Shock Delivery Research Articles

Performance and Safety of the Extravascular Implantable Cardioverter Defibrillator Through Long-Term Follow-Up: Final Results From the Pivotal Study.

Substernal lead placement of the extravascular implantable cardioverter defibrillator (EV ICD) permits both defibrillation at thresholds similar to those seen with transvenous implantable cardioverter defibrillators and effective anti-tachycardia pacing (ATP) while avoiding the vasculature and associated complications. The global Pivotal study has shown the EV ICD system to be safe and effective through 6 months, but long-term experience has yet to be published. Our aim was to report the performance and safety of the EV ICD system throughout the study. The EV ICD Pivotal study was a prospective, global, single-arm, premarket clinical study. Individuals with a Class I or IIa indication for a single-chamber implantable cardioverter defibrillator per guidelines were enrolled. Freedom from major system- or procedure-related complications and appropriate and inappropriate therapy rates were assessed through 3 years with the Kaplan-Meier method. ATP success was calculated from simple proportions. An implantation was attempted in 316 patients (25.3% female; 53.8±13.1 years of age; 81.6% primary prevention; left ventricular ejection fraction, 38.9±15.4%). Of 299 patients with a successful implantation, 24 experienced 82 spontaneous arrhythmic episodes that were appropriately treated with ATP only (38, 46.3%), shock only (34, 41.5%), or both (10, 12.2%) for a Kaplan-Meier-estimated rate of first any appropriate therapy of 9.2% at 3 years. ATP was successful in 77.1% (37/48) of episodes, and ATP use significantly increased from discharge to last follow-up visit (P<0.0001). Shock therapy was successful in 100% (27/27) of discrete, spontaneous ventricular arrhythmias. The inappropriate shock rates at 1 and 3 years were 9.8% and 17.5%, respectively, with P-wave oversensing the predominant cause. No major intraprocedural complications were reported, and the estimated freedom from system- or procedure-related major complications was 91.9% at 1 year and 89.0% at 3 years. The most common major complications were lead dislodgement (10 events; n=9 patients, 2.8%), postoperative wound or device pocket infection (n=8, 2.5%), and device inappropriate shock delivery (n=4, 1.3%). Twenty-four system revisions were performed as a result of major complications related to the EV ICD system or procedure. From implantation to study completion, the EV ICD Pivotal study demonstrated that a single integrated system with an extravascular lead placed in the substernal space maintains high ATP success, effective defibrillation, and a consistent safety profile. URL: https://www.clinicaltrials.gov; Unique identifier: NCT04060680.

Repetitive grooming behavior following aversive stimulus coincides with a decrease in anterior hypothalamic area activity.

The anterior hypothalamic area (AHA) is a key brain region for orchestrating defensive behaviors. Using in vivo calcium imaging in mice, we observed that AHA neuronal activity increases during foot shock delivery and foot-shock associated auditory cues. We found that following shock-induced increases in AHA activity, a decrease in activity coincides with the onset of grooming behavior. Next, we optogenetically activated the projections from the ventromedial hypothalamus (VMH) to the AHA and observed that photoactivation of the VMH→AHA pathway drives avoidance. Interestingly, repetitive grooming behavior occurs following cessation of stimulation. To identify changes in brain-wide activity patterns that occur due to optogenetic VMH→AHA stimulation, we combined optogenetic stimulation with positron emission tomography (PET) based metabolic mapping. This approach revealed the amygdala as a downstream area activated by the stimulation of this pathway. Our findings show that the rise and fall of AHA neuronal activity triggers repetitive grooming behavior following learned fear and optogenetic stimulation. In addition, activation of the VMH→AHA pathway triggers changes in the activity patterns of downstream brain regions that are reported to be associated with displacement grooming.Significance statement This work identifies an association between grooming behavior and anterior hypothalamic area (AHA) activity patterns. Regardless of whether the activation of the AHA is initiated by shock-associated conditioned fear or optogenetic stimulation of excitatory inputs from the ventromedial hypothalamus, repetitive self-grooming behavior emerges during the post-activation decrease in activity. Further, this work identifies that even in anesthetized mice, AHA activation serves as a trigger for downstream network changes in the amygdala and striatum, which are associated with repetitive behavior. Together, this work positions the anterior hypothalamic area as a potential etiological factor to be considered at the intersection of fear experience and subsequent repetitive behaviors.

Integrating behavioral and neurophysiological insights: High trait anxiety enhances observational fear learning.

