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.     

实验性心肌缺血大鼠心脏自主神经活性的动态变化及意义

采用心率变异（ＨＲＶ）时域及频域指标分析急性心肌缺血２４ｈ大鼠心脏自主神经功能的变化以探讨其意义。将实验动物分成三组，即正常对照组（２０只）、假手术组（２０只）与心肌缺血组（４８只），并运用动态心电图记录２４ｈ心电信号变化。结果显示：与假手术组及正常对照组分别比较，心肌缺血组正常窦性心律ＲＲ间期标准差（ＳＤＮＮ）下降（２８．９±９．４ｍｓｖｓ３４．４±１３．７ｍｓ或３５．１±１４．３ｍｓ，Ｐ均＜０．０５），低频（ＬＦ）及低频与高频的比值（ＬＦ／ＨＦ）明显增加（１８９．４±３６．５ｍｓ２／Ｈｚｖｓ５７．３±１７．８ｍｓ２／Ｈｚ或５１．８±１８．６ｍｓ２／Ｈｚ；３．８５±０．９１ｖｓ１．７６±０．６３或１．６８±０．５７，Ｐ均＜０．０１）；２４ｈ心率功率谱示心肌缺血组ＬＦ及ＬＦ／ＨＦ波动幅度较假手术组及正常对照组增高，缺血大鼠ＬＦ与ＬＦ／ＨＦ在缺血后０～３ｈ（２６７．５±１２．４ｍｓ２／Ｈｚ、４．３３±１．０８）及９～１２ｈ（２４４．７±１３．９ｍｓ２／Ｈｚ、３．９６±０．９８）期间增高显著，而在缺血后５～７ｈ（１４９．２±８．７ｍｓ２／Ｈｚ、２．０５±０．４２）内则相对较低。结果表明大鼠心肌缺血后ＨＲＶ降低主?     

冠心病心肌缺血发作时自主神经功能的变化

采用心率变异性（ＨＲＶ）自回归（ＡＲ）和快速傅立叶转换（ＦＦＴ）两种频域法对比分析５０例冠心病病人和５０例正常人ＨＲＶ的昼夜变化及心肌缺血时与无缺血时的ＨＲＶ变化，并对两种频域法进行相关性分析。结果表明：冠心病组和对照组的ＨＲＶ呈昼夜变化，白天以低频成分（ＬＦ，代表交感神经活性）占优势，夜间以高频成分（ＨＦ，反映迷走神经活性）占优势；冠心病心肌缺血病人的ＨＲＶ昼夜变化减少（ＡＲ法，ＬＦ／ＨＦ：冠心病组为２．２±０．９ＶＳ０．８±１．１，对照组为２．４±１．２ＶＳ０．３±０．８，Ｐ＜０．０５），清晨自主神经调节发生突然变化，即由迷走神经兴奋转为交感神经兴奋；劳累型心绞痛病人心肌缺血时ＬＦ增高（１６３±１３２ｍｓ２ＶＳ２４７±１６２ｍｓ２，Ｐ＜０．０５），ＨＦ减少（７５±２１ｍｓ２ＶＳ５７±１１ｍｓ２，Ｐ＜０．０５），心肌缺血次数与ＬＦ呈正相关（ｒ＝０．６７）．上午６～１０时心肌缺血发生最多。两种能谱估计法呈高度正相关（ｒ＝０．９８）。提示：劳累型心绞痛的发作与交感神经功能亢进、迷走神经张力减弱有关；清晨自主神经功能调节的突然变化可起板机作用，使此时心肌缺血的发生频度增高。     

