Takotsubo cardiomyopathy following resection of a fourth ventricle tumour

Summary

Takotsubo cardiomyopathy is a rare disorder associated with catecholamine discharge in response to episodes of stress. We present the case of a 39‐year‐old patient with no other significant medical history who suffered acute ECG changes, left ventricular dysfunction with regional wall motion abnormalities and raised cardiac enzymes following a period of severe and sustained hypertension and tachycardia associated with resection of tumour from the floor of the fourth ventricle. We believe this to be only the second case of a takotsubo cardiomyopathy related to intracranial surgery. It demonstrates the need for consideration, recognition and diagnosis of takotsubo cardiomyopathy following periods of severe peri‐operative stress.

Introduction

Takotsubo cardiomyopathy is characterised by the acute onset of reversible left ventricular dysfunction in the absence of obstructive coronary disease 1. The condition typically occurs due to episodes of severe emotional or physical stress, with the putative mechanism that the exaggerated sympathetic stimulation results in catecholamine‐induced microvascular spasm with subsequent myocardial dysfunction and stunning 2, 3.

There are multiple criteria for the diagnosis of takotsubo cardiomyopathy, with the most widely cited being the 2008 Mayo Clinic criterion. This requires:

1. Transient akinesia or dyskinesia of left ventricular apical and/or midventricular segments (classically apical ballooning and immobility)

2. No angiographic evidence of coronary artery stenosis or evidence of acute plaque rupture

3. The new ECG abnormalities (ST‐segment elevation or T‐wave inversion)

4. Absence of intracranial bleeding, phaeochromocytoma and myocarditis 4, 5.

Published reports of takotsubo cardiomyopathy complicating the peri‐operative pathway from induction to the postoperative period exist in a range of surgical specialities including general surgery, orthopaedics, obstetrics and gynaecology and neurosurgery 6. However, it is still sufficiently rare that these are reported primarily as case reports. With respect to neurosurgery only one such report relates to an intracranial operation, an endoscopic pituitary tumour adenoma resection 5, with the remainder being reported in spinal surgery.

We present a case of intra‐operative haemodynamic instability during resection of an ependymoma from the fourth ventricle resulting in stress‐induced cardiomyopathy. This became clinically apparent in the postoperative period following the administration of cyclizine. We believe this to be the first report of takotsubo cardiomyopathy complicating ependymoma resection, and one of only two reports of takotsubo cardiomyopathy complicating intracranial neurosurgery. We review the pertinent aspects of the peri‐operative literature in takotsubo cardiomyopathy. This report contributes to the body of evidence regarding recognition and diagnosis of peri‐operative TCM, which may prove critical to the management of the neurosurgical patient.

Report

A 39‐year‐old woman, with no other past medical history presented for surgical tumour resection of a fourth ventricle ependymoma. Anaesthesia was induced and maintained with target‐controlled infusions (TCI) of propofol (Schneider effect‐site (Ce)) and remifentanil (Minto effect‐site (Ce)) titrated to concentrations of 4 μg.ml⁻¹ and 4 ng.ml⁻¹, respectively. Three hours into surgery there was a rapid increase in the patient's heart rate and blood pressure to 130 bpm and 160/110 mmHg, respectively, coinciding with resection within the floor of the fourth ventricle. Surgery was stopped, the depth of anaesthesia increased (propofol Ce 3.6–6.0 μg.ml⁻¹; remifentanil Ce 5.0–8.0 ng.ml⁻¹) and a low‐dose vasopressor (metaraminol) infusion was stopped. Resolution of haemodynamic parameters occurred over 10 minutes and intravenous (i.v.) anaesthetics were reduced to propofol Ce 4.0 μg.ml⁻¹ and remifentanil Ce 6 ng.ml⁻¹. On recommencement of surgery there was a more severe and sustained haemodynamic response, with blood pressure rapidly increasing to 258/160 mmHg (mean arterial pressure 195 mmHg) and heart rate increasing to 140 bpm with dramatic ST depression (> 4.0 mm) noted on the three‐lead ECG. Surgery was immediately suspended, anaesthesia deepened (propofol Ce 6.0 μg.ml⁻¹ and remifentanil Ce 8 ng.ml⁻¹) and sevoflurane added to achieve an end‐tidal concentration of 1.3%. The surgeon confirmed patency of the cerebral aqueduct to exclude acute hydrocephalus as a cause. Despite this, the patient's heart rate and blood pressure remained elevated and i.v. 20 mmol magnesium sulphate was administered, leading to some attenuation of the high blood pressure, followed by treatment with i.v. metoprolol to a total of 4 mg, with gradual correction of haemodynamic and electrocardiographic perturbations.

