Conduction disorders and permanent pacemaker implantation are common complications in patients who undergo transcatheter aortic valve implantation (TAVI). The aim of this study was to assess the ...incidence and clinical significance of new bundle branch block in patients who underwent TAVI with the Medtronic CoreValve Revalving System (MCRS) or the Edwards SAPIEN valve (ESV). Data from 238 patients with no previous pacemaker implantation, left bundle branch block (LBBB) or right bundle branch block at baseline electrocardiography who underwent TAVI with either MCRS (n = 87) or ESV (n = 151) bioprostheses from 2007 to 2011 were analyzed. New-onset LBBB occurred in 26.5% patients (n = 63): 13.5% with the ESV (n = 20) and 50.0% with the MCRS (n = 43) (p = 0.001). Permanent pacemaker implantation was required in 12.7% of patients (n = 8) because of complete atrioventricular block (ESV n = 2, MCRS n = 4), LBBB and first degree atrioventricular block (MCRS n = 1) and new-onset LBBB associated with sinus bradycardia (MCRS n = 1). At discharge, LBBB persisted in 8.6% of ESV patients (n = 13) and 32.2% of MCRS patients (n = 28) (p = 0.001). On multivariate analysis, the only predictor of LBBB was MCRS use (odds ratio 7.2, 95% confidence interval 2.9 to 17.4, p <0.001). Persistent new-onset LBBB at discharge was not associated with overall (log-rank p = 0.42) or cardiovascular (log-rank p = 0.46) mortality. New-onset right bundle branch block was documented in 4.6% of patients (n = 11), with no statistically significant differences between the ESV and MCRS. In conclusion, new-onset LBBB is a frequent intraventricular conduction disturbance after TAVI with a higher incidence with the MCRS compared with the ESV. LBBB persists in most patients, but in this cohort, it was not a predictor of overall or cardiovascular mortality or permanent pacemaker implantation.
Robotic Magnetic Navigation for Atrial Fibrillation Ablation
Carlo Pappone, Gabriele Vicedomini, Francesco Manguso, Filippo Gugliotta, Patrizio Mazzone, Simone Gulletta, Nicoleta Sora, Simone Sala, ...Alessandra Marzi, Giuseppe Augello, Laura Livolsi, Andreina Santagostino, Vincenzo Santinelli
Forty patients (median age 57 years) underwent circumferential pulmonary vein ablation for symptomatic drug-refractory atrial fibrillation (AF) using a remote magnetic navigation system (NIOBE II, Stereotaxis Inc., St. Louis, Missouri). Ablation was performed with a 4-mm magnetic tip catheter in a temperature-controlled mode (65°C, maximum 50 W, 15 s). Maps were created using an integrated CARTO RMT (Stereotaxis Inc.) system. End point of ablation was voltage abatement >90% of bipolar electrogram amplitude, and successful ablation was obtained in 38 of 40 patients. The overall median mapping and ablation time was 152.5 min (range, 90 to 380 min). Our results demonstrate that remote magnetic navigation for AF ablation is safe and feasible, reducing fluoroscopic exposure time for the operator.
We assessed feasibility of magnetic catheter guidance in patients with atrial fibrillation (AF) undergoing circumferential pulmonary vein ablation (CPVA).
No data are available on feasibility of remote navigation for AF ablation.
Forty patients underwent CPVA for symptomatic AF using the NIOBE II remote magnetic system (Stereotaxis Inc., St. Louis, Missouri). Ablation was performed with a 4-mm tip, magnetic catheter (65°C, maximum 50 W, 15 s). The catheter tip was guided by a uniform magnetic field (0.08-T), and a motor drive (Cardiodrive unit, Stereotaxis Inc.). Left atrium maps were created using an integrated CARTO RMT system (Stereotaxis Inc.). End point of ablation was voltage abatement >90% of bipolar electrogram amplitude.
Remote ablation was successful in 38 of 40 patients without complications. The median mapping and ablation time was 152.5 min (range, 90 to 380 min) but was much longer in the first 12 patients (192.5 min vs. 148 min; p = 0.012). Median ablation time was 49.5 min (range, 17 to 154 min), but it was much shorter in the last 28 patients than in the first 12 patients (49 min vs. 70 min; p = 0.021). Patients receiving remote ablation had longer procedure times than control patients (p < 0.001) with similar mapping time but shorter ablation time on right-sided pulmonary veins. Many more mapping points regardless of their location were collected remotely (p < 0.001).
Remote magnetic navigation for AF ablation is safe and feasible with a short learning curve. Although all procedures were performed by a highly experienced operator, remote AF ablation can be performed even by less experienced operators.
We conducted a randomized, controlled trial of circumferential pulmonary-vein ablation for the treatment of chronic atrial fibrillation.
