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. 2019 Jun 1;4(6):569-574.
doi: 10.1001/jamacardio.2019.1139.

Association Between Physiological Stenosis Severity and Angina-Limited Exercise Time in Patients With Stable Coronary Artery Disease

Christopher M Cook  1 , Yousif Ahmad  1 , James P Howard  1 , Matthew J Shun-Shin  1 , Amarjit Sethi  1 , Gerald J Clesham  2   3 , Kare H Tang  2 , Sukhjinder S Nijjer  1 , Paul A Kelly  2 , John R Davies  2   3 , Iqbal S Malik  1 , Raffi Kaprielian  1 , Ghada Mikhail  1 , Ricardo Petraco  1 , Takayuki Warisawa  1 , Firas Al-Janabi  2   3 , Grigoris V Karamasis  2   3 , Shah Mohdnazri  2   3 , Reto Gamma  2 , Guus A de Waard  1 , Rasha Al-Lamee  1 , Thomas R Keeble  2   3 , Jamil Mayet  1 , Sayan Sen  1 , Darrel P Francis  1 , Justin E Davies  1
Affiliations

Association Between Physiological Stenosis Severity and Angina-Limited Exercise Time in Patients With Stable Coronary Artery Disease

Christopher M Cook et al. JAMA Cardiol. .

Abstract

Importance: Physiological stenosis assessment is recommended to guide percutaneous coronary intervention (PCI) in patients with stable angina.

Objective: To determine the association between all commonly used indices of physiological stenosis severity and angina-limited exercise time in patients with stable angina.

Design, setting, and participants: This cohort study included data (without follow-up) collected over 1 year from 2 cardiac hospitals. Selected patients with stable angina and physiologically severe single-vessel coronary artery disease presenting for clinically driven elective PCI were included.

Exposures: Fractional flow reserve (FFR), instantaneous wave-free ratio (iFR), hyperemic stenosis resistance (HSR), and coronary flow reserve (CFR) were measured invasively. Immediately after this, patients maximally exercised on a catheter-table-mounted supine ergometer until they developed rate-limiting angina. Subsequent PCI was performed in most patients, followed by repeat maximal supine exercise testing.

Main outcomes and measures: Associations between FFR, iFR, HSR, CFR, and angina-limited exercise time were assessed using linear regression and Pearson correlation coefficients. Additionally, the associations between the post-PCI increment in exercise time and baseline FFR, iFR, HSR, and CFR were assessed.

Results: Twenty-three patients (21 [91.3%] of whom were male; mean [SD] age, 60.6 [8.1] years) completed the pre-PCI component of the study protocol. Mean (SD) stenosis diameter was 74.6% (10.4%). Median (interquartile range [IQR]) values were 0.54 (0.44-0.72) for FFR, 0.53 (0.38-0.83) for iFR, 1.67 (0.84-3.16) for HSR, and 1.35 (1.11-1.63) for CFR. Mean (SD) angina-limited exercise time was 144 (77) seconds. Anatomical stenosis characteristics were not significantly associated with angina-limited exercise time. Conversely, FFR (R2 = 0.27; P = .01), iFR (R2 = 0.46; P < .001), HSR (R2 = 0.39; P < .01), and CFR (R2 = 0.16; P < .05) were all associated with angina-limited exercise time. Twenty-one patients (19 [90.5%] of whom were male; mean [SD] age, 60.1 [8.2] years) competed the full protocol of PCI, post-PCI physiological assessment, and post-PCI maximal exercise. After PCI, the median (IQR) FFR rose to 0.91 (0.85-0.96), median (IQR) iFR to 0.98 (0.94-0.99), and median (IQR) CFR to 2.73 (2.50-3.12), while the median (IQR) HSR fell to 0.16 (0.06-0.37) (P < .001 for all). The post-PCI increment in exercise time was most significantly associated with baseline iFR (R2 = 0.26; P = .02).

Conclusions and relevance: In a selected group of patients with severe, single-vessel stable angina, FFR, iFR, HSR, and CFR were all modestly correlated with angina-limited exercise time to varying degrees. Notwithstanding the limited sample size, no clear association was demonstrated between anatomical stenosis severity and angina-limited exercise time.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr J. E. Davies hold patents pertaining to the instantaneous wave-free ratio technology and reports serving as a consultant for Philips Volcano. Dr Sethi reports serving as a consultant for Philips Volcano. Drs Al-Lamee, Sen, Petraco, Cook, and Nijjer report receiving speaker’s honoraria from Philips Volcano. Drs J. E. Davies and Keeble report having received research grants from Philips Volcano. Dr Cook reported having received grants from Medical Research Council during the conduct of the study. Dr Karamasis reports having received grants and personal fees from Abbott Vascular outside the submitted work. Dr Mayet reports grants from Medical Research Council during the conduct of the study, fees from Philips Volcano outside the submitted work, and holding a patent to instanteous wave-free ratio patented by Imperial Innovation, licensed and with royalties paid. Dr Mikhail reports receiving fees from Philips Volcano, outside the submitted work. Dr Sen reports receiving grants from Philips, Medtronic, and Pfizer and personal fees from Philips, outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Association Between Angina-Limited Exercise Time and Pre–Percutaneous Coronary Intervention (PCI) Values
Scatterplots of the association between angina-limited exercise time and pre-PCI fractional flow reserve (A), instantaneous wave-free ratio (B), hyperemic stenosis resistance (C), and coronary flow reserve (D) values.
Figure 2.
Figure 2.. Association Between the Change in Exercise Time After Percutaneous Coronary Intervention (PCI) and Pre-PCI Values
Scatterplots of the association between the change in exercise time after PCI and pre-PCI fractional flow reserve (A), instantaneous wave-free ratio (B), hyperemic stenosis resistance (C), and coronary flow reserve (D) values.
See this image and copyright information in PMC

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