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Background: Tetrahydrobiopterin (BH4) and its oxidized derivative dihydrobiopterin (BH2) were found to be strongly elevated in ME/CFS patients with orthostatic intolerance (ME + OI). Objective: However, the molecular mechanism of biopterin biogenesis is poorly understood in ME + OI subjects. Here, we report that the activation of the non-oxidative pentose phosphate pathway (PPP) plays a critical role in the biogenesis of biopterins (BH4 and BH2) in ME + OI subjects. Research Design and Results: Microarray-based gene screening followed by real-time PCR-based validation, ELISA assay, and finally enzyme kinetic studies of glucose-6-phosphate dehydrogenase (G6PDH), transaldolase (TALDO1), and transketolase (TK) enzymes revealed that the augmentation of anaerobic PPP is critical in the regulations of biopterins. To further investigate, we devised a novel cell culture strategy to induce non-oxidative PPP by treating human microglial cells with ribose-5-phosphate (R5P) under a hypoxic condition of 85%N2/10%CO2/5%O2 followed by the analysis of biopterin metabolism via ELISA, immunoblot, and dual immunocytochemical analyses. Moreover, the siRNA knocking down of the taldo1 gene strongly inhibited the bioavailability of phosphoribosyl pyrophosphate (PRPP), reduced the expressions of purine biosynthetic enzymes, attenuated GTP cyclohydrolase 1 (GTPCH1), and suppressed subsequent production of BH4 and its metabolic conversion to BH2 in R5P-treated and hypoxia-induced C20 human microglia cells. These results confirmed that the activation of non-oxidative PPP is indeed required for the upregulation of both BH4 and BH2 via the purine biosynthetic pathway. To test the functional role of ME + OI plasma-derived biopterins, exogenously added plasma samples of ME + OI plasma with high BH4 upregulated inducible nitric oxide synthase (iNOS) and nitric oxide (NO) in human microglial cells indicating that the non-oxidative PPP-induced-biopterins could stimulate inflammatory response in ME + OI patients. Conclusion: Taken together, our current research highlights that the induction of non-oxidative PPP regulates the biogenesis of biopterins contributing to ME/CFS pathogenesis.
Tetrahydrobiopterin (BH4) metabolism is tightly regulated in a healthy individual. Recently, our research showed that BH4 level is upregulated in the plasma samples of ME/CFS patients with orthostatic intolerance. While investigating the molecular mechanism, our current study identified that the pentose phosphate pathway (PPP) induction is critical for the upregulated expression of BH4. A novel hypoxia-based cell culture model is introduced to study PPP in human microglial cells. Subsequently, a comprehensive RNA array study, different immunoassay, and biochemical analyses of enzyme activities confirmed that the induction of non-oxidative PPP in microglial cells enhanced expressions of PPP-regulatory genes and enzymes, induced enzyme activities, activated purine biosynthesis, and finally upregulated biopterin biogenesis.
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Background: Orthostatic intolerance (OI) is the inability to tolerate orthostatic stress during any postural change. The etiology of OI varies, and methods to obtain a specific diagnosis and plan appropriate treatment are important. The tools available within the Chinese context to swiftly identify orthostatic intolerance syndrome (OIS) are currently limited. Methods: Patients with OI symptoms were included in this study and categorized into two groups based on the results of the supine-to-stand test. Those with abnormal test results were assigned to the OIS group, while those with normal test results were placed in the non-OIS group. We evaluated the internal consistency and predictive value of the Chinese Orthostatic Discriminant and Severity Scale (ODSS) by comparing patients' scores with their physiological measurements collected during orthostatic stress tests and the results of other available questionnaires, including the orthostatic Symptom Questionnaire and Orthostatic Grading Scale (OGS). Results: Patients with OIS scored significantly higher on all three questionnaires and showed significant differences in autonomic responses during orthostatic stress tests compared with non-OIS patients. Receiver operating characteristic curve analysis showed that the orthostatic score from the ODSS had moderate predictive value for the supine test (area under the curve [AUC] = 0.754). Further subgroup analysis revealed that the orthostatic score from the ODSS had uniquely high specificity and sensitivity for identifying patients with orthostatic hypotension with abnormal cerebral blood flow (OH-U, AUC = 0.919). Conclusions: We conclude that the Chinese version of the ODSS has sufficient reliability and validity to distinguish patients with OIS and could possibly be used as a diagnostic tool for OH-U patients. Thus, the Chinese ODSS offers a beneficial screening tool for quickly assessing whether patients have OIS that requires further clinical assessment.
