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 Table of Contents  
ORIGINAL ARTICLE
Year : 2019  |  Volume : 5  |  Issue : 1  |  Page : 26-29

Is there an association of intracardiac mass with high urate level? AIM-HUL study


1 Department of Cardiology, U. N. Mehta Institute of Cardiology and Research Centre, Civil Hospital Campus, Ahmedabad, Gujarat, India
2 Department of Cardiology, Mumbai Heart Clinic, Mumbai, Maharashtra, India
3 Department of Research, U. N. Mehta Institute of Cardiology and Research Centre, Civil Hospital Campus, Ahmedabad, Gujarat, India

Date of Web Publication2-May-2019

Correspondence Address:
Dr. Kamal Sharma
Department of Cardiology, UNMICRC, Civil Hospital Campus, Asarwa, Ahmedabad - 380 016, Gujarat
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jpcs.jpcs_3_19

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  Abstract 


Context: Hyperuricemia is associated with idiopathic left atrium/left ventricular clot, and its association with other intracardiac tumors is not clear. Aim: The study aimed to establish if there is an association of intracardiac mass with high urate level. Settings and Design: This prospective study included 440 individuals, of which 330 were consecutive all comers with intracardiac mass detected on echocardiography from June 2016 to December 2017, who were compared with 110 randomly selected healthy controls undergoing echocardiography during the same without intracardiac mass in a ratio of 3:1. Materials and Methods: Imaging modalities such as transesophageal echocardiography, cardiac computerized tomography, and/or cardiac magnetic resonance imaging were done to analyze the intracardiac mass. Both the groups were analyzed for serum uric acid (SUA) levels at the time of detection of intracardiac mass. Statistical Analysis Used: Univariate analysis was done for continuous variables using Student's t-test, whereas the Chi-square test was used for the categorical data. Logistic regression analysis was performed with the presence of a mass with SUA as the dependent variable. Results: Among a total of 440 patients, 330 were cases and 110 were controls with the mean age of 47.52 ± 16.02 years (18–77 years) versus 45.23 ± 14.10 (18–73 years) years with male:female ratio of nearly 3:2 in both the groups. Mean SUA in cases was significantly higher than controls (7.60 ± 0.93 vs. 4.52 ± 1.20 mg%) (P < 0.001 with 7.6 [95% confidence interval (CI): 7.5–7.7] and 4.52 [95% CI: 4.3–4.74]) with linear logistic regression coefficient of 0.64. There was no significant difference in SUA levels among different types of intracardiac mass (P = 0.31). Conclusion: Hyperuricemia is associated with all comers of intracardiac mass with a regression coefficient of 0.64 irrespective of the nature of mass.

Keywords: Echocardiography, hyperuricemia, thrombus


How to cite this article:
Sharma K, Humane D, Jhamaria J, Jain S, Patel K, Patil S, Bhatia S, Panwar J. Is there an association of intracardiac mass with high urate level? AIM-HUL study. J Pract Cardiovasc Sci 2019;5:26-9

How to cite this URL:
Sharma K, Humane D, Jhamaria J, Jain S, Patel K, Patil S, Bhatia S, Panwar J. Is there an association of intracardiac mass with high urate level? AIM-HUL study. J Pract Cardiovasc Sci [serial online] 2019 [cited 2019 Sep 15];5:26-9. Available from: http://www.j-pcs.org/text.asp?2019/5/1/26/257602




  Introduction Top


Serum uric acid (SUA), which is the final product of purine metabolism, has been associated with the pathophysiology of several diseases, including hypertension, chronic kidney disease, congestive heart failure, metabolic syndrome type 2 diabetes mellitus, atherosclerosis with or without cardiovascular events and stroke.[1] In addition, a correlation was recently detected between hyperuricemia and the development of new-onset atrial fibrillation (AF) and increased risk of ischemic stroke in patients with AF.[2] Elevated SUA levels in patients with dilated cardiomyopathy are correlated with the severity of functional mitral regurgitation.[3] Previous studies suggested associations between hyperuricemia and endothelial dysfunction, local oxidant generation, and elevated circulating levels of systemic inflammatory mediators.

Hyperuricemia is associated with idiopathic left atrium (LA)/left ventricular (LV) clot, but its association with other intracardiac tumor is not well defined. The aim of the present study was to evaluate the clinical, echocardiographic, and SUA levels that could be a bystander rather than etiological factor in the formation of LA thrombosis. Hence, we intended to investigate the relationship between the level of SUA level and all comers. Intracardiac masses detected on echocardiography. The present study thus proposes that hyperuricemia may be a manifestation and/or bystander in intracardiac mass rather than etiology of thrombus. Hence, we evaluated whether a relationship exists between all types of intracardiac mass and SUA levels.


