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1.
Europace ; 26(2)2024 Feb 01.
Article in English | MEDLINE | ID: mdl-38262617

ABSTRACT

AIMS: Systolic blood pressure (SBP) drops recorded by 24-h ambulatory blood pressure (BP) monitoring (ABPM) identify patients with susceptibility to reflex syncope and orthostatic intolerance. We tested the hypothesis that treatments aimed to increase BP (reassurance, education, and lifestyle measures plus pharmacological strategies) can reduce SBP drops. METHODS AND RESULTS: This was a multicentre, observational proof-of-concept study performed in patients with reflex syncope and/or orthostatic intolerance and with SBP drops on a screening ABPM. Among 144 eligible patients, 111 underwent a second ABPM on average 2.5 months after start of treatment. Overall, mean 24-h SBP increased from 114.1 ± 12.1 to 121.4 ± 14.5 mmHg (P < 0.0001). The number of SBP drops <90 and <100 mmHg decreased by 61%, 46% during daytime, and by 48% and 37% during 24-h period, respectively (P < 0.0001 for all). The dose-response relationship between difference in 24-h average SBP increase and reduction in number of SBP drops reached a plateau around ∼15 mmHg increase of 24-h SBP. The reduction in SBP drop rate was consistent and significant in patients who underwent deprescription of hypotensive medications (n = 44) and in patients who received BP-rising drugs (n = 67). CONCLUSION: In patients with reflex syncope and/or orthostatic intolerance, an increase in average 24-h SBP, regardless of the implemented strategy, significantly reduced the number of SBP drops and symptom burden. A 13 mmHg increase in 24-h SBP appears to represent the optimal goal for aborting the maximal number of SBP drops, representing a possible target for future interventions. ClincalTrials.gov identifier: NCT05729724.


Subject(s)
Hypertension , Hypotension , Orthostatic Intolerance , Syncope, Vasovagal , Humans , Antihypertensive Agents/therapeutic use , Blood Pressure , Blood Pressure Monitoring, Ambulatory , Hypertension/drug therapy , Orthostatic Intolerance/diagnosis , Orthostatic Intolerance/drug therapy , Reflex , Syncope, Vasovagal/diagnosis , Syncope, Vasovagal/prevention & control , Proof of Concept Study
3.
Auton Neurosci ; 237: 102906, 2022 01.
Article in English | MEDLINE | ID: mdl-34823150

ABSTRACT

Salt supplementation is a common non-pharmacological approach to the management of recurrent orthostatic syncope or presyncope, particularly for patients with vasovagal syncope (VVS) or postural orthostatic tachycardia syndrome (POTS), although there is limited consensus on the optimal dosage, formulation and duration of treatment. Accordingly, we reviewed the evidence for the use of salt supplementation to reduce susceptibility to syncope or presyncope in patients with VVS and POTS. We found that short-term (~3 months) salt supplementation improves susceptibility to VVS and associated symptoms, with little effect on supine blood pressure. In patients with VVS, salt supplementation is associated with increases in plasma volume, and an increase in the time taken to provoke a syncopal event during orthostatic tolerance testing, with smaller orthostatic heart rate increases, enhanced peripheral vascular responses to orthostatic stress, and improved cerebral autoregulation. Responses were most pronounced in those with a baseline sodium excretion <170 mmol/day. Salt supplementation also improved symptoms, plasma volume, and orthostatic responses in patients with POTS. Salt supplementation should be considered for individuals with recurrent and troublesome episodes of VVS or POTS without cardiovascular comorbidities, particularly if their typical urinary sodium excretion is low, and their supine blood pressure is not elevated. The efficacy of the response, in terms of the improvement in subjective and objective markers of orthostatic intolerance, and any potential deleterious effect on supine blood pressure, should be routinely monitored in individuals on high salt regimes.


Subject(s)
Orthostatic Intolerance , Postural Orthostatic Tachycardia Syndrome , Syncope, Vasovagal , Blood Pressure , Dietary Supplements , Heart Rate , Humans , Orthostatic Intolerance/drug therapy , Postural Orthostatic Tachycardia Syndrome/drug therapy , Syncope, Vasovagal/drug therapy , Tilt-Table Test
4.
J Investig Med ; 68(6): 1156-1158, 2020 08.
Article in English | MEDLINE | ID: mdl-32606041

ABSTRACT

Postural orthostatic tachycardia syndrome (POTS) is estimated to impact millions of people each year. However, there is no established gold standard for its treatment. Bupropion is a norepinephrine and a dopamine reuptake inhibitor and has been implicated as a potential treatment for POTS. We performed a non-randomized retrospective chart review on 47 patients with POTS with statistical analysis evaluating for significant findings including reduced orthostasis and improvement of symptoms with the use of bupropion. Bupropion was not associated with a statistically significant improvement in orthostatic vitals but there was an overall reduction in reported syncope. While the use of bupropion does not show a statistically significant impact on orthostatic vitals in patients with POTS, it did show a degree of improvement in syncope and as such might be useful in patients with syncope-predominant POTS.


