Background: Cardiovascular diseases increase morbidity and mortality in patients with systemic lupus erythematosus (SLE).The cardiac involvement could be silent. Echocardiography can be used as a noninvasive tool for the assessment of the ventricular function.

Objectives: We sought to evaluate different echocardiographic parameters via tissue Doppler imaging and speckle-tracking echocardiography (STE) in addition to conventional echocardiography.

Patients and Methods: This case-control study was conducted in 45 SLE patients (88% female; mean age = 31.2 ± 8.2 years) and 25 healthy controls (87% female; mean age = 30.3 ± 7.7 years), matched in terms of age and sex. Both groups had no clinical signs and symptoms of cardiac problems or risk factors for cardiovascular diseases. Both SLE and control groups underwent echocardiography for the assessment of the ventricular function and the sizes and diameters of the chambers. Two-dimensional STE was used for the measurement of the left ventricular (LV) global longitudinal systolic strain.

Results: The mean duration of SLE was 5.5 ± 3.4 years in our patients. No significant difference was found between the two groups concerning the LV and left atrium size, LV ejection fraction, right ventricular (RV) systolic function, RV and LV diastolic function, and pulmonary artery pressure. The LV global longitudinal strain was less in the SLE patients (-18.56 ± 2.50% vs. -19.89 ± 1.94%; P = 0.028). The LV mass was greater, though not statistically significant, in the SLE patients (111 ± 29.54 g vs. 104.37 ± 27.39 g; P = 0.468). The interventricular septal diameter was thicker in the SLE patients (0.79 ± 0.15 cm vs. 0.77 ± 0.10 cm; P = 0.046).

Conclusions: Silent ventricular systolic dysfunction was more common in the patients with SLE than in the control group. Newer echocardiographic techniques such as two-dimensional STE provide an earlier chance for the detection of subclinical LV systolic dysfunction. Our findings were independent of the traditional risk factors.

Systemic lupus erythematosus (SLE) is an autoimmune disease occurring at any age. Cardiovascular diseases could increase morbidity and mortality in SLE patients (1). Recently, coronary heart disease and stroke have been reported more frequently than before in SLE patients. Research has shown that, in contrast to control groups, controlling the Framingham risk factors alone cannot decrease coronary heart disease and stroke in patients with SLE (2, 3). Chronic inflammation and the drugs used to treat it (e.g. corticosteroids) may have a role in increasing the frequency of cardiovascular diseases. The use of glucocorticoids has decreased death due to infection and active disease, but the persisting cardiovascular etiology could play a leading role in decreasing SLE survival. Recently, Huang et al. (4) used three-dimensional (3D) speckle-tracking echocardiography (STE) and suggested that SLE was an independent factor for the left ventricular (LV) systolic function. In two other studies, myocardial involvement was seen in as many as 40% - 50% of the SLE patients in autopsy (5), while myocardial injury was found clinically in only 7% - 10% of the SLE patients (6). The LV diastolic dysfunction, albeit clinically silent, has also been reported in SLE patients (7). The precise estimation of myocardial status in SLE patients is important for patient management.

For the screening and diagnosis of subclinical heart diseases, noninvasive techniques such as echocardiography are relatively simple and universally available; the reported results have, however, been conflicting. The present study used STE in addition to conventional echocardiography and tissue Doppler imaging (TDI) in Iranian SLE patients to assess multiple variables of systolic and diastolic ventricular function. Moreover, given the dearth of data on the right ventricle (RV) in SLE, this cardiac chamber was assessed as well.

STE has been widely used in different cardiovascular disorders to define even subtle myocardial dysfunction. Our aim was to determine whether this technique could add any further information to conventional echocardiographic imaging modalities such as two-dimensional (2D) echocardiography and TDI.

Forty-five patients with a diagnosis of SLE confirmed by an expert rheumatologist were recruited in this case-control study, conducted between 2011 and 2013. The subjects were selected consecutively from the patients visiting a rheumatologic clinic (Imam Reza Hospital). The included SLE patients did not have any clinical signs or symptoms of cardiac problems, history of heart disease, or conventional risk factors for atherosclerosis (i.e. hypertension, hyperlipidemia, diabetes mellitus, and cigarette smoking). Also enrolled were 25 healthy volunteer subjects, who were the colleagues or family members of the study author and had no clinical evidence of cardiac or systemic disorders. Having an age range and sex ratio similar to those in the SLE group was considered while selecting the controls.

