Early effects of transcatheter aortic valve replacement on cardiac sympathetic nervous function assessed by 123I-metaiodobenzylguanidine scintigraphy in patients with severe aortic valve stenosis

  • Yoshito Kadoya
  • Kan ZenEmail author
  • Nagara Tamaki
  • Nobuyasu Ito
  • Kensuke Kuwabara
  • Michiyo Yamano
  • Tetsuhiro Yamano
  • Takeshi Nakamura
  • Shigenori Matsushima
  • Katsuhiko Oka
  • Satoshi Numata
  • Hitoshi Yaku
  • Satoaki Matoba
Original Article
Part of the following topical collections:
  1. Cardiology



The effects of transcatheter aortic valve replacement (TAVR) on cardiac sympathetic nervous (CSN) function have not been fully explored. This study aimed to investigate the early (within 2 weeks) effects of TAVR on CSN function in patients with severe aortic valve stenosis (AS) using 123I-metaiodobenzylguanidine (MIBG) scintigraphy.


Of 143 consecutive patients who were scheduled to undergo TAVR, 67 (18 men; median age 86 years) were evaluated in this single-centre prospective observational study. MIBG scintigraphy was performed at baseline and 3–14 days after the TAVR procedure to evaluate the heart–mediastinum ratio (H/M) and washout rate (WR). Differences between baseline and post-TAVR MIBG parameters were analysed. MIBG parameter changes were compared with echocardiographic parameters. Furthermore, factors involved in the improvement in MIBG parameters were investigated.


All patients successfully underwent TAVR with improved echocardiographic parameters, including aortic valve area (AVA; 0.6 cm2 vs. 1.6 cm2), peak velocity (4.5 m/s vs. 2.0 m/s), mean pressure gradient (50 mmHg vs. 9 mmHg), and left ventricular ejection fraction (56% vs. 62%) (all p < 0.001). On MIBG imaging, delayed H/M significantly increased (2.57 vs. 2.68, p < 0.001), whereas WR decreased (32.2% vs. 26.8%, p < 0.001). In multivariate analysis, higher baseline WR was associated with improvement in WR (> 3%). Female sex, Clinical Frailty Scale score ≤ 5, baseline estimated glomerular filtration rate, and baseline AVA were predictors of improvement in delayed H/M (> 0.1). Baseline AVA and E/E′ were independent predictors of improvement in both WR and delayed H/M.


The CSN function was impaired in patients with AS, as assessed using MIBG scintigraphy. WR and delayed H/M improved immediately after TAVR. Improvement in CSN function may be related to echocardiographic AS severity at baseline before TAVR.


123I-Metaiodobenzylguanidine scintigraphy Cardiac sympathetic nervous Aortic valve stenosis Transcatheter aortic valve replacement 



Aortic valve stenosis


Left ventricular


Transcatheter aortic valve replacement


Cardiac sympathetic nervous




Mean aortic valve pressure gradient


Peak velocity


Aortic valve area;


Heart–mediastinum ratio


Washout rate


Author Contribution

Yoshito Kadoya collected data, performed statistical analysis, and wrote the manuscript. Kan Zen, Nagara Tamaki, Michiyo Yamano, Tetsuhiro Yamano, Takeshi Nakamura, Shigenori Matsushima, and Satoaki Matoba revised the manuscript and figures. Nobuyasu Ito and Kensuke Kuwabara collected data and revised the manuscript. Katsuhiko Oka, Satoshi Numata, and Hitoshi Yaku revised the manuscript. All the authors read and approved the final manuscript.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures were performed in accordance with the ethical standards of the institutional research committee of Kyoto Prefectural University of Medicine (no. ERB-C-1081-1) and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