Observational fear learning delineates the process by which individuals learn about potential threats through observing others' reactions. Prior research indicates that individuals with high trait anxiety (HTA) manifest pronounced fear responses in direct fear learning scenarios. However, the specific influence of trait anxiety on observational fear learning remains insufficiently explored. This study aimed to fill this gap by examining 64 university students, divided equally between those with HTA and low trait anxiety (LTA), selected from an initial pool of 483 participants. Participants were subjected to observational fear learning tasks, and their behavioral responses, physiological reactions, and brain activations were recorded. Results demonstrated that HTA participants exhibited differentiated skin conductance responses to threat and safety stimuli during the observational fear acquisition phase, notwithstanding prior assurances against shock delivery. Furthermore, during the direct test phase, HTA participants reported significantly elevated fear and shock expectancy ratings for both types of stimuli, in contrast to their LTA counterparts. Neuroimaging data, derived via functional near-infrared spectroscopy (fNIRS) revealed heightened medial prefrontal cortex activation in HTA participants when directly facing threats. This study systematically explores the influence of high trait anxiety on observational fear learning, uncovering that HTA individuals exhibit excessive fear responses. These findings highlight the critical role of trait anxiety as a significant risk factor in the development of anxiety disorders.

Implications of an Individualized Resuscitation Strategy Using Continuous Rhythm and Physiologic Status Assessment During Ongoing CPR.

Prior studies have proposed defibrillator biosignal algorithms which characterize cardiac arrest rhythm and physiologic status. We evaluated whether a novel, individualized resuscitation strategy that integrates multiple ECG and impedance-based algorithms could reduce CPR interruptions and better align rescuer actions with patient-specific physiology. In a retrospective cohort of ventricular fibrillation out-of-hospital cardiac arrests, observed rescuer actions (rhythm analysis, shock delivery, pulse checks, and drug therapy) were compared to hypothetical actions recommended by the proposed individualized strategy. Misdirected drug therapy was defined as either 1) epinephrine when the algorithm predicted a spontaneous pulse or 2) antiarrhythmic during predicted bradyasystole. Clinically avoidable actions included delivering a shock without restoring return of spontaneous circulation (ROSC) and interrupting CPR for pulse assessment when no spontaneous pulse was present. Of 390 cases, 46% survived to hospital discharge. This individualized treatment strategy achieved comparable shock decision accuracy (95% sensitivity, 98% specificity) as observed care while decreasing median CPR interruption for shock from 12 to 6 seconds. The individualized strategy also identified 17% of 597 epinephrine and 9% of 248 antiarrhythmic administrations as misdirected. Following 1334 ventricular fibrillation shocks, the frequency of post-shock ROSC was 4% when its predicted probability was low versus 22% when not. During 1088 pulse checks, pulse was present in 5% when predicted probability of spontaneous pulse was low versus 35% when not. An individualized resuscitation strategy could improve CPR interruption, medication administration, shock delivery, and pulse assessment. Prospective evaluation is required to assess clinical benefit.

The impact of shock therapy on depression development and remote prognosis in cardiac resynchronization therapy recipients.

The aim of this study was to assess the incidence and clinical significance of depression in patients with cardiac resynchronization therapy with an implantable cardioverter-defibrillator (CRT-D). The study was also to evaluate the impact of shock therapy on depression development and long-term prognosis. The prospective study encompassed 396 consecutive heart failure (HF) patients implanted with CRT-D. All patients completed the Beck Depression Inventory (BDI-II) and underwent a psychiatric examination at baseline. 221 patients free of depressive symptoms at baseline were included into the final analysis. The assessment of psychiatric status was routinely repeated every 6 months as well as after the shock delivery. The primary outcome was a composite endpoint of death or hospitalization for HF. During long-term observation (median 37.1 months) 52 (23.5%) patients suffered from an implantable cardioverter-defibrillator (ICD) shock, whereas 48 (21.8%) subjects developed depression. The incidence of new-onset depression was significantly higher in patients after shock delivery (Shock Group), CRT non-responders and subjects with atrial fibrillation. The risk for a composite endpoint was higher in the Shock Group than subjects without an ICD intervention: 57.7% vs. 25.4% and in patients with new-onset depression compared to the population free of this disorder: 62.5% vs. 24.9% (all p < 0.001). New-onset depression (HR 1.7) and an ICD shock (HR 2.1) were strong independent predictors of poor prognosis. Depression is a common mental disorder in CRT-D recipients, that adversely affects long-term prognosis. Subjects suffering from ICD shocks and those with HF progression are at higher risk of experiencing depressive symptoms.

Atrial Tachyarrhythmias With Ultra-Rapid Ventricular Response and Sudden Death in Patients Without Structural Heart Disease.

