Journal of Nuclear Cardiology

, Volume 8, Issue 2, pp 129–135 | Cite as

Dipyridamole myocardial SPECT with low heart rate response indicates cardiac autonomic dysfunction in patients with diabetes

  • Kyung-Han Lee
  • Joon Kee Yoon
  • Mun Gyu Lee
  • Sang Hoon Lee
  • Won Ro Lee
  • Byung-Tae Kim



Because dipyridamole is used to assess heart rate (HR) variability, we investigated whether a low HR response during dipyridamole single photon emission computed tomography (SPECT) in patients with diabetes indicates the presence of cardiac autonomic neuropathy (CAN).

Methods and Results

Subjects were 61 non-insulin-dependent diabetes patients without perfusion defects, myocardial infarction, or arrhythmia who underwent thallium 201 SPECT imaging. The control group comprised 28 subjects without diabetes. HR was measured during infusion of dipyridamole at a rate of 0.14 mg/kg/min, and peak-baseline ratios of 1.20 or less were defined as low. CAN severity was classified by standard autonomic function tests as severe (n = 22), mild (n = 19), or none (n = 20). HR ratios were significantly attenuated in patients with diabetes compared with those in control subjects (1.22 ± 0.12 vs 1.32 ± 0.12, P <.001). Among the patients with diabetes, HR ratios decreased as CAN severity increased from none (1.32 ± 0.10) to mild (1.23 ± 0.12, P <.05) to severe (1.13 ± 0.08, P <.005). There was good correlation between HR ratio and R-R interval ratio to deep breathing and to Valsalva, and patients with low HR ratios showed an attenuated response to both tests (all P <.001). The sensitivity and specificity of HR ratios in the detection of CAN were 77% and 74% for severe CAN and 63% and 90% for mild-to-severe CAN, respectively.


In patients with diabetes who have normal dipyridamole SPECT results, an attenuated HR response observed during stress indicates a high likelihood of CAN. Further work that assesses these results in diabetes patients with coronary artery disease is warranted.

