The following is a review of some of the major features of the 2015 Heart Rhythm Society (HRS) Expert Consensus Document on the Diagnosis and Treatment of Postural Tachycardia Syndrome, Inappropriate Sinus Tachycardia, and Vasovagal Syncope, which was recently published in HeartRhythm and can be found online at hrsonline.org.¹ This document represents the work of the HRS in collaboration with the American Autonomic Society (AAS), the American College of Cardiology (ACC), the American Heart Association (AHA), the Asia Pacific Heart Rhythm Society (APHRS), the European Heart Rhythm Association (EHRA), the Pediatric and Congenital Electrophysiology Society (PACES), and the Sociedad Latinoamericana de Estimulacion Cardiaca y Electrofisiologia (SOLAECE)-Latin American Society of Cardiac Pacing and Electrophysiology. Opinions which resulted in the work were derived from expert consensus, extensive literature review, clinical experience, and survey data, and not from clinical trials or randomized trials. 

This consensus document focuses on three primary objectives. The first is to establish the working criteria for the diagnosis of postural tachycardia syndrome (POTS), inappropriate sinus tachycardia (IST), and vasovagal syncope (VVS). The second objective is to provide guidance and recommendations on the assessment and management of each of these entities. The final objective is to identify the main areas where more knowledge is needed and where research opportunities exist.

The recommendations contained in the document follow the standard structure of such guidance documents, with class I corresponding to “is recommended” or a strong recommendation, class IIa being “can be useful” or a somewhat weaker recommendation, class IIb being “may be considered” or denoting benefit equivalent or possibly exceeding risk, and class III indicating a treatment “should not” be done or “is not recommended.” 

Postural Tachycardia Syndrome 

POTS is defined when the following are present: lightheadedness, palpitations, tremulousness, generalized weakness, blurred vision, exercise intolerance, and fatigue that occur with standing; a heart rate increase of ≥30 bpm when moving from a recumbent to a standing position for greater than 30 seconds; and the absence of orthostatic hypotension. There may be occasional fainting. POTS and vasovagal syncope are not mutually exclusive.

POTS is seen in about 0.2% of the population. The occurrence is seen most often between the ages of 15 and 25, and is seen most in women (≥75%). The condition is generally thought of as chronic, although in the majority of cases there is improvement over time.

Many mechanisms are thought to be responsible for POTS. Peripheral autonomic denervation has been reported in up to 50% of patients. This is seen as a restricted autonomic neuropathy of the small and distal postganglionic sudomotor fibers of mostly the feet and toes, leading to reduced venoconstriction and therefore venous pooling. Another finding is a reduced blood volume in about 70% of patients, accompanied by low plasma renin activity and aldosterone levels. Some patients present with plasma norepinephrine levels ≥600 pg/mL while standing, a hyperadrenergic state. Patients with POTS are often in a deconditioned state and can benefit from exercise training. Also, these patients may be highly anxious and have increased focus on bodily sensations.

Evaluation of the POTS patient should include a thorough history and examination, such as orthostatic vital signs, 12-lead electrocardiogram, thyroid function, CBC, 24-hour Holter, echocardiogram, and exercise stress testing. Chronicity of symptoms, diet, exercise, triggers, impact of symptoms, and family history should be probed. A tilt-table test may be helpful.

The treatment of POTS is usually complex and multifaceted. No randomized clinical trials have been performed and there is no general consensus on treatment. Treatment approaches fall into three general categories: nonpharmacologic, pharmacologic, and invasive interventions (the latter usually not recommended). Nonpharmacologic treatments include withdrawal of possible causative medications, increasing blood volume with greater salt and fluid intake, use of compression garments, and a supervised exercise program. These approaches should be tried first.

Pharmacologic treatments are begun if the nonpharmacologic approaches fail. Drugs are used to target specific identified problems. The hypovolemic patient may be prescribed 2-3 L of water intake per day and 10-12 g/day of salt with salt tablets. Fludrocortisone may be used for increasing volume and sodium retention. Midodrine causes constriction of veins and arteries, and thus, helps increase venous return. Intravenous saline has been used as a rescue therapy for those with worsened symptoms. Low-dose propranolol has been effective for some. Ivabradine is of interest because it slows sinus rate and does not lower blood pressure. This drug recently became available in the U.S. Pyridostigmine has been used to lower the orthostatic tachycardia, but causes adverse effects such as diarrhea, abdominal pain, and nausea. Clonidine and methyldopa have been used with patients who have major sympathetic nervous system etiologies, but both can cause drowsiness and fatigue. Modafinil has been used for the fatigue and cognitive issues these patients experience, but it can worsen tachycardia.

Invasive interventions are generally not recommended. These include sinus node modification and decompression of the cerebellar tonsils (some POTS patients have been found with herniation of their cerebellar tonsils, known as Chiari I). 

Inappropriate Sinus Tachycardia 

IST is defined by the presence of a sinus heart rate >100 bpm at rest and is associated with palpitation symptoms. The mean heart rate over 24 hours is usually >90 bpm. The prevalence of IST is estimated at 1.2%. It is thought to be a chronic condition with no known mortality.

