Case Report: Takotsubo syndrome in a postoperative patient without cardiological disease

Introduction

Takotsubo syndrome (TS), also known as stress cardiomyopathy, apical-ballooning syndrome, or broken heart syndrome, is characterized by a clinical presentation that mimics acute coronary syndrome (ACS).¹ The estimated prevalence of TS is between 2% and 3% in patients with suspected ACS, but it can be higher reaching up to 10% in women.^1,2

TS presents a transient regional systolic dysfunction of the left ventricle that is extended beyond the coronary artery supplying area and seems to follow the anatomic cardiac sympathetic innervation.^2,3 This mimics an ACS (myocardial infarction with ST-segment elevation) or unstable angina.⁴

The most frequent symptoms are chest pain, dyspnea, or syncope (75.9%, 46.9%, and 7.7%, respectively) according to the International Takotsubo Registry.⁵ There are still uncertainties concerning its pathophysiology, diagnosis, and treatment.⁶

This case report is about an elderly woman who was admitted to the hospital for surgery, but in the post-operative phase, she presented with a complication similar to ACS, which was later diagnosed as TS. Here, we report the clinical symptoms and how the patient’s condition improved.

Case report

We present a case of an unemployed 80-year-old female patient from Cajamarca, Peru with a history of arterial hypertension and type 2 diabetes for the last 10 years by which she has followed irregular treatment. She was admitted by emergency to a hospital in Lambayeque, in the North West of Peru. On admission, the patient complained of stabbing abdominal pain in the right hemiabdomen, nausea, and constant vomiting after suffering a fall from approximately one meter. Once in the emergency department, she was evaluated by the surgery service that made the diagnosis of closed abdominal trauma and Chilaiditi’s syndrome and she was taken to the operating room to undergo surgery. Findings on the laparotomy showed hepatic injury, with a portion of the colon abnormally interposed between the liver and the diaphragm. A day after admission for surgery, she was taken to the recovery room. There, she started presenting with moderate dyspnea and tachycardia. After performing a Holter electrocardiogram (ECG), sinus rhythm, paroxysmal atrial fibrillation, and infrequent ventricular extrasystoles without abnormalities in the ST-segment were found. Echocardiography was also carried out, which revealed that the patient presented 75% preserved left ventricular ejection fraction (LVEF) with preserved motility, no hypertrophy or dilation of cavities, and type 1 diastolic dysfunction. During the first five days after admission, the patient continued presenting dyspnea, which was aggravating until it became severe with added oliguria. This was a diagnostic challenge because the description on the ECG suggested ACS or some other cardiac pathology (e.g., dilated, restrictive, or hypertrophic cardiomyopathy, which were previously ruled out due to normal conserved structure in echocardiography). Seven days after admission for emergency and three days after surgery, she was admitted to the Intensive Care Unit (ICU) with a thrombolysis in myocardial infarction (TIMI) risk score of nine (probability of mortality of 35.9% over 30 days). In the ICU, the patient started with severe respiratory insufficiency, marked hypotension, and anuria, requiring intubation and ventilation support, hemodynamic support with vasopressor therapy (norepinephrine by continuous intravenous infusion at a dose of 0.12 and 004 μg/kg/min each day), and dialysis support.

The day after she was admitted to the ICU (post-operative day four), the patient presented with atrial fibrillation with a high ventricular response; then, an amiodarone infusion was administered reverting the dysrhythmia. At the moment of the dysrhythmia, serial ECG was performed in which marked negative T-waves in II, III, and augmented vector foot (aVF) leads, and all precordial leads were observed (Figure 1). Neither ST-segment disorder nor pathologic Q-waves were present. For this reason, the cardiology department performed echocardiography for the second time (post-operative day eight) where 44% LVEF systolic dysfunction, dilated left ventricle, mild mitral insufficiency, and severe aortic insufficiency with marked apical dyskinesia and contraction of basal segments were evidenced. In the cineangiogram, neither lesions nor occlusion were found in the trunk of the left coronary artery, anterior descending artery, circumflex artery, or right coronary artery (Figure 2).

