Category: Chest Pain

Intermediate-Value CTCA?

Pervasive use of CT coronary angiography has been an unnecessary feature of the evaluation of patient with low-risk chest pain for the better part of a decade now. The argument behind its use – a normal examination confers a durable protective effect – is obviously nonsensical, as this bestows agency upon the test itself. Obviously, in a low-risk population with rare adverse outcomes, there can be no reasonable expectation of value in testing.

The sensible idea, then, is to use CTCA in those patients at intermediate risk. In this trial, the stratification used was GRACE score, and the 1,748 participants in this trial were a mean of 62 years of age, and a GRACE score of 115 (SD ± 35). Patients were eligible by symptoms of an acute coronary syndrome, supported by ECG changes, an elevated troponin, or a history of ischemic heart disease. Patients were then were randomized to receive CTCA in the ED or “standard of care only”. The primary outcome was, naturally, the glorious typical cardiology trial outcome of death or non-fatal myocardial infarction at one year.

Over half of patients included demonstrated troponin levels exceeding the 99th percentile, nearly two-thirds had an abnormal ECG, and a third had known coronary artery disease. Approximately a quarter had previously undergone angiography, with a number also receiving PCI. The vast majority presented with chest pain as their initial complaint.

Most patients randomized to CTCA underwent CTCA; a small number of those randomized to standard care also underwent CTCA within 30 days, as well. About a quarter of patients in this cohort demonstrated normal coronary arteries – a fairly surprising development considering the combination of age, risk factors, elevated troponin, and abnormal electrocardiogram necessary for inclusion. Most patients with normal coronary arteries were predictably managed by medical means alone. The remaining patients demonstrated either non-obstructive coronary disease or obstructive coronary artery disease, with concordant trends towards subsequent invasive coronary angiography.

However, after all of that, even with the added information provided by CTCA, there was no difference in mortality or non-fatal myocardial infarction at one year. Delving into the complexities of subsequent resource utilization, it was noted patients undergoing CTCA were less likely to ultimately undergo invasive coronary angiography, 54.0% vs 60.8%. Similarly, patients with the initial CTCA were less likely to undergo subsequent non-invasive testing, 19.4% vs. 26.2%. Other differences in medical or preventive management did not differ by study arm.

So, a small decrease in invasive testing counterbalanced by the large baseline investment in non-invasive testing – without any clear patient-oriented benefit on health outcomes. CTCA certainly has a role in the evaluation of patients with chest pain and possible CAD, but certainly not as a routine investigation in the ED.

“Early computed tomography coronary angiography in patients with suspected acute coronary syndrome: randomised controlled trial”
https://www.bmj.com/content/374/bmj.n2106

New Troponin, Same as Old Troponin?

It doesn’t take more than a quick search through the archives to notice a great deal of gnashing of teeth over the introduction of high-sensitivity troponin. The perpetual concern: trade-offs with sensitivity and specificity, leading to downstream increased resource utilization.

This brief research letter is basically good news: the Mayo Clinic hospital system rolled out high-sensitivity troponin assays and very little changed. Looking at about 54,000 patients divided equally into pre- and post- periods, the diagnosis of myocardial infarction increased significantly. However, most of the change was coded as Type 2 MI, rather than an acute coronary syndrome, leading to little change in resource use – no difference in admissions, echocardiography, stress testing, or angiography.

There’s brief allusion in the article to the underlying protocols in place – in which patients are typically assessed using HEART, along with a system of champions and education supporting the change. Assuming these retrospective coded data accurately reflect practice, it is likely these concerted efforts prevented misinterpretation of detectable troponin levels – hence the increase in Type 2 MI. Implementation of these assays in other health systems may not reflect these same successes, but it is reasonable to expect the on-ramp for high-sensitivity troponin has likely now been long enough most are now familiar with their interpretation.

Finally, the ultimate better question might be – if high-sensitivity assays didn’t clearly impact care, what value do they confer? If there are no measurable improvements in diagnosis of acute MI, is there much utility? However, these data do not provide insight into whether there are downstream changes in medication management potentially reducing long-term cardiovascular adverse outcomes – nor, likewise, any medication changes resulting in increased costs and adverse outcomes without an improvement in cardiovascular health. And, asking these questions is likely moot, regardless – these assays are here and here to stay.

