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

Tadao Aikawa, Masanao Naya, Masahiko Obara, Noriko Oyama-Manabe, Osamu Manabe, Keiichi Magota, Yoichi M. Ito, Chietsugu Katoh, Nagara Tamaki

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

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.

Original languageEnglish
Pages (from-to)1897-1905
Number of pages9
JournalEuropean Journal of Nuclear Medicine and Molecular Imaging
Volume44
Issue number11
DOIs
StatePublished - 1 Oct 2017
Externally publishedYes

Keywords

  • C-Hydroxyephedrine
  • Contractile dysfunction
  • Heart failure with preserved ejection fraction
  • Myocardial fibrosis
  • Regional sympathetic denervation

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