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 Table of Contents  
ORIGINAL ARTICLE
Year : 2021  |  Volume : 9  |  Issue : 1  |  Page : 78-82

Association of Structure and Function of left atrial Appendage with Left atrial appendage Thrombus formation in patients with Rheumatic Heart Disease: ASFALT-RHD study


1 Department of Cardiology, U.N. Mehta Institute of Cardiology and Research Centre, Civil Hospital Campus, Asarwa, Ahmedabad, Gujarat, India
2 Department of Research, U.N. Mehta Institute of Cardiology and Research Centre, Civil Hospital Campus, Asarwa, Ahmedabad, Gujarat, India

Date of Submission19-Sep-2020
Date of Decision28-Sep-2020
Date of Acceptance07-Oct-2020
Date of Web Publication30-Mar-2021

Correspondence Address:
Dr. Sanjeev Bhatia
Department of Cardiology, U. N. Mehta Institute of Cardiology and Research Centre, Civil Hospital Campus, Asarwa, Ahmedabad - 380 016, Gujarat
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/heartindia.heartindia_40_20

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  Abstract 


Context: In patients with rheumatic heart disease (RHD), left atrial appendage (LAA) dilation and thrombus formation is widely known. LAA thrombus formation is a risk factor for stroke even in patients with sinus rhythm. The aim of this study was to determine an association between LAA structure and function with respect to thrombus formation and differences in LAA size and velocity between patients with sinus rhythm and those with atrial fibrillation (AF).
Materials and Methods: We prospectively studied LAA structure and function in 120 patients with RHD by transthoracic echocardiography and/or transesophageal echocardiography by measuring left atrial (LA) dimension, LA area, LAAmax/min, LAA ejection fraction (EF), and LAA emptying velocity.
Results: Four out of 48 patients with sinus rhythm had LAA thrombus. In 72 patients with AF, 32 had LAA thrombus. Patients with LAA thrombus had lower mean LAA EF and emptying velocity both variables P-value is same (P<0.0001 and P<0.0001) Patients with LAA thrombus had increased mean LAA max and LAA min as compared to LAA max and LAA min in patients without LAA thrombus (P 0.008 for mean LAA max and P<0.0001 for LAA min respectively). Patients with AF with LAA thrombus had greater LAAmax compared to that in patients with AF without LAA thrombus (P < 0.0001). Doppler demonstrated a recognizable sawtooth LAA outflow velocity pattern in 32 of 36 (88.9%) patients with LAA thrombus versus 32 of 84 (38.1%) patients without LAA thrombus.
Conclusions: We conclude that LAA contractility is reduced in RHD with LAA thrombus, and loss of both contractility and LAA dilation is associated with increased risk of thrombus formation and hence the risk of stroke.

Keywords: Atrial fibrillation, left atrial appendage, rheumatic heart disease


How to cite this article:
Natarajan K, Mansuri Z, Joshi D, Shukla A, Sharma V, Pandey V, Bhatia S, Patel K. Association of Structure and Function of left atrial Appendage with Left atrial appendage Thrombus formation in patients with Rheumatic Heart Disease: ASFALT-RHD study. Heart India 2021;9:78-82

How to cite this URL:
Natarajan K, Mansuri Z, Joshi D, Shukla A, Sharma V, Pandey V, Bhatia S, Patel K. Association of Structure and Function of left atrial Appendage with Left atrial appendage Thrombus formation in patients with Rheumatic Heart Disease: ASFALT-RHD study. Heart India [serial online] 2021 [cited 2021 Aug 1];9:78-82. Available from: https://www.heartindia.net/text.asp?2021/9/1/78/312482