Figure 1. A: Negative T waves, in II, III and aVF. B: Nine days after treatment, with resolution of negative T waves. aVF, augmented vector foot; aVR, augmented vector right; aVL, augmented vector left.

Figure 2. Cardiac characterization of the patient showing permeable coronary arteries with apical dyskinesia.

Suspecting ACS, anti-ischemic therapy was begun with digoxin 0.125 mg per day and cardiac enzymes were required, which resulted in an elevation of troponin T (0.35 ng/ml) and troponin I (0.55 ng/ml). The creatine phosphokinase (CK-MB) value was 30.8 IU/L. Considering these results, coronary angiography was performed in which no coronary lesions were evidenced. NT-proBNP had a value greater than 35,000 pg/ml.

The diagnosis of Takotsubo syndrome with cardiogenic shock was made. An added septic process was ruled out with cultures and procalcitonin, which were negative. To complete the diagnostic study, abdominal transmission electron microscopy (TEM) and renal echography were conducted, ruling out a neoplastic process, pheochromocytoma, or any other spreading process.

A total of 10 days after admission to the ICU (post operative day 13), the patient ceased presenting shock; so, the vasopressor infusion was discontinued (norepinephrine by continuous intravenous infusion at a dose of 0.12 and 004 μg/kg/min, which she received for two days). It should be noted that dobutamine by continuous intravenous infusion was also administered, but only for 24 hours (a dose of 5 μg/kg/min); then it was discontinued because the patient started presenting hypotension and tachyarrhythmia.

A total of 13 days after admission to the ICU (post operative day 16), continuous intravenous infusion of nitroglycerin was given at a dose of 20–40 mcg/min, which was administered for 24 hours to control coronary vasospasm. No evidence of systolic dysfunction (LVEF: 65%) was observed in control echocardiography during the infusion of nitroglycerin; motility was preserved with type 1 diastolic dysfunction, with mild aortic and mitral insufficiency, and no apical dyskinesia. On echocardiographic findings, up to the date of reversion of the clinical picture of marked systolic dysfunction, negative T-waves persisted without evidence of ST-disorder or pathological Q-waves.

Infusion of nitroglycerin was discontinued by evidence of clinical improvement. Therefore, the patient continued treatment with atorvastatin (sublingual, 40 mg/day), enoxaparin (subcutaneous injection, 40 mg/day), digoxin (intravenous, 0.125 mg/day), and daily dialysis support.

The patient was removed from mechanical ventilation, being extubated 15 days after hospitalization in the ICU (post operative day 18). She continued with non-invasive ventilator assistance for a further three days. Then, she was continued with low flow oxygen therapy with FIO₂ 0.30 via nasal cannula. After that, the patient was discharged from the Internal Medicine service with daily dialysis support because of persistent anuria. Before discharge, pheochromocytoma, intracranial involvement, previous ischemic heart disease and severe organic valvular heart disease could be excluded. The patient progressed favorably until discharge.

At three months of follow-up, the patient did not present any hospital readmission, preserved systolic function (LVEF: 62%), and no other cardiac abnormalities. However, the patient eventually reported precordial pain without becoming disabling.

Discussion

TS implies a diagnostic challenge because the initial clinical picture may be difficult to differentiate from ACS. TS is not uncommon but there are not many reports in Peru, perhaps due to the lack of adequate clinical suspicion.

It has been observed that TS affects women (85–90%) aged between 65 and 70 years old more often than men,^5,6 which is similar to what was observed in the present clinical case. This could be explained by the fact that estrogens regulate the myocardial sympathetic tone and vascularization in women of reproductive age. This sympatholytic effect of estrogens is lost after menopause, leading to an effect in the abnormality of the contraction of the left ventricle of TS.⁷ Other causes have been related to the higher frequency of emotional or physical stress.¹ TS can also appear in young women, children, and newborns.³

The etiology of Takotsubo is still uncertain but may be associated with catecholamine elevations during times of emotional or physical stress, and we believe that a post-surgical catecholamine overload and a brain-heart connection hypothesis may have caused the Takotsubo syndrome in this case report, without the need for prior cardiac pathology.^8,9 It is proposed that when faced with an unexpected and severe stress response, the autonomic nervous system synthesizes sympathetic neuronal exits and adrenomedullary hormones. The epinephrine released from the adrenal medulla and the norepinephrine from the cardiac and extracardiac sympathetic nerves reach the adrenoceptors in the blood vessels and the heart.¹ In this report the patient did not have previous cardiac complications, so this support would be based on the release of catecholamines due to stress that has an expression in the cardiac receptors.

