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The Cochrane Database of Systematic... May 2021Orthostatic hypotension is an excessive fall in blood pressure (BP) while standing and is the result of a decrease in cardiac output or defective or inadequate...
BACKGROUND
Orthostatic hypotension is an excessive fall in blood pressure (BP) while standing and is the result of a decrease in cardiac output or defective or inadequate vasoconstrictor mechanisms. Fludrocortisone is a mineralocorticoid that increases blood volume and blood pressure. Fludrocortisone is considered the first- or second-line pharmacological therapy for orthostatic hypotension alongside mechanical and positional measures such as increasing fluid and salt intake and venous compression methods. However, there has been no Cochrane Review of the benefits and harms of this drug for this condition.
OBJECTIVES
To identify and evaluate the benefits and harms of fludrocortisone for orthostatic hypotension.
SEARCH METHODS
We searched the following databases on 11 November 2019: Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE, Embase and CINAHL. We also searched trials registries.
SELECTION CRITERIA
We included all studies evaluating the benefits and harms of fludrocortisone compared to placebo, another drug for orthostatic hypotension, or studies without comparators, including randomized controlled trials (RCTs), quasi-RCTs and observational studies. We included studies in people with orthostatic hypotension due to a chronic peripheral neuropathy, a central autonomic neuropathy, or autonomic failure from other causes, but not medication-induced orthostatic hypotension or orthostatic hypotension from acute volume depletion or blood loss.
DATA COLLECTION AND ANALYSIS
We used Cochrane methodological procedures for most of the review. We developed and used a tool to prioritize observational studies that offered the best available evidence where there are gaps in the evidence from RCTs. We assessed the certainty of evidence for fludrocortisone versus placebo using GRADE.
MAIN RESULTS
We included 13 studies of 513 participants, including three cross-over RCTs and 10 observational studies (three cohort studies, six case series and one case-control study). The included RCTs were small (total of 28 participants in RCTs), short term (two to three weeks), only examined fludrocortisone for orthostatic hypotension in people with two conditions (diabetes and Parkinson disease), and had variable risk of bias (two had unclear risk of bias and one had low risk of bias). Heterogeneity in participant populations, comparators and outcome assessment methods prevented meta-analyses of the RCTs. We found very low-certainty evidence about the effects of fludrocortisone versus placebo on drop in BP in people with diabetes (-26 mmHg versus -39 mmHg systolic; -7 mmHg versus -11 mmHg diastolic; 1 cross-over study, 6 participants). For people with Parkinson disease, we found very-low certainty evidence about the effects of fludrocortisone on drop in BP compared to pyridostigmine (-14 mmHg versus -22.1 mmHg diastolic; P = 0.036; 1 cross-over study, 9 participants) and domperidone (no change after treatment in either group; 1 cross-over study, 13 participants). For orthostatic symptoms, we found very low-certainty evidence for fludrocortisone versus placebo in people with diabetes (4 out of 5 analyzed participants had improvements in orthostatic symptoms, 1 cross-over study, 6 participants), for fludrocortisone versus pyridostigmine in people with Parkinson disease (orthostatic symptoms unchanged; 1 cross-over study, 9 participants) or fludrocortisone versus domperidone (improvement to 6 for both interventions on the Composite Autonomic Symptom Scale-Orthostatic Domain (COMPASS-OD); 1 cross-over study, 13 participants). Evidence on adverse events was also very low-certainty in both populations, but indicated side effects were minimal. Observational studies filled some gaps in evidence by examining the effects in larger groups of participants, with more diverse conditions, over longer periods of time. One cohort study (341 people studied retrospectively) found fludrocortisone may not be harmful in the long term for familial dysautonomia. However, it is unclear if this translates to long-term improvements in BP drop or a meaningful improvement in orthostatic symptoms.
AUTHORS' CONCLUSIONS
The evidence is very uncertain about the effects of fludrocortisone on blood pressure, orthostatic symptoms or adverse events in people with orthostatic hypotension and diabetes or Parkinson disease. There is a lack of information on long-term treatment and treatment of orthostatic hypotension in other disease states. There is a need for standardized reporting of outcomes and for standardization of measurements of blood pressure in orthostatic hypotension.
