University of Groningen Patterns of orthostatic hypotension and the evaluation of syncope van Wijnen, Veera Kariina

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University of Groningen

Patterns of orthostatic hypotension and the evaluation of syncope

van Wijnen, Veera Kariina

DOI:

10.33612/diss.112725119

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Publication date: 2020

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van Wijnen, V. K. (2020). Patterns of orthostatic hypotension and the evaluation of syncope. Rijksuniversiteit Groningen. https://doi.org/10.33612/diss.112725119

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CHAPTER

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GENERAL INTRODUCTION

Epidemiology

Syncope is defined as a transient loss of consciousness due to transient global cerebral hypoperfusion, characterized by rapid onset, short duration and spontaneous complete recovery (1). Syncope is prevalent in younger and older subjects, with an incidence peak in younger adults around the age of 15 years and a second increase in incidence in adults from 65 years and older (Fig. 1) (2). Overall, it is estimated that approximately half of the general population will have one syncopal event during their lifetime.

Figure 1. Frequency of the complaint of fainting as a reason for visiting a general practitioner in the Netherlands. It concerns an analysis of 93 297 patient years. The arrow around 1 year is to indicate that a small peak occurs between 6–18 months (breath-holding spells). Between 2–5 years syncope is rare. From Wieling et al. Heart 2004 Sept;90 (9):1094-1100, with permission of the editor.

Syncope in the old literature and art

Syncope has been recognized as a problem for centuries and in the older literature it is referred to as lipothymia (derived from leipo [to leave] and thymia [the mind]) (3). Accounts on syncope can be found throughout literature and art. Classical paintings usually portrait syncope as a reaction to high drama and emotion, mostly in young beautiful women. When men faint in paintings, there is usually a medically serious, even life-threatening cause (4). Although syncope has been described since the beginning of medicine, the responsible pathophysiological mechanisms of syncope have only been clarified over the past 100 years (5). The basis of our understanding of the mechanisms of syncope are derived from several astute clinicians. They described the clinical profiles of vasovagal syncope, orthostatic hypotension and cardiac syncope by careful observing and detailed descriptions of a few patients, long before the technological advantages we have nowadays (5).

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Causes of syncope

In the 1980s it became possible to measure blood pressure beat-to-beat noninvasively with continuous noninvasive finger arterial blood pressure measurement. This unique technological innovation has greatly enhanced our understanding of the different pathophysiological mechanisms that underlie the fall in systemic blood pressure causing syncope (6).

Systemic blood pressure is a product of cardiac output and systemic vascular resistance, and therefore a fall in either can cause syncope. In cardiac syncope, a cardiac arrhythmia or a structural heart disease leads to insufficient pumping of the heart, which causes cardiac output to fall (1). In vasovagal syncope there is an episodic disturbance of blood pressure regulation caused by an abnormal or exaggerated autonomic response to various stimuli (7). These stimuli, like standing for a long time, pain or blood phobia, can cause a fall in cardiac output or systemic vascular resistance, and many times both mechanisms act together to a varying degree, although a fall in cardiac output is the dominant hypotensive mechanism in adults (7). Orthostatic hypotension, defined as a sustained decrease in systolic blood pressure of at least 20 mmHg or diastolic blood pressure of at least 10 mmHg within 3 minutes of standing, can be caused by a fall in cardiac output or absence of an increase in systemic vascular resistance (8). Orthostatic hypotension caused by a fall in cardiac output is mostly seen in patients with volume depletion, for instance because of hemorrhage, diarrhea or vomiting. Orthostatic hypotension as a result of impaired vasoconstrictor mechanisms can be caused by the use of vasodilatator drugs or structural changes in autonomic pathways (8).

Orthostatic blood pressure measurement

Orthostatic blood pressure measurement is one of the cornerstones in the evaluation of suspected syncope patients. To detect orthostatic hypotension, blood pressure should be measured in supine position and after 1-3 minutes of standing (8). For routine assessment of orthostatic circulatory adjustments, intermittent blood pressure measurement with an oscillometer and monitoring of the heart rate are adequate. Nevertheless, intermittent blood pressure measurement is not sufficient for evaluation of conditions in which there are sudden transient changes in the circulation, such as during orthostasis. For this purpose, continuous noninvasive finger arterial pressure measurement provides a detailed evaluation of cardiovascular control (9,10). In addition to orthostatic hypotension, continuous noninvasive orthostatic blood pressure measurement has detected several other relevant patterns of initial orthostatic hypotension related to (pre) syncope (9-11). The spectrum of patterns of initial orthostatic hypotension can largely be divided into initial orthostatic hypotension, delayed blood pressure recovery and sustained orthostatic hypotension (8,12,13).

