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 Table of Contents  
ORIGINAL ARTICLE
Year : 2020  |  Volume : 9  |  Issue : 4  |  Page : 140-144

Evaluation of Left Ventricular Function in Patients with Systemic Lupus Erythematosus: Association of Tissue Doppler and Strain Imaging with Disease Activity


1 Department of Cardiology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
2 Department of Cardiology, Jayadeva Institute of Medical Sciences and Research, Bengaluru, Karnataka, India
3 Department of Immunology and Rheumatology, IMS and SUM Hospital, Bhubaneshwar, Orissa, India
4 Department of Immunology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India

Date of Submission17-May-2020
Date of Decision03-Aug-2020
Date of Acceptance24-Aug-2020
Date of Web Publication09-Feb-2021

Correspondence Address:
Dr. Mullusoge Mariappa Harsha
Assistant Professor, Department of Cardiology, Sri Jayadeva Institute of Cardiovascular Sciences and Research, Mysore Branch, K.R.S Road, Mysore, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/JCPC.JCPC_34_20

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  Abstract 


Background: Systemic lupus erythematosus (SLE) is a connective tissue disorder with cardiovascular involvement associated with high morbidity and mortality. Routine echocardiography often misses early myocardial involvement. We intend to use tissue Doppler imaging (TDI), strain and strain rate imaging to reveal subclinical myocardial dysfunction in asymptomatic females with SLE; and its correlation with disease activity and anticardiolipin antibodies. Materials and Methods: Forty-three female SLE patients without cardiac symptoms or signs and matched healthy control group (n = 20) underwent standard echocardiography, TDI, strain and strain rate imaging. Disease activity of SLE was assessed using the SLE disease activity index (SLEDAI); ≥6 points were considered active. Results: Mean age of SLE patients was 29.86 years with a mean SLEDAI score of 4.36 ± 4.5. Standard two dimensional-Echocardiogram parameters were similar to healthy controls. SLE was associated with significantly impaired systolic myocardial velocities of left ventricle measured by TDI; medial S': 8.5 ± 1.2 versus 9.6 ± 1.0 cm/s, P = 0.007; lateral S': 9.2 ± 1.7 versus 11.4 ± 1.6 cm/s, P = 0.012); and decrease in strain (−17.2% ± 2.2% vs. −20.95% ± 2.1%; P < 0.001) and strain rate (P < 0.05). There was no significant difference with the presence of anti-cardiolipin antibodies. Patients with higher disease activity had decreased systolic myocardial velocity on TDI and strain imaging as compared to low activity patients. Conclusion: Asymptomatic SLE patients showed impairment of left ventricular systolic and diastolic function compared to healthy controls. TDI and strain imaging detects early subclinical myocardial involvement that correlates with disease activity. Such evidence of early myocardial involvement needs further evaluation to reclassify SLE disease activity and guide management.

Keywords: Echocardiogram, strain imaging, systemic lupus erythematosus, systemic lupus erythematosus disease activity index, tissue Doppler


How to cite this article:
Tewari S, Patro P, Harsha MM, Mishra R. Evaluation of Left Ventricular Function in Patients with Systemic Lupus Erythematosus: Association of Tissue Doppler and Strain Imaging with Disease Activity. J Clin Prev Cardiol 2020;9:140-4

How to cite this URL:
Tewari S, Patro P, Harsha MM, Mishra R. Evaluation of Left Ventricular Function in Patients with Systemic Lupus Erythematosus: Association of Tissue Doppler and Strain Imaging with Disease Activity. J Clin Prev Cardiol [serial online] 2020 [cited 2021 Mar 2];9:140-4. Available from: https://www.jcpconline.org/text.asp?2020/9/4/140/308975




  Introduction Top


The systemic lupus erythematosus (SLE) is a multi-organ autoimmune disease commonly affecting young women and is found to be associated with cardiovascular morbidity and mortality.[1],[2] All cardiac structures may be involved with manifestations such as pericarditis, myocarditis, conduction defects, valvular disease, and coronary artery disease (CAD). Left ventricle (LV) involvement may due to primary inflammatory processes involving myocardium or secondary to subclinical vasculitis, vascular stiffening, or preclinical CAD.[3],[4] Myocarditis has been reported in 7%–10% of SLE patients. Conventional two-dimensional (2D) echocardiography lacks sensitivity and may significantly underestimate subtle myocardial involvement in SLE patients.[5] Early recognition of myocardial involvement may help prevent myocardial dysfunction.

