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New insights on the cardiac safety factor: Unraveling the relationship between conduction velocity and robustness of propagation.

ABSTRACT: Cardiac conduction disturbances are linked with arrhythmia development. The concept of safety factor (SF) has been derived to describe the robustness of conduction, but the usefulness of this metric has been constrained by several limitations. For example, due to the difficulty of measuring the necessary input variables, SF calculations have only been applied to synthetic data. Moreover, quantitative validation of SF is lacking; specifically, the practical meaning of particular SF values is unclear, aside from the fact that propagation failure (i.e., conduction block) is characterized by SF?

SUBMITTER: Boyle PM

PROVIDER: S-EPMC6474757 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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New insights on the cardiac safety factor: Unraveling the relationship between conduction velocity and robustness of propagation.

Boyle Patrick M PM Franceschi William H WH Constantin Marion M Hawks Claudia C Desplantez Thomas T Trayanova Natalia A NA Vigmond Edward J EJ

Journal of molecular and cellular cardiology 20190122

Cardiac conduction disturbances are linked with arrhythmia development. The concept of safety factor (SF) has been derived to describe the robustness of conduction, but the usefulness of this metric has been constrained by several limitations. For example, due to the difficulty of measuring the necessary input variables, SF calculations have only been applied to synthetic data. Moreover, quantitative validation of SF is lacking; specifically, the practical meaning of particular SF values is uncl ...[more]

PMID: 30677394

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Orientation of conduction velocity vectors on cardiac mapping surfaces.

Project description:AimsElectroanatomical maps using automated conduction velocity (CV) algorithms are now being calculated using two-dimensional (2D) mapping tools. We studied the accuracy of mapping surface 2D CV, compared to the three-dimensional (3D) vectors, and the influence of mapping resolution in non-scarred animal and human heart models.Methods and resultsTwo models were used: a healthy porcine Langendorff model with transmural needle electrodes and a computer stimulation model of the ventricles built from an MRI-segmented, excised human heart. Local activation times (LATs) within the 3D volume of the mesh were used to calculate true 3D CVs (direction and velocity) for different pixel resolutions ranging between 500 μm and 4 mm (3D CVs). CV was also calculated for endocardial surface-only LATs (2D CV). In the experimental model, surface (2D) CV was faster on the epicardium (0.509 m/s) compared to the endocardium (0.262 m/s). In stimulation models, 2D CV significantly exceeded 3D CVs across all mapping resolutions and increased as resolution decreased. Three-dimensional and 2D left ventricle CV at 500 μm resolution increased from 429.2 ± 189.3 to 527.7 ± 253.8 mm/s (P < 0.01), respectively, with modest correlation (R = 0.64). Decreasing the resolution to 4 mm significantly increased 2D CV and weakened the correlation (R = 0.46). The majority of CV vectors were not parallel (<30°) to the mapping surface providing a potential mechanistic explanation for erroneous LAT-based CV over-estimation.ConclusionVentricular CV is overestimated when using 2D LAT-based CV calculation of the mapping surface and significantly compounded by mapping resolution. Three-dimensional electric field-based approaches are needed in mapping true CV on mapping surfaces.

| S-EPMC10062359 | biostudies-literature

Microenvironmental Modulation of Calcium Wave Propagation Velocity in Engineered Cardiac Tissues.

