What stress test can diagnose microvascular dysfunction in a patient with suspected coronary flow reserve (CFR) or myocardial blood flow reserve (MBFR) abnormalities?

Stress Testing for Microvascular Dysfunction

For detecting microvascular dysfunction, stress PET with myocardial blood flow reserve (MBFR) measurement is the preferred noninvasive test, followed by stress CMR with MBFR, while stress echocardiography with coronary flow velocity reserve (CFVR) is a less robust alternative. 1

Recommended Testing Hierarchy

First-Line Noninvasive Options (Class 2a Recommendations)

Stress PET with MBFR is the most strongly recommended noninvasive test for diagnosing coronary microvascular dysfunction in patients with persistent chest pain and nonobstructive CAD 1. The 2024 ESC Guidelines note that PET-CT myocardial perfusion imaging outperformed other functional imaging modalities in head-to-head comparisons 1.

• PET provides quantitative absolute myocardial blood flow measurements during both rest and stress without increasing radiation exposure or imaging time 1
• MBFR <2.0 indicates microvascular dysfunction and independently predicts major adverse cardiovascular events 1
• PET measurement of MBFR improves risk stratification particularly in women with suspected coronary microvascular dysfunction 1

Stress CMR with MBFR measurement is equally recommended (Class 2a) for diagnosing coronary microvascular dysfunction and estimating MACE risk 1.

• Quantitative myocardial perfusion mapping by CMR can identify coronary microvascular dysfunction when validated against invasive coronary physiology 1
• High-resolution CMR with quantitative analysis (calculating transmural and subendocardial myocardial perfusion reserve) has 88-90% accuracy for detecting CMD, far superior to visual assessment alone which has only 58% accuracy 2
• Stress CMR studies of MBFR show reasonable agreement with PET 1

Alternative Noninvasive Option (Class 2b Recommendation)

Stress echocardiography with CFVR measurement may be reasonable but carries a weaker recommendation (Class 2b, Level C-EO) 1.

• Transthoracic Doppler evaluation of the left anterior descending artery assesses coronary flow reserve during vasodilator stress 1
• CFVR ≤2.0 adds incremental prognostic value for death and nonfatal MI in patients with angiographically normal or near-normal coronary arteries 1
• Myocardial contrast echocardiography can measure capillary blood flow and calculate MBF reserve, which correlates with coronary stenosis severity 1, 3

Gold Standard: Invasive Testing (Class 2a Recommendation)

Invasive coronary function testing is reasonable for patients with persistent stable chest pain, nonobstructive CAD (FFR ≥0.8), and at least mild myocardial ischemia on imaging 1.

• Measures include index of microcirculatory resistance (IMR ≥25 indicates structural microvascular disease) and coronary flow reserve (CFR <2.0 indicates dysfunction) 1
• Invasive testing allows assessment of both vasospasm and endothelium-dependent/independent microvascular reactivity 1
• The combination of FFR and IMR as clinical reference reduced the false discovery rate of exercise stress tests by 25% compared to anatomic assessment alone 4

Critical Diagnostic Thresholds

• MBFR <2.0 = microvascular dysfunction 1, 5
• CFR <2.0 or <2.5 (depending on study) = impaired coronary flow reserve 1, 6
• IMR ≥25 = structural microvascular dysfunction 1
• Hyperemic subendocardial:subepicardial perfusion ratio <1.0 on CMR = inducible ischemia 6

Important Clinical Caveats

Standard exercise stress testing alone has limited utility for detecting microvascular dysfunction. Exercise ECG testing without flow measurements has a 60.7% false discovery rate when using anatomic stenosis as reference 4. In patients with suspected CMD, 82% with invasive CFR <2.5 had inducible ischemia on quantitative perfusion imaging, compared to only 22% of controls 6.

Timing matters for peripheral vascular testing: Reactive hyperemia peripheral arterial tonometry (RH-PAT/EndoPAT) should not be performed after exercise, as acute exercise abolishes the capacity to predict CMD presence 7.

Patient populations at highest risk for coronary microvascular dysfunction include women, those with diabetes, hypertension, and other insulin-resistant states 1. The 2021 AHA/ACC Guidelines specifically note that PET measurement of MBFR improves risk stratification especially for women with nonobstructive CAD 1.

Test Selection Algorithm

Test choice should be guided by local availability and expertise 1. When quantitative flow measurements are available:

1. If PET available: Use stress PET with MBFR as first choice 1
2. If CMR available but not PET: Use stress CMR with quantitative MBFR (not visual assessment alone) 1, 2
3. If neither available: Consider stress echocardiography with CFVR, recognizing its limitations 1
4. If noninvasive testing inconclusive and symptoms persist: Proceed to invasive coronary function testing with IMR and CFR measurements 1