“Implementing High-Sensitivity Cardiac Troponin T in a US Regional Healthcare System”
https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.119.045480

Potpourri

Just a quick-hit collection of articles I’ve wanted to highlight/catalogue for future reference, but couldn’t find the time for deep dives into each:

Shared Decision Making in Patients With Suspected Uncomplicated Ureterolithiasis: A Decision Aid Development Study.
For this common clinical scenario in the Emergency Department, the authors have developed a patient-facing packet to facilitate shared decision-making. However, more important than the product, is the process these authors have described for its creation. A similar roadmap could be followed to address similar opportunities in your department.

Reduction of Inappropriate Antibiotic Use and Improved Outcomes by Implementation of an Algorithm-Based Clinical Guideline for Nonpurulent Skin and Soft Tissue Infections.
Amazing – using the correct antibiotics reduces treatment failures and, likewise, treatment failures necessitating admission to the hospital. This is an effort-intensive intervention featuring provider education and individual prescribing feedback, but, given the limitations, can be considered a change management success. Whether this can be replicated at your institution will depend on many cultural factors.

Utility of INR For Prediction of Delayed Intracranial Hemorrhage Among Warfarin Users with Head Injury.
Here’s a topic with a ton of practice variation – do you admit patients with closed head injury on anticoagulation for observation? This retrospective review of those patients just on warfarin tries to make the case patients with INR <2 are safe for discharge, whereas those with higher scores are not. Again, however, the yield of observation is somewhere south of 1% in their entire therapeutic cohort, making it truly challenging to find the inflection point of value. Another opportunity for shared decision-making?

Performance of Novel High-Sensitivity Cardiac Troponin I Assays for 0/1-Hour and 0/2- to 3-Hour Evaluations for Acute Myocardial Infarction: Results From the HIGH-US Study.
A detailed look at high-sensitivity Troponin I rule-in/rule-out algorithms suggests a 0/1-hour strategy is similar to a 0/3-hour strategy. Overall, while the disposition of patients is likely to be more rapid from the 0/1 hour strategy, a greater proportion of patients ultimately fall into the “intermediate” zone requiring further observation and diagnostics. Certainly, combinations of hsTnI and other risk-stratification instruments ought to mean the majority of patients with straightforward chest pain presentations may be discharged from the Emergency Department.

Randomized Clinical Trial of IV Acetaminophen as an Adjunct to IV Hydromorphone for Acute Severe Pain in Emergency Department Patients.
In this trial, patients receiving hydromorphone were randomized to receive adjunctive treatment with IV acetaminophen or placebo. With 159 patients, they found advantages to the multi-modal approach favoring the addition of acetaminophen – but the confidence interval for their primary outcome crossed unity by 0.01. The authors conclude this is a negative trial, but it rather seems to me there’s certainly no harm in adding acetaminophen (it need not be IV) – adding it likely has a favorable effect, even if the effect size may not be large.

Effect of No Prehydration vs Sodium Bicarbonate Prehydration Prior to Contrast-Enhanced Computed Tomography in the Prevention of Postcontrast Acute Kidney Injury in Adults With Chronic Kidney Disease: The Kompas Randomized Clinical Trial.
In news surprising no one, another trial fails to show benefit of prehydration in staving off post-contrast exposure acute kidney injury. As seen on Twitter, rather than “contrast-induced nephropathy”, the clinical paradigm is effectively “contrast-adjacent nephropathy.” The impairment in renal function is associated with the underlying medical illness and not the exposure to IV contrast. Thus, no intervention – such as prehydration – can prevent such.

Coronary CT Angiography in Patients With Non-ST-Segment Elevation Acute Coronary Syndrome.
This interesting observational study evaluated patients with a diagnosis of non-ST elevation acute coronary syndrome using coronary CT angiography prior to invasive coronary angiography. The good news: CT angiography was probably useful at excluding obstructive coronary disease. The bad news: nearly 70% of patients had a coronary stenosis identified on invasive angiography, so patient selection prior to CT angiography will be important to improve the value of using it as a screen to prevent invasive angiography.

