Atrial fibrillation (AF) remains the most common arrhythmia in the United States (US).1 It has been estimated that the number of patients diagnosed with AF will increase to more than 10 million by 2050.2 The problem of AF is compounded by the increased risk of stroke,3 congestive heart failure,4 and possibly an increase in mortality.5 There have been tremendous improvements in the management of AF, with major advances in catheter ablation of AF. The past decade has witnessed a rapid advancement in the field of catheter ablation of AF, which has resulted in better outcomes compared to antiarrhythmic drug therapy.6 However, peri-procedural cerebrovascular accident (CVA) remains one of the most feared complications of AF ablation. The reported incidence of thromboembolic complications associated with AF ablation has been reported to be as high as 2%.7 There are several mechanisms responsible for CVA during the ablation procedure, including air embolism, thrombus and coagulum formation. Thrombus formation is due to activation of the coagulation cascade and requires presence of thrombin.8 It is usually related to the placement of intravascular catheters within the left atrium and may be prevented by aggressive anticoagulation,9 which in turn increases risk of bleeding complications. Coagulum is the product of heat-denatured fibrinogen and is usually created by tissue overheating.8 Coagulum formation is independent of thrombin; therefore, heparin8 or coumadin alone may not prevent its formation. Despite several strategies proposed to minimize the risk of thromboembolism during AF ablation, no single protocol completely prevents the occurrence of strokes. It is essential for the team performing the ablation procedure to be familiar with these strategies and be prepared for the inevitable but rare thromboembolic event. Ruling Out Presence of Preexisting Thrombi Pre-procedural imaging. All patients prior to AF ablation should have an evaluation for the detection of intracardiac thrombus.10 Transesophageal echocardiogram (TEE) is the gold standard for detection of left atrial (LA) thrombus within the left atrial appendage (LAA).11 The TEE should be performed in a timely fashion prior to the ablation procedure, and is usually performed within one day of the procedure in most centers.10 The TEE can also provide additional anatomical and hemodynamic information that may prove to be essential to a successful ablation procedure. Recently, there have been several studies that examined the role of CT in pre-procedural evaluation of intracardiac thrombus prior to AF ablation.12-14 Kim et al13 evaluated 223 consecutive patients who had multi-detector computed tomography (MDCT) and TEE studies within 7 days of each other. Visually identified filling defects in LAA by MDCT correspond to severe spontaneous echo contrast (SEC) and thrombus. MDCT identified all thrombi successfully when compared to TEE. However, at this time, pre-ablation CT screening may have a limited role in detection of left atrial thrombus mostly because of image quality and difficulty in distinguishing clot from pectinate muscle in the LAA.12 Preventing Thrombus Formation High-flow sheath perfusion. The transseptal approach requires multiple catheters and long sheaths to facilitate insertion and navigation of catheters. Stagnant flow through the sheath can be an important source of thrombus formation in the transseptal sheaths. Also, friction at the solid–fluid interface and frequent movements of the catheter through the sheath can cause turbulence.15 Insufficient coaxial flush can cause stasis and provoke thrombus formation.15 Continuous high-flow perfusion of the sheath may be effective in preventing stasis, significantly reducing thromboembolic risk during AF ablation.15 Therefore, all transseptal sheaths should be flushed using heparinized saline at high-flow perfusion rates (>180 cc/hr) throughout the procedure. Timing of anticoagulation. The risk of thromboembolism is primarily related to placement of catheters and sheaths in the left atrium. Thrombus can also develop in the right atrium early after vascular access is obtained.16 This risk needs to be counterbalanced with the risk of bleeding and vascular complications, which are inherently increased with early and intensive anticoagulation.8 Transseptal puncture itself can lead to thrombus formation and provide a channel for already formed thrombi to travel to the left side of the heart. Bruce et al17 demonstrated that administration of heparin after vascular access and prior to the first transseptal puncture can significantly reduce the risk of left atrial thrombus formation from 9% to 0% (pPreventing Coagulum Formation Utility of intracardiac echocardiography. Linear phased-array imaging from the right atrium provides a unique and important vantage point of the left atrium and the catheters used for AF ablation. Observation of the electrode surface during ablation can be used to titrate energy delivery and decrease