Phenylephrine alters phase synchronization between cerebral blood velocity and blood pressure in ME/CFS with orthostatic intolerance.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) with orthostatic intolerance (OI) is characterized by neurocognitive deficits perhaps related to upright hypocapnia and loss of cerebral autoregulation (CA). We performed N-back neurocognition testing and calculated the phase synchronization index (PhSI) between arterial pressure (AP) and cerebral blood velocity (CBV) as a time-dependent measurement of cerebral autoregulation in 11 control (mean age = 24.1 yr) and 15 patients with ME/CFS (mean age = 21.8 yr). All patients with ME/CFS had postural tachycardia syndrome (POTS). A 10-min 60° head-up tilt (HUT) significantly increased 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 decreased end-tidal CO2 (ETCO2; 33.9 ± 1.1 vs. 42.8 ± 1.2 Torr, P < 0.05) in ME/CFS versus control. In ME/CFS, HUT significantly decreased CBV compared with control (-22.5% vs. -8.7%, P < 0.005). To mitigate the orthostatic CBV reduction, we administered supplemental CO2, phenylephrine, and acetazolamide and performed N-back testing supine and during HUT. Only phenylephrine corrected the orthostatic decrease in neurocognition by reverting % correct n = 4 N-back during HUT in ME/CFS similar to control (ME/CFS = 38.5 ± 5.5 vs. ME/CFS + PE= 65.6 ± 5.7 vs. Control 56.9 ± 7.5). HUT in ME/CFS resulted in increased PhSI values indicating decreased CA. Although CO2 and acetazolamide had no effect on PhSI in ME/CFS, phenylephrine caused a significant reduction in PhSI (ME/CFS = 0.80 ± 0.03 vs. ME/CFS + PE= 0.69 ± 0.04, P < 0.05) and improved cerebral autoregulation. Thus, PE improved neurocognitive function in patients with ME/CFS, perhaps related to improved neurovascular coupling, cerebral autoregulation, and maintenance of CBV.NEW & NOTEWORTHY We evaluated cognitive function before and after CO2, acetazolamide, and phenylephrine, which mitigate orthostatic reductions in cerebral blood velocity. Neither CO2 nor acetazolamide affected N-back testing (% correct answers) during an orthostatic challenge. Only phenylephrine improved upright N-back performance in ME/CFS, as it both blocked hyperventilation and increased CO2 significantly compared with those untreated. And only phenylephrine resulted in improved PSI values in both ME/CFS and control while upright, suggesting improved cerebral autoregulation.

A framework to simplify paediatric syncope diagnosis.

This paper aims to improve the diagnosis of syncope and transient loss of consciousness (TLOC) in children. Diagnostic problems stem, first, from some causes spanning various disciplines, e.g. cardiology, neurology and psychiatry, while the most common cause, vasovagal syncope, is not embraced by any specialty. Second, clinical variability is huge with overlapping signs and symptoms. Third, the approach to TLOC/syncope of the European Society of Cardiology (ESC) is underused in childcare. We explain the ESC guidelines using an additional paediatric literature review. Classification of TLOC and syncope is hierarchic and based on history taking. Loss of consciousness (LOC) is defined using three features: abnormal motor control including falling, reduced responsiveness and amnesia. Adding a < 5 min duration and spontaneous recovery defines TLOC. TLOC simplifies diagnosis by excluding long LOC (e.g. some trauma, intoxications and hypoglycaemia) and focussing on syncope, tonic-clonic seizures and functional TLOC. Syncope, i.e. TLOC due to cerebral hypoperfusion, is divided into reflex syncope (mostly vasovagal), orthostatic hypotension (mostly initial orthostatic hypotension in adolescents) and cardiac syncope (arrhythmias and structural cardiac disorders). The initial investigation comprises history taking, physical examination and ECG; the value of orthostatic blood pressure measurement is unproven in children but probably low. When this fails to yield a diagnosis, cardiac risk factors are assessed; important clues are supine syncope, syncope during exercise, early death in relatives and ECG abnormalities.  Conclusions: In adults, the application of the ESC guidelines reduced the number of absent diagnoses and costs; we hope this also holds for children. What is Known: • Syncope and its mimics are very common in childhood, as they are at other ages. • Syncope and its mimics provide considerable diagnostic challenges. What is New: • Application of the hierarchic framework of transient loss of consciousness (TLOC) simplifies diagnosis. • The framework stresses history-taking to diagnose common conditions while keeping an eye on cardiac danger signs.

