Structured Approach in Syncope

Take Home Messages

• Syncope is common and is associated with morbidity, increased mortality risk and a significant healthcare burden.
• A structured approach to the evaluation and management of syncope improves diagnostic yield with fewer investigations, minimises hospitalisations without negatively impacting on longer term outcomes and reduces overall healthcare costs.
• A specialist syncope unit can help facilitate such a structured approach.

Defining the problem

Syncope is a common presentation associated with a significant healthcare burden (1), morbidity and mortality in affected individuals (2-4). In a minority, syncope may be a pre-cursor to sudden cardiac death (5-7) while for the majority the prognosis is benign (1). The management of syncope remains less than satisfactory with delays in diagnosis and excessive costs due to unstructured investigations (8) and lengthy, avoidable hospital admissions (9, 10). In this editorial I will briefly discuss how a structured approach can improve the management of syncope.

According to the 2018 European Society of Cardiology (ESC) Guidelines syncope is defined as a transient loss of consciousness due to cerebral hypoperfusion, characterized by rapid onset, short duration, and spontaneous complete recovery. At presentation the cause of syncope can be “obvious” or “undetermined”. In “obvious syncope” the diagnosis is evident early on in the assessment and patients are investigated and treated during the index presentation. Examples of “obvious syncope” include: complete heart block with extreme bradycardia (heart rate<40 bpm) and hypotension; or massive pulmonary embolism with hypoxaemia, central pleuritic chest pain and hypotension. By contrast, in “undetermined syncope” the cause is unclear and requires further evaluation. Patients with “undetermined syncope” often undergo multiple and repeated fruitless investigations, as well as lengthy and repeated hospitalisations, which place an increasing burden on healthcare resources.

Box 1 illustrates a representative case scenario of a patient with unexplained syncope and the all too familiar investigative process which often fails to lead to a diagnosis and prevention of recurrent syncope. The patient had a hospitalisation lasting 5 days and underwent 8 formal investigations (4 cardiac and 3 neurological) including a repeated electrocardiogram (ECG) holter. In box 2 a more structured approach to the patient in question is described.

What is the burden of syncope?

The PICTURE registry (Place of reveal In the Care pathway and Treatment of patients with Unexplained Recurrent Syncope) was a prospective multicentre, observational study including 650 patients who received an implantable loop recorder (ILR) for the investigation of recurrent unexplained syncope (11). In this study patients were followed up until they had a syncopal recurrence or for at least 1 year. They reported on 570 patients who had completed follow up. This is one of the largest contemporary epidemiological studies performed in syncope and provided important insights into the burden of syncope.

In the PICTURE registry, around half of patients were women (54%), average age was 61 years, and the primary indication was syncope (91%) or presyncope (7%). Hypertension was common (49%) but other cardiovascular disease less so (coronary artery disease 15%, stroke or transient ischaemic attack 10%, cardiomyopathy 3%). The median number of prior syncope episodes was 4, of which 3 were within the previous 2 years; the age of first syncope was 55 years and 70% had prior hospitalisations due to syncope. Most patients had a full diagnostic work-up before ILR implantation (68%) and had seen an average of 3 different specialists. The commonest specialties seen were cardiology (93%), general practice (63%), neurology (47%) and emergency medicine (36%). Emergency medicine was the first specialty consulted in 23% of patients. Patients underwent a median of 13 (interquartile range 9-20) tests. The commonest tests performed were standard ECG (98%), echocardiography (86%), basic laboratory tests (86%) and ambulatory ECG tests (67%). Around half of patients underwent inhospital ECG monitoring, exercise testing, orthostatic blood pressure (BP) measurements or magnetic resonance imaging or computed tomography scans. Carotid sinus massage, tilt testing and electroencephalogram were performed in around one third of patients. Electrophysiology studies and coronary angiography was performed in around one quarter of patients. In a sub-study analysis based on a medium-sized UK university hospital, the mean cost of diagnostic tests in patients with unexplained syncope was £1613 per patient and for 10% of the patients the cost exceeded £3539 (8). By contrast in 12 % of patients who had structured guideline-directed investigations the mean cost was only £709 per patient. The results of the PICTURE study appear to mirror observations from clinical experience; patients with syncope undergo multiple investigations, which are costly and often futile and despite this still have recurrent unexplained events that sometimes result in multiple hospitalisations. The PICTURE study showed that a structured approach to investigation can reduce the cost of diagnostic tests, but can it improve the diagnostic yield and patient outcomes?

