Best Evidence Interview: Predicting Syncope Outcome With BRACES
Best Evidence Interview: Predicting Syncope Outcome With BRACES
Dr. Reed was lead author of:
Reed MJ, Newby DE, Coull AJ, et al. The ROSE (Risk stratification Of Syncope in the Emergency department) study. J Am Coll Cardiol. 2010;55:722-724.
Dr. Reed is Consultant in the Department of Emergency Medicine, Royal Infirmary of Edinburgh, and Honorary Senior Lecturer in Emergency Medicine, University of Edinburgh, Scotland, United Kingdom. He has published over 35 papers covering many aspects of emergency medicine and is mainly interested in syncope, clinical decision rules, biomarkers, resuscitation, and emergency transfusion medicine. Dr. Reed is a member of the Emergency Medicine Research Group Edinburgh (EMeRGE), which is based in the Emergency Department of the Royal Infirmary of Edinburgh. EMeRGE supports individual researchers in emergency medicine, coordinates research, and works to raise the national profile of emergency medicine research.
The Risk stratification Of Syncope in the Emergency department (ROSE) study has produced the first United Kingdom-based emergency medicine-specific clinical decision rule for the management of syncope. The ROSE investigators, led by Dr. Reed and colleagues at the Royal Infirmary of Edinburgh, aimed to develop and validate a clinical decision rule that could be used to predict 1-month serious outcome and all-cause death in patients presenting with syncope to the emergency department. Syncope, defined in this study as “transient, self-limited loss of consciousness, usually leading to falling,” is a common, potentially serious condition accounting for many hospital admissions. The ROSE study was a single-center, prospective, observational study of adults presenting to the emergency department with acute syncope between 2007 and 2008. It excluded patients with persisting neurologic deficit suggestive of stroke, those previously recruited into the study; those whose collapse was related to alcohol consumption (determined according to an increased Alcometer® reading and no other cause for syncope); and those with hypoglycemia, trauma, or seizure activity with a >15-minute, witness-reported postictal phase. A clinical decision rule was devised from 550 patients in a derivation cohort and tested in a validation cohort of an additional 550 patients.
In the derivation cohort, 1-month serious outcome or all-cause death occurred in 40 (7.3%) patients. Independent predictors were found to be brain natriuretic peptide (BNP) concentration ≥ 300 pg/mL (odds ratio [OR], 7.3), positive result on a test for fecal occult blood (OR, 13.2), hemoglobin level ≤ 90 g/L (OR, 6.7), oxygen saturation of 94% (OR, 3.0), and Q wave on the presenting electrocardiogram (OR, 2.8). The ROSE rule was finalized as comprising 7 characteristics that can be remembered by the pneumonic “BRACES” as follows:
A patient is considered at high risk for serious outcome and should be considered for admission if ≥1 of these characteristics is present. In the validation cohort, 1-month serious outcome or all-cause death occurred in 39 (7.1%) patients. The ROSE rule had a sensitivity and a specificity of 87.2% and 65.5%, respectively, and a negative predictive value of 98.5%. An elevated BNP concentration alone was a major predictor of serious cardiovascular outcomes (8 of 22 events [36%]) and all-cause deaths (8 of 9 deaths [89%]).
Dr. Reed and his colleagues calculated that the ROSE rule could potentially avoid 149 unnecessary admissions at the expense of missing 4 more patients with a serious outcome and no deaths for every 1000 patients presenting with syncope. They also calculated that if the ROSE rule were incorporated into clinical practice, it could potentially save 136,000 admissions and $734 million in hospital stay costs annually in the United States.
In an accompanying editorial, David G. Benditt, MD (University of Minnesota, Minneapolis), and Ilknur Can, MD (Selçuk University, Konya, Turkey), said that Dr. Reed and his colleagues "have provided potentially valuable new insights that might assist front-line physicians in the evaluation of the need for immediate hospital stay of patients who present to the emergency department/urgent care clinic with apparent syncope/T-LOC [temporary loss of consciousness]." They described the study’s methods as possibly the strongest yet among studies of risk stratification rules for syncope/temporary loss of consciousness, but they cautioned that the ROSE rule is probably not the complete answer for assessment in all age groups and all geographic locations. "It is time for interested investigators to use these new observations in conjunction with those provided in multiple prior risk stratification reports and initiate a project dedicated to development of consensus evidence-based syncope/T-LOC risk stratification recommendations," the editorialists concluded.