Metabolic syndrome and short‐term heart rate variability in young adults

Aims Heart rate variability (HRV) can be used to estimate autonomic nervous control of the cardiovascular system. In middle‐aged subjects, the metabolic syndrome (MetS) is associated with lower HRV. We hypothesized that alterations in autonomic balance are already present in young adults with the MetS, and analysed the association of short‐term HRV with the MetS (using the National Cholesterol Education Program definition), in 1889 subjects aged 24–39 years. Methods Short‐term (3 min) HRV analysis included high‐frequency (HF), low‐frequency (LF) and total (TP) spectral components of HRV and LF/HF ratio. Results The presence of the MetS was associated with lower HF, LF and TP in men and women, and with higher LF/HF ratio in women. In men, waist circumference was the strongest individual MetS component that associated with HRV. After adjustments for age and heart rate, MetS was associated with lower HF and higher LF/HF ratio in women, but only with a lower TP in men (all P < 0.05). Conclusions MetS is associated with lower HRV in young adults. The individual components of MetS are differentially associated with HRV in men and in women. Our results are consistent with lower vagal activity and a possible increase in sympathetic predominance in women with the MetS. This sex difference in vagal activity and sympathovagal balance may partly explain the greater increase in cardiovascular risk associated with MetS in women than in men.     

Effect of pioglitazone on cardiac sympathovagal modulation in patients with type 2 diabetes

This study aims to examine the effect of pioglitazone on potential progression of autonomic damage in addition to changes in control of cardiovascular function in patients with type 2 diabetes (T2DM). Thirty patients with T2DM and 32 healthy subjects participated in the study. Sympathovagal activity, assessed by power spectral analysis (PSA) of R–R intervals variability, and blood pressure (BP) were studied during clinostatism and orthostatism in controls and patients. We have assessed blood pressure control by 24-hour monitoring of ambulatory blood pressure. Patients were treated with pioglitazone (30 mg/day) for 6 months, and then re-evaluated by PSA for heart rate variability (HRV). Reduced levels of HbA1c (P < 0.0001) and urinary albumin (P = 0.008) were observed in pioglitazone-treated patients compared to untreated baseline levels. Arterial BP remained unchanged following pioglitazone treatment. T2DM patients had reduced HRV (low-frequency power; LF; P < 0.0001 and LF/HF; LF/HF; P < 0.0001) at baseline (clinostatism) compared to controls. Baseline clinostatic differences between groups persisted after pioglitazone treatment and no effect of treatment on basal HRV variables was observed. In controls, HF decreased and LF and LF/HF ratio increased in the orthostatic position. A similar effect for HF was observed in patients, but LF and LF/HF did not increase. The normal difference between HF-power in clinostatism versus orthostatism observed for controls (P < 0.0001) was restored in patients following pioglitazone treatment (P = 0.028). A significant decrease from lying to standing position in orthostatic LF-power (P < 0.0001) and LF/HF (P < 0.0001) was also observed between patients and controls. Although no differences in autonomic control of HRV were observed between controls and patients with T2DM, significant differences were observed in sympathovagal balance following either clinostatic or orthostatic challenge. These findings provide initial evidence of a potential additional benefit afforded by pioglitazone for the improvement of cardiac sympathovagal balance in T2DM.     

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     

Modified orthostatic load for spectral analysis of short-term heart rate variability improves the sensitivity of autonomic dysfunction assessment

AimTo evaluate the impact of orthostatic load for sensitivity of short-term spectral analysis of heart rate variability (HRV) assessment of potential early autonomic dysfunction in diabetes mellitus.MethodsComparison of results of short-term time- and frequency-domain analysis of HRV during single positions and during modified orthostatic load (supine 1–standing–supine 2, each position 300 s) in diabetic subjects with good glycemic control (n=80, age 38±14, diabetes duration 16±10 years) and without autonomic neuropathy as assessed by a standard bedside reflex test battery, and in nondiabetic controls (n=150, age 40±13 years).ResultsNone of the short-term frequency-domain parameters [absolute and logarithmic (LN) values of spectral powers in total- (TF), low- (LF), and high-frequency (HF) bands and its centroid frequencies] as obtained in single positions “supine” or “standing” revealed a significant difference between well-controlled patients and healthy controls (P>.3). However, during modified orthostatic load, significant differences in ΔLN TF_{(supine 1–supine 2)} and in ΔLN LF_{(supine 1–supine 2)} as well as in ΔLN LF_{(standing–supine 2)} values between diabetic and healthy subjects were recorded [?0.2±0.5 vs. ?0.1±0.4 LN (ms²), P=.05; ?0.3±0.8 vs. 0.1±0.7 LN (ms²), P=.001 and 0.2±1.0 vs. 0.4±0.9 LN (ms²), P=.05, respectively] with insignificant intergroup differences in related centroid frequencies. This finding suggests a delayed recovery of LF spectral power in diabetic subjects after orthostatic challenge.ConclusionsWhen compared with single position measurements, the modified orthostatic load protocol improves the sensitivity of short-term HRV examination. In well-controlled diabetic subjects without cardiovascular autonomic neuropathy (as excluded by standard cardiovascular reflex testing), the delayed recovery of LF band spectral power after orthostatic load with standing up indicates diminished parasympathetic activation.     

