Left atrial appendage aneurysm: a descriptive systematic review of 177 cases

Abstract

Introduction

The left atrial appendage (LAA) is a distinct structure with unique developmental and structural characteristics. The LAA is involved in the formation of intra-atrial thrombi, particularly in patients with conditions such as atrial fibrillation and mitral valve disease. Left atrial appendage aneurysms (LAAA) are rare abnormal dilations of the LAA that may cause hazardous complications. However, there are limited data on the demographic features, clinical characteristics, management modalities, and prognosis of LAAA patients. This study aimed to conduct a systematic review of the reported cases of LAAA to explore the baseline characteristics, presentation, preferred diagnostic modalities, and optimal management of LAAA.

Methods

A systematic review was conducted following the PRISMA guidelines. We performed a literature search using MEDLINE/PubMed and Google Scholar. Eligible articles published between January 1940 and November 2022 were included. The eligibility criteria included case reports and case series of LAAA in English language articles. The data extracted included information on the authors, publication year, patient characteristics, signs/symptoms, diagnostic procedures, treatments, and outcomes.

Results

We identified 177 patients with LAAA in our study. There was a slight female predominance (50.9%), and the mean age was 29.7 years. Palpitations were the most common symptom reported, followed by shortness of breath and thromboembolic events. Transthoracic and transesophageal echocardiograms were the most common modalities for investigating and diagnosing LAAA, and the mean size of the aneurysm was 7.8 (5.7–9.6) × 5.9 (5.0-6.2) cm. Surgical resection is the treatment of choice for most patients with excellent prognoses. Older age and the presence of arrhythmia were significantly associated with thrombus formation and embolic events.

Conclusion

Left atrial appendage aneurysm is a rare but potentially life-threatening heart pathology that can lead to arrhythmias and thromboembolic events. Surgical resection appears to be the primary treatment option in the current literature, and most patients show improvement or are asymptomatic after treatment. Additionally, alternative approaches, such as transcatheter closure of LAAA, ablation, and medical treatments, have been reported as viable alternatives to surgical intervention.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12872-024-04323-x.

Introduction

During the fourth week of embryonic development, the left atrial appendage (LAA) emerges from the left wall of the major atrium [1]. In terms of its development and structure, it differs from the rest of the left atrium. The LAA is located next to the left ventricle’s free wall in the pericardium and it was thought to have a minimal role in cardiac anatomy [2]. However, because of its distinct anatomical and physiological characteristics, it can be used as a decompression chamber when left atrial pressure increases, as it does during left ventricular systole [1]. In addition, the sympathetic and parasympathetic nervous systems both supply a dense network of nerve fibers that innervate the LAA, which is involved in the synthesis of brain natriuretic and atrial peptides [3].

LAA plays a crucial role in the production of thrombi, especially in situations like atrial fibrillation and mitral valve disease. Approximately, 90% of atrial thrombi in nonrheumatic atrial fibrillation are found to be originated from the LAA. Similarly, in patients with rheumatic mitral valve disease, especially mitral stenosis, the LAA is the site of about 60% of atrial thrombi [4].

Rarely, the LAA can dilate abnormally causing left atrial appendage aneurysms (LAAA) [5]. The first reported case of LAAA was published in 1962 [6]. As of the date on which our search was conducted, 177 cases have been reported in literature. Since the first case report of LAAA [7], it has been suggested that patients with LAAA may be more susceptible to thromboembolic events. This potential increased risk is assumed to be associated with hemodynamic changes caused by the greater orifice of the appendage [8].

Despite these findings, there is limited information available about the natural history, clinical course, and effective management strategies for LAAA. The rarity of this condition has led to a lack of standardized diagnostic guidelines and treatment approaches, making it challenging for clinicians to effectively manage patients with LAAA. To address these gaps and enrich the current clinical knowledge, we systematically reviewed all published case reports and case series. This study aims to provide a comprehensive assessment of baseline characteristics, clinical presentations, diagnostic methods, and appropriate treatment strategies for patients with LAAA.

