Vdrive Evaluation of Remote Steering and Testing in Lasso Electrophysiology Procedures Study: The VERSATILE Study in Atrial Fibrillation Ablation.

INTRODUCTION: Circular mapping catheters (CMC) are an essential tool in most atrial fibrillation ablation procedures. The Vdrive™ with V-Loop™ system enables a physician to remotely manipulate a CMC during electrophysiology studies. Our aim was to compare the clinical performance of the system to conventional CMC navigation according to efficiency and safety endpoints. METHODS AND RESULTS: A total of 120 patients scheduled to undergo a CMC study followed by pulmonary vein isolation (PVI) were included. Treatment allocation was randomized 2:1, remote navigation:manual navigation. The primary effectiveness endpoint was assessed based on both successful navigation to the targeted pulmonary vein (PV) and successful recording of PV electrograms. All PVs were treated independently within and between patients. The primary safety endpoint was assessed based on the occurrence of major adverse events (MAEs) through seven days after the study procedure. Primary effectiveness endpoints were achieved in 295/302 PVs in the Vdrive arm (97.7%) and 167/167 PVs in the manual arm (100%). Effectiveness analysis indicates Vdrive non-inferiority (pnon-inferiority = 0.0405; δ = -0.05) per the Cochran-Mantel-Haenszel test adjusted for PV correlation. Five MAEs related to the ablation procedure occurred (three in the Vdrive arm-3.9%; two in the manual arm-2.33%). No device-related MAEs were observed; safety analysis indicates Vdrive non-inferiority (pnon-inferiority = 0.0441; δ = 0.07) per the normal Z test. CONCLUSION: Remote navigation of a CMC is equivalent to manual in PVI in terms of safety and effectiveness. This allows for single-operator procedures in conjunction with a magnetically guided ablation catheter.

Catheter Ablation of Ischemic Ventricular Tachycardia With Remote Magnetic Navigation: STOP-VT Multicenter Trial.

INTRODUCTION: Catheter ablation is an effective treatment of scar-related ventricular tachycardia (VT), but the overall complexity of the procedure has precluded its widespread use. Remote magnetic navigation (RMN) has been shown to facilitate cardiac mapping and ablation of VT in a retrospective series. STOP-VT is the first multicenter, prospective, single-arm and single-procedure study evaluating RMN-based mapping and ablation of post-infarction VT. METHODS: Patients with documented VT and prior MI, in whom an ICD was implanted either for primary or secondary prevention, were recruited from four EU and US centers. Either a transseptal (48 patients) or transaortic (5 patients) approach was employed to gain access for ventricular endocardial mapping/ablation during VT (entrainment mapping, activation mapping) and/or substrate mapping in sinus rhythm (elimination of fractionated/late potentials, variable extent of substrate modification) with RMN and irrigated RF ablation. The primary endpoints were as follows: (i) non-inducibility of the target VT or any other sustained VT; (ii) elimination of sustained VT/VF during ICD follow-up of up to 12 months. RESULTS: The cohort included 53 consecutive patients (median age 67 years, 49 men, median LVEF 31%). One hemodynamically unstable patient was excluded at the onset of mapping. Inducibility of sustained VT was achieved an average of 2.2 times per patient (1-8), with mean tachycardia cycle length (TCL) 374 milliseconds (179-510). Mean total procedure and fluoroscopy times were 223 minutes and 8.7 minutes, respectively; mean cumulative fluoroscopy time during mapping and ablation was 0.95 minutes; maximum power averaged 42.3 W with nominal saline 30 cc/min irrigation; mean cumulative RF time was 38 minutes. Non-inducibility of the target VT was achieved in 49/52 patients (94.2%) and non-inducibility of any VT was achieved in 38/52 patients (73.1%). A combination of RMN and manual ablation was performed in two patients, rendering one non-inducible. During the 12-month ICD follow-up period, freedom from any sustained VT/VF was observed in 30 patients (62%), of which 19 (63%) were off antiarrhythmic medications. Five patients expired during follow-up: one presented with a VT storm, but for the others, death was not related to VT/VF (MI-cardiogenic shock, pulmonary embolism, bronchogenic carcinoma, end stage heart failure). No procedural complications were reported. CONCLUSIONS: This first prospective, single-procedure, multicenter study indicates that remote magnetic navigation is a safe and effective method for catheter ablation of post-infarction VT.

Economic and Health Value of Delaying Atrial Fibrillation Progression Using Radiofrequency Catheter Ablation.

