Study Of Diagnosis, Risk Stratification, And Epidemiology In Brugada Syndrome

Chapter I: Investigation to raise the sensitivity of screening diagnosis and study of drug provocation test in Brugada syndrome[ Background]Since Brugada brothers described the clinical features of Brugada syndrome(BrS) in 1992, researching on it has always been emphasizing because of close correlation between this syndrome and sudden cardiac death(SUCD). In recent 13 years, encouraging achievements had been witnessed in molecular heritage, cellular electrophysiological mechanism, clinical and differenciate diagnosis, epidemiology, risk stratification, and drug or no drug therapy. European Society of Cardiology (ESC) published "consensus report" in 2002, and updated in 2005, which were diagnosis criteria could be accepted by most people nowadays. Specific shape of J point and ST segment elevation(J-STE) is the key diagnosis point of BrS. But J-STE of BrS often displays features of multiplicity, dynamic change and concealed form, which always result in missed diagnosis. We need sensitive methods for screening and diagnosis now eagerly. Additionally, there was no provocation test drug recommended by ESC in China, and perhaps it was one of the reasons that researching on BrS was backward in our country.[ Objectives]To improve the situation of screening and diagnosis for BrS, we designed and studied diagnosis methods of new precordial lead system ,new lead system for Holter and propafenone provocation test etc, which were suit for our national condition.[Methods]1. New precordial lead system was designed. ECG was recorded, and the number and type of J-STE and its locus in precordial were analyzed in 17patients with BrS or idiopathic Brugada syndrome ECG pattern (IBEP). Besides, the same was done in 11 healthy controls and 5 cases with RBBB.2. New lead system for Holter (BS1 and BS2) were designed and verified. It was performed in 14 patients with BrS or IBEP. Diagnosis sensitivity of J-STE of BrS was compared among new lead system of Holter, conventional CM1 lead of Holter, and surface ECG.3. Protocol of propafenone provocation test was designed, and performed in 7 patients with suspected BrS and 10 healthy controls. Ajmaline provocation test was performed in 4 patients with suspected BrS.[Results]1. Results of new precordial lead system(D The most sensitive locus of precordial of abnormal ECG of BrS was located in the second to the third costal, the middle line of thoracic bone to the left middle line of clavicle(D3-F3 in new precordial lead system). The detective ratio of abnormal ECG reached 60-90% in this center region.(2) The new precordial lead system could identify more I type J-STE, it raised 43.5 times comparison with conventional right precordial leads. Similarly, the range of distribution position was also located at left-up precordial. However the conventional right precordial leads were outside of sensitive diagnosis region of I type J-STE.(3) Abnormal ECG of all patients was identified by new precordial lead system. The number of 3 types of J-STE raised 11.62 times comparison with conventional right precordial leads. Abnormal ECG wasn't recognized in the groups of healthy control and RBBB.(D The region of J-STE in Group IBEP was larger than group BrS, and the amplitude was larger also.2. Results of new lead system of Holter?Compared with conventional CM1 lead, new lead system BS1 andBS2 raised detective ratio of J-STE of BrS significantly, especially for Itype J-STE.(D Dynamic change of J-STE could be displayed by Holter monitoring,and it is found that J-STE appeared before ventricular fibrillation or VPCepisode in one patient.(3) Incidence of inverse change (J-ST depression ) could be detected byconventional Holter lead system in patients with BrS.? J-STE was not always synchronized among different leads at thedifferent time.3. Results of drug provocation test:CD Propafenone provocation test was positive in 7 patients with concealedor atypical BrS, and was negative in 10 controls.(2) VF occurred in one patient when the dosage of propafenone reached 2mg/kg.(3) It was positive for 4 concealed BrS when the dosage of ajmaline reached 3/4 of ESC recommended. Premature ventricular beat happened in 3 patients ,and 1° AVB occurred in one patient.[Conclusions]1. The most sensitive region of abnormal ECG in patients with BrS was not located at conventional right precordial leads V^, but D2-F3 in new precordial lead system.2. New precordial lead system was sensitive and specific for screening of BrS, and it could be used to analyze the range and amplitude of J-STE.3. New lead system of Holter (BS1 and BS2) was sensitive method for screening of BrS. It could display dynamic change of J-STE also.4. Propafenone could be used as tool drug of provocation test to unmask the diagnosis of concealed and atypical BrS. The dosage of ajmaline should be reduce in Chinese to avoid complicationsChapter II: Study of risk stratification and preliminary investigation of RFCA in Brugada syndrome [Background]Up to now, ICD is the only proven effective treatment which could prevent sudden cardiac death in patients with BrS. Current challenges are how to identify and select high risk patients. Inducibility of sustained ventricular arrhythmia by EPS is one of the most acceptable criteria, but it is controversial by some researcher nowadays. Besides, recent reports points to focal ablation of VPC to prevent ventricular fibrillation in BrS, nevertheless, its mechanism is not clear completely.