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Exercise in the Postural Orthostatic Tachycardia Syndrome
Abstract
Patients with the Postural Orthostatic Tachycardia Syndrome (POTS) have orthostatic intolerance, as well as exercise intolerance. Peak oxygen uptake (VO2peak) is generally lower in these patients compared with healthy sedentary individuals, suggesting a lower physical fitness level. During acute exercise, POTS patients have an excessive increase in heart rate and reduced stroke volume for each level of absolute workload; however, when expressed at relative workload (%VO2peak), there is no difference in the heart rate response between patients and healthy individuals. The relationship between cardiac output and VO2 is similar between POTS patients and healthy individuals. Short-term (i.e., 3months) exercise training increases cardiac size and mass, blood volume, and VO2peak in POTS patients. Exercise performance is improved after training. Specifically, stroke volume is greater and heart rate is lower at any given VO2 during exercise after training versus before training. Peak heart rate is the same but peak stroke volume and cardiac output are greater after training. Heart rate recovery from peak exercise is significantly faster after training, indicating an improvement in autonomic circulatory control. These results suggest that patients with POTS have no intrinsic abnormality of heart rate regulation during exercise. The tachycardia in POTS is due to a reduced stroke volume. Cardiac remodeling and blood volume expansion associated with exercise training increase physical fitness and improve exercise performance in these patients.
Copyright © 2014 Elsevier B.V. All rights reserved.
... For patients and physical therapists that need a more structured plan, Children's Hospital of Philadelphia has modified the Dallas protocol for orthostatic intolerance patients and provided detailed guidelines on types of exercise and calendars of advancement. 90 Again, even if using a protocol, therapists should be instructed that pushing patients through dizziness is counterproductive and can even lead to vasovagal syncope. Specific exercise prescriptions can also be utilised. ...
... recumbent activity, upright stationary bike, treadmill with and without incline) can be explicitly written for an individual patient and followed for progress. [89][90][91][92][93] It must be remembered, however, that heart rate in these specific populations is often confounded by factors other than training and effort during exercise (i.e. beta-blocker use, chronotropic incompetence in Fontan patients, or suboptimal hydration status in those with orthostatic intolerance). ...
While the pathophysiology affecting patients after Fontan palliation versus those with orthostatic intolerance is quite different, a common therapeutic approach exists. Exercise training, specifically augmenting the lower extremity skeletal muscle pump, improves the suboptimal haemodynamics of “preload failure” and thus clinical outcomes for each patient group. In this review, we will describe the problematic physiology affecting these patients, examine the anatomy and haemodynamics of the skeletal muscle pump, and finally review how exercise benefits both groups of patients through augmentation of musculovenous force.
... Given such abnormal sympathetic nervous activity and reactivity in POTS (Lambert and Lambert 2014), physical reconditioning aimed at increasing exercise capability and consequent cardiac vagal modulation represents a crucial part of the therapeutic strategy . Indeed, a mild to moderate exercise training program has been found to increase orthostatic tolerance in POTS patients (Fu and Levine 2015). Fu et al. (Fu et al. 2010 showed that a 3-month exercise training program in a semi-recumbent posture, increased maximal oxygen consumption (VO 2peak ), left ventricular mass and end-diastolic volume, resulting in a significant increase in physical fitness and reduced cardiac remodeling. ...
... These symptoms tend to promote a sedentary lifestyle Dipaola et al. 2020), initiating a vicious cycle that exacerbates their physical and gravitational deconditioning. Therefore, physical re-conditioning represents a crucial part of the non-pharmacological therapeutic strategy (Brilla et al. 1998;Fu and Levine 2015;Mtinangi and Hainsworth 1998) in POTS. Physical exercise has proven to be effective in enhancing cardiac vagal modulation and arterial baroreflex function (Galbreath et al. 2011), decreasing cardiac sympathetic activity (Shibata et al. 2012), expanding blood volume (Saltin et al. 1968) and increasing cardiac size and mass (Dorfman et al. 2007), which were all abnormal in POTS. ...
Purpose
To assess the effects of two different body positions on the cardiovascular autonomic profile during a single bout of exercise in patients with postural orthostatic tachycardia syndrome (POTS).
Methods
Thirteen patients with POTS and thirteen healthy controls (C) participated in the study. ECG, respiration, beat-by-beat arterial pressure and O2 consumption (VO2) were continuously recorded while on a cycle ergometer in supine and upright positions, before and during exercise (6 min, 50 Watts). Spectral analysis of RR intervals and systolic arterial pressure (SAP) variability provided indexes of cardiac sympathovagal interaction (LF/HF ratio), cardiac vagal modulation (HFRR, high-frequency component of RR variability, ~ 0.25 Hz), sympathetic vasomotor control (LFSAP, low-frequency component of SAP variability, 0.1 Hz) and baroreflex sensitivity (BRS, αLF).
Results
While supine, patients with POTS showed lower HFRR and αLF, greater heart rate (HR), LF/HF and LFSAP, compared with C, suggesting cardiovascular sympathetic over-activity and reduced BRS. While sitting upright, POTS showed greater HR and reduced HFRR and αLF compared with C. During supine exercise, SAP, HR, LF/HF increased and HFRR and αLF decreased similarly in POTS and C. In POTS, upright sitting exercise was associated with slightly higher , a greater increase in HR whereas LFSAP was lower than in C.
Conclusion
Upright exercise was associated with excessive enhancement of HR and a blunted increase of the sympathetic vasomotor control in POTS. Conversely, supine exercise-induced hemodynamic and autonomic changes similar in POTS and C, thus making supine exercise potentially more suitable for physical rehabilitation in POTS.
... Exercise training is universally recommended and has demonstrated superiority over propranolol, in terms of improving cardiovascular hemodynamics and quality of life (QOL) [42][43][44]. This initially involves exercises that do not require an upright position, with gradual up titration in intensity and duration [44]. ...
... Exercise training is universally recommended and has demonstrated superiority over propranolol, in terms of improving cardiovascular hemodynamics and quality of life (QOL) [42][43][44]. This initially involves exercises that do not require an upright position, with gradual up titration in intensity and duration [44]. Lower extremity resistance training has also been shown to help by improving the strength of the soleal muscle pump [45]. ...
Introduction
Postural orthostatic tachycardia syndrome (POTS) is an increasingly well-recognized condition encountered in clinical practice. Diagnosis and treatment remain extremely challenging. The limited success of currently available therapies has laid the foundation for a number of experimental therapies.
Areas Covered
In this review, we will briefly outline the pathophysiology and clinical features of this syndrome, before moving on to its management, with a specific focus on experimental pharmacological therapies. Finally, we briefly discuss POTS related to the SARS CoV-2 (COVID-19) pandemic.
Expert Opinion
Despite tremendous advances, the diagnosis and management of POTS remains extremely challenging. The multitude of contributory mechanisms, which predominate to varying degrees in different patients further complicates management. Improved characterization of pathophysiological phenotypes is essential to individualize management. Lifestyle measures form the first line of therapy, followed by beta-blockers, ivabradine, fludrocortisone, and midodrine. Supplemental therapies such as iron, vitamin D and α lipoic acid are quite safe and a trial of their use is reasonable. The use of erythropoietin, IVIG, desmopressin, etc., are more specialized and nuanced alternatives. In recent years, interest has grown in the use of cardiac neuromodulation. Though preliminary, some of these therapies are quite promising.
... 36 Patients should be educated on physical counterpressure measures and exercises that can be performed in a semi-recumbent or supine position, as these can improve both mental and physical well-being. [83][84][85][86][87] For example, graded exercise combined with increased salt and water intake has been shown to significantly improve quality of life and blunt the HR increase from supine to standing. 87 Also, medications that increase HR, lower blood pressure, and may cause or worsen orthostatic intolerance should be discontinued when possible. ...
... 88 Given that the symptoms of post-COVID-19 POTS are predominantly chronic orthostatic tachycardia, a combination of graded exercise rehabilitation and medications that selectively lower HR is recommended. 31,77,83,84,87,103 For example, in the first case report of post-COVID-19 POTS, Miglis et al 37 reported complete symptom improvement after prescription of compression socks, increased salt and fluid intake, clonidine, and propranolol. Another case series found prescribing a low-dose b-blocker, rehabilitative reconditioning, and cognitive behavioral therapy yielded complete resolution of symptoms in a patient with post-COVID-19 POTS. ...
Postural Orthostatic Tachycardia Syndrome (POTS) is a complex, multisystem disorder characterized by orthostatic intolerance and tachycardia and may be triggered by viral infection. Recent reports indicate 2-14% of COVID-19 survivors develop POTS and 9-61% experience POTS-like symptoms, such as tachycardia, orthostatic intolerance, fatigue, and cognitive impairment within 6-8 months following a SARS-CoV-2 infection. Pathophysiological mechanisms of Post-COVID-19 POTS are not well understood. Current hypotheses include autoimmunity related to SARS-CoV-2 infection, autonomic dysfunction, direct toxic injury by SARS-CoV-2 to the autonomic nervous system, and invasion of the central nervous system by SARS-CoV-2. Practitioners should actively assess for POTS in patients with post-acute COVID syndrome symptoms. Given symptoms of Post-COVID-19 POTS are predominantly chronic orthostatic tachycardia, lifestyle modifications in combination with the use of heart rate-lowering medications along with other pharmacotherapies should be considered. For example, ivabradine or beta-blockers in combination with compression stockings and increasing salt and fluid intake has shown potential. Treatment teams should be multidisciplinary, including physicians of various specialties, nurses, psychologists, and physiotherapists. Additionally, more resources to adequately care for this patient population are urgently needed given the increased demand for autonomic specialists and clinics since the start of the COVID-19 pandemic. Considering our limited understanding of Post-COVID-19 POTS, further research on topics such as its natural history, pathophysiological mechanisms, and ideal treatment is warranted. This review evaluates the current literature available on the associations between COVID-19 and POTS, possible mechanisms, patient assessment, treatments, and future directions to improving our understanding of Post-COVID-19 POTS.
... These cardiac abnormalities are reversed by physical training and physical fitness. [67][68][69] However, physical exercise, particularly in cases of OH due to dysautonomy, demonstrated that orthostatic posture, immediately after exercising in the supine position, may exacerbate OH in these patients. This observation is not reproducible in healthy individuals. ...
... This observation is not reproducible in healthy individuals. [67][68][69] As a result, especially in elderly patients with NOH, physical exercise must be supervised by family members or specialized professionals to avoid injuries or falls. In this subgroup of patients, moderate physical training should be prioritized, especially for the lower limbs and physical exercises that do not generate greater gravitational stress, such as cycling in the supine position or water exercises. ...
... It is unclear if the "nonresponders" would have responded to pharmacotherapy. However, Fu and Levine (2014) found in patients with POTS that shortterm exercise, as little as three months, resulted in an increase in cardiac mass, VO2 peak, and blood volume as well, supporting Winker's findings (Fu & Levine, 2014). ...
... It is unclear if the "nonresponders" would have responded to pharmacotherapy. However, Fu and Levine (2014) found in patients with POTS that shortterm exercise, as little as three months, resulted in an increase in cardiac mass, VO2 peak, and blood volume as well, supporting Winker's findings (Fu & Levine, 2014). ...
Postural Orthostatic Tachycardia Syndrome (POTS) is an autonomic dysfunction
characterized by orthostatic symptoms including an increase in heart rate of at least 30 beats per minute (bpm) or reaching above 120 bpm soon after a postural change (Busmer, 2011). Symptoms include, but are not limited to, dizziness, nausea, palpitations, sweating, and fatigue. Twenty-five percent of those with POTS are unable to work (Busmer, 2013). One common pharmacologic treatment is beta-blockers (Lai et al 2009). There is little research into non-pharmacologic treatments, including exercise. The
purpose of this case study was to determine if physical activity alleviates physical (heart rate) and psychological (depression and anxiety) symptoms of a patient with POTS. Following eight weeks of physical activity, the patient still met the diagnostic criteria of POTS. However, her quality of life improved based on the WHOQOL-100 AND HADS scores, and she reported being able to perform more tasks at home without feeling heart palpitations. The case study showed an improvement in quality of life for the participant with POTS, but minimal changes in heart rate response following standing post-intervention.
... 7 Research by Fu and Levine has demonstrated that patients with POTS have decreased stroke volume, cardiac output and lower blood volume. [16][17][18][19] These physiological deficits contribute to symptoms such as tachycardia and shortness of breath. Exercise training programs aim to improve patients' symptom burden by addressing these underlying issues. ...
Objective: Systematically map the literature on non-pharmacological interventions for Postural Orthostatic Tachycardia Syndrome to identify and categorize interventions used, and highlight research gaps to guide future studies.
Introduction: Postural Orthostatic Tachycardia Syndrome is characterized by an excessive increase in heart rate upon standing and symptoms of orthostatic intolerance. Non-pharmacological interventions are first-line treatments. However, the breadth, characteristics, and gaps in the current evidence base have not been systematically mapped, making this scoping review necessary to guide future research directions. The question addressed by the review is: What is the current state of evidence on non-pharmacological interventions for POTS across all age groups?
Inclusion criteria: Studies on non-drug, non-procedural, and non-invasive interventions for Postural Orthostatic Tachycardia Syndrome in both children and adults will be included. Both direct (affecting patients) and indirect (benefitting but not targeting patients) interventions in any setting will be considered. Original research, systematic reviews, meta-analyses, and gray literature will be included.
Methods: A comprehensive search will be conducted across six databases (Ovid Medline, Ovid Embase, Cochrane Library, CINAHL, Scopus and Web of Science) and gray literature platforms. Searches will be limited to articles in English, Afrikaans, French, German and Korean, with no restriction on publication date. Two reviewers will independently screen title-and-abstract, and full-text, against the inclusion criteria. Data will be extracted using a standardized tool and presented to highlight key findings and research gaps. The initial draft extraction form was developed after scanning the literature and will be iteratively refined as part of protocol development.
... 1 Patients with POTS typically exhibit a lower peak oxygen uptake (VO2peak) compared to healthy sedentary individuals, indicating reduced physical fitness levels. 2 The symptoms of POTS are diverse and may include rapid heartbeat, light-headedness, fainting, fatigue, fluctuating blood pressure, exercise intolerance, nausea, anxiety, blurred vision, and headaches. 3 Treatment mostly includes self-care practices to help deal with the symptoms, although medications may be used less frequently. ...