Relationship between Autonomic Nervous System Activity and Lower Urinary Tract Symptoms: An Analysis of Heart Rate Variability in Men with Lower Urinary Tract Symptoms

Objectives: Lower urinary tract symptoms (LUTS) are common, but their etiology and mechanism remain unclear. We believe that changes in autonomic nervous system (ANS) activity may be contributory because the lower urinary tract is regulated through the sympathetic and parasympathetic nervous systems. Heart rate variability (HRV) is a tool by which autonomic nervous function can be measured; therefore, we measured and compared parameters of heart rate variability between men with LUTS and asymptomatic subjects. Methods: We studied 35 men with LUTS (mean age 50.5 ± 14.9 years) and 110 asymptomatic male volunteers who had requested a health check up (mean age 49.5 ± 5.19 years) from July 2006 to June 2008. HRV is known to be a useful tool for evaluating ANS activity, and we measured and compared HRV in the resting state. Results: The standard deviation of the N‐N interval (SDNN) and total power (TP) for patients with LUTS revealed no significant differences from those in the control group. On frequency domain analysis, there was evidence of decreased high frequency (HF) in patients with LUTS (P < 0.05), but there were no significant differences in other parameters, such as heart rate, square root of the mean squared differences of successive N‐N intervals (RMSSD), very low frequency (VLF), low frequency (LF), or LF/HF ratio. Conclusion: Patients with LUTS exhibited different HRV parameters compared with asymptomatic controls. Their decreased HF indicated that they may have had an imbalance in the autonomic nervous system.     

Impaired baroreflex sensitivity and cardiac autonomic functions are associated with cardiovascular disease risk factors among patients with metabolic syndrome in a tertiary care teaching hospital of South-India

Background & aimBaroreflex sensitivity (BRS) and heart rate variability (HRV) have been proposed to assess early autonomic dysfunction in metabolic syndrome (MetS) patients. Autonomic dysfunction in MetS patients may increase the risk of developing cardiovascular disease (CVD). However, the association of BRS and HRV with CVD risk factors remains elusive in MetS. The primary aim of this study was to assess the BRS and HRV in MetS patients among South-Indian adults and check whether BRS and HRV are associated with CVD risk factors.MethodsWe performed anthropometric indices, body composition, physiological parameters such as BRS, HRV, and other autonomic function tests in 176 subjects divided into MetS patients (n = 88) and healthy controls (n = 88). Fasting blood samples were collected for biochemical profiles and calculated insulin resistance indices, atherogenic index (AI), and rate pressure product (RPP).ResultsWhen compared to controls, we found significantly reduced BRS and an increased ratio of low-frequency (LF) to high-frequency (HF) power of HRV (LF/HF) in the MetS group. We observed significant differences in body composition and biochemical profiles among the MetS group. BRS and LF/HF ratio of HRV have shown a significant association with CVD risk factors in the MetS group.ConclusionsWe observed autonomic dysfunction as low BRS and high LF/HF ratio of HRV in MetS patients. Additionally, the present results emphasize that the association of BRS and LF/HF ratio with anthropometric, glucose, lipid parameters, and other CVD risk factors may increase the susceptibility of MetS patients to higher CVD risk.     

