Tag Archives: Heart Attack

An even quicker way to rule out heart attacks

The majority of New Zealand emergency departments look for heart muscle damage by taking a sample of blood and looking for a particular molecule called a high-sensitivity troponin T (hsTnT).  We have now confirmed that rather than two measurements over several hours just one measurement on arrival in the ED could be used to rule out heart attacks in about 30% of patients.

What did we do?

We think this is a big deal. We’ve timed this post to meet the Annas of Internal Medicine timing for when our work appears on their website – here.  What we did was to search the literature to find where research groups may have measured hsTnT in the right group of people – namely people appearing in an emergency room whom the attending physician thinks they may be having a heart attack. We also required that the diagnosis of a heart attack, or not, was made not by just one physician, but by at least two independently.  In this way we made sure we were accessing the best quality data.

Next I approached the authors of the studies as asked them to share some data with us – namely the number of people who had detectable and undetectable hsTnT (every blood test has a minimum level below which it is said to be “undetectable” in hsTnT’s case that is just 5 billionths of a gram per litre, or 5ng/L).  We also asked them to check in these patients if the electrical activity of the heart (measured by an electrocardiogram or “ECG”) looked like there may or may not be damage to the heart (a helpful test, but not used on its own to diagnose this kind of heart attack).  Finally, we asked the authors to identify which patients truly did and did not have a heart attack.

What did we find?

In the end research groups in Europe, UK, Australia, NZ, and the US participated with a total of 11 studies and more than 9000 patients.  I did some fancy statistics to show that overall about 30% of patients had undetectable hsTnT with the first blood test and negative ECGs.  Of all those who were identifiable as potentially “excludable” or “low-risk” only about 1 in 200 had a heart attack diagnosed (we’d like it to be zero, but this just isn’t possible, especially given the diagnosis is not exact).

VisualAbstract AnnalsIM 170411

Pickering, J. W.*, Than, M. P.*, Cullen, L. A., Aldous, S., Avest, ter, E., Body, R., et al. (2017). Rapid Rule-out of Myocardial Infarction With a High-Sensitivity CardiacTroponin T Measurement Below the Limit of Detection: A Collaborative Meta-analysis. Annals of Internal Medicine, 166(10). http://doi.org/10.7326/M16-2562 *joint first authors.

What did we conclude?

There is huge potential for ruling out a heart attack with just one blood test.  In New Zealand this could mean many thousands of people a year can be reassured even more swiftly that they are not having a heart attack. By excluding the possibility of a heart attack early, physicians can put more effort into looking for other causes of chest-pain or simply send the patient happily home.   While not every hospital performed had the same great performance, overall the results were good.  By the commonly accepted standards, it is safe.  However, we caution that local audits at each hospital that decides to implement this “single blood measurement” strategy are made to double check its safety and efficacy.


Acknowledgment: This was a massive undertaking that required the collaboration of dozens of people from all around the world – their patience and willingness to participate is much appreciated. My clinical colleague and co-first author, Dr Martin Than provided a lot of the energy as well as intelligence for this project. As always, I am deeply appreciative of my sponsors: the Emergency Care Foundation, Canterbury Medical Research Foundation, Canterbury District Health Board, and University of Otago Christchurch. There will be readers who have contributed financially to the first two (charities) – I thank you – your generosity made this possible, and there will be readers who have volunteered for clinical studies – you are my heroes.

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Heart attacks in NZ – are women getting a raw deal?

Yesterday the NZ Herald published an article saying doctors are failing to spot heart attacks in thousands of women.  This sounds alarming, could it be happening in NZ? Are women getting a raw deal?  Important questions.  This post looks at the study behind the media and then at how heart attacks are being diagnosed in New Zealand.

The Herald article is evidently based on press releases related to a study published to coincide with the European Society of Cardiologist’s conference currently underway in Rome and attended by some 30,000 cardiologists, other physicians, industry types, and the Pope (yep!). The study in question comes from the University of Leeds. Here’s the Leeds Uni press release.

The US red-dress logo which is their national symbol for women and heart disease

The US red-dress logo which is their national symbol for women and heart disease

The study

The study is based on an audit of UK data collected about patients between 2004 and 2013 whose final diagnosis was a heart attack (in clinical jargon a myocardial infarction, either STEMI or NSTEMI).  The full article is available here.