A total of 146 patients with a mean (+/-SD) age of 57+/-9 ...years who had chronic atrial fibrillation were randomly assigned to receive amiodarone and undergo two cardioversions during the first three months alone (the control group) or in combination with circumferential pulmonary-vein ablation. Cardiac rhythm was assessed with daily telephonic transmissions for one year. The left atrial diameter and the severity of symptoms were assessed at 12 months.
Among the 77 patients assigned to undergo circumferential pulmonary-vein ablation, ablation was repeated because of recurrent atrial fibrillation in 26 percent of patients and atypical atrial flutter in 6 percent. An intention-to-treat analysis showed that 74 percent of patients in the ablation group and 58 percent of those in the control group were free of recurrent atrial fibrillation or flutter without antiarrhythmic-drug therapy at one year (P=0.05). Among the 69 patients in the control group, 53 (77 percent) crossed over to undergo circumferential pulmonary-vein ablation for recurrent atrial fibrillation by one year and only 3 (4 percent) were in sinus rhythm without antiarrhythmic-drug therapy or ablation. There were significant decreases in the left atrial diameter (12+/-11 percent, P<0.001) and the symptom severity score (59+/-21 percent, P<0.001) among patients who remained in sinus rhythm after circumferential pulmonary-vein ablation. Except for atypical atrial flutter, there were no complications attributable to circumferential pulmonary-vein ablation.
Sinus rhythm can be maintained long term in the majority of patients with chronic atrial fibrillation by means of circumferential pulmonary-vein ablation independently of the effects of antiarrhythmic-drug therapy, cardioversion, or both. The maintenance of sinus rhythm is associated with a significant decrease in both the severity of symptoms and the left atrial diameter.
Brugada syndrome (BrS) is an inherited autosomal dominant cardiac channelopathy. Pathogenic rare mutations in the
gene, encoding the alpha-subunit of the voltage-dependent cardiac Na
channel protein ...(Nav1.5), are identified in 20% of BrS patients, affecting the correct function of the channel. To date, even though hundreds of
variants have been associated with BrS, the underlying pathogenic mechanisms are still unclear in most cases. Therefore, the functional characterization of the
BrS rare variants still represents a major hurdle and is fundamental to confirming their pathogenic effect. Human cardiomyocytes (CMs) differentiated from pluripotent stem cells (PSCs) have been extensively demonstrated to be reliable platforms for investigating cardiac diseases, being able to recapitulate specific traits of disease, including arrhythmic events and conduction abnormalities. Based on this, in this study, we performed a functional analysis of the BrS familial rare variant NM_198056.2:c.3673G>A (NP_932173.1:p.Glu1225Lys), which has been never functionally characterized before in a cardiac-relevant context, as the human cardiomyocyte. Using a specific lentiviral vector encoding a GFP-tagged
gene carrying the specific c.3673G>A variant and CMs differentiated from control PSCs (PSC-CMs), we demonstrated an impairment of the mutated Nav1.5, thus suggesting the pathogenicity of the rare BrS detected variant. More broadly, our work supports the application of PSC-CMs for the assessment of the pathogenicity of gene variants, the identification of which is increasing exponentially due to the advances in next-generation sequencing methods and their massive use in genetic testing.
Different forms of sudden cardiac death have been described, including a recently identified form of genetic arrhythmogenic disorder, named “Triadin KnockOut Syndrome” (TKOS). TKOS is associated with ...recessive mutations in the TRDN gene, encoding for TRIADIN, but the pathogenic mechanism underlying the malignant phenotype has yet to be completely defined. Moreover, patients with TKOS are often refractory to conventional treatment, substantiating the need to identify new therapeutic strategies in order to prevent or treat cardiac events. The zebrafish (Danio rerio) heart is highly comparable to the human heart in terms of functions, signal pathways and ion channels, representing a good model to study cardiac disorders. In this work, we generated the first zebrafish model for trdn loss-of-function, by means of trdn morpholino injections, and characterized its phenotype. Although we did not observe any gross cardiac morphological defect between trdn loss-of-function embryos and controls, we found altered cardiac rhythm that was recovered by the administration of arrhythmic drugs. Our model will provide a suitable platform to study the effect of TRDN mutations and to perform drug screening to identify new pharmacological strategies for patients carrying TRDN mutations.
The diffraction endstation of the NanoMAX beamline is designed to provide high‐flux coherent X‐ray nano‐beams for experiments requiring many degrees of freedom for sample and detector. The endstation ...is equipped with high‐efficiency Kirkpatrick–Baez mirror focusing optics and a two‐circle goniometer supporting a positioning and scanning device, designed to carry a compact sample environment. A robot is used as a detector arm. The endstation, in continued development, has been in user operation since summer 2017.
