Therapeutic potential of conduction system pacing as a method for improving cardiac output during ventricular tachycardia.

BACKGROUND: Ventricular tachycardia (VT) reduces cardiac output through high heart rates, loss of atrioventricular synchrony, and loss of ventricular synchrony. We studied the contribution of each mechanism and explored the potential therapeutic utility of His bundle pacing to improve cardiac output during VT. METHODS: Study 1 aimed to improve the understanding of mechanisms of harm during VT (using pacing simulated VT). In 23 patients with left ventricular impairment, we recorded continuous ECG and beat-by-beat blood pressure measurements. We assessed the hemodynamic impact of heart rate and restoration of atrial and biventricular synchrony. Study 2 investigated novel pacing interventions during clinical VT by evaluating the hemodynamic effects of His bundle pacing at 5 bpm above the VT rate in 10 patients. RESULTS: In Study 1, at progressively higher rates of simulated VT, systolic blood pressure declined: at rates of 125, 160, and 190 bpm, -22.2%, -42.0%, and -58.7%, respectively (ANOVA p < 0.0001). Restoring atrial synchrony alone had only a modest beneficial effect on systolic blood pressure (+ 3.6% at 160 bpm, p = 0.2117), restoring biventricular synchrony alone had a greater effect (+ 9.1% at 160 bpm, p = 0.242), and simultaneously restoring both significantly increased systolic blood pressure (+ 31.6% at 160 bpm, p = 0.0003). In Study 2, the mean rate of clinical VT was 143 ± 21 bpm. His bundle pacing increased systolic blood pressure by + 14.2% (p = 0.0023). In 6 of 10 patients, VT terminated with His bundle pacing. CONCLUSIONS: Restoring atrial and biventricular synchrony improved hemodynamic function in simulated and clinical VT. Conduction system pacing could improve VT tolerability and treatment.

Non-invasive biomarkers for detecting progression toward hypovolemic cardiovascular instability in a lower body negative pressure model.

Occult hemorrhages after trauma can be present insidiously, and if not detected early enough can result in patient death. This study evaluated a hemorrhage model on 18 human subjects, comparing the performance of traditional vital signs to multiple off-the-shelf non-invasive biomarkers. A validated lower body negative pressure (LBNP) model was used to induce progression towards hypovolemic cardiovascular instability. Traditional vital signs included mean arterial pressure (MAP), electrocardiography (ECG), plethysmography (Pleth), and the test systems utilized electrical impedance via commercial electrical impedance tomography (EIT) and multifrequency electrical impedance spectroscopy (EIS) devices. Absolute and relative metrics were used to evaluate the performance in addition to machine learning-based modeling. Relative EIT-based metrics measured on the thorax outperformed vital sign metrics (MAP, ECG, and Pleth) achieving an area-under-the-curve (AUC) of 0.99 (CI 0.95-1.00, 100% sensitivity, 87.5% specificity) at the smallest LBNP change (0-15 mmHg). The best vital sign metric (MAP) at this LBNP change yielded an AUC of 0.6 (CI 0.38-0.79, 100% sensitivity, 25% specificity). Out-of-sample predictive performance from machine learning models were strong, especially when combining signals from multiple technologies simultaneously. EIT, alone or in machine learning-based combination, appears promising as a technology for early detection of progression toward hemodynamic instability.

Prediction of Occult Hemorrhage in the Lower Body Negative Pressure Model: Initial Validation of Machine Learning Approaches.

