Category: Chest Pain

Comparing Unnecessary ED Chest Pain Testing

Since my last post regarding the disutility of coronary CT angiograms for the evaluation of acute chest pain in the Emergency Department was so popular, here’s more: a randomized trial testing CCTA versus stress echocardiogram.

The problem: no specific functional or anatomic testing is routinely necessary in the ED.

And, hidden in this comparison are broad results typical of testing in a “low to intermediate” population with a Diamond-Forrester pre-test probability of 28% and a TIMI score of 0 to 1. Effectively, it’s unimportant to describe their comparison because the incidence of their safety outcomes over a median follow-up of 733 days is so low its virtually impossible to detect a difference. Any Major Adverse Cardiovascular Event occurred in only 4.5% of all patients – but, restricted to the endpoints relevant to the testing performed, only 3.0% had a nonfatal myocardial infarction or cardiac arrest. Any differences in throughput and resource utilization between arms will be related to specific process and protocol implementation unique to the trial institution, so even their findings with respect to their primary outcome are not likely to be generalizable.

But, back to the futility of any test – only 10% of those enrolled were referred for cardiac catheterization, and only half of those received an intervention as a result. Another 10% or so received new or increased pharmacotherapy – likely overlapping with the population undergoing catheterization. Therefore, probably 85% of patients enrolled clearly received no specific benefit from these tests, 5% probably had some benefit, 5% were harmed (excess revascularization, serious complications), and 5% are equivocal.

And, all of this on the foundational premise these tests need to be performed widely, and in the ED. True disease is rare in this population, and the timeliness of diagnosis of CAD does not need to be made at the index visit. This is not high-value medical care.

“Coronary Computed Tomography Angiography Versus Stress Echocardiography in Acute Chest Pain: A Randomized Controlled Trial”

https://www.ncbi.nlm.nih.gov/pubmed/29909113

And Here’s Why CTCA Is Useless

In the Emergency Department, that is, at least.

A few years ago, there were several major studies evaluating the safety of a CT coronary angiogram-based study for the evaluation of chest pain in the Emergency Department. These studies consistently found the CTCA is sensitive for coronary artery plaque – and, thus, patients with troponin-negative chest pain syndromes and clear coronary arteries could be discharged from the ED.

The constant challenge, however, has been specificity – not only with respect to whether the CT can accurately detect stenoses, but the clinical relevance of the stenoses. Non-obstructive, moderate, and high-grade stenoses detected on CTCA all trigger further evaluation – either non-invasive or invasive, with subsequent interventions of uncertain clinical value.

This small propensity-matched study from a cohort of 25,251 patients undergoing CTCA picked out 234 pairs of patients, matching those who had an acute coronary syndrome during follow-up with those who did not. And, yes, those with ≥50% or ≥70% stenosis were more likely to suffer an ACS, but not my much. The vast majority – 62% – of those with an ACS in follow-up had non-obstructive coronary disease. Indeed, just over half of patients with an ACS even had their culprit lesion identified on the initial CTCA. The degree of stenosis was mildly predictive of future ACS, but plaque burden between those who suffered an event and those who did not was similar. The most predictive feature, however, was composition of non-obstructive plaque, including fibrofatty features and necrotic core.

This is why CTCA is unhelpful in the Emergency Department. It does, yes, accurately detect patients without coronary disease – but this target “low-risk” population already has such a low pretest likelihood of poor outcome the added value is nil. Then, the “true positives” from these studies – stenoses and interventions – are not equivalent to ACS prevented.

Friends don’t let friends do CTCA in the ED – it doesn’t add value or prevent adverse outcomes.

“Coronary Atherosclerotic Precursors of Acute Coronary Syndromes”
http://www.onlinejacc.org/content/71/22/2511

EDACS vs. HEART – But Why?

The world has been obsessed over the past few years with the novelty of clinical decision rules for the early discharge of chest pain. After several years of battering the repurposed Thrombolysis in Myocardial Infarction (TIMI) score, History, Electrocardiogram, Age, Risk factors and Troponin (HEART) became ascendant, but there are several other candidates out there.

