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Objective: To define and evaluate hemodynamic criteria to distinguish between classical orthostatic hypotension (cOH) and vasovagal syncope (VVS) in tilt table testing (TTT)., Methods: Inclusion criteria for VVS were a history of VVS and tilt-induced syncope defined as a blood pressure (BP) decrease and electroencephalographic changes during syncope with complaint recognition. Criteria for cOH were a history of cOH and a BP decrease meeting published criteria. Clinical diagnoses were established prior to TTT. We assessed (1) whether the decrease of systolic BP accelerated, "convex," or decelerated, "concave"; (2) the time from head-up tilt to when BP reached one-half its maximal decrease; (3) the difference between baseline heart rate (HR) and HR at BP nadir. We calculated the diagnostic yield of optimized thresholds of these features and their combinations., Results: We included 82 VVS cases (40% men, median age 44 years) and 65 cOH cases (66% men, median age 70 years). BP decrease was concave in cOH in 79% and convex in VVS in 94% (p < 0.001). The time to reach half the BP decrease was shorter in cOH (median 34 sec, interquartile range (IQR) 19-98 sec) than in VVS (median 1571 sec, IQR 1381-1775 sec, p < 0.001). Mean HR increased by 11 ± 11 bpm in cOH and decreased by 20 ± 19 bpm in VVS (p < 0.001). When all three features pointed to VVS, sensitivity for VVS was 82% and specificity was 100%. When all three pointed to cOH, sensitivity for cOH was 71% and specificity was 100%., Interpretation: These new hemodynamic criteria reliably differentiate cOH from VVS., (© 2021 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Introduction: Migraine and vasovagal syncope are comorbid conditions that may share part of their pathophysiology through autonomic control of the systemic circulation. Nitroglycerin can trigger both syncope and migraine attacks, suggesting enhanced systemic sensitivity in migraine. We aimed to determine the cardiovascular responses to nitroglycerin in migraine., Methods: In 16 women with migraine without aura and 10 age- and gender-matched controls without headache, intravenous nitroglycerin (0.5 µg·kg -1 ·min -1 ) was administered. Finger photoplethysmography continuously assessed cardiovascular parameters (mean arterial pressure, heart rate, cardiac output, stroke volume and total peripheral resistance) before, during and after nitroglycerin infusion., Results: Nitroglycerin provoked a migraine-like attack in 13/16 (81.2%) migraineurs but not in controls ( p  = .0001). No syncope was provoked. Migraineurs who later developed a migraine-like attack showed different responses in all parameters vs. controls (all p  < .001): The decreases in cardiac output and stroke volume were more rapid and longer lasting, heart rate increased, mean arterial pressure and total peripheral resistance were higher and decreased steeply after an initial increase., Discussion: Migraineurs who developed a migraine-like attack in response to nitroglycerin showed stronger systemic cardiovascular responses compared to non-headache controls. The stronger systemic cardiovascular responses in migraine suggest increased systemic sensitivity to vasodilators, possibly due to insufficient autonomic compensatory mechanisms.

Purpose: The contribution of diastolic blood pressure measurement to the diagnosis of classical orthostatic hypotension is not known. We aimed to explore the prevalence of isolated systolic and diastolic orthostatic hypotension components in patients with syncope and orthostatic intolerance., Methods: A total of 1520 patients aged >15 years with suspected syncope and/or symptoms of orthostatic intolerance were investigated in a tertiary center using tilt-table testing and continuous non-invasive blood pressure monitoring. Classical orthostatic hypotension was defined as a decline in systolic blood pressure ≥20 mmHg and/or diastolic blood pressure ≥10 mmHg at 3 min of tilt test. The prevalence of upright systolic blood pressure <90 mmHg and its overlap with isolated diastolic orthostatic hypotension was also assessed., Results: One hundred eighty-six patients (12.2%) met current diagnostic criteria for classical orthostatic hypotension. Of these, 176 patients (94.6%) met the systolic criterion and 102 patients (54.8%) met the diastolic criterion. Ninety-two patients (49.5%) met both systolic and diastolic criteria, whereas ten patients (5.4%) met the diastolic criterion alone. Of these, three had systolic blood pressure <90 mmHg during tilt test and were diagnosed with orthostatic hypotension on the grounds of low standing blood pressure. Based on patient history and ancillary test results, causes of orthostatic intolerance and syncope other than orthostatic hypotension were present in the remaining seven patients., Conclusions: An abnormal orthostatic fall in diastolic blood pressure without an abnormal fall in systolic blood pressure is rare among patients with syncope and orthostatic intolerance. Approximately 95% of patients with classical orthostatic hypotension can be identified by systolic criterion alone.

