*The study was based on Court records sent to the Department of Forensic Medicine, MU of Łódz by the Prosecutor’s Office for medico-legal opinion on the correctness of diagnostic–therapeutic management.

Subarachnoid haemorrhage (SAH) accounts for about 10-12% of all strokes [1]; 10-15% of patients with SAH die at home or during transport to hospital and the mortality among hospitalized patients during the first month is about 50%. The commonest cause of SAH (80-85%) is a ruptured aneurysm [3]. The other causes include Churg-Strauss syndrome, Wegener’s granulomatosis, arteriovenous anomalies, sickle cell anaemia, coagulopathies, anticoagulants [2].

The SAH symptoms are as follows: sudden severe headache peaking within several seconds, dizziness, nausea, vomiting, seizures, abnormal respiratory and heart rate, loss of consciousness, nuchal rigidity, photophobia [4].

The SAH-related complications include cerebral oedema, circulatory disturbances, neurogenic pulmonary oedema, water-electrolyte disorders, cerebral vasospasm with secondary ischaemia and hydrocephalus [2].

Unlike other CNS diseases, almost 99% of SAH cases show abnormal ECG findings characteristic of myocardial ischaemia: ST segment changes, prolonged QRS, prolonged QT, high or shortened T wave and cardiac arrhythmia [5]. In some SAH cases, impairment of the left ventricular contractility is detected, which may resemble the symptoms of Tako-Tsubo syndrome. Such changes may be suggestive of the primary heart disease yet may also be secondary to SAH [1].

The study presents a case of the Tako-Tsubo syndrome requiring intensive therapy.

CASE REPORT

The ambulance team called to a 57-year-old unconscious man diagnosed cardiac arrest in the mechanism of asystole. The patient was intubated; mechanical lung ventilation with the self-expanding bag and indirect heart massage were started; in total, the patient received  2 mg of adrenaline, 4 mg of atropine, 40 mEq NaHCO3, 10 mL 20% MgSO4, and 1000 mL 0.9% NaCl. After 10 min, the heart action was restored. Arterial pressure was initially 100/60 mm Hg and increased to 140/90 mm Hg. ECG showed atrial fibrillation with the ventricular rate of 140-160 min-1 and likely features of ischaemia of the lateral heart wall (Fig. 1). The patient`s neurological condition was assessed as Glasgow Coma Score 3.

On admission to ITU, the patient was critical, deeply unconscious, without reactions to voice or pain, with non-reactive pupils and irregular heart action of about 120 min-1. Catecholamines were administered. Laboratory tests revealed: pH 7.29, pCO2 53.5 mm Hg (7.1 kPa), pO2 83.2 mm Hg (11.1 kPa), HCO3 20.4 mmol L-1, BE -6, SaO2 94.3%,  elevated cardiac biomarkers (cardiac troponin I – 0.22 ng dL-1, creatinine kinase – 143 U L-1, creatinine kinase cardiac isoenzyme – 1.1 ng mL-1, myoglobin – 179 ng dL-1), hypokalaemia (2.9 mmol L-1) and leucocytosis (11.2 G L-1).

Echocardiography showed marked impairment of the left ventricular contractility with akinesis of the interventricular septum, anterior wall and apex. Due to suspicion of myocardial infarction, coronarography was performed yet no considerable constriction of coronary vessels was observed; the simultaneous pulmonary angiography excluded pulmonary embolism. Otherwise, left ventriculography disclosed substantial abnormalities of myocardial contractility with akinesis of the anterior-lateral and diaphragmatic segments as well as hypokinesis of the heart apex (Fig. 2). The left ventricular ejection fraction was 25-30%.

Due to persistent deep cerebral coma (Glasgow Coma Score 3), on hospitalization day 2, head CT was performed which showed subarachnoid haemorrhage with a haemorrhagic focus, 43x27 mm, in the left temporal lobe with symptoms of massive cerebral oedema. Angio-CT revealed lack of blood flow through the brain - only the right internal carotid artery and fine branches in the cerebellum were contrasted. A neurological consultation was held; no indications for surgical treatment were found.

During further hospitalization, the patient was in severe condition with symptoms of brain death. On day 8, the patient`s condition was agonal with bradycardia and decreased arterial blood pressure – despite high doses of catecholamines; cardiac arrest developed; resuscitation was withheld and the patient was pronounced dead.

The autopsy showed subarachnoid haemorrhage on the base and vaults of both cerebral hemispheres, a haemorrhagic focus in the left temporal lobe with perforation to the left lateral cerebral ventricle and internal haemocephalus (blood in the ventricular system), cerebral oedema with herniation of cerebellar tonsils to the greater occipital foramen (Fig. 3). Moreover, an aneurysm of the left central cerebral artery was found, which was the source of cerebral haemorrhage (Fig. 4).

DISCUSSION

The Tako-Tsubo syndrome (transient apical balloting syndrome, stress-induced cardiomyopathy, broken-heart syndrome) is characterized by transient segmental contractility dysfunction (akinesis or hypokinesis) of the apex and/or central segments of the left ventricle without coronary vasospasm found on coronarography [2]. The syndrome was first described in Japan in 1990 by Hikaru Sato in a patient with suspected myocardial infarction and its name is derived from a narrow-necked and wide-bottomed pot used for octopus fishing [2].