BACKGROUND: Radiofrequency catheter ablation (RFCA) is an established treatment for atrial fibrillation (AF) refractory to antiarrhythmic drugs. The economic value of RFCA in delaying disease progression has not been quantified. METHODS: An individual-level, state-transition health economic model estimated the impact of delayed AF progression using RFCA versus antiarrhythmic drug treatment for a hypothetical sample of patients with paroxysmal AF. The model incorporated the lifetime risk of progression from paroxysmal AF to persistent AF, informed by data from the ATTEST (Atrial Fibrillation Progression Trial). The incremental effect of RFCA on disease progression was modeled over a 5-year duration. Annual crossover rates were also included for patients in the antiarrhythmic drug group to mirror clinical practice. Estimates of discounted costs and quality-adjusted life years asssociated with health care utilization, clinical outcomes, and complications were projected over patients' lifetimes. RESULTS: From the payer's perspective, RFCA was superior to antiarrhythmic drug treatment with an estimated mean net monetary benefit per patient of $8516 ($148-$16 681), driven by reduced health care utilization, cost, and improved quality-adjusted life years. RFCA reduced mean (95% CI) per-patient costs by $73 (-$2700 to $2200), increased mean quality-adjusted life years by 0.084 (0.0-0.17) and decreased the mean number of cardiovascular-related health care encounters by 24%. CONCLUSIONS: RFCA is a dominant (less costly and more effective) treatment strategy for patients with AF, especially those with early AF for whom RFCA could delay progression to advanced AF. Increased utilization of RFCA-particularly among patients earlier in their disease progression-may provide clinical and economic benefits.

Atrial fibrillation driver identification through regional mutual information networks: a modeling perspective.

PURPOSE: Effective identification of electrical drivers within remodeled tissue is a key for improving ablation treatment for atrial fibrillation. We have developed a mutual information, graph-based approach to identify and propose fault tolerance metric of local efficiency as a distinguishing feature of rotational activation and remodeled atrial tissue. METHODS: Voltage data were extracted from atrial tissue simulations (2D Karma, 3D physiological, and the Multiscale Cardiac Simulation Framework (MSCSF)) using multi-spline open and parallel regional mapping catheter geometries. Graphs were generated based on varied mutual information thresholds between electrode pairs and the local efficiency for each graph was calculated. RESULTS: High-resolution mapping catheter geometries can distinguish between rotational and irregular activation patterns using the derivative of local efficiency as a function of increasing mutual information threshold. The derivative is decreased for rotational activation patterns comparing to irregular activations in both a simplified 2D model (0.0017 ± 1 × 10-4 vs. 0.0032 ± 1 × 10-4, p < 0.01) and a more realistic 3D model (0.00092 ± 5 × 10-5 vs. 0.0014 ± 4 × 10-5, p < 0.01). Average local efficiency derivative can also distinguish between degrees of remodeling. Simulations using the MSCSF model, with 10 vs. 90% remodeling, display distinct derivatives in the grid design parallel spline catheter configuration (0.0015 ± 5 × 10-5 vs. 0.0019 ± 6 × 10-5, p < 0.01) and the flower shaped open spline configuration (0.0011 ± 5 × 10-5 vs. 0.0016 ± 4 × 10-5, p < 0.01). CONCLUSION: A decreased derivative of local efficiency characterizes rotational activation and varies with atrial remodeling. This suggests a distinct communication pattern in cardiac rotational activation detectable via high-resolution regional mapping and could enable identification of electrical drivers for targeted ablation.

Catheter ablation and healthcare utilization and cost among patients with paroxysmal versus persistent atrial fibrillation.

