Internal nutrients dominate load and drive hypoxia in a eutrophic estuary.

The hypothesis that local hypoxia and chlorophyll concentration are spatially tethered to local, sediment-driven nutrient release was examined in a small, nutrient-impacted estuary in the Southern Gulf of St. Lawrence, Canada. Sediment reactor core samples were taken at 10 locations between 0.25 and 100% of the estuary area in spring and fall (2019) and used to estimate nitrogen and phosphate flux. Sediment organic matter, carbonate, percent nitrogen, percent carbon, δ13C, and δ15N were measured from the reactor core stations. Oxygen was recorded continually using oxygen loggers while chlorophyll and salinity were measured bi-weekly. A hydrodynamic model was used to determine water renewal time at each station. The most severe eutrophication effects were in the upper one-fifth of the estuary. There were strong local relationships between sediment biogeochemistry, hypoxia, and chlorophyll metrics but not with water renewal time. Internal nutrient loading represented 65% and 69% of total N loading, and 98% and 89% of total P loading to the estuary in June and September, respectively. Sediment nitrogen flux was highly predictable from a range of local sediment variables that reflect either nutrient content, or organic carbon enrichment in general. Percent nitrogen and percent carbon were highly correlated but sediment P flux was poorly predicted from sediment parameters examined. The highest correlations were with percent nitrogen and percent carbon. These results indicate that incorporating internal nutrient loading into nutrient monitoring programs is a critical next step to improve predictive capacity for eutrophication endpoints and to mitigate nutrient effects.

Quantifying arrhythmic long QT effects of hydroxychloroquine and azithromycin with whole-heart optical mapping and simulations.

BACKGROUND: In March 2020, hydroxychloroquine (HCQ) alone or combined with azithromycin (AZM) was authorized as a treatment for COVID-19 in many countries. The therapy proved ineffective with long QT and deadly cardiac arrhythmia risks, illustrating challenges to determine the new safety profile of repurposed drugs. OBJECTIVE: To investigate proarrhythmic effects and mechanism of HCQ and AZM (combined and alone) with high doses of HCQ as in the COVID-19 clinical trials. METHODS: Proarrhythmic effects of HCQ and AZM are quantified using optical mapping with voltage-sensitive dyes in ex vivo Langendorff-perfused guinea pig (GP) hearts and with numerical simulations of a GP Luo-Rudy and a human O'Hara-Virag-Varro-Rudy models, for Epi, Endo, and M cells, in cell and tissue, incorporating the drug's effect on cell membrane ionic currents. RESULTS: Experimentally, HCQ alone and combined with AZM leads to long QT intervals by prolonging the action potential duration and increased spatial dispersion of action potential (AP) repolarization across the heart, leading to proarrhythmic discordant alternans. AZM alone had a lesser arrhythmic effect with less triangulation of the AP shape. Mathematical cardiac models fail to reproduce most of the arrhythmic effects observed experimentally. CONCLUSIONS: During public health crises, the risks and benefits of new and repurposed drugs could be better assessed with alternative experimental and computational approaches to identify proarrhythmic mechanisms. Optical mapping is an effective framework suitable to investigate the drug's adverse effects on cardiac cell membrane ionic channels at the cellular level and arrhythmia mechanisms at the tissue and whole-organ level.

Extravasation injury in a paediatric population.

BACKGROUND: Extravasation occurs when a drug is inadvertently administered outside of the vein. Depending on the substance involved, this may lead to tissue necrosis with significant long-term morbidity. Children, particularly neonates, are particularly susceptible to extravasation with up to 70% of children in neonatal intensive care unit having some form of extravasation injury. These injuries are commonly referred to plastic surgeons for ongoing management. METHODS: We prospectively collected information on all extravasation injuries referred to the plastic surgery department in a children's hospital over an 18-month period. Data collected included the agent involved in the extravasation, treatment and outcomes. RESULTS: In total, there were 43 extravasation injuries recorded on the hospital risk management system during the period of this study. All of these were referred to the plastic surgery team for ongoing management. Five patients (11%) underwent washout of their injuries. Three patients (7%) suffered injuries, which led to significant tissue necrosis, delayed healing and prolonged morbidity. CONCLUSION: Smaller infants, particularly those being cared for in an intensive care setting, are at increased risk for extravasation injury. Early referral and treatment of high-risk extravasation injuries may reduce the incidence of tissue loss and morbidity.