Topics: Bias; Diabetes Mellitus; Domperidone; Dysautonomia, Familial; Fludrocortisone; Humans; Hypotension, Orthostatic; Observational Studies as Topic; Parkinson Disease; Pyridostigmine Bromide; Randomized Controlled Trials as Topic
PubMed: 34000076
DOI: 10.1002/14651858.CD012868.pub2 -
Clinical Cardiology Jul 2023Vasovagal syncope (VVS) is the most prevalent type of syncope and its management includes pharmacologic and non-pharmacologic interventions. Recently, studies have... (Meta-Analysis)
Meta-Analysis Review
Vasovagal syncope (VVS) is the most prevalent type of syncope and its management includes pharmacologic and non-pharmacologic interventions. Recently, studies have investigated vitamin D levels in VVS patients. In this systematic review and meta-analysis, we aim to review these studies to find possible associations between vitamin D deficiency and vitamin D levels with VVS. International databases including Scopus, Web of Science, PubMed, and Embase were searched with keywords related to "vasovagal syncope" and "vitamin D." Studies were screened and the data were extracted from them. Random-effect meta-analysis was conducted to calculate the standardized mean difference (SMD) and 95% confidence interval (CI) for vitamin D levels in comparison to VVS patients and controls. Also, VVS occurrence was measured and the odds ratio (OR) and 95% CI were calculated for comparison of vitamin D deficient cases and nondeficient individuals. Six studies were included with 954 cases investigated. Meta-analysis showed that patients with VVS had significantly lower vitamin D serum levels in comparison to non-VVS cases (SMD -1.05, 95% CI -1.54 to -0.57, p-value < .01). Moreover, VVS occurrence was higher in vitamin D-deficient individuals (OR 5.43, 95% CI 2.40 to 12.27, p-value < .01). Our findings which show lower vitamin D levels in VVS patients can have clinical implications in order for clinicians to pay attention to this when approaching VVS. Further randomized controlled trials are certainly warranted to assess the role of vitamin D supplementation in individuals with VVS.
Topics: Humans; Tilt-Table Test; Syncope, Vasovagal; Syncope; Vitamin D Deficiency; Vitamin D
PubMed: 37226313
DOI: 10.1002/clc.24035 -
International Journal of Environmental... Mar 2022Objective: Cardiovascular effects of thyroid hormones may be measured through heart rate variability (HRV). We sought to determine the impact of hyperthyroidism on HRV.... (Meta-Analysis)
Meta-Analysis Review
Objective: Cardiovascular effects of thyroid hormones may be measured through heart rate variability (HRV). We sought to determine the impact of hyperthyroidism on HRV. Design: A systematic review and meta-analysis on the impact of hyperthyroidism on HRV. Methods: PubMed, Cochrane, Embase and Google Scholar were searched until 20 August 2021 for articles reporting HRV parameters in untreated hyperthyroidism and healthy controls. Random-effects meta-analysis was stratified by degree of hyperthyroidism for each HRV parameter: RR intervals (or Normal-to-Normal intervals—NN), SDNN (standard deviation of RR intervals), RMSSD (square root of the mean difference of successive RR intervals), pNN50 (percentage of RR intervals with >50 ms of variation), total power (TP), LFnu (low-frequency normalized unit) and HFnu (high-frequency), VLF (very low-frequency), and LF/HF ratio. Results: We included 22 studies with 10,811 patients: 1002 with hyperthyroidism and 9809 healthy controls. There was a decrease in RR (effect size = −4.63, 95% CI −5.7 to −3.56), SDNN (−6.07, −7.42 to −4.71), RMSSD (−1.52, −2.18 to −0.87), pNN50 (−1.36, −1.83 to −0.88), TP (−2.05, −2.87 to −1.24), HFnu (−3.51, −4.76 to −2.26), and VLF power (−2.65, −3.74 to −1.55), and an increase in LFnu (2.66, 1.55 to 3.78) and LF/HF ratio (1.75, 1.02 to 2.48) (p < 0.01). Most parameters had ES that was twice as high in overt compared to subclinical hyperthyroidism. Increased peripheral thyroid hormones and decreased TSH levels were associated with lower RR intervals. Conclusions: Hyperthyroidism is associated with a decreased HRV, which may be explained by the deleterious effect of thyroid hormones and TSH. The increased sympathetic and decreased parasympathetic activity may have clinical implications.
Topics: Cardiovascular System; Heart; Heart Rate; Humans; Hyperthyroidism; Thyrotropin
PubMed: 35329294
DOI: 10.3390/ijerph19063606 -
Autonomic Neuroscience : Basic &... Dec 2023To address recent concerns of postural orthostatic tachycardia syndrome (POTS) occurring after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
To address recent concerns of postural orthostatic tachycardia syndrome (POTS) occurring after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19) vaccination.
