Mean Dominant Frequency Research Articles

Organized patterns of excitation during persistent atrial fibrillation in humans relate to tissue structure and activation rate

Abstract Background The contribution of organized patterns of excitation as mechanisms maintaining persistent atrial fibrillation (PAF) is questioned. Purpose We aim to analyze the relationship of focal and reentrant activities, identified with the CARTO-Finder system, with tissue structure and activation rate to explain potential link with mechanisms and outcomes. Methods 33 patients with PAF of at least 6 months (24±4 months) were admitted for right and left atrial (RA & LA) mapping with the CARTO-Finder system. The biatrial geometry, bipolar Penta-Ray`s signals (30 sec long) and activation patterns were exported for off-line analysis (MatLab environment). A fast-Fourier transform was computed on 30 sec bipolar signal length segments to compute dominant frequency (DF) and represented on atrial shells. Focal and reentrant patterns of activation were superimposed, and correlation with DF and bipolar voltage analyzed. Results Biatrial mapping was performed obtaining 15.3±5 Finder maps from the RA and 15.9±5 Finder maps from the LA. Focal activities (182±151 at the RA & 270±21 at the LA) were documented in all patients at both atria. Rotational activities (more than 2 consecutive) were documented in the left atria in 4 patients (22.5±16.8 rotations) and in the right atria in 9 patients (35.5±32 rotations). 30 sec long activation rate was higher at places with focal activities compared with areas without organized patterns (DF: 6.11±0.09 Hz vs 5.7±0.09 Hz; p<0.001). The higher the number of consecutive focal activities, the higher the tissue activation rate (DF no focal activities 5.7±0.09 Hz vs DF 1-5 focal activities 6.0±0.14 Hz vs DF>5 focal activities 6.2±0.14 Hz; p<0.001). In addition, DF at focal activities strongly correlates with DF at areas without organized patterns (Pearson 0.91; p<0.001). The bipolar voltage was higher at places with focal activities compared with areas without organized patterns (1.0±0.04 mV vs 0.5±0.04 mV; p<0.001). None of the previous were observed at places with rotational activities (DF: 5.9±0.16 Hz vs 5.7±0.09 Hz; p=0.204 & Volt: 0.6±0.08 mV vs 0.5±0.04 mV; p=0.364). During follow-up after ablation (24±7 months), a cox regression model including number of focal activities, number of rotations, mean tissue activation rate (mean DF) and bipolar voltage, identified bipolar voltage as a unique independent predictor of survival free of AF recurrence (p=0.04). Conclusions Focal activities identified with the CARTO Finder system during PAF in humans correlate with tissue structure and activation rate, suggesting a potential link with mechanisms.

Spatiotemporal stability of digital twin-guided atrial fibrillation dominant frequency sites and the clinical outcome of catheter ablation

Abstract Background Although the dominant frequency (DF) may localize the reentrant drivers of atrial fibrillation (AF), its meandering nature makes it difficult to localize as an extra-pulmonary vein (extra-PV) target. Purpose We explored and quantified the spatiotemporal stability of DF by sophisticated digital-twin maps and the association with the rhythm outcome of clinical AF catheter ablation (AFCA). Methods We retrospectively examined the DF sites in the digital twin integrated by high-density electroanatomical maps (EAM) of 170 patients previously included in the CUVIA-AF2 trial (male 70.6%, 59.2±11.3 years old, 100% persistent AF). We monitored 34 seconds of virtual AF and analyzed DF sites in 10 different left atrial (LA) regions at 3 consecutive periods (6 seconds each after 16sec induction and blanking periods). The spatiotemporal stability index (STSI) was calculated to quantify mean DF's spatial and temporal variability. During protocol-based rhythm follow-up, we assessed the atrial arrhythmia recurrence rate by dividing patients into two groups based on STSI 0.75. Results During the simulation, 108 out of 170 (63.5%) patients obtained mean DF values in all three consecutive periods. There were 26 (24.1%) patients in the stable DF group (STSI ≥0.75, Stable group) and 82 (75.9%) patients in the unstable DF group (STSI <0.75, Unstable group). Although the proportion of patients with hypertension (73.1 vs. 47.6%, p=0.041) was higher and left ventricular end-diastole diameter (51.3±3.9 vs. 49.0±4.4 mm, p=0.020) was larger in the stable DF group than in the unstable DF group, other parameters, including LA size, LA voltage, or AF ablation targets, did not differ between two groups. During the median 19 [15-22] months follow-up, the atrial arrhythmia recurrence rate of the Stable group is higher than that of the Unstable group (log-rank p=0.031, HR = 2.06, CI [1.06-4.01]) Conclusions We found that the temporally stable DF in EAM-integrated virtual AF, the potential extra-PV AF drivers, is a surrogate marker of the adverse rhythm outcome of AFCA. A prospective clinical trial targeting the spatiotemporally stable DF will be warranted.

