La tunisie Medicale - 2019 ; Vol 97 ( n°02 ) : 373-378
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Summary

Introduction :  Echocardiography is   a non invasive tool for the assessment of   systemic lupus erythematesus  (SLE)  involvement  .

Aim of study:  to investigate the cardiac involvement in patients diagnosed with SLE assessed  by echocardiography  and  to  study relationship between several factors and  cardiac manifestation .
Methods :   retrospective study  of 76 patients with diagnosis of SLE between   2008  and 2017.   All patients were asssesed by echocardiography  .Patients were  assigned  into cardiac abnormalities group    and non cardiac  abnormmalties  and  compared  to  study relations between several factors and  cardiac manifestation .
Result :Cardiac involvement was found in echocardiography in 52% of patients (40 patients.  
Echocardiographic findings showed  12 cases ( 38 %) of pericardial effusion . Valvular  abnormalities were observed in  19 cases (48 %),  Myocardium was involved in 5 cases ( 12.5 %). there were no cases  of myocarditis   , High arterial pulmonary hypertension was reported in  4  cases (10%).
Men   were  more vulnerable  to  cardiac involvement in lupus , there was signifiant relationship  between  disease  duration and cardiac abnormalities  (p 0.04 ), age  was not  associated  significantly to  echocardiographic  abnormalites ,positif antiphospholipid  antibodies(aPL+)  was   observed in  higher  frequency in   cardiac involvement  group with p<0.01 and especially in  valvular anomalies 

Conclusion : Echocardiography should be routinely indicated for evaluation of cardiac involvement during SLE. These manifestations   are most often moderate and asymptomatic. Pericardial effusion, and valvular involvement were the most frequent abnormalities.

