Standard Autonomic Function Tests Research Articles

Distribution of Cardiovascular Dysautonomia Pattern across Different Stages of Chronic Kidney Disease

Context: Autonomic dysfunction (AD) brings up cardiovascular morbidity/mortality and has been reported in chronic kidney disease (CKD). Still, the pattern of AD in CKD is elusive. Aim: To evaluate the distribution of cardiovascular dysautonomia in CKD. Material and Methods: This study was conducted on 33 CKD cases and 30 age and sex matched healthy controls. Five standard autonomic function tests were conducted, namely, heart rate response to Valsalva maneuver, deep breathing, and standing, and BP response to standing and sustained handgrip; based on which the patients were classified as normal, or having early parasympathetic, definite parasympathetic and combined damage. The total autonomic function score was also calculated. Results: All cases belonged to CKD stages of 3, 4, and 5; and came up with autonomic failure. The mean total autonomic function score was higher (P < 0.001) in CKD (5.09 ± 2.33) as compared to the control group (0.97 ± 0.24), using the unpaired “t” test. Most of the CKD patients (45.45%) were involved with combined damage. Of the three stages, combined damage struck stage 5 to the maximum extent (63.63%). Sympathetic failure always co occurred with parasympathetic failure. Conclusion: Combined autonomic failure is more conspicuous in late CKD, predominantly occurring in stage 5. The disease course may contort the parasympathetic system before the sympathetic system.

Frequency and severity of autonomic dysfunction assessed by objective hemodynamic responses and patient-reported symptoms in individuals with myasthenia gravis.

Myasthenia gravis (MG), a rare autoimmune disorder, poses diagnostic and management challenges, with increasing incidence in Europe and significant impact on patient quality of life. Despite prevalent autonomic symptoms, comprehensive assessments integrating subjective and objective measures are lacking. We aimed to investigate the prevalence and severity of autonomic dysfunction in patients with MG and healthy controls (HCs). We used beat-to-beat hemodynamic responses during standardized autonomic function tests (AFTs) and the Composite Autonomic Symptom Score 31 (COMPASS-31) questionnaire. Study participants including, 53 patients with MG and 30 age- and sex matched HCs underwent standardized cardiovascular AFTs and completed the COMPASS-31 questionnaire. Patients were categorized into Non-CAN and CAN groups based on their Cardiovascular Autonomic Neuropathy (CAN) status, as evaluated using the Composite Autonomic Scoring Scale (CASS). During the AFTs, cardiovascular parameters including heart rate, systolic blood pressure (BP), diastolic BP, mean BP, stroke volume (SV), cardiac output (CO), and total peripheral resistance (TPR) were measured. Twenty patients with MG (38%) exhibited mild CAN (CASS ≥2) with a median total CASS score of 1.00 and CASS 0.00 in HCs. Adrenergic impairment was observed in 27 patients (52%), with 13 patients (24.5%) exhibiting longer pressure recovery time after Valsalva maneuver (VM). Cardiovagal impairment was evident in 71% of patients, with abnormal results observed in 39.6% for the deep breathing test and 56.6% for the VM. CAN MG showed worse scores than HCs for the total COMPASS-31 (p < 0.001), orthostatic (OI) (p < 0.001), secretomotor (p = 0.004), and pupillomotor domains (p = 0.004). Total COMPASS-31 and OI scores were correlated with worse disease outcomes (disease duration, severity), hemodynamic parameter changes (SV, CO, TPR) during phase II late of VM, and with changes (Δtilt-supine) in Δsystolic BP, Δdiastolic BP, Δmean BP, ΔTPR during head-up-tilt test, but not with CASS score. Our findings demonstrate mild cardiovascular autonomic impairment in adrenergic and cardiovagal domains in patients with MG. Additionally, patient-reported autonomic symptoms correlated with hemodynamic changes during AFTs and worse disease outcomes and not with the grade of autonomic abnormalities. Incorporating beat-to-beat hemodynamics during AFTs may offer further insights for characterizing orthostatic intolerance symptoms in MG group.

