Cardiac Autonomic Nervous System Research Articles

Comparing pulsed field electroporation and radiofrequency ablation for the treatment of paroxysmal atrial fibrillation: design and rationale of the BEAT PAROX-AF randomized clinical trial.

Using thermal-based energy sources [radiofrequency (RF) energy/cryo energy] for catheter ablation is considered effective and safe when performing pulmonary vein isolation (PVI) in patients with paroxysmal atrial fibrillation (AF). However, treatment success remains limited and complications can occur due to the propagation of thermal energy into non-target tissues. We aim to compare pulsed field ablation (PFA) with RF ablation in terms of efficacy and safety for patients with drug-resistant paroxysmal AF. The BEAT PAROX-AF trial is a European multicentre, superiority, open-label randomized clinical trial in two parallel groups. A total of 292 participants were recruited in 9 high-volume European clinical centres in 5 countries. Patients with paroxysmal AF were randomized to PFA (FARAPULSE Endocardial Ablation System©, Boston Scientific) or RF using the CLOSE protocol with contact force sensing catheter (SmartTouch© catheter and CARTO© Biosense Webster). The primary endpoint will be the 1-year recurrence of atrial arrhythmia, and the major secondary safety endpoint will be the occurrence of acute (<7 days) procedure-related serious adverse events, or pulmonary vein stenosis, or atrio-oesophageal fistula up to 12 months. Additionally, five sub-studies investigate the effect of PFA on oesophageal safety, cerebral lesions, cardiac autonomic nervous system, durability of PVI as assessed during redo ablation procedures, and atrial and ventricular function. The study began on 27 December 2021 and concluded recruitment on 17 January 2024. Results will be available in mid-2025. The BEAT PAROX-AF trial aims to provide critical insights into the optimal treatment approach for patients with paroxysmal AF.

Continuous Peripheral Electrical Nerve Stimulation Improves Cardiac Function via Autonomic Nerve Regulation in MI Rats

BackgroundPeripheral electrical nerve stimulation (PENS) reportedly improves cardiac function after myocardial ischemia (MI) by rebalancing the cardiac autonomic nervous system. The dynamic and continuous influence of the PENS on autonomic and cardiac functioning based on cardiac self-repair is not well understood. ObjectiveThis study aimed to explore the correlations between autonomic nervous balance and functional cardiac repair after MI and to clarify the optimal acupoint selection and time course for PENS. MethodsThe activity of the superior cervical cardiac sympathetic nerve (SN) and vagus nerve (VN) was recorded to reflect the autonomic tone directly. The Millar pressure-volume loop system was used for LV diastolic and systolic functioning. Noninvasive continuous ECG and echocardiography were performed to analyse HR, HRV, and LV function. The effect of continuous PENS (cPENS) or instant PENS (iPENS) on autonomic and cardiac indications was tested. ResultsSN activity and VN activity increased as compensatory self-regulation on days 7 and 14 post-MI, followed by an imbalance of autonomic tone and cardiac dysfunction on day 28. cPENS-PC6 maintained autonomic hyperexcitability, improved myocardial systolic and diastolic abilities, and reduced myocardial fibrosis on day 28 post-MI, whereas cPENS-ST36 had a limited effect. Both iPENS-PC6 and iPENS-ST36 improved the autonomic and cardiac function of rats in the cPENS groups. ConclusionRats showed autonomic fluctuations and cardiac dysfunction 28 days post-MI. cPENS produced sympathomimetic action to sustain cardiac self-compensation, but with acupoint specificity. Based on cPENS, iPENS evoked autonomic regulation and cardiac benefits without acupoint differentiation.

Modification of heart rate variability induced by focal muscle vibration in patients with severe acquired brain injury

ABSTRACT Background/Purpose Heart rate variability (HRV) is a biomarker of autonomic nervous system (ANS) reaction in persons with severe acquired brain injury (sABI) who undergo a rehabilitation treatment, such as focal muscle vibration (FMV). This study aims to evaluate if and how FMV can modulate HRV and to compare potential differences in FMV modulation in HRV between patients with sABI and healthy controls. Methods Ten patients with sABI and seven healthy controls have been recruited. Each individual underwent the same stimulation protocol (four consecutive trains of vibration of 5 minutes each with a 1-minute pause). HRV was analyzed through the ratio of frequency domain heart-rate variability (LF/HF). Results In the control group, after performing FMV, a significant LF/HF difference was observed in the in the second vibration session compared to the POST phase. Patients with SABI treated on the affected side showed a statistically significant LF/HF difference in the PRE compared to the first vibration session. Conclusion These preliminary results suggest that FMV may modify the cardiac ANS activity in patients with sABI.

