A Mechanistically Guided Approach to Treatment of Multi-Wavelet Reentry: Experiments in a Computational Model of Cardiac Propagation

Atrial fibrillation (AF) is the most common cardiac arrhythmia in the United States today. However, treatment options remain limited despite the enormous magnitude of both AF prevalence and the associated economic cost. Of those treatment options that are available, ablation-based interventional methods have demonstrated the highest rates of long-term cure. Unfortunately, these methods have substantially lower efficacy in patients with heavier burdens of disease, thus leaving the most affected individuals with the least hope for successful treatment. The focus of this research is to develop a mechanistically guided approach towards the treatment of multi-wavelet reentry (MWR), one of the primary drivers of AF. For this purpose, we use a computational model of electrical propagation in cardiac tissue to simulate both episodes of fibrillatory activity and the ablative treatment thereof. We demonstrate that the probability of forming the reentrant circuits necessary for continuous electrical activity is a function of the shape and size of a tissue as well as its underlying cellular properties. Ablation at tissue sites with high probability of circuit formation more efficiently reduces the overall duration of fibrillatory episodes than ablation at sites with low probability. We then propose and validate in silico a parameter-based metric for predicting the propensity of an individual tissue to support fibrillation, which we term the fibrillogenicity index. Using this metric, we develop an algorithm for prospectively determining optimized, tissue-specific ablation patterns. Finally, we examine the relationship between multi-wavelet reentry and focal drivers, and demonstrate that MWR and fibrillatory conduction exist along a continuum. We examine the complex interplay between functional and structural substrates within fibrillating tissue and define the mechanisms by which they promote the perpetuation of AF. These findings present a novel theoretical framework for understanding treatment of multi-wavelet reentry driven AF and provide a set of testable predictions that can serve to guide the design of future experimental studies aimed at advancing the rational design of patient-specific ablation sets for treating AF

Introducing Opiate Addicts to the Hub and Spoke Treatment System in Vermont

Opiate abuse and addiction is an epidemic in the state of Vermont. Brandon Medical Center has recently become involved in Vermont\u27s Hub and Spoke system of medically assisted opiate addiction treatment. This project involved the development of a pamphlet for safe, low-threshold transmission of information regarding opiate addiction and entrance into this system for patient\u27s who may be suffering from this disease.https://scholarworks.uvm.edu/fmclerk/1187/thumbnail.jp

Arrhythmic Risk Stratification in Arrhythmogenic Right Ventricular Cardiomyopathy

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an heritable cardiomyopathy characterized by a predominantly arrhythmic presentation. It represents the leading cause of sudden cardiac death (SCD) among athletes and poses a significant morbidity treat in the general population. As a causative treatment for ARVC is still not available, the placement of an implantable cardioverter defibrillator (ICD) represent the current cornerstone for SCD prevention in this setting. Thanks to international ARVC-dedicated efforts, significant steps have been achieved in recent years towards an individualized, patient-centered risk stratification approach. A novel risk calculator algorithm estimating the 5 year risk of arrhythmias of patients with ARVC have been introduced in clinical practice and subsequently validated. The purpose of this article is to summarize the body of evidence that has allowed the development of this tool and to discuss the best way to implement its use in the care of an individual patient

4MOST: Project overview and information for the First Call for Proposals

We introduce the 4-metre Multi-Object Spectroscopic Telescope (4MOST), a new high-multiplex, wide-field spectroscopic survey facility under development for the four-metre-class Visible and Infrared Survey Telescope for Astronomy (VISTA) at Paranal. Its key specifications are: a large field of view (FoV) of 4.2 square degrees and a high multiplex capability, with 1624 fibres feeding two low-resolution spectrographs ($R = \lambda/\Delta\lambda \sim 6500$), and 812 fibres transferring light to the high-resolution spectrograph ($R \sim 20\,000$). After a description of the instrument and its expected performance, a short overview is given of its operational scheme and planned 4MOST Consortium science; these aspects are covered in more detail in other articles in this edition of The Messenger. Finally, the processes, schedules, and policies concerning the selection of ESO Community Surveys are presented, commencing with a singular opportunity to submit Letters of Intent for Public Surveys during the first five years of 4MOST operations

Correction to: Clinical recommendations for cardiovascular magnetic resonance mapping of T1, T2, T2* and extracellular volume: A consensus statement by the Society for Cardiovascular Magnetic Resonance (SCMR) endorsed by the European Association for Cardiovascular Imaging (EACVI).

