ArticleCirculation2012
Conduction remodeling in human end-stage nonischemic left ventricular cardiomyopathy.
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.
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Who cites it
94 citing papers in PubMed, 1 synthesis or guideline pooled it, 161 citations in OpenAlex.
- Multi-ancestry GWAS of the electrocardiographic PR interval identifies 202 loci underlying cardiac conduction.Nature communications · 2020Pooled it
- In silico predictions of action potential propagation in doxorubicin cardiotoxicity: A parametric study using preclinical 3D magnetic resonance imaging-based fibrotic left ventricle models.The Journal of physiology · 2026Article
- Regulation of Pacemaker Current in the Sinoatrial Node by Zonula Occludens-1.bioRxiv : the preprint server for biology · 2026Article
- T-World Virtual Human Cardiomyocyte. I. Development, Validation, and Cell Arrhythmogenesis.Circulation research · 2026Article
- Stem cell-derived heterocellular atrial engineered cardiac tissue with comparisons to native human atrial myocardium.American journal of physiology. Heart and circulatory physiology · 2025Article
- Myocardial characterization using late enhancement photon-counting detector CT in ventricular arrhythmia: comparison with electroanatomical mapping.Insights into imaging · 2025Article
- Cx45 regulation by kinases and impact of expression in heart failure.Journal of molecular and cellular cardiology · 2025Article
- Developing cardiac digital twin populations powered by machine learning provides electrophysiological insights in conduction and repolarization.Nature cardiovascular research · 2025Article
- Stellate Ganglia: A Key Therapeutic Target for Malignant Ventricular Arrhythmia in Heart Disease.Circulation research · 2025Review
- Lethal Arrhythmogenic Role of Left Ventricular Myocardial Interstitial Fibrosis in Apolipoprotein E/Low-Density Lipoprotein Receptor Double-Knockout Mice with Metabolic Dysfunction-Associated Steatohepatitis.International journal of molecular sciences · 2024Article
- Neutral sphingomyelinase regulates mechanotransduction in human engineered cardiac tissues and mouse hearts.The Journal of physiology · 2024Article
- Spontaneous Repolarization Alternans Causes VT/VF Rearrest That Is Suppressed by Preserving Gap Junctions.JACC. Clinical electrophysiology · 2024Article
- Molecular Pathways and Animal Models of Cardiomyopathies.Advances in experimental medicine and biology · 2024Article
- 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 · 2023Article
- Biomarkers of Atrial Fibrillation Recurrence in Patients with Paroxysmal or Persistent Atrial Fibrillation Following External Direct Current Electrical Cardioversion.Biomedicines · 2023Review
- Cannabinoid receptor agonist attenuates angiotensin II-induced enlargement and mitochondrial dysfunction in rat atrial cardiomyocytes.Frontiers in pharmacology · 2023Article
- The physics of heart rhythm disorders.Physics reports · 2022Article
- Distress-Mediated Remodeling of Cardiac Connexin-43 in a Novel Cell Model for Arrhythmogenic Heart Diseases.International journal of molecular sciences · 2022Article
- Intracellular Redistribution of Left Ventricular Connexin 43 Contributes to the Remodeling of Electrical Properties of the Heart in Insulin-resistant Elderly Rats.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2022Article
- Effect of scar and pacing location on repolarization in a porcine myocardial infarction model.Heart rhythm O2 · 2022Article
34 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
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.
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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 OpenQuestion graph.