The subjects were patients who at discharge from hospital had a heart attack diagnosis.  The authors looked at the preliminary diagnosis of patients when they first entered the hospital and compared that diagnosis to the final diagnosis of a heart attack.  The preliminary diagnosis was for about a 30% of patients not explicitly a heart attack – ie often something like “chest pain of uncertain cause.”  In the press release and news reports this was reported as a “misdiagnosis.”

Point 1:  The term “misdiagnosis” is inappropriately applied here.  While some forms of heart-attacks can be diagnosed in the ED, most can not.  Indeed, the guidelines for diagnosis of a heart attack require some blood measurements at least 6 hours apart.  Nowadays, the later blood sample is not done in the ED, but in a cardiology or general medicine ward.  That is, the ED physicians often don’t have all the data to make a definitive diagnosis – hence only a preliminary diagnosis is made. Most of the time the job of the Emergency department physicians is to rule-out some possible diagnoses and to identify patients at significant risk of a heart attack.  These patients are referred on to the specialist teams within the hospital who make the final diagnosis.*  Yesterday I was speaking with a cardiologist who was explaining how often cardiologists themselves disagreed over a diagnosis.  It ain’t easy.

The press releases and media reports emphasise that a larger proportion of women than men were likely to have a change between the preliminary and final diagnosis.  The Leeds University press release states women were 59% for a final STEMI diagnosis and 41% for a final NSTEMI diagnosis more likely than men to have a change from the preliminary diagnosis.

Point 2:  These numbers are not reported in the published paper!  Nor is anything about the differences between men and women discussed in the paper.  In the results section it is simply stated that those who had an initial diagnosis that changed were more likely to be older, female, and have a co-morbidity. There are some numbers related to this in a table. In the table I note that patients older than 61 compared with younger patients had at least (more if they were even older) the same odds of having a diagnosis changed as did females compared with males (it’s a little awkward in the paper because the odds ratio is written the opposite way around – but this can be rectified simply by taking the reciprocal of the odds ratio and comparing that).  There were also other predictors of a change in diagnosis (eg higher heart rate).  The cynic in me thinks that it may be for publicity reasons that the emphasis has been placed on the sex differences in press releases.

Point 3: What is important about the study is that in those who had a change in diagnosis the one-year mortality rates were higher.  While the suggestion is made that this is because of delay in time to treatment (known from other studies to be important), there are other potential reasons because of the differences in demographics and co-morbidities between the groups.

New Zealand

The study began at a time when the blood biomarkers indicative of a heart attack that are used now (troponins) were not in common use.  There have been several generations of markers, the latest of which are “high-sensitivity troponins.”  The authors’ recommended that:

“…our results… call for the earlier use and wider adoption of high sensitivity troponins as well as a focus on the systematic application of accelerated diagnostic protocols using risk scores rather than subjective clinical assessment.”

The good news is that New Zealand is now the only country in the world** to have accelerated diagnostic protocols using risk scores in place in every ED.  Furthermore, most ED’s are using the latest high sensitivity troponins.

In the Christchurch ED, different sex-specific thresholds of the troponin used for risk stratifying and diagnosing heart attacks are used.  This is because in the general healthy population males have slightly higher values of these troponin measurements than females.  Therefore, to avoid underdiagnoses of females a lower diagnostic threshold is used.  Furthermore, in a study we were part of and lead by our Brisbane based colleagues, using sex-specific threshold helped improvs risk prediction for future adverse events in women.

Conclusion

In New Zealand it is less likely that women are getting a raw deal.


 

*perhaps the Pope a.k.a @Pontifix [literally the “bridge builder”] could help bridge the divide between ED physicians and cardiologists – generally ED physicians rule-out heart attacks, Cardiologists rule-in heart attacks.

** although Queensland also has this and they like to think of themselves as a country sometimes

Cheesecake Files: Embargoed until

Every now and again a Journal doesn’t want us to talk publically about our own paper until it they publish it.  This is simply so they can make more of a splash with it.  This was the case of an article I have been involved with published today in the Cardiology journal of the American Medical Association*. 

What’s it about?

