QJM Advance Access originally published online on January 9, 2008
QJM 2008 101(2):127-135; doi:10.1093/qjmed/hcm140
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Self-reported symptom burden; outcome in 418 patients from the Newcastle Vasovagal (Neurocardiogenic) cohort
From the 1Falls and Syncope Service, Royal Victoria Infirmary and 2Institute of Cellular Medicine, School of Clinical Medical Sciences, University of Newcastle, UK
Address correspondence to Dr Julia L. Newton, Falls and Syncope Service/Cardiovascular Investigation Unit, University of Newcastle, Royal Victoria Infirmary, Newcastle NE1 4LP, UK. email: julia.newton{at}nuth.nhs.uk
Received 16 August 2007 and in revised form 22 October 2007
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Summary |
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Background: Natural history of Vasovagal syndrome (Neurocardiogenic; NCS) is unclear.
Aim: To examine symptoms in a large cohort with head up tilt diagnosed NCS.
Methods: Questionnaires were posted to 485 patients with NCS. Data included demographic details, age at referral, presenting and on-going symptoms (syncope, dizziness and falls), symptom frequency (daily, weekly, monthly) and burden.
Results: A total of 418 questionnaires were returned (response rate 86%), 67% female. Median age at first presentation 60 (range 10–90), with men younger (54 vs. 63; P = 0.01). Seventy percent presented with syncope. Median follow-up 5 years (1–8). At follow-up 147(35%) were asymptomatic. The asymptomatic group was older (73 vs. 65; P = 0.0001) with more males (39 vs. 29%; P = 0.04). Those presenting with syncope were more likely to be symptom-free than those with dizziness (P < 0.02). Symptom frequency was greatest for those reporting dizziness at follow-up (P < 0.05). Sixty (22%) reported symptoms never preventing activities [predominantly those reporting dizziness (P = 0.04)]. Although there was a significant reduction of symptoms overall, there was a significant increase in those reporting dizziness only (P < 0.0001).
Conclusions: Of those with NCS, 35% will be symptom-free at 5 years regardless of presenting symptom or treatment received.
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Introduction |
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Vasovagal or neurocardiogenic syndrome (NCS) is a common, benign condition that is not associated with increased mortality.1,2 NCS is characterized by hypotension with or without bradycardia, this leads to cerebral hypoperfusion which may present as symptoms of dizziness (pre-syncope) or under more profound circumstances result in collapse with loss of consciousness (syncope).3,4 Studies suggest that syncope and pre-syncope recurrence due to NCS is low5 but the follow-up period of these studies has been short.5,6
It is recognized that NCS is associated with impaired health-related quality of life (HRQOL). The severity of the HRQOL impairment is proportional to syncope frequency7,8 and considered to be as severe as that seen in other chronic diseases such as epilepsy, rheumatoid arthritis and low back pain.9,10
The perception of symptoms to the physician need not necessarily correlate with that of the patient. In fact, although for clinical studies in NCS the important endpoint is generally considered to be syncope recurrence, to patients this is often not the case, and the ‘fear of episodes’ or less severe symptoms such as pre-syncope is for an individual patient a significant symptomatic burden.
One of the questions most frequently asked in clinical practise by patients with NCS is ‘how long will it last’. The objectives of the current study were to address this question in a large cohort of patients with head up tilt (HUT) diagnosed NCS. First we determined the type of symptoms and their severity in this group, then the proportion of patients who became symptom-free and the duration of those symptoms.
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Methods |
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Study population
The derivation of the Newcastle Vasovagal Database (n = 603) has previously been reported in detail11 and briefly comprises all these patients who had been seen at the Newcastle Falls and Syncope Service (FASS), with a definitive diagnosis of NCS made between 1991 and 2001. A definitive diagnosis of NCS was when individuals developed hypotension with or without bradycardia on HUT testing with reproduction of symptoms. The unit follows a standard protocol for the assessment of patients with possible NCS. This protocol has been reported elsewhere.12
Of the 603 patients on the Vasovagal database a current address was available for 543 patients. Fifty-eight patients had died (15%), providing a study population of 485 individuals eligible to participate, the process for deriving the study cohort is shown in Figure 1.
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Data collection
To facilitate a high response rate, patients were sent a short postal questionnaire rather than a formal evaluation of quality of life. This was posted in 2003 to eligible NCS patients registered on the Newcastle Vasovagal Database. Ethical permission was obtained from the Newcastle and North Tyneside Ethical Committee.
