Invasive therapy for inherited cardiac arrhythmias: towards a better benefit-risk equilibrium Olde Nordkamp, L.R.A.

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1 UvA-DARE (Digital Academic Repository) Invasive therapy for inherited cardiac arrhythmias: towards a better benefit-risk equilibrium Olde Nordkamp, L.R.A. Link to publication Citation for published version (APA): Olde Nordkamp, L. R. A. (2015). Invasive therapy for inherited cardiac arrhythmias: towards a better benefit-risk equilibrium General rights It is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), other than for strictly personal, individual use, unless the work is under an open content license (like Creative Commons). Disclaimer/Complaints regulations If you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library: or a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible. UvA-DARE is a service provided by the library of the University of Amsterdam ( Download date: 02 Oct 2018

2 2 Syncope prevalence in the ED compared to general practice and population: a strong selection process Louise R.A. Olde Nordkamp, Nynke van Dijk, Karin S. Ganzeboom, Johannes B. Reitsma, Jan S.K. Luitse, Lukas R.C. Dekker, Win-Kuang Shen, Wouter Wieling American Journal of Emergency Medicine 2009 March;27(3):

3 32 Chapter 2 ABSTRACT Objective: We assessed the prevalence and distribution of the different causes of transient loss of consciousness (TLOC) in the emergency department (ED) and chest pain unit (CPU) and estimated the proportion of persons with syncope in the general population who seek medical attention from either their general practitioner or the ED/CPU. Methods: A review of the charts of consecutive patients presenting with TLOC at the ED/CPU of our university hospital between 2000 and 2002 was conducted. Patients younger than 12 years or with a known epileptic disorder were excluded. Age and sex of syncopal patients were compared with those in a general practice and general population data sets. Main findings and conclusions: During the study period, 0.94% of the patients visiting the ED/CPU presented with TLOC (n = 672), of which half had syncope. Only a small but probably selected group of all people with syncope visit the ED/CPU.

4 Syncope in the ED, general practice and population 33 INTRODUCTION Transient loss of consciousness (TLOC) is a symptom of both benign and potentially lethal clinical disorders. It can be caused by syncope, neurological syndromes, and psychiatric or metabolic disorders. What all these disorders have in common is that patients lose consciousness, but presentation is usually quite different. Syncope is defined as TLOC caused by a fall in systemic blood pressure resulting in a reduction in blood flow to the brain. Important causes of syncope are neurally mediated reflex-syncopal syndromes and cardiac disorders. 1, 2 For a cost-effective diagnostic approach of patients with TLOC and to permit design of clinical trials, diagnostic strategies, and health services delivery, knowledge of the epidemiology of the various causes of TLOC in different clinical settings is required. 3-5 However, the body of knowledge regarding the epidemiology of TLOC is far from complete. 2 Recent studies have shown that the lifetime cumulative incidence of syncope in the general population in subjects up to 65 years of age is between 35% and 39% About 80% of these subjects have their first episode before the age of 30 years, and most subjects with syncope are women. Only a subgroup presents to a medical doctor. In the Framingham offspring study, 44% of the participants (mean age = 51 years, range = years) with an episode of TLOC reported that they did not seek medical advice. 12 In a younger group, this percentage may even be higher because syncopal episodes in young subjects are generally considered to be innocent. 4 Whether this difference in referral pattern between young and elderly subjects indeed exists has not been studied. In The Netherlands, the prevalence of the complaint fainting in the general practice is estimated at 2 to 9 per 1000 encounters, with a peak of predominantly females in the age group between 10 and 30 years and a peak above the age of 65 years in both men and women. 4, 13 In comparison, the number of patients presenting to their general practitioner (GP) with epilepsy is about 10 times lower ( per 1000 patient years) 13-15, and also, cardiac syncope is very rare. 13 Although we know that history and physical examination are important tools to risk stratify patients with TLOC 16, 17, the demographical characteristics and clinical features of patients with TLOC presenting to the emergency department (ED), either directly or referred by their GP, have not been studied in detail. This study therefore focuses on the epidemiology of TLOC in the emergency setting. The first aim of this study is to assess the prevalence of TLOC in the ED and chest pain unit (CPU) of a university hospital in The Netherlands and to determine the frequency distribution of the different causes of the TLOC in patients presenting to the ED and CPU. The second aim is to gain insight into the selection and referral process of patients with syncope, in particular