Evaluation of suspected syncope

The assessment of syncope patients is challenging, because patients are mostly asymptomatic upon presentation. The physician needs to work like a detective, i.e. gather historical and physical clues from the patients and witnesses, and apply deductive reasoning to find the diagnosis

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(14). A thorough medical history takes time, and knowledge of relevant aspects of cardiology, neurology, internal medicine, emergency medicine, geriatrics and psychiatry are required (14). For the purpose of an efficient work up, the syncope guidelines of the European Society of Cardiology recommend an initial evaluation, consisting of a thorough medical history, combined with physical examination, including electrocardiogram and orthostatic blood pressure measurement (1). If properly performed, the initial evaluation will reveal the cause of syncope, i.e. reflex syncope, cardiac syncope or orthostatic hypotension, in the majority of cases (15).

Emergency department

Most subjects who lose consciousness will not seek medical attention (16). Suspected syncope patients that are referred to the emergency department represent a small and selected group of patients with unexplained syncope. A systematic evaluation is important, to avoid unnecessary additional tests and hospitalization (1). It has been shown that a standardized initial evaluation in the emergency department results in a high diagnostic yield, i.e. number of patients receiving a working diagnosis (15,17). However, in daily practice a standardized assessment is missing (17). Syncope patients in the emergency department are often seen by several attending physicians, foremost aimed at excluding serious life-threatening causes of syncope in their own field. As a result, unnecessary additional tests are performed, with a low diagnostic yield but high costs (18). In the end, patients learn what they ‘do not have’ instead of ‘what happened to them’ (19). Despite attempts to improve diagnostic yield by introducing diagnostic tools and guidelines, 36 - 39% of the syncope patients leave the emergency department without a diagnosis (20-22). Furthermore, 12 - 83% are admitted to the hospital because of diagnostic uncertainty (23,24). The suspicion of a possible high risk cause of syncope, such as cardiac arrhythmia, is in many cases the reason for additional testing and hospitalization (Fig. 2) (25).

Syncope unit

The syncope unit aims to provide a systematic approach in the evaluation of suspected syncope and thereby reduce unnecessary hospitalizations and diagnostic procedures and increase diagnostic yield. Several studies have shown the benefits of a syncope unit, but there is insufficient evidence available whether a syncope unit is superior to other departments in efficiency or outcomes (26). Moreover, it is unknown which patients seen at the emergency department would benefit from referral to a syncope unit.

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13 Figure 2. Flow diagram of the evaluation of suspected syncope in the emergency department. Adapted from

the syncope guideline of European society of cardiology (1) and Syncopedia.org (27).

Management of syncope patients

The principal treatment goals for patients with syncope are to prolong survival, limit physical injuries and prevent recurrences (1). The attending physician in the emergency department needs to decide whether a patient should be hospitalized, needs further evaluation at a specialist or syncope unit or can safely be discharged (Fig. 2). If the cause of syncope is clear, the patient should be treated accordingly (1). If the cause is uncertain, risk stratification is indicated. Patients with high risk characteristics, such as syncope in supine position or a history of severe structural heart disease, are suspect for a cardiac syncope and should be admitted for further testing. Patients with intermediate risk, such as older patients with orthostatic hypotension or recurrent reflex syncope, are advised to be observed for a longer period in the emergency department/ward and then referred to a syncope unit. Patients with only low characteristics, such as young age and clear prodromal symptoms before the syncopal episode, can safely be discharged. Despite these guidelines, it is uncertain which high-risk characteristics are key to decision-making and, more importantly, which care pathway will improve the patient’s condition.

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OUTLINE OF THIS THESIS

This thesis is about the evaluation and management of suspected syncope patients referred to the emergency department. The first part of this thesis focuses on different patterns of orthostatic hypotension and addresses the physiological and pathophysiological changes in blood pressure upon standing, the prevalence of these patterns and their clinical relevance. Thereafter, this thesis provides more insight into the initial evaluation of suspected (pre)syncope patients in the emergency department and the follow-up at the syncope unit.

