The Clinical Phenotype Study Of Arrhythmogenic Right Ventricular Cardiomyopathy With Left Ventricular Involvement

BackgroundArrhythmogenic right ventricular cardiomyopathy(ARVC)is widely regarded as a heart muscle disease usually with an autosomal dominant pattern of inheritance,characterized by progressive death and fibro-fatty replacement of ventricular myocardium resulting in myocardial atrophy.It was first described by Marcus and Fontaine as a disease in 1982,and has been included in the initial classification of cardiomyopathy by the World Health Group since 1955.ARVC is relatively rare with an estimated prevalence ranging from 1:5000 to 1:2000 and usually present between 20 and 50 years old.Men are more common than women.The main clinical manifestations of ARVC are frequent ventricular arrhythmias,high-risk sudden cardiac death and progressive dysfunction of the ventricular resulting in sudden cardiac death(SCD)of young people including athletes.There is no gold standard for diagnosis of ARVC,as the etiology and pathogenesis have not been fully clarified along with its incomplete penetrance of gene mutations,heterogeneous clinical manifestations,and overlap with genotypes and phenotypes of many other diseases.The classic manifestations of ARVC are abnormalities of the morphology and/or function of the right ventricle.It was traditionally viewed that the left ventricle was not or rarely involved,and the left ventricular involvement was a manifestation of the disease progressing to advanced stages.With the development of molecular genetics and imaging technology in recent years,more and more patients with left ventricular involvement especially in early stages have been found.The clinical manifestations of ARVC with left ventricular involvement are similar to classic ARVC,and it is not easy to distinguish it from other diseases in imaging.If attention is not payed enough to ARVC in the early stage,it is easy to cause missed diagnosis and misdiagnosis of patients,which seriously affects the life and prognosis of patients.ObjectiveThe study aims to explore the clinical phenotype characteristics and the relationship between left ventricular(LV)and ARVC by analyzing the general information,data of electrocardiogram(ECG),24 hours dynamic electrocardiogram(24h Holter)and echocardiographic/ultrasonic cardiogram(UCG)of ARVC with LV involvement,so as to fully understand the clinical phenotypes of ARVC and provide clinical references for identification of patients with ARVC in the early stage,contribution to reducing the rate of misdiagnosis and missed diagnosis,and the etiology and pathology research of ARVC.MethodsThe general information,data of ECG,24h Holter and UCG of patients with a definite diagnosis of ARVC was collected retrospectively in the First Affiliated Hospital of Zhengzhou University from January 01,2011 to May 31,2019.Forty-four patients were included in the study at last.They were divided into two groups according to whether there is LV involvement in UCG:LV involvement group and no LV involvement group.Clinical data of the two groups were compared and analyzed.SPSS22.0 software was used for statistical analysis.Continuous variables are summarized as x±s or M(QL,QU),while categorical variables are described as a percentage or frequency.Tests used for comparison between two groups include the student t test between two independent samples,rank sum test,and chi-square test.?=0.05(two-sided)was set as the test level,and P values of 0.05 or less was considered statistically significant.Results1.General information:Among 44 patients,the ratio of male vs.female is about 2.1:1,the average age of onset is(41± 8.2)years and the median duration from onset to diagnosis is 10(2,10)years.16 cases(36.4%)were induced by intense exercise.3 cases(7.7%)had a family history of sudden death.33 cases(75.0%)had clinical heart failure.the proportion of symptoms in order:chest congestion(63.0%),palpitations(59.1%),dyspnea(43.2%),dizziness(43.2%),nausea/vomiting(30.5%),syncope(18.2%).18 patients(40.9%)were indicated with LV involvement by UCG.In terms of gender ratio,age of onset,age of diagnosis,duration from onset to diagnosis,causes of onset(intense exercise),comorbidities(hypertension,diabetes,coronary heart disease),family history of sudden death,clinica symptoms,clinical heart failure,there was no statistically significant difference between the two groups(P>0.05).2.ECG:Epsilon waves were seen in 19 patients(43.2%).There was no T-wave inversion(TWI)in 4 patients(9.1%),and TWI exceeding V1-V3 leads was seen in 21 patients(47.7%).Compared with no LV involvement group,there were more patients with low voltage in the right chest leads only(8 cases,44.4%)in the LV involvement group(P<0.05).In terms of Epsilon wave,low voltage of QRS waves in limb leads,low voltage in chest leads and TWI,there was no statistically significant difference between the two groups(P>0.05).3.24h Holter:The number of patients with premature ventricular contraction(PVC)>500 beats/24h,sustained ventricular tachycardia(SVT),non-sustained ventricular tachycardia(NSVT),atrial flutter(AFL)/atrial fibrillation(AF)was respectively 21(47.7%),11(25.0%),25(56.8%)and 25(56.8%)cases.There were more patients with SVT(8 cases,44.4%)in the LV involvement group compared with no LV involvement group(P<0.05).There was no statistically significant difference between the two groups in other arrhythmias(P>0.05).4.UCG:Left ventricular end-diastolic diameter and left ventricular end-systolic volume were larger,and left ventricular ejection fraction was lower in LV involvement group compared with no LV involvement group(P<0.05).There were no significant differences in right ventricular end-diastolic basal diameter(RVEDD),the function of right ventricular,regurgitation in mitral and tricuspid wave between the two groups(P>0.05).Conclusions1.40.9%of ARVC patients are indicated with LV involvement by UCG.LV involvement has a significant effect on the structure and function of LV in ARVC patients,and they have more severe symptoms and worse prognosis.LV involvement is not a sign of right ventricular(RV)progression of ARVC,and may occur at any stage of the disease.2.For patients who are suspected ARVC in clinical practice and imaging findings are inconsistent with classic ARVC,differential diagnosis and follow-up should be strengthened to identify ARV C patients with atypical manifestations in the early stage and reduce the rate of misdiagnosis and missed diagnosis.