Marker Of Autonomic Dysfunction Research Articles

Decreased heart rate variability in sympathetic dominant states in Parkinson's disease and isolated REM sleep behavior disorder

IntroductionParkinson's disease (PD) presents with decreased heart rate variability (HRV) from its early stages. However, most of its evidence originates from HRV measurements in parasympathetic dominant states. In this study, we aimed to examine whether HRV in sympathetic dominant states during the head-up tilt table test (HUT) serves as a marker of autonomic dysfunction in PD and isolated REM sleep behavior disorder (iRBD). MethodsWe retrospectively assessed 102 patients with PD, 10 patients with iRBD, and 43 healthy controls. We then measured the coefficient of variation of RR intervals as an HRV parameter in sympathetic dominant states (CVRR-S) and parasympathetic dominant states (CVRR-P). Furthermore, we evaluated parameters of cardiac autonomic function, including HUT and the heart-to-mediastinum (H/M) ratio of cardiac metaiodobenzylguanidine scintigraphy. ResultsPatients with iRBD and PD at Hoehn and Yahr stage I exhibited a significantly decreased CVRR-S compared to healthy controls (controls vs. iRBD vs. PD; 1.82 ± 0.64 % vs. 1.13 ± 0.41 % vs. 1.15 ± 0.51 %, p < 0.001), although no further deterioration was observed in PD at more severe Hoehn and Yahr stages. CVRR-S showed a significant correlation with the H/M ratio in PD (r = 0.51, p < 0.001). Additionally, receiver operating characteristic (ROC) analysis revealed a larger area under the ROC curve in CVRR-S compared to that in CVRR-P for discriminating PD or iRBD from healthy controls. ConclusionHRV in sympathetic dominant states shows the potential to be a marker of autonomic dysfunction in iRBD and early-stage PD, aiding in early diagnosis and patient stratification.

LIPOPROTEIN ASSOCIATED PHOSPHOLIPASE A2 ACTIVITY IS NEGATIVELY ASSOCIATED WITH DECREASED BAROREFLEX SENSITIVITY IN HIGH NORMAL BLOOD PRESSURE

Objective: The relationship between baroreflex sensitivity (BRS) and inflammatory vascular biomarker Lipoprotein associated phospholipase A2 (Lp-PLA2) in subjects with high normal blood pressure (HNBP, prehypertensives) with a positive family history of hypertension (FHH+) to hypertension history free control subjects (FHH-) was evaluated. Design and method: A total of 24 HNBP participants (age 39.5 ± 2.5 years, 18 male/ 6 female) were studied. 14 HNBP subjects FHH+ were compared to 10 HNBP participants FHH-, being of similar age and body mass index. BRS (ms/mmHg) and BRSf (Hz/mmHg) were determined by the sequence and spectral methods (five-minute non-invasive beat-to-beat recording of blood pressure and inter-beat interval, controlled breathing at a frequency of 0.1 Hz). Venous blood was analysed for Lp-PLA2 biomarker of vascular inflammation and atherothrombotic activity. Results: A significant negative correlation between spontaneous BRS obtained by both methods and blood pressure (BP) was present (BRS spect r = –0.54, p&lt;0.001, BRS seq r = –0.59, p&lt;0.001). BRS obtained by sequence and spectral methods were reduced in HNBP FHH+ compared to group of HNBP without history of hypertension (P= 0.0317 BRS seq, P = 0.0395 BRS spect). There was no difference between both groups of HNBP subjects in BRSf values. Lp-PLA2 was significantly higher in HNBP FHH+ compared to FHH- controls (P = 0.025). Lp-PLA2 was negatively correlated with BRS obtained by sequence method (r = - 0.6758, P = 0.00028) and BRS obtained by spectral method (r = - 0.5935, P = 0.00031). Conclusions: Lipoprotein associated phospholipase A2 is negatively associated with decreased baroreflex sensitivity in subjects with high normal blood pressure and positive family history of hypertension. These findings demonstrate that reduced baroreflex sensitivity as marker of autonomic dysfunction is linked with vascular inflammation predominantly in otherwise healthy participants with positive history of hypertension that could predispose to increased risk of hypertension. Further research is needed.

Chronotropic Incompetence During Exercise Testing as a Marker of Autonomic Dysfunction in Individuals with Early Parkinson's Disease.

