In this 2-part Mind the Gap episode, we explore – and pick apart – everything you thought you knew about unstable angina. Thank you to Dr. Norma Keller for peer-reviewing this episode!

Time Stamps

  • 4:08 The basics – what is acute coronary syndrome?
  • 5:22 Clinical context matters – angina pectoris, atypical chest pain, and troponins
  • 9:42 You can’t just “cath” everyone – risk stratification to identify patients with high mortality risk
  • 14:00 TIMI isn’t perfect – the issues with the score and MACE outcomes
  • 17:58 Review of teaching points

Show Notes

  • Both unstable angina (UA) and NSTEMI are characterized by angina pectoris, defined as a sub-sternal chest pain brought on by minimal exertion or occurring at rest and lasting for >10 minutes.
  • The difference between UA and NSTEMI lies in cardiac biomarkers (aka troponin). Cardiac biomarkers are negative in UA and positive in NSTEMI.
  • Atypical chest pain doesn’t exclude ACS. It’s actually fairly common in patients with MI! In one study, up to 20% of patients with atypical chest pain symptoms were found to have ACS. Atypical symptoms are also more common in diabetics, the elderly, and women.
  • The highest risk subset of unstable angina patients, specifically those with chest pain at rest, carry a risk of MI or death of up to 25%. To figure out which patients are at this higher risk, risk stratification tools can help us (because you just can’t catheterize everyone).
  • We’ve chosen to focus on the TIMI score, which calculates risk of major adverse cardiac events, or MACE, at 14 days. Other scores include HEART and GRACE.
  • However “MACE” is a composite score including death, myocardial infarction, or urgent revascularization, a problematic combination of outcomes.
  • Urgent revascularization is synonymous with unstable angina. It’s a category for patients presenting with symptoms concerning for ACS who don’t meet criteria for myocardial infarction because their troponin is negative, but were taken to the cath lab anyway. Because this decision is based on clinical symptoms and possibly EKG findings alone, it’s a subjective diagnosis.
    • For example, a low risk patient with unstable angina comes back in 14 days with chest pain. If their troponin is still negative, so they technically still have UA and nothing worse. How does their cardiologist decide that they now warrant going to the cath lab? That’s a subjective decision, but the TIMI study included it as a hard outcome.
    • Alternatively, you can break the TIMI score down to just risk of MI and death.


S: Movies, TV, and music have influenced more of what I think I know than I’d like to admit.

J: Yeah, I’m embarrassed by how much medicine I’ve learned from TV ads or Scrubs.

S: Sadly I think agree with you.

J: Don’t worry guys, I always take it with a grain of salt, and we did go to med school.

S: Well one thing that TV usually does get right is heart attacks. Have you noticed how often that comes up?

J: Yeah, well it’s very dramatic and symbolic… but to be fair, it’s also very common. And to my credit, sometimes their recreations are spot on.

S: But not always. Take for example one of the key premises of the classic movie of the 90’s, the Saint

J: That’s not a classic

S: Where Elizabeth Shue’s character has to take a medication every day otherwise she will die of congenital heart disease

J: Yeah, ok, that wasn’t realistic. What disease were they even shooting for?

S: Haha, I’m not sure. But it is a great rainy day afternoon movie if you wanna reminisce about the 90s. One thing that TV does get right is heart attacks. Have you ever noticed how often that comes up?

J: Well its very dramatic and symbolic. Sometimes, their recreations are spot on. Case in point – I read that in the movie Vice, the actor Christian Bale actually suggested to his writer director Adam McKay that nausea and epigastric pain can be symptoms of a heart attack, so they went with that on film.

S: Crazy enough, McKay himself had a heart attack himself and recognized it because he had similar symptoms. Isn’t that crazy?

J: Super ironic

S: My favorite TV show growing up was the West Wing. Towards the end of the series, Leo suffered a heart attack in an eerily familiar scene with almost the classic caricature of the old man in the cold clutching his chest.

J: And this movie trivia goes, that’s a much sadder story, because the actor that played Leo, John Spencer, actually later died of a heart attack himself.

S: Unfortunately these classic cases happen every day, but most of the time chest pain is not really actually that clear.