Cardiopulmonary nerve stimulation as a novel therapy for cardiac autonomic nervous system modulation.

Cardiopulmonary nerve stimulation as a novel therapy for cardiac autonomic nervous system modulation.

The Intrinsic Cardiac Nervous System: From Pathophysiology to Therapeutic Implications.

The cardiac autonomic nervous system (CANS) plays a pivotal role in cardiac homeostasis as well as in cardiac pathology. The first level of cardiac autonomic control, the intrinsic cardiac nervous system (ICNS), is located within the epicardial fat pads and is physically organized in ganglionated plexi (GPs). The ICNS system does not only contain parasympathetic cardiac efferent neurons, as long believed, but also afferent neurons and local circuit neurons. Thanks to its high degree of connectivity, combined with neuronal plasticity and memory capacity, the ICNS allows for a beat-to-beat control of all cardiac functions and responses as well as integration with extracardiac and higher centers for longer-term cardiovascular reflexes. The present review provides a detailed overview of the current knowledge of the bidirectional connection between the ICNS and the most studied cardiac pathologies/conditions (myocardial infarction, heart failure, arrhythmias and heart transplant) and the potential therapeutic implications. Indeed, GP modulation with efferent activity inhibition, differently achieved, has been studied for atrial fibrillation and functional bradyarrhythmias, while GP modulation with efferent activity stimulation has been evaluated for myocardial infarction, heart failure and ventricular arrhythmias. Electrical therapy has the unique potential to allow for both kinds of ICNS modulation while preserving the anatomical integrity of the system.

Non-invasive Neuromodulation of Arrhythmias.

Dysfunction of the cardiac autonomic nervous system (CANS) is associated with various cardiac arrhythmias. Subsequently, invasive techniques have successfully targeted the CANS for the treatment of certain arrhythmias, such as sympathetic denervation for ventricular tachycardia storm. Non-invasive strategies capable of modulating the CANS for arrhythmia treatment have begun to gain interest due to their low-risk profile and applicability as an adjuvant therapy. This review provides an evidence-based overview of the currently studied technologies capable of non-invasively modulating CANS for the suppression of atrial fibrillation and ventricular arrhythmias.

Chronic Expression of Interleukin-10 Transgene Modulates Cardiac Sympathetic Ganglion Resulting in Reduced Ventricular Arrhythmia.

The cardiac autonomic nervous system (CANS) is intimately connected to the regulation of electrophysiology and arrhythmogenesis in cardiac systems. This work aimed at investigating whether interleukin-10 (IL-10) could effectively modulate CANS and suppress ischemia-induced ventricular arrhythmia (VA) through chronically acting on the cardiac sympathetic ganglion (CSG). Using an adeno-associated virus (AAV), we achieved local chronic overproduction of IL-10 in the CSG, left stellate ganglion (LSG). As a result, in the IL-10 group, we observed a decreased number of tyrosine hydroxylase-positive (TH+) cells in the LSG. IL-10 markedly downregulated the nerve growth factor, synaptophysin, as well as growth-associated protein 43 expression. In vivo, results from ambulatory electrocardiography showed that IL-10 overexpression significantly inhibited the cardiac sympathetic nervous system activity and improved heart rate variability. Meanwhile, we observed decreased LSG function as well as prolonged ventricular effective refractory period and suppressed VA after myocardial infarction (MI) in the IL-10 group. In addition, IL-10 overexpression attenuated inflammation and decreased norepinephrine levels in the myocardium after acute MI. In conclusion, our data suggest that chronic IL-10 overexpression modulates cardiac sympathetic nerve remodeling and suppresses VA induced by MI. Neuromodulation through AAV-mediated IL-10 overexpression may have the characteristics of and advantages as a potential neuroimmunotherapy for preventing MI-induced VAs.

Mast cell stabilizer, an anti-allergic drug, reduces ventricular arrhythmia risk via modulation of neuroimmune interaction.

