Effect of patisiran on myocardial deformation parameters in patients with hereditary transthyretin amyloidosis
Authors: Di Lisi D , Brighina F , Di Stefano V , Portelli M C , Ortello A , Comparato F , Cannizzo N , Damerino G , Di Caccamo L , Galassi A R , Novo G 
Published: June 2023

Funding Acknowledgements

Type of funding sources: None.

Background/Introduction

Hereditary transthyretin amyloidosis (ATTRh) is a rare autosomal dominant disease caused by transthyretin (TTR) gene mutations. It can involve several systems on the basis of ATTR gene variant, age, duration of symptoms before diagnosis. Some TTR gene variants have a predominant cardiological or neurologic or mixed phenotype, therefore patients can have only cardiac amyloidosis or only polyneuropathy or both. Recently several advances have been performed in the diagnosis and treatment of cardiac amyloidosis, especially ATTRh amyloidosis using RNA-targeting and gene editing therapies. Particularly, patisiran is a small interfering RNAs that can be used only in patients with ATTRh polyneuropathy with or without concomitant cardiac amyloidosis (stage 1 or 2). Apollo A trial sub analysis demonstrated protective effects of patisiran on the heart.

Purpose

To assess the effects of patisiran on cardiac function in patients with ATTRh amyloidosis treated with patisiran.

Methods

a prospective study was carried out enrolling 31 subjects with ATTRh (20 men, 11 women, median age 61,7 ± 10,45 years old). 7 patients (22,6%) had cardiac amyloidosis plus polyneuropathy; 13 patients (41,9%) had only polyneuropathy without cardiac involvement; 11 patients were carriers without clinical manifestations. All patients except carriers were treated with patisiran. Cardiological evaluation including electrocardiogram and echocardiogram was performed in all patients at the time of enrollment and after an average period of 20 months of patisiran therapy. Comprehensive echocardiographic evaluation included the measurement of left ventricular global longitudinal strain (GLS), relative apical sparing, apical/basal strain ratio, myocardial work index expressed as global work index (GWI), global constructive work (GCW), global work waste (GWW), and global work efficiency (GWE), left atrial reservoir strain (PALS) and atrial stiffness (LASi).

Results

the group of patients with only polyneuropathy remained clinically stable over time and all echocardiographic parameters didn’t change significantly. In patients with cardiac amyloidosis, we found a significant improvement in GLS (−12,39±3,31% at baseline vs − 16,32 ± 2,84%, p value 0,03) and in LASI (1,6±0,30 vs 1±0,5, p value 0,01). GWI, GWE and GCW increased during follow-up, GWW reduced but not significantly. Also a reduction in the relative apical sparing (1,08±0,36 vs 1,05±0,25, p value 0,85) and in apical/basal strain ratio (2,5±1,4 vs 2,37±1,59, p value 0,87) was observed. No other significant changes in echocardiographic parameters were found.

Conclusion

Patisiran seems to be effective in stabilizing cardiac disease in ATTRh, significantly improving GLS and LASI. These new echocardiographic parameters should be used to monitor response to therapy in cardiac amyloidosis. The main limitation of our study is represented by the small sample size and to confirm our results wider studies are awaited.