Orthostatic Tachycardia-Hypotensive Syndrome: A Novel Form of Orthostatic Intolerance in the Young

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Numan, Ahmed M Eldokla, Ian J Butler This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6568428/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 10 Jul, 2025 Read the published version in Pediatric Cardiology → Version 1 posted 7 You are reading this latest preprint version Abstract Purpose: Postural orthostatic tachycardia syndrome (POTS) and neurocardiogenic syncope (NCS) are frequently observed causes of orthostatic intolerance (OI). Clinical experience reveals patients with overlapping symptoms of both. This observation led to the hypothesis of orthostatic tachycardia hypotensive syndrome (OTHS), a distinct OI variant, combines POTS and NCS features. This study aims to define and characterize it. Methods: A retrospective chart review of patients presenting with OI and underwent head up tilt (HUT) between 2014 and 2020. We extracted demographic data, findings during HUT including heart rate (HR), systolic blood pressure (SBP), stroke volume (SV), near infrared spectroscopy (NIRS), syncope, cardiac asystole, and convulsions. We divided the subjects into three groups: POTS, NCS, and OTHS. Results: We included patients with POTS (n = 90), NCS (n = 86), and OTHS (n = 101). POTS patients showed higher HR (baseline, recovery, min) vs. OTHS (p = 0.047, < 0.001, < 0.001), while OTHS patients had higher HR (5min, 10min, min, max) vs. NCS (p = 0.047, < 0.001, < 0.001, < 0.001). Minimum SBP was higher in POTS vs. OTHS (p < 0.001), and OTHS patients had higher SV (baseline, recovery, min, max) vs. POTS (p = 0.006, < 0.001, 0.002, 0.005). Patients with POTS have lower baseline NIRS compared to NCS and OTHS (p = < 0.032, < 0.011). Asystole was significantly more frequent in the NCS group (n = 24, 27.9%) than in the OTHS group (n = 9, 8.9%), with p 30–40 bpm followed by hypotension leading to syncope. Postural orthostatic tachycardia syndrome (POTS) neurocardiogenic syncope (NCS) orthostatic intolerance (OI) orthostatic tachycardia hypotensive syndrome (OTHS) Autonomic testing Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction Orthostatic intolerance (OI) is characterized by the impaired ability to maintain an upright posture, resulting in symptoms or clinical signs that are alleviated by assuming a supine position. This condition must persist for a minimum of three months to meet diagnostic criteria. Symptoms of orthostatic intolerance may include lightheadedness, dizziness, visual disturbances (such as blurring or fading), generalized weakness, fatigue, palpitations, cognitive dysfunction, anxiety, nausea, dyspnea, and headache. 1 Orthostatic intolerance (OI) due to autonomic nervous system dysfunction has become increasingly recognized by healthcare professionals, particularly following the COVID-19 pandemic and related vaccinations. This condition has seen a rise in incidence and prevalence, especially among younger individuals. 2 – 4 Postural orthostatic tachycardia syndrome (POTS) and neurocardiogenic syncope (NCS) are two common clinical entities in children and adolescents with symptoms of OI and are considered to have different physiologic and clinical manifestations. 1 The Heart Rhythm Society (HRS) in 2015 published a consensus statement defining POTS as a constellation of symptoms that include, but are not limited to, palpitations, presyncope, mental clouding, nausea, anxiety, fatigue, blurry vision, and dyspnea, after assuming an upright position, improve with recumbency and must persist for at least 3–6 months. These symptoms are associated with an increase of the heart rate (HR) of more than 40 bpm (below 20 years of age) or 30 bpm (if > 20 years) or HR more than 120 bpm within 10 minutes of upright posture with no significant decrease of blood pressure. 5 NCS is defined as a sudden transient loss of consciousness (LOC) resulting from global cerebral hypoperfusion, associated with loss of postural tone with a decrease of 20 mmHg in systolic blood pressure (SBP) or 10 mmHg in diastolic blood pressure (DBP) upon upright posture but without a significant change in HR; which is followed by rapid and spontaneous supine position recovery 5 Subsequently the American College of Cardiology (ACC) and American Heart Association (AHA) issued a similar consensus statement in 2017. 6 Despite these two clear definitions, several investigators have reported an overlap between these two clinical entities. 7 8, 9 This observation of diagnostic overlap between POTS and NCS may have clinical implications in the pathophysiological understanding of their manifestations, pharmacological and clinical management, and medical records documentation. In this study, we aim to re-evaluate the physiological parameters in patients who were referred to our center for symptoms of orthostatic intolerance and autonomic dysfunction and to categorize them into POTS, NCS and a third proposed group of patients with mixed findings. We will define the third group of patients as having Orthostatic Tachycardia Hypotensive Syndrome (OTHS). We will examine the physiology of OTHS and compare it to POTS and NCS. Methods We reviewed our cohort of subjects who presented with OI symptoms for at least 3 months and underwent head up tilt table test (HUTT) during the study period of 2014–2020. HUTT in our center consists of 10 minutes of supine, 30 minutes of head up and 10 minutes of supine position recovery phase. During the three phases of HUTT, we obtain: continuous beat-beat systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), cardiac stroke volume (SV), obtained by trans-thoracic impedance method, and cerebral near infra-red spectroscopy (NIRS) as a surrogate for cerebral perfusion. 10 HUTT was performed in a quiet room with ambient temperature of 22° to 24°C. No medication or intravenous lines were utilized during the test. All patient parameters were archived digitally. 11 , 12 We divided the subjects into three groups: group 1, patients who met HRS and ACC diagnostic criteria of POTS, group 2, patients who met the HRS and ACC diagnostic criteria for NCS and group 3, patients who had mixed criteria of both POTS and NCS which we called OTHS. We recorded patients’ demographics (age, sex) and findings during HUTT including HR at the baseline before HUTT, during HUTT at 5 min and 10 min, 5 min after HUTT (recovery), and minimum and maximum HR; SBP at baseline before HUTT, during HUTT at 5 min and 10 min, 5 min after HUTT (recovery), and minimum, and maximum SBP; SV at baseline before HUTT, during HUTT at 5 min and 10 min, at 5 min after HUTT (recovery), and minimum, and maximum SV; and lastly NIRS at baseline and the minimum value. Clinical observations of cardiac asystole and convulsions during HUTT were documented in each group. Statistical analysis: All statistical analyses were performed with Statistical Package for the Social Sciences (SPSS version 25.0; IBM Corporation, Armonk, NY, USA). Categorical variables (e.g., gender and age groups) were presented as frequencies and percentages (%), while continuous variables (i.e., hemodynamics) were summarized as median and interquartile range (given that they were not normally distributed, as tested by Kolmogorov Smirnov test). Differences between categorical variables across the study groups were tested for statistical significance by the Chi-square test or Fisher’s exact test (if > 20% of expected values were less than 5). The hemodynamics variables were tested for differences between and within the study groups. Differences between study groups were tested for statistical significance by Mann-Whitney test or Kruskal Wallis test (p-values were adjusted by the Bonferroni correction for multiple comparisons). Within-group differences were tested for statistical significance using Friedman test. Survival functions were plotted as Kaplan– Meier curves and compared for statistical significance using the log- rank test. All p-values < 0.05 were considered statistically significant. All graphs were performed with GraphPad Prism (version 8.0.1. for Windows, GraphPad Software, La Jolla California USA). Results Patient characteristics (Table 1) We included patients with POTS (n = 90), NCS (n = 86), and OTHS (n = 101). Fifty-nine (64.1%) of patients with POTS were female and 33 (35.9%) were male, age ranging from 7 to 23 years, with a median of 15 years. Sixty-four (74.4%) of NCS patients were female and 22 (25.6%) were male, age ranging from 6.6 to 22 years, with a median of 15 years. Eighty-two (81.2%) of OTHS patients were female and 19 (18.8%) were male, age ranging from 9.1-21.7 years, with a median of 16 years. Autonomic testing results Heart rate (Table 1, Fig 1a) The median and interquartile range (IQR) of HR at baseline before HUTT, at 5 min &10 min of head up HUTT, at 5 min after HUTT (recovery), and minimum and maximum values in patients with POTS, NCS, and OTHS are presented in table 1. Patients with POTS have statistically significantly higher HR at baseline, at 5 min & 10 min of head up tilt, at recovery, and higher minimum and maximum values compared to those with NCS (p = 0.008, < 0.001, < 0.001, < 0.001, < 0.001, < 0.001, respectively). Patients with POTS have statistically significantly higher HR at baseline and recovery, and higher minimum value compared to those OTHS (p = 0.047, < 0.001, < 0.001, respectively). However, there was no statistically significant difference between the 2 groups at 5min, 10 min, and maximum HR changes during HUTT (p = 0.180, 1.00, 1.00, respectively). There was no statistically significant difference in HR at baseline and recovery between patients with NCS and OTHS (p = 1.00, 1.00, respectively). However, the HR at 5 min & 10 min of head up tilt, and the minimum and maximum values were higher in patients with OTHS compared to NCS (p = 0.047, < 0.001, < 0.001, < 0.001, < 0.001, respectively). Systolic blood pressure (Table 1, Fig 1b) The median and IQR of SBP at baseline before HUTT, at 5 min &10 min of head up HUTT, at 5 min after HUTT (recovery), and minimum and maximum values in patients with POTS, NCS, and OTHS are presented in table 1. Patients with POTS have statistically significantly higher SBP at 10 min of head up tilt, at recovery and higher minimum values compared to those with NCS (p = 0.026, 0.026, < 0.001, respectively). The minimum SBP was statistically significantly higher in POTS compared to OTHS (p < 0.001). However, there was no statistically significant difference in SBP between the 2 groups at 5 min & 10 min of head up tilt (p = 0.224, 0.082, respectively). There was no statistically significant difference in SBP at 10 min of head up tilt, at recovery and minimum values between patients with NCS and OTHS (p = 1.00, 1.00, 1.00, respectively). Stroke volume (Table 1, Fig 1c) The median and IQR of SV at baseline before HUTT, at 5 min &10 min of