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Orthostatic intolerance (OI) is a key symptom of long COVID; however, the pathophysiology remains unknown. Among 688 long COVID patients who visited our clinic during the period from February 2021 to April 2023, 86 patients who were suspected of having OI and who underwent an active standing test (ST) were investigated to elucidate the clinical characteristics of OI in patients with long COVID. Of the 86 patients, 33 patients (38%) were ST-positive. Nausea and tachycardia in daily life were frequent complaints in the ST-positive group. The increase in heart rate (HR) during the ST was significantly greater during a 10-min period after standing in the ST-positive group (+ 30 bpm) than in the ST-negative group (+ 16 bpm). The initial increase in diastolic blood pressure (DBP) just after standing was significantly greater in the ST-positive group (+ 14 mmHg) than in the ST-negative group (+ 9 mmHg). Serum cortisol levels in the ST-positive patients aged over 20 years were higher and growth hormone levels in the patients under 20 years of age were lower than those in the ST-negative group. Autonomous nervous symptoms, transient DBP rise with increasing HR after standing, and endocrine dysfunctions are helpful for detecting OI related to long COVID.
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Presión Sanguínea , COVID-19 , Frecuencia Cardíaca , Intolerancia Ortostática , Humanos , COVID-19/complicaciones , COVID-19/fisiopatología , COVID-19/sangre , Intolerancia Ortostática/fisiopatología , Intolerancia Ortostática/sangre , Masculino , Femenino , Persona de Mediana Edad , Adulto , Anciano , SARS-CoV-2/aislamiento & purificación , Hidrocortisona/sangre , Síndrome Post Agudo de COVID-19 , Adulto JovenRESUMEN
BACKGROUND: Pyridostigmine is hypothesized to improve neurogenic orthostatic hypotension (nOH) symptoms without causing or exacerbating supine hypertension. The objective of this review was to evaluate the safety and efficacy of pyridostigmine for management of nOH. METHODS: A literature search of PubMed, Embase, and CENTRAL was performed in December 2023 for prospective trials with a placebo or active comparator. RESULTS: Four randomized and two non-randomized studies were reviewed. Three studies utilizing a single dose, crossover design found significant differences of orthostatics using adjunctive pyridostigmine. Two studies assessing longer-term endpoints demonstrated conflicting efficacy of pyridostigmine with one trial finding significant improvement in orthostatics and symptoms after three months of therapy. Use of pyridostigmine did not lead to supine hypertension with most adverse effects being cholinergic. CONCLUSION: Pyridostigmine may be considered as an adjunctive medication in individuals with nOH refractory to standard treatment options as it carries a favorable safety profile with low risk for supine hypertension.
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This review discusses the varying definitions for post-acute sequelae of SARS CoV-2 infection (PASC) in adolescents and young adults (AYAs), symptom profiles of AYAs with PASC, and assessment and management strategies when AYAs present with symptoms concerning for PASC. Additionally, it reviews the impact that PASC can have on AYAs and includes strategies for providers to support AYAs with PASC. Finally, it concludes with a discussion around equity in the care of AYAs with possible PASC.
