Category: Cardiology

Publication Potpourri

Clearing the backlog of mildly interesting articles that will never get a full write-up – here’s a quick hit of the most interesting lucky 13!

“Lactated Ringer vs Normal Saline Solution During Sickle Cell Vaso-Occlusive Episodes”
A “target trial emulation” providing observational evidence supporting the superiority of lactated ringers solution over normal saline for the resuscitation of patients being admitted with sickle cell crises. However, only a small fraction of patients actually received LR, and those who did received smaller amounts overall. Frankly, it’s hard to separate these observations from the general concern euvolemic SCD patients are simply receiving far too much fluid during admission.
https://pubmed.ncbi.nlm.nih.gov/39250114/

“Empathy and clarity in GPT-4-Generated Emergency Department Discharge Letters”
The cold, unfeeling computer generates better feels than emergency clinicians. Bland treacle, no doubt, but generic bland treacle will beat the terse output of a distracted human any day. The question now is how to combine the two to create a better human, where suitable.
https://www.medrxiv.org/content/10.1101/2024.10.07.24315034v1

“Mitigating Hallucinations in Large Language Models: A Comparative Study of RAG- enhanced vs. Human-Generated Medical Templates”
Study number n-million demonstrating retrieval-augmented generation – that is to say, using a relatively sophisticated series of prompts to an LLM – improves output and reduces “hallucinations”. In this specific instance, the LLM was effectively mimicking the output of BMJ Best Practice templates.
https://www.medrxiv.org/content/10.1101/2024.09.27.24314506v1

“Towards Democratization of Subspeciality Medical Expertise”
This is one of the AIME demonstration projects, a Google Deepmind output in which an additional layer of “conversational” training has been superimposed upon the underlying model to improve response to consultation-style questions. In this example, the conversational training is tuned to match the response style of genetic cardiology specialists from Stanford University – and the LLM content and style was arguably rated identically to the human specialists.
https://arxiv.org/abs/2410.03741

“The Limits of Clinician Vigilance as an AI Safety Bulwark”
A nice little commentary effectively articulating the elephant in the room: humans are terrible at “vigilance”. The present state of AI/LLM deployment in clinical medicine is replete with omissions and inaccuracies, and it’s not reasonable to simply trust clinicians to catch the mistakes. That said, the five suggested strategies to address vigilance seem … precarious.
https://jamanetwork.com/journals/jama/fullarticle/2816582

“Reviewer Experience Detecting and Judging Human Versus Artificial Intelligence Content: The Stroke Journal Essay Contest”
Who wins an essay competition on controversial topics in stroke and neurology – humans or LLMs? And can reviewers accurately guess which essays are human- versus LLM-generated? The answer, rather distressingly, is that reviewers mostly couldn’t distinguish between author types, and LLM composition quality was arguably higher than human.
https://pubmed.ncbi.nlm.nih.gov/39224979/

“Invasive Treatment Strategy for Older Patients with Myocardial Infarction”
The amusingly named “SENIOR-RITA” trial in which elderly patients with NSTEMI were randomized to an invasive strategy versus a medical management strategy. While this may seem odd to those in the U.S., frailty and baseline life-expectancy are typical considerations for acute care in other countries. In these frail elderly, invasive strategies reduce downstream non-fatal MI, but had no effect on cardiovascular death or the overall composite outcome.
https://pubmed.ncbi.nlm.nih.gov/39225274/

“Thrombolysis After Dabigatran Reversal for Acute Ischemic Stroke: A National Registry-Based Study and Meta-Analysis”
Just another bit from our neurology colleagues patting themselves on the back for doing backflips in order to give everyone thrombolysis. Registry data paired with a garbage-in-garbage-out systematic review and meta-analysis just amplifies the biases prevalent in the underlying practice culture.
https://pubmed.ncbi.nlm.nih.gov/39255429/

“Tenecteplase vs Alteplase for Patients With Acute Ischemic Stroke: The ORIGINAL Randomized Clinical Trial”
This trial makes a claim to be ORIGINAL, but at this point – there’s really no general question remaining whether tenecteplase is a valid alternative to alteplase. It is reasonable to test specific doses in various populations with a goal of minimizing harms, of course.
https://pubmed.ncbi.nlm.nih.gov/39264623/

“Technology-Supported Self-Triage Decision Making: A Mixed-Methods Study”
Can laypersons improve their self-triage decision-making with use of technology? This little preprint tests the Ada Health “symptom checker” app against interaction with a ChatGPT LLM and favors use of the symptom checker. Not hardly rigorous enough to discard the chatbot as a possible tool, but certainly the LLM needs more prompt engineering and/or domain-specific training than just “out of the box”.
https://www.medrxiv.org/content/10.1101/2024.09.12.24313558v1