head up HUTT, at 5 min after HUTT (recovery), and minimum and maximum values in patients with POTS, NCS, and OTHS are presented in table 1. Patients with NCS have statistically significantly higher SV at baseline, at 5 min &10 min of head up tilt, at recovery, and higher minimum, and maximum values compared to those with POTS (p = 0.001, 0.027, 0.016, < 0.001, 0.012, 0.001, respectively). Patients with OTHS have statistically significantly higher SV at baseline, at recovery, and minimum and maximum values compared to those with POTS (p = 0.006, < 0.001, 0.002, 0.005, respectively). However, there were no statistically significant differences in SV between the groups at 5 min &10 min of head up tilt (p = 1.00, 1.00, respectively). There were no statistically significant differences in SV at baseline, at 5 min of head up tilt, at recovery, and minimum and maximum values between patients with NCS and OTHS (p = 1.00, 0.82, 1.00, 1.00, 1.00, respectively). However, the 10 min SV was slightly higher in OTHS compared to NCS (p=0.002). Near-infrared spectroscopy (Table 1, Fig 4) The median and IQR of NIRS at baseline before HUTT and minimum value in patients with POTS, NCS, and OTHS are presented in table 1. Patients with POTS have statistically significantly lower baseline NIRS compared to patients with NCS and patients with OTHS (p = < 0.032, < 0.011, respectively). However, there was no statistically significant difference in baseline NIRS between patients with NCS and patients with OTHS (p =1.00). Patients with POTS have statistically significantly higher minimum NIRS compared to patients with NCS and patients with OTHS (p = < 0.001, < 0.001, respectively). However, there was no statistically significant difference in minimum NIRS between patients with NCS and patients with OTHS (p =1.00). Syncope (Table 2, Fig 2a) The time to syncope in patients with NCS ranges from 8.2 to 21.2 min with a median of 14.1 min. Time to syncope in patients with OTHS ranges from 8.3 to 19.1 min with a median of 12.5 min. There was no statistically significant difference comparing time to syncope between NCS and OTHS (p=0.730). Survival analysis with Kaplan-Meier curve and log-rank test showed no significant differences in the survival curves between the two groups. Convulsion (Table 2, Fig 2b) The time to convulsion in patients with NCS ranges from 6.5 to 17.2 min with a median of 11.6 min. Time to convulsion in patients with OTHS ranged from 8.2 to 19.1 min with a median of 12.2 min. There was no statistically significant difference comparing time to convulsion between NCS and OTHS (p=0.310). Survival analysis with Kaplan-Meier curve and log-rank test showed no significant differences in the survival curves between the two groups. The number of male patients who had convulsion (n=11, 32.4%) was statistically significantly higher in NCS compared to those with convulsions in OTHS group (n=3, 10.0%), (p=0.031). The number of patients < 18 years old who had convulsions (n=32, 94.1%) was statistically significantly higher in NCS compared to those <18 years with convulsions in OTHS group (n=21, 70.0%), (p=0.011). Cardiac asystole (Table 2, Fig 2c) The number of patients who had cardiac asystole in NCS group (n=24, 27.9%) was significantly higher compared to those who had cardiac asystole in OTHS group (n= 9, 8.9%), (p=<0.001). Survival analysis with Kaplan-Meier curve and log-rank tests showed a significant difference existed between NCS and OTHS groups as patients in the NCS group developed cardiac asystole events more frequently at earlier time points compared to the OTHS group. Time to asystole in patients with NCS ranged from 6.7 to 16.4 min with a median of 11.7 min compared to patients with OTHS ranged from 10.4 to 14.3 min with a median of 12.2 min and there was no statistically significant difference comparing the two groups (p=0.272). Discussion Clinicians have increasingly recognized orthostatic intolerance (OI) as a result of autonomic nervous system dysfunction. Two common OI conditions, POTS and NCS, have been defined by the HRS and ACC, with a distinction emphasized between these two physiological syndromes. 5 , 6 The literature documents an overlap between POTS and NCS. In one study, 42% of 57 children diagnosed with POTS via HUTT also met criteria for NCS when HUTT duration was prolonged. 9 Researchers from The University of Toledo Medical Center reported that 18 out of 300 POTS patients diagnosed by HUTT experienced NCS. 7 Additionally, a study of 47 patients with recurrent VVS found that 26% exhibited a heart rate increase of ≥ 40 beats per minute at 5 and 10 minutes during HUT testing. 8 Although the syncope in POTS population was mentioned in these studies, but the distinctive characteristics of this physiological entity were not elaborated in these reports. OTHS: A Novel Syndrome This study introduces a novel physiological entity, Orthostatic Tachycardia Hypotensive Syndrome (OTHS), defined by the concurrent presence of orthostatic tachycardia (an increase in upright heart rate of ≥ 30 beats/minute, or ≥ 40 beats/minute for individuals under 20 years of age) and hypotension associated with syncope during tilt table testing. These findings are observed in conjunction with symptoms of orthostatic intolerance persisting for a minimum of three months. OTHS vs. NCS (Fig. 3 ) Comparison of OTHS to NCS revealed several similarities. There were no significant differences in baseline and recovery heart rates, minimum and recovery systolic blood pressure, stroke volume, or baseline and minimum near-infrared spectroscopy (NIRS) values. Additionally, the time to syncope, age, and gender of patients who experienced syncope were similar in both groups. Furthermore, there were no significant differences in time to convulsion, cardiac asystole, duration of cardiac asystole, or age/gender of patients with these conditions. However, OTHS differed from NCS in the following ways. Patients with OTHS had higher 5- and 10-minutes heart rates during head-up tilt. Convulsions were more frequent in younger male patients (< 18-year-old) with NCS. Moreover, the incidence of cardiac asystole was higher in NCS. Given the median syncope time of 12.5 minutes in the OTHS group, extending HUTT duration beyond 10 minutes may be beneficial for capturing syncope in this population. OTHS vs. POTS (Fig. 3 ) Comparison of OTHS to POTS also highlighted differences. Patients with POTS had higher baseline, minimum, and recovery heart rates, while patients with OTHS had higher baseline and recovery stroke volume. Additionally, patients with POTS had lower baseline NIRS values, but higher minimum NIRS values. While OTHS and POTS shared a significant increase in heart rate during head-up tilt, there were no significant differences in heart rate or stroke volume at 5 or 10 minutes of tilt We hypothesize that POTS, OTHS, and NCS are interrelated conditions within a spectrum of disorders characterized by dysregulation of the baroreflex-mediated sympathetic nervous system and parasympathetic withdrawal at the neurocardiovascular interface. 5 , 13 – 20 These conditions are likely triggered by distinct pathophysiological mechanisms. Our findings suggest that cardiovascular deconditioning leading to reduced stroke volume is more pronounced in patients with POTS, who also exhibit significantly elevated heart rates. Conversely, patients with NCS and OTHS demonstrate higher baseline NIRS values but lower minimum NIRS values during HUTT, indicating potential cerebral autoregulatory dysfunction that may predispose them to syncope. CONCULSION POTS and NCS are well described physiological entities and represent two different facets of autonomic disorders in children and young adults. Our study showed a novel physiological entity of dysautonomia with distinct clinical and physiological features that some are shared with both NCS and POTS. It is characterized by a combination of tachycardia, hypotension, and syncope. Further research is needed to evaluate the best treatment options for patients with OTHS. Declarations Conflict of interest: On behalf of all authors, the corresponding author states that there is no conflict of interest. Ethical approval: All human studies have been approved by the appro priate ethics committee and have therefore been performed in accord ance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments; the specific national laws have been observed. Author Contribution M.N. and A.E. and I.B. wrote the main manuscript text. M.N. and A.E. prepared figures and tables. All authors reviewed the manuscript References Stewart JM, Boris JR, Chelimsky G, et al. Pediatric Disorders of Orthostatic Intolerance. Pediatrics . Jan 2018;141(1)doi:10.1542/peds.2017-1673 Raj SR, Arnold AC, Barboi A, et al. Long-COVID postural tachycardia syndrome: an American Autonomic Society statement. Clin Auton Res . Jun 2021;31(3):365-368. doi:10.1007/s10286-021-00798-2 Eldokla AM, Mohamed-Hussein AA, Fouad AM, et al. Prevalence and patterns of symptoms of dysautonomia in patients with long-COVID syndrome: A cross-sectional study. Ann Clin Transl Neurol . Apr 8 2022;doi:10.1002/acn3.51557 Eldokla AM, Numan MT. Postural orthostatic tachycardia syndrome after mRNA COVID-19 vaccine. Clin Auton Res . 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Demographic characteristics and head tilt up hemodynamics among study groups Parameters POTS ( n = 90) NCS ( n = 86) OTHS ( n = 101) p -value Gender , n (%) Male Female 33 (35.9%) 59 (64.1%) 22 (25.6%) 64 (74.4%) 19 (18.8%) 82 (81.2%) 0.020 * Age (years) Range Median (IQR) 7.0 – 23.0 15.0 (11.0 – 17.0) 6.6 – 22.0 15.0 (13.2 – 16.8) 9.1 – 21.7 16.0 (14.1 – 17.1) 1.00 a , 0.007 *b , 0.094 c Age groups , n (%) Less than 18 years 18 – 25 years 77 (83.7%) 13 (14.1%) 74 (86.0%) 12 (14.0%) 81 (80.2%) 20 (19.8%) 0.476 d HR , median (IQR ) Baseline 5-minutes 10-minutes Recovery (5-minutes) 81.0 (67.0 – 92.0) 112.5 (103.0 – 121.0) 118.0 (108.0 – 126.0) 84.0 (70.0 – 96.0) 73.5 (64.0 – 81.0) 89.0 (79.0 – 98.0) 87.0 (76.0 – 101.0) 65.0 (58.0 – 74.0) 72.0 (66.0 – 83.0) 107.0 (100.0 – 118.0) 117.5 (109.0 – 129.0) 65.0 (58.0 – 78.0) 0.008 * a , 0.047 *b , 1.00 c <0.001 * a , 0.180 b , <0.001* c <0.001 * a , 1.00 b , <0.001* c <0.001 *a , <0.001 *b , 1.00 c p <0.001 * p <0.001 * p <0.001 * Minimum HR Maximum HR 79.0 (67.0 – 92.0) 120.0 (111.0 – 130.0) 55.0 (45.0 – 67.0) 92.5 (83.0 – 103.0) 65.0 (52.0 – 90.0) 117.0 (108.0 – 129.0) <0.001 * a , <0.001 *b , 0.001* c <0.001 *a , 1.00 b , <0.001* c SBP , median (IQR ) Baseline 5-minutes 10-minutes Recovery (5-minutes) 110.0 (104.0 – 117.0) 118.0 (110.0 – 128.0) 119.0 (112.0 – 128.0) 111.0 (101.0 – 121.0) 109.5 (101.0 – 117.0) 117.0 (107.0 – 128.0) 112.0 (100.0 – 124.0) 106.5 (99.0 – 112.0) 110.0 (104.0 – 113.0) 119.0 (112.0 – 128.0) 116.0 (107.0 – 123.0) 107.0 (99.0 – 115.0) 0.508 d 0.399 d 0.026 *a , 0.224 b , 1.00 c 0.026 *a , 0.082 b , 1.00 c p <0.001 * p <0.001 * p <0.001 * Minimum SBP Maximum SBP 95.0 (83.0 – 104.0) 122.0 (115.0 – 130.0) 73.0 (65.0 – 82.0) 119.5 (111.0 – 130.0) 75.0 (66.0 – 82.0) 121.0 (114.0 - 131) <0.001 *a , <0.001 *b , 1.00 c 0.594 d SV , median (IQR ) Baseline 5-minutes 10-minutes Recovery (5-minutes) 65.5 (56.0 – 81.0) 51.5 (44.0 – 59.0) 51.0 (43.0 – 58.0) 67.0 (53.0 – 88.0) 78.0 (63.0 – 93.0) 54.0 (49.0 – 62.0) 55.0 (49.0 – 61.0) 83.0 (69.0 – 102.0) 77.0 (63.0 – 89.0) 52.0 (47.0 – 58.0) 50.0 (44.0 – 53.0) 89.0 (71.0 – 103.0) 0.001 * a , 0.006 *b , 1.00 c 0.027 * a , 1.00 b , 0.082 c 0.016 * a , 1.00 b , 0.002* c <0.001 *a , <0.001 *b , 1.00 c p <0.001 * p <0.001 * p <0.001 * Minimum SV Maximum SV 50.0 (42.0 – 57.0) 66.0 (56.0 – 61.0) 53.5 (48.0 – 60.0) 78.0 (63.0 – 93.0) 50.0 (45.0 – 54.0) 77.0 (63.0 – 92.0) 0.012 * a , 0.002 *b , 1.00 c 0.001 * a , 0.005 *b , 1.00 c NIRS , median (IQR ) Baseline Minimum 81.0 (74.0 – 86.0) 73.0 (67.0 – 80.0) 84.0 (78.0 – 87.0) 67.0 (58.0 – 72.0) 84.0 (78.0 - 88.0) 64.0 (54.0 – 75.0) 0.032 * a , 0.011 *b , 1.00 c <0.001 *a , <0.001 *b , 1.00 c p <0.001 * p <0.001 * p <0.001 * POTS : postural orthostatic tachycardia syndrome, NCS : neurocardiogenic syncope, OTHS: orthostatic tachycardia hypotensive syndrome, IQR : interquartile range, HR : heart rate, SBP : systolic blood pressure, SV : stroke volume, NIRS : Near Infrared Spectroscopy, NA : not applicable (because syncope was a constant) Significance values adjusted by the Bonferroni correction for multiple comparisons ( a . POTS vs. NCS, b . POTS vs. OTHS, c . NCS vs. OTHS). d . Multiple comparisons were not performed since Kruskal Wallis test was not significant *. Statistically significant at 0.05 significance level (2-sided tests) Table 2. Outcomes of head tilt up in patients with NCS and OTHS Outcomes NCS ( n = 86) OTHS ( n = 101) p -value Syncope Number (%) 86 (100.0%) 101 (100.0%) NA Gender , n (%) Male Female 22 (25.6%) 64 (74.4%) 19 (18.8%) 82 (81.2%) 0.265 Age , n (%) <18 years 18 – 25 years 74 (86.0%) 12 (14.0%) 81 (80.2%) 20 (19.8%) 0.290 Time to syncope (min.) , median (IQR ) 14.1 (8.2 – 21.2) 12.5 (8.3 – 19.1) 0.730 Convulsions Number (%) 34 (39.5%) 30 (29.7%) 0.158 Gender , n (%) Male Female 11 (32.4%) 23 (67.6%) 3 (10.0%) 27 (90.0%) 0.031* Age , n (%) <18 years 18 – 25 years 32 (94.1%) 2 (5.9%) 21 (70.0%) 9 (30.0%) 0.011* Time to convulsions (min.) , median (IQR ) 11.6 (6.5 – 17.2) 12.2 (8.2 – 19.1) 0.310 Cardiac asystole Number (%) 24 (27.9%) 9 (8.9%) <0.001 * Gender , n (%) Male Female 8 (%33.3) 16 (66.7%) 2 (22.2%) 7 (77.9%) 0.686 f Age , n (%) <18 years 18 – 25 years 22 (91.7%) 2 (8.3%) 8 (88.9%) 1 (11.1%) 1.00 f Time to cardiac asystole (min.) , median (IQR ) 11.7 (6.7 – 16.4) 12.2 (10.4 – 14.3) 0.272 Duration of cardiac asystole (sec.) , median (IQR ) 5.4 (3.7 – 10.0) 10.3 (4.5 – 10.5) 0.134 NCS : neurocardiogenic syncope, OTHS: orthostatic tachycardia hypotensive syndrome, IQR : interquartile range, NA : not applicable (because syncope was a constant) *. Statistically significant at 0.05 significance level (2-sided tests) f . Fischer’s exact test Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 10 Jul, 2025 Read the published version in Pediatric Cardiology → Version 1 posted Editorial decision: Revision requested 10 Jun, 2025 Reviews received at journal 16 May, 2025 Reviewers agreed at journal 04 May, 2025 Reviewers invited by journal 01 May, 2025 Editor assigned by journal 01 May, 2025 Submission checks completed at journal 01 May, 2025 First submitted to journal 30 Apr, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6568428","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":451783836,"identity":"ee8275cd-6a52-4c41-9509-841fad75d8bb","order_by":0,"name":"Mohammed T. Numan","email":"","orcid":"","institution":"McGovern Medical School, UT Health Science Center","correspondingAuthor":false,"prefix":"","firstName":"Mohammed","middleName":"T.","lastName":"Numan","suffix":""},{"id":451783837,"identity":"b0b9e1d6-b8c9-4425-b8b8-45ad983232d5","order_by":1,"name":"Ahmed M Eldokla","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABDUlEQVRIiWNgGAWjYDACdgYDxoYCBgZ+FNEH+LQwg7QYMDBINiCLJhCjxeAAsVr4mZk3PpxhYCdvfLvH7MHHtntyujPSH35IqGCQ5xc7gFWLZDNbseEGg2TDbXfOmBvObCs2NruRYyyRcIbBcOZs7HYZHOYxk3xgwMy47UaOmTRvW0IikMHGkNjGkGBwG7sWe4iWevvNM4Ba/oK1pD9jSPyHW4sBM1DLBoPDiRskgFoYwVoSzBgSG3BrkTgM9MsMg+PJM26klUn2nEswNjvzBuiXYxI4/cLf3rzxYU9FtW3/jORtEj/KEuTMjgND7EONjTy/NHYtSIDDAMV6QspBgP0BMapGwSgYBaNgBAIApzpdt89P0mUAAAAASUVORK5CYII=","orcid":"","institution":"NY Neuromuscular Healthcare","correspondingAuthor":true,"prefix":"","firstName":"Ahmed","middleName":"M","lastName":"Eldokla","suffix":""},{"id":451783838,"identity":"b81e7207-b2b2-4e58-b5ad-d58d61ded062","order_by":2,"name":"Ian J Butler","email":"","orcid":"","institution":"UT Health Science Center","correspondingAuthor":false,"prefix":"","firstName":"Ian","middleName":"J","lastName":"Butler","suffix":""}],"badges":[],"createdAt":"2025-05-01 01:23:10","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6568428/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6568428/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s00246-025-03948-9","type":"published","date":"2025-07-10T15:57:55+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":82176643,"identity":"40ef7c88-f305-4c23-8803-2004955712ab","added_by":"auto","created_at":"2025-05-07 11:14:32","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":154817,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eComparison of changes in HR (a), SBP (b), and SV (c) between the study groups at different time points.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePOTS\u003c/strong\u003e: postural orthostatic tachycardia syndrome, \u003cstrong\u003eOTHS\u003c/strong\u003e: orthostatic tachycardia hypotensive syndrome, \u003cstrong\u003eNCS\u003c/strong\u003e: neurocardiogenic syncope, \u003cstrong\u003eHR\u003c/strong\u003e: heart rate, \u003cstrong\u003eSBP\u003c/strong\u003e: systolic blood pressure, \u003cstrong\u003eSV\u003c/strong\u003e: stroke volume.\u003c/p\u003e","description":"","filename":"fig1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6568428/v1/920eff85ec5f804b93ced9db.jpg"},{"id":82177846,"identity":"1bcbe472-70dc-4734-bce4-3e2bf021e081","added_by":"auto","created_at":"2025-05-07 11:22:33","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":173176,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eKaplan Meier curves of surviving syncope (a), convulsions (b), and cardiac asystole (c) between NCS and OTHS groups.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eOTHS\u003c/strong\u003e: orthostatic tachycardia hypotensive syndrome, \u003cstrong\u003eNCS\u003c/strong\u003e: neurocardiogenic syncope\u003c/p\u003e","description":"","filename":"fig2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6568428/v1/e77bd354a2a879aedd1bf20c.jpg"},{"id":82177845,"identity":"c40869b2-6b49-4fd3-91c3-a5850cf89129","added_by":"auto","created_at":"2025-05-07 11:22:32","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":205709,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eComparison of head up tilt test hemodynamics and outcomes between POTS, OTHS and NCS.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePOTS\u003c/strong\u003e: postural orthostatic tachycardia syndrome, \u003cstrong\u003eOTHS\u003c/strong\u003e: orthostatic tachycardia hypotensive syndrome, \u003cstrong\u003eNCS\u003c/strong\u003e: neurocardiogenic syncope, \u003cstrong\u003eHR\u003c/strong\u003e: heart rate, \u003cstrong\u003eSBP\u003c/strong\u003e: systolic blood pressure, \u003cstrong\u003eSV\u003c/strong\u003e: stroke volume, \u003cstrong\u003eHUTT\u003c/strong\u003e: head up tilt table test, \u003cstrong\u003eNIRS: \u003c/strong\u003enear-infrared spectroscopy.\u003c/p\u003e","description":"","filename":"fig3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6568428/v1/98011cf923bfb7f693a05630.jpg"},{"id":82176647,"identity":"d9fe373f-beb6-4fd4-8d15-d7aff9e26937","added_by":"auto","created_at":"2025-05-07 11:14:33","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":161560,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eComparison of changes in NIRS between POTS, OTHS and NCS.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePOTS\u003c/strong\u003e: postural orthostatic tachycardia syndrome, \u003cstrong\u003eOTHS\u003c/strong\u003e: orthostatic tachycardia hypotensive syndrome, \u003cstrong\u003eNCS\u003c/strong\u003e: neurocardiogenic \u003cstrong\u003eNIRS: \u003c/strong\u003enear-infrared spectroscopy.\u003c/p\u003e","description":"","filename":"fig4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6568428/v1/4f2bb4ceba2e12f938e702d2.jpg"},{"id":86699449,"identity":"fc8d449f-505b-4396-9e0c-b2bec9c02cf7","added_by":"auto","created_at":"2025-07-14 16:09:51","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2090329,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6568428/v1/348ebcbb-5121-4a15-975e-188cb70e5737.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Orthostatic Tachycardia-Hypotensive Syndrome: A Novel Form of Orthostatic Intolerance in the Young","fulltext":[{"header":"Introduction","content":"\u003cp\u003eOrthostatic intolerance (OI) is characterized by the impaired ability to maintain an upright posture, resulting in symptoms or clinical signs that are alleviated by assuming a supine position. This condition must persist for a minimum of three months to meet diagnostic criteria. Symptoms of orthostatic intolerance may include lightheadedness, dizziness, visual disturbances (such as blurring or fading), generalized weakness, fatigue, palpitations, cognitive dysfunction, anxiety, nausea, dyspnea, and headache.\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eOrthostatic intolerance (OI) due to autonomic nervous system dysfunction has become increasingly recognized by healthcare professionals, particularly following the COVID-19 pandemic and related vaccinations. This condition has seen a rise in incidence and prevalence, especially among younger individuals.\u003csup\u003e\u003cspan additionalcitationids=\"CR3\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003ePostural orthostatic tachycardia syndrome (POTS) and neurocardiogenic syncope (NCS) are two common clinical entities in children and adolescents with symptoms of OI and are considered to have different physiologic and clinical manifestations.\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eThe Heart Rhythm Society (HRS) in 2015 published a consensus statement defining POTS as a constellation of symptoms that include, but are not limited to, palpitations, presyncope, mental clouding, nausea, anxiety, fatigue, blurry vision, and dyspnea, after assuming an upright position, improve with recumbency and must persist for at least 3\u0026ndash;6 months. These symptoms are associated with an increase of the heart rate (HR) of more than 40 bpm (below 20 years of age) or 30 bpm (if\u0026thinsp;\u0026gt;\u0026thinsp;20 years) or HR more than 120 bpm within 10 minutes of upright posture with no significant decrease of blood pressure.