Simona Piazza

Cardiac Autonomic Patterns Preceding Occasional Vasovagal Reactions in Healthy Humans

BACKGROUND The wide range of clinical presentation of orthostatic vasovagal syncope suggests different underlying changes in the cardiac autonomic modulation. METHODS AND RESULTS To evaluate the beat-by-beat modifications in the neural control of heart period preceding a syncopal event, we studied RR interval variability in 22 healthy subjects who experienced fainting for the first time during a 90 degrees head-up tilt and in 22 control subjects by means of time-variant power spectral analysis. Sympathetic and vagal modulations to the sinoatrial node were assessed by the normalized power of the low-frequency (LF, approximately 0.1-Hz) and high-frequency (HF, approximately 0.25-Hz) oscillatory components of RR variability. When the patients were supine, no differences were observed in the hemodynamic and spectral parameters of the 2 groups. During the tilt procedure, RR, LFNU, and HFNU (NU=normalized units) values were relatively stable in control subjects. During early tilt (T1), subjects with syncope had reduced RR intervals compared with control subjects. In 13 subjects with syncope, RR decreased while LFNU and LF/HF increased in the last minute of tilt before syncope (T2). Conversely, in the remaining 9 fainters, LFNU and LF/HF decreased from T1 to T2 and HFNU increased slightly. CONCLUSIONS Two different patterns may be recognized in the cardiac autonomic changes preceding an occasional vasovagal event, namely, one characterized by a progressive increase of the marker of cardiac sympathetic modulation up to the onset of syncope, the other by a sympathetic inhibition with an impending vagal predominance. The recognition of different pathophysiological mechanisms in fainters may have important therapeutic implications.

Modifications of Cardiac Autonomic Profile Associated With a Shift Schedule of Work

BackgroundShift work is associated with an increased rate of cardiovascular diseases and accidents. Discordance between circadian rhythms of stress-related biological variables and the work-sleep schedule might explain the reduced efficiency of work. It is not clear whether a shift schedule of work may induce similar discordance in the 24-hour oscillatory pattern of the cardiac autonomic control in respect to the work-sleep periods. Methods and ResultsTwenty-two healthy male blue-collar shift workers underwent 24-hour ECG recordings during each of the 3 different shifts (first, 6 am to 2 pm; second, 2 to 10 pm; third, 10 pm to 6 am). Spectral analysis of heart rate variability over 24 hours provided the normalized markers of cardiac sympathetic (LFnu) and vagal (HFnu) modulation of the sinoatrial node activity and of the sympathovagal balance (LF/HF). LFnu and LF/HF exhibited 24-hour oscillations with different times of maximum and minimum in accordance with the working and sleeping periods, respectively. Lower values of LFnu and LF/HF suggestive of a reduced cardiac sympathetic modulation were present when the job task was performed at night compared with the values observed when the work was performed during morning and evening. ConclusionsContinuous weekly changes of time of maximum and minimum in the cardiac sympathetic and vagal autonomic control may play a role in the excessive rate of cardiovascular diseases in shift workers. The reduced values of the indexes of cardiac sympathetic modulation during night work might be related to the presence of sleepiness or diminished alertness, which in turn could facilitate errors and accidents.

Multivariate time-variant identification of cardiovascular variability signals: a beat-to-beat spectral parameter estimation in vasovagal syncope

In this paper a bivariate, time-variant model able to continuously measure the mutual interactions between heart rate and systolic blood pressure variability signals is presented. A recursive identification of the model parameters makes it possible to estimate, on a beat-to-beat basis, spectral low-frequency (LF) and high-frequency (HF) power (LF/HF ratio) and cross-spectral (coherence and phase relationships between spectral peaks) indexes during nonstationary events. These indexes can be helpful in: 1) physiological study of autonomic nervous system mechanisms of cardiovascular control and 2) quantification and clinical evaluation of the neural and mechanical links between the two signals. In addition, an estimate of baroreceptive activation (/spl alpha/-gain) is continuously extracted. Before applying the model to cardiovascular signals, the reliability of the estimated parameters was tested on simulated signals. Subsequently, the model was applied to investigating vasovagal syncope episodes, aiming at the assessment of autonomic nervous system status and autonomic role in the dynamic phenomena which lead to syncope. The proposed model, which provides noninvasive beat-to-beat evaluation of the autonomic events, may be useful in the description of the syncopal episodes and in the comprehension of the complex physiological mechanisms of syncope.