Discordant Alternans as a Mechanism for Initiation of Ventricular Fibrillation In Vitro.

Background Ventricular tachyarrhythmias are often preceded by short sequences of premature ventricular complexes. In a previous study, a restitution-based computational model predicted which sequences of stimulated premature complexes were most likely to induce ventricular fibrillation in canines in vivo. However, the underlying mechanism, based on discordant-alternans dynamics, could not be verified in that study. The current study seeks to elucidate the mechanism by determining whether the spatiotemporal evolution of action potentials and initiation of ventricular fibrillation in in vitro experiments are consistent with model predictions. Methods and Results Optical mapping voltage signals from canine right-ventricular tissue (n=9) were obtained simultaneously from the entire epicardium and endocardium during and after premature stimulus sequences. Model predictions of action potential propagation along a 1-dimensional cable were developed using action potential duration versus diastolic interval data. The model predicted sign-change patterns in action potential duration and diastolic interval spatial gradients with posterior probabilities of 91.1%, and 82.1%, respectively. The model predicted conduction block with 64% sensitivity and 100% specificity. A generalized estimating equation logistic-regression approach showed that model-prediction effects were significant for both conduction block ( P<1×10-15, coefficient 44.36) and sustained ventricular fibrillation ( P=0.0046, coefficient, 1.63) events. Conclusions The observed sign-change patterns favored discordant alternans, and the model successfully identified sequences of premature stimuli that induced conduction block. This suggests that the relatively simple discordant-alternans-based process that led to block in the model may often be responsible for ventricular fibrillation onset when preceded by premature beats. These observations may aid in developing improved methods for anticipating block and ventricular fibrillation.

Synchronization as a mechanism for low-energy anti-fibrillation pacing.

BACKGROUND: Low-energy anti-fibrillation pacing (LEAP) has been suggested as an alternative treatment in symptomatic fibrillation patients. It significantly lowers the energy required compared with standard 1-shock defibrillation. OBJECTIVE: In this study, we investigated the mechanism of arrhythmia termination by LEAP and systematically analyzed the influence of shock period and timing on the success rate of LEAP. METHODS: We induced atrial and ventricular fibrillation in isolated canine hearts and applied LEAP and standard 1-shock defibrillation to terminate the arrhythmia. We simulated the arrhythmia and LEAP using a 2-dimensional bidomain human atrial model. RESULTS: The ex vivo experiments showed successful termination of atrial fibrillation and ventricular fibrillation using LEAP, with an average 88% and 81% energy reduction, respectively, and both experiments and simulations verified that synchronization from virtual electrodes is the key mechanism for termination of arrhythmia by LEAP using modified Kuramoto phase plots and fraction of tissue excited (FTE) plots. We also observed in simulations that LEAP is more effective when the shock period is close to the dominant period and the first shock is delivered when FTE is decreasing. CONCLUSIONS: Our results support synchronization as the mechanism for arrhythmia termination by LEAP, and its effectiveness can be improved by adjusting shock period and timing.

Effects of pacing site and stimulation history on alternans dynamics and the development of complex spatiotemporal patterns in cardiac tissue.

Alternans of action potential duration has been associated with T wave alternans and the development of arrhythmias because it produces large gradients of repolarization. However, little is known about alternans dynamics in large mammalian hearts. Using optical mapping to record electrical activations simultaneously from the epicardium and endocardium of 9 canine right ventricles, we demonstrate novel arrhythmogenic complex spatiotemporal dynamics. (i) Alternans predominantly develops first on the endocardium. (ii) The postulated simple progression from normal rhythm to concordant to discordant alternans is not always observed; concordant alternans can develop from discordant alternans as the pacing period is decreased. (iii) In contrast to smaller tissue preparations, multiple stationary nodal lines may exist and need not be perpendicular to the pacing site or to each other. (iv) Alternans has fully three-dimensional dynamics and the epicardium and endocardium can show significantly different dynamics: multiple nodal surfaces can be transmural or intramural and can form concave/convex surfaces resulting in islands of discordant alternans. (v) The complex spatiotemporal patterns observed during alternans are very sensitive to both the site of stimulation and the stimulation history. Alternans in canine ventricles not only exhibit larger amplitudes and persist for longer cycle length regimes compared to those found in smaller mammalian hearts, but also show novel dynamics not previously described that enhance dispersion and show high sensitivity to initial conditions. This indicates some underlying predisposition to chaos and can help to guide the design of new drugs and devices controlling and preventing arrhythmic events.

