Semi-supervised exercise training program more effective for individuals with postural orthostatic tachycardia syndrome in randomized controlled trial.

PURPOSE: Exercise like any medication requires the correct dose; to be effective the appropriate frequency, duration, and intensity are necessary. This study aimed to assess if a semi-supervised exercise training (ET) program would be more effective at improving aerobic fitness (VO2PEAK), exercise tolerance, and symptoms in individuals with postural orthostatic tachycardia syndrome (POTS) compared to the standard of care (SOC). METHODS: Subjects were randomized to either the ET or SOC groups (n 26 vs. 23; age 33 ± 11 vs. 37 ± 10 years; VO2PEAK 66 ± 15 vs. 62 ± 15% predicted, ET vs. SOC respectively, p > 0.05). Composite Autonomic Symptom Score (COMPASS 31), 10 min stand test, and cardiopulmonary exercise test were performed at baseline and following 12 weeks. The ET group received an exercise consultation and eight semi-supervised in-person or virtual exercise sessions. RESULTS: The ET group demonstrated a greater improvement in VO2PEAK, higher or longer tolerance for baseline peak workload, and more often had a delayed symptom onset with exercise than the SOC group (ΔVO2PEAK 3.4 vs. - 0.2 mL/min/kg, p < 0.0001, ΔWorkload 19 ± 17 vs. 0 ± 10 W; Workload time 63 ± 29 vs. 22 ± 30 s; onset-delay 80% vs. 30%, p < 0.05). Individuals in the ET group reported a significant improvement in orthostatic intolerance domain score (p = 0.02), but there was not a significant difference in the improvement in total COMPASS score (- 11.38 vs. - 6.49, p = 0.09). CONCLUSION: Exercise training was more effective with greater improvements in aerobic fitness, orthostatic symptoms, and exercise tolerance for individuals with POTS when intensity and progression were personalized and delivered with minimal supervision compared to the SOC.

[A 10-year retrospective analysis of spectrums and treatment options of orthostatic intolerance and sitting intolerance in children].

OBJECTIVE: To analyze the disease spectrums underlying orthostatic intolerance (OI) and sitting intolerance (SI) in Chinese children, and to understand the clinical empirical treatment options. METHODS: The medical records including history, physical examination, laboratory examination, and imagological examination of children were retrospectively studied in Peking University First Hospital from 2012 to 2021. All the children who met the diagnostic criteria of OI and SI were enrolled in the study. The disease spectrums underlying OI and SI and treatment options during the last 10 years were analyzed. RESULTS: A total of 2 110 cases of OI and SI patients were collected in the last 10 years, including 943 males (44.69%) and 1 167 females (55.31%) aged 4－18 years, with an average of (11.34±2.84) years. The overall case number was in an increasing trend over the year. In the OI spectrum, postural tachycardia syndrome (POTS) accounted for 826 cases (39.15%), followed by vasovagal syncope (VVS) (634 cases, 30.05%). The highest proportion of SI spectrum was sitting tachycardia (STS) (8 cases, 0.38%), followed by sitting hypertension (SHT) (2 cases, 0.09%). The most common comorbidity of OI and SI was POTS coexisting with STS (36 cases, 1.71%). The highest proportion of treatment options was autonomic nerve function exercise (757 cases, 35.88%), followed by oral rehydration salts (ORS) (687 cases, 32.56%), metoprolol (307 cases, 14.55%), midodrine (142 cases, 6.73%), ORS plus metoprolol (138 cases, 6.54%), and ORS plus midodrine (79 cases, 3.74%). The patients with POTS coexisting with VVS were more likely to receive pharmacological intervention than the patients with POTS and the patients with VVS (41.95% vs. 30.51% vs. 28.08%, χ2= 20.319, P < 0.01), but there was no significant difference in the proportion of treatment options between the patients with POTS and the patients with VVS. CONCLUSION: POTS and VVS in children are the main underlying diseases of OI, while SI is a new disease discovered recently. The number of children with OI and SI showed an increasing trend. The main treatment methods are autonomic nerve function exercise and ORS. Children with VVS coexisting with POTS were more likely to take pharmacological treatments than those with VVS or POTS only.

