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PURPOSE: Hypertension is one of the major causes of cardiovascular morbidity and mortality in the USA and disproportionately affects Black women. Endothelial-derived nitric oxide (eNO) substantially regulates blood pressure in humans, and impaired NO-mediated vasodilation has been reported in the Black population. Previous studies using an NO synthase inhibitor, NG-monomethyl-L-arginine (L-NMMA) did not fully determine the NO contribution to blood pressure because of baroreflex buffering. Therefore, in the present study we used trimethaphan, a ganglionic blocker, to inhibit baroreflex buffering and study NO modulation of blood pressure in Black women during L-NMMA infusion. METHODS: L-NMMA at doses of 250 µg/kg per minute was infused in combination with trimethaphan at doses of 4 mg/min to eliminate baroreflex mechanisms. Heart rate (HR) was obtained with continuous electrocardiogram monitoring, and continuous blood pressure was measured with the volume clamp method. The increase in systolic blood pressure (SBP) during both infusions was used to estimate the contribution of NO to blood pressure. RESULTS: Ten Black (age range 30-50 years, body mass index [BMI] 30-45 kg/m2), and nine White women (age range 30-50 years, body mass index 30-45 kg/m2) were enrolled in this study. During autonomic blockade, there was no difference in the decrease in SBP between Black and White women (- 20 ± 16.45 vs. - 24 ± 15.49 mm Hg, respectively; P = 0.659). When autonomic blockade was combined with L-NMMA, Black women had a significant increase in SBP compared to White women (54 ± 13.62 vs. 39 ± 09.64 mm Hg, respectively; P = 0.022, respectively). CONCLUSION: Autonomic blood pressure regulation was similar between Black and White women. However, NO contribution to blood pressure was significantly greater in Black women compared to White women. REGISTRATION: ClinicalTrials.gov: NCT01122407.
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BACKGROUND: Obesity is associated with resistance to the metabolic (glucose uptake) and vascular (nitric-oxide mediated dilation and microvascular recruitment) actions of insulin. These vascular effects contribute to insulin sensitivity by increasing tissue delivery of glucose. Studies by us and others suggest that sympathetic activation contributes to insulin resistance to glucose uptake. Here we tested the hypothesis that sympathetic activation contributes to impaired insulin-mediated vasodilation in adult subjects with obesity. METHODS AND RESULTS: In a randomized crossover study, we used a euglycemic hyperinsulinemic clamp in 12 subjects with obesity to induce forearm arterial vasodilation (forearm blood flow) and microvascular recruitment (contrast-enhanced ultrasonography) during an intrabrachial infusion of saline (control) or phentolamine (sympathetic blockade). Insulin increased forearm blood flow on both study days (from 2.21±1.22 to 4.89±4.21 mL/100 mL per min, P=0.003 and from 2.42±0.89 to 7.19±3.35 mL/100 mL per min, P=0.002 for the intact and blocked day, respectively). Sympathetic blockade with phentolamine resulted in a significantly greater increase in microvascular flow velocity (∆microvascular flow velocity: 0.23±0.65 versus 2.51±3.01 arbitrary intensity units (AIU/s) for saline and phentolamine respectively, P=0.005), microvascular blood volume (∆microvascular blood volume: 1.69±2.45 versus 3.76±2.93 AIU, respectively, P=0.05), and microvascular blood flow (∆microvascular blood flow: 0.28±0.653 versus 2.51±3.01 AIU2/s, respectively, P=0.0161). To evaluate if this effect was not due to nonspecific vasodilation, we replicated the study in 6 subjects with obesity comparing intrabrachial infusion of phentolamine to sodium nitroprusside. At doses that produced similar increases in forearm blood flow, insulin-induced changes in microvascular flow velocity were greater during phentolamine than sodium nitroprusside (%microvascular flow velocity=58% versus 29%, respectively, P=0.031). CONCLUSIONS: We conclude that sympathetic activation impairs insulin-mediated microvascular recruitment in adult subjects with obesity.
