The human hunger sensation (HS) is a perceptive signal characterized by day-night variability (DNV). This pattern was investigated with respect to its relations with the body compartments in 22 clinically healthy subjects (CHS, 11 males and 11 females mean age: 24±2.5 years, mean BMI: 21±1.7). The DNV was investigated by means of con ventional descriptive statistics and the single cosinor method (SCM). Both procedures were applied to the orexigram, i.e., the 24-h profile of the orectic stimulus (OS) provided by each subject, who self-rated his/her HS (from 1 to 10 hunger units) every half hour. Body composition was investigated by Bioelectrical Impedance Analysis (BIA) on the day when the orexigrams were compiled. It was found that the daily HS level correlates positively with the Free Fat Body Mass (FFBM) and negatively with the Fat Body Mass (FBM). These opposite relations indicate that HS is stimulated by the needs of the FFBM, and inhibited by expansion of the FBM, and provide further evidence of the existence of an “adipostat anorectic mechanism.

In a prospective study, we evaluated the hypothesis that QT variability is abnormal in multiple system atrophy. Time and frequency domain QT variability was assessed from 24-hour Holter monitoring. Three-channel Holter monitoring was performed in all subjects and was analyzed on a homemade analyzer. The 24-hour mean QT duration was similar in multiple system atrophy patients and in control subjects Unlike QT duration, several parameters of time and frequency domain QT variability were significantly increased in multiple system atrophy patients compared to healthy controls. Time domain measures of QT variability were significantly shorter while asleep than while awake in both groups. The nighttime % reduction in time-domain QT variability tended to be smaller in patients in comparison to control subjects, but this difference did not achieve statistical significance. This is the first reporting demonstrating that QT variability is abnormal in patients with multiple system atrophy

Objective: To characterize cardiac structure and function and cardiac autonomic control in patients with subclinical and overt hyperthyroidism.Design: Thirty patients with subclinical hyperthyroidism and 30 with overt disease were selected from patients never previously treated for endocrinological disease in the outpatient clinic of our institution. Twenty normal individuals were studied as control group.Methods: Left ventricular structure and function and cardiac autonomic control were evaluated, respectively, by two-dimensional Doppler echocardiography and by 24-h Holter recording with heart rate variability analysis.Results: Patients with overt hyperthyroidism showed greater values of left ventricular end-diastolic volume (P < 0.05) and left ventricular mass (P < 0.05) than patients with subclinical disease. In addition, the mean velocity of left ventricular fibre shortening (P < 0.05) and left ventricular ejection fraction (P < 0.05) were greater in patients with overt hyperthyroidism than in patients with subclinical disease. No difference in any of these parameters was detectable between normal subjects and patients with subclinical disease. The isovolumic relaxation period was shorter in patients with subclinical hyperthyroidism than in control individuals (P < 0.05) and in patients with overt hyperthyroidism (P < 0.05). As regards cardiac autonomic control, all time and frequency domain measures decreased progressively from control individuals to patients with subclinical hyperthyroidism and those with overt disease (P < 0.001).Conclusions: Thyrotoxic patients show changes in left ventricular structure and increased echocardiographic indexes of myocardial contractility, whereas the only echocardiographic feature detectable in patients with subclinical hyperthyroidism is an increased velocity of left ventricular relaxation. Cardiac parasympathetic withdrawal is evident in patients with overt hyperthyroidism and in patients with subclinical disease.

In patients with hypertrophic cardiomyopathy (HCM), a history of syncope is associated with increased risk of sudden death, an important role in its pathophysiology being presumably played by an arrhythmic mechanism. The aim of this study was to find out whether several ventricular repolarization parameters are useful to discriminate between patients with and without syncope. The Holter recordings of three groups of subjects (HCM with syncope, HCM without syncope and normals) were analysed, and three sets of variables were measured: six spectral variables, six QT/RR slope variables and 12 QT time parameters. All three sets were submitted to tests (e.g. discriminant analysis) in order to verify the differences among the groups. Finally, classification of single subjects was carried out