Sudden cardiac death (SCD) is generally associated with life-threatening ventricular arrhythmias. Supraventricular arrhythmias are an accepted cause of SCD in Wolff-Parkinson-White syndrome and complex congenital heart disease. However, the role of atrial tachyarrhythmias (ATAs) in SCD in patients with structurally normal hearts is unclear. The goal of this study was to present data on resuscitated patients without structural heart disease (SHD), experiencing recurrent implantable cardioverter-defibrillator (ICD) shocks, who share common clinical and electrical features suggesting that ATAs can cause SCD. We describe the clinical characteristics and ICD analysis of syncopal events terminated with shock delivery in 5 young SCD survivors without SHD. Details on the follow-up after ablation of the arrhythmia causing the syncopal episode are also reported. In all patients (4 male, 1 female; median age 23 years; age range 15-47 years), a surface electrocardiogram recording in the resuscitation setting suggested ventricular fibrillation. After the index event, all patients exhibited recurrent arrhythmic syncopal episodes in a setting of elevated adrenergic tone, treated with ICD shocks. ICD interrogation suggested ATAs (atrial fibrillation in 4 patients, atrial tachycardia in 1 patient), conducting to the ventricles at rates approaching 300 beats/min, as the underlying arrhythmia leading to the syncopal events. ATA ablation abolished episodes of arrhythmic syncope and shock delivery in all patients after a median follow-up of 34months. No patient died suddenly during follow-up. Common clinical and electrical features define a distinct entity of SCD caused by ATAs with ultra-rapid ventricular response in otherwise healthy patients. Catheter ablation of the ATA is an effective treatment in these patients.

Decoding threat neurocircuitry representations during traumatic memory recall in PTSD.

The neurocircuitry mechanisms underlying recall of traumatic memories remain unclear. This study investigated whether traumatic memory recall engages neurocircuitry representations that mirror activity patterns engaged during generalized threat stimulus processing in Post Traumatic Stress Disorder (PTSD). Multivariate pattern analysis was used to train 3 decoders. A "trauma" decoder was trained on fMRI patterns during idiographic trauma versus neutral narratives in a sample of 73 adult women with PTSD. A separate cohort of 125 adult participants completed a reward and threat learning task, from which "shock" and "reward loss" decoders were trained on neural patterns during threat or reward outcome delivery, respectively. These decoders were then cross-tested on the alternative datasets, allowing analyses of the degree to which traumatic memory recall engaged neurocircuitry representations that overlap with more general aversive stimuli. Decoders were trained and tested in four networks related to salience processing as well bilateral amygdala and hippocampal masks. The shock decoder trained in a midcingulate / posterior insula network demonstrated elevated predictions for shock during traumatic versus neutral memory recall. Similarly, the trauma decoder made elevated predictions about trauma recall during shock versus no shock delivery across multiple networks related to salience processing. There was no overlap between reward loss decoder predictions and trauma memory recall or vice versa. PTSD participants with elevated re-experiencing symptoms demonstrated the highest engagement of shock activity patterns during trauma memory recall. These results suggest that trauma memory recall engages neurocircuitry representations that overlap with threat, specifically painful, stimulus delivery.

Abstract Su304: The Effect of Time to DC Shock on Return of Spontaneous Circulation in Out-of-Hospital Cardiac Arrest with Recurrent Shockable Rhythm

Objective: The optimal timing for defibrillation attempts in out-of-hospital cardiac arrest (OHCA) patients with recurrent shockable rhythms [ventricular fibrillation (VF) or pulseless ventricular tachycardia (VT)] is uncertain. This study examined the association between "time to DC shock" and the return of spontaneous circulation (ROSC) in OHCA patients with recurrent shockable rhythms. Methods: This was a retrospective analysis of data from the Salt Lake City Fire Department (SLCFD) from 2012 to 2023. Rhythm-filtering technology, used since 2012, enabled real-time and accurate interpretation of cardiac rhythms during CPR, with local protocols allowing early defibrillation for recurrent VF/ pulseless VT cases. Patients who experienced four or five episodes of shockable rhythms and received defibrillation were included. Generalized estimating equation (GEE) analysis was used to evaluate the association between time to shock preceding recurrent defibrillation and ROSC. Results: A total of 142 patients were included, with a mean age of 59.7 ± 15 years; 105 (73.9%) were male, 63 (44.4%) arrested in public locations, and 101 (71.1%) had witnessed arrests. Adjusted GEE analysis revealed that longer time to shock was associated with lower odds of achieving ROSC (OR: 0.81, 95% CI: 0.72–0.93, p = 0.005). Every one-minute delay in defibrillation is predicted to decrease the likelihood of achieving ROSC by 19%. Conclusion: In patients with recurrent shockable rhythms, every one-minute delay in delivering a shock was associated with a statistically significant 19% reduction in the chance of achieving ROSC. This finding highlights the importance of reducing the time to defibrillation in managing recurrent shockable rhythms and suggests reevaluating the current recommendation of two-minute intervals for rhythm check and shock delivery.