An attenuated heart rate response to exercise, termed chronotropic incompetence, has been reported in Parkinson's disease (PD). Chronotropic incompetence may be a marker of autonomic dysfunction and a cause of exercise intolerance in early stages of PD. To investigate the relationship between chronotropic incompetence, orthostatic blood pressure change (supine - standing), and exercise performance (maximal oxygen consumption, VO2peak) in individuals with early PD within 5 years of diagnosis not on dopaminergic medications. We performed secondary analyses of heart rate and blood pressure data from the Study in Parkinson's Disease of Exercise (SPARX). 128 individuals were enrolled into SPARX (63.7±9.3 years; 57.0% male, 0.4 years since diagnosis [median]). 103 individuals were not taking chronotropic medications, of which 90 had a normal maximal heart rate response to exercise testing (155.3±14.0 bpm; PDnon-chrono) and 13 showed evidence of chronotropic incompetence (121.3±11.3 bpm; PDchrono, p < 0.05). PDchrono had decreased VO2peak compared to PDnon-chrono (19.7±4.5 mL/kg/min and 24.3±5.8 mL/kg/min, respectively, p = 0.027). There was a positive correlation between peak heart rate during exercise and the change in systolic blood pressure from supine to standing (r = 0.365, p < 0.001). A subgroup of individuals with early PD not on dopaminergic medication had chronotropic incompetence and decreased VO2peak, which may be related to autonomic dysfunction. Evaluation of both heart rate responses to incremental exercise and orthostatic vital signs may serve as biomarkers of early autonomic impairment and guide treatment. Further studies should investigate whether cardiovascular autonomic dysfunction affects the ability to exercise and whether exercise training improves autonomic dysfunction.

Epilepsy's effect on cardiac rhythm and the autonomic nervous system.

Sudden unexpected death in epilepsy is the most common cause of death in young patients with epilepsy. The aim of this study was to evaluate changes in interictal electrocardiogram parameters and sympathetic skin responses as markers of autonomic dysfunction in patients with epilepsy and to determine their effects on the type and duration of epilepsy, frequency of seizures, and responses to treatment. A total of 97 patients with epilepsy and 94 healthy controls were recruited. We recorded their clinical and demographic characteristics and analyzed sympathetic skin response latency and amplitude, electrocardiogram recordings, and seven cardiac rhythm parameters: P-wave duration, PR segment, QRS duration, QT interval, QT interval distribution, Tpe duration, and Tpe/QT interval ratio. P-wave durations, T-wave durations, QT and QT interval durations, and Tpe and sympathetic skin response latency were significantly longer among patients with epilepsy than the controls, and their heart rate was significantly lower. However, sympathetic skin response latency and heart rate were negatively correlated, and T-wave duration, QT duration, QT interval duration, and Tpe were positively correlated. Our results from interictal electrocardiograms indicate clinically significant arrhythmias among patients with epilepsy and the correlation of such arrhythmias with sympathetic skin responses. Thus, noninvasive tests that evaluate the autonomic system should be used to predict the risk of sudden unexpected death in epilepsy among patients with epilepsy.

Delayed blood pressure recovery after exercise stress test is associated with autonomic dysfunction and pulse pressure in a middle-aged healthy group.

Delayed heart rate (HR) and blood pressure recovery after exercise test is known as the reliable indexes of autonomic dysfunction. Here we tried to evaluate the serial changes in various indicators during exercise test and correlations with recovery of HR and blood pressure in a normotensive healthy middle-aged group. A total of 122 patients without hypertension or diabetes was enrolled (mean age, 55.6 ± 11.0; male, 56.6%; mean blood pressure, 124.8 ± 16.6 / 81.5 ± 9.6 mmHg). Treadmill test was performed for evaluation of chest pain. Patients with coronary artery disease, positive treadmill test result, left ventricular dysfunction or renal failure were excluded. Heart rate recovery was calculated by subtracting the HR in the first or second minute of recovery period from the HR of peak exercise (HRR1 or HRR2). Systolic blood pressure in the 4th minute of recovery stage (SBPR4) was used to show delayed blood pressure recovery. Metabolic equivalents (METs) and HR in stage 2 to 4 were significantly correlated with both HRR1 and HRR2. Multiple regression analysis of HRR revealed significant correlation of METs and SBPR4. SBPR4 was significantly correlated with both HRR1 and HRR2 (HRR1, r = -0.376, p<0.001; HRR2, r = -0.244, p = 0.008) as well as SBP in the baseline to stage 3 and pulse pressure (r = 0.406, p<0.001). Delayed BP recovery after peak exercise test revealed significant association with autonomic dysfunction and increased pulse pressure in normotensive middle-aged healthy group. It can be a simple and useful marker of autonomic dysfunction and arterial stiffness.

