Qun-Shan Wang

Angiotensinogen polymorphisms and acquired atrial fibrillation in Chinese

Genetic predisposition may be underlying the prevalence of acquired atrial fibrillation (AF). We investigated the association between polymorphism in angiotensinogen (AGT) and angiotensin-converting enzyme gene and risk of acquired AF in a pair-matched case-control study conducted in Chinese Hans. We selected 9 single nucleotide polymorphisms (SNPs) in the AGT gene and 3 SNPs in the angiotensin-converting enzyme gene using a tagging-SNP strategy. We observed significant association between tagging-SNP rs699 (M235T), located in exon 2 of the AGT gene, and AF. The AA genotype of rs699 increased the risk of AF by 70% (95% confidence interval, 1.01-2.85; P = .044) under a recessive model (AA vs AG + GG). The significance remained after controlling for covariates age, smoking, body mass index, hypertension, diabetes, and left atrial dimension, with an increased risk of AF by 90% (95% confidence interval, 1.04-3.46; P = .036). We provide evidence that polymorphism in AGT gene may confer predisposition to acquired atrial fibrillation in Chinese Hans.

TBX5 mutations contribute to early-onset atrial fibrillation in Chinese and Caucasians

AIMS Atrial fibrillation (AF) is a common arrhythmia with an important heritable aspect. The genetic factors underlying AF have not been fully elucidated. METHODS AND RESULTS We screened six candidate genes (CAV1, KCNJ2, KCNQ1, NKX2.5, PITX2, and TBX5) for novel mutations in 139 patients of Chinese descent with early-onset AF and 576 controls. Four missense TBX5 mutations, p.R355C, p.Q376R, p.A428S, and p.S372L, were identified in evolutionarily conserved regions. We did not find any mutations in CAV1, KCNJ2, KCNQ1, NKX2.5, and PITX2. These mutations increased the expression of atrial natriuretic peptide (ANP) and connexin-40 (CX40) in the primarily cultured rat atrial myocytes but did not alter the expression of cardiac structural genes, atrial myosin heavy chain-α (MHC-α) and myosin light chain-2α (MLC-2α). Overexpression of p.R355C developed an atrial arrhythmia suggestive of paroxysmal AF in the zebrafish model. To replicate our findings, we screened TBX5 in 527 early-onset AF cases from the Massachusetts General Hospital AF study. A novel TBX5 deletion (ΔAsp118, p.D118del) was identified, while no TBX5 mutations were identified in 1176 control subjects. CONCLUSION Our results provide both genetic and functional evidence to support the contribution of TBX5 gene in the pathogenesis of AF. The potential mechanism of arrhythmia may be due in part to the disturbed expression of ANP and CX40.

Digoxin Is Associated With Increased All-cause Mortality in Patients With Atrial Fibrillation Regardless of Concomitant Heart Failure: A Meta-analysis.

Abstract: For decades, digoxin has been widely used to control ventricular rate in atrial fibrillation (AF). However, it remains controversial as to whether digoxin is associated with increased mortality in AF. In this study, we searched relevant studies that were published before December 1, 2014, in PubMed, EMBASE, and the Cochrane central databases. We systematically reviewed the references and performed a meta-analysis of 8 carefully selected studies with 302,738 patients who were included for the final analysis. It was shown that digoxin use was associated with increased risk of all-cause mortality in AF overall [hazard ratio (HR) = 1.375, 95% confidence intervals (CI), 1.201–1.574, P = 0.0001]. Subgroup analysis further revealed that digoxin was associated with increased all-cause mortality in patients with AF, which was complicated by heart failure (HF) (HR = 1.201, CI, 1.074– 1.344, P = 0.001), and in those subjects without HF (HR = 1.172, CI, 1.148–1.198, P = 0.0001). Sensitivity analyses found results to be robust. Our findings indicated that digoxin use was associated with significantly increased all-cause mortality in patients with AF regardless of concomitant HF. We suggest that digoxin should not be preferentially used over other rate control medications in AF.