Industry Payment to Vascular Neurologists: A 6-Year Analysis of the Open Payments Program From 2013 Through 2018.
As we watch our healthcare delivery system struggle and groan under the various strains and burdens, one of the culprits has always been the influence of pharmaceutical/device manufacturers targeting investments to improve uptake of their products. In this observational analysis of the OpenPayments database, these authors identified the recipients of financial support from the manufacturers of endovascular devices. About 16% of vascular neurologists received funding from industry, but over 75% could be identified as “influencers” – chiefs of staff, department chairs, or similar. Pharma et al should always be remembered they are serving the interests of owners and shareholders, and not patients and our healthcare system.

The Non-Invasive Testing for Chest Pain Half-Truth

The utility or disutility of non-invasive diagnostic testing for chest pain – CT coronary angiograms, treadmill stress testing, myocardial perfusion imaging and the like – in the Emergency Department remains controversial. A couple days ago, the daily ACEP News Bulletin e-mail referenced an article regarding non-invasive testing featuring the following statement:

“Patients who underwent noninvasive diagnostic testing after evaluation for chest pain in the” emergency department (ED) appeared to have “a lower observed rate of CV death or MI,” researchers concluded.

While this statement is not strictly untrue, it is dramatically clarified by including the next sentence from the authors’ own abstract conclusion:

“This lower rate was driven by the high-risk subgroup.”

The study cited is a propensity-matched cohort of 370,863 patients discharged from the ED after a visit for chest pain in Ontario, Canada. They created matched cohorts featuring 96,457 patients who each either underwent non-invasive cardiac testing in the Emergency Department or did not. Interestingly enough, at 90 days, those who underwent testing had a higher risk of their combined endpoint of cardiovascular death or myocardial infarction. However, by 1 year, the rate of the combined endpoint in those who underwent testing had dropped below the rate for those who did not. The hazard difference was small, however, and driven by small absolute differences in outcomes for those in the high-risk and intermediate-risk cohorts.

Rather than try and read into this study some general advantage to non-invasive testing in the Emergency Department, it would only imply testing of value would be for those who are at intermediate- or high-risk for adverse cardiovascular outcomes. Next, it also does not specifically mandate or imply the testing should be done in the ED or, based on the 90 day outcomes data, even urgently upon discharge. Finally, the newsworthy snippet also does not mention dramatic increases in downstream invasive angiography, PCI, and cardiology visits associated with those in those who underwent non-invasive testing.

The ultimate conclusion is not practice changing in the least: appropriately selected patients may be candidates for the appropriately selected test. Individualized decisions need to be made for those at intermediate- and high-risk for cardiovascular outcomes. Likewise, the relative urgency of testing ought to be determined on an individual basis – and not routinely in the ED. This is, in fact, the authors’ own conclusion – just not well-reflected by the ACEP News Bulletin.

“Clinical Effectiveness of Cardiac Noninvasive Diagnostic Testing in
Patients Discharged From the Emergency Department for Chest Pain”
https://www.ahajournals.org/doi/10.1161/JAHA.119.013824

If You Guessed “Definitely Not ACS” …

This little observational study, part of a larger troponin-centric evaluation, looked at the predictive value of clinician gestalt for acute coronary syndrome. This has been evaluated before – including by this same group – but this cohort is three times the size of their prior effort.

Of the 1,391 patient encounters included, 207 had an acute MI, and another 33 died or underwent coronary revascularization within 30 days. Only 60 patients actually fell into the category of “definitely not ACS”, and 3 of those turned out to actually have an AMI. However, adding an ECG and a troponin to the initial gestalt was ultimately 100% sensitive for acute MI said “definitely not” cohort.

The other end of the spectrum – the “definitely ACS” side – was similar, with gestalt requiring supplementation by troponin and ECG testing to confirm.