Anticipatory central command on standing decreases cerebral blood velocity causing hypocapnia in hyperpneic postural tachycardia syndrome.

Fifty percent of patients with postural tachycardia syndrome (POTS) are hypocapnic during orthostasis related to initial orthostatic hypotension (iOH). We determined whether iOH drives hypocapnia in POTS by low BP or decreased cerebral blood velocity (CBv). We studied three groups; healthy volunteers (n = 32, 18 ± 3 yr) were compared with POTS, grouped by presence [POTS-low end-tidal CO2 (↓ETCO2), n = 26, 19 ± 2 yr] or absence [POTS-normal upright end-tidal carbon dioxide (nlCO2), n = 28, 19 ± 3 yr] of standing hypocapnia defined by end-tidal CO2 (ETCO2) ≤ 30 mmHg at steady-state, measuring middle cerebral artery CBv, heart rate (HR), and beat-to-beat blood pressure (BP). After 30 min supine, subjects stood for 5 min. Quantities were measured prestanding, at minimum CBv, minimum BP, peak HR, CBv recovery, BP recovery, minimum HR, steady-state, and 5 min. Baroreflex gain was estimated by α index. iOH occurred with similar frequency and minimum BP in POTS-↓ETCO2 and POTS-nlCO2. Minimum CBv was reduced significantly (P < 0.05) in POTS-↓ETCO2 (48 ± 3 cm/s) preceding hypocapnia compared with POTS-nlCO2 (61 ± 3 cm/s) or Control (60 ± 2 cm/s). The anticipatory increased BP was significantly larger (P < 0.05) in POTS (8 ± 1 mmHg vs. 2 ± 1) and began ∼8 s prestanding. HR increased in all subjects, CBv increased significantly (P < 0.05) in both POTS-nlCO2 (76 ± 2 to 85 ± 2 cm/s) and Control (75 ± 2 to 80 ± 2 cm/s) consistent with central command. CBv decreased in POTS-↓ETCO2 (76 ± 3 to 64 ± 3 cm/s) correlating with decreased baroreflex gain. Cerebral conductance [meanCBv/mean arterial blood pressure (MAP)] was reduced in POTS-↓ETCO2 throughout. Data support the hypothesis that excessively reduced CBv during iOH may intermittently reduce carotid body blood flow, sensitizing that organ and producing postural hyperventilation in POTS-↓ETCO2. Excessive fall in CBv occurs in part during prestanding central command and is a facet of defective parasympathetic regulation in POTS.NEW & NOTEWORTHY Dyspnea is frequent in postural tachycardia syndrome (POTS) and is associated with upright hyperpnea and hypocapnia that drives sinus tachycardia. It is initiated by an exaggerated reduction in cerebral conductance and decreased cerebral blood flow (CBF) that precedes the act of standing. This is a form of autonomically mediated "central command." Cerebral blood flow is further reduced by initial orthostatic hypotension common in POTS. Hypocapnia is maintained during the standing response and might account for persistent postural tachycardia.

Creating a data dictionary for pediatric autonomic disorders.