The SLE disease activity index (SLEDAI) is a global score index developed for the assessment of SLE disease activity; has been shown to be reliable, reproducible, and sensitive to change.[6] Disease activity is associated with an increased risk of organ damage. SLEDAI has 24 features comprising clinical and laboratory findings.

Tissue Doppler imaging (TDI) technique is widely used for early detection of subtle, asymptomatic myocardial dysfunction and can be used as a reliable screening tool for subclinical cardiac involvement.[7] TDI helps in quantitative analysis of global and regional myocardial function.[8],[9] Using TDI, Yip et al. reported that patients with SLE had subclinical long- and short-axis dysfunctions of the basal segments of the LV.[10]

Strain is a measure of tissue deformation. Strain rate is the rate of change in strain. Strain rate and strain are less susceptible to translational motion and tethering artifacts and thus may be superior to tissue velocity in depicting regional or global myocardial function.[11],[12] TDI and strain imaging are noninvasive techniques, widely used to identify asymptomatic myocardial involvement. Chow et al. showed significant reduction of longitudinal function by strain and strain rate imaging in young adolescents with pediatric-onset SLE despite the normal routine standard 2-dimensional echocardiography.[13] Buss et al. showed significantly impaired systolic and diastolic myocardial velocities of the LV using TDI, strain rate and strain compared to the control group.[14]

Anticardiolipin antibodies are present in a small percentage of the general population but occur more commonly in patients with connective tissue disorders such as SLE. The persistent presence of these antibodies is strongly associated with recurrent fetal loss and arterial or venous thrombosis (primary antiphospholipid syndrome). Leung et al. showed that anticardiolipin antibodies were significantly associated with LV (global or segmental) dysfunction (four of five positive; P < 0.05).[15] The authors speculated that anticardiolipin-related microvascular thrombosis might be an underlying mechanism. However, Farzaneh-Far et al. had shown that anticardiolipin antibodies are not associated with significant abnormalities of myocardial structure, systolic function, or hemodynamics.[16] In patients with SLE, the extent to which anticardiolipin antibodies influence valvular, atherosclerotic and myocardial disease is either controversial or uncertain.

The present study is designed to use TDI, strain and strain rate imaging to assess subclinical LV myocardial involvement in SLE and whether such involvement is related to disease activity and presence of anticardiolipin antibody.


  Materials and Methods Top


Patient selection and enrolment

Forty-three young female patients with SLE between 18 and 40 years of age and 20 age-matched healthy controls were included in the study. The diagnosis of SLE was based on criteria defined by the Systemic Lupus International Collaborating Clinics (SLICC) group classification criteria.[17] The presence of cardiovascular risk factors such as hypertension, diabetes mellitus, hyperlipidemia, and smoking were noted. Patients with typical symptoms or signs of heart failure, significant valvular disease, dilated cardiomyopathy, the ejection fraction of <50%, obvious wall motion abnormalities, moderate-to-severe pulmonary arterial hypertension, pericardial effusion, bundle branch block, atrial fibrillation, serum creatinine >1.5 mg/dl, or a creatinine clearance of <30 ml/minute and with pregnancy were excluded from the study.

Clinical disease activity based on the SLEDAI score was obtained. A SLEDAI score ≥6 were considered active disease. Blood samples were investigated for renal function, C-reactive protein, C3, C4, anti-dsDNA antibodies, antinuclear antibodies, anti-cardiolipin antibodies (IgG and IgM) and erythrocyte sedimentation rate. Complete urine analysis was performed.

