Autonomic and sensory nerve dysfunction in primary biliary cirrhosis

AIM: Cardiovascular autonomic and peripheral sensory neuropathy is a known complication of chronic alcoholic and non-alcoholic liver diseases. We aimed to assess the prevalence and risk factors for peripheral sensory nerve and autonomic dysfunction using sensitive methods in patients with primary biliary cirrhosis (PBC). METHODS: Twenty-four AMA M2 positive female patients with clinical, biochemical and histological evidence of PBC and 20 age matched healthy female subjects were studied. Five standard cardiovascular reflex tests and 24-h heart rate variability (HRV) analysis were performed to define autonomic function. Peripheral sensory nerve function on median and peroneal nerves was characterized by current perception threshold (CPT), measured by a neuroselective diagnostic stimulator (Neurotron, Baltimore, MD). RESULTS: Fourteen of 24 patients (58%) had at least one abnormal cardiovascular reflex test and thirteen (54%) had peripheral sensory neuropathy. Lower heart rate response to deep breathing (P = 0.001), standing (P = 0.03) and Valsalva manoeuvre (P = 0.01), and more profound decrease of blood pressure after standing (P = 0.03) was found in PBC patients than in controls. As a novel finding we proved that both time domain and frequency domain parameters of 24-h HRV were significantly reduced in PBC patients compared to controls. Each patient had at least one abnormal parameter of HRV. Lower CPT values indicated hyperaesthesia as a characteristic feature at peroneal nerve testing at three frequencies (2000 Hz: P = 0.005; 250 Hz: P = 0.002; 5 Hz: P = 0.004) in PBC compared to controls. Correlation of autonomic dysfunction with the severity and duration of the disease was observed. Lower total power of HRV correlated with lower CPT values at median nerve testing at 250 Hz (P = 0.0001) and at 5 Hz (P = 0.002), as well as with those at peroneal nerve testing at 2000 Hz (P = 0.01). CONCLUSION: Autonomic and sensory nerve dysfunctions are frequent in PBC. Twenty-four-hour HRV analysis is more sensitive than standard cardiovascular tests for detecting of both parasympathetic and sympathetic impairments. Our novel data suggest that hyperaesthesia is a characteristic feature of peripheral sensory neuropathy and might contribute to itching in PBC. Autonomic dysfunction is related to the duration and severity of PBC

The Effects of Glucose Tolerance, Hypertension, and Race on Heart Rate Variability, QT Interval Duration, and Left Ventricular Hypertrophy in Overweight-Obese Adolescents

The prevalence of childhood obesity has increased remarkably within the past ten years with black youth disproportionately affected. Childhood obesity is linked to cardiovascular risk. Purposes of this study were to explore relationships between cardiac autonomic risk factors of heart rate variability (HRV), QT corrected (QTc) Interval duration, and Cornell voltage measures for left ventricular hypertrophy (LVH) to body mass index (BMI), relative body mass index (RBMI), and blood pressure (BP) measures, and to examine the effects of impaired glucose tolerance (IGT), hypertension, and race on these cardiac autonomic risk factors in overweight-obese adolescents. Methods: Overweight and obese adolescents (N = 128), ages 11-18 years, (60.2% black, 63.3% female) were included in this secondary data analysis. During the original study BMI, resting BP, 12-lead electrocardiogram (ECG), and 24-hour Holter measures were obtained. Overweight was defined as BMI ≥ 85th percentile on age-gender specific growth charts and obesity as ³ 95th percentile. Systolic or diastolic BP \u3e 90th percentile for age, height, and sex was considered elevated BP. An oral glucose tolerance test (1g of dextrose/kg with a maximum of 75 g) or mixed meal tolerance test [(Sustacal/Boost) (6 kcal/kg, body weight, max 360 kcal)] was conducted with IGT defined as either a fasting blood glucose ³ 100 and \u3c 126 mg/dl or 2-hr post-load glucose ³ 140 and \u3c 200 mg/dl based on the American Diabetes Association criteria. Holter data were analyzed for HRV time and frequency domain measures of circadian fluctuation (SDNN) and parasympathetic function (high frequency; HF) using Multi-parameter Arrhythmia Review Station (MARS) PC Analysis and Editing system. QTc and Cornell voltage (Sv3 + RaVL) measurements for LVH were obtained from a 12-lead ECG. Results: In the total sample, 28% had IGT, 34% had prolonged QTc, 51% met criteria for elevated BP, and none met Cornell criteria for LVH. BMI and RBMI did not correlate with HRV measures, QTc, or Cornell voltage. Systolic BP was modestly correlated to Cornell voltage (r = 0.231, p = 0.009). No significant difference was noted between glucose tolerance groups for HRV (HF, p = 0.25; SDNN, p = 0.108), QTc (p = 0.59), or Cornell voltage (p = 0.33). However, the IGT group tended to have a higher frequency of elevated BP (64% vs. 47%, χ = 3.047, p = 0.08). There was no significant difference in HF (p = 0.31), SDNN (p = 0.80), and QTc (p = 0.92) between BP groups. However, overweight-obese adolescents with elevated BP displayed significantly higher measures of Cornell voltage (0.95 mV vs. 0.76 mV, p = 0.004) than non-hypertensive peers. No significant difference was identified between blacks vs. whites for HF (p = 0.106), QTc (p = 0.599), or Cornell voltage (p = 0.965) measures, however black youth displayed significantly lower SDNN (p \u3c 0.001). The prevalence of IGT was similar between racial groups (28.57% vs. 27.45%, χ = 0.01, p = 0.890). Conclusion: Obesity alone is an independent factor for cardiovascular risk. Screening for QTc and LVH using Cornell voltage measurements for LVH using 12-lead ECG is recommended in all overweight-obese youth. Further studies examining a more diverse weight group should be considered

