Hai-Feng Shi

Beneficial effect of pioglitazone on the outcome of catheter ablation in patients with paroxysmal atrial fibrillation and type 2 diabetes mellitus

AIMS Pioglitazone, one of the peroxisome proliferator-activated receptor-gamma activators, possesses anti-inflammatory and antioxidant properties. In the present study, we sought to identify the impact of pioglitazone on the outcome of catheter ablation for paroxysmal atrial fibrillation (PAF). METHODS AND RESULTS We conducted a prospective observational cohort study of 150 consecutive patients undergoing catheter ablation of drug-refractory PAF. All patients had a history of type 2 diabetes mellitus (T2DM) and were divided based on whether they received pioglitazone before ablation or not. After grouping, 51 patients treated with pioglitazone and 99 control subjects were followed up at least 15 months after ablation. After a single ablation, sinus rhythm was maintained in 44 patients (86.3%) of the pioglitazone group vs. 70 patients (70.7%) of the control group (P = 0.034) without antiarrhythmic drug during a mean follow-up of 22.9 ± 5.1 months. The second ablation was performed in 5 patients (9.8%) from the pioglitazone group and in 24 patients (24.2%) from the control group (P = 0.034). Multivariate logistic analysis showed left atrium diameter was associated with a high risk of atrial tachyarrhythmias recurrence, and treatment with renin-angiotensin system inhibitor as well as pioglitazone was associated with a reduced atrial tachyarrhythmias recurrence rate. CONCLUSION Pioglitazone improved the preservation of sinus rhythm and reduced the reablation rate in patients with PAF and T2DM after catheter ablation.

Novel connexin40 missense mutations in patients with familial atrial fibrillation.

AIMS This research was aimed at screening connexin40, a cardiac gap junction protein alpha 5, for genetic defects in patients with familial atrial fibrillation (AF). METHODS The subjects included 218 unrelated families with lone AF and 200 ethnically matched unrelated healthy individuals as controls. The entire coding region of the connexin40 gene was sequenced initially in 218 unrelated probands with familial AF. The relatives of mutation carriers and 200 controls were subsequently genotyped for the presence of mutations identified in probands. RESULTS Three novel connexin40 mutations, p.V85I, p.L221I, and p.L229M, were identified in 3 of 218 unrelated AF families, respectively. These heterozygous missense mutations co-segregated with AF in the families and were absent in the 200 unrelated control subjects. A cross-species alignment of connexin40 protein sequences revealed that the altered amino acids were completely conserved evolutionarily. CONCLUSION The findings expand the spectrum of mutations in connexin40 linked to AF and provide new insight into the molecular aetiology involved in the pathogenesis of AF.

Pulmonary vein isolation combined with superior vena cava isolation for atrial fibrillation ablation: a prospective randomized study

AIMS Circumferential pulmonary vein isolation (CPVI) is an established strategy for atrial fibrillation (AF) ablation. Superior vena cava (SVC), by harbouring the majority of non-pulmonary vein (PV) foci, is the most common non-PV origin for AF. However, it is unknown whether CPVI combined with SVC isolation (SVCI) could improve clinical results and whether SVCI is technically safe and feasible. METHODS AND RESULTS A total of 106 cases (58 males, average age 66.0 +/- 8.8 years) with paroxysmal AF were included for ablation. They were allocated randomly to two groups: CPVI group (n = 54) and CPVI + SVCI group (n = 52). All cases underwent the procedure successfully. Pulmonary vein isolation was achieved in all cases. The procedural time and fluoroscopic time were comparable between the two groups. The mean ablation time for SVC was 7.8 +/- 2.7 min. Superior vena cava isolation was obtained in 50/52 cases. In the remaining two cases, SVCI was not achieved because of obviating diaphragmatic nerve injury. During a mean follow-up of 4 +/- 2 months, 12 (22.2%) cases in the CPVI group and 10 (19.2%) cases in the CPVI + SVCI group had atrial tachyarrhythmias (ATa) recurrence (P = 0.70). Nine of 12 cases in the CPVI group and 8/10 cases in the CPVI + SVCI group underwent reablation (P = 0.86), and PV reconnection occurred in 7/9 cases in the CPVI group and in 8/8 cases in the CPVI + SVCI group. All PV reconnection was reisolated by gaps ablation. There was no SVC reconnection in the CPVI + SVCI group. In two cases without PV reconnection from the CPVI group, SVC-originated short run of atrial tachycardia was identified and eliminated by the SVCI. At the end of 12 months of follow-up, 50 cases (92.6%) in the CPVI group and 49 (94.2%) in the CPVI + SVC group were free of ATa recurrence (P = 0.73). CONCLUSION In our series of paroxysmal AF patients, empirically adding SVCI to CPVI did not significantly reduce the AF recurrence after ablation. Superior vena cava isolation may be useful, however, in selected patients in whom the SVC is identified as a trigger for AF. However, because of the preliminary property of the study and its relatively small sample size, the impact of SVCI on clinical results should be evaluated in a large series of patients.

GATA4 loss-of-function mutations in familial atrial fibrillation

BACKGROUND Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and a major source of the substantially increased morbidity and mortality. Growing studies demonstrate that genetic defects play pivotal roles in a subgroup of AF. However, AF is a genetically heterogeneous disorder and the molecular basis of AF in a majority of cases remains unknown. METHODS The whole coding region of the GATA4 gene, which encodes a zinc-finger transcription factor essential for cardiogenesis, was analyzed in 130 unrelated probands with AF in contrast to 200 unrelated ethnically matched healthy individuals used as controls. The available family members of the probands harboring the identified mutations were genotyped. The functional effect of the mutant GATA4 was characterized using a luciferase reporter assay system. RESULTS Two novel heterozygous GATA4 mutations, p.S70T and p.S160T, were identified in 2 unrelated families with AF inherited as an autosomal dominant trait, respectively, which co-segregated with AF in each family with complete penetrance. Functional analysis showed that the mutations of GATA4 were associated with a significantly decreased transcriptional activity. CONCLUSION The findings provide new insight into the molecular mechanism involved in the pathogenesis of AF, suggesting the potential implications in the genetic diagnosis and gene-specific therapy of this common arrhythmia.