Dr. Reed, lead investigator of the ROSE study, spoke with Linda Brookes, MSc, for Medscape Cardiology to discuss how the ROSE rule might be used to identify high-risk patients among those presenting with syncope in the emergency department.
Medscape: Why did you decide to do the ROSE study?
Dr. Reed: Prior to our study there was a paucity of evidence about the risk stratification tools being used in UK [United Kingdom] hospital emergency departments. So we conducted a survey of emergency departments in the UK and Ireland to determine what syncope guidelines they were using and we found that only 18% (32 of 177 responders) use specific guidelines. Some of these are based on guidelines issued by the European Society of Cardiology (ESC), the American College of Emergency Physicians, and the American College of Physicians. There are also 2 common syncope rules that are used occasionally. One is the San Francisco Syncope Rule, which has not been universally adopted because there are many problems with it, mainly the fact that it includes characteristics that we would routinely not consider discharging someone with anyway (ie, systolic blood pressure < 90 mm Hg at triage). Also, it did not validate very well and has a very poor specificity meaning that it is likely to increase admission substantially; it performed reasonably well when it was validated internally by the San Francisco group, but when other groups looked at it, it performed very badly. So since then it is rarely used in clinical practice.
The other rule that we found being used was the OESIL [Osservatorio Epidemiologico sulla Sincope nel Lazio] rule, which was developed by Italy investigators. However, they looked at 1-year survival, and in an emergency department we are interested in what happens to our patients 1 month later; what happens after 1 year is not something we can influence particularly. So any marker or scoring system that shows how patients do in 1 year's time does not really impact on our patients. So that is why the OESIL rule has not been widely applied. There are also a couple of smaller rules, but they have not really had enough validation to be accepted. So there is not any syncope rule being used routinely in the UK and we decided to look at it ourselves in the UK population. Since emergency departments in the UK are very different to those in the United States, rules that may be useful in the United States may not be so useful in the UK.
Medscape: What are the major differences between emergency departments in the UK and the United States?
Dr. Reed: In the UK we have a 4-hour target, ie, a patient can only spend a maximum of 4 hours in an emergency department before admission, discharge, or transfer, whereas in the United States patients can spend up to 24 hours in an emergency department. So US physicians have much longer to work patients up.
Medscape: Is that target set by the government?
Dr. Reed: Yes. The target was introduced in 2004. Currently 98% of our patients must be seen and either moved on or sent home within 4 hours. So that is a big difference between the 2 countries in the time available to work patients like this up.
Medscape: How do emergency physicians overseas regard the UK 4-hour target?
Dr. Reed: Physicians in the United States do not seem to know about it. I have had a lot of contact with physicians in Canada, and they seem to feel that it would be useful to have that in their own departments. In Australia the government is introducing a similar target. It has some benefits and some drawbacks. It has benefits in that we manage to get to get things done much quicker and we get much better access to investigation, although it is not yet as good as it could be. On the other hand, it means that we do not have as long to process patients. There are some aspects that are not impacted by this target; for example, applying the Ottawa ankle rules, which are a very well established set of rules that are used throughout the world and have been validated everywhere, would not be affected by a 4-hour target. However, patients are much more likely to be admitted in the UK. Currently about 50% of emergency patients with syncope in the UK are admitted and most of them go home within 24 hours. A longer period of observation might reduce this number. With the luxury of having a patient being monitored for 6 hours, having no serious outcomes and maybe getting an echocardiogram and other tests done during that time, you would be happier to send the patient home.
Medscape: So you and your colleagues began the ROSE study in 2007?
Dr. Reed: Yes. We had done a pilot study prior to that and then we did the survey of all the UK departments to see what syncope guidelines were being used at that time.
Medscape: What definition of syncope did you apply? Does it vary according to different guidelines?
