Chest pain due to coronary artery compression in an adult with CHD.

A 47-year-old with repaired ventricular septal defect and pulmonary valve stenosis as a child presents with chronic intermittent chest pain. CT evaluation for transcatheter pulmonary valve replacement revealed right coronary artery compression between a sternal wire and dilated right ventricle. Removal of the sternal wire resulted in improved symptoms.

Assessment of comorbid symptoms in pediatric autonomic dysfunction.

PURPOSE: Pediatric patients with autonomic dysfunction and orthostatic intolerance (OI) often present with co-existing symptoms and signs that might or might not directly relate to the autonomic nervous system. Our objective was to identify validated screening instruments to characterize these comorbidities and their impact on youth functioning. METHODS: The Pediatric Assembly of the American Autonomic Society reviewed the current state of practice for identifying symptom comorbidities in youth with OI. The assembly includes physicians, physician-scientists, scientists, advanced practice providers, psychologists, and a statistician with expertise in pediatric disorders of OI. A total of 26 representatives from the various specialties engaged in iterative meetings to: (1) identify and then develop consensus on the symptoms to be assessed, (2) establish committees to review the literature for screening measures by member expertise, and (3) delineate the specific criteria for systematically evaluating the measures and for making measure recommendations by symptom domains. RESULTS: We review the measures evaluated and recommend one measure per system/concern so that assessment results from unrelated clinical centers are comparable. We have created a repository to apprise investigators of validated, vetted assessment tools to enhance comparisons across cohorts of youth with autonomic dysfunction and OI. CONCLUSION: This effort can facilitate collaboration among clinical settings to advance the science and clinical treatment of these youth. This effort is essential to improving management of these vulnerable patients as well as to comparing research findings from different centers.

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.

Arterial Baroreceptor Physiology: Differences Between Normal Subjects and Pediatric Patients with Postural Tachycardia and Neurocardiogenic Syncope.

The arterial baroreceptor reflex in children and adolescents has not been well studied in the current literature with a lack of agreed upon normal values, particularly in postural orthostatic tachycardia syndrome (POTS) or neurocardiogenic syncope (NCS). We used the sequence method and head-up tilt test (HUTT) to evaluate baroreceptor function in 3 phases: baseline supine position for 10 min, head-up position at 70° for 30 min or until syncope, and post-tilt supine reposition for 10 min. We measured the number of baroreceptor events, baroreceptor effectiveness index (BEI), and the magnitude of sensitivity of the events at each phase of HUTT. We studied 198 individuals (49 normal subjects, 67 POTS, 82 NCS) with age ranges from 8 to 21 years. The data show a statistically significant decrease in slope and BEI in patients with POTS and NCS during the head-up phase, with an increase in activity in the lag 1 and 2 portions of all phases in patients with POTS. This study provides terminology to describe baroreceptor function and identifies the slope and BEI portions of the baroreceptor reflex as the most useful objective measures to differentiate pediatric patients with POTS and NCS from normal subjects.

Orthostatic Headaches Associated With Spontaneous Intracranial Hypotension and Autonomic Dysfunction-A Case Series in Young Patients.

Background: Orthostatic headaches can be noted in spontaneous intracranial hypotension and orthostatic intolerance. We present a case series of young patients diagnosed with spontaneous intracranial hypotension and were treated for the same but subsequently developed orthostatic intolerance. Methods: We retrospectively reviewed charts for seven young patients with orthostatic headaches related to spontaneous intracranial hypotension and orthostatic intolerance. Results: Patients were diagnosed with spontaneous intracranial hypotension. Diagnosis was confirmed by identifying epidural contrast leakage and three of seven patients were noted to have early renal contrast excretion on computerized tomography myelography. Patients were treated with epidural blood patches. All patients showed persistent symptoms of autonomic dysfunction after treatment of spontaneous intracranial hypotension and orthostatic intolerance was confirmed with head-up tilt table test. Conclusions: Patients with spontaneous intracranial hypotension failing to improve following epidural blood patching should be evaluated for orthostatic intolerance.