The relationship between fall in blood pressure (BP) on standing and supine BP before standing up was studied in 75 healthy controls and in 500 patients with diabetes mellitus (DM) using conventional BP measurements. The influences of physiological (sex, age, height) and DM-related factors (type, duration, HbA1c-level, use of insulin, oral antidiabetic and anti-hypertensive medication) on BP-fall were assessed. The effects of using a fixed abnormality threshold and a new supine BP-related abnormality definition on interpretation of the test were determined. Highly significant relationships of BP-fall with supine BP were found in control and DM subjects. Slopes did not differ between these groups. Slopes for systolic BP-fall were steeper in type 1 than in type 2 DM patients. A forward stepwise regression procedure revealed that supine BP (explaining 24% of variance) and HbA1c (explaining 1%) had significant influences on systolic BP-fall. Diastolic supine BP explained 14% of diastolic BP-fall, age 3%, and sex 2%. Only supine BP was thus of practical relevance in explaining BP-fall. Taking supine BP into consideration affected test results: of 74 subjects with an abnormal conventional systolic BP-fall, 10 (13.5%) had been misclassified according to the new method, and 4 additional patients had been misclassified as normal. Classification changes were much larger for diastolic BP-fall (63% of conventionally abnormal results were reclassified as normal), but the range of diastolic BP is smaller than for systolic BP, meaning that the measurement error interferes with its clinical utility.(ABSTRACT TRUNCATED AT 250 WORDS)

In order to study the effects of baseline blood pressure and heart frequency on autonomic function tests, 75 normal subjects (aged 8-96 years) were investigated. Heart rate variability was studied at rest, during deep breathing, following standing up and during a Valsalva manoeuvre. Blood pressure changes were recorded during standing up and during sustained handgrip. Responses were described as ratios and as differences to study the efficacy of both methods. Multiple regression analysis showed that significant relationships with the resting heart rate existed for ratios but not for differences. The blood pressure rise in the sustained handgrip test showed a significant relationship with resting blood pressure regardless of the description method. As expected, relationships with age existed for all four heart rate tests regardless of the description method. The blood pressure responses were not significantly related to age. We advise that heart rate test results should be presented as differences, as this avoids the need for correction for the resting heart rate. Correction for the resting blood pressure improves the accuracy of the standing up blood pressure test. Correction for age remains necessary for heart rate tests but not for blood pressure tests.

Background: Many cardiocirculatory mechanisms are involved in the adaptation to orthostatic stress. While these mechanisms may be impaired in Fontan patients. However, it is yet unclear how Fontan patients, who exhibit a critical fluid balance, respond to orthostatic stress. Angiotensin converting enzyme inhibitors are often prescribed to Fontan patients, but they may negatively influence orthostatic tolerance. Therefore, we evaluated the response to orthostatic stress in pediatric Fontan patients before and after treatment with enalapril. Methods: Thirty-five Fontan patients (aged 14 years) with moderate-good systolic ventricular function without pre-existent enalapril treatment were included. Before and after a three-month enalapril treatment period, the hemodynamic response to head-up tilt test was evaluated by various parameters including cardiac index, blood pressure, cerebral blood flow, aortic stiffness and cardiac autonomous nervous activity. Thirty-four healthy subjects (aged 13 years) served as controls. Results: Fontan patients had a decreased cerebral blood flow and increased aortic stiffness in the supine position compared to controls, while all other factors did not differ. Patients and controls showed a comparable response to head-up tilt test for most parameters. Twenty-seven patients completed the enalapril study with a mean dosage of 0.3±0.1mg/kg/day. Most parameters were unaffected by enalapril, only the percent decrease in cardiac index to tilt was higher after treatment, but the cardiac index during tilt was not lower (3.0L/min/m2 pre-enalapril versus 2.8L/min/m2 after treatment; P = 0.15). Conclusion: Pediatric Fontan patients adequately respond to orthostasis with maintenance of blood pressure and cerebral blood flow and sufficient autonomic response. Enalapril treatment did not alter the response. Clinical trial information: Scientific title: ACE inhibition in Fontan patients: its effect on body fluid regulation (sAFE-study). The Netherlands National Trial Register: Trail NL6415. Registered 2017-07-20. Trial information: https://www.trialregister.nl/trial/6415 [ABSTRACT FROM AUTHOR]

