Cardiac Autonomic Function Tests Research Articles

Modulation of cardiac autonomic functions in patients with major depression treated with repetitive transcranial magnetic stimulation

Background Sub clinical cardiac autonomic imbalance is associated with depression. Clinical improvement produced by antidepressant therapy might alter this autonomic balance. Objectives To investigate the effect of repetitive transcranial magnetic stimulation (rTMS) therapy on autonomic functions measured by heart rate variability (HRV) in depression patients and compare it with selective serotonin re-up-take inhibitors (SSRI) therapy. Methods Consecutive drug-naïve patients of major depression based on DSM-IV-TR were recruited in this study ( n = 67). Basal Hamilton depression-rating scale (HDRS) and measures of cardiac autonomic function were recorded and compared with those after two weeks of therapy with rTMS ( n = 27) and one month after SSRI therapy ( n = 25). Results Both therapies produced comparable and significant reduction in HDRS scores. HRV measures indicated that rTMS produced significantly greater reduction in the sympathetic: parasympathetic ratio suggesting improvement in sympathovagal balance. Conventional cardiac autonomic function tests did not differentiate the two therapy effects. Conclusions rTMS not only produced antidepressant effects but also ‘‘corrected’’ the autonomic imbalance. SSRI was systemically administered and hence by direct cardiac effect, may have masked cardiac effects that would have occurred by the improvement in depression. Alternatively, the neurophysiological ‘‘correction’’ with drug therapy may have longer latency, just as with the therapeutic effects.

Autoantibodies to Autonomic Nerves Associated With Cardiac and Peripheral Autonomic Neuropathy

This study examines whether autonomic nerve autoantibodies (ANabs) are associated with development of autonomic neuropathy using a prospective study design. A group of type 1 diabetic patients were followed prospectively with regard to autonomic nerve function on four occasions. At the third examination, 41 patients were tested for ANabs (complement-fixing autoantibodies to the sympathetic ganglion, vagus nerve, and adrenal medulla), and the results were related to cardiac autonomic nerve function (heart rate variation during deep breathing [expiration/inspiration ratio] and heart-rate reaction to tilt [acceleration and brake index]) and to peripheral sympathetic nerve function (vasoconstriction after indirect cooling [vasoconstriction index]). ANabs were detected in 23 of 41 (56%) patients at the third examination. Compared with patients without ANabs (ANabs-), patients with ANabs (ANabs+) showed significantly higher frequencies of at least one abnormal cardiac autonomic nerve function test at the third examination (17 of 23 [74%] vs. 7 of 18 [39%]; P = 0.03) and fourth examination (15 of 21 [71%] vs. 4 of 16 [25%]; P < 0.01). In contrast, there was no similar difference at the first or second examination. The relative risk for ANabs(+) patients to develop cardiac autonomic neuropathy at follow-up was 7.5 (95% CI 1.72-32.80). The vasoconstriction index was more abnormal in ANabs+ than in ANabs- patients at the fourth examination (median 1.40 [interquartile range 1.58] vs. 0.35 [2.05]; P = 0.01). ANabs were associated with future development of cardiac and peripheral autonomic neuropathy in diabetic patients, implying an etiological relationship between nervous tissue autoimmunity and these diabetes complications.

Diabetic gastroparesis in association with autonomic neuropathy and microvasculopathy.

Gastroparesis is a frequent and sometimes life-threatening complication of diabetes mellitus. Autonomic neuropathy seems to be one of the most important mechanisms underlying this entity, together with the other probable pathologies. The present study was performed in order to identify an alternative to gastric scintigraphy as a screening test. The gastric emptying times of 60 subjects (Group 1: 20 insulin-dependent patients, Group 2: 20 non-insulin-dependent diabetes mellitus patients, and Group 3: 20 healthy volunteers) were monitored by gastric scintigraphy. Perception thresholds for cold, heat, and vibration were tested by a quantitative sensory test, and QTc dispersions were calculated from standard electrocardiography recordings. In addition, fasting blood glucose, hemoglobin A1c and urine beta2-microglobulin and microalbumin concentrations were determined for the patient groups. Funduscopic examination was performed by an independent ophthalmologist. Gastroparesis was determined in both patient groups, regardless of fasting blood glucose and hemoglobin A1c concentrations. A strong correlation was observed between nephropathy, retinopathy, and cardiac autonomic denervation (QTc) and gastroparesis. In conclusion, retinal and renal microvasculopathy parameters and cardiac autonomic function tests may be useful for screening diabetic patients for gastroparesis.

