Prevalence and clinical significance of coronary artery variations: a systematic review with meta-analysis

BACKGROUND: This systematic review and meta-analysis aimed to determine the prevalence and clinical relevance of main coronary artery (CA) origin and course anomalies (class A variations) in healthy populations. METHODS: This systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 and Evidence-based Anatomy guidelines. A literature search was conducted across PubMed, Google Scholar, Scopus, and Web of Science. Statistical analysis was performed in R using random-effects models, with pooled prevalence calculated through the Freeman-Tukey transformation. Subgroup, meta-regression, and leave-one-out analyses were performed to explain the source of heterogeneity. RESULTS: A total of 58 studies with 503,171 subjects were included. The pooled prevalence of typical CA anatomy was 97.89% (95% CI: 97.51-98.25), whereas main CA anomalies had a prevalence of 2.11% (95% CI: 1.82-2.70). Subgroup analysis retrieved statistically significant differences for nationality and study type, and meta-regression revealed an increasing trend of CA variants with later publication years. The most common variation was the anomalous origin of the right CA from the left sinus (0.30%), followed by a high take-off of the right CA (0.14%). Left CA anomalies were less frequent, with anomalous origin from the right sinus recorded in 0.05% of cases. Subgroup analyses revealed a higher prevalence in American populations and computed tomography-based studies. CONCLUSIONS: Main CA anomalies (class A variations) are rare but clinically significant owing to their association with ischemic events and sudden cardiac death, particularly variants with interarterial or intramural courses. Early identification through modern imaging is critical for risk stratification and clinical decision-making.