Sunday, March 18, 2018

More On Takotsubo

I posted previously on Takotsubo cardiomyopathy and an association with antidepressant therapies.  That occurred in the context of a patient with the condition that I recently treated.  At times when there is a condition that is prominent on your mind and you tend to notice it immediately as you review the literature.  In this case I noticed it in the New England Journal of Medicine as this weeks Case Records of the Massachusetts General Hospital.  If you plan on reading the case - please do that first before reading the summary that follows. Like most of these cases it is a textbook description of the way experts should think about complicated diagnoses.  I will naturally focus on what I think are the high points for psychiatrists.

The patient described was a 55- yr old woman with a history of thyroid cancer but no other chronic illnesses.  She had a history of Stevens-Johnson syndrome from cefadroxil.  She was did not smoke, drink, or use other intoxicants.  She was married and employed.  Four months before the index episode she was jogging and had pounding in the chest, diaphoresis, and nausea for about 40 minutes.  She was seen in a local ED and a mildly elevated troponin [0.055 ng/ml] that increased at 11 hours 0.415 ng/ml] , 4 normal ECGs, normal echocardiogram, and normal coronary angiogram.  A subsequent MRI scan was done and was normal.  The presumptive diagnosis was exercise related supraventricular tachycardia.  She was prescribed a beta blocker and ASA and discharged.

She resumed jogging and eventually stopped the beta blocker.  Four months later while skiing, she developed palpitations, dyspnea and weakness. she was assisted off the mountain, but developed nausea, emesis, chest pain, and shortness of breath.  In the local emergency department she was tachycardic, tachypneic, and normotensive. Her oxygen saturation was 84% on room air.  Troponin I [11.000 ng/ml] and N-terminal- pro-B-type natriuretic (NT-proBNP) [15,159 pg/ml] levels were elevated.  Bedside cardiac ultrasonography showed severe left ventricular dysfunction with apical ballooning.  She was transferred to a tertiary care center for suspected cardiogenic shock.  At that center she was noted to be critically ill and received all of the measures necessary to treat the shock including mechanical ventilation and pressors alternating with antihypertensive treatment episodes. A left ventricular assist device (LVAD) was placed. She was subsequently transferred to MGH.

There she was noted to need continued need for treatment of heart failure.  Infectious agents for myocarditis were ruled out.  Femovenoarterial extracorporeal life support was added to improve cardiac output and also because the LVAD was causing significant hemolysis.  The patient's cardiac status improved on day 3 and an endomyocardial biopsy was done when the extracorporeal life support was removed.  That biopsy was consistent with myocardial injury, myocardial toxicity, mechanical stress and treated myocarditis.  Acute myocarditis was ruled out.

A clinical diagnosis of takotsubo (stress) cardiomyopathy was made.  A consultant discussed the limited differential diagnosis of apical ballooning not associated with coronary artery disease and the associated etiologies as:

1.  Recurrent apical ballooning syndrome
2.  takotsubo cardiomyopathy
3.  Acute myocarditis
4.  Coronary vasospasm
5.  cocaine induced coronary vasoconstriction
6.  thrombosis with endogneous fibrinolysis before angiography

Several etiologies (1,2,5) may depend on similar hypersympathetic mechanisms caused by exercise, neuropsychiatric disorders,  psychiatric medications, or intoxicants causing catecholaminergic effects.  Takotsubos was described as an increasing cause of acute non-ischemic cardiomyopathy in patients admitted with acute chest pain syndromes.  In one series the disorder accounted for 7.5% of all admissions with acute chest pain.  Eventually the patient is diagnosed with pheochromocytoma as the cause for takotsubos, the adrenal tumor is resected, she regains normal cardiac function and her recovery is uncomplicated.  The staff at MGH has done another outstanding job of solving a complex medical problem and saving a crtically ill patient.

How does all of this apply to psychiatrists?  I am sure that there are some people out there who are irritated just to see a psychiatrist talking about medicine.  Well I will tell you:

1.  Cardiotoxicity of catecholamines: 

I think we have been lulled into thinking that anxiety and even panic attacks won't kill you so why worry about that patient with elevated vital signs or persistent tachycardia that won't go away?  Granted - very few of those people will develop takotsubos and even fewer will have a pheochromocytoma.  I have treated several people with takotsubos and none with a pheochromocytoma - so if I had to guess I would say the cardiomyopathy is much more common in clinical practice.  Once you know that vitals signs (including pulses) need careful monitoring and caution needs to be exercised if medications are being added that might add to the catecholaminergic burden.