[Orthostatic Intolerance: A Clinical Approach]. / Orthostatische Intoleranz: eine klinische Betrachtung.

Having suffered a syncope or dizziness are frequent reasons for admissions to an emergency ward. Carefully taken anamnesis and clinical examination are mostly leading to a correct diagnosis. Red flags like new ECG changes, syncope during physical activity or others should lead to further diagnostic steps. Orthostatic intolerance is one of the most common reasons for dizziness and/or syncope. Autonomic testing including tilt table testing has to be done carefully and judged in an overall view together with anamnesis and clinical presentation. We present a clinical approach to the wide field of orthostatic intolerance with hints for the need of further autonomic testing.

Mechanisms and management of gastrointestinal symptoms in postural orthostatic tachycardia syndrome.

Postural orthostatic tachycardia syndrome (POTS) is a disorder of orthostatic intolerance associated with many GI manifestations that can be broadly classified into two different categories: those present all the time (non-positional) and those that occur with orthostatic position change. There are also many conditions that can co-exist with POTS such as mast cell activation syndrome and the hypermobile form of Ehlers-Danlos syndrome (hEDS) that are also oftentimes associated with GI symptoms. In the current issue of Neurogastroenterology and Motility, Tai et al. explored the relationship between functional GI disorders among hEDS patients with and without concomitant POTS and showed that the hEDS-POTS cohort was more likely to have more than one GI organ involved compared to the cohort with hEDS alone, and certain GI symptoms were also more common in the hEDS-POTS cohort. In this review article, we will briefly review the literature surrounding putative mechanisms responsible for GI symptoms in POTS with an emphasis on the contributory role of concomitant hEDS and then discuss management strategies for GI symptoms in POTS.

Inspiratory muscle training improves cerebrovascular and postural control responses during orthostatic stress in older women.

PURPOSE: We aimed to investigate the effect of inspiratory muscle training (IMT) on, hemodynamic, cerebrovascular and postural balance responses during orthostatic stress, in older women. METHODS: Fourteen elderly women were assigned to perform IMT at 50% of maximal inspiratory pressure (MIP) (IMT group, n = 8) or placebo training at 5% MIP (Sham group, n = 6), in a counter-balanced order, using an inspiratory threshold device for 4 weeks. During the protocol, MIP was tested weekly once. In a second visit, blood pressure, heart rate, stroke volume, cardiac output, middle cerebral artery blood flow velocity (MCAv), and ventilation parameters were recorded continuously at rest and during orthostatic stress testing, which was conducted on a force plate to measure center-of-pressure (COP) oscillations (postural balance) and the electromyographic activity of the right medial gastrocnemius and tibialis anterior. RESULTS: IMT increased MIP from second to 4th week. The drops in MCAv, stroke volume, and cardiac output, as well as COP displacements during initial orthostasis decreased post-IMT. CONCLUSION: IMT improves the interplay of the respiratory pump, hemodynamic, cerebrovascular and postural balance responses during orthostatic stress in older women.

Canadian Cardiovascular Society Position Statement on Postural Orthostatic Tachycardia Syndrome (POTS) and Related Disorders of Chronic Orthostatic Intolerance.

