What is the recommended management for a patient with a nondiagnostic pharmacologic electrocardiogram (ECG) for ischemia, a left ventricular ejection fraction (LVEF) of 67% at rest, a low-risk myocardial perfusion study for significant ischemia and infarction, but severely decreased myocardial flow reserve in the right coronary artery (RCA) territory, suggesting possible microvascular disease?

Management of Suspected Microvascular Disease with Preserved LVEF

This patient should be managed with aggressive cardiovascular risk factor modification and guideline-directed medical therapy, specifically ACE inhibitors (or ARBs) for coronary artery disease, statins, and consideration of anti-anginal medications, without pursuing invasive coronary angiography given the low-risk perfusion study and preserved ejection fraction. 1

Risk Stratification and Clinical Context

Your patient presents with a clinical picture highly suggestive of coronary microvascular dysfunction (CMD):

• Preserved LVEF of 67% indicates no systolic dysfunction and places the patient outside high-risk categories requiring revascularization 1
• Low-risk myocardial perfusion study effectively rules out significant epicardial ischemia or infarction, making obstructive coronary artery disease unlikely 2
• Severely decreased myocardial flow reserve across all coronary territories (RCA > LAD > LCX) is the hallmark finding of CMD 3, 4
• Nondiagnostic pharmacologic ECG is common in CMD, as microvascular ischemia often doesn't produce classic ECG changes 4

Medical Management Strategy

Primary Cardiovascular Risk Factor Control

Aggressive risk factor modification is the cornerstone of CMD management and should be treated to guideline targets: 1

• Hypertension control: Target systolic BP <120 mmHg if tolerated, using ACE inhibitors, ARBs, beta-blockers, or diuretics 1
• Lipid management: Initiate high-intensity statin therapy regardless of baseline LDL, as patients with suspected CAD benefit from aggressive lipid lowering 1
• Diabetes management: If diabetic, consider SGLT2 inhibitors (empagliflozin) or GLP-1 receptor agonists (liraglutide, semaglutide), which reduce cardiovascular events and mortality 1
• Smoking cessation and weight management 1

Guideline-Directed Medical Therapy

ACE inhibitors (or ARBs if ACE-intolerant) are recommended for patients with stable coronary artery disease even without LV systolic dysfunction: 1

• This Class IIa recommendation from ESC guidelines applies to your patient with suspected microvascular CAD 1
• ACE inhibitors improve endothelial function and may ameliorate microvascular dysfunction 1

Beta-blockers should be considered if the patient has symptomatic angina, as they reduce myocardial oxygen demand and may improve symptoms in CMD 1

Calcium channel blockers (particularly non-dihydropyridines like diltiazem) can be beneficial for microvascular angina symptoms 4

What NOT to Do: Critical Pitfalls

Invasive coronary angiography is NOT recommended in this patient: 1

• The low-risk perfusion study excludes functionally significant obstructive CAD 2
• Current guidelines recommend revascularization only for functionally significant stenoses causing ischemia 1
• Angiography would likely show normal or non-obstructive coronaries, providing no therapeutic benefit 4
• The 2024 ESC guidelines emphasize that revascularization decisions must be based on functional significance of stenoses, not anatomic appearance alone 1

Avoid routine cardiac catheterization unless the patient develops high-risk features such as refractory symptoms, hemodynamic instability, or evidence of significant ischemia on repeat testing 1

Prognosis and Follow-Up

CMD is not a benign condition despite preserved LVEF: 5, 2

• Recent evidence demonstrates that patients with CMD have increased risk of cardiovascular events including myocardial infarction, need for revascularization, and cardiac death 5
• A stress perfusion CMR study showed that patients with myocardial perfusion reserve index ≤1.47 had three-fold increased risk of major adverse cardiovascular events over 5.5 years 2
• This underscores the importance of aggressive medical management rather than dismissing symptoms as "non-cardiac" 5, 3

Monitoring Strategy

Serial clinical assessment is recommended: 1

• Monitor symptom burden and functional capacity
• Consider biomarker surveillance (BNP/NT-proBNP) if symptoms worsen, as elevation may indicate progression to heart failure 1
• Repeat stress imaging only if clinical status changes significantly 1

The key principle: This patient has coronary disease (microvascular), just not obstructive epicardial disease. Treat the cardiovascular risk factors aggressively as you would any patient with established CAD, focusing on medical optimization rather than pursuing invasive procedures that won't benefit this specific pathophysiology. 1, 5, 3