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Michelle M. Kittleson, MD, PhD: Welcome to Medscape InDiscussion: Heart Failure. I’m your host, Dr Michelle Kittleson.
Stress cardiomyopathy, aka broken heart syndrome or Takotsubo cardiomyopathy, often presents dramatically, much like an acute myocardial infarction. Diagnosis can be challenging because it’s a diagnosis of exclusion.
When do we need to have a high suspicion for this relatively rare condition? What are the can’t-miss key points to cover in the history? What do you need to know about management? With me to answer these questions is the foremost expert on broken heart syndrome, Dr Ilan Wittstein from Johns Hopkins, where he’s assistant professor of medicine and directs the Advanced Heart Failure Fellowship. In addition, he was my attending when I was a cardiology fellow approximately 1 million years ago. Welcome, Ilan. It’s so great to have you.
Ilan S. Wittstein, MD: Thank you very much. It’s great to see you again, and thank you very much for the invitation to be here today.
Kittleson: You wear many hats: clinician, researcher, educator. What do you enjoy most and why?
Wittstein: I do wear several hats. I really enjoy all of the roles. I guess at the end of the day, it’s hard for me to separate being a clinician and an educator, because pretty much all of the clinical work I do is closely tied in with education of students, residents, and fellows. So I really see my role as a clinician/educator, and I cherish both roles.
Kittleson: It is amazing, isn’t it? Because the better care you take of patients, the better teacher you are, and the better teacher you are, the better care patients receive. It is a self-fulfilling prophecy. And you clearly exemplify that.
Let’s dive into stress cardiomyopathy. First, tell us how stress cardiomyopathy can present. What are the key findings in the history that should make us consider the diagnosis? What should we ask so that we don’t miss the diagnosis?
Wittstein: I think when we talk about how stress cardiomyopathy presents, we should make sure we distinguish between two groups of patients. The first group are those that present from home or outside in the community. Some people call this type A stress cardiomyopathy. The second group are people that are already in the hospital with medical illnesses and are undergoing procedures.
The people that are at home and out in the community present very similarly to an acute coronary syndrome (ACS). They often come in with chest pain and shortness of breath and have EKG changes. And for the most part, they will be treated and triaged like someone having an ACS, an acute myocardial infarction.
For those people that are in the hospital, it can definitely be more subtle. These are patients who are undergoing procedures, getting anesthesia; some of them may even be intubated. So they may not be able to complain of symptoms if they have chest pain or shortness of breath. And often in those patients, the suspicion for the diagnosis may have to rely on things like hemodynamic changes, arrhythmias, EKG changes (if EKGs are being checked), and troponin elevation (if those are checked). So it can really be quite different depending on where the patient is. About 10%-20% of patients will come in in cardiogenic shock. About 35%-45% will have clinical heart failure. And other complications that can occur are left ventricular (LV) outflow tract obstruction, arrhythmias, and embolic events, and some things that are a bit more rare, like pericarditis and even LV rupture, have been described.
Kittleson: So when you have the patient — let’s take the type A patient, they present from home — what are the typical features that should raise red flags in your mind? I’m not looking at a typical ACS. I need to delve deeper. There’s something weirder going on.
Wittstein: I think if we talk about the type A patients, again, those are the ones that are at home or out in the community, the symptoms are going to be very similar to someone having an acute myocardial infarction. The vast majority of these patients have chest pain; shortness of breath is also very common, and syncope even occurs in about 10%-15% of these patients.
So one should be suspicious if a person is complaining of chest pain or shortness of breath shortly after experiencing some kind of stressful event. Now, when we talk about a stressful event, a lot of people think of emotional triggers — and indeed those emotional triggers are not uncommon in this syndrome, but remember that acute stress does not always mean an emotional psychological stress. Patients out in the community can also be exposed to physical stresses such as strenuous exertion, extreme heat, COPD flares, asthma exacerbation, choking, even migraine headaches. All of these things should raise our suspicion for the possibility of this syndrome if something acute happens and is then followed by symptoms that sound like an acute myocardial infarction.
Kittleson: And then if we think about those type B patients, are there any classic in-the-hospital triggers for it? Or do we have to keep our minds open, our differential broad?