The current definition of postural orthostatic tachycardia syndrome (POTS) dates back to a small case series of patients with a subacute illness who presented with excessive orthostatic tachycardia and orthostatic intolerance, in the absence of another recognized disease. Conventional POTS criteria require an excessive orthostatic tachycardia in the absence of substantial orthostatic hypotension, and predominant symptoms of orthostatic intolerance, worse with upright posture and better with recumbence. POTS is a heterogeneous syndrome with likely several underlying pathophysiological processes, and not a specific disease. The primary panel for this Canadian Cardiovascular Society position statement sought to provide a contemporary update of the best evidence for the evaluation and treatment of POTS. We performed a systemic review of evidence for the evaluation of treatment of POTS using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology, and developed recommendations on the basis of the Canadian Cardiovascular Society approach to position statements. One identified problem was that numerous patients who did not meet criteria for POTS would still be given that diagnoses by providers to validate the illness even though this diagnosis is incorrect. This includes patients with postural symptoms without tachycardia, orthostatic tachycardia without symptoms, and those with orthostatic tachycardia but another overt cause for excessive tachycardia. We developed a novel nomenclature ecosystem for orthostatic intolerance syndromes to increase clarity. We also provide more clarity on how to interpret the orthostatic vital signs. These concepts will need to be prospectively assessed.

Autonomic Disorders.

Autonomic complaints are frequently encountered in clinical practice. They can be due to primary autonomic disorders or secondary to other medical conditions. Primary autonomic disorders can be categorized as orthostatic intolerance syndromes and small fiber neuropathies; the latter are associated with autonomic failure, pain, or their combinations. The review outlines orthostatic intolerance syndromes (neurally mediated syncope, orthostatic hypotension, postural tachycardia syndrome, inappropriate sinus tachycardia, orthostatic cerebral hypoperfusion syndrome, and hypocapnic cerebral hypoperfusion) and small fiber neuropathies (sensory/autonomic/mixed, acute/subacute/chronic, idiopathic/secondary, inflammatory and noninflammatory). Several specific autonomic syndromes (diabetic neuropathy, primary hyperhidrosis, paroxysmal sympathetic hyperactivity, autonomic dysreflexia), neurogenic bladder, and gastrointestinal motility disorders are discussed as well.

Postural Orthostatic Tachycardia Syndrome: Prevalence, Pathophysiology, and Management.

Postural orthostatic tachycardia syndrome (POTS) is a debilitating disease that predominantly affects young women. It is a multifactorial disorder that is characterized by severe tachycardia and orthostatic intolerance. Patients with POTS experience a variety of cardiac, neurological, and immunological symptoms that significantly reduce quality of life. In this review, a comprehensive framework is provided to aid in helping identify and treat patients with POTS. Given its heterogenous nature, it is crucial to understand each component of POTS in relation to one another instead of distinct parts. The framework highlights the overlap among the five main subtypes of POTS based on its pathophysiology (neuropathic, hypovolemic, primary hyperadrenergic, joint-hypermobility-related, and immune-related). Emphasis is placed on incorporating a multidisciplinary approach when treating patients with POTS, especially with a new focus towards immunotherapy. Although research has advanced our knowledge of POTS, there is still a critically unmet need to further our understanding and provide patients with the relief they need.

Effect of epidural blood injection on upright posture intolerance in patients with headaches due to intracranial hypotension: A prospective study.

BACKGROUND: We performed a prospective study to quantify changes in various aspects of upright posture intolerance in patients with intracranial hypotension. METHODS: Six patients were provided a standard questionnaire before, immediately after epidural blood patch injection and at follow-up visit within 1 month after epidural blood injection inquiring: (a) How long can they stand straight without any support? (b) Do they feel any sense of sickness when they sit or lie down after standing? (c) How long do they have to wait before they are comfortable standing again after they have stood straight? (d) How effectively and fast can they get up from sitting or lying position to stand straight? and (e) Rate their activities in upright posture without support on a standard vertical visual analogue scale between 100 (can do everything) and 0 (cannot do anything). RESULTS: All patients responded that they could not stand straight for ≥30 min (four responding <5 min) on pretreatment evaluation. All patients reported improvement in this measure immediately postprocedure with two reporting ≥30 min. At follow-up, three patients reported further improvement and one patient reported worsening in this measure. The magnitude of improvement ranged from 10 to 80 points increase immediately postprocedure in their ability to perform activities, while they are standing without any support on visual analogue scale. At follow-up, four patient reported additional improvement in their ability to perform activities, while they are standing without any support (ranged from 10 to 20 points increase compared with immediately postprocedure rating). CONCLUSIONS: We present semiquantitative data on various aspects of upright posture intolerance in patients with intracranial hypotension before and after epidural blood injection.