Objective
This review aims to identify the exercise rehabilitation approaches used for patients with POTS (Postural Orthostatic Tachycardia Syndrome).
Methods
An electronic literature search was conducted using the PubMed database, covering January 2005 to October 2023. Studies were included if they reported an exercise rehabilitation intervention for POTS patients and resulting clinical outcomes. Eligible study designs included randomized and non-randomized clinical trials and case reports.
Results
Initially, 34 publications were identified, but only 14 met the criteria for inclusion. After a thorough analysis, 7 studies were included in this scoping review. The majority of the studies stated aerobic exercise training significantly improves symptoms in most of the patients with orthostatic intolerance, reduces the frequency of syncope, enhances patient quality of life, and improves autonomic balance as assessed by heart rate variability analysis and cardiorespiratory endurance. Short-term exercise training was found to boost physical fitness and cardiorespiratory responses in patients with POTS. Therefore, exercise training can serve as an effective non-pharmacological therapy for managing POTS.
Conclusion
This scoping review identified different approaches used for exercise rehabilitation in POTS patients. However, more research is needed to identify the optimal exercise rehabilitation program for this patient population.
... Physical exercise plays a critical role in the management of POTS, particularly when tailored to the patient's subtype and tolerance levels. Initial exercise regimens should involve low-intensity, recumbent activities such as rowing or swimming to minimize excessive upright positioning, progressing gradually over a three-month period [41]. Clinical studies have shown that this approach can increase maximal oxygen uptake by 11%, improve left ventricular mass by 12%, and reduce orthostatic symptoms, with 53% of patients no longer meeting the diagnostic criteria for POTS after completing the program [37]. ...
Background
The global COVID-19 vaccination campaign, with 13.53 billion doses administered by early 2024, has significantly reduced severe illness and mortality. However, potential adverse effects, such as Postural Orthostatic Tachycardia Syndrome (POTS), have raised concerns. This systematic review evaluates the incidence, mechanisms, and clinical implications of POTS following COVID-19 vaccination.
Methods
A systematic search of PubMed, EMBASE, and Web of Science was conducted up to June 7, 2024, following PRISMA guidelines to identify studies related to COVID-19 vaccines and POTS. Eligible studies included randomized controlled trials, cohort studies, cross-sectional studies, case-control studies, case series, and case reports. Screening, data extraction, and quality assessment were independently performed by two reviewers using the Joanna Briggs Institute Checklists and the Newcastle-Ottawa Scale.
Results
Of the 1,531 articles identified, 10 met the inclusion criteria, encompassing a total of 284,678 participants. These studies included five case reports, two case series, one cross-sectional study, one prospective observational study, and one cohort study. The cohort study reported that the odds of new POTS diagnoses post-vaccination were 1.33 (95% CI: 1.25–1.41) compared to the 90 days prior. In contrast, the post-infection odds were 2.11 (95% CI: 1.70–2.63), and the risk of POTS was 5.35 times higher (95% CI: 5.05–5.68) post-infection compared to post-vaccination. Diagnostic findings across studies included elevated norepinephrine levels and reduced heart rate variability. Reported management strategies involved ivabradine, intravenous therapies, and lifestyle modifications.
Conclusion
The risk of POTS following COVID-19 vaccination is lower than that observed post-SARS-CoV-2 infection; however, existing studies are limited by small sample sizes and methodological variability. Further research is needed to clarify the incidence, mechanisms, and long-term outcomes of vaccine-related POTS to inform effective clinical management strategies.
... 3 However, endurance training is prioritized for the treatment of POTS because this increases the blood and plasma volumes, increases cardiac size and mass, and improves orthostatic tolerance. 4 Moreover, a study found that the leg muscle mass does not appear to be a significant determinant of tolerance to increased venous pooling in healthy controls. 5 This means that there is currently an inadequate understanding of the role of lower leg muscles on OI in patients with POTS. ...
Background: Resistance training for leg muscles is recommended for patients with postural tachycardia syndrome (POTS). However, no study has characterized the relationships between orthostatic symptoms, heart rate (HR) increase, and the mass of the lower leg muscle in patients with POTS. We sought to determine the relationships between the mass of the lower leg muscle, HR increase during the head-up tilt (HUT) test, and orthostatic symptoms in patients with POTS.Methods: We prospectively enrolled 42 patients with POTS who were older than 16 years. The muscle mass was estimated using bioelectrical impedance analysis. We used the International Physical Activity Questionnaire-Short Form to measure self-reported physical activity. All patients were asked to complete the Korean version of the Orthostatic Grading Scale (KOGS).Results: The HR increased during the HUT test by 38.7±7.88 beats/minutes. Both the HR increase during the HUT test and the total KOGS score were negatively correlated with the total metabolic equivalent of the task. The leg circumference and muscle mass were not correlated with the HR increase during the HUT test or the KOGS score.Conclusions: The leg circumference and muscle mass were not related to orthostatic symptoms in patients with POTS. Cardiac remodeling or blood volume increase may be responsible for improvement in POTS after physical activity.
... correction of anaemia and fever), venous pooling (e.g. using compression stockings [65]) and physical reconditioning with an exercise programme (e.g. recumbent exercise such as cycling and rowing is typically preferred with a graduate transition to upright exercise) [66][67][68][69][70]. Pharmacological measures may also be necessary in specific circumstances and typically include therapies such as ivabradine, β blockers, midodrine and fludrocortisone. ...
Coronavirus disease 2019 (COVID-19) can lead to ongoing symptoms such as breathlessness, fatigue and muscle pain, which can have a substantial impact on an individual. Exercise-based rehabilitation programmes have proven beneficial in many long-term conditions that share similar symptoms. These programmes have favourably influenced breathlessness, fatigue and pain, while also increasing functional capacity. Exercise-based rehabilitation may benefit those with ongoing symptoms following COVID-19. However, some precautions may be necessary prior to embarking on an exercise programme. Areas of concern include ongoing complex lung pathologies, such as fibrosis, cardiovascular abnormalities and fatigue, and concerns regarding post-exertional symptom exacerbation. This article addresses these concerns and proposes that an individually prescribed, symptom-titrated exercise-based intervention may be of value to individuals following infection with severe acute respiratory syndrome coronavirus 2.
... 60 The Levine Protocol is a 3-month exercise program that has shown efficacy in lowering heart rates and improving cardiac output in POTS patients. 61 Compression stockings are useful for decreasing lower extremity blood pooling and increasing venous return, although the stockings should reach at least the thigh for maximum benefit. In certain individuals, abdominal binders may also be beneficial by reducing abdominal venous pooling. ...
Postural orthostatic tachycardia syndrome (POTS) is a heterogeneous disorder that presents with positional tachycardia and a constellation of other symptoms. Peer-reviewed evidence for treatment options is limited. In addition, there are various associated conditions with overlapping symptoms. These factors can make the diagnosis and management of POTS a frustrating experience for both providers and patients. This paper aims to combine available scientific data with anecdotal evidence derived from extensive clinical experience to provide information on recognizing the clinical features of POTS, identifying associated conditions, and understanding treatment strategies to help providers better diagnose and manage patients with this condition.
... In cases of orthostatic intolerance without post-exertional symptoms, exercises can be started in the horizontal position to avoid autonomic dysfunction on standing up (syncope, lightheadedness and tachycardia). 67 Exercises should not be implemented if the patient has symptom exacerbation after exercise and if their daily activities are too difficult to do. Above all, it is a matter of readjusting to allow the individual to carry out activities of daily living whilst preserving their energy reserves and avoiding post-exertional malaise. ...
... Previous research has shown that patients with postural orthostatic tachycardia syndrome (POTS) experience exercise intolerance and are more deconditioned than their sedentary, but otherwise healthy counterparts [1][2][3][4][5]. Additionally, it is clear that the act of limiting physical activity to avoid symptoms can actually aggravate the condition by reducing myocardial work and causing consequential ventricular remodeling, which has been seen with prolonged bed rest [6,7]. ...
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.
... Afterwards in the same sessions, strength training will follow, with a focus on lower body and core with a starting 10 min duration with 2 sets of 10 repetition of seated leg press, leg curl, leg extension, calf raise, chest press and seated row with increasing wait and duration till 30 min as tolerable. Both aerobic and strengthening training were adapted from former studies (Fu and Levine [63]) so as to watch for the emergence of PEM which will be assessed with the DePaul Questionnaire subscale for PEM before each session. All patients will be educated regarding the importance of incorporating conservative measures that would be of help especially for postural orthostatic tachycardia syndrome ( Table 2). ...
Dysautonomia in the post-COVID-19 condition appears to affect a significant number of patients , with reports raising the incidence up to 61%, having an overlap with myalgic encephalomyeli-tis/chronic fatigue syndrome. Quality of life and daily function are significantly impacted and conservative management interventions, despite the lack of high-quality evidence to date, are needed to ameliorate disability. A total of 50 adults with a dysautonomia post-COVID-19 diagnosis based on the Ewing battery and a NASA lean test will be enrolled in a randomized single blinded controlled trial with a crossover design. Feasibility and lack of definite dysautonomia diagnosis will be the primary outcomes, while secondary outcomes will be health-related, clinical and cardiopulmonary exercise test indicators. Safety and acceptance will also be checked, primarily excluding participants with post-exertional malaise. The Long-COVID patients Causal Diagnosis and Rehabilitation study in patients with Dysautonomia (LoCoDiRE-Dys) intervention will consist of an educational module, breathing retraining and an individualized exercise intervention of biweekly sessions for two months with regular assessment of both groups. LoCoDiRe-Dys aims to be the first post-COVID-19 random-ized study in people with dysautonomia offering a multimodal intervention both in diagnosis and management. The need for evidence in effectively supporting patients is eminent.
... This was interpreted as cardiac muscle atrophy. In a subsequent publication, Fu et al. suggested that sinus tachycardia in patients with POTS is related to reduced stroke volume [7]. Their conclusion was that cardiac atrophy (low left ventricular mass index [LVMI]) results in low stroke volume. ...
Low left ventricular mass index (LVMI) is thought to limit exercise tolerance in adult patients with postural orthostatic tachy-cardia syndrome (POTS). This finding has not been studied in children. We evaluated the effect of LVMI and hemodynamics at baseline and during exercise in POTS versus controls. POTS and control subjects aged 12-18 years were prospectively enrolled. POTS patients underwent autonomic studies. An echocardiogram was performed on all patients at baseline and during exercise. LVMI, venous return from inferior vena cava (IVC-VTI), left ventricular dimension, and cardiac output were assessed at baseline and during exercise. Generalized linear modeling with mixed effects was used to perform repeated measures testing between POTS and controls. Eighteen POTS patients (14 female, aged 15.4 ± 1.4 years) and nine control subjects (six female, aged 15.0 ± 1.3 years; p = 0.44) were enrolled. At baseline, LVMI was similar in both groups. During exercise, IVC-VTI, left ventricular end-diastolic dimension and volume, and stroke volume were lower in POTS patients. Peak heart rate was higher in POTS patients, but cardiac output was similar in both groups. Exercise time was higher in the control group (11.4 ± 2.7 min vs 9.2 ± 2.1, p = 0.024). Lower venous return resulted in smaller cardiac dimension and stroke volume during exercise. Higher heart rate in POTS may compensate to achieve similar cardiac output compared with control subjects. Lower ventricular filling and earlier time to peak heart rate may explain lower exercise capacity in pediatric POTS.
... Although synonymous for the purpose of this review, individuals with hEDS experience symptoms and conditions outside of those associated with HSD (such as postural orthostatic tachycardia syndrome and dyspnea). 13,76 Symptom-and condition-specific consideration should therefore be undertaken before starting any exercise intervention. Third, the methodological heterogeneity in the included studies and in particular the variability in intervention design (eg, physiotherapy, inspiratory muscle training, closed kinetic chain exercises, lumbar spinal stabilization exercise) and outcome measures (eg, AIMS-2, HADS, Multidimensional Health Assessment Questionnaire) was not conducive to a meta-analysis. ...
Objectives
: To conduct a systematic review examining the effect of exercise and rehabilitation in people with EDS.
Data sources
: The following databases were systematically searched: Medline, Medline In-Process/ePubs, Embase, Cochrane Central Register of Controlled Trials, PsycINFO, and Cumulative Index to Nursing and Allied Health. The final time point captured by the search is November 27, 2020.
Study selection
: Eligible study designs included case-control, case-series, prospective cohort, retrospective cohort, and intervention studies of structured exercise or rehabilitation interventions. Eligible populations included adults (≥18 years of age) with EDS (all sub-types) and Hypermobility Spectrum Disorders. The search was restricted to articles published in English.
Data extraction
: Data was extracted by two independent reviewers. Risk of bias (RoB) was assessed using the Physiotherapy Evidence Database (PEDro) scale for randomized control trials (RCTs), and Risk Of Bias In Non-randomized Studies - of Interventions (ROBINS-I) for non-RCTs. Reporting quality of RCTs was assessed using the Consolidated Standards for Reporting of Trials statement with the harms-extension. Reporting was guided by the PRISMA checklist.
Data synthesis
: The search yielded ten eligible studies including 330 participants. The study designs included five RCTs, one cohort, two single-arm interventions, one retrospective, and one feasibility study. All studies showed some improvement in a physical and/or psychological outcome following the intervention period. One adverse event (non-serious) potentially related to the intervention was reported. Of the five RCTs, two were rated as high quality with low RoB using PEDro, and the majority of non-RCTs were rated as critical RoB by ROBINS-I.
Conclusions
: The results suggest that exercise and rehabilitation may be beneficial for various physical and psychological outcomes. Adequately powered and rigorous RCTs of exercise and rehabilitation interventions for people with EDS are needed.
... 16 Fu and Levine demonstrated that patients with POTS had an excessive increase in heart rate and reduced stroke volume during acute exercise compare to healthy subjects, suggesting that the tachycardia in POTS is related to decreased stroke volume rather than an abnormality of heart rate regulation. 17 Increasing evidence suggests that physical deconditioning is an important contributor to POTS symptoms, proving a rationale for physical activity as an intervention strategy for POTS. 16 There are few published studies that describe physical therapy interventions for individuals with POTS. ...