Dr. Reed: No, it is the same. Last year a definition was published by an ESC [European Society of Cardiology] Task Force that has been more universally accepted. It defined syncope as "a transient loss of consciousness (T-LOC) due to transient global cerebral hypoperfusion characterized by rapid onset, short duration, and spontaneous complete recovery." Previously there was confusion with T-LOC, which now encompasses people who have seizures. So a patient who comes in with a witnessed episode or with an episode of having lost consciousness is termed as having a T-LOC. That could be either a seizure or syncope. When you have confirmed that it is not seizure, it can then be classified as syncope. It is sometimes difficult to do, especially early on, because you do not always have a witness and the patient is unable to give a clear history of it, because they were involved in it. That is why studies in these populations sometimes include people who are classed as having a syncopal episode that was actually a seizure, because this information may not become available until later.
Medscape: At the end of the study you had developed a rule that would identify high-risk patients with an emergency presentation of syncope?
Dr. Reed: Yes. We have designed a rule that will help emergency physicians to decide which of the higher-risk patients need to be admitted. We hope that the rule will pick up a lot of patients who could go home safely so that we will be able to save people from coming into hospital. Then we can focus on the higher-risk patients and investigate them more thoroughly. As with any rule, it does need to be validated, so other groups need to see whether it performs as well in their departments. It will only be when that happens, and then if it is found to be true, that it will be universally adopted. So it could take a few years to be accepted in clinical practice. It has to be born in mind that many tools like this fall by the wayside because they do not seem to be as good as they initially appeared or they are shown not to be as useful.
Medscape: You mentioned in the report that recruitment into an external validation study is already ongoing.
Dr. Reed: Yes. There is a small external validation study going on in London, but it has been unable to obtain funding to use BNP, our key rule component. Plans are underway to validate the rule in an international multicenter study, and myself and other international colleagues who have an interest in syncope are planning to develop standardized outcome and predictor measurements in order to enable easier validation of current and future emergency department syncope rules and protocols.
Medscape: The ROSE study looked at the potential role of BNP as a risk stratification marker, and you conclude that it was particularly useful in the identification of serious cardiovascular outcomes and all-cause death.
Dr. Reed: I think the finding about BNP is particularly exciting. We were keen to look at it because my group had been doing a lot of work on BNP. It had not previously been looked at in the nature of syncope, but looking at all the evidence, we had good reason to believe that it would be a very good marker. Many studies have shown that in heart failure BNP is one of the best prognostic factors and the clinical examination finding of heart failure has been shown to be a good discriminator for patients who are at higher risk versus those who are at low risk. That was the rationale behind using BNP to determine whether it was a good risk stratification tool. At the moment we do not have any biomarkers for the syncope and our group is going to be looking at the BNP in more detail around syncope patients, about how it changes on admission, whether it has any diagnostic ability and how it differs in syncope patients compared to normal [patients]. We have just done some work in syncope patients in the emergency department, measuring serial BNP over time to see whether it validates to a patients who [are] seen a week later in the cardiology outpatient clinic or someone who is seen by their family doctor a week later, and how generalizable it is. Another interesting thing would be to see whether it would be useful for a cardiology consultant seeing a patient who has had an episode 1 week later.
Medscape:There has been some controversy about the clinical usefulness of BNP in heart failure in the United States.
Dr. Reed: There still is in the UK. It has not been widely adopted in emergency departments, but I believe that is really because in heart failure, it does not add much more above clinical examination in breathless patients. But certainly in outpatients and in family practice it is used quite frequently.
Medscape: You commented in your paper, and it was also mentioned in the accompanying editorial, that the mean age was quite high (82 ± 8 years) for the people who had BNP ≥ 300 pg/mL and that it might just be identifying people who are older and who have other evidence of structural heart disease.
Dr. Reed: Yes, it may well be. Again, that is an area of further work to see whether it is generally a marker of patients who do badly in other conditions as well. But it is the 60+ age group that are the difficult patients in managing syncopations anyway, so it is that group that is likely to have heart disease, and they are the ones that normally would have a serious outcomes -- and that is probably why BNP is picking them up. Although it was suggested that it might only be picking up patients who are old and already have heart disease, if you look at the numbers of patients who had previous ischemic heart disease, it was 48% and 28% [who] had previous MI, and only 18% were known to have previous heart failure. So BNP is not really just picking up all of those who have got heart disease, although you would expect the ones that do badly anyway are the ones who have heart disease.