The multidisciplinary consensus was to leave a small residuum of tumour for fear of provoking further life‐threatening instability. At the end of surgery, with the patient supine, PEEP and F_IO₂ were cautiously reduced while looking for evidence of cardiorespiratory impairment. The patient's trachea was extubated and she was transferred to the high dependency unit without respiratory support. Initial troponin (hsTNI) levels at 4 h postoperatively measured 1700 ng.l⁻¹ (normal range < 30 ng.l⁻¹), however, a 12‐lead ECG did not demonstrate any changes.

Nine hours following surgery, the patient received i.v. cyclizine prophylactically and this resulted in pulmonary oedema. Treatment consisted of continuous positive airway pressure (CPAP), i.v. metoprolol 2 mg, furosemide 40 mg and morphine 5 mg. Her ECG then demonstrated marked ST‐segment depression and T‐wave inversion in the inferolateral leads (Fig. 1). Echocardiography performed several hours later confirmed impaired left ventricular function with mid‐apical, inferio‐septal and inferior hypokinesis, with a degree of apical ballooning. A repeat hsTNI at 19 h had risen to 2430 ng.l⁻¹. A cardiology review raised concerns for an acute myocardial infarction but contraindications to treatment with antiplatelet therapy and clinical concern for a stress‐induced cardiomyopathy resulted in an urgent coronary angiogram being performed without any coronary abnormalities detected. Therefore, a diagnosis of takotsubo cardiomyopathy was made and ramipril 5 mg and bisoprolol 2.5 mg commenced. Symptoms of heart failure resolved over 48 h and repeat echocardiography on day 21 revealed resolution of left ventricular dysfunction with no regional wall motion abnormalities. At a 4‐month outpatient review the patient was discharged from cardiology follow‐up.

Figure 1.

ECG performed 9 h postoperatively showing widespread T‐wave inversion.

Discussion

Haemodynamic instability during posterior fossa surgery is common, with a reported incidence of 56% of brainstem tumour surgery patients 7, which could include significant increases in heart rate and blood pressure 8. The mechanism is not clearly defined but has been proposed to involve direct pressure on cranial nerve nuclei or indirect traction on cranial nerves with stimulation of the dorsal medulla oblongata 8. Unlike in our case, blood pressure rises invariably settle rapidly once the surgical stimulus is removed, with pharmacological interventions rarely required. Despite this, and perhaps surprisingly when contrasted with aneurysmal subarachnoid haemorrhages, literature reports of takotsubo cardiomyopathy involving intracranial surgery are sparse, with ours only the second to be reported.

Takotsubo cardiomyopathy is a rare disorder, and although the exact prevalence is unknown, estimates suggest the frequency to be 5.2 and 0.6 per 100,000 for women and men, respectively, with 30% of these relating to an in‐hospital surgery or procedure 6. The major pathophysiological phenomenon is a disproportionate catecholamine discharge in response to stress, therefore exaggerated anxiety about surgery or anaesthesia 6, a light plane of anaesthesia, insufficient analgesia and surgical pain or stimulus have all been suggested to be inciting factors 5. In our case, the sympathetic surge at the point of manipulation near the brainstem was almost certainly the stimulus despite what we would consider as adequate anaesthesia and analgesia.

Takotsubo cardiomyopathy may present in the peri‐operative period in a myriad of ways including pulmonary oedema, ECG changes, elevation of cardiac enzymes, hypotension, cardiogenic shock or cardiac arrest 5. The two most commonly described symptoms are acute substernal chest pain and dyspnoea, both being described on emergence 3, 5, 6. In our case despite our initial concerns of the potential for myocardial dysfunction, we were falsely reassured by the physiological stability in the immediate postoperative phase. It was only with the administration of cyclizine, our routine prophylactic management of nausea in posterior fossa surgery that symptoms and chest radiographic appearances consistent with overt pulmonary oedema occurred and were accompanied by marked ECG changes. We postulate that the temporal relationship between administration of cyclizine, tachycardia and symptoms can be explained by an exacerbation of myocardial stunning, reducing diastolic filling time and potentially an impairment of the left ventricular outflow tract associated with the regional wall motion abnormalities.

