| Objective Wilson′s disease(WD)is an autosomal recessive genetic disorder causing impaired copper excretion,which often involves the heart and mainly manifests as arrhythmia,cardiomyopathy and other structural and functional damage to the heart.Early detection of subclinical cardiac lesions in patients has far-reaching implications for disease treatment and prognosis.Based on the advantages of high sensitivity,convenience,and non-invasiveness demonstrated in the diagnosis of early cardiac lesions by RT-3DE and myocardial injury markers,we observed the performance characteristics of cardiac structure and function in WD patients,aiming to provide an objective imaging and serological basis for early cardiac involvement in WD patients for timely intervention and treatment.In addition,by observing the clinical efficacy of GDFMG combined with DMPS in the treatment of cardiac damage in WD patients with liver and kidney deficiency,we provide more theoretical support and clinical practice for GDFMG to improve ventricular remodeling and cardiac insufficiency in WD patients.Methods1.According to the inclusion criteria of both traditional Chinese medicine and Western medicine,60 eligible patients of WD who were hospitalized in the Department of Neurology at the First Affiliated Hospital of Anhui University of Traditional Chinese Medicine from December 2021 to December 2022 were selected as the WD group for this study.During the same period,30 eligible healthy volunteers were recruited as the normal group.The imaging parameters and serum markers related to cardiac function were compared between the normal group and the WD group.The details are as follows:(1)RT-3DE:(1)Cardiac structural parameters: LAD,RVD,IVST,LVD and LVPWT.(2)Cardiac function parameters: EF,SV,FS,EDV,ESV,E,A,early diastolic e’,PAP,and calculated E/A and E/e’ ratio.(2)ECG: HR,QRS duration,QT/QTc interval,P-R interval,and P wave.(3)Myocardial injury markers and inflammation Factors: Hcy,Cys C,c Tn I,NT-pro BNP,CK-MB,and hs-CRP.(4)Serum fibrosis markers: HA,CIV,LN and PIIINP.2.Based on the nadir criteria,specifically,the 60 eligible WD patients were randomly divided into a treated group(N=30)and a control group(N=30)using a random number table method.The control group was given routine treatment with DMPS for 8treatment courses(64 days),with intermittent calcium gluconate injection(last 2 days)after the first 6 days of each course.The treatment group received the same treatment as the control group,with the addition of in-house-made GDFMG.The changes in ECG results and parameters,TCMS,and 24hr-UC were compared between the two groups at baseline,as well as at the 2nd,4th,and 8th treatment courses.In addition,changes in RT-3DE results,myocardial enzyme spectrum,serum fibrosis markers,CER concentration,and clinical efficacy were recorded and compared before and after the entire treatment course.Results1.Comparison between the WD group and the normal group(1)Baseline data: Subjects in the two groups were matched in age,sex,body mass index,body surface area,cardiovascular risk factors and other baseline data(P>0.05).(2)RT-3DE:(1)There were significant differences in RT-3DE results between the two groups(P<0.05).(2)Comparison of RT-3DE parameters: Compared with normal group,there was a significant increase in LAD,RVD,LVD,IVST,LVPWT,E/e’,PAP,EDV,and ESV in WD group(P<0.01,P<0.05),but e’ and SV were significantly decreased(P<0.01).There were no significant differences in E,A,E/A,EF and FS(P>0.05).(3)ECG:(1)The incidence of abnormal electrocardiogram was significantly higher between the two groups(P<0.01).(2)Comparison of ECG parameters:Compared with normal group,HR,QRS duration,QT interval and QTc interval in WD group were significantly increased(P<0.01),the P-R interval was significantly ruduced(P<0.01),while there was no significant difference was observed in P wave between the two groups(P>0.05).(4)Myocardial injury markers and inflammatory factors: Compared with normal group,serum levels of Hcy,Cys C,NTpro BNP,CK-MB and hs-CRP in WD group were significantly increased(P<0.01,P<0.05).(5)Serum fibrosis markers: Compared with the normal group,HA,PIIINP,LN,CIV levels were significantly increased in the WD group(P<0.01).2.Effects of Gandou Fumu Granules on WD cardiac injury(1)Baseline data: The treatment group and the control group of WD patients were wellmatched in terms of gender ratio,age range,disease duration,BMI,BSA,and cardiovascular-related high-risk factors,indicating comparability(P>0.05).(2)RT-3DE: Results of RT-3DE analysis:(1)In comparison within the same treatment group before and after treatment,the RT-3DE results in the treated group showed significant improvement after treatment(P<0.05).In the control group,there was no significant difference in RT-3DE abnormality rate before and after treatment(P>0.05).There was no significant difference in RT-3DE abnormalities between the two groups before treatment(P>0.05),but the treated group showed a significant decrease in abnormality rate compared to the control group after treatment(P<0.05).