Cardiac autonomic functions derived from short-term heart rate variability recordings associated with heart rate recovery after treadmill exercise test in young individuals

Analysis of short-term heart rate variability (HRV) may provide useful information about autonomic nervous control of heart rate recovery. We studied 495 individuals (273 men), age range 19–85 years, submitted to treadmill exercise tests and short-term HRV evaluations over time (standard deviation of the normal-to-normal interval [SDNN], the square root of the mean squared differences of successive normal-to-normal intervals [RMSSD], the number of interval differences of successive normal-to-normal intervals greater than 50 ms [NN50 count], the proportion derived by dividing NN50 count by the total number of normal-to-normal intervals [pNN50]) and frequency (low-frequency power [LF], high-frequency power [HF], total power) domains. Among 495 patients, 106 patients (68 men) were elderly (age  ≥ 65 years). Male gender and hypertension were significantly higher in elderly patients. The young patients had higher HRR after exercise. HRR at 4 min (54 ± 13 vs 60 ± 12 beats/min; P = 0.003) was the most significant predictor for positive exercise test result. In the young group, both time domain measures (SDNN: correlation coefficient 0.34, P < 0.001; RMSSD: correlation coefficient 0.37, P < 0.001) and frequency domain measures (LF: correlation coefficient 0.21, P < 0.001; HF: correlation coefficient 0.13, P = 0.01; total power: correlation coefficient 0.22, P < 0.001) were significantly associated with HRR at 4 min. HRR at 4 min was significantly associated with short-term HRV of time and frequency domains in young individuals, but not elderly ones, receiving treadmill exercise 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.     

Recovery of cardiac autonomic responsiveness with low-intensity physical training in patients with chronic heart failure

BACKGROUND: A gradual worsening of autonomic control of cardiovascular function accompanies the progression of heart failure. Exercise training modulates autonomic balance, and may affect the prognosis of the disease. AIMS: The sympathovagal balance was studied after 3 months of low-intensity rehabilitation compared with conventional therapy in 45 patients with heart failure (52% ischemic, 48% idiopathic), of whom 30 underwent rehabilitation and 15 did not. In 11 rehabilitated patients we also studied the effects on autonomic profile of 6 additional months of home-based training. Rehabilitated and non-rehabilitated patients had similar NYHA class, ejection fraction, exercise pVO2; 50% assumed carvedilol (39+/-5 mg/day). METHODS AND RESULTS: Autoregressive power spectral density of RR intervals variability were assessed during 10 min of: (1) supine rest and free breathing; (2) supine rest and breathing at 20 acts/min (=vagal stimulus); (3) standing (=sympathetic stimulus). During each period, the ratio LF/HF of the individual autospectrum indicated the sympathovagal balance. After 3 months of rehabilitation, pVO2 increased (20%); LF/HF at rest was unchanged (8.7+/-1.2 vs. 9.2+/-1.2); it decreased with controlled breathing (-18%) and increased during standing (+79%) (P<0.05). These changes were more evident after 6 months of home-based training, when pVO2 was still high: LF/HF at rest was reduced (5.4+/-0.9 vs. 8.5+/-2.1), decreased during controlled breathing (-17%) and increased during standing (87%) (P<0.05). No changes in any variable were seen in non-rehabilitated patients. CONCLUSIONS: A low intensity rehabilitation program restores autonomic tone and reactivity to vagal and sympathetic stimuli. Some of these effects are already evident after the initial hospital-based phase.     

Preserved Parasympathetic Cardiac Innervation after Atrioventricular Node Modification: Evidence from Circle Maps of Respiratory Sinus Arrhythmia

Introduction: Respiratory sinus arrhythmia (RSA) and heart rate variability (HRV) are parameters of autonomic cardiac innervation. They decrease with age and after atrioventricular nodal modification (AVNM) suggesting vagal denervation in both situations. We hypothesized, however, that AVNM causes only a transient, functional decline in vagal activity, whereas aging causes permanent vagal denervation. A new method of analyzing RSA phase dynamics based on circle maps (CM) can potentially differentiate between both forms of reduced vagal activity. Methods: In 18 younger and 14 older healthy control subjects 24-hour Holter ECGs were recorded for HRV analysis. Repeated measurements of RSA were acquired during paced breathing (PB). In 16 consecutive patients undergoing AVNM the same measurements were applied before, 1 day and 3 months after the procedure. CM were calculated from consecutive RR intervals and the similarity between different CM quantified by the Kullback information gain (KIG). Results: HRV analysis revealed lower HF bands, LF bands and RSA amplitudes in older vs. younger control subjects. KIG revealed less similarity between younger and older control subjects than within the respective age groups. After AVNM a decrease in HF bands was noted in HRV analysis. Three months after AVNM, HF bands returned to pre-ablation values. CM obtained before and 1 day after AVNM displayed comparable similarity to CM acquired 1 day before and 3 months after ablation. Conclusions: In contrast to conventional HRV parameters, CM of RSA are not altered by ablation in the posteroseptal space but by aging. Thus, this new method appears to differentiate between transient autonomic modification and chronic denervation.     

