Franca Barbic

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.

Early Abnormalities of Vascular and Cardiac Autonomic Control in Parkinson’s Disease Without Orthostatic Hypotension

Cardiac autonomic abnormalities have been described in Parkinson’s disease. Little is known about possible alterations of vascular sympathetic regulatory activity in patients without orthostatic hypotension or symptoms of orthostatic intolerance. Nineteen patients with Parkinson’s disease without orthostatic hypotension (PD), 21 with orthostatic hypotension (PDOH), and 20 healthy controls underwent ECG, beat-to-beat arterial pressure, and respiration recordings while recumbent and during a 75° head-up tilt. Spectrum analysis of RR interval and systolic arterial pressure (SAP) variability provided indices of cardiac sympathovagal interaction (low frequency [LF]/high frequency [HF]) to the sinoatrial node and sympathetic vasomotor control (LFSAP). Arterial baroreceptor mechanisms were assessed by the spontaneous sequences technique and bivariate spectrum analysis (&agr; index). Plasma catecholamines provided the neurohormonal profile. At rest, hemodynamics and spectral markers of autonomic function were similar in PD and control subjects. Norepinephrine was lower in PD and PDOH than in control subjects. In PDOH, SAP was higher, whereas LF/HF ratio and LFSAP were lower compared with control subjects. During tilt, SAP was unchanged in PD; however, similar to PDOH, the increase of heart rate, LF/HF ratio, and LFSAP was blunted compared with control subjects. Baroreflex indices were unmodified in PD and PDOH compared with control subjects. Initial alterations in both cardiac and vascular sympathetic modulatory activity were found in PD and revealed by a gravitational stimulus. Prompt recognition of sympathetic abnormalities might result in earlier therapeutic intervention, reduced orthostatic intolerance, and increased quality of life.

San Francisco Syncope Rule, Osservatorio Epidemiologico sulla Sincope nel Lazio risk score, and clinical judgment in the assessment of short-term outcome of syncope.

OBJECTIVE The study aimed to compare the efficacy of the Osservatorio Epidemiologico sulla Sincope nel Lazio (OESIL) risk score, San Francisco Syncope Rule, and clinical judgment in assessing the short-term prognosis of syncope. METHODS We studied 488 patients consecutively seen for syncope at the emergency department of 2 general hospitals between January and July 2004. Sensitivity, specificity, predictive values, and likelihood ratios for short-term (within 10 days) severe outcomes were computed for each decision rule and clinical judgment. Severe outcomes comprised death, major therapeutic procedures, and early readmission to hospital. RESULTS Clinical judgment had a sensitivity of 77%, a specificity of 69%, and would have admitted less patients (34%, P < .05 vs decision rules). The OESIL risk score was characterized by a sensitivity of 88% and a specificity of 60% (admission 43%). San Francisco Syncope Rule sensitivity was 81% and specificity was 63% (admission 40%). According to both clinical rules, no discharged patient would have died. With combined OESIL risk score and clinical judgment, the probability of adverse events was 0.7% for patients with both low risk scores, whereas that for both high risk scores was roughly 16%. CONCLUSION Because of a relatively low sensitivity, both risk scores were partially lacking in recognizing patients with short-term high-risk syncope. However, the application of the decision rules would have identified all patients who subsequently died, and OESIL risk score and clinical judgment combined seem to improve the decision-making process concerning the identification of high-risk patients who deserve admission.

Priorities for emergency department syncope research

STUDY OBJECTIVES There is limited evidence to guide the emergency department (ED) evaluation and management of syncope. The First International Workshop on Syncope Risk Stratification in the Emergency Department identified key research questions and methodological standards essential to advancing the science of ED-based syncope research. METHODS We recruited a multinational panel of syncope experts. A preconference survey identified research priorities, which were refined during and after the conference through an iterative review process. RESULTS There were 31 participants from 7 countries who represented 10 clinical and methodological specialties. High-priority research recommendations were organized around a conceptual model of ED decisionmaking for syncope, and they address definition, cohort selection, risk stratification, and management. CONCLUSION We convened a multispecialty group of syncope experts to identify the most pressing knowledge gaps and defined a high-priority research agenda to improve the care of patients with syncope in the ED.

