Study On The Electrocardiogram And Mechanism Of Malignant Arrhythmia And The Gene Polymorphism Of Death Warning In Heart Failure

Background:SCN5A gene encodes the a subunit of cardiac sodium channel which drives the inward sodium current and is responsible for the intercellular conduction. Mutations in SCN5A result in a series of inherited life-threatening arrhythmias, including Brugada syndrome, long QT syndrome, early repolarization syndrome, and so on. Sodium channel blocker induced ST-segment depression was reported in some Brugada ECGs. However, patient expressing ST-segment depression along with early repolarization has not been reported.Objectives:The aim of the present study was to identify the genetic mutation underlying amiodarone induced precordial ST segment depression and lateral J wave in a patient with ventricular fibrillation, and tentatively analyze the mechanism underlying the electrocardiogram (ECG) phenotype.Methods:The ECGs and clinical data were collected and investigated carefully. The genetic testing was conducted to the proband and his relatives. Patch-clamp and immunocytochemical studies were performed in heterologously transfected human embryonic kidney 293(HEK-293) cells.Results:The proband was a 55-year north Chinese, who suffered from nocturnal dyspnea and syncope in the day work. Atrial fibrillation (AF) attack was recorded in the emergency room. After amiodarone injection, significant ST-segment depression in the precordial leads V2-V3 developed whereas J wave was noticed in the lateral leads followed by electrical storm with episodes of ventricular fibrillation (VF). ECG parameters under sinus rhythm were within normal limits except for subtle ST-segment elevation in leads V1-V3. A novel frame-shift mutation C280S*fs61 in SCN5A was identified. In cells transfected with mutant channels, no current could be recorded as expected and immunocytochemical studies confirmed the formation of truncated peptide. The kinetics of the wide-type (WT) channel were not altered when co-transfected with C280S*fs61, which suggested a functional haploinsufficiency of sodium channel may be responsible for the clinical phenotype.Conclusion:Amiodarone induced precordial ST segment depression accompanied with lateral J wave was reported in a proband suffered from early repolarization syndrome (ERS). The "loss-of-function" frame-shift mutation C280S*fs61 of sodium channel may lead to the clinical and unusual electrocardiographic phenotype.BackgroundArrhythmogenic Right Ventricular Cardiomyopathy (ARVC) is a common inherited heart disease that causes ventricular arrhythmia and sudden cardiac death in young people and athletes. Ventricular arrhythmias (VA) origin from ARVC and idiopathic right ventricular outflow tract ventricular arrhythmias (RVOT-IVA) can share the same electrocardiographic (ECG) pattern of left bundle branch block (LBBB)/inferior axis. The prognosis, however, is different. And the management strategy is divergent. Distinguishing two entities would be of great clinical significance.ObjectiveConsidering the malignant prognosis of ARVC, discriminating the two kinds of pathologies and stratifying patients with high risk through routine 12 leads ECG is of importance to clinical practice. Aim of this study was to compare the VA morphology between the two conditions.MethodsThe study included 16 ARVC and 45 (30 originated from the septum,15 from the free-wall) RVOT-IVA patients. ECG characteristics of VA episode were compared. The parameters of the ECG measurement included:(1) QRS duration (2) Precordial R-wave transition lead and (3) QRS notching. We further divide the 12 leads into 4 territories (lateral, inferior, right precordial, left precordial). The ECG was defined as to expressing "wide notched QRS" if QRS notching exists in 2 consecutive leads within the territory.ResultsCompared with RVOT-IVA patients, QRS configuration during ventricular arrhythmia in patients with ARVC had longer mean duration in all 12 leads, and significant differences existed in leads Ⅰ, Ⅱ,Ⅲ, aVL, aVF, and V1 (P＜0.05). Lead I had the largest mean difference of 25.1±5.8ms. In addition, ARVC had more R wave transition in lead V5 or later (6/16[37.5%] vs.4/45[8.9%], P＜0.01). The presence of QRS notching (15/16[93.8%] vs.36/45[80.0%], P=0.20) and the total number of leads expressing notching (2.88±2.0 vs.2.80±2.0, P=0.90) were not different between ARVD/C and idiopathic RVOT-VA. However, QRS notching existing simultaneously in lead I and aVL was more common in ARVC (43.8%vs.13.3%, p=0.011).ConclusionLonger QRS duration, later precordial R/S transition and QRS notching in lateral leads (lead I and aVL) are useful in discriminating ARVC from RVOT-IVA.BackgroundChronic heart failure (CHF) is chronic heart disease with relatively high morbidity and mortality. The incidence was increased with positive correlation with age. With the improvement of the survival rate of patients with acute myocardial infarction, CHF induced by ischemic cardiomyopathy (ICM) was increased year by year. Sudden cardiac death and pump failure is the main cause of death. In recent years, a large number of research evidence suggested that hydrogen sulfide (H2S) perform a protective role in cardiovascular system via diverse signaling profile and endogenous H2S) was considered as the third gaseous transmitter. In animal models, exogenous supplement or endogenous H2S production increase would improve the prognosis.Endogenous hydrogen sulfide (H2S) was considered as the third gaseous transmitter and exert cardio-protective actions via diverse signaling profile in ischemic cardiomyopathy (ICM) and chronic heart failure (CHF).ObjectiveTo explore the relationship between the gene variants in endogenous H2S synthesis enzymes encoding genes and the prognosis of heart failure..MethodsA total of 944 Chinese Han patients with CHF were genotyped for 7 gene variants representing four genes which involved in the endogenous synthesis of H2S, and the correlation between these SNPs and the prognosis as well as the severity of CHF was analyzed.The study continuously enrolled 944 patients with ICM induced CHF since July 2005 to December 2009 in Fu Wai Hospital. The NYHA class was II to IV class, and the LVEF was less than 50%. Follow-up study was finished in August 2014 with telephone or clinical outpatient, and primary endpoint events includ all-cause mortality, sudden cardiac death (SCD) and non-sudden cardiac death (NSCD). After preliminary experiments, a total of 7 single nucleotide polymorphisms (SNP) sites were tested in all included patients with matrix-assisted laser desorption ionization time of flight mass spectrometry (MALD-TOF MS) method. Statistical analysis was performed using SPSS17.0.ResultsDuring a median follow-up period of 65 months,332 (35.17%) all-cause deaths occurred, including 123 (37.05%) patients experienced sudden cardiac death (SCD), whereas 209 (62.95%) cases had NSCD (non-SCD). The C allele of rs2490281 on GOT-1 gene, which encodes the cytoplasmic cysteine aminotransferase (CAT), was associated with greater risk of all-cause death and NSCD after adjusting for other risk factors (hazard ratio [HR] 1.608,95% confidence interval [CI] 1.155-2.239, P=0.005; and HR 1.778,95% CI 1.181-2.676,P=0.006, respectively). In addition, multivariate regression analysis revealed that rs2490281 was also associated with increased risk of a lower left ventricular ejection fraction (LVEF<35%). (odd ratio [OR] 1.783,95% CI 1.099-2.890, P=0.019).ConclusionThe rs2490281 in GOT-1 gene may serve as an independent predictor of all-cause death in ICM related CHF patients in Chinese Han population. The observation suggested gene variants in endogenous H2S synthesis enzymes genes may influence the initial severity and prognosis of CHF.