Lower Heart Research Articles

The Effect of Immersive Virtual Reality on Dental Anxiety and Intraoperative Pain in Adults Undergoing Local Anesthesia: A Randomized Clinical Trial

Aims: This study assessed the effect of immersive virtual reality (IVR) on anxiety and intraoperative pain in adult patients undergoing dental extractions with local anesthesia. Methods: In a single-blind, randomized clinical trial from September 2022 to December 2023 at a private dental clinic, 190 patients with dental anxiety were randomly assigned to either an IVR or a control group. Primary outcomes—dental anxiety and perioperative pain—were measured using the State-Trait Anxiety Inventory (STAI), Modified Dental Anxiety Scale (MDAS), and Visual Analogue Scale (VAS) before and after the procedure. Secondary outcomes included heart rate (HR), diastolic blood pressure (DBP), and systolic blood pressure (SBP), recorded at various stages. Results: The IVR group showed significant reductions in total anxiety, state anxiety, and MDAS scores compared to the control group (p < 0.001). Pain intensity was also lower in the IVR group (p = 0.03). Additionally, heart rate (HR), systolic blood pressure (SBP), and diastolic blood pressure (DBP) were consistently lower in the IVR group across different stages. Post anesthesia, the IVR group showed notably lower mean SBP and DBP values (p < 0.001). After surgery, the IVR group also showed lower HR (p = 0.01), SBP (p < 0.001), and DBP (p < 0.001) compared to the control group. Conclusions: IVR significantly reduced STAI, STAI-S, and MDAS scores and decreased intraoperative pain compared to the control group.

Relationship Between Heart Rate and Perceived Stress in Intensive Care Unit Residents: Exploratory Analysis Using Fitbit Data.

Intensive care unit (ICU) residents are exposed to high stress levels due to the intense nature of their work, which can impact their mental health and job performance. Heart rate measured through wearable devices has the potential to provide insights into residents' self-reported stress and aid in developing targeted interventions. This exploratory study aims to analyze continuous heart rate data and self-reported stress levels and stressors in ICU residents to examine correlations between physiological responses, stress levels, and daily stressors reported. A secondary data analysis was conducted on heart rate measurements and stress assessments collected from 57 ICU residents over a 3-week period using Fitbit Charge 3 devices. These devices captured continuous physiological data alongside daily surveys that assessed stress levels and identified stressors. The study used Spearman rank correlation, point-biserial correlation analysis, 2-tailed paired t tests, and mixed-effect models to analyze the relationship between heart rate features and stress indicators. The findings reveal complex interactions between stress levels and heart rate patterns. The correlation analysis between stress levels and median heart rate values across different percentile ranges showed that lower percentile heart rates (bottom 5%, 10%, 25%, and 50%) had modest correlations with stress, whereas higher percentiles (top 50%, 25%, 10%, and 5%) did not correlate significantly (all P>.05). The 2-tailed paired t test indicated significant differences in stress levels reported in midday versus end-of-day surveys (P<.001), although these changes in stress levels were not consistently reflected in heart rate patterns. Additionally, we explored and found that stressors related to "other health" issues had the highest positive correlation with stress level changes from midday to end-of-day surveys. However, the weak effect of these stressors on peak heart rate suggests that their impact on physiological measures like heart rate is not yet clear. According to our mixed-effects model, stress levels significantly influenced heart rate variations when hierarchical data were taken into account (P=.03), meaning that as the stress level increased, there was a significant increase in mean heart rate. This study highlights the complexity of using heart rate as an indicator of stress, particularly in high-stress environments like the ICU. Our findings suggest that while heart rate is found to correlate with self-reported stress in the mixed-effect model, its impact is modest, and it should be combined with other physiological and psychological measures to obtain a more accurate and comprehensive assessment of residents' stress levels.

Neurogenic Aging After Spinal Cord Injury: Highlighting the Unique Characteristics of Aging After Spinal Cord Injury