Abstract 17924: Machine Learning Analysis of the Atrial ECG in Patients With Persistent Atrial Fibrillation Predicts Long-Term Outcomes

Background: The surface Atrial ECG (A-ECG) time and frequency domains features are not currently used clinically in patients with persistent atrial fibrillation (PeAF). Machine Learning (ML) can provide novel insight into various data sources. Research question: Can ML analysis of the A-ECG predict the outcome of catheter ablation (CA) of PeAF? Aim: To use ML Tools to assess A-ECG prediction of CA outcomes in PeAF patients at 1 and 2 years. Methods: Thirty-two patients (age 63±9 years; 71% males) with PeAF underwent two 5-minute epochs of surface ECG; 4 were excluded for significant artifacts and 2 more for unrelated clinical issues. The Pre-CA A-ECG was derived by QRST subtraction and independent component analysis filtering and divided into 50% overlap 10-second windows for spectral analysis. A-ECG mean dominant frequency DF, mean organization index and median amplitude M-AMP were computed for each lead. Freedom from atrial arrhythmia AA (Responders) was assessed at one and two years. The two 5-minute segments per patient were included in the data set. Classification Learner (Mathworks Inc., Natick, MA, USA) was used to train classifiers, looking for the minimum number of features able to explain the outcomes. Once the best (2-3) features were identified, a MATLAB program was used to visualize the decision regions and correlate with ablation outcomes. Results: ML identified A-ECG features DF and M-AMP of V 1 to well explain outcome. Specifically, an Artificial Neural Network (ANN) with 1 fully connected hidden layer of size 7 can explain the data with 90.4% accuracy. The figure shows the datasets for year 1 and year 2 CA outcomes, superimposed with ANN decision regions, for Responders and non-Responders. High DF and high M-AMP are predictors of responders and Low DF low M-AMP for non-Responders. Conclusion: ML analysis of the A-ECG is a promising tool to predict Responders to PVI CA for treatment of PeAF. This predictive algorithm needs to be tested on a prospective cohort.

The advertisement calls of Pristimantis galdi Jiménez de la Espada, 1870 and Pristimantis katoptroides (Flores, 1988) (Anura, Strabomantidae)

In this study we describe for the first time the calls of Pristimantis galdi and Pristimantis katoptroides. Recordings were obtained in Sangay National Park, Ecuador. We highlight the importance of recording P. galdi since its call has been recorded after 153 years of having been described as a species. The call of P. galdi consists of 7 to 9 short notes, the sounds of which are similar to a hammer hitting a nail, with a mean dominant frequency of 2.39 kHz. In turn, the call of P. katoptroides consists of a single note, the sound of which is similar to a metallic “tic”, with a mean dominant frequency of 1.74 kHz. We compared the advertisement calls of P. galdi, P. katoptroides and P. roni as these species share similar morphological characteristics and are grouped in the spiny green frog’s ecotype. Despite these morphological similarities, their advertisement calls are different. Obtaining calls of Pristimantis species in Ecuador might prove difficult with short-term studies due to the great sampling efforts that may be needed to get these recordings. Therefore, implementing active and passive monitoring could help improve our knowledge of acoustic signals in Ecuador’s rainfrogs.

Ablation and antiarrhythmic drug effects on PITX2 +/- deficient atrial fibrillation: A computational modeling study.

IntroductionAtrial fibrillation (AF) is a heritable disease, and the paired-like homeodomain transcription factor 2 (PITX2) gene is highly associated with AF. We explored the differences in the circumferential pulmonary vein isolation (CPVI), which is the cornerstone procedure for AF catheter ablation, additional high dominant frequency (DF) site ablation, and antiarrhythmic drug (AAD) effects according to the patient genotype (wild-type and PITX2+/− deficient) using computational modeling.MethodsWe included 25 patients with AF (68% men, 59.8 ± 9.8 years of age, 32% paroxysmal AF) who underwent AF catheter ablation to develop a realistic computational AF model. The ion currents for baseline AF and the amiodarone, dronedarone, and flecainide AADs according to the patient genotype (wild type and PITX2+/− deficient) were defined by relevant publications. We tested the virtual CPVI (V-CPVI) with and without DF ablation (±DFA) and three virtual AADs (V-AADs, amiodarone, dronedarone, and flecainide) and evaluated the AF defragmentation rates (AF termination or changes to regular atrial tachycardia (AT), DF, and maximal slope of the action potential duration restitution curves (Smax), which indicates the vulnerability of wave-breaks.ResultsAt the baseline AF, mean DF (p = 0.003), and Smax (p < 0.001) were significantly lower in PITX2+/− deficient patients than wild-type patients. In the overall AF episodes, V-CPVI (±DFA) resulted in a higher AF defragmentation relative to V-AADs (65 vs. 42%, p < 0.001) without changing the DF or Smax. Although a PITX2+/− deficiency did not affect the AF defragmentation rate after the V-CPVI (±DFA), V-AADs had a higher AF defragmentation rate (p = 0.014), lower DF (p < 0.001), and lower Smax (p = 0.001) in PITX2+/− deficient AF than in wild-type patients. In the clinical setting, the PITX2+/− genetic risk score did not affect the AF ablation rhythm outcome (Log-rank p = 0.273).ConclusionConsistent with previous clinical studies, the V-CPVI had effective anti-AF effects regardless of the PITX2 genotype, whereas V-AADs exhibited more significant defragmentation or wave-dynamic change in the PITX2+/− deficient patients.