5 34 Chapter 2 the proportion from the general population that presents to a GP and/or ED/CPU. We hypothesize that only a small proportion of the patients with syncope visit EDs, but their syncopal etiology is more often dangerous. METHODS Study population This retrospective chart review was conducted in the ED and CPU of the Academic Medical Centre in Amsterdam, The Netherlands. The study was performed with the use of the routine charts of consecutive TLOC patients in the ED and CPU. All patients presenting with an episode of TLOC to the ED or CPU between January 1, 2000, and January 1, 2002, were included. Patients with a known epileptic disorder and patients younger than 12 years were excluded. From patients who visited the ED or CPU more than once during the study period, only the first episode was included in our analysis, to estimate prevalent cases and to avoid interference of the determination of prevalence of the different diagnosis by highly frequent visitors. Setting The ED is designed for patients with acute health problems, where they can get instant access to specialized medical care. The CPU is a specialized cardiac observational unit, to which patients with suspected acute cardiac problems are referred by their GP or by the attending ED physician. On average, 98 patients are evaluated daily in the ED (90) and CPU (8). 18, 19 Patients can arrive in the ED and CPU through 3 pathways. Most patients are self-referred (ED: 81%, 18, 19 CPU: 48%). Other patients are referred by their GP or are brought in by ambulance. The area of care of this university hospital contains inhabitants. It is a relatively young (mean age = 35 years) population with a majority of nonnative inhabitants (68% 1st or 2nd generation immigrants). 20 Patient care and data collection Every patient visiting the ED and CPU was seen by an attending physician. His/her evaluation included history and clinical evaluation. The diagnosis of the patient was recorded by the physician on a standardized chart. All charts in the ED and the CPU were reviewed on a weekly basis by an experienced investigator (K.G.) 6, 7 to identify cases. The charts of patients presenting with TLOC were included and reviewed by a specialist with long-term experience in the evaluation of patients with TLOC (W.W.) 4, 6, 21 according to the guidelines on syncope of the European Society of Cardiology (ESC) 17, to determine the diagnosis of the patients. If the diagnosis was unclear, a second investigator (N.V.D.) 7, 21 evaluated the chart. In case of conflicting diagnoses or if the diagnosis remained unclear, the diagnosis was considered unknown.

6 Syncope in the ED, general practice and population 35 Diagnoses were divided into 5 categories: syncope, neurological, metabolic, and psychiatric disorders and unknown. Syncope was subdivided into the categories reflex-syncopal syndromes, orthostatic hypotension, and cardiac disorders. The study was approved by the medical ethical committee of our institution. 2 Comparison of data in other settings Our aim was to estimate the referral rate of persons with syncope by comparing the estimated number of persons with syncope in the general population with the number of patients presenting to the GP and the number of patients presenting at the ED during the same time window. To obtain these number of patients in general practice and in the general population, 3 additional sets of data were used: data from the Transition project 4, 13, 14, 22, data from an epidemiological study in medical students (incidence data at young age) 6, and data from the Cardiovascular Risk profile of native Dutch people in the Netherlands (CRANS) study (incidence data at middle age). 7 All 3 studies have been performed in the same area in The Netherlands as the current study. The methodology and results of these studies have been described in detail elsewhere. 6, 7, 14, 22 In short, the aim of the Transition project is to formally characterize and describe the domain of family practice based on episode-oriented epidemiology. In this study, long-term information concerning all presentations to general practice 14, 22 is collected. The study among medical students was performed in 394 medical students (median age = 21 years, 64% women), of whom 154 (39%) had experienced one or more syncopal episodes during their lifetime, with a median of 2 episodes. 6 The CRANS study is a cross-sectional survey on cardiovascular risk factors carried out between 2001 and 2003 in 549 native Dutch respondents, aged 35 to 60 years (mean age = 48 years), of whom 190 (35%) had experienced a median of 2 episodes of syncope during their lifetime. 7 Statistical analysis All data were entered into an SPSS database and analyzed with SPSS ( SPSS Inc, Chicago, IL). Categorical data are displayed as percentage and compared between groups using a χ 2 test. Continuous data were graphically assessed for normality. Normally distributed continuous data were described as mean (SD) and compared between groups using Student t tests. Continuous data not normally distributed were expressed as median (quartiles and range) and compared between groups using the Mann-Whitney U test. P values <.05 were considered statistically significant. From our data and the data from the Transition project, the frequency of syncope was calculated as visit rates per 1000 patient-years (number of visits for syncope per 1000 patientyears). For the calculations on our data, we assumed that all visits to the ED were made by subjects from our resource area. We presumed that the number of visiting patients not from

