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 Table of Contents  
CASE REPORT
Year : 2021  |  Volume : 5  |  Issue : 2  |  Page : 61-63

Metastatic ovarian cancer presenting as takotsubo cardiomyopathy: A case report


1 Academic Foundation Programme, North Middlesex University Hospital NHS Trust, London, United Kingdom
2 Department of Cardiology, National University Heart Centre Singapore, Singapore
3 Department of Cardiology, National University Heart Centre Singapore; Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
4 Department of Medicine, Division of Cardiology, Ng Teng Fong General Hospital, National University Health System, Singapore

Date of Submission21-Apr-2021
Date of Acceptance31-May-2021
Date of Web Publication29-Jun-2021

Correspondence Address:
Dr. Ching-Hui Sia
Department of Cardiology, 1E Kent Ridge Road, NUHS Tower Block Level 9
Singapore
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/hm.hm_29_21

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  Abstract 


A 65-year-old female presented with 2 weeks of dyspnoea, associated with orthopnoea and lower limb pitting edema. There were no prior major physical or emotional stressors. Initial investigations showed elevated N-terminal pro-B-type natriuretic peptide (NT-ProBNP), Troponin-I and dynamic ST-T changes on electrocardiogram. Coronary angiography was normal and echocardiography demonstrated apical akinesis and ballooning with normokinesis of the base of the left ventricle. A diagnosis of Takotsubo cardiomyopathy (TC) was made. The patient was initially treated for heart failure as well but a thoracentesis of pleural fluid demonstrated adenocarcinoma. Computed tomography revealed newly diagnosed metastatic ovarian adenocarcinoma. To our knowledge, TC as a presentation of undiagnosed metastatic ovarian cancer has not been reported before and we believe that this case adds to the growing literature of the link between TC and cancer.

Keywords: Left ventricular systolic dysfunction, malignancy, ovarian cancer, stress cardiomyopathy, Takotsubo cardiomyopathy


How to cite this article:
Y. Ho JS, Ming Ng TY, Cen S, Sia CH, Chan PF, Yeo TC. Metastatic ovarian cancer presenting as takotsubo cardiomyopathy: A case report. Heart Mind 2021;5:61-3

How to cite this URL:
Y. Ho JS, Ming Ng TY, Cen S, Sia CH, Chan PF, Yeo TC. Metastatic ovarian cancer presenting as takotsubo cardiomyopathy: A case report. Heart Mind [serial online] 2021 [cited 2022 Oct 2];5:61-3. Available from: http://www.heartmindjournal.org/text.asp?2021/5/2/61/319653




  Introduction Top


Takotsubo cardiomyopathy (TC) is a heart condition with transient left ventricular dysfunction, electrocardiographic findings resembling those of myocardial infarction, and the presence of raised cardiac enzymes despite a lack of coronary artery disease.[1] TC is more frequently seen in postmenopausal females and is increasingly recognized to be associated with cancers in recent studies. The pathophysiology of TC is not well established but could be attributed to increased catecholamines causing coronary microvascular impairment and myocardial toxicity, and endothelial dysfunction. The mental and physical stress of a cancer diagnosis, investigations, and treatment may contribute to TC.[2] We report a case of TC preceding the investigation for or diagnosis of metastatic ovarian cancer, and the physiological burden from the malignancy may be sufficient to trigger TC. Written informed consent from the patient was obtained for the publication of this report.


  Case Report Top


A 65-year-old female presented with shortness of breath for 2 weeks, associated with orthopnea, mild abdominal discomfort, and lower limb swelling. She was postmenopausal, a nonsmoker, and had seropositive rheumatoid arthritis on hydroxychloroquine. There were no prior major physical or emotional stressors. She was afebrile with a blood pressure of 140/90 mmHg, heart rate of 80 beats per min, and oxygen saturation of 97% on 2l nasal prongs. She was alert with dual heart sounds and decreased air entry bibasally on pulmonary auscultation. Ascites was present on abdominal examination. Bipedal pitting edema was present.