A new Amazonian species of Allobates Zimmermann & Zimmermann, 1988 (Aromobatidae) with a trilled advertisement call.

BackgroundCurrently, 58 species are assigned to the genus Allobates, with 70% of its diversity described just in the last two decades, with many additional species likely unnamed. The continuous description of these new species represents a fundamental step for resolving the taxonomy and ensuring the future conservation of the genus.MethodsUsing molecular, acoustic, and morphological evidences, we describe a new species of Allobates from Teles Pires River region, southern Amazonia, and provide accounts on the population of A. tapajos found sympatrically with the new species.ResultsThe new species is distinguished from its congeners by the coloration of thighs, venter, dorsum, and dark lateral stripe. It has four types of calls, with advertisement calls formed by relatively long trills with a mean duration of 2.29 s ± 0.65, mean of 39.93 notes ± 11.18 emitted at a mean rate of 17.49 ± 0.68 notes per second, and mean dominant frequency of 5,717 Hz ± 220.81. The genetic distance between the new species and its congeners in a fragment of the 16S mitochondrial fragment ranged between 13.2% (A. carajas) to 21.3% (A. niputidea). The sympatric Allobates population fits its morphology and acoustic with the nominal A. tapajos, but presents a relatively high genetic distance of nearly 6.5%, raising questions on the current taxonomy of this species.

Predictors of recurrence of atrial tachyarrhythmias after pulmonary vein isolation by functional and structural mapping of nonparoxysmal atrial fibrillation.

BackgroundThis study aimed to evaluate the predictors of recurrence of atrial tachyarrhythmias by structural and functional mapping: voltage, dominant frequency (DF), and rotor mapping after a pulmonary vein isolation (PVI) in nonparoxysmal atrial fibrillation (AF) patients.MethodsA total of 66 nonparoxysmal AF patients were prospectively investigated. After the PVI, an online real‐time phase mapping system was used to detect the location of rotors with critical nonpassively activated ratios (%NPs) of ≧50% in each left atrial (LA) segment, and high‐DFs of ≧7 Hz were simultaneously mapped. After restoring sinus rhythm, low‐voltage areas (LVAs < 0.5 mV) were mapped using the Advisor HD grid catheter (HDG).ResultsSixty‐four of 66 (97%) AF patients had minimum to mild LVAs regardless of an enlarged LAD and LA volume (45 ± 6.0 mm and 141 ± 29 ml). There were no significant differences in the max and mean DF values and %NPs between the patients with and without recurrent atrial tachyarrhythmias. However, there was a significant difference in the LVA/LA surface area between the patients with and without recurrent atrial tachyarrhythmias (p = .004). Atrial tachyarrhythmia freedom was significantly greater in those with LVAs of ≤3.3% than in those >3.3% after one procedure over 11.6 ± 0.8 months of follow‐up (77.1% vs. 33.3%, p < .001). In a multivariate analysis, the LVA/LA surface area after the PVI (HR 1.079; CI, 1.025–1.135, p = .003) was an independent predictor of AF recurrence.ConclusionsThe predictor of atrial tachyarrhythmia recurrence after the PVI was LVAs rather than DFs and rotors in nonparoxysmal AF patients.

Spatial Changes in the Atrial Fibrillation Wave-Dynamics After Using Antiarrhythmic Drugs: A Computational Modeling Study.

Background: We previously reported that a computational modeling-guided antiarrhythmic drug (AAD) test was feasible for evaluating multiple AADs in patients with atrial fibrillation (AF). We explored the anti-AF mechanisms of AADs and spatial change in the AF wave-dynamics by a realistic computational model.Methods: We used realistic computational modeling of 25 AF patients (68% male, 59.8 ± 9.8 years old, 32.0% paroxysmal AF) reflecting the anatomy, histology, and electrophysiology of the left atrium (LA) to characterize the effects of five AADs (amiodarone, sotalol, dronedarone, flecainide, and propafenone). We evaluated the spatial change in the AF wave-dynamics by measuring the mean dominant frequency (DF) and its coefficient of variation [dominant frequency-coefficient of variation (DF-COV)] in 10 segments of the LA. The mean DF and DF-COV were compared according to the pulmonary vein (PV) vs. extra-PV, maximal slope of the restitution curves (Smax), and defragmentation of AF.Results: The mean DF decreased after the administration of AADs in the dose dependent manner (p < 0.001). Under AADs, the DF was significantly lower (p < 0.001) and COV-DF higher (p = 0.003) in the PV than extra-PV region. The mean DF was significantly lower at a high Smax (≥1.4) than a lower Smax condition under AADs. During the episodes of AF defragmentation, the mean DF was lower (p < 0.001), but the COV-DF was higher (p < 0.001) than that in those without defragmentation.Conclusions: The DF reduction with AADs is predominant in the PVs and during a high Smax condition and causes AF termination or defragmentation during a lower DF and spatially unstable (higher DF-COV) condition.