“Class I Recalls of Cardiovascular Devices Between 2013 and 2022 : A Cross-Sectional Analysis”
A brief report looking at recalled cardiovascular devices is insufficient to make any broad conclusions, but certainly demonstrates the regulatory bar for approval is inadequate. Most did not require pre-market clinical testing, and those that did used surrogate or composite endpoints to support approval.
https://pubmed.ncbi.nlm.nih.gov/39284187/

“Effectiveness of Direct Admission Compared to Admission Through the Emergency Department: A Stepped-Wedge Cluster-Randomized Trial”
A bit of an odd question whether a patient with known requirement for admission needs to stop through the emergency department, or whether the patient can go straight to the ward. Unless a patient requires immediate resuscitation with the resources of an ED, it is very clearly appropriate for a patient to be directly admitted. That said, doing so requires new processes and practices – and this trial demonstrates such processes are feasible and safe (and almost certainly cheaper to avoid ED billing!)
https://pubmed.ncbi.nlm.nih.gov/39301600/

“Restrictive vs Liberal Transfusion Strategy in Patients With Acute Brain Injury: The TRAIN Randomized Clinical Trial”
The optimal cut-off is not known, but in this trial, the threshold for transfusion was 9g/dL – and patients randomized to the liberal transfusion strategy did better. An injured brain does not like hypotension and it does not like anemia.
https://pubmed.ncbi.nlm.nih.gov/39382241/

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.

Let’s Sell Andexxa

Have you heard the Good News (from Portola) about andexanet?

It’s an ever-changing landscape of anticoagulants and reversal agents in the Emergency Department – though, it’s not so much as a whirlwind as it is a creeping ooze. The latest developments have all been covered ad nauseum over the past few years – dabigatran, idarucizumab, factor Xa inhibitors, and coagulation factor Xa (recombinant) inactivated-zhzo (andexanet alfa). This final product, trade name Andexxa, has generally been held in a dim view over the past year by many, including yours truly, Rebel EM, the Skeptic’s Guide to Emergency Medicine, EmCrit, first10EM, the American Society of Hematology, and both the European Medicines Agency and the Food and Drug Administration’s own clinical reviewers.

There is, however, a competing viewpoint in which Andexxa is Tier 1 therapy for treatment of major bleeding in the context of of direct Xa inhibitor use – such as this recent “Recommendations of a Multidisciplinary Expert Panel” piece in Annals of Emergency Medicine. What aspect of their review differs so greatly in their affinity for Andexxa?

The expert panel meeting was convened with funds from unrestricted educational grants from Portola Pharmaceuticals and Boehringer Ingelheim to the American College of Emergency Physicians.

And, to no great surprise, the convened panel reflects the funding source:

Dr. Baugh has worked as a consultant for Janssen Pharmaceuticals and previously received research funding from Janssen Pharmaceuticals and Boehringer Ingelheim as a coinvestigator. Dr. Cornutt has received speaker’s fees from Boehringer Ingelheim. Dr. Wilson has worked as a consultant for Janssen Pharmaceuticals, Boehringer Ingelheim, BMS/Pfizer Pharmaceuticals, and Portola Pharmaceuticals, and has also received research funding from them. Dr. Mahan has served on the speaker’s bureau and as a consultant for Boehringer Ingelheim, Janssen Pharma, Portola Pharma, and BMS/Pfizer and as a consultant to Daiichi-Sankyo, WebMD/Medscape, and Pharmacy Times/American Journal of Managed Care. Dr. Pollack is a scientific consultant to Boehringer Ingelheim, Janssen Pharma, Portola Pharma, and BMS/Pfizer; he also received research support from Boehringer Ingelheim, Janssen Pharma, Portola Pharma, Daiichi-Sankyo, CSL Behring, and AstraZeneca. Dr. Milling’s salary is supported by a grant from the National Heart, Lung, and Blood Institute. He serves on the executive committee for the ANNEXA-4 and ANNEXA-I trials, the steering committee for the LEX-209 trial, and the publications committee for the Kcentra trials. He has received consulting fees or research funding from CSL Behring, Portola, Boehringer Ingelheim, Genentech, and Octapharma. He received speaker’s fees from Janssen. Dr. Peacock has received research grants from Abbott, Boehringer Ingelheim, Braincheck, CSL Behring, Daiichi-Sankyo, Immunarray, Janssen, Ortho Clinical Diagnostics, Portola, Relypsa, and Roche. He has served as a consultant to Abbott, AstraZeneca, Bayer, Beckman, Boehringer-Ingelheim, Ischemia Care, Dx, Immunarray, Instrument Labs, Janssen, Nabriva, Ortho Clinical Diagnostics, Relypsa, Roche, Quidel, and Siemens. He has provided expert testimony on behalf of Johnson & Johnson and has stock and ownership interests in AseptiScope Inc, Brainbox Inc, Comprehensive Research Associates LLC, Emergencies in Medicine LLC, and Ischemia DX LLC. Dr. Rosovsky has served as an advisor or consultant to Janssen, BMS, and Portola and has received institutional research support from Janssen and BMS. Dr. Sarode has served as a consultant for CSL Behring and Octapharma and advisor to Portola Pharmaceuticals. Dr. Spyropoulos is a scientific consultant to Janssen, Bayer, Boehringer Ingelheim, Portola, and the ATLAS Group; he also has received research support from Janssen and Boehringer Ingelheim. Dr. Woods is a scientific consultant to Boehringer Ingelheim. Dr. Williams serves as a consultant to Janssen Pharmaceuticals, Boehringer Ingelheim, and Portola Pharmaceuticals.