Methods

Study design

This study is a descriptive systematic review aimed at summarizing and analyzing all reported cases of left atrial appendage aneurysms (LAAA). We adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement criteria throughout the review process. This systematic review is registered in the International Platform of Registered Systematic Review and Meta-analysis Protocols (INPLASY) under registration number: INPLASY202470109.

Literature search

Two separate authors (AO, SA) conducted a literature search for eligible papers published between January 1940 and November 2022 using MEDLINE/PubMed and Google Scholar as secondary sources. Following that, we conducted a search using a combination of the following terms: “left atrium”, “atrial”, “appendage”, “atrial appendage”, “aneurysm”, “congenital”, and “acquired”, as well as the medical topic heading terms “atrial appendage” and “aneurysm” as search terms. The search method generated 931 articles in total. The titles and abstracts of the case reports were used to establish their eligibility. Figure 1 depicts a full PRISMA flow diagram.

Fig. 1.

Search flow diagram

Eligibility criteria

Rayyan AI software was used to remove duplicate articles from the search results. Two independent reviewers used specified eligibility criteria to analyze the retrieved papers. The eligibility screening process was divided into two stages: an initial review of titles and abstracts, followed by a thorough analysis of the whole text. The following criteria were used to choose articles: [1] they had case reports of left atrial appendage aneurysms [2], they contained case series of left atrial appendage aneurysms, and [3] they were published in English exclusively. In vitro research, animal case studies, and non-English literature were all removed.

Quality assessment

The quality of the included case reports and case series was evaluated using a structured assessment tool (Supplementary file 1). We included only peer-reviewed articles to ensure credibility. To assess quality, we utilized a modified version of the Joanna Briggs Institute (JBI) checklist for case reports and case series [9]. Criteria such as clarity of patient history, detailed description of clinical presentation, diagnostic assessment, and intervention details were evaluated to gauge the robustness of each included article.

Data extraction

For the extracted data, the authors employed a standardized data collection sheet. Two authors extracted the intended data separately, and any disputes were discussed and resolved by a third investigator. The retrieved data includes the following: author list, year of publication, baseline patient information, signs/symptoms, diagnostic procedures, therapies, and procedure outcomes.

Data synthesis

IBM SPSS v.21.0 was used to enter and evaluate the data. The continuous variables were correlated using Spearman’s rank correlations because the data did not follow a normal distribution mode. Fisher’s exact test or Pearson’s chi-square were used to compare categorical variables, where applicable. A multivariate logistic regression model was used to generate the odds ratios. Statistical significance was defined as a p-value of < 0.05. The statistical power for the multivariate logistic regression was greater than 0.80, ensuring a robust analysis. The power was calculated using established equations, where the effect size (logarithm of the odds ratio) and standard error were derived from the sample size and variance of predictor variables. The full equations used are provided in the supplementary materials (Supplementary file 2). Non-quantitative data were qualitatively synthesized.

Results

Characteristics of the patients with left atrial appendage aneurysm

177 patients with LAAA were identified and extracted from 165 case reports and case series for this investigation [10–174]. There were 90 (50.9%) females, 85 (48.0%) males, and 2 (1.1%) patients whose gender was not stated. The patients’ mean age was 29.7 ± 21.2 years (median age was 29.0 [9.0, 44.0] years) (Fig. 2). Two (1.1%) of the documented cases of left atrial appendage aneurysm were prenatal. 59 (33.3%) of the patients were under the age of 18 (pediatrics), 106 (59.9%) were adults, and 12 (6.8%) were over the age of 65 (elderly).

Fig. 2.

Age distribution of patients with LAAA

Symptoms were present in 75.1% (n = 133) of the reported cases. Palpitations were the most frequently reported symptom, affecting 42.9% (n = 76) of symptomatic individuals, followed by shortness of breath, which was stated by 27.1% (n = 48) of the patients. Furthermore, thromboembolic events were detected in 11.3% (n = 20) of patients, while chest discomfort was noted in 10.2% (n = 18) of patients, however, 24.9% (n = 44) of patients remained asymptomatic. Upon thorough physical examination, several noteworthy findings were documented. Systolic murmurs, focal neurological deficits, irregular-irregular pulses, and tachycardia were the main documented findings.

