**1. Atrial fibrillation, thromboembolic risk, and prevention**

Atrial fibrillation (AF) is the most common cardiac arrhythmia with a significant burden of disease. The prevalence is age-dependent and increases with the age [1, 2]. While it is uncommon in patients younger than 40, about 10% of the 80-year olds are affected [1, 2]. AF nowadays is prevalent in about 3% of the western population, but it is estimated that the incidence will rise over the next decades linked to the increased life expectancy [1, 2]. As in the case of

© 2017 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

other cardiovascular diseases, males are more frequently affected than females [1, 2]. Though AF rather rarely causes acute fatal complications at the time of onset, medium-term prognostic complications such as left ventricular dysfunction, cognitive decline, and utmost important cerebral ischemic stroke change AF toward a harmful cardiac disease [3]. AF accounts for 20–30% of all strokes and many patients are diagnosed with AF for the first time after they have been affected by a stroke (so-called "silent" AF) [3]. Therefore, the prognosis of AF patients is substantially determined by the risk for thromboembolic events.

#### **1.1. Thrombogenesis during atrial fibrillation**

Due to the electrical storm occurring on the atrial myocardium and the irregular ventricular excitation during AF episodes, the atrial mechanical function is impaired. Consecutively, the atrial cavities are distended, the intraatrial pressure is increased and the blood flow is reduced. These mechanisms connected to the Virchow's triad are only part of a multifactorial network leading to thrombogenesis also including the expression of prothrombotic factors [4–6]. The changes are especially prominent in the blind-ended left atrial appendage (LAA) located in front of the anterior wall of the left atrium (LA) with its ostium between the left upper pulmonary vein and the mitral valve annulus [6, 7]. The walls of the LAA are highly trabeculated which renders them thrombogenic [7]. Four general LAA shapes are described in the literature, i.e., the chicken wing, cactus, windsock, and cauliflower shaped LAA (**Figure 1A**), whereby the data of the proportional distribution substantially vary within the literature [8]. Certain LAA morphologies were identified as an independent risk factor for thromboembolic events [9, 10]. Altogether, in patients with nonrheumatic AF more than 90% of all atrial thrombi occur in the left atrial appendage (**Figure 1B**) [11].

**Figure 1.** (A) The four different left atrial appendage morphologies with (a) the chicken wing, (b) the cactus, (c) the windsock and (d) the cauliflower type. (B) Echocardiographic visualization of a left atrial appendage thrombus (\*).

#### **1.2. Pros and cons of an oral anticoagulation therapy for thromboembolic prophylaxis**

Because of these interrelationships, the risk stratification for thromboembolic events and a risk-based indication for thromboembolic prophylaxis are important pillars in the AF patient's therapy. For this purpose, the CHA<sup>2</sup> DS2 -VASc score is recommended (IA) [3]. It incorporates all the relevant risk factors for stroke in AF patients: congestive heart failure (+1), hypertension (+1), age (65–74 +1 and ≥ 75 years +2, respectively), diabetes mellitus (+1), prior stroke, transient ischemic attack (TIA) or thromboembolism (+2), vascular disease (+1), and female gender (+1). According to the current European guideline recommendations, a thromboembolic prophylaxis by oral anticoagulants is recommended for all males with a CHA<sup>2</sup> DS2 -VASc score ≥ 2 and for all females with a CHA<sup>2</sup> DS2 -VASc score ≥ 3 (IA). Furthermore, this prophylaxis should be considered in males with a CHA<sup>2</sup> DS2 -VASc score = 1 and in females with a CHA<sup>2</sup> DS2 -VASc score = 2 according to the individual characteristics and the patient's preferences (IIaB) [3]. The evaluation of biomarkers, e.g., high-sensitive troponins and natriuretic peptides, can be helpful in this context (IIbB) [3]. For several decades, vitamin K antagonists have served as the gold standard for thromboembolic prophylaxis in AF patients [12], but their clinical use is limited by an increased and substantial bleeding risk which especially harms vulnerable patients [13, 14]. The vulnerability to bleedings can be assessed by the HAS-BLED score including arterial hypertension (+1), abnormal renal (+1) or liver (+1) function, prior stroke (+1), bleeding history or predisposition (+1), labile international normalized ratio (INR) (+1), age > 65 (+1) and drugs (+1) or alcohol (+1) concomitantly [15]. While dual antiplatelet agents failed to be an effective and safe alternative to vitamin K antagonists [16], recently, non-vitamin K antagonist oral anticoagulants (NOACs), i.e., dabigatran, rivaroxaban, apixaban, and edoxaban, were gaining ground [17–20]. In the current European guidelines, these substances are preferentially recommended for all eligible nonvalvular AF patients (IA) [3]. However, stoked by a higher incidence of gastrointestinal bleedings in comparison to vitamin K antagonists and other side effects [21], patients' adherence to NOAC therapy was also shown to be limited [22].