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Estudios Cruzados , Antebrazo , Insulina , Microcirculación , Obesidad , Fentolamina , Flujo Sanguíneo Regional , Sistema Nervioso Simpático , Vasodilatación , Humanos , Antebrazo/irrigación sanguínea , Masculino , Fentolamina/farmacología , Femenino , Obesidad/fisiopatología , Vasodilatación/efectos de los fármacos , Vasodilatación/fisiología , Adulto , Sistema Nervioso Simpático/fisiopatología , Sistema Nervioso Simpático/efectos de los fármacos , Flujo Sanguíneo Regional/efectos de los fármacos , Microcirculación/efectos de los fármacos , Velocidad del Flujo Sanguíneo , Persona de Mediana Edad , Técnica de Clampeo de la Glucosa , Resistencia a la Insulina , Bloqueo Nervioso Autónomo/métodosRESUMEN
PURPOSE OF REVIEW: Long COVID affects approximately 5 million people in Africa. This disease is characterized by persistent symptoms or new onset of symptoms after an acute SARS-CoV-2 infection. Specifically, the most common symptoms include a range of cardiovascular problems such as chest pain, orthostatic intolerance, tachycardia, syncope, and uncontrolled hypertension. Importantly, these conditions appear to have endothelial dysfunction as the common denominator, which is often due to impaired nitric oxide (NO) mechanisms. This review discusses the role of mechanisms contributing to endothelial dysfunction in Long COVID, particularly in people living with HIV. RECENT FINDINGS: Recent studies have reported that increased inflammation and oxidative stress, frequently observed in Long COVID, may contribute to NO dysfunction, ultimately leading to decreased vascular reactivity. These mechanisms have also been reported in people living with HIV. In regions like Africa, where HIV infection is still a major public health challenge with a prevalence of approximately 26 million people in 2022. Specifically, endothelial dysfunction has been reported as a major mechanism that appears to contribute to cardiovascular diseases and the intersection with Long COVID mechanisms is of particular concern. Further, it is well established that this population is more likely to develop Long COVID following infection with SARS-CoV-2. Therefore, concomitant infection with SARS-CoV-2 may lead to accelerated cardiovascular disease. We outline the details of the worsening health problems caused by Long COVID, which exacerbate pre-existing conditions such as endothelial dysfunction. The overlapping mechanisms of HIV and SARS-CoV-2, particularly the prolonged inflammatory response and chronic hypoxia, may increase susceptibility to Long COVID. Addressing these overlapping health issues is critical as it provides clinical entry points for interventions that could improve and enhance outcomes and quality of life for those affected by both HIV and Long COVID in the region.
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Studying acute changes in vascular endothelial cells in humans is challenging. We studied ten African American women and used the J-wire technique to isolate vein endothelial cells before and after a four-hour lipid and heparin infusion. Dynamic changes in lipid-induced oxidative stress and inflammatory markers were measured with fluorescence-activated cell sorting. We used the surface markers CD31 and CD144 to identify human endothelial cells. Peripheral blood mononuclear cells isolated from blood were used as a negative control. The participants received galantamine (16 mg/day) for 3 months. We previously demonstrated that galantamine treatment effectively suppresses lipid-induced oxidative stress and inflammation. In this study, we infused lipids to evaluate its potential to increase the activation of endothelial cells, as assessed by the levels of CD54+ endothelial cells and expression of Growth arrest-specific 6 compared to the baseline sample. Further, we aimed to investigate whether lipid infusion led to increased expression of the oxidative stress markers IsoLGs and nitrotyrosine in endothelial cells. This approach will expedite the in vivo identification of novel pathways linked with endothelial cell dysfunction induced by oxidative stress and inflammatory cytokines. This study describes an innovative method to harvest and study human endothelial cells and demonstrates the dynamic changes in oxidative stress and inflammatory markers release induced by lipid infusion.
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Células Endoteliales , Inflamación , Estrés Oxidativo , Humanos , Estrés Oxidativo/efectos de los fármacos , Femenino , Inflamación/metabolismo , Células Endoteliales/metabolismo , Células Endoteliales/efectos de los fármacos , Adulto , Galantamina/farmacología , Molécula-1 de Adhesión Celular Endotelial de Plaqueta/metabolismo , Antígenos CD/metabolismo , Cadherinas/metabolismo , Tirosina/metabolismo , Tirosina/análogos & derivados , Tirosina/farmacología , Persona de Mediana Edad , Molécula 1 de Adhesión Intercelular/metabolismo , Lípidos/farmacologíaRESUMEN
The NET (norepinephrine transporter) is situated in the prejunctional plasma membrane of noradrenergic neurons. It is responsible for >90% of the norepinephrine uptake that is released in the autonomic neuroeffector junction. Inhibitors of this cell membrane transporter, known as norepinephrine reuptake inhibitors (NRIs), are commercially available for the treatment of depression and attention deficit hyperactivity disorder. These agents increase norepinephrine levels, potentiating its action in preganglionic and postganglionic adrenergic neurons, the latter through activation of α-1 adrenoreceptors. Previous studies found that patients with neurogenic orthostatic hypotension can improve standing blood pressure and reduce symptoms of neurogenic orthostatic hypotension after a single administration of the selective NRI atomoxetine. This effect was primarily observed in patients with impaired central autonomic pathways with otherwise normal postganglionic sympathetic fibers, known as multiple system atrophy. Likewise, patients with normal or high norepinephrine levels may benefit from NRIs. The long-term efficacy of NRIs for the treatment of neurogenic orthostatic hypotension-related symptoms is currently under investigation. In summary, an in-depth understanding of the pathophysiology of neurogenic orthostatic hypotension resulted in the discovery of a new therapeutic pathway targeted by NRI.
