Multiple organ dysfunction after mitral valve replacement in a patient with systemic lupus erythematosus complicated by Libman–Sacks endocarditis: a case report and literature review

Abstract

This case report describes a 47-year-old woman with systemic lupus erythematosus (SLE) complicated by Libman–Sacks endocarditis (LSE) who developed multiple organ dysfunction after mitral valve replacement surgery. The patient presented with a 5-day history of cough, sputum, and fever. Transthoracic echocardiography showed significant vegetations on the mitral valve. Biopsy was performed, and the pathological diagnosis was SLE complicated by LSE. After the mitral valve replacement surgery, the patient developed clinical manifestations of hepatic and renal dysfunction, cardiopulmonary failure, oliguria, and shock. The clinical symptoms significantly improved after administration of mechanical ventilation, continuous renal replacement therapy, plasma exchange, anti-inflammatory and anti-infection treatments, immunomodulatory and immunosuppressive therapies, and low-molecular-weight heparin anticoagulation. Multiple organ dysfunction after mitral valve replacement in patients with SLE complicated by LSE has rarely been reported. This report discusses the clinical manifestations, pathogenesis, and treatment of this severe complication. We hope the sharing of our experience in this case will provide a clinical basis for the treatment of severe multiple organ dysfunction after mitral valve replacement in patients with SLE complicated by LSE.

Introduction

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by immune system dysfunction that can affect multiple organs throughout the body.^1,2 Libman–Sacks endocarditis (LSE) is a cardiac manifestation of SLE that commonly involves the mitral and aortic valves and can lead to progressive valve damage requiring surgical intervention for severe complications. ³ Systemic inflammatory response syndrome (SIRS) is a common complication of cardiopulmonary bypass surgery and is associated with postoperative complications such as cardiac dysfunction, respiratory failure, acute liver and renal dysfunction, neurological dysfunction, coagulation dysfunction, and ultimately multiple organ failure. ⁴ Both SLE and SIRS are diseases closely related to the immune system, and excessive immune activation in either condition can lead to systemic organ dysfunction and even life-threatening organ failure.^1,4 This case report describes a patient with SLE complicated by LSE who developed multiple organ dysfunction after mitral valve replacement surgery. Additionally, the clinical manifestations, pathogenesis, and treatment of postoperative multiple organ dysfunction in this patient are discussed. We hope the sharing of our experience in this case can provide a clinical basis for the treatment of severe complications after mitral valve replacement in patients with SLE complicated by LSE.

