A Systematic Review of Left mainstem Quadfurcation anatomy “The Starfish Sign” - An incidental finding or a variant of concern?

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Abstract Background Left mainstem coronary artery quadrifurcation (LMQ) is a coronary variant with a wide-ranging estimated prevalence of 1.8% - 9.6%. Although often considered an incidental and benign finding, there is a dearth of literature to support this notion owing to suboptimal clinical characterisation of this phenomenon. The aim of the current manuscript was to perform a systematic review of LMQ and to describe its prevalence, associated demographics and reported clinical outcomes. We furthermore propose new nomenclature for this finding. Methods A systematic review was conducted in accordance with the PRISMA 2020 guidelines. Eligible studies were detected for inclusion into the review using web-based sources (i.e., PubMed, ResearchGate, Google Scholar) over a 20-year period from January 2005 to September 2025. Search terms included “left mainstem quadrification/quadrifurcation/quadfurcation/tertrafurcation, coronary artery branches, coronary artery anomalies, and coronary intervention” using left main quadrifurcation and its wording variants. Where available, cardiovascular risk factors and clinical outcomes were recorded. Statistics were performed using SPSS V24 and R V3.4. LMQ prevalence was estimated by pooled analysis of cadaveric series using a DerSimonian-Laird random-effects model. I2, Tau, and Q statistics were also calculated to assess heterogeneity. Publication bias was assessed by Funnel plot and Egger’s regression. In an exploratory analysis, comparative statistics were performed to assess differences between coronary angiography (CAG) and coronary computed tomographic angiography (CCTA) detection using the Chi square, Student t test and Fischer exact test, as appropriate. A p value < 0.05 was taken to be significant by convention. Results 19 studies were identified, from which 2 were excluded. The total number of patients evaluated was 757. There were 8 cadaveric series (total of 747 cases of which 44 had LMQ quadrification) and the pooled prevalence was 4.5% (95% CI: 2.53 -6.47%). There was moderate heterogeneity (I = 32.2%, Q = 12.33, p = 0.090, T = 0.00034) with Egger’s regression indicating asymmetry (intercept = -2.12, p = 0.001), suggesting small-study effects. Although limited by study numbers (k = 8), the overall risk of bias was low to moderate with consistently low bias in sample selection and measurement reliability and moderate risk in reporting completeness. There was a trend to earlier detection by CCTA compared with CAG (55.3 ± 10.8 years vs. 70 ± 8.5 years, p = 0.056; 95% CI: 0.5–31.5). Clinical characterisation of LMQ anatomy was inconsistent as was the documentation of clinical outcomes. Conclusion Pooled analysis of postmortem studies indicates the prevalence of LMQ anatomy to be 4.5%. Despite several prior reports, clinical characterisation of this phenomenon remains poor. We propose a novel name for this phenomenon “LMCA Starfish variant” along with standardised coronary branch nomenclature to help identify and increase awareness of this variant.

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