Is structured management of syncope the answer?

Brignole et al performed a large prospective multicentre observational study to evaluate the outcome of a guidelines-based structured approach to the management of patients with syncope using 2004 ESC guidelines (12). Their results were overwhelming. They analysed 891 of 941 patients referred to syncope units in general hospitals; a definitive diagnosis was made in 82% of patients. The diagnosis was made at the initial evaluation in 21% of patients and an early diagnosis in 61% following a mean 2.9 tests per patient. The diagnosis remained unexplained in a further 18% despite a mean 3.5 tests per patient. Diagnoses included reflex syncope (67%), cardiac (6%), orthostatic hypotension (4%) and non-syncope (5%). Interestingly the “unexplained syncope” patients were older than patients with a diagnosis, had a higher incidence of structural heart disease and ECG abnormalities, suffered unpredictable episodes of syncope without warning and had higher OESIL (13) and EGSYS (14) “risk scores”.

The use of a structured approach to syncope in the emergency department (ED) has been evaluated in a prospective, single-centre, randomized control trial (RCT) of patients presenting to the ED with syncope of undetermined cause (9). All patients underwent risk stratification in the ED department. High-risk patients were admitted to hospital while low-risk patients were discharged with appropriate follow up. Intermediate risk patients (n=103) were randomized to syncope unit evaluation and standard care in a 1:1 manner. The primary outcomes were diagnostic yield and hospitalisation rates. The mean age was 64 years and approximately half of patients were women. Coronary disease was present in 43%, structural heart disease in 9% and ECG abnormalities were detected in 59%. Over half of patients had a history of recurrent syncope. There was a significantly higher diagnostic yield in syncope unit (67%) patients compared to standard care (10%, p<0.001). Significantly fewer patients were hospitalised after syncope unit evaluation (43%) compared to standard care (98%) but this did not translate into a reduction in mortality, freedom from syncope or therapeutic interventions received. These results indicate that a structured approach to the management of syncope can improve diagnostic yield and that many patients can be safely discharged with no negative impact on longer-term outcomes.

In a more recent multicenter RCT assessing the efficacy of a structured ED protocol in the management of patients presenting with syncope (9), Sun and colleagues randomized 124 patients to either a structured ED observation protocol compared or standard care. Hospital admission rates (15% v 92%) and hospital length of stay (29 v 47 hours) were significantly lower in the structured observation ED protocol group, with no difference in serious outcomes 6 months following hospital discharge. The observation protocol involved risk stratification based on history, physical findings and the results of investigations performed in the ED including ECG, serial troponin and echocardiography (in patients with cardiac murmur). The ED observation arm was also more economical with index hospital costs reduced by $629. This study adds to the accumulating evidence supporting a structured approach to the management of patients presenting with syncope.

What is a structured approach to syncope?

A structured approach to syncope primarily refers to the patient with “undetermined syncope” where the cause is not obvious. An initial assessment is performed including focused history (including family history of sudden death), physical examination and simple bed-side tests including a 12 lead ECG, lying/standing BP and carotid sinus massage (15)(Box 3). The history should focus on confirming syncope, identifying features to suggest a cause and risk factors to suggest underlying cardiac pathology. The diagnosis can often be elucidated at this point and includes: reflex syncope (vasovagal or situational), orthostatic hypotension, cardiac and non-syncope. If the diagnosis still remains uncertain despite the initial evaluation further investigations may be considered and chosen based on clinical features (e.g. an echocardiogram is warranted in an elderly syncopal patient with prior myocardial infarction but may not be necessary in a young patient with reflex syncope and no high-risk features) and likelihood of detecting an abnormality (e.g. 24 hour ECG holter would be useful in a patient with daily symptoms and conduction disease on resting ECG, but unhelpful in a patient with infrequent symptoms and normal ECG). Expensive specialist tests should not be routinely performed but considered under relevant specialist guidance (e.g. electroencephalogram, electrophysiology study). Risk stratification tools (13, 14) can be helpful in an ED setting to identify patients who require hospital admission and those who can be safely discharged and managed as an outpatient. Finally, the use of a syncope specialist unit can be helpful to ensure that a structured approach is utilized in all patients with syncope.

