Evidence map›Paper›PMID 22412072›Full record

ArticleCirculation2012

Conduction remodeling in human end-stage nonischemic left ventricular cardiomyopathy.

Alexey V Glukhov, Vadim V Fedorov, Paul W Kalish, Vinod K Ravikumar, Qing Lou, Deborah Janks, Richard B Schuessler, Nader Moazami, Igor R Efimov

Open 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. Cited by 94 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
94citing papers in PubMed, 1 pooled it
11.4field-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.

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

94 citing papers in PubMed, 1 synthesis or guideline pooled it, 161 citations in OpenAlex.

  1. Pooled it
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  5. Article
  6. Article
  7. Cx45 regulation by kinases and impact of expression in heart failure.Journal of molecular and cellular cardiology · 2025
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  13. Molecular Pathways and Animal Models of Cardiomyopathies.Advances in experimental medicine and biology · 2024
    Article
  14. Complex repolarization dynamics in ex vivo human ventricles are independent of the restitution properties.Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology · 2023
    Article
  15. Review
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34 more citing papers are in PubMed but not listed here.

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 1 institution in 1 country.

Alexey V GlukhovDepartment of Biomedical Engineering, Washington University in St. Louis, MO 63130, USA.
Vadim V Fedorov
Paul W Kalish
Vinod K Ravikumar
Qing Lou
Deborah Janks
Richard B Schuessler
Nader Moazami
Igor R Efimov
Washington University in St. Louis · US

Funding

Virtual Electrode Polarization Hypothesis of DefibrillationR01HL067322 · NHLBI · WASHINGTON UNIVERSITY · PI EFIMOV, IGOR R · 2001 to 2010
$3.7M
ARRHYTHMOGENIC REMODELING IN HUMAN HEART FAILURER01HL114395 · NHLBI · WASHINGTON UNIVERSITY · PI EFIMOV, IGOR R · 2012 to 2015
$2.1M
STRUCTURE/FUNCTION OF THE PACEMAKING AND CONDUCTION SYSTEM OF THE HEARTR01HL085369 · NHLBI · WASHINGTON UNIVERSITY · PI EFIMOV, IGOR R · 2008 to 2011
$1.5M
NHLBI NIH HHS R01 HL067322NHLBI NIH HHS R01 HL085369NHLBI NIH HHS R01 HL085369 ANDNHLBI NIH HHS R01 HL114395
6 · The paper itself

Abstract

backgroundSeveral arrhythmogenic mechanisms have been inferred from animal heart failure models. However, the translation of these hypotheses is difficult because of the lack of functional human data. We aimed to investigate the electrophysiological substrate for arrhythmia in human end-stage nonischemic cardiomyopathy. METHODS AND

resultsWe optically mapped the coronary-perfused left ventricular wedge preparations from human hearts with end-stage nonischemic cardiomyopathy (heart failure, n=10) and nonfailing hearts (NF, n=10). Molecular remodeling was studied with immunostaining, Western blotting, and histological analyses. Heart failure produced heterogeneous prolongation of action potential duration resulting in the decrease of transmural action potential duration dispersion (64 ± 12 ms versus 129 ± 15 ms in NF, P<0.005). In the failing hearts, transmural activation was significantly slowed from the endocardium (39 ± 3 cm/s versus 49 ± 2 cm/s in NF, P=0.008) to the epicardium (28 ± 3 cm/s versus 40 ± 2 cm/s in NF, P=0.008). Conduction slowing was likely due to connexin 43 (Cx43) downregulation, decreased colocalization of Cx43 with N-cadherin (40 ± 2% versus 52 ± 5% in NF, P=0.02), and an altered distribution of phosphorylated Cx43 isoforms by the upregulation of the dephosphorylated Cx43 in both the subendocardium and subepicardium layers. Failing hearts further demonstrated spatially discordant conduction velocity alternans which resulted in nonuniform propagation discontinuities and wave breaks conditioned by strands of increased interstitial fibrosis (fibrous tissue content in heart failure 16.4 ± 7.7 versus 9.9 ± 1.4% in NF, P=0.02).

conclusionsConduction disorder resulting from the anisotropic downregulation of Cx43 expression, the reduction of Cx43 phosphorylation, and increased fibrosis is likely to be a critical component of arrhythmogenic substrate in patients with nonischemic cardiomyopathy.

Indexed as

Action PotentialsAnimalsArrhythmias, CardiacCardiomyopathiesConnexin 43DogsHeart FailureHumansPhosphorylationConnexin 43

Identifiers

PMID22412072
PMCPMC3351089
OpenAlexW1974493781

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

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.