Excessive Heart Rate Increase Research Articles

BS05. Orthostatic hypotension and syncope in patients with ehlers-danlos syndrome

Introduction Postural tachycardia Syndrome (POTS) is a form of chronic orthostatic intolerance where the hallmark physiological trait is an excessive increase in heart rate upon standing. POTS is a final common pathway for a number of overlapping conditions, including lower body autonomic neuropathy, elevated sympathetic tone, mast cell activation, deconditioning, the presence of certain antibodies and hypovolemia. It also has similarities to chronic fatigue syndrome, Ehlers-Danlos Syndrome (EDS), vasovagal syncope and inappropriate sinus tachycardia. EDS is an heterogeneous disorder associated with inherited abnormalities of collagen structure. Patients develop hyper-extensibility, joint hypermobility and fragile connective tissue. Patients with EDS type III frequently have symptoms of autonomic dysregulation such as palpitations, lightheadedness, chest pain, presyncope and syncope that are also common in patients with POTS. Connective tissue abnormalities in EDS could lead to vascular laxity, predipose patients to orthostatic blood pooling in the lower extremities and orthostatic intolerance. These patients might have a peripheral neuropahty that could contribute to autonomic impairment. Methods Clinical records of patients diagnosed with Ehlers Danlos treated at Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran were reviewed retrospectively during a 10 year period (1987–2017). Results 29 patients were found to have a diagnosis of EDS. The female-to-male ratio was 3:1, while the mean age was 29. One patient died due to a ruptured aortic aneurysm. 9 (34.6%) patients had a history of presyncope, 14 patients (53%) had low blood pressure and 12 (46.15%) patients had heart rate values above 80 beats per minute. Mean systolic blood pressure was 107.2 ± 16, diastolic blood pressure 67.3 mmHg ± 10.8 with a mean heart rate of 80.1 ± 11.8. The most common Ehlers Danlos phenotype found was type III, which ocurred in 5 patients (40%). Type IV was found in 5 patients (26%), 3 patients (20%) presented with type VI and only two patients with type VII and type IX, respectively. We could not have the type of 14 patients. Conclusion Although is known that patients with the EDS may present with syncope or presyncopal episodes it is not known the percentage of patients who have dysautonomic cardiovascular symptoms and signs. We found that 53% of the patients have orthostatic intolerance, 34% had syncopal episodes and 46% could be diagnosed with POTS. One patient died due to a thoracic aortic aneurysm.

CARDIOVASCULAR SYSTEM REACTIVITY TO PHYSICAL ACTIVITY DEPENDENCE ON THE CORTISOL SALIVARY CONTENT AT CHILDREN

Aim of the study - to estimate the indicators of the central haemodynamics of children of the first class in Gorno-Altaysk when conducting one-stage functional Martinet - Kushelevsky’s test depending on the level of salivary cortisol. Material and methods. An object of the research was the students of the first class of schools No. 7, 8 and 12 of Gorno-Altaysk (78 children, including 33 boys and 45 girls in the age of 7-8 years). Content of salivary cortisol and indicators of the central haemodynamics were determined when performing one-stage functional Martinet - Kushelevsky’s test (heart rate, arterial blood pressure, systolic and minute blood volume). The type of cardiovascular system reaction, the reaction quality indicator and blood circulation efficiency were defined on the basis of restoration dynamics of heart rate and arterial pressure. Correlation analysis of cardiovascular system indicators and level of salivary cortisol was carried out. Results and discussion. Cortisol level at the examined children didn’t go beyond reference values. The normotonical type of cardiovascular system reaction to physical activity was noted at 54 % of children (42 of 78), atypical types of reaction were revealed at the others: asthenic at 38 % (30 of 78), dystonic at 6 % (5 of 78) and step-type at 1 % (1 of 78). The indicator values of reaction quality of examined children demonstrate that cardiovascular system adaptation to physical activity at children is carried out due to insignificant increase in pulse pressure and excessive increase in heart rate. The performance indicator of low circulation values are caused by significant increase in heart rate in relation to the systolic pressure (the rate of circulation value is lower than optimum level at 61 % of children). Restoration of heart rate after loading at the examined children took place for the 3rd minute however the mode of this indicator restoration is of decremental character being a sign of cardiovascular system unstable condition. The positive correlation of average degree between the salivary cortisol level and HR indicators of both after physical activity and during restoration is revealed ( p < 0,05). Therefore, the cardiovascular system of children with rather high rates of free cortisol in saliva is notable for the bigger reactivity to physical activity. Conclusion. The atypical type of cardiovascular systems reaction to standard physical activity and the decremental nature of HR restoration is revealed at 46 % examined children of the first class of general education institutions No. 7, 8 and 12 of Gorno-Altaysk. The significant increase in HR after physical activity is revealed at children with higher level of salivary cortisol.

