view of the left atrium. Solid Arrow: septal pouch; (c) Axial view of the left atrium. Solid Arrow: left atrial diverticulum with broad based ostium and smooth contour.

tween LAAA and a clinical event. The multiple logistic regression analysis was adjusted for age as a continuous variable and diabetes, hypertension, dyslipidemia and sex as dichotomous variables. SAS version 9.3 (SAS In- stitute, Cary, NC) was used to conduct the analysis.

3. Results

Of the 242 patients retrospectively reviewed (144 men and 98 women), mean age was 56 SD 12 years. The most common indication for CTCA was chest pain (70%). Hypertension was present in 133 patients (55%). Forty patients (17%) had a history of diabetes. Ninety patients (37%) had a history of dyslipidemia. Detailed demographic information, medical history and CTCA indications for the study cohort are detailed in Table 1.

Among the patients, 68 (28%) demonstrated a total of 76 accessory left atrial appendages. Fifty-three patients (22%) had a combined number of 59 left atrial diverticula. Ninety-three patients (38%) had septal pouches present. The mean age was 56 SD 12 years in patients with accessory left atrial appendages, 60 SD 11 years in patients with diverticula, and 58 SD 11 in patients with septal pouches. Those patients with diverticula and septal pouches were significantly older than those without these abnormalities (p = 0.01 and p = 0.02, respectively). Patients with septal pouches were more likely to have a documented history of diabetes (OR: 2.29; 95%CI: 1.15 - 4.54) when compared to those without septal pouches. Twenty-nine patients (12%) had a documented embolic history of CVA or TIA. Ninety-five patients (39%) had a documented history of atrial fibrillation or reported palpitations. The proportion of LAAA and clinical events is detailed in Table 2. No thrombi were identified in either LAAA or the left atrial appendage in any patient.

Bivariable analysis of each LAAA independently revealed that when compared to patients without the specified abnormality, patients with a demonstrated accessory appendage or septal pouch were 2.46 (CI 1.04 - 5.79) times more likely to have a history of CVA or TIA, patients with accessory appendage were 2.55 (CI 1.43 - 4.55) times more likely to report palpitations, and patients with accessory appendage were 2.02 (CI 1.14 - 3.56) times more likely to have a history of atrial fibrillation or reported palpitations. No statistically significant clinical associations were identified with left atrial diverticula. Complete unadjusted results for the association between LAAA and clinical events are found in Table 3. After adjusting for age, sex, hypertension, dyslipidemia and diabetes via multiple logistic regression, the only clinical association retained with LAAA was a history of reported palpitations in patients with accessory appendages (OR: 1.80; CI: 1.03 - 3.16). None of the other associations between LAAA and clinical events were significantly elevated after controlling for the previously mentioned covariates.

Table 1. Demographic and clinical characteristics of patients undergoing CTCA.

*AA: accessory appendage; SP: septal pouch; SD: standard deviation.

Table 2. Proportion of LAAA and clinical events in patients undergoing CTCA (n = 242).

Table 3. Association of LAAA to arrhythmic events and embolic events, odds ratio (95% confidence interval).

4. Discussion

To our knowledge, the present data are the first to show significant associations of accessory left atrial appendages, diverticula, and septal pouches with clinical variables. Our findings are hypothesis generating as they suggest that accessory appendages may be clinically significant and should be considered for additional investigation. In this retrospective study of patients being examined for coronary disease, a higher proportion of patients with LAAA reported palpitations. Our results may hold relevant implications in the evaluation of patients with palpitations if they possess accessory left atrial appendages. In our analysis, left atrial diverticula and septal pouches appear to be benign findings clinically; however, their investigation provides a novel understanding of their associations with patient age and confounding medical history.

We have demonstrated that accessory left atrial appendages are associated in patients with reported palpitations. The prevalence of accessory appendages in our investigation (28%) is in congruence with preceding studies which have shown prevalence between 10% - 28% [6] [7] [9] [12] [21] . Moreover, accessory left atrial appendages have been implicated as the source of ectopy in patients with symptomatic atrial fibrillation refractory to medical treatment [16] [17] . Although some have contended the clinical significance of accessory appendages, describing these structures as anatomic variants as opposed to pathologic findings, the current analysis attempts to elucidate this question [6] . Two recent studies found no difference in prevalence of left atrial accessory appendages and diverticula between patients with atrial fibrillation and patients in sinus rhythm [9] [12] . The present study is novel in its examination of each LAAA as the independent variable in assessing its association with arrhythmia. Palpitations may be associated with arrhythmia; the arrhythmogenicity of accessory left atrial appendages is yet to be established but the found association suggests additional investigation may be warranted.

