Cardiovascular Autonomic Tests Research Articles

Classical and Delayed Orthostatic Hypotension in Patients With Unexplained Syncope and Severe Orthostatic Intolerance.

Background: Orthostatic hypotension (OH) is a major sign of cardiovascular autonomic failure leading to orthostatic intolerance and syncope. Orthostatic hypotension is traditionally divided into classical OH (cOH) and delayed OH (dOH), but the differences between the two variants are not well-studied. We performed a systematic clinical and neuroendocrine characterization of OH patients in a tertiary syncope unit.Methods: Among 2,167 consecutive patients (1,316 women, 60.7%; age, 52.6 ± 21.0 years) evaluated for unexplained syncope and severe orthostatic intolerance with standardized cardiovascular autonomic tests including head-up tilt (HUT), we identified those with a definitive diagnosis of cOH and dOH. We analyzed patients' history, clinical characteristics, hemodynamic variables, and plasma levels of epinephrine, norepinephrine, C-terminal-pro-arginine-vasopressin (CT-proAVP), C-terminal-endothelin-1, mid-regional-fragment of pro-atrial-natriuretic-peptide and pro-adrenomedullin in the supine position and at 3-min HUT.Results: We identified 248 cOH and 336 dOH patients (27% of the entire cohort); 111 cOH and 152 dOH had blood samples collected in the supine position and at 3-min HUT. Compared with dOH, cOH patients were older (68 vs. 60 years, p < 0.001), more often male (56.9 vs. 39.6%, p < 0.001), had higher systolic blood pressure (141 vs. 137 mmHg, p = 0.05), had lower estimated glomerular filtration rate (73 vs. 80 ml/min/1.73 m2, p = 0.003), more often pathologic Valsalva maneuver (86 vs. 49 patients, p < 0.001), pacemaker-treated arrhythmia (5 vs. 2%, p = 0.04), Parkinson's disease (5 vs. 1%, p = 0.008) and reported less palpitations before syncope (16 vs. 29%, p = 0.001). Supine and standing levels of CT-proAVP were higher in cOH (p = 0.022 and p < 0.001, respectively), whereas standing norepinephrine was higher in dOH (p = 0.001). After 3-min HUT, increases in epinephrine (p < 0.001) and CT-proAVP (p = 0.001) were greater in cOH, whereas norepinephrine increased more in dOH (p = 0.045).Conclusions: One-quarter of patients with unexplained syncope and severe orthostatic intolerance present orthostatic hypotension. Classical OH patients are older, more often have supine hypertension, pathologic Valsalva maneuver, Parkinson's disease, pacemaker-treated arrhythmia, and lower glomerular filtration rate. Classical OH is associated with increased vasopressin and epinephrine during HUT, but blunted increase in norepinephrine.

66 Simple bedside cardiovascular autonomic examinations for predicting chronotropic incompetence

Abstract Background Simple bedside cardiovascular autonomic reflex test (CARTs) are usually used to determine cardiovascular autonomic neuropathy (CAN). CAN may contribute to chronotropic incompetence (CI) which is the inability of the heart rate (HR) to rise in proportion to an increase in metabolic demand. Determination of CI is widely based on measurement of maximum HR during exercise testing. This study aimed to evaluate the role of CARTs to determine CI. Methods We included in 105 patients using a derivation and validation sampling ratio of 2:1. CARTs were performed for analyzing heart rate variation during three parasymphathetic standard tests (deep breathing, lying to standing, Valsava maneuver) and two sympathetic standard tests (systolic blood pressure from lying to standing and diastolic blood pressure during handgrip maneuver). Variables independently associated with CI in multivariable analysis in the derivation set were assigned points based on their respective odds ratios. Results CI group showed significantly lower values of among three parasympathetic standard tests (p &amp;lt; 0.05) but not significantly among two sympathetic standars tests. Valsava maneuver (OR 0.1, p &amp;lt; 0.001, 95%CI 0.001-0.004), deep breathing (OR 0.91, p = 0.025, 95% CI 0.836-0.988), and handgrip maneuver (OR 0.85, p = 0.01, 95% CI 0.744-0.961) were found to be an independent risk factor for CI from multivariate regression analysis. The accuracy of different CART parameters in the prediction of CI was described by the receiver operating curve (ROC) analysis. Regarding logistic regression model, we constructed formula of 15 - ([12 x Valsava maneuver] + [0.1 x deep breathing] + [0.2 x handgrip maneuver]) which will show negative and positive results indicating CI and non-CI, respectively. The resulting score showed good calibration and discriminatory capacity in the derivation (Hosmer-Lemeshow x² 10.051, p = 0.186, AUC = 0.878). The difference between AUCs in the derivation and validation sets was Δ = 0.122 (p = 0.174). Conclusion The decrease in heart rate variations during Valsava maneuver and deep breathing and in diastolic blood pressure during handgrip maneuver seems to be related to development of CI. Formula of CARTs score is a useful tool for predicting CI. Final score sheet based on formula Total score CI probability &amp;lt;-0.1 High probaility 0.2-0.6 Intermediate probability &amp;gt;0.6 Low probability

