Gabapentin therapy improves heart rate variability in diabetic patients with peripheral neuropathy

PurposeDiabetic cardiac neuropathy, which is characterized by reduced heart rate variability (HRV), frequently coexists with peripheral neuropathy. Gabapentin has been used for the treatment of diabetic neuropathy. We aimed to evaluate the possible effect of gabapentin treatment on autonomic function in patients with type 2 diabetes via HRV.MethodsThirty patients with type 2 diabetes mellitus and peripheral neuropathy and 28 age- and sex-matched healthy controls were consecutively registered. Each patient underwent HRV measurements, and diabetic patients were administered gabapentin. After 3 months of gabapentin therapy, HRV parameters were measured again.ResultsBaseline HRV parameters were blunted in patients with diabetes mellitus according to the controls [standard deviation of all NN intervals (SDNN, ms): 106.3±29.9 vs. 148.8±36.5, P=.001; power spectrum of the high-frequency band (HF, ms²): 133.6±98.3 to 231.4±197.6, P=.02; power spectrum of the low-frequency band (LF, ms²): 341.8±247.8 to 511.5±409.4, P=.048; LF/HF ratio: 3.3±2.4 to 2.6±1.5, P=.33]. After 3 months of treatment with gabapentin, some HRV parameters showed some improvement. SDNN (106.2±29.8 to 119.4 ± 25, P=.016) and HF (133.6±98.3 to 167.6±118.3, P=.021) increased significantly. LF/HF ratio decreased (from 3.3±2.4 to 2.3±1.9, P=.039) and LF remained unchanged (341.8±247.8 to 352.3±228.9, P=.88).ConclusionsTherapeutic doses of gabapentin not only alleviate neuropathic symptoms but also improve cardiac autonomic function in diabetic patients with peripheral neuropathy.     

Feasibility of multiple short, 40-s, intra-procedural ECG recordings to detect immediate changes in heart rate variability during catheter ablation for arrhythmias

Purpose

This study aims to evaluate a method to detect heart rate variability (HRV) changes using short ECG segments during ablation for arrhythmias.

Methods

HRV was averaged from sequentially shorter time windows from 5-min ECG recordings in 15 healthy volunteers. The 40-s window was identified as the shortest duration that yielded reproducible values in high frequency (HF) and low frequency (LF) HRV. This method was validated in patients undergoing tilt table testing to see if the expected modulation in HRV that occurs prior to syncope could be detected from multiple 40-s recordings. Lastly, this method was used to assess HRV changes in 75 patients undergoing ablation for atrial fibrillation (AF) and other arrhythmias, to see if autonomic modulation as a result of ablation could be detected. A further 14 patients had stepwise HRV measurements at different stages of the AF ablation procedure to determine whether intra-procedural HRV changes could be detected.

Results

HRV, averaged from multiple 40-s recordings, demonstrated the expected increase immediately preceding syncope compared with baseline (LF: 341?±?311?C1,536?±?1,368 ms², p?<?0.05; HF: 342?±?339?C1,628?±?1,755 ms², p?<?0.05). AF ablation, particularly following right pulmonary vein circumferential ablation, produced immediately detectable reductions in LF (153?±?251?C50?+?116 ms², p?<?0.001) and HF (86?±?195?C33?±?83 ms², p?<?0.001) without any change in RR interval (877?±?191?C843?±?220 ms, p?=?0.261). Ablation for atrial flutter did not change the mean RR interval, LF or HF HRV.

Conclusion

Averaging multiple 40-s windows give valid HF and LF HRV measurements that enable detection of intra-procedural changes. Left atrial ablation around the right-sided pulmonary veins is unique in producing reductions in HRV. This method has the potential for use as an endpoint marker for adjunctive autonomic ablation procedures.     

Effects of smoking on 24-h ambulatory blood pressure and autonomic function in normoalbuminuric insulin-dependent diabetes mellitus patients

