Juan C. Guzman

Endothelial function in patients with migraine during the interictal period.

Objectives.—The aim of this study is to evaluate endothelial function in migraineur subjects during the asymptomatic period.

Stroke and ventricular arrhythmias

Electrocardiographic abnormalities and cardiac arrhythmias are commonly noted after acute stroke. Risk of malignant ventricular arrhythmias is increased after a stroke and is associated with sudden cardiac death. Autonomic imbalance modulated by direct injury to neurogenic structures and enhanced by catecholamine storm can lead to myocardial damage and arrhythmogenesis. Experimental and clinical evidence suggests that insular cortex infarcts play a key role in autonomic dysregulation that lead to arrhythmias in the acute setting. Management of ventricular arrhythmias associated with acute stroke should focus on continuous cardiac monitoring, drug therapy, and electrolyte correction. Further research is needed to identify neurological structures involved in autonomic control and risk factors for ventricular arrhythmogenesis after acute stroke.

Usefulness of the Calgary Syncope Symptom Score for the diagnosis of vasovagal syncope in the elderly

AIMS The Calgary Syncope Symptom Score (CSSS) has been validated as a simple point score of historical features with high sensitivity and specificity for the diagnosis of vasovagal syncope (VVS) in younger populations without evidence of structural heart disease. Our purpose was to evaluate the performance of the CSSS in an elderly population with suspected VVS. METHODS AND RESULTS Hundred and eighty patients of ≥60 years of age (mean 73.4 ± 7.8) with suspected clinical diagnosis of VVS were studied. The CSSS (VVS score ≥-2) was calculated in all patients prior to undergoing head-up tilt test (HUT). A standardized HUT protocol with active nitroglycerin phase was used to reproduce syncopal symptoms as gold standard for diagnosis of VVS. Hundred and forty patients had positive HUT response. Eighty-three patients (42.3%) had CSSS ≥-2 suggesting a diagnosis of VVS. The Calgary Syncope Symptom Score sensitivity was 0.51 [95% confidence interval (CI) 0.42-0.59] and specificity 0.73 (95% CI 0.52-0.85) with positive predictive value and negative predictive value of 0.87 (95% CI 0.77-0.93) and 0.30 (95% CI 0.21-0.40), respectively. One hundred (55.6%) patients had previous history of mild cardiovascular disease documented during assessment prior to HUT. In this population sensitivity and specificity was markedly reduced: 0.13 (95% CI 0.05-0.29) and 0.70 (95% CI 0.57-0.80), respectively. CONCLUSION The CSSS has a lower sensitivity and specificity in an elderly population presenting with syncope compared to previously validated data in young adults, particularly in elderly patients with previous history of mild cardiovascular disease. A modified CSSS may be needed to improve specificity and sensitivity in this population.

Sex differences in cardiac autonomic function of depressed young adults

BACKGROUND Cardiac autonomic dysfunction has been proposed as an important contributing factor to the increased cardiovascular risk observed in major depression (MDD). However, the evidence regarding alterations in heart rate variability (HRV) in otherwise healthy depressed subjects has been inconclusive. METHODS A case-control study in 50 treatment-naïve young adults with a first MDD episode without comorbid psychiatric disorders and 50 healthy control subjects was conducted. Time- and frequency-domain indexes of HRV were determined at baseline supine and after 5-min of orthostatic stress at 60°. RESULTS There were no significant differences in the time- or frequency-domain variables of HRV between depressed patients and controls. However, a random-effect ANOVA model showed that during orthostatic stress depressed men had a reduced HRV and decreased parasympathetic activity compared to control subjects, while no differences were found between depressed women and controls. CONCLUSION These results suggest a sex-dependent relationship between major depression and cardiac autonomic dysfunction and provide one potential explanation for sex differences in the association of depressive symptoms with cardiovascular morbidity.

