Assessment of systolic ejection time as a hemodynamic marker of incipient bradycardic vasovagal syncope. A pilot study.

BACKGROUND: Detection of markers of incipient syncope in patients with vasovagal syncope (VVS), without prodromal symptom, is still an open issue. The aim of this study was to assess the behavior of heart rate (HR) and ejection time, expressed as the percentage of the corresponding cardiac cycle (ET%), in patients with bradycardic VVS with a view to providing an alarm before the event. METHODS: In 33 patients with syncope and positive tilt testing and in 33 control patients, we collected beat-to-beat data on HR, ET%, stroke volume (SV), and blood pressure (BP). The trends of HR and ET% were analyzed. A set of combined changes of HR and ET% were tested in order to select the most appropriate algorithm for detecting the incipient syncope within the 3 minutes preceding the event. RESULTS: In patients with positive tilt testing, BP significantly decreased at 3 minutes before and at the time of syncope (P < 0.0001). HR slowly rose at 3 minutes before syncope and then suddenly decreased at the time of syncope (P < 0.0001). The correlation between SV and ET% was r = 0.79 (P < 0.0001). SV and ET% significantly decreased throughout tilt testing (P < 0.0001). The selected setting for the algorithm provided sensitivity of 97% and specificity of 73%. The theoretical alarm was generated at least 9 and 5 seconds before syncope, respectively, in 76% and 85% of the subjects. CONCLUSION: The combined trends in HR and ET% may provide a marker of incipient bradycardic VVS in the majority of patients.

Do subjects with vasovagal syncope have subtle haemodynamic alterations during orthostatic stress?

AIMS: There are conflicting reports on the presence of subtle haemodynamic alterations during orthostatic stress in subjects with vasovagal syncope (VVS). The aim of the present study was to investigate whether young/middle-aged subjects with VVS show abnormal responses to orthostatic stress. METHODS AND RESULTS: Four groups of subjects underwent tilt testing (TT) during the passive phase and, if negative, after nitroglycerin administration: Group I, 20 subjects with a history of syncope and positive passive TT; Group II, 23 subjects with a history of syncope and TT positive after nitroglycerin; Group III, 23 subjects with a history of syncope and negative TT; and Group IV, 20 normal control subjects. Heart rate, systolic, diastolic, and mean blood pressure, stroke volume, cardiac output, and total peripheral resistance were computed from pressure pulsations (Modelflow). The demographic data and the values of the haemodynamic variables in the supine position did not differ significantly among the four groups. The per cent changes in these variables did not differ significantly among the four groups after 2 and 5 min of TT and among Groups II, III, and IV, 2 min after nitroglycerin administration. CONCLUSION: Young/middle-aged subjects with VVS have a normal measured haemodynamic response to orthostatic stress; therefore, the vasovagal reflex is not secondary to an impairment of the primary vasoconstrictive mechanism.

Current treatment of recurrent vasovagal syncope: between evidence-based therapy and common sense.

Vasovagal syncope is very frequent and benign and the vast majority of subjects do not need any specific treatment, but only reassurance and education. An unknown but small percentage of patients require specific treatment when syncope is very frequent or is responsible for major trauma. For these patients, there are some evidence-based therapies available and some first-line treatments appear to be established. The therapeutic choice mainly depends on the presence and duration of prodromal symptoms. In subjects aged < 70 years with well recognizable prodromes, the first-line treatment is counterpressure manoeuvres. In patients with no or minimal prodromes, but with tilt testing and carotid sinus massage (CSM) both positive, cardiac pacing appear to be the first-line therapy. However, an area of uncertainty remains, represented by patients with no or minimal prodromes and negative CSM. For these patients, appropriate treatment (drugs, tilt training, cardiac pacing, relaxation-based treatment) can be chosen by considering the clinical context, the risk of trauma and possible comorbidities, in addition to utilizing the little or controversial knowledge available, as well as common sense.

The venous system is the main determinant of hypotension in patients with vasovagal syncope.