Smoking is an important risk factor for the development and progression of diabetic nephropathy. The mechanisms by which smoking increases albuminuria and promotes nephropathy are unknown. Considering the acute pressor effect of smoking and the close association between blood pressure elevation and development of diabetic nephropathy, blood pressure increase might be implicated in the association between smoking and diabetic nephropathy. However, among nondiabetics, smokers have repeatedly been found to have lower blood pressure than nonsmokers. This is possibly mediated by an autonomic adjustment to sustained sympathetic stimulation by nicotine. Impaired modulation of the sympathovagal activity has been described in diabetes. In diabetic patients, the effect of smoking on blood pressure and autonomic function remains unclarified. We examined 24-h ambulatory blood pressure (oscillometric technique) and autonomic function (short-term power spectral analysis as well as conventional tests) in 24 smokers and 24 nonsmokers matched for sex, age, and diabetes duration. All patients were normoalbuminuric insulin-dependent diabetes mellitus patients. Smoking status was assessed by questionnaire with confirmatory determinations of urinary cotinine. Diabetic smokers had significantly higher 24-h mean arterial blood pressure (94 ± 6.7 mm Hg compared to diabetic nonsmokers 90 ± 5.8 mm Hg, P = .04) including higher diastolic nighttime blood pressure (68 ± 7.3 mm Hg v 64 ± 5.2 mm Hg, P = .03). Smokers also had significantly higher 24-h heart rate (80 ± 7.2 compared to 72 ± 9.2 beats/min, P < .001). In addition, smoking was associated with significantly reduced short-term RR interval variability (supine low frequency component) (5.45 ± 1.29 ln ms² in smokers compared to 6.31 ± 1.11 ln ms² in nonsmokers, P < .02), as well as reduced brake index (33.5 ± 14.5 in smokers v 42.1 ± 16.0 in nonsmokers, P < .05). Diabetic smokers have significantly higher 24-h blood pressure compared to diabetic nonsmokers. This finding, contrasting the effect of smoking among nondiabetics, is possibly mediated by coexisting abnormal postural responses in autonomic cardiac regulation in diabetic smokers. Blood pressure elevation, persisting throughout 24 h, might be operative in the association between smoking and development of diabetic nephropathy.     

Circadian Rhythms of Heart Rate Variability in Hypertrophic Cardiomyopathy

Background: It has been hypothesized that an interaction between sympathetic nervous activity and an abnormal myocardium plays a role in the development and progression of hypertrophic cardiomyopathy (HCM). Methods: In the present study we investigated cardiac autonomic function by 24-hour spectral analysis of heart rate variability (HRV) in 18 patients with HCM, without evidence of heart failure, and 18 controls of similar age. Results: We found a significant reduction of 24 hour variance in HCM patients relative to controls (15,000 ± 9480 ms² vs 24,720 ± 12,450 ms² respectively; p < 0.05). Moreover, a loss of the expected day-night changes in the low frequency (LF) spectral component (expressed in normalized units), and LF/HF ratio (HF; high frequency component) were observed in HCM patients. Decreased day-night changes in LF/HF ratio were previously reported in patients with mild hypertension, uncomplicated coronary disease, and after myocardial infarction, conditions in which it seems to exist a higher than normal sympathetic activity. No significant correlations were found between HRV indices and echocardiographic standard measures of systolic and diastolic function parameters. Conclusions: These data are consistent with the presence of an alteration in neural modulation of heart period in HCM patients, noninvasively detectable by continuous 24 hour HRV analysis.     

Heart rate variability evaluation in the assessment of cardiac autonomic neuropathy in patients with type 2 diabetes

IntroductionHeart rate variability (HRV) is a respected measure used in the assessment of cardiac autonomic neuropathy (CAN) and it can serve as an independent prognostic indicator of sudden arrhythmic death risk. Despite the importance of early detection, the diagnosis of CAN is often made too late, especially in diabetics. Besides the long subclinical phase of CAN, reasons for this include great diversification of employed diagnostic methods and absence of universally accepted normal values; the latter applies mostly in HRV evaluated using short-term spectral analysis (SAHRV).AimThe aim of this cross-sectional study involving patients with type 2 diabetes was to summarize the real potential of using a testing method for CAN diagnosis by short-term SAHRV, including an autonomic load imposed during an orthoclinostatic test (Supine1–Standing–Supine2, short 5-min recordings). Three different normative approaches to the postprocessing analysis of acquired data described by different authors were employed.Secondary aim of the study was to assess the benefit of rate-controlled breathing. The next aim was to compare the HRV data measured with the selected clinical and laboratory indices in patient examined.Materials and methodsThe study included 43 patients with type 2 diabetes (12 women, 31 men, mean age 51.1 ± 10.7 y) and no history of manifest CAN or serious cardiovascular illness, except uncomplicated hypertension. Using a diagnostic system DiANS PF8 with telemetric transfer of ECG and respiratory rate, series of reflex tests according to Ewing and SAHRV (Fourier tachogram analysis, window 256) during autonomic load imposed by Supine1–Standing–Supine2 test (SSS test) and during 5 min of rate-controlled, non-deepened breathing (PB, 12 cycles/min) were performed. Acquired spectral indices were analyzed and compared with normatives of 3 authors using the same recording algorithm, SSS test, but different data postprocessing analysis. These were (1) so called “functional age” of autonomic nervous system (ANS), (2) assessment of CAN severity according to age-stratified medians and percentiles, (3) assessment of CAN severity according to cumulative spectral power during the entire test (cumLFHF).ResultsAccording to the total Ewing score (ETS), 11.6% patients were categorized as CAN-free (ETS = 0), 32.6% were diagnosed with possible CAN (ETS = 1), and 55.8% labeled with manifest CAN (ETS = 2–3). Moderate correlation between ETS and individual SAHRV parameters following orthoclinostasis (test SSS) in Supine2 position was described [ms²]: TP (total power, f = 0.02–0.5 Hz): r = −0.4, p < 0.006; LF component (low frequency, 0.05–0.15 Hz): r = −0.31, p < 0.04; HF component (high frequency, 0.15–0.5 Hz): r = −0.45, p < 0.003) and the same applied to rate-controlled breathing PB (TP, [ms²]: r = −0.56, p < 0.0001; LF: r = −0.38, p < 0.018; HF: r = −0.52, p < 0.001). Moderate correlation was also found between ETS and HRV assessment using a complex indicator – “functional age of ANS” (r = 0.37, p < 0.015), ETS and cumLFHF [ms², ln ms²]: r = −0.46, p < 0.002). In most patients, significant difference between functional age of ANS and calendar age was confirmed (mean 21.8 ± 12.9 y, median 23.5 years, p < 0.0001). An attempt to assess the severity CAN using age-stratified medians and percentiles of TP, LF, HF, and LF/HF was not successful.As for SAHRV and clinical indices (anthropometric, echocardiographic, QTc, laboratory), moderate correlation between the glycated hemoglobin on one side and basic SAHRV indices (TP, LF, HF, LF/HF), functional age of ANS and cumLFHF on the other side was prominent (r = 0.36–0.53, p < 0.0004 to p < 0.02).ConclusionAssessment of CAN using evaluation of HRV can optimally be performed (and simply realized in clinical practice) using SAHRV based on short ECG recordings during autonomic load imposed by orthoclinostatic test (Supine1–Standing–Supine2) and on postprocessing data analysis using complex indicator called “functional age of ANS”. In the detailed evaluation of sympathovagal balance, it complements the screening assessment with cardiovascular reflex tests (Ewing's battery). Besides the orthoclinostatic load, pronounced vagal provocation using rate-controlled, non-deepened breathing (12 cycles/min) represents a recommended facultative load option increasing the yield of the SAHRV method.The detection and assessment of CAN severity while applying the cumulative indicator of HRV (cumLFHF) showed a good discrimination power in the frontline screening for CAN, albeit without the possibility to distinguish between the sympathetic and vagal branch of ANS.Presented cross-sectional study in type 2 diabetes mellitus demonstrated a significant autonomic dysfunction in majority patients examined, independently of diabetes duration. It supports the recommendation to assess the ANS integrity in type 2 diabetes already at diagnosis, within the initial staging of the illness. The severity of CAN correlates well with metabolic control of diabetes as evaluated by glycated hemoglobin.     

