Research in Review

• Orthostatic hypotension: evaluation and treatment
• Investigation of postural hypotension due to static prolonged standing in female workers
• The postural orthostatic tachycardia syndrome: a potentially treatable cause of chronic fatigue, exercise intolerance, and cognitive impairment in adolescents
• Diagnostic management of orthostatic intolerance in the workplace
• Syncope due to autonomic insufficiency syndromes associated with orthostatic intolerance
• Inappropriate sinus tachycardia, postural orthostatic tachycardia syndrome, and overlapping syndromes
• Excessive heart rate response to orthostatic stress in postural tachycardia syndrome is not caused by anxiety

Orthostatic hypotension: evaluation and treatment.

Maule S, Papotti G, Naso D, Magnino C, Testa E, Veglio F.

Orthostatic hypotension (OH) may be dependent upon various neurogenic and non-neurogenic disorders and conditions. Neurogenic causes include the main autonomic failure syndromes, primary (multiple system atrophy, pure autonomic failure, and autonomic failure associated with Parkinson's disease) and secondary (central nervous system diseases, peripheral neuropathies and systemic diseases). Non-neurogenic causes of OH include cardiac impairment, fluid and electrolyte loss, vasodilatation, and old age. A number of drugs may also cause OH, through their vasoactive action or by interfering with the autonomic nervous system. Symptoms of OH are debilitating, often confining patients to bed, and longitudinal studies have shown that OH increases the risk of stroke, myocardial ischemia and mortality. The therapeutic goal is to decrease the incidence and severity of postural symptoms, rather than restore normotension. In non-neurogenic OH, treatment of the underlying cause may be curative. In neurogenic OH a combination of non-pharmacological and pharmacological measures is often needed. Patient education and non-pharmacological measures represent the first step; among these interventions, fluid repletion and physical countermanoeuvres have been proven very effective. Pharmacological treatment comprises a number of agents acting on blood vessels, on blood volume or with other pressor mechanisms. The drugs most currently used are fludrocortisone and midodrine. Fludrocortisone expands the extravascular body fluid volume and improves alpha-adrenergic sensitivity. Midodrine is a peripheral, selective alpha1-adrenergic agonist that causes arterial and venous vasoconstriction. Despite the wide use of these drugs, multicentre, randomised and controlled studies for the treatment of OH are still scarce and limited to few agents and groups of patients. Pharmacological management of OH substantially improves the quality of life of patients, although it may be problematic. The development of supine hypertension and subsequent congestive heart failure should be avoided, especially in those patients with a pre-existing cardiovascular risk, such as in diabetes or ischemic heart disease.

PMID: 17346129

Investigation of postural hypotension due to static prolonged standing in female workers.

Cardiovasc Hematol Disord Drug Targets. 2007 Mar;7(1):63-70.

Kabe I, Tsuruoka H, Tokujitani Y, Endo Y, Furusawa M, Takebayashi T.

The "Just-in-Time system" improves productivity and efficiency through cost reduction while it makes workers work in a standing posture. The aim of this study was to investigate the prevalence of postural hypotension in females during prolonged standing work, and to discuss preventive methods. Twelve female static standing workers (mean age+/-standard deviation; 32+/-14 yr old), 6 male static standing workers (30+/-4 yr old), 10 female walking workers (27+/-7 yr old) and 9 female desk workers (31+/-5 yr old) in a certain telecommunications equipment manufacturing factory agreed to participate in this study. All participants received an interview with an occupational physician, and performed the standing up test before working and ambulatory blood pressure monitoring (ABPM) while working. Although the blood pressure of the standing up test did not differ among the groups, mean pulse rates on standing up significantly increased in every group. Hypotension rates in the female standing workers' group by ABPM were 9 persons of 12 participants (75%) for systolic blood pressure (SBP), and were 11 persons of 12 participants (92%) for diastolic blood pressure (DBP). There were significantly higher than those in the female desk workers' group, none of 9 participants (0%) for SBP and 2 of 9 participants (22%) for DBP. The hypotension rates both male standing and female walking worker groups did not differ. Because all 8 workers who were found to have postural hypotension by the standing up test had decreased SBP and/or DBP by ABPM, it is suggested that persons at high risk of postural hypotension during standing work could be screened by the standing up test. The mechanism of postural hypotension may be a decrease of venous return due to leg swelling, and neurocardiogenic or vasovagal response. Preventing the congestion of the lower limbs by walking, managing standing time and wearing elastic hose to keep the amount of the venous return could prevent postural hypotension during prolonged standing work.