Over the years I have encountered very many patients with persistent tachycardia and otherwise normal electrocardiograms showing sinus tachycardia. The general sequence of events at that point it to assess for causes of the tachycardia and obtain Cardiology consultation to look for inappropriate sinus tachycardia and suggest treatment if that condition is found (2).  Persistent tachycardia can lead to left ventricular hypertrophy and cardiomyopathy but that is typically rare.

I have discussed these cases with many Cardiology consultants who tell me that sinus tachycardia is "not normal" there are just no guidelines about what to do about it, especially if there is no obvious cause.  Using beta-blockers just to treat tachycardia seems like an arbitrary decision on their part based on whether the patient experiences any distress from palpitations.  Psychiatrists use beta-blockers for the same indications as well as the physical manifestations of performance anxiety.   

2.  Monitor vital signs, troponins and get timely Cardiology assessments: 

You might find yourself in an environment where you have to go the extra mile to get help from medicine or cardiology.  I found myself in a situation with patients who had chest pain and instead of transfer to medicine the decision was made to keep the patient on the psychiatric unit and measure troponins.  That is the main reason I included the troponins in the above summary.  Even the mildly elevated and trending higher troponins may be an indication of some type of milder myocardial damage. It might even be useful to discuss with the consultant that takotsubo might be a consideration.

3.  Potential risk factors for takotsubos should be considered in all patients who are assessed:

From the list in the differential there are a wide range of catecholaminergic insults that psychiatric patient may incur including prescription and street stimulants (amphetamine, methamphetamine, cocaine, synthetic cannabinoids, JWH compounds, synthetic psychedelics), antidepressant compounds and atomoxetine, intoxication and withdrawal states (3), sleep deprivation, seizures (4) and physiological factors like extreme physical or emotional distress. It is very common to see one or more of these factors present during patient assessments and in that case, a cardiac review of systems should be done.  I am cautious to not start a new drug with potential cardiac side effects until sinus tachycardia has resolved.

4.  A diagnosis of takotsubos needs to be considered in the discharge plan:     

In today's treatment environment of getting people out of the hospital as soon as possible or not admitting them in the first place acute stress induced cardiomyopathy takes on a different meaning.  In the NEJM case, the patient had the unexpected burden of catecholamines from a pheochromocytoma that had obvious toxicity on cardiac function and she recovered uneventfully once definitive treatment was completed.  What if you are a treating psychiatrist and you know your patient has this diagnosis?  The decisions that need to be made include discontinuing any potentially toxic psychiatric medications and preventing damage from other sources of catecholamines.  This is relevant if it is highly likely that the patient will be in a stressful environment or is highly likely to use some of the toxic medications.  The discharge plan needs to be modified accordingly.

That is my proactive approach to sinus tachycardia and takotsubos when it is identified.  It should be apparent that I do not take a passive stance when it comes to potential medical problems in my patients, especially when it directly affects psychiatric care and the recommended treatment plan. You don't have to be an expert in ECG or managing complex cardiac conditions but you do have to recognize when your patients health status is compromised. Saying that there has been "medical clearance" by another physician is not enough.  This approach does help define the medical skill set that every psychiatrist needs to possess. In these cases knowledge of basic cardiac conditions, basic ECG skills, and how the medical and psychiatric treatment plans need to be modified is a requirement.

George Dawson, MD, DFAPA


1:  Loscalzo J, Roy N, Shah RV, Tsai JN, Cahalane AM, Steiner J, Stone JR. Case 8-2018: A 55-Year-Old Woman with Shock and Labile Blood Pressure. N Engl J Med. 2018 Mar 15;378(11):1043-1053. doi: 10.1056/NEJMcpc1712225. PubMed PMID: 29539275.

2: Homoud MK.  Sinus tachycardia: Evaluation and management.  Piccini J Editor. UpToDate. Waltham, MA: UpToDate Inc. (Accessed on March 18, 2018.)

3: Spadotto V, Zorzi A, Elmaghawry M, Meggiolaro M, Pittoni GM. Heart failure due to 'stress cardiomyopathy': a severe manifestation of the opioid withdrawal syndrome. Eur Heart J Acute Cardiovasc Care. 2013 Mar;2(1):84-7. doi: 10.1177/2048872612474923. PubMed PMID: 24062938.

