Cardiac MRI as a possible alternative to echocardiography for therapeutic response monitoring in ATTR cardiomyopathy: a multiparametric evaluation in patisiran treated patients
Authors: Neculae G , Adam R , Badelita S , Onciul S , Jercan A , Neagu D , Draghici M , Coriu D , Popescu B A , Jurcut R 
Published: June 2023

Abstract

Funding Acknowledgements
Type of funding sources: None.

Background
Cardiac amyloidosis (CA) is characterized by the extracellular deposition of amyloid fibrils in the heart, mostly light chain (AL) and transthyretin (ATTR) amyloidosis. Recent data have improved both the recognition and treatment of ATTR CA. The therapeutic advances in ATTR CA led to improvement in survival and quality of life, but less detailed evidence is available for the myocardial changes during treatment.

Purpose
The aim of this pilot study is to evaluate cardiac response under treatment with the genetic "silencer" patisiran in patients with mixed phenotype ATTR with an indication for neuropathy, using multimodal imaging techniques.

Methods
We prospectively evaluated consecutive patients with mixed phenotype v-ATTR amyloidosis who had received patisiran for aggravated polyneuropathy since 2021. All patients had a complete clinical, paraclinical and comprehensive echocardiography evaluation including myocardial deformation assessment, prior to receiving patisiran and at most recent follow-up. Five of our patient had complementary cardiac magnetic resonance (CMR) at baseline and 1 year follow-up.

Results
We included 13 patients (mean age 48.1±5.4 yo, 4 men) monitored for the therapeutic response based on the current ESC expert consensus on the monitoring of ATTR CA. They have all been diagnosed with variant ATTR with the same mutation - Glu54Gln - with severe mixed phenotype: both cardiac involvement and autonomous and peripheral polyneuropathy. Time since first diagnosis was 3.4 ±0.8 years, and they had all received Tafamidis 20 mg before being switched to patisiran. At 1 year of treatment, there was no significant change in NYHA functional class, but 6 MWT could not be performed due to impairment related to polyneuropathy. There was no significant change in NT-proBNP during treatment (median at baseline 543 pg/ml vs follow-up 255 pg/ml, p = 0.75). Echocardiography showed no significant change in LV maximal wall thickness (MWT), LV mass index (LVMi), LVEF, stroke volume and myocardial deformation (LV GLS) (Table). Based on these echocardiographic and biological parameters we considered our patients stationary. Meanwhile, CMR confirmed no significant difference between baseline and follow-up in LVMi, MWT and LVEF. Moreover, there was no difference in the visually assessed LGE distribution, native T1, T2 and ECV values (Table, Case vignette). Based on the tissue characterization all patients were considered stable regarding ATTR-CA evolution. We found strong correlations between echo and MRI for LVEF (r=0.71), LVEDV (r=0.67) and MWT (r=0.66).

Conclusions
Even if used after more than 3 years from first diagnosis in our cohort, structural and functional cardiac parameters remain stable under patisiran therapy. Our study highlights the utility of introducing CMR as an alternative to echocardiography in ATTR-CA disease monitoring protocols, based on its high accuracy, strong correlations and complexity of derived parameters.