Project description:IntroductionIn the myocardium, rapid propagation of action potentials and subsequent calcium waves is critical for synchronizing the contraction of cardiac myocytes and maximizing cardiac output. In many pathological settings, diverse remodeling of the tissue microenvironment is correlated with arrhythmias and decreased cardiac output, but the precise impact of tissue remodeling on propagation is not completely understood. Our objective was to delineate how multiple features within the cardiac tissue microenvironment modulate propagation velocity.MethodsTo recapitulate diverse myocardial tissue microenvironments, we engineered substrates with tunable elasticity, patterning, composition, and topography using two formulations of polydimethylsiloxane (PDMS) micropatterned with fibronectin and gelatin hydrogels with flat or micromolded features. We cultured neonatal rat ventricular myocytes on these substrates and quantified cell density, tissue alignment, and cell shape. We used a fluorescent calcium indicator, high-speed microscopy, and newly-developed analysis software to record and quantify calcium wave propagation velocity (CPV).ResultsFor all substrates, tissue alignment and cell aspect ratio were higher in aligned compared to isotropic tissues. Isotropic CPV and longitudinal CPV were similar across conditions, but transverse CPV was lower on micromolded gelatin hydrogels compared to micropatterned soft and stiff PDMS. In aligned tissues, the anisotropy ratio of CPV (longitudinal CPV/transverse CPV) was lower on micropatterned soft PDMS compared to micropatterned stiff PDMS and micromolded gelatin hydrogels.ConclusionPropagation velocity in engineered cardiac tissues is sensitive to features in the tissue microenvironment, such as alignment, matrix elasticity, and matrix topography, which may underlie arrhythmias in conditions with pathological tissue remodeling.

| S-EPMC6816715 | biostudies-literature

The conduction velocity-potassium relationship in the heart is modulated by sodium and calcium.

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Fibroblast growth factor homologous factor 13 regulates Na+ channels and conduction velocity in murine hearts.

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Estimation and Validation of Cardiac Conduction Velocity and Wavefront Reconstruction Using Epicardial and Volumetric Data.

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Alternans resonance and propagation block during supernormal conduction in cardiac tissue with decreased [K(+)](o).

Project description:Cardiac restitution is an important factor in arrhythmogenesis. Steep positive action potential duration and conduction velocity (CV) restitution slopes promote alternans and reentrant arrhythmias. We examined the consequences of supernormal conduction (characterized by a negative CV restitution slope) on patterns of conduction and alternans in strands of Luo-Rudy model cells and in cultured cardiac cell strands. Interbeat intervals (IBIs) were analyzed as a function of distance during S1S2 protocols and during pacing at alternating cycle lengths. Supernormal conduction was induced by decreasing [K(+)](o). In control [K(+)](o) simulations, S1S2 intervals converged toward basic cycle length with a length constant determined by both CV and the CV restitution slope. During alternant pacing, the amplitude of IBI alternans converged with a shorter length constant, determined also by the action potential duration restitution slope. In contrast, during supernormal conduction, S1S2 intervals and the amplitude of alternans diverged. This amplification (resonance) led to phase-locked or more complex alternans patterns, and then to distal conduction block. The convergence/divergence of IBIs was verified in the cultured strands, in which naturally occurring tissue heterogeneities resulted in prominent discontinuities of the spatial IBI profiles. We conclude that supernormal conduction potentiates alternans and spatial analysis of IBIs represents a powerful method to locate tissue heterogeneities.

| S-EPMC2849079 | biostudies-literature

Techniques for automated local activation time annotation and conduction velocity estimation in cardiac mapping.

Project description:Measurements of cardiac conduction velocity provide valuable functional and structural insight into the initiation and perpetuation of cardiac arrhythmias, in both a clinical and laboratory context. The interpretation of activation wavefronts and their propagation can identify mechanistic properties of a broad range of electrophysiological pathologies. However, the sparsity, distribution and uncertainty of recorded data make accurate conduction velocity calculation difficult. A wide range of mathematical approaches have been proposed for addressing this challenge, often targeted towards specific data modalities, species or recording environments. Many of these algorithms require identification of activation times from electrogram recordings which themselves may have complex morphology or low signal-to-noise ratio. This paper surveys algorithms designed for identifying local activation times and computing conduction direction and speed. Their suitability for use in different recording contexts and applications is assessed.

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Evaluation for neurotoxicity of oxaliplatin using Nerve Conduction Velocity

Project description:Interventions: 1.Nerve Conduction Velocity 2.tuning fork Primary outcome(s): 1. Collation between NCV and oxaliplatin induced neurotoxicity 2. Collation between tuning fork and oxaliplatin induced neurotoxicity 3. Analyze the mechanism of oxaliplatin induced neurotoxicity Study Design: Single arm Non-randomized

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Identification of local atrial conduction heterogeneities using high-density conduction velocity estimation.