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Inhibidores de Captación Adrenérgica , Clorhidrato de Atomoxetina , Hipotensión Ortostática , Norepinefrina , Humanos , Hipotensión Ortostática/tratamiento farmacológico , Hipotensión Ortostática/fisiopatología , Inhibidores de Captación Adrenérgica/uso terapéutico , Inhibidores de Captación Adrenérgica/farmacología , Clorhidrato de Atomoxetina/uso terapéutico , Clorhidrato de Atomoxetina/farmacología , Proteínas de Transporte de Noradrenalina a través de la Membrana Plasmática/antagonistas & inhibidores , Proteínas de Transporte de Noradrenalina a través de la Membrana Plasmática/metabolismo , Presión Sanguínea/efectos de los fármacos , Presión Sanguínea/fisiologíaRESUMEN
PURPOSE: The specific characteristics of autonomic involvement in patients with early Parkinson's disease (PD) are unclear. This study aimed to evaluate the characteristics of autonomic dysfunction in drug-naïve patients with early-stage PD without orthostatic hypotension (OH) by analyzing Valsalva maneuver (VM) parameters. METHODS: We retrospectively analyzed drug-naïve patients without orthostatic hypotension (n = 61) and controls (n = 20). The patients were subcategorized into early PD (n = 35) and mid-PD (n = 26) groups on the basis of the Hoehn and Yahr staging. VM parameters, including changes in systolic blood pressure at late phase 2 (∆SBPVM2), ∆HRVM3, Valsalva ratio (VR), pressure recovery time, adrenergic baroreflex sensitivity, and vagal baroreflex sensitivity, were assessed. RESULTS: In the early PD group, ∆SBPVM2, a marker of sympathetic function, was significantly lower compared with that in controls (risk ratio = 0.95, P = 0.027). Receiver operating characteristic (ROC) curve analysis showed an optimal cut-off value of -10 mmHg for ∆SBPVM2 [P = 0.002, area under the curve (AUC): 0.737]. VR exhibited an inverse relationship with Unified Parkinson's Disease Rating Scale Part 3 scores in the multivariable regression analysis (VR: P = 0.038, ß = -28.61), whereas age showed a positive relationship (age: P = 0.027, ß = 0.35). CONCLUSION: The ∆BPVM2 parameter of the VM may help detect autonomic nervous system involvement in early-PD without OH. Our results suggest that sympathetic dysfunction is an early manifestation of autonomic dysfunction in patients with PD.
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Enfermedades del Sistema Nervioso Autónomo , Barorreflejo , Enfermedad de Parkinson , Maniobra de Valsalva , Humanos , Enfermedad de Parkinson/fisiopatología , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/diagnóstico , Masculino , Femenino , Estudios Retrospectivos , Anciano , Persona de Mediana Edad , Enfermedades del Sistema Nervioso Autónomo/fisiopatología , Enfermedades del Sistema Nervioso Autónomo/diagnóstico , Enfermedades del Sistema Nervioso Autónomo/etiología , Maniobra de Valsalva/fisiología , Barorreflejo/fisiología , Sistema Nervioso Simpático/fisiopatología , Presión Sanguínea/fisiologíaRESUMEN
Dysfunction of endothelial insulin delivery to muscle associates with insulin resistance. CD36, a fatty acid transporter and modulator of insulin signaling is abundant in endothelial cells, especially in capillaries. Humans with inherited 50% reduction in CD36 expression have endothelial dysfunction but whether it is associated with insulin resistance is unclear. Using hyperinsulinemic/euglycemic clamps in Cd36-/- and wildtype mice, and in 50% CD36 deficient humans and matched controls we found that Cd36-/- mice have enhanced systemic glucose disposal despite unaltered transendothelial insulin transfer and reductions in microvascular perfusion and blood vessel compliance. Partially CD36 deficient humans also have better glucose disposal than controls with no capillary recruitment by insulin. CD36 knockdown in primary human-derived microvascular cells impairs insulin action on AKT, endothelial nitric oxide synthase, and nitric oxide release. Thus, insulin resistance of microvascular function in CD36 deficiency paradoxically associates with increased glucose utilization, likely through a remodeling of muscle gene expression.