Conclusion

The evaluation and management of syncope can be challenging particularly in patients without a clear cause at the outset. A structured approach to the evaluation of syncope in such patients can help improve the diagnostic yield, guide appropriate investigations, aid decisions to admit in the ED, and reduce overall healthcare costs. Furthermore, a structured approach in “undetermined syncope” can minimise the stress experienced by patients and their responsible physicians.

References

1. Sandhu RK, Tran DT, Sheldon RS, Kaul P. A Population-Based Cohort Study Evaluating Outcomes and Costs for Syncope Presentations to the Emergency Department. JACC Clin Electrophysiol. 2018;4(2):265-73.
2. Ricci F, Fedorowski A, Radico F, Romanello M, Tatasciore A, Di Nicola M, et al. Cardiovascular morbidity and mortality related to orthostatic hypotension: a metaanalysis of prospective observational studies. Eur Heart J. 2015;36(25):1609-17.
3. Ricci F, Sutton R, Palermi S, Tana C, Renda G, Gallina S, et al. Prognostic significance of noncardiac syncope in the general population: A systematic review and meta-analysis. J Cardiovasc Electrophysiol. 2018.
4. Yasa E, Ricci F, Magnusson M, Sutton R, Gallina S, Caterina R, et al. Cardiovascular risk after hospitalisation for unexplained syncope and orthostatic hypotension. Heart. 2018;104(6):487-93.
5. Adler A, Rosso R, Chorin E, Havakuk O, Antzelevitch C, Viskin S. Risk stratification in Brugada syndrome: Clinical characteristics, electrocardiographic parameters, and auxiliary testing. Heart Rhythm. 2016;13(1):299-310.
6. Fruhwald FM, Eber B, Schumacher M, Zweiker R, Watzinger N, Klein WW. Syncope in dilated cardiomyopathy is a predictor of sudden cardiac death. Cardiology. 1996;87(3):177-80.
7. Liu Q, Li D, Berger AE, Johns RA, Gao L. Survival and prognostic factors in hypertrophic cardiomyopathy: a meta-analysis. Sci Rep. 2017;7(1):11957.
8. Edvardsson N, Wolff C, Tsintzos S, Rieger G, Linker NJ. Costs of unstructured investigation of unexplained syncope: insights from a micro-costing analysis of the observational PICTURE registry. Europace. 2015;17(7):1141-8.
9. Shen WK, Decker WW, Smars PA, Goyal DG, Walker AE, Hodge DO, et al. Syncope Evaluation in the Emergency Department Study (SEEDS): a multidisciplinary approach to syncope management. Circulation. 2004;110(24):3636-45.
10. Sun BC, McCreath H, Liang LJ, Bohan S, Baugh C, Ragsdale L, et al. Randomized clinical trial of an emergency department observation syncope protocol versus routine inpatient admission. Ann Emerg Med. 2014;64(2):167-75.
11. Edvardsson N, Frykman V, van Mechelen R, Mitro P, Mohii-Oskarsson A, Pasquie JL, et al. Use of an implantable loop recorder to increase the diagnostic yield in unexplained syncope: results from the PICTURE registry. Europace. 2011;13(2):262-9.
12. Brignole M, Ungar A, Casagranda I, Gulizia M, Lunati M, Ammirati F, et al. Prospective multicentre systematic guideline-based management of patients referred to the Syncope Units of general hospitals. Europace. 2010;12(1):109-18.
13. Colivicchi F, Ammirati F, Melina D, Guido V, Imperoli G, Santini M, et al. Development and prospective validation of a risk stratification system for patients with syncope in the emergency department: the OESIL risk score. Eur Heart J. 2003;24(9):811-9.
14. Del Rosso A, Ungar A, Maggi R, Giada F, Petix NR, De Santo T, et al. Clinical predictors of cardiac syncope at initial evaluation in patients referred urgently to a general hospital: the EGSYS score. Heart. 2008;94(12):1620-6.
15. Pasquier M, Clair M, Pruvot E, Hugli O, Carron PN. Carotid Sinus Massage. N Engl J Med. 2017;377(15):e21.
16. Brignole M, Moya A, de Lange FJ, Deharo JC, Elliott PM, Fanciulli A, et al. 2018 ESC Guidelines for the diagnosis and management of syncope. Eur Heart J. 2018;39(21):1883-948.