Immune-mediated myocarditis in fabry disease cardiomyopathy

Andrea Frustaci, Romina Verardo, Claudia Grande, Nicola Galea, Pierluca Piselli, Iacopo Carbone, Maria Alfarano, Matteo Antonio Russo, Cristina Chimenti

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Background—Glycosphingolipid accumulation in Fabry cells generates a proinflammatory response that may influence disease evolution and responsiveness to enzyme replacement therapy. This study evaluated incidence, mechanism, and impact of myocarditis in Fabry disease cardiomyopathy (FDCM). Methods and Results—Myocarditis, defined as CD3+T lymphocytes >7/mm2associated with necrosis of glycolipid-laden myocardiocytes, was retrospectively evaluated in endomyocardial biopsies from 78 patients with FDCM: 13 with maximal wall thickness (MWT) <11 mm (group 1), 17 with MWT 11 to 15 mm (group 2), 30 with MWT 16 to 20 mm (group 3), and 18 with MWT >20 mm (group 4). Myocarditis was investigated by polymerase chain reaction for cardiotropic viruses, by serum antiheart and antimyosin antibodies, and by cardiac magnetic resonance. Myocarditis was recognized at histology in 48 of 78 patients with FDCM (38% of group 1, 41% of group 2, 66% of group 3, and 72% of group 4). Myocarditis was characterized by positive antiheart and antimyosin antibodies and negative polymerase chain reaction for viral genomes. CD3+cells/mm2correlated with myocyte necrosis, antimyosin autoantibody titer, and MWT (P<0.001,r=0.79; P<0.001, r=0.84; P<0.001, r=0.61, respectively). Cardiac magnetic resonance showed myocardial edema in 24 of 78 patients (31%): 0% of group 1, 23% of group 2, 37% of group 3, and 50% of group 4. Conclusions—Myocarditis is detectable at histology in up to 56% of patients with FDCM. It is immune mediated and correlates with disease severity. It can be disclosed by antiheart/antimyosin autoantibodies and in the advanced phase by cardiac magnetic resonance. It may contribute to progression of FDCM and resistance to enzyme replacement therapy.

Original languageEnglish
Article numbere009052
JournalJournal of the American Heart Association
Volume7
Issue number17
DOIs
Publication statusPublished - Sep 1 2018

Fingerprint

Fabry Disease
Myocarditis
Cardiomyopathies
Enzyme Replacement Therapy
Magnetic Resonance Spectroscopy
Autoantibodies
Histology
Necrosis
Polymerase Chain Reaction
Disease Resistance
Antibodies
Viral Genome
Glycolipids
Muscle Cells
Edema
Cohort Studies
Viruses
T-Lymphocytes
Biopsy
Serum

Keywords

  • Cardiomyopathy
  • Fabry disease
  • Heart failure
  • Myocarditis

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Immune-mediated myocarditis in fabry disease cardiomyopathy. / Frustaci, Andrea; Verardo, Romina; Grande, Claudia; Galea, Nicola; Piselli, Pierluca; Carbone, Iacopo; Alfarano, Maria; Russo, Matteo Antonio; Chimenti, Cristina.

In: Journal of the American Heart Association, Vol. 7, No. 17, e009052, 01.09.2018.

Research output: Contribution to journalArticle

@article{3c297bc4c929430994b71092ce9be436,
title = "Immune-mediated myocarditis in fabry disease cardiomyopathy",
abstract = "Background—Glycosphingolipid accumulation in Fabry cells generates a proinflammatory response that may influence disease evolution and responsiveness to enzyme replacement therapy. This study evaluated incidence, mechanism, and impact of myocarditis in Fabry disease cardiomyopathy (FDCM). Methods and Results—Myocarditis, defined as CD3+T lymphocytes >7/mm2associated with necrosis of glycolipid-laden myocardiocytes, was retrospectively evaluated in endomyocardial biopsies from 78 patients with FDCM: 13 with maximal wall thickness (MWT) <11 mm (group 1), 17 with MWT 11 to 15 mm (group 2), 30 with MWT 16 to 20 mm (group 3), and 18 with MWT >20 mm (group 4). Myocarditis was investigated by polymerase chain reaction for cardiotropic viruses, by serum antiheart and antimyosin antibodies, and by cardiac magnetic resonance. Myocarditis was recognized at histology in 48 of 78 patients with FDCM (38{\%} of group 1, 41{\%} of group 2, 66{\%} of group 3, and 72{\%} of group 4). Myocarditis was characterized by positive antiheart and antimyosin antibodies and negative polymerase chain reaction for viral genomes. CD3+cells/mm2correlated with myocyte necrosis, antimyosin autoantibody titer, and MWT (P<0.001,r=0.79; P<0.001, r=0.84; P<0.001, r=0.61, respectively). Cardiac magnetic resonance showed myocardial edema in 24 of 78 patients (31{\%}): 0{\%} of group 1, 23{\%} of group 2, 37{\%} of group 3, and 50{\%} of group 4. Conclusions—Myocarditis is detectable at histology in up to 56{\%} of patients with FDCM. It is immune mediated and correlates with disease severity. It can be disclosed by antiheart/antimyosin autoantibodies and in the advanced phase by cardiac magnetic resonance. It may contribute to progression of FDCM and resistance to enzyme replacement therapy.",
keywords = "Cardiomyopathy, Fabry disease, Heart failure, Myocarditis",
author = "Andrea Frustaci and Romina Verardo and Claudia Grande and Nicola Galea and Pierluca Piselli and Iacopo Carbone and Maria Alfarano and Russo, {Matteo Antonio} and Cristina Chimenti",
year = "2018",
month = "9",
day = "1",
doi = "10.1161/JAHA.118.009052",
language = "English",
volume = "7",
journal = "Journal of the American Heart Association",
issn = "2047-9980",
publisher = "Wiley-Blackwell",
number = "17",

