Abnormal Myocardial Blood Flow in Three Territories with Normal Perfusion Indicates Balanced Multivessel Ischemia
Yes, abnormal myocardial blood flow (MBF) on PET/CT across all three coronary territories with normal perfusion imaging strongly suggests balanced multivessel ischemia or diffuse microvascular dysfunction, and this finding mandates further evaluation with invasive coronary angiography. 1, 2
Understanding the Phenomenon
This scenario represents a critical diagnostic pitfall where relative perfusion imaging appears falsely normal despite significant underlying disease:
Balanced ischemia occurs when all three coronary territories have equally reduced blood flow, making them appear "normal" relative to each other on standard perfusion imaging, even though absolute flow is globally reduced 1, 2, 3
The American College of Cardiology emphasizes that quantitative flow assessment allows detection of balanced multivessel disease that appears normal on relative perfusion imaging 4
Myocardial flow reserve (MFR) <2.0 across all territories is the key diagnostic finding that identifies this condition, with values <1.8 indicating significant disease 1, 5
Why This Happens
The fundamental limitation of conventional perfusion imaging:
Standard SPECT and even visual PET interpretation rely on relative tracer uptake differences between territories 2, 3
When all three vascular territories are equally compromised, no relative perfusion defect appears, creating a false-negative study 6, 7, 8
Research demonstrates that MPI underestimates ischemic burden in 31-58% of patients with multivessel disease, with many showing no perfusion defect despite FFR <0.75 or total occlusion 6, 7
Diagnostic Approach
The quantitative MBF and MFR values are more important than the visual perfusion images in this scenario:
Calculate MFR for each territory (stress MBF/rest MBF), with normal being ≥2.0 1, 5
A uniform reduction in MFR across multiple coronary territories is characteristic of either balanced epicardial disease or microvascular dysfunction 1, 2
Evaluate LVEF reserve (stress LVEF minus rest LVEF), as abnormal LVEF reserve provides incremental value for predicting left main or 3-vessel disease 9, 4
The American College of Radiology states that LVEF reserve provides significant independent value for predicting the risk of left main/3-vessel disease 9
Critical Management Steps
Proceed directly to invasive coronary angiography in symptomatic patients with this finding:
The combination of globally reduced MFR with normal perfusion images carries high risk for adverse cardiovascular events and requires anatomic definition 1, 2
Do not dismiss the patient based on "normal" perfusion images alone—this is the exact scenario where quantitative flow assessment prevents missed diagnoses 1, 6
During angiography, measure fractional flow reserve (FFR) for intermediate lesions, as FFR may be better at guiding revascularization decisions than perfusion imaging in multivessel disease 6, 7
The American Heart Association notes that nearly half of significant angiographic stenoses (47%) occur without evidence of ischemia on standard imaging 9
Distinguishing Epicardial vs. Microvascular Disease
After angiography, the pattern becomes clear:
If angiography shows multivessel obstructive CAD: This confirms balanced epicardial ischemia, and revascularization should be considered based on anatomy, symptoms, and FFR measurements 6, 7
If angiography shows no obstructive disease: The globally reduced MFR indicates microvascular dysfunction, particularly common in women, diabetics, and patients with hypertension 1, 5
For microvascular dysfunction, optimize guideline-directed medical therapy including statins, ACE inhibitors/ARBs, and aggressive risk factor modification 5
Prognostic Implications
This finding carries significant prognostic weight:
Reduced MFR independently predicts adverse cardiovascular events, even in patients with normal perfusion images 1, 4
The American College of Cardiology reports that the extent and severity of ischemia on Rb-82 PET provides powerful and incremental risk estimates of cardiac death beyond traditional risk factors 9, 4
A 2005 American Heart Association consensus found that 3-year survival rates range from 99% for women without ischemia to 85% with 3-vessel territories with ischemia 9
Common Pitfalls to Avoid
Never rely solely on visual assessment of perfusion defects—this is precisely how balanced multivessel disease gets missed 1, 6
Do not misinterpret globally reduced MFR as technical error—it represents real pathology requiring action 1
Do not assume normal perfusion images mean low risk—the quantitative flow data supersedes visual interpretation in this scenario 1, 2