Effects of passive tilt and submaximal exercise on spectral heart rate variability in ventricular fibrillation patients without significant structural heart disease

It has been shown that tilt and exercise elicit significant changes in autonomic activity in normal subjects and that submaximal exercise causes a greater reduction in heart rate variability (HRV) in animals susceptible to ventricular fibrillation (VF). Whether there is an abnormal HRV response to tilt and exercise in patients at risk of sudden cardiac death (SCD) remains unknown. Short-term HRV before and during passive tilt and exercise was studied in 12 survivors of out-of-hospital cardiac arrest with documented VF and compared with 12 age- and sex-matched normal controls. No patient had significant structural heart disease or left ventricular dysfunction. HRV was computed as total-frequency (TF, 0.01 to 1.00 Hz), low-frequency (LF, 0.04 to 0.15 Hz) and high-frequency (HF, 0.15 to 0.40 Hz) components. There was no significant difference between normal controls and SCD survivors in HRV before or during tilt or submaximal exercise testing. The HF component was significantly decreased during tilt compared with that in the supine position in both normal controls (5.85 ± 0.61 vs 5.08 ± 0.95 In(msec²), p = 0.005) and patients (5.58 ± 1.49 versus 4.74 ± 1.18 In(msec²), p = 0.003). There was again no significant change in the TF or LF components during tilt in either patients or controls. All frequency components were significantly decreased during submaximal exercise testing in both patients and controls. However, there was no significant difference in any of these tilt- and exercise-induced changes in HRV between normal controls and SCD survivors. In conclusion, passive head-up tilt and submaximal exercise induce a significant alteration of spectral HRV in survivors of SCD without significant structural heart disease similar to that in normal subjects. Short-term assessment of HRV before and during tilt and submaximal exercise does not help in identifying patients at high risk of SCD in this patient population.     

Assessment of baroreceptor-cardiac reflex sensitivity using time domain analysis in patients with IDDM and the relation to left ventricular mass index

