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IntroductionThis study aimed to clarify the relationship between the durability of pulmonary vein (PV) isolation and the time of phase transition from ice to water indicated by thawing plateau time in a cryoballoon ablation for atrial fibrillation (AF).Methods and resultsIn this retrospective study, 241 PVs from 71 patients who underwent a repeat AF ablation 526 (IQR: 412, 675) days after a cryoballoon ablation were analyzed. Reconnection was observed in 101 (41.9%) PVs of 53 patients (74.6%). Thawing plateau time (TimeTP) was defined as the time from 0°C to 10°C inside the balloon in the thawing period. Durable PV isolation was associated with significantly longer TimeTP compared with PV reconnection (26.0 vs. 11.0 s, P 25 s with a positive predictive value of 84.6% (sensitivity = 55.0%, specificity = 86.1%). In the analysis of multivariable logistic regression, location of PV reconnection (P 25 s predicts durable PV isolation.

Abstract Background Usage of active fixation bipolar left ventricular (LV) leads represents an alternative approach to the more commonly used passive fixation quadripolar leads in cardiac resynchronization therapy (CRT). We compared a bipolar LV lead with a side screw for active fixation and passive fixation quadripolar LV leads. Methods Sixty‐two patients were before CRT implantations randomly allocated to receive a bipolar (n = 31) or quadripolar (n = 31) LV leads. Speckle‐tracking radial strain echocardiography was used to define the LV segment with latest mechanical activation as the target LV segment. The electrophysiological measurements and the capability to obtain a proximal position in a coronary vein placed over the target segment were assessed. Results Upon implantation, the quadripolar lead demonstrated a lower pacing capture threshold than the bipolar lead, but at follow‐up, there was no difference. There were no differences in the LV lead implant times or radiation doses. The success rate in reaching the target location was not significantly different between the two LV leads. Conclusions The pacing capture thresholds were low, with no significant difference between active fixation bipolar leads and quadripolar leads. Active fixation leads did not promote a more proximal location of the stimulating electrode or a higher grade of concordance to the target segment than passive fixation leads.

IntroductionNon-macroreentrant atrial tachycardia (nAT) following atrial fibrillation (AF) ablation is being increasingly reported. Many issues remain to be elucidated. We aimed to characterize the fractionated potentials (FPs) in nAT and introduce a new method of cross-mapping for clarifying their roles.Methods and ResultsForty-four nATs in 37 patients were enrolled and classified into focal AT (FAT, 12), microreentrant AT (MAT, 14), and small-loop-reentrant AT (SAT, 18) groups, according to activation pattern. FP was found on all targets except in nine FATs. The ratio of FP duration to AT cycle length (TCL) was different among groups (28 ± 7% in FAT, 53 ± 11% in MAT, and 42 ± 14% in SAT, p < 0.05), and ablation duration were longer in SATs (313 ± 298 vs. 111 ± 125 s, p < 0.05). The ratio of mappable cycle length to TCL was lower in the FAT group (63 ± 22% vs. 90 ± 9% and 89 ± 8%, p < 0.05). When cross-mapping was employed, trans-potential time differences in both longitudinal and transverse direction were longer around the culprit FP for MAT (p < 0.01). After Receiver Operating Characteristic curve analysis, it is best to adopt the sum of time difference ratios in both directions ≥60% as a cut-off value for discrimination of the FPs responsible for MAT with a sensitivity of 92% and specificity of 87%.ConclusionsFP could be found on target in most nATs following a previous AF ablation. The ratio of FP duration to TCL may help for differentiation. A simple method of cross-mapping could be employed to clarify the roles of FPs.

Background: Several wireless ECG devices are commercially available for possible screening, monitoring and diagnosis of rhythms. The field is rapidly expanding, and some devices have demonstrated acceptable qualities. The objective was to evaluate the accuracy, usability and diagnostic capabilities of smartphone ECG in both patients and healthy controls. Methods: We used a commercially available smartphone ECG device, connected wirelessly to a tablet, to record a 30-s lead I ECG in 144 subjects—20 of whom repeated the test after vigorous exercise. The subjects included 94 patients under standard calculated 12-lead ECG surveillance; transcripts were obtained shortly after the smartphone ECG was acquired. Results: No significant differences were found in the QRS, frequency and QT intervals between the two modalities. Smartphone ECG recordings separated pathologic rhythms (atrial fibrillation (AF)/flutter, atrioventricular block, regular supraventricular rhythm, and pacing) from sinus rhythms with a sensitivity of 0.75 and a specificity of 0.97. The specific diagnosis of AF appeared in 11 patients and was detected with a sensitivity of 1 and a specificity of 0.94. There was a marginal decrease in the interpretability of the smartphone ECG after exercise. Inter- and intraobserver variability was low. Conclusions: Smartphone ECG accurately measures most baseline intervals and has acceptable sensitivity and specificity for pathological rhythms, especially for AF. Vigorous activity has a minor influence on the readability of the PR interval. Elderly patients may face challenges in recording a smartphone ECG correctly without assistance. According to our findings, the smartphone ECG would be applicable as a screening device for pathological rhythms. Keywords: Smartphone ECG, Atrial fibrillation, Screening, Digital health