INTRODUCTION: Detection of occult hemorrhage (OH) before progression to clinically apparent changes in vital signs remains an important clinical problem in managing trauma patients. The resource-intensiveness associated with continuous clinical patient monitoring and rescue from frank shock makes accurate early detection and prediction with noninvasive measurement technology a desirable innovation. Despite significant efforts directed toward the development of innovative noninvasive diagnostics, the implementation and performance of the newest bedside technologies remain inadequate. This poor performance may reflect the limitations of univariate systems based on one sensor in one anatomic location. It is possible that when signals are measured with multiple modalities in multiple locations, the resulting multivariate anatomic and temporal patterns of measured signals may provide additional discriminative power over single technology univariate measurements. We evaluated the potential superiority of multivariate methods over univariate methods. Additionally, we utilized machine learning-based models to compare the performance of noninvasive-only to noninvasive-plus-invasive measurements in predicting the onset of OH. MATERIALS AND METHODS: We applied machine learning methods to preexisting datasets derived using the lower body negative pressure human model of simulated hemorrhage. Employing multivariate measured physiological signals, we investigated the extent to which machine learning methods can effectively predict the onset of OH. In particular, we applied 2 ensemble learning methods, namely, random forest and gradient boosting. RESULTS: Analysis of precision, recall, and area under the receiver operating characteristic curve showed a superior performance of multivariate approach to that of the univariate ones. In addition, when using both invasive and noninvasive features, random forest classifier had a recall 95% confidence interval (CI) of 0.81 to 0.86 with a precision 95% CI of 0.65 to 0.72. Interestingly, when only noninvasive features were employed, the results worsened only slightly to a recall 95% CI of 0.80 to 0.85 and a precision 95% CI of 0.61 to 0.73. CONCLUSIONS: Multivariate ensemble machine learning-based approaches for the prediction of hemodynamic instability appear to hold promise for the development of effective solutions. In the lower body negative pressure multivariate hemorrhage model, predictions based only on noninvasive measurements performed comparably to those using both invasive and noninvasive measurements.

Latitudinal patterns in stabilizing density dependence of forest communities.

Numerous studies have shown reduced performance in plants that are surrounded by neighbours of the same species1,2, a phenomenon known as conspecific negative density dependence (CNDD)3. A long-held ecological hypothesis posits that CNDD is more pronounced in tropical than in temperate forests4,5, which increases community stabilization, species coexistence and the diversity of local tree species6,7. Previous analyses supporting such a latitudinal gradient in CNDD8,9 have suffered from methodological limitations related to the use of static data10-12. Here we present a comprehensive assessment of latitudinal CNDD patterns using dynamic mortality data to estimate species-site-specific CNDD across 23 sites. Averaged across species, we found that stabilizing CNDD was present at all except one site, but that average stabilizing CNDD was not stronger toward the tropics. However, in tropical tree communities, rare and intermediate abundant species experienced stronger stabilizing CNDD than did common species. This pattern was absent in temperate forests, which suggests that CNDD influences species abundances more strongly in tropical forests than it does in temperate ones13. We also found that interspecific variation in CNDD, which might attenuate its stabilizing effect on species diversity14,15, was high but not significantly different across latitudes. Although the consequences of these patterns for latitudinal diversity gradients are difficult to evaluate, we speculate that a more effective regulation of population abundances could translate into greater stabilization of tropical tree communities and thus contribute to the high local diversity of tropical forests.

Managing a policy paradox? Responses to textual warning labels on E-cigarette advertisements among U.S. national samples of youth overall and adults who smoke or vape.

CONTEXT: Current use and potential future uptake of e-cigarettes among youth remain public health concerns in the U.S., even as people who smoke combustible cigarettes could benefit from switching completely to e-cigarettes. The U.S. Food and Drug Administration (FDA) is considering alternative warning messages, but warnings that discourage youth from use may also deter people who smoke from switching. This study tests ten pre-registered hypotheses on effects of warning messages with national samples of youth overall and adults who smoke and/or vape. METHODS: NORC recruited 1639 adults (ages 18+) who smoke, vape, or use both products, from their probability-sampled AmeriSpeak Panel and augmented their AmeriSpeak Teen Panel with Lucid's nonprobability opt-in panel to recruit 1217 youth (ages 14-17) to participate in a web-based survey experiment. We randomly assigned respondents to view one of five warning label conditions and respond to measures of their e-cigarette risk beliefs, willingness to use e-cigarettes, and (among people who smoke or vape) considerations to quit these products. FINDINGS: Relative to the current FDA warning about nicotine, warning messages about the harms of e-cigarette use for youth brain development did not influence risk beliefs or reduce willingness to use these products among youth. Brain development warning messages did increase beliefs about these harms among adults but did not increase quit considerations among people who vape, relative to the FDA warning. Warning messages with information about chemical constituents of vaping products and the harm of these chemicals produced higher e-cigarette quit considerations than did the FDA warning among adults who vape. CONCLUSION: Potential alternative warning label messages were largely ineffective relative to the current FDA warning about nicotine, though limited evidence suggests some potential for chemical + harm messaging to encourage people who use both e-cigarettes and cigarettes to consider quitting both.

