Postural Heart Rate Changes in Young Patients With Vasovagal Marvin S. Medow, PhD,a, b Sana Merchant, MD, a Melissa Suggs, BS, MS,a Courtney Terilli, BSN,a Breige O’Donnell-Smith, MD, a Julian M. Stewart, MD, PhDa,b

BACKGROUND AND OBJECTIVES: Recurrent postural vasovagal syncope (VVS) is caused by transient abstract cerebral hypoperfusion from episodic and bradycardia; diagnosis is made by medical history. VVS contrasts with postural tachycardia syndrome (POTS), defined by chronic daily symptoms of with excessive upright tachycardia without hypotension. POTS has recently been conflated with VVS when excessive tachycardia is succeeded by hypotension during tilt testing. We hypothesize that excessive tachycardia preceding hypotension and bradycardia is part of the vasovagal response during tilt testing of patients with VVS. METHODS: We prospectively performed head-up tilt (HUT) testing on patients with recurrent VVS (n = 47, 17.9 ± 1.1 y), who fainted at least 3 times within the last year, and control subjects (n = 15, 17.1 ± 1.0 y), from age and BMI-matched volunteers and measured pressure, heart rate (HR), cardiac output, total peripheral resistance, and end tidal carbon dioxide. RESULTS: Baseline parameters were the same in both groups. HR (supine versus 5 and 10 minutes HUT) significantly increased in control (65 ± 2.6 vs 83 ± 3.6 vs 85 ± 3.7, P < .001) and patients with VVS (69 ± 1.6 vs 103 ± 2.3 vs 109 ± 2.4, P < .001). HUT in controls maximally increased HR by 20.3 ± 2.9 beats per minute; the increase in patients with VVS of 39.8 ± 2.1 beats per minute was significantly greater (P < .001). An increase in HR of ≥40 beats per minute by 5 and 10 minutes or before faint with HUT, occurred in 26% and 44% of patients with VVS, respectively, but not in controls. CONCLUSIONS: Orthostasis in VVS is accompanied by large increases in HR that should not be construed as POTS. NIH

WHAT IS KNOWN ON THIS SUBJECT: Recurrent Departments of aPediatrics, and bPhysiology, New York Medical College, Valhalla, New York postural vasovagal syncope (VVS) is defi ned by Drs Medow and Stewart were responsible for the design of the experiments, analysis, and episodic loss of consciousness resulting from interpretation of the data, and drafting the original manuscript; Dr Merchant, Ms Suggs, and hypotension. Upright heart rate is not specifi ed Dr O’Donnell-Smith were responsible for collection, assembly, and interpretation of the data; for VVS. Postural tachycardia syndrome (POTS) Mrs Terilli was responsible for subject recruitment, collection, assembly, and interpretation is defi ned by chronic symptoms and excess of the data; and all authors approved the fi nal manuscript as submitted. tachycardia while upright, without hypotension. DOI: 10.1542/peds.2016-3189 The defi nitions are mutually exclusive. Accepted for publication Jan 24, 2017 WHAT THIS STUDY ADDS: Orthostatic heart rate Address correspondence to Marvin S. Medow, PhD, New York Medical College, Center for (HR) increases in many patients with recurrent VVS. Hypotension, 19 Bradhurst Ave, Suite 1600 South, Hawthorne, NY 10532. E-mail: marvin_medow@ Although our patients with VVS did not have POTS, nymc.edu they had signifi cant HR increases when upright at PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275). 5 and10 minutes. HR increases alone do not confer Copyright © 2017 by the American Academy of Pediatrics a diagnosis of POTS. FINANCIAL DISCLOSURE: The authors have indicated they have no fi nancial relationships relevant to this article to disclose. To cite: Medow MS, Merchant S, Suggs M, et al. Postural Heart Rate Changes in Young Patients With Vasovagal Syncope. Pediatrics. 2017;139(4):e20163189

