Exploring Refractoriness as an Adjunctive Electrical Biomarker for Staging of Atrial Fibrillation

Patients diagnosed with the same subtype of atrial fibrillation according to our current classification system may differ in symptom severity, severity of the arrhythmogenic substrate, and response to antiarrhythmic therapy. Hence, there is a need for an electrical biomarker as an indicator of the arrhythmogenic substrate underlying atrial fibrillation enabling patient-tailored therapy. The aim of this review is to investigate whether atrial refractoriness, a well-known electrophysiological parameter that is affected by electrical remodeling, can be used as an electrical biomarker of the arrhythmogenic substrate underlying atrial fibrillation. We discuss methodologies of atrial effective refractory period assessment, identify which changes in refractoriness-related parameters reflect different degrees of electrical remodeling, and explore whether these parameters can be used to predict clinical outcomes

Does conduction heterogeneity determine the supervulnerable period after atrial fibrillation?

Atrial fibrillation (AF) resumes within 90 s in 27% of patients after sinus rhythm (SR) restoration. The aim of this study is to compare conduction heterogeneity during the supervulnerable period immediately after electrical cardioversion (ECV) with long-term SR in patients with AF. Epicardial mapping of both atria was performed during SR and premature atrial extrasystoles in patients in the ECV (N = 17, age: 73 ± 7 years) and control group (N = 17, age: 71 ± 6 years). Inter-electrode conduction times were used to identify areas of conduction delay (CD) (conduction times 7-11 ms) and conduction block (CB) (conduction times ≥ 12 ms). For all atrial regions, prevalences and length of longest CB and continuous CDCB lines, magnitude of conduction disorders, conduction velocity, biatrial activation time, and voltages did not differ between the ECV and control group during both SR and premature atrial extrasystoles (p ≥ 0.05). Hence, our data suggest that there may be no difference in biatrial conduction characteristics between the supervulnerable period after ECV and long-term SR in AF patients. The supervulnerable period after AF termination is not determined by conduction heterogeneity during SR and PACs. It is unknown to what extent intra-atrial conduction is impaired during the supervulnerable period immediately after ECV and whether different right and left atrial regions are equally affected. This high-resolution epicardial mapping study (upper left panel) of both atria shows that during SR the prevalences and length of longest CB and cCDCB lines (upper middle panel), magnitude of conduction disorders, CV and TAT (lower left panel), and voltages did not differ between the ECV and control group. Likewise, these parameters were comparable during PACs between the ECV and control group (lower left panel). †Non-normally distributed. cm/s = centimeters per second; mm = millimeter; ms = millisecond; AF = atrial fibrillation; AT = activation time; BB = Bachmann's bundle; cCDCB = continuous lines of conduction delay and block; CB = conduction block; CD = conduction delay; CT = conduction time; CV = conduction velocity; ECV = electrical cardioversion; LA = left atrium; LAT = local activation times; PAC = premature atrial complexes; PVA = pulmonary vein area; RA = right atrium; SR = sinus rhythm; TAT = total activation time.</p

Biomechanics of cells and tissues: What can we learn when we combine mechanical stimuli with microscopy?

Understanding the mechanical properties of biological tissues can shed light on how those tissues work and why, at times, they lose their functionality. Furthermore, a full characterization of a tissue’s viscoelastic behavior may provide relevant hints for tissue reparation and tissue engineering. To measure these properties in in-vitro or ex-vivo experiments, researchers often make use of indentation instruments, which looks at how a material deforms under the effect of a calibrated mechanical load. In the first part of my talk, I will show how this technique can be used to determine the mechanical properties of brain slices, and I will comment on which kind of information those measurements can provide. I will show, for instance, that different regions of the brain have remarkably different viscoelastic properties, which seem to be correlated with the cell density measured, in a parallel experiment, via fluorescent microscopy. As this example highlights, indentation measurements alone are often not sufficient to understand why certain tissues have certain mechanical properties. Under a (not transparent) surface, biological materials are often inhomogeneous and anisotropic. Because the indentation stress propagates several microns deep into the sample, without a proper imaging tool coupled to the indentation instrument, it is impossible to extract useful information on the mechanics of the material the sample is made of. As a point in case, I will show our latest measurements of the mechanical properties of chick embryos, where, combining indentation with optical coherence tomography (OCT), we could precisely map the stiffness of the spine from head to tail – a measurement that may provide interesting cues in the analysis of somites formation and growth. I will also show how the combination of indentation and OCT might find its way in scar and burn classification, introducing a new instrument for skin characterization that our group has just recently completed. Finally, I will show some preliminary results on the use of multiphoton imaging for tissue mechanics characterization. In this last part of the talk, I will show that it is indeed possible to look at the displacement and deformation of cells in a thin slice of tissue while the tissue is compressed by a calibrated mechanical stroke. This approach may pave the way for a much more thorough analysis of the origin of certain mechanical properties of tissues, where the contribution of the individual cells to the viscoelastic features of the materials can be finally disentangle from that of the extracellular matrix. This project was supported by LASERLABEUROPE under the EC’s Seventh Framework Program (Grant agreement No. 284464), by the European Union’s Seventh Framework Programme (FP/20072013)/ERC grant agreement no. 615170, by the Dutch Technology Foundation (STW) under the OMNE program (13183 and under the iMIT program (P11–13). Declaration of interest: Davide Iannuzzi is founder, shareholder, and advisor of Optics11