The diagnosis was mainly made by addressing one of the four criteria of Mayo Clinic for the diagnosis of TS: 1) mid and apical dyskinesia of the left ventricular segments with regional wall motion abnormalities; 2) absence of obstructive coronary artery disease; 3) appearance of new ECG abnormalities (T-wave inversion); and 4) absence of pheochromocytoma or myocarditis.¹⁰ Additionally, elevated troponin and proBNP levels were found in this case, which is frequent in patients with TS reported in international registries.⁵ Therefore, it is also considered a diagnostic criterion. However, the frequency of TS in patients with ACS is often underestimated since there is not yet full knowledge of this disease in the context of perioperative myocardial injury. It is recommended that physicians also consider the differential diagnosis in a patient admitted to the hospital with ACS and evaluate the electrocardiogram, echocardiography, and early invasive coronary angiography to rule out other possible causes of cardiomyopathy (e.g., dilated, hypertrophic, and restrictive) and ACS.

The patient was treated with norepinephrine and dobutamine at standard doses considering their significant hypotensive status. Acute stages of TS present with impaired vasodilatation and extravasation of fluid from the vasculature to the interstitial space. However, considering a cardiogenic problem, administration of the aforementioned drugs may induce additional catecholaminergic stress and precipitate TS.^6,7 As catecholamines can induce microvascular spasm or cardiac toxicity,⁶ the use of nitroglycerin controlled possible coronary insufficiency, although increased tissue sensitivity to nitric oxide is also observed in TS. Despite this, the patient showed no left ventricle outflow obstruction and presented correct evolution. It was also important to consider the complications in TS, which are common. Although lesions in cineangiogram are absent, complications like acute cardiac insufficiency (12–45%), atrial fibrillation (7–17%), cardiogenic shock (17–30%), and dysrhythmia (5–15%)^5,10,11 have been reported. Patients with TS have a high risk of developing atrial fibrillation, ranging from 7.75–17.57%.^12,13 In this report, atrial fibrillation, ventricular extrasystoles, dysrhythmia, ST-segment abnormalities, and aorta and mitral insufficiency are registered. Importantly, atrial fibrillation does not increase in-hospital mortality, but it can lead to higher levels of comorbidities such as ventricular dysrhythmias, longer hospital stays, and the development of cardiac arrest.^12,14

The prognosis of TS has been thought to be favorable as their reversible characteristic. However, these patients show considerable morbidity, mortality, and major adverse cardiovascular events similar than patients with ACS.² In this case, the patient was discharged from the hospital with clinical improvement. It has been observed that mortality rates of TS are higher in male patients than in female ones (8.4% vs. 3.6%, respectively; p<0.001).¹⁴

Most deaths occur among patients that develop unstable manifestations, including cardiac arrest or cardiogenic shock. The recovery of the left ventricular contraction is gradual, generally from 1 to 2 weeks although it can be fast (within 48 hours) or late (up to 6 weeks). However, one important problem to solve is the need to determine the risk factors and the pathophysiological mechanisms in this disease, as well as the physiology of the patient already recovered from TS. This would lead to determine, with certainty, the specific care these patients require in the long term.

Conclusions

This report showed that the diagnosis and treatment of TS is complex, although it is a relatively benign and reversible disease. In the setting of an emotional, non-cardiac, or post-traumatic stressful event, TS triggers myocardial injury with segmental anomalous, which are possibly triggered by an stress-released endothelial neurotransmitter. It is important to conduct further research on cardiac and endocrine functions to find out why this disease mostly affects women. Higher methodological quality studies should be also performed to determine the best therapeutic option for these patients.

Data availability

Consent

Written informed consent for publication of their clinical details and clinical images was obtained from the patient.