Mechanisms associated with IST are unclear, but the following seem to be implicated: increased sinus node automaticity, beta-adrenergic hypersensitivity, decreased parasympathetic activity, and impaired neurohormonal modulation.

A diagnostic workup should include a thorough history and physical, 12-lead electrocardiogram, a 24-hour Holter, urine and serum drug screening, autonomic testing, and possibly treadmill testing. POTS and IST have a similar presentation, but IST can also be provoked by emotional stress.

Treatment recommendations include seeking reversible causes of the sinus tachycardia, lifestyle changes, ivabradine, possibly fludrocortisone, volume expansion, pressure stockings, phenobarbital, clonidine, psychiatric evaluation, exercise training, and erythropoietin. Beta-blocking drugs are usually not effective. Modification or ablation of the sinus node has been performed in some cases, but there is a high rate of recurrence and significant complication rates.

Vasovagal Syncope

In order to adequately describe vasovagal syncope, it must be differentiated from the general diagnosis of syncope. The definition of syncope is a transient loss of consciousness that is associated with the inability to maintain postural tone. There is a rapid and spontaneous recovery, and no clinical features suggestive of another etiology for the loss of consciousness, such as epilepsy. Vasovagal syncope is considered a syncope syndrome that occurs with an upright posture held for greater than 30 seconds or as a response to emotional stress, pain, or in a medical setting. In addition, there may be diaphoresis, warmth, nausea, pallor, hypotension, and a bradycardia. The episode is usually followed by fatigue.

Vasovagal syncope episodes occur in 1-3% of toddlers, and its incidence increases by the age of 11. Forty-two percent of women and 32% of men will have had at least one episode by the age of 60.

The cause of vasovagal syncope is also debated. During a vasovagal syncope episode, there seems to be an ineffective vasoconstrictive response to the upright position, causing venous pooling in the legs and splanchnic regions. In addition, a paradoxical vasodilation may occur with resultant hypotension and loss of consciousness. A reduction in heart rate is present, and at times, there is asystole of the sinus and AV nodes. Recent studies have suggested that there may be two distinct groups with vasovagal syncope based on supine blood pressures.

Vasovagal syncope is diagnosed through obtaining a clinical history. The main informational categories include predisposing situations, prodromal symptoms, physical signs, and recovery time and symptoms. Some investigators have developed diagnostic scores to help define the diagnosis. Diagnostic testing should be directed toward two general approaches: determination of a substrate for a particular type of syncope, and determining whether the syncope is associated with a specific heart rhythm abnormality. Tilt-table testing is helpful if, after initial assessment is performed, the diagnosis is still uncertain. Such testing is also helpful in differentiating between convulsive syncope and epilepsy, establishing a diagnosis of pseudosyncope, and for situations in which the syncope cause is still unclear. Implantable loop recorders (ILRs) are helpful in situations in which the episodes are infrequent and there is a low risk of a fatal outcome; ILRs can last up to three years. 

Treatment approaches for vasovagal syncope should take into consideration the natural history and potential for harm against the symptom severity and treatment efficacy. Medications that cause hypotension could be reduced, as long as hypertension and heart failure are not worsened. Isometric exercise of the large muscles has proven helpful for patients who have a prodromal period. 

Tilt training was not recommended by the group, and the use of beta-blocker therapy was recommended only for those over 40. Fludrocortisone and midodrine have been used with some success. 

Use of pacemakers in the treatment of vasovagal syncope has been limited. Pacing should only be considered in very select patients, which includes those much older than 40 and who have frequent recurrences with repeated injuries, limited prodromes, and documented asystole. Tilt-table testing can be helpful in assessing who might not respond to permanent cardiac pacing. Pacing for the pediatric patient with syncope who has asystole and has not responded to medical therapy may be considered. In almost all cases where pacing has been used beneficially with syncope, dual-chamber pacing was used. 

POTS and Vasovagal Syncope in the Young

There is limited information in the pediatric literature about the treatment of POTS and vasovagal syncope. The consensus document reviewed the aspects of both conditions shared by children and adults.

The diagnosis of POTS in the pediatric patient is made through the medical history and with an orthostatic test. A heart rate increase of at least 40 bpm and symptoms of orthostatic intolerance are seen in positive tests.

For the diagnosis of vasovagal syncope, a 12-lead electrocardiogram is important, and tilt-testing should be performed in selected cases. Syncope which occurs during exercise should be investigated more thoroughly to rule out cardiomyopathy and arrhythmias.

Data on treatment in the pediatric population is sparse. Treatment with salt and fluids is usually helpful. Reassurance is also key, keeping in mind that most children stop fainting in late adolescence. Midodrine has been used in a couple of trials. 

Future Opportunities

The writers of the consensus document reiterated that little seems to be known about the natural history of these syndromes and their causes. In addition, treatment approaches vary from country to country. Because such a small population is affected by these conditions, there is a need for a network of reporting to be established with uniform criteria and definitions in place. The collection of this data will require work among all professional and national jurisdictions. 

Reference

1. Sheldon RS, Grubb BP, Olshansky B, et al. 2015 Heart Rhythm Society expert consensus statement on the diagnosis and treatment of postural tachycardia syndrome, inappropriate sinus tachycardia, and vasovagal syncope. Heart Rhythm. 2015;12(6):e41-63.