Orthostatic Stress and Baroreflex Sensitivity: A Window into Autonomic Dysfunction in Lone Paroxysmal Atrial Fibrillation.

The abnormal neural control of atria has been considered one of the mechanisms of paroxysmal atrial fibrillation (PAF) pathogenesis. The baroreceptor reflex has an important role in cardiovascular regulation and may serve as an index of autonomic function. This study aimed to analyze the baroreceptor reflex's role in heart rate regulation during upright tilt (HUT) in patients with lone PAF. The study included 68 patients with lone PAF and 34 healthy individuals who underwent baroreflex assessment. Parameters such as baroreflex sensitivity (BRS), number of systolic blood pressure (BP) ramps, and the baroreflex effectiveness index (BEI) were evaluated. The study found that PAF patients had comparable resting BPs and heart rates (HRs) to healthy individuals. However, unlike healthy individuals, PAF patients showed a sustained increase in BP with an upright posture followed by the delayed activation of the baroreceptor function with a blunted HR response and lower BEI values. This indicates a pronounced baroreflex impairment in PAF patients, even at rest. Our data suggest that together with BRS, BEI could be used as a marker of autonomic dysfunction in PAF patients, making it important to further investigate its relationship with AF recurrence after ablation and its involvement in cardiovascular autonomic remodeling.

Evaluating Diagnostic Ultrasound of the Vagus Nerve as a Surrogate Marker for Autonomic Neuropathy in Diabetic Patients.

Background and Objectives: Diagnostic ultrasound of the vagus nerve has been used to examine different polyneuropathies, and it has been suggested to be useful as a marker of autonomic dysfunction in diabetic patients. Materials and Methods: We analyzed the cross-sectional area (CSA) of the right vagus nerve of 111 patients with type 2 diabetes in comparison to 104 healthy adults and 41 patients with CIDP (chronic inflammatory demyelinating polyneuropathy). In the diabetes group, sympathetic skin response (SSR) was measured as an indicator for autonomic neuropathy. Carotid intima-media thickness (CIMT) was measured as a surrogate for atherosclerosis. Clinical symptoms of polyneuropathy were assessed using the Neuropathy Symptom Score and the Neuropathy Disability Score. Results: In total, 61.3% of the diabetes patients had clinical signs of polyneuropathy; 23.4% had no SSR at the feet as an indicator of autonomic neuropathy. Mean vagus nerve CSA did not differ in patients with and without diabetic polyneuropathy or in diabetic patients with and without SSR at the feet. No significant correlation was found between vagus nerve CSA and CIMT or SSR parameters in diabetic patients. Mean CSA of the right vagus nerve was slightly larger in diabetic patients (p = 0.028) and in patients with CIDP (p = 0.015) than in healthy controls. Conclusions: Effect sizes and mean differences were rather small so that a reliable diagnosis cannot be performed based on the vagus nerve measurement of a single person alone. Vagus nerve CSA seems not suitable as an indicator of autonomic dysfunction or cardiovascular risk in diabetic patients.

Interleukin-33 and soluble suppression of tumorigenicity 2 in scleroderma cardiac involvement

Interleukin (IL)-33 is part of the IL-1 family of cytokines and soluble suppression of tumorigenicity 2 (sST2) is part of the family of IL-1 receptors. In systemic sclerosis (SSc), IL-33 and sST2 are involved in cardiac manifestations such as diastolic dysfunction (DD), autonomic dysfunction (AD) and right ventricular–pulmonary arterial coupling assessed by tricuspid annular plane systolic excursion (TAPSE)/systolic pulmonary artery pressure (sPAP). Serum levels of IL33 and sST2 were assessed in 50 SSc patients and 14 healthy controls (HC). Clinical assessment, echocardiography and heart rate variability (HRV) analysis were performed in SSc patients. Serum levels of IL-33 and sST2 were significantly higher in SSc patients than HC. A linear positive correlation between modified Rodnan skin score and IL33 was observed. Serum values of sST2 were higher in SSc patients with DD than in patients without DD [15403 pg/ml (12,208–19,941) vs 8556 pg/ml (6820–11,036), p < 0.001]. sST2 showed a negative correlation with standard deviation of normal-to-normal RR intervals (SDNN) (r = − 0.281, p < 0.05) and positive correlation with low frequency/high frequency (LF/HF) (r = 0,349, p < 0.01). Negative linear correlation exists between sST2 and TAPSE/sPAP (r = − 0.398, p < 0.01). Serum levels of IL-33 and sST2 are higher in SSc patients than HC. Serum levels of sST2 are a potential marker of DD, AD and right ventricular–pulmonary arterial coupling.

