Postural Orthostatic Tachycardia Syndrome Patients Research Articles

Postural Orthostatic Tachycardia Syndrome (POTS) as an Adverse Event to the Human Papilloma Virus (HPV) Vaccine and Its Relationship with Ehlers–Danlos Syndrome (EDS)

Gardasil 4, a human papilloma virus vaccine, has been shown to protect against various cancers, including cervical cancer. Common side effects include injection site pain, fever, headaches, and muscle aches. In some individuals, the severe side effect of postural orthostatic tachycardia syndrome (POTS) has been reported. POTS is characterized by the abnormal response of lightheadedness, blurry vision, and dizziness while transitioning to an upright posture. POTS predominately affects women, with more than eighty-five (85) percent of POTS patients being female. POTS, on average, takes five years and eleven months to receive diagnosis. Additionally, a strong association between POTS and Ehlers–Danlos Syndrome Type III (EDS) exists. Eighty (80) percent of patients with EDS have POTS. This severe side effect indicates that providers need to be aware of this strong association of HPV vaccinations and POTS. In this report, we will present a case of a young women with a past medical history significant for EDS type III who was diagnosed with POTS after receiving Gardasil 4 vaccination. This case demonstrates the need for physicians to be aware of the association of POTS with EDS type III and HPV vaccination. Physician awareness of the associations, signs, and symptoms of POTS and earlier testing at the first presentation of signs and symptoms will limit the negative impact on patient’s quality of life.

Hyperventilation in Patients with Postural Orthostatic Tachycardia Syndrome (POTS): Effects of Tidal Volume versus Hypocapnia on Heart Rate

Background: Postural Orthostatic Tachycardia Syndrome (POTS) is a chronic form of orthostatic intolerance that significantly impacts the quality of life and day-to-day functioning of patients. POTS has an estimated prevalence of about 1%, predominantly affecting females of child-bearing age. POTS is characterized by an upright increase in heart rate (HR) of ≥30 bpm, without a drop in blood pressure. POTS is associated with chronic (≥ 3 months) upright symptoms including light-headedness, blurred vision, and cognitive dysfunction. A large proportion of POTS patients also experience hyperventilation when upright. Hyperventilation reduces arterial carbon dioxide (CO2; hypocapnia) and exacerbates tachycardia in POTS. Whether the HR response is due to increased tidal volume (VT) per se or the resulting hypocapnia is unclear. Investigating the independent effects of increased VT versus hypocapnia on HR might identify possible therapeutic targets to reduce HR in patients with POTS. Objective: We aimed to characterize the separate effects of hypocapnia and VT on HR in POTS patients. Hypothesis: We hypothesize that hypocapnia and VT will independently increase HR, with hypocapnia causing the greatest increase in HR in patients with POTS. Methods: Twenty female POTS patients (32±10 years) completed supine normocapnic and hypocapnic breathing tests. To assess the effects of hypocapnia on HR, we compared hypocapnic-hyperventilation versus normocapnic-hyperventilation with constant VT. To assess the effects of VT on HR, we compared increased VT breathing versus normal breathing with constant end-tidal CO2 (ETCO2). Breath-by-breath respiratory (VT, ETCO2) and beat-to-beat hemodynamic parameters (stroke volume [SV], HR) were continuously measured. Data were analyzed with paired t-tests, and are reported as mean ± SD. Results: ETCO2 was lower ( p<0.001) with similar VT during hypocapnia compared to normocapnia. Hypocapnia reduced SV (63.3±11.8 mL vs. 72.4±12.3 mL; p<0.001), and increased HR (99±13 bpm vs. 81±9 bpm; p<0.001). Compared to normal breathing, increased VT ( p<0.001) with constant ETCO2 led to a smaller reduction in SV (72.4±12.3 mL vs. 76.0±14.3 mL; p=0.04), and increase in HR (81±9 bpm vs. 75±9 bpm; p<0.001). Conclusion: Our results suggest that hypocapnia and increased VT independently reduce SV and increase HR in POTS patients. The increase in HR was greater during hypocapnia (+18 bpm) compared to increased VT (+6 bpm). Reducing hypocapnia presents an attractive therapeutic target. Disclosures: This work was supported by Standing up to POTS. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Sexual Dysfunction in Postural Orthostatic Tachycardia Syndrome (POTS): A Cross-Sectional, Case-Control Study.