Conduction Heterogeneity: Impact of Underlying Heart Disease and Atrial Fibrillation

Objectives: The goal of this study is to investigate the impact of various underlying heart diseases (UHDs) and prior atrial fibrillation (AF) episodes on conduction heterogeneity. Background: It is unknown whether intra-atrial conduction during sinus rhythm differs between various UHD or is influenced by AF episodes. Methods: Epicardial sinus rhythm mapping of the right atrium, Bachmann's bundle (BB), left atrium and pulmonary vein area was performed in 447 participants (median age: 67 [interquartile range (IQR): 59 to 73] years) with or without AF undergoing cardiac surgery for ischemic heart disease, (ischemic and) valvular heart disease, or congenital heart disease. Conduction times (CTs) were defined as Δ local activation time between 2 adjacent electrodes and used to assess frequency (CTs ≥ 4 ms) and magnitude of conduction disorders (in increments of 10 ms). Results: When comparing the 3 types of UHD, there were no differences in frequencies and magnitude of CTs at all locations (p ≥ 0.017 and p ≥ 0.005, respectively). Prior AF episodes were associated with conduction slowing throughout both atria (14.9% [IQR: 11.8 to 17.0] vs. 12.8% [IQR: 10.9 to 14.6]; p < 0.001). At BB, CTs with magnitudes ≥30 ms were more common in patients with AF (n = 56.2% vs. n = 36.0%; p < 0.004). Conclusions: UHD has no impact on the frequency and severity of conduction disorders. AF episodes are associated with more conduction disorders throughout both atria and with more severe conduction disorders at BB. The next step will be to determine the relevance of these conduction disorders for AF development and maintenance

Outcome measures for children with mitochondrial disease: consensus recommendations for future studies from a Delphi-based international workshop

Although there are no effective disease-modifying therapies for mitochondrial diseases, an increasing number of trials are being conducted in this rare disease group. The use of sensitive and valid endpoints is essential to test the effectiveness of potential treatments. There is no consensus on which outcome measures to use in children with mitochondrial disease. The aims of this two-day Delphi-based workshop were to (i) define the protocol for an international, multi-centre natural history study in children with mitochondrial myopathy and (ii) to select appropriate outcome measures for a validation study in children with mitochondrial encephalopathy. We suggest two sets of outcome measures for a natural history study in children with mitochondrial myopathy and for a proposed validation study in children with mitochondrial encephalopathy

Sex differences in the adult human brain:Evidence from 5216 UK Biobank participants

Sex differences in the human brain are of interest for many reasons: for example, there are sex differences in the observed prevalence of psychiatric disorders and in some psychological traits that brain differences might help to explain. We report the largest single-sample study of structural and functional sex differences in the human brain (2750 female, 2466 male participants; mean age 61.7 years, range 44–77 years). Males had higher raw volumes, raw surface areas, and white matter fractional anisotropy; females had higher raw cortical thickness and higher white matter tract complexity. There was considerable distributional overlap between the sexes. Subregional differences were not fully attributable to differences in total volume, total surface area, mean cortical thickness, or height. There was generally greater male variance across the raw structural measures. Functional connectome organization showed stronger connectivity for males in unimodal sensorimotor cortices, and stronger connectivity for females in the default mode network. This large-scale study provides a foundation for attempts to understand the causes and consequences of sex differences in adult brain structure and function