Improving Heart Rate Variability in Sleep Apnea Patients: Differences in Treatment with Auto-titrating Positive Airway Pressure (APAP) Versus Conventional CPAP

The effect of positive airway pressure treatments in different modalities on the cardiovascular consequences of the disease in sleep apnea patients is still unclear. We aimed to compare auto-titrating positive airway pressure (APAP) and conventional continuous positive airway pressure (CPAP) in terms of improving heart rate variability (HRV) in obstructive sleep apnea patients. This was a prospective study done in a tertiary research hospital. All patients underwent a manual CPAP titration procedure to determine the optimal pressure that abolishes abnormal respiratory events. Then patients underwent two treatment nights, one under APAP mode and one under conventional CPAP mode with a 1-week interval. Forty newly diagnosed obstructive sleep apnea patients were enrolled in the study. We compared heart rate variability analysis parameters between the APAP night and the CPAP night. This final analysis included the data of 28 patients (M/F: 22/6; mean age = 46 ± 10 years). Sleep characteristics were comparable between the two treatment nights, whereas all-night time domains of HRV analysis such as HF, nuLF, and LF/HF were different between APAP and CPAP nights (2.93 ± 0.31 vs. 3.01 ± 0.31; P = 0.041; 0.75 ± 0.13 vs. 0.71 ± 0.14; P = 0.027; and 4.37 ± 3.24 vs. 3.56 ± 2.07; P = 0.023, respectively). HRV analysis for individual sleep stages showed that Stage 2 LF, nuLF, nuHF, LF/HF parameters entirely improved under CPAP treatment whereas APAP treatment resulted in nonsignificant changes. These results suggest that despite comparable improvement in abnormal respiratory events with APAP or CPAP treatments, CPAP may be superior to APAP in terms of correcting cardiovascular alterations in sleep apnea patients.     

Cardiac autonomic dysfunction and health-related quality of life in patients with chronic obstructive pulmonary disease

Background and objective: COPD is associated with impaired health‐related quality of life (HRQL) and cardiac autonomic dysfunction. Data describing the association between these factors in patients with COPD are mostly lacking. The objective of this study was to evaluate whether there is an association between cardiac autonomic dysfunction and HRQL in COPD. Methods: We studied 60 patients with COPD (37 women, mean (SD) age 65.20 (7.73) years, FEV₁ % pred. 46.58 (18.53) %) and measured HRQL, as assessed by the Chronic Respiratory Disease Questionnaire, and cardiac autonomic dysfunction, as assessed by heart rate variability (HRV). Analysis of HRV was performed using a Holter‐ECG device during a recording period of 5 min. To evaluate a possible association between these factors, univariate and multivariate analyses were used. Results: There was a significant correlation between Chronic Respiratory Disease Questionnaire total score and both variables of HRV reflecting parasympathetic tone; root mean square successive difference of RR intervals (rMSSD) (r = 0.34, P = 0.012) and the density of the beat‐to‐beat oscillation in the N‐N interval of HRV in the high‐frequency band (HF power) (r = 0.35, P = 0.01). In a multivariate analysis rMSSD was found to be independently associated with HRQL after correcting for FEV₁, carbon monoxide transfer coefficient (DL_CO), 6MWD and CRP. Conclusions: Resting parasympathetic tone, as measured by HRV, is independently associated with HRQL, which emphasizes the role of cardiac autonomic dysfunction on HRQL in patients with COPD.     

