Evidence map›Paper›PMID 33481097›Full record

ArticleClinical research in cardiology : official journal of the German Cardiac Society2021

Impaired in vitro growth response of plasma-treated cardiomyocytes predicts poor outcome in patients with transthyretin amyloidosis.

Selina Hein, Jennifer Furkel, Maximilian Knoll, Fabian Aus dem Siepen, Stefan Schönland, Ute Hegenbart, Hugo A Katus, Arnt V Kristen, Mathias H Konstandin

Open access · hybridAbstract read
In one paragraph

Article in Clinical research in cardiology : official journal of the German Cardiac Society, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed, 1 pooled it
0.3field-weighted citation impact, top 45% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed, 1 synthesis or guideline pooled it, 6 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. Molecular Mechanisms of Cardiac Amyloidosis.International journal of molecular sciences · 2021
    Review
  5. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 2 institutions in 1 country.

Selina HeinDepartment of Cardiology, Angiology and Pulmonology, University Hospital Heidelberg, INF 410, 69120, Heidelberg, Germany. selina.hein@med.uni-heidelberg.de.ORCID http://orcid.org/0000-0003-0139-4200
Jennifer FurkelDepartment of Cardiology, Angiology and Pulmonology, University Hospital Heidelberg, INF 410, 69120, Heidelberg, Germany.
Maximilian KnollDepartment of Radiation Oncology, Heidelberg Ion-Beam Therapy Center (HIT), German Cancer Research Center, Heidelberg University Hospital (UKHD), Heidelberg, Germany.
Fabian Aus dem SiepenDepartment of Cardiology, Angiology and Pulmonology, University Hospital Heidelberg, INF 410, 69120, Heidelberg, Germany.
Stefan SchönlandDepartment of Hematology, Oncology and Rheumatology, Heidelberg University, Heidelberg, Germany.
Ute HegenbartDepartment of Hematology, Oncology and Rheumatology, Heidelberg University, Heidelberg, Germany.
Hugo A KatusDepartment of Cardiology, Angiology and Pulmonology, University Hospital Heidelberg, INF 410, 69120, Heidelberg, Germany.
Arnt V KristenDepartment of Cardiology, Angiology and Pulmonology, University Hospital Heidelberg, INF 410, 69120, Heidelberg, Germany.
Mathias H KonstandinDepartment of Cardiology, Angiology and Pulmonology, University Hospital Heidelberg, INF 410, 69120, Heidelberg, Germany. mathias.konstandin@med.uni-heidelberg.de.
Heidelberg University · DEGerman Cancer Research Center · DE

Funding

Aspire Grant 2016DFG KO-3900
6 · The paper itself

Abstract

objectivesDirect 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 AND

resultsProgress 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).

conclusionsAttenuated cardiomyocyte growth response after stimulation with patient plasma in vitro is an independent risk factor for adverse cardiac events in ATTR patients.

Indexed as

PlasmaAdolescentAdultAgedAged, 80 and overAmyloid Neuropathies, FamilialCell Growth ProcessesCells, CulturedFemaleFollow-Up StudiesHumansMaleMiddle AgedMyocytes, CardiacPrognosisProspective StudiesAmyloidosisHypertrophyIn-vitro assayTransthyretin

Identifiers

PMID33481097
PMCPMC8055573
OpenAlexW3126057091

What OpenQuestion holds

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LicenceCC BY
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.