The third of the big CT coronary angiography studies from the last year – and, yet again, this is positive for its primary endpoint.
However, that value of that endpoint is another matter – mean length of stay in the hospital. For the CCTA cohort, that mean was 23.2 hours and the “standard evaluation” was 30.8 hours. However, more illuminating – and further favoring CCTA – is that the median CCTA evaluation time was 8.6 hours compared with 26.7 hours in the “standard evaluation” group. Just like in the previous studies, CCTA is faster, and, for some patients, much, much faster.
But, as you can probably gather from that mean/median discrepancy, a substantial cohort in the CCTA group went on to have some pretty extensive downstream testing and prolonged hospital stays. This means, from a costs standpoint, the two strategies eventually even out. No significant safety differences were detected between the two strategies.
Now that we’ve seen the full results of ROMICAT II, CT-STAT, and ACRIN-PA, we have a pretty good idea of what this test does. If you must evaluate these low-risk chest pain patients with imaging of some sort, need to clear them out of your Emergency Department quickly, your cardiology team is excited to take on the false positives, and you’re unconcerned about the downstream harms – then CCTA is the test for you. If the potential harms, the poor specificity, and the non-functional nature of the test concerns you – then no one will fault you for dragging your feet.
The accompanying editorial gets it right – this is still a test looking for the correct application. However, we don’t just need a better test – we need a better consensus for whom we’re simply not going to test.
“Coronary CT Angiography versus Standard Evaluation in Acute Chest Pain”
Category: Cardiology
Anterior STEMI or Benign Repolarization?
As requested by @jord7an, this covers Dr. Smith’s recent Annals publication regarding the differentiation of anterior STEMI from early repolarization abnormalities. Classically, early repolarization abnormalities manifest with prominent R waves, J-point elevation, ST-segment elevation, and a concave ST-segment morphology in the precordial leads. However, physician performance in practice at differentiating this pattern from true STEMI could be better, with benign repolarization making up about 10% of anterior STEMI cath lab activations.
In short, this is a retrospective evaluation of electrocardiographic features of anterior STEMI, trying to find an accurate, reliable rule to diagnose STEMI rather than a similar “pseudoinfarction” pattern. After doing objective measurements of several possible criteria between their comparison sets of “subtle” anterior STEMI and early repolarization, they come up with this rule:
(1.196 x STE60 V3) + (0.059 x QTc) – (0.326 x RA V4)
If the result of that equation is calculated as >23.4, there’s a +LR of 9.2 for STEMI, and a -LR of 0.1 if negative. And, those are useful LRs.
So, this is probably helpful. The authors suggest this could be easily programmed into the automatic rhythm analysis software of ECG machines, which is plausible. However, both the derivation and validation of this rule were performed retrospectively. The next step, ideally, would be a prospective comparison between rule-augmented clinical decision-making and non-augmented decision-making. Unfortunately, detecting small differences in clinical performance may require large samples, and these clinical dilemmas are not common at single centers.
“Electrocardiographic Differentiation of Early Repolarization From Subtle Anterior ST-Segment Elevation Myocardial Infarction”
www.ncbi.nlm.nih.gov/pubmed/22520989
Chest Pain – Here, Your Problem Now
In the United States, a quarter of our medical malpractice payments result from missed myocardial infarctions. Therefore, in states with sub-optimal liability environments, emergency physicians are stuck in a quagmire of conflicted interests and fear of litigation if a discharged patient has an MI.
Therefore, a common strategy is to make low-risk chest pain Someone Else’s Problem. And, this article from Archives of Internal Medicine shows the internist evaluating the patient simply makes the same surrender to defensive medicine. In this retrospective cohort, 2,107 admitted patients underwent 1,474 stress tests during their two-year study period. Of those 1,474, 12.5% were abnormal. Of those 184 patients, only 11.6% underwent cardiac catheterization, and a grand total of 9 patients received a revascularization.
So, the authors suggest two salient points:
– 2,107 admissions to yield 9 (supposedly) beneficial interventions – how crazy is that?
– What about the 88.4% of patients with abnormal stress tests that didn’t undergo an invasive test within 30 days – why are we using an evaluation strategy we don’t act on?
