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Transcatheter Left Atrial Appendage Occlusion


Atrial fibrillation (AF) is the most common cardiac arrhythmia, and a major cause of stroke in the elderly. An estimated 12 to 16 million Americans will have a diagnosis of AF by 2050. The risk of stroke attributable to AF increases with age from 1.5% in the 50- to 59-year-old age group to 23.5% in the 80- to 89-year-old age group. The annual incidence of stroke in persons with untreated AF is 4.5%. Adjusted odds ratios for mortality in AF are 1.9 in women and 1.5 in men, and 1.71 overall. Women have strokes later in life, and they are more likely than men to have long-term disability and poor functional status poststroke.

Oral anticoagulation is recommended for prevention of stroke in AF (class I, level of evidence A) ; however, warfarin treatment requires frequent monitoring to maintain International Normalized Ratio (INR) between 2 and 3. In addition, a significant number of drugs commonly used by this population can potentiate warfarin action, including amiodarone, simvastatin, and omeprazole. Patients taking warfarin must also adhere to a consistent intake of vitamin K and avoid a number of dietary supplements that can affect coagulation. For example, fish oil potentiates coagulation, whereas ginseng can inhibit warfarin action. The direct thrombin inhibitor dabigatran does not require regular monitoring as does warfarin, but it has a similar risk of hemorrhage as warfarin at the higher dose of 150 mg two times daily. In addition, dabigatran and the direct Factor Xa inhibitor rivaroxaban are primarily excreted by the kidney; therefore dosages need to be adjusted in persons with chronic kidney disease. Alternative therapies are warranted, particularly in patients who are not candidates for anticoagulant therapy or who are at high risk of bleeding.

The left atrial appendage (LAA) is a prominent source of thrombi in AF, accounting for 90% of thrombi observed in patients undergoing cardioversion. In a small number of patients (3%), the LAA may be a source of focal atria tachycardia. As a result, surgical and transcatheter techniques have been explored to reduce the risk of stroke in persons with AF by occluding the LAA. The percentage of complete closure or occlusion is dependent on the modality employed and the selection of appropriate anatomy. The high variability of LAA anatomy does not allow for a “one device fits all” paradigm. Thus several devices are under clinical evaluation or preclinical assessment.

This chapter will review the risk of stroke in AF; discuss the role of the LAA in the etiology of AF-related stroke; and examine surgical, combined epicardial/endovascular, and endovascular LAA occlusion procedures in comparison with oral anticoagulant therapy. LAA occlusion in concert with electrophysiological AF ablation will also be briefly discussed. Real-world procedural considerations will be presented because there is a steep learning curve to negotiate to avoid adverse outcomes.

16.1

Risk of Ischemic Stroke in Atrial Fibrillation

History of stroke and/or transient ischemic attack (TIA) was the major predictor of stroke in patients with AF in one analysis (relative risk 2.5; 95% confidence interval [CI] 1.8 to 3.5), in addition to diabetes, hypertension, and increasing age. Several scoring systems have been proposed to assess risk of stroke in AF. The most widely used system in clinical practice is the C ongestive heart failure, H ypertension, A ge >75 years, D iabetes, and S troke score (CHADS 2 ), which combines several risk predictors into a 7-point scale ( Box 16–1 ). Patients with a CHADS 2 score of 1 or higher were more likely to have left atrium or LAA thrombus or sludge than those with a CHADS 2 score of 0 (3.9% vs. 0%, p < 0.01), and the prevalence of left atrial spontaneous echocardiographic contrast (SEC) increased with increasing CHADS 2 score (24% with score of 0; 83% with score of 4 to 6, p < 0.01). Obesity is also a risk factor for left atrial and LAA thrombus in AF. Patients with a body mass index (BMI) of 27.0 kg/m 2 or higher have a greater prevalence of nonparoxysmal AF (37% vs. 21%, p < .001) and CHADS 2 score of 1 or higher (68% vs. 49%, p < .001). A higher CHADS 2 score was also associated with increased risk of hemorrhagic stroke and death in the RE-LY trial, which compared dabigatran and warfarin in AF patients. The American College of Chest Physicians recommends no medical intervention for AF patients with a CHADS 2 score of 0.