Introduction: In patients with ictal asystole (IA) both cardioinhibition and vasodepression may contribute to syncopal loss of consciousness. We investigated the temporal relationship between onset of asystole and development of syncope in IA, to estimate the frequency with which pacemaker therapy, by preventing severe bradycardia, may diminish syncope risk. Methods: In this retrospective cohort study, we searched video‐EEG databases for individuals with focal seizures and IA (asystole ≥ 3 s preceded by heart rate deceleration) and assessed the durations of asystole and syncope and their temporal relationship. Syncope was evaluated using both video observations (loss of muscle tone) and EEG (generalized slowing/flattening). We assumed that asystole starting ≤3 s before syncope onset, or after syncope began, could not have been the dominant cause. Results: We identified 38 seizures with IA from 29 individuals (17 males; median age: 41 years). Syncope occurred in 22/38 seizures with IA and was more frequent in those with longer IA duration (median duration: 20 [range: 5–32] vs. 5 [range: 3–9] s; p <.001) and those with the patient seated vs. supine (79% vs. 46%; p =.049). IA onset always preceded syncope. In 20/22 seizures (91%), IA preceded syncope by >3 s. Thus, in only two instances was vasodepression rather than cardioinhibition the dominant presumptive syncope triggering mechanism. Conclusions: In IA, cardioinhibition played an important role in most seizure‐induced syncopal events, thereby favoring the potential utility of pacemaker implantation in patients with difficult to suppress IA. [ABSTRACT FROM AUTHOR]

An expert committee was formed to reach consensus on the use of tilt table testing (TTT) in the diagnosis of disorders that may cause transient loss of consciousness (TLOC) and to outline when other provocative cardiovascular autonomic tests are needed. While TTT adds to history taking, it cannot be a substitute for it. An abnormal TTT result is most meaningful if the provoked event is recognised by patients or eyewitnesses as similar to spontaneous events. The minimum requirements to perform TTT are a tilt table, a continuous beat-to-beat blood pressure monitor, at least one ECG lead, protocols for the indications stated below and trained staff. This basic equipment lends itself to the performance of (1) additional provocation tests, such as the active standing test, carotid sinus massage and autonomic function tests; (2) additional measurements, such as video, EEG, transcranial Doppler, NIRS, end-tidal CO2 or neuro-endocrine tests; and (3) tailor-made provocation procedures in those with a specific and consistent trigger of TLOC. TTT and other provocative cardiovascular autonomic tests are indicated if the initial evaluation does not yield a definite or highly likely diagnosis, but raises a suspicion of (1) reflex syncope, (2) the three forms of orthostatic hypotension (OH), i.e. initial, classic and delayed OH, as well as delayed orthostatic blood pressure recovery, (3) postural orthostatic tachycardia syndrome or (4) psychogenic pseudosyncope. A therapeutic indication for TTT is to teach patients with reflex syncope and OH to recognise hypotensive symptoms and to perform physical counter manoeuvres. [ABSTRACT FROM AUTHOR]