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COVID-19 , Síndrome Post Agudo de COVID-19 , Humanos , COVID-19/complicaciones , COVID-19/epidemiología , Adolescente , Adulto Joven , SARS-CoV-2RESUMEN
Background and Objectives: Heart rate variability (HRV) is defined as a physiological variation in duration between sinus beats. The aim of this study was to research and analyze the HRV between various groups of patients. Materials and Methods: A retrospective study was conducted in an outpatient setting. Patients who had undergone a tilt-table test were selected for this study and were divided into three groups based on their self-reported health anamnesis: group 1 (n = 84, mean age 45.8 ± 17.8) consisted of patients with no known orthostatic intolerance or neurodegenerative disease, group 2 consisted of patients with a known or suspected orthostatic intolerance (n = 50, mean age 46.5 ± 18.6), and group 3 consisted of patients with a known or suspected neurodegenerative disorder (n = 29, mean age 55.6 ± 20.4). During the tilt-table test, HRV frequency-domain parameters-normalized low frequency (LFnu) and high frequency (HFnu), absolute powers-absolute low frequency (LF-RRI), absolute high frequency (HF-RRI), and LF/HF ratio-were recorded during 5 min rest in the supine position. Results: Group 1 had a reduced LFnu at 52.93% (SD: 18.00) compared to group 2 at 58.57% (18.06) and group 3 at 61.80% (SD: 17.74), and group 1 had increased HFnu: group 1-47.08% (SD: 17.97), group 2-41.41% (SD: 18.03), and group 3-38.16% (SD: 14.7). LFnu and HFnu differences were statistically significant (p < 0.05). LF-RRI was reported as follows: group 1-531.32 ms2 (SD: 578.57), group 2-346.2 ms2 (SD: 447.96), and group 3-143.21 ms2 (SD: 166.96). HF-RRI was reported as follows: group 1-835.87 ms2 (SD: 1625.42), group 2-297.46 ms2 (SD: 507.15), and group 3-70.83 ms2 (SD: 75.67). LF-RRI and HF-RRI comparisons between groups were statistically significant (p < 0.001). LF/HF ratios were reported as follows: group 1-1.91 (SD: 2.29), group 2-2.43 (SD: 2.33), and group 3-2.54 (SD: 2.17). LF/HF ratio comparisons between groups were statistically significant at p < 0.05. Conclusions: This study shows that patients with known or suspected orthostatic intolerance and neurodegenerative disorders have reduced HRV, possibly caused by reduced parasympathetic modulation. HRV in patients with known or suspected neurodegenerative disorders is reduced more severely than in patients with orthostatic disorders. Other studies in HRV have indicated a possible increase of risk in cardiovascular disorders in patients with reduced HRV, and therefore, HRV analysis could be a potential clinical diagnostic tool. However, the lack of universally agreed upon methodology, reference values, and possible external and internal factor influence hinders the introduction of HRV examinations into wider clinical practice.
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Frecuencia Cardíaca , Pruebas de Mesa Inclinada , Humanos , Frecuencia Cardíaca/fisiología , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Pruebas de Mesa Inclinada/métodos , Adulto , Anciano , Intolerancia Ortostática/fisiopatología , Enfermedades Neurodegenerativas/fisiopatologíaRESUMEN
This study aimed to examine the effects of intensive antihypertensive treatment (AHT), i.e., systolic blood pressure target ≤ 140 mmHg, on cerebral blood flow, cerebral autoregulation, and orthostatic hypotension, in a representative population of frail older adults. Fourteen frail hypertensive patients (six females; age 80.3 ± 5.2 years; Clinical Frailty Scale 4-7; unattended SBP ≥ 150 mmHg) underwent measurements before and after a median 7-week AHT targeting SBP ≤ 140 mmHg. Transcranial Doppler measurements of middle cerebral artery velocity (MCAv), reflecting changes in cerebral blood flow (CBF), were combined with finger plethysmography recordings of continuous BP. Transfer function analysis assessed cerebral autoregulation (CA). ANCOVA analysed AHT-induced changes in CBF and CA and evaluated non-inferiority of the relative change in CBF (margin: -10%; covariates: pre-AHT values and AHT-induced relative mean BP change). McNemar-tests analysed whether the prevalence of OH and initial OH, assessed by sit/supine-to-stand challenges, increased with AHT. Unattended mean arterial pressure decreased by 15 mmHg following AHT. Ten (71%) participants had good quality TCD assessments. Non-inferiority was confirmed for the relative change in MCAv (95%CI: -2.7, 30.4). CA remained normal following AHT (P > 0.05), and the prevalence of OH and initial OH did not increase (P ≥ 0.655). We found that AHT in frail, older patients does not reduce CBF, impair autoregulation, or increase (initial) OH prevalence. These observations may open doors for more intensive AHT targets upon individualized evaluation and monitoring of hypertensive frail patients.Clinical Trial Registration: This study is registered at ClinicalTrials.gov (NCT05529147; September 1, 2022) and EudraCT (2022-001283-10; June 28, 2022).
