Evidence map›Paper›PMID 38802475›Full record

ArticleScientific reports2024

Cardiac myosin inhibitor, CK-586, minimally reduces systolic function and ameliorates obstruction in feline hypertrophic cardiomyopathy.

Victor N Rivas, Amanda E Crofton, Carina E Jauregui, Jalena R Wouters, Betty S Yang, Luke A Wittenburg, Joanna L Kaplan, Darren T Hwee, Anne N Murphy, Bradley P Morgan and 3 more

Abstract read
In one paragraph

Article in Scientific reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Article
  2. Review
  3. Review
  4. Review
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

13 authors.

Victor N RivasDepartment of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, 1060 William Moore Dr, Raleigh, NC, 27607, USA.
Amanda E CroftonDepartment of Medicine and Epidemiology, School of Veterinary Medicine, University of California-Davis, Davis, CA, USA.
Carina E JaureguiDepartment of Medicine and Epidemiology, School of Veterinary Medicine, University of California-Davis, Davis, CA, USA.
Jalena R WoutersDepartment of Medicine and Epidemiology, School of Veterinary Medicine, University of California-Davis, Davis, CA, USA.
Betty S YangDepartment of Medicine and Epidemiology, School of Veterinary Medicine, University of California-Davis, Davis, CA, USA.
Luke A WittenburgDepartment of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California-Davis, Davis, CA, USA.
Joanna L KaplanDepartment of Medicine and Epidemiology, School of Veterinary Medicine, University of California-Davis, Davis, CA, USA.
Darren T HweeResearch and Non-Clinical Development, Cytokinetics, Inc., South San Francisco, CA, USA.
Anne N MurphyResearch and Non-Clinical Development, Cytokinetics, Inc., South San Francisco, CA, USA.
Bradley P MorganResearch and Non-Clinical Development, Cytokinetics, Inc., South San Francisco, CA, USA.
Fady I MalikResearch and Non-Clinical Development, Cytokinetics, Inc., South San Francisco, CA, USA.
Samantha P HarrisDepartment of Physiology, University of Arizona, Tucson, AZ, USA.
Joshua A SternDepartment of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, 1060 William Moore Dr, Raleigh, NC, 27607, USA. jastern@ncsu.edu.

Funding

Training Program In Basic & Translational Cardiovascular ScienceT32HL086350 · NHLBI · UNIVERSITY OF CALIFORNIA AT DAVIS · PI Martin Cadeiras, David A. Liem · 2008 to 2026
$7.1M
Comparative Medical Science Training ProgramT32OD011147 · OD · UNIVERSITY OF CALIFORNIA AT DAVIS · PI JEROEN SAEIJ, Sara Michelle Thomasy · 2012 to 2026
$5.5M
UC Davis CTSC TL1 Administrative Supplement to Recognize Excellence in Diversity, Equity, Inclusion, and Accessibility MentorshipTL1TR001861 · NCATS · UNIVERSITY OF CALIFORNIA AT DAVIS · PI MEDICI, VALENTINA · 2016 to 2025
$4.7M
MARC at University of California, DavisT34GM136469 · NIGMS · UNIVERSITY OF CALIFORNIA AT DAVIS · PI ALDRIN V. GOMES, Crystal D Rogers · 2020 to 2026
$2.8M
UC Davis DVM/PhD Medical Scientist Training ProgramT32GM136559 · NIGMS · UNIVERSITY OF CALIFORNIA AT DAVIS · PI Xinbin Chen, Bethany Paige Cummings · 2020 to 2026
$2.2M
Defining the role of core binding factor protein interactions in osteosarcomaK01OD026526 · OD · UNIVERSITY OF CALIFORNIA AT DAVIS · PI WITTENBURG, LUKE A. · 2018 to 2022
$675k
Morris Animal Foundation D22FE-027NCATS NIH HHS TL1 TR001861NCATS NIH HHS TR001861NHLBI NIH HHS HL086350NHLBI NIH HHS T32 HL086350NIGMS NIH HHS GM136469NIGMS NIH HHS T32 GM136559NIGMS NIH HHS T34 GM136469NIH HHS K01 OD026526NIH HHS T32 OD011147NIH Office of the Director OD011147NIH Office of the Director OD026526
6 · The paper itself

Abstract

Hypertrophic cardiomyopathy (HCM) remains the most common cardiomyopathy in humans and cats with few preclinical pharmacologic interventional studies. Small-molecule sarcomere inhibitors are promising novel therapeutics for the management of obstructive HCM (oHCM) patients and have shown efficacy in left ventricular outflow tract obstruction (LVOTO) relief. The objective of this study was to explore the 6-, 24-, and 48-hour (h) pharmacodynamic effects of the cardiac myosin inhibitor, CK-586, in six purpose-bred cats with naturally occurring oHCM. A blinded, randomized, five-treatment group, crossover preclinical trial was conducted to assess the pharmacodynamic effects of CK-586 in this oHCM model. Dose assessments and select echocardiographic variables were assessed five times over a 48-h period. Treatment with oral CK-586 safely ameliorated LVOTO in oHCM cats. CK-586 treatment dose-dependently eliminated obstruction (reduced LVOTOmaxPG), increased measures of systolic chamber size (LVIDs Sx), and decreased select measures of heart function (LV FS% and LV EF%) in the absence of impact on heart rate. At all tested doses, a single oral CK-586 dose resulted in improved or resolved LVOTO with well-tolerated, dose-dependent, reductions in LV systolic function. The results from this study pave the way for the potential use of CK-586 in both the veterinary and human clinical setting.

Indexed as

Cardiac MyosinsCardiomyopathy, HypertrophicAnimalsCat DiseasesCatsCross-Over StudiesEchocardiographyFemaleMaleSystoleVentricular Outflow ObstructionCardiac MyosinsCatLeft ventricular outflow tract obstruction (LVOTO)Myosin-inhibitorObstructive hypertrophic cardiomyopathy (oHCM)Pharmacodynamics

Identifiers

PMID38802475
PMCPMC11130313

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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.