Vagal nerve stimulation in myocardial ischemia/reperfusion injury: from bench to bedside.

The identification of acute cardioprotective strategies against myocardial ischemia/reperfusion (I/R) injury that can be applied in the catheterization room is currently an unmet clinical need and several interventions evaluated in the past at the pre-clinical level have failed in translation. Autonomic imbalance, sustained by an abnormal afferent signalling, is a key component of I/R injury. Accordingly, there is a strong rationale for neuromodulation strategies, aimed at reducing sympathetic activity and/or increasing vagal tone, in this setting. In this review we focus on cervical vagal nerve stimulation (cVNS) and on transcutaneous auricular vagus nerve stimulation (taVNS); the latest has the potential to overcome several of the issues of invasive cVNS, including the possibility of being used in an acute setting, while retaining its beneficial effects. First, we discuss the pathophysiology of I/R injury, that is mostly a consequence of the overproduction of reactive oxygen species. Second, we describe the functional anatomy of the parasympathetic branch of the autonomic nervous system and the most relevant principles of bioelectronic medicine applied to electrical vagal modulation, with a particular focus on taVNS. Then, we provide a detailed and comprehensive summary of the most relevant pre-clinical studies of invasive and non-invasive VNS that support its strong cardioprotective effect whenever there is an acute or chronic cardiac injury and specifically in the setting of myocardial I/R injury. The potential benefit in the emerging field of post cardiac arrest syndrome (PCAS) is also mentioned. Indeed, electrical cVNS has a strong anti-adrenergic, anti-inflammatory, antioxidants, anti-apoptotic and pro-angiogenic effect; most of the involved molecular pathways were already directly confirmed to take place at the cardiac level for taVNS. Pre-clinical data clearly show that the sooner VNS is applied, the better the outcome, with the possibility of a marked infarct size reduction and almost complete left ventricular reverse remodelling when VNS is applied immediately before and during reperfusion. Finally, we describe in detail the limited but very promising clinical experience of taVNS in I/R injury available so far.

From the latin "re-cordis, passing through the heart": autonomic modulation differentiates migraineurs from controls when recounting a significant life event.

OBJECTIVE: The literature on clinical psychophysiology highlights the possibility of using Heart Rate Variability (HRV) as an index of psychophysical balance and resilience to stress. This study investigates the differences in stress reactivity and subsequent recovery between a group of migraineurs and healthy controls. METHODS: Socio-demographic (i.e., sex, age, profession, marital status, and level of education) and psychophysiological (HR and HRV) measures of a group of thirty subjects with migraine (26 migraineurs without aura (86.7%), 2 migraineurs with aura (6.7%), and 2 migraineurs with and without aura (6.7%)) and from thirty healthy control subjects were collected. In particular, HRV was analyzed through frequency-domain parameters, including Low-Frequency (LF; 0.04-0.15 Hz) and High-Frequency (HF; 0.15-0.4 Hz) bands as well as LF/HF ratio during a Psychophysiological Stress Profile (PSP) structured in seven phases: (1) Baseline, (2) Objective stressor 1 (Stroop Test), (3) Rest 1, (4) Objective stressor 2 (Mental Arithmetic Task), (5) Rest 2, (6) Subjective stressor (recount a significant life event), and (7) Rest 3. The LF, HF, and LF/HF ratio values were transformed into a logarithmic scale (i.e., log-LF, log-HF, and log LF/HF ratio). Additionally, LF and HF were converted into normalized units (0-100) (i.e., LF% and HF%) which, in turn, were used to obtain reactivity and recovery to stress through delta values (Δ) calculation. RESULTS: Subjects with migraine reported greater ΔLF% levels of reactivity and recovery to subjective stressor, demonstrating a prevalence of sympathetic activity while recounting a personal life event. At the same time, a lowering of the same values was found in the subjects of the group control. DISCUSSION: Our results underline the importance of conducting a psychophysiological assessment in patients with headaches because reduced stress management skills could influence the clinical manifestations of the disease, considering stress as one of the most common triggers for migraine patients.