KardioNet Digital - a structured care model involving digital tools for intersectoral communication and a patient-focused strategy for treatment of heart failure

Abstract Introduction Inefficiencies and discontinuities in care at the interfaces within Germany's healthcare system, especially between acute and outpatient care, present significant challenges in managing patients with heart failure (HF). The management complexity of HF has increased with the advent of new digital tools, though patient acceptance of these tools remains contentious. The prevention of loss of diagnostic and therapeutic information for this complex disease is crucial for cross-sectoral communication (hospital - office-based cardiologist - general practitioner) and quality of care. Purpose Our goal was to examine the impact of digital app-supported coordination of HF management across different healthcare providers from hospital discharge to the ambulatory sector and to assess patients' acceptance of a structured care program. A patient-focused digital strategy, supported by a Heart Failure Nurse (HFN), aimed to facilitate structured follow-up and patient empowerment, focusing on patient-reported outcomes and experiences (refer to Table 1). Results Out of 401 patients screened during their hospital stay for HF, only 57 (14.9% male, 12.6% female) participated in the KardioNet Digital (KND) program. NYHA classifications were I (3.5%), II (49.1%), III (40.4%), and IV (7.1%); Diagnoses included CMP (26, 45.6%), CAD (19, 33.3%), valvular HF (8, 14.0%), and others (4, 7.0%). The mean age was 55.03 years, with a notable difference in participation based on age (≥70 years: 9.5% male, 33.3% female; &amp;lt;70 years: 90.5% male, 66.7% female). Age was a significant determinant of program participation. Patients who regularly used the app benefited from several features: A total of 35 alerts (17 patients) were triggered for reasons such as bodyweight increase (2kg or more) and device-induced alerts (i.e. false shock delivery, 3x slow-VT, Syncope), leading the HFN to contact the patients. This early intervention prevented rehospitalization due to decompensation of heart failure in 11 patients (64.7%) and addressed device-related alarms for organizing an emergency hospital visit by HFN. Despite substantial incentives, such as support from an HFN and expedited appointments with specialists for follow-up therapy, refusal rates were high (refer to Table 2). Conclusion A structured, digitally supported cross-sectoral care model for heart failure patients can potentially improve care coordination and outcomes. However, the success of such programs critically depends on patient willingness and the seamless integration into existing healthcare structures. Despite valuable incentives, we observed low acceptance of the program. Even among motivated participants (14.1%), there is a significant need for substantial support and education on digital literacy for the widespread implementation of digital tools in real-world settings for the treatment of heart failure.Workflow of structured digital supportReasons for Declining Participation

Between Scylla and Charybdis: Fixed-ratio avoidance response effort and unavoidable shock extinction in humans

Avoidance of potential threat may become maladaptive when it is indiscriminate and resistant to change. Here, we investigated the resistance to change of high and low avoidance response effort when avoidance extinction involved unavoidable presentations of the aversive event (shock) in humans. Following fear conditioning, participants prevented upcoming shock delivery by responding on high (i.e., fixed ratio, FR-20) and low (FR-5) negative reinforcement schedules. Next, noneliminable shock was used for an avoidance extinction procedure whereby responding was followed by, rather than prevented, shock. During a subsequent standard extinction and response prevention test phase, we found that High effort (FR-20) avoidance would be more readily extinguished than Low effort (FR-5) avoidance. It was also predicted that fear, threat expectancy, and psychophysiological (skin conductance) responses would decrease on avoidable trials and increase on unavoidable trials before extinguishing to low levels. It was found that in the final extinction re-test phase when avoidance was possible, responding increased, particularly for low effort cues. Both fear and expectancy remained high. Individual differences on clinically relevant measures of trait anxiety, intolerance of uncertainty and experiential avoidance were associated with greater levels of fear and threat expectancy. Overall, unavoidable shock extinction may hold promise for further translational investigations of avoidance learning, extinction, and clinical treatment development.