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We aimed to describe the clinical features of patients with pure autonomic failure (PAF) preceding phenoconversion that could be useful as predictive markers for advancing α-synuclein-associated neurodegeneration of the brain. Patients diagnosed with PAF were evaluated at eight centres (seven US-based and one European) and enrolled in a longitudinal observational cohort study (NCT01799915). Subjects underwent detailed assessments of motor, sleep, olfactory, cognitive and autonomic function and were followed prospectively to determine whether they developed parkinsonism or dementia for up to 10 years. We identified incident cases of Parkinson's disease (PD), dementia with Lewy bodies (DLB) or multiple system atrophy (MSA) and computed hazard ratios for phenoconversion as functions of clinical features. A total of 209 participants with PAF with a median disease duration of 6 years (IQR: 3-10) were enrolled. Of those, 149 provided follow-up information at an office or telemedicine visit. After a mean follow-up duration of 3 years, 48 (33%) participants phenoconverted (42% to PD, 35% to DLB and 23% to MSA). Faster phenoconversion from study enrolment to any diagnosis was associated with urinary and sexual dysfunction [hazard ratio (HR) 5.9, 95% confidence interval (CI): 1.6-22 and HR: 3.6, 95% CI: 1.1-12] followed by subtle motor signs (HR: 2.7, 95% CI: 1.2-6), trouble swallowing (HR 2.5, 95% CI: 1.4-4.5) and changes in speech (HR:2.4, 95% CI:1.1-4.8) at enrolment. Subjects reporting deterioration of handwriting were more likely to phenoconvert to PD (HR: 2.6, 95% CI: 1.1-5.9) and those reporting difficulty handling utensils were more likely to phenoconvert to DLB (HR: 6.8, 95% CI: 1.2-38). Patients with a younger age of PAF onset (HR: 11, 95% CI: 2.6-46), preserved olfaction (HR: 8.7, 95% CI: 1.7-45), anhidrosis (HR: 1.8, 95% CI: 1-3.1, P = 0.042) and severe urinary problems (HR 1.6, 95% CI: 1-2.5, P = 0.033) were more likely to phenoconvert to MSA. The best autonomic predictor of PD was a blunted heart rate increase during the tilt-table test (HR: 6.1, 95% CI: 1.4-26). Patients with PAF have an estimated 12% (95% CI: 9-15%) per year annual risk following study entry of phenoconverting to a manifest CNS synucleinopathy.
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Enfermedad de Parkinson , Insuficiencia Autonómica Pura , Humanos , Masculino , Femenino , Anciano , Estudios Longitudinales , Persona de Mediana Edad , Insuficiencia Autonómica Pura/fisiopatología , Estudios Prospectivos , Enfermedad de Parkinson/fisiopatología , Enfermedad de Parkinson/complicaciones , Progresión de la Enfermedad , Enfermedad por Cuerpos de Lewy/fisiopatología , Estudios de Cohortes , Atrofia de Múltiples Sistemas/fisiopatología , Atrofia de Múltiples Sistemas/epidemiologíaRESUMEN
Although orthostatic hypotension (OH) has long been recognized as a manifestation of autonomic dysfunction, a growing body of literature has identified OH as a common comorbidity of hypertension. This connection is complex, related to pathophysiology in blood pressure regulation and the manner by which OH is derived as the difference between 2 blood pressure measurements. While traditional therapeutic approaches to OH among patients with neurodegenerative disorders focus on increasing upright blood pressure to prevent cerebral hypoperfusion, the management of OH among patients with hypertension is more nuanced; resting hypertension is itself associated with adverse outcomes among these patients. Although there is substantial evidence that intensive blood pressure treatment does not cause OH in the majority of patients with essential hypertension, some classes of antihypertensive agents may unmask OH in patients with an underlying autonomic impairment. Practical steps to manage OH among adults with hypertension start with (1) a thorough characterization of its patterns, triggers, and cause; (2) review and removal of aggravating factors (often pharmacological agents not related to hypertension treatment); (3) optimization of an antihypertensive regimen; and (4) adoption of a tailored treatment strategy that avoids exacerbating hypertension. These strategies include countermaneuvers and short-acting vasoactive agents (midodrine, droxidopa). Ultimately, further research is needed on the epidemiology of OH, the impact of hypertension treatment on OH, approaches to the screening and diagnosis of OH, and OH treatment among adults with hypertension to improve the care of these patients and their complex blood pressure pathophysiology.