Background and Purpose: Postural Orthostatic Tachycardia Syndrome (POTS) can have a debilitating effect on an individual’s quality of life. The purpose of this case report is to describe the use of interval training in an aquatic environment to decrease the symptoms of Postural Orthostatic Tachycardia Syndrome. Aquatic therapy provides benefits for individuals with cardiovascular issues, mainly through the principle of hydrostatic pressure. Hydrostatic pressure aids in shunting the blood from the extremities back to the heart, thus increasing cardiac output while reducing the individual’s heart rate. Description: An 18 year-old female high school student who had been experiencing Postural Orthostatic Tachycardia Syndrome symptoms for approximately one year. These symptoms prevented her from participating in school or recreational activities. Intervention: The patient underwent 11 sessions of an aquatic interval program. Her subjective report, heart rate, blood pressure, and rate of perceived exertion were monitored throughout each session. Outcomes: After completing physical therapy, the patient had attained all of her functional goals including standing for 45 minutes, walking between classes at school, and attending her prom. The patient reported that she had not had a fainting spell in over 4 weeks. Despite these functional gains, the patient’s Quality of Life score, as measured by the World Health Organization Quality of Life-BREF questionnaire (a condensed version of the original World Health Organization Quality of Life-100), declined in the following categories: physical health, psychological health, and environment. Discussion: The patient’s exercise-specific heart rate and rate of perceived exertion decreased as sessions progressed, demonstrating an increased activity tolerance. It is hypothesized that the positive effects of hydrostatic pressure on the cardiovascular system contributed to the improvement in exercise tolerance and ultimately to her overall conditioning and activity tolerance. The results of this case report suggest that aquatic therapy may be an appropriate exercise modality for patients with Postural Orthostatic Tachycardia Syndrome. Continued research on the effects of aquatic therapy on the symptoms of Postural Orthostatic Tachycardia Syndrome is warranted.
... Exercise induces neurochemical and structural changes mainly through contractioninduced myokines release and brain-derived neurotrophic factor (BDNF), provoking neurogenesis and synaptogenesis, particularly in the dentate gyrus of the hippocampus, which promotes brain plasticity and prevent cognitive dysfunction [120]. Indeed, exercise has proven its effectiveness in dysautonomia and POTS, quite frequent among people with post-COVID-19 syndrome, by restoring upright hemodynamics, normalizing renaladrenal responsiveness, and improving quality of life [122,123]. In addition, recent crosssection studies support the need of regular moderate exercise as a resilience factor to reduce COVID-related allostatic overload by improving mental and physical well-being [124]. ...
The coronavirus disease (COVID-19), caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection, is leading to unknown and unusual health conditions that are challenging to manage. Post-COVID-19 syndrome is one of those challenges, having become increasingly common as the pandemic evolves. The latest estimates suggest that 10 to 20% of the SARS-CoV-2 patients who undergo an acute symptomatic phase are experiencing effects of the disease beyond 12 weeks after diagnosis. Although research is beginning to examine this new condition, there are still serious concerns about the diagnostic identification, which limits the best therapeutic approach. Exercise programs and physical activity levels are well-known modulators of the clinical manifestations and prognosis in many chronic diseases. This narrative review summarizes the up-to-date evidence on post-COVID-19 syndrome to contribute to a better knowledge of the disease and explains how regular exercise may improve many of these symptoms and could reduce the long-term effects of COVID-19.
... Physical inactivity results in cardiac atrophy and hypovolemia. Early physical activity in the recumbent/horizontal position is recommended as a treatment strategy, with a gradual increase in duration and intensity as patients become more fit (34) . ...
The cardiovascular branch of autonomic nervous system (ANS) is responsible for the regulation of heart rate, blood pressure, and maintaining homeostasis during physiological stress such as exercise and standing upright. ANS constantly controls the rate and force of heart contractions and the vascular tone with the aim to maintain the sufficient tissue perfusion with oxygenated blood and secure venous return to the heart. Dysautonomias, a result of ANS malfunction, are often found in patients with cardiovascular symptoms. Apart from the most prevalent one, arterial hypertension, the cardiovascular dysautonomic continuum encompasses other important although less known conditions: postural orthostatic tachycardia syndrome, inappropriate sinus tachycardia, orthostatic hypotension and reflex syncope. Moreover, heart diseases may evoke autonomic imbalance by themselves; cardiac pump failure is usually associated with sympathetic hyperactivity, neuroendocrine vasopressor activation, higher heart rate, reduced heart rate variability and baroreflex hyposensitivity, all of which are predictors of adverse outcomes.
Cardiologists and electrophysiologist frequently see patients for the evaluation and management of unexplained syncope, orthostatic intolerance, heart rhythm abnormalities and symptoms of palpitations. Recognizing the presence of cardiac dysautonomia is an important skill which is necessary for the appropriate evaluation and treatment of these patients. Clinical presentations may overlap, and the importance of a thorough history cannot be over-emphasized. In this review we will present a cases of a patients with cardiac dysautonomia which is illustrative of a typical patient experience, followed by a review of the autonomic nervous system and discussion of prevalence, clinical presentation, and pathophysiology of common cardiac dysautonomias.
... It is recommended that the patients stand against a wall with feet 15 cm from it, starting at 5 min/d, and then gradually increasing to 20 min/d according to patients' tolerance and preference (5,98). Several training results show that exercise training can improve the symptoms and the quality of life (101)(102)(103) and is even better than propranolol in the recovery of upright hemodynamics and the normalization of renal-adrenal reactivity (101). ...
Postural tachycardia syndrome (POTS), characterized by chronic (≥6 months) orthostatic intolerance symptoms with a sustained and excessive heart rate increase while standing without postural hypotension, is common in children and adolescents. Despite the unclear pathogenesis of POTS, the present opinion is that POTS is a heterogeneous and multifactorial disorder that includes altered central blood volume, abnormal autonomic reflexes, “hyperadrenergic” status, damaged skeletal muscle pump activity, abnormal local vascular tension and vasoactive factor release, mast cell activation, iron insufficiency, and autoimmune dysfunction. A number of pediatric POTS patients are affected by more than one of these pathophysiological mechanisms. Therefore, individualized treatment strategies are initiated in the management of POTS, including basal non-pharmacological approaches (e.g., health education, the avoidance of triggers, exercise, or supplementation with water and salt) and special pharmacological therapies (e.g., oral rehydration salts, midodrine hydrochloride, and metoprolol). As such, the recent progress in the pathogenesis, management strategies, and therapeutic response predictors of pediatric POTS are reviewed here.
... The cause of POTS has not yet been established (Benarroch, 2012), though many possible disease mechanisms including autonomic denervation (Kimpinski et al., 2012;Haensch et al., 2014), autonomic autoimmunity (Ruzieh et al., 2017), hypovolemia (Benarroch, 2012;Kimpinski et al., 2012), hyperadrenergic stimulation (Kimpinski et al., 2012), and deconditioning have been proposed (Benarroch, 2012;Fu and Levine, 2015). The entity of symptoms in POTS patients is likely caused by a combination of these factors. ...
Introduction: Postural tachycardia syndrome (POTS) is a suspected dysautonomia with symptoms of orthostatic intolerance and abnormally increased heart rate while standing. We aimed to study cardiac autonomic nervous system functioning in head-up tilt (HUT) in adolescents with POTS to find out if parasympathetic tone is attenuated in the upright position.
Methods: We compared characteristics of a group of 25 (females 14/25; 56%) adolescents with POTS and 12 (females 4/12; 34%) without POTS aged 9–17 years. We compared heart rate variability with high- and low-frequency oscillations, and their temporal changes in HUT.
Results: The high-frequency oscillations, i.e., HF, attenuated in both groups during HUT (p < 0.05), but the attenuation was bigger in POTS (p = 0.04). In the beginning of HUT, low-frequency oscillations, i.e., LF, increased more in POTS (p = 0.01), but in the end of HUT, an attenuation in LF was seen in the POTS group (p < 0.05), but not in the subjects without POTS. There were no associations of previous infections or vaccinations with POTS. Subjects with POTS were sleepier and their overall quality of life was very low.
Conclusion: The results imply to an impaired autonomic regulation while standing in POTS, presenting as a lower HF and higher LF in the beginning of HUT and an attenuated LF in the prolonged standing position.
... 88 Given the unproven efficacy and the potential adverse effects of drugs currently used in POTS patients, it is prudent for clinicians to always start with more conservative strategies. Endurance and cardiovascular training (beginning in the semi-recumbant position, such as, with rowing), 89 increased water intake and other relatively harmless strategies are easy to implement and may help. Involvement in a rigorous cardiovascular exercise program has shown clear, and sustained, benefits in patients with POTS. ...
Although diagnostic criteria have been developed characterizing postural orthostatic tachycardia syndrome (POTS), no single set of criteria is universally accepted. Furthermore, there are gaps in the present criteria to identify individuals who have this condition. The reproducibility of the physiological findings, the relationship of symptoms to physiological findings, the presence of symptoms alone without any physiological findings and the response to various interventions confuse rather than clarify this condition. As many disease entities can be confused with POTS, it becomes critical to identify what this syndrome is. What appears to be POTS may be an underlying condition that requires specific therapy. POTS is not simply orthostatic intolerance and symptoms or intermittent orthostatic tachycardia but the syndrome needs to be characterized over time and with reproducibility. Here we address critical issues regarding the pathophysiology and diagnosis of POTS in an attempt to arrive at a rational approach to categorize the syndrome with the hope that it may help both better identify individuals and better understand approaches to therapy.
... [25] Symptoms are improved with exercise training. Fu et al. [26] and Fu and Levine [27] in their study on POTS patients found that exercise intervention reduced orthostatic tachycardia and improved quality of life in these patients. Other appropriate methods such as compression stockings and pharmacological agents which increase peripheral resistance or augment circulatory fluid volume would also be helpful. ...
Background: Postural orthostatic tachycardia syndrome (POTS) is an autonomic disorder characterized by the clinical symptoms of orthostatic intolerance such as light-headedness, fatigue, sweating, tremor, anxiety, palpitation, exercise intolerance, and near syncope on standing in the absence of orthostatic hypotension. Objective: The objective of this study is to evaluate the clinical profile and autonomic parameters in patients with POTS. Materials and Methods: A total of 70 patients with POTS underwent cardiovascular autonomic function tests, i.e., heart rate (HR) response to deep breathing, heart rate and blood pressure (BP) changes in Valsalva maneuver and tilt study in the autonomic laboratory of the Department of Neurology from January 2014 to February 2016 using WR Medical Works, USA. Results: Mean age of cohort was 28.07 ± 10.64 years, and there were 36 (51%) women. Light-headedness 59 (84.3%) was the most common orthostatic symptom, followed by dizziness 56 (80%), palpitation 41 (58.57%), anxiety 26 (37.14%), loss of consciousness 21 (30%), disequilibrium 19 (27.14%), visual symptoms 12 (17.14%), weakness 8 (11.43%), and shortness of breath 2 (2.86%). The average heart rate response to deep breathing was 24.79 ± 7.20 bpm. Average Valsalva ratio was 1.78 ± 0.30. During the tilt, average maximum HR increase was 43.47 ± 11.19 bpm. Conclusion: POTS is an underrecognized disorder and majority of them present with vague orthostatic symptoms ways, hence clinicians should be made aware of the symptomatology. The tilt table test with beat-to-beat monitoring of HR and BP is the standard test for diagnosis.
... Exercise performance is improved after short-term (3 months) exercise training. Specifically, stroke volume is greater and heart rate is lower at any given VO2 during exercise after training versus before training [50,51]. An evidence-based approach to manage a patient with POTS with a -reconditioning‖ program of endurance and strength training is necessary [51]. ...
Postural orthostatic tachycardia syndrome (POTS) is multifactorial clinical syndrome poorly understood but important cause of orthostatic intolerance resulting from cardiovascular autonomic dysfunction. It's defined by an excessive increase in heart rate with assumption of upright posture without orthostatic hypotension. Individuals affected by POTS are mainly young (aged between 15 years and 40 years) and predominantly female. Many overlapping pathophysiologies are behind POTS, including an autonomic neuropathy in the lower body, hypovolemia, hyperadrenergic states, mast cell activation and autoantibodies. Clinically, it's form of chronic orthostatic intolerance associated with a > 6-month history of symptoms (palpitations, dizziness and occasionally syncope) that are relieved by recumbence. POTS have similarities to a number of other disorders, e.g., chronic fatigue syndrome, Ehlers-Danlos Syndrome, vasovagal syncope, and inappropriate sinus tachycardia. We aim in this article to review the characteristics of POTS and outline possible pathophysiological mechanisms of this syndrome, as well as current and investigational treatments.
... При ПМК у дітей досить часто зустрічається по рушення серцевого ритму, виявлення якого потребує проведення добового холтерівського ЕКГ моніторингу. Серед аритмій у дітей з ПМК найчастіше виявляються синусова тахі кардія, надшлуночкові і шлуночкові екстраси столії, рідше -брадикардія [15]. ...
The article summarizes the literature data and our own findings upon the clinic, diagnosis, treatment and rehabilitation of children with hypermobility syndrome on the background of undifferentiated connective tissue dysplasia. The peculiarities of connective tissue determine the body adaptation processes, stability of organs and systems, and understanding of connective tissue metabolism features and early detection of its violations can use as a basis for preventive measures of many dysfunctions and chronic pathological conditions. Therefore, children with hypermobility syndrome and signs of undifferentiated connective tissue dysplasia should undergo a comprehensive examination to establish the functional changes of organs and systems that will ensure the timely preventive measures and, if necessary, appropriate treatment.
... Exercise and increased hydration as a part of POTS treatment has been recommended in past research (Mtinangi & Hainsworth, 1998;Winker et al., 2005;Fu et al., 2011;Joyner, 2011;White et al., 2011;Nicholson, 2015), however, some additional supportive tips may be helpful for clinicians and teams as they begin working with this patient population. Previous research has documented treatment over a lengthy period of time (up to year) allowing for a very gradual increase in physical activity (Brilla et al., 1998;Winker et al., 2005;White et al., 2011;Fu & Levine, 2015). Although it is not documented in research, anecdotally we often hear that medical providers inform patients and families that they will not be able to participate in physical activity secondary to their symptoms. ...