\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e NCS is defined as a sudden transient loss of consciousness (LOC) resulting from global cerebral hypoperfusion, associated with loss of postural tone with a decrease of 20 mmHg in systolic blood pressure (SBP) or 10 mmHg in diastolic blood pressure (DBP) upon upright posture but without a significant change in HR; which is followed by rapid and spontaneous supine position recovery \u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e Subsequently the American College of Cardiology (ACC) and American Heart Association (AHA) issued a similar consensus statement in 2017.\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eDespite these two clear definitions, several investigators have reported an overlap between these two clinical entities.\u003csup\u003e7 8, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e This observation of diagnostic overlap between POTS and NCS may have clinical implications in the pathophysiological understanding of their manifestations, pharmacological and clinical management, and medical records documentation. In this study, we aim to re-evaluate the physiological parameters in patients who were referred to our center for symptoms of orthostatic intolerance and autonomic dysfunction and to categorize them into POTS, NCS and a third proposed group of patients with mixed findings. We will define the third group of patients as having Orthostatic Tachycardia Hypotensive Syndrome (OTHS). We will examine the physiology of OTHS and compare it to POTS and NCS.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eWe reviewed our cohort of subjects who presented with OI symptoms for at least 3 months and underwent head up tilt table test (HUTT) during the study period of 2014\u0026ndash;2020. HUTT in our center consists of 10 minutes of supine, 30 minutes of head up and 10 minutes of supine position recovery phase. During the three phases of HUTT, we obtain: continuous beat-beat systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), cardiac stroke volume (SV), obtained by trans-thoracic impedance method, and cerebral near infra-red spectroscopy (NIRS) as a surrogate for cerebral perfusion.\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e HUTT was performed in a quiet room with ambient temperature of 22\u0026deg; to 24\u0026deg;C. No medication or intravenous lines were utilized during the test. All patient parameters were archived digitally.\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eWe divided the subjects into three groups: group 1, patients who met HRS and ACC diagnostic criteria of POTS, group 2, patients who met the HRS and ACC diagnostic criteria for NCS and group 3, patients who had mixed criteria of both POTS and NCS which we called OTHS.\u003c/p\u003e \u003cp\u003eWe recorded patients\u0026rsquo; demographics (age, sex) and findings during HUTT including HR at the baseline before HUTT, during HUTT at 5 min and 10 min, 5 min after HUTT (recovery), and minimum and maximum HR; SBP at baseline before HUTT, during HUTT at 5 min and 10 min, 5 min after HUTT (recovery), and minimum, and maximum SBP; SV at baseline before HUTT, during HUTT at 5 min and 10 min, at 5 min after HUTT (recovery), and minimum, and maximum SV; and lastly NIRS at baseline and the minimum value.\u003c/p\u003e \u003cp\u003eClinical observations of cardiac asystole and convulsions during HUTT were documented in each group.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis:\u003c/h2\u003e \u003cp\u003eAll statistical analyses were performed with Statistical Package for the Social Sciences (SPSS version 25.0; IBM Corporation, Armonk, NY, USA). Categorical variables (e.g., gender and age groups) were presented as frequencies and percentages (%), while continuous variables (i.e., hemodynamics) were summarized as median and interquartile range (given that they were not normally distributed, as tested by Kolmogorov Smirnov test). Differences between categorical variables across the study groups were tested for statistical significance by the Chi-square test or Fisher\u0026rsquo;s exact test (if\u0026thinsp;\u0026gt;\u0026thinsp;20% of expected values were less than 5). The hemodynamics variables were tested for differences between and within the study groups. Differences between study groups were tested for statistical significance by Mann-Whitney test or Kruskal Wallis test (p-values were adjusted by the Bonferroni correction for multiple comparisons). Within-group differences were tested for statistical significance using Friedman test. Survival functions were plotted as Kaplan\u0026ndash; Meier curves and compared for statistical significance using the log- rank test. All p-values\u0026thinsp;\u0026lt;\u0026thinsp;0.05 were considered statistically significant. All graphs were performed with GraphPad Prism (version 8.0.1. for Windows, GraphPad Software, La Jolla California USA).\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003ePatient characteristics (Table 1)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe included patients with POTS (n = 90), NCS (n = 86), and OTHS (n = 101). Fifty-nine (64.1%) of patients with POTS were female and 33 (35.9%) were male, age ranging from 7 to 23 years, with a median of 15 years. Sixty-four (74.4%) of NCS patients were female and 22 (25.6%) were male, age ranging from 6.6 to 22 years, with a median of 15 years. Eighty-two (81.2%) of OTHS patients were female and 19 (18.8%) were male, age ranging from 9.1-21.7 years, with a median of 16 years.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAutonomic testing results\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eHeart rate (Table 1, Fig 1a)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe median and interquartile range (IQR) of HR at baseline before HUTT, at 5 min \u0026amp;10 min of head up HUTT, at 5 min after HUTT (recovery), and minimum and maximum values in patients with POTS, NCS, and OTHS are presented in table 1.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePatients with POTS have statistically significantly higher HR at baseline, at 5 min \u0026amp; 10 min of head up tilt, at recovery, and higher minimum and maximum values compared to those with NCS (p = 0.008, \u0026lt; 0.001, \u0026lt; 0.001, \u0026lt; 0.001, \u0026lt; 0.001, \u0026lt; 0.001, respectively).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePatients with POTS have statistically significantly higher HR at baseline and recovery, and higher minimum value compared to those OTHS (p = 0.047, \u0026lt; 0.001, \u0026lt; 0.001, respectively). However, there was no statistically significant difference between the 2 groups at 5min, 10 min, and maximum HR changes during HUTT (p = 0.180, 1.00, 1.00, respectively).\u003c/p\u003e\n\u003cp\u003eThere was no statistically significant difference in HR at baseline and recovery between patients with NCS and OTHS (p = 1.00, 1.00, respectively). However, the HR at 5 min \u0026amp; 10 min of head up tilt, and the minimum and maximum values were higher in patients with OTHS compared to NCS (p = 0.047, \u0026lt; 0.001, \u0026lt; 0.001, \u0026lt; 0.001, \u0026lt; 0.001, respectively).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSystolic blood pressure (Table 1, Fig 1b)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe median and IQR of SBP at baseline before HUTT, at 5 min \u0026amp;10 min of head up HUTT, at 5 min after HUTT (recovery), and minimum and maximum values in patients with POTS, NCS, and OTHS are presented in table 1.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePatients with POTS have statistically significantly higher SBP at 10 min of head up tilt, at recovery and higher minimum values compared to those with NCS (p = 0.026, 0.026, \u0026lt; 0.001, respectively).\u003c/p\u003e\n\u003cp\u003eThe minimum SBP was statistically significantly higher in POTS compared to OTHS (p \u0026lt; 0.001). However, there was no statistically significant difference in SBP between the 2 groups at 5 min \u0026amp; 10 min of head up tilt (p = 0.224, 0.082, respectively).\u003c/p\u003e\n\u003cp\u003eThere was no statistically significant difference in SBP at 10 min of head up tilt, at recovery and minimum values between patients with NCS and OTHS (p = 1.00, 1.00, 1.00, respectively). \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStroke volume (Table 1, Fig 1c)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe median and IQR of SV at baseline before HUTT, at 5 min \u0026amp;10 min of head up HUTT, at 5 min after HUTT (recovery), and minimum and maximum values in patients with POTS, NCS, and OTHS are presented in table 1.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePatients with NCS have statistically significantly higher SV at baseline, at 5 min \u0026amp;10 min of head up tilt, at recovery, and higher minimum, and maximum values compared to those with POTS (p = 0.001, 0.027, 0.016, \u0026lt; 0.001, 0.012, 0.001, respectively).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePatients with OTHS have statistically significantly higher SV at baseline, at recovery, and minimum and maximum values compared to those with POTS (p = 0.006, \u0026lt; 0.001, 0.002, 0.005, respectively). However, there were no statistically significant differences in SV between the groups at 5 min \u0026amp;10 min of head up tilt (p = 1.00, 1.00, respectively). \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThere were no statistically significant differences in SV at baseline, at 5 min of head up tilt, at recovery, and minimum and maximum values between patients with NCS and OTHS (p = 1.00, 0.82, 1.00, 1.00, 1.00, respectively). \u0026nbsp; However, the 10 min SV was slightly higher in OTHS compared to NCS (p=0.002).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eNear-infrared spectroscopy (Table 1, Fig 4)\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe median and IQR of NIRS at baseline before HUTT and minimum value in patients with POTS, NCS, and OTHS are presented in table 1.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePatients with POTS have statistically significantly lower baseline NIRS compared to patients with NCS and patients with OTHS (p = \u0026lt; 0.032, \u0026lt; 0.011, respectively). However, there was no statistically significant difference in baseline NIRS between patients with NCS and patients with OTHS (p =1.00).\u003c/p\u003e\n\u003cp\u003ePatients with POTS have statistically significantly higher minimum NIRS compared to patients with NCS and patients with OTHS (p = \u0026lt; 0.001, \u0026lt; 0.001, respectively). However, there was no statistically significant difference in minimum NIRS between patients with NCS and patients with OTHS (p =1.00).