Emanating from several decades of study into the effects of the aging process after spinal cord injury (SCI), “accelerated aging” has become a common expression as the SCI accelerates the onset of age-related pathologies. However, the aging process follows a distinct trajectory, characterized by unique patterns of decline that differ from those observed in the general population without SCI. Aging brings significant changes to muscles, bones, and hormones, impacting overall physical function. Muscle mass and strength begin to decrease with a reduction in muscle fibers and impaired repair mechanisms. Bones become susceptible to fractures as bone density decreases. Hormonal changes combined with decreased physical activity accelerate the reduction of muscle mass and increase in body fat. Muscle atrophy and skeletal muscle fiber type transformation occur rapidly and in a unique pattern after SCI. Bone loss develops more rapidly and results in an increased risk of fractures in body regions unique to individuals with SCI. Other factors, such as excessive adiposity, decreased testosterone and human growth hormone, and increased systemic inflammation, contribute to a higher risk of neuropathically driven obesity, dyslipidemia, glucose intolerance, insulin resistance, and increasing cardiovascular disease risk. Cardiorespiratory changes after SCI result in lower exercise heart rates, decreased oxygenation, and mitochondrial dysfunction. While it is important to acknowledge the accelerated aging processes after SCI, it is essential to recognize the distinct differences in the aging process between individuals without physical disabilities and those with SCI. These differences, influenced by neuropathology, indicate that it may be more accurate to describe the aging process in individuals with chronic SCI as neurogenic accelerated aging (NAA). Research should continue to address conditions associated with NAA and how to ameliorate the accelerated rate of premature age-related conditions. This review focuses on the NAA processes and the differences between them and the aging process in those without SCI. Recommendations are provided to help slow the development of premature aging conditions.

Visual Indicator for Intradialytic Hypotension Prediction Using Variation and Compensation of Heart Rate

Background: To date, most intradialytic hypotension (IDH) studies have proposed technologies to comprehensively predict the occurrence of IDH using the patient’s baseline information and ultrafiltration (UF) information, but it is difficult to apply the technologies while identifying the patient’s condition in real time. Methods: In this study, we propose an IDH indicator that uses heart rate (HR) change information to identify the patient’s condition in real time and visually shows whether IDH has occurred. The data used were collected from 40 dialysis patients in a clinical trial conducted in the Artificial Kidney Unit at Yeungnam University Medical Center, Korea, from 18 July to 29 November 2023. Results: The IDH indicator infers changes in the patient’s blood pressure during dialysis by analyzing the upper and lower maximum HRs based on the real-time average HR. Medical staff can respond to IDH in real time by looking at the IDH indicator, which visually expresses changes in the patient’s HR. In addition, we propose a multilayer perceptron structure that inputs upper and lower maximum HR information based on the average HR for the time interval accumulated in real time. In learning using 40 min of data up to 5 min before IDH occurred, models using two and five layers showed excellent performance, with accuracy of 88.6% and 85.2%, respectively. Conclusions: By combining IDH visual indicators and the multi-layer perceptron method, medical staff can effectively respond to IDH in real time.

Correlation of the triglyceride-glucose index and heart rate with 28-day all-cause mortality in severely ill patients: analysis of the MIMIC-IV database

BackgroundResearch has identified a link between the triglyceride-glucose index (TyG-i) and the risk of mortality in severely ill patients. However, it remains uncertain if the TyG-i affects mortality by influencing heart rate (HR).MethodsThis study enrolled 3,509 severely ill participants from the Medical Information Mart for Intensive Care (MIMIC-IV) database who had triglyceride, glucose, and HR data upon entering the ICU. Cox regression models were applied to estimate the effect of the TyG-i and HR on 28-day all-cause mortality (ACM) and 28-day in-hospital mortality (IHM). Additionally, Kaplan-Meier (K-M) survival analysis was employed to explore outcome variations among different patient groups. The association of the TyG-i with HR, Sequential Organ Failure Assessment (SOFA) score, and Simplified Acute Physiology Score (SAPS) II was explored through linear regression analysis. Subgroup analysis explored potential interactions among patient characteristics, while sensitivity analysis gauged the robustness of the findings. Additionally, mediation analysis was conducted to assess whether elevated HR acts as an intermediary factor linking the TyG-i to both 28-day ACM and 28-day IHM.ResultsDuring the 28-day follow-up, 586 cases (16.7%) died from all causes, and 439 cases (12.5%) died during hospitalisation. Cox results showed that individuals with a heightened TyG-i and elevated HR had the highest 28-day ACM (Hazard Ratio 1.70, P-value below 0.001) and 28-day IHM (Hazard Ratio 1.72, P-value below 0.001) compared to those with a reduced TyG-i and HR. The K-M curves showed that individuals with low TyG-i and low HR had the lowest incidence of 28-day ACM and 28-day IHM. The linear analysis results evidenced that the TyG-i was independently connected to HR (beta = 3.05, P-value below 0.001), and the TyG-i was also independently associated with SOFA score (beta = 0.39, P-value below 0.001) and SAPS II (beta = 1.79, P-value below 0.001). Subgroup analysis revealed a significant association in participants without hypertension, the interaction of an elevated TyG-i and HR strongly correlated with a higher 28-day death risk (interaction P-value below 0.05). Furthermore, HR mediated 29.5% of the connection between the TyG-i and 28-day ACM (P-value = 0.002), as well as 20.4% of the connection between the TyG-i and 28-day IHM (P-value = 0.002).ConclusionFor severely ill patients, the TyG-i is distinctly correlated with HR, and elevated levels of both are strongly connected to greater 28-day ACM and 28-day IHM risks, especially in patients without hypertension. Furthermore, elevated HR mediates the connection between the TyG-i and 28-day mortality.

