Subclinical effects of long-chain fatty acid β-oxidation deficiency on the adult heart: A case-control magnetic resonance study.

Abstract

Cardiomyopathy can be a severe complication in patients with long-chain fatty acid β-oxidation disorders (LCFAOD), particularly during episodes of metabolic derangement. It is unknown whether latent cardiac abnormalities exist in adult patients. To investigate cardiac involvement in LCFAOD, we used proton magnetic resonance imaging (MRI) and spectroscopy (1 H-MRS) to quantify heart function, myocardial tissue characteristics, and myocardial lipid content in 14 adult patients (two with long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD); four with carnitine palmitoyltransferase II deficiency (CPT2D); and eight with very long-chain acyl-CoA dehydrogenase deficiency (VLCADD)) and 14 gender-, age-, and BMI-matched control subjects. Examinations included cine MRI, MR tagging, native myocardial T1 and T2 mapping, and localized 1 H-MRS at 3 Tesla. Left ventricular (LV) myocardial mass (P = .011) and the LV myocardial mass-to-volume ratio (P = .008) were higher in patients, while ejection fraction (EF) was normal (P = .397). LV torsion was higher in patients (P = .026), whereas circumferential shortening was similar compared with controls (P = .875). LV hypertrophy was accompanied by high myocardial T1 values (indicative of diffuse fibrosis) in two patients, and additionally a low EF in one case. Myocardial lipid content was similar in patients and controls. We identified subclinical morphological and functional differences between the hearts of LCFAOD patients and matched control subjects using state-of-the-art MR methods. Our results suggest a chronic cardiac disease phenotype and hypertrophic LV remodeling of the heart in LCFAOD, potentially triggered by a mild, but chronic, energy deficiency, rather than by lipotoxic effects of accumulating lipid metabolites.

• Authors: Suzan J G Knottnerus, Jeannette C Bleeker, Sacha Ferdinandusse, Riekelt H Houtkooper, Mirjam Langeveld, Aart J Nederveen, Gustav J Strijkers, Gepke Visser, Ronald J A Wanders, Frits A Wijburg, S Matthijs Boekholdt, Adrianus J Bakermans
• Journal: Journal of inherited metabolic disease (J Inherit Metab Dis) Vol. 43 Issue 5 Pg. 969-980 (09 2020) ISSN: 1573-2665 [Electronic] United States
• PMID: 32463482 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2020 The Authors. Journal of Inherited Metabolic Disease published by John Wiley & Sons Ltd on behalf of SSIEM.

Chemical References

• 3-Hydroxyacyl CoA Dehydrogenases
• Acyl-CoA Dehydrogenase, Long-Chain
• Carnitine O-Palmitoyltransferase

Topics

• 3-Hydroxyacyl CoA Dehydrogenases (deficiency)
• Acyl-CoA Dehydrogenase, Long-Chain (deficiency)
• Adolescent
• Adult
• Cardiomyopathies (pathology)
• Carnitine O-Palmitoyltransferase (deficiency)
• Case-Control Studies
• Congenital Bone Marrow Failure Syndromes (pathology)
• Female
• Humans
• Lipid Metabolism, Inborn Errors (pathology)
• Magnetic Resonance Imaging, Cine
• Magnetic Resonance Spectroscopy
• Male
• Middle Aged
• Mitochondrial Diseases (pathology)
• Muscular Diseases (pathology)
• Young Adult