Pathology and Function of Conduction Tissue in Fabry Disease Cardiomyopathy

Andrea Frustaci, Emanuela Morgante, Matteo A. Russo, Fernanda Scopelliti, Claudia Grande, Romina Verardo, Pasquale Franciosa, Cristina Chimenti

Research output: Contribution to journalArticlepeer-review

Abstract

Background - Cardiac arrhythmias are common in Fabry disease (FD) and may occur in prehypertrophic cardiomyopathy suggesting an early compromise of conduction tissue (CT). Therefore, FD X-linked and CT may be variously involved in male and female patients with FD cardiomyopathy, affecting CT function. Methods and Results - Among 74 patients with endomyocardial biopsy diagnosis of FD cardiomyopathy, 13 (6 men; 7 women; mean age, 50.1±13.5 years; maximal wall thickness, 16.7±3.7 mm) had CT included in histological specimens and 6 also at electron microscopy. CT glycolipid infiltration was defined as focal, moderate, extensive, or massive, if involved ≤30%, ≤50%, >50%, or 100% of cells; identified as loosely arranged small myocytes positive to HCN4 immunostaining, supplied by a centrally placed thick-walled arteriole. CT involvement was correlated with age, sex, and α-Gal gene mutation. CT function was evaluated by electrophysiological study and arrhythmias at Holter registration. CT infiltration was focal/moderate in 4 women with no arrhythmias and normal electrophysiological study, extensive in 3 women with atrial or ventricular arrhythmias and short HV interval, and massive in 6 men with atrial fibrillation or ventricular arrhythmias and short HV. Short PR/AH with increased refractoriness was additionally found in 3 patients with extensive/massive CT infiltration. A male patient with the shortest HV presented infra-Hissian block during decremental atrial stimulation. There was no correlation with age, maximal wall thickness, and type of gene mutation. Conclusions - CT infiltration in FD cardiomyopathy is constant in men and variable in women because of skewed X-chromosome inactivation; its extensive/massive involvement causes accelerated conduction with prolonged refractoriness and electric instability.

Original languageEnglish
Pages (from-to)799-805
Number of pages7
JournalCirculation: Arrhythmia and Electrophysiology
Volume8
Issue number4
DOIs
Publication statusPublished - Aug 22 2015

Keywords

  • arrhythmias
  • cardiac
  • cardiomyopathies
  • electron
  • Fabry disease
  • microscopy
  • mutation

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)
  • Medicine(all)

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