Medscape: How many people in UK emergency departments would be able to get point-of-care BNP at the moment?
Dr. Reed: About 5% of emergency departments in the UK have BNP testing.
Medscape: Would it be a huge shift for hospitals to adapt to do it?
Dr. Reed: It is a cost issue, so you have to show that a certain test is going to be cost beneficial. At the moment we have it as a research tool and because of the work we are doing, we have been lucky enough to acquire it through research funding at the moment. But I believe that the problem with BNP, certainly from the emergency department point of view, is that it is being marketed as being a very good tool in patients who come in with breathlessness. The problem with that is that in most cases, clinical examination is good enough to be able to determine whether it is heart failure or COPD [chronic obstructive pulmonary disease]. You do not need a BNP test to tell you that a patient has heart failure. In the community, however, it might be more helpful because patients are not as sick as the ones we see. So I do not know any emergency department in the UK that uses BNP from the heart failure point of view, but the UK National Institute for Clinical Excellence [NICE] recommends it for community practice.
Medscape: In your study you calculated potential cost savings for emergency departments in the United States. Would the rate of cost savings be similar in the UK?
Dr. Reed: We looked at the UK as well and we calculated that based on the UK Health Resource Grouping tariffs for 2008/09, incorporating the BRACES rules into clinical practice could potentially save £91 million in hospitalization costs annually in the UK alone.
Medscape: Is there likely to be a new syncope guideline specifically for the UK in future?
Dr. Reed: The NICE group in the UK is now putting together some guidelines on management of T-LOC, and we are involved on the emergency medicine side. A draft document has been issued for consultation, and the full guideline is scheduled to appear in August 2010.
Medscape: Do you believe that management of syncope can improve in the future?
Dr. Reed: I think it is important to say that we are now getting to the stage where we seem to be nailing the emergency management of patients a bit better. People are starting to be able to identify the patients who do badly, and I think that now we need to use these stratification tools to focus on higher-risk patients, and see whether something like a clinical decision unit could work up patients fairly aggressively in the first 4-6 hours after they are admitted, using echocardiography and BNP testing and tools such as the ROSE rule, and then maybe monitoring them for 6 hours. We could then get more patients home, and having worked out the rule now for serious cause, admit the smaller number of patients who still do not have any obvious cause at that point. I think a randomized trial comparing a clinical decision unit such as this versus patient admission could be the next step forward. Another possibility is a coordinated approach using rules such as ours along with biomarkers and echocardiography. There is still a lot more work to be done with emergency treatment of syncope patients, because it is still not well managed, certainly in the UK. Hopefully we can then see how we can actually affect inpatient care, because there is no evidence that anything we do in hospital makes any difference to patient outcome.
Medscape: Nothing at all?
Dr. Reed: No. Although we are now effective at picking up patients who do badly, there is no evidence that anything we do when we know they do badly makes any difference to their outcome. It is very depressing, but that is probably because so many patients get admitted in the UK. Fifty percent of patients are admitted, and that is too many to be investigated thoroughly. If we use something like this tool to focus our investigations on those patients who are at high risk, then we might start to show that we can change patients' outcome.
Medscape: Is that just the situation in the UK or everywhere?
Dr. Reed: All studies have shown that about 10%-15% of these patients do very badly within 1 month.
Medscape: Have you been able to follow up the effects of the rule you devised on longer-term outcomes in the ROSE study patients?
Dr. Reed: We have actually just finished looking at 1-year outcomes for all of our patients and also at how the rule and how BNP perform at 1 year. We are close to finishing that and hopefully our results will be published later in the year. They make fairly grim reading because they are no different from all the other studies. They show that about 15% have a primary outcome at 1 year, including 7% of patients who had died and 7% who had a serious cardiovascular outcome.
A Best Evidence Interview With Matthew J. Reed, MD, Royal Infirmary of Edinburgh, Scotland, United Kingdom
The Best Evidence Study
Dr. Reed was lead author of:
Reed MJ, Newby DE, Coull AJ, et al. The ROSE (Risk stratification Of Syncope in the Emergency department) study. J Am Coll Cardiol. 2010;55:722-724.