Background: We aimed to determine whether patients with postural orthostatic tachycardia syndrome (POTS) have sexual dysfunction compared to age-matched healthy controls. Methods: Utilizing online COMPASS-31 to evaluate dysautonomia symptom severity, Beck's Depression Inventory Second Edition (BDII), Female Sexual Function (FSF), and International Index of Erection Function (IIEF) questionnaires, we compared sexual function scores in patients with POTS to scores obtained from sex- and age-matched healthy controls via a cross-sectional case-control study. Results: A total of 160 women with POTS, mean age 30.2 ± 7.9 (range 21-50 years), had lower FSF scores than 62 healthy age-matched female controls. IIEF scores in 29 male patients with POTS with a mean age of 30.1 ± 6.0 (range 21-47) were significantly lower than in 27 healthy age-matched male controls. Female POTS patients had significantly lower scores in the sub-domains of desire, arousal, and satisfaction, while male POTS patients had significantly lower scores in erectile and orgasmic function, desire, and satisfaction than healthy controls. Predictive factors of sexual dysfunction were depression in women and age in men. The severity of autonomic symptoms correlated with sexual dysfunction in women, but this effect disappeared after controlling for depression. Conclusions: Compared to healthy controls, women and men with POTS have significant sexual dysfunction, which needs to be considered in the diagnostic and therapeutic approaches as part of comprehensive patient care.

Small fiber neuropathy in children, adolescents, and young adults with chronic orthostatic intolerance and postural orthostatic tachycardia syndrome: A retrospective study

PurposeTo determine in children, adolescent and young adult (CAYA) patients presenting with Orthostatic Intolerance (OI) or Postural Orthostatic Tachycardia Syndrome (POTS) associated with the additional symptoms of neuropathic discomfort (pain, paresthesia and/or allodynia): 1) the incidence of small fiber neuropathy, and 2) assess if there was serologic evidence for an underlying inflammatory or autoimmune state. MethodsA cohort of 109 CAYA patients with the above symptoms underwent epidermal skin biopsy for nerve fiber density. Blood biomarkers for inflammation were tested (CRP, ESR, ANA, complement (C3), thyroid function testing with antibodies (thyroid peroxidase antibody and thyroglobulin antibody), and cytokine panel 13). Patients completed a Quality of Health questionnaire. Statistical analysis was performed using Wilcoxon rank sum tests. ResultsIn CAYA patients with OI or POTS and neuropathic symptoms, skin biopsy for small fiber neuropathy was abnormal in 53 %. The sample population was predominantly female and Caucasian with moderately decreased perceived quality of health. OI /POTS patients with small fiber neuropathy had a 3-fold probability of having a positive ANA or anti-thyroid antibody, suggesting an underlying autoimmune or inflammatory process. ConclusionOur data suggest a link between OI and POTS and small fiber neuropathy. Small fiber neuropathy was found by skin biopsy in over half of the patients tested. OI and Postural orthostatic tachycardia patients with small fiber neuropathy expressed multiple markers suggesting an underlying autoimmune or inflammatory process. Future research will be done to evaluate the symptomatic implication of SFN and whether immune or pharmacologic manipulation can alter patient symptoms.

Abstract 15621: Pelvic Vein Compression in Patients Diagnosed With Postural Orthostatic Tachycardia Syndrome

Introduction: Postural Orthostatic Tachycardia Syndrome (POTS) is a condition characterized by chronic orthostatic intolerance and a significant increase in heart rate. Patients with POTS often exhibit symptoms suggestive of pelvic venous congestion. While venography is the standard method for diagnosing venous compression disorders in the abdomen and pelvis, its potential use in identifying undiagnosed venous abnormalities and its relationship in POTS patients has not been studied. Research Question: This study aimed to investigate the findings of antegrade venography and intravascular ultrasound in patients diagnosed with POTS with high suspicion of May-Thurner Syndrome (MTS) and/or pelvic congestion syndrome, based on initial diagnostic tools such as ultrasound, and who exhibited symptoms of pelvic venous insufficiency (PVI). Methods: Patients clinically diagnosed with POTS underwent antegrade venography and intravascular ultrasound due to a high suspicion of PVI. Demographic, clinical presentation, and venography findings were extracted from the electronic medical records of patients referred to Emory University for POTS/dysautonomia/long COVID evaluation. Patients were diagnosed with MTS if they demonstrated stenosis of the left common iliac vein of 50-70% with associated symptoms like pelvic pain and lower extremity swelling. Results: We identified 28 patients with POTS who had symptoms of PVI. The mean age was 31.6 years (range 18-54), and 96% were female. Doppler ultrasonography revealed venous reflux in the common femoral vein in 82% of the patients. All participants met the criteria for MTS and were referred for stenting. Additionally, 21% of those evaluated had significant bilateral iliac vein compression. Conclusions: This is the largest cohort of POTS patients with pelvic venous compression to date, and our findings suggest a potential association between venous disease and the pathophysiology of POTS. Further research is needed to establish a causal link and explore the clinical implications of venography findings after intervention with angioplasty and stenting. Understanding the venous component in POTS may aid clinicians in the earlier diagnosis and management of PVI.