Defibrillator Training in the Virtual Setting is Feasible and Improves Medical Student Self-Efficacy; A Pilot Study

Background Management of in-hospital cardiac arrest includes many component skills that require considerable training in order to gain mastery. Practicing defibrillation skills in a simulated setting improves performance and time to shock delivery but is cumbersome and costly. Virtual reality (VR) simulation training may provide an alternative platform to help medical students learn and build confidence in the critical steps required to operate a manual defibrillator. Intervention We performed a pilot study to implement a VR simulation that trains learners on the stepwise operation of a manual defibrillator. Methods We conducted a cross-sectional survey that measured the feasibility, usability, and likeability of a VR simulation among fourth-year medical students at a large urban academic medical center. Secondary outcomes included self-efficacy with operating a defibrillator before and after the VR simulation, and time to defibrillation within the simulation. Results Twenty-six participants completed the VR simulation. The majority of participants found the VR simulation easy to use (71% agreed), liked the experience (96% agreed), found it realistic (87.5% agreed), and would recommend it to their peers (96% agreed). Most students (96%) agreed that the training improved their knowledge of how to use a defibrillator, and all (100%) students agreed that they were more confident than beforehand in using the defibrillator to defibrillate a patient with cardiac arrest. Self-reported knowledge and comfort with using the defibrillator significantly improved from before to after the VR training, as did average time to defibrillation. Discussion VR simulation for defibrillator training is feasible and well-liked by senior medical students and is associated with improved self-perceived knowledge and comfort with using a manual defibrillator.

Effects of pharmacological and environmental manipulations on choice between fentanyl and shock avoidance/escape in male and female rats under mutually exclusive and non-exclusive choice conditions.

Substance use disorders are defined by persistent drug consumption despite adverse consequences. Accordingly, we developed two fentanyl-vs-shock avoidance/escape choice procedures in which male and female rats responded under a fixed-ratio (FR)1:FR1 concurrent schedule of shock avoidance/escape and IV fentanyl under either mutually exclusive or non-exclusive choice conditions. Initial experiments using a discrete-trial procedure determined behavioral allocation between mutually exclusive shock avoidance/escape and different fentanyl doses (0.32-18 μg/kg/infusion; Experiment 1). Shock intensity (0.1-0.7 mA) and shock avoidance/escape response requirement (FR1-16) were also manipulated (Experiment 2). Next, we used a free-operant procedure in which shock avoidance/escape and fentanyl were continuously available under non-exclusive conditions, and response-shock (R-S) interval (30-1000 s) was manipulated (Experiment 3). Finally, we tested the hypothesis that extended-access fentanyl self-administration would produce fentanyl dependence, establish fentanyl withdrawal as an endogenous negative reinforcer, and increase fentanyl choice in both procedures (Experiments 4 and 5). The shock avoidance/escape contingency decreased fentanyl self-administration, and rats consistently chose shock avoidance/escape over fentanyl in both choice conditions. Decreasing shock intensity or increasing shock avoidance/escape response requirement failed to increase fentanyl choice, suggesting that fentanyl and shock avoidance/escape are independent economic commodities. Increasing the R-S interval increased fentanyl choice but failed to increase shock delivery. Extended fentanyl access engendered high fentanyl intake and opioid withdrawal signs but failed to increase fentanyl choice under either choice condition. These results suggest that neither positive fentanyl reinforcement nor negative reinforcement by fentanyl withdrawal is sufficient to reduce shock avoidance/escape-maintained responding and increase foot shock as an adverse consequence.

Effects of Irradiation During Computed Tomography Scanning on the Function of Implantable Cardioverter-defibrillators.

The effect of irradiation during computed tomography (CT) imaging on implantable cardioverter-defibrillators (ICDs) has not been fully evaluated in various settings. The purposes of this study were to evaluate the occurrence of electromagnetic interference (EMI) during CT irradiation in various clinically available ICDs with phantom experiments and to determine the potential risks related to irradiation during CT imaging. Five types of clinically available ICDs from five manufacturers were tested. An ICD was combined with an electrocardiogram (ECG) simulator, mounted in a chest phantom, and subjected to CT imaging. Each ICD was irradiated at the maximal power level (tube voltage, 135 kVp; tube current, 510 mA; rotation time, 1.5 s). EMI was defined as oversensing, ventricular tachycardia/ventricular fibrillation (VT/VF) detection, noise, or shock delivery during CT imaging. For ICDs in which EMI was observed, EMI was then evaluated under 144 different irradiation conditions (tube voltage [four patterns from 80-135 kVp], tube current [six patterns from 50-550 mA], and rotation time [six patterns from 0.35-1.5 s]). Testing was also performed during irradiation at the typical doses in three clinical settings and in two settings with inappropriate irradiation of ICDs due to incorrect setup. Among the five ICDs, a shock was delivered by one ICD manufactured by Medtronic (Minneapolis, MN, USA) due to oversensing during irradiation, which occurred at the maximal power level. No oversensing was observed in other ICDs. In the malfunctioned ICD, oversensing was observed in 134 of 144 irradiation patterns, even at a low power in the ICD. The VF-detection criterion was fulfilled in 20 of 134 tests and was significantly associated with tube voltage, tube current, ration time, and tube voltage × rotation time interaction. Although oversensing was observed in three clinical settings (typical chest CT, CT coronary angiography after coronary artery bypass graft, and dynamic assessment for pleural tumors) and one situation during an incorrect scan range on the chest for head perfusion CT, they were not recognized as tachycardia beats. Oversensing was observed when scans were incorrectly set over the ICD during bolus tracking of contrast-enhanced CT. Maximal power CT imaging induced VT/VF detection and shock delivery in one model of ICD placed in a chest phantom. VT/VF detection was observed when tube voltages were high and irradiation times were longer. Oversensing can occur during inappropriate CT imaging, particularly when slices are positioned over the ICD.

