The Correlation Between Peripartum Cardiomyopathy And Autoantibodies Against Cardiovascular Receptors

BackgroundPeripartum cardiomyopathy（PPCM） is a systolic heart failure which occurs between the lastmonth of pregnancy and the first five months postpartum. It is characterized by left ventricularsystolic dysfunction and heart failure. Its pathogenesis is not clear. Autoantibodies againstβ₁-adrenergic receptors （β₁R-AABs） and M₂-muscarinic receptors （M₂R-AABs） aremainly distributed at cardiomyote, and participate in regulation of heart structure andfunction. Our preliminary studies revealed that β₁R-AABs and M₂R-AABs exsisitedin the serum of heart failure patients due to various heart disease（coronary heatdisease, hypertensive heart disease, rheumatic valvular heart disease, dilatedcardiomyopathy）. Our preliminary experiment indicated that β₁R-AABs exsisted inthe serum of PPCM patients. However, the attendance for M₂R-AABs was unclear.Whether these two autoantibodies are correlated with PPCM needs further discussion.Objective1. Vertify the hypothesis about β₁R-AABs and M₂R-AABs exsist in the PPCMpatients, what’smore, the level of β₁R-AABs and M₂R-AABs are higher in PPCMpatients than normal maternal;2. Analyse the factors associated with β₁R-AABs and M₂R-AABs.3. Vertify autobodies against cardiovascular receptors correlated with the attack ofPPCM and prognosis of the disease. MethodWe conducted study of37diagnosed PPCM patients as experimental group and36normal maternals as control group. Synthetic peptides corresponding to amino acidsequences of the second extracellular loop of the β₁and M₂were respectivelysynthesized as antigens to screen sera of37PPCM patients,36normal maternalsusing streptavidin-peroxidase enzyme-linked immunosorbent assay test （SA-ELISA）.Clinical assessment,2-dimensional echocardiographic studies and measurement ofβ₁R-AABs, M₂R-AABs were performed at presentation and one year late. By usingKruskal-Wallis test, the difference of echocardiography for patients with differentautoantibodies woule be dicussed. The factors associated with β₁R-AABs andM₂R-AABs was analyzed by using Sperman rank correlation. And the correlationbetween β₁R-AABs, M₂R-AABs and the attack of PPCM was made further analysisby the same way. Evaliation the predictive value of autobodies against cardiovascularreceptors on the attack of PPCM was made by using the logistic regression analysis.Result1. The level of β₁R-AABs and M₂R-AABs were significantly higher in PPCMpatients than normal pregnants: the positive ratios for β₁R-AABs and M₂R-AABswere59.5%（22/37） and45.9%（17/37）, while it was19.4%（7/36）（p<0.001） and16.7%（6/36）（p<0.001） in normal maternals. The Gemometric mean titer for β₁R-AABs and M₂R-AABs were1:129and1:143, while it was1:80（p=0.003） and1:53（p<0.001） in normal maternals.2. In experimental group, there were17（46%） patients with double positiveautoantibodies,5（14%） patients with single positive autoantibodies and15（40%）patients with double negative autoantibodis. Echocardiography data between threegroups had significant difference:（1） left venteicular end diastolic dimension （LVEDD）:62.5±7.1vs.56.9±1.0vs.54.8±4.3; χ²=14.411, p=0.001;（2） leftventeicular end systolic dimension （LVESD）:51.2±7.5vs.45.8±2.1vs.42.2±4.3; χ²=14.944, p=0.001;（3） left ventricular ejection fraction （LVEF）:33.7±7.9vs.38.6±1.7vs.41.9±2.9; χ²=11.879, p=0.003;（4） left ventricularfractional shortening （LVFS）:16.8±4.0vs.19.4±1.4vs.21.2±2.8; χ²=9.717,p=0.008.3. After standard treatment for1year, check echocaodiography, three groups all hadimprovement, however, the degree of improvement was different:（1） LVEDD:52.3±4.4vs.46.4±1.1vs.44.5±1.2; χ²=18.837, p<0.001;（2） LVESD:38.4±5.1vs.32.4±1.1vs.28.4±2.9; χ²=17.433, p<0.001;（3） LVEF:57.2±7.0vs.61.6±2.9vs.68.5±5.0; χ²=13.715, p=0.001;（4） LVFS:28.5±3.4vs.30.4±2.1vs.33.9±2.4; χ²=12.923, p=0.002.4. Both β₁R-AABs and M₂R-AABs had significantly positive correlation with serumexpression levels of NT-BNP, the left ventricular dimensions and New York HeartAssociation functional class （NYHA FC）（rs:0.496～0.892, p<0.01）. We also findsignificantly negative correlation between the activity of β₁R-AABs, M₂R-AABsand LVEF and LVFS （rs:-0.488～-0.568, p<0.01）.5. Univariate analysis showed several factors increased the risk for the attack ofPPCM, including autoantibodies against cardiovascular receptors, advancedmaternal age, multiple pregnancies, pregnancy-induced hypertension, and poorsocioeconomic status. Multiple Logistic analysis showed that level ofautoantibodies against cardiovascular receptors and pregnancy-inducedhypertension were an independent predictor of the attack of PPCM （autoantibodiesagainst cardiovascular receptors: OR=18.786,95%confidence interval1.926-183.262, p=0.012; pregnancy-induced hypertension: OR=17.305,95%confidence interval1.061-282.299, p=0.045）. Conclusion1. β₁R-AABs and M₂R-AABs exsisted in the serum of PPCM patients. The level ofβ₁R-AABs and M₂R-AABs were significantly elevated in PPCM patientscompared with normal maternals.2. The comparison between β₁R-AABs and M₂R-AABs double positive group, singlepositive group and double negative group found that the expansion of leftventricular and decrease of heart function: double positive group> single positivegroup> double negative group; After treatment for1year, recovery of leftventricular dimesion and heart function: double positive group<single positivegroup <double negative group. The test of β₁R-AABs and M₂R-AABs may havepredictive value for the prognosis of PPCM.3. The positive ratio and the serum titer of β₁R-AABs and M₂R-AABs weresignificantly positively correlated with left ventricular dimension, and significantlynegatively correlated with the cardiac contraction function of PPCM patients.4. The autoantibodies of cardiovascular receptors were one of the independent riskfactors for the attack of PPCM. The test of β₁R-AABs and M₂R-AABs may havepredicitive value for the attack of the disease.