This article supports the use of intensive rehabilitation for adolescents with postural orthostatic tachycardia syndrome (POTS). It includes treatment progression information as part of physical and occupational therapies. This treatment progression is supported by outcome data of 15 program participants with a primary diagnosis of POTS, often with chronic pain, POTS is found to be secondary diagnosis and still seen as a barrier to intensive treatment.
... 27,30 Inappropriate autonomic response to exercise leads to exercise intolerance, or severe fatigue as a result of low levels of exercise. 31 Symptoms are often initially triggered by a physical stressor that results in forced rest, such as surgery, pregnancy, illness, or injury. See Arnold et al, 27 for more detail about POTS diagnosis and pathophysiology. ...
... Physical reconditioning with regular exercise is the cornerstone of treatment for POTS (Sheldon et al., 2015) especially in the chronic state when physical disability has been compounded by cardiovascular deconditioning. A structured exercise program featuring endurance (aerobic) reconditioning with some resistance (strength) training for the lower body described below in detail is recommended for patients with POTS, and supervised exercise training is preferable to maximize functional capacity in these patients (Fu and Levine, 2013;Fu and Levine, 2015). This carefully structured exercise training program was initially developed for spaceflight and/or head-down bed rest countermeasures Holt et al., 2016;Iwasaki et al., 2003;Lee et al., 2014;Ploutz-Snyder et al., 2014;Shibata et al., 2010a), which has been demonstrated to be effective for the treatment of POTS in our previous studies in a research setting (Fu et al., 2010;Fu et al., 2011;Galbreath et al., 2011;Shibata et al., 2012), as well as in a community environment (George et al., 2016). ...
Recent research has demonstrated that cardiovascular deconditioning (i.e., cardiac atrophy and hypovolemia) contributes significantly to the Postural Orthostatic Tachycardia Syndrome (POTS) and its functional disability. Therefore, physical reconditioning with exercise training and volume expansion via increased salt and fluid intake should be initiated early in the course of treatment for patients with POTS if possible. The use of horizontal exercise (e.g., rowing, swimming, recumbent bike, etc.) at the beginning is a critical strategy, allowing patients to exercise while avoiding the upright posture that elicits their POTS symptoms. As patients become increasingly fit, the duration and intensity of exercise should be progressively increased, and upright exercise can be gradually added as tolerated. Supervised training is preferable to maximize functional capacity. Other non-pharmacological interventions, which include: 1) chronic volume expansion via sleeping in the head-up position; 2) reduction in venous pooling during orthostasis by lower body compression garments extending at least to the xiphoid or with an abdominal binder; and 3) physical countermeasure maneuvers, such as squeezing a rubber ball, leg crossing, muscle pumping, squatting, negative-pressure breathing, etc., may also be effective in preventing orthostatic intolerance and managing acute clinical symptoms in POTS patients. However, randomized clinical trials are needed to evaluate the efficacies of these non-pharmacological treatments of POTS.
... 65 Short-term exercise training has been shown to increase the baroreflex sensitivity in POTS patients and decrease the upright HR. 66 It is important to keep a modest expectation of activity levels in the early phase to avoid postexertional fatigue and abandonment of the program, as a gradual increase in exercise can result in significant improvement in both symptoms and orthostatic HR in patients with POTS. 65,67,68 Other lifestyle factors include adoption of good sleep hygiene to address disrupted circadian rhythm, and psychologic support, to encourage realistic expectations of integration back into the study or workplace. ...
Postural tachycardia syndrome (POTS) is the combination of an exaggerated heart rate response to standing, in association with symptoms of lightheadedness or pre-syncope that improve when recumbent. The condition is often associated with fatigue and brain fog, resulting in significant disruptions at a critical time of diagnosis in adolescence and young adulthood. The heterogeneity of the underlying pathophysiology and the variable response to therapeutic interventions make management of this condition challenging for both patients and physicians alike. Here, we aim to review the factors and mechanisms that may contribute to the symptoms and signs of POTS and to present our perspectives on the clinical approach toward the diagnosis and management of this complex syndrome.
Four adolescent female athletes across four grades were diagnosed with either psychogenic nonepileptic seizures or conversion disorder. The females underwent thorough evaluations with their primary care providers and episode and symptom tracking by their athletic trainer. Through different applications of cognitive behavioral therapy and one-on-one counseling, the disorders resolved. Teaching athletes the importance of choosing healthy coping mechanisms to stress is vital to quality mental health. It is recommended that more research be done on psychogenic nonepileptic seizures and provide an understanding to those working with the adolescent population on triggers and treatments for psychogenic nonepileptic seizures.
Postural orthostatic tachycardia syndrome (POTS), first described in 1992, remains an enigmatic, yet severely and variably debilitating, disorder. The pathophysiology of this syndrome is still not understood, and there remains no biomarker indicating the presence of POTS. Although research interest has increased in recent years, there are relatively fewer clinical and research studies addressing POTS in children and adolescents compared with adults. Yet, adolescence is when a large number of cases of POTS begin, even among adult patients who are subsequently studied. This article summarizes reported research in POTS, specifically in pediatric patients, including discussion of aspects of diagnostic criteria, risk factors and outcomes, neurohormonal and hemodynamic abnormalities, clinical assessment, and treatment. The goals of this review are increased recognition and acknowledgment of POTS among pediatric and adolescent providers, as well as to provide an understanding of reported abnormalities of homeostasis, such that symptomatic patients will be able to be recognized and appropriately managed, enabling them to return to their activities of daily living.
Orthostatic tests, which include an active orthostatic test and a passive orthostatic test, are effective tests for differentiating among causes of orthostatic intolerance, such as orthostatic hypotension (OH), postural orthostatic tachycardia syndrome (POTS), and vasovagal syncope (VVS). OH is diagnosed when the systolic blood pressure (SBP) decreases by more than 20mmHg and/or the diastolic blood pressure (DBP) decreases by more than 10mmHg as soon as the patient stands, based on the criteria of the International Autonomic Nervous Society. The passive orthostatic test has a higher sensitivity for the diagnosis of OH as compared to the active orthostatic test. On the other hand, in cases where the blood pressure decreases are seen at 3 minutes or after, the diagnosis of VVS should be considered. POTS is diagnosed if the heart rate increases by more than 30 bpm when the patient stands, in the absence of OH. Orthostatic tests are useful to understand the underlying condition in patients suffering from orthostatic dizziness and chronic dizziness.
Postural orthostatic tachycardia syndrome (POTS) is a chronic and often disabling disorder characterized by orthostatic intolerance with excessive heart rate increase without hypotension during upright posture. Patients often experience a constellation of other typical symptoms including fatigue, exercise intolerance and gastrointestinal distress. A typical patient with POTS is a female of child-bearing age, who often first displays symptoms in adolescence. The onset of POTS may be precipitated by immunological stressors such as a viral infection. A variety of pathophysiologies are involved in the abnormal postural tachycardia response; however, the pathophysiology of the syndrome is incompletely understood and undoubtedly multifaceted.
Clinicians and researchers focused on POTS convened at the National Institutes of Health in July 2019 to discuss the current state of understanding of the pathophysiology of POTS and to identify priorities for POTS research. This article, the first of two articles summarizing the information discussed at this meeting, summarizes the current understanding of this disorder and best practices for clinical care.
The evaluation of a patient with suspected POTS should seek to establish the diagnosis, identify co-morbid conditions, and exclude conditions that could cause or mimic the syndrome. Once diagnosed, management typically begins with patient education and non-pharmacologic treatment options. Various medications are often used to address specific symptoms, but there are currently no FDA-approved medications for the treatment of POTS, and evidence for many of the medications used to treat POTS is not robust.
Dyspnea in low-preload states is an underrecognized but growing diagnosis in patients with unexplained dyspnea. Patients can often experience debilitating symptoms at rest and with exertion, as low measured preload often leads to decreased cardiac output and ultimately dyspnea. In the present article, we performed a review of the literature and a multidisciplinary evaluation to understand the pathophysiology, diagnosis, and treatment of dyspnea in low-preload states. We explored selected etiologies and suggested an algorithm to approach unexplained dyspnea. The mainstay of diagnosis remains as invasive cardiopulmonary exercise testing. We concluded with a variety of nonpharmacological and pharmacological therapies, highlighting that a multifactorial approach may lead to the best results.
Postural tachycardia syndrome (POTS) is a syndrome characterized by elevated heart rate without hypotension and most commonly occurs in young females (generally <35 years of age). The prevalence of POTS is on the rise, but the etiology is still under investigation, and there appear to be multiple potential physiologic causes. The majority of these patients experience a multitude of gastrointestinal (GI) and systemic symptoms and conditions that may contribute to functional debility and poor quality of life. Although symptoms generally improve with age, they can still lead to significant issues meeting nutrition and hydration needs. This paper summarizes the understood potential pathophysiology of POTS, associated GI and nutrition issues, general treatment of POTS, and strategies to assess and meet the unique nutrition and hydration needs of these patients.
Patients with life-threatening conditions that present with syncope can be recognized promptly and appropriately with history, physical electrocardiogram (EKG), and echocardiography. Once diseases are recognized, exercise testing may be part of disease characterization and management. Exercise testing has a critical role in patients with high-risk histories of syncope, to evaluate for catecholaminergic polymorphic ventricular tachycardia (CPVT) and other unusual arrhythmia syndromes. Most patients with low severity, typical syncope will not benefit from exercise testing (or any substantial testing). For patients with more problematic symptoms, exercise testing represents a relatively low barrier test that can identify multiple contributors to symptoms. This includes deconditioning, abnormal or potentially abnormal blood pressure responses, and incidental or potentially important arrhythmias. The differences between normal and abnormal exercise responses in those with potential orthostatic syndrome overlap with normal physiology. Testing always needs to be interpreted in context.
Dizziness and vertigo are infrequent complaints in the adolescent population. For those few adolescents who seek outpatient evaluation for these complaints, the majority are diagnosed with migraine headaches, and most meet criteria for the diagnosis of vestibular migraines and/or probable vestibular migraine according to the International Classification of Headache Disorders, third edition (beta version). In addition to migraine headache, the differential diagnosis in this age group includes episodic ataxia type II; chronic daily headaches; postural orthostatic tachycardia; intracranial mass lesions; psychiatric disorders (e.g., depression or somatoform disorders); and rarely vestibular disorders, including viral labyrinthitis and Meniere's disease. Evaluation and, in the majority of cases, diagnosis are based on careful history and physical examination with neuroimaging performed for all adolescents with a history of trauma, an abnormal neurologic examination, persistent headaches, or an indication of central lesion on vestibular testing.
Neurogenic orthostatic hypotension is a highly prevalent and disabling feature of autonomic failure due to both peripheral and central neurodegenerative diseases. Community-based epidemiological studies have demonstrated a high morbidity and mortality associated with neurogenic orthostatic hypotension. It is due to impairment of baroreflex-mediated vasoconstriction of the skeletal muscle and splanchnic circulation and is caused by damage or dysfunction at central and/or peripheral sites in the baroreflex efferent pathway. Nonpharmacological and pharmacological interventions may be implemented to ameliorate the symptoms of orthostatic intolerance and improve quality of life. Many patients will be adequately treated by education, counseling, removal of hypotensive medications, and other nonpharmacological interventions, whereas more severely afflicted patients require pharmacological interventions. The first stage of pharmacological treatment involves repletion of central blood volume. If unsuccessful, this should be followed by treatment with sympathomimetic agents.
Purpose: To explore exercise beliefs and behaviours of individuals with Joint Hypermobility syndrome/Ehlers–Danlos syndrome – hypermobility type and to explore patient experiences of physiotherapy.
Methods: A cross sectional questionnaire survey design was used to collect quantitative and qualitative data from adult members of the Hypermobility Syndromes Association and Ehlers–Danlos Syndrome Support UK. Descriptive and inferential statistics were used to analyse the data. Qualitative data was analysed thematically.
Results: About 946 questionnaires were returned and analysed. Participants who received exercise advice from a physiotherapist were 1.75% more likely to report high volumes of weekly exercise (odds ratio [OR] = 1.75, 95% confidence interval [CI] = 1.30–2.36, p < 0.001) than those with no advice. Participants who believed that exercise is important for long-term management were 2.76 times more likely to report a high volume of weekly exercise compared to the participants who did not hold this belief (OR = 2.76, 95% CI = 1.38–5.50, p = 0.004). Three themes emerged regarding experience of physiotherapy; physiotherapist as a partner, communication – knowledge, experience and safety.
Conclusion: Pain, fatigue and fear are common barriers to exercise. Advice from a physiotherapist and beliefs about the benefits of exercise influenced the reported exercise behaviours of individuals with Ehlers–Danlos syndrome – hypermobility type in this survey.
• Implications for rehabilitation
• Exercise is a cornerstone of treatment for Ehlers–Danlos syndrome/Ehlers–Danlos syndrome – hypermobility type.
• Pain, fatigue and fear of injury are frequently reported barriers to exercise.
• Advice from physiotherapists may significantly influence exercise behaviour.
• Physiotherapists with condition specific knowledge and good verbal and non-verbal communication facilitate a positive therapeutic experience.
Both cardiac size and dynamics are first estimated by precordial palpation. Descriptions of auscultation include definition of a cycle’s four basic cardiac sounds. Mitral valve prolapse, owing to its variability, prevalence, and historic place in cardiac imaging, is singled out for detailed description.
Background:
Aerobic power declines with age. The degree to which this decline is reversible remains unclear. In a 30-year longitudinal follow-up study, the cardiovascular adaptations to exercise training in 5 middle-aged men previously trained in 1966 were evaluated to assess the degree to which the age-associated decline in aerobic power is attributable to deconditioning and to gain insight into the specific mechanisms involved. Methods and Results-- The cardiovascular response to acute submaximal and maximal exercise were assessed before and after a 6-month endurance training program. On average, VO(2max) increased 14% (2.9 versus 3.3 L/min), achieving the level observed at the baseline evaluations 30 years before. Likewise, VO(2max) increased 16% when indexed to total body mass (31 versus 36 mL/kg per minute) or fat-free mass (44 versus 51 mL/kg fat-free mass per minute). Maximal heart rate declined (181 versus 171 beats/min) and maximal stroke volume increased (121 versus 129 mL) after training, with no change in maximal cardiac output (21.4 versus 21.7 L/min); submaximal heart rates also declined to a similar degree. Maximal AVDO(2) increased by 10% (13.8 versus 15.2 vol%) and accounted for the entire improvement of aerobic power associated with training.