Abstract The Chiari networks are reticulated fibers of embryological remnant venous valves in the right atrium. In patients with this congenital variation, manipulation of diagnostic catheters can be difficult, and there is a substantial risk of entrapment during electrophysiological studies. We report a case of successful retraction of a diagnostic catheter entangled in the Chiari network with the use of a lead extraction tool during a scheduled atrial fibrillation ablation. Rescheduled cryoablation was performed without complication and provided a good outcome.

The live genetically-engineered oral rabies virus (RABV) variant SPBN GASGAS induces long-lasting immunity in foxes and protection against challenge with an otherwise lethal dose of RABV field strains both after experimental oral and parenteral routes of administration. Induction of RABV-specific binding antibodies and immunoglobulin isotypes (IgM, total IgG, IgG1, IgG2) were comparable in orally and parenterally vaccinated foxes. Differences were only observed in the induction of virus-neutralizing (VNA) titers, which were significantly higher in the parenterally vaccinated group. The dynamics of rabies-specific antibodies pre- and post-challenge (365 days post vaccination) suggest the predominance of type-1 immunity protection of SPBN GASGAS. Independent of the route of administration, in the absence of IgG1 the immune response to SPBN GAGAS was mainly IgG2 driven. Interestingly, vaccination with SPBN GASGAS does not cause significant differences in inducible IFN-γ production in vaccinated animals, indicating a relatively weak cellular immune response during challenge. Notably, the parenteral application of SPBN GASGAS did not induce any adverse side effects in foxes, thus supporting safety studies of this oral rabies vaccine in various species.

Background: The aim of this study was to examine the effect of radiofrequency ablation (RFA) of ventricular arrhythmias from right ventricular outflow tract (RVOT) during long-term follow-up. Methods: A follow-up analysis was conducted using an in-house questionnaire, as well as a qualitative assessment of the patients' medical records. The study population of 34 patients had a previous diagnosis of idiopathic VT or frequent PVCs from the RVOT, and received RFA treatment between 2002 and 2005. Results: The main symptoms prior to RFA were palpitations (82.4%) and dizziness (76.5%). A reduction in symptoms following RFA was reported by 91.2% of patients (p

In order to obtain Marketing Authorization for an oral rabies vaccine in the European Union, not only safety studies in the target species, red fox and raccoon dog, are required. Since baits are distributed unsupervised in the environment, specific safety studies in selected non-target species are compulsory. Furthermore, oral rabies vaccines are based on live, replication-competent viruses and thus distinct safety studies in the target species for such type of vaccines are also mandatory. Here, the results of these safety studies in target and selected non-target species for a 3rd generation oral rabies virus vaccine construct, SPBN GASGAS (Rabitec), are presented. The studies included the following species; red fox, raccoon dog, domestic dog, domestic cat, domestic pig, wild rodents. The following safety topics were investigated; overdose, repeated dose, dissemination, shedding, horizontal and vertical transmission. It was shown that SPBN GASGAS did not cause disease or any other adverse reaction in vaccinated animals and naïve contact animals. The vaccine did not disseminate within the host beyond the site of entry. No horizontal transmission was observed in wild rodents. In the target species, there was evidence that in a few cases horizontal transmission of vaccine virus could have occurred under these experimental conditions; most likely immediately after vaccine administration. The vaccine construct SPBN GASGAS meets therefore the latest revised minimal safety requirements as laid down in the European Pharmacopoeia.