Key Words

Myocardial imaging dipyridamole heart rate cardiac autonomic neuropathy 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Petrucci E, Mainardi LT, Balian V, Ghiringhelli S, Bianchi AM, Bertinelli M, et al. Assessment of heart rate variability changes during dipyridamole infusion and dipyridamole-induced myocardial ischemia: a time variant spectral approach. J Am Coll Cardiol 1996; 28: 924–34.PubMedCrossRefGoogle Scholar
  2. 2.
    Petretta M, Spinelli L, Marciano F, Vicario ML, Testa G, Signorini A, et al. Wavelet transform analysis of heart rate variability during dipyridamole- induced myocardial ischemia: relation to angiographic severity and echocardiographic dyssynergy. Clin Cardiol 1999; 22: 201–6.PubMedCrossRefGoogle Scholar
  3. 3.
    Zahedi A, Floras JS, Burns RJ. Absence of heart rate increase during inferoposterior left ventricular hypoperfusion caused by dipyridamole infusion. Can J Cardiol 1999; 15: 1345–9.PubMedGoogle Scholar
  4. 4.
    Ziegler D, Gries FA, Spuler M, Lessmann F. The epidemiology of diabetic neuropathy. Diabetic Cardiovascular Autonomic Neuropathy Multicenter Study Group. J Diabetes Complications 1992; 6: 49–57.PubMedCrossRefGoogle Scholar
  5. 5.
    Fedele D, Comi G, Coscelli C, Cucinotta D, Feldman EL, Ghirlanda G, et al. A multicenter study on the prevalence of diabetic neuropathy in Italy. Italian Diabetic Neuropathy Committee. Diabetes Care 1997; 20: 836–43.PubMedCrossRefGoogle Scholar
  6. 6.
    Ewing DJ, Campbell IW, Clarke BF. Mortality in diabetic autonomic neuropathy. Lancet 1976; 1: 601–3.PubMedCrossRefGoogle Scholar
  7. 7.
    Johnston DL, Hodge DO, Hopfenspirger MR, Gibbons RJ. Clinical determinants of hemodynamic and symptomatic responses in 2,000 patients during adenosine scintigraphy. Mayo Clin Proc 1998; 73: 314–20.PubMedCrossRefGoogle Scholar
  8. 8.
    Ewing DJ, Campbell IW, Clarke BF. Assessment of cardiovascular effects in diabetic autonomic neuropathy and prognosis implications. Ann Intern Med 1980; 92: 308–11.PubMedGoogle Scholar
  9. 9.
    Bellavere F, Balzani I, De Masi G, Carraro M, Carenza P, Cobelli C, et al. Power spectral analysis of heart-rate variations improves assessment of diabetic cardiac autonomic neuropathy. Diabetes 1992; 41: 633–40.PubMedCrossRefGoogle Scholar
  10. 10.
    Clarke B, Conradson TB, Dixon CM, Barnes PJ. Reproducibility of heart rate changes following adenosine infusion in man. Eur J Clin Pharmacol 1988; 35: 309–11.PubMedCrossRefGoogle Scholar
  11. 11.
    Homma S, Gilliland Y, Guiney TE, Strauss HW, Boucher CA. Safety of intravenous dipyridamole for stress testing with thallium imaging. Am J Cardiol 1987; 59: 152–4.PubMedCrossRefGoogle Scholar
  12. 12.
    Rongen GA, Brooks SC, Pollard MJ, Ando S, Dajani HR, Notarius CF, et al. Effect of adenosine on heart rate variability in humans. Clin Sci (Colch) 1999; 96: 597–604.CrossRefGoogle Scholar
  13. 13.
    Conradson TB, Clarke B, Dixon CM, Dalton RN, Barnes PJ. Effects of adenosine on autonomic control of heart rate in man. Acta Physiol Scand 1987; 131: 525–31.PubMedCrossRefGoogle Scholar
  14. 14.
    Spallone V, Menzinger G. Diagnosis of cardiovascular autonomic neuropathy in diabetes. Diabetes 1997; 46: S67–76.PubMedGoogle Scholar
  15. 15.
    Krolewski AS, Barzilay J,Warram JH, Martin BC, Pfeifer M, Rand LI. Risk of early-onset proliferative retinopathy in IDDM is closely related to cardiovascular autonomic neuropathy. Diabetes 1992; 41: 430–7.PubMedCrossRefGoogle Scholar
  16. 16.
    Kahn R. Proceedings of a consensus development conference on standardized measures in diabetic neuropathy. Autonomic nervous system testing. Diabetes Care 1992; 15: 1095–103.PubMedGoogle Scholar
  17. 17.
    Watt AH, Bayer A, Routledge PA, Swift CG. Adenosine-induced respiratory and heart rate changes in young and elderly adults. Br J Clin Pharmacol 1989; 27: 265–7.PubMedGoogle Scholar
  18. 18.
    De Tommaso G, Giansanti R, Badiali M, Romagnoli F, Boemi M, Sorichetti P, et al. The prevalence of cardiovascular autonomic neuropathy and of retinopathy in relation to the duration of diabetes. Funct Neurol 1989; 4: 169–71.Google Scholar
  19. 19.
    Report and recommendations of the San Antonio conference on diabetic neuropathy. Consensus statement. Diabetes 1988; 37: 1000–4.Google Scholar
  20. 20.
    Spallone V, Menzinger G. Diagnosis of cardiovascular autonomic neuropathy in diabetes. Diabetes 1997; 46(Suppl 2): S67–76.PubMedGoogle Scholar
  21. 21.
    Kreiner G, Wolzt M, Fasching P, Leitha T, Edlmayer A, Korn A, et al. Myocardial m-[123I]iodobenzylguanidine scintigraphy for the assessment of adrenergic cardiac innervation in patients with IDDM. Comparison with cardiovascular reflex tests and relationship to left ventricular function. Diabetes 1995; 44: 543–9.PubMedCrossRefGoogle Scholar
  22. 22.
    Schnell O, Kirsch C-M, Stemplinger J, Haslbeck M, Standl E. Scintigraphic evidence for cardiac sympathetic dysinnervation in longterm IDDM patients with and without ECG-based autonomic neuropathy. Diabetologia 1995; 38: 1345–52.PubMedCrossRefGoogle Scholar
  23. 23.
    Schnell O, Muhr D,Weiss M, Dresel S, Haslbeck M, Standl E. Reduced myocardial sup 123 I-metaiodobenzylguanidine uptake in newly diagnosed IDDM patients. Diabetes 1996; 45: 801–5.PubMedCrossRefGoogle Scholar
  24. 24.
    Allman KC, Stevens MJ, Wieland DM, Hutchins GD, Wolfe ER, Greene DA, et al. Noninvasive assessment of cardiac diabetic neuropathy by carbon-11 hydroxyephedrine and positron emission tomography. J Am Coll Cardiol 1993; 22: 1425–32.PubMedCrossRefGoogle Scholar
  25. 25.
    Pennell DJ, Mavrogeni SI, Forbat SM, Karwatowski SP, Underwood SR. Adenosine combined with dynamic exercise for myocardial perfusion imaging. J Am Coll Cardiol 1995; 25: 1300–9.PubMedCrossRefGoogle Scholar

Copyright information

© American Society of Nuclear Cardiology 2001

Authors and Affiliations

  • Kyung-Han Lee
    • 1
  • Joon Kee Yoon
    • 1
  • Mun Gyu Lee
    • 2
  • Sang Hoon Lee
    • 3
  • Won Ro Lee
    • 3
  • Byung-Tae Kim
    • 1
  1. 1.Department of Nuclear MedicineSamsung Medical CenterKangnam-ku, SeoulKorea
  2. 2.Internal Medicine and the Cardiovascular InstituteSamsung Medical CenterKangnam-ku, SeoulKorea
  3. 3.Sungkyunkwan University School of MedicineSamsung Medical CenterKangnam-ku, SeoulKorea

Personalised recommendations