Mast cells (MCs) are important intermediates between the nervous and immune systems. The cardiac autonomic nervous system (CANS) crucially modulates cardiac electrophysiology and arrhythmogenesis, but whether and how MC-CANS neuroimmune interaction influences arrhythmia remain unclear. Our clinical data showed a close relationship between serum levels of MC markers and CANS activity, and then we use mast cell stabilizers (MCSs) to alter this MC-CANS communication. MCSs, which are well-known anti-allergic agents, could reduce the risk of ventricular arrhythmia (VA) after myocardial infarction (MI). RNA-sequencing (RNA-seq) analysis to investigate the underlying mechanism by which MCSs could affect the left stellate ganglion (LSG), a key therapeutic target for modulating CANS, showed that the IL-6 and γ-aminobutyric acid (GABA)-ergic system may be involved in this process. Our findings demonstrated that MCSs reduce VA risk along with revealing the potential underlying antiarrhythmic mechanisms.

Alleviation of acute stress response by black pepper aroma administration

BackgroundBlack pepper is one of the most popular spices globally. As black pepper essential oil has not yet been used in the context of aromatherapy, this study examined the effect of black pepper aroma on cardiac and peripheral autonomic nervous system (ANS) activity under stressful conditions using an olfactometer to administer aroma in a precise and controlled manner to ensure reproducibility.MethodsA within-participant design experiment was conducted with 20 male university students who performed a 30-min calculation task as a short-term stressor under three aroma conditions: black pepper, ginger, and dipropylene glycol (DPG) (scentless air as a control). Each aroma was sporadically delivered (first 20 s of each 1-min interval) with the olfactometer during the task. Electrocardiograms and skin conductance level (SCL) were measured to evaluate ANS's physiological acute stress response. Subjective evaluations for the given stressful task and impressions on the types of aromas were assessed.ResultsThe physiological acute stress response induced by the short-term stressor, which is characterized by the enhancement of the heart rate (HR) and SCL and decreases in the heart rate variability (HRV), was suppressed with black pepper: the increase in HR and reduction in HRV from the baseline were 38.9% (p = 0.048 when compared with DPG) and 32.9% smaller (p = 0.002 for multiple comparisons) than those in DPG, respectively, and the increase of SCL was 15.5% smaller (p = 0.005 for multiple comparisons) than that in ginger. However, there was no significant difference in subjective scores among the conditions.ConclusionAlthough black pepper is a stimulative agent, the study findings showed that black pepper aroma alleviated the physiological acute stress response, which can be beneficial in aromatherapy under stressful conditions.

Could transcranial direct-current stimulation in the insular cortex increase exercise tolerance in patients with heart failure?

Although studies have shown that transcranial direct-current stimulation (tDCS) can improve physical performance, reduce fatigue, modulate the cardiac autonomic nervous system and increase tolerance to exercise by decreasing the rating of perceived exertion in healthy subjects, athletes, and non-athletes, it has not been examined in patients that have suffered from heart failure (HF). Despite the established benefits of physical exercise, our study investigates whether anodal electrode (a-tDCS) stimulation in the insular cortex, combined with aerobic exercise, enhances physical performance. We aim to assess its impact on inflammatory cytokines, subclinical parameters in cardiopulmonary tests, and quality of life in HFrEF patients compared to sham stimulations. To our knowledge, there are no reports in the literature of studies that have analyzed the effects of a-tDCS applied to the insular area on aerobic performance in patients with HFrEF; thus, our objective is unique and can have a great impact on cardiac rehabilitation. On the other hand, the hypothesis presented here should be approached with caution since there is a lack of clinical trials on this topic.

Heart Rate Variability Biofeedback in Adults with a Spinal Cord Injury: A Laboratory Framework and Case Series.

