Showing posts with label Takotsubo's cardiomyopathy. Show all posts
Showing posts with label Takotsubo's cardiomyopathy. Show all posts

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


References:

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. http://www.uptodate.com (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.

Conventions:

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





Monday, December 11, 2017

Takotsubo's and Antidepressants






Takotsubo's cardiomyopathy (TC) is a form of acute dilated cardiomyopathy.  It was first described in Japan in 1990 and since then there have been increasing reports of the problem.  It is an uncommon problem thought to be due to excessive catecholamines and their effects on heart muscle. A definitive source on the autonomic nervous system points out that the plasma levels of catecholamines are extreme and consistent with activation of both the sympathetic nervous system and adrenal medulla (15).  As seen in the above ventriculography the left ventricle is dilated and elongated.  The typical presentation is acute coronary syndrome (dyspnea, chest pain, syncope) with a  low to modest levels of troponin - a biomarker for cardiac tissue damage.  Electrocardiogram show T wave inversions and ST segment elevation.  Echocardiograms show  The imaging results generally show and acutely dilated and lengthened left ventricle and wall motion abnormalities. Overall this pathology represents a low number of cases with acute coronary syndrome.  Most people recover in up to 4 weeks if the diagnosis is made and the patient is treated.  That treatment may involve the discontinuation or changing of antidepressant medications.

One of the questions that psychiatrists face is whether to resume existing therapy or withhold in the case of a new diagnosis of cardiac disease.  It is not an easy decision.  At least it is not a straightforward as it used to be.  In complicated situations in the past, psychiatric medications were routinely discontinued.  Today - talking with a consultant it is much more common to hear:  "Yes those adverse reactions are possible but if the patient needs the medication - they need the medication."  There are no strict rules on the issue like there seem to have been at one point.  The ideal medication for cardiac problems in psychiatry has limited effect on cardiac conduction and is benign in terms of hemodynamics.  Those effects are difficult to predict on both an individual and group basis in that small number of cases where the response is more critical.  As an example, I contacted an expert on hypertension and he advised me that he was generally unconcerned about the two antidepressants that I end up monitoring for possible effects - buproprion and venlafaxine.  In his experience, he though they added an average of 3 mm Hg systolic hypertension and that is trivial.  I am seeing people on more medications who may have alcohol and substance use problems that can significantly compound the hypertension problem.  The blood pressure I see are considerably higher in some cases where these antidepressants are used or added.

TC was first reported in 1990.  Case reports on TC and the association with antidepressants began to show up in about 2008 with a case report involving nortriptyline (15).  A recent letter to the editor (1) points out the trend and the possible correlation based on the temporal relationship between antidepressant initiation/titration and TC (4).  In that paper the authors identified 8 cases in the literature and a case series of 6 patients.  They report their case as well as 8 additional cases and the demographic, clinical, laboratory data of all of the patients.  Eight of 9 cases were women in the age range of 37 to 82.  In each of these cases the patient was taking an SNRI (venlafaxine, desmethylvenlafaxine, and duloxetine).  The youngest patient overdosed on 2100 mg venlafaxine.  The presumed etiology in the initial cases was a stressor that lead to catecholamine excess and cardiomyocyte toxicity, but in 5/9 cases a stressor was not present.  Although the authors note the association with SNRI type antidepressant case have been reported with atomoxetine (an NRI), fluoxetine (an SSRI), with a case of serotonin syndrome, and withdrawal of antidepressant therapy.  The association in the case reports may be seem more robust that it really is.   Although the case reprts and incident of ACS are low - the sheer number of cases (one every 25 seconds in the USA) assures that even low prevalence disorders like TC will occur in significant numbers.

What are the implications for psychiatrists?  The prototype for me in this case was clozapine.  Clozapine is an atypical antipsychotic with many side effects.  The focus for most psychiatrists has been the neurophil monitoring and prevention of agranulocytosis.  Clozapine also has significant cardiac side effects including acute myocarditis with typical symptoms of myocarditis.  I think that anyone prescribing clozapine needs to be aware of these symptoms and monitor the patient for them.  In this case the cardiac review of systems is critical along with the physical examination of the patient at every visit or at least until they are on a stable dose of medication.