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Antihipertensivos , Circulación Cerebrovascular , Anciano Frágil , Hipotensión Ortostática , Ultrasonografía Doppler Transcraneal , Humanos , Femenino , Masculino , Hipotensión Ortostática/fisiopatología , Hipotensión Ortostática/tratamiento farmacológico , Circulación Cerebrovascular/efectos de los fármacos , Circulación Cerebrovascular/fisiología , Antihipertensivos/uso terapéutico , Antihipertensivos/administración & dosificación , Anciano de 80 o más Años , Anciano , Hipertensión/tratamiento farmacológico , Hipertensión/fisiopatología , Homeostasis/fisiología , Arteria Cerebral Media/diagnóstico por imagen , Arteria Cerebral Media/fisiopatología , Arteria Cerebral Media/efectos de los fármacos , Presión Sanguínea/efectos de los fármacos , Presión Sanguínea/fisiologíaRESUMEN
BACKGROUND: Data on median arcuate ligament syndrome (MALS) in children are scant. It is postulated that MALS can cause chronic abdominal pain. It is unclear what percentage of children with this condition are symptomatic and what comorbidities are associated with this syndrome. METHODS: In this retrospective study, data on consecutive patients in a single center diagnosed coincidentally with MALS during routine echocardiogram were reviewed. Symptom burden, comorbidities, and the effect of anthropometric indices on MALS were investigated. Descriptive statistics and nonparametric tests were used to describe the findings and to compare variables with normal distribution. RESULTS: Between 2013 and 2020, there were 82 children, 55 females (67%), mean age 13.9 ± 3.2 years, with MALS and complete record. Mean velocity across the stenotic area was 2.6 ± 0.4 m/s. Forty-six patients (57%) had abdominal pain. Age, gender, weight, body mass index (BMI), and Doppler velocity had no statistically significant influence on symptom occurrence. Conversely, patients with joint hypermobility and symptoms of orthostatic intolerance were more likely to have abdominal pain from MALS. Of 24 patients with joint hypermobility, 18 patients had abdominal pain (p=0.027). Thirty-eight patients with orthostatic intolerance (OI) with MALS complained of abdominal pain vs 13 patients with OI and no abdominal pain (p=<0.0001). CONCLUSION: Nearly half of patients with MALS had abdominal pain. Age, gender, weight, and the degree of stenosis had no statistically significant influence on symptom occurrence. OI, specifically postural orthostatic tachycardia syndrome (POTS), and joint hypermobility on exam predicted a higher propensity for abdominal pain in patients with MALS.
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BACKGROUND: Early postoperative mobilization is essential for early functional recovery but can be inhibited by postoperative orthostatic intolerance (OI). Postoperative OI is common after major surgery, such as total knee arthroplasty (TKA). However, limited data are available after less extensive surgery, such as unicompartmental knee arthroplasty (UKA). We, therefore, investigated the incidence of OI as well as cardiovascular and tissue oxygenation responses during early mobilization after UKA. METHODS: This prospective single-centre observational study included 32 patients undergoing primary UKA. Incidence of OI and cardiovascular and tissue oxygenation responses during mobilization were evaluated preoperatively, at 6 and 24 h after surgery. Perioperative fluid balance, bleeding, surgery duration, postoperative hemoglobin, pain during mobilization and opioid usage were recorded. RESULTS: During mobilization at 6 h after surgery, 4 (14%, 95%CI 4-33%) patients experienced OI; however, no patients terminated the mobilization procedure prematurely. Dizziness and feeling of heat were the most common symptoms. OI was associated with attenuated systolic and mean arterial blood pressure responses in the sitting position (all p < 0.05). At 24 h after surgery, 24 (75%) patients had already been discharged, including three of the four patients with early OI. Only five patients were available for measurements, two of whom experienced OI; one terminated the mobilization procedure due to intolerable symptoms. We observed no statistically significant differences in perioperative fluid balance, bleeding, surgery duration, postoperative hemoglobin, pain, or opioid usage between orthostatic intolerant and tolerant patients. CONCLUSIONS: The incidence of orthostatic intolerance after fast-track unicompartmental knee arthroplasty is low (~ 15%) and is associated with decreased orthostatic pressure responses. Compared to the previously described orthostatic intolerance incidence of ~ 40% following total knee arthroplasty, early orthostatic intolerance is uncommon after unicompartmental knee arthroplasty, suggesting a procedure-specific component. TRIAL REGISTRATION: Prospectively registered at ClinicalTrials.gov; registration number: NCT04195360, registration date: 13.12.2019.