Safety of direct oral anticoagulants in patients with atrial fibrillation aged 80 years and older: clinical risk factors

BACKGROUND: Direct oral anticoagulants (DOACs) are associated with bleeding, particularly in the geriatric population. Most studies focus on predicting major bleeding, but clinically relevant non-major bleeding (CRNMB) is equally important in practice. АIM: To assess the ability of clinical factors to predict the risk of CRNMB with the use of DOACs in patients with atrial fibrillation (AF) aged 80 years and older. MATERIALS AND METHODS: A total of 367 patients on DOACs with non-valvular AF aged 80 years and older were evaluated; the median age was 84 [82; 88] years. Key characteristics of the groups were analyzed, including gender, age, and body mass index. CHA2DS2-VASc and HAS-BLED scales were used to assess the risk of ischemic stroke and bleeding, respectively. Comorbidities, Charlson Comorbidity Index, and risk factors of chronic non-communicable diseases were considered. In addition, number of medications taken, physical examination data, history of atherosclerosis, and laboratory test results were collected. RESULTS: In univariate analysis, significant risk factors for the development of CRNMB with all DOACs included higher walking frequency (p=0.022), lower heart rate (p=0.08), and history of gastric and duodenal ulcer [odds ratio 5.34; 95% confidence interval (CI) 2.31–12.0; p 0.001]. In multivariate analysis, a model for predicting CRNMB was developed using age, type of DOAC, liver disease, acute cerebrovascular accident, history of gastric and duodenal ulcer as predictors. The resulting model had a predictive accuracy of 62.6% (95% CI 57.4–67.6), a sensitivity of 66.5% (95% CI 59.4–73.1), and a specificity of 58.2% (95% CI 50.4–65.7). CONCLUSION: The study identified specific modifiable, potentially modifiable, and non-modifiable risk factors for developing CRNMB in AF patients aged 80 years and over taking DOACs. An electronic system to support medical decision making, risk factor management, and public quality of life can be created using results of the study.

Erector spinae plane block (ESPB) enhances hemodynamic stability decreasing analgesic requirements in surgical stabilization of rib fractures (SSRFs)

ObjectiveTo evaluate the efficacy of erector spinae plane block (ESPB) on intraoperative hemodynamic stability, opioid and inhalation anesthetic requirements and postoperative analgesic effects in patients undergoing surgical stabilization of rib fractures (SSRFs).MethodsWe retrospectively reviewed 173 patients who underwent surgical stabilization of rib fractures between May 2020 and December 2023. The patients were allocated into the ESPB group or the control group. Demographic data, intraoperative hemodynamic parameters, total intraoperative opioid consumption, the average minimum alveolar concentration (MAC) of inhalational anesthetics, postoperative simple analgesics and opioid consumption and the length of hospital stay were included in the analysis.ResultsCompared with the control group, the ESPB group had a lower heart rate (HR) in the first 90 min after surgical incision and lower systolic blood pressure (SBP) and mean arterial pressure (MAP) at the beginning of surgery. Intraoperatively, a notable reduction in fentanyl consumption was observed in the ESPB group (p = 0.004), whereas no significant difference was observed in the average MAC of inhalational agents (p = 0.073). Postoperatively, the ESPB group required fewer doses of simple analgesics in the first 24 h (p < 0.001) and 48 h (p = 0.029). No statistically significant difference in the length of hospital stay (p = 0.608) was observed between the groups.ConclusionESPB was shown to enhance intraoperative hemodynamic stability, reduce opioid consumption and decrease postoperative analgesic consumption in patients who underwent SSRF. These results suggest that ESPB may serve as a valuable component of multimodal analgesia protocols for SSRF. Larger prospective studies are warranted to confirm the results and evaluate long-term outcomes.