Ruling out a heart attack in the emergency department is difficult.  Readers of this blog would have read about various other ways we’ve developed to be part of it (eg here).  They depend on many things including the type of blood measurement used and the timing of that.  These markers – called troponins – detect damage to the heart muscle.

In this study led by Ed Carlton of Southmead hospital in Bristol, UK, we evaluated whether a single measurement of very low levels of a comparatively new blood biomarker called “High-sensitivity troponin I” could alone rule out heart attacks within 30 days when someone presented to the emergency department with chest pain (Here Ed speak about the study here).

3155 patients at 5 hospitals in New Zealand (Christchurch), Australia and the UK participated of whom 291 had a heart attack (277 were having a heart attack on the day they presented to ED, the other 14 had one within 30 days).

We found that 594 (18.8%) of patients had such a high sensitivity troponin I concentration below the limit at which it could reliably be detected.  ie next to nothing. These we can say tested negative.  Three of them (0.5%) it turned out did have a heart attack.

Why the splash?

The editor got quite excited about this and another study and wrote an editorial to accompany the studies:

“To manage costs and the adverse effects of overcrowding in the ED, it is a high priority to rapidly and safely identify patients with a sufficiently low probability for acute coronary syndrome (<0.5%-1%) so that they can be discharged efficiently and avoid unnecessary testing.”

He was impressed that this study had been “tested in robustly sized, geographically diverse, clinically relevant populations.”

And concludes

“Taken together with prior studies the findings from the studies of Neumann et al and Carlton et al lend strong support to the notion that accelerated diagnostic protocols that incorporate [high sensitivity troponins] can facilitate earlier triage while maintaining an acceptable [rate of false negatives].

One of the features of interest to the readers of this US journal is that the high-sensitivity troponins are not yet available in the US, however they eventually will be and how they are used is of particular interest.

Part of a figure from the publication showing how choosing different troponin thresholds to rule-out patients affects how sensitive the test is.

Part of a figure from the publication showing how choosing different troponin thresholds to rule-out patients changes how sensitive the test is.

Why not perfection?

Of course we would love to never have a false negative (or false positive).  However, the reality of medicine is that this is not possible.  We could, of course, simply admit everyone, do more invasive tests,  or “wait and see” if they develop a heart attack. There are, though, risks as well as costs with admitting people to hospitals.  If I may speculate for a moment, the rise in superbugs resistant to antibiotics is only likely to increase those risks in the future – hence the importance of studies such as this. It is important that we get the balance of risk right.

What are the next steps?

All of New Zealand now has some kind of accelerated diagnostic pathway for chest pain patients that incorporates serial troponin measurements.  At some stage we will implement, monitor, and measure the addition of an even more accelerated rule-out for some patients with just one troponin.  Watch this space.

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* Carlton, E., Greenslade, J., Cullen, L., Body, R., Than, M. P., Pickering, J. W., Aldous, S.A., Carley, S,. Hammett, C., Kendall, J., Kevill, B., Lord, S.J., Parsonage, W.A., Greaves, K. (2016). Low concentrations of high-sensitivity cardiac troponin I at presentation in the evaluation of emergency department patients with suspected acute coronary syndrome. JAMA Cardiology. http://doi.org/10.1001/jamacardio.2016.1309

Cheesecake files: A world second for heart attacks

Going to the Emergency Department with chest pain no longer means an almost certain night in hospital.  Friday saw the publication online of our randomised controlled trial comparing two different strategies to rapidly rule-out heart attacks in people who present with chest pain to hospitals.  Here’s a précis:

What’s the problem?

  • Chest pain is common – 10% or so of presentations to ED are for chest pain.
  • Heart attacks are not so common – only ~10-15% in NZ (and less overseas*) actually have a heart attack.
  • It is devilishly difficult for most chest pain to rapidly rule out the possibility of a heart attack.
  • Consequently, most people get admitted to hospital (in 2007 93% of those presenting with chest pain).

But – led by Dr Martin Than in Christchurch and an international group including Dr Louise Cullen in Brisbane – a series of observational studies and one randomised control trial have resulted in a gradual increase in the proportion discharged.  The trial was the first of its kind, it compared standard practice at assessing chest pain to a purpose built accelerated diagnostic pathway (ADP), which we called ADAPT.   In that study 11% of patients in the standard practice (control) arm and 19.3% in the ADAPT ADP arm (experimental arm) were discharged home from ED within 6 hours.  A great improvement which led to that ADP being adopted in Christchurch hospital.