It takes time to heal a broken heart: ventricular plasticity improves heart performance after myocardial infarction in rainbow trout, Oncorhynchus mykiss.

Coronary arteriosclerosis is a common feature of both wild and farmed salmonid fishes and may be linked to stress-induced cardiac pathologies. Yet, the plasticity and capacity for long-term myocardial restructuring and recovery following a restriction in coronary blood supply are unknown. Here, we analyzed the consequences of acute (3 days) and chronic (from 33 to 62 days) coronary occlusion (i.e. coronary artery ligation) on cardiac morphological characteristics and in vivo function in juvenile rainbow trout, Oncorhynchus mykiss. Acute coronary artery occlusion resulted in elevated resting heart rate and decreased inter-beat variability, which are both markers of autonomic dysfunction following acute myocardial ischemia, along with severely reduced heart rate scope (maximum-resting heart rate) relative to sham-operated trout. We also observed a loss of myocardial interstitial collagen and compact myocardium. Following long-term coronary artery ligation, resting heart rate and heart rate scope normalized relative to sham-operated trout. Moreover, a distinct fibrous collagen layer separating the compact myocardium into two layers had formed. This may contribute to maintain ventricular integrity across the cardiac cycle or, alternatively, demark a region of the compact myocardium that continues to receive oxygen from the luminal venous blood. Taken together, we demonstrate that rainbow trout may cope with the aversive effects caused by coronary artery obstruction through plastic ventricular remodeling, which, at least in part, restores cardiac performance and myocardium oxygenation.

Abstract 11025: Markers of Heart Rate Variability Represent Strong and Independent Predictors of All-Cause Death in Heart Failure - Results from the Myovasc Study

Introduction: Although different measures of heart rate variability (HRV) have been proposed as markers of autonomic dysfunction (AD) in heart failure (HF), evidence on their clinical relevance is limited. Methods: Data from the MyoVasc study (NCT04064450; N=3,289), a prospective cohort study on chronic HF, were analyzed. Study participants received a highly standardized, 5-hour examination including 24-hour Holter ECG recording. RR intervals were extracted to evaluate HRV markers from time and frequency domain analyses, and non-linear markers derived via phase space reconstruction, phase-rectified signal averaging, and entropy analyses. HRV markers of interest were selected using a systematic literature screen, and a random survival forest model predicting cardiac death. Reference values were determined in a healthy subsample. To evaluate clinical relevance, HRV markers were investigated in multivariable Cox regression analyses for their relationship to all-cause death considering potential confounders and mediators. Results: Holter ECG recordings were available for analysis in 1,001 study participants (mean age 64.5±10.5 years; female sex: 35.4%). While the top 10 most frequently reported HRV markers in literature screen were from the time and frequency domains, the data-driven approach revealed predominantly non-linear HRV measures. Values outside reference ranges for SDANN, rMSSD, frequency bands (i.e., ULF, VLF, LF, total power, ULF MED wavelet ), acceleration capacity (AC), deceleration capacity (DC), and time lag, were strong predictors of all-cause death in Cox regression analysis (median follow-up time: 6.1 [IQR 4.7/7.1] years) adjusted for age, sex, clinical profile and medication. In linear Cox regression analyses of the total sample, LF/HF (hazard ratio per SD (HR SD ) 0.78 [95% confidence interval (CI) 0.62, 0.98], p=0.034), time lag (HR SD 1.23 [95%CI 1.05, 1.44], p=0.0095), AC (HR SD : 1.57 [95%CI 1.24, 1.99], p=0.0002), and DC (HR SD 0.67 [95%CI 0.53, 0.85], p=0.0012) were strong predictors for all-cause mortality independent of age, sex, clinical profile and medication. Conclusions: HRV markers reflecting AD are strong predictors of all-cause death in HF, suggesting clinical relevance and potential for intervention.

Orthostatic hypotension and atrial fibrillation: is there a relationship?