The questionnaire collected the following information:
- Basic demographic details
- Age at time of initial referral
- Information about presenting symptoms [blackouts (syncope), dizziness (pre-syncope) and falls] and on-going symptoms [blackouts (syncope), dizziness (pre-syncope) or falls]
- Whether or not they were still attending the FASS for review.
- Individuals were asked to select one or more symptoms [blackouts (syncope), dizziness (pre-syncope) and falls] applicable to themselves. Patients were asked about symptom frequency, (as a measure of symptom burden) and whether a symptom stopped them from doing things (as a measure of symptom severity). For each current symptom reported, patients were asked to select from one of the four categories with respect to the frequency of each symptoms (daily, weekly, monthly or less often).
Statistical analysis
The software used for statistical analysis was Minitab 13. For continuous data, graphs were first obtained to ascertain if the data were normally distributed (parametric) or skewed (non-parametric). All continuous data were non-parametric, therefore medians and inter-quartile ranges are stated and non-parametric tests (Mann–Whitney) were used to compare continuous variables. For categorical data, frequencies were measured. Differences in proportions were compared using chi-squared tests. For all tests, statistical significance level was set as P = 0.05.
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Results |
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Four hundred and eighty-five individuals were eligible to participate. Completed questionnaires were returned by 418 patients (response rate 86%). Demographic details of those returning the questionnaire are presented in Table 1. Sixty-seven percent of the total cohort was female and 33% male. Median age at first presentation to the FASS was 60 years (range 10–90) with men significantly younger [median 54(range 10–84)] compared to women (63) (P = 0.01) (Table 1).
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Patient demographics
At presentation for the first time to the FASS
The mode of first presentation to the FASS included various combinations of syncope, dizziness and falls (Figure 2). Seventy percent of patients presented with a history that included syncope, 2% presented with a history of falls only, 20% reported dizziness only. There was no difference in age or sex at presentation in those reporting dizziness, syncope or falls as part of symptom complex. However in those who reported one symptom only, those reported that they presented with falls only were significantly older (P = 0.02). This group were excluded from further analysis. Details of the presenting symptoms are outlined in Table 2.
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At the time of completion of the follow-up questionnaire
The median study follow-up period for the total group who returned questionnaires (i.e. the difference between when they were first seen in the FASS and time of completion of the questionnaire) was 5 years (range 1–8) (Table 1).
Three hundred and forty-three (84%) of the group were no longer attending the FASS unit for review at the time of the follow-up questionnaire. There was no significant difference in follow-up interval or review status according to symptom at presentation or whether or not the symptom was reported in isolation or as part of a symptom complex (data not shown). Review of medical notes confirmed that 96 of the total group had cardiovascular comorbidity (23%), and 79 (19%) were taking potentially culprit (vasoactive medication).
Comparing asymptomatic to symptomatic patients at the time of completion of the follow-up questionnaires
In order to look for any factors that might potentially predict outcome, we compared patients who remained symptomatic vs. those with no symptoms at the time of completion of the follow-up questionnaire. One hundred and forty-seven (35%) of the cohort were asymptomatic. The asymptomatic group was significantly older (73 vs. 65; P = 0.0001), had proportionately more males (39 vs. 29%; P = 0.04) and as would be expected were less likely to be under continued review in the FASS (8.3 vs. 20%; P = 0.002). Two hundred and one (48%) had been treated with conservative advise alone (increased fluid intake and counter manoeuvres), 155 (37%) with treatment with medication such as fludrocortisone, midodrine or atenolol and 62 (15%) with withdrawal of potentially vasoactive treatment.
The proportions of each presenting symptom group who at follow-up described themselves as asymptomatic are shown in Table 2. At follow-up those who had reported syncope at presentation were more likely to be symptom-free than those who reported dizziness (pre-syncope) either as part of a symptom complex (P = 0.007), or as a symptom in isolation (P = 0.02). There was no difference in those who were symptom-free at follow-up between those who had reported dizziness (pre-syncope) as part of a symptom complex and falls as part of a symptom complex (P = 0.16).
More individuals were symptom-free in the group who reported syncope only at presentation rather than syncope as part of a symptom complex (P = 0.02). There was no difference in the proportions of those who were symptom-free in the groups who reported dizziness (pre-syncope) or falls as part of a symptom complex compared with those who reported pre-syncope or falls only at presentation. Therefore syncope alone at presentation with VVS conveys the best likelihood for patients to be asymptomatic within a median of 5 years follow-up.