Shock-induced termination of reentrant cardiac arrhythmias: comparing monophasic and biphasic shock protocols.

In this article, we compare quantitatively the efficiency of three different protocols commonly used in commercial defibrillators. These are based on monophasic and both symmetric and asymmetric biphasic shocks. A numerical one-dimensional model of cardiac tissue using the bidomain formulation is used in order to test the different protocols. In particular, we performed a total of 4.8 × 10(6) simulations by varying shock waveform, shock energy, initial conditions, and heterogeneity in internal electrical conductivity. Whenever the shock successfully removed the reentrant dynamics in the tissue, we classified the mechanism. The analysis of the numerical data shows that biphasic shocks are significantly more efficient (by about 25%) than the corresponding monophasic ones. We determine that the increase in efficiency of the biphasic shocks can be explained by the higher proportion of newly excited tissue through the mechanism of direct activation.

Mechanisms of ventricular arrhythmias: a dynamical systems-based perspective.

Defining the cellular electrophysiological mechanisms for ventricular tachyarrhythmias is difficult, given the wide array of potential mechanisms, ranging from abnormal automaticity to various types of reentry and kk activity. The degree of difficulty is increased further by the fact that any particular mechanism may be influenced by the evolving ionic and anatomic environments associated with many forms of heart disease. Consequently, static measures of a single electrophysiological characteristic are unlikely to be useful in establishing mechanisms. Rather, the dynamics of the electrophysiological triggers and substrates that predispose to arrhythmia development need to be considered. Moreover, the dynamics need to be considered in the context of a system, one that displays certain predictable behaviors, but also one that may contain seemingly stochastic elements. It also is essential to recognize that even the predictable behaviors of this complex nonlinear system are subject to small changes in the state of the system at any given time. Here we briefly review some of the short-, medium-, and long-term alterations of the electrophysiological substrate that accompany myocardial disease and their potential impact on the initiation and maintenance of ventricular arrhythmias. We also provide examples of cases in which small changes in the electrophysiological substrate can result in rather large differences in arrhythmia outcome. These results suggest that an interrogation of cardiac electrical dynamics is required to provide a meaningful assessment of the immediate risk for arrhythmia development and for evaluating the effects of putative antiarrhythmic interventions.

The arterialized saphenous venous flow-through flap with dual venous drainage.

BACKGROUND: Venous flow-through flaps are well-described options for small defects where donor site morbidity is undesirable or in areas where useful local veins are in close proximity to the defect, particularly in the extremities. However, higher rates of flap loss have limited their utility. The saphenous venous flap in particular has been widely sought as a useful flap, and while arterialization of this flap improved survival rates, congestion has remained a limiting feature. We describe report a modification in the design of saphenous venous flaps, whereby an arterialized flap is provided with a separate source of venous drainage, and demonstrate survival of substantially larger venous flaps than previously reported. METHODS: In five consecutive patients, we describe three main modifications to the saphenous venous flap as previously described: (a) Using arterialized flaps only; (b) Reversing the flap to allow unimpeded flow during arterialization; and (c) Anastomosing additional vein(s) that are not connected to the central vein-especially at the periphery of the flap for true venous drainage. RESULTS: There was a 0% complete flap loss rate (with only one case of superficial partial loss), and ultimately better survival than previous series of saphenous venous flaps described to date. CONCLUSION: The success of these techniques offers the potential to re-establish flow to large segmental losses to axial arteries, offer safe and definitive flap coverage to traumatic wounds, improve the array of flap options in this setting, and minimize donor site morbidity.

Teaching cardiac electrophysiology modeling to undergraduate students: laboratory exercises and GPU programming for the study of arrhythmias and spiral wave dynamics.