Conclusions:
One hundred percent of the age-related decline in aerobic power among these 5 middle-aged men occurring over 30 years was reversed by a 6-month endurance training program. However, no subject achieved the same maximal VO(2) attained after training 30 years earlier, despite a similar relative training load. The improved aerobic power after training was primarily the result of peripheral adaptation, with no effective improvement in maximal oxygen delivery.
Introduction: Postural tachycardia syndrome (POTS) is associated with exercise intolerance, hypovolemia and cardiac atrophy, which may contribute to reduced stroke volume and compensatory exaggerated heart rate (HR) increases. Acute volume loading with intravenous saline reduces HR and improves orthostatic tolerance and symptoms in POTS, but its effect on exercise capacity is unknown. In this study, we determined the effect of intravenous saline infusion on peak exercise capacity (VO2peak) in POTS. Methods: Nineteen POTS patients participated in a sequential study. VO2peak was measured on two separate study days, following placebo or 1 L intravenous saline (NaCl 0.9%). Patients exercised on a semi-recumbent bicycle with resistance increased by 25 watts every 2 minutes until maximal effort was achieved. Results: Patients exhibited blood volume deficits (-13.4±1.4% ideal volume), consistent with mild to moderate hypovolemia. At baseline, saline significantly increased stroke volume (saline: 80±8 mL vs. placebo: 64±4 ml; p=0.010), increased cardiac output (saline: 6.9±0.5 l/min vs. placebo: 5.7±0.2 l/min; p=0.021), and reduced systemic vascular resistance (saline: 992.6±70.0 dyn-s/cm(5) vs. placebo: 1184.0±50.8 dyn-s/cm(5); p=0.011), with no effect on VO2peak, heart rate (HR) or blood pressure. During exercise, saline did not produce differences in VO2peak (saline: 26.3±1.2 mg/kg/min vs. placebo: 27.7±1.8 mg/kg/min; p=0.615), peak HR (saline: 174±4 bpm vs. placebo: 175±3 bpm; p=0.672) or other cardiovascular parameters. Conclusions: These findings suggest that acute volume loading with saline does not improve VO2peak or cardiovascular responses to exercise in POTS, despite improvements in resting hemodynamic function.
We evaluated a 22-yr-old Swedish man with lifelong exercise intolerance marked by premature exertional muscle fatigue, dyspnea, and cardiac palpitations with superimposed episodes lasting days to weeks of increased muscle fatigability and weakness associated with painful muscle swelling and pigmenturia. Cycle exercise testing revealed low maximal oxygen uptake (12 ml/min per kg; healthy sedentary men = 39 +/- 5) with exaggerated increases in venous lactate and pyruvate in relation to oxygen uptake (VO2) but low lactate/pyruvate ratios in maximal exercise. The severe oxidative limitation was characterized by impaired muscle oxygen extraction indicated by subnormal systemic arteriovenous oxygen difference (a-v O2 diff) in maximal exercise (patient = 4.0 ml/dl, normal men = 16.7 +/- 2.1) despite normal oxygen carrying capacity and Hgb-O2 P50. In contrast maximal oxygen delivery (cardiac output, Q) was high compared to sedentary healthy men (Qmax, patient = 303 ml/min per kg, normal men 238 +/- 36) and the slope of increase in Q relative to VO2 (i.e., delta Q/delta VO2) from rest to exercise was exaggerated (delta Q/delta VO2, patient = 29, normal men = 4.7 +/- 0.6) indicating uncoupling of the normal approximately 1:1 relationship between oxygen delivery and utilization in dynamic exercise. Studies of isolated skeletal muscle mitochondria in our patient revealed markedly impaired succinate oxidation with normal glutamate oxidation implying a metabolic defect at the level of complex II of the mitochondrial respiratory chain. A defect in Complex II in skeletal muscle was confirmed by the finding of deficiency of succinate dehydrogenase as determined histochemically and biochemically. Immunoblot analysis showed low amounts of the 30-kD (iron-sulfur) and 13.5-kD proteins with near normal levels of the 70-kD protein of complex II. Deficiency of succinate dehydrogenase was associated with decreased levels of mitochondrial aconitase assessed enzymatically and immunologically whereas activities of other tricarboxylic acid cycle enzymes were increased compared to normal subjects. The exercise findings are consistent with the hypothesis that this defect impairs muscle oxidative metabolism by limiting the rate of NADH production by the tricarboxylic acid cycle.
To determine whether a programme of simple, moderate exercise training increases blood volume and improves orthostatic tolerance in patients with attacks of syncope or near syncope related to orthostatic stress.
An open study in 14 patients referred with unexplained attacks of syncope, who were shown to have a low tolerance to an orthostatic stress test. Measurements were made of plasma and blood volumes, orthostatic tolerance to a test of combined head up tilt and lower body suction, and baroreceptor sensitivity by applying subatmospheric pressures to a chamber over the neck. Cardiorespiratory fitness was assessed from the relation between heart rate and oxygen uptake during a graded treadmill exercise test. Assessments were made before and after undertaking an exercise training programme (Canadian Air Force 5BX/XBX).
After the training period, 12 of the 14 patients showed evidence of improved cardiorespiratory fitness. All 12 patients were symptomatically improved; they showed increases in plasma and blood volumes and in orthostatic tolerance, and decreases in baroreceptor sensitivity. Despite the improved orthostatic tolerance, values of blood pressure both while supine and initially following tilting were lower than before training.
Exercise training has a role in the management of patients with syncope and poor orthostatic tolerance. It improves symptoms and increases orthostatic tolerance without increasing resting blood pressure.
Both chronic microgravity exposure and long-duration bed rest induce cardiac atrophy, which leads to reduced standing stroke volume and orthostatic intolerance. However, despite the fact that women appear to be more susceptible to postspaceflight presyncope and orthostatic hypotension than male astronauts, most previous high-resolution studies of cardiac morphology following microgravity have been performed only in men. Because female athletes have less physiological hypertrophy than male athletes, we reasoned that they also might have altered physiological cardiac atrophy after bed rest. Magnetic resonance imaging was performed in 24 healthy young women (32.1 +/- 4 yr) to measure left ventricular (LV) and right ventricular (RV) mass, volumes, and morphology accurately before and after 60 days of 6 degrees head-down tilt (HDT) bed rest. Subjects were matched and then randomly assigned to sedentary bed rest (controls, n = 8) or two treatment groups consisting of 1) exercise training using supine treadmill running within lower body negative pressure plus resistive training (n = 8), or 2) protein (0.45 g x kg(-1) x day(-1) increase) plus branched-chain amino acid (BCAA) (7.2 g/day) supplementation (n = 8). After sedentary bed rest without nutritional supplementation, there were significant reductions in LV (96 +/- 26 to 77 +/- 25 ml; P = 0.03) and RV volumes (104 +/- 33 to 86 +/- 25 ml; P = 0.02), LV (2.2 +/- 0.2 to 2.0 +/- 0.2 g/kg; P = 0.003) and RV masses (0.8 +/- 0.1 to 0.6 +/- 0.1 g/kg; P < 0.001), and the length of the major axis of the LV (90 +/- 6 to 84 +/- 7 mm. P < 0.001), similar to what has been observed previously in men (8.0%; Perhonen MA, Franco F, Lane LD, Buckey JC, Blomqvist Zerwekh JE, Peshock RM, Weatherall PT, Levine BD. J Appl Physiol 91: 645-653, 2001). In contrast, there were no significant reductions in LV or RV volumes in the exercise-trained group, and the length of the major axis was preserved. Moreover, there were significant increases in LV (1.9 +/- 0.4 to 2.3 +/- 0.3 g/kg; P < 0.001) and RV masses (0.7 +/- 0.1 to 0.8 +/- 0.2 g/kg; P = 0.002), as well as mean wall thickness (9 +/- 2 to 11 +/- 1 mm; P = 0.02). The interaction between sedentary and exercise LV and RV masses was highly significant (P < 0.0001). Protein and BCAA supplementation led to an intermediate phenotype with no change in LV or RV mass after bed rest, but there remained a significant reduction in LV volume (103 +/- 14 to 80 +/- 16 ml; P = 0.02) and major-axis length (91 +/- 5 to 88 +/- 7 mm; P = 0.003). All subjects lost an equivalent amount of body mass (3.4 +/- 0.2 kg control; 3.1 +/- 0.04 kg exercise; 2.8 +/- 0.1 kg protein). Cardiac atrophy occurs in women similar to men following sedentary 60 days HDT bed rest. However, exercise training and, to a lesser extent, protein supplementation may be potential countermeasures to the cardiac atrophy associated with chronic unloading conditions such as in spaceflight and prolonged bed rest.
Postural tachycardia syndrome (POTS) is characterized by excessive tachycardia without hypotension during orthostasis. Most POTS patients also report exercise intolerance. To assess cardiovascular regulation during exercise in POTS, patients (n = 13) and healthy controls (n = 10) performed graded cycle exercise at 25, 50, and 75 W in both supine and upright positions while arterial pressure (arterial catheter), heart rate (HR; measured by ECG), and cardiac output (open-circuit acetylene breathing) were measured. In both positions, mean arterial pressure, cardiac output, and total peripheral resistance at rest and during exercise were similar in patients and controls (P > 0.05). However, supine stroke volume (SV) tended to be lower in the patients than controls at rest (99 +/- 5 vs. 110 +/- 9 ml) and during 75-W exercise (97 +/- 5 vs. 111 +/- 7 ml) (P = 0.07), and HR was higher in the patients than controls at rest (76 +/- 3 vs. 62 +/- 4 beats/min) and during 75-W exercise (127 +/- 3 vs. 114 +/- 5 beats/min) (both P < 0.01). Upright SV was significantly lower in the patients than controls at rest (57 +/- 3 vs. 81 +/- 6 ml) and during 75-W exercise (70 +/- 4 vs. 94 +/- 6 ml) (both P < 0.01), and HR was much higher in the patients than controls at rest (103 +/- 3 vs. 81 +/- 4 beats/min) and during 75-W exercise (164 +/- 3 vs. 131 +/- 7 beats/min) (both P < 0.001). The change (upright - supine) in SV was inversely correlated with the change in HR for all participants at rest (R(2) = 0.32), at 25 W (R(2) = 0.49), 50 W (R(2) = 0.60), and 75 W (R(2) = 0.32) (P < 0.01). These results suggest that greater elevation in HR in POTS patients during exercise, especially while upright, was secondary to reduced SV and associated with exercise intolerance.
Patients with postural tachycardia syndrome (POTS) have excessive tachycardia without hypotension during orthostasis as well as exercise. We tested the hypothesis that excessive tachycardia during exercise in POTS is not related to abnormal baroreflex control of heart rate (HR). Patients (n = 13) and healthy controls (n = 10) performed graded cycle exercise at 25, 50, and 75 W in both supine and upright positions while arterial pressure (arterial catheter) and HR (ECG) were measured. Baroreflex sensitivity of HR was assessed by bolus intravenous infusion of phenylephrine at each workload. In both positions, HR was higher in the patients than the controls during exercise. Supine baroreflex sensitivity (HR/systolic pressure) in POTS patients was -1.3 +/- 0.1 beats.min(-1).mmHg(-1) at rest and decreased to -0.6 +/- 0.1 beats.min(-1).mmHg(-1) during 75-W exercise, neither significantly different from the controls (P > 0.6). In the upright position, baroreflex sensitivity in POTS patients at rest (-1.4 +/- 0.1 beats.min(-1).mmHg(-1)) was higher than the controls (-1.0 +/- 0.1 beats.min(-1).mmHg(-1)) (P < 0.05), and it decreased to -0.1 +/- 0.04 beats.min(-1).mmHg(-1) during 75-W exercise, lower than the controls (-0.3 +/- 0.09 beats.min(-1).mmHg(-1)) (P < 0.05). The reduced arterial baroreflex sensitivity of HR during upright exercise was accompanied by greater fluctuations in systolic and pulse pressure in the patients than in the controls with 56 and 90% higher coefficient of variations, respectively (P < 0.01). However, when baroreflex control of HR was corrected for differences in HR, it was similar between the patients and controls during upright exercise. These results suggest that the tachycardia during exercise in POTS was not due to abnormal baroreflex control of HR.
Impaired skeletal muscle oxidative phosphorylation in patients with severe mitochondrial respiratory chain defects results in disabling exercise intolerance that is associated with a markedly blunted capacity of muscle to increase oxygen utilization in relation to circulatory and ventilatory responses that increase oxygen delivery to muscle during exercise. The range of oxidative limitation and the relationship between the severity of oxidative defects and physiological responses to exercise among a broader spectrum of mitochondrial respiratory chain defects has not been defined. We evaluated oxidative capacity and circulatory and ventilatory responses to maximal cycle exercise in 40 patients with biochemically and/or molecularly defined mitochondrial myopathy (MM) associated with varying levels of exercise tolerance, and compared responses with those in healthy sedentary individuals. In the MM patients, mean peak work capacity (0.88 ± 0.6 W/kg) and oxygen uptake (VO2, 16 ± 8 ml/kg/min) were significantly lower ( P < 0.01) than in controls (mean work capacity = 2.2 ± 0.7 W/kg; VO2 = 32 ± 7 ml/kg/min), but the patient range was broad (0.17–3.2 W/kg; 6–47 ml/kg/min). Oxidative capacity in patients was limited by the ability of muscle to extract available oxygen from blood [mean peak systemic arteriovenous O2 difference (a–vO2); patients = 7.7 ± 3.5, range 2.7–17.6 ml/dl, controls = 15.2 ± 2.1 ml/dl], as indicated by a linear correlation between peak VO2 and peak systemic a–vO2 difference ( r 2 = 0.69). In the patients, the increase in cardiac output relative to VO2 (mean ΔQ/ΔVO2 = 15.0 ± 13.6; range 3.3–73) and ventilation (mean peak VE/VO2 = 65 ± 24; range 21–104) were exaggerated compared with controls (mean ΔQ/ΔVO2 = 5.1 ± 0.7; VE/VO2 = 41.2 ± 7.4, P < 0.01). There was a negative exponential relationship between ΔQ/ΔVO2 and peak systemic a–vO2 difference ( r 2 = 0.92) and between peak VE/VO2 and systemic a–vO2 difference ( r 2 = 0.53). In patients with heteroplasmic mtDNA mutations, we found an inverse relationship between the proportion of skeletal muscle mutant mtDNA and peak extraction of available oxygen during exercise ( r 2 = 0.70). We conclude that the degree of exercise intolerance in MM correlates directly with the severity of impaired muscle oxidative phosphorylation as indicated by the peak capacity for muscle oxygen extraction. Exaggerated circulatory and ventilatory responses to exercise are direct consequences of the level of impaired muscle oxidative phosphorylation and increase exponentially in relation to an increasing severity of oxidative impairment. In patients with mtDNA mutations, muscle mutation load governs mitochondrial capacity for oxidative phosphorylation and determines exercise capacity.
