Skip to main content
SpringerLink
Log in

Relationship between heart rate response and cardiac innervation in patients with suspected or known coronary artery disease

  • ORIGINAL ARTICLE
  • Published:
Journal of Nuclear Cardiology Aims and scope

Abstract

Background

Chronotropic response to pharmacological stress test is blunted in patients with autonomic neuropathy. The relationship between heart rate (HR) changes during pharmacological stress test and cardiac autonomic dysfunction has not been fully investigated. We assessed the potential interplay between HR response (HRR) and myocardial innervation in patients with suspected or known coronary artery disease (CAD).

Methods and Results

We studied 71 patients with suspected or known CAD referred to pharmacological stress myocardial perfusion imaging and 123I metaiodobenzylguanidine (123I-MIBG) cardiac scintigraphy. HRR was calculated as the maximum percent change from baseline according to the formula: (peak HR − rest HR)/rest HR × 100. 123I-MIBG heart-to-mediastinum (H/M) ratio was calculated and a late H/M ratio < 1.6 was considered abnormal. HRR progressively decreased with decreasing late H/M ratio (P for trend = 0.02) and a significant correlation between HRR and late H/M ratio (P = 0.03) was observed. The addition of HRR to a model including age, diabetes, known CAD, left ventricular ejection fraction, and stress-induced ischemia added incremental value in predicting an abnormal late H/M ratio, increasing the global chi-square from 8.09 to 13.8 (P = 0.02).

Conclusions

The relationship between HRR and cardiac sympathetic innervation in patients with suspected or known CAD confirms a strong interplay between cardiac response to stress tests and cardiac autonomic activation. This finding suggests that HRR may be used as a surrogate for assessing cardiac sympathetic function.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Figure 1
Figure 2

Similar content being viewed by others

Abbreviations

HR:

Heart rate

HRR:

Heart rate response

MPI:

Myocardial perfusion imaging

MIBG:

Metaiodobenzylguanidine

H/M:

Heart-to-mediastinum

LV:

Left ventricular ejection fraction

EF:

Ejection fraction

References

  1. Nappi C, Ponsiglione A, Acampa W, Gaudieri V, Zampella E, Assante R, et al. Relationship between epicardial adipose tissue and coronary vascular function in patients with suspected coronary artery disease and normal myocardial perfusion imaging. Eur Heart J Cardiovasc Imaging 2019;20:1379-87.

    Article  Google Scholar 

  2. Tomiyama T, Kumita S, Ishihara K, Suda M, Sakurai M, Hakozaki K, et al. Patients with reduced heart rate response to adenosine infusion have low myocardial flow reserve in (13)N-ammonia PET studies. Int J Cardiovasc Imaging 2015;31:1089-95.

    Article  Google Scholar 

  3. Senneff MJ, Geltman EM, Bergmann SR. Noninvasive delineation of the effects of moderate aging on myocardial perfusion. J Nucl Med 1991;32:2037-42.

    CAS  PubMed  Google Scholar 

  4. Schaper W. Dipyridamole, an underestimated vascular protective drug. Cardiovasc Drugs Ther 2005;19:357-63.

    Article  CAS  Google Scholar 

  5. Dhalla AK, Wong MY, Wang WQ, Biaggioni I, Belardinelli L. Tachycardia caused by A2A adenosine receptor agonists is mediated by direct sympathoexcitation in awake rats. J Pharmacol Exp Ther 2006;316:695-702.

    Article  CAS  Google Scholar 

  6. Gorur GD, Ciftci EA, Kozdag G, Isgoren S, Oc MA, Haksal C, et al. Reduced heart rate response to dipyridamole in patients undergoing myocardial perfusion SPECT. Ann Nucl Med 2012;26:609-15.

    Article  CAS  Google Scholar 

  7. Hage FG, Wackers FJ, Bansal S, Chyun DA, Young LH, Inzucchi SE, et al. The heart rate response to adenosine: A simple predictor of adverse cardiac outcomes in asymptomatic patients with type 2 diabetes. Int J Cardiol 2013;167:2952-7.