Sex hormones and reproductive factors with cardiac arrhythmia and ECG indices: a mendelian randomization study

BackgroundSex is a determinant of the incidence and etiology of arrhythmia. Observational and basic studies suggest that sex hormones are essential in this process; however, the relationship between sex hormones and arrhythmia remains unclear. Mendelian randomization (MR) was used to investigate the causal relationships between sex hormone levels, arrhythmia, and electrocardiographic (ECG) indices.MethodsLarge genome-wide association studies (GWAS) data on sex hormones, stratified by sex, from the UK biobank consortium, were used as exposure data, and data on atrial fibrillation (AF), atrioventricular block, sick sinus syndrome, paroxysmal tachycardia, and ECG indices were obtained from the FinnGen consortium and summarized large GWAS data. Inverse variance weighting or wald odds was used as the primary analytical method, and weighted medians and MR-Egger regression were used for complementary analyses. The results of the MR of sex hormones and AF from different sources were analyzed using a meta-analysis. Summary-data-based MR analysis was utilized to explore the relationship between sex-hormone related drugs and arrhythmia.ResultsIn men, genetically predicted higher estradiol concentrations were associated with a lower risk of AF (odds ratio: 0.908 [0.852–0.967]; p = 0.0029], whereas genetically predicted higher concentrations of total testosterone were associated with lower heart rate variability. Sex hormones showed no association with atrioventricular block, sick sinus syndrome, paroxysmal tachycardia, resting heart rate, P wave duration, P wave terminal force in lead V1 [PTFV1], PR interval, QRS duration, QTc [QT interval corrected by heart rate], ST duration, spatial [spQRSTa] and frontal [fQRSTa] QRS-T angles in males. In females, there was no significant evidence that sex hormones are associated with arrhythmias or ECG indices.ConclusionIn this study, we identified a potential causal relationship between estradiol and the risk of AF in males. However, there was no significant association between sex hormones and either arrhythmias or ECG indices in females. These results suggested that sex hormones may play a limited role in cardiac arrhythmias, which requires further verification.

Changes in Biomarkers of Inflammation and Oxidative Status in Dogs Subjected to Celiotomy or Video-Assisted Ovariohysterectomy.

We evaluated the surgical stress response of dogs undergoing three ovariohysterectomy (OVH) techniques. Twenty-nine healthy females were allocated into groups: celiotomy and ligature (CelioSut), celiotomy and bipolar energy (CelioBip), and a video-assisted technique using two portals and bipolar energy (VidBip). Clinical evaluation was performed, and the following blood analyses were determined: acute phase proteins (C-reactive protein and haptoglobin), white blood cell counting (WBC), and biomarkers of oxidative status. The VidBip required more time despite a smaller incision, lower heart rate, and earlier feeding and urination. All groups had high white blood cells counts; the C-reactive protein (CRP) levels peaked at 6 and 12 h in all groups and was higher in the CelioBip and VidBip groups compared to CelioSut; haptoglobin concentrations peaked at 48 h in all groups and increased in dogs of the CelioSut group. Trolox equivalent antioxidant capacity, ferric reducing ability of plasma, cupric reducing antioxidant capacity, and advanced oxidation protein were not significantly different among the groups or time points. Total thiol concentrations were lower in CelioBip and CelioSut groups. All surgical techniques induced an inflammatory and oxidative stress response, but the video-assisted technique produced early clinical recovery. The bipolar device produces fewer disturbances than suspensory ligament rupture and ligature.

The effect of the Yakson and Gentle Human Touch methods applied to preterm infants during endotracheal aspiration on pain, comfort, and physiological parameters

BackgroundPreterm infants in the neonatal intensive care unit are exposed to various painful procedures; thus, different non-pharmacological pain control techniques are used to alleviate pain. ObjectivesThe aim of this study is to determine the effect of Yakson and Gentle Human Touch (GHT) methods during endotracheal suctioning on pain, comfort, and physiological parameters response in preterm infants. DesignA randomised controlled crossover trial. SettingThis study was conducted in the neonatal intensive care unit between July 2022 and June 2023. MethodsThirty infants were included in this study based on inclusion criteria. The samples randomly received a sequence of suctioning with Yakson and GHT and routine care. Neonatal Pain Agitation and Sedation Scale (N-PASS) and COMFORTneo were used to collect the data. ResultsThe pain and comfort scores of preterm infants who received GHT and Yakson touch during and after endotracheal suctioning were statistically significantly lower than the infants in the routine care (p < 0.001). It was determined that the difference was in favour of the Yakson group (p < 0.001). The infants who received GHT and Yakson application had lower heart rates and higher oxygen saturation levels after the application compared to the control group (p < 0.001). ConclusionThe application of Yakson and GHT during endotracheal aspiration in preterm infants has been found to be effective in pain and comfort management, as well as in the regulation of physiological parameters.

Electrocardiographic Characteristics of Brugada Syndrome Type I During Exercise Stress Test.