Autonomic dysregulation and phenobarbital in patients with masked primary hypertension

IntroductionPrimary hypertension can be masked and be responsible of a severe impact on the target bodies. The purpose of this study was to see if Phenobarbital at low dose is able to decrease the sympathetic hyperactivity assessed by cardiovascular autonomic reflexes in patients with masked hypertension. Materials and methodsThis prospective study was conducted on a total of 91 patients with masked hypertension (average age 52.1 ± 10.3 years old). The cardiovascular autonomic tests performed in this group, before and after 3 months of daily oral administration of Phenobarbital, included deep breathing, hand-grip, mental stress and orthostatic tests. Statistical analysis was done using the Student's t-test, Univariate and Multivariate logistic regression analysis; p is significant if < 0.05. ResultsCardiovascular autonomic reflexes responses before and after 3 months of Phenobarbital oral administration were as follows: Vagal response (XDB) obtained on deep breathing test was of 32.6 ± 5.4% VS 30.4 ± 6.1%, (p = 0.08), alpha peripheral sympathetic response (alpha SP) obtained on hand grip test was of 35.6 ± 8.7% VS 12.0 ± 2.5%, (p < 0.001), alpha central sympathetic response (alpha SC), beta central sympathetic response (beta SC) obtained during mental stress were of respectively 29.3 ± 9.2% VS 11.8 ± 2.4%, (p < 0.001) and 11.0 ± 5.3% VS 10.4 ± 6.1%, (p = 0.2), alpha peripheral adrenergic sympathetic (alpha PAS) obtained during orthostatic test was of 25.3 ± 6.0% VS 13.0 ± 3.4%, (p < 0.001). ConclusionThese results demonstrated that Phenobarbital at low dose may have an anti-sympathetic effect in patients with masked hypertension.

Cardiovascular autonomic testing in the work-up of cerebellar ataxia: insight from an observational single center study

BackgroundCerebellar ataxias are a heterogeneous group of disorders of both genetic and non-genetic origin. In sporadic cases, two entities are recognized: multiple system atrophy of cerebellar type (MSA-C) and SAOA (sporadic adult-onset ataxia). The presence of severe cardiovascular autonomic failure reliably distinguishes MSA-C from other ataxias, but it may appear only late in the disease course.ObjectiveTo evaluate the diagnostic yield of cardiovascular autonomic function tests in the work-up of cerebellar ataxia.MethodsWe applied a cardiovascular autonomic tests battery in consecutive patients with neurodegenerative cerebellar ataxia and matched healthy controls. We recorded the presence of both orthostatic hypotension (OH) and blood pressure falls non-fulfilling the criteria of OH (non-OH BP). Sporadic cases were followed-up for an eventual conversion to MSA-C.ResultsForty-two patients were recruited, 19 of whom with sporadic disease (2 probable MSA-C, 6 possible MSA-C, 11 SAOA). Sporadic and hereditary cases showed no difference concerning ataxia severity at baseline. At head-up tilt, non-OH BP falls were detected in nine patients, but not in controls. This finding was significantly more frequent in sporadic cases (p = 0.006) and was detected in five out of seven patients that during follow-up converted to possible/probable MSA-C. Findings at standing test were normal in four out of nine cases with non-OH BP falls at head-up tilt.ConclusionsA complete cardiovascular autonomic battery with head-up tilt can detect early signs of BP dysregulation which may be missed at bed-side tests, thus warranting its application in the first line work-up of cerebellar ataxias.