PMID: 17721059

The postural orthostatic tachycardia syndrome: a potentially treatable cause of chronic fatigue, exercise intolerance, and cognitive impairment in adolescents.

Pacing Clin Electrophysiol. 2000 Mar;23(3):344-51

Karas B, Grubb BP, Boehm K, Kip K.

Head upright tilt table testing has become an accepted method to measure an individual's predisposition to autonomically mediated periods of hypotension and bradycardia severe enough to cause frank syncope. At the same time it has become increasingly apparent that less profound falls in blood pressure, while not sufficient to result in loss of consciousness, may cause symptoms such as near syncope, vertigo, and dizziness. We describe a subgroup of adolescents that have a mild form of autonomic dysfunction that exhibit disabling symptoms such as postural tachycardia and palpitations, extreme fatigue, lightheadedness, exercise intolerance, and cognitive impairment. During baseline tilt table testing at a 70 degrees angle, these patients demonstrated a heart rate increase of > or = 30 beats/min (or a maximum heart rate of > or = 120 beats/min) within the first 10 minutes upright (not associated with profound hypotension), which reproduced their clinical symptom complex. Similar observations have been made in the adult population and has been termed the postural orthostatic tachycardia syndrome (POTS). We report that POTS may also occur in adolescents and represents a mild, potentially treatable form of autonomic dysfunction that can be readily identified during head upright tilt table testing.

PMID: 10750135

Diagnostic management of orthostatic intolerance in the workplace.

Int Arch Occup Environ Health. 2003 Mar;76(2):143-50. Epub 2002 Oct 30.

Winker R, Barth A, Dorner W, Mayr O, Pilger A, Ivancsits S, Ponocny I, Heider A, Wolf C, Rüdiger HW.

OBJECTIVE: Orthostatic intolerance (OI) is a syndrome that is characterised by headache, concentration difficulties, palpitation of the heart, dizziness associated with postural tachycardia and plasma norepinephrine concentrations that are disproportionately high when the sufferer is in the upright posture. In contrast to other forms of orthostatic dysregulation - orthostatic hypotension (OH) and postural orthostatic tachycardia syndrome (POTS) - OI, hitherto, could be diagnosed only by a tilt table examination, with high expenditure. In this paper we examine the reliability and validity of a questionnaire as a screening instrument for OI.

METHODS: We studied 138 young men (mean age 21.6 years) who were undergoing military service. After a medical check and filling in the questionnaire, the participants underwent a tilt table test including monitoring of blood pressure, heart rate and plasma catecholamines, in the supine position and during 30 min of standing. The questionnaire consisted of ten items registering presence and frequency of typical OI symptoms.

RESULTS: Probands (104) showed normal tilt table test results. OI was diagnosed in 14 probands, OH in 6 and POTS in 14. The OI participants scored significantly higher in the questionnaire than the healthy subjects did: the mean score of the OI group was 22.6, the healthy participants had a mean score of 3.9. Participants with POTS had a mean score of 13.5 and subjects with OH had a mean score of 17.0. Reliability analysis showed a Cronbach's alpha of 0.888. Validity analysis showed that 93.5% of the probands with any kind of orthostatic dysregulation can be detected.

CONCLUSIONS: We were able to establish a short questionnaire as a reliable and valid screening instrument for OI. Usage of this questionnaire can simplify enormously the diagnostic management of patients with suspected OI.

PMID: 12733087

Syncope due to autonomic insufficiency syndromes associated with orthostatic intolerance.

Rom J Intern Med. 2000-2001;38-39:3-19.

Grubb B, Dan GA.

Recurrent syncope may be either a sign or a symptom and may occur due to a wide variety of very different causes. Extensive investigations into the nature of this disorder soon uncovered that it represents only one aspect of a broad, heterogenous group of disturbances of the autonomic nervous system (ANS) that can result in hypotension, orthostatic intolerance, and often syncope. Disorders of orthostatic regulation may be subgrouped into both primary and secondary forms. In primary autonomic failure syndromes, as opposed to the intermittent periods of hypotension seen in the reflex syncopes, patients could develop orthostatic intolerance due to a failure of the ANS to function under normal circumstances. Chronic autonomic insufficiency has two entities: Pure Autonomic Failure (PAF) and Multiple System Atrophy (MSA). Over the last several years, it has become apparent that a milder form of autonomic insufficiency occurs that is now referred to as the Postural Orthostatic Tachycardia Syndrome (POTS). The secondary forms of autonomic failure occur in association with a particular disease process. One of the most important things to remember are the vast number of pharmacologic agents that may either cause or worsen orthostatic hypotension. The principal feature that all of these conditions share is that normal cardiovascular regulation is disturbed resulting in postural hypotension. The comerstone of evaluation is a detailed history and physical examination. One of the physician's most important tasks is to identify whether hypotensive syncope is primary or secondary in nature, and to determine if there are any potentially reversible causes (i.e., drugs, anemia, volume depletion). It is equally important to educate the patient. Nonpharmacologic therapies are useful. Pharmacotherapy should be used cautiously in selected cases.

