What is the next best step in managing a patient with suspected multivessel coronary artery disease (CAD) and normal perfusion study results?

Management of Suspected Multivessel CAD with Normal Perfusion and Abnormal TID

Given the abnormal transient ischemic dilatation (TID >1.46) despite homogenous perfusion, proceed directly to invasive coronary angiography with fractional flow reserve (FFR) capability, as this finding is a high-risk marker for multivessel disease that may be masked by balanced ischemia on nuclear imaging. 1

Understanding the Clinical Scenario

The combination of normal perfusion with abnormal TID represents a specific high-risk pattern that warrants aggressive evaluation:

• Abnormal TID (>1.22) with normal perfusion is a recognized marker of severe, balanced multivessel CAD where global reduction in myocardial blood flow prevents detection of regional perfusion differences 2
• The preserved ejection fraction (59%) does not exclude significant multivessel disease, as balanced ischemia can maintain global function while individual territories are compromised 1
• The presence of coronary artery calcifications on non-gated CT confirms underlying atherosclerotic burden, supporting the concern for obstructive disease 3

Recommended Diagnostic Pathway

Primary Recommendation: Invasive Coronary Angiography

Invasive angiography complemented by FFR is recommended as the next step for patients with high-risk features (abnormal TID) where non-invasive testing suggests multivessel disease and revascularization is being considered for prognostic benefit 1:

• The 2019 ESC guidelines provide Class I, Level B recommendation for invasive angiography in patients with high clinical likelihood and features suggesting high event risk 1
• Invasive functional assessment (FFR) must be available and used to evaluate stenoses before revascularization, unless very high grade (>90% diameter stenosis) 1
• This approach directly addresses the limitation of nuclear imaging in detecting balanced ischemia 1

Alternative Consideration: Coronary CTA

If there are contraindications to immediate invasive angiography or if anatomical assessment is preferred first, coronary CTA represents a reasonable alternative 1:

• Coronary CTA can identify multivessel obstructive disease and left main involvement, which would be classified as CAD-RADS 4B and warrant invasive angiography 1
• However, extensive coronary calcifications (already documented on non-gated CT) may significantly limit CTA image quality and diagnostic accuracy 1
• CTA has demonstrated 95% sensitivity for detecting obstructive CAD in symptomatic patients, potentially higher than nuclear imaging 4

Why Not Repeat Functional Imaging?

Repeating functional imaging with a different modality (stress echo, CMR, or PET) is less optimal in this specific scenario:

• The abnormal TID already indicates high-risk anatomy that requires definitive anatomical assessment 2
• PET with quantitative myocardial blood flow could theoretically detect balanced ischemia through reduced flow reserve, but this adds time and may still miss the anatomical complexity needed for revascularization planning 1
• Patients with TID and multivessel disease have a 20% overall event rate (16% non-fatal MI), with significantly better outcomes after revascularization (97% vs 58% event-free survival for non-fatal MI) 2

Clinical Decision Algorithm

Step 1: Assess Symptom Severity and Medical Therapy

• If patient has severe symptoms refractory to optimal medical therapy → proceed directly to invasive angiography 1
• If symptoms are mild or well-controlled → either invasive angiography or CTA is reasonable, but invasive approach is preferred given high-risk TID 1

Step 2: Consider Coronary Calcification Burden

• Extensive calcifications favor invasive angiography over CTA due to blooming artifacts that limit CTA accuracy 1
• If calcifications are mild-moderate and well-distributed, CTA remains viable 1

Step 3: Plan for Revascularization Strategy

• If CTA is performed and shows CAD-RADS 4B (left main ≥50% or three-vessel disease >70%), proceed to invasive angiography with revascularization planning 1
• If CTA shows CAD-RADS 4A (one or two vessels with severe stenosis), functional assessment with CT-FFR or proceed to invasive angiography with FFR 1
• If invasive angiography is performed first, use FFR for all intermediate lesions (50-90%) to guide revascularization decisions 1

Critical Pitfalls to Avoid

Do not dismiss the abnormal TID based on normal perfusion patterns - this combination specifically indicates balanced ischemia from multivessel disease that nuclear imaging cannot detect 1, 2:

• TID ratio >1.22 has 95% positive predictive value for significant CAD, with 88% of cases showing multivessel disease 2
• The false reassurance of "normal perfusion" in the setting of abnormal TID can lead to delayed diagnosis and adverse events 2

Do not use coronary calcium scoring alone to guide management - while calcifications confirm atherosclerosis, they do not indicate stenosis severity or functional significance 3:

• Calcium score is a risk marker, not a diagnostic tool for obstructive disease 3
• The presence of calcifications supports the need for further evaluation but does not determine the specific next test 3

Do not perform ICA solely for risk stratification without intent to revascularize if indicated - however, in this case with abnormal TID, revascularization is being actively considered for prognostic benefit, making invasive assessment appropriate 1

Evidence Quality Considerations

The recommendation prioritizes the most recent ESC guidelines (2019-2024) which provide the highest level of evidence for diagnostic pathways 1. The CAD-RADS consensus documents (2016,2022) from multiple societies provide complementary guidance on CTA interpretation and management 1. The research evidence on TID prognostic value, while from 2011, remains the most robust data on this specific finding and demonstrates clear mortality benefit from revascularization in this population 2.