7 36 Chapter 2 our area was equal to the number of subjects from our area visiting another hospital in case of symptoms. Event rates (number of syncope events per 1000 patient years) were used for the general population (see Appendix I for calculations). The 95% confidence intervals (CIs) were calculated according to the Poisson distribution. RESULTS Characteristics of study subjects From January 1, 2000, until January 1, 2002, patients visited the ED and 5583 patients visited the CPU. Of these patients, 672 (0.94%) of presented with TLOC, 526 (0.80%) at the ED and 146 (2.6%) at the CPU. Twenty-three patients (3.4%) were referred from the ED to the CPU. They were analyzed in the ED group. Two patients visited the ED more than once. The characteristics of the patients with TLOC are displayed in Table 1. In the ED, 46% of the patients was men vs 60% in the CPU (P <.01). The median age for the entire group of patients Table 1: Characteristics of the study population Total ED CPU p-value No. of visitors No. of subjects presenting with TLOC 672 (0.94%) 526 (0.80%) 146 (2.6%) < 0.01 Male gender 327 (49%) 240 (46%) 87 (60%) < 0.01 Median age 46 (range 12-95) (quartiles 30-65) 40 (range 12-89) (quartiles 27-56) 69 (range 21-95) (quartiles 52-78) < 0.01 Age < 40 yrs 277 (41%) 263 (50%) 14 (9.6%) < 0.01 Age yrs 196 (29%) 156 (30%) 40 (27%) Age > 60 yrs 199 (30%) 107 (20%) 92 (63%) P-values are for the difference between Emergency Department (ED) and Chest Pain Unit (CPU) Emergency department Chest pain unit No. of subjects Male Female No. of subjects Male Female Age Age Figure 1: Age and sex distribution of patients presenting with TLOC to the ED and CPU

8 Syncope in the ED, general practice and population 37 was 46 years (quartiles 30-65) but was lower in patients in the ED than in those in the CPU (P <.01). Twenty-nine patients (4.3%; 23 women) were younger than 18 years, 277 (41%) patients were younger than 40 years, and 199 (30%) patients were older than 60 years. In Figure 1 the sex and age distribution of the patients is shown. 2 Distribution of diagnosis In 448 (67%) of 672 patients, a presumed or certain cause of the episode of TLOC was established. The distribution of causes of TLOC differed between the ED and the CPU (Table 2). Syncope was diagnosed equally often in the ED and CPU, in total in 336 (50%) of 672 patients. Reflex syncope was the most prevalent cause of syncope in both the ED and in the CPU, although the absolute magnitude differed (88% in ED and 43% in CPU; P <.01) (Table 2). Reflex syncope was more common in patients younger than 40 years than in patients older than 60 years (51% vs 25%, respectively; P <.01) (Table 3). Cardiac syncope was 10 times more prevalent in the CPU (18% of the patients) than in the ED (1.7% of the patients; P <.01) and was diagnosed in only 3 patients (1.1%) younger than 40 years. Of these 3 young patients, one was already known to have a cardiac condition (intermittent heart block). The other 2 patients presented with ventricular tachycardia without prior history of cardiac disease. Upon completion of their evaluation, 1 patient was found to have Brugada syndrome, the other was diagnosed with a ventricular tachycardia based on right ventricular dysplasia. In the patients older than 60 years, 26 (13%) were identified with a cardiac disorder (P <.01). Fourteen percent (n = 92) of the patients with TLOC was diagnosed with a neurological Table 2: Distribution of the different causes of TLOC in patients presenting to the ED and CPU Total n = 672 ED n = 526 CPU n = 146 p-value Syncope 336 (50%) 266 (51%) 70 (48%) - Reflex-syncopal syndromes 265 (39%) 235 (45%) 30 (21%) < 0.01 Vasovagal syncope Carotid sinus syncope Situational syncope Orthostatic hypotension 36 (5.4%) 22 (4.2%) 14 (9.6%) 0.01 Cardiac disorder 35 (5.2%) 9 (1.7%) 26 (18%) < 0.01 Cardiac arrhythmias Structural cardio-pulmonary conditions Neurological disorders 92 (14%) 88 (17%) 4 (2.7%) < 0.01 Metabolic disorders 6 (0.89%) 6 (1.1%) 0 (0%) 0.20 Psychiatric disorders 14 (2.1%) 13 (2.5%) 1 (0.68%) 0.18 Unknown 224 (33%) 153 (29%) 71 (49%) < 0.01 Neurological disorders include epilepsy, seizure, brain tumour and stroke. P-values are for the difference between ED and CPU.