Spatial relationship between left atrial roof or superior pulmonary veins and bronchi or pulmonary arteries by dual-source computed tomography: implication for preventing injury of bronchi and pulmonary arteries during atrial fibrillation ablation

AIMS Bronchi or pulmonary arteries (PAs) could be injured during atrial fibrillation (AF) ablation. Therefore, the aim of the present study was to evaluate the spatial relationship between left atrial roof or superior pulmonary veins (PVs) and neighbouring structures of AF patients and provide anatomic guidance for AF ablation to avoid injuring bronchi or PAs. METHODS AND RESULTS A dual-source computed tomography (DSCT) scan was used to depict the left atrium (LA), PVs, and nearby structures including bronchi and PAs in 58 patients with drug-refractory AF (mean age, 64 ± 9 years). The distance between LA roof or superior PVs (SPVs) and bronchi or PAs was measured. The average minimal distances from the left, middle, and right points of the LA roof to the principal bronchi were 17.0 ± 6.4, 23.7 ± 5.1, and 23.2 ± 7.7 mm, respectively. The LA roof was closer to the right PA (RPA) than the left PA (LPA) for more than 90% of patients. The average minimal distances from the left, middle, and right points of the LA roof to the PAs were 8.3 ± 5.0, 5.9 ± 3.1, and 6.0 ± 2.8 mm, respectively. The average minimal distances between the left superior pulmonary vein and bronchi or LPA were 0.32 ± 0.79 or 0.4 ± 1.0 mm, respectively. The average minimal distances between the right superior pulmonary vein and bronchi or RPA were 0.27 ± 0.94 and 0.0 ± 0.1 mm, respectively. Both of the root parts of SPVs of most patients were in direct contact with branches of trachea and PAs. CONCLUSION Dual-source computed tomography provides important imaging information for determining the relationship between LA, PVs, and neighbouring structures. Use of pre-procedural cardiac CT scans may help avoid ablation-induced injury of bronchi and PAs.

Association of the angiotensinogen M235T polymorphism with recurrence after catheter ablation of acquired atrial fibrillation

Purpose: Previous studies showed that genetic variants of the angiotensinogen (AGT) gene conferred higher risk for acquired atrial fibrillation (AF). The present study investigated whether AGT variants correlate with the clinical outcome in patients with acquired AF after catheter ablation (CA). Methods: A total of 150 acquired symptomatic drug-refractory AF patients (mean age 63.7±11.0 years, 24.6% non-paroxysmal AF) with acquired AF underwent a single CA procedure in our department and were included in this retrospective analysis. Eight tagging single nucleotide polymorphisms (tSNPs) in the AGT gene were genotyped. Standard electrocardiographs (ECGs) and 24-hour Holter recordings were performed during a median follow-up period of 57.5 months to detect AF recurrence. Results: Sixty-one patients (40.7%) suffered AF recurrences after a single CA procedure during follow up. Of the eight tSNPs, the frequency of the M allele of M235T was significantly higher in the recurrence group (28%) compared to the non-recurrence group (18%) (p=0.042). The recurrence rates of patients with the TT, MT, and MM genotypes were 34.4%, 50%, and 55.6%, respectively (ptrend=0.049). After adjusting for age, sex, body mass index, hypertension, left atrial volume index (LAVI) and other covariates, M235T increased the risk of AF recurrence in additive and dominant models with odds ratios of 2.023 (95% confidence interval (CI): 1.034–3.926, p=0.033) and 2.601 (95% CI: 1.102–6.056, p=0.025), respectively. However, in multiple correction analyses, the p values of multiple comparisons were not statistically significant (pcorrect>0.05). Conclusions: The M allele of M235T might be associated with an increased risk of AF recurrence after CA. Genotyping may thus be helpful on identifying patients with higher risks of AF recurrence after CA and developing optimal follow-up strategies. These strategies may differ and should be individualized according to patients’ genotype. Future studies are warranted to validate the potential effect of AGT M235T on AF recurrence post CA.

