Clinical And Basic Studies On Brugada Syndrome

Part One：Clinical analysis of inappropriate ICDtherapies in Chinese patients with Brugada syndromeBackground: Brugada syndrome(BrS) is an arrhythmogenic disease characterized byan increased risk of sudden cardiac death by ventricular fibrillation.Implantationcardioverter defibrillator (ICD) in high-risk patients provides continuous long-termarrhythmia protection.But in Brugada syndrome implantable cardioverter defibrillator(ICD) therapy is associated with a high rate of inappropriate therapies.Objective: In the present study, we report our experience in patients implanted withan ICD for Brugada syndrome, and explore how to effectively reduce the frequencyof inappropriate therapies.Methods: Fourteen Brugada syndrome patients (mean age42.6±12.9years;41males) were treated with an ICD and followed up termly. According to experience,theVT zone was programmed to400-320ms(150-188bmp) and the VF zone was<320ms(>188bmp). The time of onset type of arrhymia,treatments and its results ofthe episodes were investigated according the data logs of the ICD. The episodesanalysis was analyzed by two independent electrophysiologists on the basis of storedICD electrocardiogram.Results: During mean43±28.9months of follow-up,there were297episodes.178episodes were true VF (90%) in198total VF episodes，the cycle length of true VFcycle length was≤250ms.90episodes (91%) were supraventricular arrhythmias(SVT)in99total ventricular arrhythmia episodes,only9episodes were true ventricular arrhythmia,the cycle length of SVT were≥360ms. Supraventricular arrhythmiasdiscriminate in ICD, Wavelet criterion can reduce82%(72/90) inappropriatelytherapy.Conclusion: In high risk patients with BrS, the leading cause of inappropriate ICDtherapy was supraventricular arrhythmias. Programming of a high-rate VT zone(cyclelength<360ms or rate>167bmp) and applying supraventricular arrhythmiasdiscriminate in ICD(such as Wavelet criterion) in patients with BrS can reduce thefrequency of inappropriate therapies. Part two:Seasonal and circadian distributions ofventricular fibrillation in Chinese patients withBrugada syndromeBackground：It is well-known that the incidence of ventricular tachyarrhythmias isthe highest in winter and during the daytime in patients with structural heart disease.However, little is known about the seasonal and circadian distributions of ventricularfibrillation(VF) in Chinese patients with Brugada syndrome.Objective： The aim of this study was to investigate seasonal and circadiandistributions of VF in Chinese patients with Brugada syndrome.Methods：We analyzed the data of appropriate episodes for VF recorded by animplantable cardioverter defibrillator(ICD) in patients with Brugada syndrome.Results： Fourteen Brugada syndrome patients (mean age42.6±12.9years; allmales) were treated with an ICD.During43±28.9months of follow-up,178true VF episodes were analyzed. There was a significant peak from winter to spring (P=0.02).As for the circadian variation, significantly more VF occurred from midnight to6:00(P<0.0001). Electrical storms of VF occurred in four patients. The seasonal andcircadian variations of electrical storms were similar to those of the VF episodes.Conclusions：In Chinese patients with Brugada syndrome, there was a significantseasonal peak from winter to spring and a significant circadian peak from midnight toearly morning in terms of the occurrences of VF. Part Three:A preliminary exploration of utilizingserum microRNAs as potential markers for Brugadasyndrome related diseases detectionBackground：MicroRNAs(miRNAs) are a class of approximately22nu-cleotidenoncoding RNAs that mediate post-transcriptional gene regulation by binding to andrepressing specific messenger RNA targets． MiRNA closely related to manydiseases．Recent studies have found that there is abundant and stable miRNA inhuman serum,and some patients showed specific changes in miRNA expressionprofiles，suggesting that serum miRNA as a new non-invasive potential of markers fordiagnosis and prognosis assessment．But there has not been relevant in patients withBrugada syndrome(BrS) reported．Objectives：In this study,we determined the serum miRNA expression profile inpatients with Brugada syndrome in order to develop a novel diagnostic BrSbiomarker and evaluate its prediction,diagnosis value． Methods：First,an initial screen of miRNA expression was performed in serumsamples from untreated14patients with Brugada syndrome and14age and gendermatched normal by solexa sequencing．Then using RT-qPCR in serum samples(14patients with BrS,42normal controls and12first-degree relatives of BrS)for tainingset，selected a group of significant changes miRNA；validted in another cases of BrSto get a group of stable changes miRNA.Finally，ROC curves were used to evaluatethe clinical value of miRNA．Results：Solexa sequencing showed that,the serum miRNA proportion of all smallRNA molecules were23.26%and53.95%of the patients with Brugada syndrome andnormal controls，respectively．Serum miRNA expression profile in BrS patients weresignificant different from controls and13serum miRNA copy were markedly changeregulated in patients with Brugada syndrome compared with controls more than1.5times,and the difference greater than7000(12down,1up)．RT-qPCR identified aprofile of three serum miRNAs：let-7b,miR-30d and miR-140-5p to be biomarkers(P<0.001) for BrS in training set include14patients and14controls．This resultswere further confirmed in another14patients with BrS and42controls (P<0.001) forlet-7b,miR-30d and miR-140-5p.But the three miRNAs have no difference betweenthe first-degree relatives of BrS and controls. ROC curve analysis showed that,theAUC for3miRNA group of patients and normal samples was0.794．Conclusions：Serum miRNA expression profile of in patients with Brugada syndromewere significant different from controls；miRNA were down-regulate significantly inpatients with BrS；the3miRNA group can be used as a novel blood potentialbiomarker for the diagnosis of Brugada syndrome detection．...