Purpose: Vasovagal syncope (VVS) affects more women than men. We determined whether this sex ratio affects tilt table test (TTT) results. Methods: We retrospectively studied TTT outcomes in suspected VVS. TTT consisted of supine rest, a maximum 20 min of head-up tilt without and, if nitroglycerin was needed, a further maximum 20 min after nitroglycerin administration. TTT was terminated if VVS occurred. We used binary logistic regression for the entire TTT and for each phase, with VVS as outcome and age and sex as predictors. Results: TTT provoked vasovagal (pre)syncope in 494 out of 766 tests (64%). The proportion of men and women who fainted during the entire TTT did not differ significantly between the sexes (p = 0.13, corrected for age). A lower proportion of women than men had VVS in the phase without nitroglycerin (odds ratio 0.54; 95% confidence interval 0.37–0.79; p = 0.002, corrected for age), whereas a higher proportion of women than men fainted after nitroglycerin (odds ratio 1.58; 95% confidence interval 1.13–2.21; p = 0.008, corrected for age). These sex differences remained significant after correction for a history of orthostatic versus emotional triggers. The effect of sex on TTT outcome was closely associated with differences of blood pressure change upon tilt-up (lower in men in both TTT phases: without nitroglycerin p = 0.003; with nitroglycerin p = 0.05), but not with heart rate changes. Conclusion: Men were more susceptible to induction of VVS without nitroglycerin and women after it. The unexpected findings may be due to sex-specific pathophysiological differences. [ABSTRACT FROM AUTHOR]

Introduction: Orthostatic hypotension has been associated with impaired cognitive function, but cognitive function during orthostatic hypotension has hardly been studied. We studied the effect of orthostatic hypotension, induced by head-up tilt (HUT), on sustained attention in patients with autonomic failure.Methods: We studied the sustained attention to response task (SART) in the supine position and during HUT in 10 patients with autonomic failure and 10 age-matched and sex-matched controls. To avoid syncope, the tilting angle was tailored to patients to reach a stable systolic blood pressure below 100 mm Hg. Controls were all tilted at an angle of 60°. Cerebral blood flow velocity, blood pressure and heart rate were measured continuously.Results: In patients, systolic blood pressure was 61.4 mm Hg lower during HUT than in the supine position (p<0.001). Patients did not make more SART errors during HUT than in the supine position (-1.3 errors, p=0.3). Controls made 2.3 fewer errors during SART in the HUT position compared to the supine position (p=0.020). SART performance led to an increase in systolic blood pressure (+11.8 mm Hg, p=0.018) and diastolic blood pressure (+5.8 mm Hg, p=0.017) during SART in the HUT position, as well as to a trend towards increased cerebral blood flow velocity (+3.8 m/s, p=0.101).Discussion: Orthostatic hypotension in patients with autonomic failure was not associated with impaired sustained attention. This might partly be explained by the observation that SART performance led to a blood pressure increase. Moreover, the upright position was associated with better performance in controls and, to a lesser extent, also in patients. [ABSTRACT FROM AUTHOR]

It has been shown that transcutaneous electrical neurostimulation (TENS) reduces sympathetic tone. Spinal cord stimulation (SCS) has proven qualities to improve coronary, peripheral, and cerebral blood circulation. Therefore, we postulate that TENS and SCS affect the autonomic nervous system in analogous ways. In this line of thought, cervical application of TENS might be a useful and simple adjunct in the treatment of cerebrovascular disease by improving cerebral blood flow. Experiments were performed in order to assess whether cervical TENS is safe and whether an effect on cerebral blood flow velocity (CBFV) can be shown in healthy subjects. A controlled, non-randomized, phase 1 study was performed with 20 healthy volunteers. Cervical TENS was applied in several frequencies, with and without hyperventilation. Continuous registration of blood pressure, pulse, CBFV (estimated by transcranial Doppler sonography) and end-tidal carbon dioxide concentration was performed. Cervical TENS was well-tolerated by all subjects. Despite small effects on heart rate (HR) and mean arterial blood pressure (MAP), a significant effect on middle cerebral artery (MCA) blood flow velocity was not demonstrated. No effect of age, gender, current or session order on MCA, HR, or MAP was found. TENS did not influence the effect of hyperventilation. In these experiments, application of cervical TENS is proven to be a safe procedure. However, no effects on cerebral blood flow velocity could be detected, perhaps due to the intact cerebral autoregulation in the healthy volunteers. [ABSTRACT FROM AUTHOR]