Downloaded from www.aappublications.org/news by guest on September 25, 2021 PEDIATRICS Volume 139 , number 4 , April 2017 :e 20163189 ARTICLE Imposition of an orthostatic stress, form is VVS, in which ∼40% of sought to show that HR increases such as standing up, causes a rapid people experience at least 1 episode alone do not confer a diagnosis downward displacement of ∼500 throughout life, most presenting of POTS. To test this hypothesis, to 700 mL from central stores into initially during adolescence. 17, 18 the following experiments were the splanchnic and lower extremity VVS can be elicited by upright performed. vascular beds. 1 The resulting posture and by emotional stress (eg, excessive (BP) “blood phobia”). 19 VVS, if recurrent, decreases, and if uncompensated is characteristically episodic in METHODS can result in otherwise healthy patients. Unlike (OH) and orthostatic intolerance POTS, which is a form of chronic OI, Subjects (OI). Rapid circulatory compensation VVS is rarely present on a daily basis. for orthostasis occurs via the To test this hypothesis, we performed In VVS due to orthostasis (ie, postural a prospective study over a 3-year sympathetic and parasympathetic VVS), changes in HR and BP can arms of the autonomic nervous period at the Center for Hypotension, occur in the following manner. Upon which is an outpatient facility of the system for appropriate heart rate standing up, there is a brief period (HR) and BP control. 2 – 6 The normal Department of Pediatrics at New during which autonomic adjustments York Medical College, Valhalla, New baroreflex response to decreased BP 20 are initialized. Thereafter, BP York. We recruited VVS subjects involves peripheral vasoconstriction stabilizes and HR increases due and a reflex tachycardia. 7, 8 with a history of recurrent fainting to increased sympathetic activity, who had fainted at least 3 times OI is the inability to tolerate compensatory vasoconstriction within the last year (47 patients upright posture that is relieved by with venous emptying, and vagal [29 female] ranging in age from 12 21–23 recumbency, and is accompanied withdrawal. Usually, BP slowly to 20 years). We also recruited 15 by that include decreases and HR reflexively healthy nonfainting control subjects loss of consciousness (LOC), increases. Symptoms of OI can begin (9 female), ranging in age from 11 to cognitive deficits, loss of vision or within minutes of standing upright, 22 years. hearing, , headache, and if not relieved by recumbency, a fatigue, nausea and abdominal pain, later precipitous fall in BP caused by Patients who fainted were referred sweating, and tremulousness. 9 Two followed by a fall in HR to our center for investigation after common causes of OI in younger results in LOC.11, 19 experiencing at least 3 episodes of patients are vasovagal syncope (VVS) During an upright tilt test of VVS, if fainting within the last 12 months. and postural tachycardia syndrome reflex tachycardia were excessive, Data were analyzed for those 10,11 (POTS). as defined above, an erroneous patients who experienced VVS during Patients with POTS experience diagnosis of POTS might be made.24, 25 our upright tilt procedure, which chronic OI plus excessive tachycardia Such a diagnosis is incorrect on duplicated their vasovagal episodes when upright in the absence of clinical grounds because POTS that occurred in the real world, and hypotension. Symptoms occur daily, is chronic OI, whereas episodic who experienced a pre- and the almost always interfere with work VVS is not. Although a diagnosis postsyncopal postdrome as described and/or school activities, and the of syncope by laboratory testing below. None of the patients with VVS illness must be present for several requires a finding of hypotension, had daily orthostatic symptoms, and months to be diagnosed. 12 – 14 this specifically excludes a diagnosis all were fully functional between Excessive tachycardia in POTS is of POTS. syncopal episodes. We also recruited control subjects from age- and BMI- defined by an increase of HR to >120 We therefore hypothesized that beats per minute during a 10-minute matched volunteers to also undergo excessive tachycardia preceding a 70° head-up tilt (HUT). There were tilt or an increase of >30 beats per hypotension and bradycardia is often minute in adults or an increase of no differences in the ages, weight, part of the vasovagal response, and and BMI between the groups. >40 beats per minute in those can be observed during tilt table 15 younger than 19 years of age. testing of patients diagnosed with Patients with VVS gave a medical Syncope is defined as a “total loss of VVS, who are free of chronic day to history and underwent a physical consciousness due to transient global day symptoms of OI, but do have examination, electrocardiography, cerebral hypoperfusion characterized postural hypotension and therefore , and prolonged by rapid onset, short duration, and do not have POTS. And because electrocardiography monitoring if spontaneous complete recovery,” 16 we have observed orthostatic HR needed to exclude cardiac causes for which is almost always due to increases in many patients with syncope. Control subjects, recruited hypotension. The most common recurrent VVS without POTS, we by online advertising to students at