Brugada syndrome (BS) is a genetic channelopathy characterized by an increased risk of sudden cardiac death (SCD) in the absence of structural heart disease. Prognostic stratification is necessary to determine which patients are candidates for implantable cardioverter defibrillator (ICD). The present study aims to evaluate EKG changes during exercise stress tests in patients with BS and to identify any poor prognosis variables. This was an observational, case-control study. Three comparison groups were created: patients with Type 1 BS with or without prior arrhythmic events (BE and BNoE subgroups) and age- and sex-matched healthy individuals. Patients underwent EST and electrocardiographic variables were analyzed. The study recruited 36 patients with type 1 BS, 12 with prior Event (BE) and 24 without (BNoE). Patients in the BE group, in all postexercise recordings, had lower heart rates, notably in the first minute. A significant difference was also observed in the HR drop in the recovery phase, with a greater drop in relation to maximum HR in the first minute in the group of patients who had events. BS patients with prior events had a lower capacity to increase heart rate at peak effort and a greater proportional drop in the recovery phase. No relationship was observed between the occurrence of arrhythmic events and ST-segment elevation during the exercise test.

Investigating heart rate responses of children to active travel: a mixed effects modeling analysis

BackgroundThe active travel concept has gained recognition as an effective method to enhance physical activity in children’s everyday mobility. Yet, there is a notable gap of quantitative evidence on its direct impacts, especially regarding physiological outcomes that can concretely demonstrate its influences on physical intensity and overall health of children.MethodsThis study investigates the effects of active travel on children, focusing on trip-level physiological responses, specifically heart rate. Through a mixed survey design, we obtained a repeated-measures dataset from a cohort of 73 children (average age 13) across three Austrian secondary schools, each observed for 7 days. By applying mixed effects modelling approach, both fixed and random effects to children’s heart rates were explored.ResultsAccording to results from developed mixed linear models (maximum R2 = 0.22), it revealed a significant positive association between active travel mode(s) engagement and heightened physiological responses (Low, Medium and High active level of trip compare to None: β = 1.81, 5.01 and 8.34, t-value = 4.70, 10.29 and 21.34), indicating that increased usage of active travel modes led to elevated heart rate values. Additionally, subjective perceptions also played an important role in influencing children’s physiological responses. Feelings of exhausted, anxiety, and stress contributing to a higher heart rate (β = 14.79, 16.69 and 1.99, t-value = 20.42, 5.67 and 3.0), while unhappiness was associated with a lower heart rate (β = -5.96, t-value = -14.62). Effects of social interactions were also found during the trip. The presence of adults was associated with a calming effect (β = -1.92, t-value = -5.72), whereas solo travel resulted in lower heart rate compared to travel with peers (β = -1.95, t-value = -6.59).ConclusionOur article innovatively employs mixed survey methods and heart rate data to quantitatively demonstrate the positive association between engagement in active travel modes and heightened physiological responses in children, elucidating the intricate interplay of subjective perceptions and social interactions during trips, thus offering valuable insights into the health implications of active travel at a trip level. Future research will keep on leveraging survey and experimental methods.

Timolol Maleate Microspheres: An Ingenious Carrier for Sustained Release Antihypertensive Formulation

Background: Timolol maleate is classified as a BCS Class I drug and functions as a non-selective β-adrenergic receptor blocker. Its ability to lower heart rate and cardiac output has led to its widespread use in the treatment of hypertension. Objective: Timolol maleate has a short half-life and is rapidly cleared from the body, which limits its therapeutic effectiveness, requiring frequent dosing and potentially affecting patient adherence. To overcome these challenges, sustained-release microspheres of Timolol maleate were developed using the ion gelation method. Method: The ion gelation technique was employed to create the microspheres due to its various advantages, including ease of use, scalability and gentle processing conditions. Results: All batches exhibited a comparatively lower swelling index in 0.1M HCl (pH 1.2) than in SIF (pH 6.8). It was observed that increasing the concentration of sodium alginate resulted in higher drug content. The microspheres were sized between 400 and 900 μm and demonstrated excellent flow characteristics. An optimized batch achieved an entrapment efficiency of 88.83% and released 92.15% of the drug over 7 hrs. Furthermore, stability studies conducted according to ICH Q1A(R2) for 3 months at 5±3°C and 25±2°C/60±5% RH indicated no significant changes in evaluation parameters. Conclusion: The optimized Timolol maleate-loaded microspheres effectively provided sustained drug release through the membrane over 7 hrs. This study contributes to the development of improved drug delivery systems for better hypertension management, addressing the unmet needs in patient compliance. Keywords: Timolol Maleate, Microspheres, Ion gelation method, Sodium alginate, Calcium chloride, Sustained release, Hypertension