Cardiovascular autonomic reflex tests and serum FGF21 levels in overweight and normal-weight men and women

Objective We evaluated cardiovascular autonomic reflexes and serum fibroblast growth factor 21 (FGF21), a surrogate marker of mitochondrial function, in a cohort of overweight and normal-weight adults (n = 42). Methods Indices of autonomic function were monitored during supine rest, autonomic reflex tests and submaximal clinical exercise test, with heart rate variables and blood pressure measured with an automatic system. Results Markers of sympathetic dominance were accentuated in overweight adults, including elevated resting low-frequency to the high-frequency ratio for heart rate variability (203 ± 227 vs. 96 ± 42; p = .01), and handgrip diastolic blood pressure (36 ± 15 mmHg vs. 25 ± 12 mmHg; p = .01). A weak non-significant trend has been found for a negative correlation between blood pressure responses to isometric handgrip test and FGF21 in the overweight group (r = −0.37; p = .09). Conclusions Excess body weight appears to trigger sympathetic overactivity in overweight adults, yet autonomic dysregulation might not be associated with notable changes in serum FGF21.

Cardiovascular Autonomic Dysfunction Is the Most Common Cause of Syncope in Paced Patients.

Introduction: Syncope and orthostatic intolerance in paced patients constitute a common clinical dilemma. We, thus, aimed to determine the etiology of syncope and/or symptoms of orthostatic intolerance in paced patients.Methods: Among 1,705 patients with unexplained syncope and/or orthostatic intolerance that were investigated by cardiovascular autonomic tests, including Valsalva maneuver, active standing, carotid sinus massage, and tilt-testing, 39 patients (2.3%; age 65.6 years; 39% women) had a cardiac implantable electronic device (CIED). We explored past medical history, diagnoses found during cardiovascular autonomic tests, and the further clinical workup, in case of negative initial evaluation.Results: An etiology was identified during cardiovascular autonomic tests in 36 of the 39 patients. Orthostatic hypotension (n = 16; 41%) and vasovagal syncope (n = 12; 31%) were the most common diagnoses. There were no cases of pacemaker dysfunction. The original pacing indications followed guidelines (sick-sinus-syndrome in 16, atrioventricular block in 16, atrial fibrillation with bradycardia in five). Twenty-two of the 39 patients (56%) had experienced syncope prior to the original CIED implantation. Orthostatic hypotension was diagnosed in seven (32%) and vasovagal syncope in nine (41%) of these patients. Of the 17 patients that had not experienced syncope prior to the original CIED implantation, nine patients (53%) were diagnosed with orthostatic hypotension and vasovagal syncope was diagnosed in three (18%). Of the 39 patients, two had implantable cardioverter-defibrillators to treat malignant ventricular arrhythmias diagnosed after syncopal episodes.Conclusion: Cardiovascular autonomic tests reveal the etiology of syncope and/or orthostatic intolerance in the majority of paced patients. The most common diagnosis was orthostatic hypotension (40%) followed by vasovagal syncope (30%), whereas there were no cases of pacemaker dysfunction. Our results emphasize the importance of a complete diagnostic work-up, including cardiovascular autonomic tests, in paced patients that present with syncope and/or orthostatic intolerance.

Seronegative autoimmune autonomic ganglionopathy from dual immune checkpoint inhibition in a patient with metastatic melanoma