One of these is Emergency Department Assessment of Chest pain Score (EDACS), which is less well-known, but has reasonable face validity.  It does a good job identifying a “low-risk” cohort, but is more complicated than HEART. There is also a simplified version of EDACS that goes ahead and eliminates some of the complicated subtractive elements of the score. This study pits these various scores head-to-head in the context of conventional troponin testing, as well.

This is a retrospective review of 118,822 patients presenting to Kaiser Northern California Emergency Departments, narrowing the cohort to those whose initial Emergency Department evaluation was negative for acute coronary syndrome. The 60-day MACE (composite of myocardial infarction, cardiogenic shock, cardiac arrest, and all-cause mortality) in this cohort was 1.9%, most of which were acute MI. Interestingly, these authors chose to present only the negative predictive value of their test characteristics, which means – considering such low prevalence – the ultimate rate of MACE in all the low-risk cohorts defined by each decision instrument were virtually identical. Negative predictive values of all three scores depended primarily on the troponin cut-off used, and were ~99.2% for ≤0.04 ng/mL, and ~99.5% for ≤0.02 ng/mL. The largest low-risk cohort by definition was with the original EDACS rule, exceeding the HEART score classification by an absolute quantity of about 10% of the total cohort, regardless of the troponin cut-off used.

The editorial accompanying the article goes on to laud these data as supporting the use of these tools for early discharge from the Emergency Department. However, this is an outdated viewpoint, particularly considering the data showing early non-invasive evaluations are of uncertain value. In reality, virtually all patients who have been ruled-out for ACS in the ED can be discharged home, regardless of risk of MACE. The value of these scores is probably less so in determining who can be discharged, but rather in helping triage patients for closer primary care or specialist follow-up.  Then, individualized plans can be developed for optimal medical management, or for assessment of the adequacy of the coronary circulation, to prevent what MACE is feasible to be prevented.

“Performance of Coronary Risk Scores Among Patients With Chest Pain in the Emergency Department”
http://www.onlinejacc.org/content/71/6/606

“Evaluating Chest Pain in the Emergency Department: Searching for the Optimal Gatekeeper.”
http://www.onlinejacc.org/content/71/6/617

Neither Benefit Nor Harm Seen With Oxygen in Myocardial Infarction

We’ve been hanging on to the biological hypothesis of treating ischemia with supplemental oxygen for quite some time – despite some evidence to the contrary with regard to damage from oxygen free radical formation. What’s needed is a large, randomized trial – and so we have DETOX2-AMI, run through the SWEDEHEART trial registry.

This trial randomized individual patients with suspected or known myocardial infarction to continuous oxygen therapy or ambient air.  Patients were excluded from enrollment if they had oxygen saturation below 90% at baseline, or were not Swedish national citizens as necessary for long-term follow-up. These patients actually received fairly vigorous oxygen therapy, far exceeding the typical nasal cannula oxygen we see on patients arriving via EMS – patients randomized to the oxygen arm received 6 liters per minute via face mask for 6 to 12 hours.

Over the 1.5 year trial period, these authors enrolled 6,629 patients, generally evenly matched with regard to baseline clinical characteristics, and 75% of whom ultimately had a final diagnosis of myocardial infarction.  Detailed outcomes, owing to the underlying registry infrastructure, are scant – as compared to the AVOID trial, in which many patients underwent cardiac MRI to evaluate infarct size and ejection fraction. What you get are the hard outcomes: death and rehospitalization with myocardial infarction – and there is no difference, both in the short- or long-term, and in both the intention-to-treat and per-protocol analyses. The authors also include median highest troponin T as a surrogate for infarct severity and morbidity, and there is no difference there, either.

The underlying hypothesis here was to demonstrate a beneficial effect to oxygen in myocardial infarction – defined as a clinically relevant effect size of 20% lower relative risk of death – and that threshold was clearly not met.  There are some small differences with regard to oxygen delivery, as compared to AVOID, with the AVOID trial delivering oxygen at a much higher concentration.  But, effectively, the takeaway from these data is: oxygen just probably doesn’t matter enough to be clinically relevant. There’s no reason to be condescending and militant about taking the oxygen off a patient with myocardial infarction, and likewise it’s reasonable to consider it a wasteful intervention with regard to canistered oxygen supply.

