Category: Chest Pain

A Chest Pain Disposition Decision Instrument

This article has three things I like – information graphics, informed patients, and an attempt to reduce low-yield chest pain admissions.  Unfortunately, in the end, I’m not sure about the strategy.

This is a prospective study in which the authors developed an information graphic attempting to illustrate the outcome risks for low-risk chest pain presentations.  They use this information graphic as the intervention in their study population to help educate patients regarding the decision whether to be observed in the hospital with potential provocative stress testing, or whether they would like to be discharged from the Emergency Department to follow-up for an outpatient provocative test.  They were attempting to show that use of this decision aid would lead to increased patient knowledge and satisfaction, as well as reduce observation admissions for low-risk chest pain.

The good news: it definitely works.  Patients reported increased knowledge, most were happy with the decision instrument, and a significantly increased proportion elected to be discharged from the Emergency Department – 58% of the decision aid group wanted to stay vs. 77% of the “usual care” arm wanted to stay.

My only problem: this study truly exposes the invalidity of our current management of chest pain.  If these patients are low-risk and they’re judged safe enough for the outpatient strategy in this study – why are any of them being offered admission?  Of course, it’s probably because they don’t have timely follow-up, and AHA guidelines dictate stress testing urgently following the index visit.  But, truly, in an ideal world, few (if any) of these low-risk patients – such as the one who ruled in by enzymes – should be offered admission.

But, other than that, I’m all for information graphics and patient education techniques to include them in a shared decision-making process!

“The Chest Pain Choice Decision Aid : A Randomized Trial”
www.ncbi.nlm.nih.gov/pubmed/22496116

How Canada Does Chest Pain

Vancouver, Canada, to be specific.  The 37th most expensive city in the world to live in (ahead of New York and Los Angeles), a jewel on the coast of British Columbia, with breathtaking scenery, evergreens, rugged coasts, and mountains.

This is an observational series of their chest pain algorithm, and it falls into the category of “we do this and we like it” types of articles.  So, they do this, and they like it, and I can see why.

And the first thing you notice is that it is nothing like the United States.  Of the 1,116 patients they enrolled for this follow-up, they send home 25% of their potentially cardiac chest pain after an EKG and a single troponin.  These are patients whose mean age is 43 years old, and have TIMI scores of 0 or 1.  No outpatient stress test is arranged.  None of them had ACS within 30 days.

Another 20% had a negative 2-hour troponin and EKG and were sent home without outpatient stress testing, average age 49 years old and TIMI scores mostly 0 and 1.  None of them had ACS within 30 days.

Finally, at six hours, they were left with a group of 60 year old folks, 30% of their cohort, whose TIMI scores were >1.  They sent them all home, 25% of without an outpatient stress test and 75% with – and none of the no-stress cohort had ACS within 30 days.

Essentially, they send home over half their patients, aged 40 to 60 years old, and a couple cardiac risk factors – and they do fine.  We don’t really know what sort of coronary disease the patients discharged without a follow-up stress test had, and it means they probably have some false negatives in their outcomes at 30 days simply because they don’t receive any sort of additional diagnostic testing.  But, none of them had an unprovoked adverse coronary event, which counts for something.

About 20% of their patients referred for outpatient stress failed, and about half of those ultimately received a diagnosis of ACS – so, even then, in the patients they were most concerned about after negative ED testing, only 10% had ACS.  Seems like there’s room to improve here, as well.

It’s not crazy, it’s Canada.

“Safety and Efficiency of a Chest Pain Diagnostic Algorithm With Selective Outpatient Stress Testing for Emergency Department Patients With Potential Ischemic Chest Pain”
www.ncbi.nlm.nih.gov/pubmed/22221842

Glucose-Insulin-Potassium For MI?

“Investigators, led by Dr Harry Selker (Tufts Medical Center, Boston, MA), are pleased with the results, believing that after years of futile study, they have finally found some clinical evidence to support the experimental data suggesting that GIK [glucose-insulin-potassium] myocardial metabolic support could protect the heart in the ACS setting.”

…which lead to the press release tweet of “Intravenous GIK Slashes Death Risk in Acute Coronary Syndrome: CHICAGO – Glucose, insulin, and potassium given i…” by @ACEPNews.  That press release can be seen here.

There have been trials enrolling over 20,000 patients to date that have been negative.

