Venous tortuosity as a novel biomarker of rupture risk in arteriovenous malformations: ARI score

Abstract

BackgroundRisk of rupture in arteriovenous malformations (AVMs) varies considerably among series. Hemodynamic factors, especially within the venous side of the circuit, seem to be responsible but are not yet well defined. We analyzed tortuosity in the draining vein as a potential new marker of rupture in AVMs, and propose a simple index to predict AVM bleeding.MethodsA retrospective analysis of the venous angioarchitecture of brain AVMs was carried out at our center from 2013 to 2021, with special attention to venous tortuosity. After univariate analysis, the features of interest were combined to construct several predictive models using multivariate logistic regression. The best model proposed was the new AVM rupture index (ARI), which was then validated in an independent cohort.Results68 AVMs were included in the first step and 32 in the validation cohort. Venous tortuosity, expressed as at least one curve >180°, was a significant predictor of rupture (p=0.023). The proposed bleeding index consisted of: venous tortuosity (any curve of >180°), single draining vein, and paraventricular/infratentorial location. It seems to be a robust evaluation tool, with an area under the receiver operating characteristic (AUROC) curve of 0.806 (95% CI 0.714 to 0.899), consistently replicated in the independent sample (AUROC 0.759 (95% CI 0.607 to 0.911)), and with an inter-rater kappa coefficient of 0.81 .ConclusionsVenous tortuosity may serve as a predictor of bleeding in AVMs that warrants further investigation. This likely new marker was one of the three elements of the proposed ARI. ARI outperformed the predictive accuracy of previous scores, and remained consistent in an independent cohort.

The angio-architectural features of brain arteriovenous malformations: is it possible to predict the probability of rupture?

“…In fact, in our series, ruptured bAVMs were more frequently detected in older patients, supporting the hypothesis that bAVMs are not static in their shape and in hemodynamic, but evolve during lifetime. 7–10, 12 Among the angio-architectural features of bAVMs between ruptured and unruptured groups, we found a statistically significant differences into several features, both into the arterial, nidus, and venous portions. These statistically significant differences among ruptured and unruptured bAVMs support the hypothesis that angio-architectural features should be considered during treatment decision, both for newly discovered bAVMs and during follow-up.…”

“…These statistically significant differences among ruptured and unruptured bAVMs support the hypothesis that angio-architectural features should be considered during treatment decision, both for newly discovered bAVMs and during follow-up. 12–15…”

“…Previous articles have shown that the angioarchitecture of bAVMs evolves across time, 7–11 and bleeding mainly occurs when the hemodynamical balance is lost. 12 Thus, there is the needing to identify features associated with higher probability of rupture, to prevent this potentially dramatical event. 12–15…”

“…5,6 Previous articles have shown that the angioarchitecture of bAVMs evolves across time, [7][8][9][10][11] and bleeding mainly occurs when the hemodynamical balance is lost. 12 Thus, there is the needing to identify features associated with higher probability of rupture, to prevent this potentially dramatical event. [12][13][14][15] IRCCS Istituto Delle Scienze Neurologiche di Bologna, Programma Neuroimmagini Funzionali e Molecolari, Bologna, Italy 6 IRCCS Istituto Delle Scienze Neurologiche di Bologna, Programma Neurochirurgia Ipofisi, Bologna, Italia Despite several anatomic, hemodynamic, and angioarchitectural features have been identified as being more prevalent in ruptured bAVMs, no scores or classification have been developed to consider the probability of bleeding.…”

Associated genetic variants and potential pathogenic mechanisms of brain arteriovenous malformation

“…Like many other cerebrovascular disorders, bAVM is affected by both genetic predisposition and non-genetic factors. Many non-genetic factors have been investigated, including hemodynamic changes, angiogenesis, and inflammation, which play an important role in formation and rupture of lesions 2 6. Additionally, several bAVM patients have a family history of hereditary hemorrhagic telangiectasia, a genetic disease associated with variants of the genes encoding activin receptor-like kinase 1 ( ACVLR1 ) and endoglin ( ENG ), among others 7.…”