Frequency of autoantibodies and their associated clinical characteristics and outcomes in patients with dilated cardiomyopathy: A systematic review and meta-analysis

Background: Dilated cardiomyopathy (DCM) is a prevalent myocardial disorder characterized by impaired cardiac function affecting either the left ventricle or both ventricles. Accumulating evidence suggests that auto- immunity represents a key mechanism implicated in its pathogenesis, as several abundant autoantibodies have been identified in patients with the condition. However, the prevalence of these antibodies (Abs) in patients with DCM compared to that in both healthy controls (HCs) and those with ischemic cardiomyopathy (ICM), as well as their potential association with DCM, remains unclear. This study aimed to elucidate the prevalence of certain autoantibodies in patients with DCM compared to that in HCs and patients with ICM, as well as to evaluate their correlation with clinical characteristics and outcomes. Methods: A comprehensive literature search of the PubMed, Web of Science, EMBASE, the Cochrane Library, and Scopus was conducted up to March 26, 2024, and any article that fulfilled our inclusion criteria was reviewed. A meta-analysis was then conducted, using both random- and fixed-effects models. Results: A total of 38 studies met the inclusion criteria and were pulled for this analysis. Significantly higher prevalence rates of autoantibodies targeting the anti-beta 1 adrenergic receptor (beta 1-AR; odds ratio [OR] = 4.96, p = 0.000), M2 muscarinic receptor (M2-R; OR = 4.07, p = 0.000), adenine nucleotide translocator (ANT; OR = 21.18, p = 0.001) and myosin (OR = 12.26, p = 0.000) were observed in patients with DCM compared to HCs. Moreover, patients with DCM exhibited a significantly higher frequency of positive ANT Abs (OR = 34.52, p = 0.005) compared to those with ICM. Regarding clinical characteristics and outcomes, seropositivity for beta 1-AR Abs was found to be significantly correlated with New York Heart Association (NYHA) classification (standardized mean difference [SMD] = 0.78, p = 0.006), left ventricular ejection fraction (LVEF) (SMD =-1.38, p = 0.001), and heart rate (HR) (SMD = 1.505, p = 0.022). Seropositivity for anti-calcium channel Abs was significantly associated with sudden cardiac death (SCD; OR = 3.17, p = 0.000) and all-cause mortality (OR = 2.06, p = 0.008), while anti-troponin I (TnI) Abs were associated with atrial fibrillation (OR = 0.21, p = 0.042). In terms of Ab prevalence rates, significant heterogeneity in the frequency of anti-beta 1-AR Abs between studies investigating DCM and ICM may be partially explained by the detection methods used and the mean ages of the patients. Meta-regression analysis suggested that the patients' ages may partially explain the observed heterogeneity between studies regarding beta 1-AR Ab seropositivity and HR. However, the heterogeneity observed in the studies comparing the prevalences of Abs in patients with DCM vs HCs and ICM, as well as their associated clinical characteristics, could not be explained by subgroup analyses or demographic factors such as age and sex-nor by cardiac function. Conclusions: Patients with DCM are more likely to have elevated levels of anti- beta 1-AR, M2-R, ANT and myosin autoantibodies compared to HCs, as well as higher levels of ANT Abs compared to patients with ICM. Anti-beta 1-AR, calcium channel, and TnI Abs may play an essential role in DCM severity and poor prognosis. This study represents the first comprehensive meta-analysis regarding autoantibody prevalence and DCM and may thus potentially guide the clinical management of such patients. However, further research is warranted to evaluate