BackgroundImmune checkpoint inhibitors have improved clinical outcomes including survival in several malignancies but have also been associated with a range of immune-related adverse events (irAEs). Neurological irAEs are rare compared to the more typical skin, gastrointestinal, and endocrine toxicities, and are often underrecognized and challenging to diagnose. Here, we report a case of seronegative autoimmune autonomic ganglionopathy (AAG) induced by dual immune checkpoint inhibitor therapy (ICI) in a patient with metastatic melanoma.Case presentationA patient with metastatic melanoma was treated with ipilimumab and nivolumab. He developed a constellation of new symptoms including nausea, fatigue, and severe orthostatic hypotension refractory to fluid resuscitation. An infectious, cardiac, neurologic, and endocrine workup were unrevealing. Cardiovascular autonomic testing revealed poor sympathetic nervous system responses. He was diagnosed with seronegative AAG and significantly improved with immunomodulatory therapies including IVIG and steroids as well as varying doses of midodrine and fludrocortisone. He was able to restart nivolumab without recurrence of his symptoms. However, the AAG reoccurred when he was re-challenged with ipilimumab and nivolumab due to disease progression. While the AAG was manageable with steroids at that time, unfortunately his melanoma became resistant to ICI.ConclusionsImmune checkpoint inhibitors can have a wide range of unusual, rare irAEs, including neurotoxicity such as AAG. Clinicians should maintain suspicion for this toxicity so that treatment can be rapidly provided to avoid disability.

Cardiovascular autonomic neuropathy as a cause of fatigue in chronic hypoparathyroidism.

Hypoparathyroidism (hypoPT) results in an impairment of quality of life (QoL), an increase in fatigue and a higher risk of mortality. Cardiovascular autonomic neuropathy (CAN) is an impairment of the cardiovascular autonomic system and is associated with increased mortality and fatigability. Patients with hypoPT show an increased risk of CAN. However, no previous studies have investigated the association between CAN and QoL in hypoPT. To test whether CAN is associated with fatigue and impaired QOL in hypoPT patients. We enrolled 48 subjects with postsurgical hypoPT treated with calcium and calcitriol and 38 healthy subjects who underwent thyroidectomy. Subjects completed the RAND 36-Item Short Form (SF-36) Health Survey, evaluating physical (PCS) and mental (MCS) health, and fatigue score. CAN was assessed using cardiovascular autonomic reflex tests (CARTs). Participants were considered to have "early CAN" (EC) if they had one abnormal CART and "definite CAN" (DC) with two or more abnormal CARTs. Compared with controls, hypoPT population had lower fatigue scores (44.5 IQRː9 vs 38.5 IQRː12.3, P = 0.031). In the hypoPT group, only participants with DC had a lower fatigue score than subjects without CAN (DC: β: -9.55, P = 0.005) after adjusting for age, duration of disease, calcium concentration, TSH, calcitriol and calcium supplementation. No differences were found in the PCS and MCS scores in the hypoPT group. CAN may explain fatigue, a common complaint of postsurgical hypoPT patients. Further larger and prospective investigations are needed to confirm our findings.

Changes in Autonomic Nervous System in Patients with Multiple Sclerosis

AbstractBackground: Multiple sclerosis (MS) is one of the most disabling neurological disorders, in which autonomic impair-ment is not rare.Aim of Study: To assess the frequency of cardiovascular (CV) autonomic dysfunction in MS patients as well as to relate these autonomic abnormalities to the brainstem dys-functions in thoe patients evidenced by brainstem auditory evoked potential (BAEP) studies.Patients and Methods: We studied 20 patients with clin-ically definite relapsing remitting MS and 20 gender and age matched healthy control. The patients were evaluated clinically using expanded disability status scale (EDSS). Autonomic functions were evaluated with blood pressure response to both standing and static exercise (sympathetic), and 24-hour elec-trocardiographic (ECG) recording, time domain (parasympa-thetic). Brain stem auditory evoked potential was performed to all patients. Data were statistically analyzed using Epi-info software version 6.04.Results: The MS patients included 11 (55%) males and nine (45%) females with a mean age of 29.8-}8.4 years, whereas control group was composed of five (50%) males and five (50%) females with a mean age of 34.2±13.4 years. Regarding tests of CV autonomic functions, 13 (65%) patients had at least one abnormal test. The results showed statistically significant differences in all CV autonomic tests when com-paring MS patients to controls. We found significant correla-tions between autonomic tests with duration of the disease. Significant correlations were detected between autonomic tests and brainstem lesions. BAEP findings were indicative of brainstem affection and there was a significant correlation between autonomic tests and I-V inter peak latency.Conclusion: These results suggest that a significant number of patients with MS show evidence of CV autonomic dysfunc-tion, which is correlated with brainstem function.

Subclinical inflammation and endothelial dysfunction are linked to cardiac autonomic neuropathy in type 2 diabetes.