One of the authors’ takeaways: a label of “definitely not” isn’t safe enough to forgo troponin testing. However, this comes with a big caveat: the enrolled patient cohort was specifically chosen for the main study because the treating clinician judged they required evaluation for ACS. Thus, effectively by definition, “definitely not” is incompatible with the study population.

You should not use this study to justify evaluation with additional or definitive testing in those who are truly “definitely not” ACS – the cohort here was enriched by 60 year old patients with hypertension, hyperlipidemia, prior MIs, smokers, and diabetes, and it would truly be the exception for one of these patients to “definitely not” have ACS. The 28 year-old for whom you think “definitely not” can still be evaluated as you feel appropriate.

“Can emergency physician gestalt “rule in” or “rule out” acute coronary syndrome: validation in a multi-center prospective diagnostic cohort study”
https://www.ncbi.nlm.nih.gov/pubmed/31338902

Ye Big High-Sensitivity Troponin Evaluation

After many years of various studies of moderate size looking at the diagnostic performance of high-sensitivity troponin assays, now we have a new entry: the Calculation of Myocardial Infarction Risk Probabilities to Manage Patients with Suspicion of Myocardial Infarction (COMPASS-MI) project.

This is not new data, but rather the power team of Roche and Abbott pooling the results of 15 prior studies to describe the diagnostic performance of their Elecsys and Architect high-sensitivity platforms. Then, there are really two parts of this article. There is an initial analysis looking at the performance characteristics of differing combinations of initial and serial sampling of each. After that, these authors pull in several age- and comorbidity-matched comparison populations and describe the long-term 1- and 2- year outcomes of patients with differing levels of troponin concentrations.

The main product of their work, however, boils down to a set of mildly confusing wheels of data regarding the negative predictive value of various combinations of initial troponin level and serial troponin change, divided up based on whether repeat sampling was performed early or late. These cut-offs are further divided on the wheel regarding the proportion of the population with a certain risk level for 30-ay MI or death.

The end result, combined with the various massive supplementary appendicies, are massive amounts of data to help systems using these assays tailor their practice patterns to their desired level of sensitivity and specificity. The authors are not specifically prescriptive in any one cut-off, but rather try to provide as much data as possible. Prevalence of nSTEMI in their population was about 14%, meaning the negative predictive values are only generalizable to to similar patient demographics.

If you’re using these assays, this is quite important work to help assist in interpretation. If not, considering there’s no comparative data to conventional assays, it seems to have limited utility.

It should finally be noted virtually all the listed authors of this work receive some financial support from the manufacturers of these assays.

“Application of High-Sensitivity Troponin in Suspected Myocardial Infarction”
https://www.nejm.org/doi/full/10.1056/NEJMoa1803377

The Beginning of the End of Heparin for ACS?

We’ve been routinely starting anticoagulation therapy on patients diagnosed with an acute coronary syndrome for a couple decades. The evidence from the preceding era is clear – patients treated with anticoagulation plus aspirin are at much lower risk for subsequent ischemic events than those treated with aspirin alone.

However, these trials are not generalizable to most modern care for ACS. For example, the FRISC and ATACS trial discharged patients with nSTEMI or unstable angina with continued anticoagulation for weeks to months. Revascularization procedures were performed only as rescue therapy, rather than the routine early invasive strategies in use today. Dual anti-platelet and other adjunctive therapies were unavailable. So – do we actually still need the heparin?

These authors retrospectively evaluated the association between parenteral anticoagulation therapy and in-hospital death and in-hospital major bleeding. There were 6,804 patients included in their 4-year, multi-center data set, about two-thirds of whom did not receive parenteral anticoagulation prior to PCI. There were small, probably unimportant differences reported between groups, excepting one feature: time to intervention. Time to intervention was a median of 1 day in those managed without anticoagulation versus a median of 3 days in those managed with. Overall, there was no difference in in-hospital death, nor 30-day, 1-year, or 3-year death for those included in long-term follow-up. A handful of cases suffered bleeding complications, with a small absolute excess in those managed with anticoagulation.