J: Often, histories are confusing and lab tests don’t always help clear things up.

S: Yeah, part of that is because coronary artery disease is a complicated spectrum.

J: People with diabetes can have silent MIs, women are more likely to have symptoms mistakenly attributed to “anxiety”, and the elderly are more likely to have atypical symptoms like abdominal pain.

Acute Myocardial Infarction in Women: A Scientific Statement From the American Heart Association. Circulation 2016;Jan 26.

S: And we see a lot of people present to the ERs with chest pain because logically most people are afraid of getting a heart attack, so they’ll come in and get their symptoms checked out.

J: The annual incident of MI is only 0.6% [AHA 2017], so not surprisingly most people who present with chest pain actually aren’t having a heart attack.

S: But it’s on us to figure out what’s going on!

J: So today, we’re going to tackle how to approach chest pain.

S: To be fair, there’s a lot out there on how to diagnose and manage a STEMI

J: That’s an “ST segment elevation myocardial infarction”, the real deal

S: But we’re going to focus today on the not-so-obvious cases, specifically whether something is or isn’t unstable angina.

J: Our goal is to help you understand unstable angina, and the many different ways you can think about it and approach it.

S: But that’s gonna take more than one episode.

J: So we’ve broken it into 2. But we’ll still highlight all of the teaching points we’re going to cover in both episodes today.

S: And that’s because we want you guys to think of this all together. So let’s start off by reminding ourselves about (1) what is the definitions of acute coronary syndrome (or “ACS”).

J: Specifically we’ll clarify the difference between non-ST elevation MI (or NSTEMI) and unstable angina.

S: We’ll also explain these definitions in the context of the clinical history of the disease.

J: Next we’ll move on to 2) how the TIMI score came to be and its role in risk stratifying patients with ACS so you figure out who’s really at risk of bad outcomes

S: And focus on putting this all together with 3) the pathophysiology of how we think about patients with chest pain and how to incorporate presentation, risk scores, and pathophysiology into how we think about unstable angina.

J: Our hope is that by addressing it step by step, we can give you a more complete picture of how to tackle the surprisingly difficult diagnosis of ACS.

S: So let’s see if we can quit playing games with those hearts.

J: And go a little bit deeper into ACS and unstable angina.

~Queue Intro~

J: Hi, I’m Janine Knudsen

S: And I’m Steve Liu

J: Welcome to Mind the Gap

S: Many thanks to Dr. Norma Keller, Chief of Cardiology at Bellevue Hospital and Assistant Professor of Medicine at NYU, for peer-reviewing this episode.

J: Also, we want to take a minute to give a shout for our brand new website – check us out at!

J: So let’s start things off by defining terms. Acute coronary syndrome is caused by coronary artery plaque disruption leading to an abrupt reduction in blood flow, and can be accompanied by angina

S: And it’s a spectrum that includes but isn’t limited to STEMIs. There are also NSTEMIs and unstable angina, which the 2014 AHA/ACC clinical practice guidelines lumps into one overarching category called NSTE-ACS.

J: Part of the reason for this is that UA and NSTEMI are clinically indistinguishable. The AHA defines unstable angina as a pressure-like sub-sternal chest pain brought on by minimal exertion or even occurring at rest that lasts for more than 10 minutes.

S: So to differentiate them, we’re going to need lab work.

J: Yeah, what differentiates NSTEMI from UA is in it’s name – the MI stands myocardial infarction, meaning it requires positive cardiac biomarkers, which nowadays just means troponin but in the past also included CK-MB.

S: This is an important point, so let’s say it again.

J: NSTEMI has positive troponins. UA has negative troponins. Clinical presentation-wise, they are the same.

S: Just remember that troponins are not synonymous with ACS.

J: Yes, to pull from our sister Core-IM podcast “5 Pearls”…

S: …here’s a quote from Dr. Greg Katz, NYU Cardiologist:

I think about a Troponin as being either due to a coronary occlusion or not due to a coronary occlusion. And if you make that distinction and that’s the distinction that you’re trying to make in your mind, it makes you think about patients differently. And I think that all of the way that you teach people about diagnostic and clinical reasoning, it’s about giving. It’s about giving yourself away to frame a patient in your mind and get closer to making a diagnosis and closer to getting the right treatment for somebody, and so I’m alway s thinking about, do I think this one I see a Troponin I think do I think this patient has a coronary occlusion and if you frame it all in that way, it really simplifies your thinking quite a bit.

