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JAMA Jun 2019Syncope can result from a reduction in cardiac output from serious cardiac conditions, such as arrhythmias or structural heart disease (cardiac syncope), or other...
IMPORTANCE
Syncope can result from a reduction in cardiac output from serious cardiac conditions, such as arrhythmias or structural heart disease (cardiac syncope), or other causes, such as vasovagal syncope or orthostatic hypotension.
OBJECTIVE
To perform a systematic review of studies of the accuracy of the clinical examination for identifying patients with cardiac syncope.
STUDY SELECTION
Studies of adults presenting to primary care, emergency departments, or referred to specialty clinics.
DATA EXTRACTION AND SYNTHESIS
Relevant data were abstracted from articles in databases through April 9, 2019, and methodologic quality was assessed. Included studies had an independent comparison to a reference standard.
MAIN OUTCOMES AND MEASURES
Sensitivity, specificity, and likelihood ratios (LRs).
RESULTS
Eleven studies of cardiac syncope (N = 4317) were included. Age at first syncope of at least 35 years was associated with greater likelihood of cardiac syncope (n = 323; sensitivity, 91% [95% CI, 85%-97%]; specificity, 72% [95% CI, 66%-78%]; LR, 3.3 [95% CI, 2.6-4.1]), while age younger than 35 years was associated with a lower likelihood (LR, 0.13 [95% CI, 0.06-0.25]). A history of atrial fibrillation or flutter (n = 323; sensitivity, 13% [95% CI, 6%-20%]; specificity, 98% [95% CI, 96%-100%]; LR, 7.3 [95% CI, 2.4-22]), or known severe structural heart disease (n = 222; range of sensitivity, 35%-51%, range of specificity, 84%-93%; range of LR, 3.3-4.8; 2 studies) were associated with greater likelihood of cardiac syncope. Symptoms prior to syncope that were associated with lower likelihood of cardiac syncope were mood change or prodromal preoccupation with details (n = 323; sensitivity, 2% [95% CI, 0%-5%]; specificity, 76% [95% CI, 71%-81%]; LR, 0.09 [95% CI, 0.02-0.38]), feeling cold (n = 412; sensitivity, 2% [95% CI, 0%-5%]; specificity, 89% [95% CI, 85%-93%]; LR, 0.16 [95% CI, 0.06-0.64]), or headache (n = 323; sensitivity, 3% [95% CI, 0%-7%]; specificity, 80% [95% CI, 75%-85%]; LR, 0.17 [95% CI, 0.06-0.55]). Cyanosis witnessed during the episode was associated with higher likelihood of cardiac syncope (n = 323; sensitivity, 8% [95% CI, 2%-14%]; specificity, 99% [95% CI, 98%-100%]; LR, 6.2 [95% CI, 1.6-24]). Mood changes after syncope (n = 323; sensitivity, 3% [95% CI, 0%-7%]; specificity, 83% [95% CI, 78%-88%]; LR, 0.21 [95% CI, 0.06-0.65]) and inability to remember behavior prior to syncope (n = 323; sensitivity, 5% [95% CI, 0%-9%]; specificity, 82% [95% CI, 77%-87%]; LR, 0.25, [95% CI, 0.09-0.69]) were associated with lower likelihood of cardiac syncope. Two studies prospectively validated the accuracy of the multivariable Evaluation of Guidelines in Syncope Study (EGSYS) score, which is based on 6 clinical variables. An EGSYS score of less than 3 was associated with lower likelihood of cardiac syncope (n = 456; range of sensitivity, 89%-91%, range of specificity, 69%-73%; range of LR, 0.12-0.17; 2 studies). Cardiac biomarkers show promising diagnostic accuracy for cardiac syncope, but diagnostic thresholds require validation.
CONCLUSIONS AND RELEVANCE
The clinical examination, including the electrocardiogram as part of multivariable scores, can accurately identify patients with and without cardiac syncope.