We examined the effects of beta-blockers on the associations between heart rate and number of premature ventricular beats (PVBs) and on heart rate variability and myocardial ischemia in patients with coronary heart disease. After 2 weeks of run-in placebo treatment, 18 patients with coronary artery disease were randomized to a 7-day treatment with either propranolol (40 mg) three times a day or placebo. During run-in and after 7 days of treatment, patients underwent 24-hour Holter monitoring and exercise tests. We analyzed the 24-hour Holter recordings with customized software that computes the correlation between heart rate and occurrence of PVBs. We also computed spectral measures of heart rate variability on the same recordings. Propranolol caused a significant decrease in the log-transformed total number of PVBs recorded over 24 hours and during the day. The number of PVBs was much lower during the night than during the day both after placebo and after propranolol. There were no differences between the two treatments. During the day, there was a positive correlation between heart rate and the number of PVBs in all 18 patients. The mean correlation coefficients between heart rate and number of PVBs increased significantly after propranolol treatment both during the 24-hour monitoring (p < 0.05) and during the day (p < 0.05). The night-recorded correlation coefficients between heart rate and number of PVBs were not significantly different in the placebo versus propranolol group. Propranolol significantly increased the total power during the day. Placebo caused a significant decrease in the low-frequency band (LF) and a significant increase in the high-frequency band (HF) during the night compared with the day. During the day, propranolol significantly reduced LF power and increased HF power, with respect to placebo. After propranolol treatment, the values of LF and HF power during the day were comparable to those recorded at night. The LF/HF ratio decreased significantly after propranolol treatment with respect to placebo in the day and became similar to that recorded during sleep. Propranolol significantly reduced heart rate and systolic blood pressure at rest and at peak exercise and reduced signs of myocardial ischemia. Propranolol administration reduces PVBs in patients with coronary artery disease and severe ventricular arrhythmias possibly through an improvement of cardiac autonomic regulation and through anti-ischemic effects, antiarrhythmic effects, or both.

This study evaluated the effect of angiotensin II receptor blockade on cardiac autonomic control adaptation and urine output in response to acute isotonic volume load in patients with idiopathic dilated cardiomyopathy (DCM) and asymptomatic to mildly symptomatic heart failure. Left ventricular volumes and heart rate variability measurements were assessed at baseline and during intravenous saline load in 14 patients before and after 2 mo of losartan treatment. After losartan treatment, blood pressure values were lower, whereas left ventricular ejection fraction was higher (F = 79, P < 0.001), than before treatment. During saline load, ejection fraction decreased before losartan treatment (F = 5.6, P < 0.05) but did not change after treatment. Urinary volume, unchanged during saline load in untreated patients, increased after losartan (F = 9.38, P < 0. 001). Time-domain measurements that represent vagal modulation of heart rate (root-mean-square successive differences and percentage of differences between successive R-R intervals >50 ms) decreased during saline load in untreated patients (F = 3.1, P < 0.05 and F = 6.5, P < 0.01, respectively), but not after losartan. Similarly, a decrease in very low frequency (F = 3.2, P < 0.05), low-frequency (F = 2.9, P < 0.05), and high-frequency power (F = 6.1, P < 0.01) after saline load was observed only in untreated patients. In patients with DCM, losartan treatment improves the cardiac autonomic adaptation and increases urine output in response to volume overload.

This study evaluated the effects of acute isotonic volume expansion on heart rate variability (HRV) in 10 patients with dilated cardiomyopathy (DCM) and in 10 age- and sex-matched normal volunteers. Echocardiographic left ventricular volumes and HRV measurements by continuous Holter recording were assessed at baseline, at 60 and 120 min during intravenous saline load (0.9% NaCl, 0.25 ml.kg(-1).min(-1)), and 60 min after infusion was terminated. Data analysis was performed by repeated-measures ANOVA. After volume expansion, left ventricular ejection fraction increased (F = 9.8; P < 0.001) in normal subjects and decreased (F = 8.7; P < 0.001) in DCM patients. During volume expansion a significant difference was also detectable between the two groups in root-mean-square successive difference (F = 25.2; P < 0.001), percentage of differences between successive normal R-R intervals >50 ms (F = 97.6; P < 0.001), high-frequency power (F = 50.1; P < 0.001), and low-frequency power (F = 41.6; P < 0.001), all of which reflect parasympathetic modulation of heart rate; in fact, these measurements increased in normal subjects and decreased in DCM patients. In normal subjects, the increase in HRV measurements during volume expansion suggests a parasympathetic activation, mediated by stimulation of cardiopulmonary and arterial mechanoreceptors. On the contrary, in DCM patients the parasympathetic withdrawal, already detectable at baseline, increases during volume expansion.