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSyncope (Table 2, Fig 2a)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe time to syncope in patients with NCS ranges from 8.2 to 21.2 min with a median of 14.1 min. Time to syncope in patients with OTHS ranges from 8.3 to 19.1 min with a median of 12.5 min. \u0026nbsp;There was no statistically significant difference comparing time to syncope between NCS and OTHS (p=0.730). Survival analysis with Kaplan-Meier curve and log-rank test showed no significant differences in the survival curves between the two groups.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConvulsion (Table 2, Fig 2b)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe time to convulsion in patients with NCS ranges from 6.5 to 17.2 min with a median of 11.6 min. Time to convulsion in patients with OTHS ranged from 8.2 to 19.1 min with a median of 12.2 min. \u0026nbsp;There was no statistically significant difference comparing time to convulsion between NCS and OTHS (p=0.310). Survival analysis with Kaplan-Meier curve and log-rank test showed no significant differences in the survival curves between the two groups. The number of male patients who had convulsion (n=11, 32.4%) was statistically significantly higher in NCS compared to those with convulsions in OTHS group (n=3, 10.0%), (p=0.031). The number of patients \u0026lt; 18 years old who had convulsions (n=32, 94.1%) was statistically significantly higher in NCS compared to those \u0026lt;18 years with convulsions in OTHS group (n=21, 70.0%), (p=0.011).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCardiac asystole (Table 2, Fig 2c)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe number of patients who had cardiac asystole in NCS group (n=24, 27.9%) was significantly higher compared to those who had cardiac asystole in OTHS group (n= 9, 8.9%), (p=\u0026lt;0.001). Survival analysis with Kaplan-Meier curve and log-rank tests showed a significant difference existed between NCS and OTHS groups as patients in the NCS group developed cardiac asystole events more frequently at earlier time points compared to the OTHS group. Time to asystole in patients with NCS ranged from 6.7 to 16.4 min with a median of 11.7 min compared to patients with OTHS ranged from 10.4 to 14.3 min with a median of 12.2 min and there was no statistically significant difference comparing the two groups (p=0.272).\u0026nbsp;\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eClinicians have increasingly recognized orthostatic intolerance (OI) as a result of autonomic nervous system dysfunction. Two common OI conditions, POTS and NCS, have been defined by the HRS and ACC, with a distinction emphasized between these two physiological syndromes.\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eThe literature documents an overlap between POTS and NCS. In one study, 42% of 57 children diagnosed with POTS via HUTT also met criteria for NCS when HUTT duration was prolonged.\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e Researchers from The University of Toledo Medical Center reported that 18 out of 300 POTS patients diagnosed by HUTT experienced NCS.\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e Additionally, a study of 47 patients with recurrent VVS found that 26% exhibited a heart rate increase of \u0026ge;\u0026thinsp;40 beats per minute at 5 and 10 minutes during HUT testing.\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eAlthough the syncope in POTS population was mentioned in these studies, but the distinctive characteristics of this physiological entity were not elaborated in these reports.\u003c/p\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003eOTHS: A Novel Syndrome\u003c/h2\u003e \u003cp\u003eThis study introduces a novel physiological entity, Orthostatic Tachycardia Hypotensive Syndrome (OTHS), defined by the concurrent presence of orthostatic tachycardia (an increase in upright heart rate of \u0026ge;\u0026thinsp;30 beats/minute, or \u0026ge;\u0026thinsp;40 beats/minute for individuals under 20 years of age) and hypotension associated with syncope during tilt table testing. These findings are observed in conjunction with symptoms of orthostatic intolerance persisting for a minimum of three months.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec16\" class=\"Section2\"\u003e \u003ch2\u003eOTHS vs. NCS (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e3\u003c/span\u003e)\u003c/h2\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eComparison of OTHS to NCS revealed several similarities. There were no significant differences in baseline and recovery heart rates, minimum and recovery systolic blood pressure, stroke volume, or baseline and minimum near-infrared spectroscopy (NIRS) values. Additionally, the time to syncope, age, and gender of patients who experienced syncope were similar in both groups. Furthermore, there were no significant differences in time to convulsion, cardiac asystole, duration of cardiac asystole, or age/gender of patients with these conditions.\u003c/p\u003e \u003cp\u003eHowever, OTHS differed from NCS in the following ways. Patients with OTHS had higher 5- and 10-minutes heart rates during head-up tilt. Convulsions were more frequent in younger male patients (\u0026lt;\u0026thinsp;18-year-old) with NCS. Moreover, the incidence of cardiac asystole was higher in NCS.\u003c/p\u003e \u003cp\u003eGiven the median syncope time of 12.5 minutes in the OTHS group, extending HUTT duration beyond 10 minutes may be beneficial for capturing syncope in this population.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec17\" class=\"Section2\"\u003e \u003ch2\u003eOTHS vs. POTS (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e3\u003c/span\u003e)\u003c/h2\u003e \u003cp\u003eComparison of OTHS to POTS also highlighted differences. Patients with POTS had higher baseline, minimum, and recovery heart rates, while patients with OTHS had higher baseline and recovery stroke volume. Additionally, patients with POTS had lower baseline NIRS values, but higher minimum NIRS values.\u003c/p\u003e \u003cp\u003eWhile OTHS and POTS shared a significant increase in heart rate during head-up tilt, there were no significant differences in heart rate or stroke volume at 5 or 10 minutes of tilt\u003c/p\u003e \u003cp\u003eWe hypothesize that POTS, OTHS, and NCS are interrelated conditions within a spectrum of disorders characterized by dysregulation of the baroreflex-mediated sympathetic nervous system and parasympathetic withdrawal at the neurocardiovascular interface.\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan additionalcitationids=\"CR14 CR15 CR16 CR17 CR18 CR19\" citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e These conditions are likely triggered by distinct pathophysiological mechanisms. Our findings suggest that cardiovascular deconditioning leading to reduced stroke volume is more pronounced in patients with POTS, who also exhibit significantly elevated heart rates. Conversely, patients with NCS and OTHS demonstrate higher baseline NIRS values but lower minimum NIRS values during HUTT, indicating potential cerebral autoregulatory dysfunction that may predispose them to syncope.\u003c/p\u003e \u003c/div\u003e"},{"header":"CONCULSION","content":"\u003cp\u003ePOTS and NCS are well described physiological entities and represent two different facets of autonomic disorders in children and young adults. Our study showed a novel physiological entity of dysautonomia with distinct clinical and physiological features that some are shared with both NCS and POTS. It is characterized by a combination of tachycardia, hypotension, and syncope. Further research is needed to evaluate the best treatment options for patients with OTHS.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e \u003cstrong\u003eConflict of interest:\u003c/strong\u003e \u003cp\u003eOn behalf of all authors, the corresponding author states that there is no conflict of interest.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eEthical approval:\u003c/strong\u003e \u003cp\u003eAll human studies have been approved by the appro priate ethics committee and have therefore been performed in accord ance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments; the specific national laws have been observed.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eM.N. and A.E. and I.B. wrote the main manuscript text. M.N. and A.E. prepared figures and tables. All authors reviewed the manuscript\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eStewart JM, Boris JR, Chelimsky G, et al. Pediatric Disorders of Orthostatic Intolerance. \u003cem\u003ePediatrics\u003c/em\u003e. Jan 2018;141(1)doi:10.1542/peds.2017-1673\u003c/li\u003e\n\u003cli\u003eRaj SR, Arnold AC, Barboi A, et al. Long-COVID postural tachycardia syndrome: an American Autonomic Society statement. \u003cem\u003eClin Auton Res\u003c/em\u003e. Jun 2021;31(3):365-368. doi:10.1007/s10286-021-00798-2\u003c/li\u003e\n\u003cli\u003eEldokla AM, Mohamed-Hussein AA, Fouad AM, et al. Prevalence and patterns of symptoms of dysautonomia in patients with long-COVID syndrome: A cross-sectional study. \u003cem\u003eAnn Clin Transl Neurol\u003c/em\u003e. Apr 8 2022;doi:10.1002/acn3.51557\u003c/li\u003e\n\u003cli\u003eEldokla AM, Numan MT. Postural orthostatic tachycardia syndrome after mRNA COVID-19 vaccine. \u003cem\u003eClin Auton Res\u003c/em\u003e. Aug 2022;32(4):307-311. doi:10.1007/s10286-022-00880-3\u003c/li\u003e\n\u003cli\u003eSheldon RS, Grubb BP, 2nd, Olshansky B, et al. 2015 heart rhythm society expert consensus statement on the diagnosis and treatment of postural tachycardia syndrome, inappropriate sinus tachycardia, and vasovagal syncope. \u003cem\u003eHeart Rhythm\u003c/em\u003e. Jun 2015;12(6):e41-63. doi:10.1016/j.hrthm.2015.03.029\u003c/li\u003e\n\u003cli\u003eShen WK, Sheldon RS, Benditt DG, et al. 2017 ACC/AHA/HRS Guideline for the Evaluation and Management of Patients With Syncope: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. \u003cem\u003eCirculation\u003c/em\u003e. Aug 1 2017;136(5):e60-e122. doi:10.1161/cir.0000000000000499\u003c/li\u003e\n\u003cli\u003eKanjwal K, Sheikh M, Karabin B, Kanjwal Y, Grubb BP. Neurocardiogenic syncope coexisting with postural orthostatic tachycardia syndrome in patients suffering from orthostatic intolerance: a combined form of autonomic dysfunction. \u003cem\u003ePacing Clin Electrophysiol\u003c/em\u003e. May 2011;34(5):549-54. doi:10.1111/j.1540-8159.2010.02994.x\u003c/li\u003e\n\u003cli\u003eMedow MS, Merchant S, Suggs M, Terilli C, O\u0026apos;Donnell-Smith B, Stewart JM. Postural Heart Rate Changes in Young Patients With Vasovagal Syncope. \u003cem\u003ePediatrics\u003c/em\u003e. Apr 2017;139(4)doi:10.1542/peds.2016-3189\u003c/li\u003e\n\u003cli\u003eWu LJ, Wang C, Lin P, et al. [Diagnosis of vasovagal syncope in children with postural orthostatic tachycardia syndrome]. \u003cem\u003eZhongguo Dang Dai Er Ke Za Zhi\u003c/em\u003e. Nov 2011;13(11):886-8. \u003c/li\u003e\n\u003cli\u003eLankford J, Numan M, Hashmi SS, Gourishankar A, Butler IJ. 