Introduction

Systemic Lupus Erythematosus (SLE) is a chronic inflammatory autoimmune disease with multisystem involvement and a female preponderance. SLE has a wide range of cardiovascular manifestations and can involve any part of the heart. The symptoms and clinical findings are non-specific and mimic many other conditions, such that the diagnosis is based on multiple clinical factors and laboratory immunologic measures. Even though cardiac involvement is common in SLE, cardiac findings by themselves are insufficient in making the diagnosis. Cardiac involvement can occur as early as the neonatal period. Neonatal lupus is a congenital disorder linked to high circulating maternal anti-Ro/SS-A auto-antibodies which cross the placenta and result in complete heart block [1,2,3,4]. The leading cause of death in lupus patients with cardiac involvement is coronary artery disease (CAD) with the risk estimated to be at least doubled that of the general population [5]. Premature and accelerated atherosclerosis has been described as the main pathophysiology of CAD in lupus patients [5].

While it has been estimated in some studies that more than 50% of lupus patients have some sort of cardiovascular involvement, in only 10% of patients is cardiac involvement clinically evident [6, 7]. Indeed, valvular involvement may only be diagnosed after an embolic event which is usually a cerebral vascular event [8]. Echocardiography plays a major role in the non-invasive evaluation of cardiac involvement in lupus patients. Transthoracic echocardiography has been widely used but its sensitivity is limited. Transesophageal echocardiography has higher sensitivity and specificity, and thus should be used when the clinical suspicion remains high despite a negative transthoracic study [9]. In this review, we focus the discussion on the echocardiographic manifestations affecting the pericardium, the myocardium and the endocardium (Fig. 1). The prevalences of the different types of cardiac involvement have wide ranges largely due to the differences in patient population as to whether asymptomatic or symptomatic, the varying degree of disease activity and the presence or absence of antiphospholipid antibodies [1,2,3,4].

Fig. 1
figure 1

Echocardiographic manifestations of Systemic Lupus Erythematosus (SLE). CM, cardiomyopathy

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Pericardial Involvement

Pericarditis is the most common and first recognized cardiac manifestation of SLE. The prevalence of pericarditis is estimated between 12% and 48% [6]. Asymptomatic pericardial involvement is more frequent than clinical pericarditis. Lupus pericarditis presents in a similar fashion to classic pericarditis. Analysis of pericardial fluid shows exudative effusion with increased white blood cells count and predominant polymorphonuclear cells. Marked acidity with pH less than 7 may help in distinguishing lupus pericarditis from other etiologies [6]. Anti-nuclear antibodies should be requested and interpreted with caution as these antibodies are frequently positive in normal individuals. Lupus pericarditis is usually treated with a course of nonsteroidal anti-inflammatory agents and colchicine. The addition of corticosteroids may be required in refractory cases [6, 10].

Cardiac tamponade is uncommon in lupus patients. A series of more than 1300 SLE patients showed that the prevalence of tamponade is < 1% [10]. A female predominance and insidious onset have been observed among lupus patients presenting with tamponade. Tamponade physiology may develop in circumferential as well as loculated effusion where regional tamponade develops that lacks the classical hemodynamic signs [11]. Although uncommon, large pericardial effusion or cardiac tamponade have been described as the first presentations of SLE [12,13,14]. Constrictive pericarditis is rare among SLE patients. Our experience suggests that constriction needs to be considered when there are marked inflammatory changes in the pericardial fluid evidenced by loculation, septation and multiple fibrin strands as demonstrated in our case in Fig. 2.

Fig. 2
figure 2

A. Apical 4 chamber view in an SLE patient with chronic pericardial effusion showing large effusion (5 cm in diastolic diameter) with fibrin strands. B. Subcostal view of the same patient showing RV diastolic collapse. Other features (not shown) included significant respiratory flow variation and dilated, non-collapsible IVC consistent with the diagnosis of cardiac tamponade. C and D. Following pericardiocentesis, there is a significant respiratory inflow variation, pericardial thickening and leftward septal shift with inspiration. Other features (not shown) included septal bounce and annulus reversus (Septal e’ > Lateral e’) consistent with the diagnosis of effusive-constrictive pericarditis. The patient underwent surgical pericardiectomy. RV, right ventricle. IVC, inferior vena cava

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Myocardial Involvement

Myocarditis is the most distinctive feature of lupus-related myocardial involvement. However, in the recent era of corticosteroids and advanced immunomodulator therapy, clinical myocarditis is uncommon. Echocardiographic features include global hypokinesis in the absence of underlying coronary artery disease [15]. SLE has been associated with increased LV mass and diastolic dysfunction possibly secondary to inflammation-related arterial stiffness [16]. Moreover, SLE patients have impaired LV systolic function on the basis of LV ejection fraction compared to normal subjects. Advanced echocardiographic techniques like speckle tracking echocardiography (STE) may be used to measure LV global longitudinal strain (GLS) and detect myocardial dysfunction before the drop in ejection fraction occurs and may play a role in risk stratification [17].