AIMS: In patients with vasovagal syncope (VVS), a neural reflex appears the main determinant of hypotension leading to loss of consciousness; whether hypotension is mainly due to involvement of the arterial system or the venous system remains a debated issue. The aim of the present study was to assess which of these two systems is responsible for the fall in blood pressure (BP) in patients with VVS; to this end, a haemodynamic study was carried out not only before and during loss of consciousness but also during the recovery phase. METHODS AND RESULTS: Beat-to-beat recordings of heart rate (HR), BP (volume-clamp method) and stroke volume (SV) (modelflow method), cardiac output (CO), and total peripheral resistance (TPR) were made at rest, during unmedicated tilt testing (TT) and recovery from loss of consciousness in 18 patients with a history of syncope (age 45+/-23 years) and positive response to TT. Blood pressure showed a significant fall during prodromal symptoms and a further fall at the beginning of loss of consciousness, together with a fall in SV, CO, and HR, and a slight, but significant, increase in TPR. At the beginning of recovery, BP showed a significant increase and a further increase 5 min later, together with an increase in SV, CO, and HR without significant changes in TPR. CONCLUSION: These results suggest that in VVS the fall in BP is mainly caused by reduced venous return to the heart. The arterial system does not appear to be the main determinant of the fall of BP; however, the system appears unable to make the appropriate compensatory changes.

Efficacy of tilt training in the treatment of neurally mediated syncope. A randomized study.

Recurrent neurally mediated syncope represents a common clinical event and a therapeutic challenge. Recently tilt training has been proposed for the treatment of recurrent neurally mediated syncope. To evaluate the efficacy of tilt training in preventing tilt-induced syncope and its feasibility, this controlled, randomized study was undertaken. Sixty-eight consenting patients (25 males and 43 females, mean age 40 +/- 19) with recurrent neurally mediated syncope and 2 consecutive positive nitroglycerin-potentiated head-up tilt tests were randomized to tilt training (35 patients) or no treatment (controls, 33 patients). The tilt training programme consisted of daily 30-min sessions of upright standing against a vertical wall 6 days a week for at least 3 weeks, until a reevaluation tilt test (3 patients of both groups dropped out). On this third head-up tilt test, 19 (59%) of 32 tilt trained patients and 18 (60%) of 30 controls still had a positive test. Treated patients performed a mean number of 15 +/- 7 sessions (median 16) and only 11 patients (34%) did all the programmed sessions. Only 1 patient (3%) discontinued treatment because of intolerance, while all other patients did not perform tilt training adequately, because of poor compliance. Thus, in our study tilt training was not effective in reducing tilt testing positivity rate in patients with neurally mediated syncope. Because of poor compliance, tilt training appears to be a feasible treatment only for highly motivated patients, but not for the majority of patients with recurrent neurally mediated syncope.

Clinical spectrum of neurally mediated reflex syncopes.

AIMS: The clinical features of the various types of neurally mediated reflex syncope have not been systematically investigated and compared. We sought to assess and compare the clinical spectrum of neurally mediated reflex syncopes. METHODS AND RESULTS: Four hundred sixty-one patients with syncope were prospectively evaluated and 280 had neurally mediated reflex syncope. Each patient was interviewed using a standard questionnaire. A cause of syncope was assigned using standardized diagnostic criteria. Typical vasovagal syncope was diagnosed in 39 patients, situational syncope in 34, carotid sinus syncope in 34, tilt-induced syncope in 142 and complex neurally mediated syncope (positive response to both carotid sinus massage and tilt test) in 31. The clinical features of situational, carotid sinus, tilt-induced and complex neurally mediated syncope were very similar. By contrast, typical vasovagal syncope differed from other neurally mediated syncopes not only in terms of its precipitating factors (fear, strong emotion, etc.), which constituted predefined diagnostic criteria, but also in the variety of its clinical features (lower age and prevalence of organic heart disease, higher prevalence of prodromal symptoms, and of autonomic prodromes, longer duration of prodromes, higher prevalence of symptoms during the recovery phase and lower prevalence of trauma). CONCLUSION: The clinical spectrum of neurally mediated reflex syncopes demonstrates much overlap between them. However, when the afferent neural signals are localized in cortical sites, as in typical vasovagal syncope, symptoms are more frequent and of longer duration.