The impact of time to defibrillation on return of spontaneous circulation in out-of-hospital cardiac arrest patients with recurrent shockable rhythms

ObjectiveOptimal timing for subsequent defibrillation attempts for Out-of-hospital cardiac arrest (OHCA) patients with recurrent VF/pVT is uncertain. We investigated the relationship between VF/pVT duration and return of spontaneous circulation (ROSC) in OHCA patients with recurrent shockable rhythms. MethodsWe analyzed data from the Salt Lake City Fire Department (SLCFD) spanning from 2012 to 2023. The implementation of rhythm-filtering technology since 2011 enabled real-time rhythm interpretation during CPR, with local protocols allowing early defibrillation for recurrent/refractory VF/pVT cases. We included patients experiencing four or five episodes of VF and pVT rhythms and employed generalized estimating equation (GEE) regression analysis to examine the association between VF/pVT durations preceding recurrent defibrillation and return of spontaneous circulation (ROSC). ResultsAnalysis of 622 appropriate shocks showed that patients achieving ROSC had significantly shorter median VF/pVT duration than those who did not achieve ROSC (0.83 minutes vs. 1.2 minutes, p = 0.004). Adjusted analysis of those with 4 VF/pVT episodes (N = 142) revealed that longer VF/pVT durations were associated with lower odds of achieving ROSC (odds ratio: 0.81, 95% CI: 0.72–0.93, p = 0.005). Every one-minute delay in intra-arrest defibrillation is predicted to decrease the likelihood of achieving ROSC by 19%. ConclusionEvery one-minute increase in intra-arrest VF/pVT duration was associated with a statistically significant 19% decrease in the chance of achieving ROSC. This highlights the importance of reducing time to shock in managing recurrent VF/pVT. The findings suggest reevaluating the current recommendations of two minutes intervals for rhythm check and shock delivery.

Amiodarone and β-blocker combination therapy versus β-blocker monotherapy for ICD shock prevention: A meta-analysis.

While implantable cardioverter-defibrillator (ICD) shocks are a lifesaving therapy, they can negatively affect the patient's quality of life. Amiodarone is commonly combined with β-blockers (BB) in ICD recipients. However, this combination therapy's efficacy in preventing shocks compared to standard BB monotherapy is not well studied. The aim of this systematic review and meta-analysis is to determine if combined amiodarone and BB therapy improves prevention of ICD shock delivery compared to BB monotherapy. We performed a comprehensive literature search using PubMed, Cochrane, and Web of Science databases, for studies that assess the impact of amiodarone and BB versus BB monotherapy in patients with an ICD. The primary outcome was a total number of ICD shocks delivered by the end of the study period. Four studies: three retrospective studies and one randomized controlled trial (RCT), with a total of 5818 patients with ICDs, were included in the analysis. Follow-up periods ranged from 1 to 5 years. The combined amiodarone and BB group was not associated with a significantly lower number of ICD shocks compared to the BB monotherapy group (OR, 0.76; 95% CI, 0.44-1.31; P=.32). A combination therapy of amiodarone and BB was not associated with any further reduction in ICD shocks, hospitalizations, or mortality. Additional RCTs are recommended to further validate our findings.

Sudden cardiac arrest occurring in temporal proximity to consumption of energy drinks

BackgroundEnergy drinks potentially can trigger life-threatening cardiac arrhythmias. It has been postulated that the highly stimulating and unregulated ingredients alter heart rate, blood pressure, cardiac contractility, and cardiac repolarization in a potentially proarrhythmic manner. ObjectiveThe purpose of this study was to describe our experience regarding sudden cardiac arrest (SCA) occurring in proximity to energy drink consumption in patients with underlying genetic heart diseases. MethodsThe electronic medical records of all SCA survivors with proven arrhythmias referred to the Mayo Clinic Windland Smith Rice Genetic Heart Rhythm Clinic for evaluation were reviewed to identify those who consumed an energy drink before their event. Patient demographics, clinical characteristics, documented energy drink consumption, and temporal relationship of energy drink consumption to SCA were obtained. ResultsAmong 144 SCA survivors, 7 (5%; 6 female; mean age at SCA 29 ± 8 years) experienced an unexplained SCA associated temporally with energy drink consumption. Of these individuals, 2 had long QT syndrome and 2 had catecholaminergic polymorphic ventricular tachycardia; the remaining 3 were diagnosed with idiopathic ventricular fibrillation. Three patients (43%) consumed energy drinks regularly. Six patients (86%) required a rescue shock, and 1 (14%) was resuscitated manually. All SCA survivors have quit consuming energy drinks and have been event-free since. ConclusionOverall, 5% of SCA survivors experienced SCA in proximity to consuming an energy drink. Although larger cohort studies are needed to elucidate the incidence/prevalence and quantify its precise risk, it seems prudent to sound an early warning on this potential risk.