Composite autonomic severity scoring in spinocerebellar ataxia type 1 and 2

ObjectivesThe aim of the present study was to evaluate the integrity of autonomic nervous system in spinocerebellar ataxia (SCA) type 1 and 2 patients using battery of autonomic function tests and their comprehensive scoring using composite autonomic severity score (CASS). Material and methodsBattery of autonomic function test comprising of cardiovascular (baroreflex dependent and non-baroreflex dependent) and sudomotor functions were assessed in age and gender-matched SCA1 (n = 31), SCA2 (n = 40) patients along with healthy controls (n = 40). To assess the grade of autonomic abnormalities, the composite autonomic severity score (CASS) was computed using the results of the standard autonomic function tests. ResultsWe found reduction in baroreflex dependent autonomic reactivity parameters predominantly a significant fall of systolic blood pressure (<0.001) and lower 30:15 ratio (<0.001) during head up tilt in both the SCA1 and SCA2 as compared to controls. On sudomotor assessment, distal leg latency of sweat response was prolonged in SCA1 than SCA2 patients. Moderate generalized autonomic failure was commonly found amongst SCA1 (80.65%) and SCA2 (85%) patients. Severe autonomic failure was found to be more in SCA1 (6.45%) than SCA2 (2.50%) patients. ConclusionsCardiovascular autonomic function assessment in SCA1 and SCA2 patients revealed a significant impairment in the baroreflex loop integrity. Severity scoring using CASS suggests the existence of moderate autonomic failure in majority of both SCA1 and SCA2 patients.

Comparison of baroreflex sensitivity indices with standard tests of autonomic nervous system function

ObjectiveIn order to further evaluate clinical usefulness of α- and β-adrenergic components of the baroreflex sensitivity (BRS) index, the aim of this study was to compare them to standardized measures of the autonomic dysfunction. MethodsIn 275 participants (mean age 40.57 ± 15.19, range 18 to 89 years, 76.4% females) referred for testing of the autonomic nervous system, α-BRSa, β-BRSa and BRSv were compared to heart rate (HR) and blood pressure (BP) values, adrenergic and cardiovagal indices of the Composite Autonomic Severity Score (CASS) and heart rate variability (HRV) parameters. Resultsα-BRSa showed statistically significant positive correlation with HR in the supine position and negative with the adrenergic index. β-BRSa showed statistically significant negative correlation with tests for parasympathetic nervous system function. BRSv showed statistically significant negative correlation with all HR and BP parameters and positive with all HRV parameters. In a univariable logistic regression analysis, α-BRSa was a negative predictor (Exp(B) 0.866, 95% CI 0.782–0.959, p = 0.006, respectively) of the pathological adrenergic index. To differentiate between subjects with normal and pathological adrenergic index, the optimal cutoff for α-BRSa was found to be 6.741, which gave a sensitivity of 61.0% and a specificity of 56.0%. ConclusionBRSa indices showed a good correlation with standard measures of ANS function. The most promising test was α-BRSa, which performed well as a α adrenergic receptors mediated sympathetic nervous system marker.

Impact of sleep disturbances and autonomic dysfunction on the quality of life of patients with fibromyalgia.

Fibromyalgia, a painful musculoskeletal disorder is associated with sleep disturbances as well as autonomic dysfunction. Pathophysiology of fibromyalgia is yet not clear and neuroanatomical proximity of sleep and autonomic centre prompts probable involvement of the two impacting the quality of life of fibromyalgia patients. Present study was done with the objective to explore the extent of sleep disturbances and/or autonomic dysfunction in fibromyalgia and asses their impact on quality of life of fibromyalgia patients. Thirty consecutive fibromyalgia patients (diagnosed by ACR 2010) from out-patient department and 30 age-gender matched controls were enrolled after the ethical clearance. All participants were evaluated for: (1) sleep using Pittsburgh sleep quality index and medical outcomes study sleep scale-12 Revised, (2) Quality of life by 36 item short-form health survey-36v2TM and revised fibromyalgia impact questionnaire (only patients). Autonomic functions of patients were evaluated by standard cardiovascular autonomic function tests by Ewing's battery and heart rate variability (5-min) measurement. Fibromyalgia patients had increased sleep disturbances compared to controls (39.46±11, 59.61±2.31; p=0.0001) and very poor sleep quality (13.63±4.15, 3.03±1.56; p=0.0001) as well as quality of life (p=0.0001) which further deteriorated with increasing severity of fibromyalgia. Twelve patients had autonomic dysfunction but it was neither associated with sleep disturbances nor with quality of life. Mild to moderate grade fibromyalgia patients have significant sleep disturbance, poor sleep quality which remarkably impacts their quality of life. Autonomic dysfunction is not an early feature of disease. The study suggests that full spectrum of sleep disturbances and sleep quality should be explored in fibromyalgia syndrome (FMS) patients.