METHODS
We searched PubMed, Web of Science, and Scopus as of 1st June 2023. We performed a systematic review and meta-analysis of pooled POTS rate in SARS-CoV-2-infected and COVID-19-vaccinated groups from epidemiological studies, followed by subgroup analyses by characteristic. Meta-analysis of risk ratio was conducted to compare POTS rate in infected versus uninfected groups. Meta-analysis of demographics was also performed to compare cases of post-infection and post-vaccination POTS from case reports and series.
RESULTS
We estimated the pooled POTS rate of 107.75 (95 % CI: 9.73 to 273.52) and 3.94 (95 % CI: 0 to 16.39) cases per 10,000 (i.e., 1.08 % and 0.039 %) in infected and vaccinated individuals based on 5 and 2 studies, respectively. Meta-regression revealed age as a significant variable influencing 86.2 % variance of the pooled POTS rate in infected population (P < 0.05). Moreover, POTS was 2.12-fold more likely to occur in infected than uninfected individuals (RR = 2.12, 95 % CI: 1.71 to 2.62, P < 0.001). Meta-analyzed demographics for cases of post-infection (n = 43) and post-vaccination (n = 17) POTS found no significant differences in several variables between groups, except that the time from exposure to symptom onset was shorter for cases of post-vaccination POTS (P < 0.05).
CONCLUSION
Although evidence is limited for post-vaccination POTS, our study showed that POTS occur more frequently following SARS-CoV-2 infection than COVID-19 vaccination.
Topics: Humans; COVID-19; SARS-CoV-2; COVID-19 Vaccines; Postural Orthostatic Tachycardia Syndrome; Demography
PubMed: 38000119
DOI: 10.1016/j.autneu.2023.103132 -
Journal of Neurology Mar 2022To investigate the retina thickness assessed using optical coherence tomography in atypical parkinsonism in comparison with health controls (HC) and patients with... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND PURPOSE
To investigate the retina thickness assessed using optical coherence tomography in atypical parkinsonism in comparison with health controls (HC) and patients with Parkinson's disease (PD).
METHODS
PubMed and EMBASE were searched for potentially eligible studies that reported retina thickness in atypical parkinsonism [including progressive supranuclear palsy (PSP), multiple system atrophy (MSA) and corticobasal degeneration] in comparison with that of HC and PD patients from their dates of inception to Jan 24, 2021. Mean difference (μm) of the thickness of peripapillary retinal nerve fiber layer (pRNFL) and central macular thickness (CMT) were pooled with random effects model.
RESULTS
We included ten studies eligible for inclusion criteria. Average pRNFL thickness and average CMT were thinner in PSP [pooled mean difference (μm) of - 4.71, 95% CI (- 7.15, - 2.27); - 15.12, 95% CI (- 16.93, - 13.30)] and in MSA [- 5.37, 95% CI (- 6.59, - 4.15); - 5.93, 95% CI (- 11.00, - 0.87)] compared with HC, and were thinner in PSP [- 5.81, 95% CI (- 8.92, - 2.69); - 10.63, 95% CI (- 20.29, - 0.98)] and in MSA [- 0.35 μm, 95% CI (- 5.72, 5.01); - 7.42 μm [95% CI (- 12.46, - 2.38)] compared with PD. The pRNFL thickness was thinning in superior, inferior and nasal quadrants, and CMT was thinning in outer sectors in MSA compared with HC.
CONCLUSIONS
The retina thickness was significantly thinner in PSP and MSA than those in HC and PD. The specific patterns of retina thinning in MSA could be clinical importance for differentiation among atypical parkinsonism.
Topics: Humans; Multiple System Atrophy; Parkinson Disease; Parkinsonian Disorders; Retina; Tomography, Optical Coherence
PubMed: 34245345
DOI: 10.1007/s00415-021-10703-6 -
Clinical Rheumatology Oct 2023Psoriatic arthritis (PsA) is an inflammatory disease with a high prevalence of cardiovascular (CV) events due to traditional cardiovascular risk factors and increased... (Review)
Review
Psoriatic arthritis (PsA) is an inflammatory disease with a high prevalence of cardiovascular (CV) events due to traditional cardiovascular risk factors and increased systemic inflammation. In this review, our objectives were to (i) evaluate the cardiovascular events and risk factors and (ii) investigate the relationship between autonomic dysfunction and CV diseases in PsA. A systematic review of the literature was done on the Medline/PubMed, Scopus, and the Directory of Open Access Journals databases between January 2017 and July 2022. After screening and exclusions, 73 studies were included for the final review. Patients with PsA have a greater risk of CV diseases and increased traditional CV risk factors, including hypertension, diabetes mellitus, obesity, metabolic syndrome, and dyslipidemia. Although autonomic dysfunction is more common in PsA than in the general population, its relationship with increased CV diseases in these patients is still unclear. Limitations in explaining CV risk in these patient groups complicate patient assessment as cardiovascular risk factors are linked to the morbidity and mortality of PsA, and it is essential to improve an optimal screening and management strategy for CV disease. All CV risk scoring systems cannot fully assess the CV risk in these patients, so in addition to scoring systems, carotid ultrasound evaluation may be a part of the CV evaluation.