BACKGROUND: Ablation reduces atrial fibrillation (AF) burden and improves health-related quality of life. The relationship between ablation, healthcare utilization, and AF type (paroxysmal AF [PAF] vs persistent AF [PsAF]) remains unclear. OBJECTIVE: To compare changes in AF-related healthcare utilization and costs from preablation to postablation among patients with PAF and PsAF. METHODS: Patients (2794 PAF, 1909 PsAF) undergoing ablation (2016-2018) were identified using the Optum database. Outcomes included inpatient admissions, emergency department (ED) visits, office visits, cardioversion, and antiarrhythmic drug (AAD) use. Costs (2018 US$) and outcomes were compared for the year before/after ablation using the McNemar test and Wilcoxon signed rank test. RESULTS: Compared to PAF patients, PsAF patients were older (68.6 ± 9.0 years vs 67.4 ± 9.9 years, P < .0001), were less commonly female (36.3% vs 44.1%, P < .0001), and more commonly had a CHA2DS2-VASc ≥ 3(71.2% vs 62.7%, P < .0001). The 12-month postablation costs were lower for AF-specific inpatient admissions (PAF -28%, PsAF -33%), ED visits (PAF -76%, PsAF -70%), AAD prescription fills (PAF -25%, PsAF -7%), and cardioversions (PAF -59%, PsAF -55%) as compared to 12 months before ablation. Although these reductions were observed for both PAF and PsAF patients, absolute costs remained higher for PsAF. Total AF costs were higher during the 1 year after ablation vs before ablation (PAF: 11%, P < .0001; PsAF: 10%, P < .0001) owing to repeat ablation. However, in the 18-month follow-up analysis, postablation costs were overall reduced (PAF: 35%, P < .0001; PsAF: 34%, P < .0001), despite including costs from repeat ablation. CONCLUSION: Significant reductions in healthcare utilization and costs were observed among PAF and PsAF patients undergoing ablation. These data suggest a strategy of earlier ablation may reduce long-term healthcare utilization and costs.

Kv4.3 is not required for the generation of functional Ito,f channels in adult mouse ventricles.

Accumulated evidence suggests that the heteromeric assembly of Kv4.2 and Kv4.3 alpha-subunits underlies the fast transient Kv current (I(to,f)) in rodent ventricles. Recent studies, however, demonstrated that the targeted deletion of Kv4.2 results in the complete elimination of I(to,f) in adult mouse ventricles, revealing an essential role for the Kv4.2 alpha-subunit in the generation of mouse ventricular I(to,f) channels. The present study was undertaken to investigate directly the functional role of Kv4.3 by examining the effects of the targeted disruption of the KCND3 (Kv4.3) locus. Mice lacking Kv4.3 (Kv4.3-/-) appear indistinguishable from wild-type control animals, and no structural or functional abnormalities were evident in Kv4.3-/- hearts. Voltage-clamp recordings revealed that functional I(to,f) channels are expressed in Kv4.3-/- ventricular myocytes, and that mean I(to,f) densities are similar to those recorded from wild-type cells. In addition, I(to,f) properties (inactivation rates, voltage dependences of inactivation and rates of recovery from inactivation) in Kv4.3-/- and wild-type mouse ventricular myocytes were indistinguishable. Quantitative RT-PCR and Western blot analyses did not reveal any measurable changes in the expression of Kv4.2 or the Kv channel interacting protein (KChIP2) in Kv4.3-/- ventricles. Taken together, the results presented here suggest that, in contrast with Kv4.2, Kv4.3 is not required for the generation of functional mouse ventricular I(to,f) channels.

Low-energy multistage atrial defibrillation therapy terminates atrial fibrillation with less energy than a single shock.

BACKGROUND: Implantable device therapy of atrial fibrillation (AF) is limited by pain from high-energy shocks. We developed a low-energy multistage defibrillation therapy and tested it in a canine model of AF. METHODS AND RESULTS: AF was induced by burst pacing during vagus nerve stimulation. Our novel defibrillation therapy consisted of 3 stages: stage (ST) 1 (1-4 low-energy biphasic [BP] shocks), ST2 (6-10 ultralow-energy monophasic [MP] shocks), and ST3 (antitachycardia pacing). First, ST1 testing compared single or multiple MP and BP shocks. Second, several multistage therapies were tested: ST1 versus ST1+ST3 versus ST1+ST2+ST3. Third, 3 shock vectors were compared: superior vena cava to distal coronary sinus, proximal coronary sinus to left atrial appendage, and right atrial appendage to left atrial appendage. The atrial defibrillation threshold (DFT) of 1 BP shock was <1 MP shock (0.55 ± 0.1 versus 1.38 ± 0.31 J, P=0.003). Two to 3 BP shocks terminated AF with lower peak voltage than 1 BP or 1 MP shock and with lower atrial DFT than 4 BP shocks. Compared with ST1 therapy alone, ST1+ST3 lowered the atrial DFT moderately (0.51 ± 0.46 versus 0.95 ± 0.32 J, P=0.036), whereas 3-stage therapy (ST1+ST2+ST3) dramatically lowered the atrial DFT (0.19 ± 0.12 versus 0.95 ± 0.32 J for ST1 alone, P=0.0012). Finally, the 3-stage therapy was equally effective for all studied vectors. CONCLUSIONS: Three-stage electrotherapy significantly reduces the AF DFT and opens the door to low-energy atrial defibrillation at or below the pain threshold.