The authors think we might be able improve upon this practice pattern.
“Outcomes of Patients Admitted for Observation of Chest Pain”
www.ncbi.nlm.nih.gov/pubmed/22566486
Daily Aspirin Harms More Than It Helps
Patients with cardiovascular disease are routinely placed on daily, low-dose aspirin for primary prevention of cardiac events.
Unfortunately, antiplatelet effects promote other types of bleeding, while the cyclooxygenase pathway has a deleterious effect on the gastric mucosal. This 4.1 million patient propensity matched retrospective database study from Italy demonstrated approximately 2 excess cases of major bleeding events – whether intracranial or gastrointestinal – per 1000 patients treated per year.
Which is approximately the number of major cardiovascular events prevented by the daily aspirin use during the same time period.
Not specifically relevant to Emergency Medicine, but yet another example of how it’s naive to think many treatments in medicine – even those (or particularly those!) that have been part of routine practice for eons – are benefiting patients without a significant risk of harms.
“Association of Aspirin Use With Major Bleeding in Patients With and Without Diabetes”
jama.jamanetwork.com/article.aspx?articleid=1172042
ADAPT 2-Hour Rule Out
I’ve had a couple questions recently about accelerated rule-out strategies – considering they’re in the ACEP Guidelines, but the AHA seems to endorse a viewpoint that any suspicion for cardiac chest pain needs to be taken to its bitter end with a provocative test. Unfortunately, an all-in strategy doesn’t mesh quite as well with reality where the costs are astronomical, and the yield abysmal.
Conveniently, this is another recent study highlighting the use of two sets of biomarkers, two hours apart – using conventional troponin assays. This is an observational cohort study in Australia and New Zealand investigating the feasibility of their stratification instrument, with the endpoints of “Major Adverse Cardiac Events” within 30 days – an endpoint that, for once, excludes revascularizations. Specifically, the decision protocol being evaluated includes:
– Negative troponins at 0 and 2 hours from presentation.
– No new ischemic changes on ECG.
– TIMI Score of zero.
Of their 1,976 enrolled patients, 392 met these criteria and were followed for 30 days. Their single miss was reported as an nSTEMI with two initially negative troponins who subsequently had a positive 12-hour troponin. Therefore, their sensitivity for 30-day MACE is statistically 98.1% to 99.9%. This is one of the eight patients in the low-risk cohort who underwent a revascularization procedure in the course of their routine care.
Essentially, using a normal EKG, two negative sets of enzymes, and a risk-stratification instrument – TIMI, Geneva, etc. – the evidence out there lets you have a discussion with the patient regarding their overall risk for a poor outcome. If you’re stuck in a zero-miss environment, then any of these 2-hour protocols will be of no use – they all have a non-negligible miss rate. But, if you have a grey area to work with, and an otherwise relatively low-risk patient, a quick two-hour troponin helps you catch a few extra fish you otherwise would have missed.
“2-Hour Accelerated Diagnostic Protocol to Assess Patients With Chest Pain Symptoms Using Contemporary Troponins as the Only Biomarker The ADAPT Trial”
www.ncbi.nlm.nih.gov/pubmed/22578923
Glucose-Insulin-Potassium For MI?
“Investigators, led by Dr Harry Selker (Tufts Medical Center, Boston, MA), are pleased with the results, believing that after years of futile study, they have finally found some clinical evidence to support the experimental data suggesting that GIK [glucose-insulin-potassium] myocardial metabolic support could protect the heart in the ACS setting.”
…which lead to the press release tweet of “Intravenous GIK Slashes Death Risk in Acute Coronary Syndrome: CHICAGO – Glucose, insulin, and potassium given i…” by @ACEPNews. That press release can be seen here.
There have been trials enrolling over 20,000 patients to date that have been negative.
Despite all these previous negative trials, the authors believed the problem was timeliness – the critical time in which to provide metabolic support to the infarcting myocardium was in the prehospital setting, upon the earliest recognition of ACS. The original goal was to enroll 15,450 patients. They ended up with 880. Then, after data collection, they changed the primary endpoint from all-cause mortality to progression to myocardial infarction at 30 days and at 1 year. And they only have the 30 day data right now, they’ll get back to us with the 1 year outcomes. How this made the cut for publication in JAMA is outside the scope of my speculative powers.
