To heal a broken heart: How do you manage Takutsobu in the ED?
By Edom Girma
Case
51-year-old non-smoker F with isolated PMHx of breast cancer (NED 5 years s/p bilateral mastectomy) presenting to the Emergency Department with worsening LLQ abdominal pain. Patient was seen yesterday at another ED after presenting with the same complaints. Nothing significant was found during her last visit despite negative lab work, pelvic ultrasound and CT Abdomen pelvis. She was discharged following pain control + 1 dose of fluconazole for vaginal candidiasis. She is returning today with acute, severe pain starting at 2:00 AM along with nausea. Currently rates pain at 6/10. Pain was initially present in the LLQ but now feels diffusely present across her lower and LUQ abdomen. She also reports decreased appetite and constipation x1 week.
Of note, patient reported having a mild cough and low-grade fever for which she was found to be COVID positive 2 weeks ago. She otherwise denied chest pain, SOB, dizziness, fevers, hematuria, bloody stools, urinary frequency/urgency, urinary retention, and recent lower extremity swelling. She denies prior history of abdominal surgeries. No known cardiac risk factors including cocaine/tobacco use or prior family history of premature coronary artery disease. No prior DVT/PE.
Vitals: BP 124/83, Pulse 77, Temp 37C, RR 13, SpO2 99%
Relevant Physical exam: LUQ and LLQ abdominal tenderness with voluntary guarding, no rebound. Abdomen is flat and soft. Otherwise, the remainder of the exam is unremarkable.
ED Course:
Labs:
- CMP and CBC normal, Pro BNP 4, 112, hsTrop 5,226
- EKG no acute ST-T ischemic changes
Imaging:
- CT Abdomen/pelvis: mild constipation but otherwise no acute pathologic abnormalities
Pelvic US and CTA chest negative
TTE: Moderately reduced LVEF (approx. 40%), with limited images precluding assessment of regional wall motion abnormalities.
Diagnosis and Management:
The patient was admitted to cardiology service for further workup. Her troponin elevation and echo findings were attributed to stress-induced cardiomyopathy in the setting of severe abdominal pain. Patient was discharged home with Metoprolol. The cause of her abdominal pain was thought to be related to constipation which improved while admitted after bowel regimen.
Clinical Question: How do you manage Takutsobu in the ED?
Background
Stress-induced cardiomyopathy (also known as Takotsubo cardiomyopathy or “broken-heart syndrome”) is a form of non-ischemic cardiomyopathy that is classically characterized by a transient systolic dysfunction, often of the apical portion of the left ventricle. Primary stress-induced cardiomyopathy often presents in late-middle aged women in their forties to sixties with limited past medical history following an extreme emotional event (such as arguments, death of relatives, stimulant drugs or major trauma/accidents) (12), while secondary stress-induced cardiomyopathy occurs in up to one in five patients with other critical illness (10).While the exact mechanism is still being studied, it is hypothesized that an overactive sympathetic system resulting in excess catecholamines causes coronary spasm, myocardial stunning and microvascular dysfunction (2, 12). While the exact incidence is uncertain, many studies have suggested that post-menopausal women are at higher risk due to their hypo-estrogenic status. Some studies have shown that estrogen has some protective effects on the cardiovascular system including vasodilation and protection against endothelial dysfunction (8,14).
Clinically, the presentation can be similar to patients having an acute coronary syndrome but can be silent (like how our patient presented). The most common symptoms patients can present with include signs of heart failures, arrhythmias, chest pain, new onset severe mitral regurgitation and in severe cases, sudden cardiac arrest (5). With regards to our patient, we primarily suspected that her severe abdominal pain as the primary inciting factor for her presentation. However, her recent COVID infection could have played an additional role. While the role of COVID in the development of Takutsobu is still not fully explained, a recent systemic study has shown that patients with COVID-19 also experience a cytokine storm syndrome accompanied by catecholamine surge which can predispose them to developing TTS (15).
The diagnosis includes the typical cardiac lab workup and imaging studies for patients who present to the ED with ACS symptoms. While this is a diagnosis of exclusion, the Mayo Clinic has outlined 5 diagnostic criteria that should be met in order to make the diagnosis (11,16):
· Transient hypokinesis, akinesis or dyskinesis in the LV mid segments with or without apical involvement
· A single epicardial vascular distribution and a stressful trigger (Although not always present)
· Absence of obstructive coronary disease or plaque rupture
· New ECG abnormalities or modest troponin elevation
· Absence of pheochromocytoma and myocarditis
Diagnosis
Beyond an elevated and pro-BNP, TTE often can demonstrate apical ballooning (typical variant, 80% of all cases) or atypical variants with basal type hypokinesis, mid-ventricular type hypokinesis and global hypokinesis. Cardiac MRI can be used if TTE is suboptimal or if the patient has co-existing coronary artery disease. Over the years, cardiac MRI has emerged as the first line diagnostic imaging of choice as it allows clinicians to identify presence of reversible and irreversible damage as well as complications such as valvular disease and LV thrombus (6,9). Cardiac catheterization is only recommended if patients with Takutsobu present with STEMI or other additional findings concerning for coronary artery disease (5, 9).