The present study aimed to examine association between inflammatory and endothelial function biomarkers and indices of cardiac autonomic control in T2DM patients. 50 T2DM patients were recruited for this study. For cardiac autonomic function, cardiovascular autonomic reflex tests (CARTs) and heart rate variability (HRV) analysis was performed. Blood samples were collected for evaluating inflammatory and endothelial function biomarkers. Multivariable linear regression analysis adjusted for diabetes duration, glycemic control, waist circumference, hypertension, dyslipidemia, metformin, and statins was performed to examine the association between the biomarkers and cardiac autonomic function parameters. Interleukin-6 was inversely related to total power (p= .009) and low frequency power (p= .04). Interleukin-18 and high sensitivity C-reactive protein inversely correlated with measures of cardiac vagal control (p < .05). Both nitric oxide and endothelial nitric oxide synthase were positively linked with cardiac vagal control indices (p < .05) whereas endothelin-1 did not show any independent association with cardiac autonomic function parameters. Biomarkers of inflammation and endothelial function are associated with measures of cardiac vagal control and global HRV which suggest that there is some pathophysiological link between subclinical inflammation, endothelial dysfunction and cardiac autonomic dysfunction in T2DM.

Impaired Amino Acid and TCA Metabolism and Cardiovascular Autonomic Neuropathy Progression in Type 1 Diabetes.

While diabetes is characterized by hyperglycemia, nutrient metabolic pathways like amino acid and tricarboxylic acid (TCA) cycle are also profoundly perturbed. As glycemic control alone does not prevent complications, we hypothesized that these metabolic disruptions are responsible for the development and progression of diabetic cardiovascular autonomic neuropathy (CAN). We performed standardized cardiovascular autonomic reflex tests and targeted fasting plasma metabolomic analysis of amino acids and TCA cycle intermediates in subjects with type 1 diabetes and healthy control subjects followed for 3 years. Forty-seven participants with type 1 diabetes (60% female and mean ± SD age 35 ± 13 years, diabetes duration 13 ± 7 years, and HbA1c 7.9 ± 1.2%) had lower fumarate levels and higher threonine, serine, proline, asparagine, aspartic acid, phenylalanine, tyrosine, and histidine levels compared with 10 age-matched healthy control subjects. Higher baseline fumarate levels and lower baseline amino acid levels—asparagine and glutamine—correlate with CAN (lower baseline SD of normal R-R interval [SDNN]). Baseline glutamine and ornithine levels also associated with the progression of CAN (lower SDNN at 3 years) and change in SDNN, respectively, after adjustment for baseline HbA1c, blood glucose, BMI, cholesterol, urine microalbumin-to- creatinine ratio, estimated glomerular filtration rate, and years of diabetes. Therefore, significant changes in the anaplerotic flux into the TCA cycle could be the critical defect underlying CAN progression.

Early diagnosis of diabetic cardiac autonomic neuropathy by method of high-frequency ultrasonic dopplerography

Introduction. Diabetic neuropathy is the most wide-spread complication of diabetes mellitus and neuropathy is steadily progressing even with compensation of the underlying disease. The search of the new methods of treatment and diagnosis of neuropathy is required. Diabetic autonomic neuropathy lies in the base of early morbidity and mortality of diabetic patients.We estimated the potential of High-frequency Ultrasonic Dopplerography for diagnosis of autonomic neuropathy. Material and methods. 26 diabetic patients with sensorimotor neuropathy were examined. Microvascular blood flow of finger skin was assessed at rest as well as in functional tests: with cold impact and occlusion (cuff). Cardiac autonomic neuropathy was assessed using several cardiovascular autonomic reflex tests as a gold standard of diagnosis. Diagnostic values of microvascular blood flow test in detecting of cardiac autonomic neuropathy staging were evaluated in comparing with traditional modalities.Results. Cardiac autonomic neuropathy was found for all patients and definite/confirmed staging in 61.5 % cases. Initial parameters of microvascular blood flow velocity were significantly decreased in all patients in comparing with control (Vam= = (1.9±0.22); (1.7±0.51) and (6.7±0.51) sm/s in patients with early cardiac autonomic neuropathy, definite/confirmed staging and control subjects respectively, p&lt;0.05). Microvascular blood flow functional testes had great informational content for diagnosis of autonomic neuropathy (sensitivity – 100 and 58 %, specify – 50 and 80 % respectively). The algorithm of diabetic patients examination was offered for early diagnosis of autonomic neuropathy staging.Conclusions. High-frequency Ultrasonic Dopplerography allowed to separate of cardiac autonomic neuropathy stages. This study is necessary to continue for revealing of all method possibilities.