  Materials and Methods Top


This prospective study was conducted at a tertiary care Center of Western India from June 2016 to December 2017. The study included 440 individuals, of which 330 were consecutive all comers with intracardiac mass detected on echocardiography, who were compared with 110 randomly selected controls undergoing echocardiography during the same without intracardiac mass in a ratio of 3:2 of the male to female in both groups. Apart from transthoracic echocardiography, other imaging modalities such as transesophageal echocardiography (TEE), cardiac computerized tomography, and/or cardiac magnetic resonance imaging were also used to analyze the intracardiac mass further if needed. Both groups were analyzed for SUA levels at the time of echocardiography. All patients had their demographics documented. They were also evaluated for electrocardiogram and chest X-ray apart from serum hematology and biochemistry as mandated by the treating physician.

Exclusion criteria

Patients who were unwilling or too sick to participate in further evaluation as per the study design were excluded from the study. We also excluded patients with other disorders that can cause hyperuricemia such as acute or chronic renal failure, acute rheumatic fever, sepsis, inflammatory disease, extracardiac tumor or malignancy, and a history of anti-inflammatory, anticoagulant drug use that may alter SUA.

Blood samples were drawn from the antecubital vein for determination of biochemical and hemostatic parameters after overnight fasting after the echocardiography. Ethylenediaminetetraacetic acid tubes were used for an automatic blood count. The blood counts were measured using an auto hematology analyzer per the manufacturer's instructions. SUA levels were measured using an enzymatic colorimetric test.

Transthoracic two-dimensional and Doppler echocardiographic assessments were performed using a Vivid 7 with a 3.5 MHz phased array transducer (GE Medical System, Horten, Norway). Two-dimensional and pulsed wave Doppler echocardiographic studies were performed in the left lateral decubitus position with the conventional views (parasternal long- and short-axis, apical four-chamber views).

TEE was performed using commercially available echocardiography. LA thrombus was diagnosed by the presence of a clearly defined echogenic intracavitary mass with an echotexture different from that of the underlying endocardium and not due to the pectinate muscle. The presence or absence of an intracardiac mass was evaluated independently by three observers, and any discrepancy was resolved by consensus and further imaging if needed.

Ethical consideration

We adhere to the principles of the Declaration of Helsinki. All data were collected and compiled in a protected computer database. Individual data were anonymous without identifiable personal information. Institutional Ethics Committee approved the protocol of this study. Consents were obtained from all individuals by a comprehensive consenting method as provided by the institute.

Statistical analysis

The statistical calculations were performed using IBM SPSS statistic version 20 (Chicago, IL, USA). Quantitative data were expressed as mean ± standard deviation (SD) whereas qualitative data were expressed as a percentage. Univariate analysis of the continuous data was performed using Student's t-test, whereas the Chi-square test was used for the categorical data. Logistic regression was performed for uric acid as a risk factor in mass patients. The cutoff value of P < 0.05 was considered statistical significance.


  Results Top


Of total 440 cases, 330 were cases of intracardiac mass and 110 were normal healthy controls undergoing the study during the same time. The demographics were evenly matched in both the groups [Table 1]. Fatigue was more common among cases as compared to controls. Among 330 cases with intracardiac mass 196 (59.4%) had LA/left atrial appendage (LAA)/LV clot and thrombus formation, 96 (29.1%) patients had mitral valve (MV)/aortic valve vegetation and 38 (11.5%) had myxoma. SUA was found to be elevated in 330 cases with mean SUA level of 7.60 ± 0.93 mg/dl. Mean SUA level in healthy control was 4.52 ± 1.20 (Mean ± SD). Mean SUA level in patients with LA/LAA/LV clot and thrombus, vegetations, and myxoma was 7.59 ± 0.95 mg%, 7.58 ± 0.88 mg%, and 7.68 ± 0.93 mg% (Mean ± SD), respectively. There was no significant difference in SUA among different types of intracardiac mass (P = 0.31) [Table 2].
Table 1: Demographic data

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Table 2: Intracardiac mass types with uric acid level

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The other laboratory parameters with their minimum and maximum ranges were evenly matched in both groups [Table 3].
Table 3: Laboratory investigations

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The subgroup analysis revealed linear correlation between the presence of intracardiac mass and SUA with a coefficient of correlation of 0.64.


  Discussion Top


We assessed SUA level in patients with intracardiac mass and healthy controls. The most common cause of intracardiac mass is our study was LA/LAA thrombus; an intracardiac lesion can be detected by echocardiography, the differential diagnosis must include thrombus, vegetation, and a foreign body, infectious and nonbacterial thrombotic or marantic endocarditis and cardiac tumors. Rheumatic heart disease affecting the MV is still one the leading cause of LA/LAA thrombus in India. Patients with AF are known to have a high incidence of LA thrombi. However, the incidence of LA thrombosis in patients in normal sinus rhythm is also not negligible. The prevalence of LA clots in patients with MS in sinus rhythm was found to range from 2.4% to 13.5% in various studies.[4],[5] Another cause of intracardiac mass is myxoma which is the most common primary intracardiac tumor. Two-thirds of myxomas arise in the LA, whereas others arise in the RA, ventricles, SVC, or pulmonary veins.[6],[7]