Downloaded from www.aappublications.org/news by guest on September 25, 2021 2 MEDOW et al our institution, reported no clinical finger photoplethysmograph (FMS, obtained during the baseline period, illness, no OI, and had never fainted. Amsterdam, The Netherlands) on and at 5 and 10 minutes after HUT. the right forefinger or middle finger. All data were collected for 30 seconds The diagnosis of VVS was based The Finometer uses the ModelFlow before and after the time periods. on clinical history and diagnostic algorithm to estimate beat-to-beat features encompassed predisposing Patients with VVS were tilted back to cardiac output (CO) by pulse-wave situations, prodromal symptoms, supine when fainting was imminent; analysis. Before experiments began, physical signs, and postdrome imminent postural VVS was defined ModelFlow CO was calibrated against recovery and symptoms in the by a tilt-induced decrease in MAP an Innocor inert gas rebreathing CO absence of heart disease. 10 In all to <60 mm Hg or a decrease in measurement (Innovision, Denmark) patients, past fainting had been SBP <70 mm Hg associated with performed while the subject was induced by prolonged standing, symptoms of impending LOC, severe supine. Mean arterial pressure (MAP) and prodromal symptoms included lightheadedness, nausea, heat, and was calculated from systolic BP (SBP) pallor, lightheadedness, nausea with diaphoresis. By design all of the and diastolic BP as (SBP + 2*diastolic abdominal discomfort, diaphoresis, a patients who fainted developed BP)/3. We continuously computed feeling of warmth, visual scotomata, a classic vasovagal faint with total peripheral resistance (TPR) or frank loss of vision. After the hypotension followed by bradycardia by dividing MAP by the ModelFlow faint, usually lasted during the tilt. CO averaged over each cardiac less than 30 seconds once supine cycle. All measurements were made and most patients experienced Statistical Methods as previously reported. 26 Signals postsyncopal fatigue. were acquired at 200 samples/s, Baseline data for BP, HR, CO, TPR, Exclusion criteria included any multiplexed, and A/D converted by and end tidal carbon dioxide are infectious or systemic illness, using custom software. shown in absolute units in Table 1. competitive athletic training, recent All tabular results are reported After preparation for study, subjects long-term bed rest, use of nicotine as mean ± SEM, and differences remained awake and supine for 30 t containing products or pregnancy were evaluated by using tests minutes to acclimate. Baseline data within the last year. Previous and repeated measures analysis comprised continuously measured for syncope, if any, was of variance. In addition, HR data HR, BP, CO, and TPR. For purposes discontinued for at least 2 weeks were binned by multiples of 7 to of comparison, we used averaged before participation in this study. No provide for clearer observations data for the 10 minutes immediately subjects were taking neurally active of underlying distributions and for preceding the tilt test to determine or vasoactive drugs at the time of ease of visualization. Significance baseline supine values. After supine P evaluation. was established at < .05. To reduce data collections were complete, interrater variability, all data were All subjects refrained from caffeine subjects were tilted upright to 70°, collected and analyzed by the same and xanthine-containing products and all HUT studies were performed investigator throughout the entire for at least 72 hours before testing. without pharmacologic provocation. study. Results were calculated by All subjects were instructed to fast The duration of upright tilt was using GraphPad Prism version 4.0. for at least 4 hours before testing. 10 minutes in healthy volunteer This study was approved by the controls, whereas patients with Institutional Review Board of New VVS remained upright until fainting RESULTS York Medical College. All subjects 18 was imminent and was not limited There were no differences in the age or older signed an informed consent; to 10 minutes. We have previously of the 2 study groups, comparing those younger than 18 assented to demonstrated that 10 minutes in control subjects (17.1 ± 1.0 y, n = 15) participate and their parent or legal controls is sufficient time for the to patients with VVS (17.9 ± 1.1 y, guardian signed an informed consent. comparison of orthostatic changes n = 47) who had fainted at least in patients with VVS. 27, 28 Also, 3 times within the last year, nor in the Protocol near fainting occurred on average characteristics of the 2 study groups, between 10 and 11 minutes after Subjects arrived at our center at as shown in Table 2. A comparison starting upright tilt in patients with 9:30 AM and were prepared for of HR while supine versus 5 and VVS. Continuously measured HR, study while supine on an electronic 10 minutes 70° HUT revealed a BP, CO, and TPR were recorded for motorized tilt table (Colin Medical significant increase in both control offline analysis. Instruments Corp, San Antonio, (65 ± 2.6 vs 83 ± 3.6 vs 85 ± 3.7, P < TX) with a footboard. Beat-to-beat We compared data for both control .001) and patients with VVS (69 ± 1.6 BP was measured by Finometer subjects and patients with VVS vs 103 ± 2.3 vs 109 ± 2.4, P < .001).