A survey based study on sleep disturbance in postural tachycardia syndrome

BackgroundPostural tachycardia syndrome (POTS) is an autonomic disturbance characterized by an excessive increase in heart rate when an individual moves from a sitting to an upright position. POTS patients often complain of fatigue, daytime sleepiness and insomnia, but there is limited evidence to elucidate the mechanism or the prevalence of sleep-related symptoms in POTS, as well as the effect on patient quality of life. Here, we investigated the prevalence of sleep disturbances in POTS patients, as well as the use of medication and effects on daily life. MethodsA survey was administered to 30 patients with POTS. The survey contained 22 questions on various characteristics of sleep disturbances in POTS. Answers were recorded on a five-point Likert rating scale. ResultsThe majority of the patients reported fatigue (96.7%) and low energy (93.3%) during the day. Most (83.3%) patients reported that they do not feel well rested when waking up in the morning. More than half of the patients reported trouble falling asleep at night (63.3%) and maintaining sleep through the night (62.1%). Despite the frequent complaint of sleep disturbance, a very low percentage of POTS patient actually report seeking treatment. ConclusionIn this study, we explored the prevalence of sleep disturbance in patients with POTS. Almost all POTS patients reported trouble with sleep and fatigue; however, there is major discrepancy between the high percentage of symptoms and small percentage of patients seeking medical assistance for better sleep quality.

Postural Tachycardia Syndrome: Beyond Orthostatic Intolerance.

Postural tachycardia syndrome (POTS) is a form of chronic orthostatic intolerance for which the hallmark physiological trait is an excessive increase in heart rate with assumption of upright posture. The orthostatic tachycardia occurs in the absence of orthostatic hypotension and is associated with a >6-month history of symptoms that are relieved by recumbence. The heart rate abnormality and orthostatic symptoms should not be caused by medications that impair autonomic regulation or by debilitating disorders that can cause tachycardia. POTS is a "final common pathway" for a number of overlapping pathophysiologies, including an autonomic neuropathy in the lower body, hypovolemia, elevated sympathetic tone, mast cell activation, deconditioning, and autoantibodies. Not only may patients be affected by more than one of these pathophysiologies but also the phenotype of POTS has similarities to a number of other disorders, e.g., chronic fatigue syndrome, Ehlers-Danlos syndrome, vasovagal syncope, and inappropriate sinus tachycardia. POTS can be treated with a combination of non-pharmacological approaches, a structured exercise training program, and often some pharmacological support.

Hemodynamic changes of unexplained syncope patients in head-up tilt test

The purpose of this study was to observe the hemodynamic changes of unexplained syncope patients in the head-up tilt test and their correlations with age and gender. Eighty-six patients with unexplained syncope were administered the basic head-up test and nitroglycerin provocation test with continuous monitoring and recording of electrocardiogram and blood pressure changes. Basic characteristics of the patients and their hemodynamic responses throughout the tests were analyzed. All 86 patients tolerated and completed the head-up test. Forty-nine (56.98%) of the patients displayed a positive reaction, 37 (43.02%) patients displayed a negative reaction. Patients were divided into groups as follows: Group A, age ≤ 35 years; Group B, age 36-45 years; and Group C, age ≥ 46 years. Older patients were more prone to chronotropic incompetence, and younger patients were more prone to an excessive increase in heart rate. Older age correlated with the occurrence of autonomic nerve reaction disorder and mixed vasovagal syncope, whereas younger age was related to the occurrence of vasodepressor type vasovagal syncope (P < 0.01). Gender did not significantly correlate with negative or positive head-up test results (P = 0.184). During the head-up test, younger patients mainly manifested an excessive heart rate increase, whereas older patients did not have significant heart rate changes. Analyzing the hemodynamic changes in the head-up test and studying the relationships between age, gender, and hemodynamic responses are crucial to determine etiologies of syncope and select appropriate treatment.