Is There A Relationship Between Baroreflex Sensitivity, Cardiac Autonomic Function And Cardiac Repolarisation In Type 1 Patients?

Established diabetic autonomic neuropathy (DAN) carries a poor prognosis, with an increased risk of sudden death. Recently, baroreflex sensitivity (BRS) has been proposed as a sensitive marker of autonomic function in diabetes (DM). An association between DAN and abnormal cardiac repolarisation, manifest by increases in QT interval and/or QT dispersion on the ECG, has also been described. The aim of this study was to investigate the relationship between BRS and QT parameters. We have studied 28 Type 1 DM subjects (age 39 ± 10yrs (mean ± SD), DM duration 14 ± 11yrs, HbA1c 8.5 ± 1.3%) with normal cardiac autonomic function tests (DAN–) and 8 subjects (age 49 ± 13yrs, duration 22 ± 9yrs, HbA1c 9.5 ± 1.1%) with abnormal tests using standard criteria (DAN+). We measured supine BRS using sequence analysis of systolic blood pressure and pulse interval. Rate‐corrected QT (QTc) interval was measured using a high‐resolution ECG system, and QT dispersion from a 12‐lead ECG recorded at 50mm/s. Results are summarised below.Regression analysis revealed no correlation between BRS and QTc interval or QT. In summary, DAN+ patients had significantly lower BRS (p &lt; 0.001) and increased QT dispersion (p &lt; 0.01) compared to DAN− subjects, but no difference in QTc. In contrast to BRS, changes in QTc and QT dispersion may occur relatively late in the disease. BRS ms/mmHg QTc interval QT dispersion DAN− 12.7 ± 6.6 (n=28) 411 ± 22 ms (n=28) 38 ± 12 ms (n=28) DAN+ 3.9 ± 1.9 (n=8) 409 ± 22 ms (n=8) 54 ± 12 ms (n=6)

EXERCISE CAPACITY AND CARDIAC AUTONOMIC FUNCTION IN RECENT KIDNEY &amp; KIDNEY-PANCREAS TRANSPLANT RECIPIENTS

1191 This study identified the exercise capacity of kidney (K) and kidney-pancreas (KP) transplant recipients and examined the relationship between exercise capacity (peak relative VO2) and cardiac autonomic function (CAF). Between 6 to 16 weeks post-transplant, subjects completed a maximal cardiopulmonary exercise tolerance test (ETT) using the Branching protocol and performed evoked CAF tests including valsalva (VR) and sinus arrhythmia (SA). Subjects (n=27) were predominantly male (67%). African American (70%), received hemodialysis prior to transplantation (81%), never had diabetes (n=59%), and were 43.5±10.2 (mean±S.D.) years old (range 19-60 years). Peak relative VO2 was 16.1 ± 4.2 ml/kg/min and ranged from 29-60% of age predicted maximum with VANT occurring at 13.1±3.4 ml/kg/min (81% of peak VO2). No significant difference in relative VO2 existed between transplant groups (p=0.18). Non-diabetics receiving a K (n=16), diabetics who received a KP (n=6), and diabetics who received only a K (n=5) had relative VO2 (ml/kg/min) of 17.2±3.5, 15.1±2.2, and 13.5±4.8 (mean±S.D.), respectively. Clinically, four of the six KP transplant recipients (67%) exhibited early positive ETT for myocardial ischemia at this time. Three had undergone cardiac catheterization less than 6 months prior to transplantation with one requiring coronary artery bypass surgery (CABG) of 1 vessel, while a second was found to have a 40% occlusion of one vessel and the third subject's previous CABG was deemed patent. Peak VO2 was positively related to both VR (r=0.44, p≤0.05) and SA (r=0.21, p≤0.05). The exercise capacity of K and KP transplant recipients was lower than previously reported in the literature. These results emphasize the accelerated arteriosclerotic process that occurs with diabetes and the importance of maximal ETT for transplant recipients entering exercise program to detect myocardial ischemia and to prescribe exercise below VANT. Supported in part by ITNS/Fujisawa grant.