A Study of QTd as an indicator of Cardiac Autonomic Neuropathy in Type 2 Diabetes Mellitus

INTRODUCTION: Cardiac Autonomic Neuropathy (CAN) is often overlooked both in diagnosis and treatment simply because there is no widely accepted single approach to its diagnosis. Currently, Cardiovascular autonomic reflex tests (CART) are the gold standard for diagnosing CAN in persons with DM .It include four tests: (i) heart rate variation to deep breathing (ii) heart rate variation to Valsalva, (iii.) heart rate response to standing (30:15), and (iv) orthostatic hypotension. But these tests are cumbersome and not easy to perform in every patient. Therefore, there is a need of simple, non-invasive bed side test to detect early autonomic involvement in diabetes. AIMS AND OBJECTIVES: 1. To determine QTc maximum, QTc mean, QTc minimum QTc dispersion in Type2 diabetic patients. 2. Comparison of QTc maximum, QTc minimum, QTc dispersion, QTc mean in both study group and control group. 3. To study the significance of QTd as an indicator of CAN in Type 2 Diabetes mellitus. MATERIALS&METHOD: The study was conducted among patients from General Medicine wards of Government Rajaji Hospital, Madurai during the period of February 2016 to July 2016. The study included 100 cases of diabetes and 100 age and sex matched controls. Subjects believed to fulfill all eligibility criteria, and none of the exclusion criteria were included in the study. METHODOLOGY: A previously designed proforma was used to collect the demographic data, history and clinical details of the patients. A battery of five autonomic function tests are done in all cases to assess CAN. A score of 0-2 is assigned to each test. Based on the score obtained from the test, patients are divided in to three groups-severe, early and no CAN. A 12 lead ECG is taken after 10 minutes rest in all patients at 50 mm/second speed. RR interval, heart rate, QTc interval, QTc maximum, QTc minimum and QTc dispersion are calculated from the ECG. Comparisons of heart rate, QTc mean, QTc max, QTc min, QTc dispersion are made in various groups and controls and significance assessed by Students t test. Relation between age, sex, and autonomic neuropathy are assessed by Pearson correlation test. RESULTS: The average age for study group was 54 years. Among the 100 patients studied 55 were males and 45 females. Among the cases studied 62 had CAN .Of these 62, 44 had Grade 2(severe) CAN, 18 had Grade1(early) CAN .Mean heart rate was found to be high in diabetic patients compared to controls .Among the cases the heart rate was higher in those with severe CAN . QT mean ,QT minimum, QT maximum, QT dispersion was significantly more in patients with CAN than those without CAN and controls. Among those with CAN these were found to be significantly more in patients with Grade 2 CAN than those with Grade 1 CAN. CONCLUSION: Diabetics with CAN had significantly higher QTc mean, QTc maximum ,QTc minimum, QTc dispersion values compared to diabetics without CAN and controls