So why another study?

Two reasons: First, 19% still means that there are many patients being admitted who potentially don’t need to be in hospital.  Second, the ADP was based around a risk assessment tool designed to rule-in heart attacks rather than rule-out.  In the meantime, the team had constructed a purpose build risk assessment tool that in observational studies looked like it could rule out 40-50% of patients.

What is the study just published?

The world’s second randomised controlled trial of assessment of chest pain compared the ADAPT ADP in use (now the control arm) with a new ADP based on the new Emergency Department Assessment of Chest pain Score (EDACS)[the experimental arm].  The only difference between the two arms of the study was the risk assessment tool used. The tool gave a risk score. Patients with a low score, no unusual electrical activity in the heart, and no elevated heart muscle injury proteins in either of two blood samples measured 2 hours apart, were considered low risk.

An important aspect of the study was that it was pragmatic.  This means that the doctors didn’t have to follow the ADP and could decide to send a patient home, or not send them home, based on any factors they thought clinically relevant.  This makes it very tough to run a trial, but it makes the trial more “real life.”

What were the results?

558 patients were recruited.  They all volunteered and are marvellous people.  I love volunteers.

The primary outcome was the proportion of patients safely discharged home within 6 hours.  We assessed safety by looking at all medical events that happened to a patients over 30 days to check to see if any patients discharged home had a major cardiac event that could potentially have been picked up in the ED.

34% of the control arm and 32% of the experimental arm were discharged within 6 hours.  In other words, there was no difference in early discharge rates between the two arms.  The surprising feature of this is that between 2012/3 (when the first trial was run) and 2014/15 the proportion of patients the first ADP ruled out increased from 19% to 34%.  This was unexpected, but pleasing. There were no safety concerns with any patients.

The secondary outcome was simply the proportion each arm of the study classified as low risk (ie not considering whether this led to early discharge or not).  The control (ADAPT ADP) classified 31% and the experimental (EDACS ADP) 42%.  This was a real and meaningful difference which suggests that there is “room for improvement” in early discharge rates as the clinicians become more familiar with the EDACS ADP.

Since 2007 in Christchurch hospital over three times more patients who present with chest pain can be reassured from within the ED that they are not having a heart attack and discharged home (see the infographic).EDACS infographic v2

What was your role?

My role: I managed aspects of the data collection for the later 2/3rds of the patients recruited, did the statistical analysis and co-wrote the manuscript.  In reality, there were a lot of people involved, not least of whom were the wonderful research nurses and database manager who did a lot of the “grunt work”.

What now?

Over the last year all EDs in New Zealand have implemented or in the process of implementing an accelerated diagnostic pathway.  The majority have chosen to use the EDACS pathway.  I am part of a team nationwide helping implement these pathways and monitor their efficacy and safety.

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This study was funded by the Health Research Committee of New Zealand. The work was carried out with the collaboration or the University of Otago Christchurch, Christchurch Heart Institute, and the Canterbury District Health Board Emergency Department, Cardiology Department, General Medicine, and Canterbury Health Laboratories. My salary is provided through a Senior Research Fellowship in Acute Care funded Canterbury Medical Research Foundation, Canterbury District Health Board and the Emergency Care Foundation.

*Not because we have more heart attacks, just an efficient and well funded primary care sector that keeps the very low risk patients out of the ED.

**Featured Image: Creative Commons Share-Alike 3.0 http://tcsmoking.wikispaces.com/heart%20attack

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Two minds about funding heart research

Recently I had a knock on the door from an enthusiastic young man talking about heart research. Given that has been the focus of my research for the last 18 months or so I was delighted that someone was out there trying to raise money for research. However, my delight was, in retrospect,was tempered somewhat when I realised that the man was not representing a New Zealand based research group.