Glucose-induced thermogenesis, inhibition of lipid oxidation rate and autonomic dysfunction in non-diabetic obese women.

The aim of this study was to look for a relationship between autonomic dysfunction and alterations in glucose- induced thermogenesis (GIT) and lipid oxidation rate in obese non-diabetic women. 37 obese women, 20 with impaired cardiac autonomic function tests (group 1) were matched with 17 women with normal tests (group 2) according to age, weight, body mass index (BMI), waist-to-hip ratio (WHR), fat mass (FM) and fat free mass (FFM). A series of five standardized tests was carried out, three of which were based mainly on cardiac parasympathetic control (heart rate response to Valsalva, deep breathing and lying-to-standing) and two on cardiovascular sympathetic function (blood pressure response to standing and to handgrip). Energy expenditure (EE), lipid and glucose oxidation rate were determined by indirect calorimetry at fasting and after an oral glucose load (75 g). Blood glucose, insulin and catecholamines responses to glucose were examined. There was no significant difference in plasma glucose, insulin, catecholamines, metabolic rate, glucose and lipid oxidation rate at fasting and plasma glucose, insulin and catecholamine responses to glucose. GIT was slightly but not significantly lower in group 1 (24.7+/-10.4 kJ) than in group 2 (46.8+/-9.0 kJ). The cumulative glucose oxidation rate did not differ significantly in the two groups. The cumulative lipid oxidation rate was significantly lower in group 1 than in group 2 (-49.4+/-4.1 vs -30.8+/-8.0, respectively, P = 0.033). It correlated negatively with the area under the curve of insulin response (r=-0.37, P=0.04). In the multivariate analysis, both autonomic dysfunction and the area under the curve of insulin response correlated significantly with the cumulative lipid oxidation rate. This study suggests that 1) the glucose-induced inhibition of the lipid oxidation rate in obese women is greater in the patients with autonomic dysfunction; 2) a decrease in sympathetic activity is likely to be involved in this phenomenon.

Pulse oximetry for the assessment of autonomic neuropathy in diabetic patients

Altered vascular responses to various thermal stimuli correlate well with the changes of autonomic neuropathy. These responses were assessed by the use of pulse oximetry. Standard cardiac autonomic function tests were performed in normal subjects ( n = 12), diabetic patients without autonomic neuropathy ( n = 8), and diabetic patients with autonomic neuropathy ( n = 7). Autonomic functions in the same patients then were assessed by estimating the severity of vasospasm in response to cold stimulus with the help of pulse oximetry. Percentage fall in oxygen saturation at 15, 30, 60, 90, and 120 sec of exposure to cold stimulus was recorded on pulse oximeter. Time required for recovery and presence or absence of rebound rise following removal of cold stimulus were noted. In diabetics with autonomic neuropathy, the rate of fall in percentage oxygen saturation was significantly slower ( p < 0.0001), less intense ( p < 0.0001) and with delayed subsequent recovery ( p = 0.013), compared to normal subjects. Rebound rise in oxygen saturation was absent in all the diabetics with autonomic neuropathy, compared to 2 of 12 normal subjects ( p < 0.0001). We conclude that pulse oximetry may be a potentially useful, simple, and noninvasive bedside method for assessment of diabetic autonomic neuropathy.