Computational modeling for antiarrhythmic drugs for atrial fibrillation according to the genotypes

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): This work was supported by a grant [HI19C0114] from the Ministry of Health and Welfare. Additionally, the work was funded by grants [NRF-2019R1C1C100907512], and [NRF-2020R1A2B01001695] from the Basic Science Research Program run by the National Research Foundation of Korea (NRF) under the Ministry of Science, ICT &amp; Future Planning (MSIP). Background The efficacy of antiarrhythmic drugs (AAD) can vary in patients with atrial fibrillation (AF) and the PITX2 gene affects the responsiveness of AADs. We explored the virtual AAD (V-AAD) responses between wild-type and PITX2+/- deficient AF conditions by realistic in-silico AF modeling. Methods We tested the V-AADs in AF modeling integrated with patients’ 3D-computed tomography and 3D-electroanatomical mapping, acquired in 25 patients (68% male, 59.8 ± 9.8 years old, 32.0% paroxysmal type). The ion currents for the PITX2+/- deficiency and each AAD (amiodarone, sotalol, dronedarone, flecainide, and propafenone) were defined based on previous publications. Results We compared the wild-type and PITX2+/- deficiency in terms of the action potential duration (APD90), conduction velocity (CV), maximal slope of restitution (Smax), and wave-dynamic parameters, such as the dominant frequency (DF), phase singularities (PS), and AF termination rates according to the V-AADs. The PITX2+/- deficient model exhibited a shorter APD90 (p &amp;lt; 0.001), a lower Smax (p &amp;lt; 0.001), mean DF (p = 0.012), PS number (p &amp;lt; 0.001), and a longer AF cycle length (AFCL, p = 0.011). Five V-AADs changed the electrophysiology in a dose dependent manner. AAD-induced AFCL lengthening (p &amp;lt; 0.001) and reductions in the CV (p = 0.033), peak DF (p &amp;lt; 0.001) and PS number (p &amp;lt; 0.001) were more significant in PITX2+/- deficient than wild-type AF. PITX2+/- deficient AF was easier to terminate with class IC AADs than the wild-type AF (p = 0.018). Conclusions The computational modeling-guided AAD test was feasible for evaluating the efficacy of multiple AADs in patients with AF. AF wave-dynamics and electrophysiological characteristics are different among the PITX2 deficient and the wild-type genotype models. BaselineChanges after AADClass ICClass IIIWild-typePITX2+/-p-valueWild-typePITX2+/-p-valueWild-typePITX2+/-p-valueWild-typePITX2+/-p-valueAPD90, (ms)243.7 ± 33.8184.4 ± 15.5&amp;lt;0.00138.2 ± 37.343.4 ± 56.20.223275.9 ± 43.5219.0 ± 39.2&amp;lt;0.001284.9 ± 32.8233.8 ± 71.4&amp;lt;0.001CV, (m/s)0.78 ± 0.320.70 ± 0.210.347-0.15 ± 0.18-0.20 ± 0.260.0330.63 ± 0.320.53 ± 0.300.0270.60 ± 0.360.43 ± 0.33&amp;lt;0.001Mean Smax0.787 ± 0.280.531 ± 0.18&amp;lt;0.0010.005 ± 0.260.115 ± 0.24&amp;lt;0.0010.828 ± 0.310.694 ± 0.320.0030.768 ± 0.320.608 ± 0.27&amp;lt;0.001Mean AFCL, (ms)146.96 ± 24.61164.78 ± 22.730.01122.62 ± 24.5537.92 ± 32.72&amp;lt;0.001165.44 ± 36.96190.85 ± 35.61&amp;lt;0.001169.05 ± 25.26203.35 ± 34.78&amp;lt;0.001Peak DF, (Hz)10.68 ± 2.9711.82 ± 3.340.211-2.98 ± 4.94-5.46 ± 4.66&amp;lt;0.00110.01 ± 4.397.23 ± 4.20&amp;lt;0.0016.30 ± 4.325.80 ± 4.070.301Mean DF, (Hz)6.80 ± 0.886.22 ± 0.710.012-1.95 ± 2.44-2.20 ± 1.990.2065.75 ± 1.784.53 ± 2.00&amp;lt;0.0014.14 ± 2.393.69 ± 2.000.077PS Number, (N)101086 ± 9608814150 ± 24778&amp;lt;0.001-59322 ± 99288-7409 ± 27856&amp;lt;0.00150579 ± 6523611568 ± 21868&amp;lt;0.00132951 ± 558643524 ± 8302&amp;lt;0.001PS Life Span, (ms)109.36 ± 113.90102.24 ± 226.640.889-24.87 ± 72.06-41.38 ± 126.350.073103.36 ± 180.6868.05 ± 162.790.14871.91 ± 141.8655.99 ± 217.970.454Table. Effects of AADs in the Wild-type and PITX2+/- Deficiency groupAbstract Figure. Wild-type vs. PITX2+/- baseline model

Computational Modeling for Antiarrhythmic Drugs for Atrial Fibrillation According to Genotype.