About the Interviewee
Dr. Reed is Consultant in the Department of Emergency Medicine, Royal Infirmary of Edinburgh, and Honorary Senior Lecturer in Emergency Medicine, University of Edinburgh, Scotland, United Kingdom. He has published over 35 papers covering many aspects of emergency medicine and is mainly interested in syncope, clinical decision rules, biomarkers, resuscitation, and emergency transfusion medicine. Dr. Reed is a member of the Emergency Medicine Research Group Edinburgh (EMeRGE), which is based in the Emergency Department of the Royal Infirmary of Edinburgh. EMeRGE supports individual researchers in emergency medicine, coordinates research, and works to raise the national profile of emergency medicine research.
Background: The ROSE Study
The Risk stratification Of Syncope in the Emergency department (ROSE) study has produced the first United Kingdom-based emergency medicine-specific clinical decision rule for the management of syncope. The ROSE investigators, led by Dr. Reed and colleagues at the Royal Infirmary of Edinburgh, aimed to develop and validate a clinical decision rule that could be used to predict 1-month serious outcome and all-cause death in patients presenting with syncope to the emergency department. Syncope, defined in this study as “transient, self-limited loss of consciousness, usually leading to falling,” is a common, potentially serious condition accounting for many hospital admissions. The ROSE study was a single-center, prospective, observational study of adults presenting to the emergency department with acute syncope between 2007 and 2008. It excluded patients with persisting neurologic deficit suggestive of stroke, those previously recruited into the study; those whose collapse was related to alcohol consumption (determined according to an increased Alcometer® reading and no other cause for syncope); and those with hypoglycemia, trauma, or seizure activity with a >15-minute, witness-reported postictal phase. A clinical decision rule was devised from 550 patients in a derivation cohort and tested in a validation cohort of an additional 550 patients.
In the derivation cohort, 1-month serious outcome or all-cause death occurred in 40 (7.3%) patients. Independent predictors were found to be brain natriuretic peptide (BNP) concentration ≥ 300 pg/mL (odds ratio [OR], 7.3), positive result on a test for fecal occult blood (OR, 13.2), hemoglobin level ≤ 90 g/L (OR, 6.7), oxygen saturation of 94% (OR, 3.0), and Q wave on the presenting electrocardiogram (OR, 2.8). The ROSE rule was finalized as comprising 7 characteristics that can be remembered by the pneumonic “BRACES” as follows:
| B | BNP level ≥ 300 pg/mL and Bradycardia with heart rate ≤ 50 beats/min in emergency department or before hospital visit |
| R | Rectal examination showing fecal occult blood (if gastrointestinal bleeding is suspected) |
| A | Anemia with hemoglobin level ≤ 90 g/L |
| C | Chest pain associated with syncope |
| E | Electrocardiogramshowing Q wave (not in lead III) |
| S | Saturation ≤ 94% while breathing room air |
A patient is considered at high risk for serious outcome and should be considered for admission if ≥1 of these characteristics is present. In the validation cohort, 1-month serious outcome or all-cause death occurred in 39 (7.1%) patients. The ROSE rule had a sensitivity and a specificity of 87.2% and 65.5%, respectively, and a negative predictive value of 98.5%. An elevated BNP concentration alone was a major predictor of serious cardiovascular outcomes (8 of 22 events [36%]) and all-cause deaths (8 of 9 deaths [89%]).
Dr. Reed and his colleagues calculated that the ROSE rule could potentially avoid 149 unnecessary admissions at the expense of missing 4 more patients with a serious outcome and no deaths for every 1000 patients presenting with syncope. They also calculated that if the ROSE rule were incorporated into clinical practice, it could potentially save 136,000 admissions and $734 million in hospital stay costs annually in the United States.