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Artroplastia de Reemplazo de Rodilla , Intolerancia Ortostática , Osteoartritis de la Rodilla , Humanos , Intolerancia Ortostática/epidemiología , Intolerancia Ortostática/etiología , Artroplastia de Reemplazo de Rodilla/efectos adversos , Incidencia , Analgésicos Opioides , Estudios Prospectivos , Hemodinámica , Dolor , Hemoglobinas , Osteoartritis de la Rodilla/complicaciones , Resultado del TratamientoRESUMEN
Individuals with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) often experience autonomic symptoms. In the present study, we evaluated 193 adults seeking treatment for ME/CFS, who were recruited from an outpatient clinic. The participants completed a head-up tilt table test to assess two common types of orthostatic intolerance, namely, postural orthostatic tachycardia syndrome (POTS) and orthostatic hypotension (OH). During the tilt test, 32.5% of the participants demonstrated POTS or OH. The participants with either of these two common types of orthostatic intolerance were found to have more problems with sleep and post-exertional malaise as assessed by the DePaul Symptom Questionnaire; these patients also reported more physical and health function limitations. The implications of the findings are discussed.
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INTRODUCTION: Postural tachycardia syndrome (POTS) is a disorder characterized by a constellation of symptoms including lightheadedness, fatigue, and palpitations when upright, associated with an increase in the heart rate (HR) of > 30 beats per minute when changing from a lying down to standing position or head-up tilt position and not associated with orthostatic hypotension. The causes as well as the management of POTS are not quite fully understood. AREAS COVERED: We performed a literature review on the diagnosis and management of POTS, and this article includes an overview of novel pharmacotherapeutic options for the treatment of (POTS), although an effective treatment has not been established. EXPERT OPINION: POTS is a clinical syndrome characterized by a constellation of symptoms that are nonspecific. No single etiology or unified hypothesis could be identified. In fact, multiple pathophysiological mechanisms have been proposed, and none of the suggested medications have been approved by the FDA for this indication. Further understanding of the autonomic nervous system and its adjustment to standing position is needed to provide better management strategies.
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Hipotensión Ortostática , Síndrome de Taquicardia Postural Ortostática , Humanos , Síndrome de Taquicardia Postural Ortostática/diagnóstico , Síndrome de Taquicardia Postural Ortostática/tratamiento farmacológico , Hipotensión Ortostática/diagnóstico , Hipotensión Ortostática/tratamiento farmacológico , Frecuencia Cardíaca , Fatiga/complicaciones , MareoRESUMEN
BACKGROUND: Orthostatic intolerance, which includes vasovagal syncope and postural orthostatic tachycardia syndrome, is common in children and adolescents. Elevated plasma homocysteine levels might participate in the pathogenesis of orthostatic intolerance. This study was designed to analyze the plasma metabolomic profile in orthostatic intolerance children with high levels of plasma homocysteine. METHODS: Plasma samples from 34 orthostatic intolerance children with a plasma homocysteine concentration > 9 µmol/L and 10 healthy children were subjected to ultra-high-pressure liquid chromatography and quadrupole-time-of-flight mass spectrometry analysis. RESULTS: A total of 875 metabolites were identified, 105 of which were significantly differential metabolites. Choline, 1-stearoyl-2-linoleoyl-sn-glycero-3-phosphocholine, 1-(1Z-octadecenyl)-2-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-sn-glycero-3-phosphocholine, histidine, isocitric acid, and DL-glutamic acid and its downstream metabolites were upregulated, whereas 1-palmitoyl-sn-glycero-3-phosphocholine, 1-stearoyl-sn-glycerol 3-phosphocholine, sphingomyelin (d18:1/18:0), betaine aldehyde, hydroxyproline, and gamma-aminobutyric acid were downregulated in the orthostatic intolerance group compared with the control group. All these metabolites were related to choline and glutamate. Heatmap analysis demonstrated a common metabolic pattern of higher choline, 1-stearoyl-2-linoleoyl-sn-glycero-3-phosphocholine, and DL-glutamic acid, and lower sphingomyelin (d18:1/18:0), 1-stearoyl-sn-glycerol 3-phosphocholine, and 1-palmitoyl-sn-glycero-3-phosphocholine in patients with certain notable metabolic changes (the special group) than in the other patients (the common group). The maximum upright heart rate, the change in heart rate from the supine to the upright position, and the rate of change in heart rate from the supine to the upright position of vasovagal syncope patients were significantly higher in the special group than in the common group (P < 0.05). Choline, 1-stearoyl-2-linoleoyl-sn-glycero-3-phosphocholine, and DL-glutamic acid were positively correlated with the rate of change in heart rate from the supine to the upright position in vasovagal syncope patients (P < 0.05). CONCLUSIONS: The levels of choline-related metabolites and glutamate-related metabolites changed significantly in orthostatic intolerance children with high levels of plasma homocysteine, and these changes were associated with the severity of illness. These results provided new light on the pathogenesis of orthostatic intolerance.
