Modulations of human autonomic function induced by positive pressure-assisted breathing.

In order to examine the acute autonomic response in humans during and immediately after positive pressure-assisted (PPA) breathing, spontaneous cardiac baroreflex (BR) sensitivity was studied through the adaptation of consecutive RR intervals in response to spontaneous systolic blood pressure fluctuations in 11 healthy subjects. The gain (alpha-index) in baroreceptor reflex was estimated using cross-spectral analysis (RR interval variability and systolic blood pressure variability) for the low frequency (LF) and high frequency (HF) bands. All measurements were made under fixed breathing rate (12 breaths per minute), and realized consecutively at baseline level (20 min), after-short inspiratory pressure support plus positive end-expiratory airway pressure (IPS + PEEP) ventilation (15 min), again under normal conditions (20 min; recovery period) and, finally, during a standard upward orthostatic challenge test (15 min; orthostatic challenge). The spontaneous BR gain in the HF band increases slightly during ventilation (+26.1 +/- 11.7%, P<0.05) and decreases significantly during recovery without any significant alteration in mean heart rate, systolic or diastolic blood pressure. The spontaneous BR gain in the LF band decreases during IPS + PEEP ventilation (8.4 +/- 4.4 versus 12.7 +/- 6.2 ms mm(-1) Hg; P<0.05) and returns to basal level during recovery. Orthostatic challenge altered significantly the BR gain in both HF and LF bands with significant heart rate acceleration. In humans, while the parasympathetic control of heart rate and blood pressure is found moderately enhanced, the sympathetic BR drive appears significantly and transitory altered under short term IPS + PEEP ventilation with a degree of alteration comparable to those observed during orthostatic challenge.

Relationship between daily physical activity and ANS activity in patients with CHF.

PURPOSE: Heart rate variability (HRV) indices are powerful independent prognostic factors of cardiovascular events and all cause mortality in patients with chronic heart failure (CHF). This study evaluates the influence of lifestyle on HRV in CHF patients. METHODS: Thirty-nine CHF patients (33 men, ischemic/dilated cardiomyopathy (18/21), 52.4 +/- 11.2 yr, NYHA I to III, LVEF 33.4 +/- 5.1%) filled out a physical activity questionnaire providing an individual complete qualitative and quantitative picture of their physical activity and daily energy expenditure (PAEE/DEE) corrected for age, weight, severity of the condition and autonomy. Frequency and time domain indices of HRV were calculated from ECG Holter recordings on a typical weekday. Nighttime indices were calculated in order to avoid the confounding factor of physical activity that might alter 24-h frequency analysis of HRV. RESULTS: DEE was significantly different between classes I and II and classes I and III (P = 0.01 both) patients. Time spent in activities above 3 METs decreased significantly with the severity of the condition. Global and parasympathetic indices of 24-h HRV analysis were correlated to DEE and PAEE (Ptot24h = 78.80*PAEE (J x min x kg) -1061.80, R = 0.72, P < 0.0001). Multiple regression analysis revealed that PAEE was the sole independent factor on established HRV prognostic indices (P < 0.05) and especially within PAEE dimensions, only activities above 3 METs were correlated with established prognostic HRV indices (P < 0.05). CONCLUSION: These results indicate that rather than total DEE, moderate to intensive physical activity may counteract the decline in HRV with chronic heart disease. This may be linked to longer time spent in higher intensity activities, and not to total activity time.

Continuous positive airway pressure treatment improves the QT rate dependence adaptation of obstructive sleep apnea patients.