Evaluating the efficacy of an active compression brace on orthostatic cardiovascular responses.

Orthostatic intolerance, one of the principle causes of syncope, can occur secondary to concomitant venous pooling and enhanced capillary filtration. We aimed to evaluate a prototype portable calf active compression brace (ACB) designed to improve orthostatic haemodynamic control. Fourteen healthy volunteers participated in a randomized, placebo controlled, cross-over, double-blind study. Testing consisted of head-upright tilting and walking on a treadmill conducted on two consecutive days with a pair of ACBs wrapped around both calves. The ACB was actuated on one test day, but not on the other (placebo). Wearability, comfort, and ambulatory use of the ACB were assessed using questionnaires. The average calf pressure exerted by the ACB was 46.3±2.2 mmHg and the actuation pressure was 20.7±1.7 mmHg. When considering the differences between ACB actuation and placebo during tilt after supine rest there were trends for a larger stroke volume (+5.20±2.34%, p = 0.05) and lower heart rate (-5.12±2.41%, p = 0.06) with ACB actuation, with no effect on systolic arterial pressure (+4.86±3.41%, p = 0.18). The decrease in stroke volume after ten minutes of tilting was positively correlated with the height:calf circumference (r = 0.464; p = 0.029; n = 22; both conditions combined). The increase in heart rate after ten minutes of tilting was negatively correlated with the height:calf circumference (r = -0.485; p = 0.022; n = 22; both conditions combined) and was positively correlated with the average calf circumference (r = 0.539; p = 0.009; n = 22; both conditions combined). Participants reported good ACB wearability and comfort during ambulatory use. These data verify that the ACB increased stroke volume during tilting in healthy controls. Active calf compression garments may be a viable option for the management of orthostatic intolerance.

Orthostatic intolerance symptoms are associated with depression and diminished quality of life in patients with postural tachycardia syndrome.

BACKGROUND: Patients with postural tachycardia syndrome often appear depressive and report diminished quality of life (QOL). In the current study, we first evaluated if the maximal heart rate (HR) increment after standing is associated with the clinical symptoms in patients with excessive orthostatic tachycardia (OT). Next, we investigated the correlations among the symptoms of orthostatic intolerance (OI), depression, and health-related QOL in these patients. Finally we assessed if patients with minimal OI symptoms suffer from depression or diminished QOL. METHODS: We performed a comprehensive questionnaire-based assessment of symptoms in 107 patients with excessive OT with a ≥ 30 beats/min heart rate increment (or ≥ 40 beats/min in individuals aged between 12 and 19) within 10 min after standing up. An existing orthostatic intolerance questionnaire (OIQ), the Beck depression inventory-II (BDI-II), and the 36 Item Short-Form Health Survey were completed prior to any treatment. Correlation analyses among the items of the questionnaires and other parameters were performed. Additionally, patients with minimal OI symptoms were analysed separately. RESULTS: The maximal orthostatic HR increment was not associated with the clinical symptoms. The OI symptoms were significantly correlated with depression and diminished QOL. The BDI-II score demonstrated a positive linear relationship with total OIQ score (r = 0.516), and both physical and mental component summary scales of SF-36 showed a negative linear relationship with total OIQ score (r = -0.542 and r = -0.440, respectively; all p <0.001). Some OI symptoms were more strongly associated with depression, and others were more strongly related to QOL. Chest discomfort and concentration difficulties were the most influential OI symptoms for depression, while nausea and concentration difficulties were the most influential symptoms for physical and mental QOL, respectively. Dizziness and headache were the two most common complaints in patients with mild to moderate OI symptoms. In addition, subjects with minimal OI symptoms also had considerable deterioration in QOL. CONCLUSION: The OI symptoms, but not the maximal HR increment, are significantly correlated with depression and diminished QOL in patients with excessive OT. Therefore, pervasive history taking is important when encountering patients with excessive OT.