Subject(s)
Bupropion/therapeutic use , Postural Orthostatic Tachycardia Syndrome/drug therapy , Adult , Female , Humans , Male , Orthostatic Intolerance/drug therapy , Retrospective Studies , Symptom Assessment , Syncope/drug therapy , Treatment Outcome
5.
Brain Inj ; 32(2): 252-256, 2018.
Article in English | MEDLINE | ID: mdl-29190150

ABSTRACT

PRIMARY OBJECTIVE: This study aimed to investigate the effect of intravenous saline administration on orthostatic hypotension (OH) during head up tilt (HUT) and the change in the renin-angiotensin-aldosterone system before and after HUT in patients with severe acquired brain injury (ABI). RESEARCH DESIGN: The study is designed as an observational study. METHODS AND PROCEDURES: Fourteen patients with ABI, low level of consciousness and OH were monitored before, during and after HUT with non-invasive beat-to-beat blood pressure measurement, and transcranial Doppler determination of middle cerebral artery blood flow velocity. Blood samples were collected before and after two HUT sessions separated by 1 hour and saline was administered in between. MAIN OUTCOMES AND RESULTS: Patients' ability to stand upright did not change after saline administration due to OH. The patients showed signs of reduced cerebral autoregulation at both HUT sessions. The patients had a significant lower level of renin and angiotensin II but not aldosterone. CONCLUSIONS: Patients with severe ABI and OH demonstrate no improvement in standing time with reduced plasma renin and angiotensin II after two HUT sessions and 1 hour fluid administration. Research focusing on the ability to retain fluid after bed rest is warranted.


Subject(s)
Cerebrovascular Circulation/physiology , Orthostatic Intolerance/blood , Orthostatic Intolerance/drug therapy , Saline Solution/administration & dosage , Adult , Angiotensin II/blood , Blood Pressure , Brain Injuries/complications , Cohort Studies , Female , Heart Rate/physiology , Humans , Male , Middle Aged , Middle Cerebral Artery/physiopathology , Orthostatic Intolerance/complications , Renin/blood , Statistics, Nonparametric , Tilt-Table Test , Ultrasonography, Doppler, Transcranial
6.
J Appl Physiol (1985) ; 123(2): 375-386, 2017 Aug 01.
Article in English | MEDLINE | ID: mdl-28522756

ABSTRACT

Women experience orthostatic intolerance more than men, and they experience faintness more in the early follicular [i.e., low-hormone (LH)] than luteal [i.e., high-hormone (HH)] phase of the menstrual cycle. Men (n = 13, 25.8 ± 1.8 yr old) and women in the LH (days 2-5; placebo) and HH (days 18-24; high dose) phases of the menstrual cycle with (OC; n = 14, 22.0 ± 0.8 yr old) or without (NOC; n = 12, 21.8 ± 0.5 yr old) oral contraceptive (OC) use underwent the Valsalva maneuver and a supine-sit-stand protocol. Blood pressure, normalized stroke volume [stroke volume index (SVi)], cardiac output index, heart rate, end-tidal CO2, and middle cerebral artery (MCA) blood flow velocity were measured. When subjected to the Valsalva maneuver, all women had a greater increase in diastolic and mean MCA blood flow velocity than men (P ≤ 0.065), with no significant effect of menstrual cycle phase or OC use. When subjected to the supine-sit-stand protocol, men had lower MCA blood flow velocity (P < 0.038) than all women, and SVi was higher in men than in the NOC group in all postures (P < 0.011) and in the OC group in the LH phase of the menstrual cycle during standing (P = 0.010). Only men experienced higher resistance index (P < 0.001) and pulsatility index (P < 0.001) with standing. The OC group had lower end-tidal CO2 (P = 0.002) than the NOC group (P = 0.030) and men (P ≤ 0.067). SVi (P = 0.004) and cardiac output index (P = 0.008) were higher in the OC than NOC group. A tendency toward a lower mean MCA blood flow velocity (P = 0.058) and higher SVi (P = 0.059) and pulsatility index (P = 0.058) was noted in the HH than LH phase. Mean arterial pressure was higher in the OC than NOC group in the LH phase (P = 0.049) and lower in the HH than LH phase (P = 0.014). Our results indicate that cycling estrogens/progestins can influence ventilatory, cardiovascular, and/or cerebrovascular physiology.NEW & NOTEWORTHY We have found sex differences in the cerebrovascular response to the Valsalva maneuver and standing. Men have greater cerebral vasoconstriction (or women have greater cerebral vasodilation) during late phase II of the Valsalva maneuver, and the cerebrovascular resistance index increases in men, but not in women, during standing. Furthermore, our findings indicate that both the menstrual cycle phase and oral contraceptive use can influence cardiovascular function both at rest and during active standing.