Exercise in the postural orthostatic tachycardia syndrome.

Patients with the Postural Orthostatic Tachycardia Syndrome (POTS) have orthostatic intolerance, as well as exercise intolerance. Peak oxygen uptake (VO2peak) is generally lower in these patients compared with healthy sedentary individuals, suggesting a lower physical fitness level. During acute exercise, POTS patients have an excessive increase in heart rate and reduced stroke volume for each level of absolute workload; however, when expressed at relative workload (%VO2peak), there is no difference in the heart rate response between patients and healthy individuals. The relationship between cardiac output and VO2 is similar between POTS patients and healthy individuals. Short-term (i.e., 3 months) exercise training increases cardiac size and mass, blood volume, and VO2peak in POTS patients. Exercise performance is improved after training. Specifically, stroke volume is greater and heart rate is lower at any given VO2 during exercise after training versus before training. Peak heart rate is the same but peak stroke volume and cardiac output are greater after training. Heart rate recovery from peak exercise is significantly faster after training, indicating an improvement in autonomic circulatory control. These results suggest that patients with POTS have no intrinsic abnormality of heart rate regulation during exercise. The tachycardia in POTS is due to a reduced stroke volume. Cardiac remodeling and blood volume expansion associated with exercise training increase physical fitness and improve exercise performance in these patients.

Understanding the placebo effect in clinical trials for postural tachycardia syndrome

Postural tachycardia syndrome (POTS) is characterized by excessive increases in heart rate (HR) upon standing. Previous studies have shown that standing HR decreases over time in POTS patients given placebo. We hypothesized that this reduction is due to cardiovascular physiological alteration, as opposed to psychological benefit from perceived therapy. To prospectively test this hypothesis, we examined the effects of an open-label 'no treatment' intervention (NoRx) compared with a patient-blinded placebo on standing HR in POTS patients. Twenty-one POTS patients participated in a randomized cross-over trial with oral placebo versus NoRx administered at 0900 h. Seated blood pressure (BP) and HR were measured at baseline and every hour for 4 h. Similarly, BP and HR were measured while patients stood for 10 min at these time points. Standing HR decreased significantly over time with both NoRx (112±13 and 103±16 b.p.m. at baseline and 4 h, respectively) and placebo (112±14 and 102±16 b.p.m. at baseline and 4 h, respectively; Ptime<0.001), but this effect was not different between interventions (Pdrug=0.771). Postural tachycardia syndrome patients have exaggerated orthostatic tachycardia in the morning that decreases over time with either placebo or NoRx interventions, suggesting this phenomenon is due to cardiovascular physiological variation. These data highlight the need for a placebo arm in haemodynamic clinical trials in POTS and may have important implications for the diagnosis of these patients.

Melatonin Reduces Tachycardia in Postural Tachycardia Syndrome: A Randomized, Crossover Trial

Postural tachycardia syndrome (POTS) induces disabling chronic orthostatic intolerance with an excessive increase in heart rate (HR) upon standing, and many POTS patients have a hyperadrenergic state. Medications that restrain HR are a promising approach to this problem. We tested the hypothesis that melatonin will attenuate the tachycardia and improve symptom burden in patients with POTS. Patients with POTS (n = 78) underwent acute drug trials with melatonin 3 mg orally and placebo, on separate mornings, in a randomized crossover design. Blood pressure, HR, and symptoms were assessed while seated and after standing for up to 10 min prior to, and hourly for 4 h following study drug administration. The reduction in standing HR was significantly greater 2 h after melatonin compared with placebo (P = 0.017). There was no significant difference in the reduction of systolic blood pressure between melatonin and placebo, either with standing or while seated. The symptom burden was not improved with melatonin compared with placebo. Oral melatonin produced a modest decrease in standing tachycardia in POTS. Further research is needed to determine the effects of regular night-time use of this medication in POTS.