Treatment of Neurally Mediated Reflex Syncope

Neurally mediated reflex syncope, more commonly known as vasovagal syncope (VVS), remains the most common cause of transient loss of consciousness and syncope in all age groups. Most evidence assessing treatment of VVS derived from randomized clinical trials is limited. Multiple modalities of both nonpharmacologic and pharmacologic strategies have been tested, with conflicting results. The treatment of VVS has been directed toward interventions that interrupt the reflex response at different levels, hypothetically preventing the onset of syncope. This article reviews the available evidence of the different nonpharmacologic and pharmacologic therapies available for the treatment of recurrent VVS.

The effect of sham feeding on neurocardiac regulation in healthy human volunteers

BACKGROUND Distension and electrical stimuli in the esophagus alter heart rate variability (HRV) consistent with activation of vagal afferent and efferent pathways. Sham feeding stimulates gastric acid secretion by means of vagal efferent pathways. It is not known, however, whether activation of vagal efferent pathways is organ- or stimulus-specific. OBJECTIVE To test the hypothesis that sham feeding increases the high frequency (HF) component of HRV, indicating increased neurocardiac vagal activity in association with the known, vagally mediated, increase in gastric acid secretion. METHODS Continuous electrocardiography recordings were obtained in 12 healthy, semirecumbent subjects during consecutive 45 min baseline, 20 min sham feeding (standard hamburger meal) and 45 min recovery periods. The R-R intervals and beat-to-beat heart rate signal were determined from digitized electrocardiography recordings; power spectra were computed from the heart rate signal to determine sympathetic (low frequency [LF]) and vagal (HF) components of HRV. RESULTS Heart rate increased during sham feeding (median 70.8 beats/min, 95% CI 66.0 to 77.6; P<0.001), compared with baseline (63.6, 95% CI 60.8 to 70.0) and returned to baseline levels within 45 min. Sham feeding increased the LF to HF area ratio (median: 1.55, 95% C.I 1.28 to 1.77; P<0.021, compared with baseline (1.29, 95% CI 1.05 to 1.46); this increase in LF to HF area ratio was associated with a decrease in the HF component of HRV. CONCLUSIONS Sham feeding produces a reversible increase in heart rate that is attributable to a decrease in neurocardiac parasympathetic activity despite its known ability to increase vagally mediated gastric acid secretion. These findings suggest that concurrent changes in cardiac and gastric function are modulated independently by vagal efferent fibres and that vagally mediated changes in organ function are stimulus- and organ-specific.

To tilt or not to tilt: what is the question?

Syncope in children and adolescents is common, with 15 % estimated to have had at least one syncopal episode by age 18 [15, 16]. The most frequent cause of fainting in this age group is vasovagal syncope [7, 15, 16]. Although the clinical presentation of vasovagal syncope is frequently typical and the disorder is benign, further testing is sometimes necessary to confirm the diagnosis. Not infrequently, children with recurrent syncope are incorrectly diagnosed as having epilepsy. The introduction of head-up tilt testing (HUT), by Kenny and Sutton in 1986, as a diagnostic procedure in patients with unexplained syncope, improved our ability to diagnose vasovagal syncope [10]. Unfortunately, there is still no general consensus regarding the best HUT protocol and studies using different protocols report a wide range of diagnostic accuracy and specificity [4]. Few studies have assessed the usefulness of HUT in the pediatric population.

The role of Emergency Medical Services in the assessment and management of syncope