PURPOSE: Whether evaluating patients clinically, documenting care in the electronic health record, performing research, or communicating with administrative agencies, the use of a common set of terms and definitions is vital to ensure appropriate use of language. At a 2017 meeting of the Pediatric Section of the American Autonomic Society, it was determined that an autonomic data dictionary comprising aspects of evaluation and management of pediatric patients with autonomic disorders would be an important resource for multiple stakeholders. METHODS: Our group created the list of terms for the dictionary. Definitions were prioritized to be obtained from established sources with which to harmonize. Some definitions needed mild modification from original sources. The next tier of sources included published consensus statements, followed by Internet sources. In the absence of appropriate sources, we created a definition. RESULTS: A total of 589 terms were listed and defined in the dictionary. Terms were organized by Signs/Symptoms, Triggers, Co-morbid Disorders, Family History, Medications, Medical Devices, Physical Examination Findings, Testing, and Diagnoses. CONCLUSION: Creation of this data dictionary becomes the foundation of future clinical care and investigative research in pediatric autonomic disorders, and can be used as a building block for a subsequent adult autonomic data dictionary.

Postural orthostatic tachycardia syndrome: A respiratory disorder?

Postural orthostatic tachycardia syndrome (POTS) is a disorder epitomized by the story of the blind men and the elephant. Patients may see primary care internists or pediatricians due to fatigue, be referred to neurologists for "spells", to cardiologists for evaluation of pre-syncope or chest pain, to gastroenterologists for nausea or dyspepsia, and even pulmonologists for dyspnea. Adoption of a more systematic approach to their evaluation and better characterization of patients has led to greater understanding of comorbidities, hypotheses prompting mechanistic investigations, and pharmacologic trials. Recent work has implicated disordered sympathetic nervous system activation in response to central (thoracic) hypovolemia. It is this pathway that leads one zero in on a putative focal point from which many of the clinical manifestations can be explained - specifically the carotid body. Despite heterogeneity in etiopathogenesis of a POTS phenotype, we propose that aberrant activation and response of the carotid body represents one potential common pathway in evolution. To understand this postulate, one must jettison isolationist or reductionist ideas of chemoreceptor and baroreceptor functions of the carotid body or sinus, respectively, and consider their interaction and interdependence both locally and centrally where some of its efferents merge. Doing so enables one to connect the dots and appreciate origins of diverse manifestations of POTS, including dyspnea for which the concept of neuro-mechanical uncoupling is wanting, thereby expanding our construct of this symptom. This perspective expounds our premise that POTS has a prominent respiratory component.

Postural orthostatic tachycardia syndrome (POTS): Priorities for POTS care and research from a 2019 National Institutes of Health Expert Consensus Meeting - Part 2.

The National Institutes of Health hosted a workshop in 2019 to build consensus around the current state of understanding of the pathophysiology of postural orthostatic tachycardia syndrome (POTS) and to identify knowledge gaps that must be addressed to enhance clinical care of POTS patients through research. This second (of two) articles summarizes current knowledge gaps, and outlines the clinical and research priorities for POTS. POTS is a complex, multi-system, chronic disorder of the autonomic nervous system characterized by orthostatic intolerance and orthostatic tachycardia without hypotension. Patients often experience a host of other related disabling symptoms. The functional and economic impacts of this disorder are significant. The pathophysiology remains incompletely understood. Beyond the significant gaps in understanding the disorder itself, there is a paucity of evidence to guide treatment which can contribute to suboptimal care for this patient population. The vast majority of physicians have minimal to no familiarity or training in the assessment and management of POTS. Funding for POTS research remains very low relative to the size of the patient population and impact of the syndrome. In addition to efforts to improve awareness and physician education, an investment in research infrastructure including the development of standardized disease-specific evaluation tools and outcome measures is needed to facilitate effective collaborative research. A national POTS research consortium could facilitate well-controlled multidisciplinary clinical research studies and therapeutic trials. These priorities will require a substantial increase in the number of research investigators and the amount of research funding in this area.

Postural orthostatic tachycardia syndrome (POTS): State of the science and clinical care from a 2019 National Institutes of Health Expert Consensus Meeting - Part 1.