Symptomatic patients at time of completion of the follow–up questionnaire
Of the 269 (65%) who remained symptomatic at the time of completing the follow-up questionnaire, 149 (36%) reported one symptom, 68 (16%) two symptoms and 52 (13%) three symptoms at follow-up. The characteristics of those individuals with NCS who reported each symptom at follow-up compared to symptom-free individuals are shown in Tables 3–5
. At follow-up the majority of the symptomatic NCS group [245 (91%)] reported dizziness (pre-syncope), of those 132 (32%) reported pre-syncope only at follow-up. Syncope was reported by 97 (36%) of the symptomatic group with syncope only reported by 9 (2%) of the NCS group at follow-up. At follow–up, 99 (37%) of the VVS group reported falls. Those reporting falls at follow-up were older than those reporting syncope (median 60 years; P = 0.01), 8 (2%) reported falls only.
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Persistence of presenting symptom at follow-up
Persistence of syncope at follow-up
Of the 290 individuals who reported syncope at presentation, 89 (31%) reported that they still had syncope at follow-up, whilst 200 (69%) no longer experienced syncope (data not available for one individual). Those whose syncope persisted [median age 60, (IQR 48–72)], were younger than those who became syncope-free [median age 68 (IQR 53–79)] (Tables 6–8
).
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Persistence of pre-syncope at follow-up
Of those who reported dizziness (pre-syncope) at presentation n = 281, 218 (78%) continued to be symptomatic. Two hundred and thirteen (76%) continued to report pre-syncope at follow-up (Tables 6–8
) whilst 63 became symptom-free (22%). Those who continued to have pre-syncope were younger (median age 64) than those who no longer suffered pre-syncope (76 years) (P = 0.002). There was no difference in the sex distribution of those who continued to suffer pre-syncope compared with those who were pre-syncope-free (P = 0.07). The follow-up interval was longer in those who were pre-syncope-free (median 5 years) compared with those who continued to suffer pre-syncope (median 4 years) (P = 0.04).
Persistence of falls at follow-up
Of the 176 who reported falls at presentation, 75 (43%) reported that they were still falling at the follow-up review. There was no difference in age, sex or follow-up interval between persistent fallers and those who no longer fell (Tables 6–8).
Frequency of symptoms at the time of completion of the follow–up questionnaire
Of the 269 individuals who reported symptoms at follow-up, 142 (52.8%) reported a symptom frequency of monthly or less, 71 (26%) a weekly basis and 43 (16%) reported daily symptoms (Figure 3).
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The symptom frequency appeared to be greatest for those reporting dizziness (pre-syncope) at follow-up, with those reporting pre-syncope having more frequent daily and weekly symptoms than those reporting syncope or falls. Monthly symptoms were more frequently reported by those reporting pre-syncope compared to those reporting syncope (P = 0.05). Less than monthly symptom occurrence was more frequently reported by those reporting syncope compared to those reporting pre-syncope (P < 0.000). Fallers reported less than monthly symptoms more than those reporting pre-syncope (P < 0.000).
Comparison of presenting symptoms and symptoms at follow-up
Overall there was a significant reduction at follow-up of reported pre-syncope, syncope and falls. There was a significant increase in the number of individuals who reported pre-syncope only. During the time from presentation to follow-up, 32 individuals developed pre-syncope, 8 reported onset of syncope and 24 reported falls (Table 9).
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Discussion |
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This pragmatic, observational study has shown that 35% of patients attending a Syncope Clinic and diagnosed with NCS will be asymptomatic 5 years after follow-up. Asking patients to self report the impact of their symptoms importantly reflects the patients’ perception of these symptoms rather than physician judgement of outcome. This approach is important, because in chronic disease settings it has been observed that a physician's judgement of the severity of symptoms differs significantly from that of the patients.10
Our study has shown that the burden of pre-syncope at presentation is as large as that of syncope (67% of the group admitted to pre-syncope compared to 69% who reported syncope). In most vasovagal studies, only those with syncope have been included on the grounds that pre-syncope is considered hard to measure. The current study suggests that if syncope is the only symptom on which studies of NCS are based, nearly 30% of individuals who have a definitive HUT diagnosis of NCS will not be excluded from inclusion. Therefore, to fail to include those who describe vasovagal pre-syncope is to exclude a sizable proportion of the vasovagal population. This finding is important for both clinicians managing patients with pre-syncope and researchers as an impulse to create new diagnostic and therapeutic strategies. Potentially results from studies based on those with syncope may only be applicable to those with this specific symptom.
