Value of Speckle Tracking Echocardiography for Early Detection of Left Ventricular Dysfunction in Patients with Systemic Lupus Erythematosus.

BACKGROUND: Cardiac dysfunction due to systemic lupus erythematosus (SLE) may be subclinical, but those patients are at high risk for developing clinical heart failure. AIM: The aim of this study is to assess the role of speckle tracking echocardiography (STE) in the early detection of systolic dysfunction in SLE patients. PATIENTS AND METHODS: This was a case-control study. Participants were subdivided into two groups: Group 1 included 50 SLE patients and Group 2 included 50 healthy controls. Clinical evaluation, echocardiography, tissue Doppler, and STE were performed.
RESULTS: Global longitudinal strain (GLS) was significantly reduced in SLE group (-18.95 ± 2.02 vs. -21.4 ± 2.1, P < 0.001). However, there was no significant difference in left ventricular ejection fraction between both groups (P = 0.801). There was a significant positive correlation between the disease duration and age (r = 0.480, P < 0.001), pulmonary artery systolic pressure (PASP) (r = 0.628, P < 0.001), and GLS (%) (r = 0.417, P = 0.012). There was also a significant positive correlation between the disease activity index and GLS (%) (r = 0.7, P < 0.001) and PASP (r = 0.522, P < 0.001).
CONCLUSION: SLE group had GLS % lower than the control group, and this was statistically significant, denoting early systolic dysfunction. Longer duration and high SLE activity index significantly affect GLS. GLS is an excellent noninvasive tool for early detection of subclinical left ventricular systolic dysfunction in SLE patients. Copyright:

INTRODUCTION

Systemic lupus erythematosus (SLE) is a chronic autoimmune systemic inflammatory disorder that can affect many organs such as the skin, heart, joints, and kidneys.[1]

Cardiac disease is common among patients with SLE; it was found that >50% of patients with SLE have cardiac disease.[2] Hence, the American Heart Association considered patients with SLE, especially women, as a high-risk group for cardiovascular diseases.[3]

Several cardiac diseases have been reported to be involved in patients with SLE; they include pericarditis (the most common cardiac involvement occurring in 11%–54% in patients with SLE),[4] valvular regurgitation, valvular vegetation (e. g., Libman–Sacks endocarditis with a prevalence rate of 11%),[5] myocardial dysfunction, and coronary arteries disease.[6]

Cardiac involvement in SLE may be clinically silent, but it significantly affects morbidity and mortality.[7] The detection of this subclinical involvement offers better management to those patients with SLE.

Echocardiography is a noninvasive and accessible method used to assess cardiac involvement in SLE patients.[1] It can be used in screening the systolic and diastolic function, valvular dysfunction, and measure global longitudinal strain (GLS) to detect early myocardial dysfunction and subsequently prevent early mortality.

The aim of this study was to assess the left ventricular systolic function in asymptomatic SLE patients by echocardiography to detect subclinical dysfunction before developing overt clinical cardiomyopathy.

PATIENTS AND METHODS

Study design and patient selection

A single-center, case–control study that was conducted at Cardiology Department Kafr Elsheikh University Hospital, Egypt, during the period from October 2018 to May 2019 after having approval from the local ethics committee. The study enrolled one hundred patients who were subdivided into two groups. Fifty patients with SLE who fulfilled at least four of the updated revised criteria of the American College of Rheumatology for SLE diagnosis (Serositis, oral ulcers, arthritis, photosensitivity, blood disorders, renal involvement, antinuclear antibodies, immunologic phenomena, e.g., ds-DNA, anti-Smith antibodies)[8] and good left ventricular ejection fraction (LVEF) >50% as study group and fifty age, sex and risk factors matched patients as a control group. Informed consent was taken from all participants.

Patients with LVEF <50%, ischemic heart disease (diagnosed by echocardiography or stress test), congenital heart disease, any rhythm other than sinus rhythm, poor echocardiographic window, and patient refusal were excluded from the study.