Efficacy of catheter ablation and surgical CryoMaze procedure in patients with long-lasting persistent atrial fibrillation and rheumatic heart disease: a randomized trial

AIMS Catheter ablation and surgical Maze procedure are effective in treating atrial fibrillation (AF) patients. However, there is no study that compares the effect of circumferential pulmonary vein isolation (CPVI) combined with substrate ablation after valvular surgery and the concomitant Maze procedure for the treatment of AF in patients with rheumatic heart disease (RHD). The aim of this study was to compare the effectiveness of CPVI combined with substrate modification and surgical Maze procedure using Saline-Irrigated Cooled-tip Radiofrequency Ablation (SICTRA) system for the treatment of long-lasting persistent AF in patients with RHD. METHODS AND RESULTS Between January 2006 and June 2008, 99 patients with long-lasting persistent AF and RHD were randomly assigned to undergo valvular operation and CPVI combined with substrate modification 6 months after the surgery (Group A, 49 patients) or valvualr operation and concomitant Maze procedure (Group B, 50 patients). The mean follow-up periods were 15 ± 5 and 20 ± 8 months in Groups A and B, respectively. After one procedure, Group B had a significantly higher freedom from artial arrhythmias compared with Group A (82% in Group B vs. 55.2% in Group A, P < 0.001). Fifteen patients in Group A underwent a redo procedure. Six patients in Group B underwent catheter ablation and four were treated successfully. The cumulative rates of sinus rhythm were 71% in Group A and 88% in Group B (P < 0.001). CONCLUSION The concomitant Cox Maze procedure using SICTRA is more effective than subsequent CPVI combined with substrate modification in treating patients with long-lasting persistent AF and RHD.

Decreased Connexin 43 and Increased Fibrosis in Atrial Regions Susceptible to Complex Fractionated Atrial Electrograms

Background and Objectives: Complex fractionated atrial electrograms (CFAE) is distributed at preferential sites of atrium, and the mechanism underlying CFAE is not fully understood. We hypothesized that preexisting atrial abnormalities may be involved in the formation of CFAE. Methods: Twelve pigs were subjected to acetylcholine infusion and right atrial pacing to induce sustained atrial fibrillation. The shortest complex interval map was used to visualize CFAE on three-dimensional anatomic structure of left atrium, and the CFAE sites were labeled by ablation. The expression of connexin 43 (Cx43) and myocardial fibrosis were examined. Results: The expression of Cx43 at CFAE sites was significantly decreased when compared with non-CFAE sites, while myocardial fibrosis was enhanced in CFAE sites compared with non-CFAE sites. Conclusions: These results suggested that the decreased expression of Cx43 and enhanced myocardial fibrosis at CFAE sites of the left atrium may be the structure abnormalities underlying CFAE.

Efficacy, safety and outcome of catheter ablation for atrial fibrillation in octogenarians

BACKGROUND AND OBJECTIVES Catheter ablation is effective in treating patients with atrial fibrillation (AF). The aim of the study was to evaluate the safety, efficacy and outcome of catheter ablation for AF in octogenarians. METHODS AND RESULTS 377 consecutive patients were divided into three groups based on age: ≥80 years (group 1; n=49), 70-79 years (group 2; n=151), 60-69 years (group 3; n=177). The efficacy and safety for those three groups were determined. The success rate after one procedure was similar in three groups (70% in group 1, 72% in group2 and 74% in group 3, P=NS) during a mean follow-up of 18 months. Major complication rates were comparable between the three groups. However, the octogenarians were less likely to undergo a repeated procedure than other groups (8% in group 1, 15% in group 2 and 18% in group 3, P<0.05), and were more likely to remain on antiarrhythmic drugs. CONCLUSION Catheter ablation for AF attempted in octogenarians appears to be effective and with low risk. Ablation results are comparable with those noted in younger patients.

Detection of magnetic microbeads and ferrofluid with giant magnetoresistance sensors

Giant magnetoresistance sensors based on multilayers [Cu/NiFeCo]×10/ Ta were fabricated by microfabrication technology. A GMR-bridge was used to detect the magnetic MyOne beads and Ferro fluid. The dependence of the GMR-bridge signals on the surface coverage of MyOne beads was studied. The results show that the GMR sensor is capable of detecting the magnetic beads. The detectable limit of MyOne beads is about 100, and the corresponding signal output is 8 μV. The GMR bridge signal is proportional to the surface coverage of the MyOne beads. The sensitivity of the GMR bridge is inversely proportional to the feature size of the GMR sensor. The GMR bridge integrated with microfludic channel was also used for dynamic detection of ferrofluid (suspension of Fe3O4 particles). The results show that the GMR bridge is capable of detecting the flow of ferrofluid, and the sensor signals are proportional to the concentration of the ferrofluid. The detection limit of concentration of the ferrofluid is 0.56 mg/ml, and the corresponding signal is 6.2 μV.

Early Recurrences after Paroxysmal Atrial Fibrillation Ablation: When is the Proper Timing for Reablation?

Background:  Early recurrences (ERs) within 1 month after paroxysmal atrial fibrillation (AF) ablation are common and may subside in a considerable proportion of patients. Although late reablation after 3 months is recommended, the proper timing for reablation remains undetermined.