Downloaded from www.aappublications.org/news by guest on September 25, 2021 PEDIATRICS Volume 139 , number 4 , April 2017 3 TABLE 1 Cardiovascular Parameters of Control Subjects and Patients with VVS at Baseline, and 5 and 10 Minutes Following HUT Control, n = 15 VVS, n = 47 Baseline 5 min 10 min Baseline 5 min 10 min HR, beats per minute 65 ± 2.6 83 ± 3.6a 85 ± 3.7a 69 ± 1.6 103 ± 2.3ab 109 ± 2.4ab SBP, mm Hg 115 ± 2.2 120 ± 3.5 119 ± 3.9 113 ± 1.3 115 ± 2.4 97 ± 3.4ab Diastolic BP, mm Hg 58 ± 2.3 63 ± 1.5 63 ± 2.4 63 ± 1.0 68 ± 1.9a 55 ± 2.1a MAP, mm Hg 77 ± 2.1 82 ± 2.5 82 ± 2.6 80 ± 1.1 85 ± 1.7a 69 ± 2.3ab CO, L/min 5.5 ± 0.3 5.0 ± 0.3 5.0 ± 0.3 4.8 ± 0.2 5.3 ± 0.3 4.5 ± 0.2 TPR, mm Hg /L/min 17.9 ± 0.8 19.9 ± 0.9 22.2 ± 0.9a 17.8 ± 0.9 16.8 ± 1.1 16.4 ± 0.7 a P < .05 compared with baseline value. b P < .05 compared with corresponding control value.

TABLE 2 Demographic Characteristics of Control Subjects and Patients with VVS Control Subjects VVS Subjects Number (F/M) 15 (9/6) 47 (29/18) Age, y ± SEM 17.1 ± 1.0 17.9 ± 1.1 Age range, y 11–22 12–20 Height, cm 164.1 ± 3.2 166.7 ± 1.2 Weight, kg 59.5 ± 3.1 64.3 ± 1.4 BMI 21.9 ± 1.1 23.0 ± 0.4 BMI z score 0.26 0.67

FIGURE 1 A scatterplot of the time to near faint in patients with VVS. The average time to near faint (X–) for all 47 patients was 10 minutes, 40 seconds.

HUT in controls maximally increased HR by 20.3 ± 2.9 beats per minute; the increase in patients with VVS of 39.8 ± 2.1 beats per minute was significantly greater than control (P < .001). An increase in HR of >40 beats per minute by 5 and 10 minutes with HUT occurred in 26.7% and 44.4% of patients with VVS, respectively, but did not occur in controls.

Healthy control subjects did not experience symptoms of OI nor did they faint during the 10-minute HUT. The average time to faint for FIGURE 2 the patients with VVS was 640 ± 70 The change in HR (in beats per minute) measured in each control subject (Ο) and patients with VVS seconds (10 minutes, 40 seconds); (⚫) at 5 minutes and 10 minutes after imposition of an HUT. a scatterplot of these times for each patient with VVS is shown in in patients with VVS compared with supine to both 5- and 10-minute Fig 1. A comparison of measured control (P < .05). There was also a values for both controls and patients parameters is shown in Table 1, significant increase in TPR in controls with VVS. evaluated for control subjects and at 10 minutes after tilt compared patients with VVS at baseline, and with baseline (P < .001), and a The range of HR change after HUT 5 and 10 minutes after HUT. These significant decrease at 10 minutes in controls and patients with VVS values were the same for both groups for patients with VVS compared with is shown in Fig 2 at both 5 and 10 while supine (baseline) except that baseline (P < .001). The imposition minutes after HUT. Although average diastolic pressure first significantly of an orthostatic challenge by HUT HR change increased significantly increased at 5 minutes then resulted in the anticipated significant in both groups compared with their significantly decreased at 10 minutes increases in HR (P < .05) comparing respective supine values (P < .001),