Of interest is the finding in this study that 2% of those with NCS described themselves as presenting with isolated falls. The area of syncope and falls is controversial. It is recognized that carotid sinus syndrome, another cause of neurally mediated reflex syncope may present as falls. Some of these individuals have been witnessed to be amnesic for syncope.13,14 This may also be true for vasovagal syncope i.e. the episode of syncope is not recalled because of amnesia. Alternatively, the fall may happen in the prodromal pre-syncopal phase: 25 (6%) reported falls and pre-syncope. This may be related to the fact that those who presented with isolated falls were significantly older than those presenting with isolated syncope or pre-syncope. The apparent overlap between falls and syncope may also be related to a difference in understanding between the physician's description of blackout (syncope) as a symptom and that of a patient.
Further studies are needed in order to determine whether comorbidity, treatment, VASIS type reaction on head up tilt, or whether the type of tilt test protocol used to diagnose NCS predict response to treatment or natural history of NCS. On-going prospective studies examining these parameters will potentially address these issues in the near future.
At follow-up there was a reduction in all symptoms with 35% reporting that they were now symptom-free. Symptom reduction was greatest in those who reported syncope at presentation. Of those who presented with syncope, at the median follow-up interval of 5 years 36% became symptom-free. During the follow-up period, eight individuals developed syncope. Although it is probable that this new onset of syncopal symptoms is NCS, this may not be the case. Further evaluation is necessary to determine the underlying cause of this new onset syncope. Ninety-one percent of those who reported syncope at follow-up had reported syncope as a presenting symptom. Recurrences of syncope were reported by individuals up to 16 years after first presentation. Although it is not known how long individuals may experience recurrences, it has been recognized by other authors that individuals may experience syncopal episodes for years. 2,6–8,15–18
The improvement in symptoms was less efficient in those who presented with pre-syncope with only 22% of those who had originally presented with pre-syncope reported that they were symptom-free. Seventy-six percent of those who presented with pre-syncope reported continued pre-syncope at follow-up. This fits with clinical experience that pre-syncope is the most frequently reported symptom and the hardest to treat. Overall there was a reduction in numbers reporting pre-syncope at follow-up, 59% compared to 67% at presentation. However, there was an increase in the number reporting pre-syncope only at follow-up (32%) compared to presentation (21%), many patients go on to develop what might be considered by physicians to be ‘less severe’ symptoms of pre-syncope.
Most of the symptomatic group (53%) reported that their symptoms occurred monthly or less often, whilst 16% reported that they experienced weekly symptoms. Graham and Kenny17 comment that in their study the average frequency of attacks was weekly. Sheldon and colleagues16 and Rose and colleagues7 report symptom frequency as ‘a median of 0.17 spells per month’. In this study of the Newcastle cohort, 41% reported a symptom frequency of less than monthly and 54% reported symptoms more frequently than monthly. In comparison to Sheldon and Rose's populations, the Newcastle cohort has a higher frequency of events. But this will be related to the fact that the previous literature did not consider the burden of pre-syncope and were restricted to syncope only, whereas the current study includes pre-syncope and falls in addition to syncope. If one considers syncope only, in the current study, 63% reported that syncope occurred less than monthly; 34% reported that they had episodes of syncope monthly or more frequently. Twelve percent reported weekly episodes of syncope.
It could be argued that this study has several major flaws. As a tertiary referral unit the patients included may not be representative of those seen in a general hospital syncope clinic. There may be error in the measurement of the presenting symptoms as individuals were asked to record retrospectively what their presenting symptoms were some years previously. The study does not use hard endpoints but we have asked the patients their perception of their symptoms and how they affect their lives. We would suggest that rather than invalidating our results that this simply allows us to get a different perspective on disease symptoms and how they affect this patient group. In addition, the focus for management of NCS has changed over the last 15 years, with a move away from the use of medication to conservative advise (increasing fluid intake and counter manoeuvres). We would suggest that although this is not ideal, that the purpose of this pragmatic study was to describe the natural history of NCS.
In this study, the median age for the group at follow-up was 60 years. This is similar to the age of populations studied of syncope in general (50–60 years) but older than the populations studied for NCS and may reflect referral bias to our service. It is important to acknowledge however that our findings require confirmation in other centres and in a younger population.
Despite the limitations of a pragmatic, questionnaire-based, patient-orientated study, this study can draw some important conclusions for patients and clinicians working with patients with NCS. Of symptomatic individuals who have a vasovagal response on HUT test, 35% will be free of symptoms at 5 years regardless of their presenting symptom or treatment received. Pre-syncope is an important symptom. The impact it has on our patient population suggests that it should be included as an endpoint in future studies.