Finally, just for fun, to recap the anachronistic acronym MONA:

Morphine – Possible small harms, as relating to inhibition of antiplatelet agents.
Oxygen – Almost certainly irrelevant with regard to clinical outcomes.
Nitroglycerin – Likely irrelevant with regard to clinical outcomes.
Aspirin – Still good!

“Oxygen Therapy in Suspected Acute Myocardial Infarction”
http://www.nejm.org/doi/full/10.1056/NEJMoa1706222

Let’s Get Together and Ignore PERC

The “Pulmonary Embolism Rule-Out Criteria” does not, as it implies, “rule out” PE.  It does, however, generally carve out a cohort for whom objective testing may be obviated, with the implication the costs and harms from false-positives and from anticoagulation outweigh the morbidity from missed PE. It is fairly well popularized and incorporated into guidelines for PE – and, well, at the least, physicians in an academic center, on the cutting edge of medical knowledge and education, should be applying appropriately.

Or not.

This is a prospective study enrolling undifferentiated Emergency Department patients with chest pain and shortness of breath. Research staff approached patients with these general chief complaints and collected the baseline variables needed for PERC, Wells, and other baseline clinical and historical data.  They collected data on 3,204 patients, 17.5% of whom were PERC-negative. Of these, 25.5% underwent some testing for pulmonary embolism – inclusive of D-dimer, CTPA, or V/Q scanning. Then, two – 0.4% – PERC-negative patients were ultimately diagnosed with a PE. The authors also present comparative data for the PERC-positive population, with the expected higher-frequency of testing and diagnosis associated with the absence of low-risk features.

PERC is, of course, an imperfect tool, an unavoidable consequence of any decision instrument narrowing a complex clinical decision down to a handful of variables. But, at the least, patients meeting PERC ought nearly all fall into the bucket of “why were you really considering PE in the first place?”, with few exceptions. For nearly a quarter of these to start down the rabbit hole of testing for PE is low-value and harmful medical practice at a population level, regardless of the potential magnitude of individual benefit for those true positives ultimately identified.

AOr, more concisely, this is nuts.

“Pulmonary Embolism Testing among Emergency Department Patients who are Pulmonary Embolism Rule-out Criteria Negative”

http://onlinelibrary.wiley.com/doi/10.1111/acem.13270/full

Questioning the Benefit of Non-Invasive Testing for Chest Pain

Welcome to the fascinating world of instrumental variable analysis!

This is a retrospective cohort analysis of a large insurance claims database attempting to glean insight into the value of non-invasive testing for patients presenting to the Emergency Department with chest pain. Previous version of the American Heart Association guidelines for the evaluation of so-called “low risk” chest pain have encouraged patients to undergo some sort of objective testing with 72 hours of initial evaluation. These recommendations have waned in more recent iterations of the guideline, but many settings still routinely recommend admission and observation following an episode of chest pain.

These authors used a cohort of 926,633 unique admissions for chest pain and analyzed them to evaluate any downstream effects on subsequent morbidity and resource utilization.  As part of this analysis, they also split the cohort into two groups for comparison based on the day of the week of presentation – hence the “instrumental variable” for the instrumental variable analysis performed alongside their multivariate analysis. The authors made assumptions that individual patient characteristics would be unrelated to the day of presentation, but that downstream test frequency would. The authors then use this difference in test frequency to thread the eye of the needle as a pseudo-randomization component to aid in comparison.

There were 571,988 patients presenting on a weekday, 18.1% and 26.1% of which underwent some non-invasive testing within 2 and 30 days of an ED visit, respectively. Then, there were 354,645 patients presenting on a weekend, with rates of testing 12.3% and 21.3%. There were obvious baseline differences between those undergoing testing and those who did not, and those were controlled for using multivariate techniques as well as the aforementioned instrument variable analysis.

Looking at clinical outcomes – coronary revascularization and acute MI at one year – there were mixed results: definitely more revascularization procedures associated with exposure to non-invasive testing, no increase in downstream diagnosis of AMI. The trend, if any, is actually towards increased diagnoses of AMI. The absolute numbers are quite small, on the order of a handful of extra AMIs per 1,000 patients per year, and may reflect either the complications resulting from stenting or a propensity to receive different clinical diagnoses for similar presentations after receiving a coronary stent.  Or, owing to the nature of the analysis, the trend may simply be noise.