    Article  Google Scholar 

  8. Mathur S, Shah AR, Ahlberg AW, Katten DM, Heller GV. Blunted heart rate response as a predictor of cardiac death in patients undergoing vasodilator stress technetium-99m sestamibi gated SPECT myocardial perfusion imaging. J Nucl Cardiol 2010;17:617-24.

    Article  Google Scholar 

  9. Rengo G, Pagano G, Vitale DF, Formisano R, Komici K, Petraglia L, et al. Impact of aging on cardiac sympathetic innervation measured by (123) I-mIBG imaging in patients with systolic heart failure. Eur J Nucl Med Mol Imaging 2016;43:2392-400.

    Article  CAS  Google Scholar 

  10. De Rosa A, Pellegrino T, Pappatà S, Pellecchia MT, Peluso S, Saccà F, et al. Myocardial (123) I-metaiodobenzylguanidine scintigraphy in patients with homozygous and heterozygous parkin mutations. J Nucl Cardiol 2017;24:103-7.

    Article  Google Scholar 

  11. De Rosa A, Pappatà S, Pellegrino T, De Leva MF, Maddaluno G, Fiumara G, et al. Reduced cardiac 123I-metaiodobenzylguanidine uptake in patients with spinocerebellar ataxia type 2: A comparative study with Parkinson’s disease. Eur J Nucl Med Mol Imaging 2013;40:1914-21.

    Article  Google Scholar 

  12. Verberne HJ, Acampa W, Anagnostopoulos C, Ballinger J, Bengel F, De Bondt P, et al. EANM procedural guidelines for radionuclide myocardial perfusion imaging with SPECT and SPECT/CT: 2015 revision. Eur J Nucl Med Mol Imaging 2015;42:1929-40.

    Article  CAS  Google Scholar 

  13. Paolillo S, Rengo G, Pagano G, Pellegrino T, Savarese G, Femminella GD, et al. Impact of diabetes on cardiac sympathetic innervation in patients with heart failure: A 123I meta-iodobenzylguanidine (123I MIBG) scintigraphic study. Diabetes Care 2013;36:2395-401.

    Article  CAS  Google Scholar 

  14. Acampa W, Petretta M, Daniele S, Del Prete G, Assante R, Zampella E, et al. Incremental prognostic value of stress myocardial perfusion imaging in asymptomatic diabetic patients. Atherosclerosis 2013;227:307-12.

    Article  CAS  Google Scholar 

  15. 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.

    Article  Google Scholar 

  16. Pellegrino T, Petretta M, De Luca S, Paolillo S, Boemio A, Carotenuto R, et al. Observer reproducibility of results from a low-dose 123I-metaiodobenzylguanidine cardiac imaging protocol in patients with heart failure. Eur J Nucl Med Mol Imaging 2013;40:1549-57.

    Article  CAS  Google Scholar 

  17. Lymperopoulos A, Rengo G, Koch WJ. Adrenergic nervous system in heart failure: Pathophysiology and therapy. Circ Res 2013;113:739-53.

    Article  CAS  Google Scholar 

  18. de Lucia C, Piedepalumbo M, Paolisso G, Koch WJ. Sympathetic nervous system in age-related cardiovascular dysfunction: Pathophysiology and therapeutic perspective. Int J Biochem Cell Biol 2019;108:29-33.

    Article  Google Scholar 

  19. Schnell O, Muhr D, Weiss M, Kirsch CM, Haslbeck M, Tatsch K, et al. Three-year follow-up on scintigraphically assessed cardiac sympathetic denervation in patients with long-term insulin-dependent (type 1) diabetes mellitus. J Diabetes Complicat 1997;11:307-13.

    Article  CAS  Google Scholar 

  20. Scott LA, Kench PL. Cardiac autonomic neuropathy in the diabetic patient: Does 123I-MIBG imaging have a role to play in early diagnosis? J Nucl Med Technol 2004;32:66-71.