Semantic dementia: a complex and culturally influenced presentation.

SUMMARY: The variants of frontotemporal dementia (FTD) require careful differentiation from primary psychiatric disorders as the neuropsychiatric manifestations can overshadow the unique cognitive deficits. The language variants of FTD are less readily recognised by trainees despite making up around 43% of cases. This educational article presents an anonymised case of one of the language variants: semantic dementia. The cognitive deficits and neuropsychiatric manifestations (delusions and hyperreligiosity) are explored in terms of aetiology and management. By the end of the article, readers should be able to differentiate FTD from Alzheimer's disease, understand the principles of management and associated risks, and develop a multifaceted approach to hyperreligiosity in dementia.

Biological lessons for strategic resistance management.

Biological resistance to pesticides, vaccines, antibiotics, and chemotherapies creates huge costs to society, including extensive morbidity and mortality. We simultaneously face costly resistance to social changes, such as those required to resolve human-wildlife conflicts and conserve biodiversity and the biosphere. Viewing resistance as a force that impedes change from one state to another, we suggest that an analysis of biological resistance can provide unique and potentially testable insights into understanding resistance to social changes. We review key insights from managing biological resistance and develop a framework that identifies seven strategies to overcome resistance. We apply this framework to consider how it might be used to understand social resistance and generate potentially novel hypotheses that may be useful to both enhance the development of strategies to manage resistance and modulate change in socio-ecological systems.

Intermittent alternating magnetic fields diminish metal-associated biofilm in vivo.

Prosthetic joint infection (PJI) is a complication of arthroplasty that results in significant morbidity. The presence of biofilm makes treatment difficult, and removal of the prosthesis is frequently required. We have developed a non-invasive approach for biofilm eradication from metal implants using intermittent alternating magnetic fields (iAMF) to generate targeted heating at the implant surface. The goal of this study was to determine whether iAMF demonstrated efficacy in an in vivo implant biofilm infection model. iAMF combined with antibiotics led to enhanced reduction of biofilm on metallic implants in vivo compared to antibiotics or untreated control. iAMF-antibiotic combinations resulted in a > 1 - log further reduction in biofilm burden compared to antibiotics or iAMF alone. This combination effect was seen in both S. aureus and P. aeruginosa and seen with multiple antibiotics used to treat infections with these pathogens. In addition, efficacy was temperature dependent with increasing temperatures resulting in a greater reduction of biofilm. Tissue damage was limited (< 1 mm from implant-tissue interface). This non-invasive approach to eradicating biofilm could serve as a new paradigm in treating PJI.

A phylogeny of the evening primrose family (Onagraceae) using a target enrichment approach with 303 nuclear loci.