Wittstein: It’s important to keep open minds and differentials broad in dealing with this syndrome, because if you read through the literature, you see that more and more and more things have been described in association with this condition. But some of the more common things that happen in the hospital are procedures and anesthesia and surgeries.
People often come out of procedures or surgery with this condition. And frankly, if you’re not looking for it, and if you’re not checking EKGs, and if you’re not checking troponins in patients who are intubated, you may not get a history that alerts you to this. So you have to be vigilant, and you have to look for subtle changes potentially in their blood pressure, in their rhythm if they’re being monitored, et cetera. It can be quite subtle for patients who are in the hospital. And the truth is it’s probably much more common in the hospital than people realize. There was a study where they looked at about 100 patients admitted to the intensive care unit, and they looked for stress cardiomyopathy in those patients. They found that about 30% or more actually had the syndrome. And these were probably patients who would not have been diagnosed if the study hadn’t been going on.
Kittleson: So when you say “diagnosed with stress cardiomyopathy,” you mean they had an echocardiogram showing the classic findings.
Wittstein: Yes, stress cardiomyopathy is a syndrome, and there are several clinical features and diagnostic tests that need to be performed. If we could only pick one, it would probably be the echocardiogram showing the classic apical ballooning pattern, where the apex and the mid-ventricle are not contracting well, and the base of the heart is. This is a very characteristic appearance in this syndrome. But there are several other diagnostic criteria that one can look to. None of them by themselves will diagnose the syndrome, but putting them all together should definitely raise suspicion.
Kittleson: Speaking of the fact that it’s a syndrome, again, there’s no sine qua non finding to establish the diagnosis; in a sense, it is a diagnosis of exclusion. So share your diagnostic algorithm with us: What must clinicians rule out before you assign the patient a diagnosis of stress cardiomyopathy?
Wittstein: There are several things that should probably be ruled out. The first one, by far and away the most important, is an ACS. Patients that come in with stress cardiomyopathy often masquerade as an ACS; they can have EKG changes, enzyme elevation, and wall-motion abnormalities on their echo. You have to make sure you’re not dealing with a plaque rupture, a coronary thrombosis type of situation that would be called an ACS. So ruling out an ACS or myocardial infarction is very important.
But these patients also can masquerade as coronary vasospasm, like you might see in cocaine use. You need to rule out acute myocarditis, and in the modern era, particularly, immune checkpoint inhibitor (ICI) myocarditis; a lot of patients with stress cardiomyopathy actually have underlying cancer. ICI myocarditis and stress cardiomyopathy can look similar. The other things you want to rule out that can give you some of the same EKG changes are head injury and neurologic injury, and of course, make sure that your patient doesn’t have a pheochromocytoma. We know that stress cardiomyopathy is more prevalent in this group of patients. So you want to make sure you don’t miss that as well.
That is what I would say is the differential diagnosis for the things you see in stress cardiomyopathy. And there are six things that I look at to try and make the diagnosis.
Number one, I take a good history. Am I able to elicit some kind of acute stressor, whether it’s emotional or physical, that happened right before the onset of symptoms?
Number two, I look at the EKG. Patients with stress cardiomyopathy may present with ST elevation, but they often do not have reciprocal ST depression. So you want to look for that. And if you’re doing serial EKGs, you’ll often see prolongation of the QT interval and diffuse deep T-wave inversions. Those can be seen on your EKGs over the first 72 hours or so.
Number three, I look at the cardiac biomarkers. Patients with stress cardiomyopathy often have an elevated brain natriuretic peptide (BNP) level, and they’ll always (or almost always) have low-level troponins. But these troponins are out of proportion to the degree of LV dysfunction. So frequently, you’ll see a high BNP-to-troponin ratio, and that should definitely get your attention in the right clinical setting.
Number four, as I mentioned earlier, the echo is very important for looking for a ballooning pattern; the most common one is the apical ballooning pattern, but you can also have mid-ventricular ballooning and basal ballooning. These tend to be wall-motion abnormalities that don’t correspond to a vascular territory, and that should definitely raise suspicion.