A questionnaire on the systemic lupus erythematosus disease activity index (SLEDAI) was employed to evaluate the disease severity (8).

This study was carried out in accordance with the code of ethics of the World Medical Association (declaration of Helsinki) for experiments involving humans and obtained the approval of the Research Ethics Committee of Mashhad University of Medical Sciences (Registration # 2271). An informed written consent was obtained from each participant.

Both SLE and control groups underwent echocardiography (conventional, TDI, and 2D-STE).

The study population was comprised of 45 SLE patients including 38 (84.4%) females at a mean age of 31.38 ± 8.09 years and 25 healthy individuals as the control group including 19 (76%) females at a mean age of 30.20 ± 7.74 years. Both groups were matched in terms of age (P = 0.555) and sex (P = 0.391). Neither the SLE patients nor the control group had risk factors for cardiovascular diseases, including hypertension, hyperlipidemia, diabetes mellitus, cigarette smoking, and family history of cardiovascular diseases.

The SLEDAI score was 8.3 ± 5.1 in the SLE patients. The SLE duration was 5.5 ± 3.4 years. The disease severity was estimated as mild to moderate according to the calculated score. All the patients were on corticosteroid therapy, but the total daily dose of prednisolone was not high (less than 30 mg).

All the measured echocardiographic variables are depicted in Table 1.

Table 1. Echocardiographic Variables in the Systemic Lupus Erythematosus Patients and the Control Group (by Conventional Study, Tissue Doppler Imaging, and Speckle Tracking) a,b,c

The LVEF, size and thickness of the chambers, pulmonary artery pressure, and mitral and tricuspid inflows were assessed by conventional echocardiography. TDI was used to measure the systolic and diastolic functions of the RV (TDI-derived RIMP and longitudinal strain and S’ and E’ velocities) and the systolic and diastolic functions of LV (S’ and E’ velocities). The GLS was the only parameter measured by 2D-STE.

The SLE patients had a lower EF (57.21 ± 4.90 vs. 58.98 ± 3.72; P = 0.152) and mitral annulus S’ velocity (6.92 ± 1.17 cm/sec vs. 7.04 ± 1.01 cm/sec; P = 680); the difference however, did not constitute statistical significance. The GLS was significantly lower in the SLE patients than in the control group (-18.56 ± 2.50% vs. -19.89 ± 1.94%; P = 0.028).

As regards the LV diastolic dysfunction, the SLE patients did not show this condition more frequently than the controls.

The SLE patients had a greater LV mass (111 ± 29.54 g vs. 104.37 ± 27.39 g; P = 0.468) and interventricular septal thickness at end-diastole (0.79 ± 0.15 cm vs. 0.77 ± 0.10 cm; P = 0.046).

The minimum value of the tricuspid annulus was 8 cm/sec. The range for the deceleration time of the tricuspid inflow was 135 - 230 msec and the E/A and E/E’ ratios were 0.88 - 2 and 2.14 - 6.25, respectively.

None of the subjects had evidence of the RV diastolic dysfunction considering the cut-off values suggested in the latest related guideline (9).

RIMP, tricuspid annulus S’ velocity, and strain imaging (TDI-derived) were used for the assessment of the RV systolic function, which showed no significant differences between the two groups.

4.1. Inter- and Intraobserver Variability

The main echocardiographic parameter was the GLS, for which there was a high inter- and intraobserver agreement (inter-class correlation coefficient [ICC]: 0.95, 95% confidence interval [CI]: 0.8-0.98; P < 0.001 and ICC: 0.91, 95%CI: 0.67 to 0.98; P < 0.001, respectively).The intra- and interobserver agreement was worse in the assessment of the RV strain than in the RIMP (ICC: 0.86, 95%CI: 0.46 to 0.96; P < 0.001 vs. ICC: 0.83, 95%CI: 0.32 to 0.96; P = 0.007, respectively) (Table 2).