Autonomic impairment as a potential biomarker in idiopathic REM-sleep-behavior disorder.

Autonomic dysfunction is common in REM-sleep behavior disorder (RBD). Several studies have demonstrated abnormalities in heart rate variability, cardiac scintigraphy, and cardiovascular autonomic reflex testing. In addition, the type and severity of these abnormalities may correlate with rate of phenoconversion from idiopathic RBD (iRBD) to manifest neurodegenerative disease. This article summarizes the current literature on autonomic impairment in iRBD, with specific focus on the role of autonomic impairment as a potential biomarker of disease progression. REM sleep physiology and relevant anatomy is also discussed in relation to the central autonomic network and autonomic neurodegeneration.

Diagnostic performance of resting and post-exercise heart rate variability for detecting cardiac autonomic neuropathy in type 2 diabetes mellitus.

Post-exercise recovery phase is associated with clustering of various cardiovascular events and, therefore, monitoring of cardiac autonomic control via heart rate variability (HRV) during this phase may allow identification of autonomic alterations that are not evident under resting conditions in type 2 diabetes mellitus (T2DM) patients. To investigate and compare the diagnostic performance of resting and post-exercise HRV for detecting cardiac autonomic neuropathy (CAN) in T2DM patients. Forty-two T2DM patients were categorized as CAN-positive and CAN-negative based on standard cardiovascular autonomic reflex tests (CARTs). Short-term resting and post-exercise HRV after a graded exercise test were evaluated for each participant. Diagnostic performance of both resting and post-exercise HRV measures was computed using standard statistical procedures. Diagnostic testing yielded superior diagnostic performance of post-exercise HRV than resting HRV measures. Root mean square of successive differences (RMSSD) between adjacent R-R intervals (p = 0.01), percentage of consecutive N-N intervals that vary by >50 ms (pNN50) (p = 0.03) and total power (TP) (p = 0.01) were significantly better diagnostic indicators of CAN under post-exercise conditions than at rest. Predictive ability of these post-exercise HRV measures for CAN was maintained after adjusting various clinical confounders to cardiac autonomic function. Post-exercise HRV measures such as TP, RMSSD and pNN50 were found to be more accurate diagnostic tests for detecting CAN than resting HRV. Hence, monitoring of the HRV measures proposed here during exercise testing protocols may provide important diagnostic information regarding CAN in T2DM.

Nocturnal ventricular arrhythmias are associated with the severity of cardiovascular autonomic neuropathy in type 2 diabetes

Cardiovascular autonomic neuropathy (CAN) is a risk factor for arrhythmias and adverse cardiovascular events, but the relationship between CAN severity and nocturnal arrhythmias needs to be clarified. This study evaluated the association between nocturnal arrhythmias and CAN severity in patients with type 2 diabetes (T2D). In all, 219 T2D patients were recruited from January 2017 to May 2018. Subjects were classified into no CAN (NCAN), early CAN (ECAN), definite CAN (DCAN), or advanced CAN (ACAN) based on cardiovascular autonomic reflex tests (CARTs). A 24-hour electrocardiogram was recorded and daytime (0700-2300 hours) and night-time (2300-0700 hours) heartbeats were analyzed separately. After adjusting for age, the incidence of ventricular arrhythmias increased with CAN severity at night-time (18.6%, 29.9%, 36.2%, and 60.0% in the NCAN, ECAN, DCAN, and ACAN groups, respectively; Ptrend = 0.034). Patients with nocturnal ventricular arrhythmias (NVAs) had higher CART scores (2.0 ± 1.0 vs 1.5 ± 0.9; P < 0.001) and lower heart rate variability (HRV) during deep breathing (9.5 ± 5.7 vs 11.6 ± 6.6 b. p. m; P = 0.021), HRV during the Valsalva maneuver (1.2 ± 0.1 vs 1.2 ± 0.2; P = 0.006), and postural blood pressure change (-8.8 ± 15.5 vs -4.1 ± 11.2 mmHg; P = 0.023). Multivariate regression analysis revealed that CAN stage (odds ratio 1.765; 95% confidence interval 1.184-2.632; P = 0.005) was independently associated with NVAs. In T2D, CAN stage was independently associated with the presence of NVAs. Early detection, diagnosis, and treatment of CAN may help predict and prevent adverse cardiovascular events and cardiovascular mortality in diabetes.