Downloaded from www.aappublications.org/news by guest on September 25, 2021 4 MEDOW et al the increase was significantly greater only in the patients with VVS comparing 5 to 10 minutes (Δ 33.3 ± 2.3 vs 39.8 ± 2.1, P < .05). Figure 3 reveals HR changes at 5 and 10 minutes after HUT binned, to show the trend of HR increase. This figure reveals that although the responses at 5 and 10 minutes are somewhat similar for controls where the majority of subjects exhibited a change of HR of ∼20, patients with VVS exhibited a “shift to the left” indicating greatly increased HR increases at 10 minutes. This occurred in a significantly greater percentage (P < .05) of patients with VVS in whom 20 had HR increases of >40 beats per minute after HUT.

DISCUSSION Our findings reveal that HR increases, due to an orthostatic challenge, in young patients with VVS fall into the range associated with POTS in the absence of POTS. Although syncope may be due to cardiac diseases in older patients, 2 the majority of syncope in the young is due to common postural faint, denoted postural VVS. 17, 18 The vasovagal response, the association of vasodilatation with vagal-induced bradycardia, causes hypotension and a transient LOC. In our cohort of patients with VVS, TPR was reduced during FIGURE 3 orthostasis, likely due to impaired Changes in HR (in beats per minute) binned, at 5 minutes (upper panel) and 10 minutes (lower vasoconstriction. Accordingly, this panel) after the imposition of an HUT. HR changes are depicted as their relative frequency (%) of occurrence. led to a decrease of BP by 10 minutes and a reflexive HR increase; that is, a upright positioning similar to that includes characteristic prodromal compensatory tachycardia resulted. 28 observed in POTS during tilt table symptoms, physical signs such as Two common causes of OI in younger testing. However, patients with sweating, pallor, and hypotension, 11,12 patients are VVS and POTS. The postural VVS do not have POTS. And, LOC, and rapid recovery times.10, 19, 23 diagnosis of postural VVS connotes because the range of HR changes Prodromal symptoms with a diagnosis of transient upright with upright tilt is unknown in orthostasis can include progressive hypotension with rapid recovery. young patients with VVS, increases diaphoresis, flushing, sensation of What we have shown is that a large in HR elicited by tilt often result in a percentage of young patients with misdiagnosis of POTS. 24, 25 warmth, nausea, abdominal pain, postural VVS and characteristic visual blurring/loss, followed by terminal hypotension also have a The diagnosis of VVS is largely temporary LOC resulting from sinus tachycardia in response to on the basis of clinical history that hypotension and a characteristic

Downloaded from www.aappublications.org/news by guest on September 25, 2021 PEDIATRICS Volume 139 , number 4 , April 2017 5 pallor. Postdromal fatigue is frequent minutes. In fact, >40% had increases subjects with no previous history and may last for minutes to hours. of more than 40 beats per minute, of fainting 31; however, none of our Most importantly, VVS usually occurs and in 2, their HR increased by >70 control subjects fainted. Findings in without day-to-day symptoms. 10 beats per minute. And all of these patients who faint recurrently may In contrast, POTS is historically HR increases in patients with VVS not be generalizable to those who chronic, not episodic, and there is no were recorded before the onset of faint less frequently, and to subjects orthostatic LOC because there is no sudden hypotension and bradycardia. with competitive athletic training and hypotension. However, many patients Although none of these patients recent long-term bed rest. with POTS experience VVS, but had POTS and all changes in HR presyncope is much more common. 10 were recorded before they became syncopal, it is important to note that If there is hypotension and LOC with ABBREVIATIONS orthostasis, then syncope rather than some 30% of subjects with POTS also 29,30 POTS should be diagnosed by such an experience syncope. BP: blood pressure episode, provided there is rapid onset Thus, the excessive tachycardia CO: cardiac output of the episode; it is brief and recovery preceding hypotension and HR: heart rate occurs spontaneously. 11, 13 bradycardia is often part of the HUT: head-up tilt LOC: loss of consciousness In the current study, on the basis of vasovagal response in young patients, MAP: mean arterial pressure clinical criteria, all of our patients as described here in our cohort OH: orthostatic hypotension had VVS with hypotension and of patients with VVS. Therefore, OI: orthostatic intolerance transient LOC, none had chronic OI, a significant increase in HR and POTS: postural tachycardia and none had day to day symptoms. symptoms with orthostasis alone syndrome Therefore, they did not have POTS. does not confer a diagnosis of POTS. SBP: systolic blood pressure Our patients with VVS had significant All of the data were collected during TPR: total peripheral resistance increases in HR compared with HUT-table testing, which can result VVS: vasovagal syncope supine when upright at both 5 and 10 in syncope in up to 15% of healthy

