Minglong Chen

Complete Isolation of Left Atrium Surrounding the Pulmonary Veins New Insights From the Double-Lasso Technique in Paroxysmal Atrial Fibrillation

Background—Paroxysmal atrial fibrillation (PAF) can be eliminated with continuous circular lesions (CCLs) around the pulmonary veins (PVs), but it is unclear whether all PVs are completely isolated. Methods and Results—Forty-one patients with symptomatic PAF underwent 3D mapping, and all PV ostia were marked on the 3D map based on venography. Irrigated radiofrequency energy was applied at a distance from the PV ostia guided by 2 Lasso catheters placed within the ipsilateral superior and inferior PVs. The mean radiofrequency duration was 1550±511 seconds for left-sided PVs and 1512±506 seconds for right-sided PVs. After isolation, automatic activity was observed in the right-sided PVs in 87.8% and in the left-sided PVs in 80.5%. During the procedure, a spontaneous or induced PV tachycardia (PVT) with a cycle length of 189±29 ms was observed in 19 patients. During a mean follow-up of 6 months, atrial tachyarrhythmias recurred in 10 patients. Nine patients underwent a repeat procedure. Conduction gaps in the left CCL in 9 patients and in the right CCL in 2 patients were closed during the second procedure. A spontaneous PVT with a cycle length of 212±44 ms was demonstrated in 7 of 9 patients, even though no PVT had been observed in 6 of these 7 patients during the first procedure. No AF recurred in 39 patients after PV isolation during follow-up. Conclusions—Automatic activity and fast tachycardia within the PVs could reflect an arrhythmogenic substrate in patients with PAF, which could be eliminated by isolating all PVs with CCLs guided by 3D mapping and the double-Lasso technique in the majority of patients.

Electrocardiographic algorithm to identify the optimal target ablation site for idiopathic right ventricular outflow tract ventricular premature contraction

AIMS Several electrocardiographic (ECG) algorithms have been developed to identify the site of origin of ventricular premature contractions (VPCs) from right ventricular outflow tract (RVOT) based on pacemapping; however, their accuracy remains unclear. METHODS AND RESULTS We evaluated the accuracy of these algorithms in 52 consecutive patients (31 female, mean age 42.6+/-14.6 years) with successful radiofrequency ablation of RVOT-VPC as guided by 3D electroanatomical non-contact mapping (Ensite, St Jude Medical, USA) and compared with a newly proposed ECG algorithm. As guided by 3D electroanatomical mapping, the successful ablation sites of RVOT-VPC were RVOT septum (n=31), RVOT free wall (n=19), and His region (n=2). Retrospective evaluation in the initial 39 patients shows that the overall positive prediction value to identify a successful ablation site of this newly proposed ECG algorithm is 77.3% and is higher than the 73.3% by Ito et al., 73.3% by Joshi et al., and 53.8% by Dixit et al. (P>0.05). Prospective evaluation in the subsequent 13 patients also demonstrate similar high overall sensitivity (79.0%), specificity (92.7%), and positive prediction value (88.2%) to identify a successful ablation site with this newly proposed ECG algorithm. CONCLUSION On the basis of detail 3D electroanatomical mapping of successful ablation sites, a newly proposed ECG algorithm was developed to improve the sensitivity, specificity, and positive prediction value in identification of targeted ablation sites for RVOT-VPC.

Intramyocardial transplantation of undifferentiated rat induced pluripotent stem cells causes tumorigenesis in the heart.

Background Induced pluripotent stem cells (iPSCs) are a novel candidate for use in cardiac stem cell therapy. However, their intrinsic tumorigenicity requires further investigation prior to use in a clinical setting. In this study we investigated whether undifferentiated iPSCs are tumorigenic after intramyocardial transplantation into immunocompetent allogeneic recipients. Methodology/Principal Findings We transplanted 2×104, 2×105, or 2×106 cells from the established rat iPSC line M13 intramyocardially into intact or infarcted hearts of immunocompetent allogeneic rats. Transplant duration was 2, 4, or 6 weeks. Histological examination with hematoxylin-eosin staining confirmed that undifferentiated rat iPSCs could generate heterogeneous tumors in both intracardiac and extracardiac sites. Furthermore, tumor incidence was independent of cell dose, transplant duration, and the presence or absence of myocardial infarction. Conclusions/Significance Our study demonstrates that allogeneic iPSC transplantation in the heart will likely result in in situ tumorigenesis, and that cells leaked from the beating heart are a potential source of tumor spread, underscoring the importance of evaluating the safety of future iPSC therapy for cardiac disease.