As part of a 3-wk intersession workshop funded by a National Science Foundation Expeditions in Computing award, 15 undergraduate students from the City University of New York(1) collaborated on a study aimed at characterizing the voltage dynamics and arrhythmogenic behavior of cardiac cells for a broad range of physiologically relevant conditions using an in silico model. The primary goal of the workshop was to cultivate student interest in computational modeling and analysis of complex systems by introducing them through lectures and laboratory activities to current research in cardiac modeling and by engaging them in a hands-on research experience. The success of the workshop lay in the exposure of the students to active researchers and experts in their fields, the use of hands-on activities to communicate important concepts, active engagement of the students in research, and explanations of the significance of results as the students generated them. The workshop content addressed how spiral waves of electrical activity are initiated in the heart and how different parameter values affect the dynamics of these reentrant waves. Spiral waves are clinically associated with tachycardia, when the waves remain stable, and with fibrillation, when the waves exhibit breakup. All in silico experiments were conducted by simulating a mathematical model of cardiac cells on graphics processing units instead of the standard central processing units of desktop computers. This approach decreased the run time for each simulation to almost real time, thereby allowing the students to quickly analyze and characterize the simulated arrhythmias. Results from these simulations, as well as some of the background and methodology taught during the workshop, is presented in this article along with the programming code and the explanations of simulation results in an effort to allow other teachers and students to perform their own demonstrations, simulations, and studies.

Low-energy control of electrical turbulence in the heart.

Controlling the complex spatio-temporal dynamics underlying life-threatening cardiac arrhythmias such as fibrillation is extremely difficult, because of the nonlinear interaction of excitation waves in a heterogeneous anatomical substrate. In the absence of a better strategy, strong, globally resetting electrical shocks remain the only reliable treatment for cardiac fibrillation. Here we establish the relationship between the response of the tissue to an electric field and the spatial distribution of heterogeneities in the scale-free coronary vascular structure. We show that in response to a pulsed electric field, E, these heterogeneities serve as nucleation sites for the generation of intramural electrical waves with a source density ρ(E) and a characteristic time, τ, for tissue depolarization that obeys the power law τ ∝ E(α). These intramural wave sources permit targeting of electrical turbulence near the cores of the vortices of electrical activity that drive complex fibrillatory dynamics. We show in vitro that simultaneous and direct access to multiple vortex cores results in rapid synchronization of cardiac tissue and therefore, efficient termination of fibrillation. Using this control strategy, we demonstrate low-energy termination of fibrillation in vivo. Our results give new insights into the mechanisms and dynamics underlying the control of spatio-temporal chaos in heterogeneous excitable media and provide new research perspectives towards alternative, life-saving low-energy defibrillation techniques.

In vivo electrochemical characterization of tissue-electrode interface during metamorphic growth.

The domestication of insect locomotion has been recently investigated through microelectrode based systems implanted in the insect to tap into its neuromuscular system. Benefiting from developmental changes, the idea of performing such surgical implantation during metamorphic development enabled the fusion of engineered constructs to these living biological organisms. This study uses electrochemical analysis to provide a preliminary quantitative comparison of tissue-electrode coupling over the course of metamorphic development and after eclosion, where PEDOT:PSS coated gold electrodes are implanted in the insect during the early pupal stages and right after emergence. An average 1 kHz impedance of 8.9 k was obtained with pupal stage inserted electrodes, with a stored charge of 52 mC/cm2 at the interface as characterized by cyclic voltammetry 10 days after emergence. 5.1 mC/cm2 of this charge was successfully injected into the tissue through charge balanced biphasic pulses. In comparison, implanted electrodes in the adult state caused a 1 kHz impedance of 12.1 k, where the stored charge was 38 mC/cm2 with an injectable charge amount of 3.5 mC/cm2. Finally, to shed light on possible reasons for improvement in the bioelectrical coupling, equivalent circuit models were formed and the extracted parameters were correlated with metamorphic development of pupal tissue.

Control of action potential duration alternans in canine cardiac ventricular tissue.

Cardiac electrical alternans, characterized by a beat-to-beat alternation in action potential waveform, is a naturally occurring phenomenon, which can occur at sufficiently fast pacing rates. Its presence has been putatively linked to the onset of cardiac reentry, which is a precursor to ventricular fibrillation. Previous studies have shown that closed-loop alternans control techniques that apply a succession of externally administered cycle perturbations at a single site provide limited spatially-extended alternans elimination in sufficiently large cardiac substrates. However, detailed experimental investigations into the spatial dynamics of alternans control have been restricted to Purkinje fiber studies. A complete understanding of alternans control in the more clinically relevant ventricular tissue is needed. In this paper, we study the spatial dynamics of alternans and alternans control in arterially perfused canine right ventricular preparations using an optical mapping system capable of high-resolution fluorescence imaging. Specifically, we quantify the spatial efficacy of alternans control along 2.5 cm of tissue, focusing on differences in spatial control between different subregions of tissue. We demonstrate effective control of spatially-extended alternans up to 2.0 cm, with control efficacy attenuating as a function of distance. Our results provide a basis for future investigations into electrode-based control interventions of alternans in cardiac tissue.