Cutaneous manifestations of orthostatic intolerance syndromes.

Dysautonomia refers to a group of autonomic nervous system disorders that affect nearly 70 million people worldwide. One subset of dysautonomia includes syndromes of orthostatic intolerance (OI), which primarily affect adolescents and women of childbearing age. Due to the variability in disease presentation, the average time from symptom onset to diagnosis of dysautonomia is 6 years. In general, there is a paucity of dermatological research articles describing patients with dysautonomia. The objective of this review is to summarize the existing literature on cutaneous manifestations in dysautonomia, with an emphasis on syndromes of OI. A PubMed database of the English-language literature (1970-2020) was searched using the terms "dysautonomia", "orthostatic intolerance", "cutaneous", "skin", "hyperhidrosis", "hypohidrosis", "sweat", and other synonyms. Results showed that cutaneous manifestations of orthostatic intolerance are common and varied, with one paper citing up to 85% of patients with OI having at least one cutaneous symptom. Recognition of dermatological complaints may lead to an earlier diagnosis of orthostatic intolerance, as well as other comorbid conditions.

Long-COVID postural tachycardia syndrome: an American Autonomic Society statement.

COVID-19 is a global pandemic that has had a devastating effect on the health and economy of much of human civilization. While the acute impacts of COVID-19 were the initial focus of concern, it is becoming clear that in the wake of COVID-19, many patients are developing chronic symptoms that have been called Long-COVID. Some of the symptoms and signs include those of postural tachycardia syndrome (POTS). Understanding and managing long-COVID POTS will require a significant infusion of health care resources and a significant additional research investment. In this document from the American Autonomic Society, we outline the scope of the problem, and the resources and research needed to properly address the impact of Long-COVID POTS.

Point-of-Care Ultrasound in Sternal Notch Confirms Depth of Endotracheal Tube in Children.

OBJECTIVES: To determine if a saline-filled cuff seen at the suprasternal notch on ultrasound corresponds to correct endotracheal tube depth on a chest radiograph (tip at/below clavicle AND ≥ 1 cm above carina). DESIGN: Prospective observational study. SETTING: Tertiary Care Pediatric hospital. PATIENTS: Patients between the ages of 0-18 years requiring nonemergent cardiac catheterizations and endotracheal intubation with a cuffed endotracheal tube were included in the study. Children with anticipated or known difficult airways were excluded. INTERVENTIONS: Ultrasound evaluation of the neck following saline inflation of the endotracheal tube cuff. MEASUREMENTS AND MAIN RESULTS: Ultrasonography of the patient's neck was performed following intubation by a pediatric anesthesiologist. A linear probe was used in transverse axis to identify the saline-filled cuff starting at the suprasternal notch and moving cephalad. A cine-fluoroscopic image, similar to a chest radiograph, was obtained to ascertain the endotracheal tube depth after the cuff was identified sonographically. Endotracheal tube cuffs seen on ultrasound at the suprasternal notch were compared with the endotracheal tube depth on the cine-fluoroscopic image. A total of 75 children were enrolled in the study. The endotracheal tube was seen sonographically at the suprasternal notch in 70 patients of which 60 had complete data (an adequate chest radiograph available for review). Patient ages ranged from 2 months to 18 years with a median age of 4 years. The median endotracheal tube tip to carina distance was 2.4 cm (interquartile range, 1.75-3.3 cm.) The endotracheal tube tip to carina distance was greater than or equal to 1 cm in 57 out of the 60 patients. Endotracheal tube cuff at the suprasternal notch on ultrasound corresponded with correct endotracheal tube depth on chest radiograph with an accuracy of 95% (CI, 86-98%). CONCLUSIONS: Visualization of the cuff at the suprasternal notch by ultrasound demonstrates potential as a means of confirming correct depth of the endotracheal tube following endotracheal intubation.

Demographic and clinical features of pediatric patients with orthostatic intolerance and an abnormal head-up tilt table test; A retrospective descriptive study.