Subject(s)
Cerebrovascular Circulation/physiology , Contraceptives, Oral/therapeutic use , Menstrual Cycle/physiology , Middle Cerebral Artery/physiology , Posture/physiology , Valsalva Maneuver/drug effects , Valsalva Maneuver/physiology , Adult , Blood Flow Velocity/drug effects , Blood Flow Velocity/physiology , Blood Pressure/drug effects , Blood Pressure/physiology , Cerebrovascular Circulation/drug effects , Female , Heart Rate/drug effects , Heart Rate/physiology , Humans , Hypotension/physiopathology , Male , Middle Cerebral Artery/drug effects , Orthostatic Intolerance/drug therapy , Orthostatic Intolerance/physiopathology , Stroke Volume/drug effects , Stroke Volume/physiology , Vasoconstriction/drug effects , Vasoconstriction/physiology , Vasodilation/drug effects , Vasodilation/physiology , Young Adult
7.
BMC Pediatr ; 15: 117, 2015 Sep 10.
Article in English | MEDLINE | ID: mdl-26357864

ABSTRACT

BACKGROUND: Chronic Fatigue Syndrome (CFS) is a common and disabling condition in adolescence with few treatment options. A central feature of CFS is orthostatic intolerance and abnormal autonomic cardiovascular control characterized by sympathetic predominance. We hypothesized that symptoms as well as the underlying pathophysiology might improve by treatment with the alpha2A-adrenoceptor agonist clonidine. METHODS: A total of 176 adolescent CFS patients (12-18 years) were assessed for eligibility at a single referral center recruiting nation-wide. Patients were randomized 1:1 by a computer system and started treatment with clonidine capsules (25 µg or 50 µg twice daily, respectively, for body weight below/above 35 kg) or placebo capsules for 9 weeks. Double-blinding was provided. Data were collected from March 2010 until October 2012 as part of The Norwegian Study of Chronic Fatigue Syndrome in Adolescents: Pathophysiology and Intervention Trial (NorCAPITAL). Effect of clonidine intervention was assessed by general linear models in intention-to-treat analyses, including baseline values as covariates in the model. RESULTS: A total of 120 patients (clonidine group n = 60, placebo group n = 60) were enrolled and started treatment. There were 14 drop-outs (5 in the clonidine group, 9 in the placebo group) during the intervention period. At 8 weeks, the clonidine group had lower plasma norepinephrine (difference = 205 pmol/L, p = 0.05) and urine norepinephrine/creatinine ratio (difference = 3.9 nmol/mmol, p = 0.002). During supine rest, the clonidine group had higher heart rate variability in the low-frequency range (LF-HRV, absolute units) (ratio = 1.4, p = 0.007) as well as higher standard deviation of all RR-intervals (SDNN) (difference = 12.0 ms, p = 0.05); during 20° head-up tilt there were no statistical differences in any cardiovascular variable. Symptoms of orthostatic intolerance did not change during the intervention period. CONCLUSIONS: Low-dose clonidine reduces catecholamine levels in adolescent CFS, but the effects on autonomic cardiovascular control are sparse. Clonidine does not improve symptoms of orthostatic intolerance. TRIAL REGISTRATION: Clinical Trials ID: NCT01040429, date of registration 12/28/2009.


Subject(s)
Adrenergic alpha-2 Receptor Agonists/administration & dosage , Clonidine/administration & dosage , Fatigue Syndrome, Chronic/drug therapy , Fatigue Syndrome, Chronic/physiopathology , Adolescent , Adrenergic alpha-2 Receptor Agonists/blood , Clonidine/blood , Creatinine/urine , Double-Blind Method , Epinephrine/blood , Epinephrine/urine , Heart Rate/drug effects , Humans , Norepinephrine/blood , Norepinephrine/urine , Orthostatic Intolerance/drug therapy , Orthostatic Intolerance/physiopathology , Tilt-Table Test
8.
Clin Auton Res ; 25(3): 179-87, 2015 Jun.
Article in English | MEDLINE | ID: mdl-25916633