Case report

In February 2023, a 47-year-old woman presented to our hospital with a history of a productive cough and fever for 5 days. She also reported recent body weight loss and hair loss. On admission, the patient was in a sitting position, breathing with cyanotic lips. Lung auscultation revealed low breath sounds and moist rales in both lungs. The patient had been diagnosed with subacute ischemic stroke approximately 2 weeks previously (Figure 1). Laboratory investigations showed leukocytosis (white blood cell count of 12.3 × 10⁹/L), anemia (hemoglobin concentration of 83 g/L), and thrombocytopenia (platelet count of 38 × 10⁹/L). A coagulation assay demonstrated clotting activity of 86%. Liver function tests revealed elevated levels of alanine aminotransferase (ALT) (106.10 U/L) and aspartate aminotransferase (AST) (189.5 U/L), and renal function tests showed an elevated serum creatinine concentration (159 µmol/L). In addition, the patient had elevated levels of C-reactive protein (84.25 mg/L) and interleukin-6 (389.2 pg/mL) with normal procalcitonin. Serum tests for hepatitis B surface antigen and hepatitis C virus were negative. Computed tomography pulmonary angiography revealed unclear distal pulmonary arteries, with uncertain significance and possible artifacts. Multiple high-density shadows were observed in both lungs, possibly indicating infectious lesions or pulmonary edema. Echocardiography showed vegetation formation on the mitral valve with moderate to severe mitral valve regurgitation. Because of the patient’s recurrent fever and echocardiographic evidence of mitral valve vegetation formation, further testing for autoimmune antibodies and transesophageal echocardiography were performed. The laboratory results showed positivity for anti-SS-A/Ro52 antibody (+), positivity for SS-A/Ro60 antibody (+), weak positivity for anti-SS-B antibody (+−), positivity for anti-mitochondrial M2 antibody (+), an antinuclear antibody IgG concentration of >500 AU/mL, C3 concentration of 074 g/L, C4 concentration of 0.07 g/L, and negativity for anti-cardiolipin antibody IgM (−) and anti-dsDNA antibody (−). Esophageal echocardiography revealed hypoechoic masses on the mitral valve, suggestive of vegetations; mitral valve disease; and moderate mitral valve regurgitation (Figure 2). Based on the clinical presentation and diagnostic tests, the patient was diagnosed with (1) SLE with multiple organ involvement and (2) nonbacterial verrucous endocarditis with mitral valve vegetations. Before surgery, the patient had a poor general condition with abnormal coagulation function, a low platelet count, and mild abnormalities in liver and kidney function. Her symptoms were improved after treatment with methylprednisolone, hydroxychloroquine sulfate, and cyclosporine immunosuppression. One month after admission, the patient underwent mitral valve replacement under cardiopulmonary bypass. Postoperative pathological examination of a biopsy specimen indicated collagen proliferation and local mucosal degeneration with focal necrosis and calcification in the valve tissue (Figure 3). Pathological biopsy confirmed the diagnosis of SLE with LSE. On the first day after surgery, the patient presented with high fever, severe shock, oliguria, and poor spontaneous respiration. Comprehensive routine and imaging examinations revealed cardiopulmonary dysfunction, significant abnormalities in liver and kidney function, an inflammatory storm, and multiple serous fluid effusions. Specifically, liver function testing revealed a total bilirubin level of 130.9 μmol/L, indirect bilirubin level of 50.20 μmol/L, ALT level of 1298.40 U/L, and AST level of 2595.00 U/L. Renal function testing revealed a creatinine level of 271.00 µmol/L and blood urea nitrogen level of 30.70 mmol/L. Other laboratory results were as follows: N-terminal pro-brain natriuretic peptide, 19,368.14 pg/mL; prothrombin time activity, 36%; procalcitonin, >100 ng/mL; C-reactive protein, 226.41 mg/L; C3, 0.37 g/L; and C4, 0.04 g/L. Transthoracic echocardiography revealed prosthetic mitral valve replacement (the prosthesis was in place), mild tricuspid regurgitation, and a small amount of pericardial effusion. Chest and abdominal computed tomography showed multiple serous effusions. The patient received mechanical ventilation, continuous renal replacement therapy, plasma exchange, intravenous immunoglobulin, steroid shock therapy, immunosuppression, combination antibiotics (meropenem, vancomycin, and caspofungin), and sodium houttuyfonate for pulmonary inflammation. Five days later, the patient regained spontaneous respiration and the tracheal tube was removed. Liver and kidney function and inflammatory markers gradually improved to mildly abnormal levels after 1 week as evidenced by the following results: prothrombin time activity, 71%; procalcitonin, 2.02 ng/mL; total bilirubin, 34.80 μmol/L; indirect bilirubin, 9.80 μmol/L; ALT, 155.40 U/L; and AST, 98.70 U/L. C3 and C4 were within the normal range. After 11 days, the patient’s liver and kidney function and inflammatory markers returned to the normal range, and her clinical condition stabilized; thus, she was transferred out of the intensive care unit (ICU). Two months later, the patient was discharged in a healthy state. At the time of this writing, she was being followed up at the Rheumatology and Immunology Clinic of our hospital and was continuing to receive anti-SLE and anticoagulation treatment.

Figure 1.

Cranial magnetic resonance imaging approximately 2 weeks before presentation showed ischemic lesions in the (a) bilateral temporoparietal regions (arrows) and (b) left cerebellar hemisphere (arrow).

Figure 2.

Esophageal echocardiography showed (a) vegetation formation on the mitral valve and (b) mitral regurgitation.

Figure 3.

Pathological examination of the biopsy specimen revealed (a) collagen proliferation and (b) local mucosal degeneration with focal necrosis and calcification in the valve tissue.

