam and Pfizer, as well as well as research grants from Pfizer. F.D. received speaker fees and congress support from Bayer, Novartis, Alnylam, Pfizer and AOP, as well as research grants from the Austrian Society of Cardiology and Pfizer. D.B. received speaker fees and congress support from Bayer, Novartis, Alnylam, Pfizer and AOP, as well as research grants from the Austrian Society of Cardiology and Pfizer. All other authors have nothing to declare.

Data availability statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.