BACKGROUND: The evening primrose family (Onagraceae) includes 664 species (803 taxa) with a center of diversity in the Americas, especially western North America. Ongoing research in Onagraceae includes exploring striking variation in floral morphology, scent composition, and breeding system, as well as the role of these traits in driving diversity among plants and their interacting pollinators and herbivores. However, these efforts are limited by the lack of a comprehensive, well-resolved phylogeny. Previous phylogenetic studies based on a few loci strongly support the monophyly of the family and the sister relationship of the two largest tribes but fail to resolve several key relationships. RESULTS: We used a target enrichment approach to reconstruct the phylogeny of Onagraceae using 303 highly conserved, low-copy nuclear loci. We present a phylogeny for Onagraceae with 169 individuals representing 152 taxa sampled across the family, including extensive sampling within the largest tribe, Onagreae. Deep splits within the family are strongly supported, whereas relationships among closely related genera and species are characterized by extensive conflict among individual gene trees. CONCLUSIONS: This phylogenetic resource will augment current research projects focused throughout the family in genomics, ecology, coevolutionary dynamics, biogeography, and the evolution of characters driving diversification in the family.

Blood Management for the Orthopaedic Surgical Patient.

Prevention and management of anemia and blood loss in the orthopaedic patient undergoing surgery is a major concern for healthcare providers and patients. Although transfusion technology can be lifesaving, there are risks to blood products that have led to increased awareness of blood management and development of hospital patient blood management programs. Use of patient blood management can be effective in addressing preoperative anemia, a major modifiable risk factor in patients undergoing surgery. In this informational article, evidence-based practice guidelines for perioperative blood management are addressed. A case scenario is introduced focusing on a patient whose religious preference is Jehovah's Witness having "no blood wishes" undergoing elective orthopaedic surgery. Orthopaedic nurses can facilitate optimal patient blood management through multidisciplinary collaboration.

Mycorrhizal feedbacks influence global forest structure and diversity.

One mechanism proposed to explain high species diversity in tropical systems is strong negative conspecific density dependence (CDD), which reduces recruitment of juveniles in proximity to conspecific adult plants. Although evidence shows that plant-specific soil pathogens can drive negative CDD, trees also form key mutualisms with mycorrhizal fungi, which may counteract these effects. Across 43 large-scale forest plots worldwide, we tested whether ectomycorrhizal tree species exhibit weaker negative CDD than arbuscular mycorrhizal tree species. We further tested for conmycorrhizal density dependence (CMDD) to test for benefit from shared mutualists. We found that the strength of CDD varies systematically with mycorrhizal type, with ectomycorrhizal tree species exhibiting higher sapling densities with increasing adult densities than arbuscular mycorrhizal tree species. Moreover, we found evidence of positive CMDD for tree species of both mycorrhizal types. Collectively, these findings indicate that mycorrhizal interactions likely play a foundational role in global forest diversity patterns and structure.

Within-Person Modulation of Neural Networks following Interoceptive Awareness Training through Mindful Awareness in Body-Oriented Therapy (MABT): A Pilot Study.

Interoception, the representation of the body's internal state, is increasingly recognized for informing subjective wellbeing and promoting regulatory behavior. However, few empirical reports characterize interoceptive neural networks, and fewer demonstrate changes to these networks in response to an efficacious intervention. Using a two-group randomized controlled trial, this pilot study explored within-participant neural plasticity in interoceptive networks following Mindful Awareness in Body-oriented Therapy (MABT). Participants (N = 22) were assigned to either 8 weeks of MABT or to a no-treatment control and completed baseline and post-intervention assessments that included subjective interoceptive awareness (MAIA) and neuroimaging of an interoceptive awareness task. MABT was uniquely associated with insula deactivation, increased functional connectivity between the dorsal attention network and the somatomotor cortex, and connectivity changes correlated positively with changes in subjective interoception. Within the MABT group, changes in subjective interoception interacted with changes in a predefined anterior cingulate seed region to predict changes in right middle insula activity, a putative primary interoceptive representation region. While the small sample size requires the replication of findings, results suggest that interoceptive training enhances sensory-prefrontal connectivity, and that such changes are commensurate with enhanced interoceptive awareness.

Atom probe tomography using an extreme ultraviolet trigger pulse.