Background: The efficacy of antiarrhythmic drugs (AAD) can vary in patients with atrial fibrillation (AF), and the PITX2 gene affects the responsiveness of AADs. We explored the virtual AAD (V-AAD) responses between wild-type and PITX2+/−-deficient AF conditions by realistic in silico AF modeling.Methods: We tested the V-AADs in AF modeling integrated with patients' 3D-computed tomography and 3D-electroanatomical mapping, acquired in 25 patients (68% male, 59.8 ± 9.8 years old, 32.0% paroxysmal type). The ion currents for the PITX2+/− deficiency and each AAD (amiodarone, sotalol, dronedarone, flecainide, and propafenone) were defined based on previous publications.Results: We compared the wild-type and PITX2+/− deficiency in terms of the action potential duration (APD90), conduction velocity (CV), maximal slope of restitution (Smax), and wave-dynamic parameters, such as the dominant frequency (DF), phase singularities (PS), and AF termination rates according to the V-AADs. The PITX2+/−-deficient model exhibited a shorter APD90 (p < 0.001), a lower Smax (p < 0.001), mean DF (p = 0.012), PS number (p < 0.001), and a longer AF cycle length (AFCL, p = 0.011). Five V-AADs changed the electrophysiology in a dose-dependent manner. AAD-induced AFCL lengthening (p < 0.001) and reductions in the CV (p = 0.033), peak DF (p < 0.001), and PS number (p < 0.001) were more significant in PITX2+/−-deficient than wild-type AF. PITX2+/−-deficient AF was easier to terminate with class IC AADs than the wild-type AF (p = 0.018).Conclusions: The computational modeling-guided AAD test was feasible for evaluating the efficacy of multiple AADs in patients with AF. AF wave-dynamic and electrophysiological characteristics are different among the PITX2-deficient and the wild-type genotype models.

A pilot study of golexanolone, a new GABA-A receptor-modulating steroid antagonist, in patients with covert hepatic encephalopathy

Golexanolone is a novel small molecule GABA-A receptor-modulating steroid antagonist under development for the treatment of cognitive and vigilance disorders caused by allosteric over-activation of GABA-A receptors by neurosteroids. It restored spatial learning and motor coordination in animal models of hepatic encephalopathy (HE) and mitigated the effects of intravenous allopregnanolone in healthy adults in a dose-dependent fashion. Herein, we report data on the safety, pharmacokinetics (PK) and efficacy of golexanolone in adult patients with cirrhosis. Following single/multiple ascending dose studies, adults with Child-Pugh A/B cirrhosis and abnormal continuous reaction time (CRT) on screening were randomized to 3 weeks' dosing with golexanolone (10, 40 or 80mg BID) or placebo. CRT, psychometric hepatic encephalopathy score (PHES), animal naming test (ANT), Epworth sleepiness scale (ESS) and electroencephalogram (mean dominant frequency [MDF]; delta+theta/alpha+beta ratio [DT/AB]) were obtained at baseline, 10, and 21 days. Golexanolone exhibited satisfactory safety and PK. Baseline characteristics were similar between the 12 and 33 patients randomized to placebo or golexanolone, respectively. By prespecified analyses, golexanolone was associated with directionally favourable changes vs. placebo in ESS (p= 0.047), MDF (p= 0.142) and DT/AB (p= 0.021). All patients also showed directionally favourable changes in CRT, PHES and ANT, but with no statistical difference between golexanolone and placebo. Post hoc analyses taking into account the variability and improvement in CRT, PHES and ANT observed between screening and baseline suggested an efficacy signal by cognitive measures as well. Golexanolone was well tolerated and associated with improvement in cognitive performance. These results implicate GABA-A receptor-modulating neurosteroids in the pathogenesis of HE and support the therapeutic potential of golexanolone. Many patients with cirrhosis experience subtle but disabling cognitive problems, including sleepiness and poor attention span, that impair their ability to be gainfully employed or carry out activities of daily living. This pilot study tested the hypothesis that these problems with cognition, for which there is no approved treatment, might be improved by an experimental drug, golexanolone, designed to normalize the function of receptors which inhibit brain function. The results of this study suggest that golexanolone is well tolerated and may improve cognition, as reflected by measures of sleepiness, attention span and brain wave activity, paving the way for future larger studies of this promising experimental drug. EudraCT 2016-003651-30.

TRANSCUTANEOUS MULTICHANNEL ELECTROGASTROGRAPHY: NORMAL PARAMETERS IN A BRAZILIAN POPULATION.