Our case highlights how the similarities in both clinical and biochemical presentations between takotsubo cardiomyopathy and an acute coronary syndrome may lead to uncertainty in the diagnosis. Therefore, it is vital that the possibility of takotsubo cardiomyopathy is considered and if there is doubt then an urgent angiogram is performed to assist in differentiation and to better inform appropriate management. This is particularly pertinent in the postneurosurgical patient where treatment with dual antiplatelet and heparin therapy may result in bleeding with catastrophic consequences.

The immediate management of a hypertensive crisis varies according to the context, and in our case the use of magnesium sulphate was determined by its immediate access. Although this helped to reduce the mean arterial blood pressure, it exacerbated her tachycardia with an associated increase in ST‐segment depression. In retrospect, given that the most prominent theories hypothesise that the pathogenesis of takotsubo cardiomyopathy relies on the activation of adrenergic receptors 4, counteracting this mechanism with β and α‐adrenergic blocking drugs such as esmolol, metoprolol and labetalol is to be recommended. These agents’ additional benefit of improved heart rate control combined with short half‐lives. In the management of future cases we would advocate preparing easily administrable concentrations of metoprolol for this purpose. Other agents could be considered depending on the physiology. For example, where hypertension occurs without tachycardia then hydralazine, glyceryl trinitrate or sodium nitroprusside may be appropriate.

Interim management of takotsubo cardiomyopathy focuses on supportive care including diuretics, nitrates and anti‐arrhythmics, and prevention of complications. These patients may also require anticoagulation, particularly in the presence of significant apical dysfunction, to prevent thrombus formation 4, balanced against the risks of bleeding. If pharmacological support is required, exogenous catecholamine use during acute cardiogenic shock could theoretically worsen the cardiomyopathy. Therefore, some suggest severe cases may benefit from early institution of temporary mechanical support devices such as intra‐aortic balloon pump, extracorporeal membrane oxygenation or temporary ventricular assist devices 6, but these require local expertise and may necessitate anticoagulation. Milrinone as a non‐catecholamine inotropic drug may have a role, as may levosimendan 9. Pulmonary oedema may be difficult to treat as the initial hypertensive crisis promotes hydrostatic pulmonary oedema with a high protein content due to disruption of the basement membrane 10. This can precipitate an acute respiratory distress syndrome‐type picture and patients may remain PEEP‐dependant for a prolonged period.

There are no controlled data to define an optimal medical regimen, but it seems reasonable to treat these patients with the standard medications that are used for left ventricular systolic dysfunction, including β‐adrenergic antagonists, angiotensin‐converting enzyme (ACE) inhibitors and diuretics. Medications such as β‐blockers are often advocated to counteract the hyper‐catecholamine state, while ACE inhibitors or angiotensin receptor blockers may improve survival at 1 year 3, 4, 5, 6.

Patients who survive the acute episode typically recover normal ventricular function within 4 weeks 3, but it is important to note that mortality in takotsubo cardiomyopathy is similar to that of acute myocardial infarction. A 30‐day risk of major adverse cardiac and cerebrovascular events of 5.9% has been reported with a mortality rate of 5.6% per year, and the rate of stroke or transient ischaemic attack of 1.7% 1. The risk of recurrence is generally considered to be low with a cumulative incidence of recurrence of approximately 5% at 6 years 6. There are reports of recurrent episodes of takotsubo cardiomyopathy in the same patient during multiple general anaesthetics 5, thus necessitating additional vigilance.

In cases in which severe haemodynamic disturbances are potentially anticipated, the plan for management should be discussed at the World Health Organization checklist team brief, with significant intra‐operative events highlighted at the sign out, taking note of the necessary changes required in postoperative management. A high index of suspicion for takotsubo cardiomyopathy in the event of extreme surgical or physiological insults will aid in the recognition and management of this rare but serious condition.