Resting Heart Rate Variability Is Associated With Subsequent Orthostatic Hypotension: Comparison Between Healthy Older People and Patients With Rapid Eye Movement Sleep Behavior Disorder

Background: Orthostatic hypotension (OH) caused by autonomic dysfunction is a common symptom in older people and patients with idiopathic rapid eye movement sleep behavior disorder (iRBD). The orthostatic challenge test is a standard autonomic function test that measures a decrease of blood pressure during a postural change from supine to standing positions. Although previous studies have reported that changes in heart rate variability (HRV) are associated with autonomic dysfunction, no study has investigated the relationship between HRV before standing and the occurrence of OH in an orthostatic challenge test. This study aims to examine the connection between HRV in the supine position and the occurrence of OH in an orthostatic challenge test.Methods: We measured the electrocardiograms of patients with iRBD and healthy older people during an orthostatic challenge test, in which the supine and standing positions were held for 15 min, respectively. The subjects were divided into three groups: healthy controls (HC), OH-negative iRBD [OH (–) iRBD], and OH-positive iRBD [OH (+) iRBD]. HRV measured in the supine position during the test were calculated by time-domain analysis and Poincaré plots to evaluate the autonomic dysfunction.Results: Forty-two HC, 12 OH (–) iRBD, and nine OH (+) iRBD subjects were included. HRV indices in the OH (–) and the OH (+) iRBD groups were significantly smaller than those in the HC group. The multivariate logistic regression analysis for OH identification for the iRBD groups showed the model whose inputs were the HRV indices, i.e., standard deviation 2 (SD2) and the percentage of adjacent intervals that varied by more than 50 ms (pNN50), had a receiver operating characteristic curve with area under the curve of 0.840, the sensitivity to OH (+) of 1.000, and the specificity to OH (–) of 0.583 (p = 0.023).Conclusions: This study showed the possibility that short-term HRV indices in the supine position would predict subsequent OH in iRBD patients. Our results are of clinical importance in terms of showing the possibility that OH can be predicted using only HRV in the supine position without an orthostatic challenge test, which would improve the efficiency and safety of testing.

Cardiovascular Autonomic Neuropathy and Distal Symmetric Sensorimotor Polyneuropathy: These Two Diabetic Microvascular Complications do not Invariably Co-Exist.

Cardiovascular autonomic neuropathy (CAN) and distal symmetrical sensorimotor polyneuropathy (DSPN) are serious microvascular complications of diabetes mellitus (DM). Their simultaneous development remains disputable. The aim of the present study was to examine the correlation between CAN and the presence/severity of DSPN in DM. Subjects with type 1 (group A: n=51; mean age 40.4 years) and type 2 DM (group B: n=153; mean age 64.6 years) were studied. Evaluation of DSPN was based on neuropathy disability score. Assessment of CAN was based on the battery of 4 standardized cardiovascular autonomic function tests. In group A, patients with moderate/severe DSPN exhibited a 12-fold higher likelihood of CAN in univariate analysis (p=0.035). However, significance was lost after adjustment for gender, age, DM duration, and haemoglobin A1c. In group A, likelihood for CAN did not correlate with the presence of mild DSPN in univariate and multivariate analysis. In group B, likelihood of CAN was similar in patients with mild and in those with moderate/severe DSPN compared with patients without DSPN in univariate and multivariate analysis. In between group comparison CAN was similarly distributed in the 2 groups (p for interaction=0.367), in patients with no, mild and moderate/severe DSPN. CAN does not always co-exist with degrees of DSPN, ranging from mild to moderate/ severe and is similarly distributed in T1DM and T2DM patients with mild and moderate/severe DSPN and in patients without DSPN.

Diagnostic accuracy of composite autonomic symptom scale 31 (COMPASS-31) in early detection of autonomic dysfunction in type 2 diabetes mellitus.