Atom probe tomography (APT) is a powerful materials characterization technique capable of measuring the isotopically resolved three-dimensional (3D) structure of nanoscale specimens with atomic resolution. Modern APT instrumentation most often uses an optical pulse to trigger field ion evaporation-most commonly, the second or third harmonic of a Nd laser is utilized (∼λ = 532 nm or λ = 355 nm). Herein, we describe an APT instrument that utilizes ultrafast extreme ultraviolet (EUV) optical pulses to trigger field ion emission. The EUV light is generated via a commercially available high harmonic generation system based on a noble-gas-filled capillary. The centroid of the EUV spectrum is tunable from around 25 eV (λ = 50 nm) to 45 eV (λ = 28 nm), dependent on the identity of the gas in the capillary (Xe, Kr, or Ar). EUV pulses are delivered to the APT analysis chamber via a vacuum beamline that was optimized to maximize photon flux at the APT specimen apex while minimizing complexity. We describe the design of the beamline in detail, including the various compromises involved. We characterize the spectrum of the EUV light and its evolution as it propagates through the various optical elements. The EUV focus spot size is measured at the APT specimen plane, and the effects of misalignment are simulated and discussed. The long-term stability of the EUV source has been demonstrated for more than a year. Finally, APT mass spectra are shown, demonstrating the instrument's ability to successfully trigger field ion emission from semiconductors (Si, GaN) and insulating materials (Al2O3).

Graft and Patient Survival in Kidney Transplant with Deceased Donor Using KDRI (Kidney Donor Risk Index), KDPI (Kidney Donor Profile Index), and EPTS (Estimated Post-Transplant Survival) in Colombia.

BACKGROUND EPTS (Estimated Post-Transplant Survival), KDRI (Kidney Donor Risk Index), and KDPI (Kidney Donor Profile Index) were developed aiming to ameliorate donor-recipient longevity matching in kidney transplants. They are based on a prediction model made using the United States population; evidence of their use outside EEUU remains limited. The aim of this study was to describe the quality of deceased-donor kidneys and to determine recipient and graft survival, glomerular filtration rate, and incidence of delayed graft function in renal transplantation according to these indices in Cali, Colombia. MATERIAL AND METHODS In this historical cohort study, Kaplan-Meier method was used to analyze survival of recipient and graft according to the values of the indices categorized by quintiles. Glomerular filtration rate and incidence of delayed graft function were also analyzed according to KDRI and KDPI. RESULTS We included 380 patients. Medians of EPTS, KDRI, and KDPI were 24% (IQR 9-60), 0.8 (IQR 0.71-0.99), and 27% (IQR 13-49), respectively. Two-year survival was 97.8% in recipients with EPTS ≤20% and it decreased with higher values of the index. Recipient and graft survival were lower for all periods when donors had KDPI >80%. Incidence of delayed graft function was higher in patients whose donors had KDPI ≥60% (44% vs 21%). Glomerular filtration rate decreased with the highest values of KDPI for all periods. CONCLUSIONS Our study represents the initial evaluation of the usefulness of these indices in Colombia. Our results suggest that KDRI, KDPI, and EPTS may serve as valuable tools for kidney allocation in our setting. Further research with larger sample sizes is necessary to validate these indices in our population.

Fabrication of Specimens for Atom Probe Tomography Using a Combined Gallium and Neon Focused Ion Beam Milling Approach.

We demonstrate a new focused ion beam sample preparation method for atom probe tomography. The key aspect of the new method is that we use a neon ion beam for the final tip-shaping after conventional annulus milling using gallium ions. This dual-ion approach combines the benefits of the faster milling capability of the higher current gallium ion beam with the chemically inert and higher precision milling capability of the noble gas neon ion beam. Using a titanium-aluminum alloy and a layered aluminum/aluminum-oxide tunnel junction sample as test cases, we show that atom probe tips prepared using the combined gallium and neon ion approach are free from the gallium contamination that typically frustrates composition analysis of these materials due to implantation, diffusion, and embrittlement effects. We propose that by using a focused ion beam from a noble gas species, such as the neon ions demonstrated here, atom probe tomography can be more reliably performed on a larger range of materials than is currently possible using conventional techniques.

