# Update: Heart Failure in Systemic Lupus Erythermatosus
## 3 Pathophysiology and Risk Factors of Heart Failure in Systemic Lupus Erythermatosus  
Systemic lupus erythematosus may contribute to the development of heart failure through many mechanisms and heart-related diseases, especially myocarditis, cardiomyopathy, or valvular heart disease, as well as through genetic predisposition [33; 34; 35]. It is estimated that SLE may be responsible for even 50% of HF cases in this group of patients [3; 11; 19; 23]. In particular, subclinical heart failure is frequently observed in SLE patients and occurs in almost two-thirds of patients, as demonstrated by cardiac magnetic resonance imaging [31]. The pathogenesis of HF coexisting with SLE is multifactorial and still undetermined. Cardiovascular risk factors significantly associated with cardiac dysfunction in SLE include atherosclerosis, dyslipidemia, chronic kidney disease and lupus nephritis, obesity, as well as chronic inflammation. On the other hand, hypertension, myocarditis, pericarditis, and valvular heart disease are the main cardiological causes of HF development in SLE patients [8; 19; 36; 37; 38]. Furthermore, several studies have shown that the deterioration of diastolic function was associated with age and independently correlated with increased aortic stiffness [39; 40]. [PERSON] et al., in echocardiography of SLE patients with asymptomatic HF, demonstrated dysfunction of both systolic and diastolic left ventricular function compared with the control group [41], which has been confirmed in further trials [11; 29; 30; 42; 43]. SLE as a potential factor in the development of HF was also shown in one of the large, randomized trials conducted in Asia, where [PERSON] revealed a potential association between SLE and an increased risk of congestive heart failure [34]. Moreover, a study from Korea showed that SLE is an independent risk factor for the development of HF. HF was observed in 358 SLE patients and 354 control subjects (incidence rate 3.11 and 0.61 per 1000 person-years, respectively), and the risk of occurrence was determined to be 4.60 (95% confidence interval: 3.96-5.35) [14]. These results support the recognition of SLE as an independent factor in the development of HF. Therefore, the pathogenesis of HF is based on inflammation, which is an integral part of SLE. Moreover, in SLE patients, the dominant type is HF with preserved ejection fraction (HFpEF). HF with reduced left ventricular ejection fraction (HFrEF) occurs less frequently [7; 9]. As previously mentioned, the pathogenesis of HF in SLE is presumably related to microvascular myocardial dysfunction resulting from chronic inflammation [21; 44]. The main pathophysiological changes associated with HF are attributed to the influence of proinflammatoryatory cytokines (tumor necrosis factor \(\alpha\), interleukins 1, 6, 8, 10, and 15, complement component C3a, C-reactive protein, and expression of clusters of differentiation CD4 and CD8) in the myocardium. Expression of cytokines consistently causes a decrease in ventricular contractility and thus, the development of nonischemic cardiomyopathy. [PERSON] et al. observed a positive correlation between myocytes and anti-TNF antibodies, interleukins (IL-8, IL-10, IL-15), complement component C3a, and CD4 and CD8 expression [45]. Additionally, type I interferon is associated with the involvement of T cells and macrophages in immunological processes resulting in impaired endothelial function and secondary atherosclerosis [46; 47]. Similarly, accelerated oxidation of low-density lipoprotein (LDL) and increased uptake by monocytes promote the development of atherosclerosis [19; 46]. Another pathophysiological mechanism in the development of HF in SLE patients is endothelial activation leading to collagen deposition. This process results in increased stiffness and hypertrophy of cardiomyocytes as well as reduced relaxation capacity of the myocardium, which may consequently lead to the development of HFpEF. Additionally, circulating antibodies form immune complexes, enhancing the immune response in the myocardium.