Background Decreased heart rate variability (HRV), indicating derangement in cardiac autonomic control, has been reported in patients with chronic heart failure. However, the independent and incremental prognostic value of HRV over clinical data and measures of left ventricular dysfunction has been less thoroughly investigated. This study was designed to evaluate the predictive value of HRV and Poincaré plots as assessed by 24-hour Holter recording in patients with chronic heart failure. Methods Ninety-seven patients, mean age 55 ± 13 years, with radionuclide left ventricular ejection fraction ≤40% underwent echocardiographic examination and 24-hour Holter recording. Heart failure was caused by coronary artery disease in 57 patients (59%) and idiopathic dilated cardiomyopathy in 40 (41%). Results During follow-up (39 ± 18 months), 32 cardiac deaths occurred. By Cox multivariate analysis, significant predictors of death were left ventricular end-systolic volume (hazard ratio 1.04), low- to high-frequency ratio (hazard ratio 0.09), percentage of differences between successive normal R-R intervals >50 ms (hazard ratio 0.93), and age (hazard ratio 1.06). Furthermore, HRV analysis improved (P < .001) the prognostic power of a model including clinical and echocardiographic data, left ventricular ejection fraction, and ventricular arrhythmias at Holter recording, whereas the inclusion of Poincaré plots did not add further predictive value. Conclusions Our investigation demonstrated that HRV has independent and incremental prognostic value in patients with chronic heart failure and seems useful to stratify patients at high risk of cardiac death. (Am Heart J 1999;138:273-84.)

BACKGROUND Analysis of heart rate variability (HRV) is a valuable noninvasive method for quantifying autonomic cardiac control in humans and has been utilized during dipyridamole echocardiographic test to differentiate positive from negative test results. HYPOTHESIS We aimed to evaluate, by means of HRV analysis, the influence of the angiographic severity of coronary artery disease on cardiac autonomic control during dipyridamole-induced myocardial ischemia. METHODS We analyzed RR interval variability changes during dipyridamole-induced myocardial ischemia in 31 selected patients (mean age 54 +/- 9 years) with available coronary angiography and positive dipyridamole echocardiographic test. Spectral components of HRV were assessed by means of wavelet transform analysis for the last 5 min before the beginning of the test (baseline) and for 5 min after the onset of ischemia-related events (peak dipyridamole effect). RESULTS Patients were divided into three groups according to the number of coronary diseased vessels (Group A, single-vessel disease; Group B, double-vessel disease; Group C, triple-vessel disease). No difference was detectable at baseline among the three groups. After dipyridamole, low-frequency power, a measure of sympathetic modulation of heart rate, increased and echocardiographic wall motion score index worsened in all groups (p < 0.001). The increase in low-frequency power was more evident in Group C patients than in the other two groups (p < 0.005). Furthermore, after dipyridamole, a direct correlation was found between low-frequency power and wall motion score index (r = 0.59; p < 0.001). CONCLUSIONS These data suggest that HRV analysis performed during dipyridamole echocardiographic test provides useful information to assess the severity of coronary artery disease.

OBJECTIVEWe evaluated the effect of two calcium channel blockers, verapamil and felodipine, on heart rate variability in hypertensive patients.DESIGNTime and frequency domain measures of heart rate variability were obtained from 24 h Holter recording in 25 previously untreated hypertensive patients without left ventricular hypertrophy, before and after 3 months of verapamil slow-release treatment (240 mg once daily) or felodipine extended-release treatment (10 mg once daily).RESULTSBlood pressure values decreased with both drugs. Measures of heart rate variability, comparable at baseline in the two groups, were unchanged after felodipine. After verapamil, the average RR interval, the square root of the mean of the squared differences between all adjacent normal RR intervals (r-MSSD) and the percentage of differences between all adjacent normal RR intervals > 50 ms (pNN50), measures of vagal modulation of heart rate, increased (from 735 +/- 67 to 827 +/- 84 ms, P < 0.001; from 30 +/- 10 to 44 +/- 15 ms, P < 0.001; and from 3 +/- 2 to 7 +/- 6%, P < 0.01, respectively) and were higher than after felodipine. The coefficient of variation, a measure that compensates for heart rate effects, increased only after verapamil (from 5.8 +/- 1.3% to 6.6 +/- 1.0%; P < 0.05). High frequency power and its coefficient of component variance, both representing the vagal modulation of heart rate, increased after verapamil (from 5.33 +/- 0.29 to 5.80 +/- 0.27 In units, P < 0.001 and from 1.9 +/- 0.3 to 2.2 +/- 0.25%; P < 0.05). Finally, the low to high frequency power ratio, an indicator of sympathovagal balance, with a high value suggesting a sympathetic predominance, decreased after verapamil (from 2.16 +/- 0.41 to 1.36 +/- 0.35; P < 0.001), confirming the improvement in vagal modulation of heart rate.CONCLUSIONIn hypertensive patients, despite a comparable anti-hypertensive effect, verapamil, but not felodipine, has favourable effect on cardiac autonomic control.

