What is the next best step for a patient with an abnormal myocardial blood flow reserve (MBFR) in the circumflex territory and normal perfusion, considering further evaluation for coronary artery disease (CAD)?

Management of Abnormal MBFR in Circumflex Territory with Normal Perfusion

Proceed with cardiac CTA to evaluate for anatomic coronary artery disease in the circumflex territory, as abnormal myocardial blood flow reserve independently predicts major adverse cardiovascular events even when perfusion imaging appears normal, and this finding warrants anatomic correlation to guide therapeutic decision-making. 1

Rationale for Further Evaluation

Why Abnormal MBFR Matters Despite Normal Perfusion

• Reduced MBFR (<2.0) reflects abnormalities of flow within the epicardial coronary arteries and/or microvasculature and independently predicts risk of major coronary artery disease events, even when standard perfusion imaging appears normal 1

• When MBFR is reduced but perfusion appears normal, it may represent early disease that has not yet progressed to cause visible perfusion defects or may indicate microvascular dysfunction 2, 3

• In patients without obstructive CAD, reduced MBFR may signify coronary microvascular dysfunction, which is associated with increased morbidity, mortality, and impaired quality of life 1

• Even among patients with coronary artery calcium score of 0, MBFR <2.0 was present in 37.8% and was associated with higher risk of death, demonstrating that functional abnormalities can exist without obvious anatomic disease 4

Evidence Supporting Anatomic Evaluation

• The 2024 ESC guidelines recommend measuring coronary artery calcium score from unenhanced chest CT imaging to improve detection of both non-obstructive and obstructive CAD in patients selected for perfusion imaging 1

• Cardiac CTA provides anatomic correlation that helps distinguish between:

  • Obstructive epicardial disease in the circumflex territory (which may require revascularization)
  • Non-obstructive CAD with microvascular dysfunction (which requires medical optimization)
  • Truly normal coronary arteries with isolated microvascular disease 1

• The addition of dynamic CT perfusion to CTA allows improved risk stratification of patients with CTA-detected stenosis, with abnormal perfusion being an independent predictor of major adverse cardiac events even when adjusted for stenosis severity 5

Recommended Diagnostic Algorithm

Step 1: Cardiac CTA with Calcium Scoring

• Perform cardiac CTA to evaluate for anatomic stenosis in the circumflex territory and measure coronary artery calcium score 1

• This addresses the possibility of flow-limiting stenosis that may not have caused perfusion defects yet but is causing reduced flow reserve 3

Step 2: Interpretation Based on CTA Results

If obstructive CAD is found (≥50% stenosis):

• Consider invasive coronary angiography with fractional flow reserve (FFR) measurement for intermediate lesions to determine hemodynamic significance 1, 3
• Patients with CTA-detected stenosis and abnormal MBFR have significantly higher event rates (12.2% vs 1.5% annually) compared to those with stenosis but normal flow reserve 5

If non-obstructive CAD or normal coronary arteries:

• The diagnosis shifts toward coronary microvascular dysfunction, particularly if the patient is female, diabetic, or hypertensive 1
• Optimize guideline-directed medical therapy including beta-blockers, ACE inhibitors, statins, and lifestyle modifications 1
• Consider invasive coronary reactivity testing if symptoms persist despite medical therapy 1

If CTA is non-diagnostic or equivocal:

• Consider stress CMR with quantitative myocardial blood flow reserve measurement as an alternative functional assessment 1

Critical Clinical Considerations

Prognostic Implications

• MBFR measured by PET independently predicted mortality and helped identify patients with a survival benefit from early revascularization beyond the extent of myocardial ischemia 1

• Patients with ANOCA/INOCA (angina with non-obstructive coronary arteries) have increased morbidity/mortality and impaired quality of life, making early accurate diagnosis important 1

• The prognostic value of MBFR is maintained even after adjusting for perfusion defects and coronary artery calcium score 4

Common Pitfalls to Avoid

• Do not provide false reassurance based solely on normal perfusion imaging - perfusion defects only develop when abnormalities affect ≥10% of myocardium, while microvascular dysfunction often produces diffuse subendocardial defects below this threshold 2

• Do not assume that rate-pressure product correction of MBFR improves risk stratification - recent evidence shows that RPP-corrected MFR may not consistently provide accurate risk stratification in patients with MFR <2.0 6

• Do not rely on calcium scoring alone to exclude disease - functional abnormalities (reduced MBFR) can exist even with zero calcium score 4

Gender-Specific Considerations

• PET measurement of MBFR improves risk stratification particularly in women with suspected coronary microvascular dysfunction, as functional disorders leading to ANOCA/INOCA are more common in women than men 1

• A recent meta-analysis reported an overall prevalence of microvascular angina of 41% and vasospastic angina of 40% in selected patients without obstructive CAD 1