Category: Cardiology

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

Oops, Missed the Culprit

This is a rather curious study I’d never specifically see coming, which makes it potentially brilliant. We in Emergency Medicine identify our non-STEMI patients, tidy them up for admission, and bid them bon voyage. We assume their post-Emergency Department care will include non-urgent coronary angiography, and this will properly address their underlying anatomic cause.

It turns out, this may not be the case more frequently than I would have thought. This is a very interesting study in which a convenience sample of patients with non-STEMI were recruited to undergo a cardiac MRI prior to coronary angiography. Cardiologists performing the angiography were blinded to the cardiac MRI results. Following angiography, the cardiologists would identify the culprit artery, if there were one, and its associated infarct territory on an anatomic model. These results were then subsequently compared to the results of the cardiac MRI.

There were 114 patients who underwent MRI and coronary angiography. Of these, angiography identified a culprit lesion in 72 (63%). Of these, 47 were consistent with the ischemic region identified on MRI. The remainder found either a different infarct artery on MRI (10), a non-CAD diagnosis such as myocarditis (9), or no apparent ischemic hyperenhancement (6). In the remaining 42 (37%) who did not have a culprit identified on angiography, 25 of these had an ischemic territory identified on MRI, while the others had a non-CAD related diagnosis or did not find hyperenhancement. Effectively, as compared with the MRI results, the coronary angiography accurately identified a culprit or lack of culprit in 62 of 114 (54%) of cases.

There are many limitations to this article – the least of which being an author is an inventor on the patent of delayed-enhancement MRI, and holds at the minimum a professional conflict of interest in showing this technology adds value. It is non-obvious this cardiac MRI technology should be considered the “gold standard” for identification of the culprit lesion territory, or that their methods of collecting culprit lesion infarct territory is reliable. Finally, this is a small sample from just three institutions and may not be generalizable.

If these data are valid, however, it certainly raises significant issues for many studies featuring revascularization as part of a composite “major adverse cardiac events” endpoint. Frequently, much of downstream MACE consists of coronary revascularization – for good or ill – and these data might further cast doubt upon the accuracy and effectiveness of revascularization. One could imagine an MRI might even be a necessary step in evaluation of non-STEMI to avoid unnecessary or erroneous coronary intervention.

Thought-provoking, but certainly far too early to suggest change in practice.

“Identifying the Infarct-Related Artery in Patients With Non–ST-Segment–Elevation Myocardial Infarction”

https://www.ahajournals.org/doi/full/10.1161/CIRCINTERVENTIONS.118.007305

More Cardiac Stress Test Futility

Once upon a time, it was believed important to perform cardiac stress testing in patients with chest pain and potential acute coronary syndrome. Intuitively, this makes little sense – a stress test may identify obstructive coronary disease, but this is rarely the culprit for acute coronary syndrome, and certainly only rarely the cause of chest symptoms in a patient at low-risk for coronary artery disease. Unfortunately, the American College of Cardiology/American Heart Association have had a nonsensical recommendation for noninvasive testing within 72 hours of an index visit on the books for quite some time – leading, to put it mildly, to a test or two.

This observational data set evaluates the outcomes of patients in the Kaiser Southern California system who were referred for outpatient stress testing following an encounter in the Emergency Department. They tracked 7,988 patients for a month after their ED encounter, 2,497 of whom underwent stress testing within 3 days, 4,695 within 4 to 30 days, and 796 who never showed up for their referred testing. Most stress tests were exercise or pharmacologic stress ECG, with the minority stress echocardiograms or myocardial perfusion imaging.

Patients undergoing testing were not devoid of risk factors: an average age of 55 years, most were overweight, and over half had at least one risk factor for coronary artery disease. Within 30 days, fewer than 1% were diagnosed with an acute MI, and a handful of those underwent PCI or CABG. There were tiny differences between groups, as none of the patients who skipped their stress test underwent subsequent revascularization. There were no deaths in any cohort.

The narrow view here in this article is there is no apparent benefit to undergoing stress testing within 72 hours as compared with a longer timeframe. The wider view is yet another piece of information showing the general disutility of stress testing. These are not randomized cohorts, nor is 30-days a long enough window to detect any potential benefits to the stress test – as measured by decreased morbidity or mortality as relating to a timelier PCI or CABG. However, even these interventions were rare enough the effect size from any benefit is bound to be so small as to represent low-value care. It is absolutely reasonable to suggest the Bayesian pendulum for the valuation of stress testing is swinging the other direction – and those who advocate for stress tests ought to generate data to support its targeted use, rather than for the opposition to generate data contrary to its assumed routine utility.