Topics: Humans; Arthritis, Psoriatic; Cardiovascular Diseases; Heart Disease Risk Factors; Hypertension; Primary Dysautonomias; Risk Factors
PubMed: 36542174
DOI: 10.1007/s10067-022-06484-6 -
Annals of Clinical and Translational... Jun 2024Fabry disease is caused by enzymatic defects in alpha-galactosidase A that leads to the accumulation of glycosphingolipids throughout the body, resulting in a...
OBJECTIVE
Fabry disease is caused by enzymatic defects in alpha-galactosidase A that leads to the accumulation of glycosphingolipids throughout the body, resulting in a multisystemic disorder. The most common neurological manifestations are neuropathic pain, autonomic nervous system dysfunction and strokes, but some rarer neurological manifestations exist. Among these, aseptic meningitis is a possible complication. Our objectives were to measure the prevalence of this complication in a cohort of patients with Fabry disease, and to describe its clinical features.
METHODS
We conducted a retrospective review of Fabry disease patients followed at our tertiary referral center between 1995 and September 2023 with at least one episode of meningitis, and performed a systematic review to identify similar published cases.
RESULTS
Four patients out of 107 (3.7%) had at least one episode of aseptic meningitis. Our systematic review identified 25 other observations. The median age of these 29 patients was 29.0 years, the median cerebrospinal fluid leukocyte count was 24 cells/mm3 with a predominance of lymphocytes in 64.7% of cases. In 82.8% of the patients, the diagnosis of Fabry disease was unknown before the meningitis. Large artery stenosis was present in 17.2% of patients and 57.1% of patients had a recent stroke concomitant with the meningitis. Several differential diagnoses were evoked, such as multiple sclerosis or central nervous system vasculitis.
INTERPRETATION
Our study suggests that Fabry disease should be considered as a cause of aseptic meningitis. The pathophysiological mechanisms underlying meningeal inflammation remain largely unknown but may reflect the dysregulation of pro-inflammatory signaling pathways.
Topics: Humans; Fabry Disease; Meningitis, Aseptic; Adult; Male; Female; Retrospective Studies; Middle Aged; Young Adult; Adolescent; Aged; Child
PubMed: 38717582
DOI: 10.1002/acn3.52043 -
Journal of Cardiovascular Pharmacology Jul 2023Postural orthostatic tachycardia syndrome (POTS) is a clinical syndrome of inappropriate increase in heart rate on standing that has been recently also associated with...
Postural orthostatic tachycardia syndrome (POTS) is a clinical syndrome of inappropriate increase in heart rate on standing that has been recently also associated with Coronavirus Disease 2019 (COVID-19) as part of the postacute sequelae of COVID-19 (PASC) or long-COVID. We herein aimed to systematically review reported cases of POTS after COVID-19 and determine the characteristics of the subjects, the diagnostic approach used, and the treatment strategies. We searched the literature according to the following criteria: (1) diagnosis of POTS according to standard definition; (2) timely association with a probable or definite diagnosis of COVID-19; and (3) a description of the individual subject(s). We identified 21 reports meeting criteria between March 2020 and September 2022, including 68 subjects (51 females and 17 males, 3:1 ratio) with a mean age of 34 ± 12 years, with reports deriving from the United States, Norway, Sweden, Israel, Ireland, United Kingdom, Singapore, and Japan. Most cases had mild COVID-19 symptoms. The most common POTS symptoms were palpitations, chest pain, lightheadedness, and debilitating fatigue. The diagnosis was established by means of head-up tilt table or active stand test. Nonpharmacologic treatments (fluids, sodium intake, and compression stockings) were virtually always used, but largely ineffective. Subjects received different treatments, the most common being beta-adrenergic blockers (ie, propranolol), mineral corticosteroids (ie, fludrocortisone), midodrine, and ivabradine. Symptoms tended to improve over time, but most patients remained symptomatic for several months. In conclusion, POTS after COVID-19 is a clinical condition affecting young individuals, and disproportionately young women, occurring as part of PASC-long-COVID, often debilitating, which can be easily diagnosed with a thorough clinical assessment and measuring changes in orthostatic heart rate and blood pressure. POTS after COVID-19 seems to be poorly responsive to nonpharmacological treatments but with symptoms improving with pharmacological interventions. Given the limited data available, additional research is urgently needed with respect to its epidemiology, pathophysiology, and treatments.