Evaluation of syncope: focus on diagnosis and treatment of neurally mediated syncope.

Syncope, defined as a transient loss of consciousness secondary to global cerebral hypoperfusion, is common in the general population. The single most helpful "test" in the evaluation of patients with syncope is a thoughtful history, with recent evidence that structured histories are remarkably effective in arriving at a diagnosis. In addition to the history, physical examination, and electrocardiogram, arriving at a diagnosis of syncope can involve monitoring and provocative strategies. The majority of patients with syncope have neurally mediated syncope and a favourable prognosis. The management of neurally mediated syncope continues to largely revolve around education, avoidance of triggers, reassurance, and counter-pressure maneuvers. The evidence surrounding medical therapy in vasovagal syncope is not strong to date. Pacemaker therapy is reasonable in older patients with recurrent, unpredictable syncope with pauses, but should be considered as a last resort in younger patients.

Intravenous Hydration for Management of Medication-Resistant Orthostatic Intolerance in the Adolescent and Young Adult.

Orthostatic intolerance (OI) is common in teenagers (T) and young adults (A). Despite treatment with oral fluids, medication, and exercise, a significant number have symptoms from multiple organ systems and suffer low quality of life (QOL). Previous studies showed that acute intravenous (IV) hydration (IH) could help restore orthostatic tolerance; however, no data are available about the intermediate-term effects of IH. We therefore studied the efficacy of IH to improve QOL and manage medication-refractory OI patients. Our study population consisted of 39 patients (mean age = 16.1 ± 3.3) years; thirty-two were female. Average number of medications failed = 3.1. Average QOL score on self-reported OI questionnaire was 4.2 (normal QOL = 10). IV hydration consisted of normal saline (1-2 l/day, 3-7 days/week). 1) Orthostatic testing revealed Postural Orthostatic Tachycardia (24), Neurally Mediated Hypotension (14) or OI (1). 2) Average orthostatic change in heart rate was 48 ± 18 bpm. 3) IH was performed via intermittent IV access (10), PICC line (22), and Port (7). 4) Duration of IH varied from 1 week to 3.8 years (mean = 29 ± 47 weeks). 5) Overall, 79 % (n = 31) demonstrated clinically improved self-reported QOL. 6) Six patients who discontinued IH requested to restart treatment. (7) Complications consisted of upper extremity deep vein thrombosis (n = 3) and infection (n = 4). IH is an effective therapy to improve QOL in T&A with medication-resistant OI. Most patients continued to report improved QOL once IH was discontinued. IH should be considered a therapeutic option in medication-resistant OI patients with low QOL.

Effects of an artificial gravity countermeasure on orthostatic tolerance, blood volumes and aerobic power after short-term bed rest (BR-AG1).

Exposure to artificial gravity (AG) in a short-arm centrifuge has potential benefits for maintaining human performance during long-term space missions. Eleven subjects were investigated during three campaigns of 5 days head-down bed rest: 1) bed rest without countermeasures (control), 2) bed rest and 30 min of AG (AG1) daily, and 3) bed rest and six periods of 5 min AG (AG2) daily. During centrifugation, the supine subjects were exposed to AG in the head-to-feet direction with 1 G at the center of mass. Subjects participated in the three campaigns in random order. The cardiovascular effects of bed rest and countermeasures were determined from changes in tolerance to a head-up tilt test with superimposed lower body negative pressure (HUT), from changes in plasma volume (PV) and from changes in maximum aerobic power (V̇o2 peak) during upright work on a cycle ergometer. Complete data sets were obtained in eight subjects. After bed rest, HUT tolerance times were 36, 64, and 78% of pre-bed rest baseline during control, AG1 and AG2, respectively, with a significant difference between AG2 and control. PV and V̇o2 peak decreased to 85 and 95% of pre-bed rest baseline, respectively, with no differences between the treatments. It was concluded that the AG2 countermeasure should be further investigated during future long-term bed rest studies, especially as it was better tolerated than AG1. The superior effect of AG2 on orthostatic tolerance could not be related to concomitant changes in PV or aerobic power.