Topics: Age Factors; Aged; Biomarkers; Diagnosis, Differential; Electrocardiography; Female; Heart Diseases; Humans; Risk Factors; Sensitivity and Specificity; Syncope
PubMed: 31237649
DOI: 10.1001/jama.2019.8001 -
Journal of Geriatric Psychiatry and... Sep 2022Orthostatic hypotension (OH) is multifactorial in Parkinson's disease (PD). Antiparkinsonian medication can contribute to OH, leading to increased risk of falls,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Orthostatic hypotension (OH) is multifactorial in Parkinson's disease (PD). Antiparkinsonian medication can contribute to OH, leading to increased risk of falls, weakness and fatigue.
METHODS
We conducted a systematic review and meta-analysis of randomised controlled trials (RCTs) of antiparkinsonian drugs associated with OH as an adverse effect, compared to placebo. We searched EMBASE, MEDLINE and Web of Science databases until November 2020. Analysis used fixed-effects models and the GRADE tool to rate quality of evidence. Meta-analysis was performed if 3 or more studies of a drug group were available.
RESULTS
Twenty-one RCTs including 3783 patients were included comparing 6 PD drug groups to placebo (MAO-B inhibitors, dopamine agonists, levodopa, COMT inhibitors, levodopa and adenosine receptor antagonists). OH was recorded as an adverse event or measurement of vital signs, without further specification on how this was defined or operationalised. Meta-analysis was performed for MAO-B inhibitors and dopamine agonists, as there were 3 or more studies for these drug groups. In this analysis, compared with placebo, neither MAO-B inhibitors or dopamine agonists were associated with increased risk of OH, (OR 2.28 [95% CI:0.81-6.46]), (OR 1.39 [95% CI:0.97-1.98]).
CONCLUSIONS
Most studies did not specifically report OH, or reporting of OH was limited, including how and when it was measured. Furthermore, studies specifically reporting OH included participants that were younger than typical PD populations without multimorbidity. Future trials should address this, for example,, by including individuals over the age of 75, to improve estimations of how antiparkinsonian medications affect risk of OH.
Topics: Antiparkinson Agents; Dopamine Agonists; Humans; Hypotension, Orthostatic; Levodopa; Monoamine Oxidase; Parkinson Disease
PubMed: 34964392
DOI: 10.1177/08919887211060017 -
International Journal of Cardiology.... Mar 2021Initial orthostatic hypotension is a clinically relevant syndrome in older adults which has been associated with symptoms of orthostatic intolerance. The aim of this... (Review)
Review
BACKGROUND
Initial orthostatic hypotension is a clinically relevant syndrome in older adults which has been associated with symptoms of orthostatic intolerance. The aim of this systematic review was to determine the prevalence of orthostatic intolerance symptoms in older adults with initial orthostatic hypotension.
METHODS
MEDLINE (from 1946), EMBASE (from 1974) and Cochrane were searched to December 6th 2019 using the terms "initial orthostatic hypotension", "postural hypotension" and "older adults". Study selection involved the following criteria: published in English; mean or median age 65 years and diagnosis of initial orthostatic hypotension encompassed a decrease in systolic blood pressure by ≥ 40 mmHg and/or diastolic blood pressure by ≥ 20 mmHg within a maximum of 1 min following a postural change.
RESULTS
Of 8311 articles, 12 articles reporting initial orthostatic hypotension prevalence in 3446 participants with a mean age of 75 (6 SD) years (56.5% female) were included. Five initial orthostatic hypotension definition variations were utilised and symptoms were reported in six articles (968 participants, mean age 73.4 (6.1 SD) years, 56% female). The prevalence of symptoms in older adults with initial orthostatic hypotension ranged from 24 to 100% and was dependent on variations in timing or the inclusion of symptoms in the initial orthostatic hypotension definition.
CONCLUSIONS
Where orthostatic intolerance symptoms were reported, a large proportion of older adults with a diagnosis of initial orthostatic hypotension were symptomatic. However, the literature on initial orthostatic hypotension and orthostatic intolerance symptoms is scarce and a variety of definitions of initial orthostatic hypotension are utilised.
