**7. Non pharmacological stroke prevention/left atrial appendage occlusion**

AF increases the risk of stroke [70] 5 times, irrespective of Paroxysmal, Persistent or permanent nature, symptomatic or asymptomatic status, and thromboembolism occurring with AF is associated with a greater risk of recurrent stroke, more severe disability, and mortality. Role of anticoagulation in prevention of stroke and systemic embolism have been already established (**Figure 8**).

New target specific oral anticoagulation agents such as Dabigatran, Rivaroxaban, Apixaban, Edoxaban and Betrixaban are available. Some have shown superior efficacy over Coumadin while others proved non inferior to coumadin. Reversal agents

*Recent Advances in Catheter Ablation for Atrial Fibrillation and Non-pharmacological Stroke… DOI: http://dx.doi.org/10.5772/intechopen.106319*

**Figure 8.**

*Meta-analysis of landmark trials showing role of anticoagulation in patients with non valvular atrial fibrillation.*

are available. However, bleeding risk is a major concern with use of anticoagulation. Coumadin has narrow time in therapeutic range, multiple drug and food interaction and need for lifelong anticoagulation. People who cannot tolerate oral anticoagulation but are at increased risk of stroke requires non pharmacological stroke prevention. LAA is the primary source of thromboembolism in AF [71] and obliteration of LAA is associated with reduction of stroke. There are two different approaches available for LAA occlusion percutaneously. One is plugging the appendage with a device like WATCHMAN (Boston Scientific, Natick, MA) or Amplatzer cardiac plug (St. Jude Medical, Plymouth, MN). Other approach is to ligate the LAA with an epicardial approach using LARIAT device, (SentreHEART, Redwood City, CA) which requires transeptal and subxiphoid approach. With LARIAT device, Acute closure rate is high with low rate of leak however procedure success is limited due to bleeding.

Holmes et al. [72, 73] published the initial safety and feasibility data in 66 patients who underwent LAA occlusion with WATCHMAN. No strokes occurred during follow up despite discontinuation of anticoagulation, there were two patients with device embolization, two cardiac tamponade, one air embolism, two deaths not related to device. But in subsequent larger RCT and LAAO registries complication rates were much lower with increasing operator experience. PROTECT AF [72, 73] was a large multi center RCT that compared LAAO with WATCHMAN device to anticoagulation with coumadin. After 3.8 years of follow up, LAAO showed non inferiority and also superiority compared to coumadin in preventing combined outcome of stroke and embolism, cardiovascular death, all cause death. Similarly, PREVAIL [74] trial assessed the safety and efficacy of LAAO in patients with Non valvular Atrial Fibrillation (NVAF) compared to long term warfarin therapy and showed LAAO was noninferior to warfarin for ischemic stroke prevention or SE >7 days' post-procedure, and procedural safety has significantly improved. There are two large registries now CAP (Continued access to PROTECT-AF) and CAP 2 (continued access to PREVAIL) that provides long term safety and efficacy of LAAO with WATCHMAN for stroke prevention. Data from these two longest and largest registries showed LAAO with WATCHMAN device is safe and effective therapy for stroke prevention in NVAF. Though PROTECT-AF data showed non inferiority and superiority of LAAO over Warfarin, complication rates were higher. This was addressed in the subsequent PREVAIL trial. There was however, unexpectedly low rate of ischemic stroke in Warfarin cohort. This was believed to be due to relatively small patient population followed for relatively short duration. A subsequent metanalysis of these two trials by Reddy et al. [75] showed ischemic stroke/Systemic embolism rate was numerically higher with LAA Closure, but this difference did not reach statistical significance (HR: 1.71; *P* = 0.080). However, differences in hemorrhagic stroke, disabling/fatal stroke, cardiovascular/unexplained death, all-cause death, and post-procedure bleeding favored LAA closure. Procedure safety has significantly improved after next generation of WATCHMAN device called WATCHMAN FLX was designed. PINNACLE FLX [76] study enrolled around 400 patients who underwent WATCHMAN FLX implantation. Primary efficacy endpoint was effective LAA closure defined by ≤5 mm peridevice flow, secondary efficacy endpoint was ischemic stroke or systemic embolism at 24 months, primary safety end point was all cause death, ischemic stroke/systemic embolism, device or procedure related adverse event requiring surgery or major end-vascular intervention within 7 days following the procedure or hospital discharge whichever is later. Ischemic stroke occurred in 0.5%, no death, pericardial effusion or device embolization were reported, implant success rate was 99%. 96.2% of patients were able to discontinue NOAC at 45 day follow up. The next generation device WATCHMAN FLX has shown further safety and efficacy of the procedure overcoming the initial limitations of LAAO seen during PROTECT-AF trial. Currently there is another ongoing large RCT which has completed enrolling patients (OPTIONS clinical trial) that will compare safety and effectiveness of LAA closure to OAC therapy after AF ablation. CHAMPION-AF trial is ongoing and comparing WATCHMAN FLX as a first line stroke risk reduction therapy vs. NOAC for NVAF patients.

Surgical ligation of LAA is usually performed with internal sewing or stapling. Procedure is limited by bleeding, and residual stump which acts a source of thrombus. AtriClip is an external clip that is a newer technique for surgical LAA occlusion under direct visualization in patients undergoing open Cardiothoracic surgical procedure. 3.5 year follow up showed stable clips, no LAA thrombi, or neurological event, and no neck >1 cm.

Current AHA/ACC/HRS guidelines recommend as follows for non pharmacological stroke prevention (**Table 5**):


#### **Table 5.**

*AHA/ACC/HRS recommendation for non pharmacological stroke prevention.*

*Recent Advances in Catheter Ablation for Atrial Fibrillation and Non-pharmacological Stroke… DOI: http://dx.doi.org/10.5772/intechopen.106319*