PurposeDiabetic autonomic neuropathy (DAN) is a common and disabling complication of diabetes, with cardiac autonomic neuropathy (CAN) being a major cause of mortality and morbidity. Standard autonomic function tests (AFT) are cumbersome and time consuming to conduct in OPD setting.ObjectiveTo evaluate the diagnostic accuracy of composite autonomic symptom scale 31 (COMPASS-31) as a screening test for DAN.Patients and methodsA cross-sectional study which enrolled 60 type 2 diabetes individuals was conducted at a tertiary care center. Autonomic functions were evaluated by COMPASS-31 questionnaire as well as by standard Ewing's battery of tests; short-term heart rate variability; sympathetic skin response along with nerve conduction studies.ResultsThirty males and 24 females completed the study. Forty-nine (89%) participants had CAN, of which, 9 (17%) had definite CAN. Peripheral neuropathy was present in 20 (37%). COMPASS-31 scores showed no difference between “No CAN” and “Early CAN”. “Definite CAN” individuals differed significantly from “No and Early CAN” on COMPASS-31 scores and its gastrointestinal sub-domain. Receiver operating characteristic between “Definite CAN” and “No and Early CAN” showed fair accuracy with AUC of 0.731 (95% CI 0.561–0.901), sensitivity 77.8%, specificity 71.7% at a cut-off of 28.67 of COMPASS-31 score. Gastrointestinal sub-domain, at a cut-off score of 5.8, had 77.8% sensitivity, 60% specificity, and AUC was 0.748 (95% CI 0.603–0.894).ConclusionCOMPASS-31, a self-administered tool, requiring less time, qualifies as an acceptable screening tool, especially for definite CAN. However, individuals scoring low on COMPASS-31 are still required to be evaluated by Ewing’s battery to differentiate between “Early CAN” and “No CAN”.

Correlation between endogenous EPO levels and electrocardiogram scatter plot changes in patients with coronary heart disease and autonomic nerve function injury

Objective: To analyze the correlation between endogenous EPO levels and electrocardiogram scatter plot changes in patients with coronary heart disease and autonomic nerve function injury. Methods: Forty-eight patients who underwent coronary arteriography (CAG) inspection due to chronic coronary heart diseases were selected from July 2015 to October 2015. All of them were evaluated by the Ewing standard autonomic nervous function test, and were divided into Ewing(+) group and Ewing(-) group according to the results of the test. The clinical data of the patients was collected and venous blood was extracted to detect EPO level. Results: The EPO level of Ewing (+) group ((13±3) mIU/ml) was significantly higher than that of Ewing (-) group ((10±3) mIU/ml). The Lorenz scatter plot comet shapes between the two groups had a significant difference. As for the quantitative indicators of Lorenz scatterplot, length of the Ewing (+) group ((147±22) ms) was shorter than that of the Ewing (-) group ((164±24) ms) and there was no significant differences in the width between the two groups. EPO level was negatively correlated with length in both groups (r=-0.427, P=0.002), but not with width (r=0.091, P=0.539). Binary logistic regression analysis showed that EPO (OR=1.394) and diastolic blood pressure (OR=1.091) were risk factors for autonomic nervous function damage. Length (OR=0.934) was a protective factor for autonomic nervous function. ROC curve analysis showed that the area under the EPO curve was 0.737 and that under the length curve was 0.719. Conclusions: The endogenous EPO levels are associated with the changes of electrocardiogram scatter plot in patients with coronary heart disease and autonomic nerve function injury. EPO and length of scatter plot have the similar diagnostic value on predicting of autonomic nerve function injury.

Evaluation of cardiovascular autonomic function in diabetics and normal individual by using standard autonomic function tests and heart rate variability

In diabetic patients cardiac autonomic neuropathy is a serious and common complication. Unrecognized cardiac autonomic neuropathy can prove fatal in them. Objective: The present study was done for evaluation of standard cardiovascular reflex tests, heart rate variability and QTc interval as a tool in diagnosis of CAN in diabetic patients. Materials and Methods: Randomly newly detected type 2 diabetic hundreds patients attending the Out Patient Department attached to J.J.M. Medical College were selected for the study. The results were compared with 50 controls. Niviqure software was used to analyse HRV in terms of Low Frequency, High Frequency the ratio and QTc interval. Results: Our study has shown that the values of different tests were within normal limits but, the values were slightly altered in diabetic patients with CAN score > 0. (p < 0> 440. There was no significant decrease in LF, HF and LF/HF ratio. Among cardiovascular tests, hand grip test and QTc interval showed significant changes. Conclusion: In this study blood pressure response to hand grip test and QTC interval measurement have shown some promise as useful test for screening diabetics patients for CAN. Keywords: Cardiac autonomic neuropathy, Diabetes mellitus, Heart rate variability, Hand grip test, Valsalva ratio.