Catheter Ablation of Nonparoxysmal Atrial Fibrillation Using Electrophysiologically Guided Substrate Modification During Sinus Rhythm After Pulmonary Vein Isolation

Background—The high incidence of postprocedural atrial tachycardia reduces the absolute arrhythmia-free success rate of extensive ablation strategies to treat nonparoxysmal atrial fibrillation (NPAF). We hypothesized that a strategy of targeting low-voltage zones and sites with abnormal electrograms during sinus rhythm (SR-AEs) in the left atrium after circumferential pulmonary vein isolation and cavotricuspid isthmus ablation in patients with NPAF is superior. Methods and Results—A total of 86 consecutive patients with NPAF were enrolled in study group. After circumferential pulmonary vein isolation, cavotricuspid isthmus ablation and cardioversion to SR, high-density mapping of left atrium was performed. Areas with low-voltage zone and SR-AE were targeted for further homogenization and elimination, respectively; 78 consecutive sex- and age-matched patients with NPAF who were treated with the stepwise approach served as the historical control group. In the study group, 92% (79/86) were successfully cardioverted after circumferential pulmonary vein isolation and cavotricuspid isthmus ablation. Among the patients converted to SR, 70% (55/79) had low-voltage zone and SR-AE and received additional ablation, whereas in 30% (24/79) without SR-AE or low-voltage zone, no further ablation was performed. During a follow-up period of >30 months, the Kaplan–Meier estimated probability to maintain SR at 24 months was 69.8% versus 51.3%. And after a single procedure, 3.5% (3/86) developed postprocedural atrial tachycardia in study group, compared with 30% (24/78) in control group (P=0.0003). Conclusions—A strategy of selective electrophysiologically guided atrial substrate modification in SR after circumferential pulmonary vein isolation and cavotricuspid isthmus ablation is clinically more effective than the stepwise approach for NPAF ablation. Clinical Trial Registration—URL: http://clinicaltrials.gov. Unique identifier: NCT01716143.

Mesenchymal stem cell injection ameliorates the inducibility of ventricular arrhythmias after myocardial infarction in rats.

BACKGROUND Mesenchymal stem cell transplantation is a promising new therapy to improve cardiac function after myocardial infarction (MI). The electrophysiological consequences of MSC implantation has not been systematically studied. METHODS We investigated the electrophysiological and arrhythmogenic effects of mesenchymal stem cells (MSCs) therapy in experimental infarction model. Rats were subjected to MI operation by LAD ligation and randomly allocated to receive intramyocardially injection PBS (MI-PBS) or 5 × 10(5) EGFP labeled MSCs (MI-MSCs). Electrophysiological study, histological examination, and western blotting were performed 2 weeks after cell transplantation. RESULTS Programmed electrical stimulation (PES) showed a significant reduced inducible ventricular tachycardias (VTs), raised ventricular fibrillation threshold (VFT) and prolonged ventricular effective refractory period (VERP) in MSC-treated rats compared to PBS-treated animals. MSC implantation led to markedly longer action potential duration (APD) and shorter activation time (AT) in infarcted border zone (IBZ) of left ventricular epicardium compared with PBS-treated hearts. Histological study revealed that fibrotic area and collagen deposition in infarcted region were significantly lower in MI-MSC group than in MI-PBS group. Abnormal alterations of Connexin 43 including reduction and lateralization were significantly attenuated by MSC treatment. CONCLUSIONS This study provide strong evidence that MSC implantation ameliorates interstitial fibrosis and the remodeling of gap junction, attenuates focal heterogeneity of reporlarization and conduction and reduces vulnerability to VTs. The results suggest that MSC transplantation might emerge as a new preventive strategy against VAs besides improving cardiac performance in ischemic heart disease.

Connexin43 promotes survival of mesenchymal stem cells in ischaemic heart

The involvement of connexins in regulating cell growth and death has recently been reported. We have investigated whether Cx43 (connexin43) contributes to MSC (mesenchymal stem cell) survival and improves therapeutic efficacy in MI (myocardial infarction). Genetically modified Cx43 MSCs were exposed to hypoxic conditions or injected intramyocardially into a rat MI model. MSCs overexpressing Cx43, with more Bcl-2 and phosphorylated Akt, but less Bax, were relatively tolerant to hypoxic injury. After transplantation, this Cx43 overexpression enhanced cell survival and reduced infarct size, improving contractile performance. Cx43 inhibition by SiRNA reversed the effects of Cx43 overexpression. Therefore, Cx43 may act as a potential target for improving the therapeutic efficacy of MSCs in ischaemic heart disease.