The level of evidence here is not high, considering its retrospective nature and dependence on statistical adjustments.  It also cannot determine whether there are longer-term consequences or benefits beyond its one-year follow-up time-frame. Its primary value is in the context of the larger body of evidence.  At the least, it suggests we have equipoise to examine which, if any, patients ought to be referred for routine follow-up – or whether the role of the ED should be limited to ruling out an acute coronary syndrome, and the downstream medical ecosystem is the most appropriate venue for determining further testing when indicated.

“Cardiovascular Testing and Clinical Outcomes in Emergency Department Patients With Chest Pain”

http://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2633257

You’ve Got (Troponin) Mail

It’s tragic, of course, no one in this generation will understand the epiphany of logging on to America Online and being greeted by its almost synonymous greeting “You’ve got mail!” But, we and future generations may bear witness to the advent of something almost as profoundly uplifting: text-message troponin results.

These authors conceived and describe a fairly simple intervention in which test results – in this case, troponin – were pushed to clinicians’ phones as text messages. In a pilot and cluster-randomized trial with 1,105 patients for final analysis, these authors find the median interval from troponin result to disposition decision was 94 minutes in a control group, as compared with 68 minutes in the intervention cohort. However, a smaller difference in median overall length of stay did not reach statistical significance.

Now, I like this idea – even though this is clearly not the study showing generalizable definitive benefit. For many patient encounters, there is some readily identifiable bottleneck result of greatest importance for disposition. If a reasonable, curated list of these results are pushed to a mobile device, there is an obvious time savings with regard to manually pulling these results from the electronic health record.

In this study, however, the median LOS for these patients was over five hours – and their median LOS for all patients receiving at least one troponin was nearly 7.5 hours. The relative effect size, then, is really quite small. Next, there are always concerns relating to interruptions and unintended consequences on cognitive burden. Finally, it logically follows if this text message derives some of its beneficial effect by altering task priorities, then some other process in the Emergency Department is having its completion time increased.

I expect, if implemented in a typically efficient ED, the net result of any improvement might only be a few minutes saved across all encounter types – but multiplied across thousands of patient visits for chest pain, it’s still worth considering.

“Push-Alert Notification of Troponin Results to Physician Smartphones Reduces the Time to Discharge Emergency Department Patients: A Randomized Controlled Trial”
http://www.annemergmed.com/article/S0196-0644(17)30317-7/abstract

Use HEART, Or Whatever

The HEART score receives a lot of favorable press these days. It generally has face validity. It is probably superior in terms of discriminatory ability versus our venerable candidates such as TIMI and GRACE. It has been well-evaluated in multiple practice settings with reliable predictive value.

But, the final question for a decision instrument distilling a complex clinical scenario down to a five-question substrate for guiding evaluation and disposition – does it safely improve practice?

The answer is no – if you’re Dutch, in these Dutch hospitals.

In a stepped-wedge, cluster-randomized trial, these authors evaluated the effect of using HEART on patient outcomes and healthcare resource utilization. The three HEART risk categories carry general practice recommendations, in which low-risk (0-3) suggest early discharge, intermediate-risk (4-6) noninvasive testing, and high-risk (7-10) early invasive strategies. The comparator, “usual care” was, well, as usual.

With two cohorts comprising approximately 1,800 patients each, there were probably no reliable differences in care or outcomes demonstrated. The HEART low-risk cohort had a 2.0% 30-day incidence of MACE, which is similar to the safety profile described in other studies. However, the real goal of this evaluation was to determine acceptability and impact on resource utilization – and those results are decidedly mixed. Similar rates of early discharge from the ED, ED observation, inpatient admission, and downstream outpatient utilization were observed between the HEART cohort and usual care.

But, this answer from above – no impact on practice – is argued by these authors to be mostly related to non-adherence to the protocol recommendations. Most importantly, they note nearly a third of their low-risk patients were kept for prolonged ED or chest pain unit observation, and a handful more were admitted. The authors suggest there may be room for improvement in resource utilization, but they encountered entrenched cultural practice barriers.

This study was conducted between July 2013 and August 2014 – a long time ago, before most had heard of HEART. It is reasonable to suggest clinicians would now be more comfortable using this score for early discharge from the Emergency Department than during the trial period. It is probably also reasonable to suggest a more robust cultural effort backing practice change would improve adherence to recommendations – a collective departmental agreement associated with educational initiatives. Finally, usual care entailed early discharge of nearly 50% of all patients with chest pain, so your local baseline will affect whether a HEART-based protocol demonstrates improvement.