Number five, I look at the coronary angiogram, because if a person comes in with this syndrome, we would like to look at their arteries if we can. There are some patients where it’s just not possible medically, but if one can do coronary angiography or CT angiography, that’s important to make sure there’s no acute plaque rupture and thrombotic coronary occlusion. If we saw that, we would call that an ACS and not stress cardiomyopathy.
And number six — the final thing, which I think is absolutely vital — is to follow the echocardiogram serially. Stress cardiomyopathy should get better. In fact, most of the recovery in LV function is in the first 1-4 weeks. I’ve had people say to me, “I had a case of stress cardiomyopathy 5 years ago and the ejection fraction is still 10.” And what I’ll tell them is that’s not stress cardiomyopathy. That’s just cardiomyopathy. If stress cardiomyopathy occurs, LV function gets better. So one needs to see a combination of all those things to really make the diagnosis.
Kittleson: There’s nothing better than when a master clinician and educator like Dr Ilan Wittstein says, “These are the six things you need to know.” I’m totally delighted that you did that. We have the history, the ECG, the biomarkers, the echo, and the angiogram and circle back to that echocardiogram to look at the trajectory. Super helpful.
Now on to management. Are there nuances in the management of stress cardiomyopathy that differ from garden-variety cardiogenic shock or heart failure with reduced ejection fraction (HFrEF)? Share your pearls.
Wittstein: When you’re talking about the management of stress cardiomyopathy, you have to talk about the acute period and then how you manage patients once they leave the hospital and go home moving forward. I think in the acute period, most of us would agree that supportive care is the most important thing.
As I mentioned, hemodynamics and left ventricular function get better pretty fast. So if one can support patients early on, usually they make a nice recovery. But really one has to ask, when they come in acutely, are they hemodynamically stable or are they unstable?
Let’s start with the 10%-20% of patients who might be in cardiogenic shock. One of the questions to ask in this syndrome is whether or not they have LV outflow tract (LVOT) obstruction that could be causing the shock. About 25% of patients with stress cardiomyopathy have LVOT obstruction. And if they have this, one should avoid inotropes. They may need to receive fluid; they may need pressors like phenylephrine to support them. So that’s a very important thing to know.
If they don’t have LVOT obstruction, then they may be best managed with inotropes or possibly even mechanical support, like an intra-aortic balloon pump or a percutaneous continuous flow device. And there have been reports even of patients being put on extracorporeal membrane oxygenation (ECMO) to support them through that acute period. If when they come into the hospital they’re stable hemodynamically, then a lot of people recommend the same type of medication that you give for other forms of heart failure with reduced ejection fraction: beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, et cetera.
I will add that anticoagulation may be very important initially for patients with stress cardiomyopathy if they have the apical variant of this condition. Just think about it: If you form a blood clot in your apex in this condition, within a week or two the apex may be banging away after it recovers. And if a clot is there, you can certainly have an embolic event, and there’s about a 1%-2% incidence of thromboembolic events in this condition. So anticoagulation is also part of the acute treatment of this condition.
When it comes to chronic treatment, that’s a little bit more difficult. How do we treat these patients when they go home after they’ve recovered? There really are no randomized controlled trials to guide us here; it’s all been through retrospective analysis. One of the bigger registries out of Switzerland, the InterTAK registry, showed that ACE inhibitors or angiotensin receptor blockers (ARBs) increased 1-year survival, but this has not been shown in other studies.
Beta-blockers have not been shown to improve survival or to prevent recurrence of the syndrome. So my practice, and I think a lot of people do, uses standard guideline-directed medical therapy like ACE inhibitors and beta-blockers while the ejection fraction is reduced but scales back on the medicine once the ejection fraction recovers. I can think of a lot of patients that came to see me for second opinions who were on four different cardiac medications and anticoagulation who had probably recovered their LV function months earlier; they felt poorly because they had low blood pressure and slow heart rates, and scaling back on the medicine helped them feel better.
We shouldn’t forget that this is a different condition from your average patient with HFrEF, and medication should be adjusted accordingly.
Kittleson: That’s probably reason number 372 why artificial intelligence will not replace us, because recovery of stress cardiomyopathy is not the same thing as heart failure with improved ejection fraction as in the TRED-HF trial, where continuing guideline-directed medical therapy (GDMT) was important to prevent relapse. It’s a different nuanced condition, and you don’t want to put someone on the “perfect GDMT” regimen and then they feel horrible.
