| BackgroundIdiopathic left ventricular tachycardia (ILVT) is one of the common arrhythmias in patients without structural heart disease. Radiofrequency catheter ablation has become the main approach to cure ILVT. The strategy of ILVT ablation is usually based on the identification of left posterior fascicular potential (PP) and activation mapping during the tachycardia. However, both the unavailability and the unstable conditions inducing the tachycardia could impede the ablation of ILVT as well as influence the long-term successful rate of the ablation. Slow conduction zone (SCZ) has been considered associated with the successful ablation of ILVT, but the relationship between SCZ and ILVT as well as the characteristics of the substrate of ILVT are still uncertain. Thus, explore the features of substrate which associated with ILVT and using the substrate mapping to guide the ablation might improve the long-term successful rate of the ablation of ILVT.ObjectiveTo explore the features of substrate of ILVT by investigating the anatomic and electrophysiological characteristics of SCZ using electroanatomic mapping, and to identify the role of substrate mapping in the ablation of ILVT.MethodsBetween January 2009 and May 2011, ten consecutive patients (mean age 42.5±9.4 years) with ILVT were referred for radiofrequency catheter ablation in Fuwai Hospital (Beijing, China), including seven males and three females. A three-dimensional electroanatomic mapping system was used to perform mappings in all of the participants. After the three-dimensional endocardial geometry of left ventricle was created, the conduction system with PP and the SCZ with diastolic potential (DP) were mapped during both sinus rhythm and tachycardia. The areas where could record PP and DP were tagged with special landmarks to identify the anatomic characteristics of SCZ, and the entrainment mapping was performed to identify the electrophysiological features of SCZ.ResultsElectroanatomic mapping was successfully performed in seven of the ten patients during both sinus rhythm and tachycardia, and it was performed only during the tachycardia in the other three patients. The SCZ that could record DP was located at the inferoposterior septum, and the length of it was 25.2 ±2.3 mm with a conduction velocity of 0.08+0.01 m/s. There were no significant differences in these parameters between mapping during the sinus rhythm and during the tachycardia (p>0.05). The left posterior fascicular that could record PP was located at the posterior septum. The junction area of SCZ and left posterior fascicular with both DP and PP was found in seven patients during both sinus rhythm and tachycardia; in addition, the distribution of the junction area during the sinus rhythm was consistent with that during the tachycardia. In three patients, the tachycardia was mechanically terminated when mapping was performed in this junction area. Furthermore, the successful ablation sites were located in this junction area in all the participants. In the mean follow-up of 22.4±5.1 months, no ILVT recurred in any of the patients, and no patients had complications.ConclusionThe junction area formed by the SCZ and the left posterior fascicular, where could record both DP and PP, was the substrate of ILVT. It played an important role in the reentry of the ventricular tachycardia, and it could be identified and used to guide the ablation of ILVT during sinus rhythm.BackgroundSeveral genetic variants have been associated with early repolarization syndrome, however, the lack of functional validation of the mutant effects sets a limitation on the genetic test interpretation.ObjectiveTo identify mutations and underlining mechanisms associated with the early repolarization syndrome, and to investigate the effects produced by the mutation on the ion channel functions.MethodsA 67-year-old male proband, who was diagnosed with early repolarization syndrome, underwent a clinical evaluation and genetic analysis to identify genetic mutations associated with the disease. Whole-cell configuration of patch-clamp techniques and immunocytochemistry were used to explore the effects caused by the mutation and to identify the underlying mechanism of the disease.ResultsBaseline 12-lead electrocardiogram (ECG) of the proband exhibited coved ST-segment elevations which mimicked acute myocardial ischemia in lead V2-V6, and the ECG also revealed J waves in lead Ⅱ, Ⅲ, aVF and V2-V6. Polymorphic ventricular tachycardia, which was terminated successfully by direct current cardioversion, was documented on the ECG. Structural abnormalities were excluded by other examinations. One