Sex differences in cardiac transcriptomic response to neonatal sleep apnea.

Pediatric obstructive sleep apnea poses a significant health risk, with potential long-term consequences on cardiovascular health. This study explores the dichotomous nature of neonatal cardiac response to chronic intermittent hypoxia (CIH) between males and females, aiming to fill a critical knowledge gap in the understanding of sex-specific cardiovascular consequences of sleep apnea in early life. Neonates were exposed to CIH until p28 and underwent comprehensive in vivo physiological assessments, including whole-body plethysmography, treadmill stress-tests, and echocardiography. Results indicated that male CIH rats weighed 13.7% less than age-matched control males (p = 0.0365), while females exhibited a mild yet significant increased respiratory drive during sleep (93.94 ± 0.84 vs. 95.31 ± 0.81;p = 0.02). Transcriptomic analysis of left ventricular tissue revealed a substantial sex-based difference in the cardiac response to CIH, with males demonstrating a more pronounced alteration in gene expression compared to females (5986 vs. 3174 genes). The dysregulated miRNAs in males target metabolic genes, potentially predisposing the heart to altered metabolism and substrate utilization. Furthermore, CIH in males was associated with thinner left ventricular walls and dysregulation of genes involved in the cardiac action potential, possibly predisposing males to CIH-related arrhythmia. These findings emphasize the importance of considering sex-specific responses in understanding the cardiovascular implications of pediatric sleep apnea.

Long term follow-up of heart rate variability in healthcare workers with mild COVID-19.

Introduction: Prior investigations into post-COVID dysautonomia often lacked control groups or compared affected individuals solely to healthy volunteers. In addition, no data on the follow-up of patients with SARS-CoV-2-related autonomic imbalance are available. Methods: In this study, we conducted a comprehensive clinical and functional follow-up on healthcare workers (HCWs) with former mild COVID-19 (group 1, n = 67), to delineate the trajectory of post-acute autonomic imbalance, we previously detected in a case-control study. Additionally, we assessed HCWs for which a test before SARS-CoV-2 infection was available (group 2, n = 29), who later contracted SARS-CoV-2, aiming to validate findings from our prior case-control investigation. We evaluated autonomic nervous system heart modulation by means of time and frequency domain heart rate variability analysis (HRV) in HCWs during health surveillance visits. Short-term electrocardiogram (ECG) recordings, were obtained at about 6, 13 months and both at 6 and 13 months from the negative SARS-CoV-2 naso-pharyngeal swab (NPS) for group 1 and at about 1-month from the negative NPS for group 2. HCWs who used drugs, had comorbidities that affected HRV, or were hospitalized with severe COVID-19 were excluded. Results: Group 1 was split into three subgroups clinically and functionally followed at, about 6 months (subgroup-A, n = 17), 13 months (subgroup-B, n = 37) and both at 6 and 13 months (subgroup-C, n = 13) from the negative SARS-CoV-2 NPS. In subgroup-A, at 6-month follow-up compared with baseline, the spectral components in the frequency domain HRV parameters, showed an increase in normalized high frequency power (nHF) (t = 2.99, p = 0.009), a decrease in the normalized low frequency power (nLF) (t = 2.98, p = 0.009) and in the LF/HF ratio (t = 3.13, p = 0.006). In subgroup B, the comparison of the spectral components in the frequency domain HRV parameters, at 13-month follow-up compared with baseline, showed an increase in nHF (t = 2.54, p = 0.02); a decrease in nLF (t = 2.62, p = 0.01) and in the LF/HF ratio (t = 4.00, p = 0.0003). In subgroup-C, at both 6 and 13-month follow-ups, the spectral components in the frequency domain HRV parameters were higher than baseline in nHF (t = 2.64, p = 0.02 and (t = 2.13, p = 0.05, respectively); lower in nLF (t = 2.64, p = 0.02 and (t = 2.13, p = 0.05, respectively), and in LF/HF (t = 1.92, p = 0.08 and (t = 2.43, p = 0.03, respectively). A significant proportion of HCWs reported persistent COVID-19 symptoms at both the 6 and 13-month follow-ups, seemingly unrelated to cardiac autonomic balance. In group 2 HCWs, at 1-month follow-up compared with baseline, the spectral components in the frequency domain HRV parameters, showed a decrease in nHF (t = 2.19, p = 0.04); an increase in nLF (t = 2.15, p = 0.04) and in LF/HF (t = 3.49, p = 0.002). Conclusion: These results are consistent with epidemiological data suggesting a higher risk of acute cardiovascular complications during the first 30 days after COVID-19. The SARS-CoV-2 associated autonomic imbalance in the post-acute phase after recovery of mild COVID-19 resolved 6 months after the first negative SARS-CoV-2 NPS. However, a significant proportion of HCWs reported long-term COVID-19 symptoms, which dot not seems to be related to cardiac autonomic balance. Future research should certainly further test whether autonomic imbalance has a role in the mechanisms of long-COVID syndrome.

