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Utility of 18F-Flurpiridaz PET Relative Flow Reserve in Differentiating Obstructive From Nonobstructive Coronary
Diana M Lopez1, Dan Huck1, Sanjay Divakaran1
1Cardiovascular Imaging Program, Departments of Medicine and Radiology (D.M.L., D.M.H., S. Divakaran, J.M.B., B.N.W., S. Dorbala, R.B., M.F.D.C.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
Insights
Positron emission tomography derived relative flow reserve (RFR) significantly improves the diagnosis of obstructive coronary artery disease (CAD) in patients with reduced myocardial blood flow (MBF). RFR offers complementary information beyond existing PET parameters for refined CAD assessment.
Area of Science:
- Cardiovascular Imaging
- Nuclear Cardiology
- Diagnostic Accuracy
Background:
- Absolute quantification of myocardial blood flow (MBF) using positron emission tomography (PET) aids in identifying coronary artery disease (CAD).
- Differentiating MBF impairment caused by obstructive versus nonobstructive CAD remains a diagnostic challenge.
- Existing PET parameters may not fully distinguish between obstructive and nonobstructive CAD.
Purpose of the Study:
- To evaluate the incremental diagnostic value of PET-derived relative flow reserve (RFR) for diagnosing obstructive CAD.
- To assess if RFR improves the diagnostic performance beyond established PET metrics.
- To refine the diagnostic accuracy of PET in patients with reduced MBF.
Main Methods:
- Post hoc analysis of a multicenter phase III trial using 18F-flurpiridaz PET.
- Inclusion of patients with available MBF quantification; definition of reduced stress MBF (sMBF) and obstructive CAD.
- Calculation of RFR as a ratio of minimal segment sMBF to highest reference vascular territory sMBF.
- Evaluation of RFR performance using receiver operating characteristic analysis and net reclassification index.
Main Results:
- In a per-vessel analysis (n=231), 82% of vessels with reduced sMBF lacked obstructive CAD.
- RFR was significantly lower in vessels with obstructive CAD (0.55) compared to nonobstructive CAD (0.80).
- RFR independently predicted obstructive CAD in vessels with reduced sMBF (OR, 3.08; P=0.002).
- While overall discrimination did not improve (AUC 0.806 vs 0.822, P=0.11), RFR significantly improved reclassification (NRI, 0.93; P<0.0001).
Conclusions:
- Relative flow reserve (RFR) provides valuable complementary diagnostic information in PET perfusion imaging.
- RFR aids in refining the diagnosis of obstructive CAD, particularly in patients with reduced myocardial blood flow.
- This parameter enhances the diagnostic utility of PET beyond existing metrics for CAD assessment.
Background:
Absolute quantification of myocardial blood flow (MBF) on positron emission tomography perfusion imaging improves the identification of coronary artery disease (CAD). However, distinguishing MBF impairment due to obstructive CAD from nonobstructive CAD remains challenging. We aimed to evaluate the incremental diagnostic value of positron emission tomography derived relative flow reserve (RFR) in the diagnosis of obstructive CAD.
Methods:
This is a post hoc analysis of the multicenter phase III trial of 18F-flurpiridaz positron emission tomography. Patients with available MBF quantification were included. Reduced stress MBF (sMBF) was defined as sMBF below the median (2.2 mL/min per gram). Obstructive CAD on quantitative invasive coronary angiography was defined as ≥70% stenosis. RFR was calculated as a ratio of the minimal segment sMBF over the highest reference vascular territory sMBF. RFR performance for predicting obstructive CAD was evaluated through receiver operating characteristic analysis and the net reclassification index of multivariable regression models.
Results:
The study included 231 patients (71% male; 56% with established CAD) drawn from the original cohort of 755 trial participants. No patients had 3-vessel CAD. In a per-vessel-based analysis, 82% of vessels with reduced sMBF had no obstructive CAD on invasive coronary angiography. RFR was significantly lower for vessels with obstructive CAD (0.55 versus 0.80; P<0.0001). In vessels with reduced sMBF, RFR was independently associated with obstructive CAD even after accounting for stress total perfusion deficit and myocardial flow reserve (odds ratio, 3.08 [95% CI, 1.49-6.38]; P=0.002). Although the addition of RFR did not significantly improve discrimination (area under the curve, 0.806 versus 0.822; P=0.11), it significantly improved reclassification of vessels with and without obstructive CAD (net reclassification index, 0.93; obstructive CAD net reclassification index, 0.44; nonobstructive CAD net reclassification index, 0.49; P<0.0001).
Conclusions:
RFR provides complementary diagnostic information beyond existing positron emission tomography parameters and may help refine the diagnosis of obstructive CAD in patients with reduced flows.
Registration:
URL: https://clinicaltrials.gov; Unique identifier: NCT01347710.
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