Conventional two-dimensional transthoracic echocardiography

With 2D-transthoracic echocardiography (TTE), the left atrial dimensions and volume, LV dimensions, and ejection fraction were measured according to the published recommendations of the American society of echocardiography.[18] Cardiac output and cardiac index were calculated from the stroke volume estimated using the modified Simpson's method. Three consecutive cardiac cycles were acquired during breath-hold for the analysis.

Tissue Doppler and strain imaging data acquisition

Pulsed wave TDI was obtained during a brief breath-hold in an apical 4-chamber view. TDI was performed with the sample volume placed on medial and lateral mitral annulus; peak systolic (S'), early (E'), and late (A') peak diastolic velocities were measured. The cardiac cycles were recorded and the acquired data saved for offline analysis. Longitudinal strain was measured using the tissue Doppler method with sample volume placed on basal-septum, mid-septum, distal-septum, basal-lateral, mid-lateral, and distal-lateral wall in apical four chamber view. Average of all six segments considered for mean strain. Longitudinal strain rate (LSR) was studied in the same segments; peak systolic, early and late peak diastolic strain rate per second noted in each segment, and average calculated.

Statistical analysis

Data were entered using the Statistical package SPSS Version 20.0, Chicago, USA. Data were summarized using descriptive statistics: Mean, standard deviation, number, and percentage for qualitative values. The normality of data was assessed using the Shapiro–Wilk test. Statistical differences between groups were tested using the Chi-square test for qualitative variables and independent sample t-test for quantitative variables. Pearson correlation coefficient was calculated for TDI mean of the lateral and medial annulus, strain and strain rate with regard to the SLEDAI score. P ≤ 0.05 was considered statistically significant.


  Results Top


Clinical findings

The mean age of SLE patients was 29.86 ± 5.84 years and of controls was 31.25 ± 5.40 (P = 0.360). There was no difference with regard to the age, body mass index, body surface area, systolic blood pressure, diastolic blood pressure, heart rate, and hypertension between SLE patients and healthy controls [Table 1]. Nearly one-third (31%, 12/38) of the patients with SLE had hypertension; however, they had good control of blood pressure. In comparison, 15% controls (3/20) were hypertensive (P 0.142). Thirteen percent (5/38) of SLE patients had dyslipidemia. None of the SLE and control individuals were smokers or had diabetes. Mean SLEDAI score was 4.36± 4.5, with 39.5% (17/43) having high disease activity (SLEDAI ≥6). 10 (26%) SLE patients were anticardiolipin antibody positive.
Table 1: Characteristics of patients with systemic lupus erythematosus and the control group

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Transthoracic two-dimensional echocardiography

Echocardiographic parameters such as LV dimensions, septal and posterior wall thickness, LV mass, ejection fraction, and cardiac index showed no statistically significant difference between SLE patients and controls. Left atrial volume index (23.26 ± 4.78 vs. 20.92 ± 3.38 ml/m2, P = 0.057) showed trend toward higher values in SLE patients, but was not statistically significant [Table 2].
Table 2: Comparison of two dimensional-echocardiography parameters between systemic lupus erythematosus patients and controls

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Tissue Doppler imaging

TDI measurements at medial mitral annulus (Medial S') and lateral mitral annulus (Lateral S') during systole was significantly less in SLE patients compared to controls (P < 0.05). SLE patients with high disease activity had significantly lower TDI velocities in comparison with low disease activity patients. SLE patients with high disease activity had significant higher E/E' ratio compared to low disease activity (9.04 ± 2.14 vs. 7.49 ± 2.06; P = 0.022). Similar trend was seen with SLE patients compared to controls but was not statistically significant [Table 3]. There was a good correlation of TDI mean of the medial and lateral annulus to the SLEDAI score (correlation coefficient-0.52, P < 0.05).
Table 3: Comparison of tissue doppler and strain imaging in systemic lupus erythematosus patients versus controls and with high versus low disease activity