Informed consent

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


  1. 1.
    Supino PG, Borer JS, Preibisz J, Bornstein A. The epidemiology of valvular heart disease: a growing public health problem. Heart Fail Clin. 2006;2:379–93.CrossRefGoogle Scholar
  2. 2.
    Maganti K, Rigolin VH, Sarano ME, Bonow RO. Valvular heart disease: diagnosis and management. Mayo Clin Proc. 2010;85:483–500.CrossRefGoogle Scholar
  3. 3.
    Smith CR, Leon MB, Mack MJ, Miller DC, Moses JW, Svensson LG, et al. Transcatheter versus surgical aortic-valve replacement in high-risk patients. N Engl J Med. 2011;364:2187–98.CrossRefGoogle Scholar
  4. 4.
    Leon MB, Smith CR, Mack M, Miller DC, Moses JW, Svensson LG, et al. Transcatheter aortic-valve implantation for aortic stenosis in patients who cannot undergo surgery. N Engl J Med. 2010;363:1597–607.CrossRefGoogle Scholar
  5. 5.
    Leon MB, Smith CR, Mack MJ, Makkar RR, Svensson LG, Kodali SK, et al. Transcatheter or surgical aortic-valve replacement in intermediate-risk patients. N Engl J Med. 2016;374:1609–20.CrossRefGoogle Scholar
  6. 6.
    Kodali S, Thourani VH, White J, Malaisrie SC, Lim S, Greason KL, et al. Early clinical and echocardiographic outcomes after SAPIEN 3 transcatheter aortic valve replacement in inoperable, high-risk and intermediate-risk patients with aortic stenosis. Eur Heart J. 2016;37:2252–62.CrossRefGoogle Scholar
  7. 7.
    Wieland DM, Wu J, Brown LE, Mangner TJ, Swanson DP, Beierwaltes WH. Radiolabeled adrenergic neuron-blocking agents: adrenomedullary imaging with [131I]iodobenzylguanidine. J Nucl Med. 1980;21:349–53.Google Scholar
  8. 8.
    Henderson EB, Kahn JK, Corbett JR, Jansen DE, Pippin JJ, Kulkarni P, et al. Abnormal I-123 metaiodobenzylguanidine myocardial washout and distribution may reflect myocardial adrenergic derangement in patients with congestive cardiomyopathy. Circulation. 1988;78:1192–9.CrossRefGoogle Scholar
  9. 9.
    Merlet P, Valette H, Dubois-Randé JL, Moyse D, Duboc D, Dove P, et al. Prognostic value of cardiac metaiodobenzylguanidine imaging in patients with heart failure. J Nucl Med. 1992;33:471–7.Google Scholar
  10. 10.
    Nakata T, Miyamoto K, Doi A, Sasao H, Wakabayashi T, Kobayashi H, et al. Cardiac death prediction and impaired cardiac sympathetic innervation assessed by MIBG in patients with failing and nonfailing hearts. J Nucl Cardiol. 1998;5:579–90.CrossRefGoogle Scholar
  11. 11.
    Jacobson AF, Senior R, Cerqueira MD, Wong ND, Thomas GS, Lopez VA, et al. Myocardial iodine-123 meta-iodobenzylguanidine imaging and cardiac events in heart failure. Results of the prospective ADMIRE-HF (AdreView Myocardial Imaging for Risk Evaluation in Heart Failure) study. J Am Coll Cardiol. 2010;55:2212–21.CrossRefGoogle Scholar
  12. 12.
    Verschure DO, Veltman CE, Manrique A, Somsen GA, Koutelou M, Katsikis A, et al. For what endpoint does myocardial 123I-MIBG scintigraphy have the greatest prognostic value in patients with chronic heart failure? Results of a pooled individual patient data meta-analysis. Eur Heart J Cardiovasc Imaging. 2014;15:996–1003.CrossRefGoogle Scholar
  13. 13.
    Nakata T, Nakajima K, Yamashina S, Yamada T, Momose M, Kasama S, et al. A pooled analysis of multicenter cohort studies of (123)I-mIBG imaging of sympathetic innervation for assessment of long-term prognosis in heart failure. JACC Cardiovasc Imaging. 2013;6:772–84.CrossRefGoogle Scholar
  14. 14.
    Nishimura RA, Otto CM, Bonow RO, Carabello BA, Erwin JP 3rd, Guyton RA, et al. 2014 AHA/ACC guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines. J Am Coll Cardiol. 2014;63:e57–185.CrossRefGoogle Scholar
  15. 15.
    Vukasovic JL, Florenzano F, Adriazola P, Escobar E. Heart rate variability in severe aortic stenosis. J Heart Valve Dis. 1999;8:143–8.Google Scholar
  16. 16.
    Nagamatsu H, Momose M, Kobayashi H, Kusakabe K, Kasanuki H. Prognostic value of 123I-metaiodobenzylguanidine in patients with various heart diseases. Ann Nucl Med. 2007;21:513–20.CrossRefGoogle Scholar
  17. 17.