Postural orthostatic tachycardia syndrome (POTS) is a chronic and often disabling disorder characterized by orthostatic intolerance with excessive heart rate increase without hypotension during upright posture. Patients often experience a constellation of other typical symptoms including fatigue, exercise intolerance and gastrointestinal distress. A typical patient with POTS is a female of child-bearing age, who often first displays symptoms in adolescence. The onset of POTS may be precipitated by immunological stressors such as a viral infection. A variety of pathophysiologies are involved in the abnormal postural tachycardia response; however, the pathophysiology of the syndrome is incompletely understood and undoubtedly multifaceted. Clinicians and researchers focused on POTS convened at the National Institutes of Health in July 2019 to discuss the current state of understanding of the pathophysiology of POTS and to identify priorities for POTS research. This article, the first of two articles summarizing the information discussed at this meeting, summarizes the current understanding of this disorder and best practices for clinical care. The evaluation of a patient with suspected POTS should seek to establish the diagnosis, identify co-morbid conditions, and exclude conditions that could cause or mimic the syndrome. Once diagnosed, management typically begins with patient education and non-pharmacologic treatment options. Various medications are often used to address specific symptoms, but there are currently no FDA-approved medications for the treatment of POTS, and evidence for many of the medications used to treat POTS is not robust.

Tilt testing remains a valuable asset.

Head-up tilt test (TT) has been used for >50 years to study heart rate/blood pressure adaptation to positional changes, to model responses to haemorrhage, to assess orthostatic hypotension, and to evaluate haemodynamic and neuroendocrine responses in congestive heart failure, autonomic dysfunction, and hypertension. During these studies, some subjects experienced syncope due to vasovagal reflex. As a result, tilt testing was incorporated into clinical assessment of syncope when the origin was unknown. Subsequently, clinical experience supports the diagnostic value of TT. This is highlighted in evidence-based professional practice guidelines, which provide advice for TT methodology and interpretation, while concurrently identifying its limitations. Thus, TT remains a valuable clinical asset, one that has added importantly to the appreciation of pathophysiology of syncope/collapse and, thereby, has improved care of syncopal patients.

Supine Parasympathetic Withdrawal and Upright Sympathetic Activation Underly Abnormalities of the Baroreflex in Postural Tachycardia Syndrome: Effects of Pyridostigmine and Digoxin.

[Figure: see text].

The preponderance of initial orthostatic hypotension in postural tachycardia syndrome.

Reduced systolic/diastolic blood pressure (BP) by >40/20 mmHg defines initial orthostatic hypotension (IOH). Rapid resolution of hypotension and lightheadedness follows, but tachycardia may be prolonged. We aimed to examine IOH in controls and patients with postural tachycardia syndrome (POTS) using indices of spontaneous fluctuations of heart rate (HR) and systolic BP as measures of cardiac baroreflex differences. We recruited otherwise healthy IOH patients without POTS (n = 20, 16 ± 3 yr), healthy volunteers (n = 32, 17 ± 3 yr), and POTS patients (n = 39, 17 ± 4 yr). Subjects were instrumented for electrocardiography and beat-to-beat BP. After 10 min supine, subjects stood for 5 min. Following supine recovery, subjects underwent 70° head-up tilt for 10 min to test for POTS. BP, HR, and time, referenced to standing, were measured at events during standing: minimum BP, BP recovery, peak HR, HR minimum, and steady state. Baseline HR and BP were higher in POTS compared with healthy groups. IOH occurred in 13% of controls and 51% of POTS patients. The BP minimum was lower in POTS. Parasympathetic modulation of cardiac baroreflex was decreased in all POTS and control-IOH subjects. Sympathetic indices were increased. Events following BP minimum occurred progressively later in all POTS and control-IOH subjects compared with non-IOH controls. IOH is more frequent in POTS than in controls with a lower minimum BP. POTS has markedly reduced heart rate variability and baroreflex, indicating reduced HR buffering of BP. POTS-IOH and control-IOH subjects had similar peak HR despite decreased minimum BP in POTS. IOH data indicate modest parasympathetic and cardiovagal baroreflex deficits in control-IOH subjects. Parasympathetic deficits are more severe in all POTS patients.NEW & NOTEWORTHY Significant initial orthostatic hypotension (IOH) occurs in ~50% of postural tachycardia syndrome (POTS) patients and 13% of controls. Heart rate and blood pressure recovery are prolonged in IOH sustaining lightheadedness; IOH is more prevalent and severe in POTS. Altered cerebral blood flow and cardiorespiratory regulation are more prevalent in POTS. Altered heart rate variability and baroreflex gain may cause nearly instantaneous lightheadedness in POTS. IOH alone fails to confer a strong probability of POTS.