  Introduction Top


Atrial mechanical activity plays a significant role in disease course in many patients. Mechanical efficacy of left atrial appendage (LAA) is considered an important factor in A-type natriuretic peptide production, which stabilizes blood volume and pressure in the left atrium (LA) and may indirectly affect cardiac output.[1] LAA is the most frequent cardiac source of thrombi in patients with AF.[2],[3],[4] In addition, the LAA flow velocity has been used to assess the propensity for thrombus formation.[5] LAA is also an important structure in cardiac hemodynamics. Accordingly, a comprehensive assessment of LAA structure and function is now regularly sought to guide therapeutic illnesses.[6]

Atrial fibrillation (AF) (rheumatic and nonrheumatic) is an independent risk factor for stroke and peripheral emboli, contributing close to 40% of overall neurologic events.[1] In AF, the LAA is almost always the site of thrombus formation. Decision-making for anticoagulation in AF patients is a challenge, and a lot of clinical ambiguity exists regarding the best line of management in a particular patient.[7] High-quality images obtained by the above modalities play an important role in the structural and functional assessment of LAA and are also useful in risk prediction and prognostication.[6]

Echocardiography, particularly transesophageal echocardiography (TEE), remains the initial modality of choice for evaluation of LAA. It is safe, is radiation free, is inexpensive, and allows complete delineation of the LAA anatomy in almost all patients with a detailed evaluation of its function.[6] The aim of this study was to determine an association between LAA structure and function with respect to thrombus formation as well as differences in LAA size and velocity between patients with sinus rhythm and those with AF.


  Materials and Methods Top


This is a prospective, observational, single-center study, carried out in the department of cardiology of a tertiary-level interventional cardiac center in Gujarat, Ahmedabad, India. A total of 120 patients with rheumatic heart disease (dominant lesion being mitral stenosis (MS) and mitral regurgitation (MR)) and patients with cerebrovascular stroke (ischemic or hemorrhagic) with documented evidence (computed tomography or MR imaging) were included in the study. Patients with multiple comorbidities contributing to the inciting event, patients with a history of hypercoagulability, and those with genetic risk factors for stroke were excluded from the study.

The study was approved by the institutional ethics committee. This study complies with the World Medical Association Declaration of Helsinki. The clinical and demographic data of the patients were collected with the help of a predetermined data collection form. All the patients underwent a detailed clinical examination, laboratory investigations as required, electrocardiography (ECG), two-dimensional (2D) transthoracic echocardiography (TTE), and 2D and three-dimensional TEE. The principal investigations included hemoglobin, serum creatinine, and random blood sugar.

Patients were evaluated with 2D echocardiography, and LA, left ventricular (LV) end-systolic and LV end-diastolic dimensions, and ejection fraction (EF) were stressed upon. The presence and severity of the MS or MR was also evaluated. The LAA appendage was especially assessed in the short axis and looked for the presence of clot, Spontaneous echocardiographic contrast (SEC), or thrombus. Patients underwent 2D echocardiography primarily to look for LAA function as assessed by the velocity, pattern of waveforms, and the presence of SEC or thrombus. Patients were evaluated on an outpatient as well as an inpatient basis.

In all patients, LAA area was measured during LAA diastole at the onset of the ECG P wave (LAAmax) and after LAA systole at the ECG R wave (LAAmin), and LAA EF was calculated as (LAAmax − LAAmin)/LAAmax. Peak Doppler velocity was recorded from the LAA outlet.

Statistical methods

The statistical calculations were performed using IBM SPSS software version 20.0 (Chicago, IL, USA). Quantitative data were expressed as mean ± standard deviation and qualitative data were expressed in terms of number and percentage. Univariate and bivariate logistic regression analysis was performed to find out the correlation between echocardiographic finding with rhythm types and presence of thrombus. Group differences associated with P < 0.05 were considered statistically significant.


