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Concentric hypertrophic remodeling and subendocardial dysfunction in mitochondrial DNA point mutation carriers

Lookup NU author(s): Dr Matthew Bates, Dr Kieren Hollingsworth, Jane Newman, Professor Djordje JakovljevicORCiD, Professor Andrew BlamireORCiD, Dr Guy MacGowanORCiD, Professor Bernard Keavney, Professor Patrick Chinnery, Emeritus Professor Doug Turnbull, Professor Robert Taylor, Professor Mike TrenellORCiD, Professor Grainne Gorman


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Aims: Hypertrophic remodelling and systolic dysfunction are common in patients with mitochondrial disease and independent predictors of morbidity and early mortality. Screening strategies for cardiac disease are unclear. We investigated whether myocardial abnormalities could be identified in mitochondrial DNA mutation carriers without clinical cardiac involvement. Methods and results: Cardiac magnetic resonance imaging was performed in 22 adult patients with mitochondrial disease due to the m.3243A.G mutation, but no known cardiac involvement, and 22 age- and gender-matched control subjects: (i) Phosphorus-31- magnetic resonance spectroscopy, (ii) cine imaging (iii), cardiac tagging and (iv) late gadolinium enhancement (LGE) imaging. Disease burden was determined using the Newcastle Mitochondrial Disease Adult Scale (NMDAS) and urinary mutation load. Compared with control subjects, patients had an increased left ventricular mass index (LVMI), LV mass to end-diastolic volume (M/V) ratio, wall thicknesses (all P , 0.01), torsion and torsion to endocardial strain ratio (both P , 0.05). Longitudinal shortening was decreased in patients (P, 0.0001) and correlated with an increased LVMI (r ¼ 20.52, P , 0.03), but there were no differences in the diastolic function. Among patients there was no correlation of LVMI or the M/V ratio with diabetic or hypertensive status, but the mutation load and NMDAS correlated with the LVMI (r ¼ 0.71 and r ¼ 0.79, respectively, both P , 0.001). The phosphocreatine/adenosine triphosphate ratio was decreased in patients (P , 0.001) but did not correlate with other parameters. No patients displayed focal LGE. Conclusion: Concentric remodelling and subendocardial dysfunction occur in patients carrying m.3243A.G mutation without clinical cardiac disease. Patients with higher mutation loads and disease burden may be at increased risk of cardiac involvement.

Publication metadata

Author(s): Bates MG, Hollingsworth KG, Newman J, Jakovljevic DG, Blamire AM, MacGowan GA, Keavney BD, Chinnery PF, Turnbull DM, Taylor RW, Trenell MI, Gorman GS

Publication type: Article

Publication status: Published

Journal: European Heart Journal - Cardiovascular Imaging

Year: 2013

Volume: 14

Issue: 7

Pages: 650-658

Print publication date: 01/07/2013

Online publication date: 04/11/2012

Acceptance date: 05/10/2012

ISSN (print): 2047-2404

ISSN (electronic): 2047-2412

Publisher: Oxford University Press


DOI: 10.1093/ehjci/jes226

PubMed id: 23129433


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Funder referenceFunder name
Newcastle upon Tyne Hospitals NHS Foundation Trust
UK National Institute for Health Research Biomedical Research Centre for Ageing and Age-related Diseases
Penwest Pharmaceuticals
UK NHS Specialized Services
096919Z/11/ZWellcome Trust
074454/Z/04/ZWellcome Trust
CH/07/001British Heart Foundation
BH092142Wellcome Trust
G0601943Medical Research Council
G0800674Medical Research Council
G1100160Medical Research Council