Flow-Mediated Vasodilation as a Predictor of Therapeutic Response to Midodrine Hydrochloride in Children With Postural Orthostatic Tachycardia Syndrome

This study was designed to explore the value of flow-mediated vasodilation (FMD) as a predictor of therapeutic response to midodrine hydrochloride (MD) in children with postural orthostatic tachycardia syndrome (POTS). One hundred and eight children diagnosed with POTS and 20 healthy control children were enrolled. All children with POTS received MD and were followed up for 3 months. FMD of brachial artery for each participant was measured by vascular ultrasound. Symptom scores, FMD values, and head-up test (HUT)/head-up tilt test (HUTT) outcomes were investigated before and after treatment. A receiver operating characteristic curve was used to explore the value of FMD as a predictor. Baseline FMD (%) and increased heart rate (beats per minute) during HUT/HUTT were significantly greater in children with POTS compared with control children (FMD: 11 ± 3% vs 6 ± 2%, p <0.001; increased heart rate: 38 ± 9 vs 7 ± 7 beats/min, p <0.001, respectively). Before treatment, MD responders had greater FMD values than MD nonresponders (p <0.05). Symptom scores, excessive increases in heart rate during HUT, and increased FMD values were all reduced significantly after treatment (all p <0.05). The receiver operating characteristic curve for the predictive value of FMD showed the area under the curve to be 0.790 (95% confidence interval: 0.679 to 0.902; p <0.001) at 1-month and 0.803 (95% confidence interval: 0.669 to 0.936; p <0.01) at 3-month therapy. FMD of 9.85% had a high sensitivity (1-month therapy: 71.6%; 3-month therapy: 74.4%) and specificity (1-month therapy 77.8%; 3-month therapy: 80%). In conclusion, FMD is a predictor of the efficacy of MD for treating children with POTS.

Desmopressin acutely decreases tachycardia and improves symptoms in the postural tachycardia syndrome

Postural tachycardia syndrome (POTS) induces disabling chronic orthostatic intolerance with an excessive increase in heart rate on standing, and many patients with POTS have low blood volume. Increasing blood volume is a promising approach to this problem. To test the hypothesis that desmopressin (DDAVP) will attenuate the tachycardia and improve symptom burden in patients with POTS. In this protocol, patients with POTS (n = 30) underwent acute drug trials with DDAVP 0.2 mg orally and placebo, on separate mornings, in a randomized crossover design. Blood pressure, heart rate, and symptoms were assessed while seated and after standing for up to 10 minutes prior to and hourly for 4 hours following study drug. The standing heart rate was significantly lower following DDAVP than placebo (101.9 ± 14.5 beats/min vs 109.2 ± 17.4 beats/min; P <.001). Standing blood pressure was not affected (P = .28). The symptom burden improved with DDAVP (from a score of 18 ± 18 arbitrary units [AU] to 13 ± 15 AU at 2 hours) compared with placebo (from 18 ± 17 AU to 19 ± 16 AU; P = .010). Oral DDAVP significantly attenuated tachycardia and improved symptoms in POTS. The safety profile of this approach would need to be examined before it can be recommended for routine treatment of these patients.

Effect of fludrocortisone acetate on nausea and autonomic function during tilt in children with postural orthostatic tachycardia syndrome

Background: Postural orthostatic tachycardia syndrome (POTS) is an autonomic disorder characterized by excessive increase in heart rate (HR) upon upright posture. It may present with palpitations, shortness of breath, nausea, lightheadedness, and syncope. Fludrocortisone acetate (FA) is a standard treatment for the orthostatic symptoms associated with POTS. We hypothesized that in patients with POTS diagnosed by tilt table, FA improves the response of the autonomic nervous system and decreases the rate of nausea during upright tilt.

Resting heart rate and excessive heart rate increase during pre-exercise mental stress: which one predicts mortality?