Key - Words
Article


Introduction :
In the past, cardiac manifestations associated to systemic lupus erythematosus (SLE) were severe and life threatening, often leading to death. Therefore, they were frequently found in post-mortem examinations.
Nowadays cardiac manifestations are often mild and asymptomatic. However, they can be frequently recognized by echocardiography. All the anatomical heart structures can be affected during SLE severel mechanisms have been reported.
Therefore echocardiographic study should be performed periodically in SLE patients to detect cardiac abnormalities at early stage.
Aim of study: To investigate the cardiac involvement in patients diagnosed with SLE assessed by echocardiography and to reveal the characteristics of cardiac manifestations during lupus by comparing two groups of lupus patients with and without cardiac abnormalities.
Methods
We retrospectively reviewed the records of 76 patients with diagnosis of SLE. Between the periode 2008 and 2017 adressed for echocardiography. Diagnosis of SLE was confirmed previously based on the american College of Rheumatology criteria (1) .
Non-inclusion critera were patients with preexisting cardiopathies, coronary arteries disease, mixed connectivites tissue diseases.
We ghatered demographic data, clinical manifestations, lupus disease characteristics (duration and activity of SLE, treatment) and laboratory findings at the time of presentation
Laboratory evaluation included : erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) (concentrations (>6 mg/l was considered positive), antinuclear antibody (ANA) and anti-ds DNA ) and Antiphospholipid antibodies (aPL)
 In case of lacks informations about biological test we systematically realized a new laboratory dosage.
All patients were referred to our echocardiographic department in order to detect cardiac involvement, we assessed left ventricular diameter, ejection fraction and segmental motion of left ventricle, mecanism and quantification of valvulopathies, pulmonary artery pressure and analyzed the pericardium, then patients were assigned into cardiac involvement group (group A) and non-cardiac involvement group (group B). These echocardiographic parameters were compared between the 2 groups of study.
Statistics results: Quantitative variables are expressed as means ± standard deviations. Qualitative variables are expressed as percentage. Comparisons between groups were carried the chi2 test and students test in cases of qualitative or quantitative variables 
Results
Baseline characteristics of our patients were summarized in table1, a total of 76 patients with SLE were assessed, they were 69 females and 7 males. The mean duration of the disease at the time of examination was 18 to years ± 10 with extreme of (10±5 to 25±3 years).
In terms of comorbidities, 12 patients had hypertension and nine had diabete but none of them had previous cardiopathies. Clinical manifestations and laboratory tests were represented in table 1. Fighy five patients (72%) were on hydroxychloroquine, and 50 patients (65%) were on prednisolone. Immunosuppressive treatment included azathioprine was precribed in 23 patients (30%).
Cardiac involvement was found in echocardiography in 53% of patients (n=40 patients) (table 2), 15 patients were asymptomatic (37.5%).
Echocardiographic findings showed 12 cases (30%) of pericardial effusion. It was qualified as minim with posterior localizations in height cases of pericarditis, moderate and circumferential effusion in two cases and abundant with echocardiographic signs of tamponade in 2 cases
Valvular abnormalities were observed in 19 cases (48%), this included thickening without calcification of valves in all cases (figure 1A and B ), a mitral regurgitation in 11 cases, aortic involvement in 2 cases and tricuspid regurgitation in 2 cases( figure2 A and B) and verrucous“Libman Sack’s“ vegetation depending on the anterior mitral valve in four cases (figure 3 ). All the regurgitations were qualified us mild
Myocardium was involved in five cases which were symptomatic of dyspnea including a primary dilated cardiomyopathy in two cases with a mean left ventricular (LV) diameter of 58±5mm, a mean ejection fraction of 42%±2, and a global hypokinesia, all the cases had a mitral profile type III. Eccentric left ventricle hypertrophy was observed in two cases. The septum thickness was of 14 mm in one case and 13 mm in the other case. No cases of myocarditis were reported.
Pulmonary hypertension (PH) was reported in four cases. Mean systolic pulmonary arterial pressure was 59 mmHg with extremes ranging from 38 to 120 mmHg. 
Patients were assigned into cardiac abnormalities group (Group A) and non cardiac abnormalities group (group B) and compared (table 3)
Age was not associated significantly to echocardiographic abnormalities. Men seemed to develop cardiac involvement more than women, there was significant relationship between disease duration and cardiac abnormalities (p = 0.04), active disease (50%) was associated with higher frequency of cardiac involvement than disease in remission (38%) but the result was not statistically significant (p=0.1), positif (a PL +) was observed in higher frequency in cardiac involvement group with p<0.01.
Valvular manifestation was the most frequent abnormality in SLE and was more commun in case of positif (a PL+) (52% versus14%p<0.01).
Discussion
The prevalence of cardiovascular involvement in patients with SLE has been estimated to be more than 50% (2 ). This prevalence, however, varies greatly from study to study, depending on what manifestations are included and whether clinical or subclinical (asymptomatic) disease is considered.
We reported similar results in our study since echocardiography revealed cardiac involvement in 52%. 
Pericarditis is the most common cardiovascular manifestation of SLE, although often not evident clinically, and it is included in the American College of Rheumatology (ACR)(  classification criteria for SLE (1) .
The pericardium can be involved by acute and chronic inflammatory changes; granular deposition of immunoglobulin and C3, demonstrated by direct immunofluorescence, support the role of immune complexes in the development of pericarditis. 
The reported prevalence of pericardial abnormalities detected by echocardiography was 40% and up to 83% in autopsy series (3). In our Study, 15 patients with cardiac abnormalities were asymptomatic. Pericarditis effusion is usually of low abundance, no latent.
Pericardial involvement appears more frequently at SLE onset or during SLE relapses, although it can occur at any time of the disease (4). Pericarditis usually appears as an isolated attack or as recurrent episodes