Takutsobu cardiomyopathy on CT angio (N Engl J Med 2017; 377:e24 DOI: 10.1056/NEJMicm1615835)
Management
Although patients typically recover from this condition, complications such as cardiogenic shock and death rates are found to be comparable to those with acute coronary syndrome. Male patients particularly are at a higher risk for complications including having higher death rates and major adverse cardiac and cerebrovascular events (1, 8). Once the diagnosis of Takutsobo has been made, initial treatment involves aspirin, beta-blockers (although avoid if in decompensated heart failure), statins and coronary angiography. Serial imaging studies are also recommended to monitor wall motion abnormalities and recovery of the ventricular ejection fraction. Anticoagulation is only recommended for patients who have an embolic event or show evidence of thrombus on imaging. While most patients recover in a few months, complications can still occur similar to those with ACS. Some of the main complications include LV outflow tract obstruction, ventricular arrhythmias, hypotension, cardiogenic shock, permanent heart failure and thromboembolic events (3).
Conclusion
· Takostubo is a reversible cardiomyopathy that is a diagnosis of exclusion but should be suspected in patients presenting with an ACS clinical picture but in the absence of known cardiac risk factors.
· Classically follows a strong emotional trigger such as trauma but can also occur in the setting of severe pain.
· Treatment is similar to ACS management and includes aspirin, beta-blockers and statins. Patients are often followed by an outpatient clinic for serial imaging to assess recovery of LVEF.
· Most patients will recover within a few months-year but this recovery times will vary from among patients. However, despite recovery, patients are still at high risk for major complications including arrhythmias and thromboembolism but this continues to be an active research area by clinicians.
References
1. Akashi YJ and Musha H, Kida K et al. Reversible ventricular dysfunction takotsubo cardiomyopathy. Eur J Heart Fail. 2005 Dec;7(7):1171-6.
2. Awad HH, McNeal AR, Goyal H. Reverse Takotsubo cardiomyopathy: a comprehensive review. Ann Transl Med. 2018 Dec;6(23):460.
3. Baltzer Nielsen S, Stanislaus S, Saunamäki K, Grøndahl C, Banner J, Jørgensen MB. Can acute stress be fatal? A systematic cross-disciplinary review. Stress. 2019 May;22(3):286-294
4. Bruder O, Hunold P, Jochims M et al. Reversible late gadolinium enhancement in a case of Takotsubo cardiomyopathy following high-dose dobutamine stress MRI. Int J Cardiol. 2008;127:e22–4. doi: 10.1016/j.ijcard.2007.01.081.
5. Eitel I, von Knobelsdorff-Brenkenhoff F, Bernhardt P, Carbone I, Muellerleile K, Aldrovandi A, Francone M, Desch S, Gutberlet M, Strohm O, Schuler G, Schulz-Menger J, Thiele H, Friedrich MG. Clinical characteristics and cardiovascular magnetic resonance findings in stress (takotsubo) cardiomyopathy. JAMA. 2011 Jul 20;306(3):277-86
6. Medina de Chazal H, Del Buono MG, Keyser-Marcus L, Ma L, Moeller FG, Berrocal D, Abbate A. Stress Cardiomyopathy Diagnosis and Treatment: JACC State-of-the-Art Review. J Am Coll Cardiol. 2018 Oct 16;72(16):1955-1971.
7. Neil C, Nguyen TH, Kucia A et al. Slowly resolving global myocardial inflammation/oedema in Tako-Tsubo cardiomyopathy: evidence from T2-weighted cardiac MRI. Heart. 2012;98:1278–84. doi: 10.1136/heartjnl-2011-301481.
8. Khalid N, Ahmad SA, Shlofmitz E, Umer A, Chhabra L. Sex disparities and microvascular dysfunction. Int J Cardiol. 2019 May 01;282:16.
9. Kurowski V, Kaiser A, von Hof K, Killermann DP, Mayer B, Hartmann F, Schunkert H, Radke PW. Apical and midventricular transient left ventricular dysfunction syndrome (tako-tsubo cardiomyopathy): frequency, mechanisms, and prognosis. Chest. 2007 Sep;132(3):809-16.
10. Park JH, Kang SJ, Song JK, Kim HK, Lim CM, Kang DH, Koh Y. Left ventricular apical ballooning due to severe physical stress in patients admitted to the medical ICU. Chest. 2005 Jul;128(1):296-302. doi: 10.1378/chest.128.1.296. PMID: 16002949.
11. Prasad A, Lerman A, Rihal CS. Apical ballooning syndrome (Tako-Tsubo or stress cardiomyopathy): a mimic of acute myocardial infarction. Am Heart J. 2008 Mar;155(3):408-17.
12. Rivero F, Cuesta J, García-Guimaraes M, Bastante T, Alvarado T, Antuña P, Alfonso F. Time-Related Microcirculatory Dysfunction in Patients With Takotsubo Cardiomyopathy. JAMA Cardiol. 2017 Jun 01;2(6):699-700
13. Sattar Y, Siew KSW, Connerney M, Ullah W, Alraies MC. Management of Takotsubo Syndrome: A Comprehensive Review. Cureus. 2020 Jan 3;12(1):e6556. doi: 10.7759/cureus.6556. PMID: 32042529; PMCID: PMC6996473.
14. Sharkey SW, Lesser JR, Zenovich AG, Maron MS, Lindberg J, Longe TF, Maron BJ. Acute and reversible cardiomyopathy provoked by stress in women from the United States. Circulation. 2005 Feb 01;111(4):472-9.
15. Taza F, Zulty M, Kanwal A, Grove D. Takotsubo cardiomyopathy triggered by SARS-CoV-2 infection in a critically ill patient. BMJ Case Rep. 2020;13:e236561
16. Zhang L, Piña IL. Stress-Induced Cardiomyopathy. Heart Fail Clin. 2019 Jan;15(1):41-53