BACKGROUND: QT rate dependence is one of the major properties of ventricular repolarization, with its circadian and autonomic modulations. The alteration of cardiac autonomic tone occurring in obstructive sleep apnea syndrome (OSAS) patients could explain the altered rate-dependent adaptation of the myocardial repolarization. Thus, we postulated that dynamic alterations in QT interval adaptation could be ameliorated in OSAS patients under continuous positive airway pressure (CPAP) treatment. To assess ventricular repolarization features in patients with OSAS, we compared QT parameters and their dynamicities along RR intervals from 24-hour ECG. METHODS: The study groups consisted of 38 consecutive OSAS patients and 38 healthy age-matched subjects. The syndrome was confirmed for OSAS patients according to standard polysomnographic criteria (apnea plus hypopnea index: 56.9 +/- 28.4/h). A second polysomnography synchronized with 24-hour ECG Holter and realized under efficient CPAP therapy confirmed the control of sleep-related breathing disorder. RESULTS: QT length related to heart rate was found significantly altered in patients with OSAS compared with controls (QTend/RR slope: -0.126 +/- 0.031 vs -0.173 +/- 0.038; P < 0.01). This flattened relationship was significantly improved with the treatment of the OSAS (-0.151 +/- 0.051; P < 0.01 vs pretreatment status). There was no significant impact of CPAP therapy on ventricular ectopic activity as well as on static repolarization parameters (QT, RT, QTc, RTc) measured separately over daytime and nighttime. CONCLUSIONS: The prognostic implications of such findings and the protective role of CPAP treatment to prevent sudden cardiac death in OSAS need to be evaluated.

Interval training in elderly men increases both heart rate variability and baroreflex activity.

AIMS: Autonomic nervous system activity decreases continuously with age and appears to be a powerful predictor of disease and death. Attempts are thus made to reactivate autonomic drive with the intent of improving health. METHODS: We assessed maximal oxygen consumption (VO2max), autonomic nervous system activity by heart rate variability (HRV) analysis and spontaneous cardiac baroreflex activity (SBR) in eleven elderly men (73.5+/-4.2 years) before and after a 14-week program of intensive cycloergometer interval training. The standard HRV indices were calculated using time domain (mean RR, PNN50, RMSSD, SDNN, SDANN and SDNNIDX), and Fourier transform (total power, ULF,VLF, LF, LFnu, HF, HFnu and LF/HF) analyses of 24-hour, daytime and nighttime Holter recordings. The SBR was calculated from 15-minute recordings of spontaneous blood pressure and RR interval variations using the sequence (slope, slSBR) and cross-spectral (alphaSBRHF and alphaSBRLF) methods. RESULTS: After the training period,VO2max increased by 18.6 % (26.8+/-4.4 to 31.8+/-5.2 ml.kg(-1).min(-1), p<0.01). The nocturnal parasympathetic indices of HRV increased (PNN50: 3.05+/-2.21 to 5.00+/-2.87%, RMSSD: 29.1+/-7.6 to 38.8+/-10.9 ms, HF: 117+/-54 to 194+/-116 ms2/Hz, all p<0.05) as did the SBR indices (slSBR: 7.0+/-1.8 to 9.8+/-2.1 ms.mmHg(-1), p<0.01; alphaSBRHF: 6.9+/-2.2 to 10.5+/-3.7 ms.mmHg(-1), p<0.05; alphaSBRLF: 5.3+/-2.3 to 6.9+/-3.1 ms.mmHg(-1), p=0.22). CONCLUSION: Intensive endurance training in elderly men enhanced parasympathetic parameters of HRV and, interestingly, of SBR. Physiological mechanisms and long-term clinical effects on health status should be further investigated.

Refeeding normalizes the QT rate dependence of female anorexic patients.

We postulated that dynamic alterations in QT interval adaptation could characterize patients with anorexia nervosa (AN) and could be restored after weight gain. To assess ventricular repolarization features, we evaluated the QT dynamicity along RR intervals from 24-hour electrocardiographic data of patients with AN before and after refeeding. Ten young women with AN (19 +/- 3 years) were included in the study. The QT/RR slope was found significantly enhanced compared with normals (-1.82 +/- 0.62 vs -1.40 +/- 0.30; p < 0.05). This slope returned to normal range values after refeeding. The QT/RR slope was significantly correlated with the body mass index (r = 0.59; p < 0.007) in the patient group.