“Evaluation of Outpatient Cardiac Stress Testing After Emergency Department Encounters for Suspected Acute Coronary Syndrome”

https://www.sciencedirect.com/science/article/pii/S019606441930054X

Any Troponin is Bad Troponin – Gender-Specific Edition

High-sensitivity troponins mean a lower limit of detection. Picking up these lower quantitative values for circulating troponin – and new reference limits for the 99th percentile of normal – has required an adjustment in perspective with respect towards making the diagnosis of acute coronary syndrome. Now, the question with these more sensitive assays becomes: should we adjust our clinical considerations to incorporate sex-specific reference intervals?

This brief analysis from the UTROPIA study looks specifically at the downstream MACE in patients whose serial troponin measurements fall between the limit of detection and the sex-specific 99th percentile intervals. For this Abbott assay, that means 34 ng/L for men and 16 ng/L for women. In their 180-day follow-up period, they found the incidence of major adverse cardiac events was vanishingly small for those with undetectable levels of circulating troponin. However, those with any circulating troponin – even below the 99th percentile reference interval – were vastly more likely to experience an event within the next 180 days, reaching about 10% incidence of MACE. Importantly, however, the distributions of probability for downstream MACE were similar with regard to the measured value with respect to the sex-specific 99th percentile.

This confirms some of what we already knew: any troponin is bad troponin, even if it’s lower than the 99th percentile. Then, this also validates sex-specific 99th percentiles, as percentile levels conveyed similar risk between men and women.

Just another insight into the next level of sophistication for use of these assays in assessing patients with potential ACS, and for downstream anatomic assessment and preventive interventions.

“Clinical Features and Outcomes of Emergency Department Patients With High- Sensitivity Cardiac Troponin I Concentrations Within Sex-Specific Reference Intervals”

https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.118.038284

The “True” 99th Percentile for Troponin

Not. All. Troponin. Elevations. Are. Acute Coronary Syndrome.

This is just a simple, prospective, observtional study of 20,000 high-sensitivity troponin I results from a single hospital in the United Kingdom. All blood samples submitted to the lab were evaluated with a troponin assay, regardless of clinical indications or reasons for order. About half of included samples were outpatients, a quarter were Emergency Department patients, and the remainder were inpatients.

The manufacturer-stated upper limit of normal for the assay – Beckman Coulter Access AccuTnI+3, specifically – is 40 ng/L, with a coefficient of variation of less than 10% at that cut-off. Outpatients were the least likely to exceed this limit, at 2%, with an observed 99th percentile of 65 ng/L. In the Emergency Department, 6.1% exceeded the manufacturer-defined cut-off, with an observed 99th percentile of 215 ng/L. Finally, 7.3% of inpatients exceeded the manufacturer cut-off, with an observed 99th percentile of 563 ng/L.

The authors also tracked whether the patients had a troponin ordered by the clinical team, or had a final diagnosis of acute myocardial infarction, and perform some multivariate analyses with these patients excluded. Those only comprised 1,829 patients from this cohort, and excluding these patients made only small impacts upon their new “normal” 99th percentiles. Effectively, the point of this article is a reminder of the effect of concomitant illness on circulating troponin levels – and to take into account the likelihood of an ACS when interpreting troponin elevations above the manufacturer’s 99th percentile cut-off.

“True 99th centile of high sensitivity cardiac troponin for hospital patients: prospective, observational cohort study”
https://www.bmj.com/content/364/bmj.l729

Shocked: To the Cath Lab?

Just a couple weeks ago, I pointed out a recent evidence summary regarding the utility of cardiac catheterization following out-of-hospital cardiac arrest. The general between-the-lines theme of the article: sure seems useful, but the observational evidence is potentially really biased.

This, the Coronary Angiography after Cardiac Arrest (COACT) trial, is one of the randomized trials noted in that aforementioned evidence review. These authors conducted a randomized, multi-center trial enrolling patients with out-of-hospital cardiac arrest, shockable initial rhythms, unconscious on ED arrival, but no ST-segment elevation. Based on their survey of the literature, they gave themselves an 85% power to detect a 13% absolute difference in survival to 90 days, and enrolled 552 patients over three years. Patients undergoing early coronary angiography did so generally within 2 hours, while those in the delayed strategy – if they underwent angiography at all – did so several days later.