Background:
Sedentary aging has deleterious effects on the cardiovascular system, including decreased left ventricular compliance and distensibility (LVCD). Conversely, Masters level athletes, who train intensively throughout adulthood, retain youthful LVCD.
Objectives:
The purpose of this study was to test the hypothesis that preservation of LVCD may be possible with moderate lifelong exercise training.
Methods:
Healthy seniors (n = 102) were recruited from predefined populations, screened for lifelong patterns of exercise training, and stratified into 4 groups: "sedentary" (<2 sessions/week); "casual" (2 to 3 sessions/week); "committed" (4 to 5 sessions/week); and "competitive" Masters level athletes (6 to 7 sessions/week). Right heart catheterization and echocardiography were performed while preload was manipulated using lower body negative pressure and rapid saline infusion to define LV pressure-volume relationships and Frank-Starling curves.
Results:
Peak oxygen uptake and LV mass increased with escalating doses of lifelong exercise, with little change in systolic function. At baseline, LV distensibility was greater in committed (21%) and competitive (36%) exercisers than in sedentary subjects. Group LV stiffness constants (sedentary: 0.062 ± 0.039; casual: 0.079 ± 0.052; committed: 0.055 ± 0.033; and competitive: 0.035 ± 0.033) revealed: 1) increased stiffness in sedentary subjects compared to competitive athletes, whereas lifelong casual exercise had no effect; and 2) greater compliance in committed exercisers than in sedentary or casual exercisers.
Conclusions:
Low doses of casual, lifelong exercise do not prevent the decreased compliance and distensibility observed with healthy, sedentary aging. In contrast, 4 to 5 exercise sessions/week throughout adulthood prevent most of these age-related changes. As LV stiffening has been implicated in the pathophysiology of many cardiovascular conditions affecting the elderly, this "dose" of exercise training may have important implications for prevention of cardiovascular disease.
New findings
What is the central question of this study?
A smaller upright stroke volume contributes significantly to orthostatic intolerance after bed rest. The role of slowed left ventricular relaxation and diastolic suction on stroke volume during orthostatic stress after bed rest has not been previously reported. It is also unclear whether these changes are influenced by exercise training while in bed.
What is the main finding and its importance?
The reduction in left ventricular mass, volumes and Doppler parameters of relaxation and diastolic suction were greater with sedentary bed rest compared with those of subjects who performed exercise training while in bed. When left ventricular filling pressure was restored to prebed‐rest levels, Doppler parameters were also restored, suggesting that stroke volume after bed rest is more influenced by cardiac remodelling and changes in loading conditions rather than intrinsic ventricular properties.
A marked reduction in upright stroke volume (SV) contributes substantially to orthostatic intolerance after exposure to spaceflight or bed rest. It is unclear whether slowed left ventricular (LV) relaxation and diastolic suction contribute to the reduction in SV or whether these changes are influenced by exercise training while in bed. Twenty‐seven healthy adults completed 5 weeks of –6 deg head‐down bed rest (HDBR). During HDBR, nine subjects were sedentary (NOEX), while 18 performed near‐daily rowing ergometry (EX). Left ventricular mass, SV, LV end‐diastolic volume (LVEDV), pulmonary capillary wedge pressure and Doppler ultrasound indices of LV function were collected pre‐ and post‐HDBR during supine rest (twice) and during reduced LV loading (lower body negative pressure; LBNP) and increased LV loading (saline infusion). Post‐HDBR, LV mass increased in the EX group, but decreased in the NOEX group. The reduction in SV and LVEDV during supine rest and LBNP were greater with NOEX in comparison to EX after HDBR. Peak early mitral annular velocity, isovolumic relaxation time, early propagation velocity, a non‐invasive index of early diastolic filling and ventricular diastolic suction, and peak global longitudinal early strain rate were slowed during supine rest after HDBR with NOEX; however, these variables were either unaltered or the reduction was less prominent with EX. Doppler ultrasound measures of early diastolic filling, ventricular relaxation and diastolic suction were not significantly affected during LV unloading by LBNP after HDBR in either group. All Doppler indices were restored to pre‐HDBR levels in both groups during saline infusion to normalize LV filling pressure after HDBR. It is concluded that Doppler indices of dynamic LV filling were reduced in both groups after HDBR; however, these effects were more pronounced in the NOEX group. Irrespective of group, post‐HDBR Doppler parameters were restored when LV filling pressure was increased to pre‐HDBR levels during saline infusion. Therefore, the reduction in upright SV after HDBR is more influenced by changes in LV loading conditions, namely left atrial pressure in the setting of LV remodelling, rather than ventricular relaxation and diastolic suction.
New Findings
What is the central question of this study?
The study was designed to investigate the age‐ and sex‐related differences in muscle sympathetic nerve activity (MSNA) in relation to age‐ and sex‐related differences in haemodynamics, blood volume and left ventricular size and function.
What is the main finding and its importance?
Age‐related increases in MSNA were associated with decreases in blood volume in men only, and only in men was there a significant relation between MSNA and forearm vascular resistance. These results show that age and sex independently alter the neural control of blood pressure and may provide insights into the pathogenesis of hypertension.
We compared the effect of age‐ and sex‐related differences in haemodynamics, blood volume (BV) and left ventricular (LV) size and mass on resting muscle sympathetic nerve activity (MSNA) in healthy, normotensive adults. Twenty young men (19–47 years old) and 20 young women (21–46 years old) as well as 15 older men (62–80 years old) and 15 older women (60–82 years old) were studied. Cardiac output (acetylene rebreathing), total peripheral resistance, forearm vascular resistance (FVR; venous occlusion plethysmography) and MSNA were measured during supine rest. Blood volume was calculated (CO rebreathing), and LV mass, end‐diastolic (LVEDV) and end‐systolic volumes (LVESV) were measured using magnetic resonance imaging. Cardiac index ( P < 0.001 and P = 0.016), BV (both P < 0.001), LV mass ( P < 0.001 and P = 0.002), LVEDV ( P < 0.001 and P = 0.002) and LVESV (both P < 0.001) were lower in the older and female groups, respectively. Total peripheral resistance was significantly higher in the older ( P < 0.001) and female groups ( P = 0.014), but FVR was increased in the female groups ( P = 0.048) only (age, P = 0.089). The MSNA was greater in the older groups ( P < 0.001) only (sex, P = 0.228). Increased MSNA was shown to correlate with a decrease in BV ( P = 0.004) in men only when adjusted for age (women, P = 0.133). There was a positive relation between MSNA and FVR ( P = 0.020) in men but not women ( P = 0.422). There were no significant relations between MSNA and LV mass, LVEDV or LVESV. The findings suggest that the increase in resting MSNA with age may be related to the decline in BV in men only, but it is unknown whether sex differences in sympathetic adrenergic vasoconstriction occur independently of these changes.
Objective:
To determine the effect of low-dose propranolol on maximal exercise capacity in patients with postural tachycardia syndrome (POTS).
Methods:
We compared the effect of placebo vs a single low dose of propranolol (20 mg) on peak oxygen consumption (VO2max), an established measure of exercise capacity, in 11 patients with POTS and 7 healthy subjects in a randomized, double-blind study. Subjects exercised on a semirecumbent bicycle, with increasing intervals of resistance to maximal effort.
Results:
Maximal exercise capacity was similar between groups following placebo. Low-dose propranolol improved VO2max in patients with POTS (24.5 ± 0.7 placebo vs 27.6 ± 1.0 mL/min/kg propranolol; p = 0.024), but not healthy subjects. The increase in VO2max in POTS was associated with attenuated peak heart rate responses (142 ± 8 propranolol vs 165 ± 4 bpm placebo; p = 0.005) and improved stroke volume (81 ± 4 propranolol vs 67 ± 3 mL placebo; p = 0.013). In a separate cohort of POTS patients, neither high-dose propranolol (80 mg) nor metoprolol (100 mg) improved VO2max, despite similar lowering of heart rate.
Conclusions:
These findings suggest that nonselective β-blockade with propranolol, when used at the low doses frequently used for treatment of POTS, may provide a modest beneficial effect to improve heart rate control and exercise capacity.
Classification of evidence:
This study provides Class II evidence that a single low dose of propranolol (20 mg) as compared with placebo is useful in increasing maximum exercise capacity measured 1 hour after medication.
To study the frequency and degree of deconditioning, clinical features, and relationship between deconditioning and autonomic parameters in patients with orthostatic intolerance.
We retrospectively studied all patients seen for orthostatic intolerance at Mayo Clinic between January 2006 and June 2011, who underwent both standardized autonomic and exercise testing.
A total of 184 patients (84 with postural orthostatic tachycardia syndrome [POTS] and 100 without orthostatic tachycardia) fulfilled the inclusion criteria. Of these, 89% were women, and median age was 27.5 years (interquartile range [IQR] 22-37 years). Symptom duration was 4 years (IQR 2-7.8). Of the patients, 90% had deconditioning (reduced maximum oxygen uptake [VO(2max)%] <85%) during exercise. This finding was unrelated to age, gender, or duration of illness. The prevalence of deconditioning was similar between those with POTS (95%) and those with orthostatic intolerance (91%). VO(2max)% had a weak correlation with a few autonomic and laboratory parameters but adequate predictors of VO(2max)% could not be identified.
Reduced VO(2max)% consistent with deconditioning is present in almost all patients with orthostatic intolerance and may play a central role in pathophysiology. This finding provides a strong rationale for retraining in the treatment of orthostatic intolerance. None of the autonomic indices are reliable predictors of deconditioning.
Key points
Recent studies have suggested the presence of cardiac atrophy as a key component of the pathogenesis of the postural orthostatic tachycardia syndrome (POTS), similar to physical deconditioning; exercise intolerance is associated with a reduced stroke volume (SV) in POTS which may be the cause of the high heart rate (HR) at rest and during exercise.
We determined whether physical ‘reconditioning’ with exercise training improves exercise performance in POTS.
A lower SV resulted in a higher HR in POTS at any given oxygen uptake ( ) during exercise while the cardiac output ( )– relationship remained normal. was lower in POTS than healthy sedentary controls.
After 3 months of training in POTS, HR became lower at any given due to increased SV without changes in the – relationship. increased due to increased peak SV, and was proportional to total blood volume. HR recovery from exercise was faster after training than before training.
Thus, exercise training improves physical fitness and cardiovascular responses during exercise in POTS.
Abstract Recent studies have suggested the presence of cardiac atrophy as a key component of the pathogenesis of the postural orthostatic tachycardia syndrome (POTS), similar to physical deconditioning. It has also been shown that exercise intolerance is associated with a reduced stroke volume (SV) in POTS, and that the high heart rate (HR) observed at rest and during exercise in these patients is due to this low SV. We tested the hypotheses that (a) circulatory control during exercise is normal in POTS; and (b) that physical ‘reconditioning’ with exercise training improves exercise performance in patients with POTS. Nineteen (18 women) POTS patients completed a 3 month training programme. Cardiovascular responses during maximal exercise testing were assessed in the upright position before and after training. Resting left ventricular diastolic function was evaluated by Doppler echocardiography. Results were compared with those of 10 well‐matched healthy sedentary controls. A lower SV resulted in a higher HR in POTS at any given oxygen uptake ( ) during exercise while the cardiac output ( )– relationship was normal. was lower in POTS than controls (26.1 ± 1.0 (SEM) vs. 36.3 ± 0.9 ml kg ⁻¹ min ⁻¹ ; P < 0.001) due to a lower peak SV (65 ± 3 vs. 80 ± 5 ml; P = 0.009). After training in POTS, HR became lower at any given due to increased SV without changes in the – relationship. increased by 11% ( P < 0.001) due to increased peak SV ( P = 0.021) and was proportional to total blood volume. Peak HR was similar, but HR recovery from exercise was faster after training than before training ( P = 0.036 for training and 0.009 for interaction). Resting diastolic function was mostly normal in POTS before training, though diastolic suction was impaired ( P = 0.023). There were no changes in any Doppler index after training. These results suggest that short‐term exercise training improves physical fitness and cardiovascular responses during exercise in patients with POTS.
This study examined the effectiveness of a short-duration but high-intensity exercise countermeasure in combination with a novel oral volume load in preventing bed rest deconditioning and orthostatic intolerance. Bed rest reduces work capacity and orthostatic tolerance due in part to cardiac atrophy and decreased stroke volume. Twenty seven healthy subjects completed 5 wk of -6 degree head down bed rest. Eighteen were randomized to daily rowing ergometry and biweekly strength training while nine remained sedentary. Measurements included cardiac mass, invasive pressure-volume relations, maximal upright exercise capacity, and orthostatic tolerance. Before post-bed rest orthostatic tolerance and exercise testing, nine exercise subjects were given 2 days of fludrocortisone and increased salt. Sedentary bed rest led to cardiac atrophy (125 ± 23 vs. 115 ± 20 g; P < 0.001); however, exercise preserved cardiac mass (128 ± 38 vs. 137 ± 34 g; P = 0.002). Exercise training preserved left ventricular chamber compliance, whereas sedentary bed rest increased stiffness (180 ± 170%, P = 0.032). Orthostatic tolerance was preserved only when exercise was combined with volume loading (-10 ± 22%, P = 0.169) but not with exercise (-14 ± 43%, P = 0.047) or sedentary bed rest (-24 ± 26%, P = 0.035) alone. Rowing and supplemental strength training prevent cardiovascular deconditioning during prolonged bed rest. When combined with an oral volume load, orthostatic tolerance is also preserved. This combined countermeasure may be an ideal strategy for prolonged spaceflight, or patients with orthostatic intolerance.