9 38 Chapter 2 Table 3: Distribution of the different causes of TLOC per age group in patients presenting to the ED and CPU < 40 years n = years n = 196 > 60 years n = 199 Syncope 152 (55%) 91 (46%) 93 (47%) - p-value Reflex-syncopal syndromes 142 (51%) 73 (37%) 50 (25%) < 0.01 Vasovagal syncope 141 (51%) 71 (36%) 47 (24%) - Carotid sinus syncope 0 (0%) 0 (0%) 1 (0.5%) - Situational syncope 1 (0.4%) 2 (1.0%) 2 (1.0%) - Orthostatic hypotension 7 (2.5%) 12 (6.1%) 17 (8.5%) 0.01 Cardiac disorder 3 (1.1%) 6 (3.1%) 26 (13%) < 0.01 Cardiac arrhythmias 3 (1.1%) 4 (2.0%) 16 (8.0%) - Structural cardio-pulmonary conditions 0 (0%) 2 (1.0%) 10 (5.0%) - Neurological disorders 36 (13%) 34 (17%) 22 (11%) 0.17 Metabolic disorders 3 (1.1%) 1 (0.5%) 2 (1.0%) 0.79 Psychiatric disorders 10 (3.6%) 3 (1.5%) 1 (0.5%) Unknown 76 (34%) 67 (30%) 81 (41%) < 0.01 Neurological disorders include epilepsy, seizure, brain tumour and stroke. P-values are for the difference between age groups. 0.7 ED and CPU 9.3 General practice General population Figure 2: Syncope events/visits per 1000 person-years in the Netherlands

10 Syncope in the ED, general practice and population 39 disorder. This percentage was similar across age groups, and almost every patient with a neurological disorder was presented in the ED (96%). Comparison of syncopal episodes in the general population, general practice and emergency setting The precise calculations for the comparison of syncopal episodes in the different settings are attached in Appendix I. The crude cumulative rate of syncope events in the general Dutch population was approximately 18.1 per 1000 person-years (95% CI = ) in the CRANS study 7 and 39.7 per 1000 person-years (95% CI = ) in the medical students study. 6 The Transition project 22 reported 9.3 visits at the GP for syncope per 1000 person-years (95% CI = ). In the ED and CPU, we identified 0.7 visits per 1000 person-years due to syncope (95% CI = ) (Figure 2). Thus, the event rate for syncope in the general population was 1.9 to 4.3 times higher than the presentation rate in general practice. The event rate for syncope in general practice (9.3/1000 patient-years) exceeded the presentation rate in the ED/ CPU (0.7/1000 patient-years) by a factor of Both sex and age affected the background incidence in the population and the referral rate. In the general population, irrespective of age, syncope is more frequent in women than in men. The likelihood of a woman to visit a general practitioner after experiencing a syncopal episode increased from 1 out of 6.2 in women younger than 25 years to 1 out of 2.7 in women younger than 65 years (including the women younger than 25 (Figure 3). Young men were less likely to visit a GP for their syncopal episodes than were women (1/10.9 in men vs 1/6.2 in women), but this difference disappeared with higher age (1/3.4 in men vs 1/2.7 in women). Only a small proportion of patients with syncope in the general population visit the ED/ CPU, although visit rate more than doubles with higher age. In female patients older than 65 years, visit rate is 1.2 visits/1000 person-years (vs 0.6 in female patients younger than 25 years), and in male patients, 1.7 visits/1000 person-years (vs 0.1 in men younger than 25 years). More women than men younger than 65 years visit the emergency setting (0.7 vs 0.5 visits/1000 person-years), but above 65 years, there is a switch to more male patients (1.2 vs 1.7 visits/1000 person-years for women and men, respectively). 2 DISCUSSION Main findings In this study, 0.94% of the patients visiting the ED (0.80%) and CPU (2.6%) presented with TLOC. Half of the patients presenting with TLOC are diagnosed with syncope. Both in the ED (45%) and CPU (21%), reflex syncope is the main cause. Cardiac syncope is 10 times more prevalent in the CPU than in the ED (18% in the CPU vs 1.7% in the ED; P <.01). The event rate for syncope in the general population is much higher than the presentation rate in general