Ventricular Arrhythmias Arising from the Left Ventricular Outflow Tract below the Aortic Sinus Cusps: Mapping and Catheter Ablation via Transseptal Approach and Electrocardiographic Characteristics

Background—Ventricular arrhythmias (VAs) originating from the anterosuperior left ventricular outflow tract (LVOT) represent a challenging location for catheter ablation. This study investigates mapping and ablation of VA from anterosuperior LVOT via a transseptal approach. Methods and Results—This study included 27 patients with symptomatic VA, of which 13 patients had previous failed ablations. LVOT endocardial 3-dimensional mapping via retrograde transaortic and antegrade transseptal approaches was performed. Previous ECG markers for procedure failure were analyzed. In all patients, earliest activation with low-amplitude potentials was identified at the anterosuperior LVOT 5.1±2.8 mm below the aortic cusp and preceded the QRS onset by 39.5±7.7 ms only via an antegrade transseptal approach using a reversed S curve. In all patients, pace mapping failed to demonstrate perfect QRS morphology match. The anatomic location was below the left coronary cusp in 16, below the left coronary cusp/right coronary cusp junction in 8, and below the right coronary cusp in 3 patients. Radiofrequency energy resulted in rapid disappearance of VAs in all patients. ECG analysis showed aVL/aVR Q-wave amplitude ratio >1.4 in 7, lead III/II R-wave amplitude ratio >1.1 in 10, and peak deflection index >0.6 in 11 patients. There were no complications or clinical VA recurrence during a mean follow-up of 8.4±2.5 months. Conclusions—The anterosuperior LVOT can be reached via a transseptal approach with a reversed S curve of the ablation catheter. The rapid effect from radiofrequency energy indicates that the VA is most likely located under the endocardium. Also, previous ECG markers for procedure failure need further investigation.

Randomized comparison between pulmonary vein antral isolation versus complex fractionated electrogram ablation for paroxysmal atrial fibrillation.

Catheter Ablation of Paroxysmal AF. Introduction: Circumferential pulmonary vein antral isolation (PVAI) and atrial complex fractionated electrograms (CFEs) are both ablative techniques for the treatment of paroxysmal atrial fibrillation (PAF). However, data on the comparative value of these 2 ablation strategies are very limited.

Intramyocardial Injection of Pig Pluripotent Stem Cells Improves Left Ventricular Function and Perfusion: A Study in a Porcine Model of Acute Myocardial Infarction

Induced pluripotent stem (iPS) cells have the potential to differentiate to various types of cardiovascular cells to repair an injured heart. The potential therapeutic benefits of iPS cell based treatment have been established in small-animal models of myocardial infarction (MI). We hypothesize that porcine iPS (piPS) cell transplantation may be an effective treatment for MI. After a 90-minute occlusion of the left anterior descending artery in a porcine model, undifferentiated piPS cells or PBS were injected into the ischemic myocardium. Cardiac function, myocardial perfusion and cell differentiation were investigated. One week after piPS cell delivery, global left ventricular ejection fraction (LVEF) significantly decreased in both the iPS group and the PBS group compared to the Sham group (p<0.05, respectively). Six weeks after piPS cell delivery, LVEF of the iPS group significantly improved compared to the PBS group (56.68% vs. 50.93%, p = 0.04) but was still lower than the Sham group. Likewise, the piPS cell transplantation improved the regional perfusion compared to the PBS injection (19.67% vs. 13.67%, p = 0.02). The infarct area was significantly smaller in the iPS group than the PBS group (12.04% vs. 15.98% p = 0.01). PiPS cells engrafted into the myocardium can differentiate into vessel cells, which result in increased formation of new vessels in the infarcted heart. Direct intramyocardial injection of piPS cells can decrease infarct size and improve left ventricular function and perfusion for an immunosuppressed porcine AMI model.

Dynamic Substrate Mapping and Ablation of Ventricular Tachycardias in Right Ventricular Dysplasia

AbstractBackground: Ablation of ventricular tachycardias in arrhythmogenic right ventricular dysplasia (ARVD-VTs) still remains a clinical challenge. We reported the value of abnormal electrophysiological substrate mapping for guiding ablation of ARVD-VTs using a non-contact mapping system. Methods and Results: Dynamic substrate mapping was performed in three male ARVD patients during sinus rhythm. The sites of earliest activation, exit point and activation sequence were mapped for each induced VT. Three different patterns of substrates were determined in 3 patients and located in right ventricular outflow tract, anterior right ventricular wall, and anterolateral right ventricular wall, respectively. Five different clinical VTs (mean CL, 348 ± 65 ms) were induced. Of 5 VTs, three originated from or near the boundary of substrate, and two had a remote origin. One VT conducted through the substrate. Linear ablations were created between the sites of the earliest ventricular activation and the VT exit point, or across the critical isthmus. The five clinical VTs were successfully ablated with a median of 17 radiofrequency applications. One patient was treated with amiodarone for a VT not clinically observed. There were no VT recurrences during 8.6 months of follow-up. Conclusions: Defining the abnormal anatomical VT substrates is useful for understanding the mechanisms of ARVD-VTs and determining an ablation strategy. Linear ablation across a critical isthmus or between the early activation and the exit point can effectively cure these arrhythmias.