While these results in this trial are generally negative, what we see here is probably the floor for the effect of HEART on practice. At a minimum, it is as safe as advertised, and probably has room to demonstrate more robust beneficial effects on practice.

“Effect of Using the HEART Score in Patients With Chest Pain in the Emergency Department”

https://www.ncbi.nlm.nih.gov/pubmed/28437795

Troponin Sensitivity Training

High-sensitivity troponins are finally here! The FDA has approved the first one for use in the United States. Now, articles like this are not for purely academic interest – except, well, for the likely very slow percolation of these assays into standard practice.

This is a sort of update from the Advantageous Predictors of Acute Coronary Syndrome Evaluation (APACE) consortium. This consortium is intended to “advance the early diagnosis of [acute myocardial infarction]” – via use of these high-sensitivity assays for the benefit of their study sponsors, Abbott Laboratories et al. Regardless, this is one of those typical early rule-out studies evaluating the patients with possible acute coronary syndrome and symptoms onset within 12 hours. The assay performance was evaluated and compared in four different strategies: 0-hour limit of detection, 0-hour 99th percentile cut-off, and two 0/1-hour presentation and delta strategies.

And, of course, their rule-out strategies work great – they miss a handful of AMI, and even those (as documented by their accompanying table of missed AMI) are mostly tiny, did not undergo any revascularization procedure, and frequently did not receive clinical discharge diagnoses consistent with acute coronary syndrome. There was also a clear time-based element to their rule-out sensitivity, where patients with chest pain onset within two hours of presentation being more likely missed. But – and this is the same “but” you’ve heard so many times before – their sensitivity comes at the expense of specificity, and use of any of these assay strategies was effective at ruling out only half of all ED presentations. Interestingly, at least, their rule-out was durable – 30-day MACE was 0.1% or less, and the sole event was a non-cardiac death.

Is there truly any rush to adopt these assays? I would reasonably argue there must be value in the additive information provided regarding myocardial injury. This study and its algorithms, however, demonstrates there remains progress to be made in terms of clinical effectiveness – as obviously far greater than just 50% of ED presentations for chest pain ought be eligible for discharge.

“Direct Comparison of Four Very Early Rule-Out Strategies for Acute Myocardial Infarction Using High-Sensitivity Cardiac Troponin I”
http://circ.ahajournals.org/content/early/2017/03/10/CIRCULATIONAHA.116.025661

Ottawa, the Land of Rules

I’ve been to Canada, but I’ve never been to Ottawa. I suppose, as the capital of Canada, it makes sense they’d be enamored with rules and rule-making. Regardless, it still seems they have a disproportionate burden of rules, for better or worse.

This latest publication describes the “Ottawa Chest Pain Cardiac Monitoring Rule”, which aims to diminish resource utilization in the setting of chest pain in the Emergency Department. These authors posit the majority of chest pain patients presenting to the ED are placed on cardiac monitoring in the interests of detecting a life-threatening malignant arrhythmia, despite such being a rare occurrence. Furthermore, the literature regarding alert fatigue demonstrates greater than 99% of monitor alarms are erroneous and typically ignored.

Using a 796 patients sample of chest pain patients receiving cardiac monitoring, these authors validate their previously described rule for avoiding cardiac monitoring: chest pain free and normal or non-specific ECG changes. In this sample, 284 patients met these criteria, and none of them suffered an arrhythmia requiring intervention.

While this represents 100% sensitivity for their rule, as a resource utilization intervention, there is obviously room for improvement. Of patients not meeting their rule, only 2.9% of this remainder suffered an arrhythmia – mostly just atrial fibrillation requiring pharmacologic rate or rhythm control. These criteria probably ought be considered just a minimum standard, and there is plenty of room for additional exclusion.

Anecdotally, not only do most of our chest pain patients in my practice not receive monitoring – many receive their entire work-up in the waiting room!

“Prospective validation of a clinical decision rule to identify patients presenting to the emergency department with chest pain who can safely be removed from cardiac monitoring”
http://www.cmaj.ca/content/189/4/E139.full