Evidence map›Paper›PMID 29030372›Full record

ArticleCirculation. Heart failure2017

Dose-Dependent Effects of the Myosin Activator Omecamtiv Mecarbil on Cross-Bridge Behavior and Force Generation in Failing Human Myocardium.

Ranganath Mamidi, Jiayang Li, Kenneth S Gresham, Sujeet Verma, Chang Yoon Doh, Amy Li, Sean Lal, Cristobal G Dos Remedios, Julian E Stelzer

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Circulation. Heart failure, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed
–field-weighted citation impact
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

38 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. What frozen human hearts can tell us about treating heart failure.American journal of physiology. Heart and circulatory physiology · 2025
    Article
  7. Article
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  9. The Efficacy of Risk Factor Modification Compared to NADJACC. Basic to translational science · 2024
    Article
  10. Review
  11. Review
  12. Hypertrophic cardiomyopathy inThe journal of cardiovascular aging · 2024
    Article
  13. Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. 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.

Ranganath MamidiFrom the Department of Physiology and Biophysics, School of Medicine, Case Western Reserve University, Cleveland, OH (R.M., J.L., C.Y.D., J.E.S.); Center for Translational Medicine, Lewis Katz School of Medicine, Temple University, Philadelphia, PA (K.S.G); Department of Horticulture Sciences, IFAS, Gulf Coast Research and Education Center, University of Florida, Wimauma (S.V.); Sydney Heart Bank, Discipline of Anatomy & Histology, Bosch Institute, University of Sydney, Australia (A.L., S.L., C.G.d.R.).
Jiayang LiFrom the Department of Physiology and Biophysics, School of Medicine, Case Western Reserve University, Cleveland, OH (R.M., J.L., C.Y.D., J.E.S.); Center for Translational Medicine, Lewis Katz School of Medicine, Temple University, Philadelphia, PA (K.S.G); Department of Horticulture Sciences, IFAS, Gulf Coast Research and Education Center, University of Florida, Wimauma (S.V.); Sydney Heart Bank, Discipline of Anatomy & Histology, Bosch Institute, University of Sydney, Australia (A.L., S.L., C.G.d.R.).
Kenneth S GreshamFrom the Department of Physiology and Biophysics, School of Medicine, Case Western Reserve University, Cleveland, OH (R.M., J.L., C.Y.D., J.E.S.); Center for Translational Medicine, Lewis Katz School of Medicine, Temple University, Philadelphia, PA (K.S.G); Department of Horticulture Sciences, IFAS, Gulf Coast Research and Education Center, University of Florida, Wimauma (S.V.); Sydney Heart Bank, Discipline of Anatomy & Histology, Bosch Institute, University of Sydney, Australia (A.L., S.L., C.G.d.R.).
Sujeet VermaFrom the Department of Physiology and Biophysics, School of Medicine, Case Western Reserve University, Cleveland, OH (R.M., J.L., C.Y.D., J.E.S.); Center for Translational Medicine, Lewis Katz School of Medicine, Temple University, Philadelphia, PA (K.S.G); Department of Horticulture Sciences, IFAS, Gulf Coast Research and Education Center, University of Florida, Wimauma (S.V.); Sydney Heart Bank, Discipline of Anatomy & Histology, Bosch Institute, University of Sydney, Australia (A.L., S.L., C.G.d.R.).
Chang Yoon DohFrom the Department of Physiology and Biophysics, School of Medicine, Case Western Reserve University, Cleveland, OH (R.M., J.L., C.Y.D., J.E.S.); Center for Translational Medicine, Lewis Katz School of Medicine, Temple University, Philadelphia, PA (K.S.G); Department of Horticulture Sciences, IFAS, Gulf Coast Research and Education Center, University of Florida, Wimauma (S.V.); Sydney Heart Bank, Discipline of Anatomy & Histology, Bosch Institute, University of Sydney, Australia (A.L., S.L., C.G.d.R.).
Amy LiFrom the Department of Physiology and Biophysics, School of Medicine, Case Western Reserve University, Cleveland, OH (R.M., J.L., C.Y.D., J.E.S.); Center for Translational Medicine, Lewis Katz School of Medicine, Temple University, Philadelphia, PA (K.S.G); Department of Horticulture Sciences, IFAS, Gulf Coast Research and Education Center, University of Florida, Wimauma (S.V.); Sydney Heart Bank, Discipline of Anatomy & Histology, Bosch Institute, University of Sydney, Australia (A.L., S.L., C.G.d.R.).
Sean LalFrom the Department of Physiology and Biophysics, School of Medicine, Case Western Reserve University, Cleveland, OH (R.M., J.L., C.Y.D., J.E.S.); Center for Translational Medicine, Lewis Katz School of Medicine, Temple University, Philadelphia, PA (K.S.G); Department of Horticulture Sciences, IFAS, Gulf Coast Research and Education Center, University of Florida, Wimauma (S.V.); Sydney Heart Bank, Discipline of Anatomy & Histology, Bosch Institute, University of Sydney, Australia (A.L., S.L., C.G.d.R.).
Cristobal G Dos RemediosFrom the Department of Physiology and Biophysics, School of Medicine, Case Western Reserve University, Cleveland, OH (R.M., J.L., C.Y.D., J.E.S.); Center for Translational Medicine, Lewis Katz School of Medicine, Temple University, Philadelphia, PA (K.S.G); Department of Horticulture Sciences, IFAS, Gulf Coast Research and Education Center, University of Florida, Wimauma (S.V.); Sydney Heart Bank, Discipline of Anatomy & Histology, Bosch Institute, University of Sydney, Australia (A.L., S.L., C.G.d.R.).
Julian E StelzerFrom the Department of Physiology and Biophysics, School of Medicine, Case Western Reserve University, Cleveland, OH (R.M., J.L., C.Y.D., J.E.S.); Center for Translational Medicine, Lewis Katz School of Medicine, Temple University, Philadelphia, PA (K.S.G); Department of Horticulture Sciences, IFAS, Gulf Coast Research and Education Center, University of Florida, Wimauma (S.V.); Sydney Heart Bank, Discipline of Anatomy & Histology, Bosch Institute, University of Sydney, Australia (A.L., S.L., C.G.d.R.). julian.stelzer@case.edu.