Pure autonomic failure : complex abnormalities in the neural mechanisms regulating the cardiovascular system

The aim of this study was to evaluate the sympatho-vagal interaction modulating cardiovascular function and the possible impairment of baroreceptor sensitivity in patients affected by Pure Autonomic Failure (PAF). We studied 4 patients affected by PAF and 7 controls at rest and during different levels (45 degrees, 60 degrees, 90 degrees) of head-up tilt. On a different day all subjects underwent i.v. administration of phenylephrine at dosages adequate to enhance systolic blood pressure by about 20 mmHg both at rest and during 45 degrees head-up tilt. Finally, 1.5 mg atropine was infused intravenously only in the patients. Spectral analysis of RR interval and systolic arterial pressure (SAP) variabilities provided markers of sympathetic (low-frequency oscillations, about 0.1 Hz, LFRR) and vagal (high-frequency oscillations, about 0.25 Hz, HFRR) modulations of heart period and of sympathetic vasomotor activity (low-frequency oscillations of SAP variability, LFSAP). Baroreceptor mechanisms were quantified by means of the index alpha (calculated from the square root of the ratio between the powers of HF components of RR interval and SAP variabilities) and of the phenylephrine RR-SAP slope. Patients affected by PAF were characterized by a drastic decrease in total power of RR variability and by the absence of LFRR and LFSAP components. Moreover, HFRR, although largely predominant in its relative value, was also markedly reduced in its absolute value. Finally, the baroreceptive mechanisms appeared to be heavily impaired. In conclusion, PAF patients seem to be characterized by a complex alteration of neural mechanisms, which in addition to the signs of a sympathetic denervation include an impairment, at least functional, of the vagal modulation of heart rate.

Zofenopril versus Lisinopril in the Treatment of Essential Hypertension in Elderly Patients : A Randomised, Double-Blind, Multicentre Study.

AbstractBackground: Angiotensin-converting enzyme inhibitors have been proposed as first-choice drugs for antihypertensive therapy in elderly subjects because of their demonstrated efficacy and safety. However, no information is currently available on the use of zofenopril in elderly hypertensive patients. Objective: To assess the efficacy and safety of zofenopril (30 or 60mg once daily) compared with lisinopril (10 or 20mg once daily). Patients and methods: Patients aged ≥65 years with mild to moderate essential hypertension (sitting diastolic blood pressure [DBP] ≥90mm Hg and ≤110mm Hg) were included in the study. They were randomised to receive either zofenopril 30mg or lisinopril 10mg. Blood pressure and heart rate were measured at baseline and after 4 and 12 weeks of treatment. Patients underwent electrocardiography and evaluation of laboratory parameters at baseline and after 12 weeks. Ambulatory blood pressure monitoring (ABPM) was also performed at baseline and after 12 weeks. After 4 weeks drug doses were doubled in patients whose sitting DBP was ≥90mm Hg. The primary endpoint was to achieve sitting DBP values <90mm Hg or a reduction of sitting DBP >10mm Hg after 12 weeks of treatment. Results: 181 patients were randomised to treatment and 164 patients completed the study. Thirty-three patients were included in the analysis of 24-hour blood pressure monitoring. The percentage of patients with normalised sitting DBP (<90mm Hg) and the rate of treatment responders (reduction of sitting DBP ≥10mm Hg) were not significantly different between the two treatment groups (normalised: zofenopril 81.3% vs lisinopril 76.7%; responders: zofenopril 74.7% vs lisinopril 77.8%). At the end of the treatment sitting DBP was not significantly different between the two treatment groups (zofenopril 82.2 ± 6.6mm Hg vs lisinopril 82.0 ± 7.8mm Hg). Eight percent of patients experienced adverse events in the zofenopril group and 9% in the lisinopril group. A small percentage of adverse events (4%) was related to treatment and reported in the zofenopril group. Conclusions: In elderly hypertensive patients, treatment with zofenopril was effective and well tolerated. Efficacy and safety were comparable with those of lisinopril.