  Results Top


Age, gender, comorbidities, type of stroke (confirmed by imaging evidence), rhythm (sinus rhythm or AF), TTE findings, and TEE findings were used for the analysis. Anticoagulation status was also taken into account while evaluating the patients. Out of the 120 patients included in the study, 58 (48.3%) were male and 62 (51.7%) were female, with a mean age of 46.67 ± 12.84 years. Comorbidities such as hypertension and diabetes mellitus Type II were seen in 22 (18.3%) and 8 (6.7%) patients, respectively. Majority of the patients (108 [90%]) suffered from ischemic strokes. Out of these, majority were of small-vessel or lacunar strokes affecting 62 (51.7%) patients. All but one patient with hemorrhagic stroke developed the event while on anticoagulation. Majority of the patients (106 [88.3%]) had severe mitral stenosis as the dominant lesion. The average LA dimensions were also higher in patients with MS as compared to those with MR and hence contributing to higher incidence of AF.

Subgroup analysis was done on the basis of type of rhythm, as shown in [Table 1]. A total of 48 (40%) patients were in sinus rhythm of which four patients had LAA thrombus. In 72 (60%) patients with AF, 32 (44.4%) patients had LAA thrombus. In patients with AF, LAAmax was measured independent of the ECG, of these 34 patients had LAA SEC, 24 (20%) had thrombus, and 8 had both.
Table 1: Baseline characteristics and results in patients with sinus rhythm and atrial fibrillation

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Patients without LAA thrombus demonstrated a characteristic pattern of a contractile LAA apex and a mean LAA EF of 41.78 ± 12.20. Patients with LAA thrombus had a mean LAA EF of 22.78 ± 7.74 and showed a strong significant correlation between thrombus and LAA EF (P < 0.0001). Patients with LAA thrombus had a mean LAAmax of 8 ± 2.14 cm2, which was higher than that of patients without LAA thrombus (4.74 ± 1.26 cm2). These patients also had larger LAAmin (6.22 ± 1.87 cm2) compared to that in patients without LAA thrombus (2.78 ± 1.04 cm2), as shown in [Table 2]. The average emptying velocity in sinus rhythm and AF patients was 38.13 ± 9.18 and 14.19 ± 3.06 cm/s, respectively. All atrial fibrillated patients (72) had ischemic shock. There was a strong association between low emptying velocity and AF (P < 0.0001). LAA emptying velocity (14.22 ± 3.73 m/s) in patients with LAA thrombus was less than that in patients without LAA thrombus (27.86 ± 13.9 m/s). Patients with AF with LAA thrombus had greater LAAmax (7.5 ± 1.65 cm2) compared to that in patients with AF without LAA thrombus (5.05 ± 1.13 cm2) (P < 0.0001). Doppler demonstrated a recognizable sawtooth LAA outflow velocity pattern in 32 of 36 (88.9%) patients with LAA thrombus versus 32 of 84 (38.1%) patients without LAA thrombus (P < 0.0001).
Table 2: Baseline characteristics and results in patients with thrombus

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Binary logistic regression was performed for subgroup variables. It was found that LA area – 0.03 (95% confidence interval [CI]: 0.94–0.99; P 0.005) and LAA EF – 0.18 (95% CI: 0.74–0.94; P 0.002) were found to inversely correlate to rhythm types so that higher LA area and LAA EF were seen in sinus rhythm. Higher LA dimension was the strongest predictor of thrombus (0.18; 95% CI: 1.05–1.36; P 0.009).

We found a higher rate of AF in patients who underwent balloon mitral valvuloplasty (BMV) (36 [50%]) as compared to those who underwent surgery (30 [41.2%]) and were kept on medical management (6 [8.3%]) with P < 0.0001.


  Discussion Top


We performed this study to establish the association of rhythm disturbance and echocardiographic abnormalities in LAA thrombus formation. LAA segmental anatomy, which is most commonly seen, increases the prospect of thrombi.[8],[9],[10],[11]

Di Biase et al. demonstrated that LAA morphology may precipitate thrombus formation.[12] LAA blood flow velocity is another echocardiographic parameter in the assessment of LAA function. It is recorded even in patients with AF, but only reduced blood. Out of 120 patients 48.3% were male and 51.7% were female. The study by Kurzawski et al. had a slight male preponderance (61.25% of males and 38.75% of females,[13] whereas in the study by Omran et al., there were 58% of males and 42% of females. The predominant lesion in our study was mitral stenosis (106 [88.3%]).[14] Similar predominant lesion was present in studies by Uretsky et al., and Gölbaşi et al.[15],[16]