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Glicerol/análogos & derivados , Intolerancia Ortostática , Fosforilcolina/análogos & derivados , Síncope Vasovagal , Adolescente , Niño , Humanos , Ácido Glutámico , Glicerilfosforilcolina , Esfingomielinas , Colina , HomocisteínaRESUMEN
Postural orthostatic tachycardia syndrome (POTS) is characterized by an excessive heart rate (HR) response upon standing and symptoms indicative of inadequate cerebral perfusion. We tested the hypothesis that during lower body negative pressure (LBNP), individuals with POTS would have larger decreases in cardiac and cerebrovascular function measured using magnetic resonance (MR) imaging. Eleven patients with POTS and 10 healthy controls were studied at rest and during 20 min of -25 mmHg LBNP. Biventricular volumes, stroke volume (SV), cardiac output (Qc), and HR were determined by cardiac MR. Cerebral oxygen uptake (VO2 ) in the superior sagittal sinus was calculated from cerebral blood flow (CBF; MR phase contrast), venous O2 saturation (SvO2 ; susceptometry-based oximetry), and arterial O2 saturation (pulse oximeter). Regional cerebral perfusion was determined using arterial spin labelling. HR increased in response to LBNP (p < 0.001) with no group differences (HC: +9 ± 8 bpm; POTS: +13 ± 11 bpm; p = 0.35). Biventricular volumes, SV, and Qc decreased during LBNP (p < 0.001). CBF and SvO2 decreased with LBNP (p = 0.01 and 0.03, respectively) but not cerebral VO2 (effect of LBNP: p = 0.28; HC: -0.2 ± 3.7 mL/min; POTS: +1.1 ± 2.0 mL/min; p = 0.33 between groups). Regional cerebral perfusion decreased during LBNP (p < 0.001) but was not different between groups. These data suggest patients with POTS have preserved cardiac and cerebrovascular function.
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Síndrome de Taquicardia Postural Ortostática , Humanos , Síndrome de Taquicardia Postural Ortostática/diagnóstico por imagen , Presión Negativa de la Región Corporal Inferior , Gasto Cardíaco/fisiología , Circulación Cerebrovascular/fisiología , Frecuencia Cardíaca/fisiología , Presión Sanguínea/fisiologíaRESUMEN
Background: The aim was to investigate if autonomic symptoms questionnaire Composite Autonomic Symptom Score (COMPASS) 31 has different association with cardiovascular autonomic neuropathy (CAN) and diagnostic performance between type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). Methods: Seventy-nine participants with T1DM and 140 with T2DM completed COMPASS 31 before cardiovascular reflex tests (CARTs) for CAN, and assessment of symptoms, signs, vibration, and thermal perception thresholds for diabetic polyneuropathy (DPN) diagnosis. Results: COMPASS 31 total weighted score (TWS) was similar in the two groups, but significantly associated with confirmed CAN only in T1DM (P=0.0056) and not T2DM group (P=0.1768) and correlated with CARTs score more strongly in T1DM (rho=0.356, P=0.0016) than in T2DM group (rho=0.084, P=0.3218) (P=0.016). Only in T1DM and not T2DM group, the area under the receiver operating characteristic curve (AUC) reached a fair diagnostic accuracy (>0.7) for confirmed CAN (0.73±0.07 vs. 0.61±0.08) and DPN (0.75±0.06 vs. 0.68±0.05), although without a significant difference. COMPASS 31 TWS (cut-off 16.44) reached acceptable diagnostic performance in T1DM, with sensitivity for confirmed CAN 81.2% and sensitivity and specificity for DPN 76.3% and 78%, compared to T2DM group (all <70%). AUC for DPN of orthostatic intolerance domain was higher in T1DM compared to T2DM group (0.73±0.05 vs. 0.58±0.04, P=0.027). Conclusion: COMPASS 31 is more weakly related to CAN in T2DM than in T1DM, with a fair diagnostic accuracy for confirmed CAN only in T1DM. This difference supports a multifactorial origin of symptoms and should be considered when using COMPASS 31.