Short-term complexity indexes of heart period and systolic arterial pressure variabilities provide complementary information

It is unclear whether the complexity of the variability of the systolic arterial pressure (SAP) provides complementary information to that of the heart period (HP). The complexity of HP and SAP variabilities was assessed from short beat-to-beat recordings (i.e., 256 cardiac beats). The evaluation was made during a pharmacological protocol that induced vagal blockade with atropine or a sympathetic blockade (beta-adrenergic blockade with propranolol or central sympathetic blockade with clonidine) alone or in combination, during a graded head-up tilt, and in patients with Parkinsons disease (PD) without orthostatic hypotension undergoing orthostatic challenge. Complexity was quantified according to the mean square prediction error (MSPE) derived from univariate autoregressive (AR) and multivariate AR (MAR) models. We found that: 1) MSPE(MAR) did not provide additional information to that of MSPE(AR); 2) SAP variability was less complex than that of HP; 3) because HP complexity was reduced by either vagal blockade or vagal withdrawal induced by head-up tilt and was unaffected by beta-adrenergic blockade, HP was under vagal control; 4) because SAP complexity was increased by central sympathetic blockade and was unmodified by either vagal blockade or vagal withdrawal induced by head-up tilt, SAP was under sympathetic control; 5) SAP complexity was increased in patients with PD; and 6) during orthostatic challenge, the complexity of both HP and SAP variabilities in patients with PD remained high, thus indicating both vagal and sympathetic impairments. Complexity indexes derived from short HP and SAP beat-to-beat series provide complementary information and are helpful in detecting early autonomic dysfunction in patients with PD well before circulatory symptoms become noticeable.

Lateralization of expression of neural sympathetic activity to the vessels and effects of carotid baroreceptor stimulation

Human studies suggest that cardiovascular neural sympathetic control is predominantly modulated by the right cerebral hemisphere. It is unknown whether post-ganglionic sympathetic activity [muscle sympathetic nerve activity (MSNA)] shows any functional asymmetry. Eight right-handed volunteers (3 women and 5 men, 32 +/- 2 yr of age) underwent ECG, beat-by-beat blood pressure, respiratory activity, and simultaneous right and left MSNA recordings during spontaneous and controlled breathing (CB, 15 breaths/min, 0.25 Hz). Dynamic carotid baroreceptor stimulation was obtained by 0.1-Hz sinusoidal suction, from 0 to -50 mmHg, randomly applied to the right, left, and combined right and left sides of the neck during CB. Laterality was assessed by changes in the MSNA burst rate (in bursts/min, and bursts/100 beats), strength [amplitude (A) and area (AA)], and the oscillatory component at 0.1 Hz during baroreceptor stimulation. Amplitude parameters were normalized by CB burst mean amplitude and area of the same side. At rest, the right and left MSNA burst rate and total MSNA activity were similar. Conversely, the right MSNA normalized burst A(N) (1.36 +/- 0.18) and AA(N) (1.31 +/- 0.16) were larger than the left MSNA A(N) (1.04 +/- 0.09) and AA(N) (1.02 +/- 0.08). Unilateral and bilateral carotid baroreflex stimulation abolished the right prevalence of A(N) and AA(N). In conclusion, the right lateralization of sympathetic activity to the vessels is indicated by normalized burst strength parameters of bilateral MSNA recordings at rest during spontaneous breathing. Carotid baroreceptor stimulation disrupted such expression of MSNA lateralization possibly by disturbing the synchronizing action of right cerebral hemisphere.