Summary Autonomic dysfunction in insulin-dependent diabetic (IDDM) patients has been associated with abnormalities of left ventricular function and an increased risk of sudden death. A group of 30 patients with IDDM and 30 age, sex and blood pressure matched control subjects underwent traditional tests of autonomic function. In addition, baroreceptor-cardiac reflex sensitivity (BRS) was assessed using time domain (sequence) analysis of systolic blood pressure and pulse interval data recorded non-invasively using the Finapres beat-to-beat blood pressure recording system. ’Up BRS' sequences–increases in systolic blood pressure associated with lengthening of R-R interval, and ’down BRS' sequences–decreases in systolic blood pressure associated with shortening of R-R interval were identified and BRS calculated from the regression of systolic blood pressure on R-R interval for all sequences. We also assessed heart rate variability using power spectral analysis and, after expressing components of the spectrum in normalised units, assessed sympathovagal balance from the ratio of low to high frequency powers. IDDM subjects underwent 2-D echocardiography to assess left ventricular mass index. Standard tests of autonomic function revealed no differences between IDDM patients and control subjects, but dramatic reductions in baroreceptor-cardiac reflex sensitivity were detected in IDDM patients. ’Up BRS' when supine was 11.2 ± 1.5 ms/mmHg (mean ± SEM) compared with 20.4 ± 1.95 in control subjects (p < 0.003) and when standing was 4.1 ± 1.9 vs 7.6 ± 2.7 ms/mmHg (p < 0.001). Down BRS when supine was 11.5 ± 1.2 vs 22 ± 2.6 (p < 0.001) and standing was 4.4 ± 1.9 vs 7.3 ± 2.5 ms/mmHg (p < 0.003). There were significant relations between impairment of the baroreflex and duration of diabetes (p < 0.001) and poor glycaemic control (p < 0.001). From a fast Fourier transformation of supine heart rate data and using a band width of 0.05–0.15 Hz as low-frequency and 0.2–0.35 Hz as high frequency total spectral power of R-R interval variability was significantly reduced in the IDDM group for both low-frequency (473 ± 62.8 vs 746.6 ± 77.6 ms² p = 0.002) and high frequency bands 125.2 ± 12.9 vs 459.3 ± 89.8 ms² p < 0.0001. When the absolute powers were expressed in normalised units the ratio of low frequency to high frequency power (a measure of sympathovagal balance) was significantly increased in the IDDM group (2.9 ± 0.53 vs 4.6 ± 0.55, p < 0.002 supine: 3.8 ± 0.49 vs 6.6 ± 0.55, p < 0.001 standing). Thus, time domain analysis of baroreceptor-cardiac reflex sensitivity detects autonomic dysfunction more frequently in IDDM patients than conventional tests. Impaired BRS is associated with an increased left ventricular mass index and this abnormality may have a role in the increased incidence of sudden death seen in young IDDM patients. [Diabetologia (1996) 39: 1385–1391] Received: 9 April 1996 and in revised form: 19 July 1996     

Acute Effect of Insulin on Autonomic Regulation of the Cardiovascular System: A Study by Heart Rate Spectral Analysis

Insulin is suggested to have direct effects on the cardiovascular system but these are not well described. We assessed the possible influence of insulin on autonomic control of heart function. A 2-h hyperinsulinaemic euglycaemic clamp was performed in 10 healthy women (mean age 21.7 ± 1.3 years), at two different insulin infusion rates: 80 mU m⁻² and 400 mU m⁻² min⁻¹, in 7 and 3 subjects, respectively. Saline alone was infused in 4 controls. Power spectral analysis (PSA) of heart rate was recorded before and after 90–120 min of insulin infusion, as were blood pressure and heart rate. Although there were no significant changes in heart rate or blood pressure, PSA showed marked reductions of high frequency (HF) bands after insulin (2.60 ± 0.12 vs 2.09 ± 0.16 log ms², p < 0.005), as at both low and high infusion rates (2.46 ± 0.13 to 2.14 ± 0.23 log ms², p < 0.05, and 2.92 ± 0.18 to 1.98 ± 0.06 log ms², p < 0.01, respectively). There were no significant changes of low frequency (LF) bands. Densities at LF and HF did not change significantly in control studies. As HF and LF are considered to reflect parasympathetic and mainly sympathetic control respectively, our observation of an increased LF/HF ratio (0.13 ± 0.10 vs 0.63 ± 0.13, p < 0.005) may be considered an index of relative sympathetic predominance induced by insulin infusion. We conclude that insulin affects the cardiovascular system, reducing vagal influence on the heart and inducing a relative hypersympathetic tone.     

Exercise training improves cardiovascular autonomic modulation in response to glucose ingestion in obese adults with and without type 2 diabetes mellitus

This study examined the effect of aerobic exercise training on vagal and sympathetic influences on the modulations of heart rate and systolic blood pressure in response to an oral glucose load in obese individuals with and without type 2 diabetes mellitus (T2D). Beat-to-beat arterial pressure and continuous electrocardiogram were measured after a 12-hour overnight fast and in response to glucose ingestion (75 g dextrose) in obese subjects with (T2D group, n = 23) and without (OB group, n = 36) T2D before and after 16 weeks of aerobic exercise training at moderate intensity. Autonomic modulation was assessed using spectral analysis of systolic blood pressure variability (BPV), heart rate variability (HRV), and analysis of baroreflex sensitivity (BRS). Glucose ingestion significantly increased low-frequency (LF_SBP), low-frequency HRV (LF_RRI), and the ratio of low- to high-frequency components of HRV (LF_RRI/HF_RRI), and decreased the high-frequency power (HF_RRI) (P < .05). Exercise training increased LF_RRI and LF_RRI/HF_RRI responses, and reduced HF_RRI and LF_SBP to glucose ingestion in both groups (P < .05), but increased fasted BRS in the OB group only (P < .05); glucose intake had no effect on BRS (P > .05). In conclusion, a 16-week exercise training program improved cardiac autonomic modulation in response to an oral glucose load in obese adults, independently of diabetes status, and in the absence of remarkable changes in body weight, body composition, fitness level, and glycemic control.     

