An 84 year-old woman with hypertension, chronic obstructive pulmonary disease, and chronic renal insufficiency (estimated glomerular filtration, rate 38 mL/min/1.73 m²) also has paroxysmal atrial fibrillation (AF) with a CHADS₂ score of 4 and CHA₂DS₂-VASc score of 6. She suffered a stroke a year ago and was treated with tissue plasminogen activator. This was complicated by hemorrhagic transformation, resulting in expressive dysphagia. Given her history of intracranial hemorrhage, she was deemed to be a poor candidate for long-term oral anticoagulation (OAC) and was thus referred for endovascular left atrial appendage (LAA) closure. Under general anesthesia and transesophageal echocardiography (TEE) guidance, a 28-mm Amplatzer Cardiac Plug (ACP; St. Jude Medical, St. Paul, MN) was successfully deployed. The patient was discharged the following day with no complication and was commenced on dual antiplatelet therapy (aspirin 81 mg/d and clopidogrel 75 mg/d) for 3 months, followed by aspirin indefinitely.

AF is the most common cardiac arrhythmia. It affects 1% of the general population, 6% of people over the age of 65 years, and 9% of people over the age of 80 years.^1,2 With the aging population, the prevalence of AF is set to increase, and its impact on the health system is also projected to increase substantially.^3,4

AF is associated with considerable morbidity and mortality. One of the major feared morbidities associated with AF is stroke. AF is an independent risk factor for stroke, occurring in up to 19% of stroke patients over the age of 70 years.⁵ After adjusting for other risk factors, AF is associated with a 4- to 5-fold increased risk of ischemic stroke.⁵ Paroxysmal AF carries a similar risk of stroke as patients with permanent AF.⁶ Cardioembolic strokes associated with AF are generally more severe than other types of ischemic stroke and have been associated with higher 30-day and 1-year mortality.^7,8 The CHADS₂ and the CHA₂DS₂-VASc were developed as risk models to estimate risk of stroke (Tables 30-1 and 30-2) and are widely adopted in clinical practice. It is estimated that there are 800,000 strokes each year in the United States, with 1.5% of those attributed to AF in those under age 59 and 23% attributed to AF in those greater than age 80.⁵ Stroke is the number 1 cause of major morbidity in the United States and estimated to cost the healthcare system approximately $30 billion each year.

Paroxysmal AF is defined as an episode of AF that terminates spontaneously or with intervention within 7 days.⁹ Permanent or persistent are clinical labels for AF that lasts more than 7 days. It is likely that the true prevalence of AF is underestimated because it can be difficult to detect paroxysmal AF. Patients with AF may experience palpitations, chest pain, anxiety, and sweating, although it can also be clinically silent.

AF management may be divided into a few categories: rate ­control, rhythm control, and stroke prevention. In this ­chapter, we will be focusing on stroke prevention, specifically with ­percutaneous LAA closure.

OAC remains the mainstay therapy for reducing the risk of stroke in patients suffering from AF. Warfarin has been available for decades and continues to be the main OAC used for AF. It reduces the relative risk of stroke by approximately 64%. The risk of major bleeding is the most feared side effect, with an incidence of 0.5% to 1% per year; the incidence can be as high as 13% in patients older than age 80 years.¹⁰ Other barriers associated with warfarin that make it less patient friendly includes frequent laboratory monitoring, interactions with food and other medications, and its narrow therapeutic range. In fact, an important obstacle is that patients are often not in the therapeutic range. The ORBIT-AF registry revealed that only 59% of the overall measured international normalized ratio (INR) values were between 2.0 and 3.0, the time in therapeutic range (TTR).¹¹ The overall median TTR was 68% (interquartile range [IQR], 53%-79%), with the median time below TTR being 17% (IQR, 8%-29%). Even more concerning, patients with a higher risk for bleeding (by the Anticoagulation and Risk Factors in Atrial Fibrillation [ATRIA] score) or stroke (CHA₂DS₂-VASc score) had significantly lower TTR (P <.0001).