Antidepressants are generally approached in a more casual manner than antipsychotics.  Every patient needs to be carefully screened for side effects and the medication needs to be stopped or modified as indicated.  There should be more vigilance after FDA warnings about the QTc prolonging properties of antidepressants specifically citalopram. But if a patient has an arrhythmia questions on a review of systems are probably not enough.  I can say that because I take my own vitals signs and know that patients with new onset arrhythmias (atrial fibrillation, ventricular premature contractions, bigeminy, etc) are generally missed with standard blood pressure measurement systems and the patient is unaware that they are no longer in normal sinus rhythm.  In many cases tachycardia and other symptoms of acute coronary syndrome are the only findings.  These case reports illustrate to me that psychiatrists and primary care physicians prescribing these medications need to have a low threshold for testing and referral both to the emergency department and cardiology.   As previously posted - if you are in a large mental health clinic and have enough support staff - consider getting an ECG machine.  A faxed abnormal ECG and a verbal report is a sure way to get the attention of a cardiologist or emergency medicine physician.

In terms of the eventual epidemiology and pathophysiology of TC, inferring that SNRIs are definitely involved in either is highly speculative at this point.  In many ways the situation resembles the problem of seeing Vitamin D deficiency as being causative for any number of disorders when there is a high prevalence of Vitamin D deficiency in the population.  I have always seen SNRIs as better tolerated than SSRIs with a cardiac  safety profile that might be slightly better if the prolonged QTc interval issue with citalopram was real.  The best way to study the issue is to identify large numbers of patients with TC on echocardiogram and compare them to a control group and see if the correlation between SNRIs and TC is real.  As far as I know that study has not been done.

In the meantime, pay close attention to the cardiovascular status of patients on antidepressants, especially during the titration phase and if they may have a high catecholamine load inferred from clinical anxiety, exacerbations of physical illness, and stress levels. .  Use findings like tachycardia as a prompt for more focused questions and examination.

Takotsubo's cardiomyopathy is just another medical condition that can complicate psychiatric treatment - that you do not want to miss.                           




George Dawson, MD, DFAPA




References:

1: Madias JE. Venlafaxine and takotsubo syndrome: Can we learn more from published patient cases? Int J Cardiol. 2016 Dec 15;225:73-74. doi: 10.1016/j.ijcard.2016.09.133. Epub 2016 Oct 1. PubMed PMID: 27716552.

2: Conrad SK, Catalano MC, Catalano G. The Use of Fluoxetine in a Patient With Takotsubo Cardiomyopathy. J Psychiatr Pract. 2016 May;22(3):234-8. doi: 10.1097/PRA.0000000000000151. PubMed PMID: 27123803. 

3: Naguy A, Al-Mutairi H, Al-Tajali A. Atomoxetine-related Takotsubo Cardiomyopathy. J Psychiatr Pract. 2016 May;22(3):232-3. doi: 10.1097/PRA.0000000000000152. PubMed PMID: 27123802. 

4: Vasudev R, Rampal U, Patel H, Patel K, Bikkina M, Shamoon F. Selective Serotonin-norepinephrine Reuptake Inhibitors-induced Takotsubo Cardiomyopathy. N Am J Med Sci. 2016 Jul;8(7):312-5. doi: 10.4103/1947-2714.187153. PubMed PMID: 27583240.

4: Madias JE. Withdrawal of prolonged antidepressant therapy and Takotsubo syndrome. Heart Lung. 2014 Nov-Dec;43(6):578. doi: 10.1016/j.hrtlng.2014.06.053. Epub 2014 Jul 22. PubMed PMID: 25063669. 