Orthostatic hypotension (OH), a possible marker of autonomic dysfunction, reflects the inability of reflex cardiovascular mechanisms to compensate for the fall in venous return in the upright position. This is a manifestation of structural and functional abnormalities of the cardiovascular system. Significance of the orthostatic hypotension is underestimated, while it is associated with all-cause mortality and cardiovascular disease. The article reviews the relationship between atrial fibrillation (AF) and OH. The pathogenetic mechanisms of OH are considered, including various subgroups, e. g. elderly patients. The article also discusses the relationship between OH, AF and cerebrovascular complications. Available evidence suggests that impaired orthostatic hemodynamic response should be considered as a new risk factor for AF. Further research is needed for better understanding of the association between AF and OH, as well as their management.

Abstract P054: Duration Of Diabetes, Glucose Excursions, Glycemic Control, And Low Heart Rate Variability: The Atherosclerosis Risk In Communities (aric) Study

Introduction: Individuals with diabetes often have low heart rate variability (HRV)—a marker of autonomic dysfunction. How diabetes duration, glucose excursions, and poor glycemic control relate to HRV is not well characterized. Objectives: To evaluate the associations of diabetes status, duration of diabetes, and biomarkers of glucose excursions (1,5-anhydroglucitol [1,5-AG]—a measure of glycosuria) and glycemic control with HRV. Methods: We conducted a cross-sectional analysis of ARIC Study participants who underwent a 2-minute electrocardiogram at visit 4 (1996-98). We considered root mean square of successive differences in normal-to-normal R-R intervals (rMSSD, measure of parasympathetic activity), standard deviation of normal-to-normal R-R intervals (SDNN, total variability), low frequency (LF, primarily sympathetic activity), high frequency (HF, reflects parasympathetic activity), and LF/HF ratio (sympathetic-parasympathetic balance) as HRV indices. In persons with diabetes, we compared geometric means of HRV indices by diabetes duration (&lt;5 years vs ≥5 years), 1,5-AG (&lt;6 μg/mL vs ≥6 μg/mL), and glucose control (estimated A1C &lt;8% vs ≥8%). We obtained p-values from linear regressions adjusted for age and sex. Results: Among 10169 participants (mean age 63, 57% female, 22% black), participants with diabetes had significantly lower rMSSD, SDNN, LF, HF, and LF/HF ratio compared to those without diabetes ( Table ). Among the 1667 participants with diabetes, longer duration of diabetes, low 1,5-AG, and poor glycemic control were associated with lower rMSSD, SDNN, LF, and HF. No statistically significant associations were found for diabetes duration, 1,5-AG, glycemic control with LF/HF ratio. Discussion: Our results demonstrate that longer duration of diabetes, glucose excursions, and poor glycemic control are associated with some measures of low HRV. This study underscores that cardiac autonomic neuropathy is a common but overlooked complication of long-standing and/or poorly managed diabetes.

Negative association between lipoprotein associated phospholipase A2 activity and baroreflex sensitivity in subjects with high normal blood pressure and a positive family history of hypertension.

The relationship between baroreflex sensitivity (BRS) and inflammatory vascular biomarker Lipoprotein associated phospholipase A2 (Lp-PLA2) in subjects with high normal blood pressure (HNBP, prehypertensives) with a positive family history of hypertension (FHH+) and hypertension history free control subjects (FHH-) was evaluated. A total of 24 HNBP participants (age 39.5 ± 2.5 years, 18 male/ 6 female) were studied. 14 HNBP subjects FHH+ were compared to 10 HNBP participants FHH-, being of similar age and body mass index. BRS (ms/mmHg) was determined by the sequence and spectral methods (five-minute non-invasive beat-to-beat recording of blood pressure and RR interval, controlled breathing at a frequency of 0.33 Hz). Venous blood was analyzed for Lp-PLA2 biomarker of vascular inflammation and atherothrombotic activity. A significant negative correlation between spontaneous BRS obtained by both methods and systolic blood pressure (BP) was present (BRS spect r = -0.54, P<0.001, BRS seq r = -0.59, P<0.001). BRS obtained by sequence and spectral methods were reduced in HNBP FHH+ compared to the group of HNBP FHH- (P = 0.0317 BRS seq, P = 0.0395 BRS spect). Lp-PLA2 was significantly higher in HNBP FHH+ compared to FHH- controls (P<0.05). Lp-PLA2 was negatively correlated with BRS obtained by sequence method (r = -0.798, R2 = 0.636, P<0.001) in the HNBP FHH+ subjects. These findings demonstrate that reduced baroreflex sensitivity, as a marker of autonomic dysfunction, is associated with vascular inflammation, predominantly in otherwise healthy participants with a positive family history of hypertension who could predispose to increased risk of hypertension. We conclude that our transversal study suggests that a lowbaroreflex sensitivity could be an early sign of autonomic dysfunction even in the prehypertensive period, and to corroborate these findings, a longitudinal study is needed.

