Arterial Supply of the Heart

Fig. 3.80 Coronary arteries - (A) anterior diagram, (B) right coronary angiogram, (C) left coronary angiogram - Gray's Anatomy for Students

Right Coronary Artery (RCA)

• Right atrium and right ventricle
• SA node and AV node (in most people)
• Interatrial septum
• Posteroinferior one-third of the interventricular septum
• Posterior part of the left ventricle (in right dominant hearts)

Left Coronary Artery (LCA)

1. Anterior Interventricular Branch (Left Anterior Descending - LAD)

2. Circumflex Branch (LCX)

• Most of the left atrium and left ventricle
• Most of the interventricular septum (anterior two-thirds)
• AV bundle and its branches
• Lateral wall of the left ventricle (LCX)

Coronary Dominance

In clinical practice: the short LCA is called the left main stem; the anterior interventricular artery is the LAD; the posterior interventricular artery is the posterior descending artery (PDA).

Autopsy Diagnosis of Myocardial Infarction

Fig. 12.10 Progression of necrosis from subendocardial zone outward over 24 hours - Robbins & Cotran Pathologic Basis of Disease

Patterns of Infarction at Autopsy

Fig. 12.11 Left: transmural infarcts by coronary artery; Right: non-transmural patterns - Robbins & Cotran

• Transmural infarct: Full wall thickness necrosis. Caused by permanent occlusion of an epicardial vessel (atherosclerosis + thrombus). A thin rim (~0.1 mm) of subendocardial myocardium is spared by diffusion from the ventricular lumen.
• Subendocardial (nontransmural) infarct: Involves inner layers only. Occurs when a thrombus lyses before necrosis extends transmurally, or due to global hypoperfusion (shock) - in which case damage is circumferential, not limited to one vessel territory.
• Multifocal microinfarction: From small intramural vessel pathology (microembolism, vasculitis, cocaine-induced vasospasm).

Temporal Evolution of Morphologic Changes (Table 12.5)

Key Autopsy Techniques

Coronary Pathology to Document

• Evidence of atherosclerotic plaque disruption/erosion
• Superimposed thrombus (present in ~90% of cases when angiography done within 4 hrs of onset)
• Degree of luminal stenosis
• Presence of collateral vessels

Collateral Vessel Development in Chronic Coronary Artery Disease: Recent Research Summary

Background

1. Functional Role of Collaterals in Stable CAD

• Collateral flow index (CFI) correlated strongly with ischemic burden: lower FFR/iFR was associated with greater collateral recruitment (Somers' D 0.302, Pr = 0.999)
• Higher CFI was independently associated with lower pain intensity during balloon occlusion (Somers' D = 0.341, Pr = 0.999)
• Daily angina frequency showed little correlation with FFR or iFR alone - collateralization may explain the known nonlinear relationship between stenosis severity and symptom burden
• No evidence of ischemic preconditioning between sequential occlusion episodes

Clinical implication: Collateral adequacy - not stenosis severity alone - determines symptom burden in chronic stable CAD, and should be factored into revascularization decisions.

2. MicroRNA Mediators of Collateral Development (Mechanobiology)

• Patients with favorable collaterals had significantly higher CFI (0.45 ± 0.02 vs 0.38 ± 0.03, p < 0.001)
• miR-26a and miR-21 showed strong positive correlations with CFI (r = 0.715 and r = 0.663, respectively)
• let-7d and miR-663 were negatively correlated with CFI (r = -0.684 and r = -0.604)
• Significant correlations found between:
  • TGF-β and miR-126 (r = 0.673)
  • VEGF and miR-10a (r = 0.602)
• Multivariate regression identified hemoglobin, smoking, beta-blocker use, miR-26a, and miR-663 as independent determinants of CFI

Mechanistic insight: Shear stress-responsive miRNAs modulate the VEGF and TGF-β signaling axes that drive arteriogenesis and angiogenesis in CTO. These represent potential therapeutic targets and non-invasive biomarkers.

3. Endothelial Dysfunction as a Predictor of Poor Collateral Formation

• Poorly developed CCC (Rentrop grades 0-1) was present in 37.6% of patients
• Well-developed CCC group had significantly lower EASIX (median 0.44 vs 0.67, p < 0.001) and higher HDL cholesterol
• EASIX independently predicted poor collateral development: OR 2.536 per 1-SD increase (95% CI 1.734-3.710, p < 0.001)
• ROC analysis: AUC = 0.718, sensitivity 72.9%, specificity 62.1% at cutoff > 0.51
• Neutrophil-to-lymphocyte ratio was also elevated in the poor-collateral group

Clinical implication: Systemic endothelial stress - measurable via a simple, low-cost index - is a significant determinant of collateral vessel adequacy. EASIX may help risk-stratify CTO patients before revascularization planning.

4. Diabetes, Dyslipidemia, and Impaired Collateral Formation

• Patients with diabetic microvascular complications (DMC - neuropathy, nephropathy, retinopathy) had higher prevalence of collaterals (92.0% vs 75.6%, p = 0.006) and higher-grade collaterals (73.3% vs 47.6%, p = 0.001)
• A positive association was found between the number of DMC and prevalence of high-grade CCC

This challenges the assumption that diabetes uniformly impairs collaterals; chronic ischemic stimulus from microvascular disease may itself promote collateral arteriogenesis in some T2DM patients.

• Mechanisms: Altered lipid profiles cause glycoxidative modification of LDL, endothelial dysfunction, and blunting of endothelial progenitor cell (EPC) responses
• Elevated triglycerides, hypercholesterolemia, raised Lp(a), and HDL quality/quantity defects all independently impair collateral growth and maturation
• Lipid-lowering therapies (statins, PCSK9 inhibitors) may partially restore collateral capacity via anti-inflammatory and EPC-stimulating effects

5. Summary of Key Mechanisms and Biomarkers

Gaps and Future Directions

• Most CTO-collateral studies rely on angiographic Rentrop grading, which has limited resolution compared to pressure-wire CFI measurements
• The paradox of DMC and enhanced collateral formation needs prospective validation
• mechano-miR profiling (miR-26a, miR-21) and EASIX require multicenter prospective validation before clinical adoption
• Therapeutic strategies (gene therapy with VEGF, cell-based EPC therapy) have not yet shown consistent benefit in RCTs; the mRNA-VEGF delivery approach in porcine chronic ischemia models showed no therapeutic effect, highlighting translation challenges (PMID 34494459)