Cardiac autonomic neuropathy in diabetes mellitus

Background: The present study was conducted with an objective to study the prevalence of cardiac autonomic neuropathy (CAN) in patients with diabetes mellitus (DM) and its relation to duration, severity of DM, patient's age and BMI.Methods: This hospital based prospective study was conducted from August 2015 to September 2017, at M.K.C.G. Medical College Hospital, Berhampur, Odisha, India. Cross sectional study was design. A total number of 100 diagnosed patients of diabetes mellitus who were admitted in hospital or attended on OPD basis were taken for the study. Detailed history, clinical evaluation, laboratory investigations were carried out. The diagnosis of CAN was made by autonomic function tests. The CAN score of each patient was analysed. Database were generated based on age, duration of diabetes, severity of DM and BMI.Results: Out of 100 diabetic patients, 40 patients (23 males and 17 females) were selected for final analysis after excluding conditions causing cardiac autonomic neuropathy other than diabetes mellitus. All the patients were in the age group 21 to 70years. In the present study it was found that 57.5% of patients with DM had CAN and its incidence increased with severity of hyperglycemia, duration of DM, BMI and age of the patient.Conclusions: Cardiac autonomic neuropathy is a common and early complication of DM. Proper history taking to identify the symptoms related to CAN and performing simple autonomic tests in all patients of DM can identify cardiac autonomic neuropathy

Increased Short-Term Beat-To-Beat Variability of QT Interval in Patients with Acromegaly.

Cardiovascular diseases, including ventricular arrhythmias are responsible for increased mortality in patients with acromegaly. Acromegaly may cause repolarization abnormalities such as QT prolongation and impairment of repolarization reserve enhancing liability to arrhythmia. The aim of this study was to determine the short-term beat-to-beat QT variability in patients with acromegaly. Thirty acromegalic patients (23 women and 7 men, mean age+/-SD: 55.7+/-10.4 years) were compared with age- and sex-matched volunteers (mean age 51.3+/-7.6 years). Cardiac repolarization parameters including frequency corrected QT interval, PQ and QRS intervals, duration of terminal part of T waves (Tpeak-Tend) and short-term variability of QT interval were evaluated. All acromegalic patients and controls underwent transthoracic echocardiographic examination. Autonomic function was assessed by means of five standard cardiovascular reflex tests. Comparison of the two groups revealed no significant differences in the conventional ECG parameters of repolarization (QT: 401.1+/-30.6 ms vs 389.3+/-16.5 ms, corrected QT interval: 430.1+/-18.6 ms vs 425.6+/-17.3 ms, QT dispersion: 38.2+/-13.2 ms vs 36.6+/-10.2 ms; acromegaly vs control, respectively). However, short-term beat-to-beat QT variability was significantly increased in acromegalic patients (4.23+/-1.03 ms vs 3.02+/-0.80, P<0.0001). There were significant differences between the two groups in the echocardiographic dimensions (left ventricular end diastolic diameter: 52.6+/-5.4 mm vs 48.0+/-3.9 mm, left ventricular end systolic diameter: 32.3+/-5.2 mm vs 29.1+/-4.4 mm, interventricular septum: 11.1+/-2.2 mm vs 8.8+/-0.7 mm, posterior wall of left ventricle: 10.8+/-1.4 mm vs 8.9+/-0.7 mm, P<0.05, respectively). Short-term beat-to-beat QT variability was elevated in patients with acromegaly in spite of unchanged conventional parameters of ventricular repolarization. This enhanced temporal QT variability may be an early indicator of increased liability to arrhythmia