In the study of Juven et al. 1 the excessive heart rate (HR) increase during the preparation of an exercise test was indicated as a novel predictor of sudden cardiac death. The authors attributed this increase of HR to the mild mental stress caused during the pre-exercise preparation phase and …

Resting heart rate and excessive heart rate increase during pre-exercise mental stress: which one predicts mortality? Reply

We thank Dr Fourlas for his interest on our article. The main result is that the heart rate increase during a mild mental stress in preparation for exercise is a strong predictor of sudden death. Specifically, individuals with the largest heart rate increase during mild mental stress and the smallest increase in heart rate during an exercise test are at higher risk. Dr Fourlas expressed concerns …

Clinical Summaries

Clinical Summaries

Propranolol Decreases Tachycardia and Improves Symptoms in the Postural Tachycardia Syndrome

Postural tachycardia syndrome (POTS) induces disabling chronic orthostatic intolerance with an excessive increase in heart rate on standing. beta-Blockade is an appealing treatment approach, but conflicting preliminary reports are conflicting. We tested the hypothesis that propranolol will attenuate the tachycardia and improve symptom burden in patients with POTS. In protocol 1, a low dose (20 mg) was compared with placebo, and the dose response was assessed in protocol 2. In protocol 1, patients with POTS (n=54) underwent acute drug trials of propranolol 20 mg orally and placebo, on separate mornings, in a randomized crossover design. Blood pressure, heart rate, and symptoms were assessed while the patients were seated and after standing for up to 10 minutes before and hourly after the study drug. Supine (P<0.001) and standing (P<0.001) heart rates were significantly lower after propranolol compared with placebo. The symptom burden improvement from baseline to 2 hours was greater with propranolol than placebo (median, -4.5 versus 0 arbitrary units; P=0.044). In protocol 2, 18 patients with POTS underwent similar trials of high-dose (80 mg) versus low-dose (20 mg) propranolol. Although the high dose elicited a greater decrease than the low dose in standing heart rate (P<0.001) and orthostatic tachycardia (P<0.001), the improvement in symptoms at 2 hours was greater with low-dose propranolol (-6 versus -2 arbitrary units; P=0.041). Low-dose oral propranolol significantly attenuated tachycardia and improved symptoms in POTS. Higher-dose propranolol did not further improve, and may worsen, symptoms.

Excessive heart rate increase during mild mental stress in preparation for exercise predicts sudden death in the general population

The aim of this study involves the early identification, among apparently healthy individuals, of those at high risk for sudden cardiac death. We tested the hypothesis that individuals who respond to mild mental stress in preparation for exercise test with the largest heart rate increases might be at highest risk. Data from 7746 civil servants participating in the Paris Prospective Study I, followed-up for 23 years, allowed to compare heart rate changes between rest and mild mental stress (preparation prior to an exercise test) between subjects who suffered sudden cardiac death (n = 81), non-sudden (n = 129) coronary death, or death from any cause (n = 1306). The mean heart rate increase during mild mental stress was 8.9 +/- 10.8 b.p.m. Risk of sudden cardiac death increased progressively with heart rate increase during mental stress and the relative risk of the third vs. the first tertile was 2.09 (95% confidence interval, 1.13-3.86) after adjustment for confounders. This relationship was not observed for non-sudden coronary death. An important heart rate increase produced by a mild mental stress predicts long-term risk for sudden cardiac death. Heart rate changes before an exercise test may provide a simple tool for risk stratification.

Postural Tachycardia Syndrome and Reflex Syncope: Similarities and Differences

As awareness of postural tachycardia syndrome (POTS) has increased in recent years,1-3 our laboratory has received numerous patient referrals for “POTS going to faint.” These comprise patients who, during tilt table testing, have development of excessive tachycardia, sometimes gradually decreasing blood pressure and symptoms of orthostatic intolerance, followed by a simple postural faint (current designation “reflex neurocardiogenic syncope”4). Consider 2 representative teenage patients placed on a tilt table for a 20- to 30-minute supine equilibration period and then tilted upright to 70 degrees. Both have development of excessive increases in heart rate within 5 minutes of the onset of upright tilt (Figure 1). Both become lightheaded and nauseated and have development of progressive neurocognitive impairment. Respirations deepen, and end tidal carbon dioxide is significantly decreased. They are both pale and somewhat diaphoretic. Blood pressure may slowly decrease. Just before pronouncing the diagnosis of POTS, 1 patient abruptly loses consciousness in association with a rapid decrease in blood pressure and heart rate characteristic of the “vasovagal faint” variant of reflex syncope because of the decrease in blood pressure (the vaso or vascular part) followed immediately by a sudden drop in heart rate (the vagal part).5 This causes an equally abrupt change in the diagnosis from POTS to simple faint. The other patient continues to have an excessively increased heart rate and symptoms of orthostatic intolerance but has no decrease in blood pressure or heart rate, or loss of consciousness. Blood pressure and heart rate data for the representative tilt subjects are shown in Figure 1. These scenarios have fostered concerns about the clinical and physiological similarities and differences between simple faint and POTS. The answer appears to be a qualified no to clinical similarity and a qualified yes to physiological similarity. One could easily reverse this question and ask whether there are clinical and physiological differences between simple faint and POTS. The answer appears to be a qualified yes to clinical difference and a qualified no to physiological difference. The most notable differences between POTS and simple fainting are found in their clinical presentations, and therefore history taking is paramount in diagnoses. POTS is a chronic day-to-day form of orthostatic intolerance, and simple faint is most often episodic and associated with long periods of “wellness.” Figure 1 The figure shows heart rate in the top panel and mean arterial pressure in the bottom panel during upright tilt to 70 degrees. A representative patient with POTS is shown in red and a representative patient with syncope is shown in green. Excessive tachycardia ...

