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Table of Contents
ORIGINAL ARTICLE
Year : 2020  |  Volume : 10  |  Issue : 1  |  Page : 10-15

Biochemical markers for detection of intracardiac thrombosis


Department of Cardiology, Faculty of Medicine, Zagazig University, Zagazig, Egypt

Date of Submission15-Mar-2019
Date of Decision03-Apr-2019
Date of Acceptance10-Apr-2019
Date of Web Publication20-Apr-2020

Correspondence Address:
Dr. Hala Gouda Abomandour
Department of Cardiology, Faculty of Medicine, Zagazig University, Zagazig 44519
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/JICC.JICC_20_19

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  Abstract 


Aims: Intracardiac thrombus is known as the common cause of cardiogenic cerebral ischemia and a useful clinical marker of thrombogenesis. This study aimed to predict the presence of intracardiac thrombosis by noninvasive method using NT-pro-brain natriuretic peptide (BNP) and D-dimer evidenced by trans-esophageal echocardiography (TEE). Methods: A total of 200 patients were included and referred to TEE for the detection of intracardiac thrombi. Measurement of NT-Pro-BNP and D-dimer was done 2 h before the TEE examination. The patients were divided into two groups namely Group A with intracardiac thrombus and Group B without intracardiac thrombus. Results: There was an increased prevalence of intracardiac thrombus in diabetic hypertensive patients and transient ischemic attack patients. Intracardiac thrombus had significantly higher levels of Pro-BNP and D-dimer (P < 0.001). Using the receiver operating characteristic curve, the value of D-Dimer level >788 ng/ml and NT-Pro-BNP >683 ng/ml predicted the presence of intracardiac thrombus. Conclusion: High value of NT-Pro-BNP and D-dimer level can predict the presence of intracardiac thrombosis and its decreased value can predict the absence of thrombosis in patients with suspected intracardiac thrombi.

Keywords: Atrial fibrillation, intracardiac thrombosis, NT-pro-BNP, thrombogenesis, trans-esophageal echocardiography


How to cite this article:
Abomandour HG, Nashy BN, Shaker A. Biochemical markers for detection of intracardiac thrombosis. J Indian coll cardiol 2020;10:10-5

How to cite this URL:
Abomandour HG, Nashy BN, Shaker A. Biochemical markers for detection of intracardiac thrombosis. J Indian coll cardiol [serial online] 2020 [cited 2020 Dec 6];10:10-5. Available from: https://www.joicc.org/text.asp?2020/10/1/10/282972




  Introduction Top


Intracardiac thrombi can result in severe morbidity or even death from embolic events; the most accurate method for the detection of intracardiac thrombus is trans-esophageal echocardiography (TEE).[1]

Thrombi present in the left side of the heart are a common source of stroke and other arterial embolic events.[2] TEE provides a detailed visualization of the left atrium and left atrial appendage (LAA) from multiple imaging planes.[3] Patients, suffering from intracardiac thrombus, have significantly higher level of NT-Pro-BNP and D-dimer as compared to normal individuals.[4] The measurement of fibrin D-dimer levels has been advocated as a useful clinical marker of thrombogenesis.[5]

Increased natriuretic peptides are associated with a high risk of cardiovascular complications and mortality.[6]

Left atrial dysfunction detected by TEE as high spontaneous echo contrast (SEC) and low LAA flow velocity are powerful predictors for left atrial thrombi. Brain natriuretic peptide (BNP) levels are significantly and negatively correlated with LAA peak flow velocity, which is compatible with previous findings.[7] Therefore, BNP might increase among patients with atrial fibrillation (AF) and LAA dysfunction. Higher levels of BNP detected in patients with AF accompanied by transient ischemic attacks (TIAs) and acute ischemic stroke are at risk of developing left atrial thrombus.[7]

Aim of the study

This study aimed to predict the presence of intracardiac thrombosis and possibility of distal embolization using NT-pro-BNP and further correlated the findings with TEE.


  Methods Top


This study included 200 patients, who visited Zagazig University hospitals (our hospital) to carry out TEE for the exclusion of intracardiac thrombi. The selected patients had been suffering from:

  • Mitral stenosis prepared for balloon mitral valvoplasty
  • History of stroke or peripheral embolization
  • AF before cardioversion
  • Prosthetic valves.


All participants underwent complete history taking and thorough clinical examination that included age, diabetes mellitus, hypertension, smoking, hyperlipidemia, and history suggesting previous thromboembolic manifestations (stroke or TIAs).