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Enfermedades del Sistema Nervioso Autónomo , Hipertensión , Hipotensión Ortostática , Midodrina , Adulto , Humanos , Hipotensión Ortostática/diagnóstico , Hipotensión Ortostática/epidemiología , Hipotensión Ortostática/etiología , American Heart Association , Hipertensión/diagnóstico , Hipertensión/tratamiento farmacológico , Hipertensión/epidemiología , Midodrina/uso terapéutico , Midodrina/farmacología , Presión Sanguínea , Antihipertensivos/farmacología , Enfermedades del Sistema Nervioso Autónomo/diagnóstico , Enfermedades del Sistema Nervioso Autónomo/epidemiología , Enfermedades del Sistema Nervioso Autónomo/etiologíaRESUMEN
Cardiovascular autonomic dysfunction (CVAD) is a malfunction of the cardiovascular system caused by deranged autonomic control of circulatory homeostasis. CVAD is an important component of post-COVID-19 syndrome, also termed long COVID, and might affect one-third of highly symptomatic patients with COVID-19. The effects of CVAD can be seen at both the whole-body level, with impairment of heart rate and blood pressure control, and in specific body regions, typically manifesting as microvascular dysfunction. Many severely affected patients with long COVID meet the diagnostic criteria for two common presentations of CVAD: postural orthostatic tachycardia syndrome and inappropriate sinus tachycardia. CVAD can also manifest as disorders associated with hypotension, such as orthostatic or postprandial hypotension, and recurrent reflex syncope. Advances in research, accelerated by the COVID-19 pandemic, have identified new potential pathophysiological mechanisms, diagnostic methods and therapeutic targets in CVAD. For clinicians who daily see patients with CVAD, knowledge of its symptomatology, detection and appropriate management is more important than ever. In this Review, we define CVAD and its major forms that are encountered in post-COVID-19 syndrome, describe possible CVAD aetiologies, and discuss how CVAD, as a component of post-COVID-19 syndrome, can be diagnosed and managed. Moreover, we outline directions for future research to discover more efficient ways to cope with this prevalent and long-lasting condition.
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Enfermedades del Sistema Nervioso Autónomo , COVID-19 , Enfermedades Cardiovasculares , Humanos , COVID-19/complicaciones , COVID-19/fisiopatología , COVID-19/epidemiología , Enfermedades del Sistema Nervioso Autónomo/fisiopatología , Enfermedades del Sistema Nervioso Autónomo/etiología , Enfermedades del Sistema Nervioso Autónomo/diagnóstico , Enfermedades Cardiovasculares/fisiopatología , Enfermedades Cardiovasculares/epidemiología , Síndrome Post Agudo de COVID-19 , SARS-CoV-2RESUMEN
Purpose: Hyperadrenergic orthostatic hypotension is a subtype of orthostatic hypotension associated with elevated norepinephrine levels upon standing. Our previous study found that this subtype is characterized by less severe autonomic impairment compared to orthostatic hypotension with normal or low norepinephrine levels. However, long-term outcomes have not been determined. Thus, the purpose of this study was to evaluate the all-cause mortality and phenoconversion over 7 years. Methods: In this prospective observational study, 92 patients with orthostatic hypotension were recruited from the Vanderbilt Autonomic Dysfunction Center. 34 patients with upright norepinephrine levels above 600 pg/mL were included in the hyperadrenergic cohort and 58 composed the orthostatic hypotension cohort. Both cohorts were followed for 7 years while assessing all-cause mortality and phenoconversion to neurodegenerative autonomic disorders. Results: Hyperadrenergic patients showed an exaggerated orthostatic increase in norepinephrine to 938 ± 305 pg/mL upon head up tilt despite presenting with impaired autonomic reflexes. The 7-year mortality rate was 35% in the hyperadrenergic cohort compared to 22% in orthostatic hypotension (p = 0.01). The hyperadrenergic cohort had a greater phenoconversion rate to multiple system atrophy (p = 0.04), whereas the orthostatic hypotension cohort had greater phenoconversion to Parkinson's disease and dementia with Lewy bodies. Conclusions: Despite having less severe autonomic impairment, our data suggests that hyperadrenergic orthostatic hypotension has worse clinical outcomes than neurogenic orthostatic hypotension. Patients with hyperadrenergic orthostatic hypotension require careful monitoring, given that this condition may be associated with negative outcomes.