Diagnostic procedures

A chest X-ray (CXR) was performed for 138 (78.0%) of the patients. Among the 138 patients, 136 (98.5%) had abnormalities. A prominent left heart border was found in 76 (55.1%) of the patients. Other abnormalities were described as cardiomegaly in 51 (36.9%) patients and as a “mass” in 9 (6.5%) patients.

Electrocardiography (ECG) was done on 150 patients (84.7%). Among the 150 patients, 96 (64.0%) had abnormalities. The most common ECG abnormalities were atrial fibrillation (52 patients, 29.4%), atrial flutter (12 patients, 6.8%), and supraventricular or atrial tachycardia (12 patients, 6.8%). Other findings that were occasionally documented were right bundle branch block, ischemic changes large notched “P” waves, and conduction anomalies. Of the atrial fibrillation and atrial flutter patients, 14 were diagnosed using a Holter monitor.

Transthoracic echocardiogram (TTE) was performed on 163 patients (92.1%). 106 (65.0%) of the 163 individuals were diagnosed with LAAA. The mass has been described as a cyst, cavity, mass, or echo-free structure. Other abnormalities were found in 77 (43.5%) of the individuals. The most commonly reported anomalies were mitral valve regurgitation and left ventricular compression, which occurred in 29 (16.4%) and 22 (12.4%) patients, respectively. Other documented abnormalities included impaired left ventricular function, a thrombus in the left ventricle, and biatrial enlargement.

Transesophageal echocardiography (TEE) was conducted on 69 individuals (40.0%). LAAA were found in 66 (95.6%) of the patients. In addition to the diagnosis of a left atrial appendage aneurysm, the most frequently reported abnormalities in TEE findings were thrombus materials, left ventricular wall compression, and mitral regurgitation.

Cardiac catheterization was performed on 39 (22.0%) of the patients in the form of left, right, and coronary angiography. Because of advances in echocardiographic procedures and the availability of computed tomography (CT) and magnetic resonance imaging (MRI) scans, angiography is almost never employed in modern medical practice to diagnose LAAA.

CT findings were reported for 82 (46.3%) patients, and radionuclide angiography was reported for 1 (0.6%) patient. Chest and cardiac CT were the most frequently reported imaging methods for 32 (18.1%) and 23 (13.0%) patients, respectively. Other techniques included 3D CT in 9 (5.1%) patients and multiple detectors in 8 (4.5%) patients. Of the 82 patients, 77 (93.9%) were diagnosed with LAAA. Cardiac MRI was performed for 66 (37.3%) patients. Of the 66 patients, 64 (96.9%) were diagnosed with LAAA.

There was a very strong positive correlation between the length of LAAA measured after surgery and MRI (Spearman’s rho = 1.00), TEE (Spearman’s rho = 0.80), and CT (Spearman’s rho = 0.90) data. On the other hand, there was a weak correlation between the length of LAAA measured after surgery and the length of TTE (Spearman’s rho = 0.38). There was a very strong positive correlation between the diameter of LAAA measured after surgery and MRI (Spearman’s rho = 1.0), TEE (Spearman’s rho = 1.0), TTE (Spearman’s rho = 0.83), and CT (Spearman’s rho = 0.80) (Table 1).

Table 1.

Dimensions of left atrial appendage Aneurysms measured by different imaging techniques and correlation with Surgical measurements

Technique	Dimension	Mean	SD	Median	Q1	Q3	Correlation with size by surgery
Transthoracic echocardiogram	Length	6.5	2.7	6.3	4.5	8.4	0.38
	Width	5.3	3.0	5.1	3.1	6.7	0.83
Transesophageal echocardiogram	Length	7.8	3.1	7.0	5.7	9.6	0.80
	Width	5.9	1.9	5.3	5.0	6.2	1.00
CT scan	Length	7.2	2.5	7.0	5.1	9.0	0.90
	Width	5.9	2.0	5.6	4.2	7.0	0.80
MRI	Length	6.6	2.5	6.7	4.6	8.5	1.00
	Width	5.2	2.0	4.3	3.4	6.9	1.00
Surgery	Length	9.2	4.3	8.0	6.6	11.6	-
	Width	7.8	3.9	7.0	5.6	10.0	-