Punishment-induced resurgence

The phenomenon of extinction-induced resurgence is well established, but there is comparatively little experimental evidence for punishment-induced resurgence. Punishment-induced resurgence can by tested by contingent shocks following the alternative response. The purpose of Experiment 1 was to test whether low-intensity shocks, that do not decrease rate of reinforcement, result in resurgence. Four rats served as subjects. Rats were exposed to three sequential conditions: (a) variable-interval (VI) 30-s food delivery for a lever press (target response); (b) VI 30-s food delivery for a nose poke (alternative response) and extinction of the lever press; (c) VI 30-s reinforcement for a nose poke with superimposed VI 60-s shock delivery. In the final condition, shocks increased gradually from 0.1 to 0.5 mA. Experiment 2 evaluated whether an abrupt introduction of a high-intensity shock would result in resurgence. Three rats served as subjects and were exposed to three sequential conditions: (a) VI 30-s food delivery for a lever press; (b) VI 30-s food delivery for a nose poke and extinction of the lever press; (c) continued VI 30-s reinforcement for a nose poke with superimposed VI 60-s 0.6 mA shock delivery. Resurgence was observed in all subjects, including in situations in which rate of responding, but not rate of reinforcement, decreased. The present study provides additional evidence for punishment-induced resurgence, but future studies are warranted to determine the extent to which punishment can produce resurgence with or without decreases in rates of reinforcement.

A fear conditioned cue orchestrates a suite of behaviors in rats.

Pavlovian fear conditioning has been extensively used to study the behavioral and neural basis of defensive systems. In a typical procedure, a cue is paired with foot shock, and subsequent cue presentation elicits freezing, a behavior theoretically linked to predator detection. Studies have since shown a fear conditioned cue can elicit locomotion, a behavior that - in addition to jumping, and rearing - is theoretically linked to imminent or occurring predation. A criticism of studies observing fear conditioned cue-elicited locomotion is that responding is non-associative. We gave rats Pavlovian fear discrimination over a baseline of reward seeking. TTL-triggered cameras captured 5 behavior frames/s around cue presentation. Experiment 1 examined the emergence of danger-specific behaviors over fear acquisition. Experiment 2 examined the expression of danger-specific behaviors in fear extinction. In total, we scored 112,000 frames for nine discrete behavior categories. Temporal ethograms show that during acquisition, a fear conditioned cue suppresses reward seeking and elicits freezing, but also elicits locomotion, jumping, and rearing - all of which are maximal when foot shock is imminent. During extinction, a fear conditioned cue most prominently suppresses reward seeking, and elicits locomotion that is timed to shock delivery. The independent expression of these behaviors in both experiments reveals a fear conditioned cue to orchestrate a temporally organized suite of behaviors.

Relationship between ICD implantation volume and treatment parameters of patients receiving an ICD with remote monitoring.

Both highly specialized heart centres and less specialized hospitals care for patients with implantable ICDs/CRT-Ds with remote monitoring. To investigate potential differences in patient treatment according to centre's ICD implantation volume. Based on their 2012 ICD/CRT-D implantation volume, centres enrolled in the NORDIC ICD trial in Germany were assigned to one of three groups: high- (HV, n= 345), medium- (MV, n= 340) or low-volume (LV, n= 189). The HV-centres had a significant higher CRT-D proportion (41.7%; LV: 36.5%; MV: 23.2%; P𝑔𝑙𝑜𝑏𝑎𝑙< 0.001), significant shorter median procedure duration (49 min; MV: 58 min; LV: 60 min; P𝑔𝑙𝑜𝑏𝑎𝑙< 0.001) but significant longer median hospital stay (4 days; MV and LV: 3 days; P𝑔𝑙𝑜𝑏𝑎𝑙< 0.001) compared to MV- and LV-centres. The X-ray exposure was shorter in MV/HV-centres (MV: 3.4 min; HV: 3.6 min; LV: 5.5 min; P𝑔𝑙𝑜𝑏𝑎𝑙< 0.001). Only 3.5% (LV: 2.6%; HV: 3.5%; MV: 4.1%) patients received at least one delivered inappropriate shock and 2.5% (HV: 2.0%; LV: 2.6%; MV: 2.9%) patients had withheld inappropriate ICD shocks without subsequent inappropriate shock delivery within 24.5 months of median follow-up. Implantation volume-dependent differences were observed in the device selection, procedure duration and x-ray exposure duration. Remote monitoring in combination with adequate response pattern prevented imminent inappropriate shocks in all three groups.