4: Kyi HH, Aljariri Alhesan N, Upadhaya S, Al Hadidi S. Seizure Associated Takotsubo Syndrome: A Rare Combination. Case Rep Cardiol. 2017;2017:8458054. doi: 10.1155/2017/8458054. Epub 2017 Jul 24. PubMed PMID: 28811941.

Graphics Attribution:

"Levocardiography in the right anterior oblique position shows the picture of an octopus pot, which is characteristic for Takotsubo cardiomyopathy."

Hammer N, Kühne C, Meixensberger J, Hänsel B, Winkler D. Takotsubo cardiomyopathy - An unexpected complication in spine surgery. Int J Surg Case Rep (2014). Link Used per open access license.


There does not appear to be a consensus on the spelling of takotsubo and whether or not it should be capitalized or not.


  1. While you note this condition is as rare as a Pheo, my take is be wary of looking for zebras, it's quite the coup when a clinician stumbles onto something one only read about in medical school, but, a short lived thrill, certainly not for the patient.

    My concern is what you allude to per trying to get somatic colleagues to do their part, help rule out the role of somatic factors to psychological symptoms. I have caught a few arrhythmia disorders by pressing for a 72 hour Holter, once had a patient agree to a week Holter that caught the 20 minute run of A fib on day 6, but, get more resistance these days from patients and colleagues.

    Shame the DSM 5 really has forgotten the point in diagnostic assessment, the need to rule out medical and addiction factors to many illnesses. There is nothing more lame and injurious to patients to just slap on psych meds upon meds when the socioeconomic issues alone can put patients at risk for illnesses. The economic part being patients are less likely to follow up with their MD to monitor status. Another example of how wonderful Obamacare, and insurance more in general, is only about managed cost...

    Joel H

    1. Agree completely on not deferring the medical side of the evaluation. Has been my method from the outset.

      On Takotsubo - actually much more common than pheo maybe several orders of magnitude. I was just thinking this AM that if the 7.5% figure is accurate - that is a lot of cases that were missed before the condition was discovered. I know as an intern admitting people with acute chest pain it was unknown at the time. May have to do with a different echo protocol picking it up. Back in those days we had to order an M-mode and 2D and those are ancient history.

    2. In only two weeks of cardiology night float at a large university hospital I saw several cases, but they were referred to by my attendings as simply "stress" cardiomyopathy rather than Takutsubo's, which I think they reserved for more fulminant presentations in the context of emotional stressors. In this context, it meant transient declines in LVEF in the setting of critical illness (also known as ICU heart) that usually improved on followup Echos.

    3. Very interesting Simon - thanks for posting that.

    4. "My concern is what you allude to per trying to get somatic colleagues to do their part, help rule out the role of somatic factors to psychological symptoms. I have caught a few arrhythmia disorders by pressing for a 72 hour Holter, once had a patient agree to a week Holter that caught the 20 minute run of A fib on day 6, but, get more resistance these days from patients and colleagues."

      Forgot to mention that I routinely pick up afib by doing my own vitals. Even if you are in a facility where somebody else does the BPs many of the machines either don't have an arrhythmia monitor or it is ignored. I still recall a young guy with pulse irregularity who was having 30-40 VPCs/min that I picked up checking his vitals. The commonest reason I repeat them is that somebody is measuring rates > 100 bpm because they are not checked at rest.

  2. Thanks for the article. I am assuming you mean pulse >100 as tacycardia? I have taught my staff who take vitals using the automated cuff to palpate the pulse manually before and as the cuff inflates. That gives information on the rhythm and the quality of the pulse. It also serves as a bit of a check on the accuracy of the automated cuff as if the reported systolic pressure is much higher than the value on the meter when the palpated pulse vanishes then the reported systolic value may be inaccurate. I also have patients whose pulse speeds up as soon as the cuff starts to inflate. For those patients I take the pulse manually.

    1. Yes pulse > 100 = tachycardia.

      I have found that automated cuffs generally have to be double checked and that the second readings are generally lower. I think there is a tendency for the first readings to overshoot the mark until the cuff seats properly. I did a post last fall on the 11-element skill set needed for accurate BP measurement:

      The most common problems I see is:

      - the patient is not at rest and has often climbed up a flight of stairs or hurried to get to the appointment.
      - the patient is loaded up on caffeine +/- nicotine
      - wrong size BP cuff is used
      - high BPs and pulses are not questioned and never repeated