Effects of valsartan/hydrochlorothiazide and amlodipine on ambulatory blood pressure and plasma norepinephrine levels in high-risk hypertensive patients.

The efficacy and tolerability of the combination of valsartan and hydrochlorothi-azide (HCTZ) were compared with that of amlodipine in reducing ambulatory blood pressure and plasma norepinephrine levels in patients with mild to moderate hypertension and at least 1 cardiovascular risk factor. At the end of a 2-week washout period, 92 outpatients with a sitting diastolic blood pressure ≥95 and <110 mm Hg, associated with at least 1 additional risk factor, were randomly assigned to receive either valsartan 160 mg and HCTZ 12.5 mg once daily (n=46) or amlodipine 10 mg alone once daily (n=46) for 12 weeks, according to a prospective, randomized, open-label, blinded end point, parallel-group design. At the end of the washout period and after 6 and 12 weeks of active treatment, 24-hour ambulatory blood pressure monitoring was performed, and clinical blood pressure and heart rate and plasma norepinephrine levels were assessed (by high-performance liquid chromatography). Both the valsartan/HCTZ combination and amlodipine had a demonstrable antihypertensive effect, but the combination showed an antihypertensive effect significantly greater than that of amlodipine, as demonstrated by the 24-hour (P < .001), daytime (P < .001), and nighttime ambulatory blood pressure values (P < .01) and by the clinical blood pressure values at trough, which were all significantly lower. Although the trough-to-peak ratios were similar in both groups, the smoothness indexes pertaining to both systolic and diastolic pressures were significantly higher (P < .05 andP < .001, respectively) in patients receiving valsartan/HCTZ, suggesting the combination produces a more homogeneous antihypertensive effect. A significant increase in plasma norepinephrine levels was associated with amlodipine (+9% at 6 weeks, +15% at 12 weeks) but not with the valsartan/HCTZ combination. The valsartan/HCTZ combination was better tolerated than amlodipine, which was associated with a higher frequency of ankle edema. These results indicate that the combination of valsartan 160 mg and HCTZ 12.5 mg provides more sustained and homogeneous control of blood pressure than does amlodipine 10 mg in high-risk hypertensive patients, without producing reflex sympathetic activation.

Time-variant closed-loop interaction between HR and ABP variability signals during syncope

The mutual interactions existing between heart rate (HR) and arterial blood pressure (ABP) variability signals are investigated by means of a bivariate, time-variant model. The linear, parametric, closed-loop model, chosen to describe the relationships between HR and ABP spontaneous variability, is updated recursively according to the dynamic variations in the signals. In this way a beat-to-beat description of the interaction of the two signals and a beat-to-beat extraction of the relevant spectral and cross-spectral parameters are obtained. Furthermore, as a result of proper modelisation, a noninvasive measurement of the /spl alpha/-baroceptive gain is extracted on a beat-to-beat basis. The quantification of these parameters is obtained through an automatic spectral decomposition technique for an ARMA model. The parameters achieved from the proposed model are used to investigate episodes of vasovagal syncope. In particular the authors are interested in a quantitative assessment of the changes of the autonomic nervous system (ANS) behavior in the epoch preceding the episode and in the evaluation of ANS role in association with the vasovagal event.<<ETX>>

Circadian changes in vascular sympathetic activity in ambulant subjects

In 10 ambulant subjects we studied the circadian changes in sympathetic vasomotor control as assessed by the spectral power of the 0.1-Hz low-frequency component of systolic arterial pressure variability measured with a Millar phi 3F tip transducer. The low-frequency component was higher during the daytime, while the subjects were performing light physical activity, and lower during the night, thus paralleling the circadian systolic blood pressure pattern. However, the morning low-frequency rise preceded the blood pressure increase by about 3 h, suggesting that vasometer control and blood pressure control are at least partly related to different mechanisms.

