Effect of patisiran on stroke volume in hereditary transthyretin-mediated amyloidosis: insights from pressure-volume analysis of the APOLLO study.
ATTR amyloidosis
Haemodynamics
Heart failure
RNAi therapeutics
Transthyretin amyloidosis
Journal
European journal of heart failure
ISSN: 1879-0844
Titre abrégé: Eur J Heart Fail
Pays: England
ID NLM: 100887595
Informations de publication
Date de publication:
May 2023
May 2023
Historique:
revised:
11
12
2022
received:
23
04
2022
accepted:
22
01
2023
pmc-release:
01
05
2024
medline:
19
6
2023
pubmed:
25
1
2023
entrez:
24
1
2023
Statut:
ppublish
Résumé
Transthyretin-mediated (ATTR) amyloidosis is caused by deposition of transthyretin protein fibrils in the heart, nerves, and other organs. Patisiran, an RNA interference therapeutic that inhibits hepatic synthesis of transthyretin, was approved for the treatment of hereditary ATTR amyloidosis with polyneuropathy based on the phase 3 APOLLO study. We use left ventricular (LV) stroke volume (SV) to quantify LV function overtime and non-invasive pressure-volume techniques to delineate the effects of patisiran on LV mechanics in the pre-specified cardiac subpopulation of the APOLLO study. Left ventricular SV was assessed by transthoracic echocardiography at baseline, and after 9 and 18 months of therapy. To determine the mechanisms underlying changes in LV SV, non-invasive pressure-volume parameters, including the end-systolic and end-diastolic pressure-volume relationship, were derived using single beat techniques. At baseline, the mean SV was 51 ± 14 ml. At 9 months, the least-squares mean change in SV was -0.3 ± 1.2 ml for patisiran and -5.4 ± 1.9 ml for placebo (p = 0.021). At 18 months, the least-squares mean change in SV was -1.7 ± 1.3 ml for patisiran and - 8.1 ± 2.3 ml for placebo (p = 0.016). Decline in LV SV was driven by diminished LV capacitance in placebo relative to patisiran. Patisiran may delay progression of LV chamber dysfunction starting at 9 months of therapy. These data elucidate the mechanisms by which transthyretin-reducing therapies modulate progression of cardiac disease and need to be confirmed in ongoing phase 3 trials.
Identifiants
pubmed: 36693807
doi: 10.1002/ejhf.2783
pmc: PMC10277223
mid: NIHMS1868033
doi:
Substances chimiques
patisiran
50FKX8CB2Y
Prealbumin
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
727-736Subventions
Organisme : NIA NIH HHS
ID : K24 AG036778
Pays : United States
Organisme : NHLBI NIH HHS
ID : T32 HL007854
Pays : United States
Informations de copyright
© 2023 European Society of Cardiology.
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