#### **1.3. Alternatives to an oral anticoagulation therapy**

other cardiovascular diseases, males are more frequently affected than females [1, 2]. Though AF rather rarely causes acute fatal complications at the time of onset, medium-term prognostic complications such as left ventricular dysfunction, cognitive decline, and utmost important cerebral ischemic stroke change AF toward a harmful cardiac disease [3]. AF accounts for 20–30% of all strokes and many patients are diagnosed with AF for the first time after they have been affected by a stroke (so-called "silent" AF) [3]. Therefore, the prognosis of AF

Due to the electrical storm occurring on the atrial myocardium and the irregular ventricular excitation during AF episodes, the atrial mechanical function is impaired. Consecutively, the atrial cavities are distended, the intraatrial pressure is increased and the blood flow is reduced. These mechanisms connected to the Virchow's triad are only part of a multifactorial network leading to thrombogenesis also including the expression of prothrombotic factors [4–6]. The changes are especially prominent in the blind-ended left atrial appendage (LAA) located in front of the anterior wall of the left atrium (LA) with its ostium between the left upper pulmonary vein and the mitral valve annulus [6, 7]. The walls of the LAA are highly trabeculated which renders them thrombogenic [7]. Four general LAA shapes are described in the literature, i.e., the chicken wing, cactus, windsock, and cauliflower shaped LAA (**Figure 1A**), whereby the data of the proportional distribution substantially vary within the literature [8]. Certain LAA morphologies were identified as an independent risk factor for thromboembolic events [9, 10]. Altogether, in patients with nonrheumatic AF more than 90% of all atrial thrombi occur in the

**Figure 1.** (A) The four different left atrial appendage morphologies with (a) the chicken wing, (b) the cactus, (c) the windsock and (d) the cauliflower type. (B) Echocardiographic visualization of a left atrial appendage thrombus (\*).

patients is substantially determined by the risk for thromboembolic events.

**1.1. Thrombogenesis during atrial fibrillation**

236 Interventional Cardiology

left atrial appendage (**Figure 1B**) [11].

By the implication of the LAA as a primary source of thrombi for thromboembolic events in nonvalvular AF, locoregional techniques to avoid thromboembolism out of the LAA were developed. Besides the surgical resection of the LAA during open heart surgery and the epicardial LARIAT® Suture Delivery Device (SentreHEART, Redwood City, CA, USA) with limited evidence for efficacy and safety [23, 24], six CE-marked devices for transvenous catheter-based LAA closure are currently available: the WATCHMAN™ left atrial appendage closure device (Boston Scientific, Natick, MA, USA), the AMPLATZER™ Cardiac Plug (ACP) and its next generation the AMPLATZER™ Amulet™ left atrial appendage occluder (both St. Jude Medical, Minneapolis, MN, USA), the WaveCrest™ LAA Occlusion System (Coherex Medical, Salt Lake City, UT, USA), the Occlutech® LAA occluder (Occlutech, Jena, Germany) and the LAmbre™ LAA Closure System (Lifetech Science, Shenzhen, China), respectively. However, only the WATCHMAN™ device was compared to oral anticoagulation (OAC), i.e., warfarin, in a prospective randomized controlled trial (RCT) in patients eligible for OAC [25]. Long-term data revealed a noninferiority and superiority compared to OAC for preventing the combined outcome of stroke, systemic embolism, and cardiovascular death as well as superiority for cardiovascular and all-cause mortality [26]. Moreover, the PREVAIL trial stated adequate safety of the WATCHMAN™ procedure [27]. The efficacy and safety of other devices were exclusively evaluated by observational studies.