Cases of constrictive pericarditis along with pericardial tamponade are less frequently reported in the literature (4, 5). We agreed with these authors, in fact we have recorded only two cases of tamponnade.
Non-steroidal anti-inflammatory drugs and/or corticosteroids are the first line of treatment in mild pericarditis. Intravenous bolus of corticosteroid is necessary in more severe cases or if tamponade is present,
Cardiomyopathy in systemic lupus erythematosus (SLE) may be secondary to myocardial inflammation (i.e. myocarditis) or to systemic complications such as hypertension or coronary arteries disease.
The clinical detection of myocarditis ranges from 3 to 15%, although it appears to be much more common in autopsy studies, suggesting the largely subclinical nature of lupus.
Immunofluorescence studies demonstrate fine granular immune complexes and complement deposition in the walls and perivascular tissues of myocardial blood vessels, supporting the hypothesis that lupus myocarditis is an immune complex-mediated disease. Some reports demonstrate an association between anti-SSA/Ro antibodies and myocarditis associated myocarditis (6) .
Echocardiographic study cannot definitely diagnose myocarditis, but global hypokinesis, in the absence of other known causes, is strongly suggestive. Large echocardiographic series have found frequencies of global hypokinesis between 5 and 20%. However, also segmental areas of hypokinesis can be indicative of the disease (7,8) In our study we don’t found any cases of myocarditis.
Recently, other non-invasive investigations such as magnetic resonance, are employed for diagnosing myocardial involvement in SLE: T2 values sensitively indicated myocardial relaxation abnormalities, even at preclinical stage (9).
New methods like Tissue Doppler by studying systolic velocities S at the mitral annulus and 2 D strain are more reliable than EF for the detection of early LV systolic dysfunction [10]. It therefore appears much more sensitive than conventional ultrasound.This notion has been reported in several studies that have shown that despite a normal found ejection fraction, there is a decrease in LV contractility in lupus patients detected by the study of tissue Doppler velocities and 2 D strain. thus attesting to the existence of an early systolic dysfunction underestimated by echocardiography.
Echocardiographic findings in lupus cardiomyopathy include decreased ejection fraction and increased chamber size as it was identified in our study. Prolonged isovolumic relaxation time and decreased deceleration of early diastolic flow velocity and reduced E/A ratio were reported by different authors (11). The diastolic function impairment in LED is the subject of a prospective study in our laboratory.
Hypertrophic cardiomyopathy has been reported in one patient with SLE and in another with a “lupuslike” (12) illness. Whether this occurrence is truly related to the underlying connective tissue disease or merely happened in the same patient is debatable. 
Our study confirmed that valvular disease is one of the most prevalent and clinically important forms of cardiac involvement in SLE patients. Valvular lesions were detected in 48% of all patients, a similar prevalence was found in other studies (5). We noted a large spectrum of valvular diseases, ranging from thickened leaflets to moderate- dysfunction. The most frequent valvular lesions reported in SLE patients were valve regurgitations  with predilection to involve mitral and aortic valves (11).
Similar results were reported in our study since mitral valve regurgitation was the more frequent valvulopathy. An interesting finding in our study was the high frequency of valvular thickening (100%) reported by many authors (5,11), it may represent an early stage of progressive mitral valve involvement.
 Valve disease for most patients was mild. This is consistent with our findings since we noted predominant thickening and mild regurgitation of both mitral valve or aortic valve.
Libman–Sacks endocarditis is another side of characteristic findings in SLE, but has become rarer since treatment with corticosteroids was introduced (13). We agree with these authors since we found only two cases of verrucous vegetation in our work. It is defined as sterile verrucous lesions of the valvular and mural endocardium (13). Libman–Sacks vegetation’s are associated with longer disease duration, higher lupus activity, positive anticardiolipin antibodies and secondary antiphospholipid syndrome (13). 
The prevalence of pulmonary hypertension (PH) in SLE ranges from 0.5 to 17.5%, depending on whether echocardiography or right heart Catheterization is used as the gold standard for diagnosis (14).
In a recent series (15), the frequency of patients with an elevated (PH) estimated by Doppler in a population of SLE patients in a tertiary reference center is 13%. In our study, we found four cases of PH, in one case it was severe reaching 120mmhg. 
We objectivated a relationship betwen cardiac abnormalities in SLE and male gender, disease duration and positif antiphospholipidis antibodies similar results were reported (16-17). In our study, the incidence of valvular regurgitation was more frequent in SLE patients with (a PL+) than in those without (a PL+). In accordance with our results, similar studies reported a higher frequency of valvular régurgitation in SLE patients with (a PL+) (18) .

Limits
0ur study is a retrospective analysis subject to bias. The limited number of patients was another limitation this can be explained by the rarity of the disease. We don’t study many associated factors since it was a transversal echocardiographic study but we found a relation between epidemiological, clinical immulogical parameters and cardiac abnormalities in SLE that would benefit from confirmation by future randomized studies to deduce the causal nature of this relation.

CONCLUSIONS:
Our study shows that cardiac abnormalities are very common in lupus patients even when clinically asymptomatic. These manifestations are often mild. Pericardial effusion, valvular dysfunction are the most frequent abnormalities; we revaled especially the probable pathogenic role of anti-phospholipid antibodies in relation to the valvulmar anomalies.
echocardiography can be helpful as a non invasive diagnostic tool for early detection of cardiac involvement in lupus patient ,resulting in earlier treatment and reduction in mortality and morbidity rates.

No conflict of interest

Figure 1:  A and B: Valvular thickening without calcification


Figure 2:  Aortic(A) and mitral (B) regurgitation


Figure3: Libmar sacks vegetations

Reference
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