Electrogastrography (EGG) is a noninvasive technique for the assessment of gastric myoelectrical activity using electrodes placed on the abdominal surface. Changes in gastric myoelectrical activity may be associated with diseases such as gastroparesis, functional dyspepsia, nausea, and recurrent vomiting. In Brazil, no studies to date have assessed gastric myoelectrical activity using multichannel EGG in healthy individuals. To establish normal values of transcutaneous multichannel EGG in healthy Brazilian individuals. This was a prospective study including 20 healthy individuals who underwent EGG. Recording was performed during two periods: a preprandial recording was performed for 30 minutes, and a postprandial recording was performed for 30 minutes after a soft-solid meal of 400 kcal (20 grams of proteins, 60 grams of carbohydrates, and 9 grams of fat). We assessed dominant frequency (DF) parameters, %DF distribution, the instability coefficient, and the power ratio (PR). A total of 20 individuals (11 women and 9 men) with a mean age of 39.5±7.4 years were included. Mean DF (95%CI) ranged from 2.4 to 3.1 cpm in the resting phase and 2.6 to 3.2 cpm in the postprandial period. The %DF in normogastria range was >70% in all healthy individuals. We identified that only one individual did not present a positive response to the test meal, and the other 19 individuals showed a PR greater than 1. The instability coefficient did not change significantly with meal intake. Multichannel EGG may be applied in future studies to evaluate gastric motility disorders in the Brazilian population.

Anterior EEG slowing in dementia with Lewy bodies: a multicenter European cohort study

Electroencephalography (EEG) slowing with prealpha dominant frequency (DF) in posterior derivations is a biomarker for dementia with Lewy bodies (DLB) diagnosis, in contrast with Alzheimer's disease (AD). However, an intrasubject re-evaluation of the original data, which contributed to the identification of EEG DLB biomarker, showed that DF was slower in anterior than posterior derivations. We suppose this anterior-posterior gradient of DF slowing could arise in DLB from a thalamocortical dysrhythmia, differently involving the anterior and posterior cortical areas, and correlating with cognitive impairment (Mini-Mental State Examination). EEG was recorded in 144 DLB, 116 AD, and 65 controls from 7 Centers of the European DLB Consortium. Spectra were divided into delta, theta, prealpha, alpha frequency bands. In DLB, mean DF was prealpha both anteriorly and posteriorly, but lower anteriorly (p < 0.001). In 14% of DLB, DF was prealpha anteriorly, whereas alpha posteriorly. In AD and controls, DF was constantly alpha. EEG slowing in DLB correlated with cognitive impairment. Thalamocortical dysrhythmia gives rise to prealpha rhythm with an anterior-posterior gradient and correlates with impaired cognition.

Light-cardiogram, a simple technique for heart rate determination in adult zebrafish, Danio rerio

Current techniques for heart rate determination in adult zebrafish require specialist expertise and are often invasive, technically challenging and not readily transferable to other laboratories for routine assessment. Here, we present a simple, noninvasive and inexpensive light-cardiogram technique to assess heart rate and frequency in adult zebrafish. Brightfield microscope paired with a high-resolution camera and ImageJ (an open source software) were employed as core recording and processing platforms respectively. The heart was visualised ventrally and located by juxtaposing an isosceles triangle between the opercula as reference to analyse pixel intensity fluctuations generated by each cardiac cycle to derive heart rate and frequency. Compared to transparent embryos, the cardiograms generated reverse light signal oscillations, with contraction and relaxation of the heart (ventricle) corresponding to reduced and increased pixel intensities respectively. The heart rates (♂ 122.58 ± 2.15 and ♀ 121.37 ± 2.63 beat/min) and mean dominant frequency (♂ 2.04 ± 0.035 and ♀ 2.05 ± 0.048 Hz) between the sexes were not significantly (P > .05) different at 28 °C. However, the FD amplitudes between males (0.26 ± 0.03) and females (0.45 ± 0.05) were significantly different (P < .05) suggesting sex specific diastolic cardiac outputs. Collectively, the technique can be used to measure heartbeats as well as readily adaptable to record relative cardiac outputs and compare differences between physiological states (e.g. sexes). Moreover, the approach could be amenable to automation and applicable to other fish species, enabling researchers the flexibility to measure these and other critical heart health endpoint with relative ease.