Part I: Orthostatic blood pressure recovery patterns

Chapter two provides a comprehensive review on normal and abnormal blood pressure

responses that can be detected with noninvasive continuous finger arterial blood pressure monitoring during orthostasis.

Chapter three provides a review on the methodological issues of noninvasive continuous finger

arterial blood pressure measurement. Furthermore it gives a detailed protocol on how to perform the active lying-to-standing test and how to analyse continuous beat-to-beat data.

Chapter four describes the prevalence of initial orthostatic hypotension in young adults referred

to a tertiary syncope unit and the diagnostic algorithm of initial orthostatic hypotension. Also, the hemodynamic changes underlying the large fall in blood pressure upon standing are studied.

Chapter five gives insight into the frequency of normal and abnormal orthostatic blood pressure

recovery patterns in suspected syncope patients referred to the emergency department.

Chapter six investigates the hemodynamic mechanisms that underlie the abnormal orthostatic

patterns of initial orthostatic hypotension, delayed recovery and sustained orthostatic hypotension.

Chapter seven discusses the clinical significance of orthostatic hypotension at 30 seconds of

standing.

Chapter eight describes the diagnostic dilemma between delayed orthostatic hypotension and

vasovagal reflex syncope in elderly patients.

PART II: Syncope - evaluation and management

Chapter nine is a clinical audit on the usual syncope evaluation by the attending physicians

in the emergency department compared to standardized evaluation, with emphasis on history taking. The primary outcome is diagnostic accuracy, which is determined by an expert committee after long-term follow-up.

Chapter ten investigates which syncope patients initially seen in the emergency department

would benefit from referral to the syncope unit, based on patient-reported outcome measures.

Chapter eleven discusses the main findings, implications of the results and future perspectives. Chapter twelve Nederlandse samenvatting

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REFERENCES

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(2) Wieling W, Ganzeboom KS, Saul JP. Reflex syncope in children and adolescents. Heart 2004 Sep;90 (9):1094-1100. (3) Pallais JC, Schlozman SC, Puig A, Purcell JJ, Stern TA. Fainting, swooning, and syncope. Prim Care Companion CNS Disord

2011;13 (4):10.4088/PCC.11f01187.

(4) Smith P. Fainting in classical art. Int Rev Neurobiol 2006;74:79-88.

(5) Cannom DS. History of syncope in the cardiac literature. Prog Cardiovasc Dis 2013 Jan-Feb;55 (4):334-338.

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(8) Freeman R, Wieling W, Axelrod FB, Benditt DG, Benarroch E, Biaggioni I, et al. Consensus statement on the definition of orthostatic hypotension, neurally mediated syncope and the postural tachycardia syndrome. Clin Auton Res 2011 Apr;21 (2):69-72.

(9) Sprangers RL, van Lieshout JJ, Karemaker JM, Wesseling KH, Wieling W. Circulatory responses to stand up: discrimination between the effects of respiration, orthostasis and exercise. Clin Physiol 1991 May;11 (3):221-230.

(10) Wieling W, Veerman DP, Dambrink JH, Imholz BP. Disparities in circulatory adjustment to standing between young and elderly subjects explained by pulse contour analysis. Clin Sci (Lond) 1992 Aug;83 (2):149-155.

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(12) Wieling W, Krediet CT, van Dijk N, Linzer M, Tschakovsky ME. Initial orthostatic hypotension: review of a forgotten condition. Clin Sci (Lond) 2007 Feb;112 (3):157-165.

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patients with syncope: developing expertise in syncope. Eur Heart J 2014 Dec 16.

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(24) D’Ascenzo F, Biondi-Zoccai G, Reed MJ, Gabayan GZ, Suzuki M, Costantino G, et al. Incidence, etiology and predictors of adverse outcomes in 43,315 patients presenting to the Emergency Department with syncope: an international meta-analysis. Int J Cardiol 2013 Jul 15;167 (1):57-62.

(25) Cook OG, Mukarram MA, Rahman OM, Kim SM, Arcot K, Thavorn K, et al. Reasons for Hospitalization Among Emergency Department Patients With Syncope. Acad Emerg Med 2016 Nov;23 (11):1210-1217.

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