Abstract 15090: Postural Orthostatic Tachycardia Syndrome After COVID-19 Vaccination

Background: COVID-19 vaccination may be associated with postural orthostatic tachycardia syndrome (POTS) incidence, but little is known of who is at risk, their autonomic state, or how they respond to therapy. Methods: This prospective cohort study analyzed clinical data of 10 POTS clinic patients with new-onset or worsening POTS after COVID-19 vaccination. We also compared heart rate variability (HRV, via spot and ambulatory electrocardiograms (ECGs)) and skin sympathetic nerve activation (SKNA) with 24 healthy controls. Results: Patient mean age was 41.5±7.9 years with equal gender balance. Ambulatory ECG showed no major arrhythmias. Mean standing norepinephrine level was 638.2±395.3 pg/mL, with 4 patients >600 pg/mL. All patients had conditions that could raise POTS risk: prior COVID-19 infection (N=4); hypermobile Ehlers-Danlos syndrome (N=6); mast cell activation syndrome (N=3 found pre-POTS, N=3 post-POTS); and autoimmune (N=7), cardiac (N=7), neurologic (N=6), or gastrointestinal conditions (4). HRV analysis indicated lower spot (36.09 ms±49.2) and ambulatory root mean square of successive differences (46.19 ms±24, p=0.042) vs control (72.49 ms±40.8). SKNA showed a reduced mean amplitude (0.97uV±0.052, p=0.011) vs control (1.2 uV±0.31) and burst amplitude (1.67 uV±0.16, p=0.018) vs control (4.3 uV±4.3). All patients received guideline-based POTS care. After 417.2±131.4 days of follow-up, 3 patients were on ivabradine, 2 on beta blockers, 2 on midodrine, 5 on antihistamines, 4 on mast cell stabilizers, and 1 on prednisone. All patients reported improvement, although 2 with COVID-19 reinfection and 1 with small fiber neuropathy did have relapses of POTS symptoms. Conclusion: POTS patients with post-vaccine onset or exacerbation had histories of potential predisposing conditions. These suggest a potential screening approach, though referral bias is possible. Elevated standing norepinephrine levels, decreased HRV, and decreased pRR50 support a sympathetic-dominant state. Though only 2/10 patients stayed on beta blockers, 8/10 did at least transiently use them. Reduced average SKNA and burst-to-mean amplitude ratio suggest the presence of peripheral autonomic neuropathy. Patients responded to standard POTS therapy.

Abstract 14779: Whole Exome Sequencing Study in Pediatric Postural Orthostatic Tachycardia Syndrome Unveils a Path Forward From Genes to Drugs

Introduction: Postural orthostatic tachycardia syndrome (POTS) is more common in Caucasian individuals with a positive family history, while the risk in females is ~4-times of that in males. To date, the etiology of POTS is poorly understood. Hypothesis: Integrative sequencing and translational approaches to identify its genetic underpinning may better understand its pathogenesis and molecular mechanisms for the development of novel precision-based therapies. Methods: We adopted exome sequencing to evaluate the etiology and molecular mechanisms of POTS. We examined a unique collection of 87 unrelated pediatric POTS cases (61 females and 26 males, 6~21 years old), using exome sequencing. Non-relationship between individuals were validated by genome wide genotyping and identity by descent (IBD) analysis. Results: All the individuals were classified as European by principal component analysis (Figure 1). We identified 184 pathogenic (P) or likely pathogenic (LP) variants (in 162 genes). Sixty-eight (78%) cases have at least one P/LP variant. Each P/LP mutation is supported by a minimum of two databases, including ClinVar, InterVar or HGMD_Pro_2023.1. Over-representation analysis (ORA) by the DisGeNET approach showed the enriched gene sets of muscle hypotonia and epilepsy/seizures with statistical significance (FDR<E-10). Clinically, among the 87 WES patients, 41 (47%) suffered from chronic fatigue, and 13 (15%) patients have the symptoms of epilepsy, seizure or convulsion. A number of drug targets in these gene sets are highlighted, including vitamin D receptor, carbamoyl-phosphate synthase 1, methylmalonyl-CoA mutase, androgen receptor, and phenylalanine hydroxylase. Conclusions: Our results suggests that chronic fatigue and epilepsy/seizure symptoms are comorbid symptoms in POTS patients, resulting from common genetic defects. Future precision-based therapies targeting these specific genetic defects may lead to improved outcome in POTS.