We have found recently that exercise training is effective in the treatment of the postural orthostatic tachycardia syndrome (POTS). Whether this nondrug treatment is superior to "standard" drug therapies, such as β-blockade, is unknown. We tested the hypothesis that exercise training but not β-blockade treatment improves symptoms, hemodynamics, and renal-adrenal responses in POTS patients. Nineteen patients (18 women and 1 man) completed a double-blind drug trial (propranolol or placebo) for 4 weeks, followed by 3 months of exercise training. Fifteen age-matched healthy individuals (14 women and 1 man) served as controls. A 2-hour standing test was performed before and after drug treatment and training. Hemodynamics, catecholamines, plasma renin activity, and aldosterone were measured supine and during 2-hour standing. We found that both propranolol and training significantly lowered standing heart rate. Standing cardiac output was lowered after propranolol treatment (P=0.01) but was minimally changed after training. The aldosterone:renin ratio during 2-hour standing remained unchanged after propranolol treatment (4.1±1.7 [SD] before versus 3.9±2.0 after; P=0.46) but modestly increased after training (5.2±2.9 versus 6.5±3.0; P=0.05). Plasma catecholamines were not affected by propranolol or training. Patient quality of life, assessed using the 36-item Short-Form Health Survey, was improved after training (physical functioning score 33±10 before versus 50±9 after; social functioning score 37±9 versus 48±6; both P<0.01) but not after propranolol treatment (34±10 versus 36±11, P=0.63; 39±7 versus 39±5, P=0.73). These results suggest that, for patients with POTS, exercise training is superior to propranolol at restoring upright hemodynamics, normalizing renal-adrenal responsiveness, and improving quality of life.
Postural orthostatic tachycardia syndrome (POTS) is characterized by excessive tachycardia in the upright position. To test the hypothesis that patients with POTS have impaired arterial-cardiac baroreflex function, while exercise training normalizes the baroreflex function in these patients.
Seventeen POTS patients aged 27 ± 9 (mean ± SD) years underwent an exercise training program for 3 months. Arterial-cardiac baroreflex function was assessed by spectral and transfer function analysis of beat-to-beat R-R interval (RRI) and systolic blood pressure (SBP) variability in the supine position and at 60° upright tilt during spontaneous breathing before and after training. Data were compared with 17 healthy sedentary controls.
Even though upright heart rate (HR) was greater in patients than controls, indexes of RRI variability did not differ between groups. Transfer function gain (SBP to RRI), used as an index of arterial-cardiac baroreflex sensitivity was similar between patients and controls in both low- (LF, P = 0.470) and high-frequency (HF, P = 0.663) ranges. Short-term exercise training decreased upright HR and increased RRI variability in POTS patients. LF baroreflex gain increased significantly in the supine position and during upright tilt [analysis of variance (ANOVA), P = 0.04 for training], while HF gain increased modestly after training (ANOVA, P = 0.105 for training) in these patients; however, the baroreflex gains remained within the normal ranges when compared with healthy controls.
These data suggest that patients with POTS have normal arterial-cardiac baroreflex function in both supine and upright postures. Short-term exercise training increases the baroreflex sensitivity in these patients, associated with a decrease in upright heart rate.
The purpose of this study was to test the hypothesis that a small heart coupled with reduced blood volume contributes to the postural orthostatic tachycardia syndrome (POTS) and that exercise training improves this syndrome.
Patients with POTS have marked increases in heart rate during orthostasis. However, the underlying mechanisms are unknown and the effective therapy is uncertain.
Twenty-seven POTS patients underwent autonomic function tests, cardiac magnetic resonance imaging, and blood volume measurements. Twenty-five of them participated in a 3-month specially designed exercise training program with 19 completing the program; these patients were re-evaluated after training. Results were compared with those of 16 healthy controls.
Upright heart rate and total peripheral resistance were greater, whereas stroke volume and cardiac output were smaller in patients than in controls. Baroreflex function was similar between groups. Left ventricular mass (median [25th, 75th percentiles], 1.26 g/kg [1.12, 1.37 g/kg] vs. 1.45 g/kg [1.34, 1.57 g/kg]; p < 0.01) and blood volume (60 ml/kg [54, 64 ml/kg] vs. 71 ml/kg [65, 78 ml/kg]; p < 0.01) were smaller in patients than in controls. Exercise training increased left ventricular mass and blood volume by approximately 12% and approximately 7% and decreased upright heart rate by 9 beats/min [1, 17 beats/min]. Ten of 19 patients no longer met POTS criteria after training, whereas patient quality of life assessed by the 36-item Short-Form Health Survey was improved in all patients after training.
Autonomic function was intact in POTS patients. The marked tachycardia during orthostasis was attributable to a small heart coupled with reduced blood volume. Exercise training improved or even cured this syndrome in most patients. It seems reasonable to offer POTS a new name based on its underlying pathophysiology, the "Grinch syndrome," because in this famous children's book by Dr. Seuss, the main character had a heart that was "two sizes too small."
There are two possible mechanisms contributing to the excessive fall of stroke volume (and its contribution to orthostatic intolerance) in the upright position after bed rest or spaceflight: reduced cardiac filling due to hypovolemia and/or a less distensible heart due to cardiac atrophy. We hypothesized that preservation of cardiac mechanical function by exercise training, plus normalization of cardiac filling with volume infusion, would prevent orthostatic intolerance after bed rest. Eighteen men and three women were assigned to 1) exercise countermeasure (n=14) and 2) no exercise countermeasure (n=7) groups during bed rest. Bed rest occurred in the 6 degrees head-down tilt position for 18 days. The exercise regimen was prescribed to compensate for the estimated cardiac work reduction between bed rest and ambulatory periods. At the end of bed rest, the subjects were further divided into two additional groups for post-bed rest testing: 1) volume loading with intravenous dextran to normalize cardiac filling pressure and 2) no volume loading. Dextran infusion was given to half of the exercise group and all of the sedentary group after bed rest, leading ultimately to three groups: 1) exercise plus volume infusion; 2) exercise alone; and 3) volume infusion alone. Exercise training alone preserved left ventricular mass and distensibility as well as upright exercise capacity, but lower body negative pressure (LBNP) tolerance was still depressed. LBNP tolerance was maintained only when exercise training was accompanied by dextran infusion. Dextran infusion alone following bed rest without exercise maintained neither orthostatic tolerance nor upright exercise capacity. We conclude that daily supine cycle exercise sufficient to prevent cardiac atrophy can prevent orthostatic intolerance after bed rest only when combined with plasma volume restoration. This maintenance of orthostatic tolerance was achieved by neither exercise nor dextran infusion alone. Cardiac atrophy and hypovolemia are likely to contribute independently to orthostatic intolerance after bed rest.
POTS is defined as the development of orthostatic symptoms associated with a heart rate (HR) increment >or=30, usually to >or=120 bpm without orthostatic hypotension. Symptoms of orthostatic intolerance are those due to brain hypoperfusion and those due to sympathetic overaction.
We provide a review of POTS based primarily on work from the Mayo Clinic.
Females predominate over males by 5:1. Mean age of onset in adults is about 30 years and most patients are between the ages of 20-40 years. Pathophysiologic mechanisms (not mutually exclusive) include peripheral denervation, hypovolemia, venous pooling, beta-receptor supersensitivity, psychologic mechanisms, and presumed impairment of brain stem regulation. Prolonged deconditioning may also interact with these mechanisms to exacerbate symptoms. The evaluation of POTS requires a focused history and examination, followed by tests that should include HUT, some estimation of volume status and preferably some evaluation of peripheral denervation and hyperadrenergic state. All patients with POTS require a high salt diet, copious fluids, and postural training. Many require beta-receptor antagonists in small doses and low-dose vasoconstrictors. Somatic hypervigilance and psychologic factors are involved in a significant proportion of patients.
POTS is heterogeneous in presentation and mechanisms. Major mechanisms are denervation, hypovolemia, deconditioning, and hyperadrenergic state. Most patients can benefit from a pathophysiologically based regimen of management.
The 2007 Streeten Lecture focused on the idea that physical deconditioning plays a key role in the symptomology and pathophysiology of POTS. Parallels were drawn between the physiological responses to orthostatic stress seen in POTS patients and the physiological responses seen in "normal" humans after prolonged periods of bedrest, deconditioning, or space flight. Additionally, the idea that endurance exercise training might ameliorate some of these symptoms was also advanced. Finally, potential parallels between POTS, chronic fatigue syndrome, and fibromyalgia were also drawn and the potential role of exercise training as a "therapeutic intervention" in all three conditions was raised. The conceptual model for the lecture was that after some "initiating event" chronic deconditioning plays a significant role in the pathophysiology of these conditions, and these physiological changes in conjunction with "somatic hypervigilence" explain many of the complaints that this diverse group of patients have. Additionally, the idea that systematic endurance exercise training might be helpful was advanced, and data supportive of this idea was reviewed. The main conclusion is that the medical community must retain their empathy for patients with unusual conditions but at the same time send a firm but empowering message about physical activity. As always, we must also ask what do the ideas about physical activity and inactivity and the conditions mentioned above not explain?
Respiratory and hemodynamic measurements were made on 54 sedentary subjects during progressive exercise on a bicycle ergometer up to the point of maximal voluntary effort. The age range of the group was from 18 to 68 years.
The maximum tolerated exercise, as indicated by the highest achieved level of oxygen consumption (Voo2), diminished with age. Older subjects had a lower resting cardiac output (Q) than normal subjects, but an identical increase in Q with Voo2. There was no evidence of flattening of this curve as the older subjects approached highest exercise loads. Consequently, the arteriovenous oxygen difference did not increase abnormally on high loads, and the cardiac response to exercise in older subjects appeared to be adequate. The relationship between inspired air volume and heart rate with Voo2 at submaximal loads was not influenced by age.
Systolic pressure increased progressively with exercise and showed a greater change in older subjects. Total peripheral resistance at rest increased with age; but with increasing exercise, this difference progressively diminished.
The roles of absolute and relative oxygen uptake (VO2 and percent of muscle group specific VO2 max) as determinants of the cardiovascular and ventilatory responses to exercise over a wide range of active muscle mass have not previously been defined. Six healthy men performed four types of dynamic exercise--one-arm curl, one-arm cranking, and one- and two-leg cycling at four different relative work loads--25, 50, 75, and 100% of VO2 max for the corresponding muscle group. VO2 during maximal one-arm curl, one-arm cranking, and one-leg cycling averaged 20, 50, and 75%, respectively, of that for maximal two-leg cycling. Cardiac output was linearly related to VO2 with a similar slope and intercept for each type of exercise. Heart rate at a given %VO2 max was higher with larger active muscle mass. In relation to %VO2 max, systemic resistance was lower and plasma catecholamine levels were higher with larger active muscle mass. The cardiovascular responses to exercise are determined to a large extent by the active muscle mass and the absolute oxygen uptake, with the principal feature appearing to be the tight linkage between systemic oxygen transport and utilization.
To determine the function of changes in plasma volume (PV), plasma renin activity (PRA), and arginine vasopressin (AVP) in the mechanism of the reduction of resting blood pressure during exercise training, resting supine, sitting, and standing systolic (SBP) and 5th-phase diastolic (DBP) blood pressures were measured in 10 men (19-24 yr) before and after an 8-day (2 h/day) training period on a cycle ergometer. The control group (5 men) exercised at 1.4 1/min [44% peak O2 uptake (VO2 max)] at 23.8 degrees C Tdb and 50% rh, and the acclimation group at 1.5 1/min (46% VO2 max) at 39.8 degrees C Tdb and 50% rh. After acclimation, resting supine and sitting DPB decreased (P less than 0.05) by 6 and 9 mmHg, respectively. There were no significant changes in DBP in the controls or in SBP in either group. After training, PV increased by 12.2% in controls and by 17.6% after acclimation. The resting hypotension could not be attributed to changes in resting levels of PV, AVP, or PRA. However, large decreases in PV and large increases in AVP and especially PRA during acclimation exposures suggest these responses may play a role in the chronic hypotensive response.
We review the hypotheses presented to account for the anecdotal and literature-based reports that chronic endurance exercise training reduces orthostatic tolerance. The findings from cross-sectional investigations of unfit subjects and endurance athletes are examined, as well as limited data from recent investigations of the changes in orthostatic tolerance and blood pressure regulation that occur after 8 d to 8 months of endurance exercise training. Statistical models have not found wide variations in maximal aerobic power (VO2max) to contribute to the prediction of orthostatic responses. However, research data are generally consistent that the orthostatic tolerance of athletes whose VO2max exceeds 65 ml.kg-1.min-1 is lower than that of sedentary control subjects. These two findings suggest that it is exercise training, rather than VO2max, that reduces orthostatic tolerance. Findings from a recent longitudinal investigation corroborate this theory. We conclude that at least four factors associated with exercise training contribute to the development of orthostatic intolerance. These include: a) increased limb compliance (although its effect is likely to be trivial), b) eccentric ventricular hypertrophy, and c) increases in total blood volume, which may attenuate cardiopulmonary baroreflex responsiveness, shift ventricular function to a steeper portion of the ventricular compliance curve, and increase the inhibitory effect of cardiopulmonary baroreceptors on carotid baroreflex responsiveness; and d) an independent effect that reduces carotid and aortic baroreflex responsiveness. These mechanisms mimic changes observed in pathological states such as heart failure and hypertension. Our conclusions are best summarized by Greenleaf et al. (J. Appl. Physiol. 51:298-305, 1981): "Trained men can run, but they cannot stand.''