QTc and autonomic neuropathy in diabetes: effects of acute hyperglycaemia and n-3 PUFA

Background and aimsAutonomic function is also regulated by glycaemia and exerts a crucial role in the control of blood pressure and cardiac function. The disruption of this physiological mechanism impacts deeply on cardiovascular mortality in diabetes. We investigated the influence of autonomic dysfunction on QTc interval and on sympatho-vagal balance (LF/HF), in response to acute hyperglycaemia and to membrane electrical stabilization (n-3 PUFA).Methods and resultsTwenty-four type 2 diabetic patients, without (N−: n = 13) or with (N+: n = 11) autonomic neuropathy and 13 healthy subjects (C) underwent BP and ECG monitoring during a 24-h period and during a 2-h hyperglycaemic clamp. ΔQTc during the night was blunted in diabetics (0.5 ± 2.5 vs. C: 2.9 ± 2.5%, p = 0.001), and ΔLF/HF was decreased in N+ (−2.8 ± 38.2 vs. C = 34.8 ± 28.1%, p = 0.02). During hyperglycaemia, QTc increased in C; LF/HF significantly increased in C and N−. A 6-month treatment with n-3 PUFA partially restored ΔLF/HF and ΔQTc (2.1 ± 1.40, p = 0.04 vs. basal) only in N−.ConclusionHyperglycaemia increases QTc interval and sympathetic activity; electrical membrane stabilization improves autonomic function only in the absence of overt autonomic neuropathy. Strategies to prevent the disruption of autonomic function with newer approaches, other than just glucose control, should be implemented.     

Effect of hyperbaric oxygen on cardiac neural regulation in diabetic individuals with foot complications

Aims There are relatively few effective methods to treat autonomic neuropathy in patients with diabetes mellitus. Our aim was to test the hypothesis that hyperbaric oxygen therapy may restore cardiac neural regulation dysfunction in diabetic individuals with foot complications. Methods We conducted a prospective randomized controlled study in patients with diabetic foot problems. Daily heart‐rate variability analysis from 5‐min electrocardiography was used to evaluate the temporal change of cardiac neural regulation. The experimental group consisted of 23 subjects exposed to hyperbaric oxygen therapy of 202.65 kPa for 90 min every Monday to Friday for 4 weeks (20 treatments). The control group consisted of 15 age‐, sex‐ and disease‐matched subjects who were not exposed to hyperbaric therapy. Patients with medical complications and failure of wound healing were excluded to eliminate possible confounding effects. Results There was no significant difference in baseline R–R interval (RR), variance, high‐frequency power (HF), low‐frequency power (LF), and LF/HF ratio between the two groups. In the hyperbaric oxygen group there were significant increases in changes of RR (82.7 ± 16.02 ms); variance 0.88 ± 0.12 ln(ms²); HF 1.06 ± 0.18 ln(ms²); and LF 0.87 ± 0.15 ln(ms²) after the treatment. Measurements of tissue oxygen demonstrated significant increases in local tissue oxygenation in the hyperbaric oxygen group (53.0 ± 2.6 mmHg) compared with the control group (27.5 ± 3.1 mmHg), P < 0.05. Conclusion Hyperbaric oxygen therapy has a significant vagotonic effect, which is beneficial in improving cardiac neural regulation in patients with diabetic autonomic dysfunction. Diabet. Med. (2006)     

Simple function tests for autonomic neuropathy have a higher predictive value on all-cause mortality in diabetes compared to 24-h heart rate variability

AimTo compare the long-term predictive power of heart rate variability (HRV) based on 24 h ECG recordings with a battery of simple autonomic function tests with regard to all-cause mortality in diabetic individuals.Methods240 diabetic persons were randomly selected from the diabetic population. A 24-h ECG was obtained and analysed on the Pathfinder 700. In the RR Tools Program time domain and frequency domain parameters were computed. Five function tests were conducted: Valsalva ratio, heart rate response to standing (30:15 ratio), expiration/inspiration ratio (E/I ratio), orthostatic blood pressure response (Ortho BP), and increase in diastolic blood pressure during sustained handgrip.Results178 patients agreed to participate and 136 patients who completed all 5 function tests and had an acceptable ECG recording were included in the analyses. 64 individuals (47%) died during the 15½ year follow-up. Using Cox proportional hazard analyses correcting for age and gender we found that among the HRV parameters only the power in the low frequency band (LF) had an independent predictive value on all-cause mortality (p = 0.0002). Multivariate analysis of the five function tests showed that Valsalva (p = 0.002), 30:15 ratio (p = 0.037), and handgrip (p = 0.037) were independent predictors of death. When finally the independent predictors among the function tests and the HRV parameters were assessed in the same model, no significant value could be shown for LF power (p = 0.44).ConclusionThe study indicates that simple autonomic function tests are superior to HRV based on 24-h ECG recordings in predicting all-cause mortality in the diabetic population.     