Heart rate variability biofeedback (HRV-F) is a neurocardiac self-regulation therapy that aims to regulate cardiac autonomic nervous system activity and improve cardiac balance. Despite benefits in various clinical populations, no study has reported the effects of HRV-F in adults with a spinal cord injury (SCI). This article provides an overview of a neuropsychophysiological laboratory framework and reports the impact of an HRV-F training program on two adults with chronic SCI (T1 AIS A and T3 AIS C) with different degrees of remaining cardiac autonomic function. The HRV-F intervention involved 10 weeks of face-to-face and telehealth sessions with daily HRV-F home practice. Physiological (HRV, blood pressure variability (BPV), baroreflex sensitivity (BRS)), and self-reported assessments (Fatigue Severity Scale, Generalised Anxiety Disorder Scale, Patient Health Questionnaire, Appraisal of Disability and Participation Scale, EuroQol Visual Analogue Scale) were conducted at baseline and 10 weeks. Participants also completed weekly diaries capturing mood, anxiety, pain, sleep quality, fatigue, and adverse events. Results showed some improvement in HRV, BPV, and BRS. Additionally, participants self-reported some improvements in mood, fatigue, pain, quality of life, and self-perception. A 10-week HRV-F intervention was feasible in two participants with chronic SCI, warranting further investigation into its autonomic and psychosocial effects.

Rationale and design of the VAST-AF trial: A randomized controlled, blinded, clinical trial to evaluate transcutaneous vagal nerve stimulation for the prevention of persistent atrial fibrillation recurrence

BackgroundAtrial fibrillation (AF) is the most prevalent cardiac arrhythmia and is linked to significant symptoms and an elevated risk of heart failure, thromboembolism and disabling stroke. Not only do patients suffer from AF and the concomitant complications, but it is a great economic burden for healthcare systems all over the world. Despite remarkable progress in the field of AF, the basic mechanisms of AF development remain unresolved. Data suggests that the (cardiac) autonomous nervous system (ANS) plays a significant role in AF. Recent studies have shown that stimulating the ANS could have a beneficial effect on paroxysmal and postoperative AF. Consequently, this therapy could provide another viable target for treating persistent AF, as well. Study DesignThe VAST-AF trial is a prospective, double-blinded, randomized, and sham-controlled clinical trial. One hundred and twenty patients diagnosed with persistent AF and cardioversion in sinus rhythm (SR) will be randomly assigned to either transcutaneous vagal nerve stimulation (tVNS) or sham treatment in a 1:1 ratio. The primary objective of this study is to examine whether a daily tVNS reduces the recurrence rate of AF. Secondary endpoints include quality of life, time to first AF recurrence and ECG parameters of the ANS. Follow-up is scheduled at 30 days, 3 and 6 months. After 3 months, stimulation is withdrawn, and patients evaluated regarding a still detectable effect of tVNS. ConclusionThe VAST-AF trial represents the first randomized and sham-controlled study to investigate the potential benefits of transcutaneous vagal nerve stimulation on the recurrence of atrial fibrillation. Patients with persistent atrial fibrillation and successful electrical cardioversion will be assessed. A decrease in in the rate of recurrence and consecutive hospitalizations could decidedly enhance the quality of life of patients and decrease healthcare expenses. Nevertheless, it does not compete with treatments such as catheter ablation, but rather serves as an additional tool in the armamentarium of the electrophysiologist.

Prenatal fluoride exposure, offspring visual acuity and autonomic nervous system function in 6-month-old infants

BackgroundPrenatal fluoride exposure can have adverse effects on children’s development; however, associations with visual and cardiac autonomic nervous system functioning are unknown. We examined associations between prenatal fluoride exposure and visual acuity and heart rate variability (HRV) in 6-month-old infants. MethodsWe used data from Canadian mother-infant pairs participating in the Maternal-Infant Research on Environmental Chemicals (MIREC) cohort. We estimated prenatal fluoride exposure using: i) fluoride concentration in drinking water (mg/L), ii) maternal urinary fluoride adjusted for specific gravity (MUFSG; mg/L) and averaged across pregnancy, and iii) maternal fluoride intake (µg/kg/day) from consumption of water, tea, and coffee, adjusted for maternal body weight (kg). We used multivariable linear regression to examine associations between each measure of fluoride exposure and Teller Acuity Card visual acuity scores (n = 435) and assessed HRV (n = 400) using two measures: root mean square of successive differences (RMSSD) and the standard deviation of N-N intervals (SDNN) measured at 6-months of age. ResultsMedian (IQR) values for water fluoride, MUFSG, and daily fluoride intake were 0.20 (IQR: 0.13–0.56) mg/L; 0.44 (0.28–0.70) mg/L and 4.82 (2.58–10.83) µg/kg/day, respectively. After adjustment for confounding variables, water fluoride concentration was associated with poorer infant visual acuity (B = -1.51; 95 % CI: −2.14,-0.88) and HRV as indicated by lower RMSSD (B = -1.60; 95 % CI: −2.74,-0.46) but not SDNN. Maternal fluoride intake was also associated with poorer visual acuity (B = -0.82; 95 % CI: −1.35,-0.29) and lower RMSSD (B = -1.22; 95 % CI: −2.15,-0.30). No significant associations were observed between MUFSG and visual acuity or HRV. ConclusionFluoride in drinking water was associated with reduced visual acuity and alterations in cardiac autonomic function in infancy, adding to the growing body of evidence suggesting fluoride's developmental neurotoxicity.