Abstract 16323: Functional Autoantibody Analysis in Post-Acute Sequela of COVID-19 Patients With and Without Pots: A Case Control Study

Introduction: Post-Acute Sequela of COVID-19 (PASC) occurs after recovery from the initial illness. Autonomic dysfunction (AD) may explain these findings. We have previously shown orthostatic intolerance (OI) on standard Italian protocol head-up tilt table in 23 of 24 prospectively studied subjects with PASC and no prior OI. Postural orthostatic tachycardia syndrome (POTS) was noted in 4 of the 23. POTS is associated with elevated levels of autoantibodies. There is a paucity of data evaluating autoantibody presence in subjects with PASC related POTS. Hypothesis: We hypothesized that individuals with PASC related POTS would demonstrate higher levels of certain autoantibodies than controls. Methods: We recruited healthy, COVID-19 PCR negative controls, all previously vaccinated for COVID, who were age and gender matched with the 4 previously identified PASC related POTS patients. Serum was tested for autoantibodies in both groups. Results: Mean ages for the PASC related POTS and control groups were 29 and 31 years, respectively. The PASC related POTS patients had higher levels of functional autoantibodies to several G-protein coupled receptors than controls. The median values for adrenergic A1, adrenergic B2, muscarinic M4, angiotensin 2 and endothelin receptors, comparing controls to PASC related POTS patients, were 10.4 vs 27.5, 14.9 vs 38.5, 7.8 vs 29.0, 12.2 vs 29.5 and 12.6 vs 31.7 Units/ml, respectively. The small size of the 2 groups precludes meaningful statistical testing, but the box plots in Figure 1 show consistent differences in the concentration of antibody receptors seen between the 2 groups. Conclusions: Functional autoantibodies to several G-protein coupled receptors were seen in higher amount in subjects with PASC related POTS compared to healthy controls. While this is a small, case-control study, it suggests a potential autoantibody mediated mechanism that may explain some of the AD seen in PASC patients with POTS.

Psychological stress in postural orthostatic tachycardia syndrome

Background/Aims: Postural orthostatic tachycardia syndrome (POTS) is a chronic condition in which patients show a marked increase in heart rate on standing, but also suffer from a range of additional symptoms, which may include fatigue and difficulty in concentration. This study's aim was to investigate the role of psychological stress, resilience, and lifestyle as possible contributing factors in POTS onset and symptomatology. Methods: Sixty patients diagnosed with POTS at a tertiary investigation center were contacted by mail. A 64-item, online survey was developed in five sections to explore stressful events at symptom onset, present lifestyle factors, and perceptions of stress and resilience. A link was provided for the online survey to those who accepted study participation. Results: Twenty-four POTS patients completed the survey. The average age at onset of symptoms was 20 years and 4 months, with patients waiting an average of 9 years and 5 months for a POTS diagnosis. Respondents reported 54 stressful events in the 12 months leading up to the onset of their symptoms, an average of 2.48 (standard deviation [SD] = 3.24) events per person. However, the modal response was zero events. Patients with POTS had a statistically significant higher score for perceived stress (M = 19.38, SD = 8.88, P< 0.01) than the general population of Sweden (M = 13.96, SD = 5.63). However, there was no correlation between perceptions of stress and symptom severity measured by the orthostatic hypotension questionnaire. Conclusions: Swedish POTS patients have higher levels of perceived stress, similar to other disease states like chronic pain. However, no correlation between perceptions of stress and symptom severity was found. While some respondents reported many stressful events in the lead up to symptom onset, their role is unclear. Further study is required.

Evidence for Impaired Renin Activity in Postural Orthostatic Tachycardia Syndrome.

Postural orthostatic tachycardia syndrome (POTS) is a heterogeneous condition predominantly affecting autonomic control of the cardiovascular system. Its extensive symptom diversity implies multi-organ involvement that interacts in ways still requiring full exploration. Current understanding of POTS pathophysiology suggests alterations in the renin-angiotensin-aldosterone system as a possible contributing factor. Therefore, we investigated the relationship between the activity of the renin-angiotensin-aldosterone system and hemodynamic parameters in a cohort of POTS patients and controls recruited at a tertiary referral center. The case-control study included 46 patients with POTS (27 ± 9 years), and 48 healthy controls (30 ± 9 years) without orthostatic intolerance. Plasma renin activity, expressed as angiotensin I generation, and plasma aldosterone were measured by enzyme-linked immunosorbent assay and were correlated with hemodynamic parameters obtained during active standing tests. Renin activity was significantly downregulated in POTS patients compared to healthy individuals (median, 3406 ng/mL vs. 9949 ng/mL, p < 0.001), whereas aldosterone concentration did not differ between POTS and healthy controls (median, 218 pmol/L vs. 218 pmol/L, p = 0.26). A significant inverse correlation between renin activity and supine and orthostatic blood pressure levels was observed in healthy individuals (p < 0.05 for all), but not in POTS patients. Renin activity, but not aldosterone concentration, is downregulated in patients with POTS. Moreover, renin activity in POTS is dissociated from supine and standing blood pressure levels in contrast to healthy individuals. These findings suggest impaired renin function in POTS, which may direct future therapeutic approaches.

