What is the recommended management for a patient with suspected coronary artery disease, non-diagnostic pharmacologic ECG (electrocardiogram) for ischemia, left ventricular ejection fraction (LVEF) of 64%, moderate intensity area of lateral ischemia without infarct, and decreased coronary flow reserve in the territories of the left circumflex and left anterior descending (LAD) arteries?

Management of Moderate Lateral Ischemia with Preserved LVEF

This patient requires invasive coronary angiography with revascularization of functionally significant stenoses to improve symptoms and potentially reduce cardiovascular events, given the moderate-intensity lateral ischemia and decreased coronary flow reserve in multiple territories despite preserved left ventricular function. 1

Immediate Diagnostic and Therapeutic Strategy

Proceed to Invasive Coronary Angiography

• Invasive angiography is recommended as the definitive diagnostic and therapeutic approach for patients with moderate-severe ischemia on stress testing who have symptoms or high-risk features, even with preserved LVEF (64%). 1

• The presence of moderate-intensity lateral ischemia affecting the left circumflex and LAD territories with decreased coronary flow reserve indicates functionally significant multivessel disease requiring anatomic definition. 1

• While the ISCHEMIA trial showed no mortality benefit for routine invasive management in asymptomatic patients with moderate-severe ischemia, patients with anginal symptoms experienced prompt and durable symptom improvement with invasive management. 1

Functional Assessment During Angiography

• Intracoronary pressure measurement (FFR or iFR) or computation (QFR) is recommended to guide lesion selection for intervention in patients with multivessel disease. 1, 2

• This is critical because decreased coronary flow reserve in multiple territories suggests multivessel involvement, and FFR/iFR will identify which lesions are hemodynamically significant and warrant revascularization. 1

• Intracoronary imaging guidance by IVUS or OCT is recommended when performing PCI on anatomically complex lesions, particularly for left main, bifurcations, or long lesions. 1, 2

Revascularization Decision-Making

Choice Between PCI and CABG

The revascularization modality depends on the coronary anatomy found at angiography:

For Left Main or Three-Vessel Disease:

• CABG is recommended over PCI to improve long-term survival and reduce repeat revascularization, particularly if SYNTAX score is >22 or diabetes is present. 1, 3
• Recent data from ISCHEMIA participants with 3-vessel CAD showed revascularization (either PCI or CABG) was associated with 4.4 percentage point lower 4-year CV death/MI rate compared to conservative management. 4

For Two-Vessel Disease Involving Proximal LAD:

• Either CABG or PCI is recommended, with choice based on anatomic complexity, patient comorbidities, and local expertise. 1, 3

For Single or Two-Vessel Disease Not Involving Proximal LAD:

• PCI is recommended as the preferred revascularization strategy. 1, 3

For Multivessel Disease with Normal LVEF (as in this case):

• PCI is acceptable for patients with suitable coronary anatomy and normal LV function without diabetes. 1
• However, CABG should be considered if anatomic complexity is high or complete revascularization cannot be achieved with PCI. 1

Medical Therapy Optimization

Antianginal and Anti-Ischemic Therapy

While proceeding to angiography, optimize medical therapy:

• Beta-blockers are essential for reducing myocardial oxygen demand and controlling ischemia. Persistent ischemia despite beta-blockade identifies high-risk patients with threefold increased risk of cardiac events if therapy is interrupted. 5

• Add long-acting nitrates or calcium channel blockers for additional symptom control if beta-blockers alone are insufficient. 1

• Consider ranolazine as adjunctive antianginal therapy if symptoms persist despite first-line agents. 1

Secondary Prevention (Regardless of Revascularization Strategy)

• High-intensity statin therapy to achieve LDL-C <70 mg/dL (or <55 mg/dL for very high-risk patients). 1, 3

• Aspirin 75-100 mg daily for antiplatelet therapy. 1, 3

• ACE inhibitor or ARB should be considered even with preserved LVEF given the presence of CAD and ischemia. 1

• Low-dose colchicine (0.5 mg daily) is recommended to reduce MI, stroke, and need for revascularization in patients with atherosclerotic CAD. 2

Post-Revascularization Management

If PCI is Performed:

• Dual antiplatelet therapy (DAPT) with aspirin plus a potent P2Y12 inhibitor (ticagrelor or prasugrel preferred over clopidogrel) for 12 months after stent implantation. 3

• Intravenous GP IIb/IIIa inhibitor during PCI if high-risk features are present. 1

• Consider proton pump inhibitor for patients at high gastrointestinal bleeding risk on DAPT. 3

If CABG is Performed:

• Continue aspirin indefinitely. 3

• Internal mammary artery grafting to LAD is preferred when feasible. 1

Critical Pitfalls to Avoid

• Do not pursue routine periodic stress testing after successful revascularization in asymptomatic patients, as this leads to increased non-ischemic revascularization without improving outcomes. 1

• Do not revascularize lesions without functional significance (FFR >0.80 or iFR >0.89), as this increases procedural risk without benefit. 1

• Do not interrupt beta-blocker therapy in patients with documented ischemia, as this triples the risk of adverse cardiac events. 5

• Avoid routine follow-up angiography after PCI in asymptomatic patients, as this increases repeat revascularization without improving death or MI rates. 1