In an accompanying editorial, David G. Benditt, MD (University of Minnesota, Minneapolis), and Ilknur Can, MD (Selçuk University, Konya, Turkey), said that Dr. Reed and his colleagues "have provided potentially valuable new insights that might assist front-line physicians in the evaluation of the need for immediate hospital stay of patients who present to the emergency department/urgent care clinic with apparent syncope/T-LOC [temporary loss of consciousness]." They described the study’s methods as possibly the strongest yet among studies of risk stratification rules for syncope/temporary loss of consciousness, but they cautioned that the ROSE rule is probably not the complete answer for assessment in all age groups and all geographic locations. "It is time for interested investigators to use these new observations in conjunction with those provided in multiple prior risk stratification reports and initiate a project dedicated to development of consensus evidence-based syncope/T-LOC risk stratification recommendations," the editorialists concluded.
Dr. Reed, lead investigator of the ROSE study, spoke with Linda Brookes, MSc, for Medscape Cardiology to discuss how the ROSE rule might be used to identify high-risk patients among those presenting with syncope in the emergency department.
The Interview
Medscape: Why did you decide to do the ROSE study?
Dr. Reed: Prior to our study there was a paucity of evidence about the risk stratification tools being used in UK [United Kingdom] hospital emergency departments. So we conducted a survey of emergency departments in the UK and Ireland to determine what syncope guidelines they were using and we found that only 18% (32 of 177 responders) use specific guidelines. Some of these are based on guidelines issued by the European Society of Cardiology (ESC), the American College of Emergency Physicians, and the American College of Physicians. There are also 2 common syncope rules that are used occasionally. One is the San Francisco Syncope Rule, which has not been universally adopted because there are many problems with it, mainly the fact that it includes characteristics that we would routinely not consider discharging someone with anyway (ie, systolic blood pressure < 90 mm Hg at triage). Also, it did not validate very well and has a very poor specificity meaning that it is likely to increase admission substantially; it performed reasonably well when it was validated internally by the San Francisco group, but when other groups looked at it, it performed very badly. So since then it is rarely used in clinical practice.
The other rule that we found being used was the OESIL [Osservatorio Epidemiologico sulla Sincope nel Lazio] rule, which was developed by Italy investigators. However, they looked at 1-year survival, and in an emergency department we are interested in what happens to our patients 1 month later; what happens after 1 year is not something we can influence particularly. So any marker or scoring system that shows how patients do in 1 year's time does not really impact on our patients. So that is why the OESIL rule has not been widely applied. There are also a couple of smaller rules, but they have not really had enough validation to be accepted. So there is not any syncope rule being used routinely in the UK and we decided to look at it ourselves in the UK population. Since emergency departments in the UK are very different to those in the United States, rules that may be useful in the United States may not be so useful in the UK.
Medscape: What are the major differences between emergency departments in the UK and the United States?
Dr. Reed: In the UK we have a 4-hour target, ie, a patient can only spend a maximum of 4 hours in an emergency department before admission, discharge, or transfer, whereas in the United States patients can spend up to 24 hours in an emergency department. So US physicians have much longer to work patients up.
Medscape: Is that target set by the government?
Dr. Reed: Yes. The target was introduced in 2004. Currently 98% of our patients must be seen and either moved on or sent home within 4 hours. So that is a big difference between the 2 countries in the time available to work patients like this up.
Medscape: How do emergency physicians overseas regard the UK 4-hour target?
Dr. Reed: Physicians in the United States do not seem to know about it. I have had a lot of contact with physicians in Canada, and they seem to feel that it would be useful to have that in their own departments. In Australia the government is introducing a similar target. It has some benefits and some drawbacks. It has benefits in that we manage to get to get things done much quicker and we get much better access to investigation, although it is not yet as good as it could be. On the other hand, it means that we do not have as long to process patients. There are some aspects that are not impacted by this target; for example, applying the Ottawa ankle rules, which are a very well established set of rules that are used throughout the world and have been validated everywhere, would not be affected by a 4-hour target. However, patients are much more likely to be admitted in the UK. Currently about 50% of emergency patients with syncope in the UK are admitted and most of them go home within 24 hours. A longer period of observation might reduce this number. With the luxury of having a patient being monitored for 6 hours, having no serious outcomes and maybe getting an echocardiogram and other tests done during that time, you would be happier to send the patient home.
Medscape: So you and your colleagues began the ROSE study in 2007?
Dr. Reed: Yes. We had done a pilot study prior to that and then we did the survey of all the UK departments to see what syncope guidelines were being used at that time.