J: His point is of course that you always need to consider the clinical context when trying to interpret a positive troponin. The differential is long – everything from demand ischemia to myocarditis could be going on.

S: We won’t get into that now. But it’s also important to note that conversely, just because the troponin is negative, it doesn’t exclude ACS.

J: And that’s the beauty of the definition of “unstable angina”... it doesn’t require a positive troponin. But that story should still be convincing for cardiac ischemia.

S: Beauty here is relative. So classically angina is described as a retrosternal pain radiating to the left arm, that is associated with exertion.

J: But what about atypical symptoms? You know, “angina equivalents”?

S: That is my least favorite phrase.

J: Yeah, that’s why I brought it up (sarcastically) I think you’ve mentioned that once or twice

S: But it’s obviously really important to acknowledge, especially because as we mentioned earlier, atypical symptoms are more likely to occur in women. Additionally, patients with diabetes and the elderly may have hardly symptoms at all.

J: Well let’s go through a few “angina equivalents.” Just humor me. First, there’s new or worsening dyspnea on exertion.

S: Then there’s syncope, nausea /vomiting, and pleuritic chest pain.

J: And we’ll stop there, but the list goes on…

S: And to state the obvious, just because a patient has atypical features, doesn’t mean that you can take ACS off the differential:

J: In the works of AHA: “although typical characteristics increase the probability of CAD, atypical features do not exclude ACS.”

S: So when I mentioned in a previous episode that anginal equivalents drive me nuts, this is why. Of course real life doesn’t perfectly match the textbook, but this is a frustratingly real life example of just that.

J: Actually, it’s not uncommon. The AHA guidelines cite one study where atypical symptoms were incredibly common: 7% of patients with ACS had reproducible pain with palpation.

S: And that 13% had pleuritic chest pain, another 22 % had stabbing chest pain.

J: So where does that leave us? Just treat everyone for ACS? Or don’t treat anyone?

S: Or maybe, in the words of one of my old attendings, the key to just “stress them and bless them…”

J: Yup, that’s all today for our episode on chest pain, it’s impossible to know, so please stress everyone you meet.

S: Cue outro music.


J: Just kidding. I hope no one believed that.

S: The problem with that logic is that a stress test is still just that – a test.

J: If you want to use Bayesian logic (shout out to our friend Dr. Dave Wei)  you’ll need to understand your test characteristics and have a pre-test probability to help inform how you interpret your test results .

S: A test doesn’t get you out of thinking about whether or not the clinical syndrome matches.

J: After all, get an MRI on a patient and you could easily find an incidentaloma that has nothing to do with their symptoms.. The same logic holds true here. Your patient may have CAD, and they may have chest pain. But you can create any number of reasons why those two might be true-true and unrelated.

S: IncidentaloCAD

J: Doesn’t quite flow of the tongue, Steve, but yes

S: The true gold standard for diagnosing ACS is a combination of clinical assessment and cardiac catheterization, but of course the latter we can’t and probably shouldn’t do on everyone.

J: So in times in clinical uncertainty, we use a stress test to see if we should be advocating for a cath. Of course, only if the patient is stable.

S: Though with decreasing rates of cath complications you could make the argument that it’s not an entirely silly notion to cath people even when ACS is not a slam dunk.

J: Oh that pains me! But we are in the modern day of value based medicine, Steve, so I think it’s reasonable to say that cathing everyone with any chest pain remotely concerning for ACS is probably still a bad idea.

S: So to better understand “when is it worth moving on to cardiac cath?” we need to decide which patients we’re not that worried about.

Origin of the TIMI Score and Composite Outcomes

J: So to do this we’re going to move on from ACS presentations and focus on the concept of risk stratification. Specifically, estimating an individual patient’s risk based on population level data.

S: And their risk level, based on the data we have and their clinical presentation, will guide us on what to do and whom to cath.

J: To cath or not to cath? And just to be clear, when we say cath in this episode, we’re usually referring to stenting, otherwise known as percutaneous coronary intervention AKI PCI. So the real question is, to stent or not to stent?