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AIMS: Systolic blood pressure (SBP) drops recorded by 24-h ambulatory blood pressure (BP) monitoring (ABPM) identify patients with susceptibility to reflex syncope and orthostatic intolerance. We tested the hypothesis that treatments aimed to increase BP (reassurance, education, and lifestyle measures plus pharmacological strategies) can reduce SBP drops. METHODS AND RESULTS: This was a multicentre, observational proof-of-concept study performed in patients with reflex syncope and/or orthostatic intolerance and with SBP drops on a screening ABPM. Among 144 eligible patients, 111 underwent a second ABPM on average 2.5 months after start of treatment. Overall, mean 24-h SBP increased from 114.1 ± 12.1 to 121.4 ± 14.5â mmHg (P < 0.0001). The number of SBP drops <90 and <100â mmHg decreased by 61%, 46% during daytime, and by 48% and 37% during 24-h period, respectively (P < 0.0001 for all). The dose-response relationship between difference in 24-h average SBP increase and reduction in number of SBP drops reached a plateau around â¼15â mmHg increase of 24-h SBP. The reduction in SBP drop rate was consistent and significant in patients who underwent deprescription of hypotensive medications (n = 44) and in patients who received BP-rising drugs (n = 67). CONCLUSION: In patients with reflex syncope and/or orthostatic intolerance, an increase in average 24-h SBP, regardless of the implemented strategy, significantly reduced the number of SBP drops and symptom burden. A 13â mmHg increase in 24-h SBP appears to represent the optimal goal for aborting the maximal number of SBP drops, representing a possible target for future interventions. ClincalTrials.gov identifier: NCT05729724.
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Hipertensión , Hipotensión , Intolerancia Ortostática , Síncope Vasovagal , Humanos , Antihipertensivos/uso terapéutico , Presión Sanguínea , Monitoreo Ambulatorio de la Presión Arterial , Hipertensión/tratamiento farmacológico , Intolerancia Ortostática/diagnóstico , Intolerancia Ortostática/tratamiento farmacológico , Reflejo , Síncope Vasovagal/diagnóstico , Síncope Vasovagal/prevención & control , Prueba de Estudio ConceptualRESUMEN
BACKGROUND: There is an association between coronavirus disease 2019 (COVID-19) mRNA vaccination and the incidence or exacerbation of postural orthostatic tachycardia syndrome (POTS). OBJECTIVE: The purpose of this study was to characterize patients reporting new or exacerbated POTS after receiving the mRNA COVID-19 vaccine. METHODS: We prospectively collected data from sequential patients in a POTS clinic between July 2021 and June 2022 reporting new or exacerbated POTS symptoms after COVID-19 vaccination. Heart rate variability (HRV) and skin sympathetic nerve activity (SKNA) were compared against those of 24 healthy controls. RESULTS: Ten patients (6 women and 4 men; age 41.5 ± 7.9 years) met inclusion criteria. Four patients had standing norepinephrine levels > 600 pg/mL. All patients had conditions that could raise POTS risk, including previous COVID-19 infection (N = 4), hypermobile Ehlers-Danlos syndrome (N = 6), mast cell activation syndrome (N = 6), and autoimmune (N = 7), cardiac (N = 7), neurological (N = 6), or gastrointestinal conditions (N = 4). HRV analysis indicated a lower ambulatory root mean square of successive differences (46.19 ±24 ms; P = .042) vs control (72.49 ± 40.8 ms). SKNA showed a reduced mean amplitude (0.97 ± 0.052 µV; P = .011) vs control (1.2 ± 0.31 µV) and burst amplitude (1.67 ± 0.16 µV; P = .018) vs control (4. 3 ± 4.3 µV). After 417.2 ± 131.4 days of follow-up, all patients reported improvement with the usual POTS care, although 2 with COVID-19 reinfection and 1 with small fiber neuropathy did have relapses of POTS symptoms. CONCLUSION: All patients with postvaccination POTS had pre-existing conditions. There was no evidence of myocardial injuries or echocardiographic abnormalities. The decreased HRV suggests a sympathetic dominant state. Although all patients improved with guideline-directed care, there is a risk of relapse.