Despite all these previous negative trials, the authors believed the problem was timeliness – the critical time in which to provide metabolic support to the infarcting myocardium was in the prehospital setting, upon the earliest recognition of ACS.  The original goal was to enroll 15,450 patients.  They ended up with 880.  Then, after data collection, they changed the primary endpoint from all-cause mortality to progression to myocardial infarction at 30 days and at 1 year.  And they only have the 30 day data right now, they’ll get back to us with the 1 year outcomes.  How this made the cut for publication in JAMA is outside the scope of my speculative powers.

So, they enrolled folks prehospital with signs and symptoms of potential acute coronary syndrome whose prehospital EKG was read as STEMI or met the ACI-TIPI prediction instrument probability threshold of 75%.  They received the GIK solution with 90 minutes, on average.  And, the primary outcome measure was negative for progression to MI, trend favoring GIK with OR 0.88 (CI 0.66-1.13).  Negative for 30 day mortality, OR 0.72 (0.40-1.29).  For STEMI patients, negative for progression to MI, OR 0.74 (0.40-1.38), and negative for 30 day mortality, OR 0.63 (0.27-1.49).
So, yes, there is a trend.  And some subgroups even had significant trends in favor of GIK.  But for JAMA and the rest of the internet to be promoting this as practice-changing at this juncture is absolutely inappropriate.

“Out-of-Hospital Administration of Intravenous Glucose-Insulin-Potassium in Patients With Suspected Acute Coronary Syndromes:  The IMMEDIATE Randomized Controlled Trial”
http://jama.ama-assn.org/content/early/2012/03/21/jama.2012.426.full

CCTA Is A Bad Shortcut Around Bad Care

“Although an acute coronary syndrome is ultimately diagnosed in only 10 to 15% of patients who present with chest pain, the majority of these patients are admitted to hospitals, at an estimated cost of over $3 billion annually.”

This is, essentially, the statement of problem from the NEJM article, sponsored by Siemens, regarding the use of coronary CT angiograms in the Emergency Department on low-to-intermediate risk chest pain.  They are clearly huge fans of CCTA up at the University of Pennsylvania, and I hate to think it has something to do with the parade of imaging technology companies and patent applications listed as disclosures by the authors.

In this study, the authors enrolled 1,392 patients with chest pain with the goal of testing the primary hypothesis that “patients without clinically significant coronary disease on CCTA (i.e., no coronary-artery stenosis ≥50%) would have a 30-day rate of cardiac death or myocardial infarction of less than 1%.”

Good news!  They were right.  Bad news:  their entire enrolled cohort had a 30-day death or MI rate of only nearly 1%.  It’s rather incredible, really, that they have this entire article in which they sing the praises of CCTA for identifying low-risk chest pain, when in reality, they gloss over the fact that they simply could have sent home every single patient in the study without doing a single additional test and only nearly 1% would have had death or MI within 30 days.

Going back to their essential statement of problem, it might be true that CCTA were valuable if they were looking to apply it in a population and practice environment in which we were actually hospitalizing patients with a 10-15% rule-in rate.  However, the opposite of what these authors propose is the real truth – clinically identify all the low-risk chest pain and stop doing all these expensive tests!  They claim it expedites discharge from the Emergency Department, which, in theory, saves money – but it isn’t!  Despite 90% of their CCTA being negative for stenosis >50%, they still end up admitting half their CCTA cohort.  Even the negative CCTA cohort, while their length of stay is reduced to 12 hours, still means they’re being placed in observation status and billed an additional separate observation code – which in many places is a protocolized chest pain observation unit run by the Emergency Department.

This is simply a bad solution to bad baseline practice patterns.  The measurable benefit here isn’t to the patient, it’s to the malpractice risk of the physician, to Siemens and other sponsors of the study, and likely to the Emergency Departments whose billing increases for these short stay observation patients.

“CT Angiography for Safe Discharge of Patients with Possible Acute Coronary Syndromes”
http://www.nejm.org/doi/full/10.1056/NEJMoa1201163

Yet Another Highly Sensitive Troponin – In JAMA

…peddling the same tired phenomenon of magical thinking regarding the diagnostic miracle of highly sensitive troponins.  However, this one is different because it’s been picked up by the AP, CBS News, Forbes, etc. saying: “Doctors are buzzing over a new blood test that might rule out a heart attack earlier than ever before” and other such insanity.  Yes, our hearts are in atrial flutter around the water cooler about a new assay that changes sensitivity from 79.4% to 82.3% at hour 0 and 94.0% to 98.2% at hour 3.


Unless you actually read the article.

