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.
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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
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.
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.
Senneff MJ, Geltman EM, Bergmann SR. Noninvasive delineation of the effects of moderate aging on myocardial perfusion. J Nucl Med 1991;32:2037-42.
Schaper W. Dipyridamole, an underestimated vascular protective drug. Cardiovasc Drugs Ther 2005;19:357-63.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Lymperopoulos A, Rengo G, Koch WJ. Adrenergic nervous system in heart failure: Pathophysiology and therapy. Circ Res 2013;113:739-53.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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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
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DOI: https://doi.org/10.1007/s12350-020-02091-7