Uric acid is a final enzymatic product of purine metabolism. UA depends on the activity of xanthine oxidase which participates in the formation of free radical superoxide anions. The highest activity of xanthine oxidase is detected in endothelium, intestine, and liver. Among them, endothelial xanthine oxidase plays a crucial role in cardiovascular oxidative stress.[8]

The result of our study showed that the level of SUA level increased significantly in patients with intracardiac tumors. A recent meta-analysis also showed a similar result. In this analysis, six observational studies with 2381 patients were included. Meta-analysis of these studies showed that an elevated serum UA level was associated with a higher likelihood of the left atrial thrombus/left atrial spontaneous echo contrast.[9]

The precise mechanism of thrombus formation in LA in the setting of high serum levels of UA is unclear. The vascular damage induced by hyperuricemia may be important as indicated by the excessive oxidant generation and inflammatory response in vascular endothelium.[10],[11]

UA could promote tissue inflammation and deterioration of endothelial function, which may be responsible for AF and accompanying LA thrombus formation.[12]

In addition, hyperuricemia could induce proliferation of vascular smooth muscle cell and reduce the production of vascular nitric oxide leading to the development of turbulent flow and thrombus formation.[13]

Since in this study, SUA was elevated against control population irrespective of the type of intracardiac mass and there was no significant difference between various types of mass we propose that SUA may be a bystander or product of mass rather than an etiological factor as has been proposed in above-quoted studies.


  Conclusion Top


Hyperuricemia is associated with intracardiac mass. The linear correlation between the mass and SUA with a coefficient of regression of 0.64; however, in Association of Intracardiac Mass with High Urate Level study (AIM-HUL study), there was no significant difference in SUA among different types of intracardiac mass.

Financial support and sponsorship

This study was supported by U. N. Mehta Institute of Cardiology and Research Center, Ahmedabad, India (affiliated to BJ Medical College, Ahmedabad, Gujarat, India).

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Kuriyama S, Maruyama Y, Nishio S, Takahashi Y, Kidoguchi S, Kobayashi C, et al. Serum uric acid and the incidence of CKD and hypertension. Clin Exp Nephrol 2015;19:1127-34.  Back to cited text no. 1
    
2.
Kawasoe S, Kubozono T, Yoshifuku S, Ojima S, Miyata M, Miyahara H, et al. Uric acid level and new-onset atrial fibrillation in the Japanese general population- longitudinal study. Circ J 2018;83:156-63.  Back to cited text no. 2
    
3.
Yazicioǧlu MV, Avci A, Açar G, Esen Ö, Karaca O, Alici G, et al. Elevated uric acid and functional mitral regurgitation in dilated cardiomyopathy. Eur Rev Med Pharmacol Sci 2012;16:1637-41.  Back to cited text no. 3
    
4.
Davison G, Greenland P. Predictors of left atrial thrombus in mitral valve disease. J Gen Intern Med 1991;6:108-12.  Back to cited text no. 4
    
5.
Conradie C, Schall R, Marx JD. Echocardiographic study of left atrial thrombi in mitral stenosis. Clin Cardiol 1993;16:729-31.  Back to cited text no. 5
    
6.
Saidi SJ, Motamedi MH. Incidence and factors influencing left atrial clot in patients with mitral stenosis and normal sinus rhythm. Heart 2004;90:1342-3.  Back to cited text no. 6
    
7.
Lamparter S, Moosdorf R, Maisch B. Giant left atrial mass in an asymptomatic patient. Heart 2004;90:e24.  Back to cited text no. 7
    
8.
Korantzopoulos P, Letsas KP, Liu T. Xanthine oxidase and uric acid in atrial fibrillation. Front Physiol 2012;3:150.  Back to cited text no. 8
    
9.
Zhang EY, Kou L, Li M, Ng CY, Zhao JP, Li GP, et al. High uric acid level predicts left atrial thrombus or spontaneous echo contrast detected by transesophageal echocardiography: Meta-analysis and systematic review. Chronic Dis Transl Med 2016;2:27-33.  Back to cited text no. 9
    
10.
Wang H, Jacobs DR Jr., Gaffo AL, Gross MD, Goff DC Jr., Carr JJ. Longitudinal association between serum urate and subclinical atherosclerosis: The coronary artery risk development in young adults (CARDIA) study. J Intern Med 2013;274:594-609.  Back to cited text no. 10
    
11.
Rothenbacher D, Kleiner A, Koenig W, Primatesta P, Breitling LP, Brenner H. Relationship between inflammatory cytokines and uric acid levels with adverse cardiovascular outcomes in patients with stable coronary heart disease. PLoS One 2012;7:e45907.  Back to cited text no. 11
    
12.
Nishida K, Chiba K, Iwasaki YK, Katsouras G, Shi YF, Blostein MD, et al. Atrial fibrillation-associated remodeling does not promote atrial thrombus formation in canine models. Circ Arrhythm Electrophysiol 2012;5:1168-75.  Back to cited text no. 12
    
13.
Kanellis J, Kang DH. Uric acid as a mediator of endothelial dysfunction, inflammation, and vascular disease. Semin Nephrol 2005;25:39-42.  Back to cited text no. 13
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3]



 

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