Study On The Evaluation Of The Progression Of Arrhythmogenic Right Ventricular Cardiomyopathy And The Treatment To Delay Its Progressio

Background:Evidence suggests arrhythmogenic right ventricular cardiomyopathy(ARVC)is a progressive disease;however,studies that focus on evaluating the extent of disease progression and its clinical implications are scarce.The characteristic of patients with more extensive disease progression is still undetermined.Once those factors are defined,clinical trials can be designed to specifically test whether the treatment is helpful in preventing disease progression.Objective:To confirm ARVC is a progressive disease and further quantify the trend of the progression in a large cohort of patients.To determine the association between the extent of disease progression and adverse outcomes.Methods:This is a retrospective observational study that enrolled 188 patients with a definite diagnosis of ARVC as determined by 2010 task force diagnostic criteria and with available transthoracic echocardiogram of baseline and follow-up.Disease progression was determined with the linear mixed model.Subgroup analyses were further carried out to investigate the factor associated with an accelerated disease progression.The Cox regression model was used to investigate the association between the extent of disease progression and adverse outcomes.Results:In this observational study,188 patients that satisfied the 2010 task force definite diagnostic criteria were included(mean age,38.2±14.1 years;males,147[78.2%]).With a median surveillance of 4.1(IQR:2.4-6.0)years,637 transthoracic echocardiograms were conducted and analysed.The right ventricle outflow tract dilated at a rate of 0.85 mm per year(95%CI:0.71-0.99),and tricuspid annular plane systolic excursion(TAPSE)declined at 0.33 mm per year(95%CI:0.26-0.40).Vigorous exercise was associated with a faster progression of right ventricular as well as patients with age<30 years.Progression in the left ventricle was relatively slow;left ventricular end-diastolic dilated at a rate of 0.13 mm per year(95%CI:0.02-0.24),and left ventricular ejection fraction(LVEF)declined at 0.18 mm per year(95%CI:0.00-0.35).Progression speed was highly heterogeneous among patients.TAPSE progression ranged from a 4.5-mm decrease to a 2.8-mm increase per year,whereas LVEF progression ranged from an 18%decrease to a 9%increase per year.A faster decline in the LVEF(adjusted HR:1.23,95%CI:1.16-1.31,p<0.001)and TAPSE(adjusted HR:2.85,95%CI:2.00-4.17,p<0.001)were associated with an increased risk of major cardiovascular adverse outcome in multivariable analyses.A faster disease progression was also associated with a higher recurrence rate of life-threatening ventricular arrhythmia events.Conclusions:Both ventricles could involve patients with ARVC,and LV involvement tended to occur in the advanced stage due to relatively slow progression compared to RV.A faster progression rate of LVEF and TAPSE was associated with an increased risk of adverse outcomes.Long-term surveillance of disease progression should be emphasized.Background:Arrhythmogenic right ventricular cardiomyopathy(ARVC)is one of the leading causes of sudden cardiac death in young people and athlete.Current therapies mainly focus on prevention of ventricular arrhythmia(VA).Although implantable cardioverter defibrillators have been proven to be effective,repeated shock therapy,nevertheless,affects patients’quality of life.Attempts have been made to reduce the recurrence with drugs and catheter ablation,while no definite result was carried out.Multiple pieces of evidence prove that the continuous destruction of the ventricle and recurrence of VAs were paralleled with the extent of disease progression.Therapy established upon decelerating disease progression might produce unexpected results.Objective:To assess the effect of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers(ACEI/ARB)in a large cohort of patients with a definite diagnosis of ARVC.Methods:This retrospective observational cohort study included 311 patients with a median follow-up of 6 years.Grouping was determined by whether under the treatment of ACEI/ARB medication.Disease progression was surveillance by was repeated measurement of transthoracic echocardiograms,and the data were processed with the linear mixed model.Cox proportional hazard regression models were used to evaluate the association between life-threatening ventricular tachycardia events and ACEI/ARB treatment.Subgroup analyses were further carried out to investigate the effect of interaction.Results:A total of 311 patients[age,39.1±14.4 years;male,233(74.9%)]with a definite diagnosis of ARVC as determined by 2010 task force diagnostic criteria.Of these,113 patients(36.3%)received ACEI/ARB treatment during follow-up.In patients without treatment of ACEI/ARB,tricuspid annular plane systolic excursion(TAPSE)decreased 0.61 mm per year(95%CI:0.77-1.03).ACEI/ARB could decelerate this trend to 0.24 mm decrease per year(95%CI:0.31-0.42),or 60.7%(95%CI:58.9%-64.5%,P<0.001)relative reduction.ACEI/ARB treatment also slowed the dilation of the right ventricular outflow tract(1.06 mm vs.0.57 mm per year increased,P= 0.003).During the median followup of 5.96(IQR:3.74-8.61)years,65.3%(n=203)of the patients experienced life-threatening VA events,with an annual event rate of 19.8%(95%CI:17.2%-22.8%).A reduced risk of life-threatening ventricular arrhythmia was associated with ACEI/ARB treatment compared to that without ACEI/ARB treatment[55.8%vs.71.2%,crude hazard ratio(HR):0.69,95%CI:0.51-0.93,P=0.013],and this effect still existed after adjusted for age,sex,right ventricular ejection fraction,percentage of late gadolinium enhancement in the right ventricle,N-terminal pro-brain natriuretic peptide,ICD,and catheter ablation(adjusted HR:0.71,95%CI:0.52-0.96,P=0.031).Sensitivity analyses with different grouping principal showed significant results.In subgroup analyses,no significant interaction with ACEI/ARB was observed.Conclusions:ACEI/ARB medication was associated with slower disease progression and reduced risk of life-threatening ventricular arrhythmia in patients with ARVC compared to those without.This study suggests that delaying disease progression may pave a new way for the treatment of ARVC.