Stable Isotope Ratios in Hair and Teeth Reflect Biologic Rhythms

Biologic rhythms give insight into normal physiology and disease. They can be used as biomarkers for neuronal degenerations. We present a diverse data set to show that hair and teeth contain an extended record of biologic rhythms, and that analysis of these tissues could yield signals of neurodegenerations. We examined hair from mummified humans from South America, extinct mammals and modern animals and people, both healthy and diseased, and teeth of hominins. We also monitored heart-rate variability, a measure of a biologic rhythm, in some living subjects and analyzed it using power spectra. The samples were examined to determine variations in stable isotope ratios along the length of the hair and across growth-lines of the enamel in teeth. We found recurring circa-annual periods of slow and fast rhythms in hydrogen isotope ratios in hair and carbon and oxygen isotope ratios in teeth. The power spectra contained slow and fast frequency power, matching, in terms of normalized frequency, the spectra of heart rate variability found in our living subjects. Analysis of the power spectra of hydrogen isotope ratios in hair from a patient with neurodegeneration revealed the same spectral features seen in the patients heart-rate variability. Our study shows that spectral analysis of stable isotope ratios in readily available tissues such as hair could become a powerful diagnostic tool when effective treatments and neuroprotective drugs for neurodegenerative diseases become available. It also suggests that similar analyses of archaeological specimens could give insight into the physiology of ancient people and animals.

Driving and working with syncope.

Syncope is usually addressed in the Emergency Department (ED) by the doctor in charge of the clinical picture, i.e. the patients risk is stratified, a diagnostic work-up is done and a prognosis is set. Patients are ultimately admitted to hospital or discharged. However, other aspects related to syncope may deeply affect their daily lives. These include how and when to return to work and to driving, the feelings about a recent loss of consciousness, and the potential relapse of syncope. This is particularly significant if the work setting is intrinsically hazardous. These patients need adequate clinical and psychological support. For patients with syncope, two main parameters should be considered regarding returning to work and to driving. The first is to evaluate the risk of syncope recurrence and the second is to consider the expected harm if syncope does indeed occur during these activities. In the present paper we detail the problem of driving (including professional driving) and work after syncope. We propose a new quantitative model that will guide the physician in stratifying the risk for patients who have had a previous syncope event. The new model considers the syncope recurrence risk, the job task duration, and features that facilitate a syncope during work. On the basis of these variables, the global risk index for a worker is calculated. Following appropriate validation, this method might help ED and occupational physicians in their decision-making process with the goal of safely readmitting syncope patients to the workplace.

Cardiovascular parameters and neural sympathetic discharge variability before orthostatic syncope: role of sympathetic baroreflex control to the vessels

We tested the hypothesis that altered sympathetic baroreceptor control to the vessels (svBRS) and disrupted coupling between blood pressure (BP) fluctuations and muscle sympathetic activity (MSNA) discharge pattern in the low frequency band (LF, around 0.1 Hz) precede vasovagal syncope. Seven healthy males underwent ECG, BP, respiratory, and MSNA recordings at baseline (REST) and during a 15 min 80° head-up tilt, followed by a -10 mmHg step wise increase of lower body negative pressure up to presyncope. Spectral and coherence analyses of systolic arterial pressure (SAP) and MSNA variability provided the indexes of vascular sympathetic modulation, LFSAP, and of the linear coupling between MSNA and SAP in the low frequency band (around 0.1 Hz), K(2)MSNA-SAP(LF). svBRS was assessed as the slope of the regression line between MSNA and diastolic arterial pressure (DAP). Data were analyzed at REST, during asymptomatic and presyncope periods of tilt. svBRS declined during presyncope period compared to REST and asymptomatic tilt. The presyncope period was characterized by a decrease of RR interval, LFMSNA, LFSAP, and K(2)MSNA-SAP(LF) values compared to the asymptomatic one, whereas MSNA burst rate was unchanged. The reduction of svBRS producing an altered coupling between MSNA and SAP variability at 0.1 Hz, may provoke circulatory changes leading to presyncope.