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Strain imaging

Left ventricular global longitudinal strain was significantly less in SLE patients as compared to healthy controls (−17.2 ± 2.18 vs. −20.94 ± 2.15; P < 0.001). Systolic strain rate (1.18 ± 0.22 vs. 1.49 ± 0.18; P < 0.001) and diastolic strain rate was also less in SLE patients. On subgroup analysis based on disease activity, SLE patients with low disease activity had significant decrease in mean strain rate at systole, early diastole, and longitudinal strain in comparison to that of healthy controls [Figure 1]. Ten patients (23.3%) were positive for anticardiolipin antibody. There was no significant difference in TDI, strain and strain rate between SLE patients in relation to the presence of anticardiolipin antibodies [Supplementary Table 1]. There was good negative correlation between SLEDAI and strain rate (with LSRs r = −0.43, P = 0.007) and strain (r = −0.39, P = 0.03).
Figure 1: Comparison of tissue Doppler imaging systolic velocity, mean longitudinal strain and strain rate at systole among systemic lupus erythematosus patients with lower and higher disease activity using the systemic lupus erythematosus disease activity index score to that of healthy controls

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  Discussion Top


This study shows that young asymptomatic SLE patients without any cardiovascular symptoms demonstrate abnormal LV systolic function as assessed with TDI and strain imaging and correlates with disease activity. SLE patients also had abnormal LV diastolic function as assessed by strain rate. Patients with higher disease activity had significantly higher E/E' compared to those with low disease activity. Among SLE patients, no significant difference was found in the above parameters in relation to the presence of anticardiolipin antibodies.

TDI and strain imaging are useful tools for the detection of LV dysfunction and could be used as a reliable screening for subclinical cardiac manifestations in patients with increased risk for cardiovascular diseases.[6],[19] This study suggests that these methods may be used in asymptomatic SLE patients to assess the presence of LV dysfunction.

Gin et al. used TDI to evaluate LV function in patients with SLE.[20] A trend towards LV dysfunction was observed in the SLE group with lower peak systolic TDI of the mitral annulus, though it was not statistically significant. In the present study, SLE patients had a significant reduction of TDI systolic velocities at medial and lateral mitral annulus compared to healthy controls, despite normal ejection fraction and cardiac output. SLE patients with high disease activity have lower TDI systolic myocardial velocity in comparison to lower disease activity patients. Unlike Buss et al. and Allam et al., no significant decrease in diastolic myocardial velocity using TDI in SLE patients as compared to healthy individuals was seen, which might be due to different disease activity status and disease duration.[14],[21] Similar to the present study, Lee et al. had observed a higher E/E' ratio in SLE patients with high disease activity than low disease activity patients, suggesting diastolic dysfunction.[22] As described above, LV longitudinal strain was significantly less in SLE patients compared to controls and in SLE patients with high disease activity compared to low disease activity. This was in accordance with Buss et al.[14] There was a significant correlation of longitudinal myocardial dysfunction as measured by strain with disease activity SLEDAI score.

SLE due to chronic inflammatory process can alter LV structure and function and lead to subclinical vasculitis, myocarditis, and premature CAD.[4],[23] This can lead to an increased prevalence of subclinical LV dysfunction, which may be a prognostic indicator of cardiac morbidity and mortality. Since the use of steroid therapy, vasculitis and myocarditis have been decreased in SLE patients.[24] Reported CAD prevalence ranges from 6% to 10% in SLE.[4],[25] Cardiac magnetic resonance imaging (MRI) demonstrated that T2 relaxation times were significantly longer in active SLE patients compared to healthy controls; such abnormalities are a sensitive indicator of myocardial disease even in the absence of myocardial involvement clinically.[26] Tc-99 m sestamibi myocardial perfusion single-photon-emission computed tomography also demonstrated a high incidence of myocardial perfusion abnormalities in asymptomatic SLE patients without any signs of cardiac involvement.[27] Both scintigraphy and MRI may be useful in the diagnosis of myocarditis but are usually not used routinely as a screening method.

The present study has a few limitations. Tissue Doppler-based strain was used as we did not have speckle tracking at the time of the study. We did not follow-up patients with high disease activity to see the change in TDI and strain in response to therapy. The sample size was relatively small. Although all echocardiogram was done by single operator with no consequent inter-observer variation, we did not systematically study intra-observer variation.