Pacing in vasovagal syncope: Physiology, pacemaker sensors, and recent clinical trials-Precise patient selection and measurable benefit.

The role of pacing in vasovagal syncope (VVS) is considered from a physiological basis. Most VVS patients lose consciousness due to hypotension before severe bradycardia/asystole occurs. Patients who benefit from dual-chamber pacing typically are older with highly symptomatic, late-onset, frequent and severe syncope with short/no prodrome and documented severe cardioinhibition. Tilt testing is of value in patients with recurrent unexplained syncope to identify important hypotensive susceptibility stemming from reduced venous return and stroke volume (SV). A negative tilt test in vasovagal patients with spontaneous asystole documented by an implantable/insertable loop recorder is associated with lower syncope recurrence rates after pacemaker implantation. Pacing may be more effective if triggered by sensor detection of a parameter changing earlier in the reflex than bradycardia when SV may still be relatively preserved. In this regard, detection of right ventricular impedance offers promise. Conservatism is recommended, limiting pacing in VVS to a small subset of symptomatic older patients with clearly documented cardioinhibition and paying particular attention to the timing of loss of consciousness in relation to asystole/bradycardia. Understanding VVS physiology permits application of well-timed, appropriate pacing that yields benefit for highly symptomatic patients.

When Sinus Tachycardia Becomes Too Much: Negative Effects of Excessive Upright Tachycardia on Cardiac Output in Vasovagal Syncope, Postural Tachycardia Syndrome, and Inappropriate Sinus Tachycardia.

BACKGROUND: Upright posture reduces venous return, stroke volume, and cardiac output (CO) while causing reflex sinus rate (heart rate [HR]) increase. Yet, in inappropriate sinus tachycardia (IST), postural tachycardia syndrome (POTS), and vasovagal syncope (VVS), symptomatic excessive HR occurs. We hypothesized that CO reaches maximum as function of HR in all. METHODS: We recruited 12 healthy controls, 9 IST, 30 VVS, and 30 POTS patients (13-23years) selected randomly by disorder not by HR, each fulfilled appropriate diagnostic criteria. Subjects were instrumented for electrocardiography, beat-to-beat blood pressure, respiratory rate, CO-Modelflow algorithm, and central blood volume from impedance cardiography; 10-minute data were collected supine; subjects were tilted head-up for ≤10 minutes. We computed phase differences, ΔΦ, between fluctuations of HR (ΔHR) and CO (ΔCO) tabulating data when phases were synchronized, determined by a squared nonlinear phase synchronization index >0.5, describing extent/validity of CO/HR coupling. We graphed results supine, 1-minute post-tilt-up, mid-tilt, and pre-tilt-down using polar coordinates (HR-radius, ΔΦ-angle) plotting cos(ΔΦ) versus HR to determine if transition HR exists at which in-phase shifts to antiphase above which CO decreases when HR further increases. RESULTS: At baseline HR, diastolic and mean arterial pressures in IST and POTS were higher versus controls. Upright HR increased most in POTS then IST and VVS, with diverse changes in CO, SVR, and central blood volume. Each patient grouping was separately and collectively analyzed for HR change showing transition from in-phase to anti-phase (ΔΦ) as HR increased: HRtransition=115±6 (IST), 123±8 (POTS), 124±7 (VVS), P=ns. Controls never reached transitional HR. CONCLUSIONS: Excessive HR independently and equivalently reduces upright CO, in IST, POTS, and VVS.