Somehow, contrary to every other high-sensitivity troponin study, this particular highly-sensitive troponin had increased specificity as well – which simply doesn’t make sense.  If you’re testing for the presence of the exact same myocardial strain/necrosis byproduct as a conventional assay, it is absolutely inevitable that you will detect a greater number of >99th percentile values in situations not reflective of acute coronary syndrome.  The only way to increase both sensitivity and specificity is to measure something entirely different.


Or, if it suits your study aims, you can manipulate the outcomes on the back end.  In this study, the final diagnosis of ACS “was adjudicated by 2 independent cardiologists” whose diagnostic acumen is enhanced by financial support including Brahms AG, Abbott Diagnostics, St Jude Medical, Actavis, Terumo, AstraZeneca, Novartis, Sanofi-Aventis, Roche Diagnostics, and Siemens.

I am additionally not impressed by their results reporting – sensitivity and specificity, followed by the irrelevant positive predictive and negative predictive values.  Since the PPV and NPV are determined by the incidence of disease in their cohort, they’re giving us numbers that are potentially not externally valid.  Rather, they should be reporting positive and negative likelihood or odds ratios – which are relatively cognitively unwieldy, but at least not misleading, but conceptually facile, like PPV and NPV.

And this is from JAMA.  Oi.

“Serial Changes in Highly Sensitive Troponin I Assay and Early Diagnosis of Myocardial Infarction”

It’s Another Chest Pain Prediction Rule!

Yet again, the insanity of the race to a zero-miss culture funds another chest pain discharge prediction rule.  In fact, the most telling part of this paper is in the very end when they compare the chest pain admission rates of the Canadian hospitals in this article to the U.S. hospital – 18% and 20% in Canada compared to 96% in the U.S. (combined ED observation status and inpatient).  The difference in those numbers is insane – and I’m sure people could easily debate which is the preferred side of those numbers to be on.

In any event, the study is a prospective, observational data-gathering study of 64 variables related to the presentation of chest pain – some of which are objective and some of which are historical.  It’s an interesting read – in part because the inter-observer kappa for a lot of the historical variables is so terrible they weren’t even usable.  After collecting all their data, they did 30-day telephone follow-up or vital records review to evaluate the combined endpoint of death, myocardial infarction, or revascularization.

Via the magic of recursive partitioning, a patient without new EKG changes, a negative initial troponin, no history of CAD, atypical pain, and age less than 40 years separated out 7.1% of their study population that had zero 30-day outcomes.  Adding a second negative troponin six hours later for the 41-50 year group gives another 11.2% of patients that had zero outcomes.  So, a facility that admits 96% of their patients could potentially reduce admissions – but it might have less utility in Canada.

I’d rather see a two-hour second troponin than a six-hour one; it might reduce sensitivity, but it’s wholly impractical to tie up a bed in the ED for 6 hours for a patient you want to send home.  And, like most of these articles, the combined endpoint of death, MI, and revascularization is irritating.  Considering there were twice as many revascularizations as myocardial infarctions, there really ought to be more granularity in these sorts of studies with regard to the actual coronary lesions identified rather than simply lumping them into a combined endpoint.

“Development of a Clinical Prediction Rule for 30-Day Cardiac Events in Emergency Department Patients With Chest Pain and Possible Acute Coronary Syndrome”
www.ncbi.nlm.nih.gov/pubmed/21885156

How Do We Miss Aortic Dissection?

This is a retrospective look at 109 cases eventually diagnosed with aortic dissection – with a focus on the differentiating clinical features present in the 17 cases where the diagnosis was initially missed in the Emergency Department.

Confounding clinical attributes that were associated with a missed diagnosis were walk-in vs. ambulance arrival and presence of anterior chest pain.  Chest x-rays lacking a wide mediastinum were nonsignificantly associated with missed aortic dissection, and with only 55% of their diagnosis cohort having a wide mediastinum vs. 25% of their misdiagnosis cohort.  Interestingly, over 75% of each group received a d-Dimer and they were all positive in the misdiagnosis group as well as all but one in the diagnosis group.  It would seem that they order so many d-Dimers that they’ve become fatigued to its clinical usefulness due to its poor specificity.

The good news is the patients who were initially misdiagnosed had similar mortality (18% vs. 15%) – despite 7 of the 17 being treated with antithrombotic agents.  Most of the missed diagnoses were classified as undifferentiated possible ischemic chest pain, but two were diagnosed with renal colic.

As always, the main problem with missed-diagnosis literature is there’s no guarantee the authors didn’t miss another set of cases themselves.