Effect of physical activity on heart rate variability and carotid intima-media thickness in older people

We investigated the effect of physical activity on heart rate variability (HRV) and carotid intima-media thickness (IMT) in elderly subjects and the relationship between HRV and IMT. Thirty-two elderly sedentary subjects and 32 age-matched endurance athletes underwent ultrasonography of the carotid wall for measuring IMT, and 24-h ECG monitoring for measuring HRV. Elderly athletes had evidence of increased vagal activity in the time (SDANN, rMSSD, and pNN50; p < 0.01) and frequency domain (HF and LF/HF ratio, p < 0.01) with respect to sedentary subjects. Moreover, athletes showed lower IMT than control subjects (p < 0.01). In the whole population SDNN was inversely related to IMT, respectively (r = ?0.60 and r = ?0.58, p < 0.0001), while LF/HF ratio related positively to IMT. In conclusion, this study demonstrated that in aging HRV is negatively associated with IMT, a putative index of atherosclerosis, confirming cardiac autonomic neuropathy as part of the pathophysiological pathway for atherosclerosis. It confirms that the regular physical activity represents a valuable strategy to counter age-related impairments of cardiac autonomic activity and artery structural changes.     

Noninvasive ventilation can modulate heart rate variability during high-intensity exercise in COPD-CHF patients

Objectiveto assess the acute effects of non-invasive ventilation (NIV) during high-intensity exercise on heart rate variability (HRV) responses in chronic obstructive pulmonary disease (COPD) and Chronic heart failure (CHF) patients.MethodsThis was randomized, double blinded and controlled study. Fourteen patients with COPD-HF diagnosis were evaluated. The subjects underwent to the following tests: (I) cardiopulmonary exercise testing (CPET) on a cycle ergometer ramp protocol; (II) 7 days after CPET, patients randomly underwent two constant-load exercise (CLE) with NIV or Sham ventilation until tolerance limit, with 80% of the CPET peak load. R-R intervals (RRi) were continuously collected during rest, exercise and in recovery. Time and frequency domain and nonlinear heart rate variability (HRV) indices were obtained.ResultsNIV resulted in a decrease of Mean iRR, square root of the mean squared differences of successive RRi (rMSSD), RR tri index and high-frequency (HF), nu (p < 0.05) and increase of Mean HR, low-frequency (LF), nu and LF/HF (p < 0.05) during exercise when compared to rest. In addition, NIV during exercise induced lower rMSSD and Sample Entropy when compared with Sham (p < 0.05). Negative correlation was found between forced expiratory volume in 1 second (FEV_1, L) vs HF (nu) during exercise with NIV (p = 0.04; r= -0.58). Furthermore, simple linear regression showed that the FEV₁ (L) affected 30% of the HF (nu) response during the exercise with NIV.ConclusionNIV during exercise produced enhanced heart rate and autonomic responses in COPD-CHF patients. Additionally, COPD severity is negatively associated with a higher vagal response during exercise with NIV.     

No Evidence of Cardiac Autonomic Involvement in Ankylosing Spondylitis, as Assessed by Heart Rate Variability

The aim of this study was to investigate the involvement of autonomic nervous system (ANS) function by using power spectral analysis of heart rate variability (HRV) method in patients with ankylosing spondylitis (AS). The study included 94 AS patients all fulfilling the New York criteria for AS, and 49 healthy volunteers. Recordings for HRV were obtained with a PC-based high-resolution electrocardiographic system and analysed using power spectral analysis. The peak around 0.04–0.15 Hz was defined as low-frequency peak (LF) and the other, around 0.15–0.40 Hz, was defined as high-frequency peak (HF), representing mostly the sympathetic and the parasympathetic components of the ANS, respectively. The following variables were calculated and compared between groups: the LF in absolute and normalised units (LF nU); the HF in absolute and normalised units (HF nU); and LF/HF ratio. The AS group included 47 male and 47 female subjects with a mean age of 33 ± 11 years (range 16–64). In the control group there were 23 male and 26 female healthy subjects (mean age 33 ± 8; range 19–60). None of the patients or control subjects had any cardiac or neurological symptoms. Both groups were similar with respect to age and sex characteristics (p >0.05). The HRV analysis indicated that the peaks of LF, LF nU, HF, HF nU and LF/HF ratio were similar in both groups. Groups also did not differ with respect to heart rate at the time of examination. Our data demonstrated no evidence of ANS involvement as assessed by HRV analysis in AS patients. Received: 19 July 2000 / Accepted: 25 October 2000     