Medscape: What definition of syncope did you apply? Does it vary according to different guidelines?
Dr. Reed: No, it is the same. Last year a definition was published by an ESC [European Society of Cardiology] Task Force that has been more universally accepted. It defined syncope as "a transient loss of consciousness (T-LOC) due to transient global cerebral hypoperfusion characterized by rapid onset, short duration, and spontaneous complete recovery." Previously there was confusion with T-LOC, which now encompasses people who have seizures. So a patient who comes in with a witnessed episode or with an episode of having lost consciousness is termed as having a T-LOC. That could be either a seizure or syncope. When you have confirmed that it is not seizure, it can then be classified as syncope. It is sometimes difficult to do, especially early on, because you do not always have a witness and the patient is unable to give a clear history of it, because they were involved in it. That is why studies in these populations sometimes include people who are classed as having a syncopal episode that was actually a seizure, because this information may not become available until later.
Medscape: At the end of the study you had developed a rule that would identify high-risk patients with an emergency presentation of syncope?
Dr. Reed: Yes. We have designed a rule that will help emergency physicians to decide which of the higher-risk patients need to be admitted. We hope that the rule will pick up a lot of patients who could go home safely so that we will be able to save people from coming into hospital. Then we can focus on the higher-risk patients and investigate them more thoroughly. As with any rule, it does need to be validated, so other groups need to see whether it performs as well in their departments. It will only be when that happens, and then if it is found to be true, that it will be universally adopted. So it could take a few years to be accepted in clinical practice. It has to be born in mind that many tools like this fall by the wayside because they do not seem to be as good as they initially appeared or they are shown not to be as useful.
Medscape: You mentioned in the report that recruitment into an external validation study is already ongoing.
Dr. Reed: Yes. There is a small external validation study going on in London, but it has been unable to obtain funding to use BNP, our key rule component. Plans are underway to validate the rule in an international multicenter study, and myself and other international colleagues who have an interest in syncope are planning to develop standardized outcome and predictor measurements in order to enable easier validation of current and future emergency department syncope rules and protocols.
Medscape: The ROSE study looked at the potential role of BNP as a risk stratification marker, and you conclude that it was particularly useful in the identification of serious cardiovascular outcomes and all-cause death.
Dr. Reed: I think the finding about BNP is particularly exciting. We were keen to look at it because my group had been doing a lot of work on BNP. It had not previously been looked at in the nature of syncope, but looking at all the evidence, we had good reason to believe that it would be a very good marker. Many studies have shown that in heart failure BNP is one of the best prognostic factors and the clinical examination finding of heart failure has been shown to be a good discriminator for patients who are at higher risk versus those who are at low risk. That was the rationale behind using BNP to determine whether it was a good risk stratification tool. At the moment we do not have any biomarkers for the syncope and our group is going to be looking at the BNP in more detail around syncope patients, about how it changes on admission, whether it has any diagnostic ability and how it differs in syncope patients compared to normal [patients]. We have just done some work in syncope patients in the emergency department, measuring serial BNP over time to see whether it validates to a patients who [are] seen a week later in the cardiology outpatient clinic or someone who is seen by their family doctor a week later, and how generalizable it is. Another interesting thing would be to see whether it would be useful for a cardiology consultant seeing a patient who has had an episode 1 week later.
Medscape:There has been some controversy about the clinical usefulness of BNP in heart failure in the United States.
Dr. Reed: There still is in the UK. It has not been widely adopted in emergency departments, but I believe that is really because in heart failure, it does not add much more above clinical examination in breathless patients. But certainly in outpatients and in family practice it is used quite frequently.
Medscape: You commented in your paper, and it was also mentioned in the accompanying editorial, that the mean age was quite high (82 ± 8 years) for the people who had BNP ≥ 300 pg/mL and that it might just be identifying people who are older and who have other evidence of structural heart disease.
