Contemporary Evaluation of Syncope and Sinus Tachycardia

Selected Insights From a Referral Center

EP Lab Digest. 2023;23(1):20-21.

As those who evaluate patients with syncope or related conditions can attest, the differential diagnosis is key. Just as the symptoms being evaluated can range from overt transient loss of consciousness (TLOC) or near LOC, to lightheadedness or even just more vague feelings of unease, the mechanism and underlying pathology can range from reflex syncope to structural heart disease or arrhythmias to neurologic conditions or even vertigo. Starting with an open mind and letting the patient history be the guide is a core tenant of medical evaluation that especially holds true here. Beyond that, selected testing can further narrow the possibilities and help one arrive at a more firm diagnosis. The same concepts apply when evaluating a patient presenting with sinus tachycardia.

The Syncope Center at Cleveland Clinic is a specialized referral center providing outpatient evaluation and management of patients with syncope and related conditions such as orthostatic hypotension (OH) and postural orthostatic tachycardia syndrome (POTS). Over the decades of providing patient care, the processes have been continually refined in line with the accumulated experience and advancement of medical knowledge. While centered in the field of cardiology, and more specifically, cardiac electrophysiology (EP), by necessity the clinical skillset has expanded to include acumen with autonomic dysfunction, especially for syndromes of sinus tachycardia and for neurogenic orthostatic hypotension (nOH). Instead of providing a comprehensive statement on the full evaluations of syncope and sinus tachycardia,^1-4 the purpose of this manuscript is to provide selected insights resulting from the experience gained in a high-volume referral center.

Categories of Syncope and TLOC

The European Society of Cardiology classifies syncope into 3 main categories⁴: reflex syncope, OH, and cardiac syncope. All result in presumed global cerebral hypoperfusion leading to LOC.

Reflex Syncope

Under the category of reflex syncope is where one finds conditions of vasovagal syncope, carotid sinus syncope, and situational syncope. While much has been written regarding the evaluation and management of vasovagal syncope,^1,2,5 much less so has been published on situational syncope. Patients have presented to the Syncope Center with triggers of TLOC that have included micturition, defecation, deglutition, laugh, and cough, among others. Patients with frequent situational syncope can be challenging to manage, with the primary target of therapy being avoidance or mitigation of the underlying trigger. For example, in a patient with deglutition syncope, symptoms ultimately resolved with treatment of the underlying dysphagia and esophageal spasm.⁶

OH

While OH can initially be viewed as a common condition seen by cardiologists, the underlying pathology may be beyond the historical scope of cardiologists and missed unless there is clinical suspicion. For example, OH may be neurogenic in nature, such as in patients with Parkinson disease, parkinsonism, or multiple system atrophy. While the classical teaching for Parkinson disease is that other clinical signs/symptoms such as tremor or gait abnormalities present prior to OH, patients have been seen who had OH as an earlier manifestation or concern.⁷ Thus, when seeing a patient with OH, clinical suspicion should be expanded to include possible underlying neurologic conditions resulting in nOH, especially when the heart rate does not significantly increase when the blood pressure falls.

Cardiac Syncope

Cardiac syncope is where the Syncope Center provides the most classically trained expertise. Among patients seen for syncope, some have been subsequently diagnosed with structural heart disease, including hypertrophic obstructive cardiomyopathy and the less-known obstructive cardiomyopathy without severe septal hypertrophy.⁸ Others have been diagnosed with EP-centric conditions, including idiopathic paroxysmal atrioventricular block, ventricular tachycardia, or supraventricular tachycardia (SVT).

TLOC

While syncope is often the first suspected diagnosis in a patient with TLOC, it should be remembered that syncope is only one subheading under the broader category of TLOC.⁴ There have been instances when a patient seen in the Syncope Center has symptoms that were ultimately attributed to underlying seizure, severe cerebrovascular stenosis, stroke or transient ischemic attack, hypoglycemia, or sleep disorder. Additional care must be taken in patients with an overlap in conditions, for example, with bradycardia or asystole on cardiac monitoring associated with electroencephalogram (EEG)-confirmed seizure (ie, ictal asystole). In other cases, what was initially thought to be psychogenic nonepileptic seizures was subsequently shown to be convulsive syncope (ie, from a vasovagal response) on tilt table testing (TTT) with concomitant EEG. Finally, if one expands beyond TLOC into more generalized symptoms such as near LOC (near syncope), lightheadedness, and dizziness, then conditions such as vertigo, POTS, and medication effect have been diagnosed, among many others. In these cases, maintaining a somewhat broader differential, at least initially, can be useful.

Categories of Sinus Tachycardia

Apart from syncope and TLOC, many patients evaluated in the Syncope Center are seeking assistance for sinus tachycardia. While one may think sinus tachycardia to be benign, in some cases, the symptoms associated with persistent or frequently recurring sinus tachycardia can be quite debilitating.¹ Sinus tachycardia is generally divided into categories of secondary sinus tachycardia (ie, occurring as a response to an underlying primary condition) and syndromes of POTS or inappropriate sinus tachycardia (IST).³ This is assuming that the tachycardia is truly sinus tachycardia and not, for example, SVT.⁹

Specialized Evaluation of Syncope and Sinus Tachycardia

While obtaining a history, physical examination, and electrocardiogram (ECG) are class I recommendations in the evaluation of syncope,² an often forgotten but useful bedside assessment is measurement of orthostatic vital signs. Orthostatic vital sign measurement is routinely done for each patient seen in the Syncope Center and can quickly reveal conditions such as classical OH, show an increase in heart rate with stable blood pressures (eg, when assessing for POTS), correlate symptoms if they are experienced during measurement, and also assess the overall physical functioning and mobility of the patient when they are asked to stand. Beyond these basic initial assessments, risk stratification is also emphasized by the 2017 guidelines.² This means assessing for any serious medical conditions warranting hospitalization and inpatient evaluation. In the otherwise outpatient evaluation of TLOC and syncope, testing is generally tailored to the suspected diagnoses. For sinus tachycardia, while patients seen in the Syncope Center usually have already had some degree of testing, evaluation for underlying primary conditions resulting in a secondary sinus tachycardia is so vital that it should be emphasized.³ Possible primary causes may include thyroid disease, anemia, pulmonary embolism, infection, inflammation, or medication effect, among many others.