CORRECTION TO: J CARDIOVASC MAGN RESON (2017) 19: 75. DOI: 10.1186/S12968-017-0389-8: In the original publication of this article [1] the "Competing interests" section was incorrect. The original publication stated the following competing interests

Programmed Ventricular Stimulation as an Additional Primary Prevention Risk Stratification Tool in Arrhythmogenic Right Ventricular Cardiomyopathy: A Multinational Study

BACKGROUND A novel risk calculator based on clinical characteristics and noninvasive tests that predicts the onset of clinical sustained ventricular arrhythmias (VA) in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) has been proposed and validated by recent studies. It remains unknown whether programmed ventricular stimulation (PVS) provides additional prognostic value. METHODS All patients with a definite ARVC diagnosis, no history of sustained VAs at diagnosis, and PVS performed at baseline were extracted from 6 international ARVC registries. The calculator-predicted risk for sustained VA (sustained or implantable cardioverter defibrillator treated ventricular tachycardia [VT] or fibrillation, [aborted] sudden cardiac arrest) was assessed in all patients. Independent and combined performance of the risk calculator and PVS on sustained VA were assessed during a 5-year follow-up period. RESULTS Two hundred eighty-eight patients (41.0±14.5 years, 55.9% male, right ventricular ejection fraction 42.5±11.1%) were enrolled. At PVS, 137 (47.6%) patients had inducible ventricular tachycardia. During a median of 5.31 [2.89-10.17] years of follow-up, 83 (60.6%) patients with a positive PVS and 37 (24.5%) with a negative PVS experienced sustained VA (P<0.001). Inducible ventricular tachycardia predicted clinical sustained VA during the 5-year follow-up and remained an independent predictor after accounting for the calculator-predicted risk (HR, 2.52 [1.58-4.02]; P<0.001). Compared with ARVC risk calculator predictions in isolation (C-statistic 0.72), addition of PVS inducibility showed improved prediction of VA events (C-statistic 0.75; log-likelihood ratio for nested models, P<0.001). PVS inducibility had a 76% [67-84] sensitivity and 68% [61-74] specificity, corresponding to log-likelihood ratios of 2.3 and 0.36 for inducible (likelihood ratio+) and noninducible (likelihood ratio-) patients, respectively. In patients with a ARVC risk calculator-predicted risk of clinical VA events <25% during 5 years (ie, low/intermediate subgroup), PVS had a 92.6% negative predictive value. CONCLUSIONS PVS significantly improved risk stratification above and beyond the calculator-predicted risk of VA in a primary prevention cohort of patients with ARVC, mainly for patients considered to be at low and intermediate risk by the clinical risk calculator

Prospectively Quantifying the Propensity for Atrial Fibrillation: A Mechanistic Formulation

<div><p>The goal of this study was to determine quantitative relationships between electrophysiologic parameters and the propensity of cardiac tissue to undergo atrial fibrillation. We used a computational model to simulate episodes of fibrillation, which we then characterized in terms of both their duration and the population dynamics of the electrical waves which drove them. Monte Carlo sampling revealed that episode durations followed an exponential decay distribution and wave population sizes followed a normal distribution. Half-lives of reentrant episodes increased exponentially with either increasing tissue area to boundary length ratio (<i>A/BL</i>) or decreasing action potential duration (<i>APD</i>), resistance (<i>R</i>) or capacitance (<i>C</i>). We found that the qualitative form of fibrillatory activity (e.g., multi-wavelet reentry (MWR) vs. rotors) was dependent on the ratio of resistance and capacitance to <i>APD</i>; MWR was reliably produced below a ratio of 0.18. We found that a composite of these electrophysiologic parameters, which we term the fibrillogenicity index (<i>Fb = A/(BL*APD*R*C)</i>), reliably predicted the duration of MWR episodes (r² = 0.93). Given that some of the quantities comprising <i>Fb</i> are amenable to manipulation (via either pharmacologic treatment or catheter ablation), these findings provide a theoretical basis for the development of titrated therapies of atrial fibrillation.</p></div

Parameter Dependencies of MWR Behavior.

<p><i>A-C</i>: Semi-log plots of MWR half-life as a function of A/BL (<i>A</i>), APD (<i>B</i>), and RC (<i>C</i>). <i>D-F</i>: The mean number of waves per time step (shown in blue) and population variance (shown in red) as functions of A/BL (<i>D</i>), APD (<i>E</i>), and RC (<i>F</i>). <i>G-I</i>: Semi-log plots of the expected duration of reentry (calculated from the population mean and variance) as a function of A/BL (<i>G</i>), APD (<i>H</i>), and RC (<i>I</i>). Note the similar parameter dependencies of MWR half-life and expected duration.</p

Utility of the Fibrillogenicity Index.

<p>The logarithm of the MWR half-lives as a function of the fibrillogenicity index. For all randomly generated tissues, the fit is poor (<i>A</i>). Limiting the analysis to tissues displaying only MWR results in a substantially improved correlation coefficient (<i>B</i>). Using an RC/APD cutoff of 0.18 to identify likely MWR episodes further improves correlation coefficient (<i>C</i>).</p

Tissue Parameter Ranges.

<p>Ranges of model parameter values used in the virtual tissue experiments.</p><p>Tissue Parameter Ranges.</p