Effects of gender and aging on differential autonomic responses to orthostatic maneuvers

Background: There are gender differences in heart rate and blood pressure response to postural change. Also, normal aging is often associated with diminished cardiac autonomic modulation during postural change from supine to upright position. Nevertheless, the exact mechanisms of these physiological alterations are not entirely understood. Methods: A total of 362 volunteers (206 females, age range: 10–88 years) underwent continuous, noninvasive, beat‐to‐beat blood pressure and ECG recordings in supine and upright position. To calculate spontaneous baroreflex sensitivity (BRS), blood pressure and RR interval fluctuations were reconstructed using the time‐domain sequential technique. Furthermore, mean systolic and diastolic blood pressure, mean heart rate, and frequency‐domain parameters of heart rate variability (low‐frequency power [LF], low‐frequency power in normalized units [LFn] high‐frequency power [HF], high‐frequency power in normalized units [HFn], low‐/high‐frequency ratio [LF/HF], and total power [TP]) were analyzed in both supine and standing positions. To investigate age‐related differences, subjects were divided into four equally sized groups (quartile l: 10–33 years; ll: 34–42 years; III: 43–57 years; and lV: 58–88 years), as well as decades (l: 10–19 years; ll: 20–29 years; lll: 30–39 years; lV: 40–49 years; V: 50–59 years; Vl: 60–69 years; Vll: ≥ 70 years). Results: A continuous decline in BRS, LF, HF, and TP was observed with increasing age in both male and female subjects, regardless of posture. Gender comparison showed significantly higher values of LF (supine P < 0.001; upright P < 0.05), LFn (supine P < 0.001; upright P < 0.01), and TP (supine P < 0.05; upright P < 0.05) in men than women in supine and standing positions. HF revealed no gender difference and HFn (supine P < 0.001; upright P < 0.05) was larger in women. Log BRS correlated well with log LF and log HF in both supine and standing positions. Conclusions: There are significant differences in postural cardiac autonomic modulation between men and women, and the degree of autonomic response to orthostatic maneuvers varies with normal aging. These results may explain gender‐ and age‐related differences in orthostatic tolerance.     

Effect of Pursed-Lip Breathing in Patients With COPD: Linear and Nonlinear Analysis of Cardiac Autonomic Modulation

Objective: The aim of the present study was to evaluate the effect of pursed-lip breathing (PLB) on cardiac autonomic modulation in individuals with chronic obstructive pulmonary disease (COPD) while at rest. Methods: Thirty-two individuals were allocated to one of two groups: COPD (n = 17; 67.29 ± 6.87 years of age) and control (n = 15; 63.2 ± 7.96 years of age). The groups were submitted to a two-stage experimental protocol. The first stage consisted of the characterization of the sample and spirometry. The second stage comprised the analysis of cardiac autonomic modulation through the recording of R-R intervals. This analysis was performed using both nonlinear and linear heart rate variability (HRV). In the statistical analysis, the level of significance was set to 5% (p ≤ 0.05). Results: PLB promoted significant increases in the SD₁, SD₂, RMSSD and LF (ms²) indices as well as an increase in α₁ and a reduction in α₂ in the COPD group. A greater dispersion of points on the Poincaré plots was also observed. The magnitude of the changes produced by PLB differed between groups. Conclusion: PLB led to a loss of fractal correlation properties of heart rate in the direction of linearity in patients with COPD as well as an increase in vagal activity and impact on the spectral analysis. The difference in the magnitude of the changes produced by PLB between groups may be related to the presence of the disease and alterations in the respiration rate.     

Assessment of Heart Rate Variability Changes During Dipyridamole Infusion and Dipyridamole-Induced Myocardial Ischemia: A Time Variant Spectral Approach