Postural orthostatic tachycardia syndrome associated with post-acute covid-19 syndrome is not mediated through smaller hearts or contractile dysfunction

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): Swedish Heart-Lung foundation Swedish Research Council Introduction Post-acute covid-19 syndrome (PACS) is a novel condition with persistent symptoms affecting different organs. We have previously reported postural orthostatic tachycardia syndrome (POTS) as one important long-term complication. The pathophysiological mechanisms behind PACS and associated POTS are largely unknown. It has previously been suggested that POTS patients have a smaller left ventricular mass (LVM) and volume contributing to the persistent symptoms of tachycardia, however it is currently unknown if these pathophysiological mechanisms are similar in PACS associated POTS. Furthermore, it has been shown that global longitudinal strain (GLS) and global circumferential strain (GCS) are more sensitive measures of contractile function compared to ejection fraction, however it is also currently unknown if GLS and GCS differs between PACS patients with and without POTS. Purpose To elucidate if patients with PACS associated POTS have a lower LVM compared to PACS without POTS, and if GLS and GCS differ between the groups. Methods In total, 31 patients that had suffered a mild SARS-CoV-2 infection diagnosed with PACS according to the WHO criteria were enrolled in this prospective cohort study. POTS was verified by head-up tilt test; 16 patients (age 40±10 years, 94% women) were POTS positive whereas 15 (45±11 years, 93% women) were POTS negative. All patients underwent cardiac magnetic resonance imaging, and global longitudinal strain (GLS) and global circumferential strain (GCS) were calculated. Results There were no differences between the groups with regards to left ventricular dimensions or mass, Table 1. There were no differences in GLS and GCS between the two groups (GLS: PACS and POTS positive -18±2% vs PACS and POTS negative -19±2%, p=0.53; GCS: PACS and POTS positive -17±3% vs PACS and POTS negative -19±3%, p=0.16), Figure 1. Conclusions PACS-related POTS is not associated with contractile dysfunction nor differences in cardiac geometrics, providing mechanistic insights in the pathophysiology of PACS associated POTS. Other specific pathophysiological mechanisms that underlie POTS associated with PACS needs to be established.

Skin sympathetic nerve activity and nocturnal blood pressure nondipping in patients with postural orthostatic tachycardia syndrome.

Postural orthostatic tachycardia syndrome (POTS) is associated with abnormal blood pressure (BP) regulation and increased prevalence of nocturnal nondipping. We hypothesized that nocturnal nondipping of BP is associated with elevated skin sympathetic nerve activity (SKNA) in POTS. We used an ambulatory monitor to record SKNA and electrocardiogram from 79 participants with POTS (36 ± 11 years, 72 women), including 67 with simultaneous 24-h ambulatory BP monitoring. Nocturnal nondipping of BP was present in 19 of 67 (28%) participants. The nondipping group had a higher average SKNA (aSKNA) from midnight of day 1 to 0100 h on day 2 than the dipping group ( P = 0.016, P = 0.030, respectively). The differences (Δ) of aSKNA and mean BP between daytime and night-time were more significant in the dipping group compared with the nondipping group (ΔaSKNA 0.160 ± 0.103 vs. 0.095 ± 0.099 μV, P = 0.021, and Δmean BP 15.0 ± 5.2 vs. 4.9 ± 4.2 mmHg, P < 0.001, respectively). There were positive correlations between ΔaSKNA and standing norepinephrine (NE) (r = 0.421, P = 0.013) and the differences between standing and supine NE levels ( r = 0.411, P = 0.016). There were 53 (79%) patients with SBP less than 90 mmHg and 61 patients (91%) with DBP less than 60 mmHg. These hypotensive episodes were associated with aSKNA of 0.936 ± 0.081 and 0.936 ± 0.080 μV, respectively, which were both significantly lower than the nonhypotensive aSKNA (1.034 ± 0.087 μV, P < 0.001 for both) in the same patient. POTS patients with nocturnal nondipping have elevated nocturnal sympathetic tone and blunted reduction of SKNA between day and night. Hypotensive episodes were associated with reduced aSKNA.