In other words, if you come in with chest pain but nothing bad happens to your heart in the next month was that chest pain clinically relevant?

S: If a tree falls in the woods… right?

J: Yeah, and this isn’t to be zen, but the logic here is relatively sound. If we can stratify patients by risk, it makes sense to leave the low risk patients be and avoid cathing them, because nothing is likely to happen to them anyway. Especially after we factor in how effective current medications are at reducing the risk of future ACS.

S: To understand how we began to think this way, let’s take a detour and go back to the late 90s and Eugene Braunwald.

J: You guys might recognize Braunwald’s name from the famous Harvard TIMI group.

S: The TIMI group was trying tackle the fact that chest pain at rest may seem benign, but is actually a dangerous syndrome.

J: In an earlier review, they found troponin positivity at either the 0 or 6 hour mark carried a risk of death or MI of 25% at 6 month

S: And when compared to other types of chest pain, ongoing chest pain at rest had the highest rate of mortality, making it the most dangerous.

J: They wanted to figure out how to identify those 25% of patients before they died, not after

S: Generally a good idea

J: So they looked at risk factors of having a bad cardiac outcome. They started with troponin.

S: You see, we’ve known for a long time that troponin positivity correlates to increased mortality risk

J: This shouldn’t be a surprise. The more heart tissue is dying, the more likely that something serious is going on

S: – cardiac or not –

J: and the worse off you’re likely to be. Think of it as similar to your qSOFA score for sepsis.

S: They suggested checking a troponin both at the time of arrival in the ED and again at 6 hours.

J: So we’ve been doing that for literally 30 years…

S: This is where the standard practice comes from! They compared the outcomes based on if you were troponin positive or negative.

J: And when they looked at their database, they found that troponin positivity at either the 0 or 6 hour mark carried a risk of death or MI of 25% at 6 months, whereas the troponin negative group had a less than 5% chance at 6 months.

S: Given the clear differences in the troponin positive and troponin negative populations, they thought, well hey, I bet we could make a score out of that.

J: So they added in data from TIMI 11b and the ESSENCE trial, and the new UA/NSTEMI TIMI score was born.

S: Thus achieving their true goal: creating a hard to memorize score that could be used to pimp medical students for years to come.

J: Well, the components make clinical sense. It includes: age, known CAD, CAD risk factors, aspirin use, EKG changes, troponin, and repeat chest pain in 48hrs.

S: But let’s be real, you’re not gonna retain it if we just say each of the things. So let’s use a mnemonic.

J: Our Core IM team would be proud


C – known CAD

A – aspirin

R – risk factors

A – angina (again in 48 hrs)

T – troponin

S – ST changes

65 for the age

J: Can’t believe you made me just do that! Feel free to google it on your local interwebs whenever you need a refresher.

S: Other versions of this also include the HEART score which is also a mnemonic.

J: That one we won’t list because our plan was to focus on TIMI, but it’s also a useful test that helps to evaluate if your patient falls into a low risk category or not.

S: It has some similarities to TIMI including E for looking at the ECG and T for troponin positivity.

J: No! Nice try Steve. Our goal is to help you remember the purpose of these tests, not memorize them: to help us decide if a person falls into a low-risk chest pain category or not. So they can be quote-unquote ruled out. Not surprisingly we’re looking for a score that is sensitive. We don’t want to miss anything deadly.

S: We want the woods to be dead quiet.

J: Exactly, and with that in mind, let’s look at that TIMI score. What the TIMI group found was that people with low scores of 0, 1, and 2 had a low risk of all cause mortality and MI at 14 days.

S: That was around 2.9%. That’s pretty good!

J: Yes, but is it enough? After all the 2014 AHA guidelines admit that this score alone does not rule out  MI.

S: 2.9%  might suggest 3 of these outcomes of every 100 people that you see

J: But of course, you can’t just rely on TIMI. No clinician uses a score alone.

S: Cuz then we’d robots.

J: The future

S: But seriously. Clinical context simply cannot be ignored… Even if we incorporate it like the H for history in HEART

J: Steve! Stop distracting us by repeating the mnemonic

S: Okay, okay. Because ultimately, no numerical score will achieve a sensitivity of 100%, otherwise it’d be a gold standard.

