Ventricular Arrhythmias And Heart Failure Caused By The Sudden Death Early Gene Prediction

Background Imbalance of sympathetic nervous system was involved in the pathogenesis of idiopathic ventricular outflow-tract tachycardia. This study was aimed to compare the clinical characteristics of idiopathic ventricular outflow-tract tachycardia and idiopathic left ventricular tachycardia, and investigate whether the major variants in theβ1 andβ2-adrenoceptors and GNB3 C825T were associated with the two main subtypes of idiopathic ventricular tachycardia in Chinese Han population.Materials and methods Patients with idiopathic ventricular outflow-tract tachycardia and idiopathic left ventricular tachycardia from December 2005 to December 2007 were consecutively enrolled into this study. Controls were randomly selected from the community-based inhabitants. Five genetic variants, Ser49Gly and Gly389Arg in theβ1-adrenoceptor, Arg16Gly and Gln27Glu in theβ2-adrenoceptor and GNB3 C825T, were genotyped by polymerase chain reaction-restriction fragment length polymorphism analysis in this case-control study.Results A total of 227 idiopathic ventricular outflow-tract tachycardia patients and 110 idiopathic left ventricular tachycardia patients were consecutively enrolled into this study. The control group consisted of 634 subjects. The clinical characteristics of idiopathic ventricular outflow-tract tachycardia and idiopathic left ventricular tachycardia were significantly different. idiopathic ventricular outflow-tract tachycardia occurred at an older age (38.2±13.9 years vs.32.5±14.4 years, P= 0.001) and in more females (60.8% vs.31.8%, P< 0.001) than idiopathic left ventricular tachycardia. The initial episode of ventricular tachycardia provocated at sympathetic nervous activation state more frequently in idiopathic ventricular outflow-tract tachycardia than in idiopathic left ventricular tachycardia (76.7% vs.41.8%, P< 0.001). On the presentation of index clinical arrhythmia, idiopathic ventricular outflow-tract tachycardia mainly presented with frequent premature ventricular contractions, while patients of idiopathic left ventricular tachycardia mainly presented with paroxysmal sustained monomorphic ventricular tachycardia or nonsustained ventricular tachycardia (P< 0.001). Genotyping revealed that the 16Gly allele of Argl6Gly variant of β2-adrenoceptor was associated with a higher risk of idiopathic ventricular outflow-tract tachycardia (OR:1.40,95% CI:1.12-1.75, P= 0.003 in the addictive model and OR: 1.62,95% CI:1.14-2.31, P= 0.007 in the dominant model). Patients with Gly16Gln27 haplotype also had a higher risk of idiopathic ventricular outflow-tract tachycardia (OR: 1.38,95% CI:1.11-1.73, P= 0.012). Other four variants, including Ser49Gly and Arg389Gly inβ1-adrenoceptor, Gln27Glu inβ2-adrenoceptor and GNB3 C825T, did not differ between patients with idiopathic ventricular outflow-tract tachycardia and controls. In patients with idiopathic left ventricular tachycardia, no significance was found in these five variants compared with controls.Conclusions Arg16Gly inβ2-adrenoceptor is significantly associated with idiopathic ventricular outflow-tract tachycardia in Chinese Han population. Major gene variants inβ1 andβ2-adrenoceptor and GNB3 C825T may be not associated with idiopathic left ventricular tachycardia. These data suggest a different arrhythmogenic mechanism in idiopathic ventricular outflow-tract tachycardia and idiopathic left ventricular tachycardia. Background Heart failure has become an increasingly prevalent disorder with a high incidence of sudden cardiac death. Susceptibility to sudden cardiac death was considered to be a heritable trait in general population. Ca2+ cycling plays a critical role in heart failure and lethal arrhythmias. We therefore investigated whether potentially functional variants of RyR2 and L-type calcium channel genes were related to the risk of ventricular arrhythmias and sudden cardiac death in chronic heart failure in a case-control study.Materials and methods From July 2005 to January 2008, consecutive patients with chronic heart failure referred to Fu Wai Hospital were recruited. Inclusion criteria were:chronic heart failure caused by ischemic heart disease arising from coronary artery disease or chronic heart failure caused by idiopathic dilated cardiomyopathy; symptomatic heart failure with New York Heart Association (NYHA) functional class II-IV despite optimized medical therapy; and left ventricular systolic dysfunction with a left ventricular ejection fraction (LVEF)≤50% in ischemic heart disease and≤45% in dilated cardiomyopathy. Heart failure severity was defined as mild (40%< LVEF≤50%), moderate (30%< LVEF≤40%) or severe (LVEF≤30%). Controls were selected from inpatients with coronary artery heart disease but without acute coronary syndrome, unstable angina pectoris, myocardial infarction, heart failure or ventricular arrhythmias (41.2% of the control group) and from community-based inhabitants who underwent an annual health examination and were free of structural heart disease and any type of cardiac arrhythmias (58.8% of the control group). The gender and ages were matched with the cases. Participants were genotyped using ligase detection reactions for three variants, rs3766871 (G1886S) and rs790896 (G> A) in RYR2 and rs723672 (T> C) in CACNA1C. For statistical analysis, multivariate Logistic regression analysis, Cox proportional-hazards models and survival analysis were used.Results A total of 1244 chronic heart failure patients and 1032 control subjects were enrolled in this study. Genotyping analysis revealed that the A allele of rs3766871 in RYR2 was associated with increased risk of ventricular arrhythmias in heart failure patients [odds ratio= 1.66,95% CI (confidence interval)= 1.21-2.26; P= 0.002]. During a median follow-up period of 32 months in 1058 (85.0%) patients,296 (28.0%) patients died from heart failure, of whom 141 (47.6%) were sudden cardiac death. After adjustment for age, gender and suspected risk factors, patients carrying the A allele of rs3766871 had an increased risk for cardiac death [HR (hazard ratio)= 1.53, 95% CI= 1.11-2.12; P= 0.010] and sudden cardiac death [HR= 1.92,95% CI= 1.25-2.94; P= 0.003]. Patients carrying the A allele of rs790896 in RyR2 had a reduced risk for sudden cardiac death [HR= 0.65,95% CI= 0.45-0.92; P= 0.015].Conclusion The A allele of rs3766871 in RYR2 not only associates with ventricular arrhythmias but also serves as an independent predictor of sudden cardiac death, and the A allele of rs790896 in RYR2 is a protective factor against sudden cardiac death in patients with chronic heart failure.