So, they enrolled folks prehospital with signs and symptoms of potential acute coronary syndrome whose prehospital EKG was read as STEMI or met the ACI-TIPI prediction instrument probability threshold of 75%. They received the GIK solution with 90 minutes, on average. And, the primary outcome measure was negative for progression to MI, trend favoring GIK with OR 0.88 (CI 0.66-1.13). Negative for 30 day mortality, OR 0.72 (0.40-1.29). For STEMI patients, negative for progression to MI, OR 0.74 (0.40-1.38), and negative for 30 day mortality, OR 0.63 (0.27-1.49).
So, yes, there is a trend. And some subgroups even had significant trends in favor of GIK. But for JAMA and the rest of the internet to be promoting this as practice-changing at this juncture is absolutely inappropriate.
“Out-of-Hospital Administration of Intravenous Glucose-Insulin-Potassium in Patients With Suspected Acute Coronary Syndromes: The IMMEDIATE Randomized Controlled Trial”
http://jama.ama-assn.org/content/early/2012/03/21/jama.2012.426.full
CCTA Is A Bad Shortcut Around Bad Care
“Although an acute coronary syndrome is ultimately diagnosed in only 10 to 15% of patients who present with chest pain, the majority of these patients are admitted to hospitals, at an estimated cost of over $3 billion annually.”
This is, essentially, the statement of problem from the NEJM article, sponsored by Siemens, regarding the use of coronary CT angiograms in the Emergency Department on low-to-intermediate risk chest pain. They are clearly huge fans of CCTA up at the University of Pennsylvania, and I hate to think it has something to do with the parade of imaging technology companies and patent applications listed as disclosures by the authors.
In this study, the authors enrolled 1,392 patients with chest pain with the goal of testing the primary hypothesis that “patients without clinically significant coronary disease on CCTA (i.e., no coronary-artery stenosis ≥50%) would have a 30-day rate of cardiac death or myocardial infarction of less than 1%.”
Good news! They were right. Bad news: their entire enrolled cohort had a 30-day death or MI rate of only nearly 1%. It’s rather incredible, really, that they have this entire article in which they sing the praises of CCTA for identifying low-risk chest pain, when in reality, they gloss over the fact that they simply could have sent home every single patient in the study without doing a single additional test and only nearly 1% would have had death or MI within 30 days.
Going back to their essential statement of problem, it might be true that CCTA were valuable if they were looking to apply it in a population and practice environment in which we were actually hospitalizing patients with a 10-15% rule-in rate. However, the opposite of what these authors propose is the real truth – clinically identify all the low-risk chest pain and stop doing all these expensive tests! They claim it expedites discharge from the Emergency Department, which, in theory, saves money – but it isn’t! Despite 90% of their CCTA being negative for stenosis >50%, they still end up admitting half their CCTA cohort. Even the negative CCTA cohort, while their length of stay is reduced to 12 hours, still means they’re being placed in observation status and billed an additional separate observation code – which in many places is a protocolized chest pain observation unit run by the Emergency Department.
This is simply a bad solution to bad baseline practice patterns. The measurable benefit here isn’t to the patient, it’s to the malpractice risk of the physician, to Siemens and other sponsors of the study, and likely to the Emergency Departments whose billing increases for these short stay observation patients.
“CT Angiography for Safe Discharge of Patients with Possible Acute Coronary Syndromes”
http://www.nejm.org/doi/full/10.1056/NEJMoa1201163
Unneeded Stents Are Bad And Bad For You
Well past a decade into the stent era, there’s finally a growing recognition and furor over the costs and potential harms of unnecessary stenting. While interventional cardiologists are great for the bottom line of hospitals, a few high profile cases have demonstrated that PCI and stenting might be performed more than indicated.
And, not only is it costing those patients more in procedural billing, it’s likely harmful to them as well.