Echocardiography

All echocardiographic examinations were performed and recorded for offline analysis using a Philips EPIQ 7C, Release 1.7 (Philips Healthcare, Andover, MA, USA) machine with Q lab 10.4, an S5-1 probe, and simultaneous electrocardiogram (ECG) signal.[9]

Conventional echocardiography

A modified biplane Simpson's method was used to calculate left ventricular end-systolic volume (LVESV), left ventricular end-diastolic volume (LVEDV), and LVEF.[9]

Pulsed wave Doppler was used to recording trans-mitral flow at the tips of the mitral leaflets in the apical four-chamber view: Peak velocity of early (E), late (A) atrial diastolic filling of the Doppler Mitral flow and E/A ratio were calculated.[10]

Left atrial volume index (LAVI) was calculated from apical four-chamber and apical two-chamber views at end-systole and indexed by body surface area.

Tissue Doppler imaging

In the apical four-chamber view, pulsed wave tissue Doppler imaging across septal and lateral mitral annulus was used to obtain the following parameters:

Peak diastolic velocity during the early filling stage at septal, and lateral mitral annulus (é), the mean (é) was calculated

Average E/é velocities

Peak systolic myocardial velocity (S) at the septal and lateral mitral annulus, the mean (S) was calculated.[11]

Speckle tracking echocardiography

Images from the apical four-chamber, two-chamber, and three-chamber views with ECG gating were acquired. The gain settings were optimized, and the gray-scale frame-rate was kept >70 frames/s. Three cardiac cycles were acquired for each loop. All the images were acquired in breath-hold to avoid any breathing artifacts.[12] In the end-systolic frame, the endocardial border was traced in its entirety. The software generated a region-of-interest (ROI) to include the entire myocardial thickness. The width of the ROI was manually adjusted. The strain values for all the segments were recorded and averaged to obtain the GLS.

Statistical analysis

Data management and statistical analysis were performed using SPSS vs. 25 (IBM, Armonk, New York, United States). Numerical data were summarized as the means and standard deviations or medians and ranges. Categorical data were summarized as numbers and percentages. Numerical data were compared using the independent t-test, while categorical data were compared using the Chi-square test. One-way analysis of variance test was used to compare more than two groups as regards the quantitative variable. Correlation analysis was performed using Spearman's correlation. All P values were two-sided. P values < 0.05 were considered significant.

RESULTS

The mean age for the control group was (30.4 ± 7.4) and (30.8 ± 7.6) years for the SLE group with no significant difference (P = 0.923).

Six patients (12%) were diabetic in the control group, while only three patients (6%) in the SLE group with no significant difference (P = 0.486). The number of hypertensive patients was the same in the control group and SLE group 18 patients (36%) (P = 1).

The mean systolic blood pressure was (126.4 ± 13.9 vs. 126.5 ± 14.7, P = 0.931) and the mean diastolic blood pressure was (71.8 ± 6.61 vs. 82.3 ± 11.3, P = 0.878) in control group versus SLE group, respectively.

The mean disease duration was 6.43 ± 6.2 (years) with a range of (0.5–22.0), while the mean disease activity index was 16.4 ± 13.9 and the median was 9 with a range of (4–50).

Echocardiographic parameters

There was no significant difference in LVEDV (P = 0.134), LVESV (P < 0.691) and LVEF (P = 0.801) [Figure 1].

Figure 1

Comparison between systemic lupus erythematosus and control group in conventional echocardiographic parameters

There were no statistically significant differences between the control group and the SLE group regarding S-wave velocity, E-wave velocity, A-wave velocity, E/A ratio, average E/é, tricuspid regurge systolic jet velocity, and LAVI, but there was a statistically significant difference regarding mean é wave velocity. Furthermore, there were statistically highly significant differences between the control group and the SLE group regarding apical four-chamber longitudinal strain (AP4C LS), apical two-chamber longitudinal strain (AP2C LS), apical three-chamber longitudinal strain (AP3C LS) and GLS [Table 1].