PubMed: 33884364
DOI: 10.1016/j.ijchy.2020.100071 -
Blood Pressure Jun 2019Orthostatic hypotension (OH) is a common and clinically important disorder. Published papers vary regarding the definitions of OH and methodologies of evaluation....
PURPOSE
Orthostatic hypotension (OH) is a common and clinically important disorder. Published papers vary regarding the definitions of OH and methodologies of evaluation. Moreover, substantial gaps in the skills and knowledge required for assessment of OH have been reported by clinicians. We aimed to provide current information regarding the definition, classification and evaluation of OH.
METHODS
We performed a comprehensive search of medical databases, using the following keywords: "postural hypotension" or "orthostatic hypotension", combined with: "definition", "classification", "diagnosis", "evaluation" or "meaning". We selected for this review the most relevant recent publications and key papers in the field, published in the English language.
RESULTS
Current data regarding definitions, classification and the evaluation of OH are reviewed. The various aspects of OH assessment are extensively discussed. Considerable discrepancies exist between the published guidelines regarding the methodology of OH diagnosing. We propose an algorithm for OH evaluation and a standardized protocol for bedside determination of OH by healthcare providers.
CONCLUSIONS
Correct assessment of OH is essential for its accurate diagnosis. The methodology of OH evaluation has not been sufficiently standardized. We emphasize the clinical importance of the uniform investigation of OH, according to the current guidelines for OH definition and meaning.
Topics: Algorithms; Diagnostic Techniques and Procedures; Humans; Hypotension, Orthostatic; Point-of-Care Testing
PubMed: 30982364
DOI: 10.1080/08037051.2019.1604067 -
Autonomic Neuroscience : Basic &... Nov 2022Autonomic dysfunction has been occasionally described in varicella-zoster virus (VZV) infection, while few systematic reviews are available. We systematically review... (Review)
Review
BACKGROUND AND PURPOSE
Autonomic dysfunction has been occasionally described in varicella-zoster virus (VZV) infection, while few systematic reviews are available. We systematically review autonomic dysfunction due to VZV infection.
METHODS
This study followed the PRISMA guideline, and three databases were researched and included cross-sectional studies in full-length publications in the English language using appropriate search keywords.
RESULTS
A total of 102 articles were identified initially; finally 45 studies were used for review, comprising pupillomotor dysfunction in 4, sudomotor dysfunction in 2, cardiovascular dysfunction in 2, gastrointestinal dysfunction in 14, and urogenital dysfunction in 23. They can be summarized as (1) VZV infection rarely produces orthostatic hypotension, which involves diffuse sympathetic dysfunction by polyneuropathy. (2) In contrast, VZV infection produces dysfunction of the bladder and the bowel, which involves segmental parasympathetic or sympathetic dysfunction by dorsal root ganglionopathy.
CONCLUSIONS
Awareness of VZV-related autonomic dysfunction is important, because such patients may first visit a gastroenterology or urology clinic. Close collaboration among neurologists, dermatologists, gastroenterologists, and urologists is important to start early antiviral agents and maximize bowel and bladder care in such patients.
Topics: Autonomic Nervous System Diseases; Chickenpox; Cross-Sectional Studies; Herpes Zoster; Herpesvirus 3, Human; Humans
PubMed: 35863181
DOI: 10.1016/j.autneu.2022.103018 -
Neurology Sep 2014Symptomatic orthostatic hypotension (SOH) and recurrent reflex syncope (RRS) can be disabling. Midodrine has been proposed in the management of patients with these... (Review)
Review
OBJECTIVE
Symptomatic orthostatic hypotension (SOH) and recurrent reflex syncope (RRS) can be disabling. Midodrine has been proposed in the management of patients with these conditions but its impact on patient important outcomes remains uncertain. We performed a systematic review to evaluate the efficacy and safety of midodrine in patients with SOH and RRS.
METHODS
We searched multiple electronic databases without language restriction from their inception to June 2013. We included randomized controlled trials of patients with SOH or RRS that compared treatment with midodrine against a control and reported data on patient important outcomes. We graded the quality of evidence according to the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach.