BACKGROUND: Clinical presentation varies in children with Orthostatic Intolerance. This study aimed to evaluate the epidemiological and clinical characteristics of pediatric patients with orthostatic intolerance (OI) and positive head-up tilt test (HUTT). METHODS: This study was a retrospective review of clinical data from outpatients over 18 months period. RESULTS: We included 112 patients with abnormal HUTT results. Females were 78 (70%). Mean age of presentation was 15.6 years (sd: 3.3). Fifteen percent were overweight, and 14% were obese. A headache and syncope were the most frequent presenting symptoms (46% and 29% respectively). Review of systems identified more patients with headaches (84%), Syncope (61%), presyncope (87%) and abdominal pain (29%). Except for fatigue being more prevalent during a review of systems among patients with severe OI (69%) compared to those with moderate OI (46%, p = 0.02), there was no statistically significant difference in the clinical presentation between investigator-defined moderate and severe OI. Comorbidities identified in this cohort were Chiari malformations (9%), idiopathic intracranial hypertension (9%), electroencephalographic abnormalities (8%) and patent foramen ovale (43%). CONCLUSIONS: Adolescents, mainly females had OI. Patients with OI and abnormal HUTT predominantly had a headache, syncope, and presyncope during the presentation. Eliciting review of systems and using tools such as clinical questionnaire identifies significant clinical presenting features and comorbidities.

Baroreceptor activity and sensitivity: normal values in children and young adults using the head up tilt test.

BACKGROUND: Baroreceptor function in children and adolescents has not been well studied in the current literature, with a lack of agreed upon normal values. The authors hypothesize that there is a significant increase in the baroreceptor activity with a decrease in the sensitivity during the upright phase in comparison to the supine phases of the head upright tilt test (HUTT) protocol. METHODS: Baroreceptor evaluation was performed using the sequence method in 49 subjects ages 8-21 years, during the 3 phases of HUTT: supine, head up, and post-tilt supine positions. Baroreceptor Effectiveness Index (BEI) and the number and slope of baroreceptor events were recorded. RESULTS: On study of the events and slope values, there was a significant difference between the three phases of the HUTT with regard to the baroreceptor activity and sensitivity. No significant difference was found in BEI. CONCLUSIONS: Our study presents normal values of baroreceptor activity, sensitivity, and BEI in pediatric patients under controlled supine and head up position. We also present new data regarding delayed heart rate responses to pressure changes in the Lag 1 and Lag 2 parameters, which may be beneficial in diagnosis and management of pediatric patients with orthostatic intolerance.

Comparison of skin dose measurement using nanoDot® dosimeter and machine readings of radiation dose during cardiac catheterization in children.

OBJECTIVES: Direct measurement of skin dose of radiation for children using optically stimulated luminescence (OSL) technology using nanoDot® (Landauer, Glenwood, IL, USA). BACKGROUND: Radiation dose is estimated as cumulative air kerma (AK) and dosearea product based on standards established for adult size patients. Body size of pediatric patients who undergo cardiac catheterization for congenital heart disease vary widely from newborn to adolescence. Direct, skindose measurement applying OSL technology may eliminate errors in the estimate. MATERIALS AND METHODS: The nanoDot® (1 cm × 1 cm × flat plastic cassette) is applied to patient's skin using adhesive tape during cardiac catheterization and radiation skin doses were read within 24 hrs. nanoDot® values were compared to the currently available cumulative AK values estimated and displayed on fluoroscopy monitor. RESULTS: A total of 12 children were studied, aged 4 months to 18 years (median 1.1 years) and weight range 5.3-86 kg (median 8.4 kg). nanoDot® readings ranged from 2.58 mGy to 424.8 mGy (median 84.1 mGy). Cumulative AK ranged from 16.2 mGy to 571.2 mGy (median 171.1 mGy). Linear correlation was noted between nanoDot® values and AK values (R2 = 0.88, R = 0.94). nanoDot® readings were approximately 65% of the estimated cumulative AK estimated using the International Electrotechnical Commission standards. CONCLUSIONS: Application of OSL technology using nanoDot® provides an alternative to directly measure fluoroscopic skin dose in children during cardiac catheterization. Our data show that the actual skin dose for children is approximately one-third lower than the AK estimated using international standards for adult size patients.