BOX 16–1
Questionnaires for the Assessment of Stroke Risk in Atrial Fibrillation

CHADS 2

  • C ongestive heart failure: 1 point

  • H ypertension: 1 point

  • A ge >75 years: 1 point

  • D iabetes: 1 point

  • History of S troke or TIA: 2 points

CHA 2 DS 2 -VASc

  • C ongestive heart failure or left ventricular ejection fraction ≤40%: 1 point

  • H ypertension: 1 point

  • A ge ≥75 years: 2 points

  • D iabetes: 1 point

  • S troke/TIA/thromboembolism: 2 points

  • V ascular disease (myocardial infarction, peripheral arterial disease, or aortic plaque): 1 point

  • A ge 65 to 74 years: 1 point

  • S ex c ategory female: 1 point

TIA, Transient ischemic attack.

The CHADS 2 score has been modified to accommodate other risk factors for stroke in AF. Data from the Euro Heart Survey on Atrial Fibrillation were used to develop the 10-point (0 to 9) CHA 2 DS 2 -VASc score. Determinants of this score are listed in Box 16–1 . Low risk is categorized as a CHA 2 DS 2 -VASc score of 0, intermediate risk as a score of 1, and high risk as a score 2 or greater. Increased CHA 2 DS 2 -VASc score was associated with increased risk of thromboembolic events at 1 year, with 0 events per patient year in the low-risk group, 0.46 events per patient year in the intermediate-risk group, and 1.71 events per patient year in the high-risk group ( p < .0001). The European Society for Cardiology has recommended that the CHA 2 DS 2 -VASc scoring system be used if the CHADS 2 score is 0 to 1 or when a more detailed assessment of stroke risk is indicated. Patients with a CHA 2 DS 2 -VASc score of 0 had no differences in stroke risk in a population-based study, regardless of medication use. These scoring systems for stroke risk in AF are highly important because they guide selection of medical treatment or interventions.

In addition to comorbid conditions, endothelial dysfunction and platelet activation may play a role in stroke risk in AF. These characteristics are interrelated and may be associated with the obesity, hypertension, and diabetes seen in patients with metabolic syndrome. Plasma levels of von Willebrand factor (vWF) were increased in persons with AF relative to those in sinus rhythm, whereas the levels of the vWF protease, a disintegrin and metalloproteinase with a thrombospondin-type 1 motif member 13 (ADAMTS13), were decreased in AF. In this study, the vWF/ADAMTS13 ratio was negatively correlated with LAA flow velocity (r = −0.345, p = .002). Plasma soluble CD40 ligand, a marker of platelet activation, was correlated with extent of SEC (r = 0.377, p = .02); however, levels of soluble CD40 ligand were not associated with warfarin use. Soluble P-selectin and fibrin D-dimer levels, indicative of prolonged platelet activation and coagulability respectively, were increased in 17 patients with AF relative to 34 patients in a sinus rhythm control group. Endothelial dysfunction and platelet activation are thus further risk factors for stroke in AF, especially because of their potential for interaction with a prosthetic device in the LAA.

16.2

The Left Atrial Appendage

Anatomic Considerations

The LAA is derived from the embryonic left atrium. It is a blind pouch lying on the anterior surface of the heart. Normal anatomic variation in LAA morphology is shown in Figure 16–1 . An autopsy study showed that 54% of LAAs examined (n = 500) have two lobes, with 23%, 20%, and 3% having three, one, and four lobes, respectively. In addition to multiple lobes, the pectinate muscles create a trabecular structure that may promote thrombus formation. In another autopsy study, 220 casts of the LAA from patients with known medical histories were examined for the course of the principal axis and the number of lobes and finer structures. Ninety-two (42%) casts had an “extremely bent and extremely spiral” course, whereas only 16 casts (7%) had a straight course. The number of lobes and finer structures were significantly correlated with LAA volume and ostium diameter. Hearts from patients who had AF had larger LAA volumes and ostial diameters (both p < .01) and a lower number of lobes ( p < .05) than hearts from patients who were in sinus rhythm before death.

Figure 16–1, Normal anatomic variation of LAA morphology.