(2)Regarding the comparison of RT-3DE parameters,within the same treatment group before and after treatment,LAD,RVD,LVD,IVST,A,E/e’,EDV,ESV,and PAP were significantly decreased(P<0.05,P<0.01),while EF,SV,FS,E,e’,and E/A were significantly increased(P<0.05,P<0.01).LVPWT showed no significant difference(P>0.05).In the control group,LAD,RVD,LVD,IVST,PAP,EDV,and ESV were significantly decreased(P<0.05,P<0.01),while EF was significantly increased(P<0.01),and LVPWT,E,A,E/A,e’,E/e’,SV,and FS showed no significant changes compared to before treatment(P>0.05).There was no significant difference in parameters between the two groups before treatment,indicating comparability(P>0.05).Compared to the control group after treatment,the treated group showed further improvement in LAD,LVD,E/A,E/e’,e’,A,SV,ESV,EDV,and PAP(P<0.05,P<0.01),while there was no significant improvement in RVD,IVST,LVPWT,EF,and FS(P>0.05).(3)ECG:(1)ECG result analysis: Compared with before treatment in the same group,in the treatment group,the difference was statistically significant(P<0.05);in the control group,the difference was not statistically significant(P>0.05);there was no significant difference between the two groups before treatment(P>0.05);after treatment,compared with the control group,the number of cases with abnormal electrocardiogram results in the treatment group significantly decreased(P<0.05).(2)Comparison of ECG parameters: Compared with before treatment in the same group,at the 2nd course of treatment,there was no significant change in the related ECG parameters in the treatment group(P>0.05),but at the 4th and 8th courses of treatment,HR slowed down significantly,and P-wave,QRS duration,QT interval,and QTc interval were significantly shortened,while the P-R interval was significantly prolonged(P<0.05,P<0.01);in the control group,all parameters had no significant changes at the2 nd course of treatment(P>0.05),but at the 8th course of treatment,HR slowed down significantly,and P-wave,QRS duration,QT interval,and QTc interval were significantly shortened(P<0.05,P<0.01),while the P-R interval was significantly prolonged(P<0.01).Nevertheless,no significant alteration in QTc interval was observed during the 4th course of treatment(P>0.05).In the comparison between groups,there was no significant change in both groups’ data before treatment,at 2nd and 4th courses of treatment(P>0.05).At the 8th course of treatment,significant improvements in HR,P-wave,QRS duration,QT interval,QTc interval,and P-R interval were observed in the treatment group compared to the control group(P <0.05,P<0.01).(4)Myocardial injury markers and inflammatory factors:(1)In comparison with before treatment,the levels of Hcy,Cys C,NT-pro BNP,c TnⅠ,CK-MB,and hs-CRP in the serum of both groups showed a downward trend(P<0.05)after treatment;(2)In comparison between groups,both groups had a consistent baseline and were comparable(P>0.05);in comparison with the control group after treatment,the levels of Hcy,CK-MB,and hs-CRP in the serum of the treatment group showed a further downward trend(P<0.05,P<0.01);there was no significant change in Cys C,NTpro BNP,and c TnⅠ(P>0.05).(5)Serum fibrosis markers:(1)After the end of the treatment courses,the levels of HA,P Ⅲ NP,LN,and C Ⅳ in the serum of the treatment group were further decreased compared with before treatment(P<0.05);(2)Before the start of the treatment,there was no significant difference in the levels of HA,PⅢNP,LN,and CⅣ between the treatment group and the control group,indicating comparability;compared with the control group after treatment,the levels of HA,PⅢNP,and LN in the serum of the treatment group further decreased(P<0.05),while no significant change was observed in CⅣ(P>0.05).(6)TCMS:(1)Compared before and after treatment,there was no significant difference in TCMS between the two groups at the second treatment course(P>0.05),but it began to decrease at the fourth treatment course(P<0.01).(2)Compared between the two groups,there was no statistical difference in TCMS between the treatment group and the control group before treatment,at the second and fourth treatment courses(P>0.05).However,after the eighth treatment course,the treatment group showed a more significant improvement in TCMS than the control group(P<0.05).(7)Clinical efficacy rate: The total clinical efficacy rate of the treatment group was significantly higher than the control group’s rate(Z=-2.364,P<0.05).(8)24h urinary copper and CER: Throughout the treatment process,there was no significant fluctuation in CER levels before and after treatment or between the two groups(P>0.05).Compared with before treatment,the levels of 24 h urinary copper in both groups significantly increased at the second,fourth,and eighth treatment courses,with a rapid increase after the second treatment course and a gradual decrease after the fourth treatment course(P<0.01).Compared between the two groups,there was a significant difference in 24 h urinary copper between the two groups at the same treatment course after treatment(P<0.05,P<0.01).(9)Adverse reactions: There was no significant difference in the incidence of adverse reactions between the two groups of patients(P>0.05).Conclusion1.WD patients are more likely to develop subclinical cardiac damage,which may be related to the inflammatory response and fibrotic changes caused by copper deposition in myocardial tissue.2.GDFMG can better improve the TCM evidence score of WD patients,enhance copper repulsion,and improve clinical efficacy with fewer side effects and adverse reactions.3.GDFMG can effectively reduce the inflammatory response,improve myocardial injury and inhibit the fibrotic process,and play an active and important role in intervening early cardiac damage in WD. |
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