Heart rate variability in people with metabolic syndrome

Metabolic syndrome (MS) is characterized by disorders of carbohydrate and fat metabolism, which can lead to the development of cardiac autonomic neuropathy (CAN). Heart rate variability (HRV) analysis is used to assess the state of autonomic regulation. A decrease in HRV indicates unfavourable changes in autonomic regulation and the development of CAN. The purpose of this study was to compare HRV parameters in patients with metabolic syndrome and healthy individuals without signs of MS. We examined 74 patients with metabolic syndrome (mean age 54.4±1.1 years) and 61 healthy subjects (without signs of MS) (mean age 57.0±1.6 years). The results of the study indicate a significant decrease in HRV in people with MS. However, they had significantly lower values of the SDNN index (by 26%), which characterizes the overall power of neurohumoral regulation of heart rate. Differences in the indicators characterizing short-term, vagal influences were especially pronounced: in patients with MS, RMSSD (by 44%) and HF (by 69%) were lower than in controls. The activity of the baroreflex center of the medulla oblongata, assessed by the spectral power of low-frequency waves (LF), was 55% lower in patients with MS compared to controls. There were no significant differences in the mean duration of the R-R interval, the spectral power of very low frequency (VLF) waves, or the ratio of the spectral powers of low and high frequencies (LF/HF, LFn, HFn) in patients with MS compared to controls. No significant shift in the autonomic balance towards sympathicotonia was found in patients with MS. The analysis of variance confirmed the significant effect of the metabolic syndrome factor on HRV. Thus, the data obtained indicate the development of CAN in people with metabolic syndrome, which is an unfavourable prognostic sign.To assess the effect of MS on the rate of aging, the biological age (BA) of the examined people with MS was calculated. The formula for calculating BA was obtained on a group of people without MS. The method of multiple stepwise regression was used. The aging rate was calculated as the difference between biological and chronological age (CA). The average BAin the group of people with MS was 63,20±1,81years, in the control group –53.99±1.71 years (p<0.05). The difference between BAand CA is 8,81±0,94 years in the group of people with MS and -1.01±0.61 in control group (p<0.05). From this we can conclude that MS can be a factor accelerating aging

NONINVASIVE ASSESSMENT AND MODELING OF DIABETIC CARDIOVASCULAR AUTONOMIC NEUROPATHY

Noninvasive assessment of diabetic cardiovascular autonomic neuropathy (AN): Cardiac and vascular dysfunctions resulting from AN are complications of diabetes, often undiagnosed. Our objectives were to: 1) determine sympathetic and parasympathetic components of compromised blood pressure regulation in patients with polyneuropathy, and 2) rank noninvasive indexes for their sensitivity in diagnosing AN. Continuous 12-lead electrocardiography (ECG), blood pressure (BP), respiration, regional blood flow and bio-impedance were recorded from 12 able-bodied subjects (AB), 7 diabetics without (D0), 7 with possible (D1) and 8 with definite polyneuropathy (D2), during 10 minutes supine control, 30 minutes 70-degree head-up tilt and 5 minutes supine recovery. During the first 3 minutes of tilt, systolic BP decreased in D2 while increased in AB. Parasympathetic control of heart rate, baroreflex sensitivity, and baroreflex effectiveness and sympathetic control of heart rate and vasomotion were reduced in D2, compared with AB. Baroreflex effectiveness index was identified as the most sensitive index to discriminate diabetic AN. Four-dimensional multiscale modeling of ECG indexes of diabetic autonomic neuropathy: QT interval prolongation which predicts long-term mortality in diabetics with AN, is well known. The mechanism of QT interval prolongation is still unknown, but correlation of regional sympathetic denervation of the heart (revealed by cardiac imaging) with QT interval in 12-lead ECG has been proposed. The goal of this study is to 1) reproduce QT interval prolongation seen in diabetics, and 2) develop a computer model to link QT interval prolongation to regional cardiac sympathetic denervation at the cellular level. From the 12-lead ECG acquired in the study above, heart rate-corrected QT interval (QTc) was computed and a reduced ionic whole heart mathematical model was constructed. Twelve-lead ECG was produced as a forward solution from an equivalent cardiac source. Different patterns of regional denervation in cardiac images of diabetic patients guided the simulation of pathological changes. Minimum QTc interval of lateral leads tended to be longer in D2 than in AB. Prolonging action potential duration in the basal septal region in the model produced ECG and QT interval similar to that of D2 subjects, suggesting sympathetic denervation in this region in patients with definite neuropathy

Cardiovascular autonomic neuropathy in type 2 diabetic patients

Diabetes is one of the most common chronic pathologies around the world, involving treatment with general clinicians, endocrinologists, cardiologists, ophthalmologists, nephrologists and a multidisciplinary team. Patients with type 2 Diabetes Mellitus (T2DM) can be affected by cardiac autonomic neuropathy, leading to increased mortality and morbidity. In this review, we will present current concepts, clinical features, diagnosis, prognosis, and possible treatment. New drugs recently developed to reduce glycemic level presented a pleiotropic effect of reducing sudden death, suggesting a potential use in patients at risk.651566