Artificial-intelligence-based risk prediction and mechanism discovery for atrial fibrillation using heart beat-to-beat intervals.

BACKGROUND: Early diagnosis of atrial fibrillation (AF) is important for preventing stroke and other complications. Predicting AF risk in advance can improve early diagnostic efficiency. Deep learning has been used for disease risk prediction; however, it lacks adherence to evidence-based medicine standards. Identifying the underlying mechanisms behind disease risk prediction is important and required. METHODS: We developed an explainable deep learning model called HBBI-AI to predict AF risk using only heart beat-to-beat intervals (HBBIs) during sinus rhythm. We proposed a possible AF mechanism based on the model's explainability and verified this conjecture using confirmed AF risk factors while also examining new AF risk factors. Finally, we investigated the changes in clinicians' ability to predict AF risk using only HBBIs before and after learning the model's explainability. FINDINGS: HBBI-AI consistently performed well across large in-house and external public datasets. HBBIs with large changes or extreme stability were critical predictors for increased AF risk, and the underlying cause was autonomic imbalance. We verified various AF risk factors and discovered that autonomic imbalance was associated with all these factors. Finally, cardiologists effectively understood and learned from these findings to improve their abilities in AF risk prediction. CONCLUSIONS: HBBI-AI effectively predicted AF risk using only HBBI information through evaluating autonomic imbalance. Autonomic imbalance may play an important role in many risk factors of AF rather than in a limited number of risk factors. FUNDING: This study was supported in part by the National Key R&D Program and the National Natural Science Foundation of China.

Effect of pranayama on sympatho-vagal imbalance and cognitive deficit in premenstrual syndrome.

Context: Premenstrual syndrome (PMS) is a prevalent and often neglected condition that affects around 80% of women of reproductive age. In PMS, abnormal fluctuations in gonadal hormones cause altered homeostasis, resulting in sympatho-vagal imbalance and poor cognition. Aim: To compare autonomic function parameters and cognitive performance between PMS and control groups, and to study the effect of pranayama on the above parameters in PMS women. Settings and Design: It was a randomized control trial. Materials and Methods: We recruited 40 women of reproductive age who fit the inclusion criteria. They were asked to complete the Premenstrual Syndrome Screening Tool (PSST) questionnaire and were categorized as having PMS (n = 20) or not having PMS (n = 20). All study participants had their baseline CAFT, HRV, BRS, P300, and MOCA values recorded. Following that, participants in the PMS group were divided into two groups of ten at random. For 8 weeks, one group received pranayama training. Following that, all baseline data were recorded again in both the pranayama and no-intervention groups. Statistical Analysis Used: SPSS version 20 was used to analyze the data. For parametric data, the unpaired t test was used to compare between the PMS and no PMS groups, whereas the Mann-Whitney U test was employed for non-parametric data. To compare the parameters before and after intervention, the Students paired 't' test for parametric data and the Wilcoxan-signed rank test for non-parametric data were used. Results: According to the findings, autonomic function and cognition were considerably affected in the PMS group and improved significantly in the PMS group following pranayama intervention. Conclusion: Pranayama is an effective and safe non-pharmacological method for treating PMS and improving women's quality of life.

