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Quantification and Significance of Diffuse Myocardial Fibrosis and Diastolic Dysfunction in Childhood Hypertrophic Cardiomyopathy

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Abstract

The purpose of this study was to evaluate the presence of diffuse myocardial fibrosis in children and adolescents with hypertrophic cardiomyopathy (HCM) and to assess associations with echocardiographic and clinical parameters of disease. While a common end point in adults with HCM, it is unclear whether diffuse myocardial fibrosis occurs early in the disease. Cardiac magnetic resonance (CMR) estimation of myocardial post-contrast longitudinal relaxation time (T1) is an increasingly used method to estimate diffuse fibrosis. T1 measurements were taken using standard multi-breath-hold spoiled gradient echo phase-sensitive inversion-recovery CMR before and 15 min after the injection of gadolinium. The tissue–blood partition coefficient was calculated as a function of the ratio of T1 change of myocardium compared with blood. An echocardiogram and blood brain natriuretic peptide (BNP) levels were obtained on the day of the CMR. Twelve controls (mean age 12.8 years; 7 male) and 28 patients with HCM (mean age 12.8 years; 21 male) participated. The partition coefficient for both septal (0.27 ± 0.17 vs. 0.13 ± 0.09; p = 0.03) and lateral walls (0.22 ± 0.09 vs. 0.07 ± 0.10; p < 0.001) was increased in patients compared with controls. Eight patients had overt areas of late gadolinium enhancement (LGE). These patients did not show increased partition coefficient compared with those without LGE (0.27 ± 0.15 vs. 0.27 ± 0.19 and 0.22 ± 0.09 vs. 0.22 ± 0.09; p = 0.95 and 0.98, respectively). However, patients who were symptomatic (dyspnea, arrhythmia and/or chest pain) had higher lateral wall partition coefficient than asymptomatic HCM patients (0.27 ± 0.08 vs. 0.17 ± 0.08; p = 0.006). Similarly, patients with raised BNP (>100 pg/ml) had raised lateral wall coefficients (0.27 ± 0.07 vs. 0.20 ± 0.07; p = 0.03), as did those with traditional risk factors for sudden death (0.27 ± 0.06 vs. 0.18 ± 0.08; p = 0.007). Diffuse fibrosis, measured by the partition coefficient technique, is demonstrable in children and adolescents with HCM. Markers of fibrosis show an association with symptoms and raised serum BNP. Further study of the prognostic implication of this technique in young patients with HCM is warranted.

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Abbreviations

HCM:

Hypertrophic cardiomyopathy

CMR:

Cardiac magnetic resonance

T1:

Longitudinal relaxation time

BNP:

Brain natriuretic peptide

LGE:

Late gadolinium enhancement

LV:

Left ventricle

E/A:

Mitral inflow early-to-late diastolic flow ratio

IVRT:

Isovolumic relaxation time

S/D:

Pulmonary venous systolic-to-diastolic peak velocity ratio

E′lat:

Mitral lateral early diastolic tissue velocities

E′med:

Septal peak early diastolic tissue velocities

NYHA:

New York Heart Association

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Acknowledgments

Andreas Greiser is an employee of Siemens Healthcare, Erlangen, Germany. All the other authors were not consultants or employees for Siemens Healthcare and had control of inclusion of any data and information that might present a conflict of interest for Andreas Greiser. We thank Judith Wilson and Sandra Aiello for their help with the data collection.

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Authors and Affiliations

  1. Department of Pediatrics, Labatt Family Heart Centre, The Hospital for Sick Children, University of Toronto, Toronto, Canada

    Tarique Hussain, Andreea Dragulescu, Lee Benson, Shi-Joon Yoo, Howard Meng, Jonathan Windram, Derek Wong, Mark Friedberg, Luc Mertens, Michael Seed, Andrew Redington & Lars Grosse-Wortmann

  2. Department of Diagnostic Imaging, The Hospital for Sick Children, University of Toronto, Toronto, Canada

    Shi-Joon Yoo, Jonathan Windram, Derek Wong, Michael Seed & Lars Grosse-Wortmann

  3. Siemens AG Healthcare Sector, Erlangen, Germany

    Andreas Greiser

  4. Division of Imaging Sciences and Biomedical Engineering, The Rayne Institute, King’s College London, St. Thomas’ Hospital, 4th Floor, Lambeth Wing, London, SE1 7EH, UK

    Tarique Hussain

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  1. Tarique Hussain
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Correspondence to Tarique Hussain.

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Hussain, T., Dragulescu, A., Benson, L. et al. Quantification and Significance of Diffuse Myocardial Fibrosis and Diastolic Dysfunction in Childhood Hypertrophic Cardiomyopathy. Pediatr Cardiol 36, 970–978 (2015). https://doi.org/10.1007/s00246-015-1107-7

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  • DOI: https://doi.org/10.1007/s00246-015-1107-7

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