Funding

MEDICAL SCIENTIST TRAINING PROGRAMT32GM007250 · NIGMS · CASE WESTERN RESERVE UNIVERSITY · PI HUANG, ALEX YEE-CHEN · 1985 to 2023
$33.4M
TISSUE CULTURE AND HYBRIDOMA MODULEP30EY011373 · NEI · CASE WESTERN RESERVE UNIVERSITY · PI Irina A Pikuleva · 1997 to 2026
$17.7M
Functional consequences of FHC mutations in cardiac MyBPCR01HL114770 · NHLBI · CASE WESTERN RESERVE UNIVERSITY · PI STELZER, JULIAN · 2013 to 2023
$4.3M
NEI NIH HHS P30 EY011373NHLBI NIH HHS R01 HL114770NIGMS NIH HHS T32 GM007250
6 · The paper itself

Abstract

backgroundOmecamtiv mecarbil (OM) enhances systolic function in vivo by directly binding the myosin cross-bridges (XBs) in the sarcomere. However, the mechanistic details governing OM-induced modulation of XB behavior in failing human myocardium are unclear. METHODS AND

resultsThe effects of OM on steady state and dynamic XB behavior were measured in chemically skinned myocardial preparations isolated from human donor and heart failure (HF) left ventricle. HF myocardium exhibited impaired contractile function as evidenced by reduced maximal force, magnitude of XB recruitment (

conclusionsOur findings demonstrate that OM augments force generation but also prolongs the time course of XB transitions to force-bearing states in remodeled HF myocardium, which may extend the systolic ejection time in vivo. Optimal OM dosing is critical for eliciting enhanced systolic function without excessive prolongation of systolic ejection time, which may compromise diastolic filling.

Indexed as

Cardiotonic AgentsCarrier ProteinsCase-Control StudiesDose-Response Relationship, DrugHeart FailureHumansIn Vitro TechniquesMuscle StrengthMyocardial ContractionMyosin Binding Protein CMyosinsPhosphorylationProtein BindingSarcomeresSignal TransductionTime FactorsCardiotonic AgentsCarrier ProteinsMyosin Binding Protein CMyosinsomecamtiv mecarbilTroponin ITroponin TUreaheart failuremyocardiumomecamtiv mecarbilsacromeresystolic function

Identifiers

PMID29030372
PMCPMC5685665

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Registered trials

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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.