FUNDING: Funding was provided by grants RO1 HL 112736 and RO1 HL 074873 from the National Heart, Lung, and Blood Institute, and R21 NS 094644 from the National Institute of Neurologic Disorders and Stroke. Funded by the National Institutes of Health (NIH). POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential confl icts of interest to disclose. COMPANION PAPER: A companion to this article can be found online at www. pediatrics. org/ cgi/ doi/ 10. 1542/peds. 2016-4161.

REFERENCES 1. Sheriff DD, Nådland IH, Toska K. Role after heart transplantation: lack response to standing. J Appl Physiol. of sympathetic responses on the of parasympathetic reinnervation. 1980;49(5):809–814 hemodynamic consequences of rapid J Heart Lung Transplant. changes in posture in humans. J Appl 1999;18(5):399–406 9. Low PA, Opfer-Gehrking TL, McPhee Physiol (1985). 2010;108(3):523–532 BR, et al. Prospective evaluation of 5. Toda N, Ayajiki K, Okamura T. Cerebral clinical characteristics of orthostatic 2. Brack KE, Coote JH, Ng GA. blood fl ow regulation by nitric oxide: hypotension. Mayo Clin Proc. stimulation inhibits the increase in recent advances. Pharmacol Rev. 1995;70(7):617–622 Ca2+ transient and left ventricular 2009;61(1):62–97 force caused by sympathetic nerve 10. Sheldon RS, Grubb BP II, Olshansky B, stimulation but has no direct effects 6. Von Euler US. Identifi cation of et al. 2015 heart rhythm society expert alone–epicardial Ca2+ fl uorescence the sympathomimetic ergone in consensus statement on the diagnosis studies using fura-2 AM in the isolated adrenergic nerves of cattle (sympathin and treatment of postural tachycardia innervated beating rabbit heart. Exp N) with levonoradrenaline. Acta Physiol syndrome, inappropriate sinus Physiol. 2010;95(1):80–92 Scand. 1948;16:63–74 tachycardia, and vasovagal syncope. Heart Rhythm. 2015;12(6):e41–e63 3. Macarthur H, Wilken GH, Westfall 7. Borst C, Wieling W, van Brederode TC, Kolo LL. Neuronal and non- JF, Hond A, de Rijk LG, Dunning AJ. 11. Stewart JM. Common syndromes of neuronal modulation of sympathetic Mechanisms of initial heart rate orthostatic intolerance. Pediatrics. neurovascular transmission. Acta response to postural change. Am J 2013;131(5):968–980 Physiol (Oxf). 2011;203(1):37–45 Physiol. 1982;243(5):H676–H681 12. Medow MS, Stewart JM, Sanyal S, 4. Raczak G, La Rovere MT, Mortara A, 8. Ewing DJ, Hume L, Campbell IW, Murray Mumtaz A, Sica D, Frishman WH. et al. Arterial barorefl ex modulation A, Neilson JM, Clarke BF. Autonomic Pathophysiology, diagnosis, and of heart rate in patients early mechanisms in the initial heart rate treatment of orthostatic hypotension

