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Heart rate reserve during pharmacological stress is a significant negative predictor of impaired coronary flow reserve in women

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript



Evidence to date has failed to adequately explore determinants of cardiovascular risk in women with coronary microvascular dysfunction (CMVD). Heart rate responses to adenosine mirror autonomic activity and may carry important prognostic information for the diagnosis of CMVD.


Hemodynamic changes during adenosine stress were analyzed in a propensity-matched cohort of 404 patients (202 women, mean age 65.9 ± 11.0) who underwent clinically indicated myocardial perfusion 13N-ammonia Positron-Emission-Tomography (PET) at our institution between September 2013 and May 2017.


Baseline heart rate (HR) was significantly higher in patients with abnormal coronary flow reserve (CFR, p < 0.001 vs normal CFR). Accordingly, a blunted HR response to adenosine (=reduced heart rate reserve, %HRR) was seen in patients with abnormal CFR, with a most pronounced effect being observed in female patients free of myocardial ischemia (45.9 ± 34.9 vs 26.5 ± 18.0, p < 0.001 in women and 29.1 ± 16.9 vs 24.3 ± 21.7, p = 0.15 in men). Hence, a fully-adjusted multivariate logistic regression model identified HRR as the strongest negative predictor of reduced CFR in women free of myocardial ischemia, but not in men. Accordingly, receiver operating characteristics (ROC) curves for the presence of reduced CFR revealed that a %HRR <35 was a powerful predictor for abnormal CFR with a sensitivity of 81% and a specificity of 60% in women.


A blunted HRR <35% is associated with abnormal CFR in women. Taking into account HR responses during stress test in women may help to risk stratify the heterogeneous female population of patients with non-obstructive coronary artery disease (CAD).

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CG was supported by grants from the Swiss National Science Foundation (SNSF); the Olga Mayenfisch Foundation, Switzerland; the OPO Foundation, Switzerland; the Novartis Foundation, Switzerland; the Swissheart Foundation; and the Helmut Horten Foundation, Switzerland. MM was supported by the Iten-Kohaut Foundation, Switzerland.

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Correspondence to Catherine Gebhard.

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All authors have the following to disclose: The University Hospital of Zurich holds a research contract with GE Healthcare. CG has received research grants from the Novartis Foundation, Switzerland.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Our study was approved by the Cantonal Ethics Board in Zurich, Switzerland (BASEC No. 2017–01112). The need to obtain informed consent was waived by the ethics committee due to the retrospective nature of the study.

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Haider, A., Bengs, S., Maredziak, M. et al. Heart rate reserve during pharmacological stress is a significant negative predictor of impaired coronary flow reserve in women. Eur J Nucl Med Mol Imaging 46, 1257–1267 (2019).

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