Cardiac Autonomic Function Is Associated With Myocardial Flow Reserve in Type 1 Diabetes.

The link between cardiac autonomic neuropathy and risk of cardiovascular disease is highlighted as an area in which research is needed. This study was undertaken to evaluate the association between measures of cardiac autonomic function and cardiac vascular function in type 1 diabetes using new and sensitive methods. This was a cross-sectional study in patients with type 1 diabetes, stratified by normoalbuminuria (n = 30) and macroalbuminuria (n = 30), and in healthy control subjects (n = 30). Cardiac autonomic function was evaluated using heart rate variability (HRV) indices, cardiovascular autonomic reflex tests (CARTs), and cardiac 123I-metaiodobenzylguanidine (MIBG) imaging. Cardiac vascular function was assessed as myocardial flow reserve (MFR) measured by cardiac 82Rb-positron emission tomography/computed tomography. The measures of cardiac autonomic function (except low frequency-to-high frequency ratio and the Valsalva test ratio) were positively correlated to MFR in unadjusted analysis. All the HRV indices lost significance after adjustment for age and heart rate. After further adjustment for relevant cardiovascular risk factors, the late heart-to-mediastinum ratio directly measuring the function of adrenergic receptors and sympathetic integrity (from the MIBG scintigraphy) and the 30-to-15 ratio (a CART), remained positively associated with MFR (P ≤ 0.04). Cardiac autonomic dysfunction, including loss of cardiac sympathetic integrity in type 1 diabetes, is associated with and may contribute to impaired myocardial blood flow regulation.

The Investigation of the Cardiovascular and Sudomotor Autonomic Nervous System-A Review.

The autonomic nervous system as operating system of the human organism permeats all organ systems with its pathways permeating that it is involved with virtually all diseases. Anatomically a central part, an afferent part and sympathetic and parasympathetic efferent system can be distinguished. Among the different functional subsystems of the autonomic nervous system, the cardiovascular autonomic nervous system is most frequently examined with easily recordable cardiovascular biosignals as heart rate and blood pressure. Although less widely established, sudomotor tests pose a useful supplement to cardiovascular autonomic assessment as impaired neurogenic sweating belongs to the earliest clinical signs of various autonomic neuropathies as well as neurodegenerative disorders and significantly reduces quality of life. Clinically at first, the autonomic nervous system is assessed with a detailed history of clinical autonomic function and a general clinical examination. As a lof of confounding factors can influence autonomic testing, subjects should be adequately prepared in a standardized way. Autonomic testing is usually performed in that way that the response of the autonomic nervous system to a well-defined challenge is recorded. As no single cardiovascular autonomic test is sufficiently reliable, it is recommended to use a combination of different approaches, an autonomic test battery including test to measure parasympathetic and sympathetic cardiovascular function (deep breathing test, Valsalva maneuver, tilt, or pressor test). More specialized tests include carotid sinus massage, assessment of baroreceptor reflex function, pharmacological tests or cardiac, and regional hemodynamic measurements. Techniques to measure functional integrity of sudomotor nerves include the quantitative sudomotor axon reflex sweat test, analysis of the sympathetic skin response as well as the thermoregulatory sweat test. In addition to these rather established techniques more recent developments have been introduced to reduce technical demands and interindividual variability such as the quantitative direct and indirect axon reflex testing or sudoscan. However, diagnostic accuracy of these tests remains to be determined. We reviewed the current literature on currently available autonomic cardiovascular and sudomotor tests with a focus on their physiological and technical mechanisms as well as their diagnostic value in the scientific and clinical setting.

The conventional autonomic tests have still a role in differentiating multiple system atrophy from Parkinson disease?