SD = standard deviation; Q1: first quartile; Q3: third quartile, CT: Computed Tomography,

MRI: Magnetic resonance imaging

Associated congenital anomalies

In this study, associated congenital anomalies were reported in 22 (12.4%) of the patients. Of the 22 patients, 5 (22.7%) had more than one congenital anomaly. Atrial septal defects were reported in 4 (2.2%) patients, and 2 other patients had defects combined with other congenital anomalies (1.1%). Mitral regurgitation was reported in another 4 (2.2%) patients. Ventricular septal defects were reported as single or combined with other congenital anomalies in 4 (2.2%) patients.

Treatment and prognosis

For the 177 patients analyzed, treatment information was available for 165 (93.2%) patients. Among the treatment modalities employed, LAAA resection was performed in 132 (74.5%) patients. The majority of LAAA resections (108 patients, 61.0%) were conducted via median sternotomy, 7 (3.9%) patients underwent lateral thoracotomy, 6 (3.4%) patients underwent mini-thoracotomy, and one patient (0.5%) underwent endoscopic resection. Notably, 13 (7.3%) patients underwent LAAA resection, but the specific method utilized was not specified in the available data. LAAA resection was accompanied by the Maze procedure in 13 (7.3%) patients, mitral valve repair/replacement in 6 (3.4%) patients, and radiofrequency ablation in 6 (3.4%) patients.

Of those patients who underwent LAAA resection and follow-up, 94 (94.9%) reported being asymptomatic, experiencing improved symptoms, or returning to sinus rhythm. However, 4 (4%) patients exhibited persistent or recurrent symptoms, and unfortunately, 1 (0.5%) patient died during the surgical procedure. In 33 (18.6%) patients, the treatment response was not mentioned.

In terms of additional procedures, ablation served as the sole treatment for three patients, one of whom experienced arrhythmia recurrence. Two (1.1%) patients opted for transcatheter closure of the LAAA, which reported clinical improvement and suggested an alternative approach to conventional surgical methods. Furthermore, 24 (13.5%) patients were managed solely with medical treatments such as antiarrhythmic and/or anticoagulant therapies. Unfortunately, the treatment response was not mentioned for 11 (6.2%) patients, either due to loss to follow-up or pending follow-up appointments. Of the remaining patients, 10 (5.6%) reported improved symptoms, one (0.5%) experienced a recurrence of arrhythmia, and 2 (1.1%) patients passed away—one after 4 weeks and the other after 10 years due to a cerebrovascular accident complicated by septicemia during hospitalization.

Histopathological findings and thrombus size

Histopathological findings were reported for 47 (26.5%) of the patients. Fibrosis was the most commonly reported histopathological finding in 34 (72.3%) patients. Other reported histopathological findings included hypertrophy in 9 (5.1%) patients, fatty infiltration in 2 (1.1%) patients, and dysplasia in 2 (1.1%) patients. The thrombus size was mentioned for 13 (7.3%) patients. The mean length was 3.3 ± 2.0 cm (the median was 3.0 [1.8, 4.9] cm), and the mean width was 3.8 ± 2.0 cm (the median was 3.1 [2.5, 4.8] cm).

Summary of case series of LAAAs case report

A summary of the LAAA case report’s case series is shown in Table 2. Patients reported a variety of symptoms, including dyspnea, palpitations, and CVA. CXR, TTE, TEE, CT, MRI, and catheterization were among the imaging modalities used for diagnosis. The aneurysms varied in size from 2.5 cm to 9.0 cm, and some of them had clots inside of them. The majority of patients underwent surgical resection, although some required further procedures and few denied therapies. While some patients’ symptoms subsided and their cardiac rhythms returned to normal, others’ symptoms persisted.

Table 2.

