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Regional interaction between myocardial sympathetic denervation, contractile dysfunction, and fibrosis in heart failure with preserved ejection fraction: 11C-hydroxyephedrine PET study

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

This investigation aimed to identify significant predictors of regional sympathetic denervation quantified by 11C-hydroxyephedrine (HED) positron emission tomography (PET) in patients with heart failure with preserved left ventricular ejection fraction (HFpEF).

Methods

Included in the study were 34 patients (age 63 ± 15 years, 23 men) with HFpEF (left ventricular ejection fraction ≥40%) and 11 age-matched volunteers without heart failure. Cardiac magnetic resonance imaging was performed to measure left ventricular size and function, and the extent of myocardial late gadolinium enhancement (LGE). 11C-HED PET was performed to quantify myocardial sympathetic innervation that was expressed as a 11C-HED retention index (RI, %/min). To identify predictors of regional 11C-HED RI in HFpEF patients, we propose a multivariate mixed-effects model for repeated measures over segments with an unstructured covariance matrix.

Results

Global 11C-HED RI was significantly lower and more heterogeneous in HFpEF patients than in volunteers (P < 0.01 for all). Regional 11C-HED RI was correlated positively with systolic wall thickening (r = 0.42, P < 0.001) and negatively with the extent of LGE (r = −0.43, P < 0.001). Segments in HFpEF patients with a large extent of LGE had the lowest regional 11C-HED RI among all segments (P < 0.001 in post hoc tests). Multivariate analysis demonstrated that systolic wall thickening and the extent of LGE were significant predictors of regional 11C-HED RI in HFpEF patients (both P ≤ 0.001).

Conclusion

Regional sympathetic denervation was associated with contractile dysfunction and fibrotic burden in HFpEF patients, suggesting that regional sympathetic denervation may provide an integrated measure of myocardial damage in HFpEF.

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Authors and Affiliations

  1. Department of Cardiovascular Medicine, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Kita-15, Nishi-7, Kita-ku, Sapporo, 060-8638, Japan

    Tadao Aikawa, Masanao Naya & Masahiko Obara

  2. Department of Diagnostic and Interventional Radiology, Hokkaido University Hospital, Kita-14, Nishi-5, Kita-ku, Sapporo, 060-8648, Japan

    Noriko Oyama-Manabe

  3. Department of Nuclear Medicine, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Kita-15, Nishi-7, Kita-ku, Sapporo, 060-8638, Japan

    Osamu Manabe

  4. Division of Medical Imaging and Technology, Hokkaido University Hospital, Kita-14, Nishi-5, Kita-ku, Sapporo, 060-8648, Japan

    Keiichi Magota

  5. Department of Biostatistics, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Kita-15, Nishi-7, Kita-ku, Sapporo, 060-8638, Japan

    Yoichi M. Ito

  6. Department of Biomedical Science and Engineering, Faculty of Health Sciences, Hokkaido University, Kita-15, Nishi-7, Kita-ku, Sapporo, 060-8638, Japan

    Chietsugu Katoh

  7. Department of Radiology, Kyoto Prefectural University of Medicine, Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan

    Nagara Tamaki

Authors
  1. Tadao Aikawa
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  2. Masanao Naya
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  3. Masahiko Obara
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  4. Noriko Oyama-Manabe
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  5. Osamu Manabe
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  6. Keiichi Magota
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  7. Yoichi M. Ito
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  8. Chietsugu Katoh
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  9. Nagara Tamaki
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Corresponding author

Correspondence to Masanao Naya.

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Funding

This work was supported by a grant-in-aid for scientific research (grant no. JP24591742) from the Ministry of Education, Culture, Sports, Science, and Technology (M.N.).

Conflicts of interest

None.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the principles of the 1964 Declaration Helsinki and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

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Aikawa, T., Naya, M., Obara, M. et al. Regional interaction between myocardial sympathetic denervation, contractile dysfunction, and fibrosis in heart failure with preserved ejection fraction: 11C-hydroxyephedrine PET study. Eur J Nucl Med Mol Imaging 44, 1897–1905 (2017). https://doi.org/10.1007/s00259-017-3760-y

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  • DOI: https://doi.org/10.1007/s00259-017-3760-y

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