0586 An observational retrospective study of the prevalence of comorbid postural orthostatic tachycardia syndrome (POTS) in narcolepsy

Abstract Introduction Postural orthostatic tachycardia syndrome (POTS) is a clinical syndrome of dysautonomia associated with an excessive increase in heart rate following a shift to standing posture. As of 2019, POTS has a prevalence of 1-3 million (0.3-0.9%) in the United States. Narcolepsy is a chronic neurologic condition of persistent hypersomnolence irrespective of total sleep time that also is associated with REM-sleep dissociative features (i.e., cataplexy, sleep paralysis, sleep-related hallucinations). In recent years, viral infections have been established as a trigger for both neurologic conditions. Methods A manual chart review was performed for records from 11/1/2020 to 12/20/2022. The overall clinic population of narcolepsy was identified by searching the electronic medical record for the ICD-10 codes G47.411 (narcolepsy type 1 [NT1]), and G47.419 (narcolepsy type 2 [NT2]). The past medical history of these charts then was searched for a history of POTS to identify patients with both conditions. A separate chart review was performed to identify all patients with POTS in the clinic. Results Of the 1,433 total patients in the clinic population, 207 narcolepsy patients (NT1=73, 35.3%; NT2=134, 64.7%) and 24 POTS patients were identified. The co-morbid prevalence of narcolepsy with POTS was 8.7% (18, 95% CI 5.2-13.4%); of those patients with POTS, 75% had narcolepsy (95% CI 53.3-90.2%). Co-morbid prevalence was higher in NT1 (13, 17.8% with 95% CI 9.8-28.5%) than NT2 (5, 3.7% with 95% CI 1.2-8.5%). The overall co-morbid prevalence and the NT1 co-morbid prevalence was significantly higher than the overall clinic POTS population (1.26% with 95% CI 0.75-1.98%) and the general population. Conclusion The prevalence of POTS is significantly higher in narcolepsy patients than the overall general population, especially in the NT1 subgroup. Clinicians should consider screening POTS patients for narcolepsy, and vice versa. Further studies are warranted to explore the etiology of co-morbid narcolepsy and POTS. Support (if any) N/A

PO-05-237 A NOVEL STRATEGY OF AUTONOMIC REHABILITATION THERAPY FOR POSTURAL ORTHOSTATIC TACHYCARDIA SYNDROME

Postural Orthostatic Tachycardia Syndrome (POTS) is defined as a sustained increase in HR (>30 bpm) in upright position, orthostatic intolerance, and absence of hypotension. POTS is underdiagnosed and associated with functional disability. Its mechanisms include autonomic denervation, genetic disease, hypovolemia, hyperadrenergic status and deconditioning. POTS patients (pts) have difficulty to perform strengthening exercises for lower limbs and abdominal muscles due to fatigue, pain and comorbidities that make certain movements impractical without supervision. Therefore, they are unable to perform conventional free or supervised training programs. To evaluate the feasibility of a novel training protocol named as Autonomic Rehabilitation Program (ARP) and to report the outcome of patients who completed the program. Five POTS pts were studied–history, physical examination and autonomic tests. All pts were under conventional treatment with no improvement and underwent the specially designed physiotherapy program. The protocol consists in applying peripheral muscle electrostimulation with different frequencies, ranging from 5 to 50 Hertz, aiming to promote pumping contractions at 5Hz and evolving to 50Hz bands to increase the capacity for resisted contractions. We initially stimulated the bilateral antigravity muscle groups, with a 4-channel device, starting contractions promoted only by the device, with the pt completely passive. From the moment the pt felt confortable, active-assisted contractions (pt's exercises together with stimulation) were started isometrically, progressing to eccentric exercises and then to concentric and concentric-resisted exercises. Orthostatic intolerance, functional capacity,and HR before and post-ARP were evaluated. Five pts (5 females, 1 male) with an average age of 32 yo, completed ARP. Before therapy, they presented reduction of systolic index, increased HR (> 30 beats/min in relation to supine position) and low increment of TPR in upright position in the autonomic tests. After a mean follow-up of 8.6 weeks, all of them presented reduction of HR, reported significant improvement of symptoms (one of them referred total remission) and were able to initiate free conventional exercises.The ARP was well tolerated. These exercise adaptation ramps using the peripheral electrostimulation device seem to be more efficient than conventional physiotherapy. Further studies are needed to evaluate the long-term benefit of this strategy

Hypocapnia increases heart rate in patients with Postural Orthostatic Tachycardia Syndrome (POTS)