The man was collecting donations for the Heart Research Institute, an independent research group based in Sydney Australia. This is a substantial and credible organisation. I would be happy to collaborate with any of their team leaders. Looking at their website I noted one (of 12) research groups mentioned New Zealand collaborators.   I’ve written to ask if they have more. The HRI have a very professional New Zealand website which gives information on heart disease statistics in New Zealand. They indicate that they support scholarships and fellowships for New Zealanders to work with their Australian counterparts. However, I am in two minds about this group door knocking in New Zealand – one mind thinks “great” they are keen to raise money for heart research, what a good cause. The other thinks “hmmm,” don’t we have some wonderful New Zealand based heart research groups and charities – why another (not New Zealand based) one in a crowded field seeking money from a limited pool of discretionary spending?

Perhaps, to help the people of Canterbury and wherever else funds are being solicited from to make up their own minds, I can remind people of four great charitable organisations supporting heart research in New Zealand.

Heart Foundation of New Zealand: This is a wonderful organisation with a long history of supporting research in New Zealand as well as supporting individuals within New Zealand. They are the group behind the “Heart Foundation Tick” on food labels. Their website is really worth checking out… I just learnt about the “Two Ticks” now appearing on some labels. For the likes of a researcher like me they provide small, but very important, grants that enable important questions to be answered. Indeed, I have just had a paper published which a Heart Foundation grant made possible. In that paper we show that one of the latest guidelines on how to use a blood marker (used in most New Zealand hospitals) to rule out someone having a heart attack are flawed. I note, that they have in large letters on their web site that they do not do door to door fund raising.

Christchurch Heart Institute: CHI is a research group and charitable organisation within my own department, the Department of Medicine, at the University of Otago Christchurch campus (known to most Cantabs as “the med school”). Headed by Professor Mark Richards it is a world renowned group. I have the privilege (a little daunting given just how incredibly intelligent these people are) to collaborate with CHI on a number of clinical projects. The publication I mentioned was one of them. Another project, just kicking off, is investigating markers of acute kidney injury within people who have acute heart failure. They have recently expanded into social media – so you can follow them on facebook.

Canterbury Medical Research Foundation:  CMRF is a wonderful organisation – they are one of the three major sponsors of my own fellowship. My own prejudice aside, CMRF have been supporting research in Canterbury for over 50 years. One aspect of the CMRF that really impresses me is that they understand the need to support researchers and just “let them get on with it.” Cantabrians may recognise their recent campaign that has included some impressive billboards. One important plank of CMRFs work in Canterbury is their subsidiary the New Zealand Brain Institute which does important research into stroke, Alzheimer’s and Parkinson’s disease.

Emergency Care Foundation: The ECF supports research in the Emergency Department of Christchurch hospital including research into the rapid rule-out of heart attacks for patients presenting with chest pain.  I’m fortunate enough to be involved in that research and the role out of new diagnostic pathways to all emergency department in the country.  ECF also support research into the health affects of the Christchurch earthquakes.  ECF are another of my major sponsors.

Some logos of the great local charitable organisations supporting heart research

What is your number?

Last night I had the honour to speak following the AGM of the Canterbury Medical Research Foundation (CMRF).  The CMRF are a fantastic organisation I’ve talked about before.  They are also one of three sponsors of my current research fellowship.  What I talked about was volunteers and clinical trials.  Two days ago the world celebrated Clinical Trials Day in honour of James Lind who in 1747 took some men aboard a ship and started to feed them citrus fruit to see if the Spanish (who had less scurvy than the British) were on to something.  I don’t know if he used volunteers or not, but I do know that since then millions of people have volunteered to be part of clinical trials.  I salute those volunteers.  I work with people who present to the Emergency Department with chest pain or are seriously ill in the ICU.  These people are vulnerable, often scared, and are asking “Am I having a heart attack?”  Yet, despite this, when approached and asked to participate in a trial they very rarely say no.  This shows to me an incredible generosity of spirit & a heart-warming willingness to do something for someone else, even when that someone else is a mythical patient some time in the future.  I salute those volunteers.  They are my heroes.

I didn’t record the talk last night, but have tried to reproduce it this morning and present it to you now. Click HERE to access from Researchgate. It is not the same as with an audience as some of it was interactive.  However, I hope you enjoy it.  It is about 20 minutes long (100Mb) and deliberately targeted at a lay audience.

logos w uni

Major government health directive monitored for efficacy and safety

Last year I was fortunate to become part of a team at Christchurch hospital led by emergency care physician, Dr Martin Than. About 7 years ago in response to some local issues with how patients presenting with chest pain were being evaluated for potential heart attacks, Dr Than began a research program that investigated what clinical, demographic, and biological (blood) factors could best be used to safely and efficiently rule-out a heart attack.