5: Dias A, Franco E, Figueredo VM, Hebert K, Quevedo HC. Occurrence of Takotsubo cardiomyopathy and use of antidepressants. Int J Cardiol. 2014 Jun 15;174(2):433-6. doi: 10.1016/j.ijcard.2014.04.028. Epub 2014 Apr 13. PubMed PMID: 24768456. 

6: Kitami M, Oizumi H, Kish SJ, Furukawa Y. Takotsubo cardiomyopathy associated with lithium intoxication in bipolar disorder: a case report. J Clin Psychopharmacol. 2014 Jun;34(3):410-1. doi: 10.1097/JCP.0b013e3182a95a27. PubMed PMID: 24699038. 

7: Marabotti C, Venturini E, Marabotti A, Pingitore A. Delayed multifocal recurrent stress-induced cardiomyopathy after antidepressants withdrawal. Heart Lung. 2014 May-Jun;43(3):225-30. doi: 10.1016/j.hrtlng.2014.03.003. PubMed PMID: 24794783. 

8: Neil CJ, Chong CR, Nguyen TH, Horowitz JD. Occurrence of Tako-Tsubo cardiomyopathy in association with ingestion of serotonin/noradrenaline reuptake inhibitors. Heart Lung Circ. 2012 Apr;21(4):203-5. doi: 10.1016/j.hlc.2011.12.004. Epub 2012 Jan 27. PubMed PMID: 22285074. 

9: Rotondi F, Manganelli F, Carbone G, Stanco G. "Tako-tsubo" cardiomyopathy and duloxetine use. South Med J. 2011 May;104(5):345-7. doi: 10.1097/SMJ.0b013e318213f3e5. PubMed PMID: 21606714. 

10: Trohman RG, Madias C. Duloxetine-induced tako-tsubo cardiomyopathy: implications for preventing a broken heart. South Med J. 2011 May;104(5):303-4. doi: 10.1097/SMJ.0b013e318213d10f. PubMed PMID: 21606702. 

11: Forman MB, Sutej PG, Jackson EK. Hypertension, tachycardia, and reversible cardiomyopathy temporally associated with milnacipran use. Tex Heart Inst J. 2011;38(6):714-8. PubMed PMID: 22199446; PubMed Central PMCID: PMC3233339. 

12: Selke KJ, Dhar G, Cohn JM. Takotsubo cardiomyopathy associated with titration of duloxetine. Tex Heart Inst J. 2011;38(5):573-6. PubMed PMID: 22163139; PubMed Central PMCID: PMC3231522. 

13: Mehta NK, Aurigemma G, Rafeq Z, Starobin O. Reverse takotsubo cardiomyopathy: after an episode of serotonin syndrome. Tex Heart Inst J. 2011;38(5):568-72. PubMed PMID: 22163138; PubMed Central PMCID: PMC3231548. 

14: Christoph M, Ebner B, Stolte D, Ibrahim K, Kolschmann S, Strasser RH, Schön S. Broken heart syndrome: Tako Tsubo cardiomyopathy associated with an overdose of the serotonin-norepinephrine reuptake inhibitor Venlafaxine. Eur Neuropsychopharmacol. 2010 Aug;20(8):594-7. doi: 10.1016/j.euroneuro.2010.03.009. Epub 2010 May 7. PubMed PMID: 20451358. 

15: De Roock S, Beauloye C, De Bauwer I, Vancraynest D, Gurne O, Gerber B, Hantson P. Tako-tsubo syndrome following nortriptyline overdose. Clin Toxicol (Phila). 2008 Jun;46(5):475-8. doi: 10.1080/15563650701519786. PubMed PMID: 18568805. 

16: Wachira JK, Stys TP. Cardiovascular disease and bridging the diagnostic gap. SD Med. 2013 Sep;66(9):366-9. Review. PubMed PMID: 24279112.

17: Goldstein DS. Catecholamines 101. Clinical autonomic research : official journal of the Clinical Autonomic Research Society. 2010;20(6):331-352. doi:10.1007/s10286-010-0065-7.




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.