Progressive myelinated retinal nerve fibers in a 10-year-old boy with Crouzon syndrome after craniofacial surgery.

Purpose: We present a case of a 10-year-old boy with Crouzon syndrome that demonstrates progressive myelinated retinal nerve fibers (MRNF). Observations: A 10-year-old boy was referred for ophthalmic examination due to clusters of opaque white fibers around his optic nerve. Past surgical history includes craniofacial surgery at 3 years of age secondary to the deteriorating vision from increased intracranial pressure and papilledema. Upon examination (now 6.5 years post-craniofacial surgery), the patient denied any ocular complaints. The fundus examination showed progressively enlarged myelination of the retinal nerve fiber layer (right eye > left eye). Although previous cases of MRNF with Crouzon syndrome have been reported, our case is unique given its post-operative status with early onset of MRNF. Conclusion and importance: This case report documents the photographic progression of bilateral myelinated retinal nerve fibers (MRNF) in a pediatric case of Crouzon syndrome post-craniofacial surgery secondary to increased intracranial pressure and papilledema. Based on our patient, craniofacial decompression surgery may not prevent the development of MRNF. The exact mechanisms of MRNF are still being studied. Further investigations correlating craniofacial surgeries, increased intracranial pressure, and progression of myelinated retinal nerve fibers are needed to understand this process.

Interoceptive Awareness of the Breath Preserves Attention and Language Networks amidst Widespread Cortical Deactivation: A Within-Participant Neuroimaging Study.

Interoception, the representation of the body's internal state, serves as a foundation for emotion, motivation, and wellbeing. Yet despite its centrality in human experience, the neural mechanisms of interoceptive attention are poorly understood. The Interoceptive/Exteroceptive Attention Task (IEAT) is a novel neuroimaging paradigm that compares behavioral tracking of the respiratory cycle (Active Interoception) to tracking of a visual stimulus (Active Exteroception). Twenty-two healthy participants completed the IEAT during two separate scanning sessions (N = 44) as part of a randomized control trial of mindful awareness in body-oriented therapy (MABT). Compared with Active Exteroception, Active Interoception deactivated somatomotor and prefrontal regions. Greater self-reported interoceptive sensibility (MAIA scale) predicted sparing from deactivation within the anterior cingulate cortex (ACC) and left-lateralized language regions. The right insula, typically described as a primary interoceptive cortex, was only specifically implicated by its deactivation during an exogenously paced respiration condition (Active Matching) relative to self-paced Active Interoception. Psychophysiological interaction (PPI) analysis characterized Active Interoception as promoting greater ACC connectivity with lateral prefrontal and parietal regions commonly referred to as the dorsal attention network (DAN). In contrast to evidence relating accurate detection of liminal interoceptive signals such as the heartbeat to anterior insula activity, interoceptive attention toward salient signals such as the respiratory cycle may involve reduced cortical activity but greater ACC-DAN connectivity, with greater sensibility linked to reduced deactivation within the ACC and language-processing regions.

An experimental test of the mindfulness-to-meaning theory: Casual pathways between decentering, reappraisal, and well-being.