bother of the proband suffered from sudden death. Gene test showed that the proband had a novel heterozygous missense mutation of A1055G in SCN5A gene. The functional study via the patch-clamp demonstrated that the mutation of A1055G significantly decreased the peak sodium current (INa) density (-33.39±14.29 pA/pF, n=7) to 14% of that in wild type (WT) cells (-238.68±97.13 pA/pF, n=7); furthermore, the heterozygous co-expression of WT and A1055G channels also displayed a considerably reduced peak INa density (-112.69+41.66 pA/pF, n=6) compared with that of WT channels (P<0.001). In addition, the mutation shifted the steady-state inactivation curve to a more negative potential compared with the WT channels (P=0.003), while the steady-state activation curve had no significant changes (P>0.05). Confocal imaging suggested that the mutant channel had a defect of protein expressions both on the cell membrane and in the cytoplasm.ConclusionsA novel heterozygous missense mutation of A1055G in SCN5A led to’loss-of function’of the sodium channels that might account for the arrhythmogenic characteristics of early repolarization syndrome.BackgroundChronic heart failure (CHF), caused by ischemic cardiomyopathy (ICM) and nonischemic cardiomyopathy (NICM), is among the leading causes of mortality and morbidity worldwide. Sudden cardiac death (SCD), which is resulted from malignant arrhythmias, remains an important cause of mortality in patients with CHF. Thus, the prediction and prevention of SCD play essential roles in the management of patients with CHF. Low-density lipoprotein receptor-related protein 6 (LRP6) plays a critical role in regulating Wnt signaling. Dysregulated Wnt signaling contributes to high incidence of arrhythmias associated with various forms of heart disease. Thus, there might be an association between genetic variations of LRP6 and SCD.ObjectiveTo examine the association between common variants of LRP6 and prognosis of patients with CHF.MethodsFrom July 2005 to December 2009, patients with CHF referred from 10 hospitals and participants without structural heart disease in China were undergone a prospective study. Enrolment criteria including:(1) CHF caused by ICM or idiopathic dilated cardiomyopathy (DCM); (2) New York Heart Association (NYHA) functional class Ⅱ-Ⅳ despite optimized medical therapy; (3) Left ventricular ejection fraction (LVEF)≤50% in ICM and≤45% in DCM. Excluded criteria including:(1) CHF caused by other reasons except for ICM and DCM; (2) sustained arrhythmias and pacemaker dependency; (3) pregnancy, terminal illnesses (malignant tumors, severe liver and kidney dysfunctions) or other uncontrollable system disease; (4) failure of genotyping; (5) those who were reluctant to participate in the study. All the participants were followed up periodically until August 2014. The end points included all-cause death, SCD and non-SCD (NSCD). The single nucleotide polymorphism (SNP) rs2302684 was selected to evaluate the effect of LRP6 polymorphisms on the survival of the patients.ResultsA total of 1,887 patients (1,437 with CHF and 450 in the control group) were finally enrolled for the analysis. During a median follow-up of 61 months, a total of 546 (38.00%) patients died, including 201 (36.81%) cases with SCD and 345 (63.19%) cases with NSCD. No end point event occurred in the control group. Patients carrying A allele of rs2302684 had increased risks of all-cause death (HR 1.450,95% CI 1.213-1.733; P<0.001) and SCD (HR 1.844,95% CI 1.387-2.452; P<0.001). After adjusted for the other risk factors, the associations remained significant in all-cause death (HR 1.425, 95% CI 1.189-1.706; P<0.001) and SCD (HR 1.783,95% CI 1.337-2.378; P< 0.001). In patients with CHF caused by ICM, those carrying A allele of rs2302684 also had increased risks of all-cause death (HR 1.444,95% CI 1.159-1.799, P=0.001) and SCD (HR 1.958,95% CI 1.380-2.780, P<0.001). After adjusted for the other risk factors, the associations remained significant in all-cause death (HR 1.440,95% CI 1.153-1.799, P<0.001) and SCD (HR 1.911, 95% CI 1.343-2.719, P<0.001). However, there was no association between A allele of rs2302684 and prognosis in patients with CHF caused by NICM.ConclusionThe SNP rs2302684 T>A in LRP6 is associated with an increased risk of all-cause death and SCD in patients with CHF in Chinese Han population, and the association is more prevalent in patients with CHF caused by ICM. Thus, LRP6 might be added as a novel predictor of SCD and could provide an attractive and direct therapeutic target in SCD prevention. |
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