Study Of Cardiac Autonomic Neuropathy In Type 2 Diabetes Mellitus

Background: Cardiac Autonomic Neuropathy (CAN) represents a significant cause of morbidity and mortality in diabetic patients and is associated with a high risk of cardiac arrhythmias and sudden death, possibly related to silent myocardial ischemia. Cardiac autonomic function should be assessed in most dia-betic patients as it contributes to the evaluation of cardiovascular risk. The presence of CAN should lead to further awareness of possible complications and optimal control of risk factors. Knowledge of early auto-nomic dysfunction can encourage patient and physician to improve metabolic control and to use therapies such as ACE inhibitors and beta blockers, proven to be effective for patients with CAN. Objectives: 1. To as-sess the cardiac autonomic function in patients with Type2 Diabetes Mellitus (T2DM) for detection of CAN. 2. To evaluate the relationship between CAN and duration of diabetes, and glycemic control in Type 2 DM. Materials and Methods: This is a case-control study conducted in Sri DevarajUrs Medical College, Tamaka, Kolar. Sixty patients (Cases) of T2 DM aged > 40 years admitted/visiting Diabetic clinic in R.L Jalappa hospi-tal and 60 healthy non diabetic controls matched for age and sex and satisfied the inclusion and exclusion criteria and gave informed consent for the study were included in the study. All the cases and controls have undergone standard bedside cardiac autonomic function tests. They were evaluated for glycemic control with FBS, PPBS and HbA1c levels. Cases were divided into sub-groups depending on duration of diabetes and glycemic control. The relation between CAN and duration of diabetes and glycemic control was deter-mined by Statistical analysis. Results: 60 cases with diabetes and 60 controls without diabetes were includ-ed in the study. Mean age of cases was 52.38 and controls was 51.97 years. There was no significant differ-ence in age between two groups because of matching. 36 males and 24 females were included in both cases and controls.There was no difference in sex distribution which can be attributed to matching of subjects during data collection. The mean duration of diabetes among cases was 7.28 ± 3.61 years. CAN was present in 21 (35%) of diabetic patients, 13 (21.6%) cases had early features of CAN, whereas CAN was present in 2 (3.3%) of controls and was absent in 86.6% of controls. In the study it was observed that mean age of dia-betics without CAN was 48.54 ± 5.7 years, Early CAN was 52 ± 6.17 and Definitive CAN was 57.38 ± 7.2 yrs. When cases were grouped according to duration of diabetes < 5 years and >5 years, 17.6 % and 41.8% of the cases in each group respectively had CAN, which is significant. About 85.7% of the cases who had CAN have had diabetes for a duration greater than 5 years. Among cases with HbA1c levels > 7%, about 54.54% had definitive CAN and 33.3% had Early CAN. It was observed that there was significant association be-tween increased HbA1c levels and CAN. Conclusion: The present study suggests Cardiac Autonomic Neurop-athy is common in Diabetics compared to healthy individuals. Cardiac Autonomic Neuropathy is associated with increase in the age of the patient and duration of diabetes. Cardiac autonomic neuropathy is associated with poor glycemic control. KeyWords: Cardiac Autonomic Neuropathy, Glycemic Control, HbA1c, Autonomic Function Tests, Type 2 Diabetes Mellitus.

F158. Diagnostic accuracy of composite autonomic symptom scale 31 (COMPASS-31) in early detection of autonomic dysfunction in type 2 diabetes mellitus

Introduction Diabetes mellitus (DM) has become a global epidemic with an increasing prevalence due to rapid modernization and socioeconomic development. One in six people with diabetes are at a risk of developing diabetes related complications. Diabetic autonomic neuropathy (DAN) is one of the most overlooked complications despite its significant negative impact on survival and quality of life. Damage to autonomic nerve fibres that innervate the heart and blood vessels leads to cardiac autonomic neuropathy (CAN) which has a deleterious effect on cardiovascular dynamics. A useful autonomic functions screening instrument which can be used in DM patients for their autonomic symptoms is the need of the hour. Composite autonomic symptom scale 31 (COMPASS-31), derived from original COMPASS (86 questions), has been validated in patients of small fibre polyneuropathy but its use in patients of DM has not been explored. Present study was done to assess the use of this tool for an early detection of autonomic neuropathy in the patients of type 2 DM. Methods Sixty consecutive patients of type 2 DM of both gender and ages more than 18 years were enrolled from the medicine/neurology outpatient department according to the criteria laid by American Diabetic Association 2016. All patients were evaluated for fasting and postprandial blood glucose level,HbA1c, urine routine and microscopy, serum ceatinine, fundus examination, nerve conduction studies by Nihon kohden (Neuropack) electrophysiological apparatus, autonomic function testing by ewing’s battery of tests and heart rate variability measures (HRV). Basic clinicoepidemiologic data and COMPASS-31 Questionnaire were also collected from the participants. Results Of the 60 patients enrolled 6 patients could not get evaluated for the entire battery of tests and thus 54 patients with complete data were finally considered for analysis. There were 29 (53.7%) males and 25(46.3%) females. The median duration of illness was 7 yrs (minimum 2 months to maximum 24 years). None of the autonomic tests including SSR could show statistically significant association with COMPASS-31 scores. Individual domains of COMPASS-31 also did not show any association with objective autonomic tests. HRV parameters did not show any correlation with COMPASS-31 scores. Conclusion Standard autonomic function test are very time consuming and exhaustive to be performed on routine basis in outpatient department. Present study was planned to assess COMPASS-31 in diabetic patients to detect early autonomic dysfunction. To make it objective, standard autonomic function test was also done in all the patients. Although COMPASS-31 Scales has been validated in patients with small fibre polyneuropathy for assessing autonomic dysfunction, we could not get a significant association between COMPASS-31 and any of the objective tests. Probably COMPASS-31 scores alone is not a very sensitive screening tool for assessment of autonomic dysfunction among the patients of type 2 DM.

