The role of procedural factors on the outcomes of embolization followed by radiosurgery for the treatment of brain arteriovenous malformations: systematic review and proportional meta-analyses.

BACKGROUND: Multimodal therapy for brain arteriovenous malformations (bAVM) with embolization followed by stereotactic radiosurgery (E + SRS) has shown varying outcomes. Its benefits over other treatment modalities have been questioned. The goal of this systematic review was to determine the factors associated with cure and complication rates of this treatment strategy. METHODS: A literature search in Medline and Global Index Medicus, from inception to October 2023, was performed. Studies reporting relevant outcome data from bAVM patients treated with E + SRS were included. Data on several patient, lesion and procedure-related factors were collected. Embolization intent was classified as Targeted (of high-risk features), Devascularizing (feeder embolization/flow reduction) and Occluding (intent-to-cure, nidus embolization). The primary outcome was obliteration rate. Secondary outcomes were post-SRS bleeding (PSB), post-embolization neurological complications (PENC) and post-SRS neurological complications (PSNC). Subgroup analyses included embolic agent, embolization intent and radiosurgery type. Proportional meta-analyses and meta-regressions were performed. RESULTS: Forty-one studies were included in the review. The pooled obliteration rate was 56.45% (95% CI 50.94 to 61.88). Meta-regression analyses showed higher obliteration rates with Copolymers and lower obliteration rates with Devascularizing embolization. The pooled PSB, PENC and PSNC rates were 5.50%, 13.75% and 5.02%, respectively. Meta-regression analyses showed higher rates of PSB, PENC and PSNC with Devascularizing embolization, Liquid & Solid embolic agents and Targeted & Devascularizing intent, respectively. CONCLUSION: Embolic agent and embolization intent were procedural factors associated with treatment outcomes of E + SRS in the management of bAVM patients. The efficacy and safety profiles favor copolymers as embolic agents and disfavor Devascularizing as embolization intent. STUDY REGISTRATION: The protocol of the systematic review was registered in PROSPERO as CRD42023474171.

Location-based clinical and angiographic profile of brain arteriovenous malformations - a single-center observational study.

BACKGROUND: The location of brain arteriovenous malformations (bAVM) is one of the most relevant prognostic factors included in surgical, endovascular and radiosurgical scores. However, their characteristics according to location are seldom described. The goal of this study was to describe the clinical and angiographic characteristics of bAVM classified according to their location. METHODS: This retrospective observational study included patients diagnosed with bAVM and attending a national referral hospital during the period 2010-2020. Data regarding clinical and angiographic variables were extracted, including characteristics on nidus, arterial afferents, venous drainage and associated aneurysms. BAVM were classified in 8 groups according to their location: frontal, temporal, parieto-occipital, periventricular, deep, cerebellar, brainstem and mixed. Data distribution for each group was determined and between-group differences were assessed. RESULTS: A total of 269 bAVM (in 258 patients) were included. The most frequent location was parieto-occipital; and the least frequent, brainstem. Statistically significant differences were observed between groups for most studied variables, including: clinical presentation, functional status at admission; nidus size and density, classification according to the Spetzler-Martin, Buffalo and modified Pollock-Flickinger scales; number, diameter, origin and type of afferents; number, diameter, type and direction of venous drainage, retrograde venous flow; and presence and size of flow-related aneurysms. CONCLUSION: The clinical and angiographic differences observed between brain AVM groups allow the formulation of profiles according to their location.

Curative embolization of ruptured pediatric cerebral arteriovenous malformations.

INTRODUCTION: Embolization with the intention to cure has not been well studied in ruptured arteriovenous malformations (AVMs). Furthermore, the role of primary curative embolization of pediatric AVMs is uncertain. Hence, we aimed to characterize the safety and efficacy of curative embolization of ruptured pediatric AVMs and assess predictors of obliteration and complications. METHODS: A retrospective analysis of all pediatric (≤18 years) patients who underwent curative embolization of ruptured AVMs was conducted in two institutions between 2010 and 2022. The efficacy (complete angiographic obliteration after the last embolization session), recurrence (radiological recurrence of the lesion after confirmed obliteration in follow-up imaging), and safety (procedure-related complications and mortality) of the procedure were evaluated. RESULTS: Sixty-eight patients (38 females; mean age 12.4 ± 3.4 years) underwent a total of 109 embolization sessions. Median follow-up time was 18 months after embolization (ranged from 2 to 47 months). Complete angiographic obliteration was achieved in 42 patients (62%). In 30 patients (44%) the AVM was occluded with a single embolization session. Recurrence of a totally embolized lesion occurred in 9 patients (13%). Thirteen complications (11.9% of procedures) were observed, and no deaths were reported. A nidus size > 2 cm was the only independent predictor of complete obliteration (OR = 0.16; 95% CI 0.03 - 0.77; p = 0.030). CONCLUSION: Embolization of pediatric ruptured AVMs with curative intent can achieve acceptable obliteration rates. However, recurrence after complete obliteration and procedure-related complications of curative embolization of these lesions cannot be ignored. Ruptured AVMs ≤ 2 cm are adequate to achieve complete obliteration with curative endovascular management.

Multiple brain arteriovenous malformations: systematic review and individual patient data meta-analysis.