Its symptoms are often precipitated by severe emotional or physical stress [2]. Typically, patients with the Tako-Tsubo syndrome present due to sudden thoracic pain. T segments are inverted in different ECG leads (which is sometimes preceded by ST elevation) and the activity of blood cardiac enzymes is slightly increased [5, 6]. In some cases, symptoms of pulmonary oedema and cardiogenic shock are present, or even circulatory arrest can develop [6]. In fact, these symptoms are characteristic of acute coronary syndrome. In the majority of cases, however, if the patient survives, the activity of the left ventricle normalizes after several days or weeks and recurrences are rare [7, 8,  9, 10].

Left ventriculography is essential for the diagnosis of the Tako-Tsubo syndrome; yet the diagnosis should be preceded by exclusion of intracranial haemorrhage, myocarditis, hypertrophic cardiomyopathy and pheochromocytoma [2]. 

In patients with intracranial haemorrhage and other acute cerebral incidents, myocardial dysfunction may be permanent (neurogenic stunning of the myocardium), which resembles the Tako-Tsubo syndrome [10, 11, 12, 13, 14].

The syndrome affects 1-3.2% of the population and is more common in post-menopausal women (60-70 years), which is associated with decreased levels of oestrogen. Its low concentration is considered to increase the susceptibility of the myocardium to circulating catecholamines [15]. Smaller sizes of hearts are also relevant [16].

The latest studies excluded the key role of circulating catecholamines in the pathophysiology of the syndrome, which is indirectly confirmed by its cases in patients treated with adrenaline [17], in Guillian-Barre syndrome and pheochromocytoma  [19]. Moreover, increased concentration of catecholamines induced by excessive pain stimulation may also cause the Tako-Tsubo syndrome [20]. High concentrations of circulating catecholamines lead to increased production of free radicals and intracellular inflow of Ca2+. Free radical-induced dysfunction of Na+- and Ca2+-dependent transmembraneous transport results in increased Ca2+ inside the myocyte and its dysfunction [21]. A particular sensitivity of the cardiac apex to sympathetic stimulation explains the echo- and angiographic pictures observed in the Tako-Tsubo syndrome [22].

It is believed that circulatory disturbances occurring in SAH result from vegetative excitation of CNS [17, 23]. In some cases (survivors), patients with SAH or other acute cerebral incidents develop irreversible myocardial dysfunction, which mimics the Tako-Tsubo syndrome. The cases of this syndrome were described in CNS-induced seizures [15, 24]. The available literature shows that the Tako-Tsubo syndrome is most common during SAH [23, 25, 26]. Rapidly increasing intracranial pressure, stimulating the sympathetic nervous system, causes sudden release and increased concentration of catecholamines [27].

This happened in our case - the initial and main cause of deterioration of the patient`s condition was subarachnoid haemorrhage induced by a ruptured aneurysm of the left central cerebral artery and a haemorrhagic focus penetrating into the ventricular system. The pathological process triggered by primary CNS damage led to cerebral oedema and myocardial dysfunction in the form of Tako-Tsubo syndrome.

Besides the bioelectrical disturbances of the myocardium, pulmonary oedema (44-55%) and cardiogenic shock (15-45%) are observed [16]. In the majority of cases, the Tako-Tsubo syndrome is transient and the therapy provides full recovery [ 20, 23, 24, 25, 26].

In the case described, symptoms of cardiogenic shock, elevated myocardial biomarkers and marked impairment of left ventricular contractility were suggestive of myocardial infarction, which was not confirmed by coronarography. Moreover, pulmonary angiography did not reveal any abnormalities. Simultaneous ventriculography was conclusive for the final diagnosis.

The authors, evaluating the case as expert witnesses, decided that diagnostic-therapeutic management during ITU hospitalization was adequate to the patient`s clinical state and results of additional tests. Although the diagnosis of the underlying disease (i.e. intracranial haemorrhage) was delayed, in the present case, due to clinical picture and diagnostic results, this was irrelevant for the therapeutic process and its outcome. 

It should be stressed that once the Tako-Tsubo syndrome is suspected, coexisting intracranial haemorrhage, myocardial infarction, hypertrophic cardiomyopathy and adrenal pheochromacytoma should be considered.

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REFERENCES

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26.    Fujita K, Fukuhara T, Munemasa M, Numba Y, Kuyama H: Ampulla cardiomyopathy associated with aneurismal subarachnoid hemorrhage: report of 6 patients. Surgical Neurology 2007; 68: 556-561. 

27.    Masuda T, Sato K, Yamaoto S, Matsuyama N, Shimohama T: Sympathetic nervous activity and myocardial damage immediately after subarachnoid hemorrhage in a unique animal model. Stroke 2002; 33: 1671-1676.

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address:

*Anna Smędra-Kaźmirska
Katedra i Zakład Medycyny Sądowej
Uniwersytetu Medycznego w Łodzi
ul. Sędziowska 18a, 91-304 Łódź
tel. 0 - 42-654-45-36
fax 0 - 42-654-42-93
e-mail: karolanka@wp.pl

received: 18.10.2010
accepted: 11.01.2010