Left atrial appendage morphology and the risk of stroke
Article Category: Review
Online veröffentlicht: 30. Apr. 2022
Seitenbereich: 46 - 51
DOI: https://doi.org/10.47803/rjc.2021.31.1.46
Schlüsselwörter
© 2021 Emese Zsarnóczay et al., published by Sciendo
This work is licensed under the Creative Commons Attribution 4.0 International License.
Atrial fibrillation (AF) is the most common cardiac arrhythmia that can increase the risk of stroke, heart failure and hospitalization1,2,3. Around 0.4% to 1% of the general adult population has AF and this rate increases with age, especially over the age of 80, where the prevalence of AF is more than 9%4. The number of affected individuals is expected to double or even triple within the next twenty to thirty years4. In the developed countries the prevalence is higher than in the developing nations5. Moreover, the prevalence is lower in women than in men5. The most common risk factors of AF are age, hypertension, valvular and ischemic heart disease, thyroid dysfunction, obesity, diabetes, chronic obstructive pulmonary disease, chronic kidney disease and smoking6. Catheter ablation is an effective and safe procedure to treat AF. However, in many cases recurrence occurs. Approximately 20% to 45% of the patients experience a recurrence of AF within 12 months after the catheter ablation7,8.
AF can increase the risk of stroke about five times and since the elder population is constantly growing, AF will have an ascendant effect on stroke morbidity and mortality9. Moreover, stroke caused by cardioembolic events, mostly by AF is associated with a higher in-hospital mortality and stroke severity than non-AF related stroke10,11. In the setting of AF, the left atrial appendage (LAA) is the most common source of emboli12. Additionally, according to Di Biase, LAA morphology is related to the risk of stroke13. Moreover, the size of the LAA orifice area and the LAA flow velocity also influence the risk of stroke formation14. Therefore, it is absolutely necessary to understand the background of the anatomy and function of the LAA in order to understand the pathogenesis of AF-related stroke.
The LAA used to be considered as an insignificant part of the heart. It is now recognized to be a structure with important physiological, arrhythmogenic and thrombogenic components. The risk of stroke in patients with non-valvular AF is approximately five-fold higher than in patients with sinus rhythm9. LAA thrombus is present in 15% of the patients in AF15. In patients with non-valvular AF, 90% of thrombi have a predilection to form within the LAA because of reduced contractility and stasis, in contrast in valvular AF, where this rate is about 56%12. It has been proposed that there is a connection between the LAA morphology and the risk of thrombus formation in the LAA13. In the presence of LAA dysfunction, there is an increased risk of thromboembolic events and LAA dysfunction has been shown to be a strong predictor of thrombus formation16,17. As an outcome of AF, decreased LAA contraction and flow velocity can be observed with TEE which are among the strongest predictors of stroke, but there is limited use of these parameters to predict the risk of ischemic stroke16,17.
The LAA is often a finger-like, long, narrow, tubular, hooked structure originated from the main body of the left atrium (LA)18. It is formed at the 4th week of gestation as the remnant of the original embryonic LA. Its size, shape, and relationship with nearby cardiac and extracardiac structures are extremely complex and variable. In most hearts, the LAA lies anteriorly in the atrioventricular sulcus in close relation with the left phrenic nerve, the left superior pulmonary vein and the left circumflex artery. Externally, the LAA is a tubular structure with or without obvious bend and its tip points to the pulmonary artery, the right ventricular outflow tract, and the free wall of the left ventricle18. Internally, its orifice opens to the LA main chamber19. The shape of the orifice can be classified into several types. The most frequent type is oval shape, besides that it can be foot-like, triangular, water drop-like or round20,21. In most appendages, there is a well-defined orifice that continues in the neck region, but there is a wide anatomical variability in the location of the LAA ostia in relation to the venous orifices22. Lee et al proposed that the enlargement of the LAA orifice area (>3.5 cm2) is an independent risk factor of stroke in patients with non-valvular AF, even after adjustment for other risk factors due to the fact that larger LAA promotes slow blood flow, stasis and eventually thrombus formation14. The inner surface of the LAA has a single layer of endothelium and reveals complex indentations made by pectinate muscles23. The remainder of the wall in between them is paper-thin. At the borders between the inferior and the superior faces, the muscle bundles arrange like feather-type-palm-leaf24. In patients with AF, structural remodeling of the LAA with dilation of the chamber and a reduction in the number of pectinate muscles can be seen compared to patients in sinus rhythm21. The thicker muscle bundles may give the appearance of an LAA thrombus or intra-arterial mass25.