Table 2. Inter- and Intra-observer Agreement (n = 10) in the Three Main Measurements a,b

The present study confirmed the role of echocardiography in the early detection of cardiovascular dysfunction in SLE patients. We excluded patients with coronary heart disease risk factors because some studies have suggested that cardiovascular problems in patients with SLE could be attributable to the traditional coronary artery disease risk factors (such as hypertension, dyslipidemia, and diabetes mellitus), all of which may be provoked by corticosteroid therapy (11, 12). Nonetheless, the underlying disease may be atherogenic by itself through its chronic activation of the immune system (3).

The underlying inflammatory processes leading to subclinical vasculitis, myocarditis, or vascular stiffening could result in such changes in the ventricular structure as ventricular remodeling and subsequent hypertrophy (13). The greater septal thickness and LV mass (though insignificant in the latter) in SLE may be due to the increase in the afterload and systolic blood pressure. An increase in the LV mass can cause a rise in the end-diastolic volume because of the difficulty to stretch the myocardial fiber in a ventricle with reduced compliance (14).

Pieretti et al. (15) suggested that inflammation-mediated arterial stiffening was the underlying mechanism for the LV hypertrophy in SLE and that it was not exclusively a result of associated ischemic or valvular heart disease, renal failure, premature subclinical atherosclerosis, or hypertension. The increases in arterial stiffness, documented in SLE patients, seem to be directly related to the chronicity of the disease and the circulating markers of inflammation (16). The LV hypertrophy could result in stroke, coronary heart disease, congestive heart failure, and sudden cardiac death in different patient groups. Accordingly, the LV hypertrophy may be deemed a prognostic factor for cardiac morbidity and mortality in SLE patients (17). Our literature review yielded conflicting results vis-à-vis the ventricular size and function in SLE (18-25).

We found no significant differences concerning the conventional measurements of the internal systolic and diastolic diameters and functions of the chambers. The LVEF was not significantly different between the SLE and control groups in our study, chiming in with the results of the studies by Nagueh et al. (21) and Enomoto et al. (22).

In a study on 104 SLE patients compared with 104 age- and sex-matched controls, the E/E’, left atrial volume index, LV mass index, pulmonary artery pressure, and RV dimension were significantly higher in the patient group (25).

In a study by Buss et al. (23), the systolic and myocardial velocities defined by TDI were impaired in the 67 SLE patients compared to the control group; the results were confirmed by strain and strain rate imaging. In a case-control study by Wislowska et al. (24), there were no statistically significant differences in the systolic heart function between the SLE and control groups. The authors also reported that the EF was lower in the SLE patients but in the subgroups with a long disease duration. In addition, the diastolic function was impaired significantly, showing higher mitral A’ velocity and lower E’/A’ ratio, which is not compatible with our results (in both LV and RV).

There is a paucity of data on the RV function in SLE in the existing literature. In one of these few studies, Leal et al. (26) recently recruited 35 childhood-onset SLE patients and found a significant reduction in the RV longitudinal systolic strain (but not strain rate). The results of our study on an adult population showed that the systolic and diastolic function of the RV, assessed in terms of RIMP, S’ velocity, and TDI-derived strain analysis, were not impaired. We conclude that the LV seems to be more vulnerable than the right heart in SLE patients.

As was previously mentioned, for all the research on the assessment of the ventricular function mostly targeting the LVEF, S’ velocity, and TDI-derived strain, the data on 2d-STE are limited. Recently, Huang et al. (4) used 3D-STE and demonstrated that the peak systolic GLS was -18.2 ± 2.9% in their SLE patients. All the patients were followed up for one year, and no cardiovascular events or symptoms necessitating further work-up were detected. Nevertheless, it seems that a longer follow-up duration is needed to define the clinical importance of the detected LV dysfunction in an otherwise asymptomatic SLE patient.

An abnormal LV function could be detected in SLE patients even in those without cardiac symptoms or coronary heart disease risk factors. STE is a valuable method for detecting such subclinical myocardial dysfunction and seems to be superior to conventional echocardiography.

This work was extracted from a student thesis (# 900729), supported by a grant from the Research Council of Mashhad University of Medical Sciences.