The Benefits of Oral Rehydration on Orthostatic Intolerance in Children with Postural Tachycardia Syndrome.

OBJECTIVE: To evaluate whether equal volumes of oral rehydration solution (ORS) or intravenous (IV) saline provide similar improvements in cardiovascular status during controlled orthostatic challenge when administered to subjects with postural tachycardia syndrome (POTS) with orthostatic intolerance. STUDY DESIGN: We studied the neurovascular response to fluid loading during orthostatic stress using lower body negative pressure (LBNP) in 10 subjects with POTS with orthostatic intolerance and 15 controls, and on subsequent days before and 1 hour after IV saline infusion or ingestion of ORS. RESULTS: Subjects with POTS exhibited reduced tolerance to LBNP (P < .0001) compared with controls (Orthostatic Index of 35 715 ± 3469 vs 93 980 ± 7977, respectively). In POTS, following ORS but not saline infusion, cerebral blood flow velocity (CBFv) was significantly higher than that with no treatment, at -45 mm Hg (P < .0005). Although fluid loading did not confer any advantage in controls, subjects with POTS experienced a significant improvement in orthostatic tolerance following both saline infusion (100 ± 9.7 vs 134.5 ± 17.4; P < .05) and ORS (100 ± 9.7 vs 155.6 ± 15.7; P < .001) when evaluated by normalized orthostatic index (P < .001, compared with untreated baseline). CONCLUSIONS: Maintenance of CBFv may have resulted in the improved short-term orthostatic tolerance exhibited by the subjects with POTS following ORS administration. ORS is a convenient, safe, and effective therapy for short-term relief of orthostatic intolerance.

Mechanisms of tilt-induced vasovagal syncope in healthy volunteers and postural tachycardia syndrome patients without past history of syncope.

Upright tilt table testing has been used to test for vasovagal syncope (VVS) but can result in "false positives" in which tilt-induced fainting (tilt+) occurs in the absence of real-world fainting. Tilt+ occurs in healthy volunteers and in patients with postural tachycardia syndrome (POTS) and show enhanced susceptibility to orthostatic hypotension. We hypothesized that the mechanisms for hypotensive susceptibility differs between tilt+ healthy volunteers (Control-Faint (N = 12)), tilt+ POTS patients (POTS-Faint (N = 12)) and a non-fainter control group of (Control-noFaint) (N = 10). Subjects were studied supine and during 70° upright tilt while blood pressure (BP), cardiac output (CO), and systemic vascular resistance (SVR), were measured continuously. Impedance plethysmography estimated regional blood volumes, flows, and vascular resistance. Heart rate was increased while central blood volume was decreased in both Faint groups. CO increased in Control-Faint because of reduced splanchnic vascular resistance; splanchnic pooling was similar to Control-noFaint. Splanchnic blood flow in POTS-Faint decreased and resistance increased similar to Control-noFaint but splanchnic blood volume was markedly increased. Decreased SVR and splanchnic arterial vasoconstriction is the mechanism for faint in Control-Faint. Decreased CO caused by enhanced splanchnic pooling is the mechanism for faint in POTS-Faint. We propose that intrahepatic resistance is increased in POTS-Faint resulting in pooling and that both intrahepatic resistance and splanchnic arterial vasoconstriction are reduced in Control-Faint resulting in increased splanchnic blood flow and reduced splanchnic resistance.

Segmental Intracellular, Interstitial, and Intravascular Volume Changes during Simulated Hemorrhage and Resuscitation: A Case Study.

This paper describes a new combined impedance plethysmographic (IPG) and electrical bioimpedance spectroscopic (BIS) instrument and software that will allow noninvasive real-time measurement of segmental blood flow, intracellular, interstitial, and intravascular volume changes during various fluid management procedures. The impedance device can be operated either as a fixed frequency IPG for the quantification of segmental blood flow and hemodynamics or as a multi-frequency BIS for the recording of intracellular and extracellular resistances at 40 discrete input frequencies. The extracellular volume is then deconvoluted to obtain its intravascular and interstitial component volumes as functions of elapsed time. The purpose of this paper is to describe this instrumentation and to demonstrate the information that can be obtained by using it to monitor segmental compartment volume responses of a pig model during simulated hemorrhage and resuscitation. Such information may prove valuable in the diagnosis and management of rapid changes in the body fluid balance and various clinical treatments.