This is neither prospective nor a randomized trial, and there could certainly be unexamined confounding baseline characteristics favoring one treatment group over the other. The authors also note bleeding complications could be ameliorated by use of fondaparinux rather than heparinoids, but this would still be moot if there is still no benefit to anticoagulation. Finally, in-hospital mortality is a fabulous patient-oriented endpoint, but it does not tell the entire story with regard to any additional morbidity potentially resulting from anticoagulation being withheld. We should not change practice based on this level of evidence, but these data should prompt further examination and potentially prospective evaluation.

“Association of Parenteral Anticoagulation Therapy With Outcomes in Chinese Patients Undergoing Percutaneous Coronary Intervention for Non–ST-Segment Elevation Acute Coronary Syndrome”

https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2719425

The Swiss, Ruling out PE in Pregnancy

Evaluating the average Joe/Jane for pulmonary embolism is rather straightforward – but let’s not go back into that morass of practice variation and low-value over-diagnosis. This is an a study looking at how to diagnose PE during pregnancy, which is fraught with its own unique issues.

Firstly, obviously, CTPA ought to be avoided whenever possible – and moreso when there is a chance of fetal exposure. When the benefits outweigh the risks, of course, it is reasonable to proceed. Then, use of D-dimer as a tool to inform the posterior probability of PE is challenged by its steady increase in pregnancy.  This combination of issues results in general uncertainty with regard to the approach.

This is their algorithm:

Over the course of eight years, at 11 centers, these authors included 395 patients in their study – 357 of whom were evaluated per-protocol. Only a handful were assessed as “high” risk, while the bulk underwent D-dimer testing with a test threshold of 500 µg/L on the Vidas assay. The D-dimer was virtually useless, with only 46 of 392 being excluded from further evaluation. Then, the bilateral lower extremity ultrasound was basically useless, with only 7 positives out of 349 performed – resulting in 342 CTPAs. There were 19 positive CTPA, and then two of the inconclusive CTPA were ultimately diagnosed with PE by V/Q scanning.

What a mess. For those keeping score at home, that’s 7.1% yield for their evaluation of PE, and all their extra hoops prevented little radiation exposure. From a diagnostic evaluation standpoint, of course, their protocol was entirely adequate with regard to missed PE – unsurprising because most patients received all the tests in their algorithm.

The ugliest observation here is their prevalence of 7.1% is actually far lower than the prevalence observed in the non-pregnant population in Europe. Step one in fixing this approach: just apply the same gestalt to this population as the remainder of ED presentations. Then, let’s adopt the YEARS protocol, at a minimum, and consider adopting trimester-adjusted cut-offs for D-dimer. The miss rate will not be zero – but, incorporating appropriate clinical judgment, the net harms from untreated PE will be balanced by the benefit of avoided radiation, anticoagulation, and over-diagnosis.

“Diagnosis of Pulmonary Embolism During Pregnancy: A Multicenter Prospective Management Outcome Study”
http://annals.org/aim/article-abstract/2708166/diagnosis-pulmonary-embolism-during-pregnancy-multicenter-prospective-management-outcome-study

Clinical Policy: Sanity Returns to ACS

This may be the most important recent sentence in modern emergency medicine:

“… based on limitations in diagnostic technology and the need to avoid the harms associated with false-positive test results, the committee based its recommendations on the assumption that the majority of patients and providers would agree that a missed diagnosis rate of 1% to 2% for 30-day MACE in NSTE ACS is acceptable.”

It’s no longer the domain of rogue podcasters and throwaway magazine editorialists to declare our zero-miss culture destructive and self-defeating – it’s finally spelled out in black & white by our speciality society. This is not a license to kill, of course, but it is now utterly reasonable to feel as though the wind is at your back when sending an appropriately-evaluated patient home.

This clinical policy statement does not address terribly many questions, but it does jam a lot of evidence into one document in their review. Specifically, these authors ask:

1. In adult patients without evidence of ST-elevation ACS, can initial risk stratification be used to predict a low rate of 30-day MACE?

In short, yes. These authors recommend HEART as their decision instrument du jour, but also acknowledge other scores that simply do not yet have enough diverse evidence to support their use. Interestingly, they also note clinical gestalt may be just as good as any decision instrument, at least when the ECG and troponin are negative for new ischemia. Again, more prospective evidence would be required to formally enshrine such a recommendation into a clinical policy statement.

