What is multivessel disease and how is it defined in the context of coronary artery (CA) disease?

Multivessel Disease: Definition and Clinical Significance

Multivessel coronary disease is defined as angiographically significant stenosis of ≥50% in two or more epicardial coronary arteries, occurring in 40-70% of patients with acute coronary syndromes. 1

Precise Angiographic Definition

The threshold for "significant stenosis" varies by vessel location:

• ≥50% diameter stenosis for left main coronary artery disease 1
• ≥70% diameter stenosis for non-left main epicardial vessels 1, 2
• Must involve ≥2 separate epicardial coronary territories (left anterior descending, left circumflex, right coronary artery) 1

The FIRE trial operationalized this definition more specifically as nonculprit arteries with minimum vessel diameter >2.5 mm and angiographic stenosis 50-99%. 1

Clinical Prevalence and Context

Multivessel disease represents a substantial proportion of coronary presentations:

• 40-70% of NSTE-ACS patients have multivessel involvement 1
• Approximately 50% of all acute coronary syndrome patients present with multivessel disease 3
• The presence of multivessel disease fundamentally alters treatment strategy and prognosis compared to single-vessel disease 3

Anatomic Complexity Stratification

The SYNTAX score provides critical risk stratification for treatment decisions in multivessel disease 2:

• Low complexity (SYNTAX ≤22): PCI may be equivalent to CABG 2
• Intermediate complexity (SYNTAX 23-32): CABG generally preferred 2
• High complexity (SYNTAX >32): CABG clearly preferred 2

High-Risk Anatomic Patterns

Certain multivessel patterns carry particularly poor prognosis and influence revascularization strategy 1:

• Significant left main stenosis with high-complexity CAD 1
• Complex or diffuse multivessel CAD 1
• Diabetes mellitus with MVD involving the LAD 1, 2
• Multivessel CAD with severe LV dysfunction 1
• Proximal LAD involvement confers worse prognosis than distal disease 2

Critical Diagnostic Pitfall

Visual angiographic assessment alone has only 70% inter-observer concordance for stenosis severity, dropping to 51% when restricted to vessels with some stenosis. 2 This limitation necessitates physiological assessment in many cases.

Physiological Assessment Integration

When multivessel PCI is considered, fractional flow reserve (FFR <0.80) or instantaneous wave-free ratio (iFR) should be used to define true hemodynamic significance of intermediate lesions (50-70% stenosis). 2, 4 The 2025 ACC/AHA guidelines give this a Class 2b recommendation for nonculprit stenosis assessment in NSTE-ACS. 1

Prognostic Implications

Multivessel disease carries significantly higher risk of recurrent ischemic events and mortality compared to single-vessel disease. 3 The presence of preserved versus impaired ventricular function further stratifies risk:

• EF ≥50%: Requires evaluation for revascularization 2
• EF <50%: Greater survival benefit with CABG over PCI 2
• EF <35%: Requires careful myocardial viability assessment before revascularization decisions 2

Special Population: Cardiogenic Shock

In patients with ACS complicated by cardiogenic shock, multivessel disease has a fundamentally different treatment paradigm. The CULPRIT-SHOCK trial definitively showed that routine PCI of noninfarct-related arteries at the time of primary PCI results in higher rates of death or renal replacement therapy at 30 days and 1 year. 1 This represents a Class 3 Harm recommendation. 1

The critical caveat: CULPRIT-SHOCK only enrolled patients with an identifiable culprit lesion. When there is an unstable-appearing nonculprit or uncertain culprit lesion, the decision becomes more nuanced and requires individualized assessment. 1