490 High-Resolution Electrogastrogram Identifies Disturbed Gastric Slow Waves and Dysautonomia in Subjects With Dumping Syndrome

INTRODUCTION: Rapid gastric emptying is the sine qua non of Dumping Syndrome (DS), which can arise from multiple etiologies including gastric surgery and diabetes mellitus. The relationship between DS and gastric myoelectric activity is unknown, but dysautonomia may play a role. We sought to characterize features of gastric slow waves and autonomic indices among subjects with DS using the ambulatory high-resolution electrogastrogram (HR-EGG). METHODS: Eleven subjects completed 24-hour ambulatory HR-EGG. Fasting abdominal computed tomography scan was utilized for stomach localization and placement of the ambulatory HR-EGG array, consisting of 10 skin mounted electrodes. Subjects were divided into two groups: DS (4F, age 53.2 ± 9.3, BMI 31.7 ± 11, 79-93% gastric emptying at 1 hour on scintigraphy, two diabetics, one prior gastric surgery, one gastrointestinal amyloidosis) and healthy age-matched controls (4M/3F, age 47.6 ± 28, BMI 24.5 ± 3.7). All subjects completed the PAGI-SYM foregut symptom questionnaire and a diary capturing all meals and sleep/wake times. RESULTS: Subjects with DS had significantly higher mean PAGI-SYM foregut symptom severity scores (1.9 ± 1.0 vs 0.1 ± 0.1; P = 0.0007). HR-EGG showed that DS subjects had a significantly lower slow wave speed (4.6 vs 5.9 ± 0.4; P = 0.0003) and higher post-prandial power change (11 vs 3.5 ± 3.6; P = 0.002) compared to healthy controls. The global percent stomach activity throughout the 24-hour ambulatory recordings was not different between groups. DS subjects trended towards higher post-prandial area under the curve EGG activity at both the 1-hour (261.9 ± 360.7 vs 172.9 ± 137.5) and 4-hour marks (1108.8 ± 1589.4 vs 656.3 ± 442.2). In addition, subjects with DS had significantly lower heart rate variability than controls: RMSDD (39.9 ± 9.7 vs 58.1 ± 7.8) and SDNN (12.6 ± 4.2 vs 23.7 ± 3.2); no differences were noted in mean heart rate (Table 1). CONCLUSION: Ambulatory HR-EGG clearly identifies that there are spatial abnormalities of the gastric slow wave present among subjects with DS. Moreover, reduced heart rate variability - a marker of autonomic dysfunction - was observed among subjects with DS. These findings suggest that gastric dysrhythmias and autonomic disturbances should be given important consideration in the pathogenesis of Dumping Syndrome.

Insular resection may lead to autonomic function changes

ObjectiveThe aim of this study was to determine if insular damage is associated with markers of autonomic dysfunction. MethodsWe studied patients who underwent temporal lobe and/or insular resections for epilepsy surgery between April 2010 and June 2015 at University Hospitals Cleveland Medical Center (UHCMC). Presurgical T1-weighted MPRAGE, standard T1, T2 and FLAIR sequences were compared with postsurgical MRI by a neuroradiologist and classified as type 0 (no involvement of insula), type 1 (minimal involvement of insular margin), type 2 (insular involvement <25%), and type 3 (insular involvement ≥25%).Analysis of heart rate variability (HRV) was carried out in pre- and postoperative video-electroencephalography (vEEG) recording. Time-domain parameters were calculated: (mean of the RR intervals (MNN), root mean square difference of successive RR intervals (RMSSD), standard deviation of the RR intervals (SDNN), and coefficient of variation (CV)). In addition, frequency-domain parameters were calculated: low frequency (LF), high frequency (HF), and low frequency/high frequency (LF/HF). ResultsTwenty-one patients (14 females) with mean age of 36.2 ± 14.4 years (30; 22–75) were studied. Insular involvement was classified as type 0 (4 patients [19%]), type 1 (9 [43%]), type 2 (7 [33%]), and type 3 (1 [5%]). Significant decrease in RMSSD (p = 0.025) and CV (p = 0.008) was seen in insular damage types 2 and 3 compared with no or minimal insular involvement (types 0 and 1). Right-sided resections were associated with increase in LF power (p = 0.010) and the LF/HF ratio (p = 0.017). ConclusionsThis study indicates that insular resection may lead to autonomic function changes.