Initial laboratory investigations showed normal white cell count, hemoglobin, and platelet count. Sodium, potassium, urea, and creatinine were within normal ranges. Liver function tests were normal apart from albumin of 35 g/L (range: 38–48 g/L) and aspartate aminotransferase of 55 U/L (range 10–50U/L). N-terminal pro-B-type natriuretic peptide levels were 1450 pg/mL (range: 0–169 pg/mL). The calcium panel and coagulation profile were normal. Initial Troponin I level was 8.96 ug/L (range: 0–0.039ug/L) which down trended to 4.73 ug/L and then 4.24 ug/L. Chest X-ray revealed the presence of bilateral pleural effusions. The electrocardiogram was shown in [Figure 1].
Figure 1: The patient's electrocardiogram demonstrating dynamic ST elevations in the anterolateral leads and T wave inversions in the inferolateral leads

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The impression was non-ST elevation myocardial infarction complicated by heart failure. The patient was loaded with aspirin and clopidogrel. Intravenous frusemide was given for diuresis. However, a day later the patient desaturated. Transthoracic echocardiogram showed left ventricular ejection fraction (LVEF) of 20% with multiple regional wall motion abnormalities (RWMA) and akinesia of the mid-septal, anterior walls, and apical segments with mild mitral regurgitation [Figure 2].
Figure 2: Transthoracic echocardiogram Apical 4 chamber view at end-systole: Apical ballooning and akinesia present demonstrating resemblance to the Japanese Octopus Trap “Takotsubo” (arrows)

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The patient was sent to the coronary care unit for noninvasive ventilation. Repeat chest X-ray showed worsening of the left-sided effusion but the resolution of the right-sided effusion. A diagnostic and therapeutic thoracocentesis was done for the left-sided pleural effusion. Pleural cytology showed high-grade serous ovarian adenocarcinoma that was platinum sensitive. Computed tomographic scan of the thorax, abdomen, and pelvis showed metastatic ovarian carcinoma with ascites and metastases to the peritoneal, pleural cavities, and epidural space at C2 and T6-8 levels, causing T7 cord displacement. She was commenced on a chemotherapy regimen that involved 1 cycle of carboplatin/paclitaxel and eight cycles of carboplatin/doxetaxel.

Coronary angiogram done 2 weeks after admission showed normal coronary arteries. A repeat echocardiogram after 2 months demonstrated normalization of LVEF and resolution of RWMA.


  Discussion Top


To the best of our knowledge, this is the first case of TC as a presentation of undiagnosed metastatic ovarian cancer. In the absence of other major physical or emotional stressors, the newly diagnosed ovarian cancer was most likely the trigger for TC–a diagnosis guided by the mayo clinic criteria.[1]

TC, also known as stress cardiomyopathy, is characterized by acute and transient (<21 days) wall motion abnormality of the left ventricular apex, often associated with preceding emotional or physical stress, that usually resolves completely.[3] It is often diagnosed according to the revised mayo clinic criteria, which has four criteria: (1) Transient dyskinesia of the left ventricular midsegments with or without apical involvement; RWMA that extend beyond a single epicardial vascular distribution; a stressful trigger is often but not always present, (2) absence of obstructive coronary disease or angiographic evidence of acute plaque rupture, (3) new electrocardiographic abnormalities or modest elevation in cardiac troponin, and (4) absence of pheochromocytoma or myocarditis.[3]

Recent studies show that there is an increasing link between TC and malignancy. The prevalence of malignancy in patients with TC is reported to be 6.6% to 28.5%, higher than the general population.[4] The most common cancers associated with TC involve the breast, gastrointestinal tract, and respiratory tract.[4] TC is often triggered by emotional or physical stress. In patients with malignancy, there may be increased emotional and physical stress associated with the diagnosis, investigation, and often invasive diagnostic or therapeutic procedures. One case of TC was reported after uncomplicated laparoscopic port placement in a patient in ovarian cancer.[5] Chemotherapy such as 5-fluorouracil and capecitabine has been reported to be associated with TC in case reports.[2]

The physical burden of cancer alone may trigger TC, independent of the physical and emotional stresses associated with the diagnostic and treatment process, as seen in this case. There is an increased prevalence of malignancy both at the initial TC diagnosis and on follow-up of patients with TC.[6] Patients with TC have a significant increase in endothelial dysfunction and impaired vascular reactivity, leading to excessive vasoconstriction and impaired endothelium-dependent vasodilatation.[7] Vasomotor dysfunction is greater in the microcirculation than epicardial arteries, and 90% of patients have microvascular dysfunction. In malignancy, the inflammatory environment may lead to endothelial dysfunction and enhanced adrenoceptor sensitivity. Microvascular endothelial dysfunction was associated with a two-fold increased risk of solid-tumor cancer, cancer cell inflammatory signaling, and metastasis.[8] In postmenopausal females, decrease in estrogen causes increased sympathetic drive and endothelial dysfunction, which may explain why TC most commonly occurs in postmenopausal women.[9]

The psychological burden of malignancy may further increase the likelihood of triggering TC, also known as stress cardiomyopathy. Stress causes increase in sympathetic drive and surge in adrenaline and noradrenaline, which may cause microvascular spasms or direct myocardial injury by catecholamine-associated myocardial toxicity.[10] The role of catecholamines is supported by the increased levels in patients with TC after emotional stress, and induction of TC with the infusion of noradrenaline and dopamine.[2] There is evidence that tumor cells of different origins respond to catecholamines, which may stimulate cells to proliferate, disseminate and induce angiogenesis,[11] therefore catecholamine increase may encourage the development of both TC and malignancy.