The reporting of this study conforms to the CARE guidelines. ⁵ This case report contains no details regarding the patient’s identity. We obtained the patient’s consent for treatment as well as written informed consent for publication of her data. Ethical approval was not required for this study in accordance with national guidelines, which stipulate that ethical approval is not required for single case reports or case series involving two or three cases.

Discussion

SLE is a multisystem autoimmune disease characterized by immune system dysfunction.^1,2 The underlying pathogenesis remains elusive, but current theories suggest a complex interplay between certain genetic and environmental factors that lead to immune dysfunction, autoantibody production, immune complex formation, and ultimately tissue damage. ⁶ The main clinical manifestations of SLE include facial rash, photosensitivity, oral ulcers, nonerosive arthritis, pleurisy, endocarditis, pericarditis, hematologic abnormalities (thrombocytopenia, coagulation abnormalities), renal disease (proteinuria, hematuria), neurologic disease (seizures, psychosis), and cardiovascular and cerebrovascular events (endocarditis, cerebral infarction). ^{1 , 6} In the present case, the patient’s main clinical manifestations before surgery were mild liver and kidney dysfunction, a low platelet count, coagulation abnormalities, low C3 and C4 levels, subacute cerebral infarction, significant mitral valve vegetations, and moderate and severe mitral and tricuspid valve regurgitation. These clinical manifestations met the 2019 European League Against Rheumatism/American College of Rheumatology Classification Criteria for the diagnosis of SLE, and the activity was assessed as severe.^7,8 It has been suggested that cardiovascular and cerebrovascular diseases associated with LSE are usually resolved or significantly improved by traditional anti-inflammatory and anti-thrombotic therapy. ⁹ In the present case, the ICU doctors used heparin anticoagulation, methylprednisolone, hydroxychloroquine sulfate, and cyclosporine to regulate and suppress the SLE activity. After 4 days of hospitalization, the patient’s hematologic, liver, and kidney function returned to normal.

Cardiac valve involvement in patients with SLE includes valve thickening, stenosis, regurgitation, and verrucous endocarditis, with valve thickening and regurgitation being the most common. ⁶ Elevated anticardiolipin antibodies and immune-mediated inflammatory reactions in the serum of patients with SLE are thought to be the major factors contributing to cardiac valve damage.^10–12 LSE refers to overall or localized thickening of the heart valve or the formation of irregular nodules or vegetations on the valve edges. ¹³ Most patients with LSE are asymptomatic; however, some develop serious complications such as thromboembolic events, severe valve dysfunction, and superimposed bacterial endocarditis. ¹⁴ LSE has been shown to increase the incidence of thromboembolic events, may be a source of cerebral fibrin and platelet thromboembolism, and is considered an independent risk factor for cerebrovascular diseases.^13–15 In this case, the patient had a history of subacute cerebral infarction approximately 2 weeks before admission and was at high risk for another thromboembolic event. To prevent recurrence, the patient underwent mitral valve replacement and excision of the vegetations under cardiopulmonary bypass.

Cardiac surgery is associated with high surgical and perioperative risks. Additionally, various characteristic pathologies may occur during the perioperative period, including SIRS after extracorporeal circulation, cardiogenic shock and low cardiac output syndrome, arrhythmia, renal injury, stroke, and respiratory distress. ¹⁶ Extracorporeal circulation can induce SIRS in patients undergoing cardiac surgery. ⁴ SIRS refers to a cascade of reactions that occur when the body releases large amounts of inflammatory factors in response to infection or non-infectious factors such as trauma or burns, leading to an uncontrollable excessive reaction syndrome that can easily progress to life-threatening multiple organ dysfunction syndrome. ¹⁷ Multiple organ failure after mitral valve replacement requires exclusion of other causes, such as left ventricular outflow tract obstruction caused by prosthetic leaflets and acute prosthetic dysfunction. In one previously reported case, however, postoperative transesophageal echocardiography showed that the prosthesis was in place and the mitral regurgitation was significantly improved. ¹⁸ In the present case, the patient exhibited clinical manifestations of respiratory failure, heart failure, significantly abnormal liver and kidney function, high fever, severe shock, and oliguria on the first day after mitral valve replacement surgery. Based on the patient’s clinical manifestations and our clinical experience, we believe that the patient not only experienced a single episode of cardiac valve surgery-related perioperative complications but also sustained a second blow from immune system overactivity due to trauma and ischemia–reperfusion injury. This led to a resurgence of SLE and caused a second wave of the inflammatory storm, further triggering a systemic uncontrollable inflammatory response with effector cells releasing inflammatory mediators. These inflammatory mediators initiated a cascade effect that amplified the systemic inflammation, affected normal organ function, and led to multiple organ dysfunction. ¹⁷