The proarrhythmogenic role of autonomics and emerging neuromodulation approaches to prevent sudden death in cardiac ion channelopathies.

Ventricular arrhythmias in cardiac channelopathies are linked to autonomic triggers, which are sub-optimally targeted in current management strategies. Improved molecular understanding of cardiac channelopathies and cellular autonomic signalling could refine autonomic therapies to target the specific signalling pathways relevant to the specific aetiologies as well as the central nervous system centres involved in the cardiac autonomic regulation. This review summarizes key anatomical and physiological aspects of the cardiac autonomic nervous system and its impact on ventricular arrhythmias in primary inherited arrhythmia syndromes. Proarrhythmogenic autonomic effects and potential therapeutic targets in defined conditions including the Brugada syndrome, early repolarization syndrome, long QT syndrome, and catecholaminergic polymorphic ventricular tachycardia will be examined. Pharmacological and interventional neuromodulation options for these cardiac channelopathies are discussed. Promising new targets for cardiac neuromodulation include inhibitory and excitatory G-protein coupled receptors, neuropeptides, chemorepellents/attractants as well as the vagal and sympathetic nuclei in the central nervous system. Novel therapeutic strategies utilizing invasive and non-invasive deep brain/brain stem stimulation as well as the rapidly growing field of chemo-, opto-, or sonogenetics allowing cell-specific targeting to reduce ventricular arrhythmias are presented.

Autonomic nervous system imbalance during aging contributes to impair endogenous anti-inflammaging strategies.

Inflammaging refers to the age-related low grade, sterile, chronic, systemic, and long-lasting subclinical, proinflammatory status, currently recognized as the main risk factor for development and progression of the most common age-related diseases (ARDs). Extensive investigations were focused on a plethora of proinflammatory stimuli that can fuel inflammaging, underestimating and partly neglecting important endogenous anti-inflammaging mechanisms that could play a crucial role in such age-related proinflammatory state. Studies on autonomic nervous system (ANS) functions during aging highlighted an imbalance toward an overactive sympathetic nervous system (SNS) tone, promoting proinflammatory conditions, and a diminished parasympathetic nervous system (PNS) activity, playing anti-inflammatory effects mediated by the so called cholinergic anti-inflammatory pathway (CAP). At the molecular level, CAP is characterized by signals communicated via the vagus nerve (with the possible involvement of the splenic nerves) through acetylcholine release to downregulate the inflammatory actions of macrophages, key players of inflammaging. Notably, decreased vagal function and increased burden of activated/senescent macrophages (macrophaging) probably precede the development of several age-related risk factors and diseases, while increased vagal function and reduced macrophaging could be associated with relevant reduction of risk profiles. Hypothalamic-pituitary-adrenal axis (HPA axis) is another pathway related to ANS promoting some anti-inflammatory response mainly through increased cortisol levels. In this perspective review, we highlighted that CAP and HPA, representing broadly "anti-inflammaging" mechanisms, have a reduced efficacy and lose effectiveness in aged people, a phenomenon that could contribute to fuel inflammaging. In this framework, strategies aimed to re-balance PNS/SNS activities could be explored to modulate systemic inflammaging especially at an early subclinical stage, thus increasing the chances to reach the extreme limit of human lifespan in healthy status.

