Heart failure in systemic lupus erythematosus

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Abstract

Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by a constellation of cardiovascular (CV) and non-CV manifestations. Even though CV complications such as accelerated atherosclerosis and elevated risk of myocardial infarction (MI) have been recognized for many years, there is limited evidence regarding SLE and its association with heart failure (HF). Traditional risk factors of atherosclerotic CV disease, as well as various SLE manifestations and therapies, independently or together, increase the risk of HF in this population. There is a need for sufficiently powered intervention studies focusing on specific risk factors to improve CV outcomes in SLE patients.

Introduction

Systemic lupus erythematosus (SLE) is a systemic autoimmune disorder associated with chronic inflammation and immune complex deposition in involved organs. Cardiovascular (CV) manifestations of SLE are heterogeneous and may include atherosclerotic coronary artery disease (CAD), myocardial infarction (MI), myocarditis, pericarditis, conduction system disease, valvular disease, and heart failure (HF) [1]. Despite long-time recognition of the bimodal pattern of mortality in SLE patients, that is, early deaths due to SLE complications and later deaths due to CV disease [2], CV mortality in this population remains largely unchanged compared to 30 years ago [3], highlighting a potential healthcare gap. While most studies to date have focused on premature atherosclerosis and adverse CV events such as MI and stroke, data are emerging regarding elevated risk of HF in patients with SLE [2], [4], [5], [6], [7], [8], [9]. In this review, we examine the epidemiology, pathophysiology, risk factors, and management considerations for HF in SLE.

Section snippets

Epidemiology of HF in SLE

HF has been described as a modern epidemic, affecting nearly 38 million people globally [10] with an estimated prevalence of 1–12% in developed nations [11]. In the United States, an estimated 5.7 million adults are affected [12] with age- and sex-adjusted HF incidence estimated at 2.19 events per 1000 person-years [13]. Despite the significant and long-standing recognition of elevated risk of CV disease in SLE patients, epidemiologic data regarding HF in SLE are just emerging.

Nearly 2 decades

Pathophysiology and types of HF in SLE

While the exact mechanisms underlying increased risk of HF in SLE are not known, available data point to aberrant host–immune responses and chronic inflammation, which may lead to accelerated atherosclerosis and other CV risk factors. In addition, SLE has direct cardiac, vascular, and other systemic manifestations that lead to increased risk of CV disease and HF [1], [16]. Glucocorticoids and other immunosuppressive therapies of SLE may also modify the risk of HF in this population. In a

Immunologic mechanisms of accelerated atherosclerosis

The immunologic processes underlying accelerated atherosclerosis in SLE are complex and only summarized here. Briefly, increased inflammatory activity as measured elevated ESR, IL-6, TNF-α, and the SLE disease activity index (SLEDAI) are associated with low HDL levels [19], and type I interferon has been implicated in the recruitment of T cells and macrophages into atherosclerotic lesions and endothelial dysfunction [16], [20]. Enhanced LDL oxidation and increased LDL and pro-inflammatory HDL

Traditional cardiovascular risk factors

In addition to demographic risk factors, patients with SLE appear to have a higher burden of traditional CV risk factors. Furthermore, there is significant risk of MI, myocarditis, and drug-induced myocardial injury in patients with SLE, further increasing their risk of HF. Traditional CV risk factors and their impact in SLE patients are summarized in Table 2.

  • (A)

    Hypertension: Prevalence of hypertension (HTN) in SLE ranges 17–52% [4], [9], [21], [22], [23], [24], which is significantly higher

SLE manifestations as HF risk factors

  • (A)

    Myocardial dysfunction: Subclinical ventricular dysfunction in SLE is frequently observed as left ventricular systolic dysfunction (LVSD) or diastolic dysfunction (LVDD) during myocardial tissue doppler and strain echocardiography [41]. In biopsy or autopsy specimens, increase in interstitial connective tissue and myocardial scarring may be seen [42], [43]. Prevalence of subclinical LVSD and LVDD are estimated at 11.5–16% and 3.8–8%, respectively [44], [45], although recent CMR studies suggest

SLE medications and risk of HF

In general, immunomodulating therapy for SLE is thought improve CV risk profile through reduction in disease activity [5]. Currently available studies are mostly focused on CV events and data are limited in terms of specific risk of HF. A review of therapeutic agents and their associated CV risk are presented below.

  • (A)

    Hydroxychloroquine: Although hydroxychloroquine is known to prevent flares and aid long-term survival in patients with SLE, whether it reduces CV risk is less clear [78].

Management considerations

While it is apparent that risk of CV disease and HF is increased in patients with SLE, it is unknown whether modification of traditional CV risk factors will lead to the same risk reduction as in the general population [1]. For example, in the recent randomized controlled Lupus Atherosclerosis Prevention Study, atorvastatin did not slow progression of subclinical atherosclerosis over a 2-year period [97]. Still, given the large body of evidence indicating heightened risk of CV risk in SLE,

Future directions

There is an unmet need for future research studies focusing on specific CV diseases, including HF, and its risk factors to delineate the subtleties underlying each CV disease in the SLE population. In addition, sufficiently powered intervention trials are needed to help alleviate the disproportionate CV disease burden in the SLE population and further develop the evidence base underlying current management recommendations.

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    The authors have indicated there are no conflicts of interest

    1

    Equal contribution as co-first authors.

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