Abstract 14: Is Low Heart Rate Variability, a Marker of Autonomic Dysfunction, the Missing Link Between Migraine With Visual Aura and Cardioembolic Stroke?

Introduction: Migraine with visual aura (MA) has been associated with the risk of cardioembolic stroke (CES). Low heart rate variability (HRV), a marker of cardiac autonomic dysfunction, has been shown to be associated with atrial fibrillation (AF) and risk of stroke. We investigated the association between low HRV and MA. We also examined whether the MA associated CES risk can be explained by a low HRV. Methods: Participants in the Atherosclerosis Risk in Communities cohort were interviewed for migraine history in 1993-1995; during a subsequent follow-up visit (1996-1998) HRV was measured using 6-minute EKG. HRV indices were calculated using the standard deviation of RR intervals (SDNN), the mean of all normal RR intervals (MeanNN), the root mean square of successive differences of RR intervals (RMSSD), low (LF) and high (HF) frequency power, and the LF/HF ratio. All HRV measures were categorized into quintiles. Logistic regression models were used to estimate ORs adjusted for sociodemographic and comorbid confounders. Mediation analysis was conducted to test if HRV was a mediator of MA associated CES risk, using Barron-Kenny’s causal step tests. Results: Of 11,939 participants assessed for headache 426 reported MA. A total of 164 incident CES occurred over a 20-year follow-up period. After covariate adjustment, there was a strong evidence of an association between low HRV and MA. The lowest HRV quintile was associated with higher odds of MA compared with the highest quintile for SDNN (OR, 1.5, 95% CI, 1.1–2.3), RMSSD (OR, 1.4; 95% CI, 1.1–2.1), LF (OR, 1.3; 95% CI, 1.0–1.8), HF (OR, 1.5; 95% CI, 1.1–2.1), and LF/HF ratio (OR, 1.5; 95% CI, 1.1–2.0). The data also suggests HRV may be a potential mediator between MA and CES. Conclusion: MA was associated with low HRV, suggestive of chronic autonomic dysfunction among this population. Alongside prior findings showing HRV-AF, HRV-Stroke and AF-Stroke link, the association may provide the missing link between MA and Stroke (Figure).

Can decreased heart rate variability be a marker of autonomic dysfunction, metabolic syndrome and diabetes?

Epidemiological studies show an emergence of diet- and lifestyle-related diseases; Cardio-metabolic diseases (CMD) and neuropsychiatric diseases (classified as non-communicable diseases or chronic diseases). Diet and lifestyle factors can cause adverse effects on autonomic function resulting in decreased heart rate variability (HRV). Low HRV is a risk factor for CMDs. There is a need to find out new methods of early diagnosis for prevention and treatment of these problems because the neurohormonal dysfunction could be the earliest manifestation. It is possible that HRV could be a marker for the early diagnosis of these problems, because it is characterised with increased sympathetic and reduced parasympathetic activity. Several studies indicate that increased unhealthy diet, mental stress, sedentary lifestyle, tobacco, insomnia and alcoholism may be associated with neurohormonal dysfunction, which may cause decline in HRV. Majority of the chronic diseases (e.g., diabetes, hypertension, heart attack, neuropsychiatric disease and cancer) are associated with decreased HRV. The studies also indicate that solar and geomagnetic activities may influence circadian clock and hypothalamus resulting in the oxidative stress and inflammation with alteration in HRV. It is possible that reduced HRV will correlate with various stages of autonomic dysfunction, associated with chronic diseases. Simple methods need to be developed to measure HRV for early diagnosis of neurohormonal dysfunction, which may be important for early management. This review aims to find out available evidence on the role of HRV in the early diagnosis of chronic disease (with specific focus on Type 2 diabetes) and the factors affecting HRV.