S175. Sleep and autonomic disturbances in fibromyalgia: Cause or consequence?

Fibromyalgia is a major public health problem in all societies with a high impact on health care and total societal costs. Association of sleep and autonomic dysfunctions with fibromyalgia has shown varied results in different studies across the globe. Their extent of association with fibromyalgia and effect on quality of life of patients especially in India is lacking. Present study was done with the objectives to explore the association of autonomic involvement and sleep disturbances in fibromyalgia patients and to see the effect of autonomic changes and sleep disorders on the quality of life of fibromyalgia patients. It was a cross-sectional study enrolling 30 fibromyalgia patients diagnosed by ACR 2010 along with age and gender matched 30 controls. Participants were evaluated for their sleep using Pittsburgh Sleep Quality Index (PSQI) and medical outcomes study sleep scale-R (MOS-12), Quality of life(QOL) by 36 item Short-Form health survey-36v2TM (SF-36V2) and Revised Fibromyalgia Impact Questionnaire (FIQR) (only patients) and autonomic functions by heart rate variability(HRV). Patients also underwent standard autonomic cardiovascular function tests (Ewings battery of test). Ninety percent patients were females. Both groups (patients and control) were comparable in baseline characters and did not differ significantly in their baseline blood pressure and heart rate. Sleep quantity (4.63 h) of patients was far less than controls (6.86 h). Patients scored very poor on all sleep scales and significantly low (p = 0.0001) on all the domains of QOL. There was no difference in HRV of two groups. No difference could be seen between mild FIQR and moderate FIQR group when compared for HRV parameters and other autonomic function tests. Significant correlations were seen between sleep parameters and QOL in patients, both of which became poorer with increasing severity of fibromyalgia. Present study found a strong association between sleep disturbances, poor sleep quality, and poor quality of life in fibromyalgia. Autonomic dysfunctions were absent in mild to moderate grade fibromyalgia patients. Consistently poor and disturbed sleep in FM patients may lead to symptoms of fibromyalgia which together have a deteriorating effect on all the domains of quality of life. Probably, autonomic changes in FMS appear in later stage of disease and may be a consequence rather than cause of disability in FM patients. However, a long-term follow-up study is needed to address these questions as well as to unravel the natural history of FMS.

Orthostatic heart rate changes in patients with autonomic failure caused by neurodegenerative synucleinopathies.

Blunted tachycardia during hypotension is a characteristic feature of patients with autonomic failure, but the range has not been defined. This study reports the range of orthostatic heart rate (HR) changes in patients with autonomic failure caused by neurodegenerative synucleinopathies. Patients evaluated at sites of the U.S. Autonomic Consortium (NCT01799915) underwent standardized autonomic function tests and full neurological evaluation. We identified 402 patients with orthostatic hypotension (OH) who had normal sinus rhythm. Of these, 378 had impaired sympathetic activation (ie, neurogenic OH) and based on their neurological examination were diagnosed with Parkinson disease, dementia with Lewy bodies, pure autonomic failure, or multiple system atrophy. The remaining 24 patients had preserved sympathetic activation and their OH was classified as nonneurogenic, due to volume depletion, anemia, or polypharmacy. Patients with neurogenic OH had twice the fall in systolic blood pressure (SBP; -44 ± 25 vs -21 ± 14 mmHg [mean ± standard deviation], p < 0.0001) but only one-third of the increase in HR of those with nonneurogenic OH (8 ± 8 vs 25 ± 11 beats per minute [bpm], p < 0.0001). A ΔHR/ΔSBP ratio of 0.492 bpm/mmHg had excellent sensitivity (91.3%) and specificity (88.4%) to distinguish between patients with neurogenic from nonneurogenic OH (area under the curve = 0.96, p < 0.0001). Within patients with neurogenic OH, HR increased more in those with multiple system atrophy (p = 0.0003), but there was considerable overlap with patients with Lewy body disorders. A blunted HR increase during hypotension suggests a neurogenic cause. A ΔHR/ΔSBP ratio < 0.5 bpm/mmHg is diagnostic of neurogenic OH. Ann Neurol 2018;83:522-531.