Background: Postural Orthostatic Tachycardia Syndrome (POTS) is characterized by chronic orthostatic intolerance and significantly impacts quality of life of patients. POTS predominantly affects women of child-bearing age with an estimated prevalence of up to 1%. POTS is defined by an excessive increase in heart rate (HR) of ≥30 bpm within 10 minutes of upright posture, in the absence of orthostatic hypotension. POTS is associated with chronic symptoms (≥6 months) including hyperventilation (HV) in the form of hyperpnea. HV reduces arterial CO 2 (hypocapnia) and worsens tachycardia in POTS. Whether it is hypocapnia that increases HR in these patients is unclear. Studies have not investigated the effects of CO 2 on HR due to the confounding effects of posture and ventilation. Objective: We aimed to determine if hypocapnia exacerbates tachycardia in POTS patients. Hypothesis: We hypothesize that hypocapnia will increase HR in POTS. Methods: We conducted a randomized crossover trial of hypocapnic HV vs. eucapnic HV in 13 female POTS patients (34±9 y). Participants completed the supine breathing protocol: 1) HV with resultant hypocapnia, and 2) HV (with end-tidal CO 2 (ETCO 2 ) clamped at baseline). Breath-by-breath respiratory (ventilation (V E ), tidal volume (V T ), ETCO 2 , end-tidal O 2 (ETO 2 )) and beat-to-beat hemodynamics (HR, stroke volume (SV), cardiac output (CO)) were measured. Data are reported as mean±SD. Paired t-tests were used to compare respiratory and hemodynamic parameters between hypocapnic HV vs. eucapnic HV. Results: During HV, ETCO 2 was significantly lower during hypocapnia vs. eucapnia (19.6±3.7 mmHg vs. 37.4±3.5 mmHg; p&lt;0.0001). ETO 2 was greater during hypocapnia vs eucapnia (117.4±4.7 mmHg vs. 114.6±3.1 mmHg; p&lt;0.001). There was no difference in V E (22.2±6.5 L/min vs. 22.0±5.1 L/min; p=0.8) or V T (1.4±0.4 L vs. 1.4±0.3 L; p=0.9) between hypocapnia and eucapnia. HR was significantly greater during hypocapnia vs. eucapnia (99±12 bpm vs 82±10 bpm; p&lt;0.001); SV was significantly lower during hypocapnia vs. eucapnia (66±14 mL vs. 74±13 mL; p=0.02); and there was no difference in CO between hypocapnia and eucapnia (6.4±1.3 L/min vs. 6.1±1.6 L/min; p=0.3). Conclusion: Independent of ventilation, hypocapnia increases HR in patients with POTS. Our findings suggests that hypocapnia causes a reduction in SV, perhaps due to increased blood pooling in the capacitance vessels leading to reduced venous return. This work was supported by Standing up to POTS. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Sociodemographic Factors, Nutritional Status, and Inflammatory Markers in Patients with Postural Orthostatic Tachycardia Syndrome

Objectives. Postural orthostatic tachycardia syndrome (POTS) is characterized by cardiovascular autonomic dysfunction of unknown etiology with high a prevalence of gastrointestinal symptoms. The aim of the present study was to examine sociodemographic, lifestyle, and nutritional factors as well as inflammatory markers in patients with POTS. Materials and Methods. Forty-three patients with POTS and 61 healthy controls completed questionnaires about sociodemographic factors, lifestyle habits, and gastrointestinal symptoms. Blood samples were analyzed for serum levels of cobalamins, folic acid, iron, total iron-binding capacity (TIBC), ferritin, sodium, potassium, magnesium, phosphorus, albumin, high-sensitive C-reactive protein (CRP), and 25-hydroxyvitamin D (25-OH vitamin D). Results. POTS patients were predominantly women with a lower education level and were more often working part-time, on sick leave, and living alone compared with healthy controls. They reported lower alcohol intake and physical activity levels than controls. The nutrient intake was in general similar in both groups, but POTS patients had a higher intake of different drinks and reported more gastrointestinal symptoms than controls. POTS was associated with higher CRP levels (β: 1.370; 95% CI: 0.004–2.737; p = 0.049 ), lower albumin levels (β: -1.443; 95% CI: -2.648–(-0.238); p = 0.019 ), and higher sodium levels (β: 1.392; 95% CI: 0.559–2.225; p = 0.001 ). Abdominal pain ( p = 0.004 ) and intestinal symptoms’ influence on daily life ( p = 0.025 ) were negatively associated with albumin levels. Abdominal pain ( p = 0.011 ), vomiting and nausea ( p = 0.003 ), and intestinal symptoms’ influence on daily life ( p = 0.026 ) were associated with higher sodium levels. Serum levels representing iron and vitamin metabolism were equal between groups. Conclusions. POTS is associated with poorer sociodemographic status, but malnutrition cannot explain POTS or related gastrointestinal symptoms. Higher CRP and lower albumin levels suggest low-grade inflammation as one possible etiological factor.

Reduced cardiovagal baroreflex sensitivity is associated with postural orthostatic tachycardia syndrome (POTS) and pain chronification in patients with headache.