Project description:AimsAccurate determination of intra-atrial conduction velocity (CV) is essential to identify arrhythmogenic areas. The most optimal, commonly used, estimation methodology to measure conduction heterogeneity, including finite differences (FiD), polynomial surface fitting (PSF), and a novel technique using discrete velocity vectors (DVV), has not been determined. We aim (i) to identify the most suitable methodology to unravel local areas of conduction heterogeneities using high-density CV estimation techniques, (ii) to quantify intra-atrial differences in CV, and (iii) to localize areas of CV slowing associated with paroxysmal atrial fibrillation (PAF).Methods and resultsIntra-operative epicardial mapping (>5000 sites, interelectrode distances 2 mm) of the right and left atrium and Bachmann's bundle (BB) was performed during sinus rhythm (SR) in 412 patients with or without PAF. The median atrial CV estimated using the DVV, PSF, and FiD techniques was 90.0 (62.4-116.8), 92.0 (70.6-123.2), and 89.4 (62.5-126.5) cm/s, respectively. The largest difference in CV estimates was found between PSF and DVV which was caused by smaller CV magnitudes detected only by the DVV technique. Using DVV, a lower CV at BB was found in PAF patients compared with those without atrial fibrillation (AF) [79.1 (72.2-91.2) vs. 88.3 (79.3-97.2) cm/s; P < 0.001].ConclusionsAreas of local conduction heterogeneities were most accurately identified using the DVV technique, whereas PSF and FiD techniques smoothen wavefront propagation thereby masking local areas of conduction slowing. Comparing patients with and without AF, slower wavefront propagation during SR was found at BB in PAF patients, indicating structural remodelling.

| S-EPMC8576284 | biostudies-literature

Structural remodeling and conduction velocity dynamics in the human left atrium: Relationship with reentrant mechanisms sustaining atrial fibrillation.

Project description:BackgroundRate-dependent conduction velocity (CV) slowing is associated with atrial fibrillation (AF) initiation and reentrant mechanisms.ObjectiveThe purpose of this study was to assess the relationship between bipolar voltage, CV dynamics, and AF drivers.MethodsPatients undergoing catheter ablation for persistent AF (<24 months) were enrolled. Unipolar electrograms were recorded with a 64-pole basket catheter during atrial pacing at 4 pacing intervals (PIs) during sinus rhythm. CVs were measured between pole pairs along the wavefront path and correlated with underlying bipolar voltage. CV dynamics within low-voltage zones (LVZs <0.5 mV) were compared to those of non-LVZs (≥0.5 mV) and were correlated to driver sites mapped using CARTOFINDER (Biosense Webster).ResultsEighteen patients were included (age 62 ± 10 years). Mean CV at 600 ms was 1.59 ± 0.13 m/s in non-LVZs vs 0.98 ± 0.23 m/s in LVZs (P <.001). CV decreased incrementally over all 4 PIs in LVZs, whereas in non-LVZs a substantial decrease in CV was only seen between PIs 300-250 ms (0.59 ± 0.09 m/s; P <.001). Rate-dependent CV slowing sites measurements, defined as exhibiting CV reduction ≥20% more than the mean CV reduction seen between PIs 600-250 ms for that voltage zone, were predominantly in LVZs (0.2-0.5 mV; 75.6% ± 15.5%; P <.001). Confirmed rotational drivers were mapped to these sites in 94.1% of cases (sensitivity 94.1%, 95% CI 71.3%-99.9%; specificity 77.9%, 95% CI 74.9%-80.7%).ConclusionCV dynamics are determined largely by the extent of remodeling. Rate-dependent CV slowing sites are predominantly confined to LVZs (0.2-0.5 mV), and the resultant CV heterogeneity may promote driver formation in AF.

| S-EPMC6317307 | biostudies-literature

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