Hemodynamic characteristics of postural hyperventilation: POTS with hyperventilation versus panic versus voluntary hyperventilation.

Upright hyperventilation occurs in ~25% of our patients with postural tachycardia syndrome (POTS). Poikilocapnic hyperventilation alone causes tachycardia. Here, we examined changes in respiration and hemodynamics comprising cardiac output (CO), systemic vascular resistance (SVR), and blood pressure (BP) measured during head-up tilt (HUT) in three groups: patients with POTS and hyperventilation (POTS-HV), patients with panic disorder who hyperventilate (Panic), and healthy controls performing voluntary upright hyperpnea (Voluntary-HV). Though all were comparably tachycardic during hyperventilation, POTS-HV manifested hyperpnea, decreased CO, increased SVR, and increased BP during HUT; Panic patients showed both hyperpnea and tachypnea, increased CO, and increased SVR as BP increased during HUT; and Voluntary-HV were hyperpneic by design and had increased CO, decreased SVR, and decreased BP during upright hyperventilation. Mechanisms of hyperventilation and hemodynamic changes differed among POTS-HV, Panic, and Voluntary-HV subjects. We hypothesize that the hyperventilation in POTS is caused by a mechanism involving peripheral chemoreflex sensitization by intermittent ischemic hypoxia. NEW & NOTEWORTHY Hyperventilation is common in postural tachycardia syndrome (POTS) and has distinctive cardiovascular characteristics when compared with hyperventilation in panic disorder or with voluntary hyperventilation. Hyperventilation in POTS is hyperpnea only, distinct from panic in which tachypnea also occurs. Cardiac output is decreased in POTS, whereas peripheral resistance and blood pressure (BP) are increased. This is distinct from voluntary hyperventilation where cardiac output is increased and resistance and BP are decreased and from panic where they are all increased.

Postural Hyperventilation as a Cause of Postural Tachycardia Syndrome: Increased Systemic Vascular Resistance and Decreased Cardiac Output When Upright in All Postural Tachycardia Syndrome Variants.

BACKGROUND: Postural tachycardia syndrome (POTS) is a heterogeneous condition. We stratified patients previously evaluated for POTS on the basis of supine resting cardiac output (CO) or with the complaint of platypnea or "shortness of breath" during orthostasis. We hypothesize that postural hyperventilation is one cause of POTS and that hyperventilation-associated POTS occurs when initial reduction in CO is sufficiently large. We also propose that circulatory abnormalities normalize with restoration of CO2. METHODS AND RESULTS: Fifty-eight enrollees with POTS were compared with 16 healthy volunteer controls. Low CO in POTS was defined by a resting supine CO <4 L/min. Patients with shortness of breath had hyperventilation with end tidal CO2 <30 Torr during head-up tilt table testing. There were no differences in height or weight between control patients and patients with POTS or differences between the POTS groups. Beat-to-beat blood pressure was measured by photoplethysmography, and CO was measured by ModelFlow. Systemic vascular resistance was defined as mean arterial blood pressure/CO. End tidal CO2 and cerebral blood flow velocity of the middle cerebral artery were only reduced during head-up tilt in the hyperventilation group, whereas blood pressure was increased compared with control. We corrected the reduced end tidal CO2 in hyperventilation by addition of exogenous CO2 into a rebreathing apparatus. With added CO2, heart rate, blood pressure, CO, and systemic vascular resistance in hyperventilation became similar to control. CONCLUSIONS: We conclude that all POTS is related to decreased CO, decreased central blood volume, and increased systemic vascular resistance and that a variant of POTS is consequent to postural hyperventilation.