  Conclusion Top


Asymptomatic SLE patients showed impaired LV systolic and diastolic function compared to healthy controls, which was significantly associated with enhanced disease activity. Routine 2D-Echocardiography often lacks sensitivity to identify early subclinical involvement. TDI and strain imaging are useful as early indicators of LV dysfunction and for screening subclinical cardiac manifestations. The clinical significance of this dysfunction needs to be established in long-term studies to determine whether the detection of such abnormalities in otherwise asymptomatic subjects should affect their disease activity index and therapeutic management. Moreover, the use of these imaging techniques could help a better understanding of the prevalence and mechanisms of cardiac involvement in SLE patients.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Abu-Shakra M, Urowitz MB, Gladman DD, Gough J. Mortality studies in systemic lupus erythematosus. Results from a single center. I. Causes of death. J Rheumatol 1995;22:1259-64.  Back to cited text no. 1
    
2.
Ward MM. Premature morbidity from cardiovascular and cerebrovascular diseases in women with systemic lupus erythematosus. Arthritis Rheum 1999;42:338-46.  Back to cited text no. 2
    
3.
Abusamieh M, Ash J. Atherosclerosis and systemic lupus erythematosus. Cardiol Rev 2004;12:267-75.  Back to cited text no. 3
    
4.
Doria A, Iaccarino L, Sarzi-Puttini P, Atzeni F, Turriel M, Petri M. Cardiac involvement in systemic lupus erythematosus. Lupus 2005;14:683-6.  Back to cited text no. 4
    
5.
Crozier IG, Li E, Milne MJ, Nicholls MG. Cardiac involvement in systemic lupus erythematosus detected by echocardiography. Am J Cardiol 1990;65:1145-8.  Back to cited text no. 5
    
6.
Uribe AG, Vilá LM, McGwin G Jr, Sanchez ML, Reveille JD, Alarcón GS. The systemic lupus activity measure-revised, the Mexican systemic lupus erythematosus disease activity index (SLEDAI), and a modified SLEDAI-2K are adequate instruments to measure disease activity in systemic lupus erythematosus. J Rheumatol 2004;31:1934-40.  Back to cited text no. 6
    
7.
Abraham TP, Dimaano VL, Liang HY. Role of tissue Doppler and strain echocardiography in current clinical practice. Circulation 2007;116:2597-609.  Back to cited text no. 7
    
8.
Garcia MJ, Thomas JD, Klein AL. New Doppler echocardiographic applications for the study of diastolic function. J Am Coll Cardiol 1998;32:865-75.  Back to cited text no. 8
    
9.
Katz WE, Gulati VK, Mahler CM, Gorcsan J 3rd. Quantitative evaluation of the segmental left ventricular response to dobutamine stress by tissue Doppler echocardiography. Am J Cardiol 1997;79:1036-42.  Back to cited text no. 9
    
10.
Yip GW, Shang Q, Tam LS, Zhang Q, Li EK, Fung JW, et al. Disease chronicity and activity predict subclinical left ventricular systolic dysfunction in patients with systemic lupus erythematosus. Heart 2009;95:980-7.  Back to cited text no. 10
    
11.
Heimdal A, Støylen A, Torp H, Skjaerpe T. Real-time strain rate imaging of the left ventricle by ultrasound. J Am Soc Echocardiogr 1998;11:1013-9.  Back to cited text no. 11
    
12.
Urheim S, Edvardsen T, Torp H, Angelsen B, Smiseth OA. Myocardial strain by Doppler echocardiography. Validation of a new method to quantify regional myocardial function. Circulation 2000;102:1158-64.  Back to cited text no. 12
    
13.
Chow PC, Ho MH, Lee TL, Lau YL, Cheung YF. Relation of arterial stiffness to left ventricular structure and function in adolescents and young adults with pediatric-onset systemic lupus erythematosus. J Rheumatol 2007;34:1345-52.  Back to cited text no. 13
    