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Recommendations for tilt table testing and other provocative cardiovascular autonomic tests in conditions that may cause transient loss of consciousness : Consensus statement of the European Federation of Autonomic Societies (EFAS) endorsed by the American Autonomic Society (AAS) and the European Academy of Neurology (EAN). \u003cem\u003eClin Auton Res\u003c/em\u003e. Jun 2021;31(3):369-384. doi:10.1007/s10286-020-00738-6\u003c/li\u003e\n\u003cli\u003eStewart JM, Weldon A. Reflex vascular defects in the orthostatic tachycardia syndrome of adolescents. \u003cem\u003eJ Appl Physiol (1985)\u003c/em\u003e. Jun 2001;90(6):2025-32. doi:10.1152/jappl.2001.90.6.2025\u003c/li\u003e\n\u003cli\u003eVernino S, Bourne KM, Stiles LE, et al. Postural orthostatic tachycardia syndrome (POTS): State of the science and clinical care from a 2019 National Institutes of Health Expert Consensus Meeting - Part 1. \u003cem\u003eAuton Neurosci\u003c/em\u003e. Nov 2021;235:102828. doi:10.1016/j.autneu.2021.102828\u003c/li\u003e\n\u003cli\u003eLiao Y, Du JB, Tang CS, Jin HF. [Change and significance in the levels of plasma urotensin II and catestatin in children with postural orthostatic tachycardia syndrome]. \u003cem\u003eBeijing Da Xue Xue Bao Yi Xue Ban\u003c/em\u003e. Jun 18 2011;43(3):436-9. \u003c/li\u003e\n\u003cli\u003eLiao Y, Du J. Pathophysiology and Individualized Management of Vasovagal Syncope and Postural Tachycardia Syndrome in Children and Adolescents: An Update. \u003cem\u003eNeurosci Bull\u003c/em\u003e. Jun 2020;36(6):667-681. doi:10.1007/s12264-020-00497-4\u003c/li\u003e\n\u003cli\u003eLiao Y, Chen S, Liu X, et al. Flow-mediated vasodilation and endothelium function in children with postural orthostatic tachycardia syndrome. \u003cem\u003eAm J Cardiol\u003c/em\u003e. Aug 1 2010;106(3):378-82. doi:10.1016/j.amjcard.2010.03.034\u003c/li\u003e\n\u003cli\u003eYang J, Zhao J, Du S, et al. Postural orthostatic tachycardia syndrome with increased erythrocytic hydrogen sulfide and response to midodrine hydrochloride. \u003cem\u003eJ Pediatr\u003c/em\u003e. Oct 2013;163(4):1169-73.e2. doi:10.1016/j.jpeds.2013.04.039\u003c/li\u003e\n\u003cli\u003eBonyhay I, Freeman R. Sympathetic nerve activity in response to hypotensive stress in the postural tachycardia syndrome. \u003cem\u003eCirculation\u003c/em\u003e. Nov 16 2004;110(20):3193-8. doi:10.1161/01.Cir.0000147280.90339.E9\u003c/li\u003e\n\u003cli\u003eShannon JR, Flattem NL, Jordan J, et al. Orthostatic intolerance and tachycardia associated with norepinephrine-transporter deficiency. \u003cem\u003eN Engl J Med\u003c/em\u003e. Feb 24 2000;342(8):541-9. doi:10.1056/nejm200002243420803\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable 1. Demographic characteristics and head tilt up hemodynamics among study groups\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"684\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 174px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eParameters\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 120px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePOTS\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e(\u003cem\u003en\u003c/em\u003e = 90)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 120px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNCS\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e(\u003cem\u003en\u003c/em\u003e = 86)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 120px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eOTHS\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e(\u003cem\u003en\u003c/em\u003e = 101)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 150px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003ep\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGender\u003c/strong\u003e, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e33 (35.9%)\u003c/p\u003e\n \u003cp\u003e59 (64.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e22 (25.6%)\u003c/p\u003e\n \u003cp\u003e64 (74.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e19 (18.8%)\u003c/p\u003e\n \u003cp\u003e82 (81.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 150px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e0.020\u003csup\u003e*\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge\u0026nbsp;\u003c/strong\u003e(years)\u003c/p\u003e\n \u003cp\u003eRange\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eMedian (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e7.0 \u0026ndash; 23.0\u003c/p\u003e\n \u003cp\u003e15.0 (11.0 \u0026ndash; 17.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e6.6 \u0026ndash; 22.0\u003c/p\u003e\n \u003cp\u003e15.0 (13.2 \u0026ndash; 16.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e9.1 \u0026ndash; 21.7\u003c/p\u003e\n \u003cp\u003e16.0 (14.1 \u0026ndash; 17.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 150px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1.00\u003csup\u003ea\u003c/sup\u003e, \u003cstrong\u003e0.007\u003csup\u003e*b\u003c/sup\u003e\u003c/strong\u003e, 0.094\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge groups\u003c/strong\u003e, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e\n \u003cp\u003eLess than 18 years\u003c/p\u003e\n \u003cp\u003e18 \u0026ndash; 25 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e77 (83.7%)\u003c/p\u003e\n \u003cp\u003e13 (14.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e74 (86.0%)\u003c/p\u003e\n \u003cp\u003e12 (14.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e81 (80.2%)\u003c/p\u003e\n \u003cp\u003e20 (19.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 150px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.476 \u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHR\u003c/strong\u003e\u003cem\u003e, median (IQR\u003c/em\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 150px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"3\" valign=\"top\" style=\"width: 24px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 150px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eBaseline\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e5-minutes\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e10-minutes\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eRecovery (5-minutes)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e81.0 (67.0 \u0026ndash; 92.0)\u003c/p\u003e\n \u003cp\u003e112.5 (103.0 \u0026ndash; 121.0)\u003c/p\u003e\n \u003cp\u003e118.0 (108.0 \u0026ndash; 126.0)\u003c/p\u003e\n \u003cp\u003e84.0 (70.0 \u0026ndash; 96.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e73.5 (64.0 \u0026ndash; 81.0)\u003c/p\u003e\n \u003cp\u003e89.0 (79.0 \u0026ndash; 98.0)\u003c/p\u003e\n \u003cp\u003e87.0 (76.0 \u0026ndash; 101.0)\u003c/p\u003e\n \u003cp\u003e65.0 (58.0 \u0026ndash; 74.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e72.0 (66.0 \u0026ndash; 83.0)\u003c/p\u003e\n \u003cp\u003e107.0 (100.0 \u0026ndash; 118.0)\u003c/p\u003e\n \u003cp\u003e117.5 (109.0 \u0026ndash; 129.0)\u003c/p\u003e\n \u003cp\u003e65.0 (58.0 \u0026ndash; 78.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 150px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.008\u003csup\u003e*\u003c/sup\u003e\u003c/strong\u003e\u003csup\u003ea\u003c/sup\u003e\u003cstrong\u003e, 0.047\u003csup\u003e*b\u003c/sup\u003e,\u0026nbsp;\u003c/strong\u003e1.00\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003csup\u003e*\u003c/sup\u003e\u003c/strong\u003e\u003csup\u003ea\u003c/sup\u003e\u003cstrong\u003e,\u0026nbsp;\u003c/strong\u003e0.180\u003csup\u003eb\u003c/sup\u003e\u003cstrong\u003e, \u0026lt;0.001*\u003c/strong\u003e\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003csup\u003e*\u003c/sup\u003e\u003c/strong\u003e\u003csup\u003ea\u003c/sup\u003e\u003cstrong\u003e,\u0026nbsp;\u003c/strong\u003e1.00\u003csup\u003eb\u003c/sup\u003e\u003cstrong\u003e, \u0026lt;0.001*\u003c/strong\u003e\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003csup\u003e*a\u003c/sup\u003e\u003c/strong\u003e, \u003cstrong\u003e\u0026lt;0.001\u003csup\u003e*b\u003c/sup\u003e\u003c/strong\u003e, 1.00\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 150px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003ep\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u0026lt;0.001\u003csup\u003e*\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003ep\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u0026lt;0.001\u003csup\u003e*\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003ep\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u0026lt;0.001\u003csup\u003e*\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 150px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 150px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMinimum HR\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eMaximum HR\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e79.0 (67.0 \u0026ndash; 92.0)\u003c/p\u003e\n \u003cp\u003e120.0 (111.0 \u0026ndash; 130.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e55.0 (45.0 \u0026ndash; 67.0)\u003c/p\u003e\n \u003cp\u003e92.5 (83.0 \u0026ndash; 103.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e65.0 (52.0 \u0026ndash; 90.0)\u003c/p\u003e\n \u003cp\u003e117.0 (108.0 \u0026ndash; 129.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 150px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003csup\u003e*\u003c/sup\u003e\u003c/strong\u003e\u003csup\u003ea\u003c/sup\u003e\u003cstrong\u003e, \u0026lt;0.001\u003csup\u003e*b\u003c/sup\u003e, 0.001*\u003c/strong\u003e\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003csup\u003e*a\u003c/sup\u003e\u003c/strong\u003e, 1.00\u003csup\u003eb\u003c/sup\u003e, \u003cstrong\u003e\u0026lt;0.001*\u003c/strong\u003e\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSBP\u003c/strong\u003e\u003cem\u003e, median (IQR\u003c/em\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 150px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"3\" valign=\"top\" style=\"width: 24px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 150px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eBaseline\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e5-minutes\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e10-minutes\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eRecovery (5-minutes)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e110.0 (104.0 \u0026ndash; 117.0)\u003c/p\u003e\n \u003cp\u003e118.0 (110.0 \u0026ndash; 128.0)\u003c/p\u003e\n \u003cp\u003e119.0 (112.0 \u0026ndash; 128.0)\u003c/p\u003e\n \u003cp\u003e111.0 (101.0 \u0026ndash; 121.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e109.5 (101.0 \u0026ndash; 117.0)\u003c/p\u003e\n \u003cp\u003e117.0 (107.0 \u0026ndash; 128.0)\u003c/p\u003e\n \u003cp\u003e112.0 (100.0 \u0026ndash; 124.0)\u003c/p\u003e\n \u003cp\u003e106.5 (99.0 \u0026ndash; 112.