Other alternatives to warfarin have been widely explored. ­Aspirin by itself has been extensively studied, and against placebo, there is 22% relative risk (RR) reduction.^12,13 However, compared to warfarin, there was a 36% higher rate of stroke.^12–14 Even when clopidogrel was added to the aspirin regimen, it fared worse than warfarin, with a combined vascular event rate of 3.9% (vs. 5.6%; RR, 0.69; 95% confidence interval [CI], 0.57-0.85) and stroke rate of 2.4% (vs. 1.4% per years; RR, 1.72; 95% CI, 1.24-2.37; P = .001). There was no significant difference in major bleeding (2.4% vs. 2.2%).^15,16 Newer OACs have been introduced and increasingly used. Dabigatran, a direct oral thrombin inhibitor, was studied in the RE-LY trial (in 2 different doses) and showed that the 150-mg twice-a-day (BID) dosing was superior to warfarin, with a 35% lower rate of stroke and systemic embolization and similar bleeding rates, whereas 110-mg BID dosing was noninferior to warfarin in stroke and systemic embolization but had a 20% lower rate of major hemorrhage.¹⁷ Apixaban, a direct Xa inhibitor (ARISTOTLE trial), showed superiority to warfarin, with a 21% reduction in stroke and systemic embolization, 31% reduction in the risk of major hemorrhage, and 11% reduction in death.¹⁸ Furthermore, rivaroxaban, another factor Xa inhibitor, was noninferior to warfarin in the reduction of stroke and systemic embolization (21% reduction; ROCKET-AF study), with no difference in major bleeding.¹⁹

However, OAC is not tolerated in approximately 40% of patients with AF,²⁰ and thus, percutaneous catheter-based closure devices for LAA closure have become an attractive alternative to OAC for the aging population with high bleeding risk with OAC. LAA closure is the main interventional procedure pursued for stroke ­prevention with AF since TEE studies had shown that ­approximately 91% of thrombi in the setting of nonvalvular AF were located in the LAA.²¹

Multiple devices have been developed for percutaneous transcatheter LAA closure, and these will be described in more detail in the following sections.

PLAATO is the first LAA occluder system developed and consists of a self-expanding nitinol cage covered with polytetrafluoroethylene membrane. The membrane itself is laminated directly to the outer frame, facilitating direct contact with the LAA wall. This device was rigid and required significant oversizing (20%-50%) for stability. It was initially evaluated in an observational trial in North America of 64 patients with contraindications to warfarin. The trial paved the way to further trials as it revealed excellent safety and a high rate of anatomic occlusion at the time of the procedure (residual flow ≤3 mm in 98% of cases).^22,23

The European PLAATO experience was reported in 2010, in which 90% of implanted devices had successful occlusion (total of 180 patients with contraindication to warfarin).²⁴ In this cohort, there was a reported stroke risk of 2.3% as compared to the predicted 6.6% per year at a mean follow-up of 9.6 months. This procedure was found to be safe, with 1.1% mortality and 3.3% pericardial effusion that required surgical intervention. However, the device is no longer in production due to commercial reasons.

WATCHMAN

The WATCHMAN (Boston Scientific, Marlborough, MA) was the next dedicated LAA closure device to be developed (Figure 30-1). This device was initially owned by Atritech Inc. and later acquired by Boston Scientific. The device itself consists of a self-expanding nitinol frame with fixation barbs. There is a permeable polyester fabric covering the atrial surface and extending approximately half of the device’s length. This fabric is permeable to blood until endothelialization (~45 days after implantation) and therefore ideally requires the patient to remain on thromboembolic prophylaxis until that time. A TEE is required to confirm no substantial remaining flow around the device prior to ceasing OAC; following that, dual antiplatelet therapy with aspirin and clopidogrel is usually continued for a ­further 4.5 months.

WATCHMAN is currently the only device evaluated in randomized controlled trials. Briefly, there were 2 randomized trials, the PROTECT-AF and PREVAIL trials.^25,26 PROTECT-AF was a randomized noninferiority comparison trial of patients with nonvalvular AF and a CHADS₂ score ≥1. The trial randomized 707 patients in a 2:1 ratio to WATCHMAN or warfarin. WATCHMAN was found to be noninferior to warfarin for the primary end point of cardiovascular death, stroke, or systemic embolization, with the noninferiority margin set at 2. This finding was sustained throughout the follow-up at 1065, 1588, and 2621 patient-years. Of specific note, at 2621 patient-years (ie, 3.8 years), the WATCHMAN device was found to be superior to warfarin. With regard to complication rates, there was a 1.7% risk of cardiac perforation and a 3% risk of pericardial effusion and tamponade related to the procedure. This was likely due to a learning curve for the procedure, supported by a lower complication rate in subsequent registries carried out later.^27,28 The rate of periprocedural complications was 3.7% in the later registries compared to 7.7% in the initial randomized trial.