The TTT has been a cornerstone in the evaluation of patients with syncope or sinus tachycardia, with around 1000 tests performed per year in the Syncope Center (Figure 1). A 45-minute upright passive protocol is generally used without provocative maneuvers such as isoproterenol or nitroglycerin. In addition to assessing for vasovagal syncope, the 45-minute upright passive protocol is also especially helpful to assess for progressive (delayed) OH where the blood pressure decrease is only noted to occur beyond the 3 minutes of upright position that is screened by orthostatic vitals. Ancillary testing during the TTT is done in some cases, including concomitant EEG monitoring, measurement of plasma catecholamines, or carotid massage. Importantly, beat-to-beat blood pressures are measured during the test using finger plethysmography, since a vasodepressor response can at times be missed when only using traditional intermittent arm cuff measurements. The presence of a vasodepressor response may have significant clinical implications, such as when considering the possible benefit, or lack thereof, with pacemaker implantation.¹⁰ In addition to continuous telemetry, 12-lead ECGs are also performed during the TTT and provide valuable information,^11,12 such as in a case identifying an atrial tachycardia (ultimately arising from the left atrial appendage) in a patient previously presumed to have sinus tachycardia due to POTS.⁹ Finally, active stand tests are also done using the same continuous monitoring systems to assess for conditions such as initial OH, which can potentially be missed by a traditional TTT.¹³ The data from the TTTs are then entered into a web-based system that was developed in-house.

Interpretations of the TTTs are guided both by published definitions as well as by the long experience with TTT at the Syncope Center, with over 17,000 tests done to date since 2004. For example, in a patient with a clinical picture consistent with typical POTS but a heart rate increase that meets the 30 beats per minute (bpm) threshold at, for example, only 12 minutes of upright tilt instead of the espoused strict 10-minute threshold,¹⁴ there is a reasonable possibility that patient may still clinically benefit from the therapies used for classical POTS. Conversely, caution is taken when assessing patients with heart rate increases during the TTT, since not all heart rate increases during the test should be attributed to POTS, such as in the setting of musculoskeletal pain induced with assuming upright position, primary anxiety (as opposed to anxiety secondary to the symptomatic heart rate increase), underlying anemia or clinical dehydration, or residual medication effect. Thus, the term “accentuated postural tachycardia” is used on the actual TTT report provided by the Syncope Center to denote a 30 bpm heart rate increase, reserving the formal diagnosis of POTS to be ascribed separately and clinically when combining the TTT result in conjunction with the patient’s clinical presentation.

Depending on the TTT results and overall presentation, it may also be prudent to assess for autonomic dysfunction, for example, in the setting of suspected neuropathic POTS or nOH. Evaluation of autonomic function is performed in collaboration with autonomic neurology, using methods such as quantitative sudomotor axon reflex testing, deep breathing and Valsalva testing, and skin biopsy for nerve fiber density.¹⁵

In the past, specialized historical evaluations at the Syncope Center have included the I-131 tagged human serum albumin (HSA) technique to estimate blood volume¹⁴; from July 2004 to April 2018, a total of 7003 blood volume studies were done. Specialized historical testing also included evaluation of circulatory kinetics using technetium-99m RBC radionuclide imaging,¹⁴ where a hyperkinetic circulation was defined as a combination of a high cardiac index, shortened pulmonary mean transit time, and low peripheral resistance. A novel approach that is currently being used in selected patients is invasive cardiopulmonary exercise testing,¹⁶ in which right heart catheterization is performed at baseline and during exercise to provide information on many parameters but in part to assess for a phenomenon termed preload insufficiency. In essence, preload insufficiency depicts a scenario of decreased cardiac venous return that can result in blood pressure changes,¹⁷ heart rate changes, and symptoms such as shortness of breath and exercise intolerance.¹⁶ Finally, cardiac monitoring is another foundation in the evaluation of syncope and sinus tachycardia at the Syncope Center; methods include either a 24-hour Holter monitor to assess the average heart rate in a patient with suspected IST, a mobile continuous outpatient telemetry monitor to correlate symptoms with rhythm abnormalities coupled with the ability to more rapidly intervene, or an implantable loop recorder to capture elusive and rare episodes of TLOC¹⁸ (Figure 2).

Conclusion

The evaluation of patients presenting to a referral center with syncope or sinus tachycardia can be challenging, but in many cases, these patients have debilitating symptoms and diminished quality of life. In some cases, starting over with a broader differential, letting the patient be the guide, and assessing for underlying primary conditions may be what is most prudent. In other cases, selected appropriate specialized testing to arrive at a more firm diagnosis may be what is most effective. However, in many cases, compassion for the patient and their condition may be what is most appreciated. 

Disclosures: Dr Mayuga has completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. He has no conflicts of interest to report regarding the content herein.

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