ABSTRACT

INTRODUCTION: Acetylcholine (Ach) is the pre-synaptic neurotransmitter of the sympathetic nervous system. Increased pre-synaptic Ach may augment post-synaptic release of norepinephrine, thereby increasing systemic blood pressure (BP). OBJECTIVES: The primary objective of this investigation was to determine the hemodynamic effect of pyridostigmine bromide (PYRIDO: 60 mg), an Ach inhibitor (AchI), compared to no-drug (NO-D) during head-up tilt (HUT) in individuals with spinal cord injury (SCI). Secondarily, we aimed to determine the effects of PYRIDO compared to NO-D on symptoms of orthostatic intolerance (OI) and adverse event reporting (AE). METHODS: Ten individuals with SCI (C4-C7) were studied on two occasions: visit (1) NO-D and visit (2) PYRIDO. On each visit subjects underwent a progressive HUT maneuver to 15°, 25°, 35° for 5 min at each angle and 45 min at 45°. Supine and orthostatic heart rate (HR), systolic and diastolic BP (SBP and DBP), as well as monitored and symptoms of OI and AE were monitored and recorded. RESULTS: Supine hemodynamics did not differ between the trials. The significant fall in SBP during the NO-D trial was diminished with PYRIDO, and five subjects had an increased DBP during HUT with PYRIDO compared to the NO-D trial. Individuals that responded to PYRIDO with an increase in orthostatic BP had significantly lower resting HR than non-responders (p < 0.01), which suggests increased levels of pre-synaptic Ach. Subjective symptoms of OI and AE reporting did not differ between the two trials. CONCLUSIONS: These preliminary data suggest that PYRIDO is safe and may be effective at ameliorating the orthostatic fall in BP in select individuals with SCI.


Subject(s)
Cholinesterase Inhibitors/therapeutic use , Pyridostigmine Bromide/therapeutic use , Spinal Cord Injuries/physiopathology , Adult , Blood Pressure/drug effects , Cholinesterase Inhibitors/adverse effects , Female , Heart Rate/drug effects , Hemodynamics/drug effects , Humans , Male , Middle Aged , Orthostatic Intolerance/drug therapy , Orthostatic Intolerance/etiology , Pyridostigmine Bromide/adverse effects , Quadriplegia/physiopathology , Supine Position , Tilt-Table Test , Young Adult
9.
Chin Med J (Engl) ; 127(21): 3690-4, 2014.
Article in English | MEDLINE | ID: mdl-25382320

ABSTRACT

BACKGROUND: Orthostatic intolerance (OI) is a common disease at pediatric period which has a serious impact on physical and mental health of children. The purpose of this study was to investigate the effect of related factors on the prognosis of children with OI. METHODS: The subjects were 170 children with OI, including 71 males (41.8%) and 99 females (58.2%) with age from 6 to 17 (12.0±2.6) years. The effect of related factors on the prognosis of children was studied by using univariate analysis. Then, the impact of children's age, symptom score, duration, disease subtype, and treatment on patient's prognosis was studied via analysis of COX proportional conversion model. RESULTS: Among 170 cases, 48 were diagnosed with vasovagal syncope, including 28 cases of vasoinhibitory type, 16 cases of mixed type, and 4 cases of cardioinhibitory type; 115 cases were diagnosed with postural tachycardia syndrome and 7 cases with orthostatic hypotension. By using univariate analysis of Cox regression, the results showed that symptom score had a marked impact on the time of symptoms improvement of children after taking medication (P < 0.05), while other univariates had no impact (P > 0.05). Multivariate analysis using Cox proportional hazards regression model showed that the symptom score at diagnosis had a significant effect on holding time of symptoms improvement of children after taking medication (P < 0.05). Kaplan-Meier curve showed that symptom-free survival was higher in children with symptom score equal to 1 than children with symptom score equal to or greater than 2 during follow-up (P < 0.05). CONCLUSION: Symptom score is an important factor affecting the time of symptom improvement after treatment for children with OI.


Subject(s)
Orthostatic Intolerance/diagnosis , Adolescent , Child , Female , Humans , Male , Metoprolol/therapeutic use , Midodrine/therapeutic use , Orthostatic Intolerance/drug therapy , Orthostatic Intolerance/mortality , Orthostatic Intolerance/pathology , Prognosis , Proportional Hazards Models , Retrospective Studies , Saline Waters/therapeutic use , Syncope, Vasovagal/diagnosis , Syncope, Vasovagal/drug therapy , Syncope, Vasovagal/mortality , Syncope, Vasovagal/pathology
10.
J Appl Physiol (1985) ; 117(10): 1157-64, 2014 Nov 15.
Article in English | MEDLINE | ID: mdl-25277740