RESULTS
Eleven trials involving 593 patients were included in this review. Three studies addressed health-related quality of life in patients with RRS, showing improvement with midodrine: risk difference 14% (95% confidence interval [CI] -3.5 to 31.6), very low confidence. Seven studies addressed symptom improvement and provided poolable data showing improvement with midodrine in patients with SOH: risk difference 32.8% (95% CI 13.5-48), low confidence; and RRS: risk difference 63.3% (95% CI 47.6-68.2), very low confidence. Five studies reported syncope recurrence in patients with RRS showing improvement with midodrine: risk difference 37% (95% CI 20.8%-47.4%), moderate confidence. The most frequent side effects in the midodrine arm were pilomotor reactions (33.6%, risk ratio 4.58 [95% CI 2.03-10.37]).
CONCLUSIONS
Evidence warranting low/moderate confidence suggests that midodrine improves clinical important outcomes in patients with SOH and RRS.
Topics: Humans; Hypotension, Orthostatic; Midodrine; Quality of Life; Reflex; Secondary Prevention; Syncope
PubMed: 25150287
DOI: 10.1212/WNL.0000000000000815 -
Aging Clinical and Experimental Research May 2022Over the latest years different studies have investigated the possible relationship between D deficiency and occurrence of orthostatic hypotension (OH), often reaching... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Over the latest years different studies have investigated the possible relationship between D deficiency and occurrence of orthostatic hypotension (OH), often reaching controversial results. We perform an update meta-analysis providing an update overview on the association between hypovitaminosis D and orthostatic hypotension (OH) in older adults.
METHODS
Data extraction was independently performed by two authors and based upon predefined criteria. The meta-analysis was performed using a random-effects model. Statistical heterogeneity between groups was measured using the Higgins I2 statistic.
RESULTS
Eight investigations enrolling 16.326 patients (mean age 75.5 years) met the inclusion criteria and were considered for the analysis. Patients with vitamin D deficiency were more likely to have OH compared to those without (OR: 1.36, 95% CI 1.14-1.63, p = 0.0001, I2 = 43.6%). A further sub-analysis, based on three studies, estimating the risk of OH in patients with hypovitaminosis D receiving antihypertensive treatment, did not reach the statistical significance (OR: 1.40, 95% CI 0.61-3.18, p = 0.418, I2 = 53.3%). Meta-regression performed using age (p = 0.12), BMI (p = 0.73) and gender (p = 0.62) as moderators did not reveal any statistical significance in influencing OH. Conversely, physical activity, Vitamin D supplementation and use of radioimmunoassay for the measurement of vitamin D serum levels showed a significant inverse relationship towards the risk of OH (Coeff.-0.09, p = 0.002, Coeff. - 0.12, p < 0.001 and Coeff. - 0.08, p = 0.03, respectively) among patients with hypovitaminosis D. A direct correlation between the administration of antihypertensive treatment and the risk of OH in older patients with low vitamin D level was observed (Coeff. 0.05, p < 0.001).
CONCLUSIONS
Hypovitaminosis D is significantly associated with OH in older adults and directly influence by the administration of antihypertensive drugs. Conversely, physical activity, vitamin D supplementation and use of radioimmunoassay as analytic method inversely correlated with the risk of OH in older patients.