Chronotropic incompetence to exercise separates low body weight from established anorexia nervosa.

Chronotropic incompetence (CI), characterized by an attenuated heart rate (HR) response to exercise could participate to the limitation of exercise capacity in anorexia nervosa (AN). Therefore, we evaluated the role of cardiac sympathetic responsiveness in AN patients. In addition, the ambulatory value of autonomic control using spectral analysis of heart rate variability (HRV) was determined and correlated to maximal exercise performance. Twenty-two patients hospitalized for weight loss and suspicion of AN were included in the study. All performed a symptom-limited exercise test with measurement of gas exchange for chronotropic response to exercise evaluation. Holter ECG recordings allowed daytime and night-time spectral domain HRV analysis in order to evaluate the alteration of sympathetic control of HR in free-living conditions. CI defined as a failure to achieve 80% of heart rate reserve (%HRR) was observed in 13 (59%) patients (CI+). This group presented a higher body mass deficit than the group without CI (CI-; -35.1 +/- 8.7% versus -26.1 +/- 10.7%; P<0.05). Obviously, patients with a lower body mass index (BMI < 16 kg m(-2), n = 14) revealed a more severe limitation to maximal exercise with a lower peak HR, a lower peak Vo(2), and a lower maximal O(2) pulse (P<0.05). BMI was significantly correlated to peak Vo(2), maximal HR, and %HRR achieved at peak exercise. Daytime HRV parameters reflecting the sympathetic autonomic equilibrium (LF nu, LF/HF ratio) were significantly lower in CI+ patients. Blunted sympathetic response to maximal exercise is frequent and correlated to weight deficit. The present data suggest a major autonomic derangement in AN characterized by a cardiac sympathetic withdrawal.

Alteration of the QT rate dependence in anorexia nervosa.

Myocardial repolarization has been evaluated in patients with anorexia nervosa (AN) with conflicting results. The authors postulated that dynamic alterations in QT interval adaptation could characterize these patients. This study compared QT dynamicity along RR intervals from 24-hour ECG data of patients with and without AN. Twenty-five patients (23 women) fulfilling the Diagnostic and Statistical Manual (DSM IV) criteria for AN were included in the study. All underwent 24-hour ECG Holter recordings, allowing QT and RR measurements, and heart rate variability (HRV) analysis in free-living conditions. A group of 25 sex- and age-matched healthy subjects served as controls. Compared with controls, AN patients presented with relative bradycardia, more particularly during night periods but neither mean QT nor corrected mean QT length (calculated using Bazett formula) over the 24 hours of monitoring differed. However, QT/RR slope was found significantly enhanced compared with normals (-2.00 +/- 0.53 vs - 1.42 +/- 0.40) (P = 0.006): QT length related to heart rate was found longer for a heart rate <55 beats/min in AN. Mean 24-hours QT length appears unaltered in AN in the absence of electrolytic disorders. However, the QT/RR relationship was enhanced reflecting the specific autonomic imbalance encountered in this population. The clinical implications of such findings need to be discussed since an equivalent enhancement of QT/RR slope has been described after myocardial infarction in patients presenting life-threatening ventricular arrhythmias.

Heart rate increment: an electrocardiological approach for the early detection of obstructive sleep apnoea/hypopnoea syndrome.