Downloaded from www.aappublications.org/news by guest on September 25, 2021 6 MEDOW et al and vasovagal syncope. Cardiol Rev. 19. Brignole M, Alboni P, Benditt D, et al; 26. Stewart JM, Suggs M, Merchant S, 2008;16(1):4–20 Task Force on Syncope, European et al. Postsynaptic α1-adrenergic 13. Stewart JM. Chronic orthostatic Society of Cardiology. Task force vasoconstriction is impaired in intolerance and the postural on syncope, European Society young patients with vasovagal tachycardia syndrome (POTS). of Cardiology. Part 1. The initial syncope and is corrected by nitric J Pediatr. 2004;145(6):725–730 evaluation of patients with oxide synthase inhibition. Circ syncope. Europace. 2001;3(4): Arrhythm Electrophysiol. 2016; 14. Schondorf R, Low PA. Idiopathic 253–260 9(8):9 postural orthostatic tachycardia syndrome: an attenuated form of 20. Wieling W, Krediet CT, van Dijk N, 27. Stewart JM, McLeod KJ, Sanyal acute pandysautonomia? . Linzer M, Tschakovsky ME. Initial S, Herzberg G, Montgomery LD. 1993;43(1):132–137 orthostatic hypotension: review of a Relation of postural vasovagal forgotten condition. Clin Sci (Lond). syncope to splanchnic hypervolemia 15. Singer W, Sletten DM, Opfer-Gehrking 2007;112(3):157–165 in adolescents. Circulation. TL, Brands CK, Fischer PR, Low PA. 2004;110(17):2575–2581 Postural tachycardia in children and 21. Stewart JM. Mechanisms of adolescents: what is abnormal? sympathetic regulation in orthostatic 28. Taneja I, Medow MS, Glover JL, J Pediatr. 2012;160(2):222–226 intolerance. J Appl Physiol (1985). Raghunath NK, Stewart JM. Increased 2012;113(10):1659–1668 vasoconstriction predisposes to 16. Gowers WR. A lecture on vagal hyperpnea and postural faint. and vasovagal attacks. Lancet. 22. Jardine DL, Melton IC, Crozier IG, Am J Physiol Heart Circ Physiol. 1907;173:716–724 et al. Decrease in cardiac output and muscle sympathetic activity during 2008;295(1):H372–H381 17. Ganzeboom KS, Colman N, Reitsma vasovagal syncope. Am J Physiol 29. Benarroch EE. Postural tachycardia JB, Shen WK, Wieling W. Prevalence Heart Circ Physiol. 2002;282(5): syndrome: a heterogeneous and and triggers of syncope in H1804–H1809 multifactorial disorder. Mayo Clin Proc. medical students. Am J Cardiol. 2012;87(12):1214–1225 2003;91(8):1006–1008, A8 23. Hainsworth R. Pathophysiology of syncope. Clin Auton Res. 2004; 30. Mathias CJ, Low DA, Iodice V, Owens 18. Moya A, Sutton R, Ammirati F, et al; 14(suppl 1):18–24 AP, Kirbis M, Grahame R. Postural Task Force for the Diagnosis and tachycardia syndrome--current Management of Syncope; European 24. Nwazue VC, Raj SR. Confounders experience and concepts. Nat Rev Society of Cardiology (ESC); European of vasovagal syncope: postural Neurol. 2011;8(1):22–34 Heart Rhythm Association (EHRA); tachycardia syndrome. Cardiol Clin. Heart Failure Association (HFA); Heart 2013;31(1):101–109 31. Petersen ME, Williams TR, Gordon Rhythm Society (HRS). Guidelines for 25. Stewart JM. Postural tachycardia C, Chamberlain-Webber R, Sutton R. the diagnosis and management of syndrome and refl ex syncope: The normal response to prolonged syncope (version 2009). Eur Heart J. similarities and differences. J Pediatr. passive head up tilt testing. Heart. 2009;30(21):2631–2671 2009;154(4):481–485 2000;84(5):509–514

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Downloaded from www.aappublications.org/news by guest on September 25, 2021 Postural Heart Rate Changes in Young Patients With Vasovagal Syncope Marvin S. Medow, Sana Merchant, Melissa Suggs, Courtney Terilli, Breige O'Donnell-Smith and Julian M. Stewart Pediatrics 2017;139; DOI: 10.1542/peds.2016-3189 originally published online March 28, 2017;

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