Impaired Cardiovagal Activity as a Link Between Hyperglycemia and Arterial Stiffness in Adults With Type 2 Diabetes Mellitus Among an Eastern Indian Population: A Cross-sectional Study.

OBJECTIVES: Cardiac autonomic neuropathy (CAN) is one of the most common yet overlooked complications of type 2 diabetes mellitus (T2DM). Individuals with T2DM with CAN have a 5-fold higher rate of cardiovascular morbidity and mortality. The presence of CAN in T2DM could potentially lead to arterial stiffness. However, only sparse data are available suggesting any association between autonomic dysfunction and arterial stiffness in T2DM. METHODS: We recruited 80 people with T2DM and 74 healthy controls for our study. Heart rate variability (HRV) testing was performed to assess autonomic function. Assessment of arterial stiffness was done by measuring the brachial pulse wave velocity (baPWV) and augmentation index (AI). RESULTS: The time-domain parameters were significantly decreased (p<0.001) and frequency-domain parameters, such as total power and high-frequency band expressed as a normalized unit, were found to be significantly reduced in people with T2DM (p<0.001). Both baPWV and AI were significantly higher in people with T2DM compared with healthy controls (p<0.001). We observed a moderate correlation between standard deviation of normal to normal interval (SDNN) and baPWV (r=-0.437, p=0.002) and AI (r=-0.403, p=0.002). A multiple linear regression model showed an association between SDNN and arterial stiffness parameters, such as baPWV and AI, which were statistically significant (p<0.05) in a fully adjusted model that included the conventional risk factors for atherosclerosis. CONCLUSIONS: Impaired cardiovagal activity is an independent risk factor for the development of arterial stiffness. Incorporation of HRV testing into the diabetes management protocol would have potential benefits for identifying individuals at high risk of developing cardiovascular events. Hence, preventive measures can be taken as early as possible to improve patient outcomes.

Autonomic Dysfunction and Cardiovascular Risk in Patients with Rheumatoid Arthritis: Can Heart Rate Variability Analysis Contribute to a Better Evaluation of the Cardiovascular Profile of a Patient?

(1) Background: Rheumatoid arthritis (RA) is a chronic inflammatory disease of autoimmune etiology. Increased scientific evidence suggests that immune-mediated inflammatory dis-eases are associated with autonomic nervous system (ANS) dysfunction. Studies proved that autonomic imbalance is correlated with RA evolution and may explain augmented cardiovascular pathology and mortality not attributable to classical risk factors. (2) Methods: 75 patients (25 males, 50 females) with RA were submitted to standard ECG recording and 24 h Holter monitoring. Twenty-five healthy patients were used as controls. Both time (SDNN, SDANN, SDANN Index, RRmed, rMSSD, and pNN50) and frequency domain (TP, VLF, HF, LF and LF/HF) heart rate variability (HRV) parameters were obtained. Parameters were compared to controls, and correlations with the QTc-interval and inflammatory status expressed through the C-reactive protein (CRP) were evaluated. (3) Results: In patients with a CRP > 5 mg/L, HRV parameters were lower compared to controls and to patients with a CRP ≤ 5 mg/L. All HRV parameters generated by Holter monitoring are negatively correlated with CRP levels and QTc values. The number of premature ventricular contractions (PVC) recorded is correlated with SDNN, SDANN, and LF/HF values. (4) Conclusions: Our study supports recent data suggesting that in RA there is an autonomic system dysfunction strongly connected with the inflammatory status of the patient. The autonomic dysfunction can contribute to the increased risk of cardiovascular death observed in patients with RA.

Exhaustion and cardiovascular risk factors: the role of vagally-mediated heart rate variability.