The prevalence of OSAHS (obstructive sleep apnoea/hypopnoea syndrome) is high in developed countries and it is estimated that the vast majority of patients remain undiagnosed. On the basis of physiological evidence, we evaluated the frequency component of HRI (heart rate increment) as a simple and inexpensive screening tool for OSAHS detection in a first group of patients (group 1) and validated their discriminant capacity in a second group (group 2). The predictive accuracy of hourly %VLFI (frequency-domain HRI variable obtained from nocturnal ECG Holter monitoring) was analysed by comparison with an hour-by-hour respiratory disturbances index assessed by complete polysomnography in 28 consecutive clinically suspected OSAHS patients for group 1 and in 35 patients for group 2. OSAHS was present in 20 patients according to a mean hourly apnoea plus hypopnoea index >10 in group 1, and prevalence reached 77.1% in group 2. Sensitivity, specificity and positive and negative predictive accuracy were calculated and an ROC (receiver operating characteristic) curve was constructed for several polysomnographic threshold values. In group 1, hourly %VLFI appeared as an evident predictor of the apnoea/hypopnoea index (W=0.848, P<0.0001; where W is the area under the curve obtained using ROC curve analysis). Using an appropriate threshold (value > or =3.2%), %VLFI demonstrated a sensitivity of 78.1% and a specificity of 70.4%. These thresholds applied to group 2 yielded a sensitivity of 73.9% and a specificity of 76.6%. Frequency-domain analysis of the HRI appears to be a powerful tool for OSAHS prediction. The simplicity of its analysis and use makes of it a particularly well-suited variable for routine mass screening in high-risk populations undergoing ECG Holter monitoring.

Alteration of QT rate dependence reflects cardiac autonomic imbalance in patients with obstructive sleep apnea syndrome.

QT rate dependence is one of the major properties of ventricular repolarization with its circadian and autonomic modulations. The authors postulated that dynamic alterations in QT interval adaptation could help characterize patients with cardiac autonomic alterations, like those with obstructive sleep apnea syndrome (OSAS). To assess ventricular repolarization features in patients with OSAS, QT parameters and their dynamicity along RR intervals were compared from 24-hour ECG data of patients with and without this syndrome, assessing cardiac autonomic nervous system equilibrium by means of time-domain and frequency-domain analyses of heart rate variability (HRV). The study group consisted of 74 consecutive patients referred to the Sleep Laboratory for clinically suspected OSAS. The syndrome was confirmed in 30 (40.5%) patients according to standard polysomnographic criteria. QT length related to heart rate (HR) was found significantly shorter for HR < 70 beats/min in patients with OSAS(-1.32 +/- 0.35)compared with patients without OSAS(-1.99 +/- 0.40; P < 0.01). This flattened relationship was correlated with the severity of the sleep related disorder. Using multiple linear regression analysis, the apnea/hypopnea index and nocturnal normalized high frequencies (HFnu) were the most significant predictors of the QT/RR slope(R = 0.61; P < 0.0001). OSAS is significantly associated with a flattened relationship between QT duration and RR interval at low HRs. The alteration of cardiac parasympathetic tone occurring in severe OSAS patients may explain this altered rate dependent adaptation of myocardial repolarization.

Relationship among the severity of sleep apnea syndrome, cardiac arrhythmias, and autonomic imbalance.

The relationship between obstructive sleep apnea syndrome (OSAS), cardiac arrhythmias, and conduction disturbances in adults remains controversial. Early studies showed a higher prevalence than more recent and designed epidemiological studies. To clarify the actual prevalence of cardiac arrhythmias and conduction disturbances in patients referred for assessment of OSAS, a prospective cohort study was conducted: 147 consecutive patients (103 men; mean age of 54.5 +/- 10.7 years) underwent time-synchronized polysomnography and ECG Holter monitoring. OSAS was diagnosed in 66 (44.9%) of them based on an apnea hypopnea index (AHI) > or = 10. Prevalence of heart failure, of prior myocardial infarction, of hypertension, and of ventricular arrhythmias were similar in patients with or without OSAS. Nocturnal paroxysmal asystole was significantly more prevalent in OSAS patients (10.6 vs 1.2%; P < 0.02) and the number of episodes of bradycardia and pauses increased with the severity of the syndrome. Almost all bradycardic events occurred in patients with severe OSAS (AHI > 30), prolonged periods of arterial oxyhemoglobin desaturation, and low diurnal awake PaO2. Moreover, using heart rate variability analysis, nocturnal sinusal dysfunction contrasted with a blunted diurnal parasympathetic modulation of the sinus node. Frequent nocturnal nonsustained supraventricular tachycardias were predominantly found in patients with severe sleep related breathing disorders; however, an increased risk of ventricular arrhythmias was not found. Under continuous positive airway pressure treatment, the 1-year follow-up of OSAS patients with nocturnal pauses did not reveal any arrhythmic event justifying a specific intervention.