Interictal electrocardiographic alternations in patients with drug-resistant epilepsy

PurposePrevious studies suggested the possible role of autonomic dysfunction in sudden unexpected death in epilepsy (SUDEP). The aim of this study is to assess the interictal ECG alternations especially heart rate variability (HRV), as a marker of autonomic dysfunction, in patients with drug-resistant epilepsy and determine the effect of epilepsy type and duration, seizure frequency and anti-epileptic drugs (AEDs) on ECG findings. MethodsIn this comparative cross-sectional study, the interictal ECG parameters of 64 consecutive patients with drug-resistant epilepsy and the same number of age and sex-matched controls were analyzed. Epilepsy type and duration, seizure frequency, MRI findings and patients’ anti-convulsive medications were determined. ResultsOur study showed significant longer mean PR interval, shorter mean QRS duration, shorter mean QTc interval and longer corrected QT interval dispersion (QTcd) in patients with epilepsy compared to healthy subjects. The analysis of RR intervals revealed reduced RR standard deviation (SDNN), which is a marker of reduced HRV. A positive linear correlation was found between QRS duration and epilepsy duration. No significant correlation was found between taking a certain kind of AED, and ECG alternations, except for mild QTcd prolongation in patients taking valproate. ConclusionOur study showed clinically important alternations in interictal ECG parameters in patients with drug-resistant epilepsy which could result in sudden cardiac death.

Cardiovascular Autonomic Dysfunction in Patients with Cancer.

Elucidating the mechanisms that contribute to adverse cardiovascular (CV) outcomes and reduce quality of life among patients with cancer is paramount. Cancer, certain cancer drugs, radiation therapy, cancer-associated lifestyle disturbances, and cancer-independent comorbidities combine to predispose oncology patients to autonomic dysfunction (AD). This review will explore the assessment, etiology, and clinical implications of AD in cancer patients and will speculate on therapeutic and research opportunities. AD is particularly prevalent among patients with advanced cancer, but studies suggest increased prevalence across the entire continuum of cancer survivors compared to cancer-free controls. Data on cancer therapy-induced injury to the autonomic nervous system are limited to small studies. AD has been reported after cranial, neck, and mediastinal radiation therapy. Although AD has been shown to confer increased risk of adverse CV outcomes in cancer-free patients, the prognostic relevance of AD in oncology patients is less well investigated. Markers of AD including elevated resting heart rate (HR), reduced HR variability, and abnormal HR recovery have been associated with shorter survival times in various cancer cohorts. Furthermore, AD has been implicated in the etiology of cancer-related fatigue and exercise limitation. Multiple risk factors predispose oncology patients to AD, which is associated with adverse outcomes, including increased mortality, exercise limitation, and fatigue among this cohort. The contribution of AD to overall morbidity and mortality in cancer survivors has largely been overlooked to date. Further investigation is necessary to better understand cancer-treatment specific autonomic injury and to evaluate the role of various pharmacological and non-pharmacological interventions with potential to tackle the sympathovagal imbalance observed in cancer survivors.

Evidence of reduced parasympathetic autonomic regulation in inflammatory joint disease: A meta-analyses study.

Rheumatoid arthritis (RA) and spondyloarthritis (SpA) are inflammatory joint disorders (IJD) with increased risk of cardiovascular disease (CVD). Autonomic dysfunction (AD) is a risk factor for CVD, and parasympathetic AD is linked to key features of IJD such as inflammation, physical inactivity and pain. Heart-rate variability (HRV) is a marker of cardiac AD. The study objective was to compare parasympathetic cardiac AD, measured by HRV, between patients with IJD and healthy controls, using meta-analysis methodology, and to examine the impact of inflammation, physical inactivity and pain on HRV in IJD. Medline, Embase and Amed were searched. Inclusion criteria were adult case-control studies published in English or a Scandinavian language, presenting HRV data in IJD. Two measures of HRV and 3 from the Ewing protocol were selected: square root of mean squared difference of successive R-R intervals (RMSSD), high frequency (HF), Ewing protocol; standing (E-S), breathing (E-B) and Valsalva (E-V). Patients with RA, SpA and healthy controls were compared separately using random-effects meta-analyses of standardized mean differences (SMD). In all, 35 papers were eligible for inclusion. For RMSSD the pooled SMD (95% CI) RA vs. controls was -0.90 (-1.35 to -0.44), for SpA vs. controls; -0.34 (-0.73 to 0.06). For HF pooled SMD RA vs. controls was -0.78 (-0.99 to -0.57), for SpA vs. controls; -0.04 (-0.22 to 0.13). All Ewing parameters were significantly lower in cases, except for E-V which was comparable between cases and controls in patients with RA. Patients with IJD have cardiac parasympathetic AD which is related to inflammation.