Evidence mapPaperPMID 22586279Full record

ArticleCirculation2012

Ventricular assist device implantation corrects myocardial lipotoxicity, reverses insulin resistance, and normalizes cardiac metabolism in patients with advanced heart failure.

Aalap Chokshi, Konstantinos Drosatos, Faisal H Cheema, Ruiping Ji, Tuba Khawaja, Shuiqing Yu, Tomoko Kato, Raffay Khan, Hiroo Takayama, Ralph Knöll and 7 more

Registry-linked trialOpen access · bronzeAbstract read
In one paragraph

Article in Circulation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01761318 (Magnetic Resonance Assessment of Victoza Efficacy in the Regression of Cardiovascular Dysfunction In Type 2 Diabetes Mellitus), which is not on this map. Cited by 171 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
171citing papers in PubMed, 2 pooled it
18.5field-weighted citation impact, top 1% 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.

NCT01761318 phase4completedstarted 2013, after this paper: background citation

Magnetic Resonance Assessment of Victoza Efficacy in the Regression of Cardiovascular Dysfunction In Type 2 Diabetes Mellitus

Ran2013Enrolled50Registered outcomes48Posted comparisons0ConditionsCardiovascular Disease, Diabetes Mellitus Type 2, Diastolic Dysfunction, Fatty LiverArmsliraglutide, Liraglutide - Placebo
Open the trial in the graph
3 · Its place in the literature

Who cites it

171 citing papers in PubMed, 2 syntheses or guidelines pooled it, 289 citations in OpenAlex.

  1. Pooled it
  2. Ceramide Remodeling and Risk of Cardiovascular Events and Mortality.Journal of the American Heart Association · 2018
    Pooled it
  3. Trial
  4. Trial
  5. Article
  6. Review
  7. Review
  8. Review
  9. Review
  10. Review
  11. Review
  12. Mechanisms and Therapeutic Potential of Human Cardiomyocyte Proliferation.Journal of cardiovascular development and disease · 2026
    Review
  13. Article
  14. Review
  15. Article
  16. Article
  17. Article
  18. Review
  19. Article
  20. Article

111 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors at 2 institutions in 2 countries.

Aalap ChokshiColumbia University Medical Center, Center for Advanced Cardiac Care, Department of Medicine, Division of Cardiology, 622 W 168th St, PH 10, Room 203, New York, NY 10032, USA.
Konstantinos Drosatos
Faisal H Cheema
Ruiping Ji
Tuba Khawaja
Shuiqing Yu
Tomoko Kato
Raffay Khan
Hiroo Takayama
Ralph Knöll
Hendrik Milting
Christine S Chung
Ulrich Jorde
Yoshifumi Naka
Donna M Mancini
Ira J Goldberg
P Christian Schulze
Heart and Diabetes Center North Rhine-Westphalia · DEImperial College London · GB

Funding

EXTRACELLULAR REGULATION OF LIPOPROTEIN LIPASE ACTIVITYR37HL045095 · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2000 to 2005
$2.7M
Pathways of Tissue Lipid UptakeR01HL045095 · NHLBI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI Nada A. Abumrad, Ira J Goldberg · 1991 to 2024
$2.3M
Mechanisms of fatty acid uptake by cardiac muscleR01HL073029 · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2003 to 2005
$1.2M
NCRR NIH HHS UL1 RR 024156NCRR NIH HHS UL1 RR024156NHLBI NIH HHS HL073029NHLBI NIH HHS HL45095NHLBI NIH HHS K23 HL095742NHLBI NIH HHS K23 HL095742-01NHLBI NIH HHS P30 HL101272NHLBI NIH HHS P30 HL101272-01NHLBI NIH HHS R01 HL045095NHLBI NIH HHS R01 HL073029NHLBI NIH HHS R37 HL045095
6 · The paper itself

Abstract

backgroundHeart failure is associated with impaired myocardial metabolism with a shift from fatty acids to glucose use for ATP generation. We hypothesized that cardiac accumulation of toxic lipid intermediates inhibits insulin signaling in advanced heart failure and that mechanical unloading of the failing myocardium corrects impaired cardiac metabolism. METHODS AND

resultsWe analyzed the myocardium and serum of 61 patients with heart failure (body mass index, 26.5±5.1 kg/m(2); age, 51±12 years) obtained during left ventricular assist device implantation and at explantation (mean duration, 185±156 days) and from 9 control subjects. Systemic insulin resistance in heart failure was accompanied by decreased myocardial triglyceride and overall fatty acid content but increased toxic lipid intermediates, diacylglycerol, and ceramide. Increased membrane localization of protein kinase C isoforms, inhibitors of insulin signaling, and decreased activity of insulin signaling molecules Akt and Foxo were detectable in heart failure compared with control subjects. Left ventricular assist device implantation improved whole-body insulin resistance (homeostatic model of analysis-insulin resistance, 4.5±0.6-3.2±0.5; P<0.05) and decreased myocardial levels of diacylglycerol and ceramide, whereas triglyceride and fatty acid content remained unchanged. Improved activation of the insulin/phosphatidylinositol-3 kinase/Akt signaling cascade after left ventricular assist device implantation was confirmed by increased phosphorylation of Akt and Foxo, which was accompanied by decreased membrane localization of protein kinase C isoforms after left ventricular assist device implantation.

conclusionsMechanical unloading after left ventricular assist device implantation corrects systemic and local metabolic derangements in advanced heart failure, leading to reduced myocardial levels of toxic lipid intermediates and improved cardiac insulin signaling.

Indexed as

Heart-Assist DevicesAdultAgedCell LineCeramidesDiglyceridesFatty AcidsFemaleHeart FailureHumansInsulinInsulin ResistanceLipid MetabolismMaleMiddle AgedMyocardiumCeramidesDiglyceridesFatty AcidsInsulinProtein Kinase CTriglycerides

Identifiers

PMID22586279
PMCPMC3464497
OpenAlexW2061176979

What Socratic holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

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 Socratic graph.