Safety and Efficacy of opioid-sparing Anesthesia Compared with Traditional opioid-anesthesia

Objectives: The rationale of adoption opioid sparing anesthesia (OSA) is to achieve perioperative analgesia with a minimal amount of opioid combined to non-opioid adjuvants during and after surgery, namely multimodal anesthesia. The OSA approach was originally developed to overcome the known complications of opioid-based anesthesia (OA) and the present scoping review (ScR) aims at providing the clinical evidence of safety and efficacy of OSA with respect to OA. Methods: This ScR is mainly focused on studies presenting evidence on the safety and efficacy of OSA versus OA. PubMed, EMBASE databases were utilized to find relevant studies. Search strategy included the following keywords: “opioid sparing anesthesia complications, opioid sparing anesthesia efficacy, opioid sparing anesthesia safety”. The findings from the 25 included studies were categorized into the following subsections: article characteristics, goals of the studies, OSA protocols, and surgical settings analyzed. Results: In the 25 reviewed studies, evidence related to the impact of OSA versus OA was considered. Intraoperative safety and efficacy endpoints include hemodynamic stability and anesthetic/analgesic requirements. Postoperative endpoints include early cognitive dysfunction, opioid-induced bowel disorder, the physical status of mothers and newborns after labor and emergency cesarean, systemic immune and inflammation modifications, postoperative recovery, in-hospital and long-term opioid requirement, early postoperative pain, chronic postsurgical pain. The studies reported a lower intraoperative mean arterial pressure and heart rate fluctuations when α2 agonists are adopted, while no differences were recorded for other complication rates. Analysis of OSA approaches for the postoperative conditions includes α2 agonists, NMDA receptor blocking agents, gabapentinoids, nefopam hydrocloride and locoregional anesthesia techniques with a positive impact on most of the endpoints considered. Discussion: The clinical implementation of OSA encompasses the perioperative use of non-opioid drugs and locoregional anesthesia techniques. The reviewed studies reported OSA as a feasible approach to reduce opioid-related complications with no impact on patient’s safety.

Abstract 4135211: Children with the D801N Variant of the ATP1A3- Encoded Sodium-Potassium ATPase Alpha-3 Subunit Demonstrate Paradoxical QT Response to Bradycardia and Increased Ventricular Arrhythmia Risk

Introduction: Alternating hemiplegia of childhood (AHC) is a rare condition most frequently caused by mutations in ATP1A3, encoding for the alpha-3 subunit of Na + /K + -ATPase, and D801N is the most common variant. Individuals with ATP1A3-D801N have shorter corrected QT (QTc) than those with other variants and can experience ventricular arrhythmias following bradycardia; however, the mechanism of why this occurs is unknown. Goals: To analyze how QT and QTc change with heart rate in ATP1A3-D801N compared to healthy individuals. Hypothesis: Individuals with ATP1A3-D801N have increased shortening of QT and QTc at lower heart rate. Methods: In this retrospective observational study, patients seen for evaluation of AHC at Duke University Medical Center were categorized by genotype: ATP1A3-D801N, ATP1A3 non-D801N single nucleotide variant, ATP1A3 loss-of-function variant, and genotype negative. A cohort of matched healthy children was also compiled. We collected average heart rate, QT, and QTc measurements over 5-minute intervals from Holter recordings using HScribe TM software and conducted manual blinded validation to ensure accuracy. We then used linear regression to investigate the relationship between heart rate, QT, and QTc. Results: The cohort consisted of 44 patients with ATP1A3 -related phenotypes with 81 total Holter recordings (52.27% female; mean age at first Holter 8.04 years), compared to 36 healthy individuals with 57 total Holter recordings (52.78% female; mean age at first Holter 9.84 years). Patients with ATP1A3-D801N showed diminished prolongation of QT with decreasing heart rate, manifested as a reduced mean slope for heart rate vs QT compared to healthy (-0.85 ± 0.46 vs -1.52 ± 0.42, p&lt;0.0001). This blunted QT response resulted in paradoxical shortening of QTc at lower heart rate, demonstrated by an increased mean slope for heart rate vs QTc compared to healthy (0.80 ± 0.51 vs 0.22 ± 0.43, p&lt;0.0001). Further, patients with ATP1A3- related phenotypes and very short baseline QTc showed increased shortening of QT and QTc at lower heart rate compared to those with normal QTc (p=0.0025 and p=0.0013, respectively). Conclusions: Children with AHC and ATP1A3-D801N demonstrate a paradoxical shortening of QT and QTc with slowing of heart rate. The impaired prolongation of QT and resultant further shortening of QTc increase the risk of arrhythmia. We put this forward as a novel mechanism of sudden cardiac arrest in patients with ATP1A3 mutations.