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e110.0 (104.0 \u0026ndash; 113.0)\u003c/p\u003e\n \u003cp\u003e119.0 (112.0 \u0026ndash; 128.0)\u003c/p\u003e\n \u003cp\u003e116.0 (107.0 \u0026ndash; 123.0)\u003c/p\u003e\n \u003cp\u003e107.0 (99.0 \u0026ndash; 115.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 150px;\"\u003e\n \u003cp\u003e0.508\u003csup\u003e\u0026nbsp;d\u003c/sup\u003e\u003c/p\u003e\n \u003cp\u003e0.399\u003csup\u003e\u0026nbsp;d\u003c/sup\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e0.026\u003csup\u003e*a\u003c/sup\u003e\u003c/strong\u003e,\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e0.224\u003csup\u003eb\u003c/sup\u003e, 1.00\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e0.026\u003csup\u003e*a\u003c/sup\u003e\u003c/strong\u003e,\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e0.082\u003csup\u003eb\u003c/sup\u003e, 1.00\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 150px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003ep\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u0026lt;0.001\u003csup\u003e*\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003ep\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u0026lt;0.001\u003csup\u003e*\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003ep\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u0026lt;0.001\u003csup\u003e*\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 150px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 150px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMinimum SBP\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eMaximum SBP\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e95.0 (83.0 \u0026ndash; 104.0)\u003c/p\u003e\n \u003cp\u003e122.0 (115.0 \u0026ndash; 130.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e73.0 (65.0 \u0026ndash; 82.0)\u003c/p\u003e\n \u003cp\u003e119.5 (111.0 \u0026ndash; 130.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e75.0 (66.0 \u0026ndash; 82.0)\u003c/p\u003e\n \u003cp\u003e121.0 (114.0 - 131)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 150px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003csup\u003e*a\u003c/sup\u003e\u003c/strong\u003e, \u003cstrong\u003e\u0026lt;0.001\u003csup\u003e*b\u003c/sup\u003e\u003c/strong\u003e, 1.00\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003cp\u003e0.594\u003csup\u003e\u0026nbsp;d\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSV\u003c/strong\u003e\u003cem\u003e, median (IQR\u003c/em\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 150px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"3\" valign=\"top\" style=\"width: 24px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 150px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eBaseline\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e5-minutes\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e10-minutes\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eRecovery (5-minutes)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e65.5 (56.0 \u0026ndash; 81.0)\u003c/p\u003e\n \u003cp\u003e51.5 (44.0 \u0026ndash; 59.0)\u003c/p\u003e\n \u003cp\u003e51.0 (43.0 \u0026ndash; 58.0)\u003c/p\u003e\n \u003cp\u003e67.0 (53.0 \u0026ndash; 88.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e78.0 (63.0 \u0026ndash; 93.0)\u003c/p\u003e\n \u003cp\u003e54.0 (49.0 \u0026ndash; 62.0)\u003c/p\u003e\n \u003cp\u003e55.0 (49.0 \u0026ndash; 61.0)\u003c/p\u003e\n \u003cp\u003e83.0 (69.0 \u0026ndash; 102.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e77.0 (63.0 \u0026ndash; 89.0)\u003c/p\u003e\n \u003cp\u003e52.0 (47.0 \u0026ndash; 58.0)\u003c/p\u003e\n \u003cp\u003e50.0 (44.0 \u0026ndash; 53.0)\u003c/p\u003e\n \u003cp\u003e89.0 (71.0 \u0026ndash; 103.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 150px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.001\u003csup\u003e*\u003c/sup\u003e\u003c/strong\u003e\u003csup\u003ea\u003c/sup\u003e, \u003cstrong\u003e0.006\u003csup\u003e*b\u003c/sup\u003e\u003c/strong\u003e, 1.00\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e0.027\u003csup\u003e*\u003c/sup\u003e\u003c/strong\u003e\u003csup\u003ea\u003c/sup\u003e, 1.00\u003csup\u003e\u0026nbsp;b\u003c/sup\u003e, 0.082\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e0.016\u003csup\u003e*\u003c/sup\u003e\u003c/strong\u003e\u003csup\u003ea\u003c/sup\u003e, 1.00\u003csup\u003e\u0026nbsp;b\u003c/sup\u003e, \u003cstrong\u003e0.002*\u003csup\u003ec\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003csup\u003e*a\u003c/sup\u003e\u003c/strong\u003e, \u003cstrong\u003e\u0026lt;0.001\u003csup\u003e*b\u003c/sup\u003e\u003c/strong\u003e, 1.00\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 150px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003ep\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u0026lt;0.001\u003csup\u003e*\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003ep\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u0026lt;0.001\u003csup\u003e*\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003ep\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u0026lt;0.001\u003csup\u003e*\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 150px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 150px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMinimum SV\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eMaximum SV\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e50.0 (42.0 \u0026ndash; 57.0)\u003c/p\u003e\n \u003cp\u003e66.0 (56.0 \u0026ndash; 61.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e53.5 (48.0 \u0026ndash; 60.0)\u003c/p\u003e\n \u003cp\u003e78.0 (63.0 \u0026ndash; 93.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e50.0 (45.0 \u0026ndash; 54.0)\u003c/p\u003e\n \u003cp\u003e77.0 (63.0 \u0026ndash; 92.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 150px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.012\u003csup\u003e*\u003c/sup\u003e\u003c/strong\u003e\u003csup\u003ea\u003c/sup\u003e, \u003cstrong\u003e0.002\u003csup\u003e*b\u003c/sup\u003e\u003c/strong\u003e, 1.00\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e0.001\u003csup\u003e*\u003c/sup\u003e\u003c/strong\u003e\u003csup\u003ea\u003c/sup\u003e, \u003cstrong\u003e0.005\u003csup\u003e*b\u003c/sup\u003e\u003c/strong\u003e, 1.00\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNIRS\u003c/strong\u003e\u003cem\u003e, median (IQR\u003c/em\u003e)\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eBaseline\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eMinimum\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e81.0 (74.0 \u0026ndash; 86.0)\u003c/p\u003e\n \u003cp\u003e73.0 (67.0 \u0026ndash; 80.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e84.0 (78.0 \u0026ndash; 87.0)\u003c/p\u003e\n \u003cp\u003e67.0 (58.0 \u0026ndash; 72.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e84.0 (78.0 - 88.0)\u003c/p\u003e\n \u003cp\u003e64.0 (54.0 \u0026ndash; 75.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 150px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e0.032\u003csup\u003e*\u003c/sup\u003e\u003c/strong\u003e\u003csup\u003ea\u003c/sup\u003e\u003cstrong\u003e, 0.011\u003csup\u003e*b\u003c/sup\u003e,\u0026nbsp;\u003c/strong\u003e1.00\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003csup\u003e*a\u003c/sup\u003e\u003c/strong\u003e, \u003cstrong\u003e\u0026lt;0.001\u003csup\u003e*b\u003c/sup\u003e\u003c/strong\u003e, 1.00\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003ep\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u0026lt;0.001\u003csup\u003e*\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003ep\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u0026lt;0.001\u003csup\u003e*\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003ep\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u0026lt;0.001\u003csup\u003e*\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 150px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003ePOTS\u003c/strong\u003e: postural orthostatic tachycardia syndrome, \u003cstrong\u003eNCS\u003c/strong\u003e: neurocardiogenic syncope, \u003cstrong\u003eOTHS:\u0026nbsp;\u003c/strong\u003eorthostatic tachycardia hypotensive syndrome,\u003cstrong\u003e\u0026nbsp;IQR\u003c/strong\u003e: interquartile range, \u003cstrong\u003eHR\u003c/strong\u003e: heart rate, \u003cstrong\u003eSBP\u003c/strong\u003e: systolic blood pressure, \u003cstrong\u003eSV\u003c/strong\u003e: stroke volume, \u003cstrong\u003eNIRS\u003c/strong\u003e: Near Infrared Spectroscopy, \u003cstrong\u003eNA\u003c/strong\u003e: not applicable (because syncope was a constant)\u003c/p\u003e\n\u003cp\u003eSignificance values adjusted by the Bonferroni correction for multiple comparisons (\u003csup\u003ea\u003c/sup\u003e. POTS vs. NCS, \u003csup\u003eb\u003c/sup\u003e. POTS vs. OTHS, \u003csup\u003ec\u003c/sup\u003e. NCS vs. OTHS). \u003csup\u003ed\u003c/sup\u003e. Multiple comparisons were not performed since Kruskal Wallis test was not significant\u003c/p\u003e\n\u003cp\u003e*. Statistically significant at 0.05 significance level (2-sided tests)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2. Outcomes of head tilt up in patients with NCS and OTHS\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"580\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 276px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eOutcomes\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 105px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNCS\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e(\u003cem\u003en\u003c/em\u003e = 86)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 101px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eOTHS\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e(\u003cem\u003en\u003c/em\u003e = 101)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003ep\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"4\" valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSyncope\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 182px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNumber (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e86 (100.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e101 (100.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 182px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGender\u003c/strong\u003e, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e\n \u003cp\u003e\u003cem\u003eMale\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003eFemale\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e22 (25.6%)\u003c/p\u003e\n \u003cp\u003e64 (74.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e19 (18.8%)\u003c/p\u003e\n \u003cp\u003e82 (81.