Magnetic vagus nerve stimulation alleviates myocardial ischemia-reperfusion injury by the inhibition of pyroptosis through the M2AChR/OGDHL/ROS axis in rats.

Myocardial ischemia-reperfusion (I/R) injury is accompanied by an imbalance in the cardiac autonomic nervous system, characterized by over-activated sympathetic tone and reduced vagal nerve activity. In our preceding study, we pioneered the development of the magnetic vagus nerve stimulation (mVNS) system. This system showcased precise vagus nerve stimulation, demonstrating remarkable effectiveness and safety in treating myocardial infarction. However, it remains uncertain whether mVNS can mitigate myocardial I/R injury and its specific underlying mechanisms. In this study, we utilized a rat model of myocardial I/R injury to delve into the therapeutic potential of mVNS against this type of injury. Our findings revealed that mVNS treatment led to a reduction in myocardial infarct size, a decrease in ventricular fibrillation (VF) incidence and a curbing of inflammatory cytokine release. Mechanistically, mVNS demonstrated beneficial effects on myocardial I/R injury by inhibiting NLRP3-mediated pyroptosis through the M2AChR/OGDHL/ROS axis. Collectively, these outcomes highlight the promising potential of mVNS as a treatment strategy for myocardial I/R injury.

Concept: Electrical Cardiac Stimulation is Detected by the Cardiac Autonomic Nervous System with Possible Effects on the Vasovagal Reflex

Abstract A novel concept is described concerning the possible effect of right ventricular pacing stimulation being detected by the cardiac autonomic nervous system and through its afferent neuronal connection to the central autonomic nervous system (spinal cord) causing reversal or attenuation of the vasovagal reflex. This could be a direct effect of electrical stimulation or may occur by the known adverse consequences on ventricular synchrony induced by stimulation which could be right ventricular site and timing in the evolution of the vasovagal reflex dependent.

Anthracycline's Effects on Heart Rate Variability in Children with Acute Lymphoblastic Leukemia: Early Toxicity Signs-Pilot Study.

Anthracycline treatments are known to cause cardiotoxic long-term side effects in cancer survivors. Recently, a decrease in heart rate variability (HRV) has been identified in these patients, signaling autonomic dysfunction and altered cardiac fitness. This study aimed at evaluating changes in HRV in children treated with anthracyclines. A total of 35 pediatric patients with acute lymphoblastic leukemia were evaluated by means of a 24 h Holter ECG, at baseline and after reaching half the total cumulative dose of doxorubicin equivalent (120 mg/m2). Parameters of HRV were assessed, as well as any arrhythmic episodes, bradycardia and tachycardia percentages. The results showed a significant decrease in both time-domain and frequency-domain HRV parameters, following anthracycline treatment. The low-frequency (LF) to high-frequency (HF) parameters' ratio also displayed a significant difference (p = 0.035), suggestive of early cardiac autonomic dysfunction. Of note, none of the patients presented symptoms of heart disease or elevated troponins, and only two patients presented echocardiographic signs of diastolic dysfunction. The present study showed that cardiac autonomic nervous system regulation is compromised in children treated with anthracyclines even before reaching the total cumulative dose. Therefore, HRV parameters could be the first indicators of subclinical cardiac toxicity, making Holter ECG monitoring of the oncological patient a necessity.