Managing the patient with episodic sinus tachycardia and orthostatic intolerance.

Patients with episodic sinus tachycardia and associated orthostatic intolerance present a diagnostic and management dilemma to the clinician. We define this group of disorders to include sinus node reentrant tachycardia (SNRT), inappropriate sinus tachycardia (IAST), and postural orthostatic tachycardia syndrome (POTS). After a brief review of the current understanding of the pathophysiology and epidemiology of this group of disorders, we focus on the diagnosis and management of IAST and POTS. Our approach attempts to recognize the considerable overlap in pathophysiology and clinical presentation between these two heterogeneous conditions. Thus, we focus on a mechanism-based workup and therapeutic approach. Sinus tachycardia related to identifiable causes should first be ruled out in these patients. Next, a basic cardiovascular and autonomic workup is suggested to exclude structural heart disease, identify a putative diagnosis, and guide therapy. We review both nonpharmacologic and pharmacologic therapy, with a focus on recent advances. Larger randomized control trials and further mechanistic studies will help refine management in the future.

Adolescent fatigue, POTS, and recovery: a guide for clinicians.

Many teenagers who struggle with chronic fatigue have symptoms suggestive of autonomic dysfunction that may include lightheadedness, headaches, palpitations, nausea, and abdominal pain. Inadequate sleep habits and psychological conditions can contribute to fatigue, as can concurrent medical conditions. One type of autonomic dysfunction, postural orthostatic tachycardia syndrome, is increasingly being identified in adolescents with its constellation of fatigue, orthostatic intolerance, and excessive postural tachycardia (more than 40 beats/min). A family-based approach to care with support from a multidisciplinary team can diagnose, treat, educate, and encourage patients. Full recovery is possible with multi-faceted treatment. The daily treatment plan should consist of increased fluid and salt intake, aerobic exercise, and regular sleep and meal schedules; some medications can be helpful. Psychological support is critical and often includes biobehavioral strategies and cognitive-behavioral therapy to help with symptom management. More intensive recovery plans can be implemented when necessary.

Does goal-directed fluid therapy affect postoperative orthostatic intolerance?: A randomized trial.

BACKGROUND: Early mobilization is important for postoperative recovery but is limited by orthostatic intolerance (OI) with a prevalence of 50% 6 h after major surgery. The pathophysiology of postoperative OI is assumed to include hypovolemia besides dysregulation of vasomotor tone. Stroke volume-guided fluid therapy, so-called goal-directed therapy (GDT), corrects functional hypovolemia, and the authors hypothesized that GDT reduces the prevalence of OI after major surgery and assessed this in a prospective, double-blinded trial. METHODS: Forty-two patients scheduled for open radical prostatectomy were randomized into standard fluid therapy (control group) or GDT groups. Both groups received a fixed-volume crystalloid regimen supplemented with 1:1 replacement of blood loss with colloid, and in addition, the GDT group received colloid to obtain a maximal stroke volume (esophageal Doppler). The primary outcome was the prevalence of OI assessed with a standardized mobilization protocol before and 6 h after surgery. Hemodynamic and hormonal orthostatic responses were evaluated. RESULTS: Twelve (57%) versus 15 (71%) patients in the control and GDT groups (P = 0.33), respectively, demonstrated OI after surgery, group difference 14% (CI, -18 to 45%). Patients in the GDT group received more colloid during surgery (1,758 vs. 1,057 ml; P = 0.001) and reached a higher stroke volume (102 vs. 89 ml; P = 0.04). OI patients had an increased length of hospital stay (3 vs. 2 days; P = 0.02) and impaired hemodynamic and norepinephrine responses on mobilization. CONCLUSION: GDT did not reduce the prevalence of OI, and patients with OI demonstrated impaired cardiovascular and hormonal responses to mobilization.