Objectives. We sought to evaluate changes in RR interval variability during dipyridamole infusion and dipyridamole-induced myocardial ischemia.Background. Myocardial ischemia and the autonomic nervous system can be mutually interdependent. Spectral analysis of RR interval variability is a useful tool in assessing autonomic tone.Methods. We used a time variant autoregressive spectral estimation algorithm that could extract spectral variables even in the presence of nonstationary signals. Two groups were considered: group A (patients with ischemia, n = 15) with effort or mixed angina, angiographically assessed coronary artery disease and positive exercise and dipyridamole echocardiographic test results, and group B (control subjects, n = 10) with normal exercise and dipyridamole echocardiographic test results. We investigated the following variables: RR interval mean and variance, low frequency (LF) and high frequency (HF) power in normalized units, LF ratio (LF/LF_basal power), HF ratio (HF/HF_basal power) and LF/HF ratio. For each test epoch, we calculated for group A and group B the mean value ± SE of all indexes considered. Differences due to an effect either of group (ischemic vs. control) or of time (including both drug and ischemia effects) were analyzed by using analysis of variance for repeated measurements.Results. Dipyridamole injection was characterized by a reduction of all spectral components in negative test. The LF ratio was the only variable able to discriminate patients with ischemia from control subjects (p < 0.05), whereas a time effect was evident for both mean RR interval and high frequency power in normalized units (p < 0.05). The LF ratio decreased in group B from 1 ± 0.00 (basal) to 0.31 ± 0.22 (peak), and increased in group A from 1 ± 0.00 to 15.41 ± 6.59, respectively. Results of an unpaired t test comparing the peak values of the two groups were also statistically significant (p < 0.01).Conclusions. Our data show that time variant analysis of heart rate variability evidences an increase in the low frequency ratio that allows differentiation of positive from negative test results, suggesting that the electrocardiogram may contain ischemia information unrelated to ST-T variations, even if their enhancement requires a more complex data processing procedure.     

Excessive pulse pressure response to standing in community population with orthostatic systolic hypertension

The postural change of pulse pressure (PP) in the persons with orthostatic hypertension (OHT) is unclear. This study included 2849 (65.0 ± 9.3 years) community participants. Blood pressures (BPs) in supine and standing positions were measured. The differences between upright and supine BP and PP were recorded as ΔBP and ΔPP. The criteria for OHT was ΔBP ≥10 mm Hg, for orthostatic hypotension (OH) was ≤−10 mm Hg and for orthostatic normotension (ONT) was −9 to 9 mm Hg. Fasting blood lipids and glucose were measured. The supine SBP of the sOHT group were similar to that of sONT group (140.9 ± 20.2 mm Hg vs 138.2 ± 19.7 mm Hg), but significantly lower than that of sOH group (151.9 ± 19.2 mm Hg; P < .05). Their PPs were 65.3 ± 15.9, 62.8 ± 14.7, and 71.1 ± 15.1 mm Hg, respectively, and with the similar group difference like SBP. When the position changed from supine to standing, the sOHT group showed PP rise, while sOH and sONT groups showed PP reduction (3.8 ± 7.1 mm Hg vs −17.0 ± 8.5 mm Hg and −5.8 ± 6.6 mm Hg; both P < .05). Thus, the standing PP in the sOHT group was significantly higher than in the sONT (69.1 ± 18.0 mm Hg vs 57.0 ± 15.8 mm Hg; P < .05) and in the sOH (54.2 ± 15.2 mm Hg; P < .05) groups. The postural PP profile varies with the postural responses of SBP. The sOHT group has obviously increased PP and significantly higher standing PP compared with the sONT group.     

Effect of weight loss on sympatho-vagal balance in subjects with grade-3 obesity: restrictive surgery versus hypocaloric diet

Few and mostly uncontrolled studies indicate that weight loss improves heart rate variability (HRV) in grade-3 obesity. The aim of this study was to compare in grade-3 obesity surgery and hypocaloric diet on clinical and metabolic variables and on autonomic indices of HRV. Twenty-four subjects (body mass index, BMI 45.5 ± 9.13 kg/m²) underwent surgery (n = 12, gastric banding, LAGB) or received hypocaloric diet (n = 12, 1,000–1,200 kg/day). Clinical [BMI, systolic blood pressure (SBP) and diastolic blood pressure (DBP), heart rate] and metabolic variables [glucose, cholesterol, HDL- and LDL-cholesterol, triglycerides, AST and ALT transaminases] and 24-h Holter electrocardiographic-derived HRV parameters [R–R interval, standard deviation of R–R intervals (SDNN); low/high-frequency (LF/HF) ratio, and QT interval] were measured at baseline and after 6 months. The two groups were identical at baseline. BMI (?7.5 ± 3.57 kg/m², mean ± SD), glucose (?24.1 ± 26.77 mg/dL), SBP (?16.7 ± 22.19 mmHg) and DBP (?6.2 ± 8.56 mmHg) decreased in LAGB subjects (p < 0.05) and remained unchanged in controls. At 6 months, SDNN increased in LAGB subjects (+25.0 ± 37.19 ms, p < 0.05) and LF/HF ratio diminished (2.9 ± 1.84 vs. 4.9 ± 2.78; p = 0.01), with no change in controls; LF (daytime) and HF (24 h and daytime) increased in LAGB subjects, with no change in controls. Decrease in BMI correlated with SBP and DBP decrease (p < 0.05), and DBP decrease correlated with HR decrease (p < 0.05) and QT shortening (p < 0.05). Weight loss is associated with improvement of glucose metabolism, of blood pressure, and with changes in time and frequency domain parameters of HRV; all these changes indicate recovery of a more physiological autonomic control, with increase in parasympathetic and reduction in sympathetic indices of HRV.     