That’s such a good pearl. Speaking of that patient: Now the dust has settled, and they’re home and recovered. How do you counsel them on prognosis and risk for recurrence? Do you tell them never to go to a surprise party ever again?
Wittstein: That’s a great question. And I’ll be honest, one of the problems with the stress cardiomyopathy literature, when it comes to prognosis, is that over the years — now almost over the decades — cases of this were lumped together. People would present their series of 20-30 patients, and some would be stress cardiomyopathy following a stroke and would include stroke, and asthma, and emotional stress, and all of them were kind of put together.
I think logically, it would make sense that someone who develops stress cardiomyopathy after a stroke might not have the same prognosis as someone who gets it from emotional stress. So it took a while, but finally, the literature caught up with that idea, and it’s now shown that a lot of your prognosis depends on why you get stress cardiomyopathy in the first place.
We do know that there’s about a 4% in-hospital mortality with this condition across all conditions. But by far and away, the worst prognosis is someone who’s had a neurologic cause. You know, somebody who’s had a subarachnoid hemorrhage or a stroke. So neurologic triggers are associated with worse prognosis. And physical triggers are associated with worse prognosis. Your prognosis is also worse if you’re older, if you’re diabetic, if you’re a man (men have a worse prognosis than women do), and if your ejection fraction is lower at the time that you present. So if you think about the typical patient who a lot of people think about with this condition, the woman in her 60s who comes in with stress cardiomyopathy following an emotional trigger, those patients have an excellent 5-year survival — almost 95%.
If you think about a high-risk group, perhaps an older man who has a neurologic event and gets stress cardiomyopathy, the 5-year survival would drop to about 45%. So, when we think about prognosis with this condition, we should very much be thinking about why they initially came in with stress cardiomyopathy and their other comorbidities.
Kittleson: Super helpful. And it boils down in some sense to common sense. What do you think is the protoplasm of the patient sitting in front of you? Tell us: What’s the one thing you want listeners to do differently after hearing this discussion?
Wittstein: I would want them to be able to recognize the clinical features. If I think back 15 years ago, patients were not given a diagnosis when they came in with this and when they left the hospital, they were told they had some type of strange heart attack. And that was very unsettling. It’s nice to be able to tell people, “This is what you had. This is the prognosis. This is the rate of recurrence, and this is how we think you’re going to do.” So being able to recognize the clinical features is very important, as is keeping an open mind as to what stress really means when it comes to this condition.
But I would say in terms of management, this is a key point — we mentioned it before, but it’s probably worth mentioning again — this is not your standard HFrEF. We have no idea whether standard guideline-directed medical therapy is even helpful for these patients.
So we should not overmedicate them. And we should really look at how they’re doing, how their ejection fraction is doing, and don’t be afraid to scale back on medications when ejection fraction recovers, because we may be doing more harm than good with too much therapy.
Kittleson: I couldn’t have said it better myself. You got the takeaways from our foremost expert in stress cardiomyopathy, Dr Ilan Wittstein. Thank you so much for being here today.
Wittstein: Thank you very much. It was great talking to you.
Kittleson: Thanks for joining our discussion with Dr Ilan Wittstein. There’s much more ahead in the coming episodes, so be sure to check out the Medscape app and share, save, and subscribe if you enjoyed this podcast. I’m Dr Michelle Kittleson for Medscape InDiscussion.
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Resources
Takotsubo Cardiomyopathy: Review of Broken Heart Syndrome
Takotsubo Cardiomyopathy Following Cardiac Surgery
Stress Cardiomyopathy in Critical Care: A Case Series of 109 Patients
Immune Checkpoint Inhibitor-Associated Myocarditis: Manifestations and Mechanisms
Acute Stress Cardiomyopathy: Heart of Pheochromocytoma
Takotsubo Cardiomyopathy: Pathophysiology and Role of Cardiac Biomarkers in Differential Diagnosis
Clinical Features and Outcomes of Takotsubo (Stress) Cardiomyopathy
Rohit Malhotra is a medical expert and health journalist who offers evidence-based advice on fitness, nutrition, and mental well-being. His articles aim to help readers lead healthier lives.