Table 1

Comparison between the control group and Systemic lupus erythematosus regarding echocardiographic parameters

Variable	SLE group (n=50)	Control group (n=50)	T-test	P
Mean S (cm/s)
Mean±SD	9.82±0.58	9.74±0.56	0.73	0.498
Range	6.2–10.7	7.1–10.7
AP4C longitudinal strain (%)
Mean±SD	−19.19±3.18	−21.4±2.69	3.78	<0.001 (HS)
Range	−25–−12.5	−27.1–−15.2
AP2C longitudinal strain (%)
Mean±SD	−19.27±2.21	−22.8±3.0	4.25	<0.001 (HS)
Range	−23.2–−11	−29.1–−15.4
AP3C longitudinal strain (%)
Mean±SD	−17.47±2.17	−20.1±2.14	6.02	<0.001 (HS)
Range	−23–−11	−24.2–−15.4
GLS (%)
Mean±SD	−18.95±2.02	−21.4±2.1	5.56	<0.001 (HS)
Range	−23.63–−14.83	−24.8–−15.8
E velocity (cm/s)
Mean±SD	93.8±15.85	95.19±14.31	0.46	0.646
Range	67–132	69–124
A velocity (cm/s)
Mean±SD	72.96±17.54	70.1±11.21	0.234	0.476
Range	39–116	47–89
Mean e`(cm/s)
Mean±SD	15.7±1.8	16.5±1.07	2.55	0.008 (S)
Range	9.35−19.7	14.9−20
E/A ratio
Mean±SD	1.33±0.13	1.35±0.14	0.436	0.664
Range	1.16–1.92	1.1–1.6
Average E/e`
Mean±SD	6.42±1.1	5.7±1.25	1.39	0.167
Range	4.08–9.17	3.52–8.5
Pulmonary artery systolic pressure
Mean±SD	31.98±10	29.6±9.3	1.16	0.245
Range	18−68.5	18−62
TR velocity (m/s)
Mean±SD	2.12±0.26	2.4±0.35	1.51	0.132
Range	1.6–2.6	1.8–3.4
LAVI (ml/m2)
Mean±SD	21.62±3.82	21.62±2.89	0.0	1
Range	16–31	16–31

AP4C=Apical 4 chambers, AP2C=Apical 2 chambers, AP3C=Apical 3 chambers, GLS=Global longitudinal strain, TR=Tricuspid regurge, LAVI=Left atrial volume index, SD=Standard deviation, SLE=Systemic lupus erythematosus

Correlation between disease duration and studied parameters

There was statistically high significant positive correlation between the disease duration and age (r = 0.480, P < 0.001) and pulmonary artery systolic pressure (PASP) (r = 0.628, P < 0.001). Furthermore, there was statistically significant positive correlation between the disease duration and AP4C LS (%) (r = 0.341, P = 0.031), AP2C LS (%) (r = 0.389, P = 0.024), AP3C LS (%) (r = 0.403, P = 0.022), and GLS (%) (r = 0.417, P = 0.012), while there was no significant difference between the disease duration and the remaining parameters [Table 2].

Table 2

Correlation between disease duration and studied parameters

Variable	Duration of the disease
	r	P
Age (years)	0.480	<0.001
Weight (kg)	0.078	0.592
Height (cm)	−0.182	0.206
BMI (Kg/m2)	0.227	0.112
SBP (mmHg)	−0.075	0.606
DBP (mmHg)	−0.059	0.683
LVEDV (ml)	−0.245	0.087
LVESV (ml)	−0.213	0.137
LVEF (%)	0.000	0.999
AP4C LS (%)	0.341	0.031
AP2C LS (%)	0.389	0.024
AP3C LS (%)	0.403	0.022
GLS (%)	0.417	0.012
Mean é	0.145	0.314
E velocity (cm/s)	−0.105	0.467
A velocity (cm/s)	0.011	0.939
E/A	−0.095	0.511
Average E/ é	0.141	0.329
PASP	0.628	<0.001