[Objectives]To study the relationship between VF inducibility and prognosis, EPS was performed in patients with BrS or IBEP. To study the episode characteristic of ventricular arrhythmias, Holter monitoring and ICD follow-up were done in BrS with or without VF. One patient accepted experimental RFCA therapy, and the mechanisms of RFCA for prevent VF were carefully studied.[Method]1. EPS: AH and HV intervals were measured, atrial and ventricular programmed electrical stimulation was performed in five patients with BrS, and four cases with IBEP, and one patient with BrS and I ° AVB.2. Ventricular arrhythmia episode feature study: Holter monitoring was performed in seven BrS with spontaneous VF or EPS induced VF, or VF recorded by ICD (VF group), and seven without those features (N-VF group).Characteristic of VPC episode detected by Holter were compared between those two groups. Records of VF were analyzed from ICD in four patient, and features of VF episode were analyzed.3. RFCA The change of new precordial lead system ECG, the number of VPC detected by Holter monitoring, EPS inducibility, and propafenone provocation test were compared before and after RFCA in one patient with BrS. [Results]1. EPS(D VF was induced by ventricular programmed stimulation in fourpatients with syncope, which was sustained in three cases.(D Short proximal atrial fibrillation was induced by atrial programmedstimulation in five patients .Sustained atrial flutter was induced in onepatient, and PSVT in another case.(3) The HV interval was longer than normal in three patients ,one wasnear the borderline of high value .The mean HV interval of all cases wasprolonged (56.5 + 15.83ms) slightly.2. Episode characteristics of ventricular arrhythmias of BrS(D Time window of episode of VPC in VF group was nocturnal and before dawn, which was accordance with it of VF recorded by ICD, but it was not found in N-VF group.(2) In all 45 Episodes of VF analized in 2 patients with ICD implantation, all was triggered by VPC.(3) VF was triggered by clinical VPC recorded by Holter in one patient. 3.RFCA(D VPC induced by propafenone provocation test had the same morphology compared with clinical VPC in this case. ?After RFCA, it was demonstrated that J-STE disappeared in normal surface ECG and new precordial lead system ECG, the same dosage propafenone provocation test was negative, VF could not be induce byEPS ,and VPCs in Holter monitoring were reduced or disappeared. (3)New J-STE was appeared at the follow-up of 40 days, SUCD happened at the day of 106. I Conclusions]1. VF induced by EPS indicated high risk and poor prognosis, ICD was recommended in such patients.2. VPCs with episode time feature of nocturnal and before dawn, or accompanied by J-STE maybe new risk factor.3. RFCA maybe play role in substrate modification other than triggers elimination.Chapter III: Preliminary studies of prevalence of electrocardio-graphic sign of Brugada syndrome in healthy population in China. [Background]Brugada syndrome is a new clinical entity characterized by a high incidence of sudden cardiac death. The syndrome is thought to be responsible for 4-12% of all sudden deaths and at least 20% of all deaths in patients with structurally normal hearts. The prevalence of Brugada-type electrocardiogram (BS-ECG) in healthy Han Chinese remains unclear. [Objective ]To evaluate the prevalence of electrocardiographic sign of Brugada syndrome in healthy Han Chinese population. [Methods]The study subjects consisted of 1,069 consecutive government official which making annual health examination during May 11 to 29 , 2004. All subjects underwent history, physical examination, chest x-ray, and standard 12 leads ECG. The diagnostic criteria recommend by European Society of Cardiology was used to identify subjects with electrocardiographic sign of Brugada syndrome. [Results]Ten thousand and sixty-five healthy subjects (age 18-83 years, (mean 38.58±15.26) years, 805 males and 260 females) were enrolled in this study excluded four patients with cardiovascular disorders. There were 39 subjects had episodes of pre-syncope, 36 had syncope, and two had family history of sudden death. Electrocardiographic signs of Brugada syndrome were found in 8 male subjects (7.5%o) .All these carriers had saddleback type , in whom there were 4 cases with the type II...