Auditory brainstem latencies in type I (insulin-dependent) diabetic patients

Introduction: This study was undertaken to compare auditory brainstem response latencies in insulin-dependent diabetics, and to compare these findings with metabolic control, microangiopathy, neuropathy, and the duration of diabetes. Methods: Auditory brainstem latencies were studied in 53 type I diabetic patients and 42 randomly selected nondiabetic control subjects, aged between 20 and 40 years. Three different stimulus repetition rates (10, 30, and 50 Hz) were used. All subjects had normal hearing ability. Results: Wave V latencies were longer in diabetic patients when compared with those of control subjects at all repetition rates. At repetition rates of 10 and 50 Hz, diabetic patients had a prolonged I–V interwave latency, and at a repetition rate of 50 Hz, diabetics had a longer III–V interwave latency than control subjects. These findings indicate a central disturbance in the auditory pathway. Microvascular complications (retinopathy, nephropathy) and the duration of diabetes were associated with the prolongation of auditory brainstem latencies. In contrast, poor metabolic control (high fasting blood glucose and glycated hemoglobin A 1c) at the time of the present study was only marginally associated with prolonged auditory brainstem latencies. The changes in auditory brainstem latencies associated with diabetic neuropathy (measured with five cardiac autonomic nervous function tests) appeared simultaneously with microvascular complications and in patients with diabetes of long duration, and thus a causative role of diabetic neuropathy in the pathogenesis of prolonged auditory brainstem latencies remains unsolved. Conclusion: Delayed auditory brainstem latencies in type I diabetic patients are probably caused by the long duration of diabetes and the microvascular complications associated with it.

Heart rate variability in diabetic children: Sensitivity of the time- and frequency-domain methods

Heart rate variability (HRV) is a noninvasive index of the neural activity of the heart. Although also influenced by the sympathetic activity of the heart, HRV is essentially determined by the vagal stimulation of the heart. Several HRV abnormalities have been described in adults with diabetes mellitus. However, there are few data on HRV in children with diabetes mellitus. In the present study, HRV was assessed in seven healthy children, 10 diabetic children with good glycemic control and 11 diabetic children with poor glycemic control. All had normal standard cardiac autonomic function tests, obtained from 24-h Holter tapes. HRV was measured by calculating six time-domain (mean R-R interval (RR), standard deviation of the R-R interval [SDRR], standard deviation of the mean of 288 R-R intervals [SDANN], the mean of the 288 standard deviations computed for each 5-min period [SD], percentage of differences of adjacent R-R intervals of > 50 msec for the entire 24 h [pNN50], and the root mean square of successive differences [rMSSD]) and four frequency-domain (low frequency [LF], high frequency [HF], total heart rate power spectra, and LF/HF ratio) indexes. SD, pNN50, rMSSD, LF, HF and total heart rate power spectra were markedly and significantly reduced in diabetic children with poor metabolic control. The 24-h variation of low- and high-frequency components of heart rate power spectra of the latter children had a different shape. Thus, diabetic children with poor metabolic control (elevated HbA1c and B2M levels) have a low HRV compared to those diabetic children with good control and healthy children.(ABSTRACT TRUNCATED AT 250 WORDS)

The Influence of Autonomic Neuropathy on Mortality in Insulin-dependent Diabetes

Five-year survival was investigated in 506 randomly selected patients with insulin-dependent diabetes mellitus screened for autonomic neuropathy with a series of cardiac autonomic function tests. Of the 484 diabetics traced, 44 (9 per cent) had died. The cumulative 5-year mortality rate was increased more than five-fold in those with autonomic neuropathy: 27 per cent vs. 5 per cent in those with normal autonomic function. Discriminant analysis of survivors and non-survivors showed that autonomic neuropathy was the most important independent predictor of death. Among those who died, autonomic neuropathy was associated with an increased frequency of retinopathy and peripheral neuropathy and a slightly lower frequency of macrovascular disease. Autonomic neuropathy was associated with an increased mortality rate from renal failure, but not from any other causes.

A simple clinical test of pupillary autonomic function: Correlation with cardiac autonomic function tests in diabetes

A simple test of pupillary autonomic function was performed in 175 diabetic patients. The test uses Polaroid photography to measure pupil size in darkness. Small pupils due to dysfunction of the sympathetic innervation were identified in 40 patients. A significant relationship was found between darkness pupil size and three conventional cardiac autonomic function tests. Renal function was assessed from overnight albumin excretion rates and retinopathy status was determined by direct ophthalmoscopy. Pupillary and cardiac autonomic dysfunction correlated significantly with these indicators of renal and retinal dysfunction. This simple, reproducible test of pupillary function is a useful complement to cardiovascular tests in clinical diagnosis of autonomic neuropathy.