Sunday, 3 April 2016

A 1-hour rule out MI protocol in the era of high sensitive troponin assays; ready for prime time

Studies of the high sensitive troponin assays all demonstrate the same thing. Patients will rule-in for MI much quicker compared to the old conventional assays. The vast majority will do so within a few hours of onset of symptoms.

The lead author of this study, Dr Tobias Reichlin has been working his way down the impact factor ladder with his ongoing research. His most recent offer has been published in the Canadian Medical Association Journal. But don’t let this fool you. This study is important and the final nail in the coffin for the 3 or 6 hour rule-out. 

This multicentre study enrolled 1320 patients presenting to the ED with suspected MI. The algorithm they attempted to validate used a baseline and 1 hour high sensitive troponin T. They looked at the absolute values in addition changes at one hour. Two independent cardiologists adjudicated the final diagnosis with access to all of the information (including troponin values... so ok, there was some incorporation bias with the gold standard.)

Results: The sensitivity and the negative predictive value for ruling out MI was 99.6% and 99.9% respectively. This made up about 60% of their cohort. The rule-in rate was 17%. They also had an indeterminate category that only made up one quarter of the patients overall. I have cut and pasted the algorithm below.

These results are one in a long line of studies demonstrating the same thing. Consistency in the literature is always compelling. The time has come to change our local protocols to allow for the safe rapid rule-out strategy in suitable patients.

Having said this, there is one strong word of caution. Beware the early presenters. Common sense would dictate that the person developing chest pain in the parking lot of the hospital should not undergo a one hour rule-out.

Unfortunately, the manuscript of this paper did a terrible job of describing the proportion of the early presenters. A vague and unhelpful mention was made in the on-line only appendix.

Another contention was the “data snooped” cut-off’s of 12ng/ml and 52ng/ml as their low and high cut-off’s for rule-out or rule-in MI. Of course this came from the earlier derivation study, but I think that 14ng/ml and 50ng/ml should be just fine. This certainly should make it more user friendly without having a substantial impact on test characteristics. Of course this is just my opinion, so there might be differing opinions.

If you are waiting for the AHA/ACC to provide updated guidelines then don’t hold your breath. The Americans have been very slow adopters of the high sensitive troponin assays. It is now up to us to determine what is clearly ready for prime time.


Reichlin T, Twerenbold R, Wildi K, et al. Prospective validation of a 1-hour algorithm to rule-out and rule-in acute myocardial infarction using a high sensitive cardiac troponin T assay. Can Med Ass J 2015;187:1-10. doi: 10.1503/cmaj.141349

Saturday, 2 April 2016

Cardiac catheterization for survivors of out of hospital cardiac arrest; on shaky ground?

This well done review and meta-analysis examined the current evidence in support of cardiac catheterization for survivors of out of hospital cardiac arrest.

Let’s cut right to the chase.

For the primary outcome, the acute catheterization group was clearly superior with almost 60% vs. 30% in hospital survival (Odds ratio 2.77 95% CI 2.06-3.72). Survival with good neurological outcome was nearly the same.

Of course the authors conclude that early coronary angiography in patients following OHCA is associated with improved outcomes... which is true of course.

But is all of the evidence on shaky ground?


All of the studies included in this meta-analysis were observational in nature. From a pure evidence based standpoint, it is possible that all of the difference in survival could be due to selection bias and confounding rather than the real efficacy of the intervention.

All observational studies are challenged by these issues. The best way around this is to conduct a properly blinded and randomized clinical trial. Of course this is not always ethical or feasible.

But there are those who believe there is enough clinical equipoise to warrant a proper experimental trial. A quick look at demonstrates several centres (USA, Spain, Sweden, & Canada) are currently on to it. Let’s hope we get some better data.

Despite lack of definitive efficacy I’m not about to jump out of an airplane without a parachute. Currently, I think it is very reasonable to be aggressive with early angiography in suitable patients. This is especially for those with STEMI’s and/or presumed primary cardiac cause of arrest. 

In the future, let’s hope the ground doesn’t start shaking. 


Camuglia AC, Randhawa VK, Lavi S, et al. Cardiac catheterization in associated with superior outcomes for survivors of out of hospital cardiac arrest: Review and meta-analysis. Resuscitation 2014;85:1533-1540. 

Friday, 1 April 2016

Outcomes of anatomical versus functional testing for coronary artery disease; To CTA or not to CTA... that is the question

A patient with no past history of CAD presents with new symptoms suggestive of cardiac disease. Should we get a CT angiogram (CTA) anatomic test or a functional test such nuclear stress testing, stress ECG or stress echo? Which test is better?

An even more difficult question is how do we measure which test is better? Should we focus on detection of CAD or should we look for outcomes that truly matter and are patient oriented? This is a difficult question to answer. At least these authors tried.

This study randomized 10,003 office based patients mostly in the USA to either initial anatomic or functional testing. The composite primary outcome measure was death, MI, hospitalization for unstable angina, major procedural complication, foot fungus and priapism. Ok, maybe not the last two.

Even with huge statistical power, there was no difference between the two groups. Both had very low rates of the composite outcome at 3% over a median follow up time of two years. However, more patients in the CTA group underwent revascularization 6% vs. 3%. Some would call this a 100% relative increase.

Does anatomical testing (CTA) find more false positives (overdiagnosis) and as such result in morbidity & increased cost from unnecessary treatment? I think these are reasonable questions.

In the end, the vast majority of these patients did just fine. This could be a reflection of the low risk patients in the USA that get included in such studies. The initial tests were positive for CAD in only about 10% of this study population.

How can this help us in the Emergency Department? I’m not so sure. But it is a great study that demonstrates an emphasis on patient oriented outcomes rather than simply looking at test characteristics.

The initial investigation of patients with suspected cardiac disease is high risk. I would imagine that doctors will be following local convention and protocol rather than contemplating philosophical matters at the bedside. This is just my opinion, so perhaps I’m wrong... comments?


Douglas PS, Hoffman U, Patel M, et al. Outcomes of Anatomic versus Functional Testing for Coronary Artery Disease. N Engl J Med 2015;372:1291-300.

Garbage in and garbage out; A systematic review and meta-analysis of acupuncture for angina pectoris

We'll keep this brief...

This “evidence-based study” out of the Journal of Traditional Chinese Medicine used surprisingly good methods looking at the efficacy of acupuncture for a variety of cardiac problems.

But due to fatal flaws, the majority of the details and the conclusion to this paper are irrelevant. Nevertheless it does provide some great opportunity for learning & teaching critical appraisal of the literature.

This systematic review found 21 articles that investigated acupuncture for angina. Unfortunately none of them were blinded, had allocation concealment or had sham acupuncture arms. Therefore all of the proposed benefit could easily be explained by the theatrical placebo of acupuncture. All prior good quality studies of acupuncture using proper blinding have shown it is no better than placebo.

The paper does mention these methodology issues and go so far as to say “all studies were assessed as having a high or moderate risk of bias.” Had they stopped here everything would have been fine. But they made the tragic mistake of proceeding to a meta-analysis and making ludicrous conclusions.

There are some statistical truths. No amount of analysis can remove bias from a study (simple confounding is a different matter). Nor can bias be overpowered by increasing the study size.

Put another way, they completely missed the crucial backbone of meta-analysis. If all you find is rubbish, you don’t combine it in a blender and expect a golden egg to appear. You’ve still got rubbish.


Chen J, Ren Y, Tang Y, et al. Acupuncture therapy for angina pectoris: a systematic review. J Tradit Chin Med 2012;32(4):494-501.