Human FXYD2 G41R mutation responsible for renal hypomagnesemia behaves as an inward-rectifying cation channel.

A mutation in the human FXYD2 polypeptide (Na-K-ATPase gamma subunit) that changes a conserved transmembrane glycine to arginine is linked to dominant renal hypomagnesemia. Xenopus laevis oocytes injected with wild-type FXYD2 or the mutant G41R cRNAs expressed large nonselective ion currents. However, in contrast to the wild-type FXYD2 currents, inward rectifying cation currents were induced by hyperpolarization pulses in oocytes expressing the G41R mutant. Injection of EDTA into the oocyte removed inward rectification in the oocytes expressing the mutant, but did not alter the nonlinear current-voltage relationship of the wild-type FXYD2 pseudo-steady-state currents. Extracellular divalent ions, Ca2+ and Ba2+, and trivalent cations, La3+, blocked both the wild-type and mutant FXYD2 currents. Site-directed mutagenesis of G41 demonstrated that a positive charge at this site is required for the inward rectification. When the wild-type FXYD2 was expressed in Madin-Darby canine kidney cells, the cells in the presence of a large apical-to-basolateral Mg2+ gradient and at negative potentials had an increase in transepithelial current compared with cells expressing the G41R mutant or control transfected cells. Moreover, this current was inhibited by extracellular Ba2+ at the basolateral surface. These results suggest that FXYD2 can mediate basolateral extrusion of magnesium from cultured renal epithelial cells and provide new insights into the understanding of the possible physiological roles of FXYD2 wild-type and mutant proteins.

[A clinical study on improving phonation function of larynx after partial laryngectomy].

OBJECTIVE: To analyse the clinical results of reconstruction of vocal cord using sternohyoid muscle flap after partial laryngectomy and research a new repairing method to improve laryngeal function and living quality of patient. METHOD: The pronunciation of larynx is on the basic of the vibration of the vocal cord by air current. The laryngeal appearance and the function of opposite side vocal cord is very important for improving the quality of pronunciation. We developed a technique of thyroid cartilage membrane and sternohyoid muscle flap to repair the defect left by a vertical laryngectomy and reconstructed the vocal cord. The thyroid cartilage membrane was used to bridge over the upper part defect of laryngeal cavity, the sternohyoid muscle flap forming the opposite side was made a 90 degree bent toward the laryngeal cavity to repaired the lower part defect of laryngeal cavity and reconstruct a new vocal cord. The repaired larynx recovered the normal appearance. The new vocal cord participated speech. The anterior 2/3 part of both vocal cored could contacted in pronunciation of patient. The phonation function of larynx was restored. RESULT: Sixty-one cases partial laryngectomy was taken including vertical partial laryngectomy in 37 cases, extended vertical partial laryngectomy in 24. During their operations, the laryngeal defect was repaired with thyroid cartilage membrane and sternohyoid muscle flap, and a vocal cord was reconstructed in the same time. After operation, the laryngeal cavity repaired has a normal appearance, and the laryngeal satisfactory phonation effect has been obtained. 93.4% of the patients enjoyed a socially acceptable voice and rejoined normal working. CONCLUSION: A technique of thyroid cartilage and sternohyoid muscle flap to repair the defect and reconstructive vocal cord after partial laryngectomy make patient recover normal laryngeal appearance and obtain satisfactory phonation effect. Among the method of repairation for partial laryngectomy sternohyoid muscle flap should be first considered owing to its various merits: 1. abundant material. 2. convenient procedures. 3. smaller trauma. 4. satisfactory effect.

[Pearson technique in the treatment of advanced laryngeal cancer].

OBJECTIVE: To seek for a better method of treating the advanced laryngeal cancer. METHOD: Twenty-eight cases of advanced laryngeal cancer were treated with near-total laryngectomy(Pearson technique), including 11 glottic cancers(III stage, 8 cases: IV stage, 3 cases), 17 supraglottic cancers (III stage, 13 cases; IV stage, 4 cases). In the same time 26 patients had neck node dissections. All the cases had speech function reconstructions. RESULT: The speech function was obtained in 27/28(96.4%). All cases had good swallowing, 3-year survival rate is 78.6%, 5-year survival rate is 68.4%. CONCLUSION: Near-total laryngectomy can be used in most cases that might be treated with traditional total laryngectomy in the past. It can provide satisfied survival rate, good swallowing, better speech function, but breath function.

[The surgical treatment of cancer in the base of tongue].