PURPOSE: Exhaustion symptoms are known to be associated with cardiovascular disease (CVD) risk; however, the underlying mechanisms remain unclear. Autonomic imbalance, as indicated by reductions in vagally-mediated heart rate variability (vmHRV), appears to be a valid candidate for such a biological link, as it has been associated with both exhaustion symptoms and CVD risk and mortality. METHODS: The present study examined a potential mediation of vmHRV on the association between exhaustion symptoms and self-reported CVD risk factors as well as the age dependency of this mediation in a large, heterogeneous sample of the Dresden Burnout Study (N = 388; 72.9% females; Mage = 42.61, SD = 11.67). RESULTS: Results indicate that exhaustion symptoms were indirectly associated with CVD risk factors through vmHRV even after adjusting for well-known confounders (i.e., sex, body mass index, depressive symptoms). Moreover, this pattern was significant only among middle-aged (i.e., 54.27 years) and older individuals. CONCLUSIONS: Our findings add to growing evidence that autonomic imbalance may be a key biological link between exhaustion symptoms and CVD risk in middle-aged and older individuals. Implications for public health are discussed.

Hypertensive Heart Failure.

Despite overwhelming epidemiological evidence, the contribution of hypertension (HTN) to heart failure (HF) development has been undermined in current clinical practice. This is because approximately half of HF patients have been labeled as suffering from HF with preserved left ventricular (LV) ejection fraction (EF) (HFpEF), with HTN, obesity, and diabetes mellitus (DM) being considered virtually equally responsible for its development. However, this suggestion is obviously inaccurate, since HTN is by far the most frequent and devastating morbidity present in HFpEF. Further, HF development in obesity or DM is rare in the absence of HTN or coronary artery disease (CAD), whereas HTN often causes HF per se. Finally, unlike HTN, for most major comorbidities present in HFpEF, including anemia, chronic kidney disease, pulmonary disease, DM, atrial fibrillation, sleep apnea, and depression, it is unknown whether they precede HF or result from it. The purpose of this paper is to provide a contemporary overview on hypertensive HF, with a special emphasis on its inflammatory nature and association with autonomic nervous system (ANS) imbalance, since both are of pathophysiologic and therapeutic interest.

Cardiovascular reactivity to stress in long-term yoga practitioners.

Background: Bhramari Pranayama yogic breathing is a very simple exercise of voluntary breathing which mitigates stress reactivity through autonomic modulation of heart rate. Aim: To study the effects of long-term practice of the yoga breathing exercise on cardiovascular reactivity to head-up tilt (HUT) test. Methods: All the participants were subjected to a 10-item yoga questionnaire. Based on Likert scale scoring, 32 subjects (group I) were selected as long-term yogic breathing practitioners, and autonomic function tests using heart rate variability (HRV) and a provocative stress test and HUT test were conducted. Cardiovascular parameters obtained were compared with controls who had never been engaged in any form of yoga (group II). Results: A highly significant decrease in values of both high (HF) and low frequency (LF) variables was observed in group II as compared to group I. However, a highly significant rise in LF/HF has been observed in group I compared to group I (P = 0.004), further indicating a greater withdrawal of vagal tone during the HUT test and also during recovery (P = 0.001). Discussion: The results and discussion of HRV analysis during provocative tests concluded that autonomic imbalance was present in the subjects who were not exposed to any form of yoga. Thus, it is advisable to practice yoga in any form regularly to mitigate the early onset of autonomic dysfunction.

Non-dipping pulse rate and chronic changes of the kidney in patients with chronic kidney disease.