By definition, the cardinal difference between accessory appendages and diverticula of the left atrium is the composition of their wall structure. Diverticula are smooth walled, can be tubiform, and lack the pectinate muscle which define accessory appendages [6] [11] . Well characterized in the literature, the pectinate-lined left atrial appendage is an anatomic outpouching not only implicated in arrhythmia, but is also a common location for thrombus formation [14] [22] . Interestingly, pectinate muscle of the right atrium has been shown to contribute to wave breakup and fibrillatory activity and has been speculated to act as anchor points for reentry in atrial fibrillation [23] . Thus, it is conceivable that these accessory appendages in the left atrium, with trabeculated walls composed of pectinate, may serve as a nidus for atrially-based arrhythmias when compared to smooth-walled diverticula. This observation has clinical importance because evidence linking such a prevalent anatomic ab- normality to patient-reported palpitations has the potential to provide further insight into the mechanism of arr- hythmia.

This study is the first to examine the association between LAAA and embolic events in patients undergoing CTCA. The current analysis shows that association of accessory appendages or septal pouches with CVA or TIA disappears after adjusting for age, sex, hypertension, diabetes and dyslipidemia. This finding is in accord with a recent study by Tugcu et al., which found no association between septal pouches and ischemic strokes in patients evaluated by trans-esophageal echocardiography [24] . The left atrial appendage’s role in systemic embolization has been established; however, the pathogenesis of embolic events in patients with LAAA has been a subject of debate. Krishnan et al. theorized that septal pouches, which have access to the systemic circulation, comparable to the left atrial appendage, may serve as a site for thrombus formation and embolization especially during low flow states [5] . In fact, thrombi originating from aberrant spaces within the interatrial septum have been implicated in individual case reports of patients with coronary emboli and TIA [18] - [20] . Thrombi within accessory left atrial appendages and diverticula have been described in previous case reports as well [10] [13] [17] . Our findings do not show any association between diverticula and CVA or TIA. Consistent with several prior studies, our image analysis did not show evidence of thrombi within accessory appendages, diverticula or septal pouches [6] [7] [9] [12] . Nevertheless, given the high prevalence of LAAA, consideration of evaluation for thrombi within LAAA prior to electrophysiologic procedures may be useful for clinical management and risk reduction.

In the current study, patients who possess septal pouches and diverticula are statistically older than those patients without these abnormalities; no association with patient age is observed with accessory appendages. Our reported prevalence of septal pouches (38.4%) is within the range described in the literature (29.1% - 39%) [5] [24] . Our analysis has shown that patients with septal pouches are also more likely to be diabetic. The association between diabetes duration diastolic dysfunction has been shown [25] . Further, diastolic dysfunction has been frequently implicated in left atrial remodeling [26] , which could explain the formation of septal pouches in older patients with diabetes. A possible explanation for diverticula being associated with increased age is that, similar to diverticula in other tissues, focal weaknesses in the atrial wall may develop over time. Unlike septal pouches and diverticula, no association is seen in the current study between accessory appendages and patient age. This finding provides further support to the several studies which have hypothesized an embryologic origin of these structures [9] [27] .

This study is not without its limitations. Although CTCA is useful in distinguishing between the various LAAA, characterization of these structures was unable to be verified histopathologically. This being a retrospective study, ectopic activity was not individually assessed within each LAAA and was therefore determined by clinical history. Although our study was appropriately powered, it was limited by the availability and content of complete clinical histories. LAAA identified in our investigation were studied uniquely in patients undergoing CTCA. As a corollary, current findings may not reflect prevalence in the general population, and the presence of these anomalies in older patients may be due to selection bias. Previous studies have posited a congenital or embryologic origin for LAAA; however, the clinical associations of these structures have only been examined in adults. Their developmental history warrants further elucidation, as this knowledge will be invaluable to the complete clinical understanding of LAAA.

5. Conclusion

Accessory appendages, diverticula and septal pouches are highly prevalent anatomic abnormalities of the left atrium, increasingly identified by MDCT. The pectinate-lined accessory appendages have a high association with palpitations. Despite their blind-end morphology, no LAAA is associated with CVA or TIA. Septal pouches and diverticula are associated with increased patient age and, and septal pouches are additionally associated with a history of diabetes. Left atrial diverticula appear to be clinically benign. Further study of LAAA with larger prospective cohorts is warranted.

Acknowledgements

This study was funded by the Health Services Scholarship, awarded by The George Washington University School of Medicine and Health Sciences to author AVV.

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