In autonomic failure (AF), blood pressure (BP) falls upon standing which is commonly ascribed to defective vasoconstriction and excessive pooling. Observations on the amount of pooling in AF are contradictory. We evaluated pooling using strain-gauge plethysmography (SGP) during head-up tilt (HUT) with a parachute harness fixed to the tilt table to avoid muscle tension in the lower limbs and thus to maximise pooling. 23 healthy subjects and 12 patients with AF were tilted for 5 min. BP and calf volume changes, as measured by SGP, were measured continuously. Multiple regression analysis was used to examine the effect of AF on orthostatic fluid shifts after adjustment for potential confounders. Patients did not differ from controls with respect to the increase of calf volume after 5 min HUT. The acute (0–1 min) and the prolonged (1–5 min) phases of calf volume responses to HUT were also similar between patients and controls. No correlation was found between the degree of orthostatic hypotension and the orthostatic calf volume change in AF. In one patient an additional measurement was made before rising from bed in the early morning demonstrating a greater albeit small increase of calf volume upon HUT. Orthostatic fluid shifts at the level of the calf in AF are not augmented during the course of the day despite marked hypotension. However, a small increase of pooling may be expected when the patient first gets out of bed in the morning probably due to the absence of oedema. [ABSTRACT FROM AUTHOR]

Detailed history taking is of paramount importance to establish a reliable diagnosis in patients with transient loss of consciousness. In this article the clinical symptoms and signs of the successive phases of a syncopal episode are reviewed. A failure of the systemic circulation to perfuse the brain sufficiently results in a stereotyped progression of neurological symptoms and signs culminating in loss of consciousness; when transient, this is syncope. Prior to loss of consciousness the affected individual tends to exhibit unclear thinking, followed by fixation of the eyes in the midline and a ‘frozen’ appearance. Narrowing of the field of vision with loss of colour vision (‘greying’ out) and finally a complete loss of vision (hence ‘blacking’ out) occurs. Hearing loss may occur following loss of vision. This process may take as little as ∼7 s in cases of sudden complete circulatory arrest (e.g. abrupt asystole), but in other circumstances it may take longer depending on the rate and depth of cerebral hypoperfusion. Complete loss of consciousness occurs with the ‘turning up’ of the eyeballs. Profound cerebral hypoperfusion may be accompanied by myoclonic jerks. [ABSTRACT FROM PUBLISHER]

Thijs RD, van den Aardweg JG, Reijntjes RH, van Dijk JG, van Lieshout JJ. Contrasting effects of isocapnic and hypocapnic hyperventilation on orthostatic circulatory control. J App! Physiol 105: 1069-1075, 2008. First published July 10, 2008; doi: 10.1 l52/japplphysiol.00003.2008.-The effects of hyperventilation (HV) on mean arterial pressure (MAP) are variable. To identify factors affecting the MAP response to HV, we dissected the effects of hypocapnic HV (HHV) and isocapnic HV (IHV) and evaluated the effects of acute vs. prolonged HHV. In II healthy subjects the cardioand cerebrovascular effects of HHV and JHV vs. normal ventilation were examined for 15 mm in the supine position and also for 15 mm during 60° head-up tilt. The end-tidal CO2 of the HHV condition was set at 15-20 mmHg. With HHV in the supine position, mean cerebral blood flow velocity (mCBFV) declined [95% confidence interval (CI) -43 to -34%], heart rate (HR) increased (95% CI 7 to 16 beats/mm), but MAP did not change (95% CI −1 to 6 mmHg). However, an augmentation of the supine MAP was observed in the last 10 mm of HHV compared with the first 5 mm of HHV (95% Cl 2 to 12 mmHg). During HHV in the tilted position mCBFV declined (95% CI -28 to 12%) and MAP increased (95% CI 3 to II mmHg) without changes in HR. With supine IHV, mCBFV decreased (95% CI 14 to −4%) and MAP increased (95% CI Ito 13 mmHg) without changes in HR. During IHV in the tilted position MAP was further augmented (95% Cl II to 20 mmHg) without changes in CBFV or HR. Preventing hypocapnia during HV resulted in a higher MAP, suggesting two contrasting effects of HV on MAP: hypocapnia causing vasodepression and hyperpnea without hypocapnia acting as a vasopressor. [ABSTRACT FROM AUTHOR]