PMID: 15529568

Inappropriate sinus tachycardia, postural orthostatic tachycardia syndrome, and overlapping syndromes.

Pacing Clin Electrophysiol. 2005 Oct;28(10):1112-21.

Brady PA, Low PA, Shen WK.

BACKGROUND: Inappropriate sinus tachycardia (IAST) and postural orthostatic tachycardia syndrome (POTS) are syndrome complexes with some distinctive features, overlapping clinical manifestations, and potential common mechanisms. Pathogenesis of these overlapping syndromes is poorly understood. Diagnostic and therapeutic approaches have not been standardized.

PURPOSE: This article provides an overview of the definition, clinical presentation, and proposed mechanisms of IAST and other overlapping syndromes. A stepwise diagnostic approach is suggested. A multidisciplinary management scheme is outlined.

METHODS: A MEDLINE search for English-language articles on IAST, POTS, and chronic orthostatic intolerance published up to 2005 was performed. Published data incorporated with our clinical experience were synthesized and presented in this review.

RESULTS: The population of IAST is heterogeneous and underlying mechanisms are complex and likely multifactorial. Evidence suggests that both cardiac and extracardiac causes are plausible. Regional and limited autonomic neuropathies, at least in part, can provide a mechanism-based explanation of the cardiovascular indices and clinical symptoms in a significant number of patients with IAST. The regional abnormalities can be detected by autonomic testing. Among patients with IAST and evidence of autonomic dysregulation, an integrated autonomic, cardiovascular, and psychiatric management approach appears to be logical and rational when appropriate. Sinus node ablation could be considered in patients with persistent IAST in the absence of autonomic neuropathy and multisystem symptoms. Data from long-term outcomes are lacking.

CONCLUSION: The current understanding of IAST mechanisms is incomplete and management approach is not adequate. Significant effort needed in clinical research to improve therapeutic outcome.

PMID: 16221272

Excessive heart rate response to orthostatic stress in postural tachycardia syndrome is not caused by anxiety.

J Appl Physiol. 2007 Mar;102(3):896-903. Epub 2006 Nov 16.

Masuki S, Eisenach JH, Johnson CP, Dietz NM, Benrud-Larson LM, Schrage WG, Curry TB, Sandroni P, Low PA, Joyner MJ
.
Postural tachycardia syndrome (POTS) is characterized by excessive increases in heart rate (HR) without hypotension during orthostasis. The relationship between the tachycardia and anxiety is uncertain. Therefore, we tested whether the HR response to orthostatic stress in POTS is primarily related to psychological factors. POTS patients (n = 14) and healthy controls (n = 10) underwent graded venous pooling with lower body negative pressure (LBNP) to -40 mmHg while wearing deflated antishock trousers. "Sham" venous pooling was performed by 1) trouser inflation to 5 mmHg during LBNP and 2) vacuum pump activation without LBNP. HR responses to mental stress were also measured in both groups, and a questionnaire was used to measure psychological parameters. During LBNP, HR in POTS patients increased 39 +/- 5 beats/min vs. 19 +/- 3 beats/min in control subjects at -40 mmHg (P < 0.01). LBNP with trouser inflation markedly blunted the HR responses in the patients (9 +/- 2 beats/min) and controls (2 +/- 1 beats/min), and there was no HR increase during vacuum application without LBNP in either group. HR responses during mental stress were not different in the patients and controls (18 +/- 2 vs. 19 +/- 1 beats/min; P > 0.6). Anxiety, somatic vigilance, and catastrophic cognitions were significantly higher in the patients (P < 0.05), but they were not related to the HR responses during LBNP or mental stress (P > 0.1). These results suggest that the HR response to orthostatic stress in POTS patients is not caused by anxiety but that it is a physiological response that maintains arterial pressure during venous pooling.

PMID: 17110507

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