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PURPOSE: Eighty percent of patients infected by SARS-CoV-2 report persistence of one symptom beyond the 4-week convalescent period. Those with orthostatic tachycardia and orthostatic symptoms mimicking postural tachycardia syndrome, they are defined as Long-COVID POTS [LCP]. This case-control study investigated potential differences in autonomic cardiovascular regulation between LCP patients and healthy controls. METHODS: Thirteen LCP and 16 healthy controls, all female subjects, were studied without medications. Continuous blood pressure and ECG were recorded during orthostatic stress test, respiratory sinus arrhythmia, and Valsalva maneuver. Time domain and power spectral analysis of heart rate [HR] and systolic blood pressure [SBP] variability were computed characterizing cardiac autonomic control and sympathetic peripheral vasoconstriction. RESULTS: LCP had higher deltaHR (+ 40 ± 6 vs. + 21 ± 3 bpm, p = 0.004) and deltaSBP (+ 8 ± 4 vs. -1 ± 2 mmHg, p = 0.04) upon standing; 47% had impaired Valsalva maneuver ratio compared with 6.2% in controls (p = 0.01). Spectral analysis revealed that LCP had lower RMSSD (32.1 ± 4.6 vs. 48.9 ± 6.8 ms, p = 0.04) and HFRRI, both in absolute (349 ± 105 vs. 851 ± 253ms2, p = 0.03) and normalized units (32 ± 4 vs. 46 ± 4 n.u., p = 0.02). LFSBP was similar between groups. CONCLUSIONS: LCP have reduced cardiovagal modulation, but normal sympathetic cardiac and vasoconstrictive functions. Impaired parasympathetic function may contribute to the pathogenesis of Long-COVID POTS syndrome.
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BACKGROUND: Many patients with postural orthostatic tachycardia syndrome (POTS) are hypovolemic with plasma volume deficits of 10-30 %. Some also have low levels of aldosterone and diminished aldosterone-renin ratios despite elevations in angiotensin II, pointing to potential adrenal dysfunction. To assess adrenal gland responsiveness in POTS, we measured circulating levels of aldosterone and cortisol following adrenocorticotropin hormone (ACTH) stimulation. METHODS: While on a low Na+ diet (â¼10 mEq/day), 8 female patients with POTS and 5 female healthy controls (HC) received a low dose (1 µg) ACTH bolus following a baseline blood sample. After 60 min, a high dose (249 µg) infusion of ACTH was administered to ensure maximal adrenal response. Venous aldosterone and cortisol levels were sampled every 30 min for 2 h. RESULTS: Aldosterone increased in both groups in response to ACTH but was not different between POTS vs. HC at 60 min (53.5 ng/dL [37.8-61.8 ng/dL] vs. 46.1 ng/dL [36.7-84.9 ng/dL]; P = 1.000) or maximally (56.4 ng/dL [49.2-67.1 ng/dL] vs. 49.5 ng/dL [39.1-82.8 ng/dL]; P = 0.524). Cortisol increased in both groups in response to ACTH but was not different in patients with POTS vs. HC at 60 min (39.9 µg/dL [36.1-47.7 µg/dL] vs. 39.3 µg/dL [35.4-46.6 µg/dL]; P = 0.724) or maximally (39.9 µg/dL [33.9-45.4 µg/dL] vs. 42.0 µg/dL [37.6-49.7 µg/dL]; P = 0.354). CONCLUSIONS: ACTH appropriately increased the aldosterone and cortisol levels in patients with POTS. These findings suggest that the response of the adrenal cortex to hormonal stimulation is intact in patients with POTS.