ABSTRACT

Chronic fatigue syndrome (CFS) with orthostatic intolerance is characterized by neurocognitive deficits and impaired working memory, concentration, and information processing. In CFS, upright tilting [head-up tilt (HUT)] caused decreased cerebral blood flow velocity (CBFv) related to hyperventilation/hypocapnia and impaired cerebral autoregulation; increasing orthostatic stress resulted in decreased neurocognition. We loaded the baroreflex with phenylephrine to prevent hyperventilation and performed n-back neurocognition testing in 11 control subjects and 15 CFS patients. HUT caused a significant increase in heart rate (109.4 ± 3.9 vs. 77.2 ± 1.6 beats/min, P < 0.05) and respiratory rate (20.9 ± 1.7 vs. 14.2 ± 1.2 breaths/min, P < 0.05) and decrease in end-tidal CO2 (ETCO2; 42.8 ± 1.2 vs. 33.9 ± 1.1 Torr, P < 0.05) in CFS vs. control. HUT caused CBFv to decrease 8.7% in control subjects but fell 22.5% in CFS. In CFS, phenylephrine prevented the HUT-induced hyperventilation/hypocapnia and the significant drop in CBFv with HUT (-8.1% vs. -22.5% untreated). There was no difference in control subject n-back normalized response time (nRT) comparing supine to HUT (106.1 ± 6.9 vs. 97.6 ± 7.1 ms at n = 4), and no difference comparing control to CFS while supine (97.1 ± 7.1 vs 96.5 ± 3.9 ms at n = 4). However, HUT of CFS subjects caused a significant increase in nRT (148.0 ± 9.3 vs. 96.4 ± 6.0 ms at n = 4) compared with supine. Phenylephrine significantly reduced the HUT-induced increase in nRT in CFS to levels similar to supine (114.6 ± 7.1 vs. 114.6 ± 9.3 ms at n = 4). Compared with control subjects, CFS subjects are more sensitive both to orthostatic challenge and to baroreflex/chemoreflex-mediated interventions. Increasing blood pressure with phenylephrine can alter CBFv. In CFS subjects, mitigation of the HUT-induced CBFv decrease with phenylephrine has a beneficial effect on n-back outcome.


Subject(s)
Cerebrovascular Circulation/drug effects , Cognition Disorders/drug therapy , Cognition/drug effects , Fatigue Syndrome, Chronic/drug therapy , Neuropsychological Tests , Orthostatic Intolerance/drug therapy , Phenylephrine/administration & dosage , Vasoconstrictor Agents/administration & dosage , Adolescent , Adult , Attention/drug effects , Baroreflex/drug effects , Blood Flow Velocity , Blood Pressure/drug effects , Cognition Disorders/diagnosis , Cognition Disorders/physiopathology , Cognition Disorders/psychology , Fatigue Syndrome, Chronic/diagnosis , Fatigue Syndrome, Chronic/physiopathology , Fatigue Syndrome, Chronic/psychology , Female , Heart Rate/drug effects , Humans , Male , Memory/drug effects , Orthostatic Intolerance/diagnosis , Orthostatic Intolerance/physiopathology , Orthostatic Intolerance/psychology , Patient Positioning , Posture , Respiratory Rate/drug effects , Tilt-Table Test , Treatment Outcome , Young Adult
11.
Rev Med Chir Soc Med Nat Iasi ; 118(1): 75-80, 2014.
Article in English | MEDLINE | ID: mdl-24741779

ABSTRACT

UNLABELLED: Orthostatic intolerance syndrome is an important issue, having multiple etiologies and being the result of an inadequate response to changing in body position, namely the transition from supine to standing, a process that causes a series of responses regulated by the autonomic nervous system. AIM: The aim of this study was to create a profile of patients with Parkinson's disease and orthostatic hypotension, a form of orthostatic intolerance, identifying the risk factors for this condition. MATERIAL AND METHODS: We conducted a study on 41 patients with Parkinson's disease selected from 200 consecutive patients with orthostatic hypotension, hospitalized in Cardiology Clinic of Colentina Clinic Hospital which met the diagnosis criteria for orthostatic hypotension. In order to meet the inclusion criteria, all patients were evaluated according to a preset protocol: medical history, clinical and paraclinical examination, including neuro-psychiatric assessment and the orthostatic tolerance test. RESULTS AND DISCUSSION: The decline in standing blood pressure was related to the presence of hypotensive neurological drugs, especially Levodopa, in chronic treatment, but it was not influenced by age or cardiovascular co morbidities. There is an improvement in blood pressure both in supine and upright position at discharge when compared to admission values. CONCLUSION: The degree of decrease in the standing blood pressure values was correlated with the presence of potentially hypotensive neurological drugs, particularly Levodopa treatment, with a favorable effect of administration of non-pharmacological treatment and changes made in chronic neurological treatment.