This concept of “Fractional Flow Reserve” has been developing in cardiology literature to better evaluate whether a stenotic lesion is actually significantly impairing the perfusion of myocardium. These authors, part of a French cohort study called “DEFER,” are following up prior studies showing FFR-guided selective stenting for left main disease is reasonable, and looking back at what they call “small vessel” coronary disease – LAD, RCA, and LCx.
This is, unfortunately, a retrospective analysis, and there are huge differences between the groups that underwent angiography-guided PCI and the group that underwent FFR-guided PCI – but not enough difference to account for the additional hazard ratio acquired by the angiography-guided PCI. Angiography-guided PCI, in their propensity-score adjusted hazard ratio, still had significant associations with increased non-fatal MI and future revascularizations during their five-year follow-up period. Indeed, the FFR-guided PCI group that did not find any vessels requiring intervention did outstanding – suggesting this perfusion-based strategy might be better for ensuring the benefits of stents do not outweigh the risks.
“Long-Term Clinical Outcome After Fractional Flow Reserve−Guided Percutaneous Coronary Revascularization in Patients With Small-Vessel Disease”
http://www.ncbi.nlm.nih.gov/pubmed/22319067
No One Knows How To Diagnose CAD
And, once they diagnose it – it doesn’t seem like anyone knows what to do with it, considering all the brouhaha these days about potentially unnecessary PCI and stenting.
But, this is a prospective coronary CT angiography registry that was reviewed to determine whether any value was added with the CCTA over conventional stress testing in patients without known CAD. They reviewed 22,551 patient records, excluded patients with known CAD, incomplete data, and patients who hadn’t undergone a recent (<3 months) cardiac stress test, and ended up with 6,198 patients.
The point the authors seem to be trying to make is that CCTA is a better test than stress testing, but that’s only part of the story. What they note that is interesting along the way is that there is absolutely no correlation between stress testing results and CCTA results. Patients with normal, equivocal, and abnormal stress results had, essentially, the same incidence of normal, <50%, and >50% coronary stenosis. And, the hidden story about how CCTA is being used in their patient cohort is fascinating – a younger group with typical chest pain and normal stress tests referred to CCTA vs. an older group with less typical symptoms and abnormal stress tests referred to CCTA.
But, then, finally they compare both of their disparate tests to the “gold standard” of invasive angiography, and they find that both tests are awful at predicting >50% coronary stenosis. Stress testing was 60.4% sensitive and 34% specific, while CCTA was 94% sensitive and 37% specific. So, we have two tests that are wrong about the presence of disease twice as often as they’re right – and these authors are using a clinically irrelevant 50% stenosis as their “gold standard”.
Rather entertaining to observe the difficulty the cardiology literature is having reconciling all their different imaging options with clinically relevant stenoses, much less outcomes. Good thing all these inadequate tests are cheap and harmless….
“Coronary Computed Tomography Angiography After Stress Testing”
Would Free Medications Help?
It’s too bad this study doesn’t actually look at what I would have hoped it would – but it’s interesting, nonetheless. One of my hospitals is a true safety-net hospital and we see, repeatedly, repeatedly, repeatedly, the complications of neglected chronic disease. One of our frequent laments is whether the costs of recurrent acute hospitalization wouldn’t be prevented a hundred times over if we’d simply sink some costs into preventative maintenance care, free medications, etc.
This study almost looks at that. This is from the NEJM which compared the outcomes of patients following myocardial infarction, and they follow a group which receives completely free medication and a group that does not. Unfortunately, the group that does not receive free medications is still receiving heavily subsidized medication support, and is only responsible for a co-pay.
Despite only needing to come up with a co-pay, there’s a significant difference in medication compliance, with an average absolute difference in full adherence with medications of ~5-6%. With this minimal absolute difference in adherence, the full adherence group had significantly fewer future vascular events – mostly from stroke and myocardial infarction – approximately a 1% absolute decrease. There was a non-significant decrease in total costs associated with the patients who were on the full-coverage medication plan.
Now, they don’t follow-up any medication-related adverse events, so this is the most optimistic interpretation of benefits of full-coverage, but it would seem that it is overall cheaper and more beneficial to supply medications for free. And, it makes me wonder what the results of a similar cost/health-benefit study would show in our safety-net population.
“Full Coverage for Preventive Medications after Myocardial Infarction”