Search arXivSearch

arXiv · 2310.11223

Model-based Estimation of AV-nodal Refractory Period and Conduction Delay Trends from ECG

Abstract

Atrial fibrillation (AF) is the most common arrhythmia, associated with significant burdens to patients and the healthcare system. The atrioventricular (AV) node plays a vital role in regulating heart rate during AF, but is often insufficient in regards to maintaining a healthy heart rate. Thus, the AV node properties are modified using rate-control drugs. Hence, quantifying individual differences in diurnal and short-term variability of AV-nodal function could aid in personalized treatment selection. This study presents a novel methodology for estimating the refractory period (RP) and conduction delay (CD) trends and their uncertainty in the two pathways of the AV node during 24 hours using non-invasive data. This was achieved using a network model together with a problem-specific genetic algorithm and an approximate Bayesian computation algorithm. Diurnal and short-term variability in the estimated RP and CD was quantified by the difference between the daytime and nighttime estimates and by the Kolmogorov-Smirnov distance between adjacent 10-minute segments in the 24-hour trends. Holter ECGs from 51 patients with permanent AF during baseline were analyzed, and the predictive power of variations in RP and CD on the resulting heart rate reduction after treatment with four rate control drugs was investigated. Diurnal variability yielded no correlation to treatment outcome, and no prediction of drug outcome was possible using the machine learning tools. However, a correlation between the short-term variability for the RP and CD in the fast pathway and resulting heart rate reduction during treatment with metoprolol ($ρ=0.48, p<0.005$ in RP, $ρ=0.35, p<0.05$ in CD) were found. The proposed methodology enables non-invasive estimation of the AV node properties during 24 hours, which may have the potential to assist in treatment selection.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Mattias Karlsson, Pyotr G Platonov, Sara R. Ulimoen, Frida Sandberg, Mikael Wallman. 2023-10-17. Model-based Estimation of AV-nodal Refractory Period and Conduction Delay Trends from ECG. https://arxiv.org/abs/2310.11223

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related papers

Online activity prediction via generalized Indian buffet process models

Online A/B tests are the standard tool for data-driven decision-making at scale. Among the design choices with the largest impact on statistical power is the triggering mechanism: how many users to expose and for how long. This often requires forecasting user engagement, i.e., whether enough users will trigger, and when a target participation level will be reached, from limited pilot data. We introduce a Bayesian nonparametric model for predicting both new-user counts and total triggers, accommodating the heavy-tailed engagement patterns typical of web experiments. All predictive quantities can be computed without intensive numerical procedures such as Markov chain Monte Carlo (MCMC) or variational inference. We evaluate on three public datasets (over 450 public benchmark evaluations) and a proprietary benchmark drawn from 759 production A/B tests comprising 1,774 arms. Across the benchmark analyses, our models are competitive and frequently improve accuracy in forecasting new users, total triggers, and time to reach a target sample size compared with state-of-the-art competitors, especially when only a few pilot days are observed.

stat.AP

Spending Scarce Confirmatory PET Measurements: Target-Aligned Validation in A4/LEARN

Anti-amyloid therapies and blood-based biomarkers are changing Alzheimer disease workups into a two-stage measurement workflow: screen broadly with cheaper information, then spend scarce confirmatory amyloid measurements where they support the decision that will be reported. Amyloid positron-emission tomography (PET) remains one such protocol measurement for amyloid burden, but PET slots, trial budgets, and payer-facing evidence packages are finite. This paper asks a deliberately operational question: when is simple transparent PET validation enough, and when is a fitted residual-uncertainty score worth the added complexity? For a weighted protocol target, the first-order value of validating subject i is the product of target influence and residual protocol uncertainty. Generic uncertainty sampling uses only the second factor and can spend PET measurements on subjects that are hard to predict but weak for the scientific, clinical, or commercial claim. We apply this rule to the A4/LEARN PET archive, treating observed PET as a design laboratory for scarce-confirmation studies. For the primary APOE4 carrier versus non-carrier contrast in Centiloid 24-or-higher PET positivity, simple APOE4-balanced validation recovers nearly all of the target-specific gain: at PET budget 200, the confidence-interval width ratio relative to random validation is 0.923 for APOE4 balancing and 0.914 for target-specific scoring, while generic uncertainty sampling is 0.980. Other targets behave differently: target-specific scoring gives larger gains for an age-slope analysis and for cutoff-indexed PET positivity. The practical message is simple: spend scarce protocol measurements according to the claim being validated, not only according to prediction uncertainty.

stat.AP

Identifying Damage Pathways Linking Sequence Composition to Storage Failure in DNA Data Storage via High-Dimensional Mediation Analysis

DNA data storage offers extraordinary information density and long-term durability, but its reliability is limited by sequence-dependent errors introduced during synthesis and accumulated during storage. It remains unclear how sequence composition is associated with storage failure through specific molecular damage components. We develop a high-dimensional semiparametric mediation framework for survival outcomes. GC content is treated as the exposure, a high-dimensional baseline damage spectrum (a vector of per-read damage counts stratified by trinucleotide context and error type) as the mediator, and storage-quality failure as the outcome. Nonlinear covariate effects in both the mediator and survival models are approximated using deep neural networks. A three-step procedure combining product-of-coefficients screening, Smoothly Clipped Absolute Deviation (SCAD) penalized estimation, and joint significance testing is developed for mediator selection and inference. Applied to an aging experiment on electrochemically synthesized DNA, the method identifies 14 significant mediators, all corresponding to single-base deletions, with estimated mediated effects concentrated in trinucleotide contexts ending in C. These results reveal deletion-type damage as a major pathway linking sequence composition to reduced archival reliability and suggest candidate sequence features for future optimization and error-control strategies. The proposed framework thus offers a mechanism-oriented statistical approach for understanding and improving the reliability of DNA data storage.

stat.AP