Table Summary of Case series of LAAAs

Author(s)	Year	Age (years)	Gender (M/F)	Symptoms	Imaging Techniques	Key Findings	Treatment	Outcomes
Foale, R A et al. (55)	1982	43	F	CVA	CXR, TTE, Cath	4.0 cm LAA aneurysm	Surgical resection	Not mentioned
Foale, R A et al. (55)	1982	39	F	Asymptomatic	CXR, TTE	6.0 cm LAA aneurysm	Surgical resection	Not mentioned
Foale, R A et al. (55)	1982	47	F	Palpitations	CXR, TTE	2.5 cm LAA aneurysm	Declined treatment	-
Burke, RP et al. (120)	1992	37	M	CVA, AFib	CXR, TTE, Cath	9.0 × 6.0 cm LAA aneurysm	Surgical resection	Normal rhythm
Burke, RP et al. (120)	1992	29	M	Dyspnea, chest pain	CXR, TEE	4.0 × 6.0 cm LAA aneurysm	Surgical resection	Asymptomatic
Gajjar T, Desai N (88)	2011	29	M	Dyspnea	CXR, CT	LAA aneurysm	Not mentioned	-
Gajjar T, Desai N (88)	2011	48	M	Dyspnea	CXR, CT	LAA aneurysm	Not mentioned	-
Mirmohammadsadeghi M et al. (84)	2013	30	F	Fatigue	CXR, TTE, TEE, CT angio	5.0 × 4.0 cm LAA aneurysm filled with clots	Surgical resection	Not mentioned
Mirmohammadsadeghi M et al. (84)	2013	46	M	CVA	TTE	5.0 × 4.0 cm LAA aneurysm filled with clots	Surgical resection	Not mentioned
Kuiten W et al. (114)	2013	69	M	Dyspnea, AFib	CT, TTE	7.0 × 5.5 cm LAA aneurysm	Surgical resection, electrical cardioversion and amiodarone	Persistent AFib
Kuiten W et al. (114)	2013	39	M	CVA, palpitations	CXR, TTE, TEE, CT MRI	7.0 × 7.0 cm LAA aneurysm	Surgical resection	Normal rhythm
Zhang X et al. (138)	2020	4	F	Abnormal CXR	CXR, TTE	3.8 × 1.8 cm LAA aneurysm	Declined treatment	-
Zhang X et al. (138)	2020	3	M	Abnormal CXR	CXR, TTE, TEE, MRI	4.5 × 3.2 cm LAA aneurysm	Surgical resection	Correction of LAAA
Zhang X et al. (138)	2020	0.3	F	Abnormal CXR	CXR, TTE	3.8 × 2.2 cm LAA aneurysm	Declined treatment	-
Zhang X et al. (138)	2020	9	F	Abnormal TTE after mitral valvuloplasty	TTE	3.3 × 1.9 cm LAA aneurysm	Surgical resection	Not mentioned
Zhang X et al. (138)	2020	1	F	Rapid heart rate	TTE	2.9 × 1.1 cm LAA aneurysm	Surgical resection	Correction of LAAA
Sharifuzzaman M et al. (27)	2021	18	F	Palpitation, chest pain	CXR, TTE	6.0 × 9.9 cm LAA aneurysm	Surgical resection	Asymptomatic
Sharifuzzaman M et al. (27)	2021	5	M	Palpitations	CXR, TTE	LAA aneurysm	Surgical resection	Not mentioned

M: Male, F: Female, CVA: Cerebrovascular accident, CXR: Chest X-ray, TTE: Transthoracic Echocardiogram, TEE: Transesophageal Echocardiography, Afib: Atrial Fibrillation, CT: Computed Tomography, MRI: Magnetic Resonance Imaging

Factors associated with presence of arrythmia and thrombus in left atrial appendage aneurysm

The chi-square test and Fisher’s exact test showed that the presence of arrythmia was significantly associated with older age, male sex, and the presence of thrombus in LAAA (Table 3).

Table 3.

