In a symptomatic patient with global myocardial blood flow of 1.6 ml/min/g on stress PET and myocardial flow reserve <2.0 in the left anterior descending, circumflex, and right coronary artery territories, does this indicate balanced multivessel ischemia and require invasive coronary angiography with fractional‑flow reserve or instantaneous wave‑free ratio assessment?

Balanced Multivessel Ischemia with Global MBF 1.6 ml/min/g

Yes, a global myocardial blood flow of 1.6 ml/min/g on stress PET with myocardial flow reserve <2.0 across all three coronary territories indicates balanced multivessel ischemia and warrants invasive coronary angiography with FFR or iFR assessment to guide revascularization decisions. 1, 2

Understanding the Hemodynamic Significance

Quantitative PET perfusion thresholds clearly define ischemia:

• Hyperemic MBF ≤2.3 ml/min/g indicates hemodynamically significant ischemia 3
• Your patient's global MBF of 1.6 ml/min/g falls well below this threshold, confirming severe flow limitation 1, 3
• MBF reserve <2.0 in all three territories (LAD, circumflex, RCA) indicates diffuse, balanced ischemia that may be missed by relative perfusion imaging alone 1, 4

The critical insight here is that approximately 47% of angiographically significant stenoses produce no detectable ischemia on standard visual perfusion assessment 4. Quantitative PET flow measurements overcome this limitation by providing absolute values rather than relative comparisons between territories.

Why Invasive Assessment is Indicated

The 2024 ESC guidelines and 2019 ESC/EACTS guidelines provide clear direction:

• In patients with significant CAD (>70% diameter stenosis), FFR <0.80 or iwFR <0.89 defines hemodynamically significant lesions requiring revascularization 1
• For multivessel disease with complex anatomy (SYNTAX score >22), CABG is preferred over PCI 1
• Invasive coronary angiography with physiologic assessment is recommended when stress imaging demonstrates extensive ischemia 1, 5

The Diagnostic Algorithm

Follow this stepwise approach:

1. Proceed directly to invasive coronary angiography given the severe global flow impairment 1, 5

2. Perform FFR or iFR in all three major epicardial vessels to identify which stenoses are functionally significant 1, 2:

   • FFR ≤0.80 indicates flow-limiting stenosis 1, 2
   • iFR ≤0.89 indicates flow-limiting stenosis 1, 2

3. Assess SYNTAX score to determine optimal revascularization strategy 1:

   • SYNTAX >22 with multivessel disease favors CABG over PCI 1
   • Left main or proximal three-vessel disease strongly favors CABG 1

4. Consider viability assessment if fixed defects are present or LVEF is reduced, using PET, dobutamine stress echo, or cardiac MRI 5

Critical Pitfalls to Avoid

Do not rely on visual perfusion assessment alone in multivessel disease:

• Visual SPECT or CMR perfusion imaging has poor concordance with FFR in multivessel disease (kappa = 0.14-0.28) 6, 7
• Perfusion imaging underestimates ischemic territories in 36% of multivessel disease patients 6
• The "balanced ischemia" phenomenon causes all territories to appear relatively normal despite globally reduced flow 1, 4

Do not assume FFR/iFR alone provides complete hemodynamic assessment:

• 38% of vessels with low FFR or low iFR have quantitative hyperemic MBF above the ischemic threshold 3
• Resting MBF negatively correlates with iFR and can cause FFR low/iFR high discordance 3
• Combined FFR/iFR assessment provides limited approximation of true quantitative myocardial perfusion 3

Prognostic Implications

The extent of ischemia on PET carries powerful prognostic significance:

• Three-year survival is approximately 85% for patients with ischemia in three coronary territories versus 99% for those without ischemia 4
• PET-derived ischemia extent provides incremental risk estimates for cardiac death beyond traditional risk factors 4
• Low MBF reserve independently predicts mortality and identifies patients with survival benefit from early revascularization 1

Technical Considerations for Invasive Assessment

Ensure proper technique during FFR/iFR measurement:

• Use guiding catheters without distal side holes 2
• Perform pressure equalization between guiding catheter and pressure wire before advancement 2
• Administer intracoronary nitrates before measurements 2
• Avoid catheter ventricularization/damping by disengaging the guiding catheter during measurement 2

The 2011 ACC/AHA CABG guidelines support revascularization in this clinical scenario:

• CABG improves survival in patients with multivessel CAD (>70% stenosis) and evidence of extensive ischemia 1
• CABG with LIMA graft is reasonable for significant proximal LAD stenosis with extensive ischemia 1

1, 5, 2, 4, 3, 6