“Factors leading to failure to diagnose acute aortic dissection in the emergency room.”
www.ncbi.nlm.nih.gov/pubmed/21889877

ACI-TIPI For Predicting Cardiac Outcomes

In an earlier post, I noted an article that had done a systematic review finding 115 publications attempting to create or validate clinical prediction rules for chest pain.  Well, here’s number 116.

The ACI-TIPI (Acute Cardiac Ischemia Time-Insensitive Predictive Instrument) is computerized analysis software that generates a score regarding the likelihood of cardiac ischemia based on age, gender, chest pain and EKG variables.  It’s actually a product marketed and sold by Philips.  These authors tried to evaluate how predictive this instrument was for predicting 30-day events, with an interest in identifying a group that could be safely discharged from the Emergency Department.

In an institution with 55,000 visits a year, the authors recruited only 144 chest pain patients – which is the first red flag.  It doesn’t matter how good your prediction rule is if you only recruit 144 patients – your confidence intervals will be terrible, and their sensitivities for identifying 30 day cardiac outcomes are 82-100% at best.  And, yes, they did say if the ACI-TIPI score is <20, it had a purportedly useful negative predictive value.

So, I suppose this paper doesn’t really tell us much – and even if the data were better, I’m not sure the sensitivity/specificity of this ACI-TIPI calculation would meet a useful clinical threshold to reduce low-risk hospitalizations any better than clinical gestalt.  I’ll be back with you when I find risk-stratification attempt 117….

“Prognostic utility of the acute cardiac ischemia time-insensitive predictive instrument (ACI-TIPI)”
www.intjem.com/content/4/1/49

CT Coronary Angiography Proves People WIth CAD Die Sooner

This is a neat study that followed up 23,854 patients from a multicenter CTCA registry – the CONFIRM registry – over three years to evaluate their long term prognostic risk.  And – amazingly enough – the patients who had no coronary artery disease identified on their CTCA had an annualized rate of 0.28% of death from all causes.  Which seems pretty impressive, and it’s better than the people who had non-obstructive and various types of obstructive CAD on their CTCA.

But then, the hazard ratios for patients who had 3-vessel and left main disease on their CTCA was still only as high as six times more likely than the no CAD cohort – which is a lot higher in relative terms, but still not very high in absolute terms – and there were a lot of other comorbidities in these patients that would contribute to their all-cause mortality from non-cardiac causes.  So, yes, not having CAD – as well as being a generally healthy person – helps you live longer.

The question still remains where CTCA fits into an Emergency Department evaluation for chest pain.  We are seeing more and more research now that primary PCI for asymptomatic lesions isn’t any survival benefit over medical management – so identifying these lesions and admitting these patients to cardiology for intervention isn’t going to be in our future.  Considering over 55% of their cohort had either non-obstructive or obstructive disease found, now you’re going to be on the hook for making outpatient CAD risk-modification decisions after cardiology declines them.

Whether CTCA is used should be a standardized, institution-wide decision, because I don’t think anyone wants to take the weight of sorting through all this evidence and risk/benefit ratios as a lone wolf.

“Age- and Sex-Related Differences in All-Cause Mortality Risk Based on Coronary Computer Tomography Angiography Findings”
www.ncbi.nlm.nih.gov/pubmed/21835321

CCTA Only Predicts Revascularizations

This is an interesting systematic review of coronary computer tomography angiography that, I think, shows mostly that the endpoints for cardiology studies need to be re-evaluated.  The conclusion that circulates in the new has been that positive CCTA was highly predictive of coronary events – patients with >1 segment of >50% stenosis on CCTA had an 11.9% annualized rate of coronary “events” when compared to the 1.1% annualized rate of patients without any >50% stenosis.  This generates the 10.74 hazard ratio that has been circulating through the press releases trumpeting the predictive value of CCTA.

Unfortunately, this predictive value is a self-fulfilling prophecy because 62% of their “events” were revascularizations.  If you subtract out the portion that went for revascularization, the remaining all-cause mortality, cardiovascular death, nonfatal MI, UA requiring hospitalization, that’s 5% annualized rate.  Still higher than folks without any coronary stenoses at all, but you have to wonder – could we have predicted the population with a 5% cardiovascular morbidity risk without a CCTA?  Does the management decision to perform revascularization confer upon this population a cardiovascular morbidity/mortality benefit?  We are seeing a lot more in the literature showing that medical management is as advantageous as stenting, so, again, I’m not sure what the role of CCTA is – particularly from the Emergency Department.

“Meta-analysis and systematic review of the long-term predictive value of assessment of coronary atherosclerosis by contrast-enhanced coronary computed tomography angiography.”
http://www.ncbi.nlm.nih.gov/pubmed/21658564