11 40 Chapter vis / 1000 pt-y 2.0 vis / 1000 pt-y 0.6 vis / 1000 pt-y ED and CPU General prac ce General popula on Youngerthan 25 years 1 : vis / 1000 pt-y 1 : ep / 1000 pt-y 50.5 ep / 1000 pt-y male female 0.5 vis / 1000 pt-y 0.7 vis / 1000 pt-y 0-65 years 1 : vis / 1000 pt-y 8.5 vis / 1000 pt-y 1 : ep / 1000 pt-y 23.3 ep / 1000 pt-y male female 1.7 vis / 1000 pt-y 1.2 vis / 1000 pt-y Older than 65 years 22.2 vis / 1000 pt-y 20.9 vis / 1000 pt-y Unknown Unknown male female Figure 3: Event and visitation rates per 1000 person-years in the general population, general practice, and emergency settings by age and sex

12 Syncope in the ED, general practice and population 41 practice, which exceeds the presentation rate in the ED/CPU by far, indicating a strong selection in the referral of patients with syncope. Prevalence of TLOC in emergency settings The frequency of TLOC in our study of about 1% is similar to that of recent studies performed in community-based EDs in Europe. These studies have found that 0.9% to 1.7% of visits are because of TLOC In an older, frequently cited study from the United States by Day et al. 30, the prevalence was as high as 3%. However, this study also included patients visiting the ED because of complaints that might be associated with TLOC, like head trauma, strokes, and transient ischemic attacks. Only 0.8% of the patients in the study of Day et al. 30 were thought to have TLOC due to syncope or new-onset seizures, which is compatible with our and other results. 2 Distribution of diagnoses in the ED/CPU In studies 21, 23-26, 28, 29, on the epidemiology of TLOC in the ED, as in this study, approximately half of the patients with TLOC were diagnosed with a reflex syncope. Variations in results between individual studies (35%-66%) are likely because of differences in study design and inclusion criteria and differences in age in the area of care. 3 Sarasin et al. 24 found that 24% of the patients with TLOC had orthostatic hypotension, in contrast with approximately 6% in our and other studies. 21, 23, 25, 28 This high frequency of the diagnosis of orthostatic hypotension can be explained by the older population in their study (mean age = 60 years), with many patients using vasoactive medication. Furthermore, the thorough measurement of orthostatic blood pressure (6 times during a 10-minute standing period), which is longer and more frequent than advised in the ESC guidelines on syncope 17, could explain this high prevalence. 34 The percentage of neurological causes for TLOC of 14% in the present study is slightly higher than reported in most previous studies (2%-14%) 21, 23-26, 28, 31, 32, focusing on the epidemiology of TLOC in emergency settings. However, the results are not directly comparable. In most studies, patients with symptoms that were clearly compatible with a seizure disorder 23-26, 28 or patients with an already known seizure disorder presenting with a typical recurrence 21, 32 (and this study) were excluded. If all patients with epileptic episodes presenting in the emergency 30, 35 setting are included, a remarkably high percentage (32%) has been reported. Selection of patients for clinical evaluation We calculated 18.1 syncope episodes per 1000 patient-years in the (35- to 60-year-old) general population, whereas we found 39.7 episodes per 1000 patient-years in medical students. 6, 7 Recollection bias in older subjects and the peak of syncope episodes in teenagers and young adults can explain the difference between the 2 age groups in the general population.