Resting 12-lead surface electrocardiography and transthoracic echocardiography were done in all patients prior to TEE.

TEE was done in all patients with special emphasis on the LAA Doppler flow profiles and presence of LAA smoke and thrombi.[8],[9]

Laboratory tests including the evaluation of complete blood count, kidney function tests, liver function tests, and coagulation profile were performed 2 h before the TEE examination to measure NT-pro-BNP and D-dimer.


  Results Top


The results demonstrated no significant difference between both groups with regard to age and hyperlipidemia, whereas there was a significant association between intracardiac thrombus and gender. Most of the patients with intracardiac thrombus were females [Table 1]. There was a significant difference between both groups with regard to history of diabetes mellitus. Intracardiac thrombus is more likely to occur in diabetic than nondiabetic individuals. Similarly, intracardiac thrombus is more likely to occur in hypertensive patients as compared to nonhypertensive individuals. Patients with a previous history of TIA are more likely to suffer from intracardiac thrombus. Patients with intracardiac thrombus had smoking history as compared to 39.8% of patients without intracardiac thrombus [Table 1].
Table 1: Comparison between patient with intra-cardiac thrombus & patient without intra-cardiac thrombus as regard age (years), sex & risk factors

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There was no significant difference observed between groups with regard to ejection fraction. Significant association between intracardiac thrombus and SEC was examined. Most of the patients with intracardiac thrombus had SEC, with significant association between intracardiac thrombus and degree of SEC. Majority of the patients with intracardiac thrombus had severe SEC as compared to the majority of the patients without intracardiac thrombus [Table 2]. Patients with intracardiac thrombus had significantly larger left atrial diameter (LAD) and left atrial volume (LAV). Moreover, patients with intracardiac thrombus had significantly slower LAA velocity.
Table 2: Comparison between patient with intra-cardiac thrombus and patient without intra-cardiac thrombus as regard Ejection Fraction (%), SEC, LAD (mm), LAV (ml), LAA Velocity (cm/sec), & Intra-cardiac thrombus diameter

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Patients with intracardiac thrombus had significantly higher level of Pro-BNP and D-dimer concentration. There were no significant differences among the international normalized ratio (INR), total cholesterol, triglyceride, low-density lipoprotein, and high-density lipoprotein between the groups [Table 3]. Based on univariate analysis, diabetes mellitus (DM) history, smoking history, TIA history, AF history, SEC, degree of SEC, LAD, LAV, LAA velocity, INR, D-dimer concentration, intracardiac thrombosis, Killip class, and distal thromboembolic events were significantly correlated with the concentration of Pro-BNP [Table 4]. Whereas, based on step-wise linear regression analysis, the significant factors associated with high level of Pro-BNP were severe SEC, slower LAA velocity, and high D-dimer concentration.
Table 3: Comparison between patient with intra-cardiac thrombus and patient without intra-cardiac thrombus in regard of Pro BNP conc. (ng/ml), D-Dimer conc. (ng/ml), and International Normalized Ratio (INR)

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Table 4: Multivariate Analysis of explanatory variables for dependent variable (Pro BNP conc.) in all patients (n=200)

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The D-dimer concentration is highly correlated with sex, DM history, smoking history, TIA history, AF history, SEC, degree of SEC, LAD, LAV, LAA velocity, Pro-BNP concentration, and intracardiac thrombosis [Table 5]. On the basis of linear regression analysis, the significant factors associated with high level of D-dimer concentration were severe SEC and higher level of Pro-BNP.
Table 5: Stepwise Logistic regression analysis for independent predicators of Intra.cardiac thrombosis (N=100)

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On the basis of logistic regression analysis, higher level of Pro-BNP concentration was the significant independent predictor of intracardiac thrombosis. The screening test for NT-Pro-BNP predicted that 100% of patients had intracardiac thrombus, who had NT-Pro-BNP level >683 pg/ml [Table 6].
Table 6: Pro BNP concentration (pg/ml) for intra-cardiac thrombosis; ROC Analysis

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The screening test for D-dimer predicted that 100% of patients suffered from intracardiac thrombus, who had D-dimer level >788 pg/ml.