The mean LA area in patients with AF was lower than in patients with sinus rhythm(P = 0.01), which is contradictory to other studies in which mean LA area was increased. The mean LA area in the study by Kurzawski et al. was 32 cm2, whereas in the study by Uretsky et al., the mean LA area was 41 cm2.[13],[15]

Majority of patients had AF (60%) in our study, whereas in the study by Kurzawski et al., 68% of patients had AF.[13] AF is a significant contributor to LAA dysfunction. Patients with AF show predominant saw tooth pattern, lower emptying velocities, and increased presence of SEC. Tamura et al. were one of the first group of investigators who studied tissue velocity. They analyzed the LAA wall velocity (LAAWV) obtained by Tissue Doppler Imaging (TDI) from a modified TTE projection showing LAA. LAAWV <8.7 cm/s was found to be a predictor of stroke in patients with AF.[17],[18]

In our study, the average emptying velocity in patients with AF was several times (14.19 ± 3.06 cm/s) lower than that in patients with sinus rhythm. SEC was present in 24 (33.3%) patients. Kurzawski et al. showed an average velocity of 15 ± 1.8 cm/s in their study. SEC was present in 27 (58%) patients in their study.[13]

In our study, SEC was present in 54 (45%) patients and thrombus was present in a total of 10 (27.8%) patients, which were found to be significant independent predictors of results as concluded from our study (P 0.02). Presence of SEC was found higher in patients with LAA thrombus as compared to patients without thrombus (P=0.02) which makes presence of SEC as a predictor of thrombus formation in LAA. In a study by Fatkin et al., there were 61% of patients with SEC and 15% with thrombus. Kurzawski et al. showed the presence of SEC or thrombus in 75% of patients. In their study, Black et al. reported left atrial thrombus in 59% of patients.[13],[19]

In patients with mitral stenosis, LAA dysfunction is a strong predictor of development of SEC and thrombi. Successful BMV leads to improvement in the appendage function within 24–72 h and may also lead to resolution of the stroke risk. A study published by Ganeswara Reddy et al. reported the effect of BMV on LAA function in patients with symptomatic mitral stenosis in sinus rhythm.[20]


  Conclusions Top


We conclude that LA enlargement, LAA dilatation, reduced LAA EF, and reduced LAA emptying velocity are all associated with LAA thrombus formation and hence the risk of stroke. LA dimension is the strongest predictor of LAA thrombus.

Ethical approval

The study involves human participants; the study has been approved by the appropriate Institutional Ethics Committee (UNMICRC/CARDIO/2015/85) and has been performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki. This article does not contain study performed on animals by any of the authors.

Authors' contributions

Dr. Karthik Natarajan - Design, Aquisition, Dr. Zeeshan Mansuri - Analysis, Interpretation, Drafting Dr. Dinesh Joshi - Aquisition, Analysis, Drafting Dr. Anand Shukla - Conceptualization, Design, Interpretation Dr. Vishal Sharma - Aquisition, Analysis Dr. Vimlesh Pandey - Aquisition, Analysis Dr. Sanjeev Bhatia - Analysis Krutika Patel- Analysis, Drafting.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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Di Biase L, Santangeli P, Anselmino M, Mohanty P, Salvetti I, Gili S, et al. Does the left atrial appendage morphology correlate with the risk of stroke in patients with atrial fibrillation?: Results from a multicenter study. J Am Coll Cardiol 2012;60:531-8.  Back to cited text no. 12
    
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Kurzawski J, Janion-Sadowska A, Sadowski M. Left atrial appendage function assessment and thrombus identification. Int J Cardiol Heart Vasc 2017;14:33-40.  Back to cited text no. 13
    
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