13 42 Chapter 2 In general practice, a peak in the number of visits for TLOC episodes exists not only in teenagers and young adults but also in elderly (>60 years) subjects. 4, 22 In this study, elderly subjects are much more likely to visit their GP in relation to their episode than are young subjects (22.2 vs 2.0 visits/1000 patient-years for elderly vs young men, respectively; 20.9 vs 8.2 visits/1000 patient-years for elderly and young women), probably mainly because their episodes are often considered to be caused by life-threatening disorders. An even stronger selection mechanism exists for visiting the ED. We computed a crude incidence of episodes of TLOC in the ED of 0.7 visits/1000 patients-years. This is only a fraction of the number of patients with TLOC in the general population and the number of patients presenting to general practice. The frequency of 0.7 visits/1000 patient-years is lower than the frequency of 2.4 to 2.6 visits/1000 patient-years reported by the Italian groups. 23, 29 This difference can be explained by the difference in age of the resource area, which is much higher in their study populations. This age effect is compatible with the results from the Framingham study 12, in which 56% of the (older) subjects seek medical attention for their episodes, and the results of Driscoll et al. 36, which show that children and adolescents with syncope are rarely referred to medical specialists. Severe cardiac disorders are much more frequent in the ED/CPU than in general practice, and the age of the patients presenting with syncope is much higher than the age of patients with syncope in the general population. Like those of the study of Driscoll et al. 36, our data show that in emergency settings, patients younger than 40 years without a cardiac history rarely have life-threatening disorders. It therefore seems that there is a strong filter for patients with syncope, with more highrisk older patients presenting to specialized care settings, like the CPU. This filter is especially strong in the young, but correct given the very low number of serious diagnoses in these young subjects (for review, see Colman et al. 4 ). Obviously, however, the number of patients with lethal forms of syncope not presenting to a medical specialist has not been addressed in our study. Limitations There are a couple of limitations to this study. The determination of the cause of the TLOC depended on the history and physical examination and, if necessary, additional diagnostic tests, for example, electrocardiography. There was no follow-up, so the diagnosis could not be confirmed or changed over time. Although misclassification might have occurred in some patients, it is unlikely that it would have disturbed the overall distribution of diagnoses. This study describes the epidemiology of TLOC in the ED and CPU. This distinction between 2 types of emergency units and the medical system with GPs as gatekeepers might make the results less applicable to countries with a different organization of the medical system. To calculate different referral rates, we had to combine different data sets (subpopulations) rather than follow a single population across settings. This resulted in differences in pertinent factors such as characteristics of the study samples and time period during which the stud-

14 Syncope in the ED, general practice and population 43 ies were conducted. Therefore, although these different data sets all came from the same source population and used the same definitions of TLOC/syncope, the referral rates should be interpreted as providing a general picture about referral rather than exact numbers. 2 CONCLUSION The prevalence of TLOC in the ED and CPU in The Netherlands is 0.94%. Fifty percent of these patients have syncope. Only a small but probably selected high-risk group of patients with syncope are presented in the ED or CPU. This epidemiological knowledge can now be used for a cost-effective diagnostic approach of patients with TLOC and to permit the design of clinical trials, diagnostic strategies, and health services delivery. Better recognition especially of vasovagal syncope in general practice by taking good clinical history and physical examination may lead to a further decrease in patients with non high-risk syncope in the emergency settings.