OBJECTIVE: To seek for a better approach for the resection of carcinoma of the base of tongue. METHOD: From 1991 to 2000, all 21 cases of tongue base carcinoma had been removed by transhyoid pharyngotomy(11 cases), mandibulectomy(7 cases) and step-liked mandibulotomy (3 cases). RESULT: Three patients with step-liked mandibulotomy had speech disorder and dysphagy. The rest had satisfactory speech and swallowing functions. During followed-up of 2-5 years, 2 cases lost follow-up, 18 cases were alive at 2 years, 13 cases were alive at 3 years, 5 cases 5 years. CONCLUSION: Transhyoid pharyngotomy provides good exposure to resect those tumors that involve the base of tongue, epiglottis, hypopharynx and larynx.

[Using PCR method to study the EB virus DNA in NPC].

OBJECTIVE: To study the EB virus DNA distribution in paraffin-embedded tissue, peripheral blood leukocyte and serum in nasopharyngeal carcinoma patients (NPC). METHOD: PCR method, in paraffin-embedded tissue of 39 patients with NPC (NPC group-1) and 20 patients with chronic nasopharyngitis (control group-1), in peripheral blood leukocyte and serum of 24 patients with NPC (NPC group-2) and 10 patients with other head and neck carcinoma (control group-2) and 10 patients with chronic nasopharyngitis (control group-3) were used to test the presence of Epstein-Barr virus DNA. At the same time, we also measured serum EB virus VCA-IgA antibodies with enzyme-immunoassay in NPC group-2, control group-2 and control group-3. RESULT: The results showed that 28 of 39 nasopharyngeal carcinoma patients (71.8%) (NPC group-1) and 3 of 20 chronic nasopharyngitis (15%) (control group-1) were EB virus DNA positive in paraffin-embedded tissues. The difference between NPC group-1 and control group-1 was statistically significant. Ten of 24 NPC group-2 (41.67%) and 1 of 10 control group-2 (10%) were EB virus DNA positive in peripheral blood leukocyte. Control group-3 EB virus DNA was negative in peripheral blood leukocyte. The difference between NPC group-2 and control group-3 was statistically significant (P < 0.05). All of the patients' EB virus DNA were negative in serum. The difference between NPC group-2 and control group-2; 2 was statistically significant in VCA-IgA titer respectively (Ridit Test P < 0.01). CONCLUSION: EB virus DNA positive in paraffin-embedded tissues is higher than that in peripheral blood leukocyte in nasopharyngeal carcinoma patients. In serum EB virus DNA is negative. The results suggest that EB virus DNA positive from paraffin-embedded tissues to peripheral blood leukocyte to serum is decrease gradually. There must be some relationship between VCA-IgA in serum and EB virus DNA in peripheral blood leukocyte.

An antisense oligonucleotide against H1 inhibits the classical sodium current but not ICa(TTX) in rat ventricular cells.

ICa(TTX) is a sodium current component, functionally distinct from the main body of sodium current, seen in cardiac and other cells. To determine if ICa(TTX) channels are a separate isoform from the classical cardiac sodium channels, we exposed rat ventricular cells in primary culture to an antisense oligonucleotide (AON) directed against rH1 (rNav1.5): 5'-CTCCTCATACCCTCT-3'. The homologous human sequence has been identified (and confirmed by us on HEK 293 cells) as effective against hH1 expressed heterologously. Scrambled sequence (5'-CCCCCCTTATCTACT-3') controls were also included. The AON (10 microM; day 2 of exposure) reduced the classical sodium current by 69.6 % compared to untreated and 60.8 % compared to scrambled sequence (10 microM; day 2 of exposure) controls (mean +/- S.E.M. maximum peak inward current density of -8.23 +/- 0.60 pA pF-1, 18 cells, for untreated; -6.37 +/- 0.79 pA pF-1, 16 cells, for scrambled sequence; and -2.50 +/- 0.31 pA pF-1, 18 cells, for AON-treated cells). The two control groups are not significantly different from each other, but are both significantly different from the AON-treated group (P < 0.001). The inhibition was specific for sodium channels, with no significant AON effect on the L-type calcium current. This confirms that H1 generates the classical cardiac sodium current. This same AON at the same concentration and time of exposure had no significant effect on ICa(TTX) (mean of -4.72 +/- 0.55, 15 cells; -5.47 +/- 0.53, 13 cells; and -5.04 +/- 0.63 pA pF-1, 15 cells, for untreated controls, scrambled controls and AON treated, respectively). Hence, ICa(TTX), which is functionally distinct from the classical cardiac sodium current, is encoded by a distinct gene.