Comparison of valsartan and irbesartan in the treatment of mild to moderate hypertension: a randomized, open-label, crossover study

Abstract Background: Differences in the pharmacokinetic and pharmacodynamic variables of angiotensin II receptor blockers (ARBs) have been cited as potentially important causes of differential clinical efficacy with respect to the magnitude and duration of the antihypertensive response. Objective: The goal of this study was to compare the antihypertensive efficacy of valsartan versus irbesartan using 24-hour ambulatory blood pressure monitoring (ABPM) in the treatment of mild to moderate hypertension. Methods: After a 2-week placebo washout period, outpatients of both sexes aged 31 to 60 years with mild to moderate hypertension were randomly assigned to treatment with irbesartan 150 mg or valsartan 80 mg, both administered once daily, for 4 weeks. After another 2-week placebo washout period, patients were switched to the alternate regimen for an additional 4 weeks. Patients were assessed at the end of each placebo and active treatment period. At each visit, casual blood pressure (BP) and heart rate were measured and 24-hour ABPM was performed using a portable, noninvasive, fully automatic recorder. Recordings were excluded from analysis when >10% of all readings or >1 reading per hour was missing or incorrect. Trough/peak ratio was assessed in each treatment group, and the smoothness index was determined to quantify the homogeneity of the antihypertensive effect over 24 hours. Results: Forty patients (20 men and 20 women; mean age, 51 ± 7 years) were included in the study. One patient withdrew after randomization (lost at follow-up); the results are given for 39 patients. Both valsartan and irbesartan significantly lowered 24-hour, daytime, and nighttime BP values ( P 50% (valsartan, 0.65 ± 0.72 for systolic BP [SBP] and 0.62 ± 0.55 for diastolic BP [DBP]; irbesartan, 0.57 ± 0.58 for SBP and 0.69 ± 0.54 for DBP) and a similar smoothness index (valsartan, 1.26 ± 0.31 for SBP and 1.41 ± 0.17 for DBP; irbesartan, 1.32 ± 0.43 for SBP and 1.52 ± 0.43 for DBP), which suggests that their antihypertensive effect was homogeneous throughout the 24-hour period and lasted to the end of the dosing interval. Casual BP results confirmed that valsartan and irbesartan were equally effective in reducing SBP and DBP values. Conclusions: Valsartan and irbesartan are 2 ARBs with different pharmacologic properties. Valsartan is more selective for angiotensin type 1 receptors than is irbesartan; irbesartan has a longer half-life and demonstrates insurmountable antagonism. These distinct pharmacologic properties did not appear to result in different effects on the magnitude and duration of antihypertensive efficacy.

Atrial natriuretic peptide in multiple system atrophy

Central nervous system feedback loops centered on hypothalamic neurons control atrial natriuretic peptide (ANP). We evaluated the ANP response to arterial hypotension, isotonic blood volume expansion, and increase in plasma osmolality in 14 patients with multiple system atrophy (MSA). Seven of the patients were characterized by a lack of vasopressin response to hypotension (MSA type B), suggesting chronic sinoaortic denervation, and seven by a preserved response (MSA type A). Orthostatic hypotension decreased ANP in controls and type A patients, whereas ANP in type B was not affected. Isotonic saline infusion increased ANP and diuresis in controls and type A patients, whereas it did not affect ANP in type B. Osmotic load increased plasma osmolality and vasopressin in controls and MSA patients and ANP in controls and type A but not in type B patients. In MSA patients with altered afferent control of vasopressin, ANP secretion is not stimulated by blood volume expansion, osmotic load, or blood pressure, suggesting that afferent excitatory control plays a role in the release of ANP.