Subject(s)
Autonomic Nervous System/physiopathology , Orthostatic Intolerance/physiopathology , Parkinson Disease/physiopathology , Aged , Aged, 80 and over , Female , Humans , Hypotension, Orthostatic/physiopathology , Inpatients , Male , Middle Aged , Midodrine/therapeutic use , Orthostatic Intolerance/diagnosis , Orthostatic Intolerance/drug therapy , Orthostatic Intolerance/etiology , Parkinson Disease/complications , Parkinson Disease/diagnosis , Parkinson Disease/drug therapy , Prevalence , Quality of Life , Risk Factors , Severity of Illness Index , Treatment Outcome , Vasoconstrictor Agents/therapeutic use
12.
Hypertension ; 61(3): 701-6, 2013 Mar.
Article in English | MEDLINE | ID: mdl-23266540

ABSTRACT

At least half of primary autonomic failure patients exhibit supine hypertension, despite profound impairments in sympathetic activity. Although the mechanisms underlying this hypertension are unknown, plasma renin activity is often undetectable, suggesting renin-angiotensin (Ang) pathways are not involved. However, because aldosterone levels are preserved, we tested the hypothesis that Ang II is intact and contributes to the hypertension of autonomic failure. Indeed, circulating Ang II was paradoxically increased in hypertensive autonomic failure patients (52±5 pg/mL, n=11) compared with matched healthy controls (27±4 pg/mL, n=10; P=0.002), despite similarly low renin activity (0.19±0.06 versus 0.34±0.13 ng/mL per hour, respectively; P=0.449). To determine the contribution of Ang II to supine hypertension in these patients, we administered the AT(1) receptor blocker losartan (50 mg) at bedtime in a randomized, double-blind, placebo-controlled study (n=11). Losartan maximally reduced systolic blood pressure by 32±11 mm Hg at 6 hours after administration (P<0.05), decreased nocturnal urinary sodium excretion (P=0.0461), and did not worsen morning orthostatic tolerance. In contrast, there was no effect of captopril on supine blood pressure in a subset of these patients. These findings suggest that Ang II formation in autonomic failure is independent of plasma renin activity, and perhaps Ang-converting enzyme. Furthermore, these studies suggest that elevations in Ang II contribute to the hypertension of autonomic failure, and provide rationale for the use of AT(1) receptor blockers for treatment of these patients.


Subject(s)
Angiotensin II/blood , Hypertension/blood , Pure Autonomic Failure/blood , Renin/blood , Aged , Aldosterone/blood , Angiotensin II Type 1 Receptor Blockers/therapeutic use , Antihypertensive Agents/therapeutic use , Captopril/therapeutic use , Double-Blind Method , Female , Humans , Hypertension/drug therapy , Losartan/therapeutic use , Male , Middle Aged , Orthostatic Intolerance/blood , Orthostatic Intolerance/drug therapy , Pure Autonomic Failure/drug therapy , Sodium/metabolism
13.
Am J Ther ; 19(1): 7-10, 2012 Jan.
Article in English | MEDLINE | ID: mdl-20535001

ABSTRACT

There have been reports on the use of octreotide in patients with orthostatic hypotension, postural tachycardia syndrome, and orthostatic syncope. However, there are little if any data on the use of octreotide in patients who have failed multiple other medications. This study was a retrospective chart analysis and was approved by our Institutional Review Board. A total of 12 patients were identified for inclusion in this study. The diagnosis of orthostatic intolerance was based on patient history, physical examination, and response to Head Up Tilt Table testing. These patients had failed multiple medications and were ultimately treated with octreotide. In a retrospective chart review, we collected data, including demographic information, presenting symptoms, laboratory data, tilt-table response, standing heart rate, standing blood pressure before and after treatment (wherever available), and treatment outcomes. Twelve patients aged 33 ± 18 years, eight (66.7%) females, were found to have symptoms of refractory orthostatic intolerance and failed multiple regimens of medication and were ultimately treated with octreotide administration. Five patients (41.7%) had demonstrated a postural tachycardia syndrome pattern, five (41.7%) a neurocardiogenic, and two (16.6%) a dysautonomic response on a Head Up Tilt Table. Symptoms of syncope and orthostatic palpitations improved in six (50%) of the patients. Standing heart rate was significantly reduced after octreotide administration (80 ± 8 versus 108 ± 13; P < 0.05). The standing systolic blood pressure was increased after octreotide administration (107 ± 26 versus 116 ± 22). Three patients (25%) reported complete elimination of syncope, whereas another three had reduction in the frequency of their syncope. However, symptoms of fatigue improved only in two (29%) of the seven patients. Octreotide may improve symptoms in some patients with refractory orthostatic intolerance.