    Dumonteil N, Vaccaro A, Despas F, Labrunee M, Marcheix B, Lambert E, et al. Transcatheter aortic valve implantation reduces sympathetic activity and normalizes arterial spontaneous baroreflex in patients with aortic stenosis. JACC Cardiovasc Interv. 2013;6:1195–202.CrossRefGoogle Scholar
  18. 18.
    Sobajima M, Ueno H, Onoda H, Kuwahara H, Tanaka S, Ushijima R, et al. Transcatheter aortic valve implantation improves cardiac sympathetic nerve activity on 123I-metaiodobenzylguanidine myocardial scintigraphy in severe aortic valve stenosis. Circ J. 2018;82:579–85.CrossRefGoogle Scholar
  19. 19.
    Jacobson AF, Travin MI. Impact of medications on mIBG uptake, with specific attention to the heart: comprehensive review of the literature. J Nucl Cardiol. 2015;22:980–93.CrossRefGoogle Scholar
  20. 20.
    Okuda K, Nakajima K, Hosoya T, Ishikawa T, Konishi T, Matsubara K, et al. Semi-automated algorithm for calculating heart-to-mediastinum ratio in cardiac iodine-123 MIBG imaging. J Nucl Cardiol. 2011;18:82–9.CrossRefGoogle Scholar
  21. 21.
    Veltman CE, Boogers MJ, Meinardi JE, Al Younis I, Dibbets-Schneider P, Van der Wall EE, et al. Reproducibility of planar (123)I-meta-iodobenzylguanidine (MIBG) myocardial scintigraphy in patients with heart failure. Eur J Nucl Med Mol Imaging. 2012;39:1599–608.CrossRefGoogle Scholar
  22. 22.
    Kasama S, Toyama T, Sumino H, Nakazawa M, Matsumoto N, Sato Y, et al. Prognostic value of serial cardiac 123I-MIBG imaging in patients with stabilized chronic heart failure and reduced left ventricular ejection fraction. J Nucl Med. 2008;49:907–14.CrossRefGoogle Scholar
  23. 23.
    Nakajima K, Matsumoto N, Kasai T, Matsuo S, Kiso K, Okuda K. Normal values and standardization of parameters in nuclear cardiology: Japanese Society of Nuclear Medicine working group database. Ann Nucl Med. 2016;30:188–99.CrossRefGoogle Scholar
  24. 24.
    Yamazaki J, Muto H, Kabano T, Yamashina S, Nanjo S, Inoue A. Evaluation of beta-blocker therapy in patients with dilated cardiomyopathy--clinical meaning of iodine 123-metaiodobenzylguanidine myocardial single-photon emission computed tomography. Am Heart J. 2001;141:645–52.CrossRefGoogle Scholar
  25. 25.
    Cohen-Solal A, Rouzet F, Berdeaux A, Le Guludec D, Abergel E, Syrota A, et al. Effects of carvedilol on myocardial sympathetic innervation in patients with chronic heart failure. J Nucl Med. 2005;46:1796–803.Google Scholar
  26. 26.
    Takeishi Y, Atsumi H, Fujiwara S, Takahashi K, Tomoike H. ACE inhibition reduces cardiac iodine-123-MIBG release in heart failure. J Nucl Med. 1997;38:1085–9.Google Scholar
  27. 27.
    Carrió I, Cowie MR, Yamazaki J, Udelson J, Camici PG. Cardiac sympathetic imaging with mIBG in heart failure. JACC Cardiovasc Imaging. 2010;3:92–100.CrossRefGoogle Scholar
  28. 28.
    Yamamoto M, Watanabe Y, Tada N, Naganuma T, Araki M, Yamanaka F, et al. Transcatheter aortic valve replacement outcomes in Japan: Optimized CathEter vAlvular iNtervention (OCEAN) Japanese multicenter registry. Cardiovasc Revasc Med. 2018:S1553–8389(18)30569–4.Google Scholar
  29. 29.
    Shimura T, Yamamoto M, Kano S, Kagase A, Kodama A, Koyama Y, et al. Impact of frailty markers on outcomes after transcatheter aortic valve replacement: insights from a Japanese multicenter registry. Ann Cardiothorac Surg. 2017;6:532–7.CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Yoshito Kadoya
    • 1
  • Kan Zen
    • 1
    Email author
  • Nagara Tamaki
    • 2
  • Nobuyasu Ito
    • 1
  • Kensuke Kuwabara
    • 1
  • Michiyo Yamano
    • 1
  • Tetsuhiro Yamano
    • 1
  • Takeshi Nakamura
    • 1
  • Shigenori Matsushima
    • 2
  • Katsuhiko Oka
    • 3
  • Satoshi Numata
    • 3
  • Hitoshi Yaku
    • 3
  • Satoaki Matoba
    • 1
  1. 1.Department of Cardiovascular Medicine, Graduate School of Medical ScienceKyoto Prefectural University of MedicineKyotoJapan
  2. 2.Department of Radiology, Graduate School of Medical ScienceKyoto Prefectural University of MedicineKyotoJapan
  3. 3.Department of Cardiovascular SurgeryKyoto Prefectural University of MedicineKyotoJapan

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