The differentiation of MSA with predominant parkinsonism (MSA-P) from Parkinson disease (PD) or other parkinsonism disorders may be challenging in early stages of the disease. Dysautonomia may be present both in MSA-P and in PD. This study aims to evaluate the presence and features of autonomic test alteration in a cohort of unselected MSA-P and PD with dysautonomia. We enrolled 52 consecutive patients into a 5-months prospective observational study. All patients performed clinical scales (UPDRS), the Orthostatic Hypotension Questionnarie (OHT), a battery of cardiovascular autonomic tests (deep breathing, standing up, 10 min head-up tilt, Valsalva maneuver, handgrip test), and the sympathetic skin responses (SSR) recording at hands and feet, after electrical, acoustic and endogenous stimuli. 23 patients with PD and 27 with MSA were investigated, the two groups were age, sex and disease duration matched. In MSA-P we found abnormal heart rate variability compared with PD (p = 0.02), while OH did not differ. All MSA-P patients showed late-OH during Tilt Test. SSR was abnormal in 18 MSA – P patients and none of PD.

Dia­gnostics, symp­tomatology and findings in dis­eases and disorders of the autonomic nervous system in neurology

Disorders of the autonomic nervous system are more common in neurologic practice than previously recognized in diagnostic conclusions. Besides the primary involvement of the autonomic nervous system, there are sympathetic or parasympathetic (especially vagal) dysfunctions associated with other diseases of the peripheral and central nervous system. The aim of this paper is to provide a short overview of the symptomatology of autonomic dysfunctions, the examination methods of the autonomic nervous system, especially those available and applicable in clinical neurological practice, and furthemore, the clinical pictures of generalized and localized autonomic dysfunctions. The most important autonomic examinations focus on the cardiovascular system, assessing both heart rate and blood pressure changes in appropriately selected autonomic tests. The cardiovascular autonomic reflex tests and the heart rate variability assessment are here the most commonly used diagnostic tools. The examination methods of the autonomic nervous system in other systems of the human body are described in this paper in a brief overview. The latter part of this article is dedicated to selected diseases and clinical symptomatology. Among generalized (systematic) disorders of the autonomic nervous system, diabetic autonomic neuropathy and autonomic polyneuropathies of other causes are discussed in greater detail. This is followed by an overview of autonomic disturbances and dysfunctions of central origin, that may constitute either major, or minor symptoms of neurological diseases. The paper further describes clinical features of localized autonomic disturbances. A simple diagnostic scheme for basic evaluation of the autonomic functions in clinical neurological practice is proposed at the end of this paper.

Prevalence of Diabetic Neuropathy in Young Adults with Type 1 Diabetes and the Association with Insulin Pump Therapy.

The aim was to investigate the prevalence of diabetic sensorimotor polyneuropathy (DSPN) and cardiovascular autonomic neuropathy (CAN) in a Danish population of young adults with type 1 diabetes (T1D) using both established and novel measuring modalities. Furthermore, to investigate the association between continuous subcutaneous insulin infusion (CSII) treatment and these complications. CAN was assessed by cardiovascular autonomic reflex tests. DSPN was assessed not only by perception of light touch and pain, vibration perception threshold (VPT), Brief Pain Inventory (BPI), and Michigan Neuropathy Screening Instrument questionnaires but also by novel modalities: electrochemical skin conductance (ESC), sural nerve conduction velocity (SNCV), and sural nerve amplitude potential (SNAP). The study comprised 156 young adults with a mean age of 22 years (standard deviation 1.6). The prevalence of CAN and early CAN was 9% and 28.1%, respectively. Subclinical DSPN was 55.1% and confirmed DSPN was 2.6%. Prevalence of abnormal SNAP was 23.8%, SNCV was 37.1%, ESC on the hands and feet was 4% and 8%, respectively, VPT was 1.3%, and BPI questionnaire was 1.9%. No association was found between CSII treatment and the measures of DSPN and CAN. DSPN and CAN are prevalent in young adults with T1D with no association found with CSII treatment. The use of novel measuring modalities identified a higher number of subjects with DSPN compared with established measures. Screening for diabetic neuropathy in young adults may be beneficial to detect and prevent nerve damages at early stages.