14.
Buss SJ, Wolf D, Korosoglou G, Max R, Weiss CS, Fischer C, et al. Myocardial left ventricular dysfunction in patients with systemic lupus erythematosus: New insights from tissue Doppler and strain imaging. J Rheumatol 2010;37:79-86.  Back to cited text no. 14
    
15.
Leung WH, Wong KL, Lau CP, Wong CK, Liu HW. Association between antiphospholipid antibodies and cardiac abnormalities in patients with systemic lupus erythematosus. Am J Med 1990;89:411-9.  Back to cited text no. 15
    
16.
Farzaneh-Far A, Roman MJ, Lockshin MD, Devereux RB, Paget SA, Crow MK, et al. Relationship of antiphospholipid antibodies to cardiovascular manifestations of systemic lupus erythematosus. Arthritis Rheum 2006;54:3918-25.  Back to cited text no. 16
    
17.
Petri M, Orbai AM, Alarcón GS, Gordon C, Merrill JT, Fortin PR, et al. Derivation and validation of the systemic lupus international collaborating clinics classification criteria for systemic lupus erythematosus. Arthritis Rheum 2012;64:2677-86.  Back to cited text no. 17
    
18.
Lang RM, Badano LP, Mor-Avi V, Afilalo J, Armstrong A, Ernande L, et al. Recommendations for cardiac chamber quantification by echocardiography in adults: An update from the American society of echocardiography and the European association of cardiovascular imaging. J Am Soc Echocardiogr 2015;28:1-39.  Back to cited text no. 18
    
19.
Yu CM, Sanderson JE, Marwick TH, Oh JK. Tissue Doppler imaging a new prognosticator for cardiovascular diseases. J Am Coll Cardiol 2007;49:1903-14.  Back to cited text no. 19
    
20.
Gin PL, Wang WC, Yang SH, Hsiao SH, Tseng JC. Right heart function in systemic lupus erythematosus: Insights from myocardial Doppler tissue imaging. J Am Soc Echocardiogr 2006;19:441-9.  Back to cited text no. 20
    
21.
Allam NT, Darweesh HE, Hamadnalla N, Ashour ZA. Evaluation of left ventricular myocardial function in Egyptian patients with systemic lupus erythematosus: Tissue Doppler study and its relation to disease activity. Egypt Rheumatol 2013;35:217-23.  Back to cited text no. 21
    
22.
Lee SW, Park MC, Park YB, Lee SK. E/E' ratio is more sensitive than E/A ratio for detection of left ventricular diastolic dysfunction in systemic lupus erythematosus. Lupus 2008;17:195-201.  Back to cited text no. 22
    
23.
Asanuma Y, Oeser A, Shintani AK, Turner E, Olsen N, Fazio S, et al. Premature coronary-artery atherosclerosis in systemic lupus erythematosus. N Engl J Med 2003;349:2407-15.  Back to cited text no. 23
    
24.
Bidani AK, Roberts JL, Schwartz MM, Lewis EJ. Immunopathology of cardiac lesions in fatal systemic lupus erythematosus. Am J Med 1980;69:849-58.  Back to cited text no. 24
    
25.
Petri M, Perez-Gutthann S, Spence D, Hochberg MC. Risk factors for coronary artery disease in patients with systemic lupus erythematosus. Am J Med 1992;93:513-9.  Back to cited text no. 25
    
26.
Singh JA, Woodard PK, Dávila-Román VG, Waggoner AD, Gutierrez FR, Zheng J, et al. Cardiac magnetic resonance imaging abnormalities in systemic lupus erythematosus: A preliminary report. Lupus 2005;14:137-44.  Back to cited text no. 26
    
27.
Schillaci O, Lagana B, Danieli R, Gentile R, Tubani L, Barata L, et al. Technetium-99 m sestamibi single-photon emission tomography detects subclinical myocardial perfusion abnormalities in patients with systemic lupus erythematosus. Eur J Nucl Med 1999;26:713-7.  Back to cited text no. 27
    


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