    PubMed  Google Scholar 

  21. Hashimoto H, Nakanishi R, Mizumura S, Hashimoto Y, Okamura Y, Yamanaka K, et al. Prognostic values of (123) I-MIBG myocardial scintigraphy and heart rate variability in patients with heart failure with preserved ejection fraction. J Nucl Cardiol. 2018. https://doi.org/10.1007/s12350-018-01494-x.

    Article  PubMed  Google Scholar 

  22. AlJaroudi W. Heart rate and 123I-MIBG in heart failure with preserved ejection fraction: More variability and slower washout-A secret recipe for better survival. J Nucl Cardiol 2018. https://doi.org/10.1007/s12350-018-01514-w.

    Article  PubMed  Google Scholar 

  23. Bhatheja R, Francis GS, Pothier CE, Lauer MS. Heart rate response during dipyridamole stress as a predictor of mortality in patients with normal myocardial perfusion and normal electrocardiograms. Am J Cardiol 2005;95:1159-64.

    Article  Google Scholar 

  24. Agostini D, Verberne HJ, Burchert W, Knuuti J, Povinec P, Sambuceti G, et al. I-123-mIBG myocardial imaging for assessment of risk for a major cardiac event in heart failure patients: Insights from a retrospective European multicenter study. Eur J Nucl Med Mol Imaging 2008;35:535-46.

    Article  Google Scholar 

  25. Hage FG, Dean P, Iqbal F, Heo J, Iskandrian AE. A blunted heart rate response to regadenoson is an independent prognostic indicator in patients undergoing myocardial perfusion imaging. J Nucl Cardiol 2011;18:1086-94.

    Article  Google Scholar 

  26. Andrikopoulou E, Hage FG. Heart rate response to regadenoson: Making the case for its value in clinical practice. J Nucl Cardiol 2016;23:575-80.

    Article  Google Scholar 

Download references

Disclosure

C Nappi, R. Assante, E. Zampella, V. Gaudieri, G. De Simini, A. Giordano, A. D’Antonio, W. Acampa, M. Petretta, and A. Cuocolo declare that they have no financial conflicts of interest.

Author information

Authors and Affiliations

  1. Department of Advanced Biomedical Sciences, University Federico II, Via Pansini 5, 80131, Naples, Italy

    Carmela Nappi MD, PhD, Roberta Assante MD, PhD, Emilia Zampella MD, PhD, Valeria Gaudieri MD, PhD, Giovanni De Simini MD, Alessia Giordano MD, Adriana D’Antonio MD, Wanda Acampa MD, PhD & Alberto Cuocolo MD

  2. Institute of Biostructure and Bioimaging, National Council of Research, Naples, Italy

    Wanda Acampa MD, PhD

  3. Department of Translational Medical Sciences, University Federico II, Naples, Italy

    Mario Petretta MD, FAHA

Authors
  1. Carmela Nappi MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Roberta Assante MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Emilia Zampella MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Valeria Gaudieri MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Giovanni De Simini MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Alessia Giordano MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Adriana D’Antonio MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Wanda Acampa MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Mario Petretta MD, FAHA
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Alberto Cuocolo MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Alberto Cuocolo MD.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

The authors of this article have provided a PowerPoint file, available for download at SpringerLink, which summarizes the contents of the paper and is free for re-use at meetings and presentations. Search for the article DOI on SpringerLink.com.

The authors have also provided an audio summary of the article, which is available to download as ESM, or to listen to via the JNC/ASNC Podcast.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (PPTX 190 kb)

Supplementary material 2 (WAV 54792 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Nappi, C., Assante, R., Zampella, E. et al. Relationship between heart rate response and cardiac innervation in patients with suspected or known coronary artery disease. J. Nucl. Cardiol. 28, 2676–2683 (2021). https://doi.org/10.1007/s12350-020-02091-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12350-020-02091-7

Keywords

Search

Navigation