The ostium of the LAA is elliptical in shape, which may have consequences for the design of occlusion devices. The diameter and area of the LAA ostium increase progressively with the severity of AF. The pectinate muscles within the LAA may be misread as thrombi on two-dimensional (2D) transesophageal echocardiography (TEE), and they may hinder the success of LAA ligation or occlusion. Use of real-time three-dimensional (3D) TEE can help distinguish between pectinate muscles and thrombi ; however, a poor 2D image often predicts an inconclusive real-time 3D TEE result. In addition, 2D TEE underestimates the size of the LAA ostium relative to real-time 3D TEE, which can impact the choice of device size.

Diagnostic Considerations

TEE and computed tomography angiography (CTA) are effective modalities to assess left atrial and LAA anatomic and functional features that may increase thrombogenesis in AF. SEC on TEE, which may reflect microemboli, is increased in AF. The highest amount of SEC is negatively correlated with LAA velocity. Patients with AF and thrombus have lower LAA velocity than patients without thrombus (no thrombus, 32 ± 21 cm/sec; with thrombus, 9 ± 6 cm/sec; p < .001. AF patients with a history of stroke also have larger LAA depth and neck dimensions. Increased left atrial volume index (odds ratio [OR] 1.02; p = .018) and lower left ventricular ejection fraction (OR 1.02; p = .05) on TEE measurement can predict LAA thrombus formation. Transthoracic echocardiography (TTE) with measurement of LAA wall velocity (LAWV) was used to assess risk of recurrent stroke in AF patients. In this study, patients with TTE-LAWV less than 8.7 cm/sec were more likely to experience recurrent cerebrovascular events (hazard ratio 5.05; 95% CI 2.25 to 11.36). The combination of low LAA flow velocity, endothelial dysfunction, platelet activation, and procoagulant state may thus set up an ideal environment for thrombus formation in the LAA.

CTA has become an important tool to assess LAA morphology. The image quality may be compromised at times by poor timing of contrast appearance in the LAA. CTA gives an excellent 3D understanding of the orientation of the appendage relative to the pulmonary artery, the number of lobes, and the shape of the appendage as well as the orientation of the appendage—posterior, lateral, or anterior. CTA has become essential in the deployment of the SentreHEART LARIAT device (SentreHEART, Palo Alto, Calif.). Wang et al have categorized LAA morphology into four categories based on CTA analysis: (1) wind sock (one long, dominant lobe; 46.7% of patients studied); (2) cauliflower (short length with complex internal structure; 29.1%); (3) chicken wing (one prominent bend in LAA; 18.3%); and (4) cactus (dominant central lobe with secondary lobes; 5.9%). The ostium shape and LAA location relative to the left superior pulmonary vein can also be categorized by CTA. Patients who have AF with the chicken wing LAA morphology are less likely to have a history of stroke or TIA than the other LAA morphologies (OR 0.21, 95% CI 0.05 to 0.91; p = 0.04).

Indications for Left Atrial Appendage Occlusion and Patient Selection

The primary drug used for medical management of stroke risk in AF has been warfarin. As discussed, for many patients warfarin is either not tolerated or interferes with other medications or lifestyle. Major gastrointestinal bleeding and hemorrhagic stroke are principal adverse events with warfarin or the newer oral anticoagulants. Two bleeding risk scales have been validated for patients on oral anticoagulant therapy, with the acronyms HEMORR 2 HAGES and HAS-BLED. The constituents of these scales are listed in Box 16–2 . The HAS-BLED scale outperformed the HEMORR 2 HAGES scale in the SPORTIF trial of the direct thrombin inhibitor ximelagatran and warfarin in showing a stepwise increase in rates of major bleeding with higher scores. Patients with a high risk of bleeding are natural choices for LAA occlusion, with the caveat that these devices are noninferior to warfarin regarding stroke prevention.

BOX 16–2
Questionnaires for the Assessment of Bleeding Risk in Patients with Atrial Fibrillation on Oral Anticoagulant Therapy

HEMORR 2 HAGES

Unless otherwise indicated, each item in the mnemonic receives 1 point.

  • H epatic or renal disease

  • E thanol abuse

  • M alignancy

  • O lder (age >75 years)

  • R educed platelet count or function

  • R ebleeding risk: 2 points

  • H ypertension (uncontrolled)

  • A nemia

  • G enetic factors associated with increased bleeding propensity

  • E xcessive fall risk

  • S troke

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