Someone turning up at the doors of the Emergency Department with chest pain desperately wants to hear those reassuring words “You are not having a heart attack.” Unfortunately, for the ED staff this a very difficult conclusion to come to rapidly. As a result, around the world, as many as 90% of patients being assessed for possible heart attack end up being admitted to hospital overnight or longer, although only 20% of them end up being diagnosed with a heart attack. Obviously this is not good for the patient or the hospital – especially given tight budgets and lack of bed space. Dr Than’s work addressed the problem with a large multi-national observational study which assessed if a decision making pathway (called an accelerated diagnostic pathway or ADP for short) could increase the proportion of patients who could potentially not be admitted to hospital instead referred for some outpatient testing(1). This was further refined in another observational study which reduced the number of blood biomarkers that needed testing(2). Finally, and uniquely a randomised controlled trial of the new ADP verse standard practice was run at Christchurch Hospital. This was very successful, nearly doubling the proportion of patients who could be discharged to outpatient care within 6 hours of arriving in the ED(3). More has been done since on refining the ADP … but that is for another post.

The Ministry of Health liked what they saw as did ED physicians and Cardiologists throughout the country. This has resulted in the MOH asking all EDs within New Zealand to implement an accelerated diagnostic protocol. In doing so they will join all of Queensland, and a sprinkling of hospitals throughout the world that have recently adopted an ADP. This kind of positive outcome to local research is what every scientist dreams of, and Dr Than and his team have a right to be proud. But wait, as they say, there is more. Thanks to a Health Innovation Partnership grant from the Health Research Committee we are able to put in place a mechanism to monitor the effect and safety of an ADP at eight hospitals around New Zealand. This is where I come in, as I am collecting, collating and analysing the data for this project.   It is very exciting to be involved not only in helping implement a change of practice, but to be able to assess if that change is effective across a range of New Zealand hospitals from major inner-city hospitals to small rural hospitals, each of which has to adapt an ADP to meet their own particular circumstances. As I write Middlemore, North Shore, Wellington, Hutt Valley, Nelson and Christchurch hospitals all have new ADPs in place. Most if not all EDs will have them by the end of the year.

Some of where accelerated diagnostic pathways have been implemented.

Some of where accelerated diagnostic pathways have been implemented.

The model of observational research -> randomised controlled trial -> local implementation with further research -> mandatory national implementation -> research the effect of that change on local and national levels -> refine processes etc, is I believe a very good one and one that should be standard practice for major health initiatives. The MOH, HRC, and various district health boards that have bought into this process should be commended. There are other similar initiatives happening around the country and a look forward to when as a health consumer I can have confidence in any procedure I may face as been similarly thoroughly assessed.

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Thanks to my Acute Care Fellowship sponsors: Sponsors

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and to the grant funding body:

HRC

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References

  1. Than, M. P., Cullen, L., Reid, C. M., Lim, S. H., Aldous, S., Ardagh, M. W., et al. (2011). A 2-h diagnostic protocol to assess patients with chest pain symptoms in the Asia-Pacific region (ASPECT): a prospective observational validation study. Lancet, 377(9771), 1077–1084. doi:10.1016/S0140-6736(11)60310-3
  2. Than, M. P., Cullen, L., Aldous, S., Parsonage, W. A., Reid, C. M., Greenslade, J., et al. (2012). 2-Hour accelerated diagnostic protocol to assess patients with chest pain symptoms using contemporary troponins as the only biomarker: the ADAPT trial. Journal of the American College of Cardiology, 59(23), 2091–2098. doi:10.1016/j.jacc.2012.02.035
  3. Than, M. P., Aldous, S., Lord, S. J., Goodacre, S., Frampton, C. M. A., Troughton, R., et al. (2014). A 2-hour diagnostic protocol for possible cardiac chest pain in the emergency department: a randomized clinical trial. JAMA Internal Medicine, 174(1), 51–58. doi:10.1001/jamainternmed.2013.11362