{
  "abstract": "Background and aims: The risk of atrial fibrillation (AF) is higher in endurance athletes. Pulmonary vein isolation (PVI) is effective in this group, implicating pulmonary vein (PV) remodelling, but underlying mechanisms are unclear. This study investigated if endurance training remodels PV sleeves and the PV-left atrial (LA) junction to promote PV triggers and a permissive peri-antral substrate for AF. Methods: In canine and murine endurance-running models, in vivo PV-LA mapping, ex vivo PV electrophysiology, intracellular action potential (AP) profiling with machine learning classification, histology, bulk RNA-seq, and subcellular-resolution spatial transcriptomics of PV-LA tissue were performed. These findings were incorporated into biophysically detailed computer models of human PV cardiomyocytes and a 3D human LA. Results: Training produced an athlete's heart phenotype and increased AF inducibility. In vivo, trained animals showed PV-LA conduction slowing and increased rotational activity. Ex vivo, trained PVs showed enhanced β-adrenergically evoked firing, prolonged burst activity, and a higher proportion of pacemaker-like APs. Spatial transcriptomics revealed discrete PV myocyte subpopulations with training upregulated Hcn4, Cacna1d, and Cacna1g (enhancing automaticity), downregulated Scn5a and Gja1 (slowing conduction), and enriched profibrotic/inflammatory signalling (Tnfα, Il6) alongside fibroblast expansion and extracellular matrix deposition. In silico, these changes reproduced faster spontaneous PV firing and sustained re-entry. Conclusions: Endurance training drives coupled electrical, structural, and inflammatory PV-LA remodelling that provides both trigger and substrate for AF. These data support why PV-targeted strategies can be effective in athletic AF and nominate modifiable pathways including HCN4-linked automaticity and TNFα-associated signalling.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": null,
  "author_total": 30,
  "authors": [
    {
      "name": "Luca Soattin"
    },
    {
      "name": "Leila Topal"
    },
    {
      "name": "Roman Tikhomirov"
    },
    {
      "name": "Daniele Lagomarsino-Oneto"
    },
    {
      "name": "Sami Al-Othman"
    },
    {
      "name": "Angela Lee"
    },
    {
      "name": "Sushant Saluja"
    },
    {
      "name": "Tibor Hornyik"
    },
    {
      "name": "Zoltán Husti"
    },
    {
      "name": "Jenő Antal Pintér"
    },
    {
      "name": "Aiman Saleh A Mohammed"
    },
    {
      "name": "Matthew Smith"
    },
    {
      "name": "Alice Francis"
    },
    {
      "name": "Megan Mckie"
    },
    {
      "name": "Eleonora Torre"
    },
    {
      "name": "Alexandra Polyák"
    },
    {
      "name": "Attila Farkas"
    },
    {
      "name": "Bo Hjorth Bentzen"
    },
    {
      "name": "Bernard Keavney"
    },
    {
      "name": "Norbert Nagy"
    },
    {
      "name": "Norbert Jost"
    },
    {
      "name": "Barbara Casadei"
    },
    {
      "name": "Matteo Mangoni"
    },
    {
      "name": "Mark Boyett"
    },
    {
      "name": "Michael Colman"
    },
    {
      "name": "Steven Niederer"
    },
    {
      "name": "András Varró"
    },
    {
      "name": "Gwilym Morris"
    },
    {
      "name": "István Baczkó"
    },
    {
      "name": "Alicia D’souza"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/3g17n7w091hth.bib",
  "cited_by": 0,
  "doi": "10.1093/eurheartj/ehag358",
  "fulltext_url": null,
  "id": "3g17n7w091hth",
  "issns": [
    "0195-668X",
    "1522-9645"
  ],
  "landing_url": "https://hal.science/hal-05845239v1",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "hal",
      "0.sdv"
    ],
    [
      "hal",
      "1.sdv.bc"
    ],
    [
      "hal",
      "1.sdv.mhep"
    ],
    [
      "hal",
      "2.sdv.mhep.csc"
    ],
    [
      "openalex",
      "2705|Cardiac electrophysiology and arrhythmias"
    ]
  ],
  "openalex": "W4407697149",
  "pdf_url": "https://hal.science/hal-05845239/document",
  "pmcid": null,
  "pmid": "42178147",
  "published": "2026-05-25",
  "publisher": "Oxford University Press (OUP)",
  "ris": "https://research.draconitic.com/paper/3g17n7w091hth.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:03Z",
      "native_id": "hal-05845239",
      "source": "hal",
      "url": "https://hal.science/hal-05845239v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "hal:1.sdv.bc",
      "subfield": "cell-biology"
    },
    {
      "field": "medicine",
      "origin": "hal:2.sdv.mhep.csc",
      "subfield": "cardiovascular"
    }
  ],
  "title": "Endurance exercise remodels pulmonary vein sleeve myocytes and promotes a proarrhythmic atrial substrate",
  "title_text": "Endurance exercise remodels pulmonary vein sleeve myocytes and promotes a proarrhythmic atrial substrate",
  "type": "peer-reviewed",
  "updated_at": "2026-11-01T12:20:45Z",
  "url": "https://research.draconitic.com/paper/3g17n7w091hth",
  "venue": "European Heart Journal",
  "versions": []
}