Pediatric Disorders of Orthostatic Intolerance.

Orthostatic intolerance (OI), having difficulty tolerating an upright posture because of symptoms or signs that abate when returned to supine, is common in pediatrics. For example, ∼40% of people faint during their lives, half of whom faint during adolescence, and the peak age for first faint is 15 years. Because of this, we describe the most common forms of OI in pediatrics and distinguish between chronic and acute OI. These common forms of OI include initial orthostatic hypotension (which is a frequently seen benign condition in youngsters), true orthostatic hypotension (both neurogenic and nonneurogenic), vasovagal syncope, and postural tachycardia syndrome. We also describe the influences of chronic bed rest and rapid weight loss as aggravating factors and causes of OI. Presenting signs and symptoms are discussed as well as patient evaluation and testing modalities. Putative causes of OI, such as gravitational and exercise deconditioning, immune-mediated disease, mast cell activation, and central hypovolemia, are described as well as frequent comorbidities, such as joint hypermobility, anxiety, and gastrointestinal issues. The medical management of OI is considered, which includes both nonpharmacologic and pharmacologic approaches. Finally, we discuss the prognosis and long-term implications of OI and indicate future directions for research and patient management.

Autologous Adipose Stem Cell Therapy for Autonomic Nervous System Dysfunction in Two Young Patients.

Postural orthostatic tachycardia syndrome and neurocardiogenic syncope are clinical manifestations of autonomic nervous system dysfunction (dysautonomia) that can lead to impaired daily functions. We report two young patients presenting with dysautonomia and autoimmune disease who both received autologous adipose stem cells (ASCs) infusions. This report is the first description of ASCs therapy for patients with combined dysautonomia and autoimmune disease. Case 1: A 21-year-old female presented at 12 years of age with escalating severe dysautonomia with weight loss and gastrointestinal symptoms. She had elevated autoantibodies and cytokines and received multiple immune modulation therapies. Her dysautonomia was treated by volume expanders, vasoconstrictors, and beta blockers with mild improvement. She received ASCs about 2 years before this report with dramatic improvement in her dysautonomia and autoimmune symptoms with a 10 kg weight gain. Case 2: A 7-year-old boy presented at 2 years of age with polyarthritis. At 5 years of age, he manifested orthostatic intolerance. He received immune modulatory therapies with mild improvement. He received ASCs and showed marked improvement of his dysautonomia and immune symptoms. Dysautonomia symptoms of these two patients improved significantly after modulation of autoimmune components by ASC therapy. Favorable clinical responses of these two cases warrant further case-control studies.

Dominant Transmission Observed in Adolescents and Families With Orthostatic Intolerance.

BACKGROUND: Orthostatic intolerance is typically thought to be sporadic and attributed to cerebral autonomic dysfunction. We sought to identify families with inherited autonomic dysfunction manifest as symptomatic orthostatic intolerance to characterize mode of inheritance and clinical features. METHODS: Sixteen families with two or more first- or second-degree relatives with autonomic dysfunction and orthostatic intolerance were enrolled. A clinical diagnosis of autonomic dysfunction defined by symptomatic orthostatic intolerance diagnosed by head-up tilt table testing was confirmed for each proband. Clinical features and evaluation were obtained from each proband using a standardized intake questionnaire, and family history information was obtained from probands and available relatives. RESULTS: Comprehensive pedigree analysis of 16 families (39 individuals with orthostatic intolerance and 40 individuals suspected of having orthostatic intolerance) demonstrated dominant transmission of autonomic dysfunction with incomplete penetrance. Affected individuals were predominantly female (71.8%, 28/39; F:M, 2.5:1). Male-to-male transmission, although less common, was observed and demonstrated to transmit through unaffected males with an affected parent. Similar to sporadic orthostatic intolerance, probands report a range of symptoms across multiple organ systems, with headaches and neuromuscular features being most common. CONCLUSIONS: Familial occurrence and vertical transmission of autonomic dysfunction in 16 families suggest a novel genetic syndrome with dominant transmission, incomplete penetrance, and skewing of the sex ratio. Elucidation of potential genetic contributions to orthostatic intolerance may inform therapeutic management and identification of individuals at risk. Adolescent evaluation should include identification and treatment of potential at-risk relatives.