Circadian Variation of Heart Rate Variability in Postinfarction Patients With and Without Life-Threatening Ventricular Tachyarrhythmias

Circadian Variation of HRV. Introduction: Determination of heart rate variability (HRV) is widely used for noninvasive assessment of cardiac autonomic tone. A decreased HRV is associated with an increased mortality in patients surviving an acute myocardial infarction. There are, however, only sparse data about the circadian variation of different components of HRV that may be linked to the well-known circadian fluctuations in the occurrence of sudden death. In addition, the potential prognostic impact of circadian variations of HRV has not been examined. Methods and Results: The present study compared the circadian variation of HRV from 14 postinfarction patients who had survived at least one episode of out-of-hospital cardiac arrest (cardiac arrest group) with that of 14 age- and sex-matched patients without a history of malignant arrhythmias after their index infarct (control group). Several time- and frequency-domain measures of HRV were assessed from 24-hour Holter recordings. Circadian variations of high- (HF), low- (LF), and total-frequency (TF) components were determined by calculating for each parameter the hourly difference from the day's mean. The average of these differences was calculated for every hour as well as for predefined day and night periods. There was no significant difference between the two groups with regard to HRV indices that predominantly reflect vagal tone, such as SDNN (78 ± 25 vs 96 ± 24 msec), pNN50 (2.7%± 4.6% vs 4.9%± 4.2%), or HF (6.3 ± 3.0 vs 7.8 ± 3.2 msec; cardiac arrest vs control group). There was also no significant difference in the circadian variation of LF or TF between the two groups during daytime and nighttime. However, a significant difference in circadian variation of HF was found during daytime (0.02 ± 0.5 vs -0.6 ± 0.5 msec; P = 0.006) and nighttime (0.19 ± 0.64 vs 1.5 ± 0.75 msec; P = 0.0002). In cardiac arrest survivors, there was no difference in the mean deviation of HF between the day-and the nighttime periods. Conclusions: These results show an almost complete abolition in circadian variation of parasympathetic tone in postinfarction patients surviving an episode of out-of-hospital cardiac arrest, whereas circadian variation of sympathetic tone is comparable to that of postinfarction patients without arrhythmic episodes. These findings indicate that determination of diurnal variation of HRV may add to the prognostic value of HRV with respect to identifying patients at high risk of sudden death.     

心肌缺血大鼠的心率功率谱变化及其与心脏性猝死关系的研究

采用心率变异（ＨＲＶ）频域指标定量评价心肌缺血大鼠的心脏自主神经功能变化及其与心脏性猝死（ＳＣＤ）的关系。Ｈｏｌｔｅｒ监测仪记录假手术组（２０只）及心肌缺血后存活组（５４只）与ＳＣＤ组（３６只）大鼠的心电信号。结果显示存活组或ＳＣＤ组大鼠于心肌缺血初始１５ｍｉｎ内的低频（ＬＦ）及低频／高频比值（ＬＦ／ＨＦ）较假手术组明显升高〔ＬＦ（ｍｓ２／Ｈｚ）：１９８．８±４１．３或２２６．７±５６．４ｖｓ６５．４±１９．６，Ｐ均＜０．０１；ＬＦ／ＨＦ：４．０８±１．１或５．１２±１．４ｖｓ１．８７±０．７，Ｐ均＜０．０１〕，而且ＳＣＤ组大鼠的ＬＦ与ＬＦ／ＨＦ较存活组增高〔ＬＦ（ｍｓ２／Ｈｚ）：２２６．７±５６．４ｖｓ１９８．８±４１．３，Ｐ均＜０．０５；ＬＦ／ＨＦ：５．１２±１．４ｖｓ４．０８±１．１，Ｐ＜０．０５〕，各组间ＨＦ无明显变化；ＳＣＤ组大鼠于ＳＣＤ发生前１５ｍｉｎ内，心率功率谱动态变化表现为ＬＦ及ＬＦ／ＨＦ随死亡时间的濒临而呈进行性升高（Ｐ＜０．０１及０．０５）。表明大鼠心肌缺血后其交感神经活性明显亢进，ＨＲＶ降低与ＳＣＤ的发生密切相关。