Topics: Male; Humans; Female; Young Adult; Adult; Middle Aged; Postural Orthostatic Tachycardia Syndrome; Post-Acute COVID-19 Syndrome; COVID-19; Adrenergic beta-Antagonists; Midodrine; Heart Rate
PubMed: 37094584
DOI: 10.1097/FJC.0000000000001432 -
Journal of Hypertension Oct 2016The systematic review and meta-analysis aims to determine the efficacy and safety of droxidopa in the treatment of orthostatic hypotension, following its recent... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
The systematic review and meta-analysis aims to determine the efficacy and safety of droxidopa in the treatment of orthostatic hypotension, following its recent approvals in the United States.
METHODS
MEDLINE, EMBASE, PubMed, Cochrane Controlled Trials Register, Web of Science, ProQuest, and the WHO Clinical Trials Registry were searched. Studies were included if they randomized adults with orthostatic hypotension to droxidopa or to control, and outcomes related to symptoms, daily activity, blood pressure, or adverse events. Data were extracted independently by two reviewers. Risk of bias was judged against the Cochrane risk of bias tool and quality of evidence measured using Grading of Recommendations Assessment, Development and Evaluation criteria. A fixed-effects model was used for pooled analysis.
RESULTS
Of 224 identified records, four studies met eligibility, with a pooled sample size of 494. Study duration was between 1 and 8 weeks. Droxidopa was effective at reducing dizziness [mean difference -0.97 (95% confidence interval -1.51, -0.42)], overall symptoms [-0.52 (-0.98, -0.06)] and difficulty with activity [-0.86 (-1.34, -0.38)]. Droxidopa was also effective at improving standing SBP [3.9 (0.1, 7.69)]. Rates of adverse events were similar between droxidopa and control groups, including supine hypertension [odds ratio 1.93 (0.87, 4.25)].
CONCLUSION
Droxidopa is well tolerated and effective at reducing the symptoms associated with neurogenic orthostatic hypotension without increasing the risk of supine hypertension.
REGISTRATION
PROSPERO ID CRD42015024612.
Topics: Antiparkinson Agents; Blood Pressure; Droxidopa; Humans; Hypotension, Orthostatic; Posture; Registries
PubMed: 27442791
DOI: 10.1097/HJH.0000000000001043 -
Journal of Neurology Apr 2024Anti-IgLON5 disease is a rare but potentially reversible cause of cognitive impairment, sleep disturbances, dysautonomia, and movement disorders. It is an autoimmune... (Review)
Review
BACKGROUND
Anti-IgLON5 disease is a rare but potentially reversible cause of cognitive impairment, sleep disturbances, dysautonomia, and movement disorders. It is an autoimmune encephalitis which, due to its insidious onset, could mimic neurodegenerative disorders, and multiple symptoms overlap with those seen in dementia with Lewy bodies (DLB). We hypothesized that the symptomatology and findings in patients with anti-IgLON5 disease overlapped with that of DLB.
OBJECTIVES
To assess the commonality of features in anti-IgLON5 disease and DLB and identify potential red flags for anti-IgLON5 disease in patients undergoing diagnostic evaluation for DLB.
METHODS
We searched in MEDLINE, Web of Science, and Embase from inception on December the 8th, 2022 with the search term "IgLON5". We performed a systematic review of case reports and case series of anti-IgLON5 disease, and two reviewers independently extracted data on symptoms and findings. Frequencies of symptoms were compared with consensus criteria for DLB.
RESULTS
We included 57 studies with 127 individual case reports of anti-IgLON5 disease (mean age 63 years at diagnosis, median symptom duration 2 years). Cognitive dysfunction was reported in 45% of cases, REM-sleep behavioral disorder in 15%, and 14% had parkinsonism. Respiratory insufficiency was reported in 37%, and bulbar symptoms in 67%.
CONCLUSIONS
We found a significant overlap between anti-IgLON5 disease and DLB. We propose that anti-IgLON5 disease should be considered in young patients with DLB with chorea, gaze palsy, early dysphagia, or prominent respiratory symptoms. Our study contributes to the emerging knowledge on symptoms and biomarkers in anti-IgLON5 disease.
Topics: Humans; Middle Aged; Lewy Body Disease; Cognitive Dysfunction; Sleep Apnea, Obstructive; REM Sleep Behavior Disorder; Sleep Wake Disorders; Encephalitis; Hashimoto Disease
PubMed: 38195895
DOI: 10.1007/s00415-023-12145-8