Associations between the presence of arrhythmia and demographic and clinical variables

	Absence of arrhythmia		Presence of arrhythmia
Variable	n	%	n	%	Chi-square/Fisher’s exact test	p value
Age category
Pediatric	42	23.8	17	9.6	20.4	< 0.001
Adult	42	23.8	64	36.1
Elderly	2	1.1	10	5.6
Gender
Male	30	9.8	55	31.1	11.7	0.003
Female	55	17.2	35	19.8
Not Mentioned	1	0.6	1	0.6
Presence of thrombus in left atrial appendage aneurysm
Yes	11	6.2	28	15.8	8.1	0.006
No	76	43	62	35

P < 0.05 was considered to indicate statistical significance

When these variables were retained in a multivariate logistic model (Table 4), older patients were 5.1-fold (95% CI: 2.3–11.4) more likely to have arrythmia compared to younger patients, male patients were 4.4-fold (95% CI: 2.1–9.1) more likely to have arrythmia compared to female patients, and patients who had thrombus in the LAAA were 3.0-fold (95% CI: 1.3–6.9) more likely to have arrythmia compared to the patients who did not have thrombus in the LAAA. The patients who received anticoagulants were less likely to have thrombus in LAAA (Fisher’s exact test = 11.6, p = 0.001). The chi-square test and Fisher’s exact test showed that the presence of thrombus in LAAA was significantly associated with mortality, older age, and the presence of arrythmia (Table 5).

Table 4.

Multivariate logistic model for identifying the predictors of arrhythmia

						95% CI for OR
Variable	β	SE	Wald	p value	OR	Lower	Upper
Age	1.63	0.41	15.67	< 0.001	5.1	2.3	11.4
Gender	1.48	0.37	16.29	< 0.001	4.4	2.1	9.1
Presence of thrombus in left atrial appendage aneurysm (n = 39)	1.10	0.42	6.73	0.009	3.0	1.3	6.9

SE = standard error; CI = confidence interval; OR = odds ratio

Table 5.

Associations between the presence of thrombus in left atrial appendage aneurysms and demographic and clinical variables

	Absence thrombus in left atrial appendage aneurysm		Presence of thrombus in left atrial appendage aneurysm
Variable	n	%	n	%	Chi-square/Fisher’s exact test	p value
Mortality
No	138	78	36	20.3	10.4	0.011
Yes	0	0.0	3	1.7
Age category
Pediatric	51	28.8	8	4.5	4.8	0.091
Adult	80	45.2	26	14.7
Elderly	7	4	5	2.8
Presence of arrythmia
No	76	43	11	6.2	8.1	0.006
Yes	62	35	28	15.8

We observed a significant association between the presence of tachyarrhythmias and various clinical outcomes. Specifically, patients with tachyarrhythmias were more likely to experience adverse outcomes such as recurrent atrial flutter and persistent atrial fibrillation, compared to those without arrhythmias. For example, of the patients with tachyarrhythmias, 33.3% showed persistent arrhythmias or recurrence of atrial flutter, while 50% experienced stable sinus rhythm post-treatment. In contrast, patients without tachyarrhythmias more frequently achieved asymptomatic states and stable sinus rhythms following treatment, with 62.5% showing complete resolution of symptoms.

Discussion

This systematic review provides a comprehensive assessment of 177 cases of LAAA, a rare condition characterized by localized or diffuse dilation of the left atrial appendage. We found a slight predominance in female patients (50.9%), with a mean age of 29.7 years. The most common presenting symptoms were palpitations, shortness of breath, and thromboembolic events. Transthoracic and transesophageal echocardiograms were the preferred diagnostic modalities, and surgical resection emerged as the most frequently utilized treatment, with favorable prognoses. Older age and the presence of arrhythmia were significantly associated with thrombus formation and embolic events. There was a role of tachyarrhythmias in shaping clinical outcomes for patients with LAAA. Patients with tachyarrhythmias were more likely to experience recurrent atrial flutter or persistent atrial fibrillation, suggesting that the presence of arrhythmias in LAAA patients may indicate a more severe disease course or complications such as thrombus formation. Furthermore, our results indicate that achieving stable sinus rhythm is a key determinant of favorable outcomes, with patients without tachyarrhythmias showing higher rates of symptom resolution and overall improvement.

LAAA is a rare condition with significant clinical implications, yet knowledge regarding its etiology, presentation, and management remains limited. The first documented case of LAAA dates back to 1962 by Parmley LF Jr. [6], and only 177 cases have been reported in the literature since then. LAAA can either be congenital or acquired, with congenital LAAA arising from abnormalities such as pectinate muscle dysplasia, whereas acquired LAAA is associated with left atrial enlargement due to mitral valve diseases or other myocardial pathologies [158].