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Vacunas contra la COVID-19 , COVID-19 , Síndrome de Taquicardia Postural Ortostática , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , COVID-19/prevención & control , Vacunas contra la COVID-19/efectos adversos , Síndrome de Taquicardia Postural Ortostática/diagnóstico , Síndrome de Taquicardia Postural Ortostática/epidemiología , Síndrome de Taquicardia Postural Ortostática/etiología , Vacunación/efectos adversos , Vacunas de ARNm/efectos adversosRESUMEN
INTRODUCTION: Activation of muscles during standing is recommended to activate the skeletal muscle pump, increasing venous return and increasing blood pressure (BP) in people with orthostatic hypotension (OH). AIM: The aim of this study is to determine if increasing the strength of the lower limb muscles can improve the effectiveness of the venous pump and postural BP in older people with OH. METHODS: Ten older people with OH underwent an 8-week lower limb strengthening intervention. Repeated measurements of orthostatic BP, calf venous ejection fraction (EF) and muscle strength took place before, during and after intervention. RESULTS: The intervention increased calf muscle strength by 21% (interquartile range: 18-28), p = 0.018, from a median baseline of 38 (34-45) kg. Participants had normal levels of venous EF 64% (51-75) at baseline, with little to no venous reflux. The median ejection volume at baseline was 44 (36-58) mL per calf. Despite increasing muscle strength, venous EF did not increase (percentage change -10% (-16 to 24), p = 0.8) and systolic BP drop did not improve (percentage change 0% (-17 to 16), p = 1.0). Similarly, visual analysis of individual case-series trends revealed increasing muscle strength with no clinically meaningful change in EF or orthostatic BP. CONCLUSIONS: Muscle strengthening exercise does not increase the effectiveness of the skeletal muscle pump and is not an efficacious intervention for OH. As there is little to no venous pooling in the calf during standing in older people with OH, below knee compression is unlikely to be clinically effective.
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Hipotensión Ortostática , Humanos , Anciano , Hipotensión Ortostática/diagnóstico , Hipotensión Ortostática/terapia , Presión Sanguínea/fisiología , Músculo Esquelético , Ejercicio Físico , PiernaRESUMEN
BACKGROUND: Bier anemic spots, cyanosis with urticaria-like eruption (BASCULE) syndrome is a recently described entity with episodic urticarial lesions and white anemic halos on a background of erythrocyanosis, commonly affecting the lower extremities. Possible association with autonomic dysfunction remains poorly understood. Existing publications are limited, but the condition is suggested as highly underrecognized. OBJECTIVE: To further characterize clinical and epidemiologic data for BASCULE syndrome. METHODS: We performed an IRB-approved retrospective chart review on patients with BASCULE syndrome evaluated at Mayo Clinic from April 2021 to November 2022. RESULTS: A total of 17 patients were identified (13 female, 4 male). Median age of onset was 12 years (range 9-17). Lower extremities were involved in all patients (17). Most patients were symptomatic with pruritus (8) or burning pain (8); three were asymptomatic. Triggers were standing (11), hot showers or hot environments (7), or no clear trigger (4). Autonomic dysfunction was present in 10 patients. Treatment responses were observed from propranolol (3) and high-dose cetirizine (1). CONCLUSION: Novel epidemiologic data from 17 pediatric and young adult patients with BASCULE syndrome further supports an association with autonomic dysfunction and suggests a higher prevalence than previously acknowledged.