Introduction: An insufficient decrease in nocturnal pulse rate (PR), non-dipping PR, reflects autonomic imbalance and is associated with cardiovascular events and all-cause mortality. We aimed to investigate the clinical and microanatomical structural findings associated with the non-dipping PR status in patients with chronic kidney disease (CKD). Methods: This cross-sectional study included 135 patients who underwent ambulatory blood pressure monitoring and kidney biopsy concurrently at our institution between 2016 and 2019. Non-dipping PR status was defined as (daytime PR-nighttime PR)/daytime PR <0.1. We compared clinical parameters and microstructural changes in the kidney between patients with and without non-dipping PR, including 24 h proteinuria, glomerular volume, and Mayo Clinic/Renal Pathology Society Chronicity Score. Results: The median age was 51 years (interquartile range: 35-63), 54% of which were male, and the median estimated glomerular filtration rate was 53.0 (30.0-75.0) mL/min/1.73 m2. Non-dipping PR status was observed in 39 patients. Patients with non-dipping PR were older and had worse kidney function, higher blood pressure, greater prevalence of dyslipidemia, lower hemoglobin levels, and a larger amount of urinary protein excretion than patients with dipping PR. Patients with non-dipping PR had more severe glomerulosclerosis, interstitial fibrosis, tubular atrophy, and arteriosclerosis. In the multivariable analysis, the severe chronic changes of the kidney were associated with non-dipping PR status after adjusting for age, sex, and other clinical parameters (odds ratio = 20.8; 95% confidence interval, 2.82-153; P = 0.003). Conclusion: This study is the first to indicate that non-dipping PR is significantly associated with chronic microanatomical changes in the kidneys of patients with CKD.

A Systematic Review of Clinical Psychophysiology of Obsessive-Compulsive Disorders: Does the Obsession with Diet Also Alter the Autonomic Imbalance of Orthorexic Patients?

(1) Background: A new mental illness is attracting the attention of researchers and mental health professionals. Orthorexia nervosa (ON) is a possible new mental disorder, the main symptom of which is an obsessive and insecure focus on healthy foods and consequent compulsive behaviors. There is a common consensus among researchers that ON is considered partly overlapping with obsessive-compulsive disorders (OCDs). (2) Methods: MEDLINE and Scopus were searched for articles published in the last 10 years regarding the psychophysiological aspects of OCD and ON. Eight studies met the eligibility criteria. The inclusion criteria encompassed adults diagnosed with OCD and/or ON. However, only studies involving OCD patients were found. (3) Results: Some research groups have shown that OCD disorders can be considered among anxiety disorders because they are characterized by anxious hyper activation. Other research, however, has shown profiles characterized by low psychophysiological reactivity to stressful stimuli. Despite this, there seems to be a consensus on the poor inhibition abilities, even when activation is low, and the dissociation between cognitive and psychophysiological activation emerged. (4) Conclusions: However discordant, some points seem to bring the researchers to agreement. In fact, there is consensus on conducting a multidimensional assessment that can measure all of the aspects of suffering (cognition, emotion, and behavior) and highlight the poor body-mind integration. This clinical approach would make it possible to propose interventions aimed at treating some mental illnesses such as food obsession that can paradoxically impair the psychophysical balance. Nevertheless, the applied systematizing approach to existing studies on ON is very much needed for better understanding of the psychophysical nature of this new mental illness and its implications for prevention and treatment.

Aortic thoracic neuromodulation in heart failure with preserved ejection fraction.

The inadequacy of medical therapies for heart failure with preserved ejection fraction (HFpEF) is driving the development of device-based solutions targeting underlying pathophysiologic abnormalities. The maladaptive autonomic imbalance with a reduction in vagal parasympathetic activity and increased sympathetic signalling contributes to the deterioration of cardiac performance, patient fitness, and the increased overall morbidity and mortality. Thoracic aortic vagal afferents mediate parasympathetic signalling, and their stimulation has been postulated to restore autonomic balance. In this first-in-man experience with chronic stimulation of aortic vagal afferents (Harmony™ System, Enopace, Israel), we demonstrate improved left atrial remodelling and function parallel with improved left ventricular performance. The observed favourable structural and functional cardiac changes remained stable throughout the 1 year follow-up and were associated with improved symptoms and physical fitness. The current experience warrants further validation of the endovascular stimulation of aortic thoracic afferents as a new interventional approach for device-based treatment in HFpEF.

Impact of Cardiac Autonomic Dysfunction on Cognitive Event-Related Potential in Type 2 Diabetes Mellitus Patients: A Cross-Sectional Study.