Depending on where it occurs, LAAA can alternatively be categorized as extrapericardial or intrapericardial. Left atrial appendage weakening leads to the intrapericardial form, and the following diagnostic requirements have been proposed: origination from an apparently healthy atrial chamber, clear connection to the atrial cavity, situated inside the pericardium, and aneurysm disruption of the left ventricle [44]. The extrapericardial kind is connected to a pericardial defect that can herniate and develop into aneurysmal dilatation. It is well recognized that the extrapericardial variant has a better prognosis [175]. Despite these criteria for categorizing LAAA types, it is usually difficult to distinguish them clearly in many cases.

Our findings indicated that LAAA can present at any age, although the majority of cases occur in the second or third decade of life. The introduction of fetal echocardiography has made it possible to diagnose LAAA prenatally, emphasizing the importance of early detection to prevent complications. Despite a slight female predominance, the risk factors for the development of LAAA are not well understood, and more extensive studies are needed to identify predisposing factors for this condition.

The clinical presentation of LAAA is heterogeneous, with a significant number of patients remaining asymptomatic. When symptoms occur, palpitations, shortness of breath, and thromboembolic events are most common. Determining whether these symptoms are directly caused by LAAA or related to underlying cardiac disorders can be challenging, as LAAA may serve as a substrate for atrial tachyarrhythmias or contribute to arrhythmias through abnormalities in the conduction system. However, no study has definitively established the role of LAAA in the origin of atrial arrhythmias using electrophysiological investigations, leaving a gap in the understanding of the arrhythmogenic potential of LAAA [171].

Additionally, associated abnormalities in the conduction system can contribute to the development of arrhythmias. However, no study has definitively established the origin of atrial arrhythmias specifically from LAAA using electrophysiological investigations. Less commonly, it can irritate the left phrenic nerve, which causes hiccups [116], and push the left recurrent laryngeal nerve, creating a persistent cough [176]. In the majority of cases, the physical examination results appear normal or may reveal certain findings, such as systolic murmurs (most commonly), focal neurological deficits, irregular-irregular pulses, or tachycardia.

Diagnosing LAAA can be challenging due to the nonspecific nature of most symptoms. Initial diagnostic tests commonly used include CXR and ECG analyses. While these tests lack specificity, they can show certain abnormalities that are often observed in the majority of patients, such as a prominent left heart border on CXR and the presence of atrial fibrillation and/or flutter on ECG. In patients with LAAA, chest X-ray revealed a mass-like enlargement in 98.5% of patients. This finding indicates that CXR is an excellent initial workup for these patients. Furthermore, such findings on CXR and ECG should prompt physicians to perform a more specific form of imaging.

In the cases documented in the literature, TTE, TEE, CT scan, cardiac MRI, and cardiac catheterization were the most frequently used cardiac imaging modalities. With 65% sensitivity, TTEs can be somewhat useful for diagnosis. However, TTE results frequently characterize LAAA as echo-free structures, cysts, cavities, or masses, requiring additional diagnostic testing. Since cardiac catheterization is invasive and has been superseded by safer alternatives, it is the least commonly used diagnostic technique. With their high sensitivity (93.9%) and ability to perform enhanced anatomical detail imaging, CT scans enable the investigation of congenital anomalies and the relationship between LAAA and surrounding tissues. TEE and cardiac MRI had the highest sensitivities for diagnosing LAAA (95.6% and 96.9%, respectively). These parameters are useful for detecting thrombi and are strongly correlated with the length and diameter of the LAAA, as measured post-surgery.

Surgery is the main treatment modality for LAAA, whether symptomatic or not. Various effective techniques, including median sternotomy, left thoracotomy, mini-thoracotomy, and minimally invasive endoscopic approaches, have been reported for aneurysmectomy. Recently, a unique noninvasive method of transcatheter closure for LAAA was described [156]. In our study, surgical resection was performed in more than 75% of the patients. Histopathologic examination of LAAA tissue revealed fibrosis in most patients. Less commonly, hypertrophy, fatty infiltration, or dysplasia can be observed. Generally, the prognosis following surgical resection is favorable, with a success rate of 94.9% and minimal complications in patients with a reported follow-up. Only 4% of patients experienced persistent or recurrent symptoms, and one patient died during the surgical procedure [59].