J: But let’s not move on from the TIMI score just yet. Some of you may have googled it and are now wondering…

S:  “Didn’t you guys say TIMI score of 1 to 2 had a 2.9% risk… that’s not what MDCalc says at all!”

J: You’ll probably see that for TIMI scores of 0 and 1, there’s about a 5% risk and for TIMI of 2, there’s an 8% risk.

S: Wait so are we liars?

J: Well you we were specific that we were only citing numbers for MI and mortality.

S: Ah and that higher 5% and 8% from the TIMI score also include the risk of urgent revascularization.

J: All of these outcomes together are commonly called MACE or major adverse cardiac events. To summarize, we’re talking about: death, MI, and need for urgent revascularization.

S: But in the words of the wise sage Big Bird: one of these things is not like the others, one of these things just doesn’t belong… but what does urgent revascularization mean?

J: Well if something is ACS but it doesn’t result in death or an MI, then by definition it has to be unstable angina.

S: As we already described, unstable angina patients present with a concerning story and maybe even EKG changes, but they do not have a positive troponin to support their diagnosis.

J: So by default they don’t have an MI. They don’t meet criteria for STEMI or NSTEMI, and therefore are classified as UA.

S: But as we discussed, we can’t stop there. We have to use the TIMI score to figure out of they are high or low risk of death or MI.

J: So remember we’re interpreting TIMI outcomes after 14 days. If you have someone you saw with unstable angina that gets urgently revascularized within 14 days of you seeing them, but still never had an MI or died, you have to wonder, what convinced their doctor to take them to the cath lab the second time? Their troponin is still negative.

S: Also what did they see?

J: Ask any interventionalist you meet, and they’ll say they’ve seen multiple cases in their careers of patients with negative biomarkers but with catheterization findings that were concerning for MI physiology.

S: And we should be clear, UA definitely does exist and it can be dangerous. But using it as an outcome in TIMI opens up some questions.  I mean, ask yourself, what’s the inevitable outcome of UA that we are trying to avoid?

J: MI or death.

S: So while it’s reasonable to say that people diagnosed with UA were caught before those bad outcomes, the thinking can become a little circular and therefore problematic.

J: Yeah, most people have improvements in cardiac chest pain after a cath whether you’re dealing with stable or unstable angina. But beyond feeling better, the question should be whether cathing the patient saved them from death or MI, but once you’ve cathed them it can be hard to tell.

S: This highlights the challenge of interpreting these major adverse cardiac outcomes aka MACE as a group.

J: Two of the three outcomes, MI and death, are clear. The last one, UA, is a real outcome, but can be more challenging and subjective to diagnose.

S: So next time we’re going to try to delve a little deeper into these ideas. We’ll focus on understanding the pathophysiology of unstable angina and using all of the things we have discussed to understand unstable angina.

J: To get to the bottom of it, we have to go beyond TIMI and HEART scores and enter into a debate over whether or not unstable angina is clinically relevant.

S: But that’s all we’re going to talk about for now. To recap, we’ve covered the definitions of unstable angina and acute coronary syndrome.

J: ACS is clinical syndrome caused by loss of coronary artery blood flow from an obstructing plaque, and it’s a spectrum from STEMI to NSTEMI to UA. Both NSTEMI and UA patients have a clinical story convincing for ACS, but NSTEMIs have positive troponins and UA does not.

S: With both NSTEMIs and UAs, it’s important to know the danger of bad outcomes, because we can’t just cath everyone. If you’re not sure if the patient has UA and might be low risk, they probably wouldn’t need invasive testing. That’s what the TIMI score was designed to do.

J: But it’s important to understand what the TIMI score is trying to predict. That’s the risk of MACE, or major adverse cardiac events, in 14 days, a catch-all that includes MI/death but also includes urgent revascularization, a very subjective outcome. So we prefer to break it down to risk of MI/death only.

S: So for a TIMI score of 0 to 1pts, this clarifies the risk of outcomes we can clearly define  from 5% to 2.9%.

J: So that actually is all for today on our podcast.

S: Cue outro music.

J: For real this time.


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