Takotsubo syndrome (TTS), also known as stress cardiomyopathy, apical ballooning syndrome and broken heart syndrome, is an acute and transient left ventricular (LV) myocardial dysfunction, which can occur in the setting of a severe psychological or physical stress event, most often occurring 1 to 5 days before.1 TTS’s clinical presentation might be indistinguishable from an acute coronary syndrome (ACS) with respect to symptoms, electrocardiographic (ECG) changes and biomarkers. Since its first report in 1990 by Sato et al,2 TTS remains with no reliable non-invasive diagnostic approach, leaving coronary angiography with left ventriculography as the gold standard diagnostic tool to reject or to ratify this diagnosis to this days.3,4 Typically, it occurs in postmenopausal women with few cardiovascular risk factors.1,3–5
The exact pathophysiology of TTS is still unknown.6 Besides anecdotal case reports describing the occurrence of TTS in the setting of malignancy and chemotherapy, the role of chemotherapy and tumor in the development of TTS with regard to physical and emotional stress remains unclear.7 It has been suggested that the treatment of the malignancy itself is associated with the development of TTS.8
Herein we describe a case of a 38-year-old female patient without history of cardiovascular disorder who developed TTS during a brachytherapy session to treat an endocervical adenocarcinoma.
Case Report
A 38-year-old female presented with an abnormal pap smear in January 2018 without local or systemic manifestations. A biopsy was performed and the patient was diagnosed with endocervical adenocarcinoma. A staging magnetic resonance imaging (MRI) of the pelvis and a positron emission tomography – computed tomography (PET-CT) were performed, which showed a hypermetabolic bulky lesion arising from uterine cervix (SUV max: 23.0), without parametrial, bladder, rectal involvement, or distant metastasis. Clinical staging based on International Federation of Gynecology and Obstetrics (FIGO) classified the disease in FIGO IIA1.
The patient started chemoradiotherapy with cisplatin 40mg/m2 weekly, and high dose-rate brachytherapy starting in the fourth week of external beam irradiation. At the end of the third session (four brachytherapy sessions programmed), during applicator removal, although under anesthesia, the patient developed a ventricular tachycardia with pulse, followed by cardiopulmonary arrest in ventricular fibrillation. After two minutes of cardiopulmonary resuscitation, return of spontaneous circulation was achieved, and the patient was admitted to an intensive care unit.
During the investigation, ECG showed ST-segment elevation in lead II and in AVF, and prolonged QT interval of 470 msec (Figure 1). There was a rise in the levels of serum creatine kinase-MB (CKMB) level to 10.4 ng/mL (normal limit: < 5.0 ng/mL), serum troponin-I level was 2.04 ng/ml (normal limit: < 0.16ng/ml) and natriuretic peptide B levels (BNP) to 233 pg/mL (normal limit: < 100 pg/mL). Transthoracic echocardiogram showed marked LV dysfunction, with akinesia of all apical and middle segments of LV wall, with estimated LV ejection fraction (LVEF) of 30% (Figure.2). The coronary angiography demonstrated no obstructive lesions in the coronary arteries and moderate hypokinesia of the anterior and inferior apical segments of LV wall (Figure 3.). Holter showed rare and isolated polymorphic ventricular premature beats and signs of heart dysautonomia with parasympathetic depression and adrenergic predominance. A cardiac MRI was performed seven days after the event showing circumferential mid-ventricle hypokinesia associated with LV systolic dysfunction, however with a significant improvement of the global LV contractility (Figure 4A and Figure 4B), absence of myocardial fibrosis in the late gadolinium enhancement sequences (Figure 4C), signs of myocardial edema in the LV wall in T2-weighted sequences and moderate pericardial effusion (Figure 4D), suggestive with Takotsubo cardiomyopathy.
Treatment with carvedilol 3.125 mg twice daily and enalapril 2.5 mg twice daily (titrating the dose up to the maximum dose tolerated by the patient) was initiated. The levels of troponin-I returned to the normal range after 4 days, CKMB levels after 6 days and BNP in 12 days. Fifteen days after the event, the patient presented with chest pain, and pericarditis was diagnosed. Repeat echocardiogram after 12 days of the TTS event, showed remarkable improvement in LV function, with LVEF of 68%, preserved biventricular function and small pericardial effusion. The patient was treated with Ibuprofen 800 mg three times per day and Colchicine 0.5 mg twice daily for three months, with good response and no signs of recurrence. The cardiac MRI was repeated two months later, showing a preserved biventricular contractility, a physiological pericardial effusion, and no late gadolinium enhancement suggestive of myocardial fibrosis. Once complete cardiac recovery was achieved, she was able to resume brachytherapy, and the remaining application was performed 15 days later as an inpatient condition and under rigorous monitoring, uneventfully. The total cancer treatment time was 64 days.
The patient received further adjuvant treatment with cisplatin 50 mg/m2 plus gemcitabine 100 mg/m2, with discontinuation after one cycle due to severe myelotoxicity. Further, she continued her therapy with carvedilol and enalapril for approximately 6 months when she spontaneously decided to interrupt the treatment. The patient remains in follow-up with sustained complete response from the cancer as demonstrated by pelvic MRI and clinical examination performed every six months for two years until the time that this manuscript was submitted to publication.