We found that mortality due to LAAA is significantly associated with the presence of a thrombus. The presence of a thrombus is associated with the presence of arrhythmia, older age, and male sex. For individuals who are not suitable for surgery, medical management should focus on treating atrial tachyarrhythmia and thromboembolic complications. Mortality was reported in two patients treated with medical therapy [48, 107]. However, it is not possible to compare the outcomes of surgical and medical management, as most patients treated medically are either lost to follow-up or pending follow-up appointments.

In cases where a preoperative or intraoperative echocardiogram detects a thrombus or a large LAAA, cardiopulmonary bypass is used to minimize the risk of thrombus dislodgement during aneurysm manipulation. Minimally invasive endoscopic techniques can safely remove LAAAs without left atrial or appendage thrombi, effectively eliminating the risk of thromboembolism and tachyarrhythmia. However, resection of giant LAAAs may result in dysmorphic atrial tissue, increasing the likelihood of atrial tachyarrhythmia. Therefore, for patients with large LAAAs, atrial fibrillation, or biatrial enlargement, concurrent consideration of Cox-Maze III type or other ablative procedures during LAAA resection is recommended [177].

Limitations

We must acknowledge several constraints in our research. Our review was limited to studies available in the English language. Moreover, this review was based on a retrospective analysis of cases reported in the existing literature, which introduces an inherently high risk of bias associated with case reports and case series. These types of studies often have limited sample sizes, a lack of control groups, and are subject to publication bias, where more unusual or positive outcomes are preferentially reported. Additionally, the statistical analysis conducted in this review involved data pooled from different reports. The variability in data suggests potential heterogeneity, which may be due to differences in performed interventions and outcome measures. As such, the results reported in this review should be interpreted cautiously, considering the presence of this heterogeneity. Another important limitation is the limited number of reports on large LAAA. The accumulation of more data in the future could allow for a comprehensive meta-analysis. It is also important to note that asymptomatic cases of LAAA may go unnoticed, resulting in an underrepresentation of the broader patient population with LAAA. Furthermore, the absence of a universally accepted definition for LAAA adds to the complexity and potential inconsistencies in our findings.

Conclusion

LAAA is a rare condition characterized by the expansion of the left atrial appendage. It can be congenital or acquired, gradually increasing in size and posing a risk of thromboembolism. Surgical intervention is crucial for managing LAAA, for which favorable outcomes have been reported. LAAA may coexist with other congenital anomalies. Currently, diagnostic imaging, such as echocardiography and MRI, can play a key role in the evaluation of LAAAs. Based on the pooled data, MRI and TEE showed an excellent degree of correlation to post-surgical LAAA dimensions when compared to other modalities. More data are still needed to allow drawing more solid conclusions on the best ways to evaluate LAAA and optimize treatment strategies.

Electronic supplementary material

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Abbreviations

LAA

Left Atrial Appendage

LAAA

Left Atrial Appendage Aneurysm

PRISMA

Preferred Reporting Items for Systematic Reviews and Meta-Analyses

INPLASY

International Platform of Registered Systematic Review and Meta-Analysis Protocols

SPSS

Statistical Package for the Social Sciences

CXR

Chest X-ray

ECG

Electrocardiography

TTE

Transthoracic Echocardiogram

TEE

Transesophageal Echocardiography

CT

Computed Tomography

MRI

Magnetic Resonance Imaging

CVA

Cerebrovascular accident

Author contributions

All authors contributed to the study’s conception and design. SA, AO, and MA were involved in literature review, screening, and data extraction. RS conducted the statistical analysis. The initial draft of the manuscript was written by AO/SA, and all authors provided comments on previous versions. YD oversaw each stage of the study and provided the required comments when needed. All authors read, reviewed, and approved the final manuscript.

Funding

The authors declare that they did not receive any financial support for the conduct of this research.

Data availability

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.