According to Veinot et al, the number of LAA lobes ranged from 1 to 4, but the most frequent occurrence is the two-lobe type25. An increased number of lobes are associated with the presence of thrombus because of the blood stasis26. In the first year after catheter ablation, in patients who maintained sinus rhythm, a clearly visible decrease in LA and LAA volumes can be seen, but the number of lobes remains the same, therefore the number of LAA lobes is not influenced by LAA remodeling during AF26.
Generally, transesophageal echocardiography (TEE) should be used to get a detailed assessment of the LAA and characterize LAA morphology27. With multi-detector computed tomography (MDCT) and magnetic resonance imaging (MRI), high-quality images of the LAA can be obtained. In a recent study, Di Base et al categorized LAA morphology into 4 types13:
The categories of the LAA morphology according to DiBiase et al can be seen in Figure 1.
Figure 1
Morphologies of the LAA. The categorization of LAA morphologies according to DiBiease et al.
These results could have a relevant impact on the anticoagulation management of patients with a low-intermediate risk for stroke/TIA.
Nevertheless, this is not the only categorization of LAA morphologies. Rosendael et al also categorized LAA morphologies into four types with MDCT, but with another classification when instead of „cactus”, they used „swan” if LAA presented a second sharp curve folding the structure back. Their study demonstrated that MDCT can also provide an exact assessment of the LAA geometry. In their analysis, windsock was the most prevalent morphology of the LAA28.
The categorization of LAA morphologies according to Rosendael et al. E: cactus: the primary structure is one dominant central lobe with secondary lobes inferiorly and superiorly28.
Few cases have been reported, that described the congenital absence of the LAA. This extremely rare cardiac anomaly is usually encountered as an incidental finding during routine imaging for other purposes. Due to the very few cases, the physiological consequences of this entity are unknown. Hypothetically, the risk of stroke in patients without LAA should be lower after all the anatomical source of thrombi is absent29. The identification of the absence of LAA can be achieved with the use of TEE, MDCT or cardiac MRI30.
LAA function has reservoir, contractile, electric and endocrine components, that can provide essential information about the risk of clot formation, embolic events and success of cardioversion27.
LAA volume is normally about 30% of the entire LA volume, thus not just the LA main chamber has a reservoir function during LA pressure, volume overload or left ventricular systole, but the LAA too19. Furthermore, LAA is 2.6 times more distensible than the LA main chamber31. During early diastole, LAA acts like a conduit for blood passing through to the left ventricle from the left pulmonary veins. In late diastole, LAA importantly contributes role in increasing the left ventricular filling by functioning as an active contractile chamber32.
LAA contractile function can be characterized by the LAA flow velocity which can be measured with pulse-wave Doppler on TEE (Figure 2).
Figure 2
The measurement of LAA flow velocity with pulse wave Doppler. This image represents a decreased LAA flow velocity (27.2 cm/s) in a patient with AF. Courtesy Heart and Vascular Center of Semmelweis University, Budapest, Hungary.
During sinus rhythm, a characteristic quadriphasic flow pattern can be seen33:
Early diastolic emptying velocity: a first passive contraction during the early phase of the ventricular diastole. This phase includes the opening of the mitral valve followed by a fall in the LAA pressure and the distension of the left ventricle causing external compression of the LAA. The normal early diastolic emptying velocity ranges between 20–40 cm/s34,35,36. Late diastolic emptying velocity: the late diastolic emptying velocity is caused by an active contraction of the LAA during atrial systole. It has been reported to significantly increase thromboembolic risk 14. The normal late diastolic emptying velocity ranges between 50–60 cm/s34,35,36. Lee et al proposed that a decreased LAA flow velocity (<37 cm/s) and enlarged LAA orifice area (>3.5 cm2) are associated with a greater risk of stroke14. Therefore, the evaluation of the LAA contraction flow could be an important part in the assessment of stroke risk. LAA filling: this is a retrograde and negative wave that is a consequence of the LAA relaxation. The normal LAA filling velocity ranges between 40–50 cm/s34,35,36. Systolic reflection waves: low inflow and outflow waves during ventricular systole34,35,36.
