What does a stress test showing normal myocardial perfusion but abnormal electrocardiogram (EKG) changes with dynamic responses to a vasodilator indicate?

Stress Test with Normal Perfusion but Abnormal EKG After Vasodilator

A stress test showing normal myocardial perfusion but abnormal EKG changes with dynamic responses to a vasodilator indicates a discordant result that is associated with significant coronary artery disease (CAD), particularly multivessel disease, and carries a higher cardiac event rate than typically expected with normal perfusion imaging alone.

Clinical Significance and Interpretation

This discordant finding—ischemic ECG changes during vasodilator stress with normal perfusion imaging—is uncommon, occurring in only 0.7-0.9% of patients undergoing vasodilator stress testing 1, 2. However, when present, it carries important diagnostic and prognostic implications:

Diagnostic Implications

The presence of ischemic ECG changes with normal perfusion strongly suggests significant CAD despite the normal perfusion images. Studies demonstrate that when coronary angiography is performed in these patients, the vast majority (92-100%) have significant CAD 3, 2:

• 75% have multivessel coronary artery disease 3
• 25% have single-vessel disease 3
• Among 12 patients who underwent angiography or autopsy, 11 had multivessel CAD, indicating false-negative perfusion imaging 2

This represents a false-negative perfusion study rather than a false-positive ECG. The normal perfusion images fail to detect the underlying ischemia that manifests on ECG 2.

Prognostic Implications

The cardiac event rate is substantially elevated compared to typical normal perfusion studies:

• Cardiac death or nonfatal MI rate: 4% at 1 year, 10% at 2 years, and 14% at 3 years 2
• This is significantly higher than the <1% annual event rate typically associated with normal perfusion imaging 4
• ST depression ≥1 mm during vasodilator stress with normal perfusion does not provide additional risk stratification in some cohorts, but the presence of multivessel disease explains the elevated risk 1

Patient Demographics and Clinical Context

This discordant pattern occurs predominantly in specific patient populations:

• 88% are women, with mean age 67 ± 10 years 2
• 60% Hispanic, 40% African American in one cohort 3
• High prevalence of cardiovascular risk factors: hypertension (80%), diabetes (50%), dyslipidemia (75%) 3
• Typical or atypical chest pain present in most cases 3

Mechanism and Pathophysiology

The discordance between normal perfusion and ischemic ECG changes during vasodilator stress occurs through distinct mechanisms:

Vasodilator-Induced Changes

Vasodilators (adenosine, dipyridamole, regadenoson) cause maximal coronary arteriolar vasodilation, resulting in increased flow to territories supplied by normal epicardial arteries 4. In the presence of obstructed arteries, the "steal phenomenon" may occur, where blood is directed away from territories supplied by stenotic vessels 4.

ECG Changes Without Perfusion Defects

• Ischemic ECG changes occur at relatively high heart rates (mean 101 ± 15 bpm) during vasodilator infusion 2
• Changes persist for 6.8 ± 4.7 minutes after drug termination 2
• The perfusion imaging may miss subtle or balanced ischemia in multivessel disease 2
• Microvascular dysfunction or endothelial dysfunction may contribute to ECG changes without detectable perfusion defects 4

Clinical Management Algorithm

Immediate Assessment

When encountering this discordant pattern, proceed with the following structured approach:

1. Verify the ECG changes are truly ischemic:

   • ST-segment depression ≥1 mm in multiple leads
   • Dynamic changes that develop during or after vasodilator administration
   • Exclude baseline ECG abnormalities that could confound interpretation 4

2. Review the perfusion images carefully:

   • Confirm truly normal perfusion (no fixed or reversible defects)
   • Assess for artifacts (attenuation, motion, low count statistics) 4
   • Consider ECG-gated images for additional functional information 4

Risk Stratification

Assess additional high-risk markers that may be present:

• Blunted heart rate response to vasodilator (lowest tertile associated with hazard ratio 2.1 for mortality and 2.9 for cardiac death/MI) 5
• Abnormal hemodynamic response (significant hypotension or hypertension) 4, 6
• Prolonged duration of ECG changes after vasodilator termination 2
• Multiple cardiovascular risk factors, particularly in older women 2

Definitive Evaluation

Given the high prevalence of significant CAD, coronary angiography is warranted to assess the presence and extent of disease 3, 2:

• This is particularly important because 75% will have multivessel disease requiring potential revascularization 3
• Eight of 49 patients (16%) in one series required coronary revascularization 2
• Angiography allows for definitive diagnosis and guides therapeutic decisions

Alternative Considerations

If angiography is not immediately feasible or contraindicated:

• Consider alternative stress imaging modalities (stress echocardiography, stress CMR) to corroborate findings 4
• Initiate aggressive medical management for CAD risk factors
• Close clinical follow-up with low threshold for invasive evaluation if symptoms develop

Common Pitfalls and Caveats

Critical Pitfalls to Avoid

Do not dismiss ischemic ECG changes simply because perfusion imaging is normal. This combination represents a high-risk scenario requiring further evaluation 2.

Do not assume the ECG changes are false-positive. In this specific context (vasodilator stress with normal perfusion), the ECG changes are more likely to represent true ischemia with false-negative perfusion imaging 3, 2.

Recognize that standard risk stratification based on normal perfusion imaging does not apply. The annual event rate is 10-fold higher than typical normal perfusion studies 2.

Technical Considerations

Ensure adequate vasodilator stress was achieved:

• Verify appropriate dosing and administration of vasodilator agent 6
• Confirm absence of caffeine intake within 12 hours (can cause false-negative perfusion results) 7, 6
• Check for medications that may interfere with vasodilator effect 7

Consider factors that may cause false-negative perfusion imaging:

• Balanced ischemia in multivessel disease (all territories equally affected) 2
• Microvascular disease without epicardial stenosis 8
• Technical limitations of SPECT imaging (resolution, attenuation) 4

Special Population Considerations

In older women, this pattern is particularly common and clinically significant:

• 88% of patients with this discordant pattern are women 2
• Higher pretest probability of microvascular disease
• May represent endothelial dysfunction or small vessel disease 4

In African American and Hispanic populations:

• High association with significant CAD when this pattern is present 3
• Consider cultural and socioeconomic factors affecting access to follow-up care
• Ensure appropriate counseling about the need for angiography

Differential Diagnosis

While significant CAD is the most likely explanation, consider alternative causes:

• Microvascular dysfunction without obstructive CAD 8
• Coronary vasospasm during vasodilator administration (paradoxical response)
• Severe left ventricular hypertrophy causing subendocardial ischemia 4
• Cardiac allograft vasculopathy in transplant recipients 8