@article{Ahmed-Jushuf:2026:10.1161/CIRCULATIONAHA.125.078738,
author = {Ahmed-Jushuf, F and Foley, MJ and Chotai, S and Rajkumar, CA and Wang, D and Simader, FA and Macierzanka, K and Chiew, K and Misra, S and Williams, R and Konstantinou, K and Din, JN and Mohdnazri, SR and O'Kane, PD and Haworth, P and Nijjer, SS and Seligman, H and Keeble, TR and Davies, JR and Clesham, G and Hinton, J and Spratt, JC and Dungu, JN and Knight, D and Kotecha, T and Harrell, FE and Howard, JP and Francis, DP and Shun-Shin, MJ and Al-Lamee, RK},
doi = {10.1161/CIRCULATIONAHA.125.078738},
journal = {Circulation},
title = {Determining the Physiological Threshold for Angina (ORBITA-FIRE): A Double-Blind, Randomized, Placebo-Controlled Study.},
url = {http://dx.doi.org/10.1161/CIRCULATIONAHA.125.078738},
year = {2026}
}

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TY  - JOUR
AB  - BACKGROUND: In stable coronary artery disease, the primary goal of percutaneous coronary intervention (PCI) is symptom relief. Fractional flow reserve (FFR) and nonhyperemic pressure ratios such as resting full-cycle ratio (RFR) are used to guide revascularization. Although these indices correlate with myocardial ischemia, they have never been validated against the onset of angina. The physiological thresholds for angina (FFRangina and RFRangina) at rest and during exercise remain undefined. METHODS: ORBITA-FIRE (Finding the Invasive Threshold for Symptom Relief in Exertional Angina) was a multicenter, double-blind, randomized, placebo-controlled study in patients with stable angina and single-vessel coronary artery disease. After imaging-guided PCI, an in-stent balloon was incrementally inflated until angina occurred at rest. This angina threshold was verified against placebo inflation, and corresponding FFRangina and RFRangina values were recorded at symptom onset. The protocol was repeated during low- and high-intensity exercise to assess changes in angina thresholds with increasing cardiac workload. RESULTS: Sixty-five patients were enrolled (mean age, 63.9±8.7 years; 74% male; 69% hypertensive; 23% diabetic; 91% with Canadian Cardiovascular Society class II-III angina). Median pre-PCI FFR was 0.59 (interquartile range [IQR], 0.46-0.70) and RFR was 0.61 (IQR, 0.40-0.82). Median FFRangina at rest was 0.29 (IQR, 0.23-0.35), increasing to 0.38 (IQR, 0.30-0.48) during low-intensity exercise and 0.45 (IQR, 0.36-0.55) during high-intensity exercise. RFRangina similarly increased from 0.22 (IQR, 0.16-0.30) at rest to 0.26 (IQR, 0.18-0.36) and 0.32 (IQR, 0.23-0.46) during low- and high-intensity exercise. All thresholds were significantly lower than clinical diagnostic cut points (P<0.001). Lower FFRangina and RFRangina thresholds were associated with greater symptom reproducibility across rest, low- and high-intensity exercise conditions (FFRangina: P=0.008
AU  - Ahmed-Jushuf,F
AU  - Foley,MJ
AU  - Chotai,S
AU  - Rajkumar,CA
AU  - Wang,D
AU  - Simader,FA
AU  - Macierzanka,K
AU  - Chiew,K
AU  - Misra,S
AU  - Williams,R
AU  - Konstantinou,K
AU  - Din,JN
AU  - Mohdnazri,SR
AU  - O'Kane,PD
AU  - Haworth,P
AU  - Nijjer,SS
AU  - Seligman,H
AU  - Keeble,TR
AU  - Davies,JR
AU  - Clesham,G
AU  - Hinton,J
AU  - Spratt,JC
AU  - Dungu,JN
AU  - Knight,D
AU  - Kotecha,T
AU  - Harrell,FE
AU  - Howard,JP
AU  - Francis,DP
AU  - Shun-Shin,MJ
AU  - Al-Lamee,RK
DO  - 10.1161/CIRCULATIONAHA.125.078738
PY  - 2026///
TI  - Determining the Physiological Threshold for Angina (ORBITA-FIRE): A Double-Blind, Randomized, Placebo-Controlled Study.
T2  - Circulation
UR  - http://dx.doi.org/10.1161/CIRCULATIONAHA.125.078738
UR  - https://www.ncbi.nlm.nih.gov/pubmed/42100816
ER  - 

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