Syncope is defined as a transient loss of consciousness and postural tone followed by prompt spontaneous recovery and is caused by a transient reduction in blood flow to the reticular activating system of the brain. Syncope is a common reason for calling the Emergency Medical Services (EMS) and accounts for 1–1.5% of emergency department (ED) visits with 13–83% of these resulting in hospital admission [1,2]. The identification of patients at high risk and differentiating these from thosewhomay have amore benign etiology remain a challenge for physicians assessing syncopal patients in the ED [2]. The EMS are often the first to arrive at the scene of a syncopal patient and are involved in the preliminary assessment of these patients and offer initial medical assistance. The EMS are therefore oftenwell placed to gain valuable clinical informationwhichmay aid in determining the cause of syncope. However, the assessment findings of the EMS may not always be taken into account in determining the potential cause of syncope. The value of this initial first response assessment, and the impact it has on decisionmaking in the EDhave not been previously evaluated. This retrospective study was aimed to analyze the findings of the EMS and to determine their contribution in the management of syncopal patients. Three blinded investigators reviewed the electronic charts of all consecutive patients presenting with syncope to the ED at three academic hospitals from the Hamilton Health Sciences Corporation, Ontario, Canada, over a three month period. The time of arrival of the EMS, their initial assessment findings and their relationship with the final diagnosis were evaluated. A total of 23,701 patients were seen in the ED during the screening period. Syncope was the reason for presentation in 343 patients (1.44%). Of these, 226 patients (66%) were assessed by the EMS with an arrival time of (mean±SD) 7±5.8 min. The mean age was 69±22 years with 65% being female. The EMS recorded abnormal findings in 56/226 patients (25%) with bradycardia (b50 bpm) reported in 6 patients (11%), tachycardia (N100 bpm) in 18 patients (32%), hypotension (b90/50 mm Hg) in 18 patients (32%), hypertension (N150/90 mm Hg) in 21 patients (37%) and loss of consciousness in 4 patients (7%). The proportion of patients in whom a discharge diagnosis was achieved in the ED and the proportion of patients subsequently diagnosed with vasovagal syncope following review of their electronic charts are summarized in Table 1. There was no significant difference in the number of patients in whom a discharge diagnosis was reached by ED physicians, irrespective of whether they had been assessed by the EMS or not. All patients who had been assessed by the EMS with a tentative diagnosis of vasovagal syncope were discharged home avoiding hospital admission. Following review of the electronic charts by the study investigators, the number of patients diagnosed with vasovagal syncope was 67% higher in those patients assessed by the EMS. Despite the limitations inherent to a retrospective analysis, the results from the present study were striking and strongly suggest that the EMS assessment of syncopal patients failed to have any impact on the number of patients in whom a discharge diagnosis was reached and implies that this assessment may often be overlooked by busy ED physicians. Our chart review indicates that the proportion of patients diagnosed with vasovagal syncope was 1.7 fold higher in those assessed by the EMS compared to those patients not assessed. This finding suggests that the EMS assessment may provide invaluable clinical information which if taken into consideration may have aided ED physicians in reaching a diagnosis of vasovagal syncope, thus potentially avoiding unnecessary hospital admissions and their associated costs [3]. We postulate that this is likely to be related to the rapid assessment by the EMS of syncopal patients in close proximity to the episode where hemodynamic and rhythm disturbances are most likely to be apparent. Given the transient episodic nature of syncope it is not surprising that relevant clinical findings at the time of an event may have resolved by the time patients are evaluated in the ED. The findings of this brief report highlight the importance of early assessment by the EMS, and suggest that if their findings are taken into account as part of the overall assessment of syncopal patients presenting to the ED, a significant proportion may be easily stratified as low risk with vasovagal syncope, potentially reducing unnecessary hospital admissions and costs. The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology (Shewan and Coats, 2010; 144:1–2).

Cardiovascular testing in patients with postural tachycardia syndrome and Ehlers-Danlos type III: authors' response