BMI=Body mass index; SBP=Systolic blood pressure; DBP=Diastolic blood pressure; LVEDV=Left ventricular end diastolic volume; LVESV=Left ventricular end systolic function; LVEF=Left ventricular ejection fraction; AP4C LS=Apical 4 chambers longitudinal strain; AP2C LS=Apical 2 chambers longitudinal strain; AP3C LS=Apical 3 chambers longitudinal strain; GLS=Global longitudinal strain; PASP=Pulmonary artery systolic pressure

Correlation between systemic lupus erythematosus disease activity index and studied parameters

There was statistically high significant positive correlation between the disease activity index and AP4C LS (%) (r = 0.679, P < 0.001), AP2C LS (%) (r = 0.654, P < 0.001), GLS (%) (r = 0.7, P < 0.001) and PASP (r = 0.522, P < 0.001) and there was also statistically significant positive correlation between the disease activity index and AP3C LS (%) (r = 0.311, P = 0.042) while there was no significant difference between the disease activity index and the remaining parameters [Table 3 and Figure 2] illustrate the bull's eye of the LV longitudinal strain of one patient with SLE and one healthy control patient.

Table 3

Correlation between systemic lupus erythematosus disease severity index and studied parameters

Variable	Correlation of disease activity index of SLE
	R	P
Age (years)	0.123	0.453
Height (cm)	0.034	0.972
BMI (kg/m2)	0.222	0.342
SBP (mmHg)	0.112	0.441
DBP (mmHg)	0.234	0.098
LVEDV (ml)	0.276	0.081
LVESV (ml)	0.071	0.891
LVEF (%)	0.114	0.622
AP4C LS (%)	0.679	<0.001
AP2C LS (%)	0.654	<0.001
AP3C LS (%)	0.311	0.042
GLS (%)	0.7	<0.001
PASP	0.522	<0.001
Mean é	0.124	0.467
E velocity (cm/s)	0.155	0.326
A velocity (cm/s)	0.176	0.791
E/A	0.234	0.063
Average E/ é	0.302	0.054

SLE=Systemic lupus erythematosus, BMI=Body mass index; SBP=Systolic blood pressure; DBP=Diastolic blood pressure; LVEDV=Left ventricular end diastolic volume; LVESV=Left ventricular end systolic volume; LVEF=Left ventricular ejection fraction; AP4C LS=Apical 4 chambers longitudinal strain; AP2C LS=Apical 2 chambers longitudinal strain; AP3C LS=Apical 3 chambers longitudinal strain; GLS=Global longitudinal strain; PASP=Pulmonary artery systolic pressure

Figure 2

Bull's eye of left ventricular longitudinal strain, (a) patient with systemic lupus erythematosus (global longitudinal strain = −16.1%) and (b) healthy control patient (global longitudinal strain = −25.6%)

DISCUSSION

The advances in treatment modalities of SLE have diminished the rate of death due to infections in those patients. However, death due to cardiac causes still plays a vital role in lupus.[13]

Cardiac involvement has been reported in 40%-50% in an autopsy of patients with SLE, while only 7%–10% are diagnosed during the patients' lifetime.[7]

In our study, we aimed to assess left ventricular systolic function in SLE patients by conventional, two-dimensional speckle tracking echocardiography (STE) for early detection of subclinical left ventricular systolic dysfunction in this group of patients before overt clinical cardiomyopathy ensues.

In our study, the SLE group had lower values of longitudinal strain parameters (AP4C LS, AP2C LS, AP3C LS, and GLS) than the control group with a highly statistically significant difference (P < 0.001). However, there was no significant difference between the two groups in LVEF.

These results are in agreement with those obtained by Nikdoust et al.[14] who found that the results of AP2C LS decreased significantly in the SLE group in comparison with the healthy controls (P = 0.005), in AP3C LS was (P = 0.006), and in LV GLS was (P = 0.02).

Similarly, Du Toit et al.[15] reported that GLS decreased significantly in lupus myocarditis patients in comparison to the healthy control group (P < 0.001).