To evaluate the long-term immunogenicity of the live-attenuated, oral rabies vaccine SPBN GASGAS in a full good clinical practice (GCP) compliant study, forty-six (46) healthy, seronegative red foxes (Vulpes vulpes) were allocated to two treatment groups: group 1 (n = 31) received a vaccine bait containing 1.7 ml of the vaccine of minimum potency (106.6 FFU/mL) and group 2 (n = 15) received a placebo-bait. In total, 29 animals of group 1 and 14 animals of group 2 were challenged at 12 months post-vaccination with a fox rabies virus isolate (103.0 MICLD50/mL). While 90% of the animals offered a vaccine bait resisted the challenge, only one animal (7%) of the controls survived. All animals that had seroconverted following vaccination survived the challenge infection at 12 months post-vaccination. Rabies specific antibodies could be detected as early as 14 days post-vaccination. Based on the kinetics of the antibody response to SPBN GASGAS as measured in ELISA and RFFIT, the animals maintained stable antibody titres during the 12-month pre-challenge observation period at a high level. The results indicate that successful vaccination using the oral route with this new rabies virus vaccine strain confers long-term duration of immunity beyond one year, meeting the same requirements as for licensure as laid down by the European Pharmacopoeia.

The most recent treatment option of medically refractory heart failure includes cardiac resynchronization therapy (CRT) by biventricular pacing in selected patients in NYHA functional class III or IV heart failure. The widely used marker to indicate left ventricular (LV) asynchrony has been the surface ECG, but seems not to be a sufficient marker of the mechanical events within the LV and prediction of clinical response. This review presents an overview of techniques for identification of left ventricular intra- and interventricular asynchrony. Both manuscripts for electrical and mechanical asynchrony are reviewed, partly predicting response to CRT. In summary there is still no gold standard for assessment of LV asynchrony for CRT, but both traditional and new echocardiographic methods have shown asynchronous LV contraction in heart failure patients, and resynchronized LV contraction during CRT and should be implemented as additional methods for selecting patients to CRT.

Biological evolution progresses by essentially three different mechanisms: (I) optimization of properties through natural selection in a population of competitors; (II) development of new capabilities through cooperation of competitors caused by catalyzed reproduction; and (III) variation of genetic information through mutation or recombination. Simplified evolutionary processes combine two out of the three mechanisms: Darwinian evolution combines competition (I) and variation (III) and is represented by the quasispecies model, major transitions involve cooperation (II) of competitors (I), and the third combination, cooperation (II) and variation (III) provides new insights in the role of mutations in evolution. A minimal kinetic model based on simple molecular mechanisms for reproduction, catalyzed reproduction and mutation is introduced, cast into ordinary differential equations (ODEs), and analyzed mathematically in form of its implementation in a flow reactor. Stochastic aspects are investigated through computer simulation of trajectories of the corresponding chemical master equations. The competition-cooperation model, mechanisms (I) and (II), gives rise to selection at low levels of resources and leads to symbiontic cooperation in case the material required is abundant. Accordingly, it provides a kind of minimal system that can undergo a (major) transition. Stochastic effects leading to extinction of the population through self-enhancing oscillations destabilize symbioses of four or more partners. Mutations (III) are not only the basis of change in phenotypic properties but can also prevent extinction provided the mutation rates are sufficiently large. Threshold phenomena are observed for all three combinations: The quasispecies model leads to an error threshold, the competition-cooperation model allows for an identification of a resource-triggered bifurcation with the transition, and for the cooperation-mutation model a kind of stochastic threshold for survival through sufficiently high mutation rates is observed. The evolutionary processes in the model are accompanied by gains in information on the environment of the evolving populations. In order to provide a useful basis for comparison, two forms of information, syntactic or Shannon information and semantic information are introduced here. Both forms of information are defined for simple evolving systems at the molecular level. Selection leads primarily to an increase in semantic information in the sense that higher fitness allows for more efficient exploitation of the environment and provides the basis for more progeny whereas understanding transitions involves characteristic contributions from both Shannon information and semantic information.

The most recent treatment option of medically refractory heart failure includes cardiac resynchronization therapy (CRT) by biventricular pacing in selected patients in NYHA functional class III or IV heart failure. The widely used marker to indicate left ventricular (LV) asynchrony has been the surface ECG, but seems not to be a sufficient marker of the mechanical events within the LV and prediction of clinical response. This review presents an overview of techniques for identification of left ventricular intra- and interventricular asynchrony. Both manuscripts for electrical and mechanical asynchrony are reviewed, partly predicting response to CRT. In summary there is still no gold standard for assessment of LV asynchrony for CRT, but both traditional and new echocardiographic methods have shown asynchronous LV contraction in heart failure patients, and resynchronized LV contraction during CRT and should be implemented as additional methods for selecting patients to CRT.