We appreciate the letter by Drs. Blitshteyn and Fries [1] in response to our recent research letter describing the cardiovascular profile in a small sample of individuals with postural orthostatic tachycardia syndrome (POTS) and Ehlers–Danlos Syndrome type III (EDSIII) compared to sexand age-matched controls [2]. We agree that there is much work remaining to be conducted to comprehensively examine potential differences between POTS ? EDSIII and controls and that there is considerable benefit to be gained from assessments of the cardiovascular system under stress. However, we assert that due to the lack of prior examinations in this field, there is still benefit to our resting assessments, as the symptom of orthostatic intolerance does not necessarily stem from a similarly dynamic physiological cause. In our study [2], we chose to assess arterial stiffness, as measured by carotidfemoral pulse wave velocity (cfPWV), as a static index of large artery viscoelastic behaviour. More than simply a marker of atherosclerosis, cfPWV estimates the pressurebuffering capacity of the arterial wall by measuring the speed of a forward pulse wave through large conduit arteries. High levels of arterial stiffness have serious consequences to central pressure augmentation, left ventricular afterload and end-organ damage [3]; however, the consequences of severely low levels of arterial stiffness are completely unknown. With the understanding that individuals with POTS ? EDSIII are generally free from earlyonset atherosclerosis, we hypothesized that these individuals might, in fact, be at the opposite end of the stiffness spectrum, with systemically compliant arteries contributing to poor hemodynamic management during orthostatic challenge. As recently suggested by Blitshteyn and Fries [4], our hypothesis is in line with the theory that reduced preload may explain exercise intolerance in the POTS population, potentially secondary to altered control of the peripheral arterial system caused by pathologically increased arterial compliance—although our data do not support this theory. While we further hypothesized that reduced physical activity may have confounded our ability to detect reduced arterial stiffness in individuals with POTS, we do not suggest that reduced habitual activity is a potential cause of the symptomology of POTS, as the etiology is likely related to the dysautonomia central to the condition. While cfPWV would also likely change with varying degrees of orthostatic challenge, measurement of cfPWV during tilt might also be confounded by autonomic reflexes, the complex relationship between cfPWV and heart rate or gravity itself, leading to complex interpretation. However, other cardiovascular parameters may reveal unique information during orthostatic stress. In fact, relatively novel indices of regional cardiac energetics (such as left ventricular rotational mechanics, as presented in our study [2]) have recently been demonstrated to be regulated by different myocardial wall mechanics at rest versus during exercise, potentially revealing new information about central haemodynamics [5]. With regards to the potential role of adrenergic antibodies in orthostatic intolerance, we & Maureen J. MacDonald macdonmj@mcmaster.ca

Arterial stiffness characterization in patients with Postural Orthostatic Tachycardia Syndrome and Ehlers-Danlos Syndrome Type 3

Background: Patients with postural tachycardia syndrome (POTS) oftenhave lowblood volumeand are advised to increase sodium intake to restore intravascular volume. However, the benefit of a high-sodium diet has not been systematically examined in POTS. Methods: We studied 12 female POTS patients (mean± SD; 34 ±9 years, BMI 23 ± 3 kg/m) and 8 female healthy control subjects (HC; 29 ± 4 years, BMI 24 ± 3 kg/m) randomly assigned to 6 days of low (LS; 10 mEq/day) or high sodium (HS; 300 mEq/day) diet and then crossed-over. Procedures performed on Day 6 included: posture study, plasma volume (PV) measurement by I-albumin, maximal oxygen consumption (VO2max) using a supine bicycle ergometer, and cardiac output (CO) and stroke volume (SV) assessments by the inert gases rebreathing technique in the flat and tilted head-up positions. Results: PV was significantly higher after HS than LS in POTS patients (PV: 2706 ± 110 ml vs. 2390 ± 89 ml, P b 0.001). Orthostatic tachycardia was reduced in POTS with HS (49 ± 16 bpm vs. 63 ±11 bpm, P = 0.001), but still increased compared with HC (49 ± 16 bpm vs. 23 ± 11 bpm, P = 0.001). Upright SV was significantly higher after HS than LS in POTS (35 ± 11ml vs. 25 ± 7ml, P = 0.023) but remained lower than HC (35 ± 11 ml vs. 52 ± 16 ml, P = 0.033). Upright CO and VO2max did not differ significantly between POTS for either LS or HS. Conclusions: HS diet caused a reduction in orthostatic tachycardia, and increased PV and SV in POTS patients. Patients with POTS experienced improvement in their condition in association with higher sodium intake, but did not ‘normalize’ compared with HC.