Plasma galanin response to head-up tilt in normal subjects and patients with recurrent vasovagal syncope.

Neurohumoral factors may contribute to cardiovascular changes associated with vasovagal syncope (VVS). Galanin (GAL) is a neuropeptide, widely distributed in the central and peripheral nervous systems, that interacts with both sympathetic and vagal systems as well as with neurotransmitters, such as serotonin. We investigated the changes in plasma GAL and catecholamine levels during head-up tilt (HUT) test in patients with recurrent VVS. Twenty-two patients (11 women, aged 33.1 +/- 4.2 years) with a history of VVS and 10 healthy subjects (5 women, aged 38.0 +/- 5.8 years) underwent HUT test (60 degrees, 45 minutes). GAL and catecholamine plasma levels were measured in the supine position, during HUT and, in patients with positive response, at presyncope, syncope, and after recovery of consciousness. Thirteen patients developed syncope during HUT, whereas no healthy subjects had a positive response. In healthy subjects, GAL did not change during HUT. By contrast, in patients with a history of VVS and a negative response to tilting (no syncope), GAL significantly (P <.001) increased in response to tilting (supine, 10.2 +/- 0.6 pmol/L; tilting, 18.1 +/- 1.1 pmol/L at 45 minutes) and correlated positively with the increases in blood pressure (BP) and heart rate (HR). In patients with a positive response, GAL did not change either before the loss of consciousness or during syncope. In patients with a positive response, norepinephrine (NE) significantly (P <.001) increased during tilting and then remained practically unchanged during syncope, whereas epinephrine (E) significantly (P <.001) increased during tilting and then showed further significant increases at presyncope and syncope. In conclusion, this study shows that circulating GAL levels progressively increase in correlation with the cardiovascular parameters during a negative HUT in patients with a history of VVS, whereas they remain unchanged in healthy subjects. Moreover, in the patients with tilting-induced syncope GAL does not change either before or during loss of consciousness. These data suggest a role for endogenous GAL in the adaptive responses to acute orthostatic stress preventing syncope in susceptible individuals.

Mechanism of syncope in patients with positive adenosine triphosphate tests.

OBJECTIVES: We prospectively evaluated the mechanism of syncope in patients with positive adenosine triphosphate (ATP) tests (defined as the induction of atrioventricular [AV] block with a ventricular pause >/=6 s after an intravenous bolus of 20 mg ATP). BACKGROUND: Patients with unexplained syncope tend to have more positive ATP tests results than those without syncope. METHODS: An implantable loop recorder (ILR) was inserted in 36 ATP-positive patients (69 +/- 10 years; 22 women; median of 6 syncopal episodes); 15 of them also had a positive response to tilt testing. RESULTS: During the follow-up of 18 +/- 9 months, 18 patients (50%) had syncopal recurrence and 16 (44%) had an electrocardiographically documented episode: AV block (n = 3: paroxysmal in 2 and permanent in 1), AV block followed by sinus arrest (n = 1), sinus arrest (n = 5), sinus bradycardia <40 beats/min (n = 2), normal sinus rhythm (n = 2), sinus tachycardia (n = 1), rapid atrial fibrillation (n = 1), and ectopic atrial tachycardia (n = 1). Bradycardia was documented in a total of 11 cases (69%), and a long ventricular pause (4 to 29 s) was present in eight cases (50%). All three patients with ILR-documented AV block had previously had a negative tilt test, whereas seven of eight with ILR-documented sinus bradycardia or sinus arrest had previously had a positive tilt test. CONCLUSIONS: In patients with adenosine-sensitive syncope, the mechanism of syncope is heterogeneous, although bradycardia is the most frequent finding. Adenosine triphosphate-induced AV block predicts AV block as the mechanism of spontaneous syncope in only a few tilt-negative patients.