It is also in agreement with the results obtained by Bakhoum et al.[16] who found that STE showed a significantly lower GLS in the SLE group (P < 0.001). Similar results were obtained by Buss et al.[17] and Guşetu et al.[18] who reported that longitudinal strain was significantly reduced in the SLE group (P < 0.05 and P = 0.001, respectively). In a metanalysis done by Di Minno et al.[19] to evaluate the role of speckle tracking in patients with SLE, they found that GLS was significantly lower in SLE patients than non-SLE controls (P < 0.001).

The GLS was early impaired in SLE patients before deterioration of LVEF, indicating an increase in the prevalence of subclinical myocardial involvement of those patients. This can be explained by the accumulation of inflammatory markers in subendocardium leading to myocarditis, vasculitis, and preterm coronary artery disease. Hence, early detection of subclinical myocardial involvement is crucial to decrease morbidity and mortality.

Furthermore, from these results, the reduction of longitudinal strain precedes the reduction of LVEF. Hence, it can be used as a predictor for early detection of systolic dysfunction rather than conventional LVEF.

In our study, The SLE group had lower values of mean é velocity than the control group with P = 0.05.

These results are in agreement with the results obtained by Bakhoum et al.[16] and Du Toit et al.[15] who reported that the mean é velocity wave decreased significantly in the SLE group of patients (P = 0.01) and (P < 0.001), respectively.

In our study, there was a statistically significant positive correlation between duration of SLE and the age of studied cases, AP4C LS, AP2C LS, AP3C LS, GLS, and PASP. Furthermore, there was a statistically significant positive correlation between the SLE activity index and AP4C LS, AP2C LS, AP3C LS, GLS, and PASP.

In a study by Acar et al.[20] who studied the relationship between SLE activity index, GLS, aortic stiffness, and left ventricular diastolic function found that SLE disease activity index was negatively correlated with GLS (r = −0.45, P = 0.002).

Furthermore, in the results obtained by Guşetu et al.[18] patients with longer disease duration had significantly lower strain and strain rate parameters (r = −0.025, P = 0.03 and r = −0.241, P = 0.037, respectively). Buss et al.[17] reported that patients with higher disease activity index have lower strain and strain rate values (P < 0.05).

Mirfeizi et al.[21] found that patients with higher disease severity index and longer disease duration had higher pulmonary artery pressure rates (r = 0.34, P = 0.024) and (r = 0.43, P = 0.004), but there was no correlation found between disease severity index or disease duration and left ventricular systolic function parameters. This may be attributed to the differences in clinical demographics, disease duration, and severity index from our study.

Furthermore, Du Toit et al.[15] showed no significant correlation between SLE activity index, disease duration, and GLS. This can be explained by their inclusion criteria. They included clinically evident lupus myocarditis patients who were excluded from our study.

In the current study, disease duration and severity index can affect the systolic function. However, some studies did not report the correlation between them. Regular echocardiographic examination to SLE patients is recommended for early detection of cardiac involvement.

The effect of drug therapy on echocardiographic parameters, primarily GLS, should be investigated. As to our knowledge, no studies investigate the role of hydroxychloroquine or other drugs used in the treatment of SLE on the improvement of GLS value in those patients. More extensive studies with longer follow-up period are recommended to assess whether the impairment of GLS will improve or remain unchanged.

CONCLUSION

SLE group had GLS % lower than the control group, and this was statistically significant, denoting early systolic dysfunction. Longer duration and high SLE activity index significantly affect GLS. GLS is an excellent noninvasive tool for early detection of subclinical left ventricular systolic dysfunction in SLE patients.

Study limitation

Some limitations were noted in our study, including the limited number of patients in the study, and strict exclusion criteria may explain this.

The patients diagnosed with subclinical LV dysfunction did not undergo additional imaging or invasive tests as myocardial perfusion imaging or coronary angiography to exclude ischemic causes of this subclinical dysfunction. No follow-up was done to those patients. Hence, more extensive studies with follow-up period are recommended.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.