The design and the basic performances of the diffraction endstation of the NanoMAX beamline of MAX IV Laboratory in Lund are presented. Designed to perform scanning diffraction, the endstation is adapted to single‐particle imaging as well as scanning fluorescence microscopy, tomography, and 2D and 3D ptychography in forward and Bragg geometries, using high‐flux nanofocused (coherent) X‐ray beams in the energy range between 5 and 28 keV.
Few data on atrial fibrillation (AF) progression from the first paroxysmal episode are available.
The purpose of this study was to assess the progression of AF not due to potentially reversible ...causes in patients treated according to current guidelines recommendations that also include catheter ablation.
Among 402 screened patients with first AF, 106 patients (mean age 57.5 years) were selected and followed for 5 years. Of these patients, 54 had lone AF and 52 had comorbidities.
Fifty patients (61.1% with lone AF) had no further recurrence after 5 years. The remaining 56 patients within 19 months after the first episode developed recurrent paroxysmal AF requiring long-term antiarrhythmic drug therapy, which was continued in 45 patients and was stopped because of intolerance/failure in 11 patients who underwent catheter ablation. AF became persistent in 24 of the 45 patients on antiarrhythmic drug therapy and then permanent in 16, of whom 6 had refused catheter ablation at the time of persistence. No AF recurrences or AF progression occurred after ablation. Kaplan-Meier curves demonstrated that patients with comorbidities were more likely to progress than were those with lone AF (P <.001) and that patients who underwent catheter ablation were at lower risk for progression to permanent AF than were those on antiarrhythmic drug therapy (P = .029). Age, diabetes, and heart failure (P <.001) predict final progression to permanent AF.
Patients with first AF and comorbidities are at higher risk for rapid progression to permanent AF, and age, diabetes, and heart failure are independent predictors. Catheter ablation rather than antiarrhythmic drug therapy is beneficial in eliminating recurrences delaying arrhythmia progression.
X‐ray fluorescence microscopy performed at nanofocusing synchrotron beamlines produces quantitative elemental distribution maps at unprecedented resolution (down to a few tens of nanometres), at the ...expense of relatively long measuring times and high absorbed doses. In this work, a method was implemented in which fast low‐dose in‐line holography was used to produce quantitative electron density maps at the mesoscale prior to nanoscale X‐ray fluorescence acquisition. These maps ensure more efficient fluorescence scans and the reduction of the total absorbed dose, often relevant for radiation‐sensitive (e.g. biological) samples. This multimodal microscopy approach was demonstrated on human sural nerve tissue. The two imaging modes provide complementary information at a comparable resolution, ultimately limited by the focal spot size. The experimental setup presented allows the user to swap between them in a flexible and reproducible fashion, as well as to easily adapt the scanning parameters during an experiment to fine‐tune resolution and field of view.
This work presents the implementation of combined high‐resolution X‐ray in‐line holography and X‐ray fluorescence microscopy within the same experimental setup at a hard X‐ray nanofocusing beamline. In‐line holography provides morphological information by recovering electron density maps, even on weakly scattering or low‐contrast samples; X‐ray fluorescence provides complementary chemical information by producing element‐specific mass density maps.
The subcutaneous implantable cardioverter defibrillator (S-ICD) is a relatively novel alternative to the transvenous ICD for the treatment of life-threatening ventricular arrhythmias, and is ...currently used in the clinical practice of several centers. The aim of this analysis was to describe current Italian practice regarding S-ICD implantation and its evolution over the years.
We analyzed 607 consecutive patients (78% male, 48 ± 16 years) who underwent S-ICD implantation in 39 Italian centers from 2013 to 2017.
Structural cardiomyopathy was present in 78% of patients and 30% of patients received their device for secondary prevention. The proportion of patients with dilated cardiomyopathy and with left ventricular ejection fraction ≤35% increased from ≤2014 to 2017 (from 38% to 58%, from 33% to 53%, respectively; both p < 0.05). Almost all procedures (97%) were performed in electrophysiology laboratories. Over the last 4 years, the 2-incision implantation technique has been widely adopted, with sub- or inter-muscular positioning of the generator, under local anesthesia or deep sedation (≤2014 versus 2017: all p < 0.001). Defibrillation testing was performed in 81% of patients. Shock energy of ≤65 J was successful in 93.9% of patients and the overall cardioversion success rate at ≤80 J was 99.8%.
Our analysis confirmed that the S-ICD continues to be preferentially used in specific patients (younger, less frequently with dilated cardiomyopathy and low ejection fraction.). Nonetheless, we noted a trend toward the wider use of S-ICD in patients with dilated cardiomyopathy and systolic dysfunction over the years. Novel approaches have been adopted while the acute efficacy of the system has remained stably high.
•This nation-wide registry provided original data on the Italian current practice of S-ICD implantation.•Over the last 4 years the surgical technique has evolved.•Although the S-ICD seems to be preferred in specific patients, we noted a trend toward the wider use of S-ICD over the years.
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