Acute ischaemia after subarachnoid haemorrhage, relationship with early brain injury and impact on outcome: a prospective quantitative MRI study.

OBJECTIVE: To determine if ischaemia is a mechanism of early brain injury at the time of aneurysm rupture in subarachnoid haemorrhage (SAH) and if early MRI ischaemia correlates with admission clinical status and functional outcome. METHODS: In a prospective, hypothesis-driven study patients with SAH underwent MRI within 0-3 days of ictus (prior to vasospasm) and a repeat MRI (median 7 days). The volume and number of diffusion weighted imaging (DWI) positive/apparent diffusion coefficient (ADC) dark lesions on acute MRI were quantitatively assessed. The association of early ischaemia, admission clinical status, risk factors and 3-month outcome were analysed. RESULTS: In 61 patients with SAH, 131 MRI were performed. Early ischaemia occurred in 40 (66%) with a mean DWI/ADC volume 8.6 mL (0-198 mL) and lesion number 4.3 (0-25). The presence of any early DWI/ADC lesion and increasing lesion volume were associated with worse Hunt-Hess grade, Glasgow Coma Scale score and Acute Physiology and Chronic Health Evaluation II physiological subscores (all p<0.05). Early DWI/ADC lesions significantly predicted increased number and volume of infarcts on follow-up MRI (p<0.005). At 3 months, early DWI/ADC lesion volume was significantly associated with higher rates of death (21% vs. 3%, p=0.031), death/severe disability (modified Rankin Scale 4-6; 53% vs. 15%, p=0.003) and worse Barthel Index (70 vs. 100, p=0.004). After adjusting for age, Hunt-Hess grade and aneurysm size, early infarct volume correlated with death/severe disability (adjusted OR 1.7, 95% CI 1.0 to 3.2, p=0.066). CONCLUSIONS: Early ischaemia is related to poor acute neurological status after SAH and predicts future ischaemia and worse functional outcomes. Treatments addressing acute ischaemia should be evaluated for their effect on outcome.

Reversal of coagulopathy using prothrombin complex concentrates is associated with improved outcome compared to fresh frozen plasma in warfarin-associated intracranial hemorrhage.

BACKGROUND: There are no studies demonstrating that prothrombin complex concentrates (PCC) improves outcome compared FFP in patients with warfarin-associated intracranial hemorrhage. METHODS: A prospective, observational study was conducted of patients who received PCC (Bebulin VH), FFP, or PCC + FFP. All groups received vitamin K 10 mg IV. INR reversal (<1.4), adverse events (venous thromboembolism, myocardial infraction, pulmonary edema), major hemorrhage (new or worsened intracranial hemorrhage, anemia requiring transfusion or GI bleed), and 3-month functional outcome were compared between the groups using Chi squared and logistic regression analysis. RESULTS: Of 64 patients, PCC alone was used in 16 (mean dose 48 IU/kg), FFP alone in 25 (mean dose 12.5 ml/kg), and PCC + FFP in 23 (median doses 47.4 IU/kg and 11.4 ml/kg, respectively). INR correction occurred in 88, 84, and 70 %, respectively. There were no differences in time to INR correction or adverse events between the groups, but FFP alone was associated with more major hemorrhage after administration (52 %, OR 5.0, 95 % CI 1.6-15.4, P = 0.006) and PCC with less (6 %, OR 0.1, 95 % CI 0.01-0.8, P = 0.033). After adjusting for age, admission GCS, initial INR, and bleed type, the use of PCC was associated with a lower risk of death or severe disability at 3-months (adjusted OR 0.02, 95 % CI 0.001-0.8, P = 0.039), while FFP alone was associated with a higher risk (adjusted OR 51.6, 95 % CI 1.2-2163.1, P = 0.039). CONCLUSIONS: PCC adequately corrected INR without any increase in adverse events compared to FFP and was associated with less major hemorrhage and improved 3-month outcomes in patients with warfarin-associated intracranial hemorrhage.

The Modified Ablation Guided by Ibutilide Use in Chronic Atrial Fibrillation (MAGIC-AF) Study: clinical background and study design.

BACKGROUND: Beyond pulmonary vein isolation (PVI), adjuvant ablation at the sites of complex fractionated atrial electrograms (CFAE) has been shown to improve the long-term success of catheter ablation of persistent atrial fibrillation (AF). However, this approach often requires extensive ablation due to the widespread distribution of CFAE within the left atrium. An optimal strategy would identify areas of CFAE which, when selectively targeted with ablation, result in AF termination with an acceptable long-term freedom from AF. It is possible that the intraprocedural administration of an antiarrhythmic drug may help accomplish this. OBJECTIVE: The Modified Ablation Guided by Ibutilide Use in Chronic AF (MAGIC-AF) Study is an international multicenter prospective randomized double-blinded clinical trial assessing the utility of the intraprocedural administration of 0.25 mg of intravenous ibutilide before performing CFAE ablation. The primary efficacy endpoint of this study will be the freedom from AF at 1 year after a single procedure off antiarrhythmic agents. Safety endpoints will include procedural and radiofrequency ablation time as well as overall procedural complication rate. METHODS: Patients undergoing a first ever catheter ablation procedure for persistent AF will be included. Individuals with hypertrophic cardiomyopathy, complex congenital heart disease including atrial septal defects, and ejection fraction <35% will be excluded from the study. All patients will first undergo PVI. Those patients who remain in AF will then be randomized in a 1:1 fashion to receive either 0.25 mg intravenous ibutilide or saline placebo followed by a CFAE based ablation strategy. Two hundred randomized patients will be enrolled in this study-100 in each study arm. CONCLUSION: The MAGIC-AF study will assess the utility of a combined pharmaco-ablative strategy in patients with persistent AF undergoing a CFAE based ablation strategy.