Abstract 4137186: No Room for Chronotropic Incompetence in Living Fontan Patients: Enhanced Heart Rate Increase in Response to Exercise to Compensate Low Stroke Volume Reserve

Background: Fontan patients reveal decreased peak exercise performance in combination with low peak heart rate (HR), which is frequently interpreted as chronological incompetence. This is counterproductive as HR increase has to be enhanced to compensate limited stroke volume increase in Fontan physiology. Methods: Cardiopulmonary exercise testing (CPET) data in asymptomatic Fontan patients and age-matched control subjects were retrospectively studied. Peak and submaximal CPET parameters were obtained by cycle ergometer. Chronotropic capacity was assessed by peak HR/peak [WR/kg] and submaximal slope of HR/[work rate (WR)/kg] (ΔHR/Δ[WR/kg]) for males and females, separately. Results: Table 1 presents CPET data of Fontan patients (51) and controls (65). Fontan patients showed significantly lower peak HR, peak WR, peak oxygen consumption (VO2)/kg, %predicted maximum VO2, and peak oxygen pulse (pOP)/kg than controls in both sexes whereas peak HR/peak [WR/kg] was significantly higher in Fontan patients, indicating higher HR at the maximum effort in Fontan patients than in controls. Fontan patients showed higher ΔHR/Δ[WR/kg], a marker for HR-dependency, and lower Δ[VO2/kg]/ΔHR, a surrogate of stroke volume, suggesting higher HR was compensating lower stroke volume during submaximal phase of exercise in Fontan patients. Figure 1 demonstrates a linear relationship between ΔHR/ΔWR and peak HR/peak WR in both sexes. Male Fontan patients revealed a comparable trend with controls, whereas female Fontan patients showed higher HR increase at the peak exercise effort than controls with the same ΔHR/ΔWR, suggesting more limited stroke volume reserve than male Fontan patients. Conclusions: Fontan patients showed higher HR-response to exercise than controls in both sexes due to limitation in stroke volume increase. Our data indicate that lower peak HR in Fontan patients results from early exhaustion due to limited stroke volume reserve rather than primary chronotropic incompetence.

Pupil size correlates with heart rate, skin conductance, pulse wave amplitude, and respiration responses during emotional conflict and valence processing.

Pupil size is a non-invasive index for autonomic arousal mediated by the locus coeruleus-norepinephrine (LC-NE) system. While pupil size and its derivative (velocity) are increasingly used as indicators of arousal, limited research has investigated the relationships between pupil size and other well-known autonomic responses. Here, we simultaneously recorded pupillometry, heart rate, skin conductance, pulse wave amplitude, and respiration signals during an emotional face-word Stroop task, in which task-evoked (phasic) pupil dilation correlates with LC-NE responsivity. We hypothesized that emotional conflict and valence would affect pupil and other autonomic responses, and trial-by-trial correlations between pupil and other autonomic responses would be observed during both tonic and phasic epochs. Larger pupil dilations, higher pupil size derivative, and lower heart rates were observed in the incongruent condition compared to the congruent condition. Additionally, following incongruent trials, the congruency effect was reduced, and arousal levels indexed by previous-trial pupil dilation were correlated with subsequent reaction times. Furthermore, linear mixed models revealed that larger pupil dilations correlated with higher heart rates, higher skin conductance responses, higher respiration amplitudes, and lower pulse wave amplitudes on a trial-by-trial basis. Similar effects were seen between positive and negative valence conditions. Moreover, tonic pupil size before stimulus presentation significantly correlated with all other tonic autonomic responses, whereas tonic pupil size derivative correlated with heart rates and skin conductance responses. These results demonstrate a trial-by-trial relationship between pupil dynamics and other autonomic responses, highlighting pupil size as an effective real-time index for autonomic arousal during emotional conflict and valence processing.