Medium to long-term echo follow-up after ventricular septal defect device closure.

OBJECTIVE: We aimed to assess the medium to long-term results of echocardiographic follow-up of perimembranous and muscular ventricular septal defect closure with various Amplatzer devices. METHODS: We successfully closed ventricular septal defects percutaneously in 45/49 patients. There were 35 perimembranous and 10 muscular ventricular septal defects. The median age and weight was 8.50 years (range 2-36.70 years) and 24 kg (range 10-106 kg), respectively. The median size of the ventricular septal defect was 7 mm (range 3-14 mm) on transthoracic echocardiography, 6 mm (range 4-15 mm) on transesophageal echocardiography, and 6 mm (range 3-14 mm) on left ventricular angiography. The median pulmonary-to-systemic blood flow ratio was 1.40 (range 1.0-3.0). RESULTS: In the 49 attempted cases, the procedure was successful in 45, with a success rate of 91.84%. At a mean follow-up of 54.50 months, echocardiography showed complete closure in 41 (91%) patients and 4 (9%) had a tiny (1-2 mm) residual defect. New-onset aortic regurgitation was seen in 6 (13.3%) patients at 54.50 months, but it was mild in nature. Tricuspid valve regurgitation was observed in 13 (29%) patients at 54.50 follow-up, of whom 10 (22%) had mild and 3 (7%) had moderate regurgitation. CONCLUSION: Transcatheter closure of perimembranous and muscular ventricular septal defects is effective, however, these patients need to be followed up regularly to detect device-related problems, specifically, aortic and tricuspid valve regurgitation.

Cerebral blood flow during HUTT in young patients with orthostatic intolerance.

PURPOSE: To investigate patterns of change in cerebral perfusion during head-up tilt testing (HUTT) in children and young adults with autonomic dysfunction. METHODS: We utilized near-infrared spectroscopy (NIRS) to estimate bilateral cerebral perfusion patterns during HUTT in 71 adolescents and young adults with a diagnosis of autonomic dysfunction. In addition, we used transthoracic impedance to measure cardiac stroke volume and thus infer autonomic tone, heart rate, and blood pressure during the test. Cerebral blood-flow wave-patterns were then visually analyzed and associated with clinical symptoms and measures of cardiovascular and autonomic function. RESULTS: Visual analysis of contour changes in head NIRS values during phases of HUTT revealed variable patterns of cerebral blood flow, some specifically associated with severe symptomatology (i.e., syncope). We also observed an inequality in blood flow of the cerebral hemispheres in many patients. Finally, we observed changes in cardiac stroke volume during HUTT, as previously reported, that related to changes in head NIRS. CONCLUSION: These results confirm a decrease in cerebral blood flow during HUTT as assessed by head NIRS in patients with autonomic dysfunction. Specifically, we have profiled the cerebral blood flow contours throughout the phases of HUTT, which add insight into the clinical spectrum of the disorder and may correlate with clinical severity.

Cardiac asystole during head up tilt (HUTT) in children and adolescents: is this benign physiology?