The prognosis of TC is thought to be good with full recovery in most patients; however, those with TC and malignancy have poorer prognosis. A large cohort of 1064 TC patients showed that those with TC and malignancy were more likely to require invasive or noninvasive respiratory support, and had increased long-term mortality.[6] Prompt screening and diagnosis of malignancy are clinically important in patients with TC, which has significant prognostic implications and allowed timely treatment of ovarian cancer in this case. Further research is needed to elucidate the mechanisms behind the increasingly recognized association between TC and malignancy.

Strengths and limitations

The main limitations of this case report were that the associations identified by have other unidentified explanations and may not be generalizable to other cases. The possibility of other emotional or physical stressors could not be completely excluded, although this was investigated through thorough history taking and clinical investigations. This novel case was valuable in highlighting TC as a previously unreported manifestation of metastatic ovarian cancer.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understand that name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

CHS was supported by the National University of Singapore Yong Loo Lin School of Medicine's Junior Academic Faculty Scheme.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Ono R, Falcão LM. Takotsubo cardiomyopathy systematic review: Pathophysiologic process, clinical presentation and diagnostic approach to Takotsubo cardiomyopathy. Int J Cardiol 2016;209:196-205.  Back to cited text no. 1
    
2.
Desai A, Noor A, Joshi S, Kim AS. Takotsubo cardiomyopathy in cancer patients. Cardiooncol 2019;5:7.  Back to cited text no. 2
    
3.
Medina de Chazal H, Del Buono MG, Keyser-Marcus L, Ma L, Moeller FG, Berrocal D, et al. Stress cardiomyopathy diagnosis and treatment: JACC State-of-the-art review. J Am Coll Cardiol 2018;72:1955-71.  Back to cited text no. 3
    
4.
Angelini P, Uribe C. Is transient takotsubo syndrome associated with cancer? Why, and with what implications for oncocardiology? J Am Heart Assoc 2019;8:e013201.  Back to cited text no. 4
    
5.
Hope E, Smith M, Zeligs K, Hamilton CA, Miller C. Takotsubo cardiomyopathy following laparoscopic port placement in a patient with ovarian cancer. Gynecol Oncol Case Rep 2012;3:16-7.  Back to cited text no. 5
    
6.
Cammann VL, Sarcon A, Ding KJ, Seifert B, Kato K, Di Vece D, et al. Clinical features and outcomes of patients with malignancy and takotsubo syndrome: Observations from the international takotsubo registry. J Am Heart Assoc 2019;8:e010881.  Back to cited text no. 6
    
7.
Patel SM, Lerman A, Lennon RJ, Prasad A. Impaired coronary microvascular reactivity in women with apical ballooning syndrome (Takotsubo/stress cardiomyopathy). Eur Heart J Acute Cardiovasc Care 2013;2:147-52.  Back to cited text no. 7
    
8.
Toya T, Sara JD, Corban MT, Taher R, Godo S, Herrmann J, et al. Assessment of peripheral endothelial function predicts future risk of solid-tumor cancer. Eur J Prev Cardiol 2020;27:608-18.  Back to cited text no. 8
    
9.
Kuo BT, Choubey R, Novaro GM. Reduced estrogen in menopause may predispose women to takotsubo cardiomyopathy. Gend Med 2010;7:71-7.  Back to cited text no. 9
    
10.
Pelliccia F, Kaski JC, Crea F, Camici PG. Pathophysiology of takotsubo syndrome. Circulation 2017;135:2426-41.  Back to cited text no. 10
    
11.
Chen H, Liu D, Yang Z, Sun L, Deng Q, Yang S, et al. Adrenergic signaling promotes angiogenesis through endothelial cell–tumor cell crosstalk. Endocr Relat Cancer 2014;21:783-95.  Back to cited text no. 11
    


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  [Figure 1], [Figure 2]



 

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