L. SPINELLI,1 M. PETRETTA,1 F. MARCIANO,2 G. TESTA,1 M. A. E. RAO,1 M. VOLPE,3 AND D. BONADUCE1 1Institute of Internal Medicine, Cardiology and Heart Surgery, University of Naples Federico II, 80131 Naples; 2Institute of Cybernetics, National Research Council, 80072 Naples; and 3Department of Experimental Medicine and Pathology, University of Rome ‘‘La Sapienza,’’ 00161 Rome, and Istituto di Ricovero e Cura a Carattere Scientifico, Istituto Neurologico Mediterraneo, 86077 Pozzilli, Italy

PURPOSE:We aimed to evaluate in a longitudinal study the effect of intensive training on cardiac autonomic control in athletes using 24-h heart rate variability analysis.METHODS:Time and frequency domain measures of heart rate variability were calculated from 24-h Holter monitoring in 15 high level bicyclists (mean age 21 +/- 4 yr) after 1 month of detraining and after 5 months of vigorous training. At the same times echocardiographic left ventricular mass and dimensions and maximal oxygen consumption (VO2max) were assessed.RESULTS:In detrained athletes, VO2max values, left ventricular mass and dimensions, and time and frequency domain measures of vagal modulation of heart rate were higher than in a group of untrained subjects of similar age while heart rate and the low-to-high frequency ratio were lower, indicating an enhanced vagal modulation of heart rate in athletes as compared with that in control subjects. After 5 months of vigorous training, left ventricular mass and dimensions and VO2max increased in athletes, while heart rate decreased further. In contrast, no changes were detectable in time and frequency domain measures of heart rate variability over the entire 24-h and in both waking and sleeping hours.CONCLUSIONS:This study demonstrates that an increased cardiac vagal control is detectable in detrained athletes; however, after intensive training, despite a significant decrease in heart rate, time and frequency domain measures of heart rate variability reflecting cardiac vagal control remain unchanged. Thus, other mechanisms than changes in cardiac autonomic control could be involved in determining the profound bradycardia of athletes.

Evaluation of dynamic changes of QT dispersion (QTd) during Holter monitoring would have applicability to clinical practice. However, the analysis of QTd variability on Holter ECG recordings has not yet been reported. We are now able to perform time and spectral domain analysis of QTd variability on Holter recordings using a homemade analyzer. An automatic interactive algorithm performed the analysis of the QRS-T complexes and measured QT duration from Holter recorded X, Y and Z leads in 10 healthy subjects. QTd was calculated as the difference between the longest and the shortest QT interval, measured on each simultaneous 3-lead ECG recording. Whether evaluation of QTd variability is of clinical significance needs further evaluation, especially when high risk patients are assessed.

Hunger sensation (HS) is a perception with a daily (circadian) and within-day (ultradian) recursive pattern. In human beings, circadian repeatability was investigated by means of the Single Cosinor method, while the ultradian recursivity was investigated by means of the spectral analysis, both applied to the 24-h HS profile (orexigram). Orexigrams were provided by each subject investigated, who self-rated her subjective orectic stimulus (OS) (from 1 to 10 hunger units) every half hour. The study was performed in 19 female patients aged 13-52 newly diagnosed as in the first episode of Anorexia Nervosa Restricting Type, with a BMI below 18.7 The control group consisted of 10 clinically healthy women aged 21 to 52 years with a BMI from 23 to 25. Two types of orexigrams were found. The first was characterized by a low profile with negligible ultradian variability, in which the HS circadian rhythm (CR) was still detectable, bu the power spectrum (PS) was composed of unusual ultradian components associated with a very diminished amplitude for the circadian harmonics. The second was characterized by an almos regular profile, in which the ultradian variability was clearly detectable, the CR regularly fluctuat ed, and the PS was almost regularly composed. These findings indicate that anorectic patients (AP) can be recognized by their orexigram as “hyporectic”, or “eurectic”. Therefore, the term “anorexia” seems to be appropriate for AP who exhibit the first type of orexigram (anorectic aphagia nervosa), whereas the second identifying those who could be defined as suffering from “eurectic aphagia nervosa”.