Frequent and prolonged asymptomatic episodes of paroxysmal atrial fibrillation revealed by automatic long-term event recorders in patients with a negative 24-hour Holter.

The presence, frequency, and duration of episodes of paroxysmal atrial fibrillation (PAF) is difficult to establish. This is caused by the limited duration of standard Holter recordings and to the unsatisfactory yield of patient-triggered event recorders, because of asymptomatic events and of an inconsistent use of the patient dependent triggering function. A prospective cohort of 65 consecutive patients with recurrent palpitations and a negative 24-hour ECG Holter was investigated by means of a cardiac event recorder bearing continuous automatic arrhythmia analysis and storage. Over a mean duration of 77 +/- 36 hours, episodes of PAF were diagnosed in 20 (31%) patients, who had a total of 37 episodes; mean duration of PAF episodes was 7 hours 50 minutes +/- 8/hours 45 minutes (minimum 45 minutes, maximum 28 hours). Eleven (55%) of these 20 patients were asymptomatic and would have remained undiagnosed without the automatic mode of the event recorder. Asymptomatic PAF episodes were longer than symptomatic ones (10 hours 30 minutes +/- 6 hours 30 minutes vs 4 hours 50 minutes +/- 4 hours, P < 0.05). In addition, episodes of sustained paroxysmal supraventricular tachycardia (PSVT) were diagnosed in 39 (57%) patients, of whom 34 (87%) were symptomatic. In this prospective cohort, a second standard 24-hour monitoring would have missed 44% of the patients with PAF or PSVT and a classical patient-triggered event recorder 13%. In patients still complaining of palpitations after one negative 24-hour Holter, numerous, prolonged, and often asymptomatic episodes of PAF can be revealed by long-term automatic event recorders. These devices should help clarify the clinical consequences of such episodes.

Quantification of cumulated physical fatigue at the workplace.

Quantification of physical fatigue remains a challenge. We hypothesized that its effects on central autonomic nervous system activity could be explored for such a quantification. To test this relationship, we prospectively measured central autonomic nervous activity through nocturnal heart rate variability (HRV) in six French garbage collectors, aged 32.1+/-4.3 years, twice a week during 3 consecutive weeks of work, and during the following week of rest. Eight healthy sedentary males formed a control group. HRV indices were calculated by applying standard temporal domain and wavelet transform analyses to standard ECG recordings. During the 3 consecutive weeks of work, there was a significantly progressive decrease in HRV indices, particularly pNN50 (-34.2%, P<0.05), as well as the high (-33.3%, P<0.05) and low (-22.2%, P<0.01) frequency components of wavelet transform, while there was an increase, although non-significant, of the ratio of low to high frequencies (9.1%). During the resting period, there was a significant recovery of HRV indices, notably of its high (50.0%, P<0.05) and low (28.6%, P<0.05) frequency components. No such changes occurred in the control group. A central signature of cumulated physical fatigue can thus be detected and quantified through nocturnal autonomic nervous system activity. Its characteristics are those of a progressive parasympathetic withdrawal.

Autonomic adaptations to intensive and overload training periods: a laboratory study.