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Glándulas Suprarrenales , Hormona Adrenocorticotrópica , Síndrome de Taquicardia Postural Ortostática , Glándulas Suprarrenales/efectos de los fármacos , Humanos , Hormona Adrenocorticotrópica/administración & dosificación , Hormona Adrenocorticotrópica/farmacología , Síndrome de Taquicardia Postural Ortostática/tratamiento farmacológico , Aldosterona/sangre , Estudios de Casos y Controles , Hipovolemia , Hidrocortisona/sangre , Masculino , Femenino , Adulto , Persona de Mediana EdadRESUMEN
OBJECTIVE: To evaluate the relationship between postural orthostatic tachycardia syndrome (POTS) and pregnancy. DESIGN: Cross-sectional survey. SETTING: International. SAMPLE: A total of 8941 female patients with a diagnosis of POTS. METHODS: Data from the survey were analysed using descriptive measures and stratified for comparisons. MAIN OUTCOME MEASURES: Symptom course of POTS during pregnancy. Secondary outcomes included pregnancy loss, POTS onset during pregnancy and the impacts of a comorbid diagnosis of Ehlers-Danlos syndrome or an autoimmune disorder on symptoms during pregnancy. RESULTS: Overall, 40.8% (n = 3652) of participants reported one or more pregnancies. Most participants experienced worsening of symptoms in the first (62.6%) and third (58.9%) trimesters and 3 months after pregnancy (58.7%), and 81.1% experienced worsening symptoms at any point in their pregnancy. Most participants with worsening symptoms in the first trimester also experienced worsening symptoms in the second (61.6%) and third (68.1%) trimesters, but if they improved in the first trimester then this improvement persisted in the second and third trimesters. Of participants who reported that POTS was triggered by a specific event (41.3%), 8.1% reported pregnancy as the trigger for the onset. CONCLUSIONS: Postural orthostatic tachycardia syndrome symptoms in the first trimester of pregnancy may help predict symptom course throughout the duration of pregnancy. Some individuals may experience an initial onset of POTS during pregnancy. This novel information may guide clinicians in counselling patients with POTS who are planning pregnancy.
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Aborto Espontáneo , Síndrome de Ehlers-Danlos , Síndrome de Taquicardia Postural Ortostática , Embarazo , Humanos , Femenino , Síndrome de Taquicardia Postural Ortostática/diagnóstico , Síndrome de Taquicardia Postural Ortostática/epidemiología , Estudios Transversales , Síndrome de Ehlers-Danlos/diagnóstico , Síndrome de Ehlers-Danlos/epidemiología , ComorbilidadAsunto(s)
Barorreflejo , COVID-19 , Humanos , Presorreceptores , Sistema Nervioso Simpático , Presión Sanguínea , Vías AferentesRESUMEN
BACKGROUND: Supine hypertension affects most patients with orthostatic hypotension (OH) due to autonomic failure, but it is often untreated for fear of worsening OH. We hypothesized that increasing intrathoracic pressure with continuous positive airway pressure (CPAP) had a Valsalva-like blood-pressure-lowering effect that could be used to treat nocturnal supine hypertension in these patients, while reducing nocturnal pressure diuresis and improving daytime OH. METHODS: In Protocol 1, we determined the acute hemodynamic effects of increasing levels of CPAP (0, 4, 8, 12, and 16 cm H2O, 3 minutes each) in 26 patients with autonomic failure and supine hypertension studied while awake and supine. In Protocol 2 (n=11), we compared the effects of overnight therapy with CPAP (8-12 cm H2O for 8 hours) versus placebo on nocturnal supine hypertension, nocturnal diuresis and daytime OH in a 2-night crossover study. RESULTS: In Protocol 1, acute CPAP (4-16 cm H2O) decreased systolic blood pressure in a dose-dependent manner (maximal drop 22±4 mmHg with CPAP 16) due to reductions in stroke volume (-16+3%) and cardiac output (-14±3%). Systemic vascular resistance and heart rate remained unchanged. In Protocol 2, overnight CPAP lowered nighttime systolic blood pressure (maximal change -23±5 versus placebo -1±7 mmHg; P=0.023) and was associated with lower nighttime diuresis (609±84 versus placebo 1004±160 mL; P=0.004) and improved morning orthostatic tolerance (AUC upright SBP 642±121 versus placebo 410±109 mmHg*min; P=0.014). CONCLUSIONS: CPAP is a novel nonpharmacologic approach to treat the supine hypertension of autonomic failure while improving nocturia and daytime OH. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03312556.