Vascular senescence controls the neuro-cardiac interface in the aging heart

Abstract Aging is a major risk factor for impaired cardiovascular function. The aging heart is characterized by vascular dysfunction, increased hypertrophy, fibrosis and electrophysiological alterations. Studies show impaired endothelial cell (EC) function associates with senescence in aging. Since vessels and nerves align, and this interplay is critical for tissue homeostasis, we studied whether an impairment of the neuro-vascular interface may contribute to age-associated pathologies in the heart. To study the innervation of the aging mouse heart, we histologically assessed the cardiac autonomic nervous system in 3- and 20-month old mice using the pan-neuronal marker Tuj1 and the sympathetic marker TH. Interestingly, sympathetic innervation of the left ventricle, especially around arteries, was reduced by 0.66±0.07-fold with aging (p&amp;lt;0.05) indicating that aging reduces innervation of the left ventricle. Similar findings were observed in premature aging models of TERT-KO and EC-transgenic progeria mice. Electrophysiological studies confirmed an increased incidence of ventricular arrhythmias and reduced heart rate variability in aged mice. To determine the potential contribution of neurovascular cells, we analyzed gene expression of isolated ECs in aging mouse hearts by bulk RNA sequencing. Aging significantly induced the expression of genes associated with GO-terms related to neuronal cell death and axon injury. Sema3a, an axon repelling factor, was significantly increased in ECs of aged mice hearts, which was confirmed by qPCR and by histology (p&amp;lt;0.05). Next we determined the mechanism of Sema3a regulation. We show that miR-145 acts as an up-stream regulator of Sema3a expression. miR-145-/- mice showed increased Sema3a expression and reduced cardiac innervation. We observed an increase in acidic β-gal activity as a marker for cellular senescence in the aging heart, particularly in the proximate arterial space. In addition, Sema3a expression was significantly increased in senescent ECs in vitro, thus suggesting a putative role for senescence to impair cardiac innervation. To test whether eliminating senescent cells may restore left ventricular axon density, we treated 18-month old mice with a combination of the two senolytic drugs dasatinib and quercetin, which are known to deplete senescent cells in vivo. After 2 months of treatment, cellular senescence was reduced by 0.4±0.1-fold (p&amp;lt;0.05) in aged hearts. Endothelial expression of Sema3a was also reduced. Importantly, senolytic treatment restored ventricular innervation, augmented heart rate variability, and normalized electrophysiological abnormalities (all p&amp;lt;0.05). In conclusion, we show that aging augments axon repelling signals in ECs and reduces left ventricular innervation. The depletion of senescent cells prevented age-induced impairment of innervation and normalized electrophysiological abnormalities suggesting a critical role of senescence-associated axon repulsion in the aging heart.

Abstract 15076: Long-Term Recurrence Free Survival in Second Generation Cryoballoon Ablation for Persistent Atrial Fibrillation: It’s All About the Autonomic Nervous System

Introduction: Cryoballon (CB)-guided pulmonary vein isolation (PVI) is an accepted treatment option for atrial fibrillation (AF). The cardiac autonomic nervous system (ANS) plays a crucial role in the regulation of AF. Hypothesis: ANS modulation has an impact on patients’ AF free survival following CB-ablation. The aim of this observational clinical trial was to analyze the impact of vagal reactions (VRs), as a surrogate parameter for ANS modulation, on the long-term outcome of CB-ablation in patients with persistent AF (PERS AF). Methods: Data from consecutive PERS AF patients treated with a CB-guided PVI for symptomatic drug refractory AF between 2013-2023 were analyzed. VRs were defined as bradycardia &lt; 40 beats/min, asystole or higher-degree atrioventricular block. All patients were continuously followed up in our outpatient clinic. AF-recurrence was defined as AF lasting &gt; 30 seconds beyond a 3-month blanking period. Results: A total of 250 consecutive patients (mean age 63.9 ± 10.0 years, 70% male) were included. VRs were recorded in 61 patients (24%). The mean follow-up duration amounted to 84±14 months. Within this observation period 101 patients (40%) developed AF recurrence a mean of 1.75 ± 0.80 times. Re-ablation procedures were performed in 61 patients (60%) a mean of 1.28 ± 0.55 times. Reconnected PVs were documented in 41 cases (67%). An additional substrate modification was performed in 34 procedures (42%). Patients with procedure associated VRs presented with a significantly higher estimated AF-free survival rate compared to those without (log-rank p-value=0.016) (Figure1). Multivariate analyses revealed the days to first AF recurrence following primary CB-ablation as an independent predictor for AF-free survival (CI 0.841-0.928, HR, 0.883, p&lt;0.01). Conclusions: CB-ablation procedure associated VRs seem to be associated with a favorable long-term outcome in PERS AF. Thus, our findings may influence future CB-ablation strategies.