P: 52 Visual Analysis of the EEG Performs Better Than Standard Spectral Analysis in the Clinical Setting

BACKGROUND: The electroencephalogram (EEG) provides objective information useful for detecting and monitoring hepatic encephalopathy (HE); its acquisition does not require patient co-operation and there are no learning effects. The ISHEN guideline (Guérit et al, 2009) states that 'the EEG classification based on visual pattern recognition, although informative, does not allow reliable grading' and that 'quantitative (computer-based) analysis may improve the reliability of EEG assessment'. However, this recommendation was rated as weak and uncertain. This study aims to compare the performance of visual and spectral analysis of the EEG for the diagnosis of any degree of HE. METHODS: The study population comprised of 137 healthy controls (53% men: mean [range] age 39 [17–75] yr) and 226 patients with cirrhosis (66% men; mean age 54.8 [26–80] yr) classified, based on clinical status and PHES results, as neuropsychologically unimpaired (n = 127) or as having minimal (n = 21) or overt (n = 78) HE. A researcher with no previous experience received basic training in EEG analysis. She was asked to select 60 to 100 sec of recording, preferably from the P3-P4 montage, from the 403 anonymized patient/control EEG records and to estimate the visual wave frequency in a representative epoch, marking her selection. Spectral analysis of the EEG was undertaken on the same 60 to 100 sec of recording and the mean dominant frequency (MDF) and %theta power obtained (Jackson et al, 2016). The performances of the visual and spectral assessment of the EEG for the diagnosis of any degree of HE were compared. RESULTS: The diagnostic performance for the diagnosis of any degree of HE was comparable between the visual assessment of background activity (ROC: threshold 8.75 Hz; AUC 0.84; sensitivity 77.4%; specificity 74.5%) and the spectral %theta power (ROC: threshold 23%; AUC 0.81; sensitivity 74.8%; specificity 78.4%). However, the visually assessed background activity provided better separation of the patients in relation to their neuropsychiatric status that either of the spectral variable. Thus, significant differences were observed in the visual background activity between all patient groups and healthy controls and between patients with minimal and overt HE, whereas significant differences in spectral variables were only observed in the patients with overt HE (Figure 1). CONCLUSIONS: The ISHEN statement that 'visual assessment of the EEG, does not allow reliable grading' and that 'quantitative analysis may improve the reliability of EEG assessment is not supported by the findings in this study.

P: 53 Extent of Sarcopenia Does Not Correlate With Degree of Minimal Hepatic Encephalopathy in patients on Treatment for Hepatric Encephalopathy

BACKGROUND: Minimal hepatic encephalopathy affects over half of the patients with cirrhosis. It leads to deterioration of quality of life due to cognitive deficit. Both presence of sarcopenia and portosystemic shunts have been implicated in development of minimal hepatic encephalopathy. We retrospectively assessed the significance of sarcopenia and presence of portosystemic shunts in patients with minimal hepatic encephalopathy. METHODS: Patients with cirrhosis of liver attending the liver clinic at University of Padua underwent a detailed elective outpatient assessment for neurocognitive function. This included Psychometric Hepatic Encephalopathy Score (PHES), computer based tests, and EEG. We then selected patients who underwent a computed tomography for any reason within 3 months of the neurocognitive assessment. The degree of sarcopenia and presence of portosystemic shunts was evaluated on the scan. Presence of more than one shunt was accounted and adjusted for appropriately using a physiological approach previously described. RESULTS: A total of 120 patients had a CT scan within 3 months of the neurocognitive assessment. Of these, 100 were found to be suitable for analysis. Mean age of the patients was 59 ± 9.6 yrs and 73% were males. Median Child Pugh score was 8 (IQR 6–10) and MELD was 12 (IQR 10–18). Alcohol and viral etiologies responsible for 40% and 39% cases respectively. Based on Psychometric Hepatic Encephalopathy Score (PHES), 39% had minimal hepatic encephalopathy. Medication details were available for 87 patients, 70% of whom were on some form of treatment of hepatic encephalopathy with lactulose, antibiotics, or probiotics. The degree of cognitive dysfunction (PHES) correlated significantly with education (r = 0.33), shunt size (r = −0.45), and degree of hyperammonemia (r = −0.48), but not with sarcopenia or degree of hepatic dysfunction. Correlation between total effective shunt size and PHES was more pronounced in women (r = −0.68). Upon multivariate analysis, none of these variables predicted PHES. EEG mean dominant frequency correlated significantly with total effective shunt size (r = −0.30), ammonia (r = −0.34), and Child-Pugh score (r = −0.38). None of the parameters significantly correlated with critical flicker frequency. There was no difference in the degree of sarcopenia among patients with and without MHE or history of overt HE. Moreover, degree of sarcopenia did not correlate with PHES, critical flicker frequency, ammonia level, or Child-Pugh score. Effective size of portosystemic shunt was higher in patients with MHE. CONCLUSIONS: Among patients with cirrhosis on anti-encephalopathy treatment, presence of sarcopenia does not correlate with neurocognitive parameters. Presence of large portosystemic shunts correlated with neurocognitive impairment.

A new species of Amazophrynella (Anura: Bufonidae) with two distinct advertisement calls.