Cardiac asystole during HUTT has been described by some investigators as a benign finding with no major sequelae. Our aim in this study is to correlate the severity of clinical symptoms and physiologic findings prior and during the asystole occurrence. This is a retrospective study review of 536 patients who underwent HUTT for dysautonomia symptoms for the last 3 years. HUTT in our institution consists of 10 min in supine, 30 min of head up at 70°, and recline to supine for 10 min. Physiologic parameters recorded include continuous heart rate, BP, cardiac stroke volume, brain blood flow by near-infra red spectroscopy, sympathetic and parasympathetic tones. Patients' complaints and signs during HUTT were recorded. Follow-up was conducted up to 34 months. Cardiac asystole was defined as the absence of ventricular activity for ≥3 s with cessation of BP signal for the same period on the monitor. Of the 536 patients studied, 25 patients developed cardiac asystole (4.7%). The asystolic group age was 15.1 + 3.8 years and weighed 56.7 + 21 kg. All the patients fainted and were not able to complete the test with average head up time of 13.8 + 7.1 min. The cardiac asystole duration was 9.2 + 5.8 s. Sixteen patients developed convulsions during the asystole. There was sudden intense vagal tone prior to and during the asystole. Brain perfusion was significantly decreased in all the patients after head up and sharply dropped by 20-35% in patients who developed convulsions. All patients completely recovered their consciousness after reposition to supine. During recovery, there was overshoot of the brain perfusion above the baseline for several minutes and the HR returned to baseline. Follow-up of these patients: only one patient had a single lead pacemaker, otherwise the 24 patients had no cardiac pacing and were treated by medical therapy. During mean follow-up of 19 + 10 months, five patients developed syncope which resolved after optimizing medical therapy. Cardiac asystole due to neurocardiogenic syncope and dysautonomia has high association with brain anoxia that can lead to convulsions. Such patients require intense medical therapy and close observation with possible intervention by cardiac pacing if prolonged asystole occurs. There is a concern of consequence future brain function.

Impact of isoproterenol infusion on BIS and metabolic values in pediatric patients undergoing electrophysiology studies.

STUDY OBJECTIVE: To study changes in BIS values and metabolic parameters during an infusion of isoproterenol in pediatric patients. DESIGN: Retrospective study approved By Committee For The Protection Of Human Subjects at University Of Texas Medical School at Houston. SETTING: University-affiliated children's hospital. MEASUREMENTS: The records of pediatric patients undergoing general anesthesia for electrophysiology procedures were analyzed. Electronic data collected included Bispectral Index (BIS) values, anesthetics (eg, opioids, expired concentration of inhaled anesthetics, muscle relaxants), hemodynamic values (ie, heart rate, invasive blood pressure), respiratory parameters [ie, tidal volume, respiratory rate, end-tidal CO2 (ETCO2)], and routine arterial blood gases. These parameters were analyzed 10 minutes prior to the start of the isoproterenol infusion (T-pre) and 10 minutes after isoproterenol had reduced the cardiac cycle length by 20% (T-infusion). MAIN RESULTS: Of the 29 records that were screened, 22 met the above criteria (mean age 13 ± 5 yrs). BIS values increased by an average of 8 (33 ± 8 to 41 ± 10; P < 0.001) during the isoproterenol infusion. Statistically significant increases in ETCO2 (median 33 - 36 mmHg; P = 0.01), PaCO2 (35 - 38 mmHg; P = 0.002), and lactate (1.1 -1.5 mg/dL; P < 0.001) occurred with infusion of isoproterenol. Patients undergoing controlled mechanical ventilation showed an increase in ETCO2 (mean 34 ± 6 mmHg to 37 ± 5 mmHg; P = 0.001) whereas those breathing spontaneously had an increase in minute ventilation (average increase 111 ± 30 mL/kg). CONCLUSIONS: Isoproterenol increases metabolic, respiratory, and BIS values in pediatric patients during general anesthesia. We recommend the use of BIS, close monitoring of ETCO2, and careful titration of anesthetics during isoproterenol infusion, especially when lighter planes of general anesthesia are requested for pediatric electrophysiologic procedures.

Ibn Al Nafis: his seminal contributions to cardiology.

Ibn Al Nafis, born 1213, was the first to discover the "circulation lesser" and describe the blood flow from the right ventricle to the lungs then back to the left ventricle 300 years before William Harvey. He bravely rejected the theory of Galen (130-200 AD) and Avicenna (980-1037 AD) which stated that the blood from the right ventricle passes through "invisible" holes in the ventricular septum to the left ventricle. Also was the first to note that the nourishment of the heart muscle is coming from the coronary arteries rather than from the inside of the ventricular cavity as described by earlier scholars.