Abstract 16706: Women With Coronary Vascular Dysfunction Have Heightened Emotional Responses to Mental Stress With Attenuated Recovery

Introduction: Coronary vascular dysfunction (CVaD) is associated with major adverse outcomes, recurrent chest pain, and can be triggered by mental stress. Hypothesis: We hypothesized that women with CVaD have heightened emotional response and attenuated recovery compared to reference control (RC) women. Methods: Women diagnosed with CVaD (cases, n=57, age: 57±1 years) by abnormal adenosine or acetylcholine response during invasive coronary function testing were enrolled in Cardiac Autonomic Nervous System Study and compared to age-matched, asymptomatic RCs women (n=25, age: 56±3 years), free of cardiac or risk factor history. All underwent two 4-minute standardized mental stress tests - anger recall and mental arithmetic - followed by 15 minutes of recovery. Emotional arousal (tension, anxious, depressed) and chest pain were assessed via self-reported Likert scale at baseline, after stress, and after recovery. The difference between post-stress or post-recovery and baseline scores was used to evaluate stress provocation and recovery. Increased differences indicate more provocation or recovery attenuation. We utilized multivariate models adjusted for anti-anginal medications, statins, and aspirin or traditional cardiovascular risk factors and chest pain to assess associations between CVaD and chest pain or emotional arousal, respectively. Results: The two groups did not differ in hemodynamic response to mental stress (p&gt;0.05). In multivariate models, CVaD status was associated with more stress-provoked chest pain (β 1.24 [0.1, 2.4], p=0.03) and more attenuated chest pain recovery (β 1.5 [0.6, 2.3], p=0.001) than RC. Similarly, after adjustment, cases were associated with more stress-provoked anxiety (β 1.2 [0.2, 2.2], p=0.02) and tension (β 1.2 [0.001, 2.4], p=0.05) while having more attenuated recovery of anxiety (β 1.1 [0.1, 2.0], p=0.02) and tension (β 1.1 [0.2, 2.0], p=0.02) compared to RC. There were no differences in feelings of depression between the two groups. Conclusions: Response to mental stress is heightened with attenuated recovery in women with CVaD. An improved understanding of mechanisms in stress response and CVaD is needed for potential therapeutic targets that may improve angina and quality of life.

Heart rate variability and cardiovascular risk factors in patients with rheumatoid arthritis: A longitudinal study.

It is established that the risk of cardiovascular disease (CVD) is increased in patients with Rheumatoid Arthritis (RA). Heart rate variability (HRV) is a method for evaluating the activity in the cardiac autonomic nervous system. Our aim was to assess the longitudinal development of HRV in patients with RA and compare with healthy controls. Furthermore, we wanted to investigate associations between HRV, inflammatory disease activity and cardiovascular complications in patients with RA over time. HRV was assessed with frequency-domain analysis at baseline and after five years in 50 patients with early RA, all being younger than 60years. HRV indices were age-adjusted based on the estimated age-dependency in 100 age and sex matched healthy controls. Additionally, clinical data including serological markers, disease activity, and blood pressure were collected from the patients. Eleven years after inclusion CVD was assessed. At baseline, patients with RA presented with lower HRV compared to controls during deep breathing (6 breaths/min), paced normal breathing (12 breaths/min) and after passive tilt to the upright position. No significant change in HRV was observed at the five-year follow-up. A significant negative correlation was found between HRV parameters and systolic blood pressure (SBP) at baseline. A significant positive correlation was found between heart rate and inflammatory markers at baseline but not after five years. Nine patients had developed CVD after 11years, but no significant association was found with baseline HRV data. This study showed that patients with RA have autonomic imbalance both at an early stage of the disease and after five years, despite anti-rheumatic medication, but no correlation between HRV and inflammation markers were observed. Reduced HRV was also significantly negatively correlated with increased SBP. Hypertension is a common finding in patients with RA. Thus, significant decline of HRV could be a useful early marker for development of hypertension in patients with RA.