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

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Angina, Stable / physiopathology*
  • Angina, Stable / surgery
  • Cardiac Catheterization
  • Coronary Stenosis / physiopathology*
  • Coronary Stenosis / surgery
  • Exercise Test
  • Exercise Tolerance / physiology*
  • Female
  • Fractional Flow Reserve, Myocardial / physiology
  • Humans
  • Male
  • Middle Aged
  • Percutaneous Coronary Intervention*
  • Severity of Illness Index