15 44 Chapter 2 REFERENCE LIST 1. Kapoor WN. Syncope. N Engl J Med 2000;343: Thijs RD, Wieling W, Kaufmann H, van DG. Defining and classifying syncope. Clin Auton Res 2004;14 Suppl 1: Sheldon RS, Serletis A. Epidemiologic aspects of transient loss of consciousness/syncope. Syncope and Transient Loss of Consciousness: Multidisciplinary Management.Malden: Blackwell Publishing; p Colman N, Nahm K, Ganzeboom KS, Shen WK, Reitsma J, Linzer M, Wieling W, Kaufmann H. Epidemiology of reflex syncope. Clin Auton Res 2004;14 Suppl 1: Kapoor WN. Syncope-past, present and future. Clin Auton Res 2004;14 Suppl 1: Ganzeboom KS, Colman N, Reitsma JB, Shen WK, Wieling W. Prevalence and triggers of syncope in medical students. Am J Cardiol 2003;91:1006-8, A8. 7. Ganzeboom KS, Mairuhu G, Reitsma JB, Linzer M, Wieling W, van Dijk N. Lifetime cumulative incidence of syncope in the general population: a study of 549 Dutch subjects aged years. J Cardiovasc Electrophysiol 2006;17: Thijs RD, Kruit MC, van Buchem MA, Ferrari MD, Launer LJ, van Dijk JG. Syncope in migraine: the population-based CAMERA study. Neurology 2006;66: Sheldon RS, Sheldon AG, Connolly SJ, Morillo CA, Klingenheben T, Krahn AD, Koshman ML, Ritchie D. Age of first faint in patients with vasovagal syncope. J Cardiovasc Electrophysiol 2006;17: Serletis A, Rose S, Sheldon AG, Sheldon RS. Vasovagal syncope in medical students and their firstdegree relatives. Eur Heart J 2006;27: Chen LY, Shen WK, Mahoney DW, Jacobsen SJ, Rodeheffer RJ. Prevalence of syncope in a population aged more than 45 years. Am J Med 2006;119: Soteriades ES, Evans JC, Larson MG, Chen MH, Chen L, Benjamin EJ, Levy D. Incidence and prognosis of syncope. N Engl J Med 2002;347: Wieling W, Ganzeboom KS, Krediet CT, Grundmeijer HG, Wilde AA, van Dijk JG. [Initial diagnostic strategy in the case of transient losses of consciousness: the importance of the medical history]. Ned Tijdschr Geneeskd 2003;147: Okkes IM, Oskam SK, Lamberts H. From complaint to diagnosis. Episode data from general practice. Bussum: Coutinho; Foets M, Sixma H. A national study on disease and activities in general practise. Report on health and health behavior in the general practise population. Utrecht: Nivel; Huff JS, Decker WW, Quinn JV, Perron AD, Napoli AM, Peeters S, Jagoda AS. Clinical policy: critical issues in the evaluation and management of adult patients presenting to the emergency department with syncope. Ann Emerg Med 2007;49: Brignole M, Alboni P, Benditt DG, Bergfeldt L, Blanc JJ, Thomsen PE, Gert van DJ, Fitzpatrick A, Hohnloser S, Janousek J, Kapoor W, Kenny RA, Kulakowski P, Masotti G, Moya A, Raviele A, Sutton R, Theodorakis G, Ungar A, Wieling W, Priori SG, Garcia MA, Budaj A, Cowie M, Deckers J, Burgos EF, Lekakis J, Lindhal B, Mazzotta G, Morais J, Oto A, Smiseth O, Menozzi C, Ector H, Vardas P. Guidelines on management (diagnosis and treatment) of syncope-update Executive Summary. Eur Heart J 2004;25: Piek JJ. Emergency room in numbers. Available from accessed on Annual report 2000, Academic Medical Center - University of Amsterdam; First Cardiac Aid. Amsterdam; 2000.

16 Syncope in the ED, general practice and population O&S. Core numbers Amsterdam Available from accessed on van Dijk N., Boer KR, Colman N, Bakker A, Stam J, van Grieken JJ, Wilde AA, Linzer M, Reitsma JB, Wieling W. High diagnostic yield and accuracy of history, physical examination, and ECG in patients with transient loss of consciousness in FAST: the Fainting Assessment study. J Cardiovasc Electrophysiol 2008;19: Lamberts H, Okkes IM. Transition project. Available from accessed on Brignole M, Menozzi C, Bartoletti A, Giada F, Lagi A, Ungar A, Ponassi I, Mussi C, Maggi R, Re G, Furlan R, Rovelli G, Ponzi P, Scivales A. A new management of syncope: prospective systematic guideline-based evaluation of patients referred urgently to general hospitals. Eur Heart J 2006;27: Sarasin FP, Louis-Simonet M, Carballo D, Slama S, Rajeswaran A, Metzger JT, Lovis C, Unger PF, Junod AF. Prospective evaluation of patients with syncope: a population-based study. Am J Med 2001;111: Blanc JJ, L her C, Gosselin G, Cornily JC, Fatemi M. Prospective evaluation of an educational programme for physicians involved in the management of syncope. Europace 2005;7: Crane SD. Risk stratification of patients with syncope in an accident and emergency department. Emerg Med J 2002;19: Ammirati F, Colivicchi F, Minardi G, De LL, Terranova A, Scaffidi G, Rapino S, Proietti F, Bianchi C, Uguccioni M, Carunchio A, Azzolini P, Neri R, Accogli S, Sunseri L, Orazi S, Mariani M, Fraioli R, Calcagno S, De LF, Santini M. [The management of syncope in the hospital: the OESIL Study (Osservatorio Epidemiologico della Sincope nel Lazio)]. G Ital Cardiol 1999;29: Blanc JJ, L her C, Touiza A, Garo B, L Her E, Mansourati J. Prospective evaluation and outcome of patients admitted for syncope over a 1 year period. Eur Heart J 2002;23: Disertori M, Brignole M, Menozzi C, Raviele A, Rizzon P, Santini M, Proclemer A, Tomasi C, Rossillo A, Taddei F, Scivales A, Migliorini R, De ST. Management of patients with syncope referred urgently to general hospitals. Europace 2003;5: Day SC, Cook EF, Funkenstein H, Goldman L. Evaluation and outcome of emergency room patients with transient loss of consciousness. Am J Med 1982;73: Farwell D, Sulke N. How do we diagnose syncope? J Cardiovasc Electrophysiol 2002;13:S Ammirati F, Colivicchi F, Santini M. Diagnosing syncope in clinical practice. Implementation of a simplified diagnostic algorithm in a multicentre prospective trial - the OESIL 2 study (Osservatorio Epidemiologico della Sincope nel Lazio). Eur Heart J 2000;21: Brignole M, Disertori M, Menozzi C, Raviele A, Alboni P, Pitzalis MV, Delise P, Puggioni E, Del GM, Malavasi V, Lunati M, Pepe M, Fabrizi D. Management of syncope referred urgently to general hospitals with and without syncope units. Europace 2003;5: Sarasin FP, Louis-Simonet M, Carballo D, Slama S, Junod AF, Unger PF. Prevalence of orthostatic hypotension among patients presenting with syncope in the ED. Am J Emerg Med 2002;20: Thijs RD, Granneman E, Wieling W, van Dijk JG. [Terms in use for transient loss of consciousness in the emergency ward; an inventory]. Ned Tijdschr Geneeskd 2005;149: Driscoll DJ, Jacobsen SJ, Porter CJ, Wollan PC. Syncope in children and adolescents. J Am Coll Cardiol 1997;29:

17 46 Chapter 2 Appendix Appendix I: Calculations Persons under 25 years Women Data Episodes/visits per 1000 person-years General population women experienced a total of (95% CI: ) episodes during a mean total follow-up of 21.0 years General practice visits were made for syncope in (95% CI: ) person-years ED and CPU 51 visits were made for syncope in 2 years, or 25.5 per year. The resource area for our institution consists of women under 25 years 0.64 (95% CI: ) Men Data Episodes/visits per 1000 person-years General population men experienced a total of 58 episodes 21.7 (95% CI: ) during a mean total follow-up of 21.7 years General practice visits were made for syncope in (95% CI: ) person-years ED and CPU 12 visits were made for syncope in 2 years. The resource area consists of men under 25 years 0.15 (95% CI: ) Total For both the general practice and the ED and CPU, the total can be calculated with the above-mentioned numbers of visits and person-years. This is not possible with the numbers of the general population 6, because for the calculation of the total we included 17 students of which the gender (now irrelevant) was missing. Therefore there were 394 students who experienced 333 episodes in total in 21.4 years, resulting in 39.7 episodes/1000 person-years (95% CI: ).

18 Syncope in the ED, general practice and population years Women Data Episodes/visits per 1000 person-years General population of 278 women experienced a total of (95% CI: ) episodes of fainting in 47.3 years (mean age) General practice visits were made for syncope in (95% CI: ) person-years ED and CPU 152 visits were made for syncope in 2 years. The resource area consists of women under 65 years 0.69 (95% CI: ) 2 Men Data Episodes/visits per 1000 person-years General population 7 77 of 271 men experienced a total of (95% CI: ) episodes of fainting in 47.7 years (mean age) General practice visits were made for syncope in (95% CI: ) person-years ED and CPU 104 visits were made for syncope in 2 years. The resource area consists of men under 65 years 0.46 (95% CI: ) Total The total can be calculated with the above-mentioned numbers. Persons above 65 years Women Data Episodes/visits per 1000 person-years General practice visits were made for syncope in (95% CI: ) person-years ED and CPU 39 visits were made for syncope in 2 years. The resource area consists of women above 65 years 1.2 (95% CI: ) Men Data Episodes/visits per 1000 person-years General practice visits were made for syncope in (95% CI: ) person-years ED and CPU 41 visits were made for syncope in 2 years. The resource area consists of men above 65 years 1.7 (95% CI: ) Total The total can be calculated with the above-mentioned numbers.