Effect of age on clinical impact and mid-term denervation in patients undergoing cardioneuroablation

Cardioneuroablation (CNA) represents a promising therapy for recurrent vasovagal syncope (VVS), extrinsically driven atrioventricular block (AVB) and sinus node dysfunction (SND). However, effectiveness in patients aged 50 and above is not well-established. In this prospective study of patients referred for CNA, we compared syncope and pacemaker implantation free survival, heart rate (HR) variability (HRV) and quality of life between two age groups: group A (< 50 years) and B (≥ 50 years). A total of 50 patients were included (17 Group A and 33 Group B). The etiologies comprised VVS (56%), AVB (22%), and SND (22%). After a median follow-up of 17.0 (12.5–26.0) months, there were no differences of the combined endpoint of syncope or pacemaker implantation free-survival between groups (29.4.% vs. 21.2%; p-log-rank = 0.736). 84% of the entire cohort remained free from syncope, with a better but not significant syncope free survival in the older group (23.5% vs. 12.1%; p-log rank = 0.486). There were no differences in pacemaker implantation rate (A 5.9% vs. B 17.6%; p log-rank = 0.658). Notably, older patients had lower HR values post-procedure compared to younger patients (68.9 ± 13.3 vs. 80.4 ± 16.3 bpm; p = 0.012). Both groups exhibited a decrease in HRV parameters and an improvement in quality of life. In conclusion, CNA has comparable clinical benefits for patients aged 50 and above in terms of syncope or pacemaker implantation free survival and HRV reduction when compared to younger patients.

Effects of concentric and eccentric exercise regimens on bioenergetic efficiency of lymphocytes in sedentary males.

Eccentric exercise training (EET) increases physical performance while having lower metabolic demand than concentric exercise training (CET). Whether EET influences bioenergetic efficiency in peripheral blood mononuclear cells (PBMCs) remains unclear. This study investigates the effects of EET and CET on PBMC phenotypes and mitochondrial functions in blood. Thirty three sedentary healthy males were randomly assigned to either EET (n=11) or CET (n=11) that performed at progressively increased from 60% to 80% of maximal absolute workload for 30min/day, 5days/week for 6weeks, or a control group (n=11) that did not receive any exercise intervention. A graded exercise stress test (GXT) was performed before and after the intervention. PBMC phenotypes and mitochondrial respiratory capacity were analyzed using flowcytometry and high-resolution respirometry, respectively. In the same absolute workload, EET elicited lower heart rate and rating of perceived exertion than CET. However, EET as CET increased the VO2 level at the ventilatory threshold. Notably, both EET and CET increased central memory (CD45RO+/CD62+/CD3+) T cells and decreased effector memory T cells reexpressing CD45RA (CD45RA+/CD62-/CD3+). Moreover, the two exercise regimens diminished the loss of mitochondrial membrane potential (ΔΨm) caused by GXT, increased maximal/reserve O2 consumption rates (OCR), and bioenergetic health index in intact PBMCs and enhanced complex I-/II-related OCR in PBMCs with a substrate-rich environment. EET improves aerobic fitness with a lower cardiovascular response to exercise than CET. Moreover, EET as CET reduces senescent T-cell distribution in blood and improves PBMC bioenergetic efficiency by stabilizing ΔΨm and increasing capacity of oxidative phosphorylation.

Mechanisms of the Native American pain inequity: predicting chronic pain onset prospectively at 5 years in the Oklahoma Study of Native American Pain Risk.

A pain inequity exists for Native Americans (NAs), but the mechanisms are poorly understood. The Oklahoma Study of Native American Pain Risk (OK-SNAP) addressed this issue and recruited healthy, pain-free NAs and non-Hispanic Whites (NHWs) to attend 2 laboratory visits and assessed mechanisms consistent with the biopsychosocial model of pain: demographics, physical variables, psychosocial factors, and nociceptive/pain phenotypes. Then participants were surveyed every 6 months to assess for chronic pain onset. Results at the 2-year follow-up found that NAs were ∼3x more likely than NHWs to develop chronic pain. Moreover, psychosocial factors (discrimination, stress, pain-related anxiety), cardiometabolic load (higher body mass index and blood pressure, lower heart rate variability), and impaired inhibition of spinal nociception partly mediated the pain inequity. The present study examined mechanisms of chronic pain at the 5-year follow-up for OK-SNAP. Results found that the NA pain inequity worsened-NAs were 4x more likely to develop chronic pain (OR = 4.025; CI = 1.966, 8.239), even after controlling for baseline age, sex assigned at birth, income, and education. Moreover, serial mediation models replicated paths from the 2-year follow-up that linked psychosocial variables, cardiometabolic load, and impaired inhibition of spinal nociception to chronic pain onset. Further, 2 new significant paths were observed. One linked discrimination, stress, sleep problems, and facilitated pain perception to increased pain risk. The other linked discrimination with higher spinal nociceptive threshold and pain risk. These results provide further evidence for a NA pain inequity and identify multiple psychosocial, cardiometabolic, and pronociceptive targets for primary interventions.