2. In adult patients with suspected acute NSTE ACS, can troponin testing within 3 hours of ED presentation be used to predict a low rate of 30-day MACE?

Here the authors have only Level C recommendations, which means their recommendations are based on low levels of evidence. Overall, they are weakly in favor of using of high-sensitivity troponins alone, or repeat conventional troponin testing as part of a risk-stratification or accelerated diagnostic pathway.

3. In adult patients with suspected NSTE ACS in whom acute MI has been excluded, does further diagnostic testing (eg, provocative, stress test, computed tomography [CT] angiography) for ACS prior to discharge reduce 30-day MACE?

Please no: “Do not routinely use further diagnostic testing (coronary CT angiography, stress testing, myocardial perfusion imaging) prior to discharge in low-risk patients in whom acute MI has been ruled out to reduce 30-day MACE.”  Take that, CCTA proponents.  They give an expert consensus recommendation of 1 to 2 week primary care follow-up when feasible, or consideration of observation when no follow-up is possible.

The fourth question posed deals with use of P2Y12 and
glycoprotein IIb/IIIa inhibitors in the ED, and is met basically with a shrug.

So!  Go forth and provide good medical care – specifically, high-value medical care, further freed from the mental oubliette of zero-miss.

“Clinical Policy: Critical Issues in the Evaluation and Management of Emergency Department Patients With Suspected Non–ST-Elevation Acute Coronary Syndromes”
https://www.ncbi.nlm.nih.gov/pubmed/30342745

HEART Outcomes in the “Real World”

There are two parallel universes in medicine – the “real world”, where most physicians practice, and the “academic world”, where most research is performed. Then, these disparate universes are scattered across the physical world, with its rich tapestry of cultures, further complicating the generalizability of any one set of observations.

This example demonstrates this effect on outcomes from the HEART Score, typically applied for its utility in disposition of those with Low (0-3) scores. Scores in this range have been generally observed to have a 6 week rate of Major Adverse Cardiac Events in the 0.7 to 1.7% range. However, these outcomes are subject to those aforementioned limitations – mostly academic centers, frequently across the pond.

These results are from a prospective evaluation of practices and outcomes regarding the approach to chest pain in the Emergency Department, ongoing at Kaiser Permanente Southern California. In this study, clinicians have been routinely recording the HEART Score in the context of chest pain evaluation since May 2016, allowing for the abstraction of this score in structured data. This analysis captured all Kaiser members evaluated in the ED who were not diagnosed with an acute myocardial infarction at the index visit, and gathered outcomes from their data warehouse.

Based on 29,196 ED encounters, 59% were “low risk”, and most of the remainder were “intermediate risk” (4-6). The overall rate of 6 week MACE was only 0.4% in the low risk group and 2.4% for intermediate risk, with most MACE being driven by revascularization. Only 0.2% of low risk and 1.0% of intermediate risk suffered death or acute myocardial infarction within 30-days. These authors then go on to suggest a HEART Score of 5 should rather be considered the cut-off for safe discharge from the ED, the maximum at which 30-day death or AMI was ~1% , which would represent ~89% of ED visits.

These data may represent our best insight yet into the pragmatic application of HEART in U.S. EDs, where certain semi-subjective aspects or misinterpretation of score elements serve to skew the scores higher.  Rather than 0-3 representing a low-risk cohort, it is probably more likely 0-5 as these authors report.  This ties into our general risk-averse nature, which tends to result in virtually universal over-triage of most complaints in the ED, as our other over-testing trends would indicate.  These data also probably serve as a lesson to those who promote the application of other decision instruments in the ED, as we’ve recently seen with the Canadian Head CT Rule for minimal risk head injury, or potential indication creep from the Ottawa Subarachnoid Rule – we must exercise caution regarding downstream unintended consequences and low-value care as a result.

“The HEART Score for Suspected Acute Coronary Syndrome in U.S. Emergency Departments”
https://www.ncbi.nlm.nih.gov/pubmed/30286933