Introduction: Type 2 diabetes mellitus (T2DM) is a chronic metabolic condition that is responsible for various long-term complications. Cognitive impairment is one of the most common complications, but the underlying mechanisms are still undetermined. The autonomic imbalance is a major cause for CVS morbidity in T2DM which could also potentially affect cognition. But there is sparse data available in the literature to prove the association between autonomic dysfunction and cognitive impairment. Methodology: We recruited 40 T2DM patients and 40 healthy controls. The assessment of cognitive functions was done by cognitive P300 event-related potential (ERP) and MoCA. Heart rate variability (HRV) was done to assess autonomic function. Results: The P300 ERP latency in Fz, Cz and Pz sites was significantly prolonged in T2DM patients (P < 0.001). We found moderate correlation is present between P300 latency and total power (r = -0.466, P < 0.01) and LFnu (r = -0.423, P < 0.01) in T2DM patients. The total power and HbA1C show independent association with P300 latency after adjustment for confounding factors like age and duration of diabetes (P < 0.05). Conclusion: As the incidence of Alzheimer's disease is rising among T2DM patients increasing their dependency, making necessary lifestyle measures at earliest to improve autonomic balance may prevent or delay the onset of cognitive decline and alleviate its consequences and improve the quality of life in T2DM patients.

Neuromodulation devices for heart failure.

Autonomic imbalance with a sympathetic dominance is acknowledged to be a critical determinant of the pathophysiology of chronic heart failure with reduced ejection fraction (HFrEF), regardless of the etiology. Consequently, therapeutic interventions directly targeting the cardiac autonomic nervous system, generally referred to as neuromodulation strategies, have gained increasing interest and have been intensively studied at both the pre-clinical level and the clinical level. This review will focus on device-based neuromodulation in the setting of HFrEF. It will first provide some general principles about electrical neuromodulation and discuss specifically the complex issue of dose-response with this therapeutic approach. The paper will thereafter summarize the rationale, the pre-clinical and the clinical data, as well as the future prospectives of the three most studied form of device-based neuromodulation in HFrEF. These include cervical vagal nerve stimulation (cVNS), baroreflex activation therapy (BAT), and spinal cord stimulation (SCS). BAT has been approved by the Food and Drug Administration for use in patients with HfrEF, while the other two approaches are still considered investigational; VNS is currently being investigated in a large phase III Study.

Correlation of serum HDL level with HRV indices using multiple linear regression analysis in patients with type 2 diabetes mellitus.

AIMS/OBJECTIVES: To determine the correlation between serum HDL levels with HRV indices in patients with T2DM. MATERIALS AND METHODS: The study included 120 type 2 DM patients aged 35-65 years of either sex by simple random sampling. One-minute HRV was analyzed during deep breathing and fasting serum HDL levels was estimated in all patients. Data were analyzed using SPSS 20.0. Karl Pearson's correlation coefficient for relationship and Multiple linear regression analysis was applied for assessment of the influence of independent variables (HRV Indices) on a dependent variable (serum HDL levels). P < 0.05 was considered statistically significant. RESULTS: Significant negative correlation was observed between serum HDL levels with Mean HR (r = 0.7422, p < 0.001)), LFnu (r = -0.6172, p < 0.001) and ratio of LF/HF (r = 0.5333, p < 0.001). But significant positive correlation was observed between serum HDL levels with HFnu (r = 0.6438, p < 0.001), SDNN, (r = 0.7495, p < 0.001)), RMSSD (r = 0.6348, p < 0.001) and pNN50 % (r = 0.8187, p < 0.001). CONCLUSIONS: Our findings suggest that HDL-C level and all other HRV indices are dependent on each other in patients with T2DM. Most of these patients with low HDL-C level might be associated with autonomic imbalance; this in turn is detected by a simple bedside test of 1-minute HRV during deep breathing.