Successful retrieval of a broken circular mapping catheter after entrapment in the tricuspid valve apparatus

Introduction Invasive electrophysiology study and catheter ablation are relatively safe procedures with only rare complications. A circular mapping catheter is commonly used to localize abnormal foci within the atria and thoracic vein. Entrapment of the circular mapping catheter in the mitral valve (MV) apparatus has been reported previously by Wu et al, who noted serious complications following the catheter retrieval procedure. In the present case, the circular catheter was inadvertently mispositioned into the right ventricle, entrapped, and broken in the tricuspid valve (TV) apparatus during the mapping of premature atrial complexes (PACs) from the right atrium (RA) in a patient with frequent episodes of palpitation who underwent a cardiac electrophysiology study (EPS) and eventually catheter ablation. In the present case report, we describe the successful retrieval of the fragment by a percutaneous transfemoral venous approach.

Risk factors responsible for atrial fibrillation development between symptomatic patients with concealed or manifest atrioventricular accessory pathways

Background Patients with manifest atrioventricular accessory pathways (mAPs) have a greater tendency to develop atrial fibrillation (AF) compared with patients with concealed atrioventricular accessory pathways (cAPs). However, the risk factors of developing AF in patients with various atrioventricular accessory pathways (APs) are not clear. Methods This retrospective study included 460 symptomatic patients with either cAPs (n = 246) or mAPs (n = 214) who underwent electrophysiological study and successful radiofrequency catheter ablation of APs. Clinical and electrophysiological characteristics were compared between cAPs and mAPs and between AF and non-AF groups with cAPs or mAPs. Independent risk factors of AF were analyzed using multivariate logistic regression. Results AF was more frequent in mAPs group than in cAPs group (23.4% vs 9.8%, p < 0.01). Clinical features were similar between cAPs and mAPs. Anterograde conduction properties served as the major electrophysiological feature of mAPs. Multivariate analysis indicated that mAPs, hypertension, post-ablation P wave dispersion (Pd), N-terminal proB-type natriuretic peptide (NT-proBNP) and creatinine were independent risk factors of AF in the complete cohort. Hypertension, post-ablation Pd and high-sensitivity C-reactive protein (hsCRP) were independent risk factors of AF in cAPs group. Post-ablation Pd, NT-proBNP, creatinine and shorter effective refractory period of anterograde accessory pathways (AAP ERP) were independent risk factors of AF in mAPs group. Conclusions Results from this study demonstrate that the risk factors of AF are not homogenous between concealed and manifest APs, which might suggest heterogeneous pathogenesis of AF in these two types of APs.

Adenosine Sensitivity is Associated with Ablation Success Rate and Recurrence Rate with Nonirrigated Catheters in Patients with Ventricular Premature Contractions/Tachycardia from the Ventricular Outflow Tract

Background: A high ablation success rate for ventricular arrhythmia (VA) from outflow tract has been achieved, but some of them cannot be eliminated from endocardium. We investigated the association between adenosine sensitivity and ablation success/recurrence rates with a nonirrigated or an irrigated catheter. Methods: According to adenosine test, all patients were divided into a sensitive group (S group) or an insensitive group (I group). The patients of each group were randomized into a nonirrigated catheter (NA) subgroup or an irrigated catheter (IA) subgroup with a 2:1 ratio. Results: In S group of 122 patients (84 in NA subgroup), the ablation success rate was similar between two subgroups (94.7% vs. 90.5%, P > 0.05), but in I group of 94 patients (60 in NA subgroup), it was higher in IA subgroup (94.1%) than that in NA subgroup (73.3%, P < 0.05). The success rate using nonirrigated catheter was significantly higher in S group (90.5%) than that in I group (73.3%, P < 0.01), and the recurrence rate was lower in S group than that in I group (1.3%, vs. 13.6%, P < 0.05). On the contrary, the success rate and the recurrence rate using irrigated catheter were similar between S group and I group (94.7%, 94.1%, P > 0.05, vs. 2.8%, 6.3%, P > 0.05). Conclusions: Adenosine insensitivity is associated with a lower success rate and a higher recurrence rate for VA patients undergoing nonirrigated catheter ablation. Thus, irrigated catheters should be the first choice for VA ablation in adenosine insensitive patients.