Control of action potential duration alternans in canine ventricular tissue.

Cardiac action potential duration alternans is characterized by a beat-to-beat alternation in action potential waveform. Its presence has been putatively linked to the onset of lethal cardiac arrhythmias. Previous studies, which have been limited to cardiac Purkinje fibers, have shown that closed-loop alternans control techniques, which apply a succession of externally administered cycle perturbations, provide ineffectual spatial alternans elimination. A more complete understanding of alternans control in the more clinically relevant ventricular tissue is needed. Here, we study the spatial dynamics of alternans and alternans control in arterially perfused canine right ventricular preparations using optical mapping. We quantified the spatial efficacy of alternans control across 2.5 cm of tissue, focusing primarily on differences in spatial control within several sub-regions of tissue. Our results provide a basis for future investigations into multi-electrode-based control interventions of alternans in cardiac tissue.

Wireless transmission of cardiac action potentials with ultrasonically guided insertion of silicon probes.

This paper reports on the coupling of ultrasonically guided cardiac probes with wireless transmission of cardiac action potentials for applications in monitoring the 3D electrical onset of ventricular fibrillation. An application specific integrated circuit has been designed with a 40 dB amplifying stage and a frequency modulating oscillator to wirelessly transmit the recorded action potentials. Combined with the ultrasonically inserted cardiac probe that reduces penetration force, this system demonstrates the initial results in wireless monitoring of 3D action potential propagation.

Transmural ultrasound-based visualization of patterns of action potential wave propagation in cardiac tissue.

The pattern of action potential propagation during various tachyarrhythmias is strongly suspected to be composed of multiple re-entrant waves, but has never been imaged in detail deep within myocardial tissue. An understanding of the nature and dynamics of these waves is important in the development of appropriate electrical or pharmacological treatments for these pathological conditions. We propose a new imaging modality that uses ultrasound to visualize the patterns of propagation of these waves through the mechanical deformations they induce. The new method would have the distinct advantage of being able to visualize these waves deep within cardiac tissue. In this article, we describe one step that would be necessary in this imaging process-the conversion of these deformations into the action potential induced active stresses that produced them. We demonstrate that, because the active stress induced by an action potential is, to a good approximation, only nonzero along the local fiber direction, the problem in our case is actually overdetermined, allowing us to obtain a complete solution. Use of two- rather than three-dimensional displacement data, noise in these displacements, and/or errors in the measurements of the fiber orientations all produce substantial but acceptable errors in the solution. We conclude that the reconstruction of action potential-induced active stress from the deformation it causes appears possible, and that, therefore, the path is open to the development of the new imaging modality.

Off-site control of repolarization alternans in cardiac fibers.

Repolarization alternans, a beat-to-beat alternation in action potential duration, has been putatively linked to the onset of cardiac reentry. Anti-alternans control strategies can eliminate alternans in individual cells by exploiting the rate dependence of action potential duration. The same approach, when applied to a common measuring/stimulating site at one end of a cardiac fiber, has been shown to have limited spatial efficacy. As a first step toward spatially distributed electrode control systems, we investigated "off-site" control in canine Purkinje fibers, in which the recording and control sites are different. We found experimentally that alternans can be eliminated at, or very near, the recording site, and that varying the location of the recording site along the fiber causes the node (the location with no alternans) to move along the fiber in close proximity to the recording site. Theoretical predictions based on an amplitude equation [B. Echebarria and A. Karma, Chaos 12, 923 (2002)] show that those findings follow directly from the wave nature of alternans: the most unstable mode of alternans along the fiber is a wave solution of a one-dimensional Helmholtz equation with a node position that only deviates slightly from the recording site by an amount dependent on electrotonic coupling. Computer simulations using a Purkinje fiber model confirm these theoretical and experimental results. Although off-site alternans control does not suppress alternans along the entire fiber, our results indicate that placing the node away from the stimulus site reduces alternans amplitude along the fiber, and may therefore have implications for antiarrhythmic strategies based on alternans termination.