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

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.

Neurocardiogenic Syncope and Related Disorders of Orthostatic Intolerance

Received September 14, 2004; revision received January 31, 2005; accepted March 9, 2005. “We shall not cease from exploration and the end of all our exploring will be to arrive where we started and know the place for the first time” — —T.S. Eliot, Four Quartets Syncope, defined as transient loss of consciousness and postural tone with spontaneous recovery, has both challenged and perplexed physicians since the dawn of recorded time. The earliest written accounts come from Hippocrates, and the word syncope itself is derived from an old Greek term meaning “to cut short” or “interrupt.” Recurrent episodes of syncope may result from a large number of different disorders, all of which cause a transitory reduction in cerebral blood flow sufficient to disturb the normal functions of the brain. Over the last 2 decades, considerable attention has been given to types of syncope that occur due to a centrally mediated (or “reflex”) fall in systemic blood pressure, a condition that has been referred to as vasovagal (and later neurocardiogenic) syncope. However, research into the nature of this disorder revealed that it is but one aspect of a broad and varied group of disturbances in the normal functioning of the autonomic nervous system (ANS), each of which may result in orthostatic intolerance, hypotension, and ultimately syncope. Continued investigations into the nature of these similar yet different disorders has led to the development of a system of classification that attempts to more accurately reflect our understanding of these conditions and their interrelationships.1 The present system of classification has proven both functional and clinically relevant and includes a group of disorders that most investigators have thought to be principally autonomic in nature. Because both the cardiologist and the cardiac electrophysiologist frequently are expected to both diagnose and treat these conditions, the following …

Acetylcholinesterase Inhibition Improves Tachycardia in Postural Tachycardia Syndrome

Postural tachycardia syndrome (POTS) induces disabling chronic orthostatic intolerance notable for an excessive increase in heart rate that occurs on standing. Many current therapeutic strategies focus on sympatholysis, but the alternative strategy of enhancing cardiovagal tone has not been studied. The objective of this study was to test the hypothesis that acetylcholinesterase inhibitors will attenuate the tachycardia and improve symptom burden in patients with POTS. Seventeen patients with POTS underwent acute drug trials of pyridostigmine 30 mg orally and placebo, on separate mornings, in a randomized crossover design. Blood pressures, heart rate, and symptoms were assessed while patients were seated and after they had been standing for up to 10 minutes both before the study drug was given and at 2 and 4 hours after study drug. The heart rate was significantly lower at 2 hours after pyridostigmine than after placebo (100+/-16 versus 111+/-14 bpm, P=0.001). Pyridostigmine significantly decreased the standing heart rate from baseline (119+/-16 bpm) at 2 hours (104+/-16 bpm, P<0.001) and 4 hours (100+/-16 bpm, P<0.001) after administration. There was no significant change in blood pressure. The decrease in symptom burden within 4 hours after study drug was significantly greater with pyridostigmine than placebo (-10.4+/-14.0 AU versus 0.6+/-7.5 AU, P<0.025). Acute acetylcholinesterase inhibition significantly attenuated tachycardia in POTS. There was also an improvement in symptom burden with this promising therapy.