For patients with LSE who develop multiple organ dysfunction after mitral valve replacement, the following treatments are available. Fluid supplementation, oxygen therapy, and symptomatic treatment are usually sufficient for patients with mild symptoms such as low-grade fever, tachypnea, and tachycardia. ¹⁹ Severe SIRS causes targeted organ damage or major organ dysfunction and should be actively treated once it occurs. ¹⁹ Eliminating excessive inflammatory factors and inhibiting excessive inflammatory responses are the keys to immunomodulatory treatment for patients with SIRS, and blocking the progression of SIRS to multiple organ dysfunction syndrome is the main treatment goal. ⁴ Continuous renal replacement therapy and plasma exchange have been widely used to treat various critical illnesses in recent years.^20,21 These interventions can simulate the renal clearance pattern of water and solutes, continuously and significantly removing a variety of solutes including inflammatory mediators from the body, thus maintaining a stable internal environment.^20,21 Moreover, they can remove excess inflammatory mediators and endotoxins from the body through filtration and adsorption, reduce the re-stimulation of inflammatory cells, and avoid the cascade reactions stimulated by inflammatory mediators. ²² Patients with acute myocardial injury or heart failure should immediately receive high-flow oxygen therapy, intravenous diuretics, methylprednisolone sodium succinate, and short-term antibiotic therapy. ²³ For patients with acute lung injury or acute respiratory distress syndrome, treatment should include mechanical ventilation, antibiotics, fluid restriction, and corticosteroids. ²⁴ Currently, there are no specific treatment methods for liver failure; therefore, supportive measures such as adequate calorie supplementation, control of systemic infections, or application of a molecular adsorbent recirculation system for treating liver failure can only be administered to allow time for damaged liver cells to recover and regenerate. ²⁵ In patients with acute kidney injury, sufficient fluids, diuretics, and sodium bicarbonate should be administered to alkalize the urine, and symptomatic supportive treatment should also be given. Hemodialysis is necessary if renal function continues to deteriorate and acute renal failure occurs.^19,22 In the present case, the patient developed multiple organ dysfunction on the first day after surgery; however, her liver and kidney function, coagulation function, and inflammatory indicators gradually improved and returned to normal levels by approximately the 10th day after surgery with treatment by mechanical ventilation; continuous renal replacement therapy and plasma exchange; human immunoglobulin; methylprednisolone pulse therapy; chloroquine sulfate and cyclosporine immunosuppression for SLE; combination therapy with meropenem, vancomycin, and capreomycin to combat infection; and ceftazidime avibactam to inhibit pulmonary inflammation. On the 11th day after surgery, the patient’s condition stabilized and she was transferred out of the ICU. At the time of this writing, she was continuing treatment in the general ward.

In conclusion, we have described a patient with SLE complicated by LSE who developed multiple organ dysfunction after mitral valve replacement surgery. The patient developed an immune activation cascade due to surgical trauma, ischemia–reperfusion injury, and SLE flare, which led to systemic multiple organ dysfunction. After suppressing the SLE activity, clearing the inflammatory cells, and providing targeted therapy, the patient’s clinical symptoms improved significantly. Given the complex pathogenesis of SLE and SIRS, more clinical and basic research is needed to better understand the clinical course and prognosis of SLE and SIRS, which will allow researchers to develop updated and more targeted treatment methods. We hope this case provides clinical guidance for the treatment of severe multiple organ dysfunction following mitral valve replacement surgery in patients with LSE.