During tachycardia, LAA emptying velocity shows an increased flow. Early and late diastolic emptying velocities decrease with age and women tend to have lower emptying velocities than men37.
During AF, variable amplitude and irregularity of emptying and filling can be seen with lower velocities16,17. It can be characterized by a saw-tooth emptying pattern or no visible active emptying pattern. On TEE, turbid LAA emptying peak flow velocity, LAA fractional area change and decreased LAA velocities can be observed. The listed abnormalities of the LAA function, especially when no visibly active emptying can be seen, are associated with increased risk of thrombus formation due to the blood stasis in the LA and LAA16,17.
The LAA functions as an endocrine organ too. It contains stretch sensitive receptors that respond to changes in atrial pressure by natriuretic peptide secretion. LAA produces approximately 30% of all cardiac atrial natriuretic peptides (ANP)38. An animal study proposed that LAA has a significant role in normal cardiac function. When increased pressure in the LAA occurs, diuresis, natriuresis and increased heart rate can be observed39. Thus, LAA plays an important role in the maintenance of normal fluid hemostasis.
As mentioned before, LAA is the most prevalent source of thrombi in non-valvular AF. The pathogenesis of thrombus formation in AF is multifactorial. The three factors that are thought to contribute to thrombosis were described by Virchow: (1) endothelial or endocardial damage or dysfunction and related structural changes; (2) hemodynamic changes, such as blood stasis or turbulence; (3) increased coagulability40. In AF, there is a prothrombotic or hypercoagulable state caused by abnormal changes in blood flow, atrial wall, and blood components. Abnormal changes in coagulation and hemostasis such as increased turnover of fibrin or abnormal concentrations of prothrombotic factors have been described in AF41,42. Increased amount of D-dimer found to be a predictor of subsequent thromboembolic events in patients with AF. Indeed, D-dimer can be useful in identifying low-risk patients, whereby a low amount of D-dimer predicts a low risk of stroke43,44. An increased rate of von Willebrand factor (vWF) is a mark of endothelial damage and dysfunction45. Tissue factor and vWF are increased in patients with AF who have a history of cardiogenic thromboembolism46. Changes in the atrial tissue, such as inflammation and fibrosis can also lead to a prothrombotic state in AF. There is a clear influence of increased levels of inflammatory markers in the pathogenesis of AF, thus inflammation can also be the consequence of the prothrombotic state during AF47. CTA can estimate the presence of LAA thrombi and by performing an affirmative delayed phase the determination of pseudothrombus and thrombus can be achieved. CTA images of pseudothrombus and thrombus are represented in Figure 3.
Figure 3
Differentiation between pseudothrombus (A-B) versus genuine thrombus (C-D).
The LAA is a frequent site of thrombus formation in AF, since this common cardiac arrhythmia cause a prothrombotic or hypercoagulable state by reducing the contractility of the appendage wall, causing abnormal blood stasis and dilation of the LAA chamber40. These listed complications of AF promote thrombus formation, thus systemic embolism can occur. The size and shape of the LAA and its orifice is extremely complex and variable. Previous studies have conflicting results regarding the association between LAA morphologies and the risk of stroke/TIA. Di Biase et al. categorize LAA shapes into four types: windsock, cauliflower, chicken wing and cactus13. They suggested that chicken wing morphology is protective against ischemic stroke, while non-chicken wing shapes might be associated with an increased risk of stroke. However, other studies demonstrated that patients with a history of stroke are more likely to have cauliflower morphology48,49. This can be explained by the multilobular aspect of the cauliflower shape.
The shape and size of the LAA orifice is highly variable. In a recent study, Lee et al have reported that the enlargement of the LAA orifice area and decreased LAA flow velocity are associated with an increased risk of stroke14.