Autonomic dysfunction has been reported in patients with hypertrophic cardiomyopathy. To evaluate the influence of different clinical and echocardiographic features of the disease on sympathovagal balance, as assessed by heart rate variability, 33 patients with hypertrophic cardiomyopathy and 33 healthy volunteers underwent echocardiographic examination and 24-hour electrocardiogram Holter recording. Measures of vagal modulation of heart rate were lower in patients with hypertrophic cardiomyopathy than in controls, particularly in those exhibiting syncope, exertional chest pain, dyspnea, or moderate or severe mitral regurgitation. Furthermore the age-corrected multiple regression analysis showed that the parasympathetic cardiac control was inversely related to left atrial dimension and directly related to left ventricular end-systolic dimension. Therefore in hypertrophic cardiomyopathy the parasympathetic withdrawal is more evident in patients with symptoms than in those without; the reduction in left ventricular end-systolic dimension and the increase in left atrial size are the echocardiographic features that most influence the sympathovagal balance.

A depressed heart rate variability (HRV) is a powerful predictor of poor outcome in myocardial infarction patients. The beneficial effect of specific interventions on its recovery has been reported, but data concerning calcium antagonists are scarce. We evaluated the effect of a phenylalkylamine derivative, verapamil, and a dihydropyridine derivative, felodipine, on time- and frequency-domain measurements of HRV by 24-hour Holter monitoring in 60 patients with acute myocardial infarction (AMI). After a first Holter recording (65 ± 8 hours from the onset of symptoms), patients were randomly assigned to continue standard treatment or to also receive verapamil retard (120 mg 3 times daily) or felodipine extended-release (10 mg/day). Holter recording was repeated after 7 days. After verapamil, mean RR interval increased from 823 ± 92 to 907 ± 95 ms and the SD of all normal RR (NN) intervals (SDNN) from 99 ± 24 to 120 ± 30 ms (p < 0.01); the root mean square successive difference (r-MSSD) and the percent of differences between adjacent NN intervals >50 ms (pNN50) also increased (p < 0.01). After felodipine, only SDNN increased (p < 0.01). Regarding frequency-domain measurements, after receiving verapamil, very low frequency, low- and high-frequency powers increased (p < 0.01), whereas the low- to high-frequency ratio decreased (p < 0.01). After receiving felodipine, very lowfrequency power increased (p < 0.01), whereas lowand high-frequency powers and the low- to high-frequency ratio remained unchanged. This study demonstrates that verapamil, but not felodipine, improves HRV in the early phase after AMI.

Little is known to what extent heart rate and its circadian variations can influence QT dispersion (QTd). Thus we studied the relationship between RR and QTd in 10 healthy subjects (6 M, 4 F mean age 32/spl plusmn/11 years). Beat-to-beat automated measurement of RR and QT was performed on a home-made analyzer. QTd was automatically measured for each beat on X, Y and Z leads. Mean hourly RR and QTd values were calculated for each 60 min period of 24-hour Holter recordings. A significant linear relationship was found between mean hourly RR and QTd values (r=.47; p=0.02). Hourly median RR values showed the expected circadian variation, with a nocturnal peak between 3 and 6 A.M. Similarly, there was a circadian rhythm in hourly median QTd values, with a prominent peak between the hours 2 and 3 A.M. In conclusion, in healthy subjects QTd is weakly correlated to RR and shows a circadian variation.

BACKGROUND AND HYPOTHESIS:Alteration in sympathovagal balance may be a mechanism of increased cardiovascular mortality and sudden death of patients with anorexia nervosa. This study was undertaken to characterize cardiac autonomic control in patients with anorexia nervosa by means of heart rate variability analysis.METHODS:Heart period variability by 24-h Holter recording was evaluated in 13 young women with anorexia nervosa, 10 constitutionally thin women, and 10 women of normal weight.RESULTS:High-frequency power, a measure of parasympathetic modulation of heart rate, and all-time domain measures of heart rate variability were higher in patients with anorexia nervosa than in thin women and in those of normal weight. Thin women showed lower values of total power and of most components of power spectrum.CONCLUSIONS:Our data demonstrate an increased vagal tone in young women with anorexia nervosa. The marked increase in parasympathetic activity, not in response to an increase in sympathetic activity, could be detrimental and may contribute to the higher cardiovascular mortality of these patients.

The authors measured heart rate variability (HRV) during dipyridamole test (DET) in 36 patients with suspected coronary artery disease (CAD) who underwent coronary angiography for chest pain evaluation. The authors considered Group A: no CAD and negative DET results; Group B: CAD and negative DET; Group C: CAD and positive DET. After dipyridamole, in Group B and C, HRV measures of cardiac vagal control decreased and sympathetic activity increased; differently, in Group A all components of HRV decreased. Therefore, in CAD patients dipyridamole infusion induced a parasympathetic withdrawal with sympathetic predominance despite a negative DET. HRV analysis seems to be able to detect this autonomic disturbance, improving the diagnostic accuracy of DET in patients with suspected CAD