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<p>Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, driven by electrical and structural remodeling that promotes proarrhythmic substrates. Interindividual variability in susceptibility to remodeling triggers, such as myocardial ischemia, suggests the involvement of genetic determinants. Ischemic heart failure (IHF) was induced by a 90-min occlusion of the left anterior descending artery in pigs. After 30&#xa0;days, animals underwent in vivo assessments, including right and left heart catheterization, electrocardiography, and electrophysiological studies, with AF inducibility tested by burst pacing. Atrial fibrosis was quantified using Masson’s trichrome staining, and remodeling-associated gene expression was analyzed by quantitative PCR. Genetic background was assessed through single-nucleotide polymorphism (SNP) genotyping using the Porcine SNP60 BeadChip, with data analyzed against reference SNP datasets. Following myocardial infarction, all animals developed IHF with reduced ejection fraction and increased AF susceptibility. Overall, IHF was associated with enhanced atrial fibrosis, but a subset of animals displayed no fibrotic remodeling. Genetic analysis identified two groups of pigs with different genetic backgrounds within the cohort: a Pietrain-dominant and a Landrace-dominant background. Pietrain-dominant pigs developed significantly more atrial fibrosis, whereas Landrace-dominant pigs exhibited a pronounced shortening of the atrial effective refractory period. Differential regulation of fibrosis-associated genes, including <i>FN</i>, <i>MMP2</i>, <i>TGFB</i>, and <i>JNK1</i>, was observed between genetic backgrounds. These findings indicate that genetic background is associated with distinct patterns of atrial remodeling in response to IHF, influencing key determinants of AF susceptibility.</p>

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Genetic background is associated with distinct patterns of proarrhythmogenic remodeling leading to atrial fibrillation in pigs with ischemic heart failure

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月8日

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  • Zhihao Zhang,
  • Julia Vlcek,
  • Christina Heger,
  • Valerie Pauly,
  • Nora Hesse,
  • Dominik Schüttler,
  • Daphne Merkus,
  • Eckhard Wolf,
  • Ivica Medugorac,
  • Stefan Kääb,
  • Philipp Tomsits,
  • Sebastian Clauss

摘要

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, driven by electrical and structural remodeling that promotes proarrhythmic substrates. Interindividual variability in susceptibility to remodeling triggers, such as myocardial ischemia, suggests the involvement of genetic determinants. Ischemic heart failure (IHF) was induced by a 90-min occlusion of the left anterior descending artery in pigs. After 30 days, animals underwent in vivo assessments, including right and left heart catheterization, electrocardiography, and electrophysiological studies, with AF inducibility tested by burst pacing. Atrial fibrosis was quantified using Masson’s trichrome staining, and remodeling-associated gene expression was analyzed by quantitative PCR. Genetic background was assessed through single-nucleotide polymorphism (SNP) genotyping using the Porcine SNP60 BeadChip, with data analyzed against reference SNP datasets. Following myocardial infarction, all animals developed IHF with reduced ejection fraction and increased AF susceptibility. Overall, IHF was associated with enhanced atrial fibrosis, but a subset of animals displayed no fibrotic remodeling. Genetic analysis identified two groups of pigs with different genetic backgrounds within the cohort: a Pietrain-dominant and a Landrace-dominant background. Pietrain-dominant pigs developed significantly more atrial fibrosis, whereas Landrace-dominant pigs exhibited a pronounced shortening of the atrial effective refractory period. Differential regulation of fibrosis-associated genes, including FN, MMP2, TGFB, and JNK1, was observed between genetic backgrounds. These findings indicate that genetic background is associated with distinct patterns of atrial remodeling in response to IHF, influencing key determinants of AF susceptibility.