The current definition of postural orthostatic tachycardia syndrome (POTS) dates back to a small case series of patients with a subacute illness who presented with excessive orthostatic tachycardia and orthostatic intolerance, in the absence of another recognized disease. Conventional POTS criteria require an excessive orthostatic tachycardia in the absence of substantial orthostatic hypotension, and predominant symptoms of orthostatic intolerance, worse with upright posture and better with recumbence. POTS is a heterogeneous syndrome with likely several underlying pathophysiological processes, and not a specific disease. The primary panel for this Canadian Cardiovascular Society position statement sought to provide a contemporary update of the best evidence for the evaluation and treatment of POTS. We performed a systemic review of evidence for the evaluation of treatment of POTS using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology, and developed recommendations on the basis of the Canadian Cardiovascular Society approach to position statements. One identified problem was that numerous patients who did not meet criteria for POTS would still be given that diagnoses by providers to validate the illness even though this diagnosis is incorrect. This includes patients with postural symptoms without tachycardia, orthostatic tachycardia without symptoms, and those with orthostatic tachycardia but another overt cause for excessive tachycardia. We developed a novel nomenclature ecosystem for orthostatic intolerance syndromes to increase clarity. We also provide more clarity on how to interpret the orthostatic vital signs. These concepts will need to be prospectively assessed.

La définition actuelle du syndrome de tachycardie orthostatique posturale (STOP) remonte à une petite série de cas de patients atteints d’une maladie subaiguë qui présentaient une tachycardie orthostatique excessive et une intolérance orthostatique, en l’absence d’une autre maladie reconnue. Selon les critères classiques, le STOP implique une tachycardie orthostatique excessive en l’absence d’hypotension orthostatique marquée, ainsi que des symptômes prédominants d’intolérance orthostatique, s’aggravant en position verticale et s’atténuant en position allongée. Le STOP est une entité hétérogène où interviennent probablement plusieurs processus physiopathologiques sous-jacents; il ne s’agit pas d’une maladie en tant que telle. Le principal groupe d’experts à l’origine de cet énoncé de position de la Société canadienne de cardiologie a cherché à présenter les données probantes les plus récentes et les meilleures en matière d’évaluation et de traitement du STOP. Nous avons effectué un examen systématique des données probantes aux fins d’évaluation du traitement du STOP conformément à la méthodologie GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) et formulé des recommandations fondées sur le cadre de référence relatif aux énoncés de position de la Société canadienne de cardiologie. Notre démarche a notamment fait ressortir une problématique, où un diagnostic de STOP avait été posé chez de nombreux patients malgré l’incongruence de leur état et des critères définissant le syndrome. Un tel diagnostic erroné avait notamment été prononcé chez des patients présentant des symptômes posturaux en l’absence de tachycardie, une tachycardie orthostatique asymptomatique ou encore une tachycardie orthostatique en présence d’une autre cause manifeste de tachycardie excessive. Par souci de clarté, nous avons élaboré un nouvel écosystème de classification des syndromes d’intolérance orthostatique. Dans la même optique, nous avons également précisé les critères d’interprétation des signes vitaux orthostatiques. Ces concepts devront être l’objet d’une évaluation prospective.

1. Introduction and Rationale

1 Schondorf R.

Low P.A. Idiopathic postural orthostatic tachycardia syndrome: an attenuated form of acute pandysautonomia?. The current definition of postural orthostatic tachycardia syndrome (POTS) dates back to 1993.This initial report was a small case series of patients with a subacute onset illness who presented with an excessive orthostatic tachycardia and orthostatic intolerance, in the absence of another recognized disease.

Table 1 Chronic orthostatic intolerance syndromes: diagnostic hemodynamic and symptom criteria Condition Hemodynamic criteria Clinical criteria Associated comorbidities Duration of symptoms POTS Sustained increase in heart rate ≥ 30 bpm in adults (older than 19 years) or 40 bpm in children/adolescents (younger than 19 years), from supine position to upright within 10 minutes of standing, and absence of orthostatic hypotension (decrease in systolic blood pressure > 20 mm Hg or diastolic blood pressure > 10 mm Hg Orthostatic intolerance symptoms: • Lightheadedness

• Palpitation (“heart racing”)

• Tremulousness

• Atypical chest discomfort Other symptoms not associated with changes in position: • Sleep disturbance

• Headaches

• Chronic fatigue

• Exercise intolerance and deconditioning

• Perceived cognitive impairment (“brain fog”)

• Peripheral acrocyanosis (“POTS feet”)

• Frequent nausea

• Mild diarrhea, constipation, bloating, unspecific abdominal pain (“irritable bowel syndrome”) None > 3 Months POTS plus Same as POTS Same as POTS and 1 or more: • Gastric emptying problems