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Hipertensión , Hipotensión Ortostática , Insuficiencia Autonómica Pura , Humanos , Presión de las Vías Aéreas Positiva Contínua , Estudios Cruzados , Hipertensión/tratamiento farmacológico , Presión SanguíneaRESUMEN
BACKGROUND: Standard autonomic testing includes a 10-minute head-up tilt table test to detect orthostatic hypotension. Although this test can detect delayed orthostatic hypotension (dOH) between 3 and 10 minutes of standing, it cannot detect late-onset dOH after 10 minutes of standing. METHODS: To determine whether Valsalva maneuver responses can identify patients who would require prolonged head-up tilt table test to diagnose late-onset dOH; patients with immediate orthostatic hypotension (onset <3 minutes; n=176), early-onset dOH (onset between 3 and 10 minutes; n=68), and late-onset dOH (onset >10 minutes; n=32) were retrospectively compared with controls (n=114) with normal head-up tilt table test and composite autonomic scoring scale score of 0. RESULTS: Changes in baseline systolic blood pressure at late phase 2 (∆SBPVM2), heart rate difference between baseline and phase 3 (∆HRVM3), and Valsalva ratio were lower and pressure recovery time (PRT) at phase 4 was longer in late-onset dOH patients than in controls. Differences in PRT and ∆HRVM3 remained significant after correcting for age. A PRT ≥2.14 s and ∆HRVM3 ≤15 bpm distinguished late-onset dOH from age- and sex-matched controls. Patients with longer PRT (relative risk ratio, 2.189 [1.579-3.036]) and lower ∆HRVM3 (relative risk ratio, 0.897 [0.847-0.951]) were more likely to have late-onset dOH. Patients with longer PRT (relative risk ratio, 1.075 [1.012-1.133]) were more likely to have early-onset than late-onset dOH. CONCLUSIONS: Long PRT and short ∆HRVM3 can help to identify patients who require prolonged head-up tilt table test to diagnose late-onset dOH.
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Hipotensión Ortostática , Humanos , Presión Sanguínea/fisiología , Frecuencia Cardíaca/fisiología , Hipotensión Ortostática/diagnóstico , Postura/fisiología , Estudios Retrospectivos , Pruebas de Mesa Inclinada , Maniobra de Valsalva/fisiologíaRESUMEN
BACKGROUND: Droxidopa, indicated for the treatment of symptomatic neurogenic orthostatic hypotension, can be challenging for patients to access owing to manufacturer and payer restrictions, and requires close monitoring to ensure safety and effectiveness. OBJECTIVE: This practice report describes the development and outcomes of an integrated neurology specialty pharmacy team for droxidopa management. PRACTICE DESCRIPTION: An integrated health-system specialty pharmacy (HSSP) connected to an academic institution with integrated specialty pharmacists working in collaboration with the providers in both the neurology and autonomic disfunction clinic. PRACTICE INNOVATION: In May 2017, the integrated HSSP developed droxidopa management services. Based on clinic-identified needs, the specialty pharmacy team completed droxidopa access requirements (insurance approval and affordability), provided comprehensive medication education at droxidopa initiation, and developed and executed droxidopa titration and monitoring plans in collaboration with providers. While patients were on droxidopa therapy, specialty pharmacist staff (pharmacists and technicians) monitored patients for safety and response to therapy and communicated with the health care team through the shared electronic health record. EVALUATION METHODS: We performed a retrospective cohort analysis of adult patients with at least 3 fills of droxidopa using the integrated specialty pharmacy services from May 2017 to April 2020. Outcomes included persistence (defined as lack of 60-day gap in treatment), adherence (calculated using pharmacy claims and proportion of days covered [PDC]), and number and type of pharmacist interventions after droxidopa initiation. RESULTS: Of the 83 patients reviewed, 60 patients (72%) were persistent on droxidopa therapy over the study period. The median PDC was 0.98 (interquartile range 0.90-1.00). Over 36 months, the specialty pharmacist performed 60 interventions after droxidopa initiation, most related to dose changes, drug-drug interaction management, and medication reconciliation. CONCLUSION: The development of integrated specialty pharmacy services for patients prescribed droxidopa resulted in high droxidopa persistence and adherence. Interventions from the specialty pharmacist ensured droxidopa remained safe and appropriate for patients.