This work is effectively an advertorial, masquerading as serious academic literature, and part of a well-executed marketing and promotional campaign by the manufacturers of these drugs – particularly Portola, which is having difficulty getting Andexxa on formulary due its cost and controversial clinical data. This publication in Annals is just one of many sponsored products:

The further afield these pseudo-guidelines permeate, the more likely the product – the $25k or $50k a dose Andexxa – is incorporated into hospital formularies and local practice. These also have implications for risk-management assessments, in which the costs – passed along to the patient or payor – are far outweighed by the potential liability of a decision to make the drug unavailable for treatment.

It should be clear from all the non-conflicted opinion the role of Andexxa is yet to be clearly established, with true RCT evidence unfortunately years away. To state otherwise – and to make Tier 1 recommendations – is simply misleading.

“Anticoagulant Reversal Strategies in the Emergency Department Setting: Recommendations of a Multidisciplinary Expert Panel”
https://www.annemergmed.com/article/S0196-0644(19)31181-3/fulltext

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

Women are Just as Typical as Men?

It’s somewhat dogmatic in medicine to teach men and women present with differing symptoms during myocardial infarction. Women are, as they say, more likely to have “atypical” symptoms.

This study differs slightly from previous accounting of the presenting symptoms of men and women with potential cardiac ischemia. This is a pre-planned, prospective analysis accompanying the High-STEACS trial, featuring in part an evaluation of gender-specific cut-offs for high-sensitivity troponin. As part of this trial, rather than using a typical “conventional” troponin cut-off for the 99th percentile of 50 ng/L, they used 16 ng/L for women and 34 ng/L for men. These cut-offs were correlated with clinical information to determine the diagnosis of type I myocardial infarction, generating a prevalence of 16% for men and 12% for women among the 1,941 included in the analysis.

Among these, authors found similar prevalence of “typical” symptoms – dull, tight, pressure, aching, crushing, in the chest, arm or jaw – in women as men considered for potential acute coronary syndrome. Among those ultimately diagnosed with type I MI, women were actually slightly more likely to manifest “typical” symptoms – 77% versus 59%. The authors did not find the presence of multiple “typical” symptoms to have a terribly useful positive likelihood ratio for MI in either women or men.

Unfortunately, these data run into unavoidable selection bias: “All patients over 18 years of age in whom the attending clinician requested cardiac troponin for suspected acute coronary syndrome were eligible for inclusion.” Therefore, the so-called “atypical” presentation in which ACS was not suspected – i.e., the women with “atypical” presentations – would be, by definition, missed. It may be the difference between men and women is not as great as originally thought – but these data cannot definitively answer the question.

“Presenting Symptoms in Men and Women Diagnosed With Myocardial Infarction Using Sex-Specific Criteria”
https://www.ahajournals.org/doi/10.1161/JAHA.119.012307

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

ECLS in AMI

Acute myocardial infarction complicated by cardiogenic shock has dismal outcomes. Pharmacologic therapy, intra-aortic balloon pumps, ventricular assist devices, et cetera, all have limitations. So, why not extracorporeal life support (ECLS)? Well, for one, it’s resource-intensive, expensive, and little high-quality evidence supports its use. But, on the other hand, it’s fancy and magical and reputed to beget miracles.

Published as a brief research report, this small article describes an open-label pilot of 42 patients suffering cardiogenic shock, randomized to ECLS or no mechanical circulatory support. The primary outcome was left-ventricular ejection fraction at 30 days, with multiple secondary outcomes crammed into their short bit.

The short answer: zero difference – median 50% vs. 50.8%, and no reason to tell you which is which because they’re the same. Mortality favored ECLS at 19% vs. 33%, but these outcomes and their survival curves are so entwined there is no reliable difference to be made from this small sample – and moreso even because the control group had greater illness burden at baseline. Process outcomes, such as intensive care unit length-of-stay and duration of mechanical ventilation favored the control cohort, as expected, given the relative resource intensity of ECLS.

The new sexy thing is always alluring and presumed to be better, but as these authors conclude: “This raises an urgent call for randomized controlled trials assessing survival as primary endpoint.”

“Extracorporeal Life Support in Cardiogenic Shock Complicating
Acute Myocardial Infarction”
https://www.ncbi.nlm.nih.gov/pubmed/31072581