Orbital floor reconstruction: a case for silicone. A 12 year experience.

INTRODUCTION: Controversy still exists regarding the choice of implant material for orbital floor reconstructions, in particular the use of silicone. We aimed to evaluate the long-term outcomes of orbital floor reconstructions with silicone versus other non-silicone implants. PATIENTS AND METHODS: We conducted a 12 year retrospective review of patients who had orbital floor reconstructions for fractures at the Royal Hobart Hospital, Tasmania, Australia, from 1995 to 2007. Surgical admission notes, CT reports, operation records, outpatient notes, and complications were recorded. Long-term follow-up consisted of a structured telephone interview assessing patient outcomes and satisfaction, including ongoing disability, following orbital floor repair. RESULTS: Eighty one patients were identified as having had orbital floor reconstruction with an implant. Mean long-term follow-up was 63 months. Outcomes of Silicone implants (n=58) were compared to non-silicone implant materials (n=23) including titanium mesh, 'Lactasorb', 'Resorb-X', autologous cartilage, and bone graft. Statistically significant advantages in the silicone group were found in the number of patients with palpable implants (24% vs 63%, p=0.005), the number of patients without any complaint (67% vs 32%, p=0.004), and the number of patients requiring subsequent surgery for complications related to their implants (5% vs 23%, p=0.046). CONCLUSION: The appropriate use of silicone implants for orbital floor reconstruction can have good results, contrary to much of the literature, with low complication rates including an acceptably low rate of infection and extrusion, as well as high patient satisfaction. To establish definite guidelines for best surgical practise, particularly amongst synthetic implant materials, prospective study is required.

Effects of hypocalcemia on electrical restitution and ventricular fibrillation.

We have shown previously that verapamil reduces the slope of the action potential duration (APD) restitution relation, suppresses APD alternans and converts ventricular fibrillation (VF) into a periodic rhythm. To determine whether these effects result primarily from reduction of the APD restitution slope, as opposed to alteration of calcium dynamics unrelated to restitution, we tested the effects of hypocalcemia ([CaCl2]=31-125 microM) in canine ventricle. At normal [CaCl2] (2.0 mM), the slope of the APD restitution relation was >1, APD alternans occurred during rapid pacing and VF was inducible. During hypocalcemia the slope of the restitution relation remained >1 and the magnitude of APD alternans was unchanged. VF still was inducible and the mean cycle length and the variance of the FFT spectra during VF were not altered significantly. These results suggest that reduction of APD restitution slope, rather than blockade of ICa per se, is responsible for the antifibrillatory effects of verapamil in this model of pacing-induced VF, lending further support to the idea that APD restitution kinetics is a key determinant of VF.

Termination of atrial fibrillation using pulsed low-energy far-field stimulation.

BACKGROUND: Electrically based therapies for terminating atrial fibrillation (AF) currently fall into 2 categories: antitachycardia pacing and cardioversion. Antitachycardia pacing uses low-intensity pacing stimuli delivered via a single electrode and is effective for terminating slower tachycardias but is less effective for treating AF. In contrast, cardioversion uses a single high-voltage shock to terminate AF reliably, but the voltages required produce undesirable side effects, including tissue damage and pain. We propose a new method to terminate AF called far-field antifibrillation pacing, which delivers a short train of low-intensity electric pulses at the frequency of antitachycardia pacing but from field electrodes. Prior theoretical work has suggested that this approach can create a large number of activation sites ("virtual" electrodes) that emit propagating waves within the tissue without implanting physical electrodes and thereby may be more effective than point-source stimulation. METHODS AND RESULTS: Using optical mapping in isolated perfused canine atrial preparations, we show that a series of pulses at low field strength (0.9 to 1.4 V/cm) is sufficient to entrain and subsequently extinguish AF with a success rate of 93% (69 of 74 trials in 8 preparations). We further demonstrate that the mechanism behind far-field antifibrillation pacing success is the generation of wave emission sites within the tissue by the applied electric field, which entrains the tissue as the field is pulsed. CONCLUSIONS: AF in our model can be terminated by far-field antifibrillation pacing with only 13% of the energy required for cardioversion. Further studies are needed to determine whether this marked reduction in energy can increase the effectiveness and safety of terminating atrial tachyarrhythmias clinically.