Orthostatic hypertension: An underestimated cause of orthostatic intolerance

To investigate the frequency and mechanism of orthostatic hypertension (OHT) in patients with orthostatic intolerance. We retrospectively reviewed 1033 consecutive case series of orthostatic intolerance that underwent autonomic function tests including a head-up tilt test. OHT was defined as a paradoxical orthostatic increase in systolic blood pressure (BP) of at least 20 mmHg during the tilt. We collected autonomic parameters during the standardized autonomic function tests, which included the beat-to-beat derived hemodynamic parameters during the tilt table test and compared them with age and sex-matched normal controls and the orthostatic hypotension (OH) group with orthostatic symptoms. We identified 38 (3.7%) patients who showed OHT during the tilt. The increase in mean systolic BP during the tilt was 26.5 mmHg. Approximately 87% (33/38) of the OHT patients showed an increase in total peripheral resistance during the tilt. The mean increase in total peripheral resistance from a supine baseline was significantly higher in OHT patients compared to normal controls, but the OH group showed a decrease in mean total peripheral resistance during the tilt. A select few patients with orthostatic dizziness can show OHT during the tilt and they have signs of increased peripheral resistance. OHT may be considered in the differential diagnosis of orthostatic intolerance.

Left Ventricular Diastolic Dysfunction (LVDD) & Cardiovascular Autonomic Neuropathy (CAN) in Type 2 Diabetes Mellitus (DM): A Cross-Sectional Clinical Study.

Cardiovascular autonomic neuropathy (CAN) is one of the major complications of Diabetes Mellitus (DM) seen in a significant number of patients, which is often ignored and is also least frequently diagnosed. It can be diagnosed by performing five standard non-invasive bedside autonomic function tests based on Cardiovascular reflexes, which are quite cumbersome. Studies have revealed an increase in mortality in the diabetic patients with CAN due to silent cardiac ischemia, sudden cardiac death, arrhythmias. The precursor of diabetic cardiomyopathy is Left ventricular diastolic dysfunction (LVDD). In the present study we are studying the association between LVDD and CAN, in order to identify high mortality risk patients by performing 2D Echo and looking at LVDD instead of performing the cumbersome bedside cardiovascular autonomic function tests. To study the association between LVDD and CAN in patients with Type 2 DM. This study is a cross-sectional observational study with a sample size of 100. Both outpatients and inpatients between 35 y and 65 y of age with Type 2 DM coming to Department of General Medicine, KIMS hospital, Bangalore were studied from November 2011 to October 2013.Patients with macrovascular complications, Hypertension, congenital & acquired heart diseases etc. were excluded from the study. The standard five autonomic function tests based on cardiovascular reflexes and 2D Echo were performed. Individual scores for each of the five tests were added to produce Ewing's score. Ewing's score of >2.5 is positive for CAN. Chi-square/ Fisher Exact test has been. There was a significant association between individual non-invasive bedside tests of Ewing's score and LVDD. Significant association was also seen between LVDD and positive Ewing's score. Positive Ewing's score is strongly associated with LVDD in patients with Type 2 DM in this study .This suggests that patients with LVDD have CAN and hence, are at increased risk of sudden cardiac death. As bedside tests are cumbersome, patients with LVDD on 2D Echo can be concluded to have CAN.