The pathophysiology of vasovagal syncope (VVS) is reviewed, focusing on hemodynamic aspects. Much more is known about orthostatic than about emotional VVS, probably because the former can be studied using a tilt table test (TTT). Recent advances made it possible to quantify the relative contributions of the three factors that control blood pressure: heart rate (HR), stroke volume (SV) and total peripheral resistance (TPR). Orthostatic VVS starts with venous pooling, reflected in a decrease of SV. This is followed by cardioinhibition (CI), which is a decrease of HR that accelerates the ongoing decrease of BP, making the start of CI a literal as well as fundamental turning point. The role of hormonal and other humoral factors, respiration and of psychological influences is reviewed in short, leading to the conclusion that a multidisciplinary approach to the study of the pathophysiology of VVS may yield new insights. [ABSTRACT FROM AUTHOR]

We report a 20-year- old sportsman with frequent attacks of lightheadedness, chest pain, blurred vision and falls during and shortly after exercise. Cardiac and pulmonal evaluation and routine autonomic function tests were normal apart from a relatively high resting heart rate (70 bpm) compared to endurance-trained men. In view of the relation to exercise, the patient was asked to cycle with maximal effort on an ergometer with continuous blood pressure (BP), heart rate (HR) and electroencephalogram (EEG) registration. Immediately after cessation of exercise a brief hypotensive period (75/45 mmHg) occurred together with sinus tachycardia (180 bpm) during which the patient experienced his typical complaints. We hypothesized that our patient's symptoms were primary related to sympathetic failure. As water drinking has been demonstrated to raise sympathetic activity rapidly, we undertook a second cycling test after ingestion of 1000 mL tap water. Symptoms nor hypotension recurred. Because of the short lasting press or effect and its minimal side effects, we suggest water drinking as simple and possible effective therapy for idiopathic exercise-related syncope. [ABSTRACT FROM AUTHOR]

A 47 year old woman with pure autonomic failure complained of dizziness during emotional stress. Emotional stimuli have not previously been reported to cause hypotension in patients with autonomic failure. In the patient, ambulatory blood pressure recording revealed severe hypotension (50/30 mm Hg) after a stressful event. During a tilt table test, hyperventilation was shown to cause a significant fall of blood pressure. This suggests that emotional stress can induce hypotension, probably through hyperventilation, in subjects with autonomic failure. [ABSTRACT FROM AUTHOR]

While facial autonomic signs are prominent during cluster headache (CH) attacks, cardiovascular autonomic changes have been described in few CH patients. Cardiovascular autonomic function tests (AFT) can be used to assess general autonomic function in CH patients in different stages of the disease. We aimed to assess whether general autonomic function is changed in CH patients during a cluster period. AFT was performed both during a cluster period, but outside an actual attack, and outside a cluster period in 18 patients. Heart rate variability was studied at rest, during deep breathing, after standing up and during a Valsalva manoeuvre. Blood pressure (BP) changes were recorded at rest, during standing up and during sustained handgrip. Measurements during and outside the cluster period were compared using the paired t-test. AFT measurements revealed no significant differences between the two measurements, except for diastolic BP in rest, which was higher during the cluster period [80.3 (SD 12.2) vs. 74.8 (SD 9.0), P = 0.04]. Autonomic dysfunction during a cluster period, but outside an attack, does not include systemic cardiovascular control. [ABSTRACT FROM AUTHOR]