Emotion regulation ideally promotes subjective well-being in addition to relieving distress. Mindfulness-to-Meaning theory (MMT) proposes that well-being interventions follow a common pathway to promote wellness using two intermediate stages: decentering from initial stress appraisals followed by positive reappraisal of life events-linking a broadened state of awareness with narrative meaning-making. A preregistered (https://osf.io/c2xzd) evaluation of the MMT compared online, 3-week adaptations of established well-being interventions in a postsecondary student sample. The study (N = 131) employed a four-arm randomized trial design, featuring (a) control, (b) mindfulness, (c) stress mindset, and (d) blended mindfulness and stress mindset training conditions. The MMT pathway accounted for change in well-being across all models, mindfulness training consistently promoted positive reappraisal despite an absence of reappraisal instructions, and an exploratory cross-lagged analysis found decentering facilitative of subsequent reappraisal. However, the stress mindset intervention failed to improve well-being relative to control, limiting capacity for causal inference; post hoc analyses, therefore, focused on the more efficacious mindfulness training conditions. The MMT accounted for change in well-being across all levels of analysis, although well-being changes were also supported by direct effects of mindfulness training and decentering, with only partial mediation through the complete MMT pathway. These findings support MMT as a process model for well-being but suggest that decentering and reappraisal only partially account for the salutary effects of well-being interventions. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

A machine learning approach towards the differentiation between interoceptive and exteroceptive attention.

Interoception, the representation of the body's internal state, plays a central role in emotion, motivation and wellbeing. Interoceptive sensibility, the ability to engage in sustained interoceptive awareness, is particularly relevant for mental health but is exclusively measured via self-report, without methods for objective measurement. We used machine learning to classify interoceptive sensibility by contrasting using data from a randomized control trial of interoceptive training, with functional magnetic resonance imaging assessment before and after an 8-week intervention (N = 44 scans). The neuroimaging paradigm manipulated attention targets (breath vs. visual stimuli) and reporting demands (active reporting vs. passive monitoring). Machine learning achieved high accuracy in distinguishing between interoceptive and exteroceptive attention, both for within-session classification (~80% accuracy) and out-of-sample classification (~70% accuracy), revealing the reliability of the predictions. We then explored the classifier potential for 'reading out' mental states in a 3-min sustained interoceptive attention task. Participants were classified as actively engaged about half of the time, during which interoceptive training enhanced their ability to sustain interoceptive attention. These findings demonstrate that interoceptive and exteroceptive attention is distinguishable at the neural level; these classifiers may help to demarcate periods of interoceptive focus, with implications for developing an objective marker for interoceptive sensibility in mental health research.

Ventricular Conduction Stability Noninvasively Identifies an Arrhythmic Substrate in Survivors of Idiopathic Ventricular Fibrillation.

Background Idiopathic ventricular fibrillation (VF) is a diagnosis of exclusion following normal cardiac investigations. We sought to determine if exercise-induced changes in electrical substrate could distinguish patient groups with various ventricular arrhythmic pathophysiological conditions and identify patients susceptible to VF. Methods and Results Computed tomography and exercise testing in patients wearing a 252-electrode vest were combined to determine ventricular conduction stability between rest and peak exercise, as previously described. Using ventricular conduction stability, conduction heterogeneity in idiopathic VF survivors (n=14) was compared with those surviving VF during acute ischemia with preserved ventricular function following full revascularization (n=10), patients with benign ventricular ectopy (n=11), and patients with normal hearts, no arrhythmic history, and negative Ajmaline challenge during Brugada family screening (Brugada syndrome relatives; n=11). Activation patterns in normal subjects (Brugada syndrome relatives) are preserved following exercise, with mean ventricular conduction stability of 99.2±0.9%. Increased heterogeneity of activation occurred in the idiopathic VF survivors (ventricular conduction stability: 96.9±2.3%) compared with the other groups combined (versus 98.8±1.6%; P=0.001). All groups demonstrated periodic variation in activation heterogeneity (frequency, 0.3-1 Hz), but magnitude was greater in idiopathic VF survivors than Brugada syndrome relatives or patients with ventricular ectopy (7.6±4.1%, 2.9±2.9%, and 2.8±1.2%, respectively). The cause of this periodicity is unknown and was not replicable by introducing exercise-induced noise at comparable frequencies. Conclusions In normal subjects, ventricular activation patterns change little with exercise. In contrast, patients with susceptibility to VF experience activation heterogeneity following exercise that requires further investigation as a testable manifestation of underlying myocardial abnormalities otherwise silent during routine testing.