Impaired in vitro growth response of plasma-treated cardiomyocytes predicts poor outcome in patients with transthyretin amyloidosis.
Clin Res Cardiol
; 110(4): 579-590, 2021 Apr.
Article
em En
| MEDLINE
| ID: mdl-33481097
ABSTRACT
OBJECTIVES:
Direct toxic effects of transthyretin amyloid in patient plasma upon cardiomyocytes are discussed. However, no data regarding the relevance of this putative effect for clinical outcome are available. In this monocentric prospective study, we analyzed cellular hypertrophy after phenylephrine stimulation in vitro in the presence of patient plasma and correlated the cellular growth response with phenotype and prognosis. METHODS ANDRESULTS:
Progress in automated microscopy and image analysis allows high-throughput analysis of cell morphology. Using the InCell microscopy system, changes in cardiomyocyte's size after treatment with patient plasma from 89 patients suffering from transthyretin amyloidosis and 16 controls were quantified. For this purpose, we propose a novel metric that we named Hypertrophic Index, defined as difference in cell size after phenylephrine stimulation normalized to the unstimulated cell size. Its prognostic value was assessed for multiple endpoints (HTX death/heart transplantation; DMP cardiac decompensation; MACE combined) using Cox proportional hazard models. Cells treated with plasma from healthy controls and hereditary transthyretin amyloidosis with polyneuropathy showed an increase in Hypertrophic Index after phenylephrine stimulation, whereas stimulation after treatment with hereditary cardiac amyloidosis or wild-type transthyretin patient plasma showed a significantly attenuated response. Hypertrophic Index was associated in univariate analyses with HTX (hazard ratio (HR) high vs low 0.12 [0.02-0.58], p = 0.004), DMP (HR 0.26 [0.11-0.62], p = 0.003) and MACE (HR 0.24 [0.11-0.55], p < 0.001). Its prognostic value was independent of established risk factors, cardiac TroponinT or N-terminal prohormone brain natriuretic peptide (NTproBNP).CONCLUSIONS:
Attenuated cardiomyocyte growth response after stimulation with patient plasma in vitro is an independent risk factor for adverse cardiac events in ATTR patients.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Plasma
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Neuropatias Amiloides Familiares
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Miócitos Cardíacos
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Processos de Crescimento Celular
Tipo de estudo:
Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Adolescent
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Adult
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Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Clin Res Cardiol
Assunto da revista:
CARDIOLOGIA
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Alemanha