Topics: Aged; Antihypertensive Agents; Humans; Hypotension, Orthostatic; Vitamin D; Vitamin D Deficiency; Vitamins
PubMed: 34628636
DOI: 10.1007/s40520-021-01994-w -
Maturitas Jul 2024The association between cognitive disorders and orthostatic hypotension (OH) has been empirically explored, but the results have been divergent, casting doubt on the... (Meta-Analysis)
Meta-Analysis Review
The association between cognitive disorders and orthostatic hypotension (OH) has been empirically explored, but the results have been divergent, casting doubt on the presence and direction of the association. The objective of this meta-analysis was to systematically review and quantitatively synthesize the association of OH and cognitive function, specifically mean score on the Mini-Mental State Examination (MMSE), cognitive impairment and incident dementia. A Medline search was conducted in May 2022 with no date limit, using the MeSH terms "orthostatic hypotension" OR "orthostatic intolerance" OR "hypotension" combined with the Mesh terms "cognitive dysfunction" OR "Alzheimer disease" OR "dementia" OR "cognition disorder" OR "neurocognitive disorder" OR "cognition" OR "neuropsychological test". Of the 746 selected studies, 15 longitudinal studies met the selection criteria, of which i) 5 studies were eligible for meta-analysis of mean MMSE score comparison, ii) 5 studies for the association of OH and cognitive impairment, and iii) 6 studies for the association between OH and incident dementia. The pooled effect size in fixed-effects meta-analysis was: i) -0.25 (-0.42; -0.07) for the mean MMSE score, which indicates that the MMSE score was lower for those with OH; ii) OR (95 % CI) = 1.278 (1.162; 1.405), P < 0.0001, indicating a 28 % greater risk of cognitive impairment for those with OH at baseline; and iii) HR (95 % CI) = 1.267 (1.156; 1.388), P < 0.0001, indicating a 27 % greater risk of incident dementia for those with OH at baseline. Patients with OH had a lower MMSE score and higher risk of cognitive impairment and incident dementia in this meta-analysis of longitudinal studies. This study confirmed the presence of an association between OH and cognitive disorders in older adults.
Topics: Humans; Hypotension, Orthostatic; Cognitive Dysfunction; Dementia; Longitudinal Studies; Mental Status and Dementia Tests
PubMed: 38604094
DOI: 10.1016/j.maturitas.2023.107866 -
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 -
Archives of Physical Medicine and... Feb 2015To systematically review the literature on nonpharmacologic treatment of orthostatic hypotension. (Review)
Review
OBJECTIVE
To systematically review the literature on nonpharmacologic treatment of orthostatic hypotension.
DATA SOURCES
MEDLINE, Cumulative Index to Nursing and Allied Health Literature, Embase, Cochrane Central Register of Controlled Trials, and SPORTDiscus were searched for human studies written in the English language between January 1980 and April 2013. Reference lists of relevant articles were reviewed for citations to expand the data set.
STUDY SELECTION
Prospective experimental studies assessing nonpharmacologic interventions for management of orthostatic drop in blood pressure in various patient populations were included. All studies identified through the literature search were reviewed independently in duplicate. Of the 642 studies, 23 met the selection criteria.
DATA EXTRACTION
Two reviewers independently extracted data for analysis, including systolic and diastolic blood pressure and orthostatic symptoms in response to postural challenge before and after the intervention. All 23 studies were assessed in duplicate for risk of bias using the Physiotherapy Evidence Database scale for randomized controlled trials and the Downs and Black tool for nonrandomized trials.
DATA SYNTHESIS
There were 8 identified nonpharmacologic interventions for management of orthostatic hypotension under 2 general categories: physical modalities (exercise, functional electrical stimulation, compression, physical countermaneuvers, compression with physical countermaneuvers, sleeping with head up) and dietary measures (water intake, meals). Owing to the clinically diverse nature of the studies, statistical comparison (meta-analysis) was deemed inappropriate. Instead, descriptive comparisons were drawn. Levels of evidence were assigned.
CONCLUSIONS
Strong levels of evidence were found for 4 of the 8 interventions: functional electrical stimulation in spinal cord injury, compression of the legs and/or abdomen, physical countermaneuvers in various patient populations, and eating smaller and more frequent meals in chronic autonomic failure. However, this conclusion is based on a limited number of studies with small sample sizes. Further research into all interventions is warranted.
Topics: Compression Bandages; Drinking Behavior; Electric Stimulation Therapy; Exercise; Humans; Hypotension, Orthostatic; Meals; Muscle Contraction; Posture
PubMed: 25449193
DOI: 10.1016/j.apmr.2014.09.028