Non-cephalgic symptoms including orthostatic intolerance, fatigue, and cognitive impairment, are common in patients with chronic headache disorders and may result from alterations in the autonomic nervous system. However, little is known about the function of autonomic reflexes, which regulate cardiovascular homeostasis and cerebral perfusion in patients with headache. Autonomic function testing data from patients with headache collected between January 2018 and April 2022 was retrospectively analyzed. Through review of EMR we determined headache pain chronicity and patient self-report of orthostatic intolerance, fatigue, and cognitive impairment. Composite Autonomic Severity Score (CASS), CASS subscale scores, and cardiovagal and adrenergic baroreflex sensitivities were used to quantify autonomic reflex dysfunction. Descriptive analyses (Mann-Whitney-U or χ2, as appropriate) determined associations between autonomic reflex dysfunction and POTS as well as chronic headache. Binomial logistic regression adjusted for age and sex. Spearman's rank correlation determined the association between the total CASS score and the number of painless symptoms reported by each participant. We identified 34 patients meeting inclusion criteria, of whom there were 16 (47.0%) with orthostatic intolerance, 17 (50.0%) with fatigue, 11 (32.4%) with cognitive complaints, and 11 (32.4%) with Postural Orthostatic Tachycardia Syndrome (POTS). The majority of participants had migraine (n = 24, 70.6%), were female (n = 23, 67.6%) and had a chronic (>15 headache days in a month) headache disorder (n = 26, 76.5%). Reduced cardiovagal baroreflex sensitivity (BRS-V) independently predicted chronic headache [aOR: 18.59 (1.16, 297.05), p = 0.039] and POTS [aOR: 5.78 (1.0, 32.5), p = 0.047]. The total CASS was correlated with the total number of non-painful features in the expected direction (r = 0.46, p = 0.007). Abnormal autonomic reflexes may play an important role in pain chronification and the development of POTS in patients with headache.

Autonomic Nerve Involvement in Post-Acute Sequelae of SARS-CoV-2 Syndrome (PASC).

The novel SARS-CoV-2 virus and resulting COVID-19 global pandemic emerged in 2019 and continues into 2022. While mortality from COVID-19 is slowly declining, a subset of patients have developed chronic, debilitating symptoms following complete recovery from acute infection with COVID-19. Termed as post-acute sequelae of SARS-CoV-2 syndrome (PASC), the underlying pathophysiology of PASC is still not well understood. Given the similarity between the clinical phenotypes of PASC and postural orthostatic tachycardia syndrome (POTS), it has been postulated that dysautonomia may play a role in the pathophysiology of PASC. However, there have been only a few studies that have examined autonomic function in PASC. In this retrospective study, we performed an analysis of autonomic nerve function testing in PASC patients and compared the results with those of POTS patients and healthy controls. Our results suggest that a significant number of PASC patients have abnormal autonomic function tests, and their clinical features are indistinguishable from POTS.

Postural Tachycardia Syndrome and COVID-19: Focus on Ivabradine Therapy.

In this article we discuss the association of postural orthostatic tachycardia syndrome (POTS) with coronavirus-19 (COVID-19), ivabradine's unique mechanism of action, and its use in POTS patients. We highlight the pathophysiology and common etiologies of POTS, including preceding viral infections, vaccines, trauma, surgeries, and other stressors. COVID-19, a viral illness, has been associated with POTS through a variety of mechanisms that are not yet well understood. The initial management strategy for POTS is largely nonpharmacological, focusing on increasing venous return to the heart through physical therapy or other exercise activities. Ivabradine is a selective inhibitor of the funny sodium channels within the sinoatrial node. This unique mechanism of action allows for the reduction of heart rate without any effect on the heart's ionotropic activity. With an increase in the number of POTS cases, especially during the COVID pandemic, the importance of utilizing new medications and management strategies for POTS becomes imperative. Though ivabradine is currently only approved for the management of patients with coronary artery disease and heart failure by the Food and Drug Administration (FDA), it has also proven to be effective at reducing symptoms among patients with refractory POTS, and thus, should be considered for the management of patients who do not respond to initial treatment strategies.

Postural Orthostatic Tachycardia Syndrome (POTS): A Frequently Missed Diagnosis

Postural orthostatic tachycardia syndrome (POTS) is a debilitating chronic illness that involves a sustained tachycardia upon standing and causes multisystem symptoms. Although POTS affects millions, in 2019, more than two-thirds of providers had never heard of POTS. Most POTS patients (83%) have reported being misdiagnosed with a psychological condition, and some wait decades for a proper diagnosis or treatment. Understanding the relationship between autonomic compensation and hemodynamic stability can help a provider recognize and manage POTS. The purpose of this report is to provide nurse practitioners with a practical guide to recognizing, diagnosing, managing, and educating patients with POTS.