Cardiac Involvement And Its Related Factors In Autoimmune Diseases By Echocardiography: A Sevenyear Single-center Study

Background:Autoimmune disease(AD)is a group of diseases characterized by the presence of autoantibodies,which lead to multiple tissue and organ damage.The damage of cardiovascular system is an independent risk factor for increased mortality in these patients.Cardiac structural and functional changes without clinical symptoms are often neglected by doctors in AD,the prognosis is often poor when cardiac damage is aggravated to significant clinical symptoms.In fact,even light cardiac involvement is an independent risk factor for increased mortality.However,the current data on the morbidity and manifestations of cardiac involvement in AD only come from a small sample of studies involving a few types of autoimmune diseases.In addition,the autoantibody spectrum and pathophysiological mechanism of AD are different,whether there are differences in the types of heart involvement is unknown.Echocardiography is a non-invasive method,can qualitatively and quantitatively evaluate the structure and function of the heart.It is widely used in clinic and has irreplaceable advantages in other examinations.Based on this,this study intends to retrospectively incorporate the echocardiography of patients with AD hospitalized in Rheumatology and Immunology Department of our hospital in the past seven years,summarize its echocardiographic characteristics and explore the detection rate and manifestation of cardiac involvement in different AD in the real world.On this basis,to explore the effects of factors related to the disease and its treatment on cardiac structure and function in the common types of autoimmune diseases.And to explore the risk factors for impaired left ventricular diastolic function in patients with AD.Accordingly,to increase clinicians’ understanding and attention to the cardiac involvement of AD,and to provide evidence for the study of the mechanism of cardiac damage of AD.Part ⅠPurpose To analyze the clinical characteristics and the manifestation types of cardiac involvement among different types of AD patients.Methods This study retrospectively enrolled patients diagnosed with AD and underwent echocardiography hospitalized in Rheumatology and Immunology Department of Hospital from 2011 to 2017.Demographic information,discharge diagnosis,medication,echocardiographic reports were extracted.The diagnosis were determined and modified based on the data and further subdivided into systemic lupus erythematosus(SLE),rheumatoid arthritis(RA),idiopathic inflammatory myopathy(IIM),sj ogren’s syndrome(SS),overlap syndrome(OS),spondyloarthropathy(SpA),systemic sclerosis(SSc),gouty arthritis(GA),small vessel vasculitis(SVV),Behcet disease(BD),autoimmune liver diseases(AILD),mixed connective tissue disease(MCTD),adult onset Still’s disease(AOSD)and takayasu arteritis(TA).Cardiac structural function measurements in echocardiography and qualitative diagnosis of cardiac structural abnormalities were obtained.Left cardiac involvement was defined as at least one of following abnormalities:left atrial enlargement,left ventricular enlargement,left ventricular thickening,reduced left ventricular global systolic function,left ventricular segmental motor abnormality,left ventricular filling perssere increase,mitral valve moderate or greater regurgitation,aortic valve moderate or greater regurgitation,mitral stenosis/thickening/calcification,aortic stenosis/thickening/calcification.Results A total of 7310 AD patients were involved in this study,including SLE(28.5%),RA(20.0%),IIM(11.7%),SS(8.5%),OS(6.5%),SpA(6.5%),SSc(5.6%),and GA,SVV,BD,AILD,MCTD,AOSD,and TA(totaling 12.7%).According to echocardiographic findings,left cardiac involvement(n=3361,46.0%)was the most common abnormalities in AD patients,mainly including left atrial enlargement(24.9%),left ventricular hypertrophy(15.8%)and left ventricular filling perssere increase(23.8%).Left ventricular systolic dysfunction was rarely seen(1.8%)among AD patients.With the most common SLE as the control group,patients in RA,GA and AILD groups had greater LAD(RA vs.GA vs.AILD vs.SLE:31.6±4.9 vs.34.7±5.7 vs.32.0±5.1 vs.31.0±4.9mm;P<0.001);patients in RA and GA groups had thicker IVST(RA vs.GA vs.SLE:9.7 ±1.9 vs.10.5 ± 1.8 vs.9.4 ± 1.7mm,P<0.001).In the GA group,LVPWT was thicker(GA vs.SLE:9.4± 1.2 vs.8.9± 1.9mm,P<0.001);a higher rate of left ventricular filling perssere increase was found in the GA group(GA vs.SLE:28.8%vs.24.4%,P<0.05).With the most common SLE(46.0%)as the control group,the detection rate of left ventricular involvement was higher only in GA(67.0%,P<0.001),RA(54.4%,P<0.001),SVV(54.2%,P=0.048)and OS(51.2%,P=0.042)groups than in SLE.The detection rates of MCTD(36.3%),AOSD(27.4%),BD(25.2%)and SpA(25.0%)groups were lower than those of SLE(all P<0.05).The detection rate of left ventricular involvement in IIM(42.5%),SS(42.9%),SSc(45.3%),TA(49.4%)and AILD(51.2%)groups was similar to that of SLE.Conclusions In this study,we found that SLE,RA and IIM were the most common types in AD patients.Left heart involvement is the most prominent type of cardiac involvement in AD patients,and the detection rate of left heart involvement varies among different AD patients.GA,RA and SVV are the disease types with high detection rate of left heart involvement.Part ⅡPurpose To compare and analyze the similarities and differences of traditional cardiovascular disease risk factors,inflammatory indicators and structural and functional changes of left heart among patients with three common types of AD(SLE/RA/IIM),and to explore the related factors of left cardiac involvement.Methods In the second part,we focused on patients with clear diagnosis of SLE,RA and IIM,and they had complete echocardiography,and cardiac structure and function measurement data and text field description in the report sheet were complete.Demographic data,clinical data,and the results of the last laboratory examination before discharge were obtained:(1)General indicators:It mainly includes blood routine indexes,liver function indexes,renal function indexes(SUA),and lipid indexes.