Subject(s)
Blood Pressure/drug effects , Octreotide/therapeutic use , Orthostatic Intolerance/drug therapy , Postural Orthostatic Tachycardia Syndrome/drug therapy , Adolescent , Adult , Fatigue/drug therapy , Fatigue/etiology , Female , Heart Rate/drug effects , Humans , Male , Middle Aged , Orthostatic Intolerance/physiopathology , Postural Orthostatic Tachycardia Syndrome/physiopathology , Retrospective Studies , Syncope/drug therapy , Syncope/etiology , Syncope, Vasovagal/drug therapy , Syncope, Vasovagal/physiopathology , Tilt-Table Test , Treatment Outcome , Young Adult
14.
Clin Auton Res ; 22(3): 151-3, 2012 Jun.
Article in English | MEDLINE | ID: mdl-22190289

ABSTRACT

Postural tachycardia syndrome (POTS) refers to the presence of orthostatic intolerance symptoms with a heart rate increment ≥ 30 bpm, usually up to ≥ 120 bpm. Pathophysiology and POTS's clinical presentation are heterogeneous and its prognosis is uncertain. We reviewed the major clinical characteristics of POTS patients and assessed their long-term follow-up. Our series results, one with the longest follow-up, illustrate POTS as a clinical entity with variable, but usually benign outcome, in which most patients can reassume their daily activities without great limitations, after proper diagnosis and treatment are made.


Subject(s)
Autonomic Nervous System Diseases/diagnosis , Autonomic Nervous System Diseases/physiopathology , Orthostatic Intolerance/diagnosis , Orthostatic Intolerance/physiopathology , Postural Orthostatic Tachycardia Syndrome/diagnosis , Postural Orthostatic Tachycardia Syndrome/physiopathology , Adult , Autonomic Nervous System Diseases/drug therapy , Female , Follow-Up Studies , Humans , Male , Orthostatic Intolerance/drug therapy , Postural Orthostatic Tachycardia Syndrome/drug therapy , Retrospective Studies , Young Adult
15.
J Appl Physiol (1985) ; 111(1): 40-7, 2011 Jul.
Article in English | MEDLINE | ID: mdl-21512154

ABSTRACT

Octreotide is a somatostatin analog that constricts the splanchnic circulation, thereby improving orthostatic tolerance. We tested the hypotheses that octreotide improves orthostatic tolerance by 1)increasing cardiac filling (right atrial) pressure via reductions in vascular capacity; 2) by causing an upward (i.e., cranial) shift of the hydrostatic indifferent point; and 3) by increasing arterial pressure via a reduction in total vascular conductance. Studies were carried out in acepromazine-sedated, hexamethonium-treated atrioventricular-blocked conscious dogs lightly restrained in lateral recumbency. Beat-by-beat cardiac output was held constant via computer-controlled ventricular pacing at rest and during 30 s of 30° head-up tilt. Octreotide (1.5 µg/kg iv) raised right atrial pressure by 0.5 mmHg and raised mean arterial pressure by 11 mmHg by reducing total vascular conductance (all P < 0.05). Right atrial pressure fell by a similar amount in response to tilting before and after octreotide, thus there was no difference in location of the hydrostatic indifferent point. These data indicate that octreotide improves orthostatic tolerance by decreasing total vascular conductance and by increasing cardiac filling pressure via a reduction in unstressed vascular volume and not by eliciting a cranial shift of the location of the hydrostatic indifferent point.


Subject(s)
Conscious Sedation , Gravitation , Orthostatic Intolerance/physiopathology , Posture , Splanchnic Circulation , Stress, Physiological , Vasoconstriction , Animals , Atrial Function, Right , Atrioventricular Block/physiopathology , Blood Pressure , Cardiac Output , Cardiac Pacing, Artificial , Dogs , Hydrostatic Pressure , Octreotide/pharmacology , Orthostatic Intolerance/drug therapy , Orthostatic Intolerance/etiology , Splanchnic Circulation/drug effects , Tilt-Table Test , Time Factors , Vasoconstriction/drug effects , Vasoconstrictor Agents/pharmacology
17.
Am J Ther ; 18(6): 449-52, 2011 Nov.
Article in English | MEDLINE | ID: mdl-20393343