Circadian Mechanisms of Prefrontal Cortex Dependent Memory in Trace Fear Conditioning

Abstract Circadian rhythms are physiological and behavioral processes that follow an approximately 24-hour cycle. They arise from internal biological clocks, which are synchronized mainly by environmental light. Fear-based mental disorders, such as post-traumatic stress disorder (PTSD), are associated with disruptions in circadian rhythms. Understanding this relationship is important for developing more effective treatments. In delayed fear conditioning, the most common form of fear conditioning, the presentation of a tone (conditioned stimulus) is paired with a foot shock (unconditioned stimulus), causing experimental subjects to associate tone presentation with shock delivery. In trace fear conditioning, a brief temporal gap occurs between the tone and foot shock, causing different brain circuits to get engaged. Past work in our laboratory and others has shown circadian rhythms in the extinction of delayed conditioned fear. More recent work in our laboratory has shown that the recall of trace conditioned fear similarly exhibits a rhythm, with recall being stronger during the inactive phase of the rest-activity cycle. The purpose of this experiment was to test whether stronger recall for trace fear is dependent on the time of conditioning or the time of recall. Additionally, I analyzed brain tissue to assess whether rhythms in behavior were reflected in circadian and activity-dependent gene expression in the prefrontal cortex. Rats were fear conditioned at either ZT4 (the inactive phase) or ZT16 (the active phase) and then underwent fear recall after 24 h (same time of day as training), 36 h (opposite time of day as training), and 48 h (same time of day as training). Results showed an interaction between the time of training and the interval between training and testing for trace fear conditioning. Specifically, ZT4 rats showed strong fear recall at all intervals, whereas ZT16 rats showed increased recall over a greater recall interval. The mRNA expression of Per1, a key circadian gene, showed opposite results, with the ZT4 expression decreasing over recall intervals and ZT16 expression remaining constant. For c-Fos, an immediate early gene whose expression is used to approximate recent neuronal activation, mRNA expression tended to be higher at ZT16 regardless of the time of training. Notably, however, ZT4-36 h rats showed higher c-Fos expression than ZT16-36 h rats in the infralimbic but not prelimbic prefrontal cortex, suggesting differential engagement of the prelimbic cortex during trace fear recall. These results suggest that learned fear may be consolidated more quickly during the inactive phase, leading to signs of prefrontal engagement at later recall intervals during the active phase. In turn, these findings pave the way for circadian assessments, treatments, and prevention for fear-based mental disorders in clinical settings. Lay Summary Circadian rhythms are physiological and behavioral processes that follow an approximately 24-hour cycle. They arise from internal biological clocks, which are synchronized mainly by environmental light. Fear-based mental disorders, such as post-traumatic stress disorder (PTSD), are associated with disruptions in circadian rhythms. Understanding this relationship is important for developing more effective treatments. In trace fear conditioning, a brief temporal gap occurs between the presentation of the tone (conditioned stimulus) and foot shock (unconditioned stimulus). Recent work in our laboratory has shown that the recall of trace conditioned fear exhibits a rhythm, with recall being stronger during the inactive phase of the rest-activity cycle. The purpose of this experiment was to test whether stronger recall for trace fear is dependent on the time of conditioning or the time of recall. Additionally, I analyzed brain tissue to assess whether time-of-day differences in behavior were reflected in circadian and activity-dependent gene expression in the prefrontal cortex. Rats were fear conditioned at either ZT4 (the inactive phase) or ZT16 (the active phase) and thenunderwent fear recall after 24 h, 36 h, and 48 h. Results showed that for behavior the time of testing for trace fear conditioning, ZT4, is what was the most important, and ZT16 rats increase in freezing behavior over a time interval. Per1 mRNA expression in the PFC showed opposite results with the ZT4 expression decreasing over recall intervals and ZT16 expression remaining constant. The time of recall interval was the most important for c-Fos neuronal activity in the PFC. These results show that learned fear behavior is expressed more during the inactive phase training, ZT4, but the neuronal circuitry shows more memory consolidation during the ZT16 recall intervals. These findings suggest that learned fear may be expressed differently through underlying neuronal circuits than through behavior in clinical settings. For the full text, please visit https://scholar.colorado.edu/concern/undergraduate_honors_theses/x059c890d.