Autonomic dysfunction in chronic persistent dizziness

ObjectiveTo investigate the autonomic dysfunction in patients with chronic persistent dizziness using standardized autonomic function tests. MethodsWe prospectively recruited 18 patients with chronic persistent dizziness after excluding other causes with extensive investigations. A standardized battery of autonomic tests including the head up tilt (HUT) test, Valsalva maneuver (VM), and heart rate (HR) response to deep breathing was performed. ResultsApproximately eighty percent of the patients showed at least one abnormality in autonomic tests. Two patterns of autonomic abnormality were identified: sympathetic failure, including abnormal decrease in blood pressure (BP) during HUT test or abnormal sympathetic indices related with the BP recovery during late phase II and phase IV during VM, and sympathetic hyperactivity, including abnormal increase in HR response during HUT test or an exaggerated phase IV response manifesting increased β-adrenergic tone during VM. ConclusionsAutonomic dysfunction is frequently found in patients with chronic persistent dizziness after excluding other causes with extensive investigations. Sympathetic failure or hyperactivity may be postulated as one of the possible causes of chronic persistent dizziness. Clinicians should be aware of the possibility of autonomic dysfunction in patients with chronic dizziness, even if the dizziness is not orthostatic but persistent.

A Study to assess, the Extent of Autonomic Dysfunction Based on the Standard Cardiovascular Tests in Different Grades of Alcoholics

Aim: Autonomic system is the one which extensively supplies the inner organs. Much attention is not given to it clinically and there are few tests available to assess it. The tests which are available are less used in patients to assess the autonomic function. Alcoholism is a factor which affects most of the system in the human body. Its effect on autonomic nervous system is extensive. As a result of this autonomic failure there would be damage to multiple systems. Study design: In this study the effect of alcoholism in a group of people grading them as social drinkers, chronic alcoholics and alcoholic cirrhotics have been done using the seven standard autonomic function tests. The extent of autonomic damage in all these different groups was done. The results were compared against a group of controls. Results: There was autonomic damage observed in all three groups with a distribution of 50% mild damage and 30% of moderate damage in social drinkers. A 20% of severe damage (combined damage) in chronic alcoholics and 90% of severe damage in alcoholic cirrhotics were obtained. A significant difference was observed between all groups of alcoholics and the controls (p< 0.01) Conclusion: The extent of autonomic damage seems to be underestimated in alcoholics. More care should be given to high social drinkers as they too exhibited autonomic damage. Also these simple tests should be performed as a routine on all alcoholics for an early detection of the situation.

Spectrum of autonomic dysfunction in orthostatic dizziness

ObjectiveTo investigate the frequency and detailed spectrum of autonomic dysfunction in patients with orthostatic dizziness (OD). MethodsOver 20months, 217 consecutive patients with OD as a presenting symptom of orthostatic intolerance were enrolled. The distribution and severity of autonomic dysfunction were measured by the composite autonomic severity score (CASS), which was derived from a standard autonomic function test including Finapres for recording of the beat-to-beat blood pressure. Sympathetic indexes (SIs) were calculated from the Valsalva maneuver (VM). ResultsApproximately 83% of patients showed at least one abnormal autonomic testing result. We classified OD into 11 groups according to the patterns of autonomic dysfunctions. The most common pattern was generalized autonomic failure of sympathetic adrenergic and parasympathetic cardiovagal functions (n=60). Patients with delayed OH had larger BP increases during late phase II of the VM (p=0.04), showed greater phase IV overshoot (p=0.04), and had a smaller pressure recovery time increase (p=0.02) than patients with classic OH. Each SI showed the strongest correlation with the CASS adrenergic subscores. ConclusionsOD can present with a board spectrum of autonomic dysfunctions. SignificanceThis investigation could be useful in understanding the pattern and mechanism of autonomic dysfunction associated with OD.

Sympathetic hyperactivity in children of hypertensive parents.

Hypertension is a global problem. Positive family history of hypertension is one of the risk factors for being hypertensive in future life for their children. Hyperactive sympathetic nervous system is reported in children of hypertensive parents. The main objective of the study was to observe the magnitude of alterations in autonomic reactivity following the standard autonomic function tests in normotensive male offsprings of both-hypertensive and normotensive parents. Fifty young and healthy male subjects between 19-24 yr of age got examined for autonomic reactivity. Twenty five of them were having family history of hypertension (study group) while the remaining were the children of normotensive parents (control group). Non invasive autonomic function tests as per Ewing's criteria were performed in all the subjects. The resting heart rate, systolic and diastolic blood pressures were not significantly raised in subjects of study group. The sympathetic function tests as assessed by rise in diastolic blood pressure following cold pressor test and hand grip test were highly significant in study group as compared with control one. However, the vagally mediated tests, for heart rate responses, denoting parasympathetic functions were similar in both groups. It seems that there is increased sympathetic activity in children of hypertensive parents without parasympathetic modulation in early life. It may predispose them to hypertension in their later life.