coagulum formation by monitoring microbubble formation.22 Scattered microbubbles reflect early tissue overheating, and dense microbubbles reflect impending impedance rise. Profuse, dense microbubble formation detected by ICE can be used as a surrogate to titrate power downward before impedance rise and coagulum formation.22 Also, ICE allows earlier detection of thrombus at the transseptal sheath site and appropriate suction and removal.9 After ICE detection of left atrial thrombus, the sheath and catheter on which thrombus is identified should be withdrawn into the right atrium as a single unit under careful ICE image monitoring, and removed from the body under careful hemodynamic and oxygen saturation monitoring.9 Most procedures can be continued after therapeutic ACT (>300 seconds) is confirmed. Managing Thromboembolic Complications It is important to realize that despite taking all the necessary precautions, thromboembolic complications may occur. It is essential that the team performing the ablation procedure be prepared to handle such a complication. Multidisciplinary Approach At our institution, the collaboration between the cardiologists and the neuroendovascular team, in evaluating all patients prior to undergoing AF ablation, has allowed us to optimize the time to treatment for patients having a peri-operative CVA. Studies have shown that 5-10% of the patients in the emergency department who present with an acute ischemic stroke meet criteria for interventional treatment.23 This limiting factor, in addition to organizing interventional staff to get access to the target intra- or extracranial lesion, is a challenge faced by neurointerventionalists across the country. From our experience at our institution, patients with peri-operative CVAs have had better revascularization/reperfusion outcomes and ultimately better neurological improvement in their NIH Stroke Scale (NIHSS) than those reported in the literature. This is mostly due to the fact that their time to treatment has been within an hour from diagnosis. Role of CT Perfusion When severity and duration of ischemia determine irreversible brain damage, imaging modalities used in acute stroke play an essential role. When radiographically assessing an acute ischemic stroke, the anatomical location of the disease process in addition to the physiologic changes at the neuronal level need to be addressed. The most widely used imaging modality in acute stroke is a noncontrast computed tomography (NCCT) of the brain.24 However, perfusion imaging, with either CT or MRI, in acute stroke allows one to not only assess anatomic location, but also cerebral blood flow, cerebral blood volume, and mean transit time.24 These parameters allow assessment of ischemic territory, cerebral vascular reserve, and reversible perfusion for guided therapy.24 Ultimately, advanced modalities in CT and MR imaging enable us to understand the underlying physiological changes associated with ischemic tissue.25,26 For this reason, at our institution we have employed the use of CT perfusion studies to assess the viability of brain function during an acute stroke. Minimizing Neurological Sequelae Modalities of recanalization in stroke intervention procedures. The choice of treatment modality for acute CVA is based on length of symptoms upon diagnosis of CVA, NIHSS at presentation, and CT perfusion data showing a relative percentage of salvageable ischemic tissue. Currently, recombinant tissue plasminogen activator (tPA) is the only FDA-approved thrombolytic agent to be used intravenously during acute stroke in the United States. Based on the National Institute of Neurological Disorders and Stroke (NINDS) trial,27 intravenous tPA is an acceptable treatment for acute ischemic stroke, if a patient presents within three hours of symptoms and has no exclusion criteria for treatment. Studies such as the PROACT II trial28 and the MERCI trial29,30 showed the efficacy of percutaneous procedures, such as intra-arterial administration of tPA up to six hours post insult, and mechanical embolectomy up to eight hours, respectively. Recanalization rates have been shown to be highest with mechanical embolectomy procedures and lowest with IV-tPA.31 Neurointerventionalists are able to determine patient selection for percutaneous intravenous thrombolysis versus intra-arterial tPA based on the location of the occluded artery, NIHSS and risk of intracranial hemorrhage. In the setting of AF ablation, the risk of bleeding complications is higher. Thus, this patient selection may benefit from the experience of neurointerventionalists and their use of intra-arterial tPA. Regardless of the modality used, the treatment goal remains safe optimization of revascularization. This review demonstrates that with careful patient preparation, procedural safety, and an orchestrated systematic and multidisciplinary approach, thromboembolic events during AF ablation may be prevented, and if not so, their neurological complications minimized.