There was a nonsignificant difference between both groups with regard to ejection fraction. There was a significant association between Pro-BNP concentration and SEC, where most of the patients with high Pro-BNP concentration had SEC. Patients with high Pro-BNP concentration had significantly larger LAD and significantly larger LAV, but as regard LAA velocity, patients with high Pro-BNP concentration had significantly slower LAA velocity [Table 7].
Table 7: Comparison between patient with High Pro BNP concentration & patient with Low Pro BNP concentration as regard Ejection Fraction (%), SEC, LAD (mm), LAV (ml) & LAA Velocity (cm/sec) & Intra-cardiac thrombus diameter

Click here to view


There was a significant association between intracardiac thrombus and Pro-BNP concentration, with most of the patients with high Pro-BNP concentration had intracardiac thrombosis and most of the thrombi were LAA thrombus (94.1%) [Table 7] and [Table 8].
Table 8: Comparison between patient with High Pro BNP concentration & patient with Low Pro BNP concentration as regard intra-cardiac thrombosis

Click here to view



  Discussion Top


The present study depicted that patients with intracardiac thrombus had significantly higher level of NT pro-BNP as compared to patients without intracardiac thrombus. Heppell et al.[10] reported that low LAA velocity is the predictor of thrombus formation. Whereas, another study confirmed that left atrial dysfunction parameter such as low LAA flow velocity is a powerful predictor of left atrial thrombus formation.[11] LAA flow velocity was found to be correlated with SEC. On the contrary, decrease of LAA velocity is associated with increasing severity of SEC.[9] Similarly, left atrial SEC is also correlated with a hypercoagulable state that may result in thromboembolism.[12]

Okada et al.[7] demonstrated that left atrial dysfunction parameters such as low LAA flow velocity and high SEC grade are powerful predictors of left atrial thrombus formation. These results are consistent with the findings of the present study. BNP levels are negatively correlated with LAA peak velocity, which is compatible with previous findings. Therefore, BNP might be increased in patients with AF and LAA dysfunction. Congestive heart failure is also an independent predictor of left atrial thrombus, which complicates ischemic stroke along with AF. The BNP levels (as a marker of congestive heart failure) are elevated in patients with ischemic stroke and AF. High BNP levels in patients with AF accompanied by acute ischemic stroke and TIA are at high risk for left atrial thrombus.[7]

The results further stated high level of NT Pro-BNP as a significant predictor of intracardiac thrombosis. Okada et al.[7] concluded that high levels of NT pro-BNP could serve as a useful marker of left atrial thrombus in patients with AF accompanied by acute ischemic stroke and TIA. Left atrial dysfunction parameters such as low LAA flow velocity and high SEC are powerful predictors of left atrial thrombus formation. Therefore, BNP might be increased in patients with AF and LAA dysfunction. Sahin et al.[13] reported that BNP levels were not significantly correlated with LAA function, and no correlation was found between BNP and LAA thrombi. This may be due to difference in the nature of patients as they studied 84 permanent AF patients with different etiologies (20 with mitral stenosis, 44 with hypertension, and 20 with hyperthyroidism). The difference in the results may be due to the different types of kits used for both studies.

D-dimer was found to be a significant predictor of intracardiac thrombosis. Danese et al.[14] demonstrated that D-dimer is considered a universal standard among the various biomarkers that reflect the activation of coagulation and fibrinolysis. Several studies have assessed its diagnostic and prognostic role in AF. Our study demonstrated that D-dimer values may be associated with the presence of atrial thrombosis. The D-dimer values may be predictive of primary adverse outcomes and even death. It is also correlated with cerebral infarction volume and a useful parameter for assessing the degree of hypercoagulability of AF patients after cardiac infraction. Therefore, D-dimer assessment may become an integral part of the clinical decision-making in patients with AF.

The study has evaluated that the concentrations of NT-pro-BNP and D-dimer are regarded as a useful screening method for patients at risk for intracardiac thrombi and thromboembolism. High values of NT-pro-BNP and D-dimer level can predict the possible presence of intracardiac thrombosis and its low value can predict the absence of thrombosis. Higher levels of both the biomarkers can help in the prediction of distal embolization in patients with intracardiac thrombi. NT-pro-BNP and D-dimer can be considered as reflective of pro-thrombogenic state. The increase in their concentration indicates the formation of thrombus. Therefore, NT-pro-BNP and D-dimer values can be used to predict the presence of intracardiac thrombi and it may improve the risk stratification for thromboembolism. It is recommended that the evaluation of NT-pro-BNP and D-dimer levels in patients with suspected intracardiac thrombi is necessary because these tests can help to predict any previous thrombus or occurrence of distal thromboembolic events.