(2)Non-specific inflammatory markers.(3)Immune related indicators.Results Clinical characteristics,cardiac involvement and risk factors of the three most common ADs,SLE(1831),RA(1270)and IIM(768),were analyzed based on Part Ⅰfindings.Both SLE and RA had higher proportions of patients with hypertension(SLE vs.RA vs.IIM:22.3%vs.24.2%vs.13.3%,P<0.001)and renal insufficiency(SLE vs.RA vs.IIM:7.8%vs.4.9%vs.1.0%,P<0.001),and were significantly higher than those in the IIM group.In addition,the proportion of patients with left atrium enlargement,left ventricular thickening,left ventricular filling perssere increase,and left ventricular involvement(P<0.05)were also higher than those in the IIM group.SLE,RA and IIM were divided into subgroups with or without cardiovascular risk factors,namely,SLE cardiovascular risk factors(+)group(n=580,31.7%)and(-)group(n=1251,68.3%),according to the patients with or without cardiovascular disease or risk factors(i.e.hypertension,diabetes,coronary heart disease,renal insufficiency and thyroid dysfunction).RA cardiovascular risk factors(+)group(n=444,35.0%)and(-)group(n=826,65.0%);And IIM cardiovascular risk factors(+)group(n=186,24.2%)and(-)group(n=582,75.8%).Patients in the cardiovascular risk factor(+)group had larger left atria(P<0.001),thicker left ventricles(P<0.001),and left ventricular filling pressure increased more significantly(P<0.001)in each disease group.Among the patients with cardiovascular risk factors(-),a higher proportion of SLE(34.9%),RA(44.1%)and IIM(35.4%)were associated with left cardiac involvement.In patients without cardiovascular risk factors,multivariate logistic regression analysis using left cardiac involvement as dependent variable showed that age(OR=1.351,95%CI=1.275-1.433,P<0.001),SUA(OR=1.299,95%CI=1.1541.463,P<0.001),albumin(OR=1.204,95%CI=1.082-1.338,P=0.001),complement C3(OR=1.260,95%CI=1.085-1.463,P=0.002)were independent risk factors.Age(OR=1.378,95%CI=1.288-1.474,P<0.001)and SUA(OR=1.238,95%CI=1.058-1.449,P=0.009)were independent risk factors for left cardiac involvement in RA patients.Age(OR=1.343,95%CI=1.244-1.450,P<0.001)were independent risk factors for left cardiac involvement in IIM patients.Conclusions The proportion of left cardiac involvement in SLE and RA was significantly higher than that in IIM,but the proportion of cardiovascular risk factors such as hypertension and renal insufficiency was also significantly higher than that in IIM.In patients without cardiovascular risk factors,there was still a high proportion of patients in the three groups with left cardiac involvement.Age,SUA and AD disease related factors(such as complement)were independent related factors for structural and functional changes in the left heart.Part ⅢPurpose To explore the correlation between serum uric acid(SUA)level and cardiac involvement in patients with AD.Methods Adult patients with definite diagnosis of AD were included,and patients complicated with gout,arrhythmia(atrial fibrillation or flutter),or other heart disease(coronary heart disease,cardiomyopathy,valvular heart disease,or congenital heart disease)were excluded.Based on the echocardiographic indicators obtained in the first part of the study,left ventricular diastolic dysfunction(LVDD)was defined by at least one of the following features as(1)LV hypertrophy(LVH),and/or(2)left atrial enlargement(LAE),and/or(3)E/e’≥13,and LVEF≥50%.Multivariate logistic regression model was adopted to measure the association between SUA or other risk factors and LVDD.Results A total of 5873 patients with AD met the inclusion and exclusion criteria,including 4563 women(77.7%),an overall mean age of 45± 16 years,an average SUA level of 300± 115μmol/L,and 1299 patients(22.1%)with hyperuricemia.LVDD(n=2417,41.2%)had the highest proportion,followed by valvular lesion in 21.8%,pericardial effusion in 15.2%and pulmonary hypertension in 4.2%patients.When the patients were grouped according to the SUA quartiles(i.e.Q1:49-222μmol/L,n=1464;Q2:223-283μmol/L,n=1468;Q3:284-362μmol/L,n=1469;Q4:363996μmol/L,n=1472),the prevalence of LVDD increased from Q1 to Q4(33.9%,38.5%,41.0%and 51.2%,respectively,p<0.05).After adjusted for other risk factors(including age,sex,comorbidities,use of cytotoxic drugs or DMARDs,CRP),the patients in Q2,Q3 and Q4 had 1.354 folds,1.477 folds and 2.009 folds of the chance in LVDD when those in Q1 served as a reference.Conclusions LVDD was commonly observed in AD patients,with a detection rate of nearly 1/2,and was independently associated with increased SUA.These findings indicate a potential significance of SUA lowering in the management of LVDD.