ESC Heart Failure (Aug 2025)

Electron microscopic findings predict clinical outcomes in patients with non‐ischaemic cardiomyopathy

  • Rie Higuchi,
  • Shozo Konishi,
  • Tomohito Ohtani,
  • Fusako Sera,
  • Misato Chimura,
  • Machiko Kanzaki,
  • Themistoklis Katsimichas,
  • Masahiro Seo,
  • Tetsuya Watanabe,
  • Takahiro Okumura,
  • Toyoaki Murohara,
  • Hiroyuki Takahama,
  • Atsushi Okada,
  • Chisato Izumi,
  • Masaru Hatano,
  • Issei Komuro,
  • Yoshihiko Ikeda,
  • Yoshihiro Asano,
  • Hatsue Ishibashi‐Ueda,
  • Yasushi Sakata

DOI
https://doi.org/10.1002/ehf2.15255
Journal volume & issue
Vol. 12, no. 4
pp. 2441 – 2449

Abstract

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Abstract Aims Electron microscopy reveals microstructural alterations in cardiomyocyte nuclei and myofilaments in non‐ischaemic cardiomyopathy (NICM), particularly in dilated cardiomyopathy (DCM). Nevertheless, the correlation between such observations and clinical outcomes, including prognosis and left ventricular reverse remodelling (LVRR), remains unclear. This study aimed to examine the association between electron microscopic findings and outcomes in patients with NICM. Methods In this multicentre, prospective, observational study, 170 patients with NICM with reduced ejection fraction (EF) 35% with a 10% unit absolute increase, were collected 1 year post‐biopsy. Results A total of 148 patients were finally analysed. Discontinuous nuclear envelopes and myofilament injuries were observed in 17 (11%) and 46 (31%) patients with NICM, respectively. The incidence of cardiac events at 1 year did not differ between groups with discontinuous and continuous nuclear envelopes [12% vs. 6%, odds ratio (OR): 2.05, 95% confidential interval (CI): 0.40–10.6, P = 0.391], whereas the LVRR rate was significantly lower in the discontinuous group than in the continuous group (24% vs. 52%, OR: 0.29, 95% CI: 0.08–0.92, P = 0.036). The incidences of cardiac events and LVRR at 1 year differed between the injured and preserved myofilament groups (15% vs. 3%, OR: 6.64, 95% CI: 1.32–33.5, P = 0.022; 15% vs. 64%, OR: 0.10, 95% CI: 0.04–0.25, P < 0.001, respectively). These associations between electron microscopic findings and clinical outcomes persisted, even in patients who were finally diagnosed with DCM. Conclusions Discontinuous nuclear envelopes were associated with a reduced LVRR rate, whereas injured myofilaments were correlated with higher 1 year cardiac events and a decreased LVRR. Evaluation of electron microscopic images in diagnostic endomyocardial biopsy can facilitate risk stratification of NICM or DCM with reduced EF.

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