The heart rate response to adenosine: A simple predictor of adverse cardiac outcomes in asymptomatic patients with type 2 diabetes

Fadi G. Hage, Frans J.Th Wackers, Shanti Bansal, Deborah A. Chyun, Lawrence H. Young, Silvio E. Inzucchi, Ami E. Iskandrian

Research output: Contribution to journalArticlepeer-review


Background: The Detection of Ischemia in Asymptomatic Diabetics (DIAD) study demonstrated a low 5-year hard cardiac event rate. We hypothesized that a blunted heart rate response (HRR, maximum percent change) to adenosine, a simple marker of cardiac autonomic neuropathy, will identify a cohort at higher cardiac risk. Methods: In DIAD, 518 participants were randomized to screening adenosine myocardial perfusion imaging (MPI) and had available data. HRR < 20% was considered abnormal. The primary endpoint was a composite of nonfatal myocardial infarction and cardiac death. Results: During 4.7 ± 0.9 years of follow-up 15 (3%) participants experienced the primary outcome. Participants with lower HRR experienced more events than those with higher HRR (8%, 3%, 1%, for HRR < 20% (n = 79), 20-39% (n = 182) and ≥ 40% (n = 257), respectively, p = 0.01). In a Cox proportional regression model that included MPI abnormalities and HRR, both were independently associated with cardiac events (p for model < 0.001). HRR < 20% was associated with 9-fold increased risk (p = 0.007) and moderate/large abnormal MPI was associated with 6-fold increased risk (p = 0.004). Participants with both abnormal MPI and HRR (n = 8) were at highest risk for cardiac events (38%) whereas those with HRR ≥ 40%, irrespective of MPI abnormalities (n = 234), were at extremely low risk (≤ 1%, log-rank p < 0.001). Conclusions: In DIAD, abnormal HRR to adenosine infusion is an independent predictor of cardiac events. This easily obtained marker of cardiac autonomic neuropathy identifies asymptomatic patients with type 2 diabetes mellitus at increased risk, particularly when associated with abnormal MPI, who may warrant further testing and more aggressive cardiovascular risk factor management.

Original languageEnglish (US)
Pages (from-to)2952-2957
Number of pages6
JournalInternational Journal of Cardiology
Issue number6
StatePublished - 2013


  • Adenosine
  • Autonomic function
  • Heart rate
  • Myocardial perfusion imaging
  • Type 2 diabetes mellitus

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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