Although the association between duration of AF and worsening of blood stasis has been reported previously, the duration of AF was not specified in this study. The sample size of this study was limited as only 100 patients were enrolled, out of which 17 patients suffered intracardiac thrombus. A slight elevation was reported in D-dimer level among patients without intracardiac thrombosis due to comorbid conditions causing intravascular or extravascular cross-linked fibrin turnover such as renal failure, liver impairment, acute or chronic infection, hypertension, and surgery. Moreover, elevation in NT-pro-BNP levels was also reported in patients without intracardiac thrombosis due to conditions such as asymptomatic or symptomatic left ventricular dysfunction, coronary artery disease, and myocardial ischemia.

Limitations of the study

It is necessary for the physicians to have adequate opportunities for the evaluation of intracardiac thrombosis. Advanced studies must be conducted to improve the approaches for diagnosis and treatment of intracardiac thrombosis.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Sen S, Laowatana S, Lima J, Oppenheimer SM. Risk factors for intracardiac thrombus in patients with recent ischaemic cerebrovascular events. J Neurol Neurosurg Psychiatry 2004;75:1421-5.  Back to cited text no. 1
    
2.
Tatli S, Lipton MJ. CT for intracardiac thrombi and tumors. Int J Cardiovasc Imaging 2005;21:115-31.  Back to cited text no. 2
    
3.
Turhan S, Ozcan OU, Erol C. Imaging of intracardiac thrombus. Cor Vasa 2013;55:e176-83.  Back to cited text no. 3
    
4.
Frost SD, Brotman DJ, Michota FA. Rational use of D-dimer measurement to exclude acute venous thromboembolic disease. Mayo Clin Proc 2003;78:1385-91.  Back to cited text no. 4
    
5.
Kelly J, Rudd A, Lewis RR, Hunt BJ. Plasma D-dimers in the diagnosis of venous thromboembolism. Arch Intern Med 2002;162:747-56.  Back to cited text no. 5
    
6.
Hijazi Z, Wallentin L, Siegbahn A, Andersson U, Christersson C, Ezekowitz J, et al. N-terminal pro-B-type natriuretic peptide for risk assessment in patients with atrial fibrillation: Insights from the ARISTOTLE trial (Apixaban for the prevention of stroke in subjects with atrial fibrillation). J Am Coll Cardiol 2013;61:2274-84.  Back to cited text no. 6
    
7.
Okada Y, Shibazaki K, Kimura K, Matsumoto N, Iguchi Y, Aoki J, et al. Brain natriuretic peptide is a marker associated with thrombus in stroke patients with atrial fibrillation. J Neurol Sci 2011;301:86-9.  Back to cited text no. 7
    
8.
Daniel WG, Erbel R, Kasper W, Visser CA, Engberding R, Sutherland GR, et al. Safety of transesophageal echocardiography. A multicenter survey of 10,419 examinations. Circulation 1991;83:817-21.  Back to cited text no. 8
    
9.
Fatkin D, Kelly R, Feneley MP. Left atrial appendage blood velocity and thromboembolic risk in patients with atrial fibrillation. J Am Coll Cardiol 1994;24:1429-30.  Back to cited text no. 9
    
10.
Heppell RM, Berkin KE, McLenachan JM, Davies JA. Haemostatic and haemodynamic abnormalities associated with left atrial thrombosis in non-rheumatic atrial fibrillation. Heart 1997;77:407-11.  Back to cited text no. 10
    
11.
Hart RG, Halperin JL. Atrial fibrillation and stroke: Concepts and controversies. Stroke 2001;32:803-8.  Back to cited text no. 11
    
12.
Vincelj J, Sokol I, Jaksić O. Prevalence and clinical significance of left atrial spontaneous echo contrast detected by transesophageal echocardiography. Echocardiography 2002;19:319-24.  Back to cited text no. 12
    
13.
Sahin T, Acar E, Celikyurt U, Kılıc T, Kozdag G, Agacdiken A, et al. Relation of hs-CRP and BNP levels with the atrial spontaneous echo contrast and thrombi in permanent atrial fibrillation patients with different etiologies. Med Sci Monit 2012;18:CR78-87.  Back to cited text no. 13
    
14.
Danese E, Montagnana M, Cervellin G, Lippi G. Hypercoagulability, D-dimer and atrial fibrillation: An overview of biological and clinical evidence. Ann Med 2014;46:364-71.  Back to cited text no. 14
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8]



 

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