• Intractable vomiting

• Severe constipation

• Neurogenic bladder

• Severe chronic pain

• Intractable headaches

• Significant flushing anaphylaxis symptoms

• Severe food intolerances • Hypermobile Ehlers-Danlos syndrome

• Hypermobile spectrum disorder

• Mast cell activation disorder

• Chronic fatigue syndrome/ME

• Celiac disease

• Autoimmune disorder

• Chronic migraines

• Cerebrospinal fluid leak

• Mitochondrial mutations disorders

• Multiple sclerosis Same as POTS PSWT No evidence of orthostatic tachycardia and orthostatic hypotension Orthostatic intolerance symptoms as with POTS and 1 or more:

• Gastric emptying problems

• Intractable vomiting

• Severe constipation

• Neurogenic bladder

• Severe chronic pain

• Intractable headaches

• Significant flushing anaphylaxis symptoms

• Severe food intolerances None Same as POTS PSWT plus No evidence of orthostatic tachycardia and orthostatic hypotension Orthostatic intolerance symptoms as with POTS and 1 or more:

• Gastric emptying problems

• Intractable vomiting

• Severe constipation

• Neurogenic bladder

• Severe chronic pain

• Intractable headaches

• Significant flushing anaphylaxis symptoms

• Severe food intolerances • Hypermobile Ehlers-Danlos syndrome

• Hypermobile spectrum disorder

• Mast cell activation disorder

• Chronic fatigue syndrome/ME

• Celiac disease

• Autoimmune disorder

• Chronic migraines

• Cerebrospinal fluid leak

• Mitochondrial mutations disorders

• Multiple sclerosis Same as POTS PTOC Same as POTS Same as POTS Secondary identifiable cause: • Acute hypovolemia

• Endocrinopathy

• Anemia

• Anxiety and panic attacks

• Medication side effects

• Recreational drugs effects

• Prolonged or sustained bed rest Transient bpm, beats per minute; ME, myalgic encephalomyelitis; POTS, postural orthostatic tachycardia syndrome; PSWT, postural symptoms without tachycardia; PTOC, postural tachycardia of other cause. The conventional criteria for POTS ( Table 1 ) require excessive orthostatic tachycardia in the absence of substantial orthostatic hypotension. In addition to the hemodynamic criteria, POTS requires predominant symptoms of orthostatic intolerance, with symptoms that are worse with upright posture and better with recumbence. POTS is a syndrome, and not a specific disease. It is also a heterogeneous disorder with likely several underlying pathophysiological processes. The hope is that discrete subtypes will be identified over time, each with a specific underlying pathophysiology and targeted treatment.

The primary panel for this Canadian Cardiovascular Society (CCS) position statement sought to provide a contemporary update of the best evidence for the evaluation and treatment of POTS. We performed a systemic review of evidence for the evaluation of treatment of POTS, and developed recommendations on the basis of the CCS approach to position statements.

1 Schondorf R.

Low P.A. Idiopathic postural orthostatic tachycardia syndrome: an attenuated form of acute pandysautonomia?. As our discussions progressed, a larger problem of nomenclature that inhibited effective communication became apparent, and this contributed to mistaken diagnoses of POTS. One issue was that even within the expert panel, there was disagreement about whether POTS was a purely cardiovascular and hemodynamic disorder, or one that could be associated with other disorders with systemic (and nonhemodynamic) presentations. Some believed that if a patient had another condition (eg, Ehlers-Danlos syndrome) that they should not be diagnosed with POTS because they would not have been included in the original report.However, this group with comorbid conditions comprise a significant population in our clinics diagnosed with POTS. It is likely that the natural history, prognosis, and response to treatment are different between this “pure” group and that with the comorbid conditions, and therefore it was important to develop a language that conveys those differences.

Another problem that surfaced was that numerous patients who did not meet criteria for POTS would arrive at our clinics diagnosed with POTS. This might be because of a misunderstanding of the POTS criteria in the broader medical community. Another issue is that for a patient who is unwell, the diagnosis of POTS can provide hope and validation of illness. These include patients with severe symptoms of orthostatic intolerance, but who did not meet the excessive orthostatic tachycardia criterion. This group also includes patients who suffered from symptoms of orthostatic intolerance and from excessive orthostatic tachycardia, and who have a condition that precludes the diagnosis of POTS (eg, prolonged bedrest or medications that exacerbate orthostatic tachycardia).

The primary panel sought to describe the ecosystem of chronic orthostatic intolerance that included POTS, and also the related disorders that did not meet POTS criteria. Some of these related disorders require treatment, similar to POTS, whereas others (eg, asymptomatic postural tachycardia) might not require treatment. Importantly, we did not expand the definition of POTS beyond the American Autonomic Society statement, although we did try to provide clarity to specific aspects of that definition. These newly described disorders were created on the basis of expert opinion of the primary panel and will need to be evaluated to determine if further modifications are required. It was clear to the primary panel that something was required, and this was its attempt to address the issue.