In cross-sectional comparisons, several investigators have reported highly trained endurance athletes to have a prevalence toward orthostatic hypotension and intolerance compared with average fit individuals. These observations have raised concern that regular exercise designed to increase aerobic capacity may impair regulatory mechanisms of blood pressure control and that perhaps certain populations of individuals with a predisposition for fainting exhibit an inability to elevate heart rate, vasoactive hormones, and peripheral resistance during an orthostatic challenge. In longitudinal experiments, when exercise training was performed by subjects who increased their aerobic capacity by 20% but maintained VO2max below 50 ml.kg-1.min-1, tolerance to lower body negative pressure (LBNP) was increased by 28%. Exercise training did not compromise baroreflex functions despite evidence of increased resting vagal cardiac tone and reduced sympathetic tone. In contrast to fainters, increased orthostatic tolerance in the exercised-trained subjects was associated with no alteration in their ability to elevate heart rate, vasoactive hormones, and peripheral resistance at peak LBNP. However, cardiac output and mean arterial blood pressure were maintained during higher submaximal LBNP levels by a 20% increase in stroke volume. The elevation in stroke volume during LBNP after training was associated with blood volume expansion.(ABSTRACT TRUNCATED AT 250 WORDS)
To characterize the idiopathic postural orthostatic tachycardia syndrome (POTS), we reviewed the records of all patients aged 20 to 51 who presented to the Mayo Autonomic Reflex Laboratory and who exhibited tachycardia at rest or during head-up tilt. These patients were usually women who experienced an acute onset of persistent lightheadedness and fatigue or gastrointestinal dysmotility. In seven patients, a viral illness may have preceded the onset of symptoms. In two instances, signs and symptoms of a small-fiber sensory neuropathy were present. Laboratory evaluation of autonomic function revealed increased diastolic blood pressure to tilt (5/16), increased Valsalva ratio, marked decrease in phase II of the Valsalva maneuver with normal phase IV overshoot, and normal forced respiratory sinus arrhythmia. Abnormal quantitative sudomotor axon reflex test and thermoregulatory sweat test and an excessive orthostatic increase of catecholamines were found in some patients. We conclude that in many instances POTS may be a manifestation of a mild form of acute autonomic neuropathy.
Measurement of peak Vo2 has become an accepted method to select patients for cardiac transplantation. Some investigators have suggested that the addition of exercise hemodynamic measurements can further enhance risk stratification because these measurements may identify patients with a noncardiac limitation to exercise.
Accordingly, we performed maximal bicycle exercise with respiratory gas analysis and hemodynamic measurements in 65 patients (47 men, 18 women) 53 +/- 10 years old (mean +/- SD) who underwent a transplant evaluation at Columbia Presbyterian Medical Center. Skeletal muscle oxygenation of the vastus lateralis during exercise was assessed with near-infrared spectroscopy. Exercise hemodynamic, ventilatory, and muscle oxygenation measurements were obtained in all patients. For each subject, a linear correlation was derived between Vo2 and pulmonary artery saturation (PA Sao2). The slope of this relationship and a theoretical Vo2max at a PA Sao2 of 0% (Vo2 intercept) was derived. Baseline measurements were left ventricular ejection fraction, 22 +/- 9%; pulmonary capillary wedge pressure (PCWP), 16 +/- 10 mm Hg; cardiac index (CI), 2.1 +/- 0.5 L. min-1. m-2; and PA Sao2, 53 +/- 8%. The cardiac output response to exercise was categorized as normal or abnormal by comparison to the linear equation of peak Vo2 versus peak cardiac output as described by Higginbotham. Exercise measurements were peak Vo2, 12.1 +/- 3.0 mL.kg-1.min-1; Vo2 intercept, 19.1 +/- 5.5 mL. kg-1.min-1; PCWP, 31 +/- 11 mm Hg; CI, 3.8 +/- 1.3 L.min-1.m-2; and PA Sao2, 27 +/- 9%. Only 6% of patients exhibited a normal cardiac output response to exercise. Multivariate analysis was performed with peak Vo2, Vo2 intercept, skeletal muscle oxygenation at end exercise, and peak exercise hemodynamic variables. Only left ventricular stroke work and left ventricular stroke work index were shown to be predictive of survival.
Addition of exercise hemodynamic measurements to noninvasive metabolic stress testing minimally improves risk prognostication in patients with severe heart failure.
Peak exercise oxygen consumption (Vo2), a noninvasive index of peak exercise cardiac output (CO), is widely used to select candidates for heart transplantation. However, peak exercise Vo2 can be influenced by noncardiac factors such as deconditioning, motivation, or body composition and may yield misleading prognostic information. Direct measurement of the CO response to exercise may avoid this problem and more accurately predict prognosis.
Hemodynamic and ventilatory responses to maximal treadmill exercise were measured in 185 ambulatory patients with chronic heart failure who had been referred for cardiac transplantation (mean left ventricular ejection fraction, 22 +/- 7%; mean peak Vo2, 12.9 +/- 3.0 mL. min-1.kg-1). CO response to exercise was normal in 83 patients and reduced in 102. By univariate analysis, patients with normal CO responses had a better 1-year survival rate (95%) than did those with reduced CO responses (72%) (P < .0001). Survival in patients with peak Vo2 of > 14 mL.min-1.kg-1 (88%) was not different from that of patients with peak Vo2 of < or = 14 mL.min-1.kg-1 (79%) (P = NS). However, survival was worse in patients with peak Vo2 of < or = 10 mL.min-1.kg-1 (52%) versus those with peak Vo2 of > 10 mL.min-1.kg-1 (89%) (P < .0001). By Cox regression analysis, exercise CO response was the strongest independent predictor of survival (risk ratio, 4.3), with peak Vo2 dichotomized at 10 mL. min-1.kg-1 (risk ratio, 3.3) as the only other independent predictor. Patients with reduced CO responses and peak Vo2 of < or = 10 mL.min-1.kg-1 had an extremely poor 1-year survival rate (38%).
Both CO response to exercise and peak exercise Vo2 provide valuable independent prognostic information in ambulatory patients with heart failure. These variables should be used in combination to select potential heart transplantation candidates.
It is presently unclear how gender, aging, and physical activity status interact to determine the magnitude of the rise in cardiac output (Qc) during dynamic exercise. To clarify this issue, the present study examined the Qc-O2 uptake (Vo2) relationship during graded leg cycle ergometry in 30 chronically endurance-trained subjects from four groups (n = 6-8/group): younger men (20-30 yr), older men (56-72 yr), younger women (24-31 yr), and older women (51-72 yr). Qc (acetylene rebreathing), stroke volume (Qc/heart rate), and whole body Vo2 were measured at rest and during submaximal exercise intensities (40, 70, and approximately 90% of peak Vo2). Baseline resting levels of Qc were 0.6-1.2 l/min less in the older groups. However, the slopes of the Qc-Vo2 relationship across submaximal levels of cycling were similar among all four groups (5.4-5.9 l/l). The absolute Qc associated with a given Vo2 (1.0-2.0 l/min) was also similar among groups. Resting and exercise stroke volumes (ml/beat) were lower in women than in men but did not differ among age groups. However, older men and women showed a reduced ability, relative to their younger counterparts, to maintain stroke volume at exercise intensities above 70% of peak Vo2. This latter effect was most prominent in the oldest women. These findings suggest that neither age nor gender has a significant impact on the Qc-Vo2 relationships during submaximal cycle ergometry among chronically endurance-trained individuals.
This preliminary study attempted to identify the frequency of orthostatic hypotension (OH) in community dwelling older adults who volunteered to participate in an 8-week, heavy-resistance, strength-training program. It also assessed the effect of the strength-training program on OH.
From a larger study (n = 53) on high-resistance strength training in older adults (mean age 71.4 +/- 6.6 years), a subset of subjects (n = 24), mean age 71.0 +/- 5.8 years, was evaluated who met at least one criterion for OH. All subjects were tested for resting blood pressures (BP) and heart rates (HR) in the supine, sitting, and standing positions. Also noted was their response to orthostatism in rising from a cot after 10 minutes and rising from a chair after 5 minutes. The subset was not different from the overall group in gender ratio, age, or effect of medication on BP. The treatment was an 8-week strength-training program at 80% of their one repetition maximum.
Significant changes (P < 0.05) were shown in supine diastolic BP (+3.2 mm Hg), sitting systolic BP (-3.9), and standing HR (+4.9 beats per minute). In response to the orthostatic challenge, significant (P < 0.05) improvements were shown in systolic BP (+9.7 mm Hg), diastolic BP (+4.7), and HR (+3.2 beats per minute) for the rise from chair, and in diastolic BP (+6.7 mm Hg) rise from the cot.
These data show that OH is not uncommon (45%) in community dwelling older adults. A strength training program in older adults has little effect on resting BP, but elicits a positive adaptation to an orthostatic challenge.
Orthostatic intolerance after bed rest is characterized by hypovolemia and an excessive reduction in stroke volume (SV) in the upright position. We studied whether the reduction in SV is due to a specific adaptation of the heart to head-down tilt bed rest (HDTBR) or acute hypovolemia alone.
We constructed left ventricular (LV) pressure-volume curves from pulmonary capillary wedge pressure and LV end-diastolic volume and Starling curves from pulmonary capillary wedge pressure and SV during lower body negative pressure and saline loading in 7 men (25+/-2 years) before and after 2 weeks of -6 degrees HDTBR and after the acute administration of intravenous furosemide. Both HDTBR and hypovolemia led to a similar reduction in plasma volume. However, baseline LV end-diastolic volume decreased by 20+/-4% after HDTBR and by 7+/-2% after hypovolemia (interaction P<0.001). Moreover, SV was reduced more and the Starling curve was steeper during orthostatic stress after HDTBR than after hypovolemia. The pressure-volume curve showed a leftward shift and the equilibrium volume of the left ventricle was decreased after HDTBR; however, after hypovolemia alone, the curve was identical, with no change in equilibrium volume. Lower body negative pressure tolerance was reduced after both conditions; it decreased by 27+/-7% (P<0.05) after HDTBR and by 18+/-8% (P<0.05) after hypovolemia.
Chronic HDTBR leads to ventricular remodeling, which is not seen with equivalent degrees of acute hypovolemia. This remodeling leads to a greater decrease in SV during orthostatic stress after bed rest than hypovolemia alone, potentially contributing to orthostatic intolerance.
Impaired skeletal muscle oxidative phosphorylation in patients with severe mitochondrial respiratory chain defects results in disabling exercise intolerance that is associated with a markedly blunted capacity of muscle to increase oxygen utilization in relation to circulatory and ventilatory responses that increase oxygen delivery to muscle during exercise. The range of oxidative limitation and the relationship between the severity of oxidative defects and physiological responses to exercise among a broader spectrum of mitochondrial respiratory chain defects has not been defined. We evaluated oxidative capacity and circulatory and ventilatory responses to maximal cycle exercise in 40 patients with biochemically and/or molecularly defined mitochondrial myopathy (MM) associated with varying levels of exercise tolerance, and compared responses with those in healthy sedentary individuals. In the MM patients, mean peak work capacity (0.88 +/- 0.6 W/kg) and oxygen uptake (VO(2), 16 +/- 8 ml/kg/min) were significantly lower (P < 0.01) than in controls (mean work capacity = 2.2 +/- 0.7 W/kg; VO(2) = 32 +/- 7 ml/kg/min), but the patient range was broad (0.17-3.2 W/kg; 6-47 ml/kg/min). Oxidative capacity in patients was limited by the ability of muscle to extract available oxygen from blood [mean peak systemic arteriovenous O(2) difference (a-vO(2)); patients = 7.7 +/- 3.5, range 2.7-17.6 ml/dl, controls = 15.2 +/- 2.1 ml/dl], as indicated by a linear correlation between peak VO(2) and peak systemic a-vO(2) difference (r(2) = 0.69). In the patients, the increase in cardiac output relative to VO(2) (mean DeltaQ/DeltaVO(2) = 15.0 +/- 13.6; range 3.3-73) and ventilation (mean peak VE/VO(2) = 65 +/- 24; range 21-104) were exaggerated compared with controls (mean DeltaQ/DeltaVO(2) = 5.1 +/- 0.7; VE/VO(2) = 41.2 +/- 7.4, P < 0.01). There was a negative exponential relationship between DeltaQ/DeltaVO(2) and peak systemic a-vO(2) difference (r(2) = 0.92) and between peak VE/VO(2) and systemic a-vO(2) difference (r(2) = 0.53). In patients with heteroplasmic mtDNA mutations, we found an inverse relationship between the proportion of skeletal muscle mutant mtDNA and peak extraction of available oxygen during exercise (r(2) = 0.70). We conclude that the degree of exercise intolerance in MM correlates directly with the severity of impaired muscle oxidative phosphorylation as indicated by the peak capacity for muscle oxygen extraction. Exaggerated circulatory and ventilatory responses to exercise are direct consequences of the level of impaired muscle oxidative phosphorylation and increase exponentially in relation to an increasing severity of oxidative impairment. In patients with mtDNA mutations, muscle mutation load governs mitochondrial capacity for oxidative phosphorylation and determines exercise capacity.
In the present study oxygen uptake, cardiac output, stroke volume (dye-dilution technique) and oxygen content of arterial blood were determined in 11 women and 12 men, 20–31 years of age, at rest, and when performing submaximal and maximal work. At rest plasma volume (T-1824) and heart volume were determined. Sitting on the bicycle ergometer the stroke volume was 40–90% (mean 63%) of the maximum attained during exercise. Maximal stroke volume was essentially reached at a workload with an oxygen uptake of about 40% of the maximum and a heart rate about 110. No tendency to a decrease in stroke volume was noticed when maximal work was performed. The variation in stroke volume was ±4% during exercise in the range from 40 to 100% of the individual's aerobic work capacity. The maximal cardiac output was 18.5 liters/min for women and 24.1 liters for men. The correlation between heart volume on one side and maximal stroke volume and cardiac output on the other side was high and the expected one from the dimension of the individual. On submaximal as well as maximal exercise the women had a higher cardiac output per liter oxygen uptake than the men, and this can be explained by the lower concentration of hemoglobin in the women's blood.
cardiac function during exercise; cardiac output stroke volume; cardiac output and arterial O2 content
Submitted on October 3, 1963
Postural tachycardia syndrome (POTS) diagnosis and treatment: basics and new developments.
- Raj S.R.
- Levine B.D.
Raj, S.R., Levine, B.D., 2013. Postural tachycardia syndrome (POTS) diagnosis and treatment: basics and new developments. http://crmcardiosourceorg/Learn-from-the-Experts/2013/02/POTS-Diagnosis-and-Treatment.