Multiple brain arteriovenous malformations (bAVM) are rare neurovascular lesions usually related to genetic syndromes. Its management is not well established given its rarity. The objective of this study was to describe the clinical and angiographic features of published cases and to explore their associations with treatment outcomes. We performed a literature search of published cases in Medline and the Regional Index Medici. Additional cases were searched in our single-center registry. Data on the proportions of patients and clinical and angiographic characteristics were extracted. The study outcomes were nidal instability in patients who underwent staged treatment and radiological cure in patients who underwent treatment using any treatment modality. Logistic regression models for the study outcomes were analyzed. Data on the proportions of multiple bAVM patients were summarized with meta-analyses of proportions. We included 118 patients (reported in 68 studies) from the literature and 6 cases identified in our registry. A total of 124 patients harboring 339 bAVM nidi were included in the analyses. Differences between syndromic and non-syndromic cases were observed. The logistic regression analyses showed that angiographically occult untreated bAVM was associated (OR 14.37; 95% CI 2.17 to 95.4) with nidal instability after staged treatment, and deep (OR 5.11; 95% CI 1.51 to 17.27) and eloquent (OR 3.91; 95% CI 1.22 to 12.52) locations were associated with residual disease after treatment. Inconsistent reporting of relevant data throughout the included studies undermined the planned analyses. Some prognostic factors were found to be related to the study outcomes. Study Registration: The protocol of the systematic review was registered in PROSPERO as CRD42021245814.

Ranolazine for stable angina pectoris.

BACKGROUND: Stable angina pectoris is a chronic medical condition with significant impact on mortality and quality of life; it can be macrovascular or microvascular in origin. Ranolazine is a second-line anti-anginal drug approved for use in people with stable angina. However, the effects of ranolazine for people with angina are considered to be modest, with uncertain clinical relevance. OBJECTIVES: To assess the effects of ranolazine on cardiovascular and non-cardiovascular mortality, all-cause mortality, quality of life, acute myocardial infarction incidence, angina episodes frequency and adverse events incidence in stable angina patients, used either as monotherapy or as add-on therapy, and compared to placebo or any other anti-anginal agent. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase and the Conference Proceedings Citation Index - Science in February 2016, as well as regional databases and trials registers. We also screened reference lists. SELECTION CRITERIA: Randomised controlled trials (RCTs) which directly compared the effects of ranolazine versus placebo or other anti-anginals in people with stable angina pectoris were eligible for inclusion. DATA COLLECTION AND ANALYSIS: Two authors independently selected studies, extracted data and assessed risk of bias. Estimates of treatment effects were calculated using risk ratios (RR), mean differences (MD) and standardised mean differences (SMD) with 95% confidence intervals (CI) using a fixed-effect model. Where we found statistically significant heterogeneity (Chi² P < 0.10), we used a random-effects model for pooling estimates. Meta-analysis was not performed where we found considerable heterogeneity (I² ≥ 75%). We used GRADE criteria to assess evidence quality and the GRADE profiler (GRADEpro GDT) to import data from Review Manager 5.3 to create 'Summary of findings' tables. MAIN RESULTS: We included 17 RCTs (9975 participants, mean age 63.3 years). We found very limited (or no) data to inform most planned comparisons. Summary data were used to inform comparison of ranolazine versus placebo. Overall, risk of bias was assessed as unclear.For add-on ranolazine compared to placebo, no data were available to estimate cardiovascular and non-cardiovascular mortality. We found uncertainty about the effect of ranolazine on: all-cause mortality (1000 mg twice daily, RR 0.83, 95% CI 0.26 to 2.71; 3 studies, 2053 participants; low quality evidence); quality of life (any dose, SMD 0.25, 95% CI -0.01 to 0.52; 4 studies, 1563 participants; I² = 73%; moderate quality evidence); and incidence of non-fatal acute myocardial infarction (AMI) (1000mg twice daily, RR 0.40, 95% CI 0.08 to 2.07; 2 studies, 1509 participants; low quality evidence). Add-on ranolazine 1000 mg twice daily reduced the fervour of angina episodes (MD -0.66, 95% CI -0.97 to -0.35; 3 studies, 2004 participants; I² = 39%; moderate quality evidence) but increased the risk of non-serious adverse events (RR 1.22, 95% CI 1.06 to 1.40; 3 studies, 2053 participants; moderate quality evidence).For ranolazine as monotherapy compared to placebo, we found uncertain effect on cardiovascular mortality (1000 mg twice daily, RR 1.03, 95% CI 0.56 to 1.88; 1 study, 2604 participants; low quality evidence). No data were available to estimate non-cardiovascular mortality. We also found an uncertain effect on all-cause mortality for ranolazine (1000 mg twice daily, RR 1.00, 95% CI 0.81 to 1.25; 3 studies, 6249 participants; low quality evidence), quality of life (1000 mg twice daily, MD 0.28, 95% CI -1.57 to 2.13; 3 studies, 2254 participants; moderate quality evidence), non-fatal AMI incidence (any dose, RR 0.88, 95% CI 0.69 to 1.12; 3 studies, 2983 participants; I² = 50%; low quality evidence), and frequency of angina episodes (any dose, MD 0.08, 95% CI -0.85 to 1.01; 2 studies, 402 participants; low quality evidence). We found an increased risk for non-serious adverse events associated with ranolazine (any dose, RR 1.50, 95% CI 1.12 to 2.00; 3 studies, 947 participants; very low quality evidence). AUTHORS' CONCLUSIONS: We found very low quality evidence showing that people with stable angina who received ranolazine as monotherapy had increased risk of presenting non-serious adverse events compared to those given placebo. We found low quality evidence indicating that people with stable angina who received ranolazine showed uncertain effect on the risk of cardiovascular death (for ranolazine given as monotherapy), all-cause death and non-fatal AMI, and the frequency of angina episodes (for ranolazine given as monotherapy) compared to those given placebo. Moderate quality evidence indicated that people with stable angina who received ranolazine showed uncertain effect on quality of life compared with people who received placebo. Moderate quality evidence also indicated that people with stable angina who received ranolazine as add-on therapy had fewer angina episodes but increased risk of presenting non-serious adverse events compared to those given placebo.