Here we describe a new species of the toad genus Amazophrynella (Bufonidae) from the south margin of the Amazon River in Santarém, state of Pará, Brazilian Amazonia. The new species can be diagnosed by (1) medium body size for the genus: adult females 19.5-20.4 mm SVL, adult males 13.0-14.5 mm SVL; (2) snout acuminate in lateral view; (3) Finger I larger and robust; (4) Finger I nearly equal in size than Finger II; (5) palmar tubercle rounded, covering ¼ of hand; (6) pigmented callus in Finger I in males; in life: (7) brown stain on throat and chest; (8) black dots on venter. Males emit two distinct advertisement calls: the call type 1 consists of a relatively long note (mean 0.248 s) with a mean dominant frequency of 3526 Hz. The call type 2 is arranged in bouts of 6 to 22 notes with mean dominant frequency of 3450 Hz and much shorter note durations (mean 0.034 s). In this study we also redescribe the advertisement call of A. minuta, which also emits a second call type.

A new species of Leptobrachella (Anura: Megophryidae) from southern Guangxi, China.

This study describes a new member of the genus Leptobrachella, Leptobrachella shangsiensis sp. nov., based on morphological, acoustic and molecular analyses from southern Guangxi, China. L. shangsiensis sp. nov. differs from its congeners by a combination of the following characters: (1) SVL 24.9-29.4 mm in 11 males and 30.8-35.9 mm in 5 females, (2) black supratympanic fold with dark reddish rim, (3) ventrolateral glands distinct, forming a broken line, (4) ventral surface yellowish creamy-white with marble texture, (5) iris copper in the upper and silver in the lower fifth and (6) toe webbing basal and narrow lateral fringes. The male advertisement call of L. shangsiensis sp. nov. consists of one note per call, lacking an introductory note, with a mean dominant frequency of 5.5-6.5 kHz at the ambient temperature of 21.5ºC. Uncorrected sequence divergences between L. shangsiensis sp. nov. and all homologous DNA sequences available for the 16S rRNA gene were found to be > 5.9%. L. shangsiensis sp. nov. occurs in an evergreen forest in Shiwandashan National Nature Reserve located at an elevation of 450-550 m.

Evaluation of gastric motility through surface electrogastrography in critically ill septic patients. Comparison of metoclopramide and domperidone effects: A pilot randomized clinical trial

Introduction and aimsCritically ill patients present with a broad spectrum of gastrointestinal motility disorders that affect the digestive tract. Our aim was to compare the effect of two prokinetic drugs on gastric electrical rhythm in critically ill septic patients, measured through surface electrogastrography (EGG). Material and methodsA prospective triple-blinded randomized study was conducted on 36 patients admitted to the intensive care unit (ICU) with the diagnosis of septic shock. They were randomized to receive metoclopramide or domperidone. We assessed dominant frequency (DF), percentage distribution over time, and dominant power (DP), which represents the strength of contraction, before and after administration of the study drugs. ResultsReliable electrogastrograms were achieved in all patients. In relation to the distribution of DF over time, 64% of patients had dysrhythmia, the mean baseline DF was 2.9 cpm, and the mean DP was 56.5μv After drug administration, 58% of the patients had dysrhythmia, the mean DF increased to 5.7 cpm (P<.05), and the DP did not change (57.4μv2). There were no significant differences between drugs. In the metoclopramide group, the baseline DF was 2.1 cpm and the baseline DP was 26.1μv2. The post-drug values increased to 5.4 cpm and 34.1μv2, respectively. In the domperidone group, the baseline DF was 3.7 cpm and the baseline DP was 86.9μv2. After drug administration, the DF increased to 6.1 cpm and the DP decreased to 83.5μv2. ConclusionsBoth metoclopramide and domperidone similarly increased the DF of gastric pacemaker activity and improved gastric motility by restoring a normogastric pattern. Gastric dysmotility is frequent in septic patients.

A quantitative EEG and MRI analysis of intermittent temporal slowing in the elderly

ObjectiveWhereas the correlation between diffuse slowing of EEG activity and neurodegenerative diseases such as Alzheimer’s disease is well established, intermittent slowing over the temporal regions, which is a frequent finding in the elderly, does not have a specific clinical correlate. In this study, we compared quantitative EEG parameters between patients with temporal slowing with no signs of neurological disease and controls to evaluate cortical function in the temporal lobes and other cerebral regions. We also compared the width of the temporal lobes on magnetic resonance imaging (MRI). MethodsMean dominant frequency and relative power in delta, theta, alpha, and beta frequency bands were examined in 20 patients older than 60 years with intermittent temporal slowing and 20 age-matched controls without significant lesions on MRI or medical conditions known to affect the EEG. Furthermore, the correlation between the frequency of temporal slowing and the mean dominant frequency and the width of the medial temporal lobes on MRI were examined. ResultsMean dominant frequency and the relative power in the beta frequency band was lower in patients with temporal slowing than in controls in all of the cortical regions examined. No significant correlation was found between the frequency of slowing and the mean dominant frequency. There was no significant difference in the width of the medial temporal lobes. ConclusionsIntermittent temporal slowing was correlated with diffusely reduced mean dominant frequency and a shift in relative power to lower frequency bands. SignificanceThe results suggest that subclinical diffuse cerebral pathology may be present in subjects with intermittent temporal slowing, but prospective studies including tests of cognitive function, cerebral perfusion, metabolic status, and advanced neuroimaging should be conducted.