ABSTRACT

Many patients who suffer from orthostatic intolerance (OI) may also have severe fatigue and extreme exercise intolerance. In some of these patients, fatigue may be so severe that they are unable to maintain employment. In some, even the activities of the daily living may be compromised. We report on the use of modafinil in a subgroup of patients who failed therapy with commonly used medication for fatigue in patients with OI. The study was approved by the institutional review board. A retrospective nonrandomized analysis was preformed on 60 patients evaluated at our autonomic center for OI from 2003 to 2010. The diagnosis of OI was based on patient history, physical examination, and reponse to head up tilt table testing. All these patients had fatigue as their predominant symptom. Multiple trials of stimulants including methylphenidate, amphetamine, or dextroamphetamine failed to provide symptomatic relief of fatigue in these patients. Each patient received modafinil (100-200 mg daily). The mean follow-up period was 9 ± 3 months. A treatment was considered successful if it provided symptomatic relief from fatigue for the patient. Sixty patients, age 29 ± 15, 52 women were included in the analysis. Migraine (57%) and joint hypermobility syndrome (33%) were common comorbidities. Out of 60 patients, 40 patients reported initial improvement with initiation of modafinil therapy. Twenty patients reported no change in their symptoms of fatigue. Of the 40 patients who showed initial improvement in their symptoms 4 had eventual recurrence of fatigue after 3 months of modafinil therapy. Thirty-six patients continued to demonstrate symptom relief from fatigue for more than 6 months. In a selective group of patients of OI, modafinil may improve fatigue.


Subject(s)
Benzhydryl Compounds/therapeutic use , Central Nervous System Stimulants/therapeutic use , Fatigue/drug therapy , Orthostatic Intolerance/drug therapy , Activities of Daily Living , Adolescent , Adult , Fatigue/etiology , Female , Humans , Male , Middle Aged , Modafinil , Orthostatic Intolerance/complications , Retrospective Studies , Tilt-Table Test , Treatment Outcome
18.
Europace ; 13(3): 427-30, 2011 Mar.
Article in English | MEDLINE | ID: mdl-21062792

ABSTRACT

AIMS: Postural orthostatic tachycardia syndrome (POTS) is associated with tachycardia on orthostasis. Patients frequently report palpitations, presyncope, and fatigue. Conventional therapy is effective in less than 60%. Case reports suggest ivabradine (a selective sinus node blocker, with no effect on blood pressure) may alleviate POTS-related symptoms. This is a retrospective case-series. METHODS AND RESULTS: Postural orthostatic tachycardia syndrome patients prescribed ivabradine were identified from the pharmacy database. Case notes were reviewed and participants completed a symptom assessment tool. Twenty-two patients were identified. Data were available from 20. Eight patients reported reduced tachycardia and fatigue and four reported only reduced tachycardia. The most common reason for discontinuing ivabradine was lack of efficacy (n = 6). Five patients reported side-effects resulting in two discontinuing treatment. CONCLUSION: This retrospective case series indicates that 60% of patients treated with ivabradine report a symptomatic improvement. A randomized controlled trial accessing the efficacy of ivabradine in POTS is indicated, particularly in patients resistant to, or intolerant of, conventional therapy.


Subject(s)
Benzazepines/therapeutic use , Orthostatic Intolerance/drug therapy , Tachycardia/drug therapy , Adult , Benzazepines/adverse effects , Benzazepines/pharmacology , Case-Control Studies , Fatigue/epidemiology , Female , Heart Rate/drug effects , Heart Rate/physiology , Humans , Incidence , Ivabradine , Male , Middle Aged , Orthostatic Intolerance/epidemiology , Orthostatic Intolerance/physiopathology , Retrospective Studies , Sinoatrial Node/drug effects , Sinoatrial Node/physiopathology , Tachycardia/epidemiology , Tachycardia/physiopathology , Treatment Outcome
19.
Orv Hetil ; 151(46): 1904-7, 2010 Nov 14.
Article in Hungarian | MEDLINE | ID: mdl-21044941

ABSTRACT

Chronic orthostasis intolerance or postural tachycardia syndrome (POTS) is a common problem, which is related to the more severe forms of autonomic neuropathy. Upright posture regularly elicits uncomfortable symptoms in these patients, which impairs their quality of life. We present a typical case, where orthostatic hemodynamic response was significantly improved by ingestion of 500 ml tap water. This simple measure could be a potent, long-term therapeutic tool.


Subject(s)
Blood Pressure , Heart Rate , Hypotension, Orthostatic/drug therapy , Postural Orthostatic Tachycardia Syndrome/diagnosis , Postural Orthostatic Tachycardia Syndrome/drug therapy , Water/administration & dosage , Adolescent , Female , Humans , Hypotension, Orthostatic/complications , Hypotension, Orthostatic/diagnosis , Hypotension, Orthostatic/physiopathology , Orthostatic Intolerance/complications , Orthostatic Intolerance/diagnosis , Orthostatic Intolerance/drug therapy , Orthostatic Intolerance/physiopathology , Postural Orthostatic Tachycardia Syndrome/etiology , Postural Orthostatic Tachycardia Syndrome/physiopathology , Time Factors , Treatment Outcome
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