}

TY - JOUR

T1 - Immune-mediated myocarditis in fabry disease cardiomyopathy

AU - Frustaci, Andrea

AU - Verardo, Romina

AU - Grande, Claudia

AU - Galea, Nicola

AU - Piselli, Pierluca

AU - Carbone, Iacopo

AU - Alfarano, Maria

AU - Russo, Matteo Antonio

AU - Chimenti, Cristina

PY - 2018/9/1

Y1 - 2018/9/1

N2 - Background—Glycosphingolipid accumulation in Fabry cells generates a proinflammatory response that may influence disease evolution and responsiveness to enzyme replacement therapy. This study evaluated incidence, mechanism, and impact of myocarditis in Fabry disease cardiomyopathy (FDCM). Methods and Results—Myocarditis, defined as CD3+T lymphocytes >7/mm2associated with necrosis of glycolipid-laden myocardiocytes, was retrospectively evaluated in endomyocardial biopsies from 78 patients with FDCM: 13 with maximal wall thickness (MWT) <11 mm (group 1), 17 with MWT 11 to 15 mm (group 2), 30 with MWT 16 to 20 mm (group 3), and 18 with MWT >20 mm (group 4). Myocarditis was investigated by polymerase chain reaction for cardiotropic viruses, by serum antiheart and antimyosin antibodies, and by cardiac magnetic resonance. Myocarditis was recognized at histology in 48 of 78 patients with FDCM (38% of group 1, 41% of group 2, 66% of group 3, and 72% of group 4). Myocarditis was characterized by positive antiheart and antimyosin antibodies and negative polymerase chain reaction for viral genomes. CD3+cells/mm2correlated with myocyte necrosis, antimyosin autoantibody titer, and MWT (P<0.001,r=0.79; P<0.001, r=0.84; P<0.001, r=0.61, respectively). Cardiac magnetic resonance showed myocardial edema in 24 of 78 patients (31%): 0% of group 1, 23% of group 2, 37% of group 3, and 50% of group 4. Conclusions—Myocarditis is detectable at histology in up to 56% of patients with FDCM. It is immune mediated and correlates with disease severity. It can be disclosed by antiheart/antimyosin autoantibodies and in the advanced phase by cardiac magnetic resonance. It may contribute to progression of FDCM and resistance to enzyme replacement therapy.

AB - Background—Glycosphingolipid accumulation in Fabry cells generates a proinflammatory response that may influence disease evolution and responsiveness to enzyme replacement therapy. This study evaluated incidence, mechanism, and impact of myocarditis in Fabry disease cardiomyopathy (FDCM). Methods and Results—Myocarditis, defined as CD3+T lymphocytes >7/mm2associated with necrosis of glycolipid-laden myocardiocytes, was retrospectively evaluated in endomyocardial biopsies from 78 patients with FDCM: 13 with maximal wall thickness (MWT) <11 mm (group 1), 17 with MWT 11 to 15 mm (group 2), 30 with MWT 16 to 20 mm (group 3), and 18 with MWT >20 mm (group 4). Myocarditis was investigated by polymerase chain reaction for cardiotropic viruses, by serum antiheart and antimyosin antibodies, and by cardiac magnetic resonance. Myocarditis was recognized at histology in 48 of 78 patients with FDCM (38% of group 1, 41% of group 2, 66% of group 3, and 72% of group 4). Myocarditis was characterized by positive antiheart and antimyosin antibodies and negative polymerase chain reaction for viral genomes. CD3+cells/mm2correlated with myocyte necrosis, antimyosin autoantibody titer, and MWT (P<0.001,r=0.79; P<0.001, r=0.84; P<0.001, r=0.61, respectively). Cardiac magnetic resonance showed myocardial edema in 24 of 78 patients (31%): 0% of group 1, 23% of group 2, 37% of group 3, and 50% of group 4. Conclusions—Myocarditis is detectable at histology in up to 56% of patients with FDCM. It is immune mediated and correlates with disease severity. It can be disclosed by antiheart/antimyosin autoantibodies and in the advanced phase by cardiac magnetic resonance. It may contribute to progression of FDCM and resistance to enzyme replacement therapy.

KW - Cardiomyopathy

KW - Fabry disease

KW - Heart failure

KW - Myocarditis

UR - http://www.scopus.com/inward/record.url?scp=85054498547&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85054498547&partnerID=8YFLogxK

U2 - 10.1161/JAHA.118.009052

DO - 10.1161/JAHA.118.009052

M3 - Article

AN - SCOPUS:85054498547

VL - 7

JO - Journal of the American Heart Association

JF - Journal of the American Heart Association

SN - 2047-9980

IS - 17

M1 - e009052

ER -