SLE related cardiomyopathy, like almost all other cardiac manifestation, is a diagnosis of exclusion that can be made after ruling out more common causes like coronary artery disease and hypertensive heart disease. Etiology has not been clearly defined but may be related to microvascular damage and diffuse small vessel disease. The risk of heart failure morbidity and mortality is substantially increased in lupus patients. There is an estimated > 2.5-fold increased risk of hospitalization and > 3.5-fold increased risk of mortality among SLE patients with heart failure compared to general population with heart failure [18]. A reversible form of restrictive cardiomyopathy related to hydroxychloroquine therapy has been described. It is thought to be related to hydroxychloroquine toxicity which can be reversed with cessation of the drug [19]. It is safe to say that hydroxychloroquine toxicity is rare within the therapeutic dose range used in SLE patients.

Endocardial Involvement

The valvular dysfunction related to SLE can be categorized into masses or vegetations (Libman-Sacks endocarditis), valvular thickening, valvular regurgitation and infrequently valvular stenosis [20]. In 1924, Libman and Sacks described the first case of lupus-related sterile endocarditis. Libman-Sacks vegetations are non-infective thrombotic sterile vegetations which develop on the heart valves, most commonly mitral valve (Fig. 3), chordae tendinea or endocardial surfaces [21]. Transesophageal echocardiogram (TEE) produces high resolution images and is superior to transthoracic echocardiogram (TTE) in diagnosing these valve lesions [9, 22]. While the finding of Libman-Sacks endocarditis is quite common, estimated to be found in 10% of SLE patients, it is rarely related to clinically significant valve disease [23]. Infective endocarditis should always be in the consideration, because it is difficult to differentiate infective vegetation from Libman-Sacks vegetation based on the morphologic features. Nonetheless the latter is more likely if the vegetation is located at the leaflet base and not the closure line of the leaflet. Treatment of these vegetations includes starting anticoagulation for larger lesion or when embolic phenomena occur, and optimizing immunosuppression once infection has been excluded.

Fig. 3
figure 3

A. TEE in a young patient with SLE and history of stroke shows a small mass [6 × 6 mm] attached to the atrial aspect of the distal anterior leaflet [A2 scallop) consistent with a Libman-Sacks vegetation. B. Mild to moderate mitral regurgitation. C and D. Repeated TEE following anticoagulation with warfarin and optimization of immunosuppressive therapy shows complete resolution of the mass and reduction in mitral regurgitation severity. TEE, transesophageal echocardiogram

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Other valvular manifestations include valvulitis with significant valve dysfunction in form of regurgitation or less commonly stenosis. The most affected valves are the mitral valve (Fig. 4) and the aortic valve [24]. The key feature in distinguishing SLE-related valve dysfunction from rheumatic involvement is the diffuse valve thickening and lack of fusion at the commissures.

Fig. 4
figure 4

A. TEE in a young patient with SLE showing restricted posterior mitral leaflet motion resulting in severe mitral regurgitation. B. 3D view of the mitral valve showing a restricted posterior mitral valve leaflet with no commissural fusion. C. Continuous wave Doppler of mitral inflow demonstrating increased transvalvular mitral gradients. The patient underwent surgical mitral valve replacement. TEE, transesophageal echocardiogram

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A meta-analysis of 21 studies with a total of 2163 SLE patients, of which a quarter had valvular lesions, showed a significant association between anticardiolipin antibodies positivity with valvular dysfunction (relative risk of 1.55; confidence interval, 1.10–2.18) [25].

Discussion

As demonstrated in this review, SLE can involve all layers of the heart from pericardium to endocardium. Additionally, it involves the epicardial coronary arteries, conduction system and great vessels. Echocardiography reliably detects regional wall motion abnormalities due to coronary artery disease, but it cannot differentiate the underlying predisposing conditions [6]. Cardiac involvement tends to be subtle and non-specific with the majority of patients being asymptomatic. Therefore, a high index of suspicion is needed to make the diagnosis. As a rule of thumb, cardiac involvement of SLE is a diagnosis of exclusion which can be made once more common pathologies have been excluded.

Transthoracic echocardiography is a useful screening tool for cardiac manifestations of SLE as it covers a wide range of these manifestations keeping in mind transesophageal echocardiogram has a better sensitivity and specificity for diagnosis of certain manifestations like Libman-Sacks vegetations. The role of periodic echocardiographic monitoring should be individualized based on the result of the initial examination and the patient’s disease activity.

Management of SLE patients with cardiac involvement generally involves specific therapy for the heart along with optimizing SLE therapy for any evidence of active disease.

Conclusion

SLE patients can present with a wide range of cardiovascular manifestations. Echocardiography plays an important role in diagnosis, guiding management decisions and monitoring of cardiac involvement in lupus patients.