PURPOSE: Looking for practical and reliable markers of fatigue is of particular interest in elite sports. One possible marker might be the autonomic nervous system activity, known to be well affected by physical exercise and that can be easily assessed by heart rate variability. METHODS: We designed a laboratory study to follow six sedentary subjects (32.7 +/- 5.0 yr) going successively through 2 months of intensive physical training and 1 month of overload training on cycloergometer followed by 2 wk of recovery. Maximal power output over 5 min (Plim5'), VO(2) and standard indices of heart rate variability were monitored all along the protocol. RESULTS: During the intensive training period, physical performance increased significantly VO(2peak) : +20.2%, < 0.01; Plim5': +26.4%, < 0.0001) as well as most of the indices of heart rate variability (mean RR, Ptot, HF, rMSSD, pNN50, SDNNIDX, SDNN, all < 0.05) with a significant shift in the autonomic nervous system toward a predominance of its parasympathetic arm (LF/HF, LFnu, HFnu, < 0.01). During the overload training period, there was a stagnation of the parasympathetic indices associated to a progressive increase in sympathetic activity (LF/HF, < 0.05). During the week of recovery, there was a sudden significant rebound of the parasympathetic activity (mean RR, HF, pNN50, rMSSD, all < 0.05). After 7 wk of recovery, all heart rate variability indices tended to return to the prestudy values. CONCLUSION: Autonomic nervous system status depends on cumulated physical fatigue due to increased training loads. Therefore, heart rate variability analysis appears to be an appropriate tool to monitor the effects of physical training loads on performance and fitness, and could eventually be used to prevent overtraining states.

Cardiac interbeat interval increment for the identification of obstructive sleep apnea.

The prevalence of obstructive sleep apnea syndrome (OSAS) is high in developed countries but its diagnosis is costly. Based on physiological evidence, the frequency component of heart rate variability (HRV) was evaluated as a simple and inexpensive diagnostic tool in OSAS. The predictive accuracy of frequency-domain HRV variables obtained from 24-hour ECG Holter monitoring (the power spectral density of the interbeat interval increment of very low frequencies, "VLFIpsd," and its percentage over the total power spectral density, "% VLFI"), and of established time-domain HRV variables were analyzed by comparison with respiratory disturbances indexes assessed by complete polysomnography in 124 consecutive patients (98 men aged 53.8 +/- 11.2 years) with clinically suspected OSAS. OSAS was present in 54 (43.5%) patients according to standard criteria. Using receiver operating characteristic curve analysis, two of the three most powerful predictors were frequency-domain variables: % VLFI (W = 0.80, P < 0.0001), and VL-FIpsd (W = 0.79, P < 0.0001). Using a multiple logistic regression analysis, %VLFI was the most strongly associated with diseased status (adjusted OR: 8.4; 95% CI: 3.4-19.5). Using an appropriate threshold, %VLFI demonstrated a diagnostic sensitivity of 87%. A 3-month continuous positive airway pressure treatment significantly improved the same parameter. Frequency-domain analysis of the interbeat interval increment appears as a powerful tool for OSAS diagnosis and follow-up. The simplicity of its analysis and of its use makes of it a well-suited variable for mass screening of OSAS patients.

High accuracy of automatic detection of atrial fibrillation using wavelet transform of heart rate intervals.

Permanent and paroxysmal AF is a risk factor for the occurrence and the recurrence of stroke, which can occur as its first manifestation. However, its automatic identification is still unsatisfactory. In this study, a new mathematical approach was evaluated to automate AF identification. A derivation set of 30 24-hour Holter recordings, 15 with chronic AF (CAF) and 15 with sinus rhythm (SR), allowed the authors to establish specific RR variability characteristics using wavelet and fractal analysis. Then, a validation set of 50 subjects was studied using these criteria, 19 with CAF, 16 with SR, and 15 with paroxysmal AF (PAF); and each QRS was classified as true or false sinus or AF beat. In the SR group, specificity reached 99.9%; in the CAF group, sensitivity reached 99.2%; in the PAF group, sensitivity reached 96.1%, and specificity 92.6%. However, classification on a patient basis provided a sensitivity of 100%. This new approach showed a high sensitivity and a high specificity for automatic AF detection, and could be used in screening for AF in large populations at risk.