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e0.265\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 182px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge\u003c/strong\u003e, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e\u0026lt;18 years\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e18 \u0026ndash; 25 years\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e74\u0026nbsp;(86.0%)\u003c/p\u003e\n \u003cp\u003e12\u0026nbsp;(14.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e81\u0026nbsp;(80.2%)\u003c/p\u003e\n \u003cp\u003e20\u0026nbsp;(19.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e0.290\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 182px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTime to syncope (min.)\u003c/strong\u003e,\u003cem\u003e\u0026nbsp;median (IQR\u003c/em\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e14.1 (8.2 \u0026ndash; 21.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e12.5 (8.3 \u0026ndash; 19.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e0.730\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"4\" valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eConvulsions\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 182px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNumber (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e34 (39.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e30 (29.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e0.158\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 182px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGender\u003c/strong\u003e, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e\n \u003cp\u003e\u003cem\u003eMale\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003eFemale\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e11 (32.4%)\u003c/p\u003e\n \u003cp\u003e23 (67.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e3 (10.0%)\u003c/p\u003e\n \u003cp\u003e27 (90.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e0.031*\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 182px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge\u003c/strong\u003e, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e\u0026lt;18 years\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e18 \u0026ndash; 25 years\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e32\u0026nbsp;(94.1%)\u003c/p\u003e\n \u003cp\u003e2\u0026nbsp;(5.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e21\u0026nbsp;(70.0%)\u003c/p\u003e\n \u003cp\u003e9\u0026nbsp;(30.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e0.011*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 182px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTime to convulsions (min.)\u003c/strong\u003e,\u003cem\u003e\u0026nbsp;median (IQR\u003c/em\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e11.6 (6.5 \u0026ndash; 17.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e12.2 (8.2 \u0026ndash; 19.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e0.310\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"4\" valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCardiac asystole\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 182px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNumber (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e24 (27.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e9 (8.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003csup\u003e*\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 182px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGender\u003c/strong\u003e, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e\n \u003cp\u003e\u003cem\u003eMale\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003eFemale\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e8 (%33.3)\u003c/p\u003e\n \u003cp\u003e16 (66.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e2 (22.2%)\u003c/p\u003e\n \u003cp\u003e7 (77.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e0.686 \u003csup\u003ef\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 182px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge\u003c/strong\u003e, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e\u0026lt;18 years\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e18 \u0026ndash; 25 years\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e22\u0026nbsp;(91.7%)\u003c/p\u003e\n \u003cp\u003e2\u0026nbsp;(8.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e8\u0026nbsp;(88.9%)\u003c/p\u003e\n \u003cp\u003e1\u0026nbsp;(11.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e1.00 \u003csup\u003ef\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 182px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTime to cardiac asystole (min.)\u003c/strong\u003e,\u003cem\u003e\u0026nbsp;median (IQR\u003c/em\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e11.7 (6.7 \u0026ndash; 16.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e12.2 (10.4 \u0026ndash; 14.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e0.272\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 182px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDuration of cardiac asystole (sec.)\u003c/strong\u003e,\u003cem\u003e\u0026nbsp;median (IQR\u003c/em\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e5.4 (3.7 \u0026ndash; 10.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e10.3 (4.5 \u0026ndash; 10.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.134\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eNCS\u003c/strong\u003e: neurocardiogenic syncope, \u003cstrong\u003eOTHS:\u0026nbsp;\u003c/strong\u003eorthostatic tachycardia hypotensive syndrome,\u003cstrong\u003e\u0026nbsp;IQR\u003c/strong\u003e: interquartile range, \u003cstrong\u003eNA\u003c/strong\u003e: not applicable (because syncope was a constant)\u003c/p\u003e\n\u003cp\u003e*. Statistically significant at 0.05 significance level (2-sided tests)\u003c/p\u003e\n\u003cp\u003e\u003csup\u003ef\u003c/sup\u003e. Fischer\u0026rsquo;s exact test\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"pediatric-cardiology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"pedc","sideBox":"Learn more about [Pediatric Cardiology](http://link.springer.com/journal/246)","snPcode":"246","submissionUrl":"https://submission.nature.com/new-submission/246/3","title":"Pediatric Cardiology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Postural orthostatic tachycardia syndrome (POTS), neurocardiogenic syncope (NCS), orthostatic intolerance (OI), orthostatic tachycardia hypotensive syndrome (OTHS), Autonomic testing","lastPublishedDoi":"10.21203/rs.3.rs-6568428/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6568428/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose:\u003c/h2\u003e \u003cp\u003ePostural orthostatic tachycardia syndrome (POTS) and neurocardiogenic syncope (NCS) are frequently observed causes of orthostatic intolerance (OI). Clinical experience reveals patients with overlapping symptoms of both. This observation led to the hypothesis of orthostatic tachycardia hypotensive syndrome (OTHS), a distinct OI variant, combines POTS and NCS features. This study aims to define and characterize it.\u003c/p\u003e\u003ch2\u003eMethods:\u003c/h2\u003e \u003cp\u003eA retrospective chart review of patients presenting with OI and underwent head up tilt (HUT) between 2014 and 2020. We extracted demographic data, findings during HUT including heart rate (HR), systolic blood pressure (SBP), stroke volume (SV), near infrared spectroscopy (NIRS), syncope, cardiac asystole, and convulsions. We divided the subjects into three groups: POTS, NCS, and OTHS.\u003c/p\u003e\u003ch2\u003eResults:\u003c/h2\u003e \u003cp\u003eWe included patients with POTS (n\u0026thinsp;=\u0026thinsp;90), NCS (n\u0026thinsp;=\u0026thinsp;86), and OTHS (n\u0026thinsp;=\u0026thinsp;101). POTS patients showed higher HR (baseline, recovery, min) vs. OTHS (p\u0026thinsp;=\u0026thinsp;0.047, \u0026lt;\u0026thinsp;0.001, \u0026lt;\u0026thinsp;0.001), while OTHS patients had higher HR (5min, 10min, min, max) vs. NCS (p\u0026thinsp;=\u0026thinsp;0.047, \u0026lt;\u0026thinsp;0.001, \u0026lt;\u0026thinsp;0.001, \u0026lt;\u0026thinsp;0.001). Minimum SBP was higher in POTS vs. OTHS (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), and OTHS patients had higher SV (baseline, recovery, min, max) vs. POTS (p\u0026thinsp;=\u0026thinsp;0.006, \u0026lt;\u0026thinsp;0.001, 0.002, 0.005). Patients with POTS have lower baseline NIRS compared to NCS and OTHS (p\u0026thinsp;=\u0026thinsp;\u0026lt;\u0026thinsp;0.032, \u0026lt; 0.011). Asystole was significantly more frequent in the NCS group (n\u0026thinsp;=\u0026thinsp;24, 27.9%) than in the OTHS group (n\u0026thinsp;=\u0026thinsp;9, 8.9%), with p\u0026thinsp;\u0026lt;\u0026thinsp;0.001.\u003c/p\u003e\u003ch2\u003eConclusions:\u003c/h2\u003e \u003cp\u003eOTHS is a form of OI characterized by initial orthostatic tachycardia with increased HR\u0026thinsp;\u0026gt;\u0026thinsp;30\u0026ndash;40 bpm followed by hypotension leading to syncope.\u003c/p\u003e","manuscriptTitle":"Orthostatic Tachycardia-Hypotensive Syndrome: A Novel Form of Orthostatic Intolerance in the Young","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-05-07 11:14:28","doi":"10.21203/rs.3.rs-6568428/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-06-10T16:57:46+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-05-17T02:17:19+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"227232665547320160255801316194505670338","date":"2025-05-05T02:06:04+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-05-01T15:06:28+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-05-01T08:00:44+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-05-01T07:58:55+00:00","index":"","fulltext":""},{"type":"submitted","content":"Pediatric Cardiology","date":"2025-05-01T01:20:44+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"pediatric-cardiology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"pedc","sideBox":"Learn more about [Pediatric Cardiology](http://link.springer.com/journal/246)","snPcode":"246","submissionUrl":"https://submission.nature.com/new-submission/246/3","title":"Pediatric Cardiology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"a6b45a2e-4666-4a7c-a589-1bf0fc469279","owner":[],"postedDate":"May 7th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-07-14T16:04:10+00:00","versionOfRecord":{"articleIdentity":"rs-6568428","link":"https://doi.org/10.1007/s00246-025-03948-9","journal":{"identity":"pediatric-cardiology","isVorOnly":false,"title":"Pediatric Cardiology"},"publishedOn":"2025-07-10 15:57:55","publishedOnDateReadable":"July 10th, 2025"},"versionCreatedAt":"2025-05-07 11:14:28","video":"","vorDoi":"10.1007/s00246-025-03948-9","vorDoiUrl":"https://doi.org/10.1007/s00246-025-03948-9","workflowStages":[]},"version":"v1","identity":"rs-6568428","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6568428","identity":"rs-6568428","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}