Overall – no difference. Survival to 90 days did not differ between groups at 64.5% for immediate angiography and 67.2% for delayed, nor did any secondary outcomes regarding post-resuscitation morbidity or neurologic survival. Of course, the key element being: unless an intervention occurs, there likely won’t be any effect. Only about a third of patients in each group underwent revascularization during their hospital stay, meaning any difference in overall survival would ultimately need be affected by outcomes in this specific population. Absent a massive effect size, the results observed are basically as expected.

So, I think the basic takeaway here is – within the limitations of this small sample – immediate angiography is not supported as a universal strategy for patients with OHCA, shockable rhythms, and lack of ST-segment elevation. It appears either a delayed strategy, or one guided by yet-to-be-determined clinical features, is preferred.

“Coronary Angiography after Cardiac Arrest without ST-Segment Elevation”

https://www.nejm.org/doi/full/10.1056/NEJMoa1816897

The “OHCA to the Cath Lab?” Update

STEMI: cardiac catheterization.

Out of hospital arrest: now what?

This scientific statement provides a lovely – and detailed – overview of the state of the science regarding which survivors of cardiac arrest should be considered for cardiac catheterization. They start with the easiest of answers: arrest with return of circulation and ST-segment elevation on a 12-lead ECGs are likely to benefit from catheterization. Then, patients with persistent ventricular fibrillation or ventricular tachycardia are, similarly, highly likely to have coronary artery disease and a suspected culprit lesion precipitating their arrest.

Now, the trickier issue remains what to do with those who do not have ST-segment elevation on their ECG. Pooled data from registry and observational studies indicates the prevalence of coronary artery disease is between 25-50%, while a potential culprit lesion is identified about 25-35% of the time. The data from these same studies indicates a substantial survival advantage for those – and this is the key word – selected for cardiac catheterization, and in whom percutaneous coronary intervention is performed. The authors go on to note at least nine randomized trials are underway or planned to address the utility of catheterization in the subgroup without STE.

Lastly, the authors note the emerging role of VA-ECMO in cardiac arrest. With only a handful of patients from observational registries, survival with cerebral performance category 1 or 2 has been observed in 15-40% of patients. This is, again, likely subject to selection bias, but remains a potentially promising approach. The ARREST trial, evaluating such a strategy, is ongoing with completion expected in 2023.

At the minimum, it is a worthwhile review article for anyone looking to catch up to speed – even if there isn’t much within to change current thinking or practice, at the moment.

“The Evolving Role of the Cardiac Catheterization Laboratory in the Management of Patients With Out-of-Hospital Cardiac Arrest A Scientific Statement From the American Heart Association”
https://www.ahajournals.org/doi/10.1161/CIR.0000000000000630

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 Fourth Universal Definition of Myocardial Infarction

You’ve seen Sepsis-3 – but did you miss MI-4?  Not, unfortunately, a James Bond reference – but the “long-awaited” 2018 Fourth Universal Definition of Myocardial Infarction.

Effectively, the crux of this document is to help specifically describe cardiac injury and differentiate the MI and non-MI causes of troponin elevation. This ties to tweezing out the difference between “myocardial injury” and “myocardial infarction”. “Myocardial injury” simply describes circulating cardiac troponin levels ≥99th percentile, and can be acute or chronic. “Myocardial infarction”, on the other hand, is effectively myocardial injury plus supporting evidence for acute myocardial ischemia.

Exciting, I know!

Finally, to recap, the five (six?) types of myocardial infarction:

  • Type 1 – Myocardial ischemia and troponin levels ≥99th percentile resulting from atherosclerosis and thrombosis, encompassing STEMI and NSTEMI.
  • Type 2 – Myocardial ischemia and troponin levels ≥99th percentile resulting from thophysiologic mechanisms leading to a mismatch of oxygen supply and demand.
  • Type 3 – Sudden death suspected to be from new cardiac ischemia, specifically when cardiac biomarkers are not available.
  • Type 4a – Coronary intervention-related MI with troponin levels more than 5 times the 99th percentile, or rising troponin levels, and other supporting evidence for new ischemia within 48 hours of PCI and relating to a specific procedural complication.
  • Type 4b – Same criteria as Type 1 MI, but related to stent/scaffold thrombosis, absent a specific procedural complication.
  • Type 5 – Effectively Type 4a, but with troponin levels 10 times the 99th percentile, and associated with complications from CABG.

Just keeping up, keeping up.

“Fourth Universal Definition of Myocardial Infarction (2018)”
http://www.onlinejacc.org/content/early/2018/08/22/j.jacc.2018.08.1038

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