Orthostatic blood pressure changes and diabetes duration

To determine the prevalence and the associated clinical characteristics of orthostatic hypotension and orthostatic hypertension in patients with diabetic sensorimotor polyneuropathy (DSP).MethodsA single-center retrospective cross-sectional study was conducted on 200 DSP patients who had 3-minute orthostatic measures as part of the standard clinic evaluation. We measured the heart rate (HR) and blood pressure (BP) supine and again after 3 min of standing.ResultsThe prevalence of orthostatic hypotension was 19.5% and that of orthostatic hypertension was 23%. Subjects with orthostatic hypotension had significantly longer diabetes duration than subjects who were normotensive and those with orthostatic hypertension. Quantitatively, BP changes from supine to standing correlated with diabetes duration (R = 0.306; P = 0.0582) and age (R = 0.434; P = 0.006) in subjects with orthostatic hypotension.ConclusionsOrthostatic hypertension and orthostatic hypotension are frequent in patients with DSP. Orthostatic hypertension is associated with shorter diabetes duration than orthostatic hypotension.     

Inadequate sympathovagal balance in response to orthostatism in patients with unexplained syncope and a positive head up tilt test

AIM—To analyse the immediate response of heart rate variability (HRV) in response to orthostatic stress in unexplained syncope.
SUBJECTS—69 subjects, mean (SD) age 42 (18) years, undergoing 60° head up tilt to evaluate unexplained syncope.
METHODS—Based on 256 second ECG samples obtained during supine and upright phases, spectral analyses of low (LF) and high frequency (HF) bands were calculated, as well as the LF/HF power ratio, reflecting the sympathovagal balance. All variables were measured just before tilt during the last five minutes of the supine position, during the first five minutes of head up tilt, and just before the end of passive tilt.
RESULTS—Symptoms occurred in 42 subjects (vasovagal syncope in 37; psychogenic syncope in five). Resting haemodynamics and HRV indices were similar in subjects with and without syncope. Immediately after assuming the upright posture, adaptation to orthostatism differed between the two groups in that the LF/HF power ratio decreased by 11% from supine (from 2.7 (1.5) to 2.4 (1.2)) in the positive test group, while it increased by 11.5% (from 2.8 (1.5) to 3.1 (1.7)) in the negative test group (p = 0.02). This was because subjects with a positive test did not have the same increment in LF power with tilting as those with a negative test (11% v 28%, p = 0.04), while HF power did not alter. A decreased LF/HF power ratio persisted throughout head up tilt and was the only variable found to discriminate between subjects with positive and negative test results (p = 0.005, multivariate analysis). During the first five minutes of tilt, a decreased LF/HF power ratio occurred in 33 of 37 subjects in the positive group and three of 27 in the negative group. Thus a decreased LF/HF ratio had 89% sensitivity, 89% specificity, a 92% positive predictive value, and an 86% negative predictive value.
CONCLUSIONS—Through the LF/HF power ratio, spectral analysis of HRV was highly correlated with head up tilt results. Subjects developing syncope late during continued head up tilt have a decrease in LF/HF ratio immediately after assuming the upright posture, implying that although symptoms have not developed the vasovagal reaction may already have begun. This emphasises the major role of the autonomic nervous system in the genesis of vasovagal (neurally mediated) syncope.


Keywords: heart rate variability; vasovagal syncope; head up tilt test     

Increased sympathetic modulation and decreased response of the heart rate variability in controlled asthma

Objective: To compare the autonomic modulation of heart rate (HR) in asthmatic and healthy volunteers to correlate it with the forced expiratory volume in the first second (FEV₁). Methods: Ten healthy and 14 asthmatic volunteers were included in this cross-sectional study. The volunteers underwent a cardiopulmonary exercise test, spirometry and a register of both resting heart rate variability (HRV) in the supine and seated positions along with HRV during the respiratory sinus arrhythmia maneuver (M-RSA). Results: At rest in supine, asthmatic volunteers presented a higher HR (77.1?±?9.9 vs. 68.7?±?8.7?bpm), shorter interval between two R waves (R-Ri) (807.5?±?107.2 vs. 887.5?±?112.7?ms) when compared with the healthy volunteers, respectively. Moreover, in the frequency domain of HRV, there was increased low frequency (LF) index (50.4?±?17.1 vs. 29.2?±?11.1?n.u.) and decreased high frequency (HF) index (49.4?±?17.1 vs. 70.7?±?11.1?n.u.). During the M-RSA, the asthmatic presented higher HR (82.6?±?10.0 vs. 72.4?±?7.6?bpm) and lower values of R-Ri (746.4?±?92.1 vs. 846.4?±?81.4?ms) and approximate entropy (ApEn) (0.7?±?0.0 vs. 0.8?±?0.1). FEV₁ was strongly correlated with the change of the continuous beat-to-beat variability of HR (SD2) index from the seated to the supine position (r?=?0.78). Conclusion: Controlled asthma in adults appears to induce an increased sympathetic modulation and attenuated response to the postural changes and the M-RSA. Furthermore, there is a correlation between the airways’ obstruction and HRV, especially during postural changes.