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Acknowledgement |
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Ethical permission was given by the Newcastle and North Tyneside Ethical Committee
Conflict of interest: None declared.
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References |
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1. Soteriades ESE, Evans JC, Larson M, Chen MH, Chen L, Benjamin E J, et al. Incidence and prognosis of syncope. N Engl J Med (2002) 347:878–85.
2. Linzer M, Pontinen M, Gold DT, Devine G, Felder A, Brooks WB. Impairment of physical and psychosocial function in recurrent syncope. J Clin Epidemiol (1991) 44:1037–43.[CrossRef][Web of Science][Medline]
3. Brignole M, Alboni P, Benditt DG, Bergfeldt L, Blanc J-J, Bloch Thomsen PE, et al. Task Force on Syncope ESoC. Guidelines on the management (diagnosis and treatment) of syncope. Eur Heart J (2001) 22:1256–306.
4. Parry S, Kenny RA. Tilt table testing in the diagnosis of unexplained syncope. Q J Med (1999) 92:623–29.[Web of Science]
5. Baron-Esquivias G PA, Cayuela A, Valle JI, Fernandez JM, Arana E, Fernandez M, et al. Long term outcome of patients with asystole induced by head-up tilt test. Eur Heart J (2002) 23:483–89.
6. PerezParedes M AF, Villaneuva JGS, Sanchez RF, Ordonez EE, Ortega Mg, Callero EG, et al. Prognosis and long-term follow-up in patients with syncope of unknown origin and cardiac asystole induced by head up tilt test. Rev Esp Cardiol (1997) 50:314–19.[Web of Science][Medline]
7. Rose MS, Koshman ML, Spreng S, Sheldon R. The relationship between health-related quality of life and frequency of spells in patients with syncope. J Clin Epidemiol (2000) 53:1209–16.[CrossRef][Web of Science][Medline]
8. Baron-Esquivias G GS, Aquilera A, Campos A, Romero N, Cayuela A, Valle JI, et al. Short-term evolution of vasovagal syncope: influence on quality of life. Int J Cardiol (2005) 102:315–19.[CrossRef][Web of Science][Medline]
9. Linzer M, Gold D T, Pontinen M, Divine GW, Felder A, Brooks B. Recurrent syncope as a chronic disease:preliminary validation of a disease-specific measure of functional impairment. J Int Med (1994) 9:181–6.[Web of Science]
10. Linzer M, Felder A, Hackel A, Brunetti LL, Perry AJ, Brooks WB. Functional disability due to syncope and pre-syncope. Clin Res (1988) 36:714A.
11. Newton JL, Kenny RA, Lawson J, Frearson R, Donaldson P. Prevalence of family history in vasovagal syncope and haemodynamic responses to head up tilt in first degree relatives- preliminary data for the Newcastle cohort. Clin Auton Res (2003) 13:22–6.[CrossRef][Web of Science][Medline]
12. Kenny RA, O'Shea D, Parry SW. The Newcastle protocols for head-up tilt table testing in the diagnosis of vasovagal syncope, carotid sinus hypersensitivity and related disorders. Heart (2000) 83:564–9.
13. Shaw FE, Kenny RA. The overlap between falls and syncope in the elderly. Postgrad Med J (1997) 73:635–9.
14. Kenny RA, Traynor G. Carotid sinus Syndrome-clinical characteristics in elderly patients. Age Ageing (1991) 20:449–54.
15. Kenny RA, Ingram A, Bayliss J, Sutton R. Head-up tilt: a useful test for the investigating unexplained syncope. Lancet (1986) 1:1352–55.[CrossRef][Web of Science][Medline]
16. Sheldon R, Sexton E, Koshman ML. Usefulness of clinical factors in predicting outcomes of positive tilt tests in patients with syncope. Am J Cardiol (2000) 85:360–4.[CrossRef][Web of Science][Medline]
17. Graham LA, Kenny RA. Clinical characteristics of patients with vasovagal reactions presenting as unexplained syncope. Europace (2001) 3:141–6.
18. Ruiz GA, Peralta A, Gonzalez-Zuelgaray, Duce E. Evolution of patients with clinical neurocardiogenic (vasovagal) syncope not subjected to specific treatment. Am Heart J (1995) 130:345–50.[CrossRef][Web of Science][Medline]
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  B. Flint, C. Baker, M. Freeston, and J. L. Newton Level of psychosocial impairment predicts early response to treatment in vasovagal syncope Europace, February 1, 2009; 11(2): 231 - 236. [Abstract] [Full Text] [PDF]
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