Dr. Reed: Yes, it may well be. Again, that is an area of further work to see whether it is generally a marker of patients who do badly in other conditions as well. But it is the 60+ age group that are the difficult patients in managing syncopations anyway, so it is that group that is likely to have heart disease, and they are the ones that normally would have a serious outcomes -- and that is probably why BNP is picking them up. Although it was suggested that it might only be picking up patients who are old and already have heart disease, if you look at the numbers of patients who had previous ischemic heart disease, it was 48% and 28% [who] had previous MI, and only 18% were known to have previous heart failure. So BNP is not really just picking up all of those who have got heart disease, although you would expect the ones that do badly anyway are the ones who have heart disease.
Medscape: How many people in UK emergency departments would be able to get point-of-care BNP at the moment?
Dr. Reed: About 5% of emergency departments in the UK have BNP testing.
Medscape: Would it be a huge shift for hospitals to adapt to do it?
Dr. Reed: It is a cost issue, so you have to show that a certain test is going to be cost beneficial. At the moment we have it as a research tool and because of the work we are doing, we have been lucky enough to acquire it through research funding at the moment. But I believe that the problem with BNP, certainly from the emergency department point of view, is that it is being marketed as being a very good tool in patients who come in with breathlessness. The problem with that is that in most cases, clinical examination is good enough to be able to determine whether it is heart failure or COPD [chronic obstructive pulmonary disease]. You do not need a BNP test to tell you that a patient has heart failure. In the community, however, it might be more helpful because patients are not as sick as the ones we see. So I do not know any emergency department in the UK that uses BNP from the heart failure point of view, but the UK National Institute for Clinical Excellence [NICE] recommends it for community practice.
Medscape: In your study you calculated potential cost savings for emergency departments in the United States. Would the rate of cost savings be similar in the UK?
Dr. Reed: We looked at the UK as well and we calculated that based on the UK Health Resource Grouping tariffs for 2008/09, incorporating the BRACES rules into clinical practice could potentially save £91 million in hospitalization costs annually in the UK alone.
Medscape: Is there likely to be a new syncope guideline specifically for the UK in future?
Dr. Reed: The NICE group in the UK is now putting together some guidelines on management of T-LOC, and we are involved on the emergency medicine side. A draft document has been issued for consultation, and the full guideline is scheduled to appear in August 2010.
Medscape: Do you believe that management of syncope can improve in the future?
Dr. Reed: I think it is important to say that we are now getting to the stage where we seem to be nailing the emergency management of patients a bit better. People are starting to be able to identify the patients who do badly, and I think that now we need to use these stratification tools to focus on higher-risk patients, and see whether something like a clinical decision unit could work up patients fairly aggressively in the first 4-6 hours after they are admitted, using echocardiography and BNP testing and tools such as the ROSE rule, and then maybe monitoring them for 6 hours. We could then get more patients home, and having worked out the rule now for serious cause, admit the smaller number of patients who still do not have any obvious cause at that point. I think a randomized trial comparing a clinical decision unit such as this versus patient admission could be the next step forward. Another possibility is a coordinated approach using rules such as ours along with biomarkers and echocardiography. There is still a lot more work to be done with emergency treatment of syncope patients, because it is still not well managed, certainly in the UK. Hopefully we can then see how we can actually affect inpatient care, because there is no evidence that anything we do in hospital makes any difference to patient outcome.
Medscape: Nothing at all?
Dr. Reed: No. Although we are now effective at picking up patients who do badly, there is no evidence that anything we do when we know they do badly makes any difference to their outcome. It is very depressing, but that is probably because so many patients get admitted in the UK. Fifty percent of patients are admitted, and that is too many to be investigated thoroughly. If we use something like this tool to focus our investigations on those patients who are at high risk, then we might start to show that we can change patients' outcome.
Medscape: Is that just the situation in the UK or everywhere?
Dr. Reed: All studies have shown that about 10%-15% of these patients do very badly within 1 month.
Medscape: Have you been able to follow up the effects of the rule you devised on longer-term outcomes in the ROSE study patients?
Dr. Reed: We have actually just finished looking at 1-year outcomes for all